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Adamantinomatous craniopharyngioma is a grade 1 tumor that arises in a sellar/suprasellar location. Despite being a grade 1 tumor, there is high recurrence and endocrinal insufficiency. Malignancy arising in craniopharyngioma is extremely rare, has a dismal prognosis, and is currently not included as a separate entity in the World Health Organization Classification of Central Nervous System 5th edition. Here we describe a case of adamantinomatous craniopharyngioma and its malignant counterpart. The malignant part had unique histomorphology and basaloid cells with pseudoglandular architecture and a myxoid background. It bore a striking resemblance to adenoid cystic carcinoma. Both the benign and malignant counterparts were beta‐catenin and SOX‐2 positive, providing proof of the malignant part arising from the benign part. Tumors like squamous cell carcinoma and odontogenic ghost cell carcinoma have been described in cranipharyngioma. This case study is the first to describe this unique morphology of adenoid cystic carcinoma‐like features. The possibility of adenoid cystic carcinoma was excluded by immunohistochemistry. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is one of the most devastating injuries which causes either complete or partial loss of movement, balance, muscular coordination and endurance. Electromagnetic field (EMF) stimulation has been shown to reduce muscle atrophy and fiber-type switching and improves muscle function in a hindlimb suspension model. The present study aims to elucidate the therapeutic potential of EMF stimulation on motor neuron excitability, soleus muscle morphology and function in complete SCI rats. Thirty-six adult male Wistar rats were randomly divided into Sham, SCI and SCI+EMF groups. Complete transection was done at the T13 spinal level, followed by whole-body EMF exposure for 7 or 14 days. Hyper-reflexia, muscle atrophy, reduction in twitch and tetanic force with earlier onset of fatigue was evident in the SCI group. EMF stimulation showed significant improvement in H and M wave parameters, H/M ratio, muscle twitch and tetanic force, fusion frequency and fatigability. A significant increase in regenerating myofibers and reduction in muscle degeneration following EMF was evident on histopathological examination. Further, EMF significantly increased myogenic protein levels responsible for muscle regeneration. Our study demonstrates for the first time the potential of EMF to modulate motor neuron excitability and muscle contractile function in SCI rats through activity-dependent mechanisms. [ABSTRACT FROM AUTHOR]

Subependymal giant cell astrocytoma (SEGA) is a World Health Organization grade 1 neoplasm, which, due to its dubious morphologic features, may be misdiagnosed as a high-grade tumor at times. This tumor shows binary immunoexpression including both glial and neural markers, leading to a state of diagnostic quandary. Recent evidences have surmised the diagnostic utility of thyroid transcription factor 1 (TTF-1), spurring us to study the practicality of this marker in distinguishing SEGAs from its mimics. In this study, TTF-1 immunohistochemistry using clone 8G7G3/1 (1:50) was performed in 38 cases of SEGA, 30 cases of central neurocytoma, 10 cases each of intraventricular glioblastoma and ependymoma, and 5 cases of cortical tubers. Additionally, serine/threonine-protein kinase B-Raf (BRAFV600E) mutation, a common genetic alteration in pediatric low-grade-glial tumors with neuronal-differentiation, was analyzed using Ventana immunohistochemistry platform. TTF-1 immunopositivity was seen in all 38 cases (100%) of SEGAs, with 20 cases (52.6%) showing diffuse (>50% of tumor area) expression while focal (<50%) immunopositivity was seen in 18 cases (47.3%). None of the cases demonstrated serine/threonine-protein kinase B-Raf immunolabeling. Barring 2 cases of neurocytoma (6.6%), all other cases including ependymoma, glioblastoma, and cortical tubers were immunonegative for TTF-1. The congruous finding of TTF-1 expression in SEGA and cells of the developing neuroepithelium in the medial ganglionic eminence hint toward a primogenitor cell with neoplastic potential in the presence of impelling factors. [ABSTRACT FROM AUTHOR]

Granular cell astrocytoma (GCA) is an aggressive variant of astrocytoma characterized by predominantly round-to-polygonal cells with abundant eosinophilic granular cytoplasm. This tumor usually lack the morphological signatures of conventional astrocytoma and are devoid of typical features which define a malignant neoplasm, leading to potential misdiagnosis. We report GCA in a 50-year-old man presenting with severe headache along with vertiginous sensation and sensory seizures of left upper limb for past two months. Imaging showed multiple intra-axial, hyperintense space-occupying lesions in bilateral anterior temporal lobe, left parietal lobe, left thalamus and cerebellum, raising possibility of lymphoma/metastases. Histopathologic examination revealed sheets of large polygonal cells with distinct cellular outline, ample amount of eosinophilic PAS-positive granular cytoplasm, eccentrically placed irregular, round-to-ovoid nuclei with occasional prominent nucleoli. On immunohistochemistry, tumor cells were diffusely immunopositive for Olig2, S100, EMA, lysozyme and CD68, and they were immunonegative for GFAP, LCA, pan-CK, TTF-1, TFE-3, PAX-8, SOX10, MAP2, MBP, NF, H3K27M, H3K27me3, p53, IDH1 (R132H), CD1a, langerin and BRAFV600E. Numerous scattered macrophages were highlighted by CD163. MIB 1-labelling-index was approximately 5%–6%. Overall features were congruous with final diagnosis of GCA. GCAs behave in a belligerent manner irrespective of their morphologic grade as they are seen to exhibit genetic alterations similar to glioblastoma. Thereby, they warrant early diagnosis for conducive patient management. [ABSTRACT FROM AUTHOR]

