Hepatosplenic T-cell lymphomas (HSTCLs) are a recently described variant of an aggressive lymphoma. Patients present with B-symptoms (fever, weight loss, and night sweats), massive hepatosplenomegaly, no lymphadenopathy, moderate anemia, and marked thrombocytopenia. This is an aggressive lymphoma with most patients dying within 2 years of diagnosis.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/Electron Microscopy Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION AGE RANGE-MEDIAN 2-3rd decades SEX (M:F) Males
DISEASE ASSOCIATIONS CHARACTERIZATION
Hepatosplenic gamma/delta T-Cell Lymphoma in Immunocompromised Patients Report of Two Cases and Review of Literature
Waqar A. Khan, MD, Lelia Yu, MD, Arthur B. Eisenbrey, MD, PhD, Domnita Crisan, MD, PhD, Abdul Al Saadi, PhD, Bruce H. Davis, MD, Rebecca C. Hankin, MD, and Joan C. Mattson, MD
Am J Clin Pathol 2001;116:41-50 Abstract quote
We describe 2 male patients in whom hepatosplenic gamma/delta T-cell lymphoma (HSTL) developed 6 and 10 years after renal transplantation. The onset was abrupt with systemic symptoms, cytopenia, and hepatosplenomegaly. The histologic examination of the spleen (case 1), liver, and bone marrow revealed sinusoidal infiltrates of markedly abnormal lymphocytes. The neoplastic cells in these cases were CD2+, CD3+, CD4–, CD5–, CD7+, CD8+, CD16+, CD56+, betaF1-negative, and TIA-1-negative. Both cases displayed clonal rearrangement of the T-cell receptor (TCR) delta gene and the TCR beta gene. The spleen in case 1 was positive for Epstein-Barr virus genome and showed TCR-gamma gene rearrangement by polymerase chain reaction. Isochromosome 7 [i(7)(q10)] was found in each case. Both patients died within 4 months of diagnosis.
HSTL has been reported in only 5 renal transplant recipients. HSTL may be relatively more frequent in immunocompromised patients compared with the general population.
PATHOGENESIS CHARACTERIZATION Chromosomal abnormalities
Genes Chromosom Cancer 1995;12:161–4.
Karyotypic studies frequently show an isochromosome 7q, which may be accompanied by trisomy 8 and loss of a sex chromosome
Clonal TCR rearrangements Clonal gamma and delta TCR sometimes with beta chain gene rearrangements
HISTOLOGICAL TYPES CHARACTERIZATION General
Small to intermediate-size lymphoma cells preferentially infiltrate the splenic red pulp cords and sinuses, hepatic sinusoids, and bone marrow sinuses
Leukemic phase may develop as the disease progresses with circulating tumor cells generally agranular
Cytoplasmic granules have been detected by electron microscopy in some cases
Splenic infiltrates were primarily in the red pulp, with prominent packing of the sinuses with frequent marked reduction or complete loss of white pulp
Hepatic involvement was sinusoidal, with sparing of portal tracts in most cases
Bone marrows had infiltrates were generally localized to the sinuses and interstitium with occasional diffuse involvement and nodular aggregates rarely
Lymphomatous infiltrates tended to partially involve the interstitium and sinuses of lymph nodes
VARIANTS ALPHA-BETA T-CELL LYMPHOMAS Hepatosplenic alpha-beta T-Cell Lymphomas A Report of 14 Cases and Comparison With Hepatosplenic gamma-delta T-Cell Lymphomas
Am J Surg Pathol 2001;25:285-296
This study describes the clinicopathologic features of 14 hepatosplenic alpha-beta T-cell lymphomas expressing alpha-beta TCR chains.
They occurred in 11 women and 3 men with a median age of 36 years. Clinical presentation was similar to that described previously for hepatosplenic gamma-delta T-cell lymphomas, except for the female preponderance and age distribution (5 patients younger than 13 years of age and 5 patients older than 50 years of age). Disease distribution was primarily in the splenic red pulp and hepatic sinusoids, although liver infiltrates were largely periportal in four cases. Bone marrow involvement, observed in eight patients, was usually interstitial and/or within the sinuses. Lymph nodes were involved in five patients, although lymphadenopathy was demonstrable in only two.
Ten cases were composed of intermediate-size tumor cells with round/oval nuclei, slightly dispersed chromatin, inconspicuous nucleoli, and scant to moderate amounts of cytoplasm. Four lymphomas contained primarily large cells with irregular nuclei, dispersed chromatin, discernible nucleoli, and moderate to abundant cytoplasm. Tumor cells in all 14 lymphomas were cytotoxic T-cells; 13 co-expressed natural killer cell–associated antigens and showed T-cell clonality. Three lymphomas were associated with Epstein-Barr virus. Two of four cases had an isochromosome 7q. Eleven patients are dead, eight within a year of diagnosis, and two patients have maintained complete remissions after combination chemotherapy.
These data show that hepatosplenic T-cell lymphomas include an alpha-beta-subtype. This group, along with the previously recognized group, should be recognized as phenotypically heterogeneous subtypes of the same disease
Hepatosplenic gamma/delta T-Cell Lymphoma in Bone Marrow A Sinusoidal Neoplasm With Blastic Cytologic Features
Francisco Vega, MD, PhD
L. Jeffrey Medeiros, MD
Carlos Bueso-Ramos, MD, PhD
Dan Jones, MD, PhD
Raymond Lai, MD, PhD
Rajyalakshmi Luthra, PhD
Lynne V. Abruzzo, MD, PhD
Am J Clin Pathol 2001;116:410-419 Abstract quote
We report 8 cases of hepatosplenic T-cell lymphoma (HSTCL) involving bone marrow and correlate histologic findings with disease progression.
