Marie Therese Manipadam

Gastrointestinal lymphomas: Pattern of distribution and histological subtypes: 10 years experience in a tertiary centre in South India

BACKGROUND AND AIM Gastrointestinal tract (GIT) is one of the major sites of extra-nodal lymphomas constituting 10-15% of all non-Hodgkins lymphoma cases and about 30-40% of extra-nodal lymphomas. Considerable variation exists in the literature with respect to incidence of the various histological subtypes and sites of involvement. This study was undertaken to ascertain the anatomic distribution, histological subtypes and sites of all GIT lymphomas presenting to a tertiary referral hospital in southern India. MATERIALS AND METHODS The histological material of 361 patients over a period of 10 years (2001-2010), with histopathological diagnosis of lymphoma involving the GIT (both primary and secondary), was analyzed retrospectively. All lymphomas were reclassified according to the World Health Organization 2008 classification. RESULTS These 361 cases include 336 primary and 25 cases of lymphomas, where the involvement was secondary. Primary lymphomas consisted of 267 males (79.64%) and 68 females (20.24%) with a male:female ratio of 3.93:1. The mean age was 45 years (range 3-88). Diffuse large B-cell lymphoma (DLBCL) was the commonest subtype (222 cases; 66.71%), followed by low-grade marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT) type (34 cases; 10.12%) and Burkitts lymphoma (35 cases; 10.48%). The commonest site was stomach (180 cases; 53.57%), followed by small intestine (79 cases; 23.51%) and large intestine (68 cases; 20.23%), respectively. There were some uncommon types of GIT lymphomas documented during the study. CONCLUSION In this largest retrospective single centre study from India, we establish that the pattern of distribution of primary GIT lymphomas (PGLs) in India is similar to the western literature in that the stomach is the commonest site of PGL and DLBCL is the commonest histological subtype. Immunoproliferative small intestinal disease cases were seen in this study, which is uncommon in the west.

Primary myelolipoma presenting as a nasal cavity polyp: a case report and review of the literature

IntroductionMyelolipomas are rare, benign tumors comprising mature adipose tissue and hematopoietic elements. The vast majority occur within the adrenal glands, but extra-adrenal myelolipomas have also been reported in the presacral region, retroperitoneum, mesentery, stomach, spleen, liver, mediastinum and lungs. Here, we present a case of primary myelolipoma occurring in an unusual site: the nasal cavity. To the best of our knowledge, we believe that this location for extra-adrenal myelolipoma has not been previously described in the literature.Case presentationWe report a case of primary myelolipoma occurring in the nasal cavity of a 48-year-old Asian woman. We describe the etiology, pathology and differential diagnosis of extra-adrenal myelolipomas, and review the literature.ConclusionsWe chose to present this case because of its unusual location. Although myelolipomas are rare, we conclude that they it should be considered in the differential diagnosis of lesions in this site.

Frequency and distribution of lymphoma types in a tertiary care hospital in South India: analysis of 5115 cases using the World Health Organization 2008 classification and comparison with world literature

Abstract This study aimed to analyze the distribution of lymphoid neoplasms in a single tertiary care center in India using the World Health Organization (WHO) 2008 classification. Histological material of 5115 patients with histopathological diagnosis of lymphoma, diagnosed over a period of 10 years (2001–2010), was analyzed retrospectively. Hodgkin lymphoma (HL) constituted 21.3% (n = 1089) and non-Hodgkin lymphomas (NHLs) constituted 78.7% (n = 4026). Of these, B-cell neoplasms accounted for 78.6% (n = 3166) and T-cell/natural killer (NK)-cell neoplasms 20.2% (n = 815) of the NHLs. The commonest subtype of NHL was diffuse large B-cell lymphoma (n = 1886, 46.9%). The frequency of peripheral T-cell/NK-cell lymphomas in this study was higher than in the Western literature but less than the frequency documented in some Asian countries. Similar to the Western literature but in contrast to previous Indian studies, peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (n = 238) was the commonest histological subtype of T-cell/NK-cell NHL in this study and constituted 5.9% of the total NHLs. Mixed cellularity (MC-CHL) (n = 488, 45%) was the major subtype of HL. Primary extranodal lymphoma (ENL) accounted for 32.8% (n = 1321) of all NHLs and most frequently involved the gastrointestinal tract. This study also documents the frequency of many rare types of lymphoma in South India.

