To see the other types of publications on this topic, follow the link: Cancer cell pleomorphism.
Journal articles on the topic 'Cancer cell pleomorphism'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Cancer cell pleomorphism.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Caruso, Rosario A., Ciro Familiari, Giuseppe Giuffré, and Giovanni Mazzeo. "Pleomorphic Carcinoma of the Gallbladder: Report of a Case." Tumori Journal 77, no. 6 (December 1991): 523–26. http://dx.doi.org/10.1177/030089169107700615.
Full textAbstract:
The authors report a rare case of primary pleomorphic carcinoma of the gallbladder in a 70-year-old woman. A polypoid tumor protruded into the lumen from the fundus of the gallbladder. Characteristic histologic findings Included a general lack of architectural cohesiveness, marked pleomorphism, presence of mononucleated and multinucleated giant cells, extensive necrosis, leukocyte-tumor cell phagocytosis or cannibalism. Immunoreactivity for cytokeratin, carclnoembryonic antigen and epithelial membrane antigen as well as histochemical positivity for mucins demonstrated the epithelial nature of the tumor. The neoplasm behaved aggressively; the patient died of metastases 9 months after the operation.
2
Bussolati, Gianni, Caterina Marchiò, Laura Gaetano, Rosanna Lupo, and Anna Sapino. "Pleomorphism of the nuclear envelope in breast cancer: a new approach to an old problem." Journal of Cellular and Molecular Medicine 12, no. 1 (October 23, 2007): 209–18. http://dx.doi.org/10.1111/j.1582-4934.2007.00176.x.
Full text
3
Klemen, H., F. M. Smolle-Jüttner, and H. H. Popper. "Morphological and immunohistochemical study of typical and atypical carcinoids of the lung with clinico-pathological correlation." Endocrine-Related Cancer 1, no. 4 (1994): 53–62. http://dx.doi.org/10.1677/erc.0.0010053.
Full textAbstract:
ABSTRACT Typical and atypical carcinoids are neuroendocrine epithelial lung tumours which are difficult to distinguish. Confusion has been introduced by designating atypical carcinoids as well differentiated neuroendocrine carcinomas and including some tumours which are large cell neuroendocrine carcinomas. We therefore investigated 32 typical and 23 atypical carcinoids of the lung, and 9 combined forms of atypical carcinoid and small cell carcinoma. The following parameters were each independently correlated in a multivariate analysis with 10-year survival data: nuclear and nucleolar polymorphism, mitotic counts, vascular invasion, lymph node metastasis, structural pattern, location of the tumours, immunohistochemistry, age and sex of the patients. Typical carcinoids were characterized by an absence of vascular invasion and lymph node metastases, and a mean mitotic rate of 0.75/10 high power fields (HPFs), while atypical carcinoids were characterized by vascular invasion and/or metastases, a mean mitotic rate of 4.25/10 HPFs and nuclear pleomorphism. Combined forms of atypical carcinoid and small cell carcinoma were characterized by vascular invasion, metastases and a mean mitotic rate of 20.7/10 HPFs. Vascular invasion, lymph node metastases, mitotic counts and nuclear pleomorphism significantly correlated with 10-year survival data, whereas location, size and structural pattern of the tumour, age and sex did not correlate with survival. All tumours were positive for cytokeratins and at least two out of three general neuroendocrine markers. However, positive reactivity for different peptides, hormones, and neurotransmitters did not correlate with one of the structural subtypes of carcinoid or with patient survival.
4
Li, Jiayu, Yehan Zhou, Yunzhu Li, and Yang Liu. "Nuclear Morphological Characteristics in Breast Cancer: Correlation with Hormone Receptor and Human Epidermal Growth Factor Receptor 2." Analytical Cellular Pathology 2021 (November 12, 2021): 1–10. http://dx.doi.org/10.1155/2021/3037993.
Full textAbstract:
Background. Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the common diagnostic/prognostic markers in breast cancer. Few articles have recently reported the correlation between cytology and molecular subtypes. We combined nuclear morphological characteristics with HR and HER2 status to observe the relationship and provide ideas for machine learning. Methods. We reanalyzed fine-needle aspiration cytology samples and core-needle puncture histological specimens from 142 patients with invasive breast cancer between March 2019 and December 2019, and the findings were compared with the two groups (HR+/HER2- and HR-/HER2+) following nuclear cytomorphological features: nuclear/cytoplasmic ratio, difference of nuclear size, nuclear pleomorphism, chromatin feature, nuclear membrane and nucleoli, and Nottingham grading. Results. Two groups were significantly associated with the difference of nuclear size, nuclear pleomorphism, and nucleoli ( P < 0.001 ) and consistent with histological grading ( P < 0.001 ). Moreover, nucleolar characteristics of size and number had obviously statistical significance ( P < 0.001 ). Multiple micro-nucleoli were frequently seen in the HR+/HER2- group compared with the HR-/HER2+ group which mostly were observed centered medium-large nucleoli. We described four interesting nuclear morphologies in the experiment. Conclusions. There were significant differences in nuclear characteristics between two groups. HR and HER2 status not only might be predicted in cytological samples, but some specific nuclear morphological features might have potential value to help us understand molecular function and predict more information.
5
Petersen, Richard C. "Free-Radical Polymer Science Structural Cancer Model: A Review." Scientifica 2013 (2013): 1–17. http://dx.doi.org/10.1155/2013/143589.
Full textAbstract:
Polymer free-radical lipid alkene chain-growth biological models particularly for hypoxic cellular mitochondrial metabolic waste can be used to better understand abnormal cancer cell morphology and invasive metastasis. Without oxygen as the final electron acceptor for mitochondrial energy synthesis, protons cannot combine to form water and instead mitochondria produce free radicals and acid during hypoxia. Nonuniform bond-length shrinkage of membranes related to erratic free-radical covalent crosslinking can explain cancer-cell pleomorphism with epithelial-mesenchymal transition for irregular membrane borders that “ruffle” and warp over stiff underlying actin fibers. Further, mitochondrial hypoxic conditions produce acid that can cause molecular degradation. Subsequent low pH-activated enzymes then provide paths for invasive cell movement through tissue and eventually blood-born metastasis. Although free-radical crosslinking creates irregularly shaped membranes with structural actin-polymerized fiber extensions as filopodia and lamellipodia, due to rapid cell division the overall cell modulus (approximately stiffness) is lower than normal cells. When combined with low pH-activated enzymes and lower modulus cells, smaller cancer stem cells subsequently have a large advantage to follow molecular destructive pathways and leave the central tumor. In addition, forward structural spike-like lamellipodia protrusions can leverage to force lower-modulus cancer cells through narrow openings. By squeezing and deforming even smaller to allow for easier movement through difficult passageways, cancer cells can travel into adjacent tissues or possibly metastasize through the blood to new tissue.
6
Koike, Etsuko, Keiichi Iwaya, Akinori Watanabe, Shinji Miyake, Eiichi Sato, and Takashi Ishikawa. "Association between Breast Cancer Recurrence and Cellular Dissociation Assessed Using Fine-Needle Aspiration." Acta Cytologica 60, no. 5 (2016): 413–20. http://dx.doi.org/10.1159/000448508.
Full textAbstract:
Objective: To determine the associations between breast cancer recurrence and cytological findings of fine-needle aspiration cytology (FNAC). Study Design: The study included 117 women who had undergone a modified radical mastectomy for invasive ductal carcinoma of the breast. FNAC samples of these patients were reexamined, and cytological findings, such as cellular dissociation, nuclear pleomorphism, nuclear atypia, chromatin pattern, and nuclear size, were scored. Uni- and multivariate analyses were performed to determine the prognostic significance of the cytological findings. Corresponding cancer tissues were immunostained for estrogen receptor, progesterone receptor, human epidermal growth factor 2 (HER2), p53, and E-cadherin to determine their associations with cytological findings. Coexpression of Arp2 and WAVE2 was also examined immunohistochemically as a cell locomotion signal. Results: Cellular dissociation (p = 0.0259) and nuclear size (p = 0.0417) were significantly associated with cancer recurrence. Multivariate analysis showed that cellular dissociation and histological grade were significant independent predictors of cancer recurrence. Cellular dissociation was found to be associated with coexpression of Arp2 and WAVE2 (p = 0.0356) and HER2 (p = 0.0469). Conclusion: The cytological finding of cell dissociation was associated with the activation of Arp2 and WAVE2 signals and was an independent predictor of recurrence.
7
Montironi, Rodolfo, Alessia Cimadamore, Antonio Lopez-Beltran, Marina Scarpelli, Gaetano Aurilio, Matteo Santoni, Francesco Massari, and Liang Cheng. "Morphologic, Molecular and Clinical Features of Aggressive Variant Prostate Cancer." Cells 9, no. 5 (April 25, 2020): 1073. http://dx.doi.org/10.3390/cells9051073.
Full textAbstract:
The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.
8
Blanco, Rancés, Charles E. Rengifo, Mercedes Cedeño, Milagros Frómeta, Enrique Rengifo, and Mayra Ramos-Suzarte. "Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma." Journal of Histology 2013 (May 29, 2013): 1–8. http://dx.doi.org/10.1155/2013/827089.
Full textAbstract:
At present, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs) for a better understanding of tumor biology and genetics of lung tumors. For this reason, we evaluated the tissue expression of carcinoembryonic antigen (CEA) and ior C2 (a cell surface O-linked glycoprotein carbohydrate chain TAA) in lung carcinomas, as well as its correlation with a variety of clinicopathological features. The tissue expression of CEA was evidenced in 22/43 (51.16%) lung carcinomas and it was correlated with mitotic activity, cell pleomorphism indexes, and age of patients. The expression of ior C2 was observed in 15/43 (34.88%) tumors but no correlation with the clinicopathological features mentioned above was obtained. No correlation between both CEA and ior C2 antigens expression and the overall survival (OS) of non-small-cell lung cancer patients was also observed. However, CEA-negative patients displayed higher OS rates as compared with positive ones (69.74 versus 58.26 months). Our results seem to be in agreement with the role of CEA expression in tumor cell proliferation, inhibition of cell polarizations and tissue architecture distortion. The significance of ior C2 antigen in these malignancies and it potential use in diagnosis, prognosis, and/or immunotherapy must be reevaluated.
9
Strosberg, J. R., D. Coppola, A. Neumann, and L. Kvols. "Clinicopathologic analysis of well, moderately and poorly differentiated gastroenteropancreatic neuroendocrine tumors." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 15028. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.15028.
Full textAbstract:
15028 Background: Pathologic features used to classify neuroendocrine tumors include mitotic rate, pleomorphism and Ki-67 index. Based on these criteria, neuroendocrine tumors are classified into well, moderately, and poorly-differentiated categories. But whereas this nomenclature is conventionally employed, it is not well defined in the field of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In particular, ‘moderately-differentiated‘ GEP-NETs are not formally recognized as a distinct category, and the clinical behavior of these tumors has not been described. Our classification of GEP-NETs is based on cell mophology and mitotic index, with well-diferentiated tumors displaying monomorphic appearance and rare mitoses (<2/10HPF), poorly differentiated tumors consisting of pleomorphic cells with a high mitotic index (>10/10HPF) and moderately-differentiated tumors displaying intermediate morphology and mitotic rate (2–10/10HPF). Methods: We performed an institutional chart analysis of patients with metastatic GEP-NETs, selecting all poorly and moderately differentiated cases and randomly selecting an equal number of patients with well differentiated tumors. The primary endpoint was overall survival. Results: A total of 83 cases were analyzed (28 well, 28 moderately, and 27 poorly differentiated). Overall survival correlated strongly with histological classification. At 2 years, survival rates among patients with well, moderately and poorly differentiated tumors were 100%, 57% and 22% respectively (p<0.001). De-differentiation of tumors was associated with a decreased rate of pentetreotide scan positivity, decreased rates of neuroendocrine hormone secretion and more widespread organ metastases. Conclusions: The classification of GEP-NETs into three histologic categories (well, moderately and poorly differentiated) correlates strongly with survival. Other features of neuroendocrine tumors (such as secretion of hormones and expression of somatostatin receptors) also correlate with histological classification. ‘Moderately- differentiated‘ neuroendocrine tumors should be recognized as a subset of GET-NETs with a prognosis that is distinct from well and poorly differentiated tumors. No significant financial relationships to disclose.
