Outcome of C3 glomerulopathy patients: largest single-centre experience from South Asia.

BACKGROUND: C3 glomerulopathy (C3G) is related to dysfunction of alternative complement pathway (ACP) because of its hyperactivation. Triggering factors and genetic profile are likely to be different in developing countries as compared to the Western world. Data regarding C3G from South Asian is scanty. STUDY DESIGN: In the present study, 115 patients of C3G from 2012 to 2017 were analyzed. Clinical details were reviewed; serological levels of C3, C4, complement factor H or B and autoantibody testing was done by nephelometry/ELISA. Limited genetics workup for CFH and CFHR5 genes was done. RESULTS: The prevalence of C3G was 1.52%. There was no difference in demographic and histopathologic profiles of C3G patients. Majority of patients had low functional assay and C3 levels. C3 nephritic factor was present in 47.5% of DDD and 38.6% of C3GN. Autoantibodies to CFH were present more often in the patients of C3GN (29.5%) than DDD (12.5%). Autoantibodies to CFB were equally common in both groups. Past history of infections was present in one-third patients and monoclonal paraproteins were present only in two patients. No pathogenic variants were noted in CFH/CFHR5 gene. On follow-up (3.2 + 1.6 years), complete and partial remission was achieved in one-fourth patients and 26% had resistance disease. About 40% progressed to ESRD and 18 underwent renal transplantation of which nine had a post-transplant recurrence. CONCLUSIONS: Indian cohort had some differences in the immunological and genetic profile when compared to the Western literature; most significant was the absence of monoclonal immunoglobulins as a trigger for C3G.

Adult Pilomyxoid Astrocytoma with Hemorrhage in an Atypical Location.

Pilomyxoid astrocytomas (PMAs) are generally seen in young children and tend to occur in the hypothalamic-chiasmatic region. Their presence in other parts of the brain in the nonpediatric age group is uncommon. In addition, hemorrhage in such low-grade tumors is an occasional event. We describe a case of PMA that presented with spontaneous bleed in an atypical location (temporoparietal region) in an adult. A concise literature of the cases of PMA which were associated with bleed is also presented. Occasionally, low-grade tumors such as PMA may present with bleed. These benign looking neoplasms behave differently from the commonly occurring pilocytic astrocytomas (PAs) and should be considered as a differential. It is important to differentiate these from PA, as the management and prognosis differs.

Rosette-forming and papillary glioneuronal tumors - A clinicopathological and molecular analysis.

INTRODUCTION: Rosette-forming glioneuronal tumors (RGNT) and papillary glioneuronal tumors (PGNT) account for < 1% of brain tumors. Genetic data regarding RGNT and PGNT is still evolving. We aimed to perform a detailed clinicopathological analysis on rosette-forming and papillary glioneuronal tumors and to evaluate these for common, known genetic mutations. MATERIALS AND METHODS: Our cohort consisted of 6 cases of these rare glioneuronal tumors diagnosed over a period of 5 years. IDH1, ATRX, p53, and BRAF V600E mutations were evaluated on immunohistochemistry, and cases of RGNT were screened for the mutations in PIK3CA gene at hotspots exon 4, 9, and 20. RESULTS AND CONCLUSIONS: Our findings confirm the presence of PIK3CA gene mutations in RGNT along with two novel mutations in PIK3CA gene, of which one is proposed to be of prognostic significance.
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Therapeutic Challenges in the Management of Bleeding Duodenal Gastrointestinal Stromal Tumor: a Case Report and Review of Literature.

INTRODUCTION: Duodenum is an uncommon site for the gastrointestinal stromal tumors (GISTs). Though the principles of management are the same of that elsewhere in the gastrointestinal tract, the anatomical complexity poses challenges in deciding the most appropriate treatment. A bleeding GIST further compounds the difficulty in managing such patients. CASE REPORT: A twenty-eight-year-old female presented with bleeding duodenal lesion secondary to mucosal ulceration. Imaging confirmed large heterogeneous lesion arising from the second part of duodenum. Surgery was planned in view of persistent blood transfusion requirement. Pancreaticoduodenectomy was done and the patient had an uneventful postoperative period. DISCUSSION: Review of literature of duodenal GIST especially regarding the tough decisions that have to be made in the diagnosis and management of bleeding lesions has been done. CONCLUSION: The availability of various options in addressing bleeding duodenal GIST should make the surgeon choose the best modality for the patient weighing the pros and cons of each modality.

Surgery for Abdominal Tuberculosis in the Present Era: Experience from a Tertiary-Care Center.