Lipogenic differentiation in ependymoma is an infrequent occurrence with very few reported cases. The grading was done solely based on the histomorphology and molecular subtyping was not described in such ependymomas. New molecular classification divided ependymomas in nine different subgroups, of which supratentorial location tumor usually exhibits C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B fusion proteins. A 46-year-old female presented with headache and right-sided parapresis. Radilogy revealed a large intraxial left parietooccipital mass lesion, which histologically and immuohistochemically confirmed as anaplastic ependymoma with extensive lipogenic changes. The ependymal origin of the tumor was corroborated by the immunohistochemistry and ultrastructural studies. Molecular studies for C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B fusion proteins were negative. This is the first documentation of fusion negative supratentorial anaplastic ependymoma with lipogenic differentiation. This novel finding needs further reinforcement by similar studies to identify its impact on the disease outcome. [ABSTRACT FROM AUTHOR]

Glycogen branching enzyme deficiency/Andersen disease can manifest with a spectrum of clinical phenotypes, making the diagnosis difficult. An 11-year-old Pakistani boy presented with a history of progressive weakness and delayed milestones. Echocardiography showed features of dilated cardiomyopathy. He was suspected to have congenital myopathy and was evaluated further. Muscle biopsy showed subsarcolemmal accumulation of basophilic material, which stained positively with Periodic acid-Schiff reagent (diastase-resistant). Ultrastructural examination revealed accumulation of structurally abnormal forms of filamentous glycogen, confirming the diagnosis as Andersen disease. As histopathological and immunohistochemical evaluation of muscle biopsies is not always diagnostic, ultrastructural examination may serve as a valuable adjunct in difficult cases. [ABSTRACT FROM PUBLISHER]

Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma found to have malignant potential and poorer prognosis. It is characterized by the predominance of epithelioid cells and frequent association with tuberous sclerosis. Its usual age of presentation is between the fourth and fifth decades of life, and only a single case has been reported in the pediatric age group. In this study, we report a case of epithelioid angiomyolipoma in a 4-year-old child with features of tuberous sclerosis, which is the youngest age of presentation. [ABSTRACT FROM AUTHOR]

Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma found to have malignant potential and poorer prognosis. It is characterized by the predominance of epithelioid cells and frequent association with tuberous sclerosis. Its usual age of presentation is between the fourth and fifth decades of life, and only a single case has been reported in the pediatric age group. In this study, we report a case of epithelioid angiomyolipoma in a 4-year-old child with features of tuberous sclerosis, which is the youngest age of presentation. [ABSTRACT FROM AUTHOR]

Uterus-like mass is an extremely rare choristoma of müllerian origin arising in association with neural tube defects. In this article, we describe the case of a 9-year-old girl with spina bifida, a mass lesion within the conus, and a subcutaneous lipoma in the lumbosacral region. Histopathological examination of the conus lesion revealed a uterus-like structure comprising of endometrial glands and stroma surrounded by fascicles of smooth muscle. This case differs from the few previously described cases in absence of neurological symptoms and early age at diagnosis. Thorough histopathological examination of resected tissue is therefore recommended for the diagnosis of this rare entity, as it may not have a typical presentation in all instances. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The involvement of the ovaries in lymphomatous processes is a relatively rare phenomenon. Secondary involvement as a part of systemic disease is common as compared to de novo primary lymphoma. Mostly, primary ovarian lymphomas are diffuse large B cell type, whereas the precursor lymphoblastic lymphomas are extremely rare and only four cases have been reported previously. We herein describe a case of primary precursor B lymphoblastic lymphoma involving both ovaries in a 28-year-old woman which was detected incidentally and spread into the blood after 7 months; consequently she succumbed to the disease. [ABSTRACT FROM AUTHOR]

Occurrence of extrarenal Wilms' tumor, in the lumbosacral region, as such or as a component of immature teratoma is an extremely uncommon condition and this diagnosis is almost always postsurgical. We report a case of immature teratoma in the lumbosacral region which was composed of mature teratomatous components and Wilms' tumor as an immature component. This 20-day-old male child presented with a swelling over the lower back at birth. Imaging of the spine revealed spina bifida and tethered cord. Excision of soft tissue swelling and detethering of the cord was performed. This case represents the fourth reported case of lumbosacral Wilms' tumor as a component of immature teratoma associated with spinal dysraphism. We discuss possible mechanisms and clinical characteristics of extrarenal Wilms' tumor and present a short review of the literature. [ABSTRACT FROM AUTHOR]

Clear cell variant of ependymoma is a rare entity which morphologically mimics oligodendroglioma and poses a diagnostic dilemma. We describe three cases of clear cell ependymoma in male children which were supratentorial in location. On microscopic examination, these tumors were composed of sheets of clear cells and resembled oligodendroglioma. Electron microscopy confirmed the ependymal nature of these tumors. Clear cell ependymomas are rare and aggressive tumors. More cases need to be reported to determine their therapeutic responsiveness and prognosis. [ABSTRACT FROM AUTHOR]

Abstract: The occurrence of intradural spinal teratomas in association with spinal dysraphism is uncommon and even rarer is renal differentiation in a teratoma. We report two rare cases of patients with spinal dysraphism, split cord malformation and intraspinal teratomas with renal differentiation in a boy of 1 year and a girl of 3 years of age. Surgical excision of the mass, detethering of the cord and repair of the lipomyelomeningocele was done. Pathologic examination in both the cases revealed features of a mature teratoma with nephrogenic differentiation in the form of elements of mature renal tissue. To the best of our knowledge, spinal teratoma with renal component has not been described previously. [Copyright &y& Elsevier]

