A small cell variant of ALK-positive, CD8-positive anaplastic large cell lymphoma with primary subcutaneous presentation mimicking subcutaneous panniculitis-like T-cell lymphoma

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is an uncommon non-Hodgkin's lymphoma of T-cell origin, the majority of which express CD4 and show frequent pan-T-cell antigen loss. While most cases of ALK+ ALCL have the common pattern characterized by anaplastic morphology with hallmark cells, a less common but well-recognized variant with a small cell pattern may pose a diagnostic challenge. We report a case of ALK+ ALCL with small cell morphology and CD8 subset restriction in a 53-year-old male patient who presented primarily with multiple recurrent subcutaneous nodules with histopathologic features simulating a subcutaneous panniculitis-like T-cell lymphoma (SPTCL). The case was initially diagnosed as SPTCL but was reconsidered as ALK+ ALCL when the incidental finding of CD30 positivity on a subsequent biopsy prompted an ALK immunostain, which turned out to be positive in the neoplastic T-cells. The diagnosis of ALK+ ALCL, small cell variant, was then confirmed by detection of an ALK gene rearrangement by FISH analysis. This report highlights a case of ALK+ ALCL with a deceiving clinical and histopathologic presentation, and emphasizes the value of immunohistochemical panel studies and genetic tests in such cases to avoid diagnostic errors.     

Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan

CD56 is an important marker for prospecting clinicopathologic features of cytotoxic T-cell and natural killer (NK)/T-cell lymphomas. We examined 22 cases of subcutaneous panniculitis-like lymphoma and classified these into CD56-positive and CD56-negative groups. The 11 CD56-negative cases were mainly in the younger age group and had systemic subcutaneous nodules without ulceration. They exhibited subcutaneous invasion by medium-sized lymphoma cells, scattered erythrophagocytosis, patchy necrosis, and little tumor invasion in the superficial dermis. Their lymphoma cells had characteristics of CD3 epsilon-, CD8-, TcR beta F1-, T-cell intracellular antigen (TIA)1-, and granenzyme B-positive cytotoxic T cells and were negative for apoptosis-promoting proteins CD95 (Fas), Bax, CPP32 (caspase 3), and p53 (DO7). Ten patients were alive despite clinical signs of hemophagocytic syndrome and relapses in 7 cases. The 11 CD56-positive cases had systemic ulcerative skin tumors composed of pleomorphic lymphoma cells with massive necrosis and little erythrophagocytosis involving the subcutis and also often the whole dermis. Their tumor cells were positive for CD3 epsilon, TIA1, granenzyme B, CD95, CD95L (Fas ligand), Bax, and CPP32. Three cases were of the TcR beta F1-positive phenotype, 1 was of the TcR gamma/delta-positive T-cell phenotype, and 6 were of the TcR beta F1- and TcR gamma/delta-negative NK/T-cell phenotype. Six cases were p53 (DO7) positive. Seven cases had complications of liver dysfunction and cytopenia, and 8 died of disease. One CD56-negative case and 3 CD56-positive cases had nuclear signals of Epstein-Barr virus-encoded RNA in their lymphoma cells. The 2 groups had significantly (P <0.01) different prognoses by Kaplan-Meier and log-rank methods. Patients with CD56-negative and CD56-positive groups had statistically different clinicopathologic, immunohistologic, and functional findings and prognoses.     

血管内NK/T细胞淋巴瘤的研究进展

血管内NK/T细胞淋巴瘤(intravascular NK/T cell lymphoma,IVNKTL)罕见,其特征性表现为肿瘤性淋巴细胞选择性生长于血管腔内.不同地域患者临床表现多样且缺乏特异性,因此临床诊断困难.IVNKTL具有病程进展快、伴EBV感染、好发于亚洲,且以中国人多发等特点.在肿瘤未累及到多器官前进行早期诊治可有效改善IVNKTL患者的预后.     

