Rekha A Nair

RNA Interference Using c-Myc–Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models

In this article, we report the development and preclinical validation of combinatorial therapy for treatment of cancers using RNA interference (RNAi). RNAi technology is an attractive approach to silence genes responsible for disease onset and progression. Currently, the critical challenge facing the clinical success of RNAi technology is in the difficulty of delivery of RNAi inducers, due to low transfection efficiency, difficulties of integration into host DNA and unstable expression. Using the macromolecule polyglycidal methacrylate (PGMA) as a platform to graft multiple polyethyleneimine (PEI) chains, we demonstrate effective delivery of small oligos (anti-miRs and mimics) and larger DNAs (encoding shRNAs) in a wide variety of cancer cell lines by successful silencing/activation of their respective target genes. Furthermore, the effectiveness of this therapy was validated for in vivo tumor suppression using two transgenic mouse models; first, tumor growth arrest and increased animal survival was seen in mice bearing Brca2/p53-mutant mammary tumors following daily intratumoral treatment with nanoparticles conjugated to c-Myc shRNA. Second, oral delivery of the conjugate to an Apc-deficient crypt progenitor colon cancer model increased animal survival and returned intestinal tissue to a non–wnt-deregulated state. This study demonstrates, through careful design of nonviral nanoparticles and appropriate selection of therapeutic gene targets, that RNAi technology can be made an affordable and amenable therapy for cancer. Mol Cancer Ther; 14(5); 1259–69. ©2015 AACR.

Solitary plasmacytoma of the metacarpal bone in an adolescent

Solitary plasmacytoma of the bone (SPB) is a plasma cell neoplasm that usually presents as a lytic lesion mainly localized within the axial skeleton. The occurrence of SPB in young individuals is exceedingly rare, but has been sporadically reported before. We report a case of SPB involving metacarpal bone in a 16-year-old male with a prior history of trauma at the same site.

Burkitt's lymphoma of the humerus

Burkitts lymphoma is an uncommon form of non-Hodgkins lymphoma (NHL) in adults and represents < 5% of NHL adults. Burkitts lymphoma involving primarily the appendicular skeleton is rarely described. We present the case of a young man with primary Burkitts lymphoma involving the humerus as the only site of disease. He received R hyper CVAD and local irradiation and is in complete remission at 24 months.

Primary diffuse large B-cell lymphoma of the central nervous system in pineal gland: Report of a rare case with review of literature.

1. Gla ser B, Landau H, Smilovici A, Nesher R. Persistent hyperinsulinaemic hypoglycaemia of infancy: Long-term treatment with the somatostatin analogue Sandostatin. Clin Endocrinol (Oxf) 1989;31:71-80. 2. Prashanth GP, Kurbet SB. Comment on persistent hyperinsulinemic hypoglycemia of infancy. J Indian Assoc Pediatr Surg 2013;18:92. 3. James C, Kapoor RR, Ismail D, Hussain K. The genetic basis of congenital hyperinsulinism. J Med Genet 2009;46:289-99. 4. Jain M, Singh S, Madan NK, Choudhury SR. Diffuse nesidioblastosis of the pancreas in a neonate with seizures. Indian J Pathol Microbiol 2011;54:864-6. 5. Arun S, Rai Mittal B, Shukla J, Bhattacharya A, Kumar P. Diffuse nesidioblastosis diagnosed on a Ga-68 DOTATATE positron emission tomography/computerized tomography. Indian J Nucl Med 2013;28:163-4.

Adult T cell leukemia/lymphoma complicated by proliferation of large B cells: a diagnostic dilemma

Peripheral T cell lymphomas are clinically and pathologically complex and generally associated with overall poor prognosis and aggressive clinical course. In recent years, there is a greater recognition of abnormal B cell expansion as a component of T cell lymphomas especially those derived from follicular helper T cells. Most of these B cells are EBV positive and show a wide range of morphology which includes large mononuclear cells and Hodgkin-like cells. The number of the abnormal B cells can also vary. It is possible to misdiagnose this entity as a B cell lymphoma, Hodgkin lymphoma, composite lymphoma, or reactive lymphoid proliferation based on the number and morphology of the proliferating B cells. Herein, we report the case of an 82-year-old woman who presented with cervical lymphadenopathy, excision biopsy of which showed diffusely arranged atypical small- to medium-sized cells with irregular nuclei admixed with large number of immunoblast-like large cells. Immunophenotyping showed the small- to medium-sized cells to be CD20 negative, CD3 positive, and CD5 positive and showed downregulation of CD7. These cells were CD25 positive and showed a high MIB 1 labelling index. The large cells were CD20 positive and CD30 positive and showed EBV-encoded small nuclear RNA (EBER) positivity. Serum HTLV-1 estimation was positive. Molecular studies showed TCR gene rearrangement and a polyclonal population of B cells. Based on morphology, immunoprofile, and molecular studies, a diagnosis of adult T cell leukemia/lymphoma complicated by proliferation of large B cells was given. The presence of large B cell proliferation in adult T cell leukemia/lymphoma is an exceptionally rare phenomenon.

