Neuroendocrine carcinoma of ovary: Hitherto rare entity in primary ovarian tumors.

Neuroendocrine neoplasms (NEN) of the female genital tract are extremely uncommon. These tumors can be broadly divided into well differentiated (carcinoid) and poorly differentiated NEN (small cell and large cell carcinomas). Occurrence of neuroendocrine carcinomas (NECs) in ovary has rarely been reported. These high-grade malignant tumors have a fulminant clinical course with a short period of survival, even when diagnosed at an early stage. We hereby report two cases of primary neuroendocrine carcinoma of the ovary.

Clinico-Pathological Characteristics and Mutational Analysis of Gastrointestinal Stromal Tumors from India: A Single Institution Experience.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common type of mesenchymal neoplasm of gastrointestinal tract. The incidence of GIST in India is not known and its treatment strategy in our country is largely derived from studies in other global populations. Some of the most important features of this type of cancer include its size, site of origin, mitotic index, histology and Immunohistochemistry. In this report we have studied these parameters in the Indian GIST patients presenting at our center. Additionally, we have also studied the mutational spectrum of these GISTs by next generation sequencing. METHODS: Thirty one Indian patients of GIST were enrolled in this study and information regarding age, gender, tumor location and size was collected from their records. Immunohistochemistry studies were performed by the pathologist. Mutational analysis of these samples was performed by next generation sequencing. RESULTS AND DISCUSSION: The most common site of GIST occurrence in our study was stomach. The tumor size for all 31 patients ranged between 0.6 cms to 20 cms. A spindle-cell pattern was present in 24 out of 31 of the cases. 29 out of 31 subjects were positive for CD117 expression. C-KIT was the most highly mutated gene indentified in our patients. Apart from these findings we observed many similarities as well as dissimilarities between the results of our study and literature published previously. CONCLUSIONS: The dissimilarities in the results of our study and published literature could be attributed to the genetic or ethnic differences that exist between the Indian population and other global populations. The results of our study warrant a need to conduct studies of GIST in a much larger population of India. Such large scale studies may also help in better treatment and/or prevention of GIST in developing countries like India.

Role of Immunohistochemistry in the Subtyping of Periampullary Adenocarcinoma.

Context. Subtyping of periampullary adenocarcinoma into intestinal and pancreatobiliary subtypes has emerged as an important prognostic factor with potential therapeutic implications. This distinction on morphology alone is often difficult with significant interobserver variability. Objective. To analyze the usefulness of a panel of immunohistochemistry (IHC) markers as an aid to morphologic subtyping of periampullary adenocarcinoma. Design. A total of 172 periampullary adenocarcinomas were classified morphologically by 3 study pathologists. Interobserver agreement was assessed in each case. Cases were then typed using a predetermined IHC panel (comprising CK7, CK20, MUC1, and CDX2). Results. Morphologically, 66 (38.4%) cases were intestinal, 56 (32.6%) pancreatobiliary, 25 (14.5%) mixed, 16 (9.3%) poorly differentiated, 6 (3.5%) mucinous, and 3 (1.7%) signet ring cell adenocarcinoma. Concordant diagnosis was reached in 138 cases (80.2%) with moderate overall interobserver agreement (κ = 0.47). Concordance was higher in morphologically distinct mucinous (100%; κ = 0.94) and signet ring cell subtypes (100%; κ = 1.0) than in intestinal (84.6%; κ = 0.47) and pancreatobiliary (82.1%; κ = 0.43) types. Concordance was poor for mixed (64%; κ = 0.27) and poorly differentiated (68.8%; κ = 0.76) tumors. IHC subtyped 79 cases (46%) as pancreatobiliary, 73 (42.4%) as intestinal, and was inconclusive in 20 cases (11.6%). IHC helped classify 21 out of 25 (84%) mixed and 10 out of 16 poorly differentiated (62.5%) adenocarcinomas. Combination of histology and IHC classified 161 of the total 172 cases (93.6%). Conclusion. Use of an IHC panel aids in subtyping of periampullary adenocarcinomas, especially in tumors with mixed morphology and poor differentiation.

All ileo-cecal ulcers are not Crohn's: Changing perspectives of symptomatic ileocecal ulcers.

