Non-Nodal CD5-Negative Mantle Cell Lymphoma with Secondary TP53 Deletion.

Mantle cell lymphoma is a non-Hodgkin lymphoproliferative neoplasm with several clinical and morphologic variants linked, primarily, through genetic derangement of the cyclin D1 locus. Aberrant phenotypes have been described, though prognostic data in such cohorts are limited due to a paucity of cases. We report a case of mantle cell lymphoma with non-nodal clinical presentation, aberrant loss of CD5 expression, and concomitant cytogenetic deletion of 17p. While non-nodal disease is often associated with an improved prognosis in mantle cell lymphoma, this 67-year-old patient experienced a more challenging clinical course with a poor initial response to chemotherapy. Therefore, this case may represent a type of non-nodal mantle cell lymphoma with a prognosis similar to that of classical cases due to the additional phenotypic and genetic alterations found in this patient.

Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia.

AIMS: Near-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics and therefore, presumed to have an unfavourable prognosis. Our aim is to further characterise the clinical, morphological, cytogenetic and prognostic features of NT/T-AML. METHODS: We searched our cytogenetic laboratory database from 1991 to 2012 to reveal 13 cases of NT/T-AML. Each case was evaluated with regard to its demographics, morphology, immunophenotype and prognosis. Specific morphological features included blast size, irregularity of nuclear contours, cytoplasmic vacuoles, and presence and lineage of dysplasia. RESULTS: Eleven men and two women had a median age of 68 years. Blasts were predominately large (11/13). Eight of 13 patients had AML with myelodysplasia-related changes. Sixty-nine per cent of patients achieved complete remission (CR). Median overall survival (OS) was 8.6 months. CR rate and median OS in cases with ≥ 5 cytogenetic abnormalities were 71% and 6 months, compared with 67% and 18.1 months in cases with <5 abnormalities. CONCLUSIONS: NT/T-AML occurs in older males, exhibits large blast size and is associated with myelodysplasia. Unlike previously reported data, our study reveals an overall better prognosis in this older population with NT/T-AML than was expected for a complex karyotype AML. Cytogenetic complexity independent of ploidy status did not greatly affect the high CR rates, but did appear to be a better estimation of prognostic risk in terms of median OS.

Primary central nervous system Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a clinicopathologic study of five cases.

We report five cases of primary central nervous system (CNS) Epstein-Barr virus (EBV)-positive lymphoma of the elderly. This represented an incidence of 4 % of primary CNS diffuse large B-cell lymphoma (DLBCL) after EBV screening in 134 cases. All five patients were 65 years or older with no previous history of congenital or iatrogenic immune deficiencies. The histologic morphology of all the cases was DLBCL, with variable amounts of necrosis. The cell of origin (COO) as determined by the Hans algorithm disclosed germinal center type in 2 cases and non-germinal center type in 3 cases. MYC translocation was not detected, and MYC overexpression was detected in only one case. Three patients died shortly after diagnosis, and the remaining 2 patients were in complete remission for 2 and 10 years, respectively. We conclude that EBV+ DLBCL among the elderly is uncommon in primary CNS lymphoma in the Eastern United States. The patients usually present with a single mass lesion with headache and sensorimotor symptoms. The histologic morphology is DLBCL, but clonal T-cell gene rearrangement may be detected. The outcome varies from case to case and appears to be unrelated to the COO or MYC status.

Composite ALK-negative anaplastic large cell lymphoma and small lymphocytic lymphoma involving the right inguinal lymph node.

Anaplastic large cell lymphoma and small lymphocytic lymphoma are two lymphoid malignancies with completely distinct morphologies and natural histories. We present a rare case of composite anaplastic large cell lymphoma and small lymphocytic lymphoma in an inguinal lymph node of an otherwise healthy 47-year-old male patient. Immunohistochemical and molecular studies identified the two populations clearly. Their separation is imperative as anaplastic large cell lymphoma can be an aggressive neoplasm and easily overlooked in cases of small lymphocytic lymphoma with a small population of anaplastic large cell lymphoma cells.

Biclonal light chain gammopathy with aberrant CD33 expression in secondary plasma cell leukemia.