Primary bone natural killer/T cell lymphoma,nasal type without EBV infection: a case report

Primary bone NK/T cell lymphoma is very rare. We report a case of 52-year-old man of primary bone NK/T cell lymphoma and then progressed to NK leukemia. The patient had low-grade fever for 4-month, and Ultrasonic B revealed a diffuse hepatosplenomegaly without lymphadenopathy. PET scanning showed increased FDG uptake in many bones of the whole body. The diagnosis was established by bone specimen. These neoplastic cells demonstrated a typical immunophenotype of CD56, CD3, CD2 and MPO positive, and CD5, CD20, CD30, PAX-5, CD4 and CD8 negative. Primary bone ENKTL is very rare; it should be made with the combination of clinical feature, PET-CT image, and pathological characteristics, and should be distinguished from other lymphomas or leukemia involved in bone.     

Blastic natural killer cell lymphoma arising from the mediastinum with terminal deoxynucleotidyl transferase expression

Blastic natural killer (NK) cell lymphoma/leukemia is a relatively rare NK cell malignancy. We report the second case of blastic NK cell lymphoma arising from the mediastinum with an aggressive clinical course. The patient was a 63-year-old Japanese man with an anterior mediastinum tumor. The biopsy specimen showed diffuse proliferation of tumor cells with frequent mitotic figures and apoptotic bodies. Both angiocentric features and small foci of coagulative necrosis were found in this section. The tumor cells had medium to large nuclei with a fine chromatin pattern, inconspicuous nucleoli and scanty cytoplasm. The nuclear contour was oval to moderately irregular, showing slight pleomorphism as compared with typical lymphoblastic lymphoma. The tumor cells were positive for CD2, CD56 and terminal deoxynucleotidyl transferase, but negative for other T-cell antigens, B-cell antigens and myeloid markers. In situ hybridization for Epstein-Barr virus encoded small ribonucleic acid 1 was negative.     

皮下脂膜炎样T细胞淋巴瘤的细胞毒颗粒相关蛋白TIA—1的表达及 …

目的 认识皮下脂膜炎样Ｔ细胞淋巴瘤（ＳＰＴＣＬ）的临床和病理特点。研究细胞毒颗粒相关蛋白ＴＬＡ－１在ＳＰＴＣＬ中的表达及与Ｅｐｓｔｅｉｎ－Ｂａｒｒ（ＥＢ）病毒感染的关系。方法 和ＴＩＡ－１、ＣＤ４５ＲＯ、ＣＤ３、ＣＤ２０和ＣＤ６８等抗体作免疫组织化学ＡＢＣ法染色应用ＥＢＥＲ１／２原位杂交检测ＥＢ病的潜伏感染。结果 １７例ＳＰＴＣＬ男女之比１：１．１．中位发病年龄２４岁,主要表现为下肢、躯干无症状性     

Clinicopathologic study of nasal T/NK-cell lymphoma among the Japanese

A high prevalence of nasal lymphoma expressing a T- or natural killer (NK)-cell phenotype (NTCL) with frequent association of Epsteln-Barr virus (EBV) has been indicated in Asians. To Characterize NTCL among the Japanese, the clinlcopathdogic features of 32 cases were evaluated and the casses worn also analyzed for EBV-RNA using an ISH method. Morphologically, 31 cases were Identified by atypical pleomorphic lymphoid infiltrates with polymorphous, anglcentric, and necrotic features. Their lymphoma cells ranged in size from small to large and were mixed in varying proportion from case to case. The other one case showed a monomorphic 'blastic' appearance. EBV-encoded small RNA (EBER) was detected in the neoplastic cells of 27 of the 32 cases examined. In the five EBV-negative cases, one was the 'blastic' type. Clonal T-cell receptor gene rearrangement was detected in none of seven cases examined. The patients had a median follow-up of 9 months (range, 1 month to 14 years and 11 months). The Kaplan-Meler estimate of overall survival was 49% at 5 years, correlating with clinical stage. These data support the concept that most cases of NTCL are identified as tumors with T/NK-cell characteristics and EBV association, distincity different from other peripheral T-cell lymphomas. Furthermore, the one case of an EBV-negative 'blastic' variant appears not to fit well Into the pleomorphic category but more closely resembles the pathologic features of extranasal angiocentric lymphoma with lymphoblastold appearance. This study also showed no clear difference in clinical aspects other than the original site or in prognosis, between NTCL and extranasal angiocentric lymphomas despite the higher incidence of EBV association and the tendency for that peculiar anatomical site to be restricted to the former group.     