Context.-Muscle biopsy is at present the gold standard for the diagnosis of idiopathic inflammatory myopathies (IIMs), which include dermatomyositis, polymyositis, and inclusion body myositis. Currently, there is no definite diagnostic marker that helps in the discrimination of different subgroups of IIMs and the discrimination of IIMs from other clinical and morphologic mimics. Major histocompatibility complex (MHC) class I and II antigens are not expressed on normal muscle fibers. Objective.-To determine the diagnostic utility of MHC class I and II antigen expression on the muscle biopsies from patients with various neuromuscular disorders and to validate its addition in the existing diagnostic armamentarium. Design.-Expression of MHC class I and II antigen was studied on 126 muscle biopsies, of which 62 were IIMs and 64 were controls (taken from patients with other neuromuscular disorders). Results.-When compared with controls, the sensitivity of MHC class I expression for diagnosis of IIMs was 88.7% (100%, 81.6%, and 100% for dermatomyositis, polymyositis, and inclusion body myositis, respectively), with a specificity of 89.1%. The specificity of MHC class II expression was 100% for all IIMs. Conclusion.-Detection of MHC class I and II antigen expression is extremely helpful in the diagnosis of IIMs and has high sensitivity and specificity, especially in dermatomyositis. This expression can be used as a diagnostic tool in discriminating IIMs from other muscle diseases in which it is either absent or weakly expressed. [ABSTRACT FROM AUTHOR]

Central neurocytomas (CN) are uncommon tumors of the central nervous system, most descriptions of which available in the literature are in the form of isolated case reports and small series. Owing to this rare incidence, diagnosis and management of this neoplasm remain controversial. Usually, these tumors affect lateral ventricles of young adults and display characteristic neuroimaging and histomorphologic findings. Neurocytomas often mimic oligodendrogliomas when confirmation of diagnosis rests on immunohistochemistry, ultrastructure, and genetic studies. Extraventricular neurocytomas, situated entirely within the brain parenchyma and spinal cord, have also been reported. Typically, CN are associated with a favorable outcome although cases with more aggressive clinical course with recurrences are not unknown. MIB-1 labeling index (LI) of >2% often heralds poor prognosis and tumour recurrence. Safe maximal resection is presently considered the ideal therapeutic option, with best long-term prognosis in terms of local control and survival. The role of adjuvant radiotherapy apparently seems to benefit patients with incomplete resection and in atypical neurocytoma. Utility of other therapeutic regimen, however, remains shrouded in controversy. Epidemiology, histogenesis, clinical profile, histology, neuroimaging and therapeutic modalities of neurocytomas have been comprehensively reviewed, with special emphasis on CN and extraventricular neurocytomas and their atypical counterparts. [ABSTRACT FROM AUTHOR]

Background: Surgical management of intractable epilepsies is currently an established mode of therapy in various clinical settings. Aims: To retrospectively evaluate the neuropathological findings in both temporal and extratemporal lobe resections in such patients. Materials and Methods: The study included resected specimens from patients with intractable epilepsy managed at a tertiary care hospital of India, during a 10-year period (1995-2004). Results: A total of 153 patients, with mean age of 19.4 years and male predominance (73.2%) were included in the study. Overall, there was a predilection for the temporal lobe (73.2%), while 41 cases were extratemporal in location. On histopathology, mesial temporal sclerosis (MTS) (24.8%) was the commonest lesion, followed by tumors (19.6%) and isolated focal cortical dysplasia (FCD - 15.11%). Other less common findings included Rasmussen encephalitis, non-specific gliosis and vascular malformations. In addition, 20.9% (32 cases) had dual lesions, majority of which included FCD with ganglioglioma (15 cases) or with dysembryoplastic neuroepithelial tumor (12 cases). In the temporal lobe, neoplasms and dual lesions formed the majority (apart from MTS), unlike dual lesions followed by neoplasms and FCD, in the extratemporal location. Conclusion: This series demonstrates that most patients with chronic intractable epilepsy have significant histopathological findings and highlights the neuropathological spectrum of such lesions, in the Indian context. This was similar to that reported from the West, but different from the single Indian series available in the literature. Further, the overall profile of temporal lobe lesions was not different from the Extratemporal ones. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) Patients generally have a dismal prognosis, with median survival of 10-12 months. GBM with long-term survival (LTS) of ≥ 5 years is rare, and no definite markers indicating better prognosis have been identified till date. The present study was undertaken to evaluate GBMs with LTS in order to identify additional correlates associated with favourable outcome. The cases were evaluated for relevant clinicopathological data, proliferation index and expression of tumortumour suppressor gene (p53), cyclin-dependant kinase-inhibitors (p27 and p16) and epidermal growth factor receptor (EGFR) proteins. Six cases of GBM with LTS with an average survival of 9 years (range 5-15 years) were identified. All were young patients with mean age of 27 years (range 8-45 years). Histology of three cases was consistent with conventional GBM, while two showed prominent oligodendroglial component admixed with GBM areas. One was a giant cell GBM, which progressed to gliosarcoma on recurrence. The mean MIB-1LI was 12% (range 6-20%). p53 was immunopositive in 4 out of 5 cases. EGFR and p27 were immunonegative in all, whereas p16 was immunonegative in 3 out of 5 cases. Currently, in the absence of specific molecular and genetic markers, GBM in young patients should be meticulously evaluated for foci of oligodendroglial component and/or giant cell elements, in addition to proliferative index and p53 expression, since these probably have prognostic connotations, as evident in this study. The role of p16 and p27 however needs better definition with study of more number of cases. [ABSTRACT FROM AUTHOR]

