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Journal articles on the topic 'Atypical lymphocytes'

Author: Grafiati

Published: 4 June 2021

Last updated: 13 June 2025

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1

Lahdelma, RL, H. Katila, M. Hirata-Hibi, L. Andersson, B. Appelber, and R. Rimón. "Atypical lymphocytes in schizophrenia." European Psychiatry 10, no. 2 (1995): 92–96. http://dx.doi.org/10.1016/0924-9338(96)80319-1.

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SummaryBlood was drawn from 18 inpatients fullfilling the DSMIII criteria for schizophrenia and their 15 age- and sex-matched clinically infection-free controls before and after neuroleptic treatment. Blood films were stained with MGG solution, mixed, and subsequently read in random order by one observer. The lymphocytes were examined by light microscopy and classified into six types: normal lymphocytes, Downey type I atypical lymphocytes, Downey type III atypical lymphocytes, stress lymphocytes, plasmocytoid lymphocytes, and large granular lymphocytes. Downey type I and III atypical lymphocytes were classified into small, medium, and large lymphocytes. Schizophrenic patients had significantly more Downey type III medium size cells before treatment (p = 0.019 before treatment and p = 0.056 after treatment) and less Downey type I small size cells (p = 0.113 before treatment and p = 0.026 after treatment). Our study supports the idea of a possible subgroup of schizophrenia exhibiting immunological aberrations. In the present study, we found morphologically more specified cells which could be involved in this alteration.

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2

Cunha, B. A. "Atypical lymphocytes in acute malaria." Archives of Internal Medicine 157, no. 10 (1997): 1140–41. http://dx.doi.org/10.1001/archinte.157.10.1140.

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3

Bonoan, Jose T. "Atypical Lymphocytes in Acute Malaria." Archives of Internal Medicine 157, no. 10 (1997): 1140. http://dx.doi.org/10.1001/archinte.1997.00440310106015.

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4

Salib, Christian, Pallavi Khattar, Jinjun Cheng, and Julie Teruya-Feldstein. "Atypical Peripheral Blood Cell Morphology in COVID-19 (Sars-CoV-2) Patients from Mount Sinai Health System in New York City." Blood 136, Supplement 1 (2020): 26–27. http://dx.doi.org/10.1182/blood-2020-142581.

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INTRODUCTION Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies have suggested that COVID-19 positive patients present with leukopenia, lymphopenia, neutrophilia, thrombocytopenia, and higher neutrophil: lymphocyte ratio (NLR) and monocyte: lymphocyte ratio (MLR). More recently, we reported hypersegmented granulocytes and COVID-19 infection in Blood. 2020 Jun 11;135(24):2196. Neutrophil hypersegmentation has been closely associated with vitamin B12, folate and iron deficiencies, as well as methotrexate use, chemotherapy toxicity, uremia, heat stroke, myelodysplasia and Boucher-Neuhäuser Syndrome. Initially, these cytomorphologic changes may easily be overlooked or dismissed as non-specific reactive changes. In this study, we expand our initial observation on our index case to a larger case series. To the best of our knowledge, this is the largest case series to describe the concurrent lymphocyte and unique granulocyte atypia associated with SARS-CoV-2 infection. METHODS Study Design 2,199 patients were hospitalized in the Mount Sinai Health System from Feb 27 to April 2, 2020 with confirmed COVID-19 positivity. Data obtained for this study was covered under an Institutional Review Board (IRB) waiver, HS#:12-00133 GCO#1:12-036(0001-08) Inclusion criteria 50 peripheral blood smears flagged for Pathologist review from March 13 - April 20, 2020 at Mount Sinai Hospital Clinical Hematology Laboratory were included in this study. All suspected COVID-19 cases were confirmed using real-time polymerase chain reaction (RT-PCR) assay to test nasal and pharyngeal swab specimens, per WHO guidelines. Of the 50 COVID-19 positive peripheral blood smears, 39 slides were scanned and imaged with Scopio Labs X100 Full Field Digital Microscope. The X100 provided high resolution oil-immersion level images of large scanned areas. https://scopiolabs.com/hematology/ 19 peripheral blood smears were blindly and independently reviewed by 4 Hematopathologists (CS, PK, JC, JTF), with particular emphasis on granulocyte cytomorphology and percent of hypersegmented neutrophils present (defined as neutrophils with 5 or more nuclear lobes in at least 3% of cells or presence of 6 or more lobes). Atypical lymphocyte morphology was also evaluated and categorized as Downey type I, II, III or plasmacytoid, while monocyte morphology was assessed for unusual nuclear folds and features. Evaluation of platelets and other abnormalities were noted. The presence and degree of significant cytologic atypia was recorded and compared to 20 COVID-19 negative blood smears. RESULTS 16 of the 19 (84%) COVID-19 positive cases showed hypersegmented neutrophils, and all 19 harbored atypical lymphocytes and monocyte morphology, with giant platelets. In contrast, 5 of the 20 (25%) COVID-19 negative cases showed hypersegmented neutrophils, with 2 patients displaying atypical monocytes; none showed atypical lymphocytes or giant platelets (p = 0.022). Concurrent laboratory values showed no evidence of vitamin B12 or folate deficiency. Representative images are summarized in Figure 1 (A-C, 5-6 lobed neutrophils; D-E atypical plasmacytoid lymphocytes, G-I atypical monocytes, J-L giant platelets). CONCLUSION We report atypical hypersegmented neutrophils with toxic cytoplasmic change, atypical monocytes, plasmacytoid lymphocytes, and giant platelets in peripheral blood smears of COVID-19 patients which are significantly higher than in control COVID-19 negative patients. Figure 1 Disclosures Teruya-Feldstein: Edge Anthem: Consultancy.

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5

Raharjo, Budiono, and Solichul Hadi. "HIGH FLUORESCENT LYMPHOCYTE COUNT EXAMINATION IN DENGUE HEMORRHAGIC PATIENTS WITH SYSMEX XN-1000 HEMATOLOGY ANALYZER." INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 25, no. 2 (2019): 207. http://dx.doi.org/10.24293/ijcpml.v25i2.1443.