Adrenal extranodal NK/T‐cell lymphoma diagnosed by fine‐needle aspiration and cerebrospinal fluid cytology and immunophenotyping: A case report

The cytologic findings of an extranodal NK/T‐cell lymphoma (NKTCL) presenting as a large adrenal mass with leptomeningeal involvement diagnosed by CT‐guided fine‐needle aspiration and cerebrospinal fluid (CSF) cytology are described. The 65‐year‐old Caucasian patient presented with progressive headache and multiple cranial nerve neuropathies. Magnetic resonance imaging showed leptomeningeal enhancement surrounding the conus medullaris and cauda equine, and a subsequent PET/CT demonstrated a large right adrenal gland mass. Fine‐needle aspiration of the adrenal mass showed occasional large pleomorphic cells with prominent nucleoli, moderate amounts of cytoplasm, and rare large cells with sparse cytoplasmic granules admixed with numerous small lymphocytes. Initial flow cytometry from this sample showed no clonal B‐cell population. Immunoperoxidase stains performed on the cell block/core specimen showed that the large atypical cells were positive for CD2, CD30, CD43 and CD56, TIA‐1, granzyme, and perforin, but for none of the other T‐cell markers used (CD3, CD4, CD5, CD8, CD45RO), which stained the abundant background lymphocytes. A CSF specimen showed similar neoplastic cells and flow cytometry showed an NK‐cell population with aberrant immunophenotype. The cytologic findings of the neoplastic cells and the extensive panel of immunoperoxidase stains allowed the diagnosis of NKTCL, which was confirmed by the subsequent flow‐cytometric immunophenotyping performed on the CSF. This is, to the best of our knowledge, the first case of NKTCL diagnosed by FNA of the adrenal gland and by CSF cytology. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Subcutaneous panniculitis-like T-cell lymphoma in a 25-year-old male patient with sickle cell disease

Sickle cell disease (SCD) is a hereditary blood disorder that often has multiple comorbidities. Patients occasionally develop malignant neoplasms, but the risk of lymphoma in SCD is currently unknown. Here, we report a unique case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a 25-year-old male patient with SCD. The patient suffered from episodes of sickling crisis since his initial SCD diagnosis and had been treated with supportive care. Hydroxyurea was added at the age of 23 years old. Two years later, he presented with right cheek swelling, and the biopsy showed a lymphohistiocytic infiltrate within adipose tissue resembling lobular panniculitis. Immunohistochemistry demonstrated CD8/β-F1-positive T-cells around the fat vacuoles, with a high proliferative index. The histopathologic features suggested a diagnosis of SPTCL. A subsequent TCRβ gene rearrangement analysis detected a clonal amplicon, confirming the diagnosis. Because of the lack of systemic symptoms, the patient received conservative therapy with prednisone and responded well with resolution of his right cheek swelling within one month. To the best of our knowledge, this is the first reported case of SPTCL associated with SCD. The proposed lymphomagenesis in the setting of SCD is also discussed.     

Extranodal mantle cell lymphoma mimicking marginal zone cell lymphoma

AIM: We report a case of mantle cell lymphoma masquerading as a marginal zone cell lymphoma. METHODS AND RESULTS: In the initial manifestation in the palatine tonsils, the neoplastic cells were found to grow exclusively within the marginal zones of secondary follicles which showed a preserved mantle zone. The few immunostains performed showed a B-cell phenotype including an immunoglobulin light chain restriction. The extranodal manifestation, the growth pattern, and the immunophenotype led to the diagnosis of an extranodal marginal zone B-cell non-Hodgkin's lymphoma (NHL). The specimen from the relapse occurring 8 months later exhibited diffuse monomorphous cells co-expressing B-cell antigens and CD5, CD43 and cyclin D1, leading to the diagnosis of mantle cell lymphoma. Re-investigation of the initial biopsy revealed that the neoplastic cells within the marginal zones had a mantle cell lymphoma immunophenotype expressing cyclin D1, the immunoglobulin heavy chains IgD and IgM and partly CD5. Both lesions harboured identical clonal immunoglobulin gene rearrangements proving that they represented different manifestations of the same lymphoma. CONCLUSION: This case emphasizes the importance of broad immunohistological investigation of B-cell NHLs involving the marginal zone.     