10
Kanda, Hiroaki, Noriyuki Furuta, Yutaka Takazawa, Reiko Furuta, Keisuke Ae, Yuko Sugiyama, and Yuichi Ishikawa. "Cytological Findings of Gastrointestinal Stromal Tumor-Derived Bone Metastasis." Acta Cytologica 62, no. 5-6 (2018): 430–35. http://dx.doi.org/10.1159/000492709.
Full textAbstract:
Objective: Procedures for diagnosing bone tumors should be rapid and minimally invasive. Thus, cytological examinations are more useful for such purposes than histological examinations. In order to identify cytomorphological findings that could be used to diagnose bone metastasis from gastrointestinal stromal tumors (GIST), previous cases were reviewed. Study Design: Cytological samples of 7 lesions from 4 patients with GIST-derived bone metastasis, which were obtained from 2001 to 2017 at the JFCR Cancer Institute Hospital, were reviewed. Results: The metastasis of GIST to the bone was clinically suspected before the cytological and histological examinations in all cases since they all involved other metastatic lesion(s), and characteristic osteolytic lesions were detected on radiological images. Although various cell shapes were encountered, spindle cell proliferation was seen in all cytological samples. No pleomorphism was apparent. Characteristic nuclear findings were observed. All of the cases could be diagnosed as GIST-derived bone metastasis. Conclusion: GIST-derived bone metastasis can be diagnosed by examining cytological samples.
11
Ogden, Julia, Caroline Dive, and Carlos Lopez Garcia. "Abstract 5948: Modeling lung squamous cell carcinoma progression using primary human bronchial basal cells." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5948. http://dx.doi.org/10.1158/1538-7445.am2022-5948.
Full textAbstract:
Abstract Background: Lung squamous cell carcinoma (LUSC) arises from the accumulation of genetic driver alterations in bronchial basal cells. LUSC genomes lack obvious actionable mutations and present with a high degree of inter-tumor heterogeneity. Tractable, patient relevant models are needed to study LUSC pathogenesis and investigate the role of recurrent genomic alterations in driving cancer progression. Therefore, we are developing a tractable human model of LUSC progression to increase our understanding of this disease. Methods: To investigate the contribution and co-operation of frequently mutated genes (TP53 and CDKN2A) and commonly deregulated pathways (SOX2/P63, PI3K/AKT and KEAP1/NRF2 pathways) in driving LUSC progression, we genetically engineered primary human bronchial basal cells. This culminated in eight basal cell mutants harboring ubiquitous LOF alterations in TP53 and CDKN2A combined with additional pathway alterations. To assess the function of the genetic alterations in LUSC progression, we investigated proliferation using cell cycle analysis and colony forming assays. Air-liquid interface organotypic cultures were used to model histological changes in the bronchial epithelium driven by different combinations of mutations. The resultant cultures were analyzed for changes in histology indicative of LUSC progression using immunostaining to evaluate changes to epithelial cell proliferation, and expression of LUSC biomarkers. Results: Increases in proliferation were driven by inactivation of TP53, CDKN2A and PTEN, whereas SOX2 overexpression inhibited mutant basal cell proliferation. LUSC alterations also drove striking phenotypic changes in 3D organotypic cultures of the bronchial epithelium. All mutant cultures displayed thickening of the bronchial epithelium and significantly increased cellularity (p<0.001), indicating hyper-proliferation. SOX2 overexpression inhibited mucociliary differentiation and drove the appearance of a disordered epithelium with clear cellular and nuclear pleomorphism, indicative of high-grade premalignant lesions. Conclusions: We developed a basal cell model of recurrent LUSC genetic alterations. This approach is unique due to [1] the use of primary human cells and [2] the representation of interpatient heterogeneity and developmental stages by introducing different combinations of pathway alterations. Early results indicate that basal cells carrying cumulative alterations display increasingly complex phenotypes with features of low and high-grade premalignant lesions. Further work is required to assess the tumorigenicity of mutant cells. Citation Format: Julia Ogden, Caroline Dive, Carlos Lopez Garcia. Modeling lung squamous cell carcinoma progression using primary human bronchial basal cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5948.
12
Marinca, Mihai Vasile, Irina Draga Caruntu, Ludmila Liliac, Simona Eliza Giusca, Andreea Marinca, and Lucian Miron. "Role of an extended pathology exam in risk classification of testicular germ cell tumors (GCTs)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e15032-e15032. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e15032.
Full textAbstract:
e15032 Background: The 1997 IGCCCG Consensus classification provides clinicians with enough information to efficiently choose between treatment options for most GCT patients. Nevertheless, therapy is ineffective in 5-10% of cases (even more in less developed countries), and about the same numbers experience severe side effects. This exploratory study aims to assess the impact of more rigorous and detailed pathology examination on improving the assignation of these patients to prognostic groups and, consequently, making optimal therapeutic decisions. Methods: Predefined features were reviewed on histology slides from 39 GCT patients followed-up for a median of 48.28 months. We designed a uniform pathology protocol, focused on identifying potential new prognostic factors. Categorical and continuous variables were quantified using light microscopy and computer-aided morphometry and, due to the small sample size, their statistical correlation was analyzed by exact tests and Spearman’s rho, respectively. Significant (2-sided p-value <0.05, under sample size reserve) coefficient values were entered in hierarchical cluster analysis (HCA). Results: Favorable IGCCCG group, presence of seminoma, glandular tissue pattern, presence and histoarchitecture of lymphocytic infiltrate associated better survival rates and lower risk of progression. Invasion of the epididymis and spermatic cord, presence of teratoma, choriocarcinoma and yolk-sac elements, papillary pattern and cell pleomorphism predicted poorer outcomes. HCA yielded 2 significantly distinct patient groups in terms of overall survival (p=0.018) and time to progression (p=0.080), but not disease-free survival (p=0.614). Conclusions: Quantification of tumor subtypes and other histology features of GCTs (e.g. necrosis, tissue patterns, inflammation) is feasible and, if standardized, may prove useful in optimal selection of risk groups, when performed by an experienced pathologist.
13
Khosh Kish, Ealia, Muhammad Choudhry, Yaser Gamallat, Sabrina Marsha Buharideen, Dhananjaya D, and Tarek A. Bismar. "The Expression of Proto-Oncogene ETS-Related Gene (ERG) Plays a Central Role in the Oncogenic Mechanism Involved in the Development and Progression of Prostate Cancer." International Journal of Molecular Sciences 23, no. 9 (April 26, 2022): 4772. http://dx.doi.org/10.3390/ijms23094772.
Full textAbstract:
The ETS-related gene (ERG) is proto-oncogene that is classified as a member of the ETS transcription factor family, which has been found to be consistently overexpressed in about half of the patients with clinically significant prostate cancer (PCa). The overexpression of ERG can mostly be attributed to the fusion of the ERG and transmembrane serine protease 2 (TMPRSS2) genes, and this fusion is estimated to represent about 85% of all gene fusions observed in prostate cancer. Clinically, individuals with ERG gene fusion are mostly documented to have advanced tumor stages, increased mortality, and higher rates of metastasis in non-surgical cohorts. In the current review, we elucidate ERG’s molecular interaction with downstream genes and the pathways associated with PCa. Studies have documented that ERG plays a central role in PCa progression due to its ability to enhance tumor growth by promoting inflammatory and angiogenic responses. ERG has also been implicated in the epithelial–mesenchymal transition (EMT) in PCa cells, which increases the ability of cancer cells to metastasize. In vivo, research has demonstrated that higher levels of ERG expression are involved with nuclear pleomorphism that prompts hyperplasia and the loss of cell polarity.
14
Khosh Kish, Ealia, Muhammad Choudhry, Yaser Gamallat, Sabrina Marsha Buharideen, Dhananjaya D, and Tarek A. Bismar. "The Expression of Proto-Oncogene ETS-Related Gene (ERG) Plays a Central Role in the Oncogenic Mechanism Involved in the Development and Progression of Prostate Cancer." International Journal of Molecular Sciences 23, no. 9 (April 26, 2022): 4772. http://dx.doi.org/10.3390/ijms23094772.
Full textAbstract:
The ETS-related gene (ERG) is proto-oncogene that is classified as a member of the ETS transcription factor family, which has been found to be consistently overexpressed in about half of the patients with clinically significant prostate cancer (PCa). The overexpression of ERG can mostly be attributed to the fusion of the ERG and transmembrane serine protease 2 (TMPRSS2) genes, and this fusion is estimated to represent about 85% of all gene fusions observed in prostate cancer. Clinically, individuals with ERG gene fusion are mostly documented to have advanced tumor stages, increased mortality, and higher rates of metastasis in non-surgical cohorts. In the current review, we elucidate ERG’s molecular interaction with downstream genes and the pathways associated with PCa. Studies have documented that ERG plays a central role in PCa progression due to its ability to enhance tumor growth by promoting inflammatory and angiogenic responses. ERG has also been implicated in the epithelial–mesenchymal transition (EMT) in PCa cells, which increases the ability of cancer cells to metastasize. In vivo, research has demonstrated that higher levels of ERG expression are involved with nuclear pleomorphism that prompts hyperplasia and the loss of cell polarity.
15
Xiang, Yan, Li Li, Mark Zarella, Katarzyna Brzezinska, Kareem Hosny, Steve Hou, and Fernando Garcia. "B-Cell lymphoma 2 Protein Expression and Established Clinicopathologic Features in Breast Cancers." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S51. http://dx.doi.org/10.1093/ajcp/aqz113.035.
Full textAbstract:
Abstract Objectives B-cell lymphoma 2 (Bcl-2) proto-oncogene alterations are involved in tumor genesis and play a vital role in regulating cell apoptosis. The objective of this research is to determine the prognostic value of quantitative expression of the Bcl-2 protein in breast cancer. Methods This study investigated a series of 158 primary breast cancers for Bcl-2 protein expression. Results were correlated with clinicopathologic features (age, tumor size, tubule formation, nuclear pleomorphism, mitotic count, and Nottingham prognostic index: NPI) and a panel of markers of established or presumed predictive values. Results Bcl-2 H-score (multiplied by staining intensity and percentage of positive cells) was observed to have a significant reversed correlation with the Magee Equation 1, 2, 3 (P1 < .001, P2 < .001, P3 < .001, r1 = –0.36, r2 = –0.34, r3 = –0.34). High proliferative activity as assessed by Ki-67 (>25%) staining negatively associated with Bcl-2 H-score (P = .03). Low Bcl-2 H-score was associated with old age (age >63, P = .039). Bcl-2 cytoplasm percent positive score was negatively associated (P = .02, n = 92) with overexpression of p53 (positive percentage >1.5). High Bcl-2 H-score was also associated with tumor size (T >1.5 cm, P = .034), but there was no significant correlation observed between Bcl-2 expression and the NPI calculated using the size of the lesion, the number of involved lymph nodes, and the grade of the tumor (NPI >3.4, P = .317). Conclusion (1) This study reports a correlation between Bcl-2 H-score and all three Magee equation values. (2) Bcl-2 H-score provides prognostic value better than percentage of positive cells. (3) This study further reports a correlation between Bcl-2 H-score and age, tumor size, Ki-67, and p53, irrespective of the type of adjuvant therapy received and across molecular subtypes. Collectively, these results establish the rationale for introduction of semiquantitative expression of the Bcl-2 protein to improve prognostic stratification of breast cancer patients.
