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1/22. gamma delta T-cell lymphoma: a clinicopathologic study of 6 cases including extrahepatosplenic type.

    We report 6 cases of gamma delta T-cell lymphoma (GDTL) among 115 peripheral T-cell lymphomas over a 12-year period. All patients exhibited extranodal lymphomas, comprising 3 hepatosplenic, 1 cutaneous, 1 intestinal, and 1 thyroidal lymphoma. Despite therapies, all but 1 patient died of disease within 16 months of diagnosis. The cytologic features of lymphoma cells in 4 of 5 cases examined were very similar: coarsely reticulated nuclear chromatin, multiple small nucleoli, abundant faintly eosinophilic granular cytoplasm, and focal angiocentric proliferation. All 6 lymphomas showed Cd3 CD4-CD8-/ phenotype. CD56 was positive in 3 cases, 1 of which was also CD16 positive. perforin and T-cell intracellular antigen-1 were positive in all 5 cases examined. Southern blot analysis revealed clonal gene rearrangements of the T-cell receptor delta-chain gene in all 5 cases examined. Based on these findings, together with a review of the literature, GDTLs seem to have several common lineage-specific features, although clinical presentation and course of GDTL are heterogeneous.
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2/22. Extranodal peripheral T-cell lymphoma with angiocentric growth pattern and Epstein-Barr viral dna associated affecting paratesticular soft tissue.

    Peripheral T-cell lymphomas are uncommon, accounting for only 10% to 15% of all non-Hodgkin lymphomas and their classification has been controversial. We report a case of peripheral T-cell lymphoma with angiocentric growth pattern which presented as a paratesticular tumoral nodule in a 47-year-old-man. Formalin-fixed paraffin-embedded samples from the paratesticular tumor and non-infiltrated adjacent tissue were submitted to histological, immunohistochemical, polymerase chain reaction (PCR)-based and in situ hybridization analysis. Histopathologically, there was a lymphomatous infiltrate in the paratesticular soft tissue, composed of a variable mixture of medium-sized to large cells with large cytoplasm and irregular-shaped nuclei, together with blood vessel destruction, necrosis and karyorrhexis. Immunohistochemical study revealed a high p53 expression in neoplastic cells that showed T cytotoxic immunophenotype, failing to express the natural killer (NK)-cell antigen CD56. A monoclonal rearrangement of the T-cell receptor (TCR) gamma gene by a PCR technique was demonstrated. Type-A Epstein-Barr Virus (EBV) dna was detected by PCR-based analysis. A combined in situ hybridization and immunohistochemical study revealed that most cells labeled positive for EBV rna showed immunostaining with the CD45RO antibody. Based on the above results, the case reported was classified as extranodal peripheral T-cell lymphoma with cytotoxic phenotype and EBV associated. The present case does not fit neatly into any of the specific types of peripheral T-cell lymphomas of the REAL classification, so a diagnosis of peripheral T-cell lymphoma unspecified was made.
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3/22. Peripheral T-cell lymphoma with aberrant expression of CD79a and CD20: a diagnostic pitfall.

    Immunohistochemical studies are increasingly used for the routine diagnosis of lymphomas as it is widely accepted that lymphomas of different cell lineages vary in their prognosis and response to therapy. A case of peripheral T-cell lymphoma with aberrant expression of B-cell-associated antigens L-26 (CD20) and mb-1 (CD 79a) is described. The disease pursued an aggressive clinical course, and the patient died of disease 6 weeks after presentation. Immunohistochemical studies demonstrated expression of both T- and B-cell-associated antigens, including CD3, CD8, CD43, TIA-1, CD20, and CD79a. Other markers expressed by the tumor cells included CD56 and S-100. Of interest, betaF-1 staining for the beta chain of T-cell receptor (TCR) complex was positive in the small admixed T lymphocytes but was negative in the tumor cells, raising the possibility of a gamma/delta T-cell lymphoma. Molecular studies by polymerase chain reaction (PCR) demonstrated clonal TCR-gamma chain gene rearrangement without evidence for a clonal rearrangement of the immunoglobulin heavy chain gene. PCR for HHV-8 related sequences was negative. Mb-1 is an IgM-associated protein that was thought to be restricted to normal and neoplastic B cells. Although its coexpression has been reported in up to 10% cases of precursor T-cell lymphoblastic lymphoma, the coexpression of both CD20 and CD79a has not been described in mature T-cell malignancies. Biphenotypic lymphomas associated with HHV-8 have been reported in immunodeficiency, but no evidence of immune deficiency was identified, and studies for EBV and HHV-8 were negative. This case illustrates that no marker has absolute lineage specificity and that immunophenotypic studies should always be performed with panels of monoclonal antibodies. Moreover, cases with ambiguous phenotypes may require genotypic studies for precise lineage assignment.
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4/22. Primary bony peripheral T-cell lymphoma mimicking nasal type NK/T-cell lymphoma: a case report.

