Pseudonodular T cell lymphoblastic lymphoma

T cell lymphoblastic lymphoma usually presents as a rapidly growing lymphoma with histologic features of a diffuse, poorly-differentiated small cell lymphoma with a high mitotic rate. This report describes a patient who presented with an aggressive small cell lymphoma that morphologically had a nodular pattern. Repeated biopsy and use of cell surface markers resulted in reclassifying the cell type as T cell lymphoblastic and in recognizing the original pattern as pseudonodular. The routine application of these immunologic techniques in patients with lymphoma may lead to more accurate diagnoses and improved treatment.     

FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma

Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40·0%) of 55 T-ALL and 7 (50·0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14·6%) of 55 T-ALL and 3 (21·4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30·9%) of 55 T-ALL and 6 (42·9%) of 14 T-NHL patients. Three (5·4%) T-ALL and two (1·4%) T-NHL patients had mutations in both FBXW7 and NOTCH1 . FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95·5% (95% CI, 71·9–99·4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63·6%, P  = 0·007 and 78·8%, P  = 0·023, respectively).     

Large cell lymphoma complicating acute lymphoblastic leukemia

Non-Hodgkin's lymphoma (NHL) is a very rare complication of acute lymphoblastic leukemia (ALL). We present the pathologic, clinical, immunologic, and ultrastructural features of the third reported example of NHL following successfully treated ALL. This white girl developed ALL with predominantly L1 cells at 3.5 yr of age. The lymphoblasts were terminal deoxynucleotidyl transferase (TdT) positive and were non-B, non-T cells. She achieved a complete remission with standard induction therapy and has remained in continuous complete remission. Four and one- third years after the onset of ALL, she developed multifocal, pleomorphic large cell lymphoma of the small bowel, which resulted in episodes of intussusception and obstruction. These pleomorphic and frequently multinucleated lymphoma cells lacked TdT, common ALL antigen, and all tested markers of B cell, T cell, and histiocyte differentiation. Following three small bowel resections, systemic multiagent chemotherapy, and abdominal irradiation, she is currently free of disease.     

Cell surface characterization of malignant T cells from lymphoblastic lymphoma using monoclonal antibodies: evidence for phenotypic differences between malignant T cells from patients with acute lymphoblastic leukemia and lymphoblastic lymphoma

A series of monoclonal antibodies was used for the characterization of malignant T cells from 21 patients with lymphoblastic lymphoma (LL). The tumor population from these patients showed a marked degree of phenotypic heterogeneity and a proportion (one-third) of patients had tumor cells that did not conform exactly with the cells normally detected in the thymus. However, these cell populations could be related to the early or common or late thymocyte population (about one- third of the patients in each category). This contrast, with the characterization of malignant T cells from 43 patients with acute lymphoblastic leukemia (ALL) that could be related to either early or common thymocytes, with an exception of two patients categorized as having a tumor population related to late thymocytes. Further phenotypic differences between cells from ALL and LL could be demonstrated by investigation with two additional monoclonal antibodies, A50 and U4. Among patients with malignant T cells related to common thymocyte, 0/12 patients with ALL had cells recognized by A50, where 5/8 patients with LL had A50+ cells. Among patients with early thymocytes, only patients with ALL had cells recognized by U4. In addition, 5 LL patients had cells reactive with J5, a monoclonal antibody recognizing the common ALL antigen (CALLA). Since CALLA was found on cells related to common and late thymocytes, CALLA is neither lineage specific, nor can it be viewed as being peculiar to malignant lymphoid cells arrested at very immature stages of differentiation.     

Lymphoblastic lymphoma: an immunophenotype study of 26 cases with comparison to T cell acute lymphoblastic leukemia

A series of 26 lymphoblastic lymphomas (LLs) and 13 T cell acute lymphoblastic leukemias (ALLs) were investigated using a battery of monoclonal antibodies applied to tissue frozen sections. Twenty-one of the LLs were of T lineage. All but one of the T cell LLs were of immature thymic phenotype, mostly corresponding to stage II cortical thymocyte development. The T cell LLs expressed Leu-1 in 100%, Leu-4 and Leu-9 in 95%, and Leu-5 in 85% of the cases. The high percentage of Leu-4 expression in this series is probably due to detection of cytoplasmic antigen with our methods. One LL was of pre-B or B cell and two cases were of common ALL phenotype. Two cases were of undefined phenotype, expressing markers of both B and T cell differentiation. Pediatric cases showed a greater tendency toward T cell phenotype than did adult cases. The cases of T cell ALL were immunophenotypically similar to the cases of T cell LL but showed a tendency toward a more immature phenotype.     

