Somanath Padhi

A 10-year retrospective study of hemangioblastomas of the central nervous system with reference to von Hippel–Lindau (VHL) disease

We aimed to analyze the clinical, radiological, surgicopathological and clinical outcome data of patients who underwent surgery for central nervous system (CNS) hemangioblastoma (HBL) with or without von Hippel-Lindau (VHL) disease. The clinico pathological and radiological findings, management and clinical outcome of patients with CNS HBL (operated between 2000 and 2009) were analyzed retrospectively. The differences between sporadic and VHL-associated HBL were analyzed. Forty-nine patients (28 male, 21 female) underwent surgery for CNS hemangioblastoma. Thirty-nine patients (80%) harbored sporadic HBL whereas 10 (20%) had VHL disease. The mean age at diagnosis for VHL-associated HBL was 32 years when compared to 40 years in sporadic HBL. The lesions were solitary in 41 patients and multiple in eight. The cerebellum was the most common site of HBL (35/49, 71%). Six patients with sporadic and two with VHL disease had spinal lesions. On imaging (available in 43/49 patients), a cyst with a mural nodule was the most common finding, seen in 16 patients (37.2%) whereas nine patients (21%) had solid and cystic lesions. Clinical presentation, radiological features, and histomorphology of HBL with or without VHL disease were similar. Multiple cysts in the pancreas, kidney, broad ligament, epididymis, clear cell renal cell carcinoma, phaeochromocytoma and retinal angiomas were the visceral manifestations seen in patients with VHL disease. Of all patients with VHL disease, three required multiple surgeries for new lesions and one died of renal failure and sepsis. Among the patients with sporadic disease (31/39), two died of surgical complications, one died of postoperative sepsis, three were lost to follow-up and the remainder had resolution of symptoms at 1year following surgery. We concluded that the diagnosis of VHL disease is important as management is more difficult and lifelong follow-up and counseling are required in these patients and for their at-risk relatives.

Pancreatic Extragastrointestinal Stromal Tumors, Interstitial Cajal Like Cells, and Telocytes

CONTEXT The discovery and subsequent ultrastructural characterization of the interstitial Cajal like cells (now called telocytes) in virtually every anatomic sites of the human body, by Laurentiu M Popescu and co-workers, have dramatically improved the understanding the function of these cells and pathogenesis of extragastrointestinal stromal tumors (EGIST). Pancreatic extragastrointestinal stromal tumors (pEGIST), phenotypically similar to pancreatic interstitial Cajal like cells, are extremely rare with an unpredictable biological behavior. OBJECTIVE To review the clinicopathological, radiological, immunohistochemical, and therapeutic outcome data of all reported cases of pEGIST, and highlight the developments in the field of pancreatic interstitial Cajal like cells/telocytes. METHODS A systematic review of English literature (January 2000 to July 2012) was done by using the search engine of PubMed, PubMed Central, Google Scholar, and the Directory of Open Access Journals. RESULTS There have been 19 reported cases of pEGIST during the last decade, over an age range of 31 to 84 years (mean: 56 years) with equal gender predilection ((male:female ratio: 9:10). Preoperative radiological characteristics have been mostly nondiagnostic though these were used, in some, for tissue diagnosis. Majority of pEGIST were localized to pancreatic head (8/19, 42.1%), and 15 of 19 patients (78.9%) were symptomatic at first presentation. The mean size ranged from 2.5 to 35cm (mean: 14 cm). Histomorphological features were that of predominantly spindle cell tumor which consistently expressed c-KIT/CD117 and CD34 by immunohistochemistry, making these two as the most sensitive markers at this site. RESULTS from studies involving discovery on gastrointestinal stromal tumor 1 (DOG-1), the most specific biomarker of GIST/EGIST, has been inconclusive and this was found to be positive in one case only. Neoadjuvant chemotherapy with imatinib mesylate and sunitinib were used in few cases, and genetic analysis of c-KIT proto-oncogene was done in two. By univariate analysis, none of the clinicopathological parameters, except surgical resection with microscopic free margin (R0 resection) (P<0.05), were found to be an important indicators of outcome. CONCLUSION The biological behavior of pEGIST, at present, seems unpredictable which requires indefinite period of follow-up. Large number of such cases with genetic analysis supplemented with immunohistochemistry studies will hopefully throw more light in these tumors.