Extranodal NK/T‐cell lymphoma,nasal type of the uterine cervix: A case report

We report a rare case of extranodal NK/T‐cell lymphoma, nasal type of the uterine cervix that showed cytologic features mimicking cervical cancer. A 65‐year‐old woman presented with vaginal bleeding. Gynecological examination revealed a bulky tumor of the cervix. A conventional Papanicolaou‐stained cervical smear showed hypercellularity consisting of numerous variably sized cohesive clusters that mimicked epithelial tumors, with a necrotic and inflammatory background. A small number of individually scattered cells were also identified. These scattered cells showed pleomorphic, often cleaved, or horseshoe‐shaped nuclei and pale cytoplasm. Biopsy specimens revealed a diffuse growth of atypical cells with an angiocentric pattern. Extensive necrosis and infiltration of inflammatory cells were present. There were numerous mitotic figures. The tumor cells were positive for CD45RO, CD3ε, CD56, granzyme B, TIA‐1, CD7, and Epstein–Barr virus (EBV)‐encoded small RNA (EBER) by in situ hybridization, and negative for cytokeratin, chromogranin A, synaptophysin, CD4, CD5, CD8, CD20, and CD30. Based on these findings, this tumor was diagnosed as extranodal NK/T‐cell lymphoma, nasal type of the uterine cervix. Diagn. Cytopathol. 2016;44:430–433. © 2016 Wiley Periodicals, Inc.     

Cutaneous intravascular natural killer/T cell lymphoma with peculiar immunophenotype

Intravascular lymphoma (IVL) is a rare entity. Most cases are a variant of extranodal diffuse large B cell lymphoma, and fewer than 10% of the published cases are of T cell origin. Only intravascular B cell lymphoma is recognized as a distinct entity in the most recent World Health Organization (WHO) classification of lymphoproliferative disorders. We describe a case of cutaneous natural killer (NK)/T IVL, with a cytotoxic immunophenotype and Epstein–Barr virus (EBV) positivity. However, our case was immunohistochemically negative not only for T cell receptor (TCR)‐βF1 and TCR‐γ (TCR‐silent), but also for CD56, making it the first triple‐negative NK/T IVL case to be described. We urge recognition of this NK/T cell lineage intravascular lymphoma due to its particular immunophenotypical profile and its unvarying relationship with EBV. Its occurrence should not be considered a coincidence, but rather a key aspect of the pathogenic background of this haematological neoplasm.     

皮下脂膜炎样T细胞巴瘤的病理分析及基因诊断

目的：探讨皮下脂膜炎样T细胞巴瘤（SPTCL）的基因诊断方法及病理特点,方法：在组织学诊断的基础上,辅以免疫组织化学,并利用PCR技术检测石蜡切片标本IgH及TCRβ基因重排。结果：将3例原考虑为结节性非化脓性脂膜炎的病例确诊为皮下脂膜炎样T细胞巴瘤。患者均为青壮年,起病较急,表现为皮下结节伴红斑,镜下见异型淋巴细胞浸润皮下脂肪组织间质,呈脂膜炎样改变,可见核碎裂、局灶性坏死及泡沫状组织细胞,免疫表型：LCA＋,UCHL－1＋,Mac387-,TCR-β基因重排＋,IgH基因重排－。结论：皮下脂膜炎样T细胞淋巴瘤具有较特殊的病理组织学特征,基因诊断等新技术手段是皮下脂膜炎样T细胞淋巴瘤鉴别诊断的有效方法。     

NK/T cell lymphoma involving mediastinum: report of a case and review of literature

Extranodal natural killer (NK)/T-cell lymphoma is a very aggressive malignant neoplasia with a poor prognosis. Herein we reported a case of NK/T cell lymphoma involving mediastinum. It was a 28-year-old Chinese male patient. The tumor cells were medium-sized, had irregularly folded nuclei, and inconspicuous or small nucleoli with coagulative necrosis. The tumor cells were positive for CD3ε, TIA-1, but negative for CD56. In situ hybridization revealed that tumor cells also expressed Epstein-Barr virus encoded RNA. To our knowledge, this is the first case of NK/T cell lymphoma involving mediastinum.     