16
Ullah, A., S. Heneidi, P. Biddinger, N. Patel, C. Wehrle, M. Sinkler, Z. Klaassen, E. Kruse, F. Nichols, and G. Wallace. "Paraneoplastic Limbic Encephalitis Secondary To Mixed Non-Seminomatous Germ Cell Tumours." American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S55—S56. http://dx.doi.org/10.1093/ajcp/aqaa161.119.
Full textAbstract:
Abstract Casestudy: Testicular tumors account for 1–2% of all tumors in men, with 95% of these being germ cell tumors. The main risk factor for the development of testicular cancer is cryptorchidism. Paraneoplastic limbic encephalitis is a rare sequela of testicular tumor associated with anti-Ma2 and KLH11 antibodies. The most effective treatment for paraneoplastic limbic encephalitis is treatment of the primary malignancy. We present a 41-year-old male that presented to the emergency department with two weeks of episodic alteration of consciousness and memory disturbances. Negative neurologic evaluation and imaging led to concern for a paraneoplastic process from a distant malignancy. CT imaging revealed an enlarged, necrotic para-aortic lymph node and subsequent ultrasound demonstrated a right sided testicular mass. Right radical orchiectomy was performed. Microscopically, the mass consisted of mixed respiratory epithelium, gastrointestinal glands and squamous epithelium with keratinization consistent with a post-pubertal testicular teratoma with associated in-situ germ cell neoplasia. Resection of the para-aortic mass revealed large anaplastic cells with epithelioid features, nuclear pleomorphism and frequent mitoses. Immunostaining was positive for Pan-Keratin and OCT4, consistent with poorly differentiated embryonal carcinoma. Resection of the primary and metastatic disease, as well as treatment with corticosteroids resulted in resolution of the encephalitis. This presentation of severe neurological disturbances in the setting of a metastatic mixed nonseminomatous germ cell tumor represents a rare presentation of paraneoplastic limbic encephalitis.
17
Gustafsson, Ulf, Curt Einarsson, Lennart C. Eriksson, Virgil Gadaleanu, Staffan Sahlin, and Bernhard Tribukait. "DNA Ploidy and S-Phase Fraction in Carcinoma of the Gallbladder Related to Histopathology, Number of Gallstones and Survival1." Analytical Cellular Pathology 23, no. 3-4 (2001): 143–52. http://dx.doi.org/10.1155/2001/469630.
Full textAbstract:
Gallstones are a risk factor for the development of gallbladder cancer. We studied DNA ploidy and cell cycle composition by flow cytometry in archival specimens from 52 gall bladder carcinomas in relation to histopathological grade, tumour stage, gallstone number and survival. 69% of the gallbladder carcinomas showed aneuploidy. All tumours with single stones (N=11) were aneuploid while only 61% of tumours with multiple stones (N=41) were aneuploid (p=0.002). DNA aneuploidy was related to increase in T‐category (p=0.01), grade (p=0.02), and nuclear pleomorphism (p=0.0005). The distribution of DNA ploidy shifted from tetraploid in low stage towards triploid positions in high stage tumours (p=0.02) combined with higher S‐phase values in triploid tumours (p=0.05). S‐phase fraction increased during development from normal tissue to dysplasia, cancer in situ and cancer in diploid cases (p=0.0002), and further at the change from diploid to aneuploid (p=0.004). At a median cancer specific survival time of four months patients with diploid tumours had a better survival than those with aneuploid tumours (p=0.02). In multivariate analysis of the tumour characteristic, only T‐category and tumour grade were independent prognostic factors. The shift from diploid to aneuploid and the further shift of ploidy within aneuploid tumours are in agreement with the concept of a clonal development of gallbladder cancer. These changes are combined with a stepwise increase in the fraction of S‐phase cells. Low frequency of symptoms in single stone patients may be the reason for detection of malignancy at a late stage of tumour development.
18
Lulla, Rishi, Konstantina Svokos, Kristine Pelton, Douglas Anthony, Mehdi Touat, and Keith L. Ligon. "HGG-52. SUSTAINED RESPONSE TO CRIZOTINIB MONOTHERAPY IN AN INFANT WITH GOPC-ROS1 FUSED CONGENITAL HEMISPHERIC GLIOMA." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii353. http://dx.doi.org/10.1093/neuonc/noaa222.332.
Full textAbstract:
Abstract Recent studies identified the presence of ALK/ROS/NTRK/MET alterations in a subset of infantile hemispheric gliomas. We report a case of GOPC-ROS1 fused congenital hemispheric glioma with a sustained response to crizotinib. An infant born at 28 weeks gestation was diagnosed with a large hemispheric mass at 2 weeks of life. The tumor was partially resected at 7 weeks of life. Histological evaluation confirmed a neoplasm with a spindle cell growth pattern, hypercellularity, nuclear pleomorphism, endothelial proliferation and necrosis consistent with glioblastoma. Fresh tissue was submitted for targeted panel sequencing (Oncopanel) which identified the presence of a GOPC-ROS1 fusion (exon 36:intron 4). This was confirmed by copy number analysis which showed a focal intragenic deletion with a breakpoint in ROS1 on 6q22. Given the lack of preclinical native models for ROS1 and other congenital kinase-driven gliomas, live cells were utilized to attempt to establish a patient derived cell line (organoid/neurosphere model) and intracranial patient derived xenograft model, the results of which are pending and will be reported. The GOPC-ROS1 rearrangement was structurally predicted to respond to kinase inhibitors with activity against ROS1 and crizotinib was started at 280 mg/m2/dose twice daily at 6 months of life with progressive tumor noted on imaging. Three months after initiating therapy, a 56% reduction in the tumor size and subsequent imaging revealed additional response. Our report is the first to demonstrate clinical response to crizotinib in a GPOC-ROS1 fused congenital glioblastoma and describe the development of a renewable resources for future analysis.
19
Warner, Wayne A., Deborah J. Wong, Fernando Palma-Diaz, Terry Y. Shibuya, and Jamil Momand. "Clinicopathological and Targeted Exome Gene Features of a Patient with Metastatic Acinic Cell Carcinoma of the Parotid Gland Harboring an ARID2 Nonsense Mutation and CDKN2A/B Deletion." Case Reports in Oncological Medicine 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/893694.
Full textAbstract:
We describe the presentation, treatment, clinical outcome, and targeted genome analysis of a metastatic salivary acinic cell carcinoma (AciCC). A 71-year-old male presented with a 3 cm right tail of a parotid lesion, first detected as a nodule by the patient seven months earlier. He had a right total parotidectomy with cranial nerve VII resection, right facial nerve resection and grafting, resection of the right conchal cartilage, and right modified radical neck dissection. The primary tumor revealed AciCC with two distinct areas: a well-differentiated component with glandular architecture and a dedifferentiated component with infiltrative growth pattern associated with prominent stromal response, necrosis, perineural invasion, and cellular pleomorphism. Tumor staging was pT4 N0 MX. Immunohistochemistry staining showed pankeratin (+), CD56 (−), and a Ki67 proliferation index of 15%. Upon microscopic inspection, 49 local lymph nodes resected during parotidectomy were negative for cancer cells. Targeted sequencing of the primary tumor revealed deletions of CDKN2A and CDKN2B, a nonsense mutation in ARID2, and single missense mutations of unknown significance in nine other genes. Despite postoperative localized radiation treatment, follow-up whole body PET/CT scan showed lung, soft tissue, bone, and liver metastases. The patient expired 9 months after resection of the primary tumor.
20
Lin, Tsu-Feng, Wun-Rong Lin, Marcelo Chen, Shuen-Han Dai, Fang-Ju Sun, Wei-Kung Tsai, and Allen W. Chiu. "Compare fuhrman nuclear and chromophobe tumor grade on chromophobe RCC." Open Medicine 14, no. 1 (April 13, 2019): 336–42. http://dx.doi.org/10.1515/med-2019-0032.
Full textAbstract:
AbstractBackgroundChromophobe renal cell carcinoma (chRCC) has a favorable prognosis. Due to irregular nuclei and nuclear pleomorphism, chRCC has a high Fuhrman nuclear grade (FNG). The chromophobe tumor grade (CTG) is a novel three-tier grading system that has been reported to be a better prognosticator than the traditional FNG. We compared the two nuclear grading systems in terms of patients’ clinical outcomes.Patients and MethodWe performed this retrospective chart review of all patients with chRCC from 2000 to 2017. All pathologic features and CTG and FNG results were re-evaluated.ResultEighteen patients’ records were reviewed with a mean follow-up of 70.6 months. The nuclear grading distribution was as follows: FNG 2, 56%; FNG 3, 39%; FNG 4, 5%; CTG 1, 78%; CTG 2, 17%; and CTG 3, 6%. Only one patient died. This patient had adrenal invasion, lung metastasis, sarcomatoid change and tumor necrosis, and the tumor was graded as FNG 4 and CTG 3. Overall survival was associated with both FNG and CTG.ConclusionChromophobe RCC was associated with a low rate of cancer-specific death and sarcomatoid differentiation. Both FNG and CTG were associated with overall survival.
21
Laksmi, Lidya Imelda, Ilham Ari Seja, and Syah Mirsya Warli. "The Association between Tumor Budding Peritumoral and Histologic Grade in Penile Squamous Cell Carcinoma." Open Access Macedonian Journal of Medical Sciences 10, B (April 2, 2022): 920–26. http://dx.doi.org/10.3889/oamjms.2022.8592.
Full textAbstract:
ABSTRACTIntroduction Squamous cell carcinoma (SCC) is the largest type of Penile Cancer, which is usually lymphomatous that spreads to the inguinal lymph nodes. Inguinal lymph node metastases are the most important factor in predicting survival in penile SCC and therapy choices. Tumor budding is a biological phenomenon that has been described in malignancies and have both predictive and independent significant prognostic. Lack of information about tumor budding in penile SCC. This study determines whether there is a correlation between tumor budding peritumoral with histological grade in penile SCC.
Materials and Methods : Samples are taken from the paraffin blocks of patients diagnosed with penile SCC. The tumor budding peritumoral evaluation was classified as less 5 buds (low grade) and five or more buds (high grade) using H&E staining. Histological grade of penile SCC is assessed based on the WHO, and ISUP grade scoring system evaluated based on nuclear pleomorphism with varying amounts of keratin production, which is divided into 3 grade; grade I (well-differentiated carcinoma), grade II (moderately differentiated carcinoma), grade III (poorly differentiated carcinoma). The correlation of tumor budding peritumoral with histopathological grade in penile SCC was analyzed statistically.
Results The mean age of SCC patient was 51.16 years old with range 60-69 years old had the most respondents. The glans penis is the most prevalent site for a tumor, with stage IIIB is being the most dominant stage. The majority of the samples were from lymph node metastases. The majority of peritumoral budding tumors (60.7 percent) had high-grade budding.
Conclusions This research discovered a significant correlation between peritumoral budding tumors and grade histopathology of Penile SCC (p-value = 0.0005).