Serum high sensitivity C-reactive protein, nitric oxide metabolites, plasma fibrinogen, and lipid parameters in Indian type 2 diabetic males

AIMS Inflammation is postulated to play a role in diabetogenesis and its further vascular complications. The aim was to assess the inflammatory and lipid parameters in patients of type 2 diabetic mellitus with or without complication. MATERIAL AND METHODS Serum high sensitivity C-reactive protein (hs-CRP), nitric oxide metabolite (NO(X)), fibrinogen, and lipid parameters were measured in eighty type 2 diabetic males (40-65 years) without (n=40, group B) and with complication (16 retinopathy, group C; 24 hypertension, group D); and compared with 40 healthy, age and sex matched nondiabetic males (group A) from the general population. RESULT The mean age of subjects and fasting plasma glucose among groups A, B, and C+D were 51.0 ± 7.1 vs. 48.7 ± 5.7 vs. 50.2 ± 6.1 years (p>0.05); and 96.7 ± 10.4 vs. 134.3 ± 27.8 vs. 136.4 ± 29.8 mg/dl (p<0.001) respectively. Patients with retinopathy were older, with longer duration of diabetes, and high fasting plasma glucose (p<0.001). The mean hs-CRP, NO(X), fibrinogen, TC, TG, and LDL(C) varied significantly (p<0.001) between control and diabetics. hs-CRP, NO(X), and fibrinogen were found to be highest in retinopathy group whereas no significant (p>0.05) difference was noted between groups B and D in relation to hs-CRP and NO(X). TC and LDL(C) were significantly (p<0.001) high among group B patients. Significant positive correlation was observed between all three inflammatory markers in all categories of patients; between FPG, hs-CRP, and fibrinogen among patients with hypertension; between FPG, hs-CRP, and NO(X) in patients with retinopathy. However, none of the lipid parameters showed any significant correlation with any of the inflammatory markers in any group of patients studied. CONCLUSION Low grade systemic inflammation, in association with dyslipidemia, plays a role in diabetogenesis and its complications.

Hemophagocytic lymphohistiocytosis: An unusual complication in disseminated Mycobacterium tuberculosis.

Background: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of disseminated Mycobacterium tuberculosis (MTB). The clinical course of tuberculosis-associated HLH (TB-HLH) has been reported to be unpredictable. Materials and Methods: Here we describe the clinicopathological features, laboratory parameters, management, and outcome data of a patient who satisfied the 2004 diagnostic criteria for HLH secondary to disseminated MTB; we also do a systematic review of the international literature on TB-HLH. The literature review (January 1975–March 2014) found that HLH complicated the clinical course of 63 tuberculosis patients (41 males, 22 females, mean age = 45 ± 23.5 years) with a high mortality rate of 49% (31/63 died). The mean serum ferritin level (n = 44/63) was 5963 ng/mL (range 500–38,539 ng/mL); and a higher proportion (54.2%) of patients had pancytopenia at presentation. On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03–7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08–19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16–6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51–7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis. Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66–3.22, P = 0.35) did not alter the outcome in these patients. Conclusion: HLH should be considered as a differential diagnosis in patients with tuberculosis who present with cytopenias, organomegaly, and coagulopathy. Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality. The utility of immunosuppressive/immunomodulator therapy lacks general concensus among treating physicians, and warrants further studies.

Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially life threatening, hyper inflammatory syndrome of diverse etiologies. Cardinal signs include prolonged fever, organomegaly, and persistent unexplained cytopenias. In spite of the well known diagnostic criteria put forth by HLH society, this continues to pose great diagnostic challenge in both pediatric and adult intensive care settings. We describe 4 adult (2 males, 2 females, aged 19, 29, 40, and 17 years) and 3 pediatric (2 males, 1 female, aged 1 month, 6 months, and 12 years) patients with secondary HLH who satisfied the HLH-2004 diagnostic criteria. Definite evidence of hemophagocytosis was noted in 4 patients on initial bone marrow examination. The underlying etiologies were as follows: Rickettsia tsutsugamushi (case 1), autoimmune disorder (case 2), systemic onset juvenile idiopathic arthritis (sJIA) (case 3), unknown bite (possibly a venomous snake) (case 4), Plasmodium vivax (case 5), Cytomegalo virus (case 6), and Mycobacterium tuberculosis (case 7). In one patient, hemophagocytosis was presumed to have been exacerbated by administration of granulocyte monocyte colony stimulating factor (GMCSF) for severe neutropenia. Two patients died with disseminated intravascular coagulation (DIC) and multi organ failure within few days of HLH diagnosis. Immunosuppressive therapy was started in 3 patients, and etoposide was started in one patient only. Due to lack of specificity of diagnostic criteria, diagnosing and differentiating HLH from its closest mimickers like sepsis/septic shock may be quite challenging in critically ill patients. Therefore, increasing awareness among physicians is essential for early diagnosis and effective therapy to reduce the mortality.

