Haplogroup heterogeneity of LHON patients carrying the m.14484T>C mutation in India

Purpose: To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber Hereditary Optic Neuropathy (LHON) patients carrying the m.14484T>C mutation. Methods: Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants. Results: In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male:female = 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e. F1c1, M31a, U2a, M*, I1, M6, M3a1 and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON. Conclusions: Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease

Major histocompatibility complex class I expression can be used as a diagnostic tool to differentiate idiopathic inflammatory myopathies from dystrophies

Aim: Utility of major histocompatibility complex (MHC) Class I antigen immunostaining was studied to differentiate idiopathic inflammatory myopathies from dystrophies. Materials and Methods: Forty muscle biopsies including seven dermatomyositis (DM), six polymyositis (PM), two sporadic inclusion body myositis (sIBM), 20 dystrophies (one Duchenne, three Becker′s, four alpha, one gamma sarcoglycanopathy, nine limb girdle, one myotonic and one fascioscapulohumeral muscular dystrophy) and five controls were stained with antibody for MHC Class I antigen (Novocastra clone W6/32 HL 1:100 dilution). Results: Polymyositis and sIBM showed MHC class I antigen positivity along sarcolemma of single and small groups of muscle fibers. The regenerating fibers in the perifascicular area in DM showed intense cytoplasmic positivity of MHC class I antigen. Muscle fibers in all dystrophies except regenerating fibers and control normal muscle were negative for MHC. Capillaries and lymphocytes were positive controls. There were no false positives in the study. Conclusion: MHC Class I immunostaining can be used as a complementary diagnostic tool for the diagnosis of idiopathic inflammatory myopathies

Isolated malakoplakia of inguinal lymph node: A rare case report

Malakoplakia is rare chronic inflammatory disorder which commonly affects urinary tract. Though it has been reported in several sites outside the urinary tract, isolated lympnode involvement is extremely uncommon. Herein we present a case of 20 year old male with right inguinal lymphnodal mass. Histological findings including special stains and immunohistochemistry findings were characteristic of malakoplakia. This case is being presented to create awareness for inclusion of this entity in the differential diagnosis of lymphadenopathy

Cerebral Aspergillus arteritis with bland infarcts: A report of two patients with poor outcome

Two patients with cerebrovascular aspergillosis, in the form of arteritis, thrombosis and bland infarcts are reported. One patient had systemic lupus erythematosus with disseminated aspergillosis in lungs, kidneys and brain. The other patient was immunocompetent and had sphenoid sinusitis. Both the patients were diagnosed at autopsy only, despite extensive imaging and laboratory studies. High index of clinical suspicion and early aggressive antifungal therapy are required since definite diagnostic modalities are not available

Astroblastoma with bone invasion

Astroblastoma is a rare tumor belonging to the family of primary glial neoplasms. They are classified as neuroepithelial tumors; however, the World Health Organization grading is still not established. We report the case of a 4-year-old child who presented with an intra-axial space occupying lesion which turned out to be an astroblastoma. A complete excision was done and there was no recurrence at 20 months follow-up. This case report highlights the presence of such unusual tumor with invasion to the calvarium and reviews the current literature

An unusual case of large posterior fossa neurenteric cyst involving bilateral cerebellopontine angle cisterns : report of a rare case and review of literature

Background: Intracranial neurenteric cysts are rare cystic masses of endodermal origin lined with mucin producing low columnar or cuboidal epithelium. Approximately 141 cases have been reported so far. Most of the posterior fossa neurenteric cysts are typically small, located anteriorly to the brainstem in the midline or in the cerebellopontine angle cistern area. Case Report: We present a rare, histologically proven case of a large lobulated intracranial neurenteric cyst measuring 4.2 centimeters in the maximal transverse dimension and involving bilateral cerebellopontine angle cisterns. We also present a review of the literature on this uncommon finding. Conclusions: Imaging features of neurenteric cyst are non-specific and it should be considered in the differential diagnosis for any intracranial extraaxial cystic lesion