Leflunomide with low-dose everolimus for treatment of Kaposi’s sarcoma in a renal allograft recipient

Current treatment of Kaposis sarcoma is reduction of immunosuppression with or without addition of mammalian target of rapamycin inhibitors (mTORi). Akt signalling plays a central role in oncogenesis of Kaposis sarcoma. We describe a case of multifocal Kaposis sarcoma in a renal allograft recipient, which showed unsatisfactory early response to immunosuppression reduction along with everolimus therapy but completely resolved after adding leflunomide. mTORi impair Kaposis sarcoma oncogenesis by inhibiting mTOR downstream from the Akt signalling. Leflunomide inhibits Akt phosphorylation. This synergistic effect may be beneficial in treatment of Kaposi sarcoma and needs to be explored in trials.

Automated Segmentation of Nuclei in Breast Cancer Histopathology Images.

The process of Nuclei detection in high-grade breast cancer images is quite challenging in the case of image processing techniques due to certain heterogeneous characteristics of cancer nuclei such as enlarged and irregularly shaped nuclei, highly coarse chromatin marginalized to the nuclei periphery and visible nucleoli. Recent reviews state that existing techniques show appreciable segmentation accuracy on breast histopathology images whose nuclei are dispersed and regular in texture and shape; however, typical cancer nuclei are often clustered and have irregular texture and shape properties. This paper proposes a novel segmentation algorithm for detecting individual nuclei from Hematoxylin and Eosin (H&E) stained breast histopathology images. This detection framework estimates a nuclei saliency map using tensor voting followed by boundary extraction of the nuclei on the saliency map using a Loopy Back Propagation (LBP) algorithm on a Markov Random Field (MRF). The method was tested on both whole-slide images and frames of breast cancer histopathology images. Experimental results demonstrate high segmentation performance with efficient precision, recall and dice-coefficient rates, upon testing high-grade breast cancer images containing several thousand nuclei. In addition to the optimal performance on the highly complex images presented in this paper, this method also gave appreciable results in comparison with two recently published methods—Wienert et al. (2012) and Veta et al. (2013), which were tested using their own datasets.

Immunomorphologic profile and Epstein-Barr virus status of a cohort of 35 cases of extranodal natural killer/T-cell lymphoma, nasal type of upper aerodigestive tract from a tertiary care center in South India.

Abstract Extranodal natural killer (NK)/T-cell lymphoma, nasal type (EN-NK/T-NT) is a lymphoma of NK-cell or cytotoxic T-cell origin, which occurs most commonly in the upper aerodigestive tract. We have studied the immunomorphologic profile and Epstein–Barr virus (EBV) status of a cohort of 35 cases of EN-NK/T-NT of the upper aerodigestive tract (UADT) diagnosed in our institution during the period May 2002 to April 2012. At our institution these lymphomas constitute 0.7% of total non-Hodgkin lymphomas (NHLs) and 5.1% of total peripheral T-cell lymphomas (PTCLs). The median age at diagnosis was 40 years with a male-to-female ratio of 4:1, and the most common site of involvement was the nasal cavity. Morphologically, the neoplastic cells were predominantly medium sized in most cases. Necrosis and angiocentricity were common histologic features. Thirty cases (85.7%) showed NK-cell immunophenotype, CD3+ (29/30, 96.7%), CD56+ (30/30, 100%) and TIA1/Granzyme B+ (30/30, 100%). Five cases (14.3%) showed cytotoxic T-cell immunophenotype, CD3+ (5/5, 100%), CD56− (5/5, 100%) and TIA1/Granzyme B+ (5/5, 100%). EBV-encoded RNA-in situ hybridization (EBER-ISH) was positive in all 35 cases, whereas EBV latent membrane protein-1 (EBVLMP1) was positive in only 19/35 (54.3%) of cases. In conclusion, this is the first large study from India to report the immunomorphologic profile and EBV association of EN-NK/T-NT, which is known to have geographic variation. The frequency of these lymphomas in our study is comparable to that of Western and European countries and much less than that of Far Eastern countries.

Myoepithelial carcinoma arising in recurrent pleomorphic adenoma in maxillary sinus

Myoepithelial carcinoma is characterized by nearly exclusive myoepithelial differentiation and evidence of malignancy. It may arise de novo or in preexisting benign tumors including pleomorphic adenoma and benign myoepithelioma. A 39-year-old lady presented with painless progressive swelling on the right cheek and right side of palate. On surgery, there was a mass in right maxillary sinus which was surgically excised and diagnosed on histopathology as pleomorphic adenoma. Subsequently, there were two recurrences. The first recurrence was in the right maxilla after 2 years that was removed surgically and diagnosed as pleomorphic adenoma. One year later, she came with rapidly progressive swelling in bilateral cheeks and face. Intraoperatively, there was a large tumor in both maxillary sinuses with extensive local infiltration. Histologically, it was diagnosed as myoepithelial carcinoma. Carcinoma ex pleomorphic adenoma is usually a high grade malignancy. It occurs most commonly in parotid gland followed by submandibular glands, minor salivary glands and occasionally in sublingual gland. To the best of our knowledge, this is the first case of myoepithelial carcinoma arising in a recurrent pleomorphic adenoma in the maxillary sinus.