    Primary bony lymphomas are rare, and nearly all are high-grade B-cell lymphomas. Natural killer (NK)/T-cell lymphomas are highly aggressive lymphomas of NK- or T-cell lineage with predominant extranodal presentation and are divided into nasal and nasal-type (extra-nasal). We report a primary bony peripheral T-cell lymphoma mimicking NK/T-cell lymphoma, nasal type. A 22-year-old Taiwanese male presented with a frontal skull bone mass noted for 3 weeks, and received craniectomy with tumor removal. His tumor showed extensive coagulative necrosis with angioinvasion by large lymphoma cells expressing CD2, CD8, CD16, CD43, CD45, CD45RO, CD56, T-cell intracellular antigen-1, and granzyme B, but not CD3, CD4, CD20, CD57, CD68, and betaF1. in situ hybridization for Epstein-Barr virus-encoded mRNA was negative. polymerase chain reaction study of formalin-fixed tissue showed clonal rearrangement of the T-cell receptor-gamma chain gene. The diagnosis was peripheral T-cell lymphoma, unspecified subtype. The initial stage was I(EA). His lymphoma was refractory to chemotherapy, and bony metastases developed in the right iliac bone 2 months later. He died of disease after 6 months without autopsy. We emphasize the importance of detailed immunohistochemical and gene rearrangement studies for the classification of malignant lymphomas via a very rare primary bony lymphoma of peripheral T-cell subtype.
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5/22. Gamma delta T-cell neoplasms: a clinicopathological study of 11 cases.

    BACKGROUND: The majority of T-cell neoplasms express T-cell antigen receptor (TCR) alpha beta on their cell surface, and a few cases show the TCR gamma delta phenotype. Recently, a variety of gamma delta T-cell neoplasm was recognized; however, its clinicopathological features have not been extensively analyzed. Here we report the results of a clinicopathological study of 11 cases of gamma delta T-cell neoplasm. patients AND methods: During the 11-year period from 1989 to 1999, 104 patients with T-cell neoplasms were examined by flow cytometric analysis and/or immunohistochemical analysis. Tumor cells from all 104 patients expressed one or more of the T-cell antigens-CD2, CD3, CD5 and CD7. Forty-nine of the 104 cases of T-cell neoplasms were examined immunophenotypically for TCR alpha beta/gamma delta subsets. RESULTS: Expression of TCR gamma delta on tumor cells was found in five (33%) of 15 patients with precursor T-cell lymphoblastic leukemia/lymphoma, one (25%) of four with T-cell granular lymphocytic leukemia and five (26%) of 19 with peripheral T-cell lymphoma (PTCL), whereas no expression was found in 11 patients with adult T-cell leukemia-lymphoma. Primary sites of the five patients with gamma delta PTCL were as follows: lymph node, three; skin, one and liver, tonsil and skin, one. The courses of the three patients with gamma delta PTCL of nodal onset were very short (3, 5 and 9 months, respectively), and they were all resistant to combination chemotherapies. CONCLUSIONS: Although gamma delta T-cell neoplasm constitutes a heterogeneous population, it is important to examine the expression of TCR with the view to identifying possible poor prognostic subgroups, such as primary nodal gamma delta T-cell lymphoma.
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6/22. Primary central nervous system cytotoxic/suppressor T-cell lymphoma: report of a unique case and review of the literature.

