DLBCL Subtypes and Prognosis Based on Immunophenotyping

DLBCL is the most common type of NHL diagnosed in the world. It is a highly heterogeneous disease with variable prognosis and is generally managed with standard chemo-immunotherapy and its variations. Immunohistochemistry has been found to be useful method to both sub-classify and to predict prognosis of this disease. IHC utilises various CD markers like CD10, BCL2 and IRF4 to divide DLBCL into GCB and non-GCB subtype. In clinical trials, GCB subtype has been shown to have a better prognosis and a response to treatment when compared to non-GCB subtype. Double hit/double expressor is a newer variant of DLBCL that stains positive for MYC and BCL2 or BCL6 and has been found to do better with more aggressive forms of therapy. Significance of various other CD markers is still largely unknown and further research is required in this area to better elucidate their clinical application

Acute Philadelphia Chromosome Positive Biphenotypic Leukemia Presenting with Bilateral Orbital Chloroma: A Rare Case Report

Introduction: Chloromas are characteristically formed by the extramedullary soft tissue infiltration by the immature myeloid malignant cells. Such extramedullary masses are most commonly seen in acute myeloid leukemia usually in the M2, M4, M5 subtypes of the AML FAB classification. However, it has been reported to rarely present only in pediatric patients with acute lymphoblastic leukemia.Presentation of the case: We encountered an unusual case of a young male, who presented with proptosis of both eyes followed by fever and fatigue. On evaluation, he was diagnosed to have bilateral orbital chloroma which was due to infiltration by leukemic cells of acute leukemia. Flowcytometry revealed features confirming an acute biphenotypic leukemia. Subsequently, cytogenetic evaluation revealed the leukemic cells to be Philadelphia chromosome positive.Conclusion: To our knowledge, this is the first case of bilateral orbital choloroma due to Philadelphia positive biphenotypic acute lymphoblastic leukemia

Pancreatic neuroendocrine tumor in an individual with Von Hippel Lindau syndrome. A case report and review literature

Von Hippel Lindau (VHL) disease is a heritable cancer syndrome characterized by VHL gene mutation in 3p chromosome. Mutations occur at the exons. Rarely mutations at introns have been reported. It leads to accumulation of Hypoxic ischemic factor α (HIF α) which in turn leads to uncontrolled cellular proliferation. Few reports of pancreatic neuroendocrine tumors (PNETs) are there in the literature. Most of them are associated with a mutation in the exon of VHL gene. Association with intron mutation is not there. Here we are reporting a case of PNET in a patient who has a simultaneous mutation both at the exon and the intron

Presynaptic BK channel localization is dependent on the hierarchical organization of alpha-catulin and dystrobrevin and fine-tuned by CaV2 calcium channels

BACKGROUND: Large conductance, calcium-activated BK channels regulate many important physiological processes, including smooth muscle excitation, hormone release and synaptic transmission. The biological roles of these channels hinge on their unique ability to respond synergistically to both voltage and cytosolic calcium elevations. Because calcium influx is meticulously regulated both spatially and temporally, the localization of BK channels near calcium channels is critical for their proper function. However, the mechanism underlying BK channel localization near calcium channels is not fully understood. RESULTS: We show here that in C. elegans the localization of SLO-1/BK channels to presynaptic terminals, where UNC-2/CaV2 calcium channels regulate neurotransmitter release, is controlled by the hierarchical organization of CTN-1/alpha-catulin and DYB-1/dystrobrevin, two proteins that interact with cortical cytoskeletal proteins. CTN-1 organizes a macromolecular SLO-1 channel complex at presynaptic terminals by direct physical interaction. DYB-1 contributes to the maintenance or stabilization of the complex at presynaptic terminals by interacting with CTN-1. We also show that SLO-1 channels are functionally coupled with UNC-2 calcium channels, and that normal localization of SLO-1 to presynaptic terminals requires UNC-2. In the absence of UNC-2, SLO-1 clusters lose the localization specificity, thus accumulating inside and outside of presynaptic terminals. Moreover, CTN-1 is also similarly localized in unc-2 mutants, consistent with the direct interaction between CTN-1 and SLO-1. However, localization of UNC-2 at the presynaptic terminals is not dependent on either CTN-1 or SLO-1. Taken together, our data strongly suggest that the absence of UNC-2 indirectly influences SLO-1 localization via the reorganization of cytoskeletal proteins. CONCLUSION: CTN-1 and DYB-1, which interact with cortical cytoskeletal proteins, are required for the presynaptic punctate localization of SLO-1 in a hierarchical manner. In addition, UNC-2 calcium channels indirectly control the fidelity of SLO-1 puncta localization at presynaptic terminals. We suggest that the absence of UNC-2 leads to the reorganization of the cytoskeletal structure that includes CTN-1, which in turn influences SLO-1 puncta localization