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Sysmex XN-1000 hematology analyzer is an automated 5-part diff analyzer (eosinophils, basophils, neutrophils, lymphocytes, and monocytes). In the calculated area, the type of difference between the Sysmex hematology device and other hematology devices is Immature Granulocyte (IG), Nucleated Red Blood Cell (NRBC), and High Fluorescent Lymphocytes Count (HFLC). The cells calculated in the HFLC area are atypical lymphocytes. In patients with dengue hemorrhagic fever, it is often found atypical lymphocytes called blue plasma lymphocytes. The purpose of this study was to determine the description of HFLC in patients with dengue fever using the hematology analyzer Sysmex XN-1000. A descriptive retrospective study was conducted during April-May 2017. The subjects of the study were adult patients diagnosed with dengue hemorrhagic fever with WHO criteria. Of the 47 samples of Dengue Hemorrhagic Fever (DHF) patients, the average HFLC results were between 2.0-32.3%, which was 11.5%, while the average range of normal HFLC values was between 0.0-1.4% and was 0.3%. In cases of DHF, there is an increase in HFLC. This is likely to be attributed to atypical lymphocyte increase in dengue hemorrhagic fever. Further research with more varied samples still needs to be done.

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6

Khvastunova, A. N., L. S. Al-Radi, O. S. Fedyanina, F. I. Ataullakhanov, A. I. Vorobiev, and S. A. Kuznetsova. "Unusual nuclear form hairy cells in hairy cell leukemia discovered using a lymphocyte-binding anti-CD antibody microarray." Clinical Medicine (Russian Journal) 96, no. 7 (2018): 667–72. http://dx.doi.org/10.18821/0023-2149-2018-96-7-667-672.

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Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder constituting about 2% from all leukemia cases and characterized by typical “hairy” morphology of tumor lymphocytes. We describe an HCL case with atypical nuclear shapes (lymphocytes with clover-leaf-like, horse-shoe-like, ring-shaped nuclei and binuclear cells were present). Morphology and immunophenotype of circulating leukemic cells were studied using a cell-binding microarray - a transparent plastic slide with immobilized monoclonal antibodies against surface antigens of lymphocytes. The cell-binding microarray with immobilized anti-CD11c, anti-CD103 and anti-CD123 permits to study a lymphocyte population enriched with hairy cells. Hairy cells with atypical nuclei constituted 3% of all lymphocytes and 15% of all hairy cells. This unusual hairy cell morphology is the first described in Russia and was found in one out of 85 HCL cases in our practice.

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7

Amaker, Barbara H., Nitya R. Ghatak, Sean A. Jebraili, Andrea Ferreira-Gonzalez, and Michael J. Kornstein. "Primary T-Cell–Rich B-Cell Lymphoma Masquerading as a Meningioma." Archives of Pathology & Laboratory Medicine 124, no. 11 (2000): 1700–1703. http://dx.doi.org/10.5858/2000-124-1700-ptcrbc.

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Abstract Primary dural lymphoma is rare, and few of the small number of cases reported to date have been classified using immunohistochemical techniques. To our knowledge, we report the first case of T-cell–rich B-cell lymphoma (diffuse mixed small cell and large cell) presenting as a solitary intracranial dural mass. Cytologic and frozen sections prepared during intraoperative consultation revealed a polymorphic population of lymphocytes suspicious for an inflammatory process. Permanent sections of the dura showed a diffusely infiltrating mass composed of mature lymphocytes peppered with large atypical lymphocytes. Immunohistochemical stains identified the small lymphocytes as T cells (CD3 and CD43) and the large atypical lymphocytes as B cells (CD20). Evidence of rearranged immunoglobulin heavy-chain genes demonstrated B-cell monoclonality. Differentiating between inflammatory and neoplastic lymphocytic masses of the dura obviously has important therapeutic and prognostic significance and may require immunohistochemical and molecular techniques.

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8

Rudolf, Sebastian, Peter Schlenke, Andreas Broocks, et al. "Search for atypical lymphocytes in schizophrenia." World Journal of Biological Psychiatry 5, no. 1 (2004): 33–37. http://dx.doi.org/10.1080/15622970410029905.

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9

Massey, Paul R., Kari A. Wanat, Campbell L. Stewart, et al. "CD30 Positive Atypical Lymphocytes in Perniosis." American Journal of Dermatopathology 36, no. 9 (2014): 730–33. http://dx.doi.org/10.1097/dad.0000000000000109.

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10

Vergé, Véronique, and Ranya Soufan. "COVID-19–induced atypical pulmonary lymphocytes." Blood 136, no. 19 (2020): 2241. http://dx.doi.org/10.1182/blood.2020007613.

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11

Malacarne, Paolo, and Bruno Dallapiccola. "Mitotic Activity of Circulating Atypical Lymphocytes." Scandinavian Journal of Haematology 7, no. 5 (2009): 314–17. http://dx.doi.org/10.1111/j.1600-0609.1970.tb01906.x.

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12

Tsaparas, Yotis F., Malcolm L. Brigden, Richard Mathias, Eva Thomas, Janet Raboud, and Patrick W. Doyle. "Proportion Positive for Epstein-Barr Virus, Cytomegalovirus, Human Herpesvirus 6, Toxoplasma, and Human Immunodeficiency Virus Types 1 and 2 in Heterophile-Negative Patients With an Absolute Lymphocytosis or an Instrument-Generated Atypical Lymphocyte Flag." Archives of Pathology & Laboratory Medicine 124, no. 9 (2000): 1324–30. http://dx.doi.org/10.5858/2000-124-1324-ppfebv.

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Abstract Objectives.—To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients. Design.—We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag. Setting.—A large outpatient laboratory system. Intervention.—Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV. Results.—The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P = .006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P = .016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P = .097). Conclusions.—A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.

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13

Girodon, François, Laurence Faivre, Nelly Devillier, Paule Marie Carli, and Marc Maynadié. "Atypical large granular lymphocytes in a child." British Journal of Haematology 123, no. 2 (2003): 192. http://dx.doi.org/10.1046/j.1365-2141.2003.04492.x.

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14

Sato, Yoshihiro, Naoki Hachiya, Haruko Kuno, Takeshi Asoh, and Kotaro Oizumi. "Cerebrospinal fluid atypical lymphocytes in Japanese encephalitis." Journal of the Neurological Sciences 160, no. 1 (1998): 92–95. http://dx.doi.org/10.1016/s0022-510x(98)00233-0.

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15

Barreiro Arcos, María Laura, Gabriela Gorelik, Alicia Klecha, Ana María Genaro та Graciela A. Cremaschi. "Thyroid hormones increase inducible nitric oxide synthase gene expression downstream from PKC-ζ in murine tumor T lymphocytes". American Journal of Physiology-Cell Physiology 291, № 2 (2006): C327—C336. http://dx.doi.org/10.1152/ajpcell.00316.2005.