Keywords: Tumor budding, peritumoral, histopathological grade, penile SCC
22
Stepanov, Yurij, Lidiya Mosijchuk, and Oksana Petishko. "Histological criteria of differential diagnostics of pre-cancer changes in the gastric mucosa." JOURNAL OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE, no. 1-2 (January 17, 2021): 38–45. http://dx.doi.org/10.37621/jnamsu-2020-1-2-5.
Full textAbstract:
Objective: to analyze the immunohistochemical and morphometric features of intestinal metaplasia, intraepithelial neoplasia and undefined gastric intraepithelial neoplasia. Materials and methods. During video gastroscopy using the video endoscopic system EVIS EXERA III with an Olympus 190 gastroscope (Japan), biopsy specimens of 40 patients with chronic atrophic gastritis were obtained. Immunohistochemical studies allowed the formation of groups: intestinal metaplasia (cell proliferation exclusively in the intestinal metaplasia growth zone), indefinite intraepithelial neoplasia (single cells in a state of proliferation in the foveolar zone of glands) and intraepithelial neoplasia (pronounced activation of proliferation, decreased apoptotic activity in the intestinal metaplasia growth zone). Morphometric indicators such as the nuclear-cytoplasmic ratio and nuclear ellipticity coefficient were also calculated. Results. It was found that in intestinal metaplasia, the ratio of Caspase-3 positive cells to Ki-67 positive cells approaches 1 in all zones, while the nuclear-cytoplasmic ratio significantly increases, and the ellipticity coefficient of the nuclei decreases. In cases of undetermined intraepithelial neoplasia, the proliferation / apoptosis index increases significantly in the surface-foveolar zone and the adjacent glands, but decreases in the growth zone of intestinal metaplasia, which indicates the activation of protective mechanisms outside the metaplastic zones. Similar changes, but more pronounced, took place with intraepithelial neoplasia. Nuclei pleomorphism, which is a sign of more severe structural changes in the gastric mucosa, was characterized by a reduced number of goblet cells in the foci of intestinal metaplasia, noticeable fluctuations in the average deviation of the diameter and area of the nuclei of epithelial cells. Mononuclear infiltration of the lamina propria was least likely to accompany intestinal metaplasia and, most often, vague intraepithelial neoplasia. Conclusions. The combined use of immunohistochemical and morphometric methods of research allowed us to develop histological criteria for the differential diagnosis of precancerous changes in the gastric mucosa, which will contribute to adequate monitoring of patients with atrophic gastritis. Key words: differential diagnosis, intestinal metaplasia, undefined intraepithelial neoplasia of the gastric mucosa, immunohistochemistry, morphometry, nuclear-cytoplasmic ratio, nuclear ellipticity coefficient.
23
Conceição, Alexsandro Machado, Rachel Livingstone Felizola Soares De Andrade, Carlos Alberto Palmeira Sarmento, Karine Dos Santos Souza, and Emerson Ticona Fioretto. "Squamous Cell Carcinoma in Chinese Hamsters (Cricetulus griseus)." Acta Scientiae Veterinariae 46 (March 12, 2018): 4. http://dx.doi.org/10.22456/1679-9216.86282.
Full textAbstract:
Background: The companion animal market has changed over the years. The number of people living in small apartments has increased; as a result, the demand for small pets such as exotics, fish, and small rodents has also increased due to their smaller space requirements and ease of handling and care. Pets help relieve anxiety and stress in people suffering from social issues. Small rodents are usually bred in specific cages with cellulose or wood shaving bedding, and fed with commercially available diets. Small rodent clinics struggle due to the lack of scientific reports on some diseases and therapies. To date, the oncology literature is too limited to develop better diagnosis and treatment methods. Here, we report three cases of squamous cell carcinoma in the mandibular region of Chinese hamsters (Cricetulus griseus).Case: Three adult male hamsters averaging 1.5 years old, from different pet stores, bred under home conditions by different owners in Sergipe, Brazil, were brought to the Dr. Vicente Borelli Hospital at Pio X University for exotic veterinary care. Each animal had been bred alone in a specific breeding cage. Each had a history of apathy, loss of appetite, andrapid deformity of the facial region. Radiographs showed areas of bone involvement and extensive injury, with partial resorption of the left ramus and angle of the mandibular region. Due to the location of the tumor mass, the clinical status, and limitations in systemic treatment, euthanasia was recommended for each animal. After anamnesis, the animals weresubjected to clinical assessment. A firm and well-circumscribed mass was identified on palpation. In case A, it compromised the left mandible from the angle to the body and extended to the maxillary soft tissues and left superior lips. In case B, it extended from the ramus to the symphysis on the left side and to the maxillary region, similar to case A. In case C,it extended on both sides of the mandible symphysis, with no alterations in the maxillary soft tissues. Following clinical examination, each animal underwent laterolateral and dorsoventral radiographic examination; no images were suggestive of pulmonary metastasis. However, an expansive mandibular lesion with partial resorption, suggestive of bone neoplasia,was detected. The animals were dehydrated and in clinical distress, and euthanasia was recommended. Histopathological examination of samples from the tumor sites revealed moderate cellular and nuclear pleomorphism and proliferation of neoplastic keratinocytes, suggestive of squamous cell carcinoma, a malignant tumor of epidermal keratinocytes with a highly invasive and aggressive nature.Discussion: The number of reports in the literature of cancer in small rodent companion animals has lead us to believe that neoplasms in these animals are misdiagnosed and/or that their prevalence is underreported. The literature describes that the tumor incidence in hamsters is 3-40%, and that the incidence is higher in male rodents. This incidence range increases the analysis of cancer in these animals from rare to middle-frequent what do not contribute to the animals’ clinics and to small rodent therapeutics. Differential diagnosis of squamous cell carcinoma and other tumor types should be addressed, especially osteosarcomas. Histopathological examination is essential to clarify the etiopathogenesis.Keywords: rodents, neoplasm, keratinocytes.
24
Fujita, J., K. Hummel, and Y. Xu. "Pulmonary Tumor Thrombotic Microangiopathy (PTTM) Caused by Metastatic Ovarian High-Grade Serous Carcinoma: A Rare Case Report and Literature Review." American Journal of Clinical Pathology 158, Supplement_1 (November 1, 2022): S33—S34. http://dx.doi.org/10.1093/ajcp/aqac126.060.
Full textAbstract:
Abstract Introduction/Objective Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare entity, and often diagnosed in postmortem. PTTM is usually presented as unexplained dyspnea in a patient with known or unknown history of cancer. Tumor microemboli mainly affect the pulmonary microvasculature. PTTM is resulting from coagulation cascade activation secondary to tumor microemboli induced fibrin clot formation and fibrocellular intimal proliferation. Methods/Case Report The patient is a 65-year-old female with past medical history of ovarian high-grade serous carcinoma, and presented to the hospital with chest pain and shortness of breath. Coronary angiography showed no new obstructive disease. Echocardiogram revealed markedly elevated right ventricular systolic pressure (65-70 mmHg), indicated pulmonary hypertension. Computed tomography of the chest revealed diffuse bilateral ground glass and solid centrilobular nodules, with no pulmonary emboli identified. She developed worsening hypoxia and expired. A lung-restricted autopsy was performed. Literature review was conducted. The important gross findings included multiple firm and red-brown nodules (approximately 0.1 cm) in bilateral lungs. Microscopic examination revealed the lung parenchyma demonstrated numerous tumor microemboli in the pulmonary arterioles and occasionally in the small arteries. The tumor microemboli consist of tumor cells with various degree of fibrin deposition and fibrocellular intimal proliferation. The tumor cells were epithelioid with moderate to marked nuclear pleomorphism, occasional cytoplasmic vacuoles, frequent apoptosis and necrosis. Immunohistochemical stains for PAX-8 and WT1 highlight the tumor microemboli. These findings are consistent with PTTM secondary to metastatic ovarian high-grade serous carcinoma. Rare cases of PTTM associated with ovarian cancer were found in PubMed. Results (if a Case Study enter NA) NA. Conclusion PTTM has poor prognosis. There are no sensitive diagnostic modalities, and majority of them are diagnosed at autopsy. We have found four reported PTTM cases caused by metastatic ovarian cancer in PubMed, including one case of clear cell carcinoma and three cases of low-grade serous carcinoma. Our current report of PTTM is associated with high-grade serous carcinoma, which is not seen in the literature. The awareness of PTTM is necessary for patients with ovarian cancer.
25
Pramanik, Sharmila, Eric Yang, and Wendy Wu. "Cytologic studies of in vivo fallopian tube specimens in patients undergoing salpingo-oophorectomy." Cytojournal 17 (August 10, 2020): 19. http://dx.doi.org/10.25259/cytojournal_7_2020.
Full textAbstract:
Objectives: Recent research shows that most high grade ovarian cancer (OC) originates from the fallopian tube (FT). Cytologic evaluation of FT cells may enable early detection of OC. Material and Methods: This was a prospective study with patients enrolled from 3 centers (October 2016– August 2017). Forty-two women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or undergoing risk-reducing surgery for BRCA mutations were included in the study. At the time of scheduled surgery, a novel catheter was used to collect FT cells through hysteroscopy. A pathologist blinded to surgical or pathologic findings evaluated FT cytology, and results were compared to pathology. Results: Of the 61 samples collected, 72% (44/61) met the adequacy criteria (≥5 clusters of cells with 20 cells in each cluster). Cytology classification criteria were established and applied to adequate samples. Forty-four samples were benign with mixed population of cells with round, oval, and spindled nuclei; 2-dimensional clusters; columnar cell configuration; flat sheets; cilia presence; no/mild nuclear pleomorphism; no nuclear membrane irregularities; and no nucleoli. Five samples had benign features with reactive nuclear and cytoplasmic changes and/or background inflammation, which were categorized as “reactive atypia.” Two malignant samples had features of 3-dimensional (3D) clusters, loss of mixed population of cells; increased nuclear/cytoplasmic ratio; nuclear membrane irregularity and nucleoli presence. Three samples with some but not all of malignant features were categorized as “neoplastic” (anisonucleosis; small nucleoli and features suggestive of 3D clusters). Malignant/ neoplastic samples were labeled as “Positive” (n = 5) while benign/reactive samples were labeled as “Negative” (n = 39). A high concordance rate (95%, 42/44) was observed between cytology results and histology. Conclusions: We characterized cytologic features for pathologically distinct FT samples collected in vivo using a novel catheter and demonstrated its value in detecting OC.
26
Bagriacik, Emin Umit, Mustafa Kemali Baykaner, Melek Yaman, Gizem Sivrikaya, Emre Durdağ, Hakan Emmez, GökçeÖztürk Fincan, Alp Özgün Börcek, Ahmet Eren Seçen, and Sevim Ercan. "Establishment of a Primary Pleomorphic Xanthoastrocytoma Cell Line." Neurosurgery 70, no. 1 (May 27, 2011): 188–97. http://dx.doi.org/10.1227/neu.0b013e3182262c5b.
Full textAbstract:
Abstract BACKGROUND Anaplastic pleomorphic xanthoastrocytoma is an aggressively growing, malignant, and eventually fatal tumor of the central nervous system. Testing chemotherapeutic drug sensitivity under in vitro conditions would be a useful strategy to determine sensitive or resistant drugs for fatal brain cancers. OBJECTIVE To establish primary cell cultures of excised tumor tissue from pleomorphic xanthoastrocytoma–bearing patients and to test their sensitivity against various anticancer chemotherapy drugs. METHODS Prepared suspensions of the excised tumor tissue from a patient who had a recurrent grade 3 pleomorphic xanthoastrocytoma was cultured in culture dishes until cells began to grow. Immunofluorescent and immunohistochemical visualizations were performed using confocal and light microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in comparison with 3H-thymidine incorporation assay was used to test cellular toxicity of several anticancer drugs. RESULTS We established vigorously growing primary cells of the tumor. Drug sensitivity testing was conducted successfully. CONCLUSION Primary cell cultures of surgically removed tumor tissues may be useful in studies of cancer biology and chemotherapeutic drug sensitivity for recurrent malignant brain tumors, particularly for anaplastic pleomorphic xanthoastrocytoma.
