Adrenal Oncocytic Pheochromocytoma: Insights From a Challenging Diagnostic Journey.

Pheochromocytomas are rare adrenal medulla tumors originating from chromaffin cells, accounting for 10% of primary adrenal neoplasms. Oncocytic variants of pheochromocytomas are rare and have been reported in only 150 cases. This report describes the case of a 60-year-old female who arrived with a non-functional adrenal tumor. This case report emphasizes the importance of a comprehensive histological and immunohistochemical study for diagnosing this rare diagnostic entity and its potential diagnostic pitfalls.

Histopathological Spectrum of Gliomas and Its Immunohistochemical Correlation in a Tertiary Care Setup.

Introduction Central nervous system (CNS) tumors pose significant diagnostic challenges due to their varied morphological and differentiating characteristics. Modern advancements in immunohistochemistry (IHC) and molecular pathology have greatly enhanced prognostication, screening, and therapeutic management. Gliomas, a type of tumor originating from glial cells in the CNS, can develop from astrocytes, oligodendrocytes, or ependymal cells. According to the 2021 update, the classification of diffuse gliomas is primarily based on the presence or absence of isocitrate dehydrogenase (IDH1/2) mutations. IDH-wildtype gliomas (glioblastomas) have a significantly poorer prognosis compared to IDH-mutant gliomas (astrocytomas and oligodendrogliomas). Gliomas are highly infiltrative and resistant to treatment, making them largely incurable regardless of their grade and prognosis. Objective This study aimed to determine the histopathological diversity of gliomas and its correlation with protein expressions of IDH, ATRX gene (α-thalassemia/mental retardation syndrome X-linked), Ki-67, and p53 mutations (tumor suppressor gene-53), according to the 2021 World Health Organization (WHO) Classification of CNS Tumors, Fifth Edition. Methods This descriptive cross-sectional study was carried out in the Department of Pathology at a tertiary care center, focusing on various types of gliomas received over a two-year period. A total of 54 specimens of gliomas received from the Department of Neurosurgery were subjected to histopathological examination. Sections were stained using hematoxylin and eosin (H&E), and IHC was performed using four markers (IDH, ATRX, p53, Ki-67) in each case. Results were analyzed according to the 2021 WHO Classification of CNS Tumors, Fifth Edition. Results The majority of individuals were between the age group of 40 and 60 years, showing a male predominance (65%). The most common site was the frontal lobe. Glioblastoma constituted the largest proportion (46.2%) of the total cases, followed by astrocytoma (20.3%), oligodendroglioma (18.5%), pilocytic astrocytoma (7.4%), and ependymoma (7.4%). All 11 cases of astrocytoma exhibited IDH mutation and ATRX loss, with p53 positive in the majority of cases. Strong nuclear p53 immunohistochemical positivity in >10% of tumor nuclei correlates with TP53 mutations. Among 25 cases of glioblastoma, IDH was negative, ATRX was retained in all cases, and 11 cases were positive for p53 mutation. For oligodendroglioma, out of 10 cases, IDH mutation was positive, and ATRX was retained in all cases. p53 mutation was not seen in any case. All cases of pilocytic astrocytoma were negative for IDH and p53 mutations, with ATRX retained in all cases. In all cases of ependymoma, IDH and p53 mutations were negative, and ATRX was retained in all cases. Glioblastomas exhibited the highest Ki-67 expression. Conclusion The 2021 WHO Classification of CNS Tumors, Fifth Edition, was updated, building on previously established concepts and continuing to evolve. The final diagnosis of gliomas relies on a comprehensive combination of clinical evaluation, neuroimaging, pathological examination, and molecular analysis. Nonetheless, histopathological examination, along with IHC, remains the cornerstone of diagnosis.

Pigmented Conjunctival Nevus: A Mystery Solved by Histopathology.