Clinicopathological Profile of Pure Neuroendocrine Neoplasms of the Esophagus: A South Indian Center Experience

Purpose. Neuroendocrine neoplasms (NENs) of the esophagus are very uncommon with only a few studies published worldwide. Studies on clinical profile, management, and outcomes are very uncommon. Methods. We report the largest single institution retrospective review of 43 patients of pure esophageal NENs out of our registry of gastrointestinal neuroendocrine tumors treated between 2005 and 2014. Data on the incidence, tumor location, clinical symptoms, stage at presentation, grading, treatment protocol, and treatment outcomes was collected and analyzed. Results. Among 1293 cases of esophageal cancers, pure esophageal NENs were diagnosed in 43 cases. The mean patient age was 55.8 years. The male : female ratio was 1.5 : 1. 81.4% of the tumors were located in the lower third of the esophagus and gastroesophageal junction. Neuroendocrine carcinomas (NEC; G3) accounted for the vast majority of NENs (83.7%). 53.5% patients were Stage IV and 32.5% were Stage III at presentation. The combined median survival of stages II and III patients was 18.25 months, with treatment. The median survival of treated patients with metastatic disease was 6.5 months. Conclusion. Esophageal NENs most commonly were neuroendocrine carcinomas, presented in metastatic stage and were associated with poor prognosis. Grade 2 (G2) tumors had better outcomes than NEC (G3). In nonmetastatic disease, presence of lymph node metastasis and unresectable disease had poorer outcomes

Head and Neck Lymphomas: Tip of the Iceberg?

ABSTRACT Background: Lymphomas comprise around 5% of all head and neck neoplasms and is the second most common extra nodal non hodgkin's lymphoma (NHL). However there is sporadic data on this entity from the subcontinent and hence we undertook this study. Methodology: This retrospective observational study was conducted at a tertiary care oncology center in India on diagnosed cases of NHL between January 2007 and December 2013. All patients were diagnosed based on histopathology and immunohistochemistry. Staging work up was done in all patients. Patients were considered as primary Head and Neck lymphomas if there was head and neck as the predominant site with or without regional lymph node involvement. Results: A total of 39 patients were studied. The age at presentation ranged from 29 to 78 years. The most common site of presentation was oral cavity (26%; n=10), followed by parotid and thyroid (18% each; n=7), eye (12%, n=5), maxilla (8%; n=3), paranasal sinuses (8%; n-=3) cheek (8%, n=3), and nasal cavity (2%, n=1). 41% (n=16) cases were in stage I, 43% (n=17) in stage II, 3% (n=1) in stage III, and 13% (n=5) were in stage IV. Most common histology was DLBCL (71%; n=28), followed by plasmablastic (10%; n=4), marginal zone (8%, n=3), mantle cell (3%; n=1), follicular lymphomas (5%; n=2), and NK/T cell lymphoma (3%; n=1). Most of the patients were of low risk (67%; n=26), followed by intermediate (23%; n=9), and high risk (10%; n=4). Patients were treated with anthracycline based chemotherapy +/-radiotherapy. In this study, stage I and stage II patients had a better prognosis and overall survival, median OS 28 months and 11 months, respectively. In stage III and IV, it was 7 and 3 months, respectively. According to site, the best median overall survival was seen with parotid (27 m), paranasal sinus (26m), and oral cavity (23 m), followed by thyroid (18 m) nasal cavity (17 m), maxilla (11 m), eye (8 m), and cheek (7 m)