27
Marrinucci, Dena, Kelly Bethel, Daniel Lazar, Jennifer Fisher, Edward Huynh, Peter Clark, Richard Bruce, Jorge Nieva, and Peter Kuhn. "Cytomorphology of Circulating Colorectal Tumor Cells: A Small Case Series." Journal of Oncology 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/861341.
Full textAbstract:
Several methodologies exist to enumerate circulating tumor cells (CTCs) from the blood of cancer patients; however, most methodologies lack high-resolution imaging, and thus, little is known about the cytomorphologic features of these cells. In this study of metastatic colorectal cancer patients, we used immunofluorescent staining with fiber-optic array scanning technology to identify CTCs, with subsequent Wright-Giemsa and Papanicolau staining. The CTCs were compared to the corresponding primary and metastatic tumors. The colorectal CTCs showed marked intrapatient pleomorphism. In comparison to the corresponding tissue biopsies, cells from all sites showed similar pleomorphism, demonstrating that colorectal CTCs retain the pleomorphism present in regions of solid growth. They also often retain particular cytomorphologic features present in the patient's primary and/or metastatic tumor tissue. This study provides an initial analysis of the cytomorphologic features of circulating colon cancer cells, providing a foundation for further investigation into the significance and metastatic potential of CTCs.
28
Naghashpour, Mojdeh, Reza Setoodeh, Lynn C. Moscinski, and Lubomir Sokol. "Clinicopathologic Characteristics and Outcome of Histiocytic and Dendritic Cell Neoplasms: A Single Institutional Experience." Blood 116, no. 21 (November 19, 2010): 2813. http://dx.doi.org/10.1182/blood.v116.21.2813.2813.
Full textAbstract:
Abstract Abstract 2813 Background: Tumors of histiocytes and dendritic cells are rare hematopoietic neoplasms of myeloid derived macrophages, and myeloid and mesenchymal stem cell derived dendritic cells. Criteria for diagnosis include morphologic and immunophenotypic evidence of histiocytic or dendritic cell differentiation, utilizing a panel of immunohistochemical markers and exclusion of lymphoid, epithelial, stromal and melanocytic phenotype. Clinical course is variably aggressive to indolent based on the tumor type and grade, with limited therapeutic options. Methods: Fifteen consecutive cases with the diagnoses of Histiocytic Sarcoma (7/15), Langerhans Cell Tumor (4/15), Interdigitating Dendritic Cell Sarcoma (2/15), Indeterminate Cell Histiocytosis (1/15), and Reticulum Dendritic Cell Tumor (1/15), evaluated at Moffitt Cancer Center between years 1989 to 2010, were retrieved from the institutional electronic database. Diagnoses were confirmed according to the WHO 2008 classification of hematopoietic neoplasms. Clinical and demographic data, treatment regimens and outcomes were extracted and analyzed. Results: Seven patients were males and eight were females. Median age at diagnosis was 60 years (range 18–90). The primary sites of involvement included, lymph node (4, 26%), skin or soft tissue (8, 54%), and bone marrow (3, 20%). Three out of seven (42%) patients with histiocytic sarcoma, had bone marrow involvement. Histopathologically, histiocytic sarcoma cases showed sheets of non-cohesive large epitheloid cells with oval to irregular nuclei, vesicular chromatin and abundant eosinophilic cytoplasm, with variable degrees of pleomorphism, with positivity for CD68 and lysozyme immunostains. IDC sarcoma cases were composed of sheets of spindled cells with vesicular chromatin and marked cytologic atypia, positive for S-100 and vimentin. Langerhans cell tumors were composed of large cells with grooved and folded nuclei, fine chromatin, inconspicuous nucleoli, and moderately abundant eosinophilic cytoplasm, with variable degree of nuclear atypia, positive for CD68, CD1a and S-100. Indeterminate cell tumor was composed of cells with abundant cytoplasm and oval to spindle shape nuclei, positive for S-100, CD68, and CD1a. Reticulum Dendritic Cell tumor shows effacement of lymph node architecture with spindle cells in storiform pattern, positive for S100, actin, and CD45. Eleven out of fifteen patients (73%) underwent resection of primary site of disease and seven (47%) of them received adjuvant chemotherapy most frequently antracycline-based. Three patients with histiocytic sarcoma died with a median survival of 48 months (range 12–48); two had disease recurrence and one developed secondary AML. Three patients with localized Langerhans cell histiocytosis involving skin were treated with complete excision of lesion or topical steroids and showed no evidence of local or systemic recurrence. Two out of 15 patients (13%) developed secondary malignancy (AML, MDS) due to prior chemotherapy for their primary disease. Median overall survival was 24 months (range 4 –168). Conclusion: Accurate diagnosis of histiocytic and dendritic cell neoplasms requires a combination of histomorphologic examination in conjunction with ancillary immunohistochemical study. Clinical course of this very rare group of disorders is heterogeneous, ranging from aggressive behavior with a poor outcome in patients with systemic manifestations to indolent in localized disease. Although a majority of patients with localized disease can achieve durable remission using currently available treatment strategies, patients with systemic or recurrent disease need novel therapeutic approaches based on better understanding of the biology of these disorders. Disclosures: No relevant conflicts of interest to declare.
29
Conley, Anthony P., Wei-Lien Wang, John A. Livingston, Vinod Ravi, Jen-Wei Tsai, Ali Ali, Davis R. Ingram, et al. "MAGE-A3 Is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma." Cancers 11, no. 5 (May 15, 2019): 677. http://dx.doi.org/10.3390/cancers11050677.
Full textAbstract:
Melanoma-associated antigen 3 (MAGE-A3) expression is generally restricted to the placenta and germline cells of the testis, but it may also be expressed in sarcoma and other cancers and is associated with poor prognosis. Immunotherapy approaches targeting MAGE-A3 in other cancers have shown mixed results in the clinic, however, use of cancer testis antigens such as MAGE-A3 may have therapeutic value in the treatment of soft tissue sarcomas. Based on the recent success of anti-programmed death-1 (PD-1) therapy in undifferentiated pleomorphic sarcoma, we hypothesize that MAGE-A3-based immunotherapies may also provide benefits in this sarcoma type. We analyzed MAGE-A3 expression of sarcoma subtypes available in the Cancer Genome Atlas and Cancer Cell Line Encyclopedia and show that undifferentiated pleomorphic sarcoma/myxofibrosarcoma (UPS/MFS) expresses this potential target gene. We have identified high protein expression by tissue microarray of 106 UPS cores. We also found that high MAGE-A3 mRNA and protein expression is associated with worse overall survival in UPS/MFS. Furthermore, our results show no human leukocyte antigen (HLA) expression loss and relatively high lymphocyte infiltration by lymphocyte specific protein tyrosine kinase (LCK) marker expression. Based on these results, we propose targeting MAGE-A3 in UPS/MFS by immunotherapy techniques.
30
Pohl, U., and Santhosh Nagaraju. "Metachronous oligodendroglial tumours with different IDH mutational profile in a young patient." Neuro-Oncology 23, Supplement_4 (October 1, 2021): iv9—iv10. http://dx.doi.org/10.1093/neuonc/noab195.021.
Full textAbstract:
Abstract Aims Oligodendroglioma is molecularly defined by mutation of isocitrate dehydrogenase (IDH) and 1p19q codeletion. IDH mutation is an early driver of tumorigenesis, via its oncometabolite 2-hydroxyglutarate, regardless of the exact mutational subtype in homologues IDH1 or IDH2. IDH mutant cells then acquire 1p19q codeletion, with haploinsufficiency likely to contribute to oncogenesis by reduced expression of genes on 1p and 19q, as well as mutations in TERT, FUBP1 (on 1p31.1) in ~30% and CIC (on 19q13.2) in ~>60% of 1p19q-codeleted gliomas. We present a case of a young patient with metachronous oligodendroglial tumours, initially thought to represent contralateral recurrence of the same disease. However, IDH mutation analysis in each tumour revealed distinct types of mutations, involving both IDH1 and IDH2, indicating different cellular lineages of tumorigenesis. We aim to present this unusual combination by illustrating the histology and molecular profile, and review the literature with regards to multifocal but molecularly distinct glioma. Method Case: The patient is a 33 year old man initially presenting with seizures, who was found to have a frontal lobe lesion (hence called tumour 1) with focal radiological enhancement, followed by a contralateral lesion in the parietal lobe 6 months later (hence designated as tumour 2). He underwent separate surgical debulking, and each time, tumour tissue was histologically and genetically examined. Testing included targeted mutation screening by immunohistochemistry and PCR based methods, pyrosequencing for MGMT methylation analysis, FISH for chromosomal LOH analysis of 1p and 19q, immunohistochemistry for mismatch repair enzymes and next generation sequencing. Results Histology of tumour 1 revealed a neoplasm with uniform cells, round nuclei and oligodendroglioma-like clear cell change, without mitoses, microvascular proliferation or necrosis. Immunohistochemistry showed absence of IDH1 R132H mutation, retained expression of ATRX and no altered p53 staining. The ki-67 index reached 6%. Sequencing of IDH1/2 mutations revealed a rare IDH2 mutation (non-/R172K). FISH confirmed codeletion of 1p19q, and the integrated diagnosis was oligodendroglioma, IDH mutant and 1p19q codeleted, WHO grade II. Histology of tumour 2 demonstrated oligodendroglioma morphology in areas, but more cellular and nuclear pleomorphism and focally brisk mitotic activity (7 mitoses in 10 hpf; ki67 index 20%), while both microvascular proliferation and necrosis were absent. Immunohistochemistry showed IDH1 R132H mutation and retained ATRX, while p53 was not expressed. FISH studies confirmed codeletion of 1p19q, and the integrated diagnosis was anaplastic oligodendroglioma, IDH mutant and 1p19q codeleted, WHO-2016 grade III. NGS data and MMR results are compared. Conclusion We present a patient with two histologically similar, but molecularly distinct oligodendroglial tumours affecting both cerebral hemispheres. Apart from the grade, the important difference is the presence of different IDH mutations, 1) a rare IDH2 mutation (non-R172K) and 2) the common IDH1 (R132H) mutation. While both types of IDH mutations identified are known to occur in oligodendroglioma, the difference clearly indicates two distinct lineages of tumorigenesis, especially as IDH mutation is considered an early event in gliomagenesis. IDH2 mutations are often associated with oligodendrogliomas, while IDH1 R132H is recognised to be frequent in both diffuse oligodendroglial and astroglial neoplasms. Multifocal divergent gliomas have been described previously but oligodendrogliomas with differing IDH mutations in the same patient have not knowingly been reported yet. Importantly, though therapeutically irrelevant here, multicentric gliomas do not automatically imply relatedness. However, a common origin or predisposition (here, even predating IDH mutation) may not be ruled out.
31
Zakka, Katerina Mary, Renjian Jiang, Olatunji B. Alese, Walid Labib Shaib, Christina Wu, Joel Wedd, Marty T. Sellers, Madhusmita Behera, Bassel F. El-Rayes, and Mehmet Akce. "Clinical outcomes of hepatocellular carcinoma variants compared to hepatocellular carcinoma." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 435. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.435.