AIM: To investigated clinical, endoscopic and histopathological parameters of the patients presenting with ileocecal ulcers on colonoscopy. METHODS: Consecutive symptomatic patients undergoing colonoscopy, and diagnosed to have ulcerations in the ileocecal (I/C) region, were enrolled. Biopsy was obtained and their clinical presentation and outcome were recorded. RESULTS: Out of 1632 colonoscopies, 104 patients had ulcerations in the I/C region and were included in the study. Their median age was 44.5 years and 59% were males. The predominant presentation was lower GI bleed (55, 53%), pain abdomen ± diarrhea (36, 35%), fever (32, 31%), and diarrhea alone (9, 9%). On colonoscopy, terminal ileum was entered in 96 (92%) cases. The distribution of ulcers was as follows: Ileum alone 40% (38/96), cecum alone 33% (32/96), and both ileum plus cecum 27% (26/96). The ulcers were multiple in 98% and in 34% there were additional ulcers elsewhere in colon. Based on clinical presentation and investigations, the etiology of ulcers was classified into infective causes (43%) and non-infective causes (57%). Fourteen patients (13%) were diagnosed to have Crohn's disease (CD). CONCLUSION: Non-specific ileocecal ulcers are most common ulcers seen in ileo-cecal region. And if all infections are clubbed together then infection is the most common (> 40%) cause of ulcerations of the I/C region. Cecal involvement and fever are important clues to infective cause. On the contrary CD account for only 13% cases as a cause of ileo-cecalulcers. So all symptomatic patients with I/C ulcers on colonoscopy are not Crohn's.

Primary mediastinal lymphomas, their morphological features and comparative evaluation.

BACKGROUND: Primary mediastinal lymphoma is an uncommon tumor. Hodgkin's lymphoma (HL), primary mediastinal B-cell lymphoma (PMBCL), and T-lymphoblastic lymphoma are the most common primary mediastinal lymphomas. Key morphological and immunohistochemistry (IHC) features play a very crucial role in diagnosis as well as further categorization. MATERIALS AND METHODS: In this study, the morphological spectrum and histological features of 32 cases of primary mediastinal lymphomas diagnosed over 5 years were studied and morphological and IHC features of PMBCL versus HL were compared. Features of PMBCL were also compared against a control group of systemic diffuse large B-cell lymphoma. RESULTS: Although PMBCL and HL are known to show overlapping morphological features, it was observed that presence of clear cells and compartmentalizing fibrosis in PMBCL; and classical Reed-Sternberg cells and dense inflammatory background in HL are important morphological clues while evaluating the biopsies. PMBCL showed diffuse, strong and uniform CD20 positivity; whereas CD30 showed focal/patchy, weak to moderate and heterogeneous expression, wherever found positive. As against this, HL showed diffuse, strong and uniform CD30 positivity; and focal/patchy, weak to moderate and heterogeneous CD20 expression, if found positive. CD20, CD3, and CD30 were sufficient in most of the cases while diagnosing PMBCL and HL. CONCLUSION: This study emphasizes the critical examination of IHC markers. Only positive expression in neoplastic cells is not sufficient to make a diagnosis, equal importance should be given to percentage, intensity, pattern, and type of positivity. Apart from basic IHC described above; CD15, leukocyte common antigen and fascin played an important role in differentiating HL and PMBCL in select doubtful cases.

Primary dorsal spine primitive neuroectodermal tumor in an adult patient: Case report and literature review.

Primary spinal primitive neuroectodermal tumor (psPNET) is a rare entity with few cases reported in literature. We report a case of a 50-year-old female who presented to us with paraplegia and was diagnosed with extradural dorsal spine psPNET. The diagnosis was not suspected at presentation or on radiology but was established on histopathological examination. It is important to distinguish it from central nervous system primitive neuroectodermal tumors and from other spinal tumors since it follows a different clinical course and therapeutic outcome.

Morphological spectrum of mediastinal lesions with special emphasis on evaluation of needle biopsy: An experience from a tertiary care hospital.

BACKGROUND & OBJECTIVES: Mediastinal lesions are uncommon and are infrequently encountered in routine clinical practice. Hence, there is a need for more elaborate studies of mediastinal lesions to make the pathologists and clinicians aware of the large spectrum of these lesions. The present study describes the histomorphological spectrum of various mediastinal lesions in a tertiary care hospital in India, along with the discussion of some unusual and interesting cases. Considering the limited diagnostic material obtained in guided biopsies, the adequacy of such tissue for providing a definite opinion was also evaluated. METHODS: This was a retrospective study performed on 125 mediastinal masses diagnosed on surgically resected specimens as well as needle biopsies over a period of two years (January 2012-December 2013). A few cases had inadequate diagnostic material, making a total of 116 cases which were further evaluated. RESULTS: A total of 116 patients of mediastinal lesions were included in the study. Most of the lesions were in 21-30 yr age group, with male:female ratio of 1.7:1. Anterior mediastinal compartment was most commonly involved. Majority of the cases (62.1%) were of neoplastic nature, with benign tumours (34.5%) being more common than malignant ones (27.6%). Thymoma followed by lymphoma constituted the most common mediastinal tumours. One-third of the total cases were diagnosed on needle biopsy samples. All cases where needle biopsy was followed by resection specimen showed concordant diagnosis. The percentage adequacy of biopsy was 91.7 per cent and the diagnostic accuracy was 100 per cent. INTERPRETATION & CONCLUSIONS: This study provides the histomorphological spectrum and biological diversity of the mediastinal lesions. It also emphasizes that biopsy is sufficiently adequate, with the help of a comprehensive immunohistochemistry panel, for providing a definite diagnosis in majority of cases.