Pancreatic neuroendocrine tumor in an individual with Von Hippel Lindau syndrome. A case report and review literature

Von Hippel Lindau (VHL) disease is a heritable cancer syndrome characterized by VHL gene mutation in 3p chromosome. Mutations occur at the exons. Rarely mutations at introns have been reported. It leads to accumulation of Hypoxic ischemic factor α (HIF α) which in turn leads to uncontrolled cellular proliferation. Few reports of pancreatic neuroendocrine tumors (PNETs) are there in the literature. Most of them are associated with a mutation in the exon of VHL gene. Association with intron mutation is not there. Here we are reporting a case of PNET in a patient who has a simultaneous mutation both at the exon and the intron

Aflibercept as a second-line therapy in metastatic colorectal cancer: A limited Indian experience

Introduction: Aflibercept in combination with FOLFIRI has been shown to improve overall survival in the pivotal VELOUR study. Aflibercept has not yet been marketed in India. Sanofi has made available this drug for Indian patients under a program called Named Patient Access Program (NPP). We present a limited clinical experience with the use of aflibercept at our center. Materials and Methods: We analyzed the data of the patients who received aflibercept under NPP. Aflibercept was given in combination with FOLFIRI as second-line for patients who progressed on oxaliplatin based therapy. Aflibercept was given at 4 mg/kg intravenous (IV) every 15 days. Chemotoxicities were assessed as per CTCAE. Response evaluation was done every four cycles. Results: Five patients were enrolled. The median age was 34 years. The median number of aflibercept cycles administered was 12. Common grade 2/3 toxicities were mucositis, diarrhea, neutropenia thrombocytopenia, and hypertension seen in three (60%), three (60%), two (40%), two (40%), and one patient respectively. After four cycles, the response was assessed as: One complete remission (CR), three partial remissions (PR), and one progressive disease (PD). Three patients completed 12 cycles of chemotherapy and aflibercept. At the end of 12 cycles, one patient still in CR and two patients were in PR. Four patients were alive till date. Conclusion: As we had very less number of patients, it was very difficult to compare it with VELOUR data. It is one of option as second-line in metastatic colorectal cancer (mCRC) who progressed on oxaliplatin chemotherapy. Mucositis, diarrhea, and hematological toxicity were the most common toxicity in our patient

Epidemiology and outcomes of nasopharyngeal carcinoma: Experience from a regional cancer center in Southern India

Context: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. There are limited data on epidemiology and outcomes of NPC reported from Southern India. Settings and Design: Retrospective analysis. Materials and Methods: We analyzed our hospital data between January 2005 and December 2011 with NPC and analyzed their demographic parameters and outcomes with therapy. Results: A total 143 cases of NPC were identified. Median age at presentation was 35 years with male predominance. Majority (84%) of the cases had the WHO Type 3 histology. Nodal metastasis at presentation was seen in 90% of the cases, majority being bilateral. Distant metastasis was seen in 16% of the cases, most commonly at bone, lung, and liver. Concurrent chemoradiation with weekly cisplatin was offered to 84.7% of localized disease while 80% of these also received adjuvant chemotherapy. Complete remission and partial remission were achieved in 66.1% and 15.2% of the cases, respectively. Weekly cisplatin was well tolerated with Grade 3–4 toxicity seen in 22% of cases. At a median follow-up of 20 months, 2-year progression-free survival and overall survival were 67.2% and 79.5%, respectively. Statistical Analysis Used: SPSS software version 20. Conclusion: NPC is a rare head and neck malignancy in Southern India, presenting with advanced stage and more propensity to distant metastasis. It has good outcomes to concurrent chemoradiation with weekly schedule of cisplatin being well-tolerated regime. Further prospective studies to test this schedule and other novel agents in this potentially curable malignancy are warranted