ABSTRACT:Lately, STK11 adnexal tumors have been described in patients with Peutz-Jeghers syndrome (PJS), showing overlap with other adnexal tumors, especially female adnexal tumor of probable Wolffian origin (FATWO). To date, there is no documentation of this tumor from the Indian subcontinent. A 25-year-old female with mucocutaneous pigmented macules presented with acute abdominal pain along with a family history of surgical resection for gastrointestinal polyps in her mother and sister. Imaging revealed a well-defined, cystic right adnexal mass, distinct from the ovary, measuring 4.1 cm. Her colonoscopic examination was unremarkable. She underwent paraovarian cystectomy. Histopathological examination revealed a tumor composed of epithelioid cells arranged in various growth patterns with mild nuclear atypia. Immunohistochemically, the tumor cells were positive for pan-keratin, calretinin, CD10, FOXL2, and androgen receptor, the latter in 50% of the tumor cell nuclei. Initially, a diagnosis of FATWO was considered. Targeted next-generation sequencing revealed a pathogenic STK11 exon 4 frameshift mutation (c. 574dup), which was subsequently confirmed as a germline alteration on peripheral blood testing by Sanger sequencing, thereby establishing the diagnosis of an STK11 tumor with PJS. The differential diagnoses of this tumor and the judicious application of immunohistochemical stains, along with genetic testing (including high-throughput molecular testing in a clinical context) for an exact diagnosis, are discussed herein. A literature review including the molecular results of this rare tumor is also presented.
ABSTRACT Meissnerian neurofibroma is an extremely rare histological variant of neurofibroma, with less than ten reported cases of prominent differentiation toward pseudo-meissnerian bodies in the literature. The presence of focal or sparsely scattered pseudo-meissnerian bodies in neurofibromas is well documented in diffuse and plexiform types. It is also seen in various peripheral nerve sheath tumors, including schwannomas, as well as in congenital melanocytic nevi and neural crest hamartomas. The complete excision of the lesion is considered to be curative. We hereby present a rare case of prominent meissnerian differentiation in neurofibroma in a 26-year-old female.
ABSTRACT Extranodal NK/T-cell lymphoma (ENKTL) of the central nervous system (CNS) is very rare. We herein report a case of ENKTL originating from the CNS in a 79-year-old woman. The patient presented with episodic seizures, left-sided limb weakness, altered mental status, and dysarthria for more than 1 month. Radiological examination revealed a solitary mass in the (laterality) frontal lobe of the brain, which was surgically removed. Histopathology revealed a tumor showing diffuse growth of large anaplastic cells with multiple reniform nuclei, horseshoe nuclei, and doughnut-like nuclei. Immunohistochemically, the tumor cells were diffusely positive for CD3, CD30, Gramazyme B, and TIA1 and negative for ALK and CD56. It was almost misdiagnosed as ALK-negative anaplastic large cell lymphoma, but positivity for cytotoxic markers and EBER-ISH helped establish the diagnosis of ENKTL. To the best of our knowledge, this anaplastic variant of ENKTL has not been reported in the CNS. We present this case to describe an uncommon aggressive variant of ENKTL at CNS as a rare location with diagnostic pitfalls.
ABSTRACT Paraquat, a toxic herbicide, continues to be widely used in developing nations despite restrictions and severe health risks. Several cases of poisoning have been reported due to intentional ingestion, producing dose-dependent clinical manifestations, chiefly targeting the lungs and kidneys. However, only a few cases have been reported in pregnancy. We report mortality due to paraquat-induced lung injury in a young pregnant woman, in whom the poisoning occurred following the ingestion of paraquat-contaminated soil as part of pregnancy-induced pica. The case underscores the critical need for early recognition and intervention.
ABSTRACT Almost all retinal pigment epithelial (RPE) adenocarcinomas are clinically diagnosed as choroidal melanomas. Retinal adenoma and adenocarcinoma appear black in color. A 63-year-old woman presented with progressive visual loss in her right eye with intermittent throbbing pain. A brownish pigmented choroidal mass was identified occupying the entire intraocular cavity with hemorrhagic foci. Histopathology revealed an infiltrative epithelial neoplasm with ill-defined glandular differentiation and moderate cytological atypia. Immunohistochemical staining with epithelial membrane antigen, cytokeratin 7, HMB-45, and S-100 favored a RPE origin of the lesion. RPE adenocarcinoma is exceedingly uncommon, but should be included in the differential diagnosis of pigmented intraocular tumors. Histopathology, combined with immunohistochemistry, is essential for accurate diagnosis.