    Peripheral T-cell lymphoma primary to the central nervous system is a rare occurrence. The authors report a case of an 89-year-old woman who presented with a 3-month history of worsening confusion and recent onset of headache, nausea and vomiting, and upper limb tremors. Computed tomography and magnetic resonance imaging examinations demonstrated a 4.5-cm solitary brain mass in the right basal ganglia with compression along the ventricular system. No other lesion was found in the patient. Histologic and immunohistochemical studies of a stereotactic biopsy of the mass showed a T-cell lymphoproliferative lesion positive for CD3, CD8, CD57, and T-cell intracellular antigen 1 and negative for CD4, CD56, CD30, anaplastic lymphoma kinase, and CD20. A monoclonal T-cell receptor-gamma gene rearrangement was detected by polymerase chain reaction analysis of genomic dna isolated from paraffin-embedded tumor tissue sections. These findings were consistent with peripheral T-cell lymphoma of cytotoxic/suppressor phenotype, resembling the phenotype of T-cell large granular cell leukemia. To the authors' best knowledge, this represents the first reported case of primary brain T-cell lymphoma with a cytotoxic/suppressor immunophenotype. A brief review of the literature of primary brain T-cell lymphoma is also presented.
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7/22. Successful treatment of a patient with subcutaneous panniculitis-like T-cell lymphoma with high-dose chemotherapy and total body irradiation.

    A 24-yr-old man was referred for fever, right cheek swelling, subcutaneous tumor and liver dysfunction. physical examination showed an elastic hard subcutaneous tumor on the right cheek, left axillary lymph node swelling and multiple small subcutaneous tumors in the trunk. Laboratory examinations showed elevated levels of transaminase, soluble interleukin-2 receptor and ferritin. biopsy of the subcutaneous tumor showed proliferation of medium-sized cells with abundant clear cytoplasm and hyperchromatic nuclei among the subcutaneous fat tissues. These cells showed CD3 , CD4-, CD8 , CD56- and CD20- phenotype and possessed cytotoxic molecules such as granzyme B and T-cell intracellular antigen-1. bone marrow aspiration showed proliferation of small numbers of abnormal lymphocytes with severe hemophagocytosis. He was thus diagnosed as having subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and treated with dose-escalated CHOP regimen. After three courses of the chemotherapy, he was further treated with high-dose chemotherapy and total body irradiation (TBI) with autologous peripheral blood stem cell rescue. Thereafter, he has been in remission for more than 2 yr. We consider that SPTCL with hemophagocytosis is an extremely aggressive disease, and high-dose chemotherapy and TBI should be included for the choice of the treatment.
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8/22. Peripheral T-cell lymphoma of AILD (angioimmunoblastic lymphadenopathy with dysproteinemia) type involving gastrointestinal tract. A morphologic, phenotypic and genotypic study.

    A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which showed widespread involvement of the gastrointestinal tract is reported. A lymph node biopsy specimen showed the characteristic histological features of AILD. During the progression of the illness, lymphomatous lesions developed in the gastrointestinal tract, complicated by cytomegalovirus infection. A double immunoenzymatic study using a combination of Ki-67 antibody and antibodies against surface antigens demonstrated that CD3 , CD4 , and/or T-cell receptor (TCR) beta cells were predominant (67-68%) among the population of proliferating Ki-67% cells, rather than CD8 or CD22 cells. Clonal rearrangement of the TCR beta chain gene was also detected. These findings provide further evidence for the neoplastic nature of lesions of this type, and the diagnosis of peripheral T-cell lymphoma.
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9/22. Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis.

    A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.
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10/22. Specific cutaneous lesions in a CD8 peripheral T-cell lymphoma.

    Histopathologic, immunohistochemical, and ultrastructural studies were carried out on cutaneous lesions of a 43-year-old man with an aggressive peripheral T-cell lymphoma involving the lung, central nervous system, bone marrow, and skin. Some results are distinctive and not previously reported, such as extremely strong epidermotropism, aberrant CD8 immunophenotype with lack of one pan T antigen (CD5), and giant cytoplasmic granules. We discuss these features comparing them with other hematologic malignancies usually involving the skin, such as cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, angiocentric lymphomas, and malignant histiocytosis.
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