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Regulation of cell proliferation by thyroid hormone (TH) has been demonstrated, but the effect of THs and the mechanisms involved in lymphocyte activity have not been elucidated. Differential expression of PKC isoenzymes and high nitric oxide synthase (NOS) activity have been described in tumor T lymphocytes. We have analyzed the direct actions of TH on normal T lymphocytes and BW5147 T lymphoma cells in relation to PKC and NOS activities. THs increased tumor and mitogen-induced normal T lymphocyte proliferation. PKC isoenzyme-selective blockers impaired these effects in both cell types, indicating the participation of Ca2+-dependent and -independent isoenzymes in normal and tumor cells, respectively. TH actions were blunted by extra- and intracellular Ca2+ blockers only in normal T lymphocytes, whereas NOS blockers impaired TH-induced proliferation in T lymphoma cells. Incubation for 24 h with TH induced a rise in total and membrane-associated PKC activities in both cell types and led to a rapid and transient effect only in tumor cells. THs increased atypical PKC-ζ expression in BW5147 cells and classical PKC isoenzymes in mitogen-stimulated normal T cells. TH augmented NOS activity and inducible NOS protein and gene expression only in tumor cells. Blockade of PKC and the atypical PKC-ζ isoform inhibited TH-mediated stimulation of inducible NOS and cell proliferation. These results show, for the first time, that differential intracellular signals are involved in TH modulation of lymphocyte physiology and pathophysiology.

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16

Joshi, Anagha A., Gayathri B. R., and Swathi Kulkarni. "Correlation of thrombocytopenia with degree of atypical lymphocytosis as a prognostic indicator in dengue." International Journal of Research in Medical Sciences 5, no. 9 (2017): 4041. http://dx.doi.org/10.18203/2320-6012.ijrms20173979.

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Background: Dengue viral infections may occur as epidemics and are of public health concern in India especially due to high mortality in advanced stages. Early diagnosis and treatment reduces the mortality significantly. To assess the utility of atypical lymphocyte counts with relation to platelet counts as a marker for severe dengue.Methods: A total of 132 serologically proven (by rapid card method) cases of dengue with atypical lymphocytosis (≥10%) and thrombocytopenia (<150×109/l) were analyzed during November 2016. The complete blood counts (obtained from automated hematology analyzer and Leishman stained peripheral smears) were analyzed.Results: Dengue infections were mostly seen in younger age (12-25 years) with slight male predominance. The relevant haematology findings noted were leukopenia in 36% and severe thrombocytopenia (<50×109/l) in 57% of cases. The differential count showed lymphocytosis in 64% with significant (≥20%) atypical lymphocytes in 52% which inversely correlated with platelet counts. Atypical lymphocytosis (≥20%) was noted in 9% of cases with mild as against 32% of severe thrombocytopenia.Conclusions: Atypical lymphocyte count can be used as predictor of severe thrombocytopenia and severe dengue. This helps in early diagnosis and proper management and drastic reduction in mortality.

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17

Kokai, Masahiro, Yoshio Morita, Hiroko Fukuda, and Noboru Hatotani. "Immunophenotypic studies on atypical lymphocytes in psychiatric patients." Psychiatry Research 77, no. 2 (1998): 105–12. http://dx.doi.org/10.1016/s0165-1781(97)00152-2.

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18

Roberts, Toni, Michael Linenberger, and Xueyan Chen. "Atypical lymphocytes and eosinophilia in primary cytomegalovirus mononucleosis." British Journal of Haematology 171, no. 4 (2015): 441. http://dx.doi.org/10.1111/bjh.13590.

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19

Inoue, Susumu. "‘CLOVER LEAF’NUCLEUS OF ATYPICAL LYMPHOCYTES IN INFECTIOUS MONONUCLEOSIS." British Journal of Haematology 70, no. 3 (2008): 381–83. http://dx.doi.org/10.1111/j.1365-2141.1988.0381a.x.

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20

Inoue, Susumu. "‘CLOVER LEAF’NUCLEUS OF ATYPICAL LYMPHOCYTES IN INFECTIOUS MONONUCLEOSIS." British Journal of Haematology 70, no. 3 (1988): 381–83. http://dx.doi.org/10.1111/j.1365-2141.1988.tb02499.x.

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21

Steele, K. E., G. K. Saunders, and G. D. Coleman. "T-cell-rich B-cell Lymphoma in a Cat." Veterinary Pathology 34, no. 1 (1997): 47–49. http://dx.doi.org/10.1177/030098589703400108.

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T-cell-rich B-cell lymphoma is a neoplasm recognized in humans in which a neoplastic proliferation of large B lymphocytes is present amid a background of reactive T lymphocytes. A 13-year-old Domestic Shorthair cat developed a mass in the region of the left parotid gland. Histologically, the mass was composed of scattered large atypical cells within a dense background of uniform small lymphoid cells. Immunohisto-chemically, the large cells were uniformly labeled using antiserum directed against the B-lymphocyte marker BLA.36, whereas labeling of nearly all of the small cells was limited to the T-lymphocyte marker CD3. The histomorphologic and immunohistochemical features of this unique feline neoplasm are characteristic of T-cell-rich B-cell lymphoma of humans.

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22

Kokai, M., K. Ohara, Y. Morita, and N. Hatotani. "Atypical lymphocytes in late phase activation of psychiatric patients." Biological Psychiatry 42, no. 1 (1997): 234S. http://dx.doi.org/10.1016/s0006-3223(97)87868-7.

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23

Karalyan, Z. A., Z. R. Ter-Pogossyan, L. O. Abroyan, et al. "Characterization of the atypical lymphocytes in African swine fever." Veterinary World 9, no. 7 (2016): 792–800. http://dx.doi.org/10.14202/vetworld.2016.792-800.

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24

Gérard, Delphine, Sylvain Henry, and Benoît Thomas. "SARS‐CoV‐2: a new aetiology for atypical lymphocytes." British Journal of Haematology 189, no. 5 (2020): 845. http://dx.doi.org/10.1111/bjh.16730.

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25

MAKINO, Shinya, and Junta KAMURA. "Cytophagic Histiocytic Panniculitis with Atypical Lymphocytes in Peripheral Blood." Internal Medicine 31, no. 11 (1992): 1317–21. http://dx.doi.org/10.2169/internalmedicine.31.1317.

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26

Felsenstein, D., W. P. Carney, V. R. Iacoviello, and M. S. Hirsch. "Phenotypic Properties of Atypical Lymphocytes in Cytomegalovirus-Induced Mononucleosis." Journal of Infectious Diseases 152, no. 1 (1985): 198–203. http://dx.doi.org/10.1093/infdis/152.1.198.