Cyclin D1 expression in multiple myeloma by immunohistochemistry: Case series of 14 patients and literature review.

Background: Cyclin D1 dysregulation is an early and unifying oncogenic event in patients of multiple myeloma (MM). This may be detected up to 30% cases by immunohistochemistry (IHC) and up to 40-50% cases by molecular studies. However, studies on the clinical significance of cyclin D1 dysregulation in MM have been inconclusive. We aimed to study the pattern of cyclin D1 expression in MM by IHC and correlate with selected clinicopathologic features. Materials and Methods: Formalin fixed, decalcified, bone marrow trephine sections from 14 symptomatic patients of MM (13 newly diagnosed and one relapsed) were subjected to cyclin D1 IHC by using a rabbit monoclonal antibody to cyclin D1 (clone EPR2241). Results: Cyclin D1 expression (in ≥10% tumor cell nuclei) was observed in 8 of 14 cases (57%). Cyclin D1 positive (+) group had significantly lower hemoglobin level (P = 0.03) than cyclin D1 negative (−) group (n = 6); though both groups showed no statistical significance (P > 0.05) in regard to age, gender, Durie and Salmon stage, lytic bone lesions, light chain phenotype, creatinine, calcium, lactate dehydrogenase, leukocyte and platelet count and bone marrow histology. Ten of 14 (71.5%) showed a favorable response (follow-up; 7 days to 34 months) to thalidomide and/or bortezomib based chemotherapeutic regimen. Four of eight cyclin D1− patients showed complete response, two had a partial response (PR) and two died of the disease; whereas 4/6 cyclin D1 − patients had PR, one refused definitive therapy and one was lost to follow-up (P > 0.05, Fischers exact test). Conclusion: IHC may be a feasible tool for the demonstration of cyclin D1 expression on adequately processed trephine biopsy specimen in MM patients in a resource poor setting. Negative IHC results should be correlated with molecular techniques for prognostication.

Cytogenetic profile of pediatric acute lymphoblastic leukemia (ALL): analysis of 31 cases with review of literature

Abstract Pre treatment diagnostic cytogenetics is one of the most important prognostic indicators of pediatric acute lymphoblastic leukemia (ALL).Bone marrow aspirate samples of 31 cases of pediatric ALL were analyzed by routine G- Banding technique. Karyotype analysis was done as per International System for Cytogenetic Nomenclature (ISCN), 2005 criteria. Sixteen out of 31 (51.2%) cases were hypodiploid (2n<46), 10/31(32.0%) hyperdiploid (2n>46) and 5/31(16.0%) aneuploid. Among hypodiploid groups, nine (29.0%) had modal chromosome number as 31–39, five (16.0%) as 40–45 and two (6.5%) as 25–30. Among hyperdiploid group, 07(22.5%) had modal chromosome number as 51–60 followed by 2n=47–50 (three cases, 6.5%). The chromosomes (Chr.) 2, 10, 12, 15, 17, 19 were commonly deleted in hypodiploid cell lines whereas gain of Chr. 4, 8, 10, 14and 20 were observed in hyperdiploid group. Translocations t(10;14),t(9;22),t(2;22),t(8;22) andt(4;11)were seen in 04(12.8%),03(9.6%),and02(6.4%each) and one case respectively. To conclude a high proportion of cases in this study showed adverse cytogenetic parameters such as hypodiplody and translocations such as t(10;14),t(9;22),t(2;22),t(8;22)andt(4;11).

Correlation of narrow band imaging endoscopy and histopathology in the diagnosis of nonerosive reflux disease.