Gamma/delta T cell lymphoma

A 54-year-old woman complained of fever and hepato-splenomegaly. The pathological findings of a liver biopsy specimen revealed the infiltration of lymphocytes in the sinusoids and that of the laparoscopically resected spleen revealed the infiltration of lymphocytes in the red pulp, which was positive for CD3, CD43, CD45RO and T-cell intracellular antigen-1 (TIA-1) and was negative for betaF1, while the white pulp was spared. Genetic analysis of the spleen cells revealed the rearrangement of T-cell receptor (TCR) Cbeta1, Jdelta1 and Jgamma. Epstein-Barr virus (EBV) genomic DNA was detected in the spleen cells. Atypical lymphocytes appeared in the peripheral blood and bone marrow, chromosomal analysis revealed del (13) (q12 q14), trisomy 8 and breakage of RB gene. Elevated level of serum vascular endothelial growth factor (VEGF) was observed. Hepatosplenic gammadelta T cell lymphoma (GDTL) was diagnosed. The patient was treated with chemotherapy by cyclophosphamide, hydroxydoxorubicin, vincristine and prednisolone (CHOP), however, it was ineffective, and the patient died of hemorrhage from the lymphoma involvement of the intestine 5 months after the onset of disease.     

Peripheral T cell lymphoma in Asia

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T- and NK-cell neoplasms, the incidence of which is higher in Asian countries than in Western countries. Although its etiology is mainly unknown, several risk factors (such as genetic factors, abnormal immunity, environmental factors, and infectious causes) have been proposed. PTCL are classified based on a combination of several parameters, including morphology, site of presentation, viral status, immunophenotype, and specific genetic alterations. Their classification is ongoing, with the emergence of new entities and refinement of existing entities because of the development of diagnostic markers and new genetic alterations. This review presents epidemiologic data for PTCL in Asia, together with recent progress in the pathology of PTCL compared with the WHO 2008 classification.     

T cell acute lymphoblastic leukemia/lymphoma: a human cancer commonly associated with aberrant NOTCH1 signaling

PURPOSE OF REVIEW: Although constitutively activated forms of the NOTCH1 receptor are potent inducers of T cell acute lymphoblastic leukemia/lymphoma when expressed in the bone marrow stem cells of mice, the known involvement of NOTCH1 in human T cell acute lymphoblastic leukemia/lymphoma has been restricted to very rare tumors associated with a (7;9) chromosomal translocation involving the NOTCH1 gene. This picture has changed dramatically in the past year with the discovery of frequent mutations involving NOTCH1 in human T cell acute lymphoblastic leukemia/lymphoma. RECENT FINDINGS: NOTCH1 point mutations, insertions, and deletions producing aberrant increases in NOTCH1 signaling are frequently present in both childhood and adult T cell acute lymphoblastic leukemia/lymphoma and are detected in tumors from all major molecular subtypes. These observations are particularly important in the light of experiments using human and murine T cell acute lymphoblastic leukemia/lymphoma cell lines indicating that NOTCH1 signals are required for sustained growth and, in a subset of lines, survival. This inference is based in part on experiments conducted with small molecule inhibitors of gamma-secretase, a protease required for normal NOTCH signal transduction and the activity of the mutated forms of NOTCH1 found commonly in human T cell acute lymphoblastic leukemia/lymphoma. SUMMARY: These findings support a central role for aberrant NOTCH signaling in the pathogenesis of human T cell acute lymphoblastic leukemia/lymphoma, and they provide a rationale for trials of NOTCH inhibitors, such as gamma-secretase antagonists, in this aggressive human malignancy.     

T cell lymphoblastic lymphoma in parotidectomy for Warthin’s tumor: case report and review of the literature

Lymphomas associated with Warthin’s tumor (WT) are extremely uncommon and the majorities are of B cell type. We report the simultaneous occurrence of T-cell lymphoblastic lymphoma (T-LBL) and WT in an 81-year-old patient, who presented with fever, night sweats and enlargement of the right parotid gland. The parotidectomy specimen showed a WT with extensive replacement of the lymphoid stroma by T-LBL, but preservation of the oncocytic epithelium. Staging investigations revealed mediastinal and abdominal lymphadenopathy, bilateral pleural effusions and bone marrow infiltration, in keeping with stage IVB disease. The patient received combination chemotherapy treatment but responded poorly, and died three months after diagnosis. To our knowledge, this is the first case report of T-LBL involving WT. The present study indicates that the lymphoid stroma in WT belongs to the systemic lymphoid tissue and can be involved in disseminated lymphoma. It highlights the importance of careful examination of WT’s lymphoid stroma for the possible presence of any coexistent malignancy.