Full textAbstract:
435 Background: There is no consensus regarding treatment for HCC variants. Clinical outcomes of HCC variants differ from pure HCC. The aim of this study is to compare clinicopathological characteristics, treatment, and outcomes of HCC variants with pure HCC. Methods: Patients with HCC and variants with 8170/3-8175/3 and 8180/3 ICD-O-3 codes were identified from National Cancer Database between 2004 and 2013. Univariate and multivariate survival analyses were conducted to analyze the association between histology and overall survival (OS). Results: 80,280 patients were identified; pure HCC 78,461 (97.7%), fibrolamellar (FLHCC) 310 (0.4%), scirrhous 161 (0.2%), spindle cell 72 (0.1%), clear cell 487 (0.6%), pleomorphic 23 (0.0%), and combined HCC and cholangiocarcinoma (mixed HCC) 766 (1.0%). 76.7% were male and 72% Caucasian. The mean age was similar in all except FLHCC (37.9 vs. 60.9-64.1 years, p < 0.001). Liver transplant was performed in 10.1% of pure HCC, 14.5% of mixed HCC, 16.2% of scirrhous, 6.9% of spindle cell, 8.8% of clear cell, 8.7% of pleomorphic, and 3.2% of FLHCC (p < 0.001). Pure HCC (10.57%) underwent surgical resection less often than variants; FLHCC (54.8%), clear cell (34.5%), mixed HCC (29.8%), spindle cell (33.3%), pleomorphic (34.8%), and scirrhous (9.9%) (p < 0.001). Ablation was performed in 9.8% of pure HCC, and in up to 8.7% of HCC variants. More than a third of all patients received chemotherapy; pure HCC (42.3%), mixed HCC (38.5%), scirrhous (31.1%), spindle cell (36.1%), clear cell (35.5%), pleomorphic (34.8%), and FLHCC (41.3%). FLHCC had the best 5-year OS (38.7%), spindle cell and pleomorphic had the worst (9.6% and 13.0%). In univariate and multivariate analyses, fibrolamellar histology, female sex, diagnosis between 2009 and 2013, treatment at academic center, well/moderately differentiated histology, early stage, and chemotherapy was associated with better OS compared to pure HCC, male sex, diagnosis between 2004 and 2008, treatment at community cancer program, poorly differentiated, late stage, and no chemotherapy (p < 0.001). Conclusions: HCC variants underwent surgical resection more often than HCC. FLHCC had the best 5-year OS. Liver transplant is commonly performed in HCC variants.
32
Begum, SM Khodeza Nahar, M. Alamgir Chowdhury, Afroza Suraya Mojumder, and Omid Khan. "Squamous Cell Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland A Case Report with Clinicopathological Review." Journal of Medicine 16, no. 2 (November 5, 2015): 118–21. http://dx.doi.org/10.3329/jom.v16i2.25442.
Full textAbstract:
Pleomorphic adenoma, though essentially benign can undergo malignant transformation. This is the case report of a 72 year old male with a giant tumor of parotid gland measuring 20.0X18.0X16.5cm & weighing 7 kg. Pleomorphic adenoma can rarely transform into carcinoma ex pleomorphic adenoma over time as it enlarges; moreover, histologically, squamous cell carcinoma (SCC) is exceedingly rare. Patient developed the tumor for a period over 20 years & it caused withdrawal from social contact. The tumor gradually enlarged without any pain or other complication except for rapid growth & pain a year before. Postoperative facial function and local control of tumor was achieved. Despite Of having a cancer with significant extracapsular invasion, our patient did not present any metastatic focus. Besides morphological patterns, authors need to categorize invasive carcinoma ex pleomorphic adenoma according to its potentiality to metastasize. Various parameters which can predict malignant transformation in pleomorphic adenoma is also yet to be explored.J MEDICINE July 2015; 16 (2) : 118-121
33
Snipes, G. Jackson, Dikran S. Horoupian, Lawrence M. Shuer, and Gerald D. Silverberg. "Pleomorphic granular cell astrocytoma of the pineal gland." Cancer 70, no. 8 (October 15, 1992): 2159–65. http://dx.doi.org/10.1002/1097-0142(19921015)70:8<2159::aid-cncr2820700825>3.0.co;2-c.
Full text
34
Athanasios, Petrou, Papalambros Alexandros, Brennan Nicholas, Karles Dimitrios, Bramis Kostantinos, Manzelli Antonio, and Papalambros Efstathios. "Pleomorphic Giant Cell Carcinoma of the Pancreas with Hepatic Metastases—Initially Presenting as a Benign Serous Cystadenoma: A Case Report and Review of the Literature." HPB Surgery 2010 (December 20, 2010): 1–5. http://dx.doi.org/10.1155/2010/627360.
Full textAbstract:
Introduction. Pleomorphic giant cell pancreatic cancer is a very rare and aggressive pancreatic neoplasm. A case of pleomorphic giant cell pancreatic cancer presenting as a cystic lesion and in association with a serous cystadenoma presents a unique case which has not been described before. Case Presentation. A 44-year-old alcoholic man presented with abdominal pain, vomiting, and weight loss. Initially, imaging suspected a pancreatic pseudocyst measuring 4.2 cm. Endoscopic ultrasound- (EUS-) guided fine-needle aspiration revealed a serous cystadenoma. With conservative intervention only (fluid resuscitation, analgesia, and antiemetics) the patient improved and was discharged under close observation. Follow-up scan at four months revealed minimal change. Three months later, he was admitted acutely. Repeat scans demonstrated mild cyst enlargement with new liver lesions. Laparoscopic biopsy revealed pleomorphic giant cell carcinoma with the organ of origin the pancreas. Conclusion. This unusual case highlights the challenges in managing pancreatic cystic lesions and emphasizes the importance of considering less common forms of pancreatic cystic masses when the findings are atypical for the presentation. Surgical excision in these cases over conservative steps may be the most appropriate management.
35
Mikos, Eryk, Joanna Dmochowska, Karol Kanon, Sara Moqbil, and Wanesa Góralczyk. "DIAGNOSIS OF PLEOMORPHIC XANTHOASTROCYTOMA." Journal of Education, Health and Sport 11, no. 9 (September 23, 2021): 457–61. http://dx.doi.org/10.12775/jehs.2021.11.09.059.
Full textAbstract:
Introduction. Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic cancer of the central nervous system that is classified as grade II according to the WHO score. It accounts for 1% of primary brain tumors. It is mainly located in the temporal lobe and belongs to a group of tumors called long-term epilepsy associated tumors. Surgical tumor resection is the treatment of choice.
Brief description of the state of knowledge. The non-invasive method of PXA diagnostics is neuroimaging, which is based on computer tomography (CT) and magnetic resonance imaging (MRI). In the image, PXA presents as a solid tumor undergoing contrast enhancement, located supratentorial, with frequent peripheral cystic components.
The characteristic histologic picture for PXA is the presence of highly pleomorphic, fusiform or round, large astrocytes with single or multiple cell nuclei. Lymphoplasmic infiltrates are visible within the tumor. The most common mutations associated with the occurrence of this cancer are mutations in the BRAF V600E gene.
Conclusions. PXA is a very rare tumor of the central nervous system (CNS) that can recur and spread throughout the CNS. Imaging tests, i.e. CT and MRI, allow for precise imaging of the lesion, however, it is necessary to perform a histopathological examination to make a final diagnosis. The rarity of this cancer assimilates diagnostic problems. Therefore, further molecular research is needed to develop more efficient diagnostics.
36
Karakuzu, Ozgur, Apostolia Maria Tsimberidou, Veronica R. Holley, Abha Adat, Sapna Pradyuman Patel, Anil K. Sood, Anthony Paul Conley, et al. "Targeting innate immunity with BXCL701 in combination with pembrolizumab in patients with advanced solid cancers: Phase 2 basket study." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 2558. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.2558.
Full textAbstract:
2558 Background: BXCL701 is an oral competitive inhibitor of dipeptidyl peptidases (DPPs), primarily DPP8/9, which triggers the inflammasome to alert and prime immune cells, leading to induction of IL-18 and IL-1ß. BXCL701 therefore, can induce an innate immune reaction and tumor inflammation, bridging between innate and adaptive immunity, potentially leading to synergistic anticancer activity when combined with PD-1 antibody pembrolizumab. Methods: This is a phase 2, open-label, single-center study (NCT04171219) of oral BXCL701 0.3 mg BID on days 1-14 and intravenous pembrolizumab 200 mg on day 1 of a 21-day cycle with a safety lead-in to evaluate RECIST/iRECIST response rate in patients with advanced solid cancers. After confirming safety and dose limiting toxicities (DLT) in the first 6 patients, additional patients are being enrolled to an immune checkpoint inhibitors (iCPI) naïve cohort and iCPI pretreated cohort. Each cohort is planned to enroll 9 patients in the first stage, and if a partial (PR) or complete response (CR) is observed the cohort is expanded to a total of 17 patients in the second stage. The treatment is considered promising if at least 3 PRs or CRs are observed in a cohort of 17 patients. Results: As of February 11, 2021, 16 patients were treated; 5 patients (prostate cancer, endometrial cancer, liposarcoma, basal cell carcinoma, squamous cell carcinoma of unknown primary) were enrolled in the iCPI naïve cohort and 11 patients (leiomyosarcoma [2], squamous cell carcinoma of unknown primary, triple negative breast cancer, uveal melanoma, melanoma, uterine myxoid sarcoma, pleomorphic sarcoma, colorectal cancer, anaplastic astrocytoma, prostate cancer) were enrolled to iCPI pretreated cohort. Among all 16 patients, there was 1 episode of grade 4 hypotension (recovered) and 1 episode of grade 5 hypotension attributed to BXCL701, which resulted in implementation of risk-mitigation strategies such as gradual dose escalation and blood pressure monitoring. In the CPI naïve cohort, of 4 patients with available imaging, 1 had a PR (microsatellite stable endometrial cancer [-62%]) and 1 durable stable disease (SD -10%, basal cell carcinoma on therapy for 6+ months). In the CPI pretreated cohort, of 9 patients with available imaging, 1 had a PR (-31%, uveal melanoma) and 3 durable SD (-22%, pleomorphic sarcoma on therapy for 8+ months; +4%, squamous cell carcinoma of unknown primary on therapy for 6 months; +5%, uterine myxoid sarcoma on therapy for 6 months). Conclusions: BXCL701 in combination with pembrolizumab demonstrated encouraging signals of activity in selected difficult-to-treat cancers. Prespecified efficacy endpoints were met in the first stage and both cohorts will proceed to second-stage of the study Clinical trial information: NCT04171219.
37
Cuevas, Elisa, Carlos Ortiz-hidalgo, Horacio Oliva, and Carmen Rivas. "Primary Pleomorphic T-cell Lymphoma of the Spleen." Leukemia & Lymphoma 9, no. 3 (January 1993): 265–67. http://dx.doi.org/10.3109/10428199309147380.
Full text
38
Surien, Omchit, Siti Fathiah Masre, Dayang Fredalina Basri, and Ahmad Rohi Ghazali. "Chemopreventive Effects of Oral Pterostilbene in Multistage Carcinogenesis of Skin Squamous Cell Carcinoma Mouse Model Induced by DMBA/TPA." Biomedicines 10, no. 11 (October 28, 2022): 2743. http://dx.doi.org/10.3390/biomedicines10112743.
