Medical and and Review of the Literature Malignant hictiocytosis histi - PDF document

Medical and and Review of the Literature Malignant hictiocytosis histiocytic lymphoma of the mononuclear phago- for Diagnosis Cells are negative for T cell-associated antigens, and antigens associated with monocyte/macrophage origin including Myelomonocytic antigens: Monocyte-macrophage antigens: Antibodies associated with other reactivity with of monocytelmacrophage lineage: CDllb, CDllc, CD13, CD14, CD15, CD36, CD68, a,-antitrypsin, a,-antichymotrypsin HLA-DR, CD43, rearrangement studies" aIt is generally assumed that rearrangements are only cells, respectively. also have used this criterion. Nevertheless, we are that such rearrangements been described occasionally in from other lineages well, known cross-lineage rearrangements. immunoglobulin and antigen receptor gene rearrangement studies lymphoma (ALCL) other hematopoietic plasm [&13]. results point to the rarity these entities, sporadic cases exist which meet criteria for histiocytic disorder disorder As most cases of MH and THL are proven to be other hematologic disorders, the clinical features traditionally associated with these syn- dromes should also this article current literature histiocytic malignancies, including our experience other reevaluation studies, to illustrate the overall rarity neoplasms. The clinical presentation have true histiocytic malignancies discussed. Given the frequent overlap entities, the presenting feature and MH will be discussed together histiocytic malignancies. From 1967 to 1992 Minnesota. The diagnosis originally made clinical examination, laboratory find- ings, radiographic studies, morphologic interpreta- eosin-stained biopsy sections. 1992 we reanalyzed the pathologic characteristics patients incorporating large panel peroxidase antibody stains reactive against myelomonocytic antigens archival paraffin- lished elsewhere elsewhere In brief, the antibodies used included CD30 (ber (epithelial cells, some lymphomas), CD45 hematopietic), CD20 (B cell), MB-2 CD45RO (T lysozyme (myelomono- CD36 (monocyte/macrophage), CD Sternberg cells), (neural origin cells, Langerhans cells). Frozen material Literature Review for Inclusion Histiocytic Malignancy medline computerized identify studies case reports determined to have histiocytic malignancy strict criteria criteria 19,201 (Table I). Hist

iocytic malignancies are negative for and show macrophage associated antigens including CD 1 b, CD13, CD14, CD15, CD33, CD36, CD68, MAC-387. Cytoplasmic enzymes often present specific enough to determine determine 161. Isolated reactivity antibodies associated known to macrophage lineage cell markers suggests air-dried material cells are positive for nonspecific esterase, negative for lymphomas lacking cell antigens, histiocytic markers, show ev- rearrangement stud- stud- cases lacking rearrangement analysis were not included included Patients developing acute monocytic leukemia after initial diagnosis of MH THL were excluded as these most likely locytic sarcomas [28,29]. Patients diagnosed lignant histocytic disorder cell lineage also excluded The clinical features all criteria true histiocytic neoplasms are focal involve- ment with extranodal presentation. systemic symptoms were sporadically was absent splenomegaly noted 2 patients. presented with a clinical syndrome resembling topenia, fever, systemic symptoms. studies excluded for gene rearrangement analysis, discussion given the large series. Sonneveld et al. al. described 12 patients the diagnosis studies. These patients clinical syndrome resembling including lymphaden- (92%), splenomegaly (75%), thrombocytopenia (92%), anemia (92%), cytopenia (67%), similar retrospective seven patients typing reports a lower incidence associated with with 121. All patiens had fever and gen- eralized lymphadenopathy and 50% reported weight 42% and on hematologic While these represent true histiocytic neoplasms, generalizations concerning these data should guarded. Gene rearrangement studies not performed a lymphoid lineage positive anaplastic erally show T or cell lineage patients demonstrating a or indeterminate lineage. the literature reveals macrophage-associated antigens which lack T or cell lineage rangement studies studies 1,321. The clinical features further evaluated clinically unique. in Table presented with focal involvement lymph node extranodal involvement. one patient, hepatosplenomegaly a feature systemic features reported. Hematologic data provided. One tient presented with a clinical hepatomegaly, lymphadenopathy, systemic Patients From 14 patients the Univer- available for review. patients orig- MH were as having ot

