Long term clinical outcomes of adult hematolymphoid malignancies treated at Tata Memorial Hospital: An institutional audit

Introduction: There is paucity of data from India about the outcomes of patients with various hematological malignancies. Since its formation in 2009, the adult hematolymphoid disease management group of the Tata Memorial Centre is dedicated to the treatment of hematological malignancies alone. In this report, we present the outcomes of patients treated at our centre over a 5 year period for various haematological malignancies in both transplant and non-transplant setting. Methods: This is a retrospective analysis of all patients registered in adult hematolymphoid disease management group between 1st January 2010 to 31st December 2014. Patients not treated at our centre were excluded from survival analysis. The cut off date for survival analysis was 31st January 2016. Results: Overall, 1869, 3633 and 544 patients with acute leukemias, various lymphomas and myeloma respectively were registered at our centre from 1st January 2010 to 31st December 2014. Of these, 1178 (63%), 3091 (85%) and 454 (83%) respectively received treatment at our centre. The cumulative probability of 5 year overall survival for patients with acute leukemias, Hodgkin's lymphoma, non-Hodgkin lymphoma and myeloma treated at our centre is 40%, 85%, 78% and 40% respectively. Four hundred and fifteen stem cell transplants were done between 14th November 2007 to 31st December 2014 with 46% being allogeneic and 54% being autologous. The 5 year overall survival of patients with allogenic and autologous transplant was 52% and 63% respectively. Conclusions: This is the largest single centre data on outcomes of various haematological malignancies from India. This real world data identifies areas which need further attention to improve outcomes.

Morphological spectrum of leukemic mantle cell lymphoma.

Background: Leukemic involvement in mantle cell lymphoma (MCL) is common, and can be secondary to nodal or extranodal disease or can be de-novo. There is paucity of literature that describes the morphological spectrum. Aim: This study was aimed at studying the morphological spectrum of leukemic MCL and to correlate the morphology with other features. Materials and Methods: Twenty six such cases diagnosed over a period of four years were studied. Peripheral blood and bone marrow aspiration smears stained with Wrights stain were examined by three hematopathologists. Immunophenotyping was done using multicolor flow cytometry. Fluorescence in situ hybridization (FISH) done in 12 cases showed t(11;14)(q13:q32). Results: Six cases had de-novo leukemic involvement; while 20 cases had secondary involvement. Morphologically, the cells were small (less than twice the size of red blood cell) or large. Small cell morphology in turn showed irregular nuclear border (n=13) or round nuclear contour (n=6). Large cells had blastic morphology (n=5) or had central prominent nucleoli resembling prolymhphocytes (n=2). Twenty cases showed characteristic immunophenotype of CD5+/CD19+/CD20+/FMC7+/CD10-/CD23- and light chain restrictions. Three cases expressed CD23 and two cases were negative for FMC7. Five out of 12 cases, where FISH was done, showed cytogenetic abnormalities in addition to t(11;14)(q13;q32). Conclusion: Morphological spectrum of leukemic MCL ranges from small cells resembling chronic lymphocytic leukemia (CLL) or follicular lymphoma (FL) to large cell mimicking prolymphocytic leukemia (PLL) or acute leukemia. Large cell morphology was associated with more frequent additional cytogenetic abnormality as well as a poorer outcome.

Clinico-pathological profile of Hairy cell leukemia: Critical insights gained at a tertiary care cancer hospital.

Context: Hairy cell leukemia (HCL) is a rare, low grade, B-cell neoplasm with a characteristic morphologic and immunophenotypic profile. It has to be distinguished from chronic lymphoproliferative disorders because of different treatment protocol and clinical course. Aims: To evaluate clinicopathological features including immunophenotypic analysis of cases diagnosed as HCL. Materials and Methods: The present study included 28 cases diagnosed over a period of nine years (2002-2010). Clinical presentation, complete blood count, bone marrow aspirate, and flow cytometric analysis of cases were reviewed. Treatment and follow-up details (ranging from 3-90 months) were noted. Results: This study revealed 28 cases (referrals-7, indoor-21), aged 26-69 years with a median age of 47 years, with a male predominance (M:F=6:1). The presenting complaints were weakness (80%) followed by fever (56%) and abdominal pain. Physical examination revealed splenomegaly in most patients (92%) and hepatomegaly in a minority (28%). The common laboratory features were anemia in 23 cases, pancytopenia in 14 cases, while two patients had leukocytosis and three patients had normal WBC count. Dry tap was observed in 84% of the cases where hairy cells constituted 16-97% of non-erythroid nucleated cells. Tartarte resistant acid phosphate staining was positive in all the eight cases where it was done. CD5 was negative in all the cases, while CD10 was expressed in three cases (13%) and CD23 in five cases (19%). Conclusions: Though pancytopenia is common, occasional patient can present with normal blood counts or leukocytosis. Few unusual findings include presence of lymphadenopathy, absence of palpable splenomegaly, and expression of CD23 and CD10 by the leukemic cells.