Full textAbstract:
Skin squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. Pterostilbene is a natural compound proven to exhibit various pharmacological properties, including chemo-preventive effects. This study aimed to explore the chemo-preventive effect of oral pterostilbene during initiation, promotion or continuous on multistage skin SCC mouse models induced by 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-acetate (TPA). The experimental design consists of five groups of female Institute of Cancer Research (ICR) mice, with two control groups of vehicle and cancer. Three oral pterostilbene groups consisted of orally administered pterostilbene during initiation, promotion, or continuously. Oral pterostilbene significantly reduced the number and volume of tumours. Oral pterostilbene demonstrated less severe skin histology changes compared to the cancer control group, with less pleomorphic in the cells and nuclei, and the basement membrane remained intact. Our results showed fewer invasive tumours in oral PT-treated groups than in cancer groups that displayed mitotic bodies, highly pleomorphic cells and nuclei, and basement membrane invasion. The cell proliferation marker (Ki-67) was reduced in oral pterostilbene-treated groups. Overall, oral pterostilbene is a promising chemo-preventive intervention due to its anti-initiation and anti-promotion on skin carcinogenesis. Thus, the potential molecular mechanisms of oral pterostilbene chemo-prevention agent should be explored.
39
You, Hye Jin, Eun-Young Lee, Abu Rayhan, Hyun Guy Kang, June Hyuk Kim, and Jongwoong Park. "Abstract B009: Establishing new cell lines from undifferentiated pleomorphic sarcoma for sarcoma research." Clinical Cancer Research 28, no. 18_Supplement (September 15, 2022): B009. http://dx.doi.org/10.1158/1557-3265.sarcomas22-b009.
Full textAbstract:
Abstract Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma (MFH), is a high-grade soft-tissue sarcoma (STS). Despite of importance, there are very few models for study. Here, we have established and characterized UPS-derived cell lines. Cells were obtained UPS tissues by mincing followed by extracting or dissociating using enzymes and cultured by regular culture environment. Cells were maintained and immortal for months without artificial treatment and tumorigenic in vivo study. The tissues from in vivo study and tissues from patients were compared if it is representative for UPS by immunohistochemistry. Transcriptome from tissues and cell lines were compared. Several genes were identified as specific in tumor tissues and cell lines. Fusion genes were also identified. This study showed that new UPS cell lines might be a good resource for UPS study to get new insights. Citation Format: Hye Jin You, Eun-Young Lee, Abu Rayhan, Hyun Guy Kang, June Hyuk Kim, Jongwoong Park. Establishing new cell lines from undifferentiated pleomorphic sarcoma for sarcoma research [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B009.
40
Klaver, Yarne, Maud Rijnders, Astrid Oostvogels, Rebecca Wijers, Marcel Smid, Dirk Grünhagen, Kees Verhoef, Stefan Sleijfer, Cor Lamers, and Reno Debets. "Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes." Journal for ImmunoTherapy of Cancer 8, no. 2 (August 2020): e000271. http://dx.doi.org/10.1136/jitc-2019-000271.
Full textAbstract:
IntroductionLocal T-cell immunity is recognized for its contribution to the evolution and therapy response of various carcinomas. Here, we investigated characteristics of tumor-infiltrating lymphocytes (TILs), as well as T-cell evasive mechanisms in different soft tissue sarcoma (STS) subtypes.MethodsLiposarcoma, gastrointestinal stromal tumor (GIST), leiomyosarcoma, myxofibrosarcoma and pleomorphic sarcomas were assessed for T-cell numbers and phenotypes using flow cytometry. Next-generation sequencing was used to analyze T-cell receptor repertoire, mutational load, immune cell frequencies, and expression of immune-related genes.ResultsGIST, myxofibrosarcoma and pleomorphic sarcoma showed high numbers of CD8+ TILs, with GIST having the lowest fraction of effector memory T cells. These TILs coexpress the immune checkpoints PD1, TIM3, and LAG3 in myxofibrosarcoma and pleomorphic sarcoma, yet TILs coexpressing these checkpoints were near negligible in GIST. Fractions of dominant T-cell clones among STS subtypes were lowest in GIST and liposarcoma, whereas mutational load was relatively low in all STS subtypes. Furthermore, myeloid-derived cells and expression of the costimulatory ligands CD86, ICOS-L and 41BB-L were lowest in GIST when compared with other STS subtypes.ConclusionSTS subtypes differ with respect to number and phenotypical signs of antitumor responsiveness of CD8+ TILs. Notably, GIST, myxofibrosarcoma and pleomorphic sarcoma harbor high numbers of CD8+ T cells, yet in the GIST microenvironment, these T cells are less differentiated and non-exhausted, which is accompanied with a relatively low expression of costimulatory ligands.
41
Janku, Filip, Apostolia Tsimberidou, Veronica Holley, Abha Adat, Ozgur Karakuzu, Greg Call, Gabriele Urschel, Diane Healey, and Vincent O’Neill. "382 Targeting innate immunity with BXCL701 in combination with pembrolizumab in patients with advanced solid cancers: phase 2 basket study." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A407. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0382.
Full textAbstract:
BackgroundBXCL701 is an oral competitive inhibitor of DPPs, primarily DPP8/9, that activates inflammasome mediated pyroptosis. BXCL701 therefore, can induce an innate immune reaction and tumor inflammation, bridging between innate and adaptive immunity, potentially leading to synergistic anticancer activity when combined with PD-1 antibody pembrolizumab.MethodsThis is a phase 2, open-label, single-center study (NCT04171219) of oral BXCL701 0.3 mg BID on days 1–14 and intravenous pembrolizumab 200 mg on day 1 of a 21-day cycle with a safety lead-in to evaluate RECIST/iRECIST response rate in patients with advanced solid cancers. After confirming safety and dose limiting toxicities (DLT) in the first 6 patients, additional patients are being enrolled to a PD-1/PD-L1 antibodies (ab) naïve cohort and PD-1/PD-L1 ab pretreated cohort. Each cohort is planned to enroll 9 patients, and if a partial (PR) or complete response (CR) is observed the cohort is expanded to a total of 17 patients. The treatment is considered promising if at least 3 PRs or CRs are observed in a cohort of 17 patients.ResultsAs of August 24, 2020, 14 patients were treated; 5 patients (prostate cancer, endometrial cancer, uveal melanoma, liposarcoma, basal cell carcinoma) were enrolled in the PD-1/PD-L1 ab naïve cohort and 9 patients (leiomyosarcoma, squamous cell carcinoma of unknown primary, melanoma, myxoid sarcoma, pleomorphic sarcoma, colorectal cancer, anaplastic astrocytoma, prostate cancer) were enrolled to PD-1/PD-L1 ab pretreated cohort. Among all 14 patients, there was 1 episode of grade 4 hypotension (recovered) and 1 episode of grade 5 hypotension attributed to BXCL701. In the PD-1/PD-L1 ab naïve cohort, of 3 patients with available imaging, 2 had a PR (uveal melanoma previously treated with PD-1/OX40 fusion protein [-31%] n=1; and microsatellite stable endometrial cancer [-62%], n=1). In the PD-1/PD-L1 ab pretreated cohort, there were no objective responses in 5 patients with available imaging; however, a patient with pleomorphic sarcoma refractory to PD-1 antibody monotherapy demonstrated a tumor shrinkage of -18% on the first restaging imaging.ConclusionsBXCL701 in combination with pembrolizumab demonstrated encouraging signals of activity in selected difficult-to-treat cancers. Mitigation strategies to prevent events of high-grade hypotension are being implemented to allow the enrollment continuation.Trial RegistrationNCT04171219Ethics ApprovalThe study was approved by MD Anderson IRB
42
Holdbrook, Daniel Aitor, Malay Singh, Yukti Choudhury, Emarene Mationg Kalaw, Valerie Koh, Hui Shan Tan, Ravindran Kanesvaran, et al. "Automated Renal Cancer Grading Using Nuclear Pleomorphic Patterns." JCO Clinical Cancer Informatics, no. 2 (December 2018): 1–12. http://dx.doi.org/10.1200/cci.17.00100.
Full textAbstract:
Purpose Nuclear pleomorphic patterns are essential for Fuhrman grading of clear cell renal cell carcinoma (ccRCC). Manual observation of renal histopathologic slides may lead to subjective and inconsistent assessment between pathologists. An automated, image-based system that classifies ccRCC slides by quantifying nuclear pleomorphic patterns in an objective and consistent interpretable fashion can aid pathologists in histopathologic assessment. Methods In the current study, histopathologic tissue slides of 59 patients with ccRCC who underwent surgery at Singapore General Hospital were assembled retrospectively. An automated image classification pipeline detects and analyzes prominent nucleoli in ccRCC images to classify them as either low (Fuhrman grade 1 and 2) or high (Fuhrman grade 3 and 4). The pipeline uses machine learning and image pixel intensity–based feature extraction techniques for nuclear analysis. We trained classification systems that concurrently analyze different permutations of multiple prominent nucleoli image patches. Results Given the parameters for feature combination and extraction, we present experimental results across various configurations for the classification of a given ccRCC histopathologic image. We also demonstrate that the image score used by the pipeline, termed fraction value, is correlated ( R = 0.59) with an existing multigene assay–based scoring system that has previously been demonstrated to be a strong indicator of prognosis in patients with ccRCC. Conclusion The current method provides an objective and fully automated way by which to process pathologic slides. The correlation study with a multigene assay–based scoring system also allows us to provide quantitative interpretation for already established nuclear pleomorphic patterns in ccRCC. This method can be extended to other cancers whose corresponding grading systems use nuclear pattern information.
43
Branca, Giovanni, Valeria Barresi, Antonio Ieni, Eleonora Irato, and Rosario Alberto Caruso. "Pleomorphic Carcinoma of the Colon: Morphological and Immunohistochemical Findings." Case Reports in Gastroenterology 10, no. 2 (May 26, 2016): 233–40. http://dx.doi.org/10.1159/000446577.
Full textAbstract:
Pleomorphic carcinoma is an aggressive neoplasm defined by the World Health Organization (WHO) as a poorly differentiated (squamous cell carcinoma or adenocarcinoma) or undifferentiated carcinoma in which at least 10% spindle and/or giant cells are identified, or as a carcinoma constituted purely of spindle and giant cells. Although this entity has initially been shown in the lung, it has been described also in extrapulmonary locations, with only one report for a colonic site. A 65-year-old woman developed a caecal tumour. Gross examination revealed an endophytic/ulcerative mass 7 cm in length. Microscopically, the tumour was a poorly differentiated adenocarcinoma with a pleomorphic component that occupied more than 10% of the specimen. The tumour shared these histopathological findings with pulmonary giant cell carcinoma but differed in other clinicopathological features such as a pushing growth pattern, stage pT3N1, and an uneventful outcome 24 months after operation. The pleomorphic component showed morphological and immunohistochemical features compatible with mitotic catastrophe, a non-apoptotic cell death occurring in cycling cells after aberrant mitosis. These features included multinucleation, micronucleation, atypical mitoses, foci of geographic necrosis, as well as immunohistochemical overexpression of p53 and Ki-67. The interpretation of the pleomorphic component as morphological expression of mitotic catastrophe may be useful in comprehending the pathogenesis of this rare neoplasm, and it may have practical implications as a potential cancer therapeutic target.
44
Broggi, Giuseppe, Lucia Salvatorelli, Davide Barbagallo, Francesco Certo, Roberto Altieri, Elena Tirrò, Michele Massimino, et al. "Diagnostic Utility of the Immunohistochemical Expression of Serine and Arginine Rich Splicing Factor 1 (SRSF1) in the Differential Diagnosis of Adult Gliomas." Cancers 13, no. 9 (April 26, 2021): 2086. http://dx.doi.org/10.3390/cancers13092086.