her hematologic the immuno- peroxidase antibody The results this study studies. One possible histiocytic gene rearrangement therefore uncertain. Review of cases previously diagnosed as histiocytic malignancies using immunophenotyping gene rearrangement analysis. The these studies are summarized Approximately 164 have been with the cases being into Ki- cases), T or cell lymphomas or some other category disorder (7 the diagnosis reevaluation. These studies, however, not performed and the possibility or T cell be ruled cases were Ki-1 lymphoma possible histiocytic negative for T cell addition to CD30 (Ki-1 the exception rearrangement studies were not lineage for these lesions cannot [9]. Tumor cells the case expressed histiocytic antigens or T cell lineage rearrangement studies. This case possible histiocytic True Histiocytic the criteria for histiocytic tumors or THL reveals marked paucity lineage has gene rearrangcment et al., 1985 1985 Isaccson et al., 1985 1985 Delsol et al., 1988 1988 Cattoretti et al., 1990 [8] Van der Valk et al., 1990 [9Id Wilson et al., 1990 1990 Sonneveld et al., 1990 [11Ie [11Ie 6 4 27 10 12 15 12 13 TABLE 11. Results of Malignant Histiocytosis Reevaluation Studies" New diagnosis Stein et al., 1985 cell type rearrangement studies mixed lineage cell lymphoma unclassified (possible cell lymphoma cell type cell type lymphoma, uncertain rearrangement studies gene rearrangement mixed lineage 5 T cell lymphoma cell lymphomas rearrangement studies cell lymphoma T cell lymphoma, probable cell type Ki-1 lymphoma, possible 3 T cell Ki-1 lymphoma, cell type lymphoma, uncertain malignant histiocytosis malignant histiocytosis lymphoma, histiocytic lineage Immunophenot yping rearrangement studies at., 1992 1992 Own patients patients 11 9 1 Ki-l lymphoma, histiocytic lineage unclassified (questionable 1 Ki-l lymphoma, cell type cell type lymphoma, lineage indeterminate possible histiocytic neoplasm Ki-1 positivity) infectious associated hemophagocytic syndrome; interdigitating reticulum cell. originally diagnosed number not immunoglobulin heavy rearrangement only. studies were not had complete immunophenotyping which were previously diagnosed not stated. dIncludes one positive lymphoma with expression of monocyte-macrophage numbers immunophenotyping (IP) cell di

fferentiation studies. This case is included in Table cell lineage not ruled rearrangement studies. T and cell markers and express histiocytic antigens. studies done in only rearrangement studies warrants further discussion given large number this series series The clini- cal features patients with histiocytic lineage immunophenotyping are described. group presented high incidence systemic symptoms Splenomegaly, hepatomegaly, were noted in the pre- section, while cases from this study may represent Malignant Histiocytosis Clinical Features Patients With Possible Histiocvtic Malignancies* Spl Lym Biop BM BM 141 Sedage S u r v i v a al., 1991 1991 MI30 Yes NA - - Kamesaki et al., al., Milchgrub et al., 1992 [I71 Franchino et al., 1988 [I81 1 I 1 F14 1 Yes Yes - + + Lym - Chemotherapy 3 months MI60 MI38 NA NA - - + I1 mass - Chemotherapy + - SD1 - SDlenectomv DF 2 years *Includes only patients with expression antigens, lack antigens, and negative T and B cell rearrangement studies. Pan, pancytopenia; Hep, hepatomegaly; splenomegaly; Lym, lymphadenopathy; Pos Biop, positive biopsy; BM, hone marrow; Rx, treatment; skin: Lu, lungs; Med, mediastinum; ileal; ABMT, autologous hone marrow transplantation; Clinical Features Patients With Possible Histiocytic Malignancies Expressing symptoms Pan Hep Spl Levine et et 4 F142 Pos Biop BM Rx Survival No NA - -+ G1 mass - Chemotherapy DF 4 months Chemotherapy Cr, NA Chemotherapy Multiple 8 years No NA - - Carbone et al., 1990 1990 Banks et al., 1990 [32] Lym, hep, Chemotherapy Expired at all et al., al., 10 NA NA NA NA NA NA NA NA *Includes only antigens, lack absence of and B cell B cell immunoglobulin pancytopenia; Hep, hepatomegaly; Spl, splenomegaly; Biop, positive biopsy; BM, bone Sk, skin; gluteal; ABMT, autologous marrow transplantation; free; NA, not addressed. histiocytic neoplasms, generalizations concerning these data should be guarded T cell other studies lymphoma demon- entities. Prior to the molecular tech- used to classify hematopoietic the basis wasting, pancytopenia, a systemic proliferation malignant ap- be Ki- anaplastic large cell lymphoma other hematologic disorder. clinical features tradi- tionally associated with histiocytic neoplasms should also be questioned and necessitates further these studies rarity of MH and