BACKGROUND: The role of surgery in abdominal tuberculosis is being redefined, as many patients will be candidates for endoscopic dilatation rather than open surgery. METHODS: A retrospective analysis was done of the surgical procedures performed in patients with abdominal tuberculosis in a large tertiary-care center in North India. Details such as clinical presentations, previous history of tuberculosis, any anti-tubercular therapy (ATT), Mantoux skin test results, and the surgical procedures and findings were recorded. Short-term outcomes also were analyzed. RESULTS: Thirty-five patients (26 male) were included, and the median age at presentation was 24 years (range 12-80 years). Sixteen patients had received prior ATT for abdominal tuberculosis. The indication for surgery was intestinal obstruction, perforation, and bleeding in 23 (66%), 10 (29%), and 2 (6%) respectively. Twenty-eight patients had intestinal strictures, with the ileum being the most common site (n = 21). Perforation was present in 10 patients, of which six had multiple perforations. Cocoon abdomen was present in four patients, two of whom had associated small-bowel stricture. Among 33 patients who underwent bowel resection, 14 had ileo-cecal resection/right hemicolectomy. The rest had small-bowel resection. Primary anastomosis and stoma creation was performed in 12 (36%) and 21 (64%), respectively. Post-operative intra-abdominal collections (p = 0.02) and incision dehiscence (p = 0.05) were more common in patients having stoma creation. CONCLUSION: Surgical intervention is warranted in a subset of patients with abdominal tuberculosis and may be required in patients with recurrent intestinal obstruction or pain, intestinal perforation, or gastrointestinal bleeding.

IDH1, ATRX, and BRAFV600E mutation in astrocytic tumors and their significance in patient outcome in north Indian population.

BACKGROUND: According to the current World Health Organization (WHO) classification of central nervous system (CNS) tumors (2016), histological diagnosis of gliomas should be supplemented by molecular information. This study was carried out to determine the frequency of isocitrate dehydrogenase 1 (IDH1), ATRX, and BRAF V600E mutations in different grade astrocytomas and their prognostic value. METHODS: Eighty cases of astrocytoma (15 pilocytic astrocytoma, 25 diffuse astrocytoma, 15 anaplastic astrocytoma, and 25 glioblastoma) with follow-up information were analyzed using immunohistochemistry for IDH1 mutant protein, ATRX, p53, and BRAF. Sanger sequencing was carried out for IDH1 exon 4 and BRAF exon 15. RESULTS: All pilocytic astrocytoma and primary glioblastoma cases were negative for IDH1 mutation. IDH1 mutation was detected in 80% (20/25) DA and 87% (13/15) AA cases. IDH1 R132H was the commonest IDH1 mutation (94.1%) and immunohistochemistry showed 100% sensitivity and specificity to detect this mutation. Loss of nuclear ATRX expression was found in 87% (20/23) and 100% (14/14) DA and AA cases, respectively. IDH1 mutant DA patients had longer overall survival than IDH1 wild cases, although this difference was not significant (79.5 months vs. 42.5 months, P value 0.417). BRAF V600E mutation was not detected in any astrocytic tumor. CONCLUSIONS: IDH1 and ATRX mutations are very common in diffuse astrocytoma and anaplastic astrocytoma, while they are rare in pilocytic astrocytoma and glioblastoma. Immunohistochemistry for IDH1 and ATRX can successfully characterize the diffuse gliomas into molecularly defined groups in majority of the cases. BRAF V600E mutation is rare in astrocytic tumors in Indian population.

Medulloblastoma with myogenic and/or melanotic differentiation does not align immunohistochemically with the genetically defined molecular subgroups.

The World Health Organization classification of central nervous system neoplasms (2016 update) recognizes 4 histological variants and genetically defined molecular subgroups within medulloblastoma (MB). MB with myogenic differentiation is one of the rare variants, which is usually recognized as a pattern alongside the known histological variants. Because of its rarity, less is known about its molecular landscape and importantly about its placement in the current molecular schema. We aimed to analyze this rare variant for expression of 3 immunohistochemical markers conventionally used in molecular stratification of MB. Demographic profile and imaging details with survival outcome were also analyzed. Sixty-five MB cases were molecularly stratified using immunohistochemical markers (YAP1, GAB1, ß-catenin). MB with myogenic differentiation and MB cases showing variable immunoreactivity with the above 3 antibodies were further evaluated for smooth muscle actin, desmin, myogenin, and HMB45. Seven cases were categorized as MB with myogenic and/or melanotic differentiation. Age ranged from 2 to 40 years with a male-to-female ratio of 1:1.3. In 4 cases, myogenic or melanotic differentiation was evident on histology, whereas in 3, differentiation was highlighted only with muscle markers. Interestingly, all 7 cases showed variable immunoreactivity with 3 molecular markers and did not follow the conventionally accepted algorithm used for molecular stratification. Follow-up period ranged from 9 to 57 months. Overall survival revealed a varied pattern, with 3 deaths and 4 patients being alive with no evidence of disease at last follow-up. Our results provide evidence that these variants are distinct and do not align immunohistochemically with the currently recognized genetic subgroups.