Non-Hodgkin lymphoma in childhood and adolescence: frequency and distribution of immunomorphological types from a tertiary care center in South India

BackgroundThere is a dearth of published literature on the frequency and distribution of pediatric and adolescent non-Hodgkin lymphoma (NHL) in India according to the 2001 WHO classification. The aim of this study was to record the distribution of the different subtypes, analyze the major subtypes, and compare it with the published data from other countries. A review of pediatric NHL statistics from population-based cancer registries was included in this study.MethodsThe study was conducted using information retrieved from the files of our institution. A total of 467 patients with lymphoma (excluding mycosis fungoides) were recorded in the under 20 years group over a period of 6 years, of which 252 patients suffered from NHL. The demographic characteristics, frequency and distribution of different subtypes were noted and compared with published reports from other parts of the world.ResultsT-lymphoblastic lymphoma/leukemia constituted the majority (32.1%) of all NHLs in children and adolescents in our study. The other major subgroups were Burkitt’s lymphoma, anaplastic large cell lymphoma, and diffuse large B cell lymphoma. Burkitt’s lymphoma in this study had clinical presentations similar to those seen in western countries.ConclusionsThe distribution of different subtypes of lymphoma in pediatric and adolescent NHL in India differs considerably from that in western countries and other eastern countries.

Kikuchi-Fujimoto disease: Clinical and laboratory characteristics and outcome

Introduction: Kikuchi-Fujimoto disease is an uncommon disorder with worldwide distribution, characterized by fever and benign enlargement of the lymph nodes, primarily affecting young adults. Awareness about this disorder may help prevent misdiagnosis and inappropriate investigations and treatment. The objective of the study was to evaluate the clinical and laboratory characteristics of histopathologically confirmed cases of Kikuchis disease from a tertiary care center in southern India. Materials and Methods: Retrospective analysis of all adult patients with histopathologically confirmed Kikuchis disease from January 2007 to December 2011 in a 2700-bed teaching hospital in South India was done. The clinical and laboratory characteristics and outcome were analyzed. Results: There were 22 histopathologically confirmed cases of Kikuchis disease over the 5-year period of this study. The mean age of the subjects’ was 29.7 years (SD 8.11) and majority were women (Male: female- 1:3.4). Apart from enlarged cervical lymph nodes, prolonged fever was the most common presenting complaint (77.3%). The major laboratory features included anemia (54.5%), increased erythrocyte sedimentation rate (31.8%), elevated alanine aminotransferase (27.2%) and elevated lactate dehydrogenase (LDH) (31.8%). Conclusion: Even though rare, Kikuchis disease should be considered in the differential diagnosis of young individuals, especially women, presenting with lymphadenopathy and prolonged fever. Establishing the diagnosis histopathologically is essential to avoid inappropriate investigations and therapy.

Usefulness of Succinate dehydrogenase B (SDHB) immunohistochemistry in guiding mutational screening among patients with pheochromocytoma‐paraganglioma syndromes

Genetic testing of pheochromocytomas (PCC) and paragangliomas (PGL), although expensive, is gradually becoming a part of the routine laboratory investigation for patients with PCC‐PGL syndrome. Recently, Succinate dehydrogenase B (SDHB) immunochemistry has been shown to be an excellent indicator of germline mutations in the SDH genes and could help significantly reduce cost. This study assesses the utility of SDHB immunohistochemical analysis when used to guide genetic analysis, with emphasis on cost benefits it could provide in a resource‐limited setting. Forty‐four cases of PCC/PGL characterized by genetic analysis were included to determine their SDHB expression pattern by immunohistochemistry. SDHB antibody expression was negative among three cases each, with SDHB and SDHD mutations. Immunohistochemistry results were positive for all three cases of RET, a single case of neurofibromatosis and for two cases with Von Hippel‐Lindau (VHL) mutations while the remaining two cases with VHL mutations showed a diffuse ‘cytoplasmic blush’. Thirty of the remaining 31 samples demonstrated positive staining and were negative for mutations, while a lone sample that was negative for staining and mutation was not included in the final analysis as the internal control for the sample was not adequately stained. Cost analysis in our settings showed that triaging with SDHB immunohistochemistry could potentially reduce costs by USD 320–500 per patient. SDHB immunohistochemistry, when used as a guide to genetic testing, can significantly reduce the effort, time and costs of testing among patients with PCC‐PGL, a huge benefit in resource limited settings.