a small number ture which appear to histiocytic origin nosologic concepts lymphoma and contemporary ana- These cases express surface antigens associated with monocyte-histiocyte origin and gene rearrangement studies. A group plasms exists appear to be of histiocytic origin but addition express the senting clinical features groups were further determine the clinical features associated with true histiocytic neoplasms diagnosed by contempo- clinical presenta- tion of histiocytic neoplasms lacks a consistent clinical patients have one or more focal lesions extranodal proliferations. and cytopenias were sporadically neoplasms of histiocytic lineage and presented with one or more focal sites of and extranodal proliferations. Systemic symptoms were noted in patients. Hematologic data were from each presented with clinical features must be numbers of patients with histiocytic neoplasms nophenotyping were excluded from evaluation due to lack of rearrangement studies. feel this exclu- sion criteria studies have shown lymphomas have clonal T cell antigen and T cell-associated antigens, express histiocytic antigens, and would have been misclassified the absence rangement studies studies We recognize that rearrangements are specific exclusively occasional myeloid tumors show history of manuscript we recommended a diag- nosis of where immu- results support a histiocytic lineage T cell cell related is of interest that most previously diagnosed as Ki-1 positive anaplastic large cell lymphoma. While lymph node and/or skin involvement the most a small subset patients present pancytopenia, hepatosplenome- lymphadenopathy, fever, and wasting wasting Some authors theorize the clinicopathologic syndrome previously described as fact represent a sub- of Ki- and suggests the basis basis This theory is speculative and needs confirmation further studies. lymphoma have the 5q35 abnormality which which The possibility that the present cases of histiocytic neoplasms may related to a localized form cytic leukemia M5b) cannot It is known monocytic leukemia may present a extramedul- lary mass without blood and marrow involvement involvement Results of immunophenotyping and gene rangement studies would mia and histiocytic lymphomas. Morphologically M5b is composed of monoblasts, promonocytes, and histioc