Primary giant cell tumor of the female breast: a diagnostic red herring with therapeutic implications.

Primary giant cell tumor of the female breast is extremely rare. Major diagnostic difficulty is encountered not only by the surgeon but also by the radiologist and pathologist. Pathologically, it is similar to the bone and soft tissue counterparts. However, this is not always true. We describe a patient presenting clinically as cystosarcoma phyllodes and histopathological examination revealed a primary giant cell tumor which was confirmed by immunohistochemistry and electron microscopy. Interestingly, an intimate relationship between the mononuclear component of the tumor cells with eosinophils and mast cells was observed electron microscopically.

Lipid-Rich Carcinoma of the Breast With Unusual Clinical and Histopathological Features.

Lipid-rich carcinoma of the breast is a rare form of invasive breast carcinoma of special type. Most cases are grade 3, hormone receptor negative, and associated with aggressive clinical behavior. We report an unusual case of lipid-rich carcinoma with morphological and immunophenotypical features different from those of cases reported so far in the literature. The index case underscores the fact that there is no consensus with regard to the exact nature of this tumor. Hence, larger studies are needed to draw meaningful conclusions.

Gallbladder tuberculosis camouflaging as gallbladder cancer - case series and review focussing on treatment.

INTRODUCTION: Gallbladder tuberculosis, in an endemic region, is a common infectious etiology affecting a rare organ. The high prevalence of carcinoma gallbladder in the endemic regions of tuberculosis, like India, poses diagnostic dilemma. CASE SERIES: We are reporting three cases of gallbladder tuberculosis mimicking carcinoma gallbladder of which the first two cases were operated with a presumptive diagnosis of malignancy. The third case presented to us after laparoscopic cholecystectomy elsewhere and on evaluation was found to have disseminated tuberculosis. DISCUSSION: The lack of pathognomonic clinical and radiological characters results in histological surprise of gallbladder tuberculosis following surgery performed for other indications like malignancy. In preoperatively diagnosed patients medical management plays pivotal role in management. Surgery is required in symptomatic patients. On the other hand, histologically proven cases following surgical resection require antitubercular therapy. CONCLUSION: Previous history of tuberculosis or concomitant tuberculosis at other sites may provide clue to the diagnosis of biliary tuberculosis. Antitubercular treatment after surgery plays an important role in preventing further dissemination.

Vascular complications of tuberculous meningitis: An autopsy study.

AIMS: Vascular complications have the most serious consequences in patients with tuberculous meningitis (TBM). Although stroke is seen in approximately 20% of patients with TBM, the underlying vascular damage and infarction are much more extensive. This study has been undertaken to study the pathology at different levels of cerebral vessels and their resultant complications in TBM. MATERIALS AND METHODS: Fifty-one postmortem TBM brains were examined over a period of 16 years (1997-2012). The vascular pathology was studied in detail. Changes in middle cerebral artery (MCA) and basilar artery (BA) and their branches at different levels were analyzed in all cases. RESULTS: The age of the patients ranged from 3 months to 72 years. Infarcts were found in 37 cases, among which they were grossly visible in 27 cases. Macroscopic infarcts were more common in MCA territory whereas microscopic infarction was more in BA distribution-brainstem and cerebellum. Vascular involvement was almost universal, with smaller branches of both MCA (94%) and BA (100%) carrying the brunt of the disease, whereas the larger branches were variably involved. Infiltrative lesions were most common at all levels; necrotizing lesions were more common in smaller branches, whereas proliferative changes were seen more in larger branches. CONCLUSION: This study showed extensive damage of cerebral vessels in TBM, which was responsible for the presence of widespread infarctions. Microscopic infarctions in the brainstem and cerebellum were much more common than reported by radiological studies. Thus, more aggressive management of TBM is required to combat its vascular complications.

Oral administration of encapsulated bovine lactoferrin protein nanocapsules against intracellular parasite Toxoplasma gondii.