Plasma cell leukemia is a rare neoplastic proliferation of circulating plasma cells. Clonal proliferations of plasma cells, such as in plasma cell leukemia or plasma cell myeloma, are typically characterized by production of a monoclonal heavy and/or light chain immunoglobulin. We present a case of a secondary plasma cell leukemia arising from plasma cell myeloma with dual expression of lambda and kappa light chains along with aberrant expression of CD33, CD20, and dim CD56. This case emphasizes the importance of recognizing aberrant immunophenotypes in plasma cell leukemias and represents the first reported case of biclonal light chain expression in a secondary plasma cell leukemia.

Composite B-cell and T-cell lineage post-transplant lymphoproliferative disorder of the lung with unusual cutaneous manifestations of mycosis fungoides.

We present the case of a 17-year-old male kidney transplant recipient who presented initially with dermatologic symptoms and was found to have histologic changes in the skin that were consistent with mycosis fungoides. Shortly after this diagnosis was made, imaging studies demonstrated multifocal interstitial and airspace consolidation in both lungs. Physical examination revealed no lymphadenopathy or hepatosplenomegaly, but an open lung biopsy revealed an Epstein-Barr virus (EBV)-negative monomorphic T-cell posttransplant lymphoproliferative disorder (PTLD) with a concomitant EBV-positive B-cell PTLD involving the same lesion of the lung. Polymerase chain reaction analysis demonstrated clonal T-cell receptor gene rearrangements in both the skin and the lung biopsies. Interestingly, 1 clone was shared between the skin and lung while a second clone was present only in the lung. To our knowledge, this is the first reported case of a PTLD presenting in the skin in which there was a subsequent discovery of composite, bilineal B- and T-cell PTLD of the lung.

Concomitant occurrence of sinus histiocytosis with massive lymphadenopathy and nodal marginal zone lymphoma.

Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, is a rare self-limiting disorder of histiocytes with unknown etiology. Sinus histiocytosis with massive lymphadenopathy is most common in children and young adults and is characterized by painless lymphadenopathy. Histologically there is a proliferation of sinus histiocytes with lymphophagocytosis or emperipolesis. On rare occasions, SHML has been associated with lymphoma, usually involving different anatomic sites and developing at different times. We report a case of concomitant SHML and nodal marginal zone lymphoma involving the same lymph node without involvement of other nodal or extranodal sites. The presence of concomitant SHML within the lymph node involved by nodal marginal zone lymphoma may represent the responsiveness of SHML histiocytes to B-cell-derived cytokines in lymphoproliferative disorders. To our knowledge, this is the first description of concomitant occurrence of SHML and nodal marginal zone lymphoma.

Effector mechanisms of the anti-cancer immune responses of macrophages in SR/CR mice.

SR/CR (spontaneous regression/complete resistance) mice resist multiple types of cancer cells injected at numbers that are lethal to wild type (WT) mice. When the anti-tumor response was examined, leukocytes of the innate immune system, including neutrophils (PMN), macrophages and NK cells, infiltrated the tumor site for a multipronged killing response. Each cell type had independent killing activity against the cancer cells. A second aspect of this multipronged response was that cancer cells could be killed either via necrosis in vivo or via apoptosis by purified macrophages. Lymphoid cells displayed perforin (pfp) and granzymes (gzm) as effector molecules, but macrophages produced reactive oxygen species (ROS) and secreted serine proteases to kill the cancer cells. However, SR/CR macrophages did not use the well-studied tumoricidal mechanism of reactive nitrogen species (RNS) production. We previously demonstrated that macrophages tightly bound cancer cells in rosettes, and we show here that macrophages required contact with the target cells in order to unleash their cytotoxic mechanisms. Once SR/CR mice survived challenge with cancer cells, they produced antibodies that recognized the cancer cells. However, the antibodies were not required for killing by SR/CR macrophages through antibody-dependent cell-mediated cytotoxicity (ADCC) and did not enable wild type macrophages to kill target cells. In summary, purified SR/CR macrophages killed cancer cells in a non-ADCC manner via apoptosis induced by ROS and serine proteases.