Extranodal follicular dendritic cell sarcoma of the lung.

Follicular dendritic cell sarcoma (FDCS) is a rare, mesenchymal neoplasm that may be nodal or extranodal in location. Lung involvement is rare. It is a slow-growing, painless tumor with a frequent capacity to recur and metastasize. We present a case of extranodal FDCS of the lung with an unusual presentation. A 34-year-old man presented with the complaints of haemoptysis and chest pain. A large left perihilar mass with endobronchial component was found on radiological evaluation. On endobronchial biopsy and mediastinal tru-cut biopsy, differential diagnoses of an inflammatory myo-fibrohistiocytic lesion and leiomyosarcoma were provided on the basis of morphological features of bipolar spindled cells arranged in intersecting fascicles and storiform patterns and immunophenotyping. A pneumonectomy was performed for the mass on which further immunohistochemical evaluation with CD21, CD35, and D2-40 finally helped form a diagnosis of FDCS. The patient recovered well from the surgery and has been on follow-up ever since. Owing to the rarity of this condition and its non-specific clinical features, FDCS is often misdiagnosed in the absence of appropriate immunohistochemistry. An of awareness of its morphological features and immunophenotype is, thus, necessary to provide early treatment and follow-up in order to prevent its recurrence and metastasis.

Large granular lymphocytic leukemia: a brief review.

LGL leukemia is a rare chronic lymphoproliferative disorder of cytotoxic lymphocytes which can be immunophenotypically either T cell or NK cell-derived. According to the World Health Organization classification, it can be divided into three subtypes: chronic T-cell leukemia and chronic natural killer cell lymphocytosis, and aggressive natural killer cell LGL leukemia. Clonal proliferation of large granular lymphocytes can be because of stimulation of various molecular pathways namely JAK-STAT3 pathway, FAS/FAS-L pathway, RAS-RAF-1-MEK1-ERK pathway, PI3K/AKT pathway, NF-KB pathway, and Sphingolipid Rheostat pathways. The most common clinical features presenting with this leukemia are neutropenia, anemia, thrombocytopenia. This leukemia is also associated with various autoimmune conditions. It usually has an indolent course except for the aggressive NK cell LGL leukemia. The cause of death in the indolent cases was mostly due to infectious complications related to the neutropenia associated with the disease. The rarity of the disease coupled with the availability of only a handful of clinical trials has been a hindrance to the development of a specific treatment. Most of the cases are managed with immunomodulators. The advances in the knowledge of molecular pathways associated with the disease have brought few targeted therapies into the limelight. We discuss here the evolution, epidemiology, demographic profile, pathophysiology, differential diagnosis, the available treatment options along with the survival and prognostic variables which may help us in better understanding and better management of the disease and hopefully, paving the way for a targeted clinical approach.

Clinicopathological and laboratory parameters of plasma cell leukemia among Indian population.

BACKGROUND: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm distinguished by extensive clonal expansion of plasma cells in the bone marrow (BM) and peripheral blood (PB). PCL is divided into two subtypes: primary (pPCL) originates de novo without preceding multiple myeloma, while secondary (sPCL) comprises a leukemic modification that occurs as a late manifestation from previous multiple myeloma (MM). pPCL and sPCL are clinically and biologically two different entities. The molecular mechanisms of the development of PCL, either primary or secondary, remain poorly understood. We aim to present 5 years of data on clinical profiles and treatment outcomes of pPCL and sPCL patients treated at our cancer hospital in India and to find a predictive parameter of the development of PCL in cases of MM. METHODS: In this study, we retrospectively reviewed and evaluated the clinicopathological features, laboratory parameters, immunophenotypic profile, and patient outcomes of 17 PCL cases diagnosed among 180 plasma cell dyscrasia patients during the study period to establish a correlation between pPCL & sPCL for diagnosis and management of PCL. RESULTS: A total of 17 PCL patients were diagnosed among 180 plasma cell dyscrasia patients during the study period. Among PCL patients, 9 cases had pPCL (52.94% of all PCL patients), and 8 cases had sPCL (47.06% of all PCL patients). Peculiar differences were seen between the two PCL types. Both types of PCL had a younger age at the time of diagnosis, having elevated BM plasma cell infiltration percentage, frequent anemia, thrombocytopenia, elevated beta-2-microglobulin (B2M) levels, raised LDH levels, and positive M-protein in both serum and urine. In addition, SFLC assay and Immunofixation assay showed higher κ and lower λ in pPCL compared with sPCL (P<0.05). Higher Renal insufficiency was also observed in pPCL compared to sPCL (P=0.335). The survival and response to treatment of PCL patients remain considerably poor, sPCL exhibit shorter overall survival (OS) than pPCL with (median 1.75 months vs. 7 months respectively, P=0.1682). Plasma cell leukemia (PCL) needs to be diagnosed early and requires prompt initiation of treatment before patients get complications. CONCLUSION: Our study characterizes the clinical and laboratory features of pPCL and sPCL and may aid physicians in prognosticating the course of disease of their patients. However, future multicentre studies are the need of the hour to develop accurate diagnostic criteria and establish the efficacy of therapeutic regimens.

Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia.

Acute myeloid leukemia (AML) is a complex, aggressive myeloid neoplasm characterized by frequent somatic mutations that influence different functional categories' genes, resulting in maturational arrest and clonal expansion. AML can arise de novo (dn-AML) or can be secondary AML (s-AML) refers to a leukemic process which may arise from an antecedent hematologic disorder (AHD-AML), mostly from a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or can be the result of an antecedent cytotoxic chemotherapy or radiation therapy (therapy-related AML, t-AML). Clinical and biological features in secondary and therapy-related AML are distinct from de novo AML. Secondary and therapy-related AML occurs mainly in the elderly population and responds worse to therapy with higher relapse rates due to resistance to cytotoxic chemotherapy. Over the last decade, advances in molecular genetics have disclosed the sub-clonal architecture of secondary and therapy-related AML. Recent investigations have revealed that cytogenetic abnormalities and underlying genetic aberrations (mutations) are likely to be significant factors dictating prognosis and critical impacts on treatment outcome. Secondary and therapy-related AML have a poorer outcome with adverse cytogenetic abnormalities and higher recurrences of unfavorable mutations compared to de novo AML. In this review, we present an overview of the clinical features of secondary and therapy-related AML and address the function of genetic mutations implicated in the pathogenesis of secondary leukemia. Detailed knowledge of the pathogenetic mechanisms gives an overview of new prognostic markers, including targetable mutations that will presumably lead to the designing and developing novel molecular targeted therapies for secondary and therapy-related AML. Despite significant advances in knowing the genetic aspect of secondary and therapy-related AML, its influence on the disease's pathophysiology, standard treatment prospects have not significantly evolved during the past three decades. Thus, we conclude this review by summarizing the modern and developing treatment strategies in secondary and therapy-related acute myeloid leukemia.

An updated account on molecular heterogeneity of acute leukemia.

The progress in the field of personalized therapy has been the backbone for the improved mortality and morbidity figure in cancer especially with reference to acute leukemia. The same has been supported by evolving research and development in the field of genomics. The newer discoveries of mutations and the account of already discovered mutations have been playing a pivotal role to refine management strategy. Here, in this review, we are giving an account of relevant mutations and their potential role in the pathogenesis of acute leukemia. The article discusses the old and newly discovered mutations in acute myeloid/lymphoblastic leukemia. The various pathways and cross-talks between the mutations have been briefly described to develop insight towards their contributory and consequent role in the neoplastic process. The article is to sensitize the students, clinicians, and researchers towards the recent updates and development in genomics of acute leukemia.

Molecular update on biology of Wilms Tumor 1 gene and its applications in acute myeloid leukemia.

Wilms tumor gene 1 (WT1) is an important gene which is involved in growth and development of many organs. It is identified as a tumor suppressor gene in nephroblastoma. However, its role as a tumor oncogene has been highlighted by many studies in haematological as well as non haematological malignant neoplasm. The expression of WT1 on leukemic blast cells sensitised us to explore its impact on neoplastic phenomenon. WT1 is has been found both mutated as well as over expressed in different subsets of acute myeloid leukemia (AML). WT1 is a gene has been used as a biomarker for diagnosis, monitoring of minimal residual disease (MRD) and detection of relapse for molecular remission in AML. It also has potential of being a predictive molecular predictive biomarker for the treatment of leukemic cases after allogeneic transplantation. The WT1 specific expression on blast cells and its interaction with cytotoxic T cell has also been explored for its potential usage WT1 based immunotherapy. Here, we are reviewing molecular updates of WT1 gene and discuss its potential clinical applications as a predictive molecular biomarker for diagnosis, as MRD detection and as immunotherapy in AML.