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27

Kweon, Oh Joo, Mi-Kyung Lee, and Hye Ryoun Kim. "Evaluation of the Flagging Performance of the Hematology Analyzer Sysmex XN Series on the Basis of “Q Values”." Archives of Pathology & Laboratory Medicine 142, no. 1 (2017): 83–88. http://dx.doi.org/10.5858/arpa.2016-0502-oa.

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Context.— In the XN series of hematology analyzers (Sysmex, Kobe, Japan), the probability of the presence of abnormal cells is indicated by flags based on Q values. Objective.— To evaluate the Q value performance of the Sysmex XN-20 modular analyzer. Design.— The interinstrumental concordance, intrainstrumental precision, and diagnostic accuracy of Q values, with tested flags of “blasts/abnormal lymphocytes,” “atypical lymphocytes,” and “blasts,” were investigated. Results.— Absolute concordance rates in flagging between 2 analyzers ranged from 69.8% to 80.8%, and κ values ranged from 0.43 to 0.61. In samples with absolute related cell counts lower than 100/μL, the values ranged from 0.31 to 0.52. For intrainstrumental precision, standard deviations ranged from 4.8 to 23.9 for the blasts/abnormal lymphocytes, from 18.7 to 59.1 for the blasts, and from 11.0 to 23.0 for the atypical lymphocytes. Using a default Q value cutoff, diagnostic accuracy values based on the area under the curve, sensitivity, and specificity were, respectively, 0.910, 90.9%, and 72.2% for blasts/abnormal lymphocytes; 0.927, 84.9%, and 89.8% for blasts; and 0.865, 74.4%, and 84.9% for atypical lymphocytes. The diagnostic accuracy of Q values was much lower in samples with absolute related cell counts lower than 100/μL than in those 100/μL or higher. Conclusions.— Q values of the Sysmex XN-20 analyzer were found to be imprecise and irreproducible, especially with samples containing a small number of pathologic cells. Adjustments in the Q value threshold may help in the detection of these cells.

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Bhar, Vikrant Singh, Vasudha Gupta, Mahak Sharma, Rishi Dhawan, Shilpi Modi, and Mona Vijyaran. "Rare Coexistence of Acute Monoblastic Leukemia with Chronic Lymphocytic Leukemia." Case Reports in Hematology 2018 (November 6, 2018): 1–4. http://dx.doi.org/10.1155/2018/6452843.

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Acute monoblastic leukemia (AMoL) is a rare hematopoietic neoplasm, and simultaneous occurrence of acute monoblastic leukemia with chronic lymphocytic leukemia is very rare and only a few cases have been reported in the literature. We here report a rare case of dual hematological malignancy in an 85-year-old male. The peripheral blood and bone marrow examination revealed dual population of atypical cells, comprising large cells with opened-up chromatin having monocytic appearance and small mature-appearing lymphocytes. Flowcytometric immunophenotyping confirmed the monocytic lineage of cells, whereas small lymphocytes showed the immunophenotype consistent with chronic lymphocytic leukemia (CLL). The final diagnosis was made as acute monoblastic leukemia with associated CLL. This is a rare case scenario, and this highlights the importance of careful morphological examination and flowcytometric immunophenotyping in the exact characterization of hematopoietic malignancies.

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Faude, Sophia, Jane Wei, Kavitha Muralidharan, et al. "Absolute lymphocyte count proliferation kinetics after CAR T-cell infusion impact response and relapse." Blood Advances 5, no. 8 (2021): 2128–36. http://dx.doi.org/10.1182/bloodadvances.2020004038.

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Abstract CD19-directed chimeric antigen receptor (CAR) T cells show characteristic proliferation kinetics after infusion that correlate with response. Clearance of circulating disease, B-cell aplasia (BCA), and cytokine release syndrome (CRS) are used to observe CAR T-cell function, given the lack of commercial CAR T-cell measurement assays. We investigated the utility of common hematology laboratory parameters in 166 patients with B-cell acute lymphoblastic leukemia (B-ALL) who were treated with CAR T-cell therapy targeting CD19. CAR T-cell infusion was followed by disappearance of circulating blasts in 86% of patients at a median of 6 days. After a lag phase, there was a rapid expansion in absolute lymphocyte count (ALC) in the second week that coincided with the appearance of atypical lymphocytes. The expansion phase was followed by a contraction phase with a concomitant decrease in atypical lymphocytes. In vitro CAR T-cell studies showed similar kinetics and morphological changes. Peak ALC and overall expansion was greater in sustained responders compared with that in nonresponders. Patients with early loss of BCA and those with eventual CD19+ minimal residual disease/relapse showed lower overall lymphocyte expansion compared with the controls. Pleomorphic lymphocytosis was noted in the cerebrospinal fluid at post-CAR time points. We conclude that lymphocyte counts and differential can also be used to evaluate CAR T-cell expansion after infusion, along with BCA and CRS. This is the first report to characterize the morphology of CAR T cells and determine the utility of lymphocyte kinetics.

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30

Dittman, William A. "Pyknotic Lymphocytes In Infectious Mononucleosis." Blood 122, no. 21 (2013): 4732. http://dx.doi.org/10.1182/blood.v122.21.4732.4732.

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Context Pyknotic lymphocytes were infrequently observed in routine blood film evaluation of patients with clinical infectious mononucleosis. A marked increase in frequency was observed in 1995-1997. Objective To characterize the cause of these changes. Design Collection of samples from patients (25) with clinical infectious mononucleosis to ascertain the effect of anticoagulant and/or time lapse on lymphocytes and to correlate with monospot or Epstein-Barr virus antibody testing. Control samples (33), mixed hematopoietic disease (29) and lymphoproliferative disorders (36) were obtained also. Additional patients (53), identified by variant lymphocyte morphology during routine CBC’s, were verified by monospot or EBV testing and slides were made at 24 and 48 hours for differentials. Finally, single specimens (86) were obtained to establish predictability or correlation between pyknotic cells and monospot testing Setting Inpatient and outpatient hematology laboratory. Results Patients with clinical infectious mononucleosis demonstrated 8-10% pyknotic lymphocytes in 24 and 48 hour samples in all three anticoagulants (see Figure 1) compared with controls, “other diseases” (Table 2) and lymphoproliferative disorders (Table 3). An unexpected predictive correlation of pyknotic cells with positive monospot or Epstein-Barr Virus antibodies was demonstrated when pyknotic cells were seen with or without significant atypical lymphocytes during daily routine differential counting. Conclusion Observation of pyknotic lymphocytes adds a significant and inexpensive element to the diagnosis of infectious mononucleosis and consideration of Cytomegalic Virus infection in older patient Disclosures: No relevant conflicts of interest to declare.