Inflammatory juvenile conjunctival nevi (IJCN) is a rare type of nevus and its clinical presentation overlaps with that of malignant conjunctival melanoma. It is a benign lesion that has been described to progress to melanoma in some cases. IJCN may clinically mimic melanoma due to its rapid growth features and atypical histology. Thus, its accurate diagnosis by histopathology is a prerequisite for proper management. Here, we present a case of conjunctival lesion mimicking melanoma clinically.

Exploring the Histopathological Landscape of Urinary Bladder Diseases: A Tertiary Care Center Study.

Introduction Urinary bladder lesions encompass a wide spectrum, from benign inflammatory conditions to malignant neoplasms, presenting diagnostic and therapeutic challenges. Urothelial carcinoma predominates among bladder malignancies, exhibiting diverse clinical presentations and prognoses. Objective This study aimed to delineate the histopathological spectrum of urinary bladder lesions and correlate demographic profiles, clinical features, and cystoscopic findings with various bladder lesions. Methods This prospective descriptive observational study spanned 24 months at a tertiary care center, involving 65 cases of urinary bladder biopsies, including transurethral resection of bladder tumors, cystoscopic biopsies, and cystectomy specimens. The histopathological examination followed the WHO 2022 classification of urinary bladder tumors and the American Joint Committee on Cancer eighth edition staging. Clinical data, including age, gender, cystoscopic findings, and presenting symptoms, were correlated with histopathological diagnoses to explore the spectrum of bladder lesions. Results Neoplastic lesions predominated, constituting 92.3% of cases, with urothelial carcinoma comprising 83.33% of these cases. Among neoplastic lesions, invasive high-grade urothelial carcinoma (36.7%) and non-invasive low-grade papillary urothelial neoplasm (20.0%) were the most frequently observed subtypes. Non-neoplastic lesions accounted for 7.7%, including various forms of cystitis. Hematuria was the predominant presenting symptom (81.5%), while cystoscopic examinations revealed that most lesions were situated in the lateral bladder wall. High-grade urothelial carcinomas were mostly associated with muscularis propria invasion. Conclusion This study underscores the critical role of histopathological examination in diagnosing and managing urinary bladder diseases and distinguishing between non-neoplastic and neoplastic lesions. Urothelial carcinoma, prevalent among older age groups, often demonstrated muscle invasion indicative of high-grade tumors. Including the muscle layer in cystoscopic biopsies is crucial for an accurate diagnosis. Conversely, though less common, non-neoplastic conditions encompass various forms of cystitis. These findings highlight the importance of precise diagnostic tools such as cystoscopy and histopathological examination for the early detection and management of bladder neoplasms. Histopathological assessment offers essential prognostic guidance, aids in precise staging and grading, and directs tailored treatment strategies.

Subependymal Giant Cell Astrocytomas Without Tuberous Sclerosis: A Case Report on a Rare Medical Condition.

Subependymal giant cell astrocytomas (SEGAs) are benign, slow-growing, noninvasive tumors frequently associated with the tuberous sclerosis complex (TSC). The tumor's location and the patient's age should be considered carefully before diagnosis. Considering SEGA as a differential diagnosis, even in adult patients without TSC, is essential. In the present case, a 22-year-old male presented with a progressive headache, dizziness, and blurring of vision. Radiological investigations confirmed the site of the tumor, and a positive expression of thyroid transcription factor 1 in the ganglion cell component, along with the absence of germline mutation in TSC1 and TSC2, led to the final diagnosis of SEGA without TSC.

Pulsations as a Signal of Danger: A Case of Scalp Cirsoid Aneurysm.

