Role of intra-operative squash cytology in rosette-forming glioneuronal tumor of the fourth ventricle: a case report.

Rosette-forming glioneuronal tumor (RGNT) of the 4th ventricle is a newly described WHO grade I brain tumor included in recent WHO classification of CNS tumors. It is a biphasic tumor thought to originate from pluripotent progenitor cells of subependymal plate. Intra-operative diagnosis plays an important role, as complete surgical excision is the treatment of choice. We are reporting a case of RGNT in a 19 years-old young male emphasizing the intra-operative pathological pointers and their role in accurate diagnosis for the suitable surgical intervention.

Primary optic nerve sheath schwannoma: a case report.

BACKGROUND: The optic nerve is an unusual site of schwannoma as it lacks Schwannoma cells on it. We report a primary optic sheath schwannoma and to review the literature. CASE REPORT: A 29-year old female presented with progressive painless non-pulsatile proptosis. Ocular examination revealed only axial proptosis. Imaging showed a well-defined intraconal mass abutting optic nerve. A left frontal craniotomy with orbitotomy and tumor excision was done. The tumor was well encapsulated, posteriorly attached to optic nerve without any plane, probable site of origin. The postoperative duration was uneventful without any complications. The histopathology examination confirms the diagnosis of schwannoma. CONCLUSIONS: We suggest to consider orbital optic nerve schwannoma in differential diagnosis of orbital tumors despite its exceedingly rare occurrence.

Complex spinal dysraphism: myelomenigocele associated with dorsal bony spur, split cord malformation type I, syringomyelia, lipoma and tethered cord.

Variations in split cord malformation (SCM) are known. However, association of SCM type I with myelomeningocele along with same level dorsal bony spur has not been described previously. We report a 1-year old male child who presented with these findings with associated syringomyelia, lipoma and tethered cord.

Quantitative proteomic analysis of GnRH agonist treated GBM cell line LN229 revealed regulatory proteins inhibiting cancer cell proliferation.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) receptor, a rhodopsin-like G-protein coupled receptor (GPCR) family member involved in GnRH signaling, is reported to be expressed in several tumors including glioblastoma multiforme (GBM), one of the most malignant and aggressive forms of primary brain tumors. However, the molecular targets associated with GnRH receptor are not well studied in GBM or in other cancers. The present study aims at investigating the effect of GnRH agonist (Gosarelin acetate) on cell proliferation and associated signaling pathways in GBM cell line, LN229. METHODS: LN229 cells were treated with different concentrations of GnRH agonist (10-10 M to 10-5 M) and the effect on cell proliferation was analyzed by cell count method. Further, total protein was extracted from control and GnRH agonist treated cells (with maximum reduction in cell proliferation) followed by trypsin digestion, labeling with iTRAQ reagents and LC-MS/MS analysis to identify differentially expressed proteins. Bioinformatic analysis was performed for annotation of proteins for the associated molecular function, altered pathways and network analysis using STRING database. RESULTS: The treatment with different concentrations of GnRH agonist showed a reduction in cell proliferation with a maximum reduction of 48.2% observed at 10-6 M. Quantitative proteomic analysis after GnRH agonist treatment (10-6 M) led to the identification of a total of 29 differentially expressed proteins with 1.3-fold change (23 upregulated, such as, kininogen-1 (KNG1), alpha-2-HS-glycoprotein (AHSG), alpha-fetoprotein (AFP), and 6 downregulated, such as integrator complex subunit 11 (CPSF3L), protein FRG1 (FRG1). Some of them are known [KNG1, AHSG, AFP] while others such as inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), ITIH4, and LIM domain-containing protein 1 (LIMD1) are novel to GnRH signaling pathway. Protein-protein interaction analysis showed a direct interaction of KNG1, a hub molecule, with GnRH, GnRH receptor, EGFR and other interactors including ITIH2, ITIH4 and AHSG. Overexpression of KNG1 after GnRH agonist treatment was validated using Western blot analysis, while a significant inhibition of EGFR was observed after GnRH agonist treatment. CONCLUSIONS: The study suggests a possible link of GnRH signaling with EGFR signaling pathways likely via KNG1. KNG1 inhibitors may be investigated independently or in combination with GnRH agonist for therapeutic applications.

51-year old man with tingling, burning and progressive limb weakness.