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Laharwani, H., K. Perrizo, S. Jain, and J. Lam. "A Rare Case of Chronic Lymphoproliferative Disorder of NK Cells with an Unusual Expression of CD57." American Journal of Clinical Pathology 154, Supplement_1 (2020): S101. http://dx.doi.org/10.1093/ajcp/aqaa161.221.

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Abstract Introduction/Objective Natural Killer cells (NK-cells) malignancies are extremely rare and the two NK-cell disorders involving the peripheral blood and bone marrow include chronic lymphoproliferative disorder of NK-cells (CLPDNK) and aggressive NK-cell leukemia (ANKL). ANKL is EBV associated with a prevalence in Asian adults and a fulminant clinical course leading to death within 2 months. Methods A 76-year-old female with a history of iron deficiency anemia presented for evaluation of lymphocytosis (78 TH/mm) and negative EBV with extreme fatigue, weight loss, and worsening weakness from the past 8 months. Results The peripheral and bone marrow aspirate showed an increase in granular lymphocytes with bland nuclei and abundant pale-staining cytoplasm containing fine to coarse azurophilic granules with no evidence of nuclear atypia. Flow cytometry demonstrated an atypical lymphocytic cell population comprising &gt;50% of total marrow and peripheral blood lymphocytes demonstrating loss of CD56 and diminished CD7 expression. The analysis showed atypical lymphocytes with the following immunophenotype: CD2, CD8 (the majority, at least 75%),CD7 (dim), CD38, CD11c (subset) with no expression of CD3, CD5, CD4, CD56, or CD11c. Flow cytometry is important as it helps in the phenotypic detection of aberrancy. A broad panel of immunohistochemical stains revealed scattered positivity for CD3, CD4, CD7, CD8, TIA-1, granzyme, perforin, and tryptase and negative for CD56 and CD57. Our top differential with a similar clinical course included T-cell large granular lymphocytic leukemia which is characterized by a clonal proliferation of mature cytotoxic T cells and also has an indolent course. They show CD3 positivity by flow cytometry along with co-expression of NK cell-associated markers (CD16 and CD57), and variable expression of other pan T cell markers such as CD2, CD5, CD7. It is found incidentally in patients having cytopenias with a persistent increase in circulating mature NK-cells. Of note, the PET scan revealed splenomegaly with no other significant findings.The patient was started on steroids and is currently doing well. Conclusion Thus, overall morphologic, immunophenotypic, and molecular results with negative expression of surface or cytoplasmic CD3 as well as the absence of TCR expression were most consistent with CLPD-NK with an unusual expression of CD57 expression detected in flow cytometry.

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Wu, Mark L., Hau C. Kwaan, and Charles L. Goolsby. "Atypical Hairy Cell Leukemia." Archives of Pathology & Laboratory Medicine 124, no. 11 (2000): 1710–13. http://dx.doi.org/10.5858/2000-124-1710-ahcl.

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Abstract The morphologic differential diagnosis of mature B-cell neoplasms with cytoplasmic projections includes splenic lymphoma with villous lymphocytes and hairy cell leukemia. Although the classification of hairy cell leukemia is not universally recognized, 3 variants have been described, namely, classic, variant, and Japanese variant, each of which has different clinical and immunophenotypic features. Classic hairy cell leukemia is virtually always CD11c+, CD25+, and CD103+. Variant and Japanese variant hairy cell leukemias are usually CD11c+, always CD25−, and occasionally CD103+. Each variant is characteristically CD10−. We present a case of hairy cell leukemia with a unique immunoprofile in that the cells were CD10+, CD25+, and CD103−, and we review the criteria helpful in differentiating “hairy” B-cell neoplasms. This case emphasizes the variability of hairy cell leukemia and the need to correlate all clinical and pathologic data in reaching a diagnosis.

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Weinberg, Samuel E., Amir Behdad, and Peng Ji. "Atypical lymphocytes in peripheral blood of patients with COVID‐19." British Journal of Haematology 190, no. 1 (2020): 36–39. http://dx.doi.org/10.1111/bjh.16848.

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Satou, Takao, Tadao Uesugi, Yuka Nakai, Yoshiyuki Hayashi, Motohiro Imano, and Shigeo Hashimoto. "Case of adrenal lymphangioma with atypical lymphocytes in aspirate cytology." Diagnostic Cytopathology 29, no. 2 (2003): 87–90. http://dx.doi.org/10.1002/dc.10322.

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French, R. A., S. E. Seitz, and V. E. O. Valli. "Primary Epitheliotropic Alimentary T-cell Lymphoma with Hepatic Involvement in a Dog." Veterinary Pathology 33, no. 3 (1996): 349–52. http://dx.doi.org/10.1177/030098589603300315.

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The anatomic forms of lymphoma are multicentric, alimentary, thymic, cutaneous, and leukemic. Correlations between cell type and topographic distribution of lymphomas is not well documented, but there are more plasmacytoid tumors in the gut, skin, and spleen, which suggests that these are areas of malignant transformation preceded by a period of benign immune hyperplasia. Alimentary forms of lymphoma can be preceded by lymphocytic-plasmacytic enteritis. In the present case, an epitheliotropic alimentary form of T-cell lymphoma with hepatic involvement and concomitant lymphocytic-plasmacytic enteritis was diagnosed in an 8-year-old male Labrador Retriever. The lymphoma was characterized by the accumulation of atypical lymphocytes in the lamina propria and mucosal epithelium of the jejunum. The lymphocytes were identified as T-cell lineage using a polyclonal rabbit antisera to the human pan-T-cell determinant CD-3. The “homing” nature of the neoplasm resembles the epidermotropic form of cutaneous T-cell lymphoma.

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Pukhalskaya, Tatsiana, Bruce R. Smoller, David M. Menke, and Olayemi Sokumbi. "A Previously Unrecognized Granulomatous Variant of Gamma-Delta T-Cell Lymphoma." Dermatopathology 8, no. 2 (2021): 221–28. http://dx.doi.org/10.3390/dermatopathology8020027.