Cirsoid aneurysms, formerly identified as arteriovenous malformations (AVMs), represent infrequent vascular anomalies primarily localized within the scalp. These anomalies are typified by the absence of interposing capillaries, giving rise to extensively vascularized, expanded conduits connecting arterial feeders and venous outflows. This report details a case of a 13-year-old male afflicted with a cirsoid aneurysm in the scalp, who presented with swelling on the left frontal region, accompanied by headache and pulsatile sensations. Definitive diagnosis was achieved through radiological and histopathological examinations. Scalp cirsoid aneurysms may either be congenital in nature or arise following traumatic incidents, with clinical manifestations typically surfacing in the third decade of life. Common clinical presentations encompass a palpable, pulsatile subcutaneous mass, throbbing headaches, tinnitus, and cosmetic concerns. Diverse therapeutic strategies, including surgical excision, endovascular embolization, and percutaneous injection of sclerosing agents, can be employed contingent upon the particular characteristics of the lesion.

Clinicopathological Significance of Tumor Budding in Breast Carcinoma.

BACKGROUND: Tumour budding Tuberculosis is a new prognostic marker whose role in breast cancer is still under evaluation. Our aim was to study Tuberculosis in breast carcinoma and correlate it with other prognostic markers. METHODS: A descriptive cross-sectional study was conducted over 2 years on 75 invasive breast carcinoma specimens and biopsies. Hematoxylin and Eosin sections were examined for tumour grade, stage, molecular subtype, necrosis, lymphovascular invasion inflammation and counting of Tuberculosis. Lymph node metastasis was studied only in mastectomies. TB was defined as a cluster of 1-5 tumour cells and counted in 10 consecutive 400X fields. The cut-off for high grade TB was taken as ?10 per 10 HPFs. Immunohistochemical staining was done for molecular subtyping and differentiating Tuberculosis from mimickers. Statistical analysis was done using chi square test and Fischer's exact test. RESULTS: Tuberculosis was present in 66/75 cases; 53% (n=35) were high grade. Among these, majority were of T2 (74%, n= 26), grade 2 (52%, n= 18), luminal A (34%, n= 12), had 3+ inflammation (46%, n= 16) and peripheral tumour buds (54%). Necrosis and lymphovascular invasion were absent in 77% and 71%, respectively. Lymph node metastasis was seen in 63% (n= 25/28) cases. Statistically significant association (p= 0.016) was observed between degree of inflammation and Tuberculosis grade. However, no significant association was observed between TB and other prognostic markers of breast carcinoma. CONCLUSIONS: In our study, association of Tuberculosis with different prognostic markers was appreciated but was not statistically significant. However, it highlights need for standardization of Tuberculosis reporting.

Unmasking the Mystery of Renal Neoplasm in a Perimenopausal Woman: A Case Report.

Mixed epithelial and stromal tumor (MEST) is a benign, complex, and rarely encountered renal neoplasm. This case involves a 46-year-old perimenopausal woman who presented with symptoms, such as abdominal pain, burning sensation during urination, increased urinary frequency, and hesitancy. Computed tomography (CT) urography revealed an exophytic, heterogeneously hyperdense mass originating from the interpolar and lower pole parenchyma of the left kidney, suggesting a neoplastic origin. Due to concerns about malignancy and the presence of local symptoms, a laparoscopic-assisted left radical nephrectomy was performed. Histopathological examination of the excised tissue revealed a biphasic neoplasm consisting of epithelial and stromal elements. The epithelial component exhibited cysts and glands of variable sizes, lined by columnar cells and surrounded by stromal tissue. The diagnosis of MESTs of the kidney was established and confirmed through immunohistochemistry. This unique type of benign kidney tumor can be effectively managed through conservative surgery and is associated with a favorable prognosis.

Primary Cardiac Lesions: A Case Series of Five Rare Cases.

Although cardiac lesions have been known to the existence since the Middle Ages, a search on Google or PubMed for 'cardiac lesions' yields very few results. There are few original articles, case series, or clinical trials available on these rare but significant lesions. Cardiac lesions are usually asymptomatic and are detected only incidentally. Symptoms, if present, are varied and depend on the location of the area involved. The overall prevalence of primary cardiac tumors is between 0.17% and 0.19%. Cardiac tumors may be primary (benign or malignant) or metastatic (malignant). Only 25% of primary cardiac tumors are malignant, whereas metastatic tumors to the heart are 30 times more common. The aim of this case series is to highlight the clinical picture, presenting signs and symptoms, and the line of diagnosis of five such primary cardiac lesions that otherwise could remain undiagnosed until a late stage.