Characterization of cryptic rearrangements, deletion, complex variants of PML, RARA in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation t(15;17)(q22;q21) leading to the disruption of Promyelocytic leukemia (PML) and Retionic Acid Receptor Alpha (RARA) followed by reciprocal PML–RARA fusion in 90% of the cases. Fluorescence in situ hybridization (FISH) has overcome the hurdles of unavailability of abnormal and/or lack of metaphase cells, and detection of cryptic, submicroscopic rearrangements. In the present study, besides diagnostic approach we sought to analyze these cases for identification and characterization of cryptic rearrangements, deletion variants and unknown RARA translocation variants by application of D-FISH and RARA break-apart probe strategy on interphase and metaphase cells in a large series of 200 cases of APL. Forty cases (20%) had atypical PML–RARA and/or RARA variants. D-FISH with PML/RARA probe helped identification of RARA insertion to PML. By application of D-FISH on metaphase cells, we documented that translocation of 15 to 17 leads to 17q deletion which results in loss of reciprocal fusion and/or residual RARA on der(17). Among the complex variants of t(15;17), PML–RARA fusion followed by residual RARA insertion closed to PML–RARA on der(15) was unique and unusual. FISH with break-apart RARA probe on metaphase cells was found to be a very efficient strategy to detect unknown RARA variant translocations like t(11;17)(q23;q21), t(11;17)(q13;q21) and t(2;17)(p21;q21). These findings proved that D-FISH and break-apart probe strategy has potential to detect primary as well as secondary additional aberrations of PML, RARA and other additional loci. The long-term clinical follow-up is essential to evaluate the clinical importance of these findings.

Primary intestinal T cell lymphomas in Indian patients - In search of enteropathic T cell lymphoma.

Objective: This series of six intestinal T cell lymphomas (ITCL) attempts to document enteropathy-associated T cell lymphoma (EATCL) in India. Materials and Methods: A total of six ITCL were selected from 170 gastrointestinal lymphomas in last 10 years. Results: The cases studied included EATCL (4), ITCL with a CD4 positive phenotype (1) and ITCL NK/T cell type (1). Of the four EATCL, two occurred in the ileum, one in right colon and one in duodenum. In three EATCL cases, there was history of celiac disease or lactose intolerance and enteropathic changes were noted in the adjacent mucosa. These tumors had CD3+/CD8+/CD56 (+/-)/CD4-/ Granzyme B+ immunophenotype. One EATCL was monomorphic small cell type (type II EATCL) with a CD3+/CD8-CD56+/CD4-/ Granzyme B+ phenotype. EBER- ISH (Epstein Barr virus coded RNA's- in situ hybridization) revealed positive tumor cells in ITCL NK/T cell type and in bystander cells in three EATCL. Conclusion: ITCL are rare in Indian patients but do occur and comprise a mixture of the enteropathic and non-enteropathic subtypes.

Epithelioid trophoblastic tumor of uterus presenting as an ovarian mass: a diagnostic and therapeutic dilemma.

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor and often poses a diagnostic and therapeutic challenge to the involved clinicians. We report a case of epithelioid trophoblastic tumor in a young woman which involved the uterus, parametrium and the right ovary. Misdiagnosis as a choriocarcinoma led to improper treatment and progressive disease. Microscopically it revealed a relatively monotonous population of epithelioid cells arranged in nests with hyaline-like matrix surrounding the tumor cells. Differential diagnosis between placental site trophoblastic tumor and carcinoma was ruled out based on histology and immunohistochemistry. The patient developed lung and brain metastasis after 10 months and is alive with disease 1(1/2) years thereafter and is taking palliative chemotherapy. The patient had beta-HCG level of 85.1 mIU/mL at the time of diagnosis; but just before metastasis, the levels rose. Awareness of the histological features of ETT is essential to avoid misdiagnosis, as it represents a tumor which is primarily treated by surgery rather than with chemotherapy.

Metachronous gastric diffuse large B-cell lymphoma and adenocarcinoma.

The development of gastric carcinoma in a patient with gastric lymphoma is rare. Helicobacter pylori is a common etiologic agent for both these conditions. We report a 38-year-old lady who was initially diagnosed to have gastric lymphoma and developed early gastric carcinoma on follow up. She was operated on for the carcinoma and is in complete remission since.

Retro-peritoneal plasmacytoma: a case report and review of literature.

Solitary Extramedullary Plasmacytoma (EMP) is an uncommon neoplasm. When diagnosed, head and neck region is its most likely location. Rarely, it may occur in the retro-peritoneum. We report a 44 year old man with solitary extramedullary plasmacytoma in the retro peritoneum (RPEMP). The patient did not show response to three cycles of VAD chemotherapy. Thereafter Surgical excision of the mass was performed successfully. This is probably the first case report from Indian subcontinent.