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Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an extremely rare and aggressive T-cell neoplasm with complex heterogeneity. We present a series of two patients who presented with firm, subcutaneous nodules and were diagnosed with PCGD-TCL. In both cases, biopsies demonstrated a both superficial and deep adnexotropic infiltrate comprised of angiocentric, medium- to large-sized atypical lymphocytes. The infiltrate extended into the panniculus. Immuno–histochemical stains highlighted atypical lymphocytes that expressed CD3, CD8 and CD56 but were negative for EBV ISH. A brisk histiocytic response with focal aggregation into granulomas was highlighted with a PG-M1 stain. The atypical lymphocytes were positive for gene rearrangements on a TCR delta stain and negative for βF-1. CT and PET scan in one of the two patients demonstrated diffuse, subcutaneous, ground-glass foci; hypermetabolic soft tissue nodules; and lymphadenopathy in the lungs, as well as splenomegaly. A diagnosis of histiocyte-rich PCGD-TCL was rendered. A histiocyte-rich, granulomatous variant of γδ T-cell lymphoma is extremely rare. Its potentially misleading resemblance to inflammatory granulomatous conditions could pose a diagnostic pitfall in this already challenging condition. This variant may resemble granulomatous mycosis fungoides and granulomatous slack skin syndrome, but it has a distinct, aggressive clinical outcome.

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He, Xuefeng, Wu Depei, Xiao Ma, Yanan Zhou, Chengcheng Fu, and Weiyang Li. "Atypical T Cell Prolymphocytic Leukemia – One Case Report." Blood 116, no. 21 (2010): 4332. http://dx.doi.org/10.1182/blood.v116.21.4332.4332.

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Abstract Abstract 4332 Here we reported one case of atypical T cell prolymphocytic leukemia. The 38-year female was admitted to our hospital for fatigue and night sweat. She complained of fatigue and night sweat for one month and accompanied by gum bleeding. Physical examination showed anemia and massive spleen extending to umbilical level. Blood routine test indicated pancytopenia (detailed info: Wbc 0.66×109/L,Hb 82g/L,Plt 60×109/L)and elevated proportion of lymphocytes. Blood biochemistry and routine serum tumor marker were normal. Mutation of JAK2V617F was negative. Marrow film showed many atypical mature lymphocytes which expressed mature T cell markers. Marrow biopsy showed a SLL-like scene and accompanied by local fibrosis, immunochemical stains strong CD3, CD45-R0, CD43 and weak CD5, MPO. Repeated TCR β rearrangement indicated positive. PET/CT scan could not find specific elevated SUV lesions. This patient may be diagnosed as atypical T cell prolymphocytic leukemia despite her lymphocytopenia and unpalpable peripheral lymph nodes. She received one cycle of CVP (cyclophosphamide, Vincristine and prednisone) and another cycle of CHOP(cyclophosphamide, Adriamycin, Vincristine and prednisone). Her blood cell count partly recovered and she was preparing for following high dose chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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Cotter, Paul F. "Atypical lymphocytes and leukocytes in the peripheral circulation of caged hens." Poultry Science 94, no. 7 (2015): 1439–45. http://dx.doi.org/10.3382/ps/pev157.

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Abraham, G., M. Vas, S. Vas, and P. Blake. "Cloudy Effluent with Atypical Lymphocytes in a CAPD Patient: Case Report." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 9, no. 4 (1989): 349. http://dx.doi.org/10.1177/089686088900900425.

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Togar, Başak, Hasan Turkez, Abdulgani Tatar, et al. "The genotoxic potentials of some atypical antipsychotic drugs on human lymphocytes." Toxicology and Industrial Health 28, no. 4 (2011): 327–33. http://dx.doi.org/10.1177/0748233711410919.

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Win, N., and S. C. Davies. "‘Clover leaf’ nuclei in atypical lymphocytes during acute Toxoplasma gondii infection." Clinical & Laboratory Haematology 12, no. 1 (2008): 111–12. http://dx.doi.org/10.1111/j.1365-2257.1990.tb01119.x.

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Batinac, Tanja, Gordana Zamolo, Nives Jonjić, et al. "Angioimmunoblastic Lymphadenopathy with Dysproteinemia following Doxycycline Administration." Tumori Journal 89, no. 1 (2003): 91–95. http://dx.doi.org/10.1177/030089160308900120.

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Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a primary lymphoproliferative T-cell disorder, currently classified as a peripheral T-cell non-Hodgkin's lymphoma. AILD is characterized by generalized lymphadenopathy, hepatosplenomegaly, immunological abnormalities, polyclonal hypergammaglobulinemia and anemia. We report a case of AILD in an 80-year-old male who presented with a generalized pruritic maculopapular eruption and fever following doxycycline administration. The maculopapular rash progressed to formation of confluent nodules, plaques and finally erythroderma with lymphadenopathy and hepatosplenomegaly. Blood analysis revealed an elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinemia. Lymph node biopsy showed almost complete effacement of the nodal architecture with diffuse proliferation of small vessels forming an arborizing network, surrounded by atypical lymphocytes, usually CD3+ CD4+ and occasionally CD3 + CD8+. There were also larger cells (immunoblastic shape) that displayed CD20 positively, some scattered plasma cells, and eosinophils. Histology of a cutaneous lesion showed spongiosis and infiltration of the epidermis by atypical lymphocytes with large hyperchromatic nuclei, perivascular dermal lymphocytic infiltrate (CD3+) mixed with plasma cells and occasional large immunoblasts (CD20+). During hospitalization the patient developed hemolytic anemia (Coombs positive) and lung metastases. The prognosis of AILD is generally poor, with a median survival of less than 20 months. Our patient died two and a half months after the diagnosis was made due to sepsis caused by Staphylococcus aureus isolated in hemoculture.

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Okwundu, Nwanneka, Felicia Ekpo, Jessica Ghaferri, and David Fivenson. "Atypical Presentation of Lichen Planopilaris: Presentation of Two Cases and Review." Journal of Clinical Research in Dermatology 7, no. 1 (2020): 1–5. http://dx.doi.org/10.15226/2378-1726/7/1/001107.

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Lichen Planopilaris (LPP) is an uncommon scalp disorder of unknown etiology and prevalence. It is thought to be an autoimmune process triggered by unknown genetic and/or environmental factors that attack hair follicles of the scalp. LPP has been reported to mimic or present in association with various autoimmune diseases and immunomodulatory therapies. We present two atypical case of LPP in Caucasian patients; the first is a patient with generalized pruritus, skin eruptions, and scalp hair loss. Biopsy of the lesions revealed exocytosis of atypical lymphocytes at the Dermo-Epidermal Junction (DEJ) and formation of small Pautrier’s microabscesses in the interfollicular epidermis as well as a robust lymphocytic inflammatory infiltrate with destruction of perifollicular appendages. This led us to the diagnosis of LPP-like Folliculotropic Mycosis Fungoides (FMF). The second case is a patient with a history of Systemic Lupus Erythematosus (SLE) who presented clinically with perifollicular erythema and alopecic patches, with loss of follicular ostia on the frontal and vertex scalp and evidence of follicular tufting. Histologically, she had decreased number of follicles with a peri-infundibular lymphocytic infiltrate and vacuolization at the Dermoepidermal Junction (DEJ) and there was also thickening of the basement membrane highlighted with a periodic acidic Schiff stain. This led to a diagnosis of SLE/LPP overlap. Keywords: Lichen Planopilaris (LPP); Cicatricial; Alopecia; Frontal Fibrosing Alopecia (FFA), Folliculotropic Mycosis Fungoides (FMF), Lichen Planus (LP).