Toxoplasma gondii is a deadly intracellular parasite known to reside in every nucleated cell and known to cause severe complications in immunocompromised host. Standard drugs are cost effective and cause side effects, therefore, there is a necessity for a new drug molecule with immunomodulatory potential. Lactoferrin (Lf) is a natural milk protein, which has shown antimicrobial properties in its nanoformulation using alginate chitosan calcium phosphate bovine lactoferrin nanocapsules (AEC-CCo-CP-bLf-NCs). The present study was aimed to analyze and compare the effect of bovine Lf (bLf) in its native as well as nanoformulation (AEC-CCo-CP-bLf-NC) against coccidian parasite T. gondii. In vitro analysis has shown a significant increase in nitric oxide production and low parasitemia in in vitro cell culture model. In vivo BALB/c mice model have been used to develop human toxoplasmosis model. After treatment with NCs it has substantially increased the bioavailability of the protein and showed comparatively increased levels of reactive oxygen species, nitric oxide production, and Th1 cytokine which helped in parasite clearance. The mechanism of action of NCs has been clarified by immunoreactivity analysis, which showed accumulation of Lf in macrophages of various visceral organs, which is the site of parasite multiplication. Effect of NCs has significantly decreased (P<0.05) the parasite load in various organs and helped survival of mice till day 25 postinfection. Fe metabolism inside the mice has been found to be maintained even after administration of mono form of Lf, this indicates novelty of Lf protein. From the present study we concluded that nanoformulation did not reduce the therapeutic potential of Lf protein; however, nanoformulation has enhanced the stability of the protein and shown anti-toxoplasmal activity. Our study presents for the first time nanoformulation of Lf protein against Toxoplasma, which has advantages over the standard drug therapy without any side effects.

Gangliocytic Paraganglioma With Atypical Immunohistochemical Features Presenting as Extrahepatic Biliary Obstruction.

Gangliocytic paraganglioma is a rare benign tumor of upper gastrointestinal tract that most commonly involves the second part of duodenum. The tumor is detected incidentally on imaging in most of the cases. However, presentation with extrahepatic biliary obstruction is extremely rare. We recently encountered a 50-year-old male patient who was evaluated for extrahepatic biliary obstruction and was found to have a periampullary mass on imaging. The patient underwent pylorus-preserving pancreaticoduodenectomy along with liver biopsy and hepatoduodenal lymph node dissection. On histopathological examination, a tumor was detected in the periampullary region of duodenum, which was confirmed to be gangliocytic paraganglioma on immunohistochemistry along with atypical histological and immunohistochemical features.

Unusual Clinical Presentation and Role of Decompressive Craniectomy in Herpes Simplex Encephalitis.

Decompressive craniectomy in pediatric central nervous infections with refractory intracranial hypertension is less commonly practiced. We describe improved outcome of decompressive craniectomy in a 7-year-old boy with severe herpes simplex encephalitis and medically refractory intracranial hypertension, along with a brief review of the literature. Timely recognition of refractory intracranial hypertension and surgical decompression in children with herpes simplex encephalitis can be life-saving. Additionally, strokelike atypical presentations are being increasingly recognized in children with herpes simplex encephalitis and should not take one away from the underlying herpes simplex encephalitis.

Bronchial mucous gland adenoma presenting as massive hemoptysis: A diagnostic dilemma.

Mucous gland adenoma of the lung is an uncommon benign tumor that histologically resembles the mucus-secreting component of tracheobronchial gland. The majority arises within the main, lobar, or segmental bronchi but parenchymal involvement had also been reported. We herein present a case of mucous gland adenoma arising from the left lower lobe bronchus. The 32-year-old female presented with massive hemoptysis, productive cough, and dyspnoea and was clinically misdiagnosed as tuberculosis. Radiology proved to be inconclusive. This case highlights the importance of a complete lung work up in patients presenting with signs of respiratory tract infections.

Secretory meningioma: a diagnostic pitfall.

CONTEXT: Secretory meningioma is a rare subtype of meningiomas, displaying epithelial and secretory differentiation of meningothelial cells. It has unique radiological, morphological, and immunohistochemical features, but runs a benign course. Radiological picture because of the variable degrees of peritumoral edema can be confused with aggressive neoplasms. Morphologically, it is difficult to distinguish secretory meningioma from other tumors having a clear cell appearance and aggressive clinical behavior. MATERIALS AND METHODS: Retrospective analysis over a period of 16 years (1997-2012) brought out five cases diagnosed as secretory meningioma. The slides were restained and subject to special stains and immunohistochemistry and the clinical details were retrieved. RESULTS: On histopathology, the tumors showed a characteristic vacuolated appearance due to the presence of variably sized intracytoplasmic lumina. Another unique feature was the presence of hyaline inclusions within these intracytoplasmic lumina and in the intercellular spaces. These inclusions were periodic acid-Schiff positive diastase-resistant, yellowish-orange on Elastic Van Giesson stain and strongly carcinoembryonic antigen positive. CONCLUSION: Owing to its rarity and unique morphology secretory meningioma poses a diagnostic challenge to the pathologists. As this tumor follows a benign course, it is crucial to correctly diagnose this entity to avoid unnecessary over treatment.