Immunophenotypic analysis demonstrated mature, aberrant gamma/delta T-cell immunophenotypes. Isochromosome 7q was identified in 4 cases; 1 case showed the t(7;14)(q34;q13). Seven of 7 cases tested had monoclonal TCR gamma gene rearrangements.
The initial diagnostic bone marrow biopsy specimens were hypercellular with a frequently subtle, predominantly sinusoidal infiltrate of atypical small to medium-sized lymphoid cells. In all cases, aspirate smears at diagnosis and in subsequent specimens contained malignant cells that resembled blasts, some with fine cytoplasmic granules. With progression, the pattern of HSTCL in bone marrow biopsy specimens became increasingly interstitial, and the neoplastic cells became larger. In aspirate smears, the proportion of blasts increased. Seven patients died; 1 was lost to follow-up. Autopsy performed on 1 patient demonstrated malignant cells within vascular channels in all organs sampled, with relatively little tumor formation, resembling intravascular lymphoma at these sites.
HSTCL often can be recognized in bone marrow by its unique combination of a sinusoidal pattern in core biopsy specimens and blastic cytology in aspirate smears.
Hepatosplenic gammadelta-T-cell lymphoma with leukemic course after renal transplantation.
Steurer M, Stauder R, Grunewald K, Gunsilius E, Duba HC, Gastl G, Dirnhofer S.
Division of Haematology and Oncology, University Hospital Innsbruck, Innsbruck; the Institute for Medical Biology and Human Genetics and the Department of Pathology, University of Innsbruck, Innsbruck, Austria; and the Institute of Pathology, University of Basel, Basel, Switzerland.
Hum Pathol 2002 Feb;33(2):253-258 Abstract quote
Hepatosplenic gammadelta-T-cell lymphoma (HSTCL) is a rare extranodal T-cell non-Hodgkin's lymphoma (T-NHL) with only 46 well-documented cases in medical literature. Notably, a relatively high number of these case reports (15%) describe the occurrence of HSTCL after solid organ transplantation.
We describe the case of a 45-year-old man who developed a leukemic HSTCL 5 years after renal transplantation and continous immunosuppression with cyclosporine A and prednisolone. After a rapid clinical course, the patient died and autopsy was performed. The malignant lymphocytes showed a natural killer-like gammadelta-T-cell phenotype (CD2(+), CD3(+), CD7(+), TCR gammadelta(+), CD56(+), TIA-1(+), CD4(-), CD8(-), and TCR alphabeta(-)) and infiltrated the sinusoids of liver and the red pulp of the spleen. Cytogenetically, an isochromosome 7q, trisomy 8, Y-loss, and a translocation t(1;4) was detectable.
This case shows the difficulties of recognizing HSTCL early in the clinical course and underlines that all types of T-NHL, nodal as well as extranodal, have to be considered in the differential diagnosis of posttransplantation lymphoproliferative disorders. Moreover, HSTCL seems to occur as a specific late complication of solid organ transplantation.
SPECIAL STAINS/IMMUNOPEROXIDASE/OTHER CHARACTERIZATION Special stains Immunoperoxidase
Hum Pathol 1997;28:674–85.
Am J Surg Pathol 1995;19:718–26.
The lymphoma cells are typically CD2+, CD3+, CD4-, CD5-, CD7+, CD8–, TCR–, and TCR+
Natural killer (NK) cell–associated antigens such as CD16 and CD56, and cytotoxic granule-associated proteins are often expressed
Direct immunofluorescence (DIF) Indirect immunofluorescence (IIF) Electron microscopy (EM)
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION
Hepatosplenic T-Cell Lymphoma An Unusual Case With Clinical, Histologic, and Cytogenetic Features of Hepatosplenic T-Cell Lymphoma
Felipe Suarez, M.D.; Iwona Wlodarska, Ph.D.; Françoise Rigal-Huguet, M.D.; Martin Mempel, M.D.; Nadine Martin-Garcia; Jean-Pierre Farcet, M.D.; Georges Delsol, M.D.; Philippe Gaulard, M.D.
From the Département de Pathologie and EA2348 (F.S., N.M.-G., P.G.) and the Service d'Immunologie Biologique (J.-P.F.), CHU Henri Mondor, Créteil, France; the Center for Human Genetics (I.W.), University of Leuven, Belgium; the Service d'Hématologie (F.R.-H.) and the Service d'Anatomie Pathologique (G.D.), Hôpital Purpan, Toulouse, France; and the Unité INSERM 277 (F.S., M.M.), Biologie moléculaire du gène, Institut Pasteur, Paris, France.
Am J Surg Pathol 2000;24:1027-1032 Abstract quote
Hepatosplenic T-cell lymphoma is a recently identified entity in which lymphoma cells bearing the T-cell receptor (TCR) infiltrate the sinusoids of the liver and the sinuses of the splenic red pulp and bone marrow, without lymph node involvement. It is also characterized by a recurrent cytogenetic finding, isochromosome 7q (i7q10).
The authors report a case of hepatosplenic lymphoma of T-cell phenotype that shares the same clinical, histologic, and cytogenetic characteristics of the previously described hepatosplenic T-cell lymphoma. Fluorescent in situ hybridization performed with chromosome 7 probes showed the typical pattern of isochromosome 7q. Genomic analysis of the TCR locus failed to detect a clonal rearrangement.
This unique case of hepatosplenic lymphoma of T-cell phenotype supports the possibility that lymphoid populations of different or phenotype that share similar homing and presumably functional properties could give rise to lymphomas displaying similar clinical and pathologic findings.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Survival The disease is aggressive, and most patients die within 2 years of diagnosis, even if a remission is achieved initially
Am J Surg Pathol 1997;21:781–90.
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