Cystic presentation of primary hepatic neuroendocrine tumour: a case report with a brief review of literature.

Neuroendocrine tumours (NETs) are a rare type of tumours that arise from the neuroendocrine cells which are distributed throughout the body. Of all the gastrointestinal tumours only 1-2% account for NETs. They have an extremely low incidence of 0.17% arising in the intrahepatic bile duct epithelium. Majority of hepatic NETs occur as a result of metastases from the primary NETs. Most cases of primary hepatic NET (PHNET) present as a solid nodular mass. However, predominantly cystic PHNET is extremely rare which mimics other cystic space-occupying lesions clinically and radiologically as seen in this case.

Piecing Together a Puzzle of Exceptional Lesions: A Retrospective Study of a Potpourri of 160 Space-Occupying Lesions of the Central Nervous System.

Introduction Central nervous system (CNS) lesions are rare and histologically heterogenous, and carry serious potential for patient morbidity and mortality. A retrospective epidemiological review of CNS neoplasms is of great importance for future research because it can demonstrate the changes in the spectrum of CNS lesions of a population, unveil the possible associated risk factors, and indicate the potential therapeutic methods for various neoplastic and non-neoplastic lesions. Neurosurgeons have always shown an obsession with a good neuropathological diagnosis in intracranial and extracranial lesions. This obsession need not be overemphasized as it helps the clinician plan an adequate surgical/treatment strategy to optimize outcomes and minimize morbidity. Methods This study included a spectrum of 160 biopsies of patients with space-occupying lesions of the CNS during a period of two years (2019-2021). All the cases were studied and analyzed, and their histological typing/grading was done. The cases were graded and categorized according to the 2016 WHO Classification of CNS Tumors. Results Among 160 cases, the study showed a slight male preponderance of 100 (62.5%) cases. The maximum number of cases, 37 (23%) cases, was in the age group of 41-50 years. Clinically, the commonest complaints were headache and seizures. The most common location of tumor was supra-tentorial, comprising around 96 (60%) cases, of which 27 (28%) cases were located in the frontal lobe. There were four (2.5%) cases that had non-neoplastic lesions and the rest 156 (97.5%) cases had neoplastic lesions. Malignant lesions outnumbered the benign lesions, comprising of 82 (51.25%) cases. Among the neoplastic lesions, the highest cases were of astrocytoma, 48 (30.76%) cases, followed by meningioma, 42 (26.92%) cases. Also, 21 extremely rare and unusual cases were encountered. Conclusion The present study reflects the diversity of histopathological spectrum of CNS lesions in our center. In-depth studies from across various hospitals are required to have representative data on the incidence, epidemiological profile, and etiology of CNS lesions in India.

Undetectable Free Aromatic Amino Acids in Nails of Breast Carcinoma: Biomarker Discovery by a Novel Metabolite Purification VTGE System.