Peripheral T cell and natural killer (NK) T cell lymphomas: a clinicopathological study from a single Australian centre

McKelvie P A, Thompson P A & Tam C S
(2012) Histopathology  61, 212–233 Peripheral T cell and natural killer (NK) T cell lymphomas: a clinicopathological study from a single Australian centre Aims: Using pathological and clinical review, to identify all cases diagnosed as peripheral T cell and natural killer (NK) T cell lymphoma over 10 years from one metropolitan Australian hospital. Methods and results: Subtyping was performed using World Health Organization (WHO) 2008 criteria and a comprehensive immunohistochemical panel. Clinical data including follow‐up were obtained. There were 47 cases, including 11 peripheral T cell lymphomas, not otherwise specified (NOS), nine extranodal NK T cell lymphomas, nasal type (eight nasal), eight primary cutaneous anaplastic large cell lymphomas, seven angioimmunoblastic T cell lymphomas, three anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphomas, four ALK‐negative anaplastic large cell lymphomas, three enteropathic T cell lymphomas and two subcutaneous panniculitis‐like T cell lymphomas. Follow‐up of 46 of 47 cases (median time 45 months) revealed that 50% (23 of 46) of patients died. Five‐year survival rates were: peripheral T cell lymphoma, NOS 39%; angioimmunoblastic T cell, 43%; nasal NK T 67%; ALK‐negative anaplastic large cell lymphoma 67% (at 2 years); ALK⁺ anaplastic large cell lymphoma 33%; subcutaneous panniculitis‐like T cell lymphomas 100%; primary cutaneous anaplastic large cell lymphoma 86%; and enteropathic T cell lymphoma 33% (at 1 year). One patient with Lennert lymphoma suffered four late cutaneous relapses. Conclusions: This first Australian clinicopathological series of peripheral T cell and NK T cell lymphoma shows epidemiological and survival data similar to those for Europe and North America.     

Cutaneous granulocytic sarcoma mimicking immunoblastic large cell lymphoma

A peculiar case of cutaneous granulocytic sarcoma without leukemic manifestation (so-called aleukemic leukemia cutis) that developed in the skin of the back of a 69-year-old man is reported. A skin biopsy specimen showed atypical cells with a prominent nucleolus proliferating around dermal blood vessels and along adnexa without epidermotropism. Atypical cells similar to those of the skin had infiltrated diffusely into the interfollicular area of an inguinal lymph node. Flow cytometric and immunohistochemical studies with a panel of monoclonal antibodies revealed neoplastic cells that had a biphasic phenotype of myeloid and T cell precursors. They expressed CD13, CD15, CD33, lysozyme, CD3epsilon, CD4, CD7 and terminal deoxynucleotidyl transferase (TdT). Gene analysis showed no rearrangement of the immunoglobulin heavy chain or T cell receptor beta and gamma genes. Ultrastructurally, the tumor cells exhibited a few intracytoplasmic electron-dense granules and well-developed rough endoplasmic reticulum with an occasional whorling arrangement. The initial diagnosis was immunoblastic large cell lymphoma, and the patient was treated with six courses of ProMACE-CytaBOM. In spite of the high-grade cytological characteristics of this tumor, the patient has been free of disease for 5 years.     