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

Celiac disease and Helicobacter pylori infection in children: Is there any Association?

BACKGROUND AND AIM: Helicobacter pylori (HP) infection can influence the inflammatory and immune responses in the gut and may therefore play a role in the development of gluten-related enteropathy in genetically susceptible individuals. Our objective was to assess the relationship between celiac disease and HP infection in children. METHODS: Children (1-18 years) diagnosed as celiac disease (CD) (n = 324) with submission of gastric and duodenal biopsies and duodenal histology having Marsh grade III features were eligible for the study. Non-celiac patients referred for endoscopy were selected as controls. We studied proportion of HP prevalence in children with confirmed CD as compared with HP prevalence in reference group comprising non-celiac children referred for endoscopy. We also evaluated predictors of HP infection in children with celiac disease. RESULTS: Of the 324 participants with CD, gastric HP was seen in 37 (11.4%) patients. The prevalence of HP in patients without CD (50%, P < 0.001) was significantly higher. Among patients with CD, HP infection was most frequent in patients with Marsh IIIa. In the stepwise regression analysis for risk factors of HP infection in CD patients: presence of gastritis, hemoglobin, and absence of scalloping were found to be independent predictors in a multivariate setup. CONCLUSION: Celiac disease and gastric HP infection have inverse relationship that raises the question whether development of HP infection confers protection against CD.

Melanosomal melanin pigment in pleomorphic xanthoastrocytoma, evidence for neuronal-glial origin: A case report with review of the literature.

We describe a unique case of pleomorphic xanthoastrocytoma (PXA) in a 19-year-old male presenting with the chief complaint of seizures. On radiology, the tumor was located in the temporal lobe. It was cortically based and solid cystic in nature. Light microscopy showed pleomorphic large polygonal cells with inclusions, nuclear clustering, lipidization, and foamy cytoplasm intermingled with spindle cells arranged in sweeping pattern and focally containing cytoplasmic brownish black pigment. The pigment stained black with Fontana-Masson stain and bleached with potassium permanganate. Gomori silver stain showed reticulin fibers surrounding individual tumor cells as well as groups of cells. On immunohistochemistry, tumor cells were positive for GFAP, S-100 and focally for synaptophysin and CD34 but negative for HMB-45. CD34 revealed a specific membranous pattern around individual cells as well as groups of cells along the fibers replicating a reticulin pattern. The ultrastructural examination showed supporting melanosomes, thus confirming the melanin pigment. Sequencing for BRAF V600E showed a heterozygous mutation. To our knowledge only five cases of PXA with melanin pigment have been reported and none of which described BRAF V600E mutation analysis. This case provides further insight into the origin and pathogenesis of pigmented astrocytic tumor, additionally highlighting the characteristic CD34 staining pattern.

T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra-operative squash smear.

We present a rare case of primary pituitary T cell lymphoma/leukemia (T-LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55-year-old woman highlighting the importance of intra-operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar-suprasellar region with non-visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra-operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma-like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T-LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra-operative cytology.

Evaluation of chromosome 1q gain in intracranial ependymomas.

Ependymomas are relatively uncommon gliomas with poor prognosis despite recent advances in neurooncology. Molecular pathogenesis of ependymomas is not extensively studied. Lack of correlation of histological grade with patient outcome has directed attention towards identification of molecular alterations as novel prognostic markers. Recently, 1q gain has emerged as a potential prognostic marker, associated with decreased survival, especially in posterior fossa, high grade tumors. Cases of intracranial ependymomas were retrieved. Tumors were graded using objective criteria to supplement WHO grading. Fluorescence in situ hybridization for 1q gain was performed on formalin-fixed paraffin embedded sections. Eighty-one intracranial ependymomas were analyzed. Pediatric (76%) and infratentorial (70%) ependymomas constituted the majority. 1q gain was seen in 27 cases (33%), was equally frequent in children (34%) and adults (32%), supratentorial (37%) and infratentorial (32%) location, grade II (33%) and III (25%) tumors. Recurrence was noted in 24 cases and death in 7 cases with 5-year progression-free and overall-survival rates of 37% and 80%, respectively. Grade II tumors had a better survival than grade III tumors; histopathological grade was the only prognostically significant marker. 1q gain had no prognostic significance. 1q gain is frequent in ependymomas in Indian patients, seen across all ages, sites and grades, and thus is likely an early event in pathogenesis. The prognostic value of 1q gain, remains uncertain, and multicentric pooling of data is required. A histopathological grading system using objective criteria correlates well with patient outcome and can serve as an economical option for prognostication of ependymomas.