Background: Metabolic reprogramming in breast cancer is depicted as a crucial change in the tumor microenvironment. Besides the molecular understanding of metabolic heterogeneity, appreciable attention is drawn to characterizing metabolite profiles in tumor tissue and derived biological fluids and tissue materials. Several findings reported on the metabolic alterations of free aromatic amino acids (FAAAs) and other metabolites in biological fluids. Furthermore, there is a significant gap in the development of a suitable method for the purification and analysis of metabolite biomarkers in nails of cancer patients. Methods: To address the metabolite alterations, specifically FAAA levels in nails, fingernail clippings of breast cancer patients (N = 10) and healthy subjects (N-12) were used for extraction and purification of metabolites. Here, we reported a novel and specifically designed vertical tube gel electrophoresis (VTGE) system that helped in the purification of metabolites in the range of 100-1,000 Da from nail materials. Here, the VTGE system uses 15% polyacrylamide under non-denaturing and non-reducing conditions, which makes eluted metabolites directly compatible with LC-HRMS and other analytical techniques. Qualitative and quantitative determination of FAAAs in nail lysates was done in positive ESI mode of the Agilent LC-HRMS platform. Results: The analysis on collected data of nail metabolites clearly suggested that FAAAs including tryptophan, tyrosine, phenylalanine, and histidine were undetectable in nail lysates of breast cancer over healthy subjects. This is a first report that showed highly reduced levels of FAAAs in nails of breast cancer patients. Furthermore, the present observation is in consonance with previous findings that showed cancer cachexia and high amino acid catabolism in breast cancer patients that drive metabolite-led cancer growth and proliferation. Conclusion: This paper provides a proof of concept for a novel and specifically developed VTGE process that showed first evidence on the undetectable level of FAAAs in nails of breast cancer patients as metabolite biomarkers. Here, the authors propose the potential use of a VTGE-assisted process to achieve metabolomic discovery in nails of breast cancer and other tumor types.

Immunoglobulin G4-related chronic sclerosing sialadenitis: An emerging entity.

Chronic sclerosing sialadenitis is associated with the immunoglobulin G4 (IgG4)-related disease (RD) spectrum. IgG4-RD is a newly recognized immunomediated fibroinflammatory condition characterized by several features: a tendency to form tumefactive lesions at multiple sites, lymphoplasmacytic infiltrate, fibrosis and obliterative phlebitis. Often but not always, the serum IgG4 concentrations are also elevated. Immunohistochemistry for IgG4 is helpful to clinch the diagnosis. Here, we describe a case of 65-year-old male with IgG4-related chronic sclerosing sialadenitis of the s ubmandibular gland. We have discussed the histopathological criteria to diagnose this entity.

Induction of Apoptotic Death and Cell Cycle Arrest in HeLa Cells by Extracellular Factors of Breast Cancer Cells

Background: There are evidences on the role of extracellular factors in cellular communication between cancer cells and non-cancerous cells to support tumor progression and a phenomenon of cancer cachexia. However, evidences are scarce to show the effects of extracellular factors from one carcinoma microenvironment upon growth and survival of another carcinoma. Methodology: To address the above issue, we have selected excised breast carcinoma tissue samples and in vitro grown MCF-7 sources of extracellular factors and tested their effects to evaluate growth and proliferation inhibitory potential against a cervical carcinoma cell line HeLa. Results: Data from the in vitro experiments like Trypan blue dye exclusion, MTT assay, cell cycle assay and annexin V/PI staining lead us to suggest that the extracellular factors collected from the culture medium of in vitro grown MCF-7 and excised breast carcinoma tissue play an apoptosis inducing and cell cycle arrest role in HeLa. In these in vitro experiments, we detected the presence of up to 40-50% apoptotic cell death in HeLa cells and increase in G2-M cell cycle phase from 11%-25% due to treatment with extracellular factors from human breast carcinoma cells. Discussion and Conclusion: These observations are novel and suggest that extracellular factors from breast carcinoma play an apoptosis inducing and growth inhibitory role upon on HeLa cells. This study can also support the concept of cancer cachexia and a possible hypothesis for rare chance of synchronous two or more primary tumor in a single patient.

A rare case of signet ring cell lymphoma: Diagnosis aided by immunofluorescent staining.

Signet ring cell lymphomas are the proliferations of malignant lymphoid cells containing cytoplasmic vacuoles or globules which displace the nuclei, imparting it a signet ring appearance. This rare tumor is a variant of non-Hodgkin lymphoma. Signet ring appearance is due to cytoplasmic accumulation of immunoglobulin or vacuoles derived from multivesicular bodies. These cells, particularly with cytoplasmic vacuoles, may be mistaken for adenocarcinoma cells. We are presenting one such case where immunofluorescence helped us to demonstrate the immunoglobulins on fine needle aspiration smears. This is an innovative technique and has not been reported earlier. Our aim of presenting this case is to review the awareness of this rare lymphoma among pathologists to give due consideration for avoiding inappropriate investigations and treatment.