A probable identical Epstein-Barr virus clone-positive composite lymphoma with aggressive natural killer-cell leukemia and cytotoxic T-cell lymphoma

The patient was a 52-year old woman with a history of mosquito-bite hypersensitivity since childhood. In July 2011, she developed pyrexia, headaches, and nausea, and Epstein-Barr virus (EBV)-positive aggressive natural killer leukemia (ANKL) was diagnosed on the basis of both a peripheral blood and bone marrow examination. An inguinal lymph node biopsy, on the other hand, revealed EBV-positive cytotoxic T-cell lymphoma plus the presence of a small number of EBV-positive ANKL cells, and a diagnosis of EBV-positive composite lymphoma was made. Both the cytotoxic T-cell lymphoma and ANKL exhibited EBV terminal repeat (Southern blot analysis) monoclonal patterns, and they were almost the same size, approximately 9.0 kb. If it was the identical EBV clone, it is possible that EBV infected progenitor cells common to both NK cells and T cells, that the progenitor cells then differentiated into NK cells and T cells, a chronic active Epstein-Barr virus infection developed, and neoplastic transformation occurred. If it was not the identical EBV clone, fairly similar EBVs must have infected NK cells and T cells separately, and they then underwent neoplastic transformation. Because the mechanism by which EBV infects NK cells or T cells is still unknown, we concluded that this case is also important from the standpoint of elucidating it. We are currently in the process of conducting gene analyses to determine whether the fairly similar EBVs that infected the ANKL and cytotoxic T-cell lymphoma are the identical clone.     

Nodal T/NK-cell lymphoma of nasal type: a clinicopathological study of six cases

Aims:  To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein–Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement ( n  = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type ( n  = 21).
Methods and results:  All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3ε+, CD4−, CD5−, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor γ-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences.
Conclusions:  Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.     

Peripheral CD4+ CD8- γδ T cell lymphoma: A case report with multiparameter analyses

A 72-year-old Japanese man presented with CD4+ T cell receptor (TCR) γδ T cell lymphoma involving bilateral cervical lymph nodes. No involvement by tumor was observed in the liver, spleen, nasal cavity, or bone marrow throughout his clinical course. Although the tumor adequately responded to chemotherapy and irradiation, he relapsed with short remission and a slowly aggressive clinical course, and died 24 months after onset. Simultaneous expression of TCRγδ with other T-cell antigens on the lymphoma cells was analyzed by 3-color flow cytometry (3-FCM), and showed a unique phenotype CD3+ CD4+ CD8− CD7− CD5+ CD2++ TCRαβ (WT31)- βF1-TCRγδ1 (11F2)+ TCRδ1+. Cytogenetic analysis showed 79–81 and structural abnormalities consisting of del(1) (p11) and i(17)(q10). But no abnormality was identified in chromosome 7. DNA analysis revealed gene rearrangements of TCRγ and δ, while a nongerm line band in TCRβ was aberrantly seen. These observations suggest a new subtype of γδ T-cell lymphoma, which is characterized by CD4 positivity and by a clinical course not as aggressive as other predominant subtypes.     

Expression of cytotoxic molecule TIA-1 in malignant lymphomas mimicking fulminant hepatitis

Involvement of malignant lymphoma in the liver inducing fuiminant hepatic failure has rarely been reported. There fore, a close association between some lymphoma types with severe liver damage and the mechanism underlying the liver damage is intriguing. Three malignant lymphoma cases, which were clinically diagnosed as fulminant hepatitis, were collected from the autopsy records of Kawasaki Medical School (Kurashiki, Japan). All three cases were characterized by the presence of hepatosplenomegaly without superficial lymph node swelling, high elevation of transaminase and lactate dehydrogenase (LDH; especially LDH-2), and a quite aggressive clinical course. Immuno-histochemlcally, the tumor cells in all three cases were positive for T cell intracellular antlgen VIA-l), which is a cytolytic protein in cytotoxic T and natural klller (NK) cells. The lymphomas were CD8⁺ perlpheral T cell lymphoma (case l), CD56⁺ T/NK cell lymphoma (case 2), and T cell lymphoma in a patient with mosquito hypersensitivity (case 3). Epstein-Barr virus infection was demonstrated on the tumor cells of cases 2 and 3 using an in situ hybridization method and those cases showed high titers of serum interferon-γ and Fas. Frequent apoptosis of liver cells, where the lymphoma cells had infiltrated, was revealed by a terminal deoxyribosyl transferase-mediated deoxyuridine nick end-labeling (TUNEL) method. The findings in this study suggest that fulminant hepatic injury is closely associated with cytotoxic molecule TIA-1 expression of the lymphoma cells and that some specific mechanism may be involved In liver damage.