Role of mTOR signaling pathway in the pathogenesis of subependymal giant cell astrocytoma - A study of 28 cases.

BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are slow-growing benign intraventricular tumors, the pathogenesis of which is debated. Recent studies have shown that tuberous sclerosis complex (TSC) 1 and TSC2 genes are linked to the mammalian target of rapamycin (mTOR) cell signaling pathway. We aimed to analyze TSC1 and TSC2 gene mutation, hamartin and tuberin protein expression, and protein expression of mTOR signaling cascade in a series of SEGA to determine their role in pathogenesis. MATERIALS AND METHODS: Twenty-eight SEGA cases were retrieved from archival material. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue using antibodies against tuberin, hamartin, phospho-p70S6 kinase, S6 ribosomal protein, phospho-S6 ribosomal protein, phospho-4E-BP1, Stat3, and phospho-Stat3. Mutation analysis of TSC1 (exons 15 and 17) and TSC2 (exons 33, 39, and 40) was done by DNA sequencing. RESULTS: Loss of immunoexpression of either hamartin or tuberin was found in 19 cases (68%). Pathogenic point mutations in selected exons of TSC1 and TSC2 genes were present in 5 of 20 cases studied. Robust expression of mTOR downstream signaling molecules phospho-p70S6 kinase (100%), S6 ribosomal protein (82%), phospho-S6 ribosomal protein (64%), phospho-4E-BP1 (64%), and Stat3 (100%) was seen. Four cases (14%) showed immunopositivity for phospho-Stat3. There was no significant correlation of these markers with immunoloss of tuberin and hamartin. SIGNIFICANCE: There is a definite role for TSC1 and TSC2 genes in the pathogenesis of SEGA as evidenced by loss of protein expression and presence of mutations. Strong expression of mTOR downstream signaling proteins indicates activation of mTOR pathway in these tumors, suggesting that proteins in this pathway may have the potential to serve as therapeutic targets in these patients.

Systemic and local levels of fetuin-a in calcified mitral valves of rheumatic heart disease.

BACKGROUND AND AIM OF THE STUDY: Fetuin-A is a circulating glycoprotein that inhibits ectopic calcification. The study aim was first, to assess serum fetuin-A level in patients with calcified rheumatic mitral valve disease (RMVD), and second, to demonstrate the presence of fetuin-A by immunohistochemistry (IHC) in calcified RMVD which, to date, has not been verified in other studies. METHODS: The study group comprised 68 adult patients with isolated RMVD and normal renal function. Of these patients, 34 (27 males, seven females; mean age 33.44 +/- 9.0 years) had severe calcification (Wilkins calcium score 3 or 4) and 34 (25 males, nine females; mean age 30.8 +/- 8.5 years) had mild calcification (Wilkins calcium score 1 or 2). A group of 32 age- and gender-matched healthy subjects (25 males, seven females; mean age 29.5 +/- 4.6 years) served as controls. Baseline serum fetuin-A levels were measured using an enzyme-linked immunosorbent assay (ELISA), while Wilkins calcium scores were assessed using either transthoracic or transesophageal echocardiography. Serum levels of calcium, phosphorus and alkaline phosphatase were assessed in all subjects. Histopathological examinations of ten severely calcific rheumatic mitral valves were made and compared with 10 non-calcified rheumatic mitral valves, all of which had undergone mitral valve replacement. RESULTS: Serum fetuin-A levels were significantly lower in RMVD patients than in controls (108.83 +/- 7.1 versus 114.46 +/- 3.32 ng/ml; p = 0.014). However, there was no significant difference in fetuin-A level between patients with severe (C3/C4) versus mild calcification (C1/C2) (108.84 +/- 7.82 versus 108.82 +/- 6.36 ng/ml; p = NS). No correlation of fetuin-A was seen with serum high-sensitivity C-reactive protein, calcium, phosphorus and alkaline phosphatase, or with Wilkins' calcium score. IHC analyses revealed the presence of fetuin-A in the mesenchymal matrix and calcified area of calcific valves, while minimal to absent fetuin-A deposition was detected in the mesenchymal matrix of non-calcified mitral valves. CONCLUSION: Serum fetuin-A levels were significantly decreased in patients with calcific RMVD. The present study was the first to demonstrate fetuin-A in the calcified mitral valve of rheumatic etiology, and suggests its possible role in the pathophysiology of calcific mitral valve disease. Further studies are required, however, to determine therapeutic implications.