ytic malignancies are reportedly composed of malignant appearing monocytes greater variation and nuclear morphology morphology 1 ,141, a distinction which may Careful consideration must before a histiocytic neoplasm It is clear much work in the nancies remains to be done. A diagnosis a true cytic neoplasm should considered unless strict pathologic criteria are met as paper. Only appropriate pathologic techniques are cases can progress identifying these patients and determining the cell the clinical tion, appropriate treatment, and outcome. is used neoplasms can Jaffe ES: Malignant histiocytosis and true histiocytic lymphomas. “Surgical Pathology Lymph Nodes and Related Saunders, 1985, DB: Malignant lymphoma (monocyte/macrophage) origin. Cancer 5 Malignant histio- cytosis (true diagnosed cases at University associated antigen reactive and neoplastic lymphoid tissue: Evidence that cells and histiocytic malignancies are derived from activated lymphoid Blood 66:848-858, RA, Sklar immunoglobulin and ments in histiocytic Pathol 121:369-373, 1985. analysis of eight cases with multiparameter stud- Lab Invest 62:307(53-A), 1990. 24. Hibi Malignant histiocytosis Clinical, cytochemical, and studies of seven Human Pathol 25. Abe R, Akaike High incidence chromosomal abnormalities in malignant histiocytosis. 65:2689-2696, 1990. Malignant histiocytosis (true Clinicopathologic study T, Ga Uveitis, a presenting malignant histiocytosis. Haematologica 28. Koo malignancy associated with a malignant teratoma in a patient with 46XY gonadal dysgenesis. Am J Surg Pathol 29. Doll Greenberg BR: leukemia terminating malignant histiocytosis. Hematol Pathol 30. Oka Kojima M: Malignant histiocytosis: A report of three cases. Arch Pathol Lab Med 116: Boiocchi BD, Volper K: Histopathologic, and genotypic analysis of anaplastic large-cell lymphomas that express his- tiocyte-associated antigens. 32. Banks Anaplastic large cell (Ki-1) lym- phoma with histiocytic phenotype simulating carcinoma. analysis of large express the 34. Greer Stein R: patients with Ki-1 anaplastic large-cell J Clin Oncol9:539-547, 1991. 5q35bp chromosomal abnormality characterizes positive anaplastic cell lymphomas offering a new definition of malignant histiocytosis in Nouv Rev Kaneko Y, Frizzera N, Sakurai A novel translocati

on, childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis. Blood 73:80&813, Vardiman JW: Morphology in (CD3O)-positive non-Hodgkin’s is correlated with and presence a unique 14305-316, 1990. 38. Odom BC, Tannous Hammond GD: Acute monoblastic leukemia: A unique 14:l-10, 1990. Diagnostic and prog- monocytic leukemia: An analysis Hematol69:247-252, 1988. 40. Watanaba Fujita A: Cutaneous involvement a presenting feature of monocytic leukemia: Morphological Mason DY: Malignant the intestine: A ccll lymphoma. Lancet 2:688- Stein H, Mason DY: epithelial membrane antigen interleukin-2 receptor anaplastic large cell lymphomas. Diag- nostic value so-called malignant histiocytosis. Malignant histiocytosis. A phenotypic and genotypic investiga- Am J Pathol 136:1009-1019, van Oostveen Meijer CJ: Phenotypic and genotypic analysis of large- formerly classified true histiocytic lymphoma: an unusual Leuk Res 14:337- Warnke RA: Malignant histiocytosis. A reassessment previously reported 1975 based paraffin section immunophe- studies. Cancer 66:530-536, 1990. van Lom Clinicopathological diagnosis and treatment malignant histio- cytosis. Br J Haematol75:511-516, Ho Y, true histiocytic different phenotypes malignant histiocytosis. Pathol 138: 1404, 1991. nant histiocytosis in childhood: A distinctive CD3O-positive clini- copathological entity associated wi(h a chromosomal translocation Diagn Pathol D: Malignant lymphomas true histiocytic histological, imniunophenotypic, and geno- Pathol 160:9-17, Peterson BA: lymphoma. Semin 16. Kamesaki Malignant histiocytosis with rearrange- ment of heavy chain gene and phage lineage. Cancer Warnke RA: Malignant histiocytic neoplasms of the small intes- Am J Surg Pathol 18. Franchino Ubriaco A, Knowles DM: A clinicopathologically distinctive primary splenic histiocytic neo- J Surg Pathol 19. Weiss dendritic cell proliferations. In: “Neo- plastic Hematopathology.” 20. Bucksky P, Favara Malignant histiocytosis and large cell childhood: Guidelines for differential diagnosis. Report tiistiocyte Society. Med Pedi- Oncol22:200-203, 1994. 21. Weiss Large-cell hematolymphoid neoplasms 22. Salyer Malignant histiocytosis a patient with acquired immunodeficiency syndrome-related complex. Arch Pathol Lab Med 114:376-378, H: True 199