Background: Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy.Aims: We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease.Materials and Methods: Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation.Results: Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms.Conclusion: It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication. [ABSTRACT FROM AUTHOR]

The article describes the case of an 18-year-old male who developed angiocentric glioma (AG). The patient presented with complex partial seizures since the age of 4 years. AG refers to a rare tumor of the central nervous system (CNS) in children and young adults, and accounts for 2.3% of tumors associated with chronic pediatric epilepsy.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery. [ABSTRACT FROM AUTHOR]

Astroblastoma is an uncommon circumscribed glial tumor mostly involving the cerebral hemisphere. The characteristic molecular alteration is meningioma (disrupted in balanced translocation) 1 (MN1) rearrangement. No definite World Health Organization grade has been assigned as both low‐ and high‐grade tumors are known to occur. Tumors in the spine are extremely rare; to date only three cases have been reported in the literature. A vigilant microscopy and ancillary testing aid in diagnosis when the tumors present in unusual locations, as in our case. The prompt differentiation of this tumor from its mimickers is a mandate as modalities of management are different and not clearly established. [ABSTRACT FROM AUTHOR]

Cutaneous epithelioid angiomatous nodule (CEAN) represents a recently described benign vascular proliferation. We report a case affecting a 28-year-old man who presented with painful nodules on his glans penis. The patient is symptom-free 18 months after tumor excision. This is the first report of CEAN occurring on the glans penis. Kaushal S, Sharma MC, Ramam M, Kumar U. Multifocal cutaneous epithelioid angiomatous nodules of the penis. [ABSTRACT FROM AUTHOR]

Malacoplakia is an unusual chronic granulomatous inflammation that commonly occurs in the urinary tract. It is rarely encountered in the head and neck region, and only a handful of such cases have been described. We report a case of malacoplakia in a 50-year-old woman who presented with a mass in the vallecula that was clinically suspected of being malignant. This case illustrates the importance of recognizing this unusual benign lesion, which closely mimics a malignancy on clinical examination. [ABSTRACT FROM AUTHOR]

Familial hyperpigmentation, or melanosis universalis hereditaria, is a rare hyperpigmentary disorder with onset in infancy. Here, we describe monozygotic twins with similar pattern of progressive hyperpigmentation with onset in early neonatal period without any family history. Histopathological examination showed increased melanin throughout the epidermis. Although hereditary defects may influence melanogenesis resulting in a pigmentary anomaly, the pathogenesis of hyperpigmentation in this case remains unclear. [ABSTRACT FROM AUTHOR]

Although cavernous hemangiomas and a few cases of angiosarcoma in the urinary bladder have been described, only a single case of epithelioid hemangioendothelioma of the urinary bladder has been documented in English publications, to date. Therefore, the biologic properties of epithelioid hemangioendothelioma in this location are uncertain. We report the clinical and pathologic findings of a case of primary epithelioid hemangioendothelioma of the urinary bladder in a 17-years-old boy. The tumor was treated by transurethral resection. [Copyright &y& Elsevier]

Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas are considered the gold standard treatment for Cushing disease (CD). Even with various recent advances in management, disease persistence and recurrence are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64% to 93%. This study aims to determine the various clinical, biochemical, radiological, and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-κB, and SHH pathway activation and to study the protein expression of activation markers of these pathways (i.e., c-Fos, c-Jun, GLI-1, pMEK, NR4A1, and p44) in functioning corticotroph pituitary adenomas. From January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n = 174 surgeries) for CD with a median follow-up of 8.1 years (range, 1–13.29 years) were ambispectively analyzed. The preoperative clinical, biochemical, and radiological features, operative findings, postoperative clinical and biochemical data, and histopathological and molecular profiles were retrieved from the electronic medical records. The patients were followed up to assess their remission status. Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for pediatric patients, and 12 surgeries were for patients with Nelson syndrome. In the primary surgery cohort, 74.3% were female, and the average age was 28.73 ± 10.15 years. Of the primary surgery cohort, 75% of the patients experienced remission compared with 47.4% after revision surgery. The remission rate for the pediatric patients was 55.5%. The postoperative day 1 plasma cortisol (P < 0.001; area under the curve, 0.8894; range, 0.8087–0.9701) and adrenocorticotropic hormone (P < 0.001; area under the curve, 0.9; range, 0.7386–1) levels were seen to be strong independent predictors of remission in the primary surgery cohort. The remission rate after endoscopic TSS was greater than that after microscopic TSS in patients undergoing primary surgery (81.08% vs. 57.14%; P = 0.008). The presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (P = 0.020). On stratifying by surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of nonremission (odds ratio, 38.1; 95% confidence interval, 4.2–348.3) compared with endoscopically operated patients with adenoma found on HPE. A lower immunoreactivity score for NR4A1 was found to correlate with higher remission rates (P = 0.074). However, none of the molecular markers studied (i.e., c-Fos, c-Jun, GLI-1, pMEK, and p44) showed a significant correlation with the preoperative cortisol values. The remission rate after primary surgery is higher than that after revision surgery and is lower for pediatric patients than for adults. The postoperative day 1 plasma cortisol and adrenocorticotropic hormone levels are strong independent predictors of remission in the primary surgery cohort. An endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate; thus, endoscopy should be the approach of choice for these patients with the goal of identification of an adenoma on HPE. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Current molecular research has shown the several oncogenic pathways that give rise to the peripheral T‐cell lymphoma, not otherwise defined (PTCL, NOS) subtypes, which alter prognosis and might have predictive value. This study was conducted to assess the immunohistochemistry (IHC) algorithm by Amador et al for the subtyping of PTCL, NOS and determine its applicability in relation to the clinicopathological profile.This study included 43 patients with PTCL, NOS diagnosis. Following the use of IHC for the transcription factors GATA3, TBX21, CCR4, and CXCR3, two pathologists subtyped the samples. Comprehensive clinicopathological correlation was carried out.Applying the algorithm of Amador et al., cases were classified into GATA3 (20), TBX21 (15), and unclassified (8) subtypes. No significant association with clinical parameters of subtypes or CD4/ CD8 positivity was observed. Although a higher proportion of cases in the TBX21 subgroup showed a polymorphic population compared with the GATA3 subgroup, which had a monomorphic population, no significant p‐value (0.111) was observed. Two Lennert lymphomas were classified into the GATA3 subgroup. Multivariate analysis showed no significant difference in overall survival (p‐value = 0.105) and progression‐free survival (p‐value = 0.0509) between IHC‐defined subtypes; trends indicate that overall survival and progression‐free survival are worse in the GATA3 subgroup.Although the algorithm is reproducible, a proportion of cases remains unclassifiable and may require additional investigation and gene expression profiling. The GATA3 subgroup was found to have a monomorphic population with a poor overall prognosis and thus requires a larger sample size for validation. [ABSTRACT FROM AUTHOR]