Study of biomarkers p53, Ki-67, Bcl-2, and VEGF in pterygium.

PURPOSE: To study the biomarkers present in primary pterygium samples of patients of Indian ethnicity and compare it with the samples obtained from the unaffected conjunctiva of the same eye. METHODS: A prospective case-control study of 17 eyes in patients above 10 years of age with primary pterygium who underwent pterygium excision using limbal conjunctival autograft technique. The pterygium samples (cases) and conjunctival samples (controls) were sent for immunohistochemical (IHC) staining for the following biomarkers: p53, Bcl-2, Ki-67, and vascular endothelial growth factor (VEGF). RESULT: The immunohistochemistry of the samples and the controls revealed p53 positivity in 47.05% of pterygium samples and 29.4% of controls ( P < 0.587). Nine cases each in pterygium and control samples were positive for Ki-67 expression. Differences in the staining pattern between the two groups were not statistically significant ( P < 1.000). Bcl-2 positivity was seen in 10 pterygium samples (58.8%) and 12 controls (70.5%), with no statistical difference between the two groups ( P < 0.455). VEGF expression was seen in both epithelial and endothelial cells of the samples and controls, with no statistical difference between the two groups, with P = 1.000 for the epithelial staining and P = 0.637 for endothelial staining. CONCLUSION: The expression of biomarkers was comparable in both groups. We conclude that pterygium, against common belief, might not be a localized disease process but a global ocular phenomenon where the apparently healthy tissue also has some ongoing disease process at a molecular level.

Analysis of Histomorphologic/Molecular Association and Immune Checkpoint Regulators in Epithelioid Glioblastoma and Pleomorphic Xanthoastrocytoma: Are These Tumors Potential Candidates for Immune Checkpoint Blockade?

Accurate diagnosis of Epithelioid glioblastoma (eGB) and pleomorphic xanthoastrocytoma (PXA) is sometimes challenging owing to overlapping histologic and genetic features. There are limited reports on the immune profile of these tumors. In this study, we assessed 21 PXA [15 PXA Grade 2 (PXAG2); 6 PXA Grade 3 (PXAG3)] and 14 eGB for their histopathological and molecular association. Further, their immune profile was compared with GB, IDH1 wild-type (wt) (n-18). Morphologically, PXAG2 mostly differed from eGB; however, it was occasionally difficult to differentiate PXAG3 from eGB due to their epithelioid pattern and less obvious degenerative features. PXAG2 showed predominantly diffuse, whereas variable positivity for epithelial and glial markers was seen in PXAG3 and eGB. All cases showed retained nuclear ATRX and INI-1 . H3K27M or IDH1 mutation was seen in none. P53 mutation was more common in eGB, followed by PXAG3, and least common in PXAG2. BRAF V600E mutation was observed in 66.67% PXAG2, 33.33% PXAG3, and 50% eGB, with 100% concordance between immunohistochemistry (IHC) and sequencing. Thirty-six percent eGB, 33% PXAG3, and 61% PXAG2 harbored CDKN2A homozygous deletion. EGFR amplification was observed in 14% eGB and 66% of GB, IDH wt. PDL1 and CTLA-4 expression was higher in eGB (71.4% and 57.1%), PXAG3 (66.6% and100%), and PXAG2 (60% & 66.7%) as compared with GB, IDH wt (38.8% and 16.7%). Tumor-infiltrating lymphocytes were also observed in a majority of eGB and PXA (90% to 100%) in contrast to GB, IDH wt (66%). This analysis highlights the homogenous molecular and immune profile of eGB and PXA, suggesting the possibility that histologically and molecularly, these two entities represent 2 ends of a continuous spectrum with PXAG3 lying in between. Higher upregulation of PDL1, CTLA-4, and increased tumor infiltrating lymphocytes in these tumors as compared with GB, IDH wt suggests potential candidature for immunotherapy.