Recurrent solitary fibrous tumor in distal lower extremity: An extremely rare entity.

Solitary fibrous tumor (SFT) represents a spectrum of mesenchymal tumors, encompassing tumors previously termed hemangiopericytoma, as having intermediate biological potential. Though they can occur at any site, lower distal extremity is a rare site and recurrence in it is extremely rare. Behavior of SFT is unpredictable. Histomorphology and clinical follow-up have poor correlation. The most important single indicator of clinical outcome is complete excision of the tumor at the time of primary presentation. Tumors with positive margins require close follow-up for several years owing to the potential for late local recurrence.

Cytomorphologic spectrum of Hashimoto's thyroiditis and its clinical correlation: A retrospective study of 52 patients.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease and it is more prevalent in Asians. The incidence of HT seems to be increasing in the recent times. It is one of the most common cause of hypothyroidism. The purpose of this study is to review the cytomorphologic spectrum of HT and correlate it with clinical findings including thyroid function and antibody profile. MATERIALS AND METHODS: We retrospectively analyzed the fine-needle aspiration (FNA) features of 52 HT patients. Based on cytomorphologic features patients were categorized into three groups. Clinical findings including thyroid function and thyroid peroxidase (TPO) antibody profile were correlated with cytomorphologic features in all three groups. RESULTS: Majority of the patients were females and in 2(nd), 3(rd) and 4(th) decades. Diffuse goiter and thyroid hypofunction were the common findings. Significant number of patients had thyroid hyperfunction. Increased lymphocytes on the background and lymphocytic infiltration of thyroid follicular cell clusters in cytology smears were diagnostic of HT. The 32 patients showed elevated titers of TPO antibodies. In the early stages and mild form of the disease, results of thyroid function and anti TPO antibodies are quite variable. CONCLUSIONS: HT is a disease of young and middle age and mostly occur in females. Clinical findings alone may not be adequate for definitive diagnosis. FNA is the gold standard for diagnosis. In the presence of abundant colloid, follicular hyperplasia or co-existing neoplasm, careful interpretation of cytology smears should be done. Aspiration from more than one site minimizes the diagnostic pitfalls.

A Cross-sectional Study of Direct Immunofluorescence in the Diagnosis of Immunobullous Dermatoses.

BACKGROUND: Autoimmune blistering diseases are a group of bullous disorders characterized by pathogenic antibodies directed at the target antigens, which are components of the desmosomes or adhesion complex at the dermoepidermal junction. Direct immunofluorescence (DIF) is invaluable in the diagnosis of these lesions. AIM: The aim of this study was to evaluate the sensitivity of DIF in immunobullous dermatoses and to study the pattern of DIF. The study also aims to correlate DIF with clinical and histologic findings and to analyze discrepancies. MATERIALS AND METHODS: Total 100 biopsies received over a period of 2 years in the Department of Pathology were analyzed. DIF, histopathology and clinical data were reviewed. RESULTS: Out of 100, 89 cases showed DIF patterns concordant with clinical/histologic diagnosis. The sensitivity of DIF was 94.44% (51/58) in the pemphigus and 84% (21/25) in the bullous pemphigoid (BP) group, 100% each in dermatitis herpetiformis (2/2) and linear IgA disease (1/1). A total of 11 histologically proven cases of immunobullous lesions were DIF negative-four (three of pemphigus vulgaris and one of BP) due to having no epidermis, three (cases of BP) owing to sampling/technical errors and the remaining four (cases of pemphigus vulgaris) due to being on treatment. CONCLUSION: Immunofluorescence helps confirm the diagnosis of bullous lesions in which there is clinical and the histopathologic overlap. Sampling errors contributed to false negative (FN) results.