Profiling of peripheral T-cell lymphomas in Kerala, South India: A 5-year study

Background: Peripheral T-cell lymphomas (PTCLs) are non-Hodgkins lymphomas (NHLs) with considerable variation in incidence across the world. They show a wide variety of clinicopathological features and generally associated with poor clinical outcome. Lymphoma data from different geographic regions will definitely aid in routine clinical practice and research work. PTCLs are reported with a higher frequency in Asia as compared to Western countries. Objective: The objective of this study was to analyze the frequency and distribution of PTCLs diagnosed in a tertiary care cancer center in Kerala. Materials and Methods: This was a retrospective study carried out in the Division of Pathology, Regional Cancer Centre, Thiruvananthapuram, for 5 years from January 1, 2011, to December 31, 2015. All PTCLs diagnosed during this period were reviewed and then classified according to the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Statistical significance of the results was evaluated using Chi-square test. Results: Among the total 3108 cases of lymphomas diagnosed at our center, 2404 cases were NHLs (77.35%). PTCLs (n = 333) contributed 13.85% of all NHLs. Among these, PTCL, not otherwise specified, constituted the most common subtype (92 cases, 27.63%), followed by angioimmunoblastic T-cell lymphoma (79 cases, 23.72%), anaplastic large cell lymphoma (75 cases, 22.52%), mycosis fungoides (28 cases, 8.40%), and adult T-cell leukemia/lymphoma (ATLL) (28 cases, 8.40%). Conclusion: This is the largest study on PTCLs reported from Kerala. We document that the frequency of PTCLs is higher than that reported from Western studies. The frequency of ATLL reported from Kerala is much higher than that reported from other states.

Composite lymphomas: Experience from a tertiary cancer center in Kerala, South India

OBJECTIVES Composite tumors are defined as tumors in which there are two different intermixed histologic types. Our objective was to study the clinical and pathologic features of five cases of composite lymphoma. MATERIALS AND METHODS Our study included five patients of composite lymphoma diagnosed over a period of 5 years. Clinical presentation, hematological parameters including peripheral smear, bone marrow aspirate, and histopathological examination of lymph node including immunohistochemistry (IHC) were studied. Treatment and follow-up details were also noted. RESULTS All the five cases were in the adult age group ranging from 44 to 72 years. All the cases were composite follicular lymphoma (FL) and mixed cellularity classical Hodgkin lymphoma (CHL). Diagnosis in all cases was suspected on morphology by identification of distinct neoplastic follicles in FL and classic Reed-Sternberg cells in CHL and confirmed by IHC. CONCLUSION Although rare, composite lymphomas should be kept in mind. Careful histopathological examination of lymph node with identification of distinct morphological features along with IHC helps to arrive at the definitive diagnosis.

Mediastinal Mass with Hyper-eosinophilia in a Young Boy -A Diagnostic Dilemma.

Mediastinal masses in children comprises of a heterogeneous group of tumours. In such cases, biopsy and histological analysis are mandatory for planning of treatment. We have reported an unusual aetiology for a mediastinal mass in a young boy presenting with features of Superior Vena Caval Obstruction (SVCO) who also had marked blood and marrow eosinophilia mimicking Chronic Eosinophilic Leukaemia (CEL). We have also discussed the differential diagnoses of mediastinal tumours with hyper-eosinophilia and possible therapeutic implications.

Adult T-cell leukemia/lymphoma: Unusual immunophenotype by flow cytometry

I n d I a n J o u r n a l o f P a t h o l o g y a n d M I c r o b I o l o g y 5 9 ( 4 ) , o c t o b e r d e c e M b e r 2 0 1 6 569 2009;115:1234‐44. 6. Böhm S, Faruqi A, Said I, Lockley M, Brockbank E, Jeyarajah A, et al. Chemotherapy response score: Development and validation of a system to quantify histopathologic response to neoadjuvant chemotherapy in tubo‐ovarian high‐grade serous carcinoma. J Clin Oncol 2015;33:2457‐63.

Cytokeratin-positive interstitial reticulum cells in the lymph node: A potential pitfall.

Editor, Cytokeratin‐positive interstitial reticulum cells (CIRCs) are an infrequent finding seen in lymph nodes with diverse etiologies. They are commonly seen in nodes free of but draining malignant tumors and in Kikuchi’s lymphadenitis (necrotizing histiocytic lymphadenitis) and also seen infrequently in nodes showing a range of reactive inflammatory processes, primary, and metastatic neoplasms. CIRC appear to represent a subset of the so‐called “fibroblastic reticulum cells” of lymph nodes. Their function remains undetermined; their increase in diverse lymphadenopathies suggests that they partake in nodal reactions to injury. It remains unclear whether the increase in CIRC relative number is due to proliferation or to cytokeratin (CK) gene induction processes, but their presence and potential capability to undergo hyperplasia with dysplastic forms should alert pathologists to possible diagnostic pitfalls.[1]