Aim of the study: Activating Transforming factor 3 (ATF3) is a stress induced gene and closely associated with neuro-inflammation while Transforming growth Factor Beta (TGFβ) signalling is also reported to be involved in neuro-inflammation and hyper-excitability associated with drug resistant epilepsy. Animal model studies indicate the involvement of ATF3 and TGFβ receptors to promote epileptogenesis. Human studies also show that TGFβ signalling is activated in MTLE-HS. However, lack of studies on ATF3 and TGFβRI expression in MTLE-HS patients exists. We hypothesize that ATF3 and TGFβRI might be expressed in hippocampi of patients with MTLE-HS and playing role in epileptogenesis. Materials & methods: Protein expression of ATF3 and TGFβRI was performed by western blotting. Localisation of ATF3 was performed by immunohistochemistry and immunoflorescence. Results: Protein expression of ATF3 and TGFβRI was significantly up-regulated in hippocampi of patients as compared to controls. Also ATF3 IR was significantly expressed in hippocampi of patients and ATF3 was expressed predominantly in cytoplasm as compared to nucleus. No correlation was found between ATF3 expression and epilepsy duration and seizure frequency. Conclusions: ATF3 and TGFβRI are both important players in neuro-inflammation and might potentiate epileptogenesis in these patients. [ABSTRACT FROM AUTHOR]

Background: Spinal atypical teratoid rhabdoid tumor (AT/RT) is an extremely rare tumor and represents less than 2% of all AT/RTs. Methods: Available medical literature on spinal AT/RT in English was retrieved from PubMed and comprehensively reviewed. Clinical presentation, diagnosis, management, prognosis, and outcome in patients with spinal AT/RT have been elucidated by citing a case of extradural AT/RT of the cervicodorsal spine. Results: The age at presentation is usually less than 3 years. The most common site is the cervicodorsal spine. The most frequent tumor location is intradural extramedullary. A contrast-enhanced magnetic resonance imaging (MRI) of the entire neuraxis is the imaging modality of choice. The incidence of leptomeningeal dissemination is high (15–30%). Histopathological examination shows an admixture of primitive neuroectodermal, mesenchymal, and epithelial elements along with rhabdoid cells. Loss of SMARCB1/INI1 is considered pathognomonic of AT/RT. Maximal safe resection of tumor is the initial management of choice. Thereafter focal radiotherapy for localized tumor or craniospinal irradiation for leptomeningeal dissemination should be considered. Post-operative intensive polychemotherapy including intrathecal and high-dose chemotherapy (with autologous stem cell rescue) is usually considered to optimize survival. Typically, the time to recurrence and overall survival are less than 6 and 12 months, respectively. However, with judicious multimodality management long-term survivors are increasingly being recognized. The illustrative patient was a 18-month-old girl diagnosed with extradural AT/RT of the cervicodorsal spine (C3-D1), who was managed with maximal safe resection of tumor, multiagent chemotherapy (ICE-ifosfamide, carboplatin, etoposide) and focal RT to the tumor bed—50.4 Gy/28 fractions/5.5 weeks. At the last follow-up visit, 30 months after surgery, she had complete clinicoradiological response. Conclusion: Multimodal treatment comprising maximal safe resection of tumor, multiagent chemotherapy (ICE), and focal RT can lead to successful outcome in patients with localized spinal AT/RT, under the age of 3 years. [ABSTRACT FROM AUTHOR]

Spinal cysticercosis is a very uncommon manifestation of neurocysticercosis, which is caused by the larvae of Taenia solium. Here, we present a rare case of isolated lumbar intradural extramedullary neurocysticercosis, initially thought to be Tarlov cyst. A 40-year-old man, presented with low backache for 1-year with radiation of pain to right leg for 3 months. The patient was treated successfully with the surgical removal of the cyst, followed by medical treatment. Spinal neurocysticercosis should be considered in the differential diagnosis in high-risk populations, with new symptoms suggestive of a spinal mass lesion. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. Methods: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. Results: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. Conclusion: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration. [ABSTRACT FROM AUTHOR]