Ectopic Pancreas in the Duodenojejunal Flexure-Computed Tomographic and Endoscopic Ultrasonographic Images.

Ectopic pancreas is a rare entity where the pancreatic tissue has no anatomic and vascular contact with the main body of the pancreas and has its own duct system and vascular supply. A detailed clinical report with contrast-enhanced computed tomography (CT) and endoscopic ultrasonography (EUS) imaging findings of a 40-year-old male came with vague symptoms. CT showed a well-defined homogeneously enhancing mass lesion in the duodenojejunal (DJ) flexure. EUS revealed a well-defined hypoechoic mass lesion in the submucosal layer of the DJ flexure. Surgical resection of the mass was performed, and histopathological examination of specimen confirmed the pancreatic tissues. Here, we have described the CT and EUS imaging features which can help to differentiate the ectopic pancreas from the gastrointestinal submucosal tumours.

Plasma Epstein Barr virus (EBV) DNA as a biomarker for EBV associated Hodgkin lymphoma.

OBJECTIVE: To assess plasma Epstein-Barr virus (EBV) DNA as a biomarker of tumour burden at diagnosis and during therapy in children with Hodgkin lymphoma. DESIGN: Case-control study, with prospective follow-up of the Hodgkin lymphoma cohort (2007-2012). SETTING: Pediatric Hematology Oncology unit of a tertiary care hospital in Delhi. PATIENTS: Thirty children with Hodgkin lymphoma and 70 sex and age-matched controls (benign lymphadenopathy 19, non-lym-phoid malignancy 29, Burkitt lymphoma 5, healthy children 17). INTERVENTION: Positive EBV-staining on immunohistochemistry was defined as EBV-associated Hodgkin lymphoma. Plasma EBV real-time quantitative polymerase chain reaction (PCR) was tested at presentation, after first and last chemotherapy cycles, and on follow-up. MAIN OUTCOME MEASURES: Plasma EBV quantitative PCR was compared between cases and controls. Its kinetics was assessed during and after chemotherapy. RESULTS: EBV quantitative PCR was positive in 19 (63%) Hodgkin lymphoma cases (range 500 to 430,000 copies/mL), with 87.5% accuracy (kappa=0.69) as compared with EBV immunohistochemistry. Sensitivity and specificity of the quantitative PCR were 87.5% and 81.8%, respectively. Only boys showed positive EBV immunohistochemistry and,or quantitative PCR positivity. All controls were quantitative PCR negative. All quantitative PCR positive cases with follow up blood sample showed EBV clearance after the first cycle. A quantitative PCR negative case in long-term remission became positive at relapse. EBV status did not influence survival. CONCLUSION: Plasma EBV-DNA, detectable in EBV-associated Hodgkin lymphoma, becomes undetectable early after initiating therapy. It can be used as a biomarker of treatment response in EBV-associated Hodgkin lymphoma.

Lack of any association of the CTLA-4 +49 G/A polymorphism with breast cancer risk in a North Indian population.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an important protein involved in the regulation of the immune system. The +49 G/A polymorphism is the only genetic variation in the CTLA-4 gene that causes an amino acid change in the resulting protein. It is therefore the most extensively studied polymorphism among all CTLA-4 genetic variants and contributions to increasing the likelihood of developing cancer are well known in various populations, especially Asians. However, there have hiterto been no data with respect to the effect of this polymorphism on breast cancer susceptibility in our North Indian population. We therefore assayed genomic DNA of 250 breast cancer subjects and an equal number of age-, sex- and ethnicity-matched healthy controls for the CTLA-4 +49 G/A polymorphism but no significant differences in either the gene or allele frequency were found. Thus the CTLA-4 +49 G/A polymorphism may be associated with breast cancer in other Asians, but it appears to have no such effect in North Indians. The study also highlights the importance of conducting genetic association studies in different ethnic populations.