Fungal infections as a contributing cause of death: An autopsy study

Context: With the continuing rise in the number of immunocompromised patients, the incidence of invasive mycoses has increased. Various studies have reported the trends of fungal infections in autopsies. Because of limitations in antemortem clinical diagnosis owing to lack of sensitive diagnostic tools, information regarding frequency and pathogenesis of fungal infections is largely dependent on autopsy studies. Aim: To study the prevalence of fungal infections at autopsy spanning a period of 20 years and to document recent trends, prevalence of various fungi over decades along with underlying predisposing factors and pathological findings. Settings and Design: Retrospective study. Materials and Methods:All autopsies between 1988 and 2007 were reviewed and all cases showing fungal infections were analyzed. The clinical details and demographic data were retrieved from medical records. Representative sections from all organs were stained with hematoxylin and eosin stain and special stains including Gomori′s silver methenamine (GMS) and per-iodic acid Schiff (PAS). Culture details were noted, wherever available. Results: A total of 401 autopsies were performed during the study period. Fungal infections were identified in 35 (8.7%) of these cases. Leukemia was the commonest risk factor. The commonest pathogen in the present study was Aspergillus sp. The commonest single organ involved was brain (n = 18). Culture positivity was seen in 23.8% cases. Conclusion: The study highlights various predisposing factors and organisms in autopsy series. Existing diagnostic modalities are not sensitive to ensure antemortem diagnosis of fungal infections

Pulmonary zygomycosis: A clinicopathological study

Background and Objective: Zygomycosis is an emerging infection worldwide. Pulmonary zygomycosis (PZ) is uncommon with only few reported series from India. Materials and Methods: All cases of PZ diagnosed on histopathology between 1995 and 2008 were included. Clinical and imageological findings were noted in all cases. Routine hematoxylin and eosin-stained sections were studied to assess the pathology; Gomori′s methenamine silver (GMS), periodic acid Schiff were done for delineating fungal morphology. Culture reports were collected wherever available. Treatment and outcome details were noted. Results: Seven patients were diagnosed with PZ during the study period, which included six males and one female patient. Six of these had diabetes mellitus (DM) and one patient was on chemotherapy for the treatment of Hodgkin′s lymphoma. Fever and cough were the most common presenting features. Consolidation with or without cavitation was seen in six patients and lung abscess with fungal ball in one patient. All six patients with DM had upper lobe involvement and four had multiple lesions. Histological sections revealed necrotizing inflammation, hemorrhagic infarcts and angioinvasion. Culture was available in two patients, which grew Rhizopus oryzae. Five patients succumbed to disease and remaining two were lost to follow-up. Conclusion: Diabetes mellitus is the most common predisposing factor for PZ and carries high mortality

Steroid therapy in drug induced acute interstitial nephritis- Retrospective analysis of 83 cases

Drug-induced acute interstitial nephritis (DIAIN) is a common cause of acute deterioration of renal function. Early diagnosis and discontinuation of the offending drug usually lead to recovery of renal function. Steroid administration further hastens the recovery. However, the outcome of steroid-treated DIAIN is not well studied in the Indian scenario. We aimed to study the clinical profile and one-year renal outcome of DIAIN patients treated with steroids. We performed a retrospective study in biopsy-proven acute interstitial nephritis (AIN) and presumptive DIAIN patients who did not respond to discontinuation of the offending drug after five days of the diagnosis of AIN. Eighty-three DIAIN patients were included who were treated with 500 mg of methylprednisolone for three consecutive days followed by prednisolone of 0.5–1 mg/kg tapered over four to six weeks. We evaluated clinical profile, serum creatinine (SCr), and need of renal replacement therapy at the end of one year. We divided the patients into two groups: 1st as complete responders group (CR) when SCr is <1.5 mg/dL at the end of one year and 2nd as incomplete responders (IR) when it is ≥1.5 mg/dL and evaluated the outcome between two groups. In total, there were 39 (47%) CR and 44 (53%) were IR. Diabetes mellitus, present in a significant number of cases 27 (33%) was associated with poor response to steroids. Most common offending agents recognized were antibiotics (34%), nonsteroidal anti-inflammatory drugs (25%), herbal medications (13%), proton pump inhibitors (10%), and miscellaneous drugs (18%). There was no correlation between drug category and response to steroids. Interstitial fibrosis in renal biopsy was associated with poor response to steroids (4 cases in CR and 35 cases in IR, P ≤0.0001). Neutrophilic predominance in biopsy was associated with favorable response to steroids. Initial SCr and initial the requirement of dialysis support was not helpful in predicting the response to steroids and final recovery