Background: Non-invasive biomarkers for early chemotherapeutic response in Ewing sarcoma family of tumors (ESFT) are useful for optimizing existing treatment protocol. Purpose: To assess the role of diffusion-weighted magnetic resonance imaging (MRI) in the early evaluation of chemotherapeutic response in ESFT. Material and Methods: A total of 28 patients (mean age = 17.2 ± 5.6 years) with biopsy proven ESFT were analyzed prospectively. Patients underwent MRI acquisition on a 1.5-T scanner at three time points: before starting neoadjuvant chemotherapy (baseline), after first cycle chemotherapy (early time point), and after completion of chemotherapy (last time point). RECIST 1.1 criteria was used to evaluate the response to chemotherapy and patients were categorized as responders (complete and partial response) and non-responders (stable and progressive disease). Tumor diameter, absolute apparent diffusion coefficient (ADC), and normalized ADC (nADC) values in the tumor were measured. Baseline parameters and relative percentage change of parameters after first cycle chemotherapy were assessed for early detection of chemotherapy response. Results: The responder:non-responder ratio was 21:7. At baseline, ADC ([0.864 ± 0.266 vs. 0.977 ± 0.246]) × 10−3mm2/s; P = 0.205) and nADC ([0.740 ± 0.254 vs. 0.925 ± 0.262] × 10−3mm2/s; P = 0.033) among responders was lower than the non-responders and predicted response to chemotherapy with AUCs of 0.6 and 0.735, respectively. At the early time point, tumor diameter (27% ± 14% vs. 4.6% ± 10%; P = 0.002) showed a higher reduction and ADC (75% ± 44% vs. 52% ± 72%; P = 0.039) and nADC (81% ± 44% vs. 48% ± 67%; P = 0.008) showed a higher increase in mean values among responders than the non-responders and identified chemotherapy response with AUC of 0.890, 0.723, and 0.756, respectively. Conclusion: Baseline nADC and its change after the first cycle of chemotherapy can be used as non-invasive surrogate markers of early chemotherapeutic response in patients with ESFT. [ABSTRACT FROM AUTHOR]

Malacoplakia is an unusual chronic granulomatous inflammation that commonly occurs in the urinary tract. It is rarely encountered in the head and neck region, and only a handful of such cases have been described. We report a case of malacoplakia in a 50-year-old woman who presented with a mass in the vallecula that was clinically suspected of being malignant. This case illustrates the importance of recognizing this unusual benign lesion, which closely mimics a malignancy on clinical examination. [ABSTRACT FROM AUTHOR]

Multinucleated giant cells are commonly encountered in histopathology and are mostly a clue to diagnosis but sometimes pose a diagnostic confusion. The present study elucidates a case series of giant cell lesions (GCL) with emphasis on differential diagnosis and other investigations that contribute towards arriving at a final diagnosis. We also intended to devise an algorithmic approach for the accurate pathological characterization of these lesions. All the cases reported in the department from January 2018 to June 2019 were reviewed by pathologists and the total number of lesions where giant cells were diagnostic or an additional finding were included in this study. Twenty-five cases out of 1000 biopsies were diagnosed based on giant cell morphology. The most frequent lesions were central giant cell granuloma, followed by cherubism, hyperparathyroidism, peripheral giant cell granuloma, tuberculosis, and hybrid lesion. A systematic approach towards differential diagnosis for such cases and a diagnostic algorithm was devised which is being followed as per the reported spectrum of GCL. Radiological, serology, and sometimes ancillary staining techniques are essential for the accurate histopathological diagnosis of giant cell lesions. Our diagnostic algorithm helps narrow down the spectrum of investigations necessary to characterize these lesions, enabling for a swifter and more confident identification of the pathologies. [ABSTRACT FROM AUTHOR]

Case Presentation: A 50-year-old woman who was a nonsmoker presented to the out-patient-department with history of dry cough and breathlessness on exertion for the past 4 months along with onset of dull aching chest pain for the last 2 weeks. Her breathlessness had gradually deteriorated to the point that she experienced dyspnea even on walking a few steps on level ground. Loss of appetite and significant weight loss during the same period also formed part of her clinical semiology. There was no history of fever, night sweats, orthopnea, paroxysmal nocturnal dyspnea, hemoptysis, dysphagia, hoarseness of voice, edema, headache, visual disturbance, weakness of any extremity, or drooping of eyelids. Her medical history revealed that she had undergone hysterectomy 8 years earlier for removal of a probable uterine mass, for which no documentation was available. [ABSTRACT FROM AUTHOR]