Full textAbstract:
Background: The aim of this study was to investigate the immunohistochemical expression and distribution of serine and arginine rich splicing factor 1 (SRSF1) in a series of 102 cases of both diffuse and circumscribed adult gliomas to establish the potential diagnostic role of this protein in the differential diagnosis of brain tumors. Methods: This retrospective immunohistochemical study included 42 glioblastoma cases, 21 oligodendrogliomas, 15 ependymomas, 15 pilocytic astrocytomas, 5 sub-ependymal giant cell astrocytoma and 4 pleomorphic xanthoastrocytomas. Results: Most glioblastoma (81%), oligodendroglioma (71%), sub-ependymal giant cell astrocytoma (80%) and pleomorphic xanthoastrocytoma (75%) cases showed strong SRSF1 immunoexpression, while no detectable staining was found in the majority of ependymomas (87% of cases) and pilocytic astrocytomas (67% of cases). Conclusions: The immunohistochemical expression of SRSF1 may be a promising diagnostic marker of astrocytomas and oligodendrogliomas and its increased expression might allow for excluding entities that often enter into differential diagnosis, such as ependymomas and pilocytic astrocytomas.
45
Loskutov, Juergen, Manuela Regenbrecht, Rica Sauer, Sabine Finkler, Maya Niethard, Christoph Reinhard, and Christian Regenbrecht. "Abstract 6224: The bad, the ugly and the ultra-rare: All cancers are equal in the face of personalized medicine." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6224. http://dx.doi.org/10.1158/1538-7445.am2022-6224.
Full textAbstract:
Abstract Cancer represents a huge health problem worldwide and is well-recognized as an extremely heterogeneous disease affecting all the tissues and organs. The incidence of the particular cancer type is directly connected to the availability of specific medication and amount of the research focused on it, resulting in a high unmet medical need for treatment options for rare cancers. Currently, NCI defines “rare cancer” as cancer with an incidence rate below 15 per 10^5 people per year and recently the term “ultra-rare cancer” was defined as cancer with an incidence rate below 1 per 10^6 people per year. These encompass drastically understudied entities, usually with poor prognosis and grim outlook for an improvement in treatment. Low incidence of such cancers makes development of targeted therapies not interesting from a commercial point of view and completely abolishes the possibility of large-scale clinical trials. Therefore, a personalized medicine approach appears to be the most promising strategy for the patients to get adequate care. Here we report our experience with personalized oncology solutions for rare and ultra-rare cancers. We utilized patient derived 3D (PD3D) cultures to evaluate prospective therapeutic options in these exceptional cases to support the oncologists in providing personalized care to the patients. Fresh surgical specimens underwent several steps of mechanical and chemical dissociation. Subsequently, cell aggregates were seeded into 24 well plates in matrix-like scaffolds and allowed to grow until they started forming colonies. After harvesting, the cells underwent pathology evaluation to confirm origin and diagnosis. Therapies, recommended by the case leading oncologist, were used for drug sensitivity testing after transferring cells semi- automatically to 384-well plates. Over the last 18 months, we handled 6 cases classified as rare or ultra-rare cancers. The diagnoses included: clear cell sarcoma, extra-skeletal myxoid chondrosarcoma, CIC-rearranged round cell sarcoma, pleomorphic liposarcoma, cardiac angiosarcoma and clear cell endometrial carcinoma. In all cases we were able to successfully establish PD3D cultures and perform a drug screen, identifying a potential treatment for the patient. Overall, our results indicate that it is feasible to utilize our testing strategy for rare and ultra-rare cancer entities. Further research and rigorous follow up is required to confirm the benefit of the personalized approach vs current strategies. However, a demand for personalized care in such cases is clearly visible. Citation Format: Juergen Loskutov, Manuela Regenbrecht, Rica Sauer, Sabine Finkler, Maya Niethard, Christoph Reinhard, Christian Regenbrecht. The bad, the ugly and the ultra-rare: All cancers are equal in the face of personalized medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6224.
46
Wijesinghe, Harshima Disvini, and Ajith Malalasekera. "Giant Cell Urothelial Carcinoma of Bladder." Case Reports in Urology 2021 (July 15, 2021): 1–5. http://dx.doi.org/10.1155/2021/8021947.
Full textAbstract:
Giant cell urothelial carcinoma is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumours. It is an aggressive tumour with a poor prognosis that usually presents at an advanced stage. It is characterized histologically by pleomorphic giant cells. We discuss a case of giant cell urothelial carcinoma presenting at an early stage in a previously well 62-year-old woman. Histology showed a tumour comprising pancytokeratin positive bizarre mononuclear and multi-nuclear giant cells admixed with areas of conventional urothelial carcinoma and carcinoma in situ. Three-month follow-up cystoscopy and magnetic resonance imaging showed no evidence of recurrence or pelvic lymphadenopathy.
47
Fu, Kai, Guohua Yu, Chengfeng Bi, Hongxia Cheng, Lynette Smith, Ji Yuan, Hina Naushad, et al. "Mantle cell lymphoma: initial report from the North American Mantle Cell Lymphoma Consortium." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 8035. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.8035.
Full textAbstract:
8035 Background: The goal of the North American Mantle Cell Lymphoma (MCL) Project is to evaluate the clinical, biological, and genomic markers that affect the outcome of patients with MCL. Methods: We have retrospectively studied the clinical and pathological features of 307/421 patients diagnosed with MCL between January 2000 to December 2012 from 23 institutions across North American. Results: The male to female ratio of MCL patients was 3.5:1, with a median age of 66 years (range: 24-106 years). Approximately 29% of patients (78/269) presented with B symptoms and 257 (257/307, 83.7%) patients had extranodal involvement at diagnosis. Median follow-up was 7.1 years (range, 0.03 to 16.6 years) with the five-year PFS and OS at 27.8%, and 54.4%, respectively. Univariate analysis revealed that the following factors were significantly associated with both inferior OS and PFS ( p< 0.05): older age (≥60 years), presence of B symptoms, advanced Ann Arbor stage, elevated LDH, low platelets (≤100K/ml), blastoid/pleomorphic cytology, Ki67 proliferation ≥30%, circulating tumor cells, no transplantation (vs. transplantation), and allogeneic (vs. autologous) stem cell transplantation. In addition, large tumor size (maximal diameter > 3cm), high WBC ( > 10×103/ml), CD5 or CD23 positivity, and a complex karyotype were associated with inferior OS ( p< 0.05). Multivariate Cox regression analysis showed age (≥ 60y; p= 0.0028, HR = 2.44, 95% CI: 1.36-4.38) and high LDH ( p= 0.0062, HR = 2.19, 95% CI: 1.25-3.84) were the two factors predicting the clinical outcome. MIPI-c, a commonly used prognostic scoring system which includes Ki67, stratified the 100 MCL cases into four group with distinct clinical outcomes ( p< 0.001). Using readily-available clinical and pathological variables, we developed a simple and robust scoring system, MIPI-P (pathology), which consisted of age (≥60 years), LDH (high), Ki67 index (≥30%), Ann Arbor stage (III/IV), and cytological type (blastoid/pleomorphic), each contributing one point. The MIPI-P system stratified 104 MCL cases into three distinct groups ( p< 0.001). Median survival for the different groups were: low grade (0-1 points): 11.8 years; intermediate grade (2-3 points): 4.9 years; and high grade (4-5 points): 1.6 years. We further validated this system in an independent cohort of 33 MCL cases and confirmed that the modified MIPI-P provided robust prognostic predication ( p= 0.014). Conclusions: The clinical and biologic characteristics of MCL can provide information assisting with the prognosis of patients with MCL.
48
Kinoshita, Ichita, Denan Jin, Masaaki Higashino, Tetsuya Terada, Yoshitaka Kurisu, Shinji Takai, and Ryo Kawata. "Increase in Chymase-Positive Mast Cells in Recurrent Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland." International Journal of Molecular Sciences 22, no. 23 (November 23, 2021): 12613. http://dx.doi.org/10.3390/ijms222312613.
Full textAbstract:
Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFβ1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.
49
Paner, Gladell P., Jatin Gandhi, Bonnie Choy, and Mahul B. Amin. "Essential Updates in Grading, Morphotyping, Reporting, and Staging of Prostate Carcinoma for General Surgical Pathologists." Archives of Pathology & Laboratory Medicine 143, no. 5 (March 13, 2019): 550–64. http://dx.doi.org/10.5858/arpa.2018-0334-ra.
Full textAbstract:
Context.— Within this decade, several important updates in prostate cancer have been presented through expert international consensus conferences and influential publications of tumor classification and staging. Objective.— To present key updates in prostate carcinoma. Data Sources.— The study comprised a review of literature and our experience from routine and consultation practices. Conclusions.— Grade groups, a compression of the Gleason system into clinically meaningful groups relevant in this era of active surveillance and multidisciplinary care management for prostate cancer, have been introduced. Refinements in the Gleason patterns notably result in the contemporarily defined Gleason score 6 cancers having a virtually indolent behavior. Grading of tertiary and minor higher-grade patterns in radical prostatectomy has been clarified. A new classification for prostatic neuroendocrine tumors has been promulgated, and intraductal, microcystic, and pleomorphic giant cell carcinomas have been officially recognized. Reporting the percentage of Gleason pattern 4 in Gleason score 7 cancers has been recommended, and data on the enhanced risk for worse prognosis of cribriform pattern are emerging. In reporting biopsies for active surveillance criteria–based protocols, we outline approaches in special situations, including variances in sampling or submission. The 8th American Joint Commission on Cancer TNM staging for prostate cancer has eliminated pT2 subcategorization and stresses the importance of nonanatomic factors in stage groupings and outcome prediction. As the clinical and pathology practices for prostate cancer continue to evolve, it is of utmost importance that surgical pathologists become fully aware of the new changes and challenges that impact their evaluation of prostatic specimens.
50
Ogawa, Kaoru, Akira Kurose, Akihisa Kamataki, Kenichiro Asano, Kosuke Katayama, and Hidekachi Kurotaki. "Giant cell glioblastoma is a distinctive subtype of glioma characterized by vulnerability to DNA damage." Brain Tumor Pathology 37, no. 1 (October 26, 2019): 5–13. http://dx.doi.org/10.1007/s10014-019-00355-w.
Full textAbstract:
Abstract Giant cell glioblastoma (GC-GBM) consists of large cells with pleomorphic nuclei. As a contrast to GC-GBM, we defined monotonous small GBM (MS-GBM) as GBM that consists of small cells with monotonous small nuclei, and compared the DNA damage as well as other pathological features. GC-GBM showed minimal invasion (< 2 mm) and focal sarcomatous areas. TERTp was wild type in GC-GBM but mutant in MS-GBM. OLIG2 expression was significantly higher in MS-GBM (P < 0.01) (77% in MS-GBM and 7% in GC-GBM). GC-GBM showed significantly higher DNA double-strand breaks (DSBs) compared with MS-GBM (P < 0.01) (76% in GC-GBM and 15% in MS-GBM). Nearly, all large cells in GC-GBM underwent DSBs. Thus, significant DSBs in GC-GBM might be induced by an innate lesser stemness characteristic and be followed by mitotic slippage, resulting in polyploidization and the large pleomorphic nuclei. We conclude that GC-GBM is a distinctive subtype of glioma characterized by its vulnerability to DNA damage and that wild-type TERTp and lower OLIG2 function might induce this feature. Notably, even large pleomorphic nuclei with severe DSBs demonstrated Ki67 positivity, which alerts pathologists to the interpretation of Ki67 positivity, because cells with large nuclei undergoing severe DSBs cannot be recognized as proliferating cells that contribute to tumor aggressiveness.