ABSTRACT Primary neuroendocrine tumors (NETs) of the kidney are exceedingly rare, with an estimated incidence of only 0.13 per 1 million individuals. Their rarity is attributed to the absence of native neuroendocrine cells within the renal parenchyma. These tumors span the WHO grading spectrum, with well-differentiated lesions reported most frequently. They may also occur in association with congenital anomalies such as horseshoe kidney. In this study, we present a new case of a 33-year-old female diagnosed with a primary renal NET at our hospital. She underwent imaging studies, surgical excision, and histopathological and immunohistochemical analysis. The findings suggest that these tumors are rare and have nonspecific clinical and imaging features. The diagnosis heavily relies on immunohistochemical analysis. Primary renal well-differentiated NETs are associated with low malignant potential and a favorable prognosis. Surgical resection is the preferred treatment, and long-term follow-up is necessary to monitor the patient’s condition.
BACKGROUND:Mast cells accumulate in peritumoral tissue in cutaneous malignancies and various other malignancies and contribute to a permissive microenvironment for carcinogenesis. They promote tumor angiogenesis by inducing neovascularization. Most cases of oral squamous cell carcinoma (OSCC) are moderately to well differentiated, whereas poorly differentiated cases are rare. The objective of the study is to evaluate tumor mast cell density across different histological grades of OSCC in patients of a tertiary care center of Northeast India. MATERIALS AND METHODS:The study included 139 patients diagnosed histopathologically, and mast cell density was analyzed by toluidine blue stain; density was counted in hotspots (nhpf). Poorly differentiated OSCC ( n = 2) was analyzed descriptively. Well-differentiated versus moderately differentiated OSCC was compared using t -test or Mann-Whitney U test (Statistical Package for the Social Sciences v25). RESULTS:Well-differentiated OSCC: 70 (50.4%), moderately differentiated OSCC: 67 (48.2%), and poorly differentiated OSCC: 2 (1.4%). There was no statistically significant difference in mast cell density between well-differentiated versus moderately differentiated grades ( P = 0.068), although variations in mean values were noted. Density was lower in poorly differentiated OSCC cases. CONCLUSIONS:Our study results showed no statistically significant difference in mast cell density among OSCC grades. Larger poorly differentiated OSCC samples are needed for future studies.
ABSTRACT Interdigitating dendritic cell sarcoma (IDCS) is a rare malignancy originating from dendritic cells, which participate in immune response activity as antigen-presenting cells by stimulating T lymphocytes. We report the case of a 24-year-old man who experienced an involuntary 20 kg weight loss over 2 months, combined with a steadily growing, painless lump in his right upper abdomen. Upon examination, a hard, nontender, immobile mass measuring 16 × 16 cm was found in the right hypochondrium. A massive, well-defined hypodense lesion covering all segments of the liver’s right lobe was excised and was diagnosed as IDCS due to its characteristic histomorphological and immunohistochemical features.
BACKGROUND:Anti-endomysial antibody (EMA) has demonstrated high specificity and reasonable sensitivity for the diagnosis of celiac disease (CeD). We aimed to evaluate the diagnostic accuracy of EMA in our patients with CeD. MATERIALS AND METHODS:In this prospective study, we included patients of treatment-naïve CeD as cases who were recruited under an Indian National CeD Biorepository and had already tested positive for IgA anti-tTG, hence diagnosed as CeD based on standard criteria. Patients with other enteropathies, functional dyspepsia and gastroesophageal reflux disease, in whom IgA anti-tTG was negative, were taken as controls. Both cases and controls underwent testing for EMA using an immunofluorescence-based assay (Inova Diagnostic, USA). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS:The mean age of patients with CeD and controls was 28.3 ± 12.2 and 35.5 ± 10.72, respectively ( P < 0.001). EMA was positive in only 50.9% (141 of 277) patients with CeD, while in the control group, 1 out of 90 (1.1%) had positive EMA. The sensitivity, specificity, PPV, and NPV were 50.9, 98.9, 99.3, and 39.6%, respectively. Diagnostic odds ratio, positive LR, and negative LR were 92.3, 45.8, and 0.49, respectively. CONCLUSION:EMA test has high specificity and low sensitivity. Only half of adult CeD patients had positive EMA.