Role of corneal collagen cross-linking in pseudophakic bullous keratopathy: a clinicopathological study.

OBJECTIVE: To evaluate the clinical and histopathologic changes induced by collagen cross-linking (CXL) in pseudophakic bullous keratopathy (PBK). DESIGN: Randomized, prospective, interventional study. PARTICIPANTS: Twenty-four patients with PBK were included in the study. METHODS: Twenty-four patients with PBK underwent CXL followed by keratoplasty at 1 or 3 months. Twelve patients underwent penetrating keratoplasty 1 month after CXL (group A) and the remaining 12 patients underwent penetrating keratoplasty 3 months after CXL (group B). The main outcome measures were assessed at 1 week and 1 month for all patients and at 3 months for 12 patients only. The corneal buttons underwent histopathologic and immunofluorescence evaluation. MAIN OUTCOME MEASURES: Visual acuity, ocular discomfort (tearing, redness, pain), corneal haze, central corneal thickness, histopathologic evaluation, and immunofluorescent microscopy. RESULTS: Mean visual acuity showed a significant improvement after CXL, from 1.925 ± 0.173 before surgery to 1.75±0.296 at 1 month after surgery (P = 0.010), but deteriorated to 1.81 ± 0.23 at 3 months. Symptomatic relief after CXL was at a maximum at 1 month, with a worsening trend at 3 months. Eighteen patients showed a reduction in corneal haze 1 month after CXL. The effect was maintained in 9 of 12 patients at 3 months. The mean central corneal thickness decreased significantly from 846.46 ± 88.741 to 781.0 ± 98.788 µm at 1 month (P<0.01) after CXL, but increased to 805.08±136.06 µm at 3 months. Immunofluorescence microscopy revealed anterior stromal compaction in 7 of 12 patients (58.3%) in group A and in 5 of 12 patients (41.6%) in group B. Staining of keratocyte nuclei with 4',6-diaminido-2-phenylindole dihydrochloride (Molecular Probes, Carlsband, CA) revealed a relative uniform distribution throughout the stroma. CONCLUSIONS: Collagen cross-linking causes symptomatic relief and a decrease in central corneal thickness and anterior stromal compaction in PBK. However, the effect decreases with time and depends on disease severity.

Sphenoid wing lymphoplasmacyte-rich meningioma with occasional emperipolesis closely simulating an intracranial Rosai-Dorfman disease: a diagnostic dilemma.

In lymphoplasmacyte-rich meningioma (LRM) meningothelial whorls are overshadowed by exuberant infiltration by lymphocytes, plasma cells and few histiocytes. Hence, lesions with lymphoplasmacytic proliferation form the histological differentials. We describe the, to the best of our knowledge, first case of LRM with occasiona emperipolesis, creating a diagnostic dilemma with Rosai-Dorfman disease (RDD), around the region of sphenoid wing. LRM was favored due to the presence of epithelial membrane antigen (EMA) and vimentin positive meningothelial whorls, forming approximately 10% of the tumor tissue. Documentation of such cases may help to understand the importance of inflammatory cells and meningothelial whorls, as a manifestation of host response at the leptomeninges.

Coexistent Rosai Dorfman disease and Langerhans cell histiocytosis in an Orbital mass: A Case Report.

INTRODUCTION: Rosai Dorfman disease (RDD) is a rare benign histiocytic proliferative disorder of lymph node sinuses. Langerhans cell histiocytosis (LCH) is a solitary or multisystem clonal proliferation of abnormal dendritic cells (Langerhans cells) with varied presentations. The co-occurrence of these two entities is quite rare. CASE DESCRIPTION: A six-year-old boy presented with multiple mass lesions in the neck since two years and a nodular lesion in right upper eyelid for the past 4 months. He was diagnosed with tubercular lymphadenitis 2 years back, and was given a course of anti-tubercular therapy (ATT) elsewhere. No improvement was seen. Fine needle aspiration cytology (FNAC) of the cervical lymph nodes revealed reactive lymphadenitis while lymph node biopsy showed features of RDD. Excision biopsy of the orbital mass showed features of both RDD and LCH. The patient was started on tablet prednisolone. Six months later, complete resolution of lymph node enlargement and remaining orbital mass was noted. Post operative contrast enhanced Magnetic Resonance Imaging of head and neck was normal. CONCLUSION: The coexistence of RDD and LCH may be a result of divergent differentiation from a common lineage or a de novo phenotypic evolution.