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Oscier, David G., Andrew Thompsett, Delin Zhu, and Freda K. Stevenson. "Differential Rates of Somatic Hypermutation in VH Genes Among Subsets of Chronic Lymphocytic Leukemia Defined by Chromosomal Abnormalities." Blood 89, no. 11 (1997): 4153–60. http://dx.doi.org/10.1182/blood.v89.11.4153.

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Abstract Chronic lymphocytic leukemia (CLL) is a B-cell tumor involving small lymphocytes that generally express the CD5 antigen and low levels of surface Ig. Within this definition, there is heterogeneity among cases in cell morphology, karyotypic abnormalities, and clinical course. Trisomy 12, the most frequent karyotypic abnormality, is commonly found in a subset of CLL with atypical morphology. It has also been associated with advanced disease, and possibly with a less favorable prognosis. A further subset of cases with abnormalities involving chromosome 13q14 have typical lymphocyte morphology. Occasionally, the two abnormalities are found together. To assess the clonal history of the cell of origin in disease subsets defined by these two chromosomal abnormalities, we investigated the usage of VH genes and the pattern of somatic mutation in 10 cases of trisomy 12 with atypical morphology and eight cases of 13q14 abnormality with typical morphology. In addition, four cases with both chromosomal abnormalities were analyzed. Results confirm a common usage of the VH1 family in all subsets. However, the patterns of somatic mutation were distinct, with cases of trisomy 12 showing a minimal level of mutation (mean ± SD, 0.34% ± 0.86%) and cases of 13q14 abnormality showing significant levels (6.5% ± 1.67%). The four cases with both abnormalities showed a mixed pattern. All mutated cases had intraclonal homogeneity, and three of 10 had a pattern indicative of antigen selection. These results suggest that the clonal history of the two subsets of CLL may differ.

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Remold-O'Donnell, E., C. Zimmerman, D. Kenney, and FS Rosen. "Expression on blood cells of sialophorin, the surface glycoprotein that is defective in Wiskott-Aldrich syndrome." Blood 70, no. 1 (1987): 104–9. http://dx.doi.org/10.1182/blood.v70.1.104.104.

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Abstract Sialophorin, previously called gpL115, is the heavily sialylated surface protein that is defective in lymphocytes of Wiskott-Aldrich syndrome patients. Using the monoclonal antibody L10 as a probe, sialophorin expression was detected on isolated T lymphocytes and thymocytes, B cell lines, monocytes, neutrophils, and platelets, but not on erythrocytes, fibroblasts, and glioblastoma cells. This unusual distribution pattern suggests that sialophorin is expressed on all circulating cells except erythrocytes. Trace amounts of the sialophorin molecules on lymphocytes are incompletely sialylated, but significant amounts of the molecules on thymocytes are incompletely sialylated. The molecular form of sialophorin on T lymphocytes, thymocytes, and monocytes is the previously characterized species of apparent mol wt 115,000. A newly described sialophorin species of apparent mol wt 135,000 was found on neutrophils and platelets. The 115,000 lymphocyte/monocyte form and the 135,000 platelet/neutrophil form were shown to be substantially similar. The two forms have approximately the same content of sialylated O-linked carbohydrate units since both undergo the same atypical shift in electrophoretic mobility on desialylation. Both contain the epitope recognized by the monoclonal antibody L2 and the epitope recognized by L10 antibody. Moreover, evidence from another study indicates that the polypeptide portions are identical, cumulatively suggesting that 115,000 sialophorin and 135,000 sialophorin are identical except for the presence on the latter of additional neutral saccharide residues.

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46

Remold-O'Donnell, E., C. Zimmerman, D. Kenney, and FS Rosen. "Expression on blood cells of sialophorin, the surface glycoprotein that is defective in Wiskott-Aldrich syndrome." Blood 70, no. 1 (1987): 104–9. http://dx.doi.org/10.1182/blood.v70.1.104.bloodjournal701104.

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Sialophorin, previously called gpL115, is the heavily sialylated surface protein that is defective in lymphocytes of Wiskott-Aldrich syndrome patients. Using the monoclonal antibody L10 as a probe, sialophorin expression was detected on isolated T lymphocytes and thymocytes, B cell lines, monocytes, neutrophils, and platelets, but not on erythrocytes, fibroblasts, and glioblastoma cells. This unusual distribution pattern suggests that sialophorin is expressed on all circulating cells except erythrocytes. Trace amounts of the sialophorin molecules on lymphocytes are incompletely sialylated, but significant amounts of the molecules on thymocytes are incompletely sialylated. The molecular form of sialophorin on T lymphocytes, thymocytes, and monocytes is the previously characterized species of apparent mol wt 115,000. A newly described sialophorin species of apparent mol wt 135,000 was found on neutrophils and platelets. The 115,000 lymphocyte/monocyte form and the 135,000 platelet/neutrophil form were shown to be substantially similar. The two forms have approximately the same content of sialylated O-linked carbohydrate units since both undergo the same atypical shift in electrophoretic mobility on desialylation. Both contain the epitope recognized by the monoclonal antibody L2 and the epitope recognized by L10 antibody. Moreover, evidence from another study indicates that the polypeptide portions are identical, cumulatively suggesting that 115,000 sialophorin and 135,000 sialophorin are identical except for the presence on the latter of additional neutral saccharide residues.

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Yoshino, Yuka, James K. Chambers, Taichi Nakamori, et al. "Primary cerebellar lymphoma with Hodgkin lymphoma–like morphology in a cat." Journal of Veterinary Diagnostic Investigation 29, no. 5 (2017): 707–10. http://dx.doi.org/10.1177/1040638717704239.