Background /Aim: Narrow band imaging (NBI) is a novel, innovative high-resolution endoscopic technique, which utilizes spectral narrow band filter for the visualization of mucosal patterns and microvasculature. Nonerosive reflux disease (NERD) is a type of gastroesophageal reflux disease (GERD) and it is characterized by reflux symptoms without mucosal breaks on white light endoscopy (WLE). Biopsies from distal esophagus of GERD patients show group of histologic features such as basal cell hyperplasia, elongation of lamina propria papillae, and inflammatory cells. The present study was undertaken to evaluate diagnostic utility of NBI endoscopy and biopsy study in NERD patients and also to correlate NBI endoscopy findings with histologic features of GERD. Patients and Methods: A total of 71 cases of NERD having symptom score more than 10 and those not having erosion on WLE were recruited prospectively and underwent NBI endoscopic examination. Two mucosal biopsies were taken at 3 cm above the squamocolumnar junction. Results: Histologic features of GERD were seen in 50 (70.4%) out of 71 cases. No significant correlation between NBI endoscopic findings with histologic features of GERD was found. Conclusion: The present study showed that histopathologic evaluation of distal esophageal mucosa has promising diagnostic value over NBI endoscopy in NERD patients. Use of newly introduced NBI technique requires tremendous familiarity for the detection of the cases of NERD, which show histologic features of GERD.Background /Aim: Narrow band imaging (NBI) is a novel, innovative high-resolution endoscopic technique, which utilizes spectral narrow band filter for the visualization of mucosal patterns and microvasculature. Nonerosive reflux disease (NERD) is a type of gastroesophageal reflux disease (GERD) and it is characterized by reflux symptoms without mucosal breaks on white light endoscopy (WLE). Biopsies from distal esophagus of GERD patients show group of histologic features such as basal cell hyperplasia, elongation of lamina propria papillae, and inflammatory cells. The present study was undertaken to evaluate diagnostic utility of NBI endoscopy and biopsy study in NERD patients and also to correlate NBI endoscopy findings with histologic features of GERD. PATIENTS AND METHODS A total of 71 cases of NERD having symptom score more than 10 and those not having erosion on WLE were recruited prospectively and underwent NBI endoscopic examination. Two mucosal biopsies were taken at 3 cm above the squamocolumnar junction. RESULTS Histologic features of GERD were seen in 50 (70.4%) out of 71 cases. No significant correlation between NBI endoscopic findings with histologic features of GERD was found. CONCLUSION The present study showed that histopathologic evaluation of distal esophageal mucosa has promising diagnostic value over NBI endoscopy in NERD patients. Use of newly introduced NBI technique requires tremendous familiarity for the detection of the cases of NERD, which show histologic features of GERD.

Primary adrenal non Hodgkin lymphoma: Changing trends

Primary adrenal lymphoma’s pathogenesis is multifactorial, with various mechanisms suggested, including 1) immune dysregulation (immune deficiency and autoimmunity, the most common); 2) originating from hematopoietic tissue resting within a single adrenal gland; 3) p53 and c-KIT gene mutation. The so-called “homing mechanism” (i.e., originating from hematopoietic tissue resting within one adrenal gland and gravitational migration to the contralateral side) may also partly explain the bilaterality common in this malignancy (2). The adrenal gland, like the thyroid, is normally devoid of lymphoid tissue; immune dysregulation predisposes to forming polyclonal lymphoid infiltrate (acquired mucosa associated lymphoid tissue) and subsequent clonal evolution into lymphoma, in which Epstein-Barr virus and JC polyoma virus play a role (3,4).

Selective myelosuppression following yellow phosphorus ingestion.

Toxicity from accidental and intentional ingestion of yellow phosphorus, ubiquitously present in fireworks and rodenticides, has recently become more frequent. Gastrointestinal, renal, neurologic, and cardiovascular manifestations are common, with mortality of 23 per cent to 73 per cent. Reports of haematological abnormalities are rare. We report only the second case of severe neutropenia secondary to selective myelosuppression in a 14-year-old girl following intentional ingestion of yellow phosphorus. Leucocyte counts recovered spontaneously without further complications. Our case indicates that, besides hepatic and renal function monitoring, physicians should meticulously monitor blood counts in such cases for early detection of marrow suppression. Further studies are required to elucidate the complex mechanisms and significance of this unusual toxicity of yellow phosphorus.