Classification of endoscopic ultrasound guided fine needle aspiration cytology of pancreatic space occupying lesions by Papanicolaou Society of Cytopathology System: A five year study.

BACKGROUND: Majority of the pancreatic cancer patients present at an advanced stage and have poor 5 year survival rate. Thus, there is a need for early detection of pancreatic cancer with the initiation of the therapy. MATERIALS & METHODS: This is a retrospective study including all the endoscopic ultrasound guided (EUS) guided pancreatic FNAs from 2016 to 2020. The aspirate smears were analyzed and classified according to The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSCPC). RESULTS: A total of 245 EUS guided FNAs from pancreatic lesions were included. Cyto-histological correlation was done wherever available. Category I (non diagnostic) accounted for 40 cases (16%) cases, Category II (negative) comprised of 44 cases (18%); and Category III (Atypical) had 5 cases (2%). Category IV neoplastic-benign category included 3 cases of serous cystadenoma, while neoplastic-others category included pancreatic neuroendocrine tumors (n = 21), solid pseudo-papillary neoplasms (SPEN) (n = 12) and mucinous cystic neoplasms (n = 4). A total of 7 cases (2.8%) were reported in Category V (Suspicious). A diagnosis of adenocarcinoma (Category VI) was rendered in 105 cases (42.8%) cases. Rarer types included non Hodgkins lymphoma (n = 3) and one case of primary undifferentiated carcinoma with osteoclastic giant cells. Cyto-histological correlation in all categories was available in 58 cases with 8 false negative cases. Thus overall sensitivity of EUS guided FNAC was found to be 87.8% with a diagnostic yield of 83.6% while sensitivity in diagnosing adenocarcinoma was 96.9%. CONCLUSION: The present study highlights the spectrum of EUS guided FNA of pancreatic lesions in a subset of North Indian population and classified them according to PSCPC. EUS guided FNAC is a sensitive investigation which plays a crucial role in confirming the diagnosis of pancreatic space occupying lesions (SOLs) in advanced stage.

Anastrozole-mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: an initial perspective.

The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole-CypD complex is more stable than cyclosporin A (CsA)-CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings.Communicated by Ramaswamy H. Sarma.

Multicentric extranodal Rosai Dorfman disease--a cytological diagnosis, with histological corroboration.

BACKGROUND: Rosai Dorfman disease (RDD) typically presents with massive bilateral cervical lymphadenopathy, a viral-like prodrome, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Other lymph nodes may be less commonly involved. Extranodal RDD is quite rare, and orbital disease accounts for only 10% of the extranodal sites of involvement. Multicentric disease has also been described, which is usually accompanied by lymphadenopathy either initially or later in the disease course. CASE: We report an extremely rare extranodal multicentric disease in a diabetic patient, presenting with bilateral orbital involvement, causing ocular motility restriction, which was diagnosed on aspiration cytology of the orbital mass. This was followed in quick succession by new mass lesions in the lower back and infratemporal fossa. On extensive work-up, no lymphadenopathy was detected. The patient responded well to surgical debulking of the orbital lesions and systemic steroids. CONCLUSION: Fine needle aspiration cytology can be effectively applied for early diagnosis of multicentric extranodal RDD. Surgical debulking in such cases may be supplemented by systemic steroids.

Challenges in the Management of Upper Lid Keloid.

A middle-aged lady presented with a firm, nontender mass on the left upper lid and area behind the left ear following lid reconstruction with postauricular graft for cicatricial ectropion 11 months prior. She had a similar mass on the right shin. She was diagnosed as a case of multiple keloids. Intralesional injection of triamcinolone acetonide suspension and 5-Fluorouracil (5-FU) in the upper lid keloid resulted in ulceration of its surface. Surgical excision, injection of 5-FU in the keloid bed with temporal forehead flap reconstruction, was performed. Occurrence of inadvertent postoperative wound infection with Acinetobacter baumannii was treated with local dressing with colistimethate sodium. Adjuvant therapy with topical imiquimod cream 5% was given subsequently for 24 weeks with no recurrence of the lid keloid after 16 months. The patient was managed using a combination of conservative and surgical therapy and multidisciplinary team work and kept on a long term follow-up.