Low-grade dysembryoplastic neuroepithelial tumors (DNTs) are a frequent cause of drug-refractory epilepsy. Molecular mechanisms underlying seizure generation in these tumors are poorly understood. This study was conducted to identify altered genes in nonneoplastic epileptogenic cortical tissues (ECTs) resected from DNT patients during electrocorticography (ECoG)-guided surgery. RNA sequencing (RNAseq) was used to determine the differentially expressed genes (DEGs) in these high-spiking ECTs compared to non-epileptic controls. A total of 477 DEGs (180 upregulated; 297 downregulated) were observed in the ECTs compared to non-epileptic controls. Gene ontology analysis revealed enrichment of genes belonging to the following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: (i) glutamatergic synapse; (ii) nitrogen metabolism; (iii) transcriptional misregulation in cancer; and (iv) protein digestion and absorption. The glutamatergic synapse pathway was enriched by DEGs such as GRM4, SLC1A6, GRIN2C, GRM2, GRM5, GRIN3A, and GRIN2B. Enhanced glutamatergic activity was observed in the pyramidal neurons of ECTs, which could be attributed to altered synaptic transmission in these tissues compared to non-epileptic controls. Besides glutamatergic synapse, altered expression of other genes such as GABRB1 (synapse formation), SLIT2 (axonal growth), and PROKR2 (neuron migration) could be linked to epileptogenesis in ECTs. Also, upregulation of GABRA6 gene in ECTs could underlie benzodiazepine resistance in these patients. Neural cell-type–specific gene set enrichment analysis (GSEA) revealed transcriptome of ECTs to be predominantly contributed by microglia and neurons. This study provides first comprehensive gene expression profiling of nonneoplastic ECTs of DNT patients and identifies genes/pathways potentially linked to epileptogenesis. [ABSTRACT FROM AUTHOR]

Atrophic kidney-like lesion (AKLL) is a provisional renal entity with distinct morphological and immunohistochemical features. It characteristically resembles thyroid-like follicular renal cell carcinoma (RCC) of kidney, an emerging renal entity. Very few patients of AKLL have been reported in the literature. We are hereby describing the clinicopathological features of AKLL in a 38-year-old man. The patient was incidentally found to have a renal mass and underwent radical nephrectomy. The morphological and immunohistochemical findings revealed features of AKLL. The patient on 24 months' post-operative period follow-up is alive without recurrence or metastasis. [ABSTRACT FROM AUTHOR]

The article describes the case of a 7-year-old female child who was admitted to a private institution with severe abdominal pain and generalized tonic-clonic seizures. She was diagnosed with primary diffuse leptomeningeal (PDL) supratentorial primitive neuroectodermal tumor (sPNET) based on the biopsy and pathological findings obtained after performing various tests on the girl. The girl received a palliative chemotherapy treatment after being referred to the oncology department. [ABSTRACT FROM AUTHOR]

Introduction: We compare the clinical efficacy of the new bougieinternal urethrectomy (BIU) with internal urethrotomy and urethroplasty to treat urethral stricture disease. Methods: We prospectively studied 186 people with urethral stricture disease. Of these, 84 were identified for urethroplasty and 102 for internal urethrotomy (endoscopic urethrotomy). Among the 84 identified for urethroplasty, 52 received BIU (Group 1) and the remaining 32 received urethroplasty. Among the 102 identified for internal urethrotomy, 58 received BIU (Group 2) and the remaining 44 received the internal urethrotomy. After surgery, we evaluated the clinical efficacy of the BIU (operative invasions, voiding flow rates, complications, sequelae) compared with the endoscopic treatment and urethroplasty. Results: Patient age ranged from 20 to 70 years. The follow-up period was 2 years. In the BIU Group 1, the BIU Group 2, and the internal urethrotomy (endoscopic treatment), the length of strictures were 2.9 ± 1.5, 2.8 ± 1.3, 1.6 ± 0.7, and 1.5 ± 0.6, respectively. In the BIU Group 1, the urethroplasty, the BIU Group 2, and the internal urethrotomy (endoscopic treatment), the amount of bleeding was 34.1 ± 17.1, 172.2 ± 29.8, 28.5 ± 9.8, and 49.7 ± 13.6 mL, respectively. In the BIU Group 1, the urethroplasty, the BIU Group 2, and the internal urethrotomy, the recurrence rates were 5.8%, 86%, 6.8% and 25%, and the average flow rates were 18.1 ± 4.8, 13.1 ± 3.9, 18.2 ± 3.6, 10.1 ± 3.1 mL/s, respectively. There was no sequealae (sexual dysfunction, penile change) in both BIU groups. Conclusions: The new BIU could be considered first-line treatment in all patients with indications for visual internal urethrotomy and urethroplasty. [ABSTRACT FROM AUTHOR]

X-linked myopathy with excessive autophagy (XMEA) is a rare, recently characterized type of autophagic vacuolar myopathy caused by mutations in the VMA21 gene. It is characterized by slowly progressive weakness restricted to proximal limb muscles and generally has a favorable outcome. The characteristic histological and ultrastructural features distinguish this entity from other mimics, notably Danon disease. XMEA is an under recognized disease and should be considered in the differentials of slowly progressive myopathy in children. Awareness of this rare entity is also important for the pathologists in order to distinguish it from other causes of vacuolar myopathy in view of its favourable prognosis. We report the first genetically confirmed case of XMEA from India in an 8-year-old boy which was diagnosed based on the characteristic light microscopic and ultrastructural findings on muscle biopsy and subsequently confirmed by mutation analysis. The differential diagnostic considerations are also discussed. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is an aggressive hematolymphoid malignancy that arises from non Langerhans histiocytes and usually involves the skin, lymph nodes, and intestine. The involvement of the central nervous system (CNS) is a rare occurrence with around 30 cases being reported in English literature. Morphological and immunohistochemical evidence of histiocytic differentiation is essential for diagnosis. Prognosis is very poor and consensus on treatment is not available mainly due to its rarity. We report two cases of HS with varied clinical presentation and pathological findings and elucidate the diagnostic challenges of this rare entity. [ABSTRACT FROM AUTHOR]