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A 4-y-old cat exhibited neurologic signs such as wobbling, right head tilt, and intention tremor, and MRI revealed a mass in the cerebellum. The cat died 5 mo after initial presentation, and no neoplastic lesions, other than the cerebellar mass, were observed at autopsy. Histologically, large atypical cells resembling Hodgkin cells, with single large inclusion-like nucleoli, and those resembling Reed–Sternberg cells, with symmetrically arranged nuclei, had infiltrated the left side of the cerebellum and were admixed with small lymphocytes. These atypical cells were positive for feline leukemia virus (FeLV), CD20, BLA36, vimentin, p16, p53, and Pax5, and negative for CD3, CD79a, and Iba1 by immunohistochemistry. Multiplex PCR for immunoglobulin heavy-chain gene rearrangement revealed monoclonal proliferation of B-lymphocytes. We describe this feline primary cerebellar B-cell lymphoma that displayed Hodgkin lymphoma–like tumor cells with FeLV protein expression.

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Ouederni, Monia, MONIA BEN KHALED, Samia Rekaya, Ilhem Ben Fraj, Fethi Mellouli, and Mohamed Bejaoui. "A 9month-old-boy with atypical hemophagocytic lymphohistiocytosis." Mediterranean Journal of Hematology and Infectious Diseases 9, no. 1 (2017): e2017057. http://dx.doi.org/10.4084/mjhid.2017.057.

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Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes. Often, Hemophagocytic lymphohistiocytosis is an acquired syndrome. We report a case of a 9 month-old-boy presented with hepatosplenomegaly, severe anemia requiring repeated transfusions, thrombocytopenia, hypertriglyceridemia and very high hyperferritinemia. These clinical features of Hemophagocytic lymphohistiocytosis prompted a wide infectious and auto-immune request to be performed. After a wide diagnostic workup, he was referred to the immune hematologic unit, for hemophagocytic lymphohistiocytosis suspicion with unknown cause.

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Ouederni, Monia, MONIA BEN KHALED, Samia Rekaya, Ilhem Ben Fraj, Fethi Mellouli, and Mohamed Bejaoui. "A 9month-old-boy with atypical hemophagocytic lymphohistiocytosis." Mediterranean Journal of Hematology and Infectious Diseases 9, no. 1 (2017): e2017057. http://dx.doi.org/10.4084/mjhid.2017.57.

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Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes. Often, Hemophagocytic lymphohistiocytosis is an acquired syndrome. We report a case of a 9 month-old-boy presented with hepatosplenomegaly, severe anemia requiring repeated transfusions, thrombocytopenia, hypertriglyceridemia and very high hyperferritinemia. These clinical features of Hemophagocytic lymphohistiocytosis prompted a wide infectious and auto-immune request to be performed. After a wide diagnostic workup, he was referred to the immune hematologic unit, for hemophagocytic lymphohistiocytosis suspicion with unknown cause.

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McClain, Kenneth L., Yasodha Natkunam, and Steven H. Swerdlow. "Atypical Cellular Disorders." Hematology 2004, no. 1 (2004): 283–96. http://dx.doi.org/10.1182/asheducation-2004.1.283.

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Abstract Some immunologic diseases are characterized by profound loss or primary dysfunction of a given population of cells. The atypical cellular disorders discussed here all bear some similarities in that abnormal proliferations of lymphocytes and macrophages or dendritic cells result in lymphadenopathy, skin rashes, bone lesions and infiltrations of nearly any other organ system. What are the similarities and the differences between Langerhans cell histiocytosis (LCH), sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease, and Castleman’s disease (CD)? Studies on LCH have some advantages since it was described before the others, and organized clinical trials have been done since the 1980s. The understanding of SHML benefited from a registry maintained by Drs. Rosai and Dorfman. CD was described fifty years ago and for one subtype has the most clearly defined etiology (HHV-8 infection) of the three atypical cellular disorders discussed here. In Section I, Dr. Kenneth McClain examines the unanswered question of whether LCH is a malignant clonal disorder or an inflammatory response triggered by aberrant cytokine expression or a virus. Advocates of the malignant proliferation theory rest their case primarily on the following two points: Clonality of the CD1a+ Langerhans cells was demonstrated by analysis of the human androgen receptor in patients with single bone lesions (Low Risk) or multisystem disease including spleen, liver, bone marrow, or lung (High Risk). Although no consistent chromosomal abnormalities have been reported, loss of heterozygosity (LOH) has been defined by comparative genomic hybridization. Those in the “inflammatory response” camp note that non-clonal proliferation of Langerhans cells in adult pulmonary LCH also have LOH by the same method. The pathologic cells have not been successfully grown in culture or immune-deficient mice and don’t have a “malignant” morphology. While the basic scientific arguments continue, important advances in the treatment of LCH have been made by international collaborations of the Histiocyte Society. Risk groups have been clearly defined and the response to therapy after the initial 6 weeks is known to be the strongest prognostic variable for outcome. In Section II, Dr. Yasodha Natkunam reviews the features of SHML, which most often presents as painless cervical lymphadenopathy, although many patients can have extranodal involvement as well. These sites include the skin, respiratory tract, bone, lung, gastrointestinal tract, and brain. The diagnosis rests on finding intact lymphocytes in the cytoplasm of activated macrophages as well as accumulation of mature plasma cells. Hemolytic or non-hemolytic anemias, hypergammaglobulinemia, and elevated erythrocyte sedimentatin rate (ESR) are often found with SHML. An intriguing finding of human herpesvirus (HHV)-6 viral proteins in SHML has been reported in several patients, but needs further study. SHML associated with lymphoproliferations triggered by defects in apoptosis are discussed since this mechanism may provide a clue to the etiology. Therapy for SHML varies greatly in reported case series. Many patients have spontaneous regression or resolution after surgical removal of isolated node groups. Others with systemic involvement may benefit from chemotherapy, but no clinical trials have been done. In Section III, Dr. Steven Swerdlow clarifies key features of the four types of CD. Localized cases are divided into the hyaline vascular type and plasma cell type. Both are usually cured by surgical excision and have symptoms mainly of a mass lesion, although the latter often also has constitutional symptoms. The two types are distinguished largely by the nature of the follicles and the number of interfollicular plasma cells. Interleukin (IL)-6 expression is increased in the plasma cell type. Multicentric CD of the plasmablastic type is most often found in HIV-positive patients with coincident HHV-8 infection. Many have lymphomas or Kaposi sarcomas. Other cases of multicentric CD are also most like the plama cell type, however, with disseminated disease and constitutional symptoms. A wide variety of anti-neoplastic drugs, radiation therapy, anti-IL-6 and rituximab or atlizumab have been used with varying success in patients with multicentric CD. Clinical trials are needed for SHML and CD and registration of adult and pediatric patients on current LCH trials are encouraged.

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