Adrenal incidentaloma: A case of pheochromocytoma with sub-clinical Cushing's syndrome.

Adrenal incidentalomas (AIs) are a cluster of different pathologies, but AIs with dual functional aspects are very rare. We report a case of AI with the evidence of both pheochromocytoma and sub-clinical Cushing's syndrome. A 42-year-old female patient presented with the history of abdominal pain. Abdominal computed tomography revealed right adrenal mass suggestive of pheochromocytoma. On endocrine evaluation, she admitted history of intermittent headache and palpitations for 4 years and was on treatment for hypertension and diabetes. There were no signs and symptoms suggestive of Cushing's syndrome. The laboratory data demonstrated 10 times raised 24-h urinary fractionated metanephrines with non-suppressible serum cortisol after 2-day low-dose dexamethasone suppression test. She underwent right-sided adrenalectomy with subsequent resolution of both pheochromocytoma and hypercortisolism. Patient was discharged in good clinical condition.

Orbital myeloid sarcoma presenting as massive proptosis.

A 10-year-old boy presented with right proptosis for 8 months. The eyeball was grossly pushed down, with diffuse corneal haze and non-reactive pupil. Systemic examination was normal. Previous investigations in another centre included a computerized tomography scan, which showed a well-defined enhancing retro-bulbar mass, a non-contributory fine needle aspiration cytology and a biopsy showing fibrocollagenous tissue with moderate lympho-monocytic infiltrate suggestive of non-specific inflammation. PET-CT scan revealed the presence of enlarged fluoro-deoxyglucose-avid cervical and mesenteric lymph nodes. Biopsy of the retro-bulbar mass was repeated in our centre. It showed fibrocollagenous and skeletal muscle tissue infiltrated by lymphoid follicles, dispersely lying lymphocytes and plasma cells, and admixed large atypical cells with vesicular nuclei, prominent nucleoli and scanty cytoplasm, strongly positive for myeloperoxidase, CD43 and CD99 immunohistochemistry. Hemogram was normal. Bone marrow aspiration/biopsy and CSF showed no evidence of acute myeloid leukemia. The child received chemotherapy in another centre and is in complete remission 6 months after completion.

Intestinal mucormycosis: a rare entity in pediatric oncology.

Mucormycosis is increasingly emerging as an important cause of invasive fungal infection in immunocompromised patients. Intestinal mucormycosis is extremely rare, difficult to diagnose, and has dismal prognosis. We report two children with acute lymphoblastic leukemia and intestinal mucormycosis. Despite surgery and appropriate antifungal therapy, only one survived. Literature review showed only 10 other childhood cancer cases with intestinal mucormycosis. All had abdominal pain preceding gut perforation. All except one had leukemia and majority were in induction phase of therapy. Only 5 of these 12 children survived. Other than appropriate antifungal therapy, early surgery and rising neutrophils aid in recovery.

48-year-old woman with a cerebellopontine angle mass.

Intracranial chondromas are rare benign neoplasms with an estimated incidence rate of 0.2­0.3%. They usually occur at the skull base, or arise from the dura and leptomeninges. Rarely, they have been reported at the cerebellopontine (CP) angle. Here we describe an interesting case of CP angle chondroma which was clinically and radiologically diagnosed as schwannoma and meningioma.

26-year-old man with a cerebellar mass.

Medulloblastoma accounts for only 1% of all adult CNS tumors. Recently, we have encountered a case of medulloblastoma in a 26 year old man with divergent differentiation including myoblastic, glial, osteoblastic and chondroblastic differentiation. Here we present the results of immunohistochemical staining using several specific antibodies with a discussion and a review of literature.

Synchronous gastric gastrointestinal stromal tumor (GIST) and other primary neoplasms of gastrointestinal tract: report of two cases.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract with a malignant potential. However, uncommonly they can be associated with synchronous tumors of different histogenesis. We herein report two cases of gastric GIST with synchronous tumors. The first case is of a 50-year-old male patient who was suspected with GIST of stomach and was incidentally found to have an associated duodenal neuroendo-crine neoplasm. The second case is of a 62-year-old male who, while undergoing surgery for a primary colon adenocarcinoma, was incidentally detected to have a coexistent gastric GIST initially suspected to be a metastatic nodule. Coexistence of gastric GIST with neuroendocrine tumor is extremely rare. To the best of our knowledge this is the second case of gastric GIST coexisting with duodenal neuroendocrine tumor to be reported in the literature. Similarly, association of GIST with adenocarcinoma is uncommon. We herein analyze the pathological findings of two such cases, and we review the malignant potential of these synchronous tumors.