Prothymosin-α (PTMA), a nuclear protein, is strikingly associated with unfavorable clinical outcomes in many cancers. However, no information about its clinical relevance in glioma was available. Therefore in the present study, we evaluated the prognostic utility of this protein in a cohort of 81 glioma patients. The PTMA expression was assessed by immunohistochemical analysis, quantitative PCR, and Western blotting. Furthermore, the association of PTMA with clinicopathological features and molecular alterations were assessed in the patient cohort and validated in multiomics datasets, The Cancer Genome Atlas (TCGA; n=667) and Chinese Glioma Genome Atlas (CGGA; n=1013). We observed an increase in PTMA expression with increasing histological grades of this malignancy. PTMA immunostaining also displayed a strong positive association with the MIB-1 index. Univariate analysis revealed a superior prognostic value of PTMA to predict overall survival (OS) as compared with the routinely used markers (p53, isocitrate dehydrogenase (IDH) 1 (IDH1), α-thalassemia/intellectual disability syndrome X-linked (ATRX), and Ki-67). Interestingly, in Cox regression analysis it emerged as an independent predictor of OS (hazard ratio (HR) = 13.71, 95% CI = 5.96-31.52, P<0.0001). Thus, our results demonstrate the potential prognostic utility of PTMA in glioma which may prove useful in the management of this deadly malignancy. [ABSTRACT FROM AUTHOR]

Cell cycle regulator genes are major target of mutation in many human malignancies including glioblastomas (GBMs). CDKN2A is one such tumor suppressor gene which encodes p16INK4a protein and serves as an inhibitor of cell cycle progression. Very few studies are available regarding the association of CDKN2A deletion with p16 protein expression in GBMs. There is limited data on the frequency of CDKN2A deletion in different age groups. The aim of the present study was to analyze the frequency of CDKN2A gene deletions in GBM and correlate CDKN2A deletional status with (i) age of the patient (ii) p16 protein expression and (iii) other genetic alterations, namely EGFR amplification and TP53 mutation. A combined retrospective and prospective study was conducted. Sixty seven cases were included. The patients were grouped into pediatric (≤18 years), young adults (19-40 years) and older adults (>40 years). CDKN2A and EGFR status were assessed by Fluorescence in situ Hybridization.TP53 mutation was analyzed by PCR based method. p16 expression was assessed using immunohistochemistry. CDKN2A deletion was noted in 40.3% cases of GBM with majority being homozygous deletion (74%). It was commoner in primary GBMs (65.8%) and cases with EGFR amplification (50%). A variable frequency of CDKN2A was observed in older adults (42.3%), young adults (44%), and pediatric patients (31.25%). The difference however was not statistically significant. There was statistically significant association between CDKN2A deletion and p16 immunonegativity with a high negative predictive value of immunohistochemistry. [ABSTRACT FROM AUTHOR]

Bowen's disease commonly presents as a solitary asymptomatic plaque involving head and neck region or lower limbs. We present a case of a sixty seven-year-old man with an itchy, oozy, crusted solitary plaque on the right ring finger of eighteen months duration with histopathology consistent with Bowen's disease. The lesion was initially treated with topical 5% imiquimod but due to relapse and inadequate response to a second course, complete surgical excision followed by full thickness skin grafting was done. Recurrence after about 6 months in the form of a small papule adjacent to the initial site was also treated with excision. This report highlights the potential of Bowen's disease to mimic more common dermatoses and a high index of suspicion, supported by histopathology, is required to diagnose and treat it without delay, which in turn may require a multimodality approach. We also reviewed the current literature on the same. [ABSTRACT FROM AUTHOR]

Assessment of promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene has recently gained importance in molecular profiling of high-grade gliomas. It has emerged not only as an important prognostic marker but also as a predictive marker for response to temozolomide in patients with newly diagnosed glioblastoma. Further, recent studies indicate that MGMT promoter methylation has strong prognostic relevance even in anaplastic (grade III) gliomas, irrespective of therapy (chemotherapy or radiotherapy). This article provides an overview of its use as a predictive and prognostic biomarker, as well as the methods employed for its assessment and use in therapeutic decision making. [ABSTRACT FROM AUTHOR]

This study examines variation of morphologic features, including emperipolesis, during the evolution of a case of Rosai Dorfman Disease (RDD). A 44-year-old male patient with RDD affecting the salivary glands, cervical lymph nodes, nasal and maxillary sinus mucosa had a waxing and waning course over two and a half years, with episodic sudden increase in size followed by involution and then a static course with moderate sized swellings. Multiple aspirations and biopsies were performed, which form the basis of this study. Four classical cases of RDD on aspirates and another four on biopsy were analyzed for comparison, with quantification of the number of lymphocytes engulfed by histiocytes (emperipolesis). Three nasal biopsies and one salivary gland excision of the index case, performed during acute exacerbation, showed chronic inflammation and foamy histiocytes without emperipolesis, the aspirate showing emperipolesis nil in 45%, 1-3 lymphocytes in 15%, 4-10 in 36% and .10 in 4%. Two aspirations and one lymph node biopsy done from static phase showed classical features of RDD with extensive emperipolesis, the aspirate from left cervical lymph node showing emperipolesis nil in 2%, 1-3 in 5%, 4-10 in 35% and .10 in 58% while right cervical lymph node aspirate showed emperipolesis nil in 9%, 1-3 in 21%, 4-10 in 29% and .10 in 41%. A biopsy performed from involuting cervical lymph node showed extensive apoptosis and vasculitis without foamy histiocytes or emperipolesis. For comparison, eight classical RDD cases showed abundant emperipolesis with mild variation. Emperipolesis is variable in RDD depending on disease activity, which has differential diagnostic relevance and demonstrates the natural history of this rare disease. [ABSTRACT FROM AUTHOR]