ABSTRACT:Hidradenocarcinoma (HC) is an extremely rare malignant tumor originating from skin appendages, accounting for approximately 6% of malignant sweat gland tumors and less than 0.001% of all tumors. Sweat gland carcinoma with endocrine mucin-producing sweat gland carcinoma belongs to the category of low-grade cutaneous neuroendocrine carcinoma. Due to its extremely low incidence, lack of distinct clinical manifestations, and multiple pathological features, the clinicopathological diagnosis is challenging, often leading to misdiagnosis. To date, fewer than 20 cases have been reported in the literature. Low-grade cutaneous neuroendocrine carcinoma (LGNECS) has been proposed as a novel primary skin tumor with neuroendocrine differentiation. This study presents the clinicopathological characteristics of two cases of LGNECS and conducts a literature review. In case 1, the biopsy suggested squamous cell carcinoma (SCC), and in case 2, the biopsy indicated a tumor derived from skin appendages. However, postoperative histopathological examinations in both cases diagnosed low-grade sweat gland carcinoma with neuroendocrine differentiation. LGNECS poses significant challenges to clinicopathological diagnosis. Case 1: An 86-year-old male presented with a nodular lesion on the left temporal region, which had been present for one year. The lesion, measuring 3.5 × 2.5 cm, was ulcerated with partial crusting. Biopsy initially suggested SCC. However, the postoperative diagnosis was low-grade sweat gland carcinoma with neuroendocrine differentiation. Case 2: A 74-year-old female developed red papules on the lumbosacral region three years ago, each approximately 1 cm in size, accompanied by skin ulceration. The lesion was initially not considered significant. Over time, the mass increased in size and developed a foul odor. Biopsy suggested sweat gland carcinoma, and the postoperative diagnosis confirmed low-grade sweat gland carcinoma with neuroendocrine differentiation. Both patients received no treatment after surgery and have been followed up for 4 to 16 months, with no recurrence or metastasis observed. Sweat gland carcinoma with neuroendocrine differentiation is extremely rare, and biopsy is prone to misdiagnosis. A definitive diagnosis requires a comprehensive analysis of postoperative specimens combined with immunohistochemical studies. This study reports two cases of sweat gland carcinoma with neuroendocrine differentiation, providing valuable insights for clinicians and pathologists.
ABSTRACT:In some patients, ascending aortic aneurysms or dissections produce aortitis, not associated with clinical or investigational evidence of infective or non-infective vasculitis or systemic diseases. This type of aortitis is termed clinically isolated aortitis, which is often a surprise finding in surgical pathological material. We report a series of five such cases in patients in their fifth decade of life with an almost equal sex distribution.
ABSTRACT:Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid neoplasm that poses diagnostic difficulty on preoperative fine-needle aspiration (FNA) cytology. In this retrospective study, eight cases diagnosed as NIFTP on histopathology between January 2019 and January 2022 were retrieved from the pathology department, and their corresponding FNA cytology smears were reviewed to assess cytomorphological features. The most frequent cytological findings observed in the current study were architectural abnormalities, predominantly crowded cell clusters with a microfollicular pattern. Nuclear features included nuclear overlapping and enlargement, eccentric nucleoli, irregular nuclear membranes, pale chromatin, nuclear grooves, and elongated nuclear contours. Intra-nuclear cytoplasmic inclusions were not identified in any of the cases. On cytological categorization, most cases were reported as suspicious for follicular neoplasm. These findings indicate that while certain architectural and nuclear features are consistently observed in NIFTP on cytology, they are not specific enough to allow a definitive preoperative diagnosis. Identification of NIFTP on FNA cytology therefore remains challenging, emphasizing the need for cautious interpretation and histopathological correlation.
ABSTRACT:Pathology and laboratory medicine is undergoing a transformation, moving from its roots in morphology to becoming a dynamic, multimodal field at the heart of precision medicine. This review outlines how diagnostic pathology has developed over time from morbid anatomy, gross dissections, and microscopy to advancements through histochemistry, immunohistochemistry, flow cytometry, molecular diagnostics, clinical genomics, digital pathology, and computational pathology. A systematic search of the English-language literature was conducted in PubMed (2000-2025). The MeSH terms and keywords used focused on traditional pathology, pathology trends, molecular techniques, digital pathology, artificial intelligence, multimodal data fusion, precision diagnostics, and precision medicine to inform this narrative review. Key advances in different eras are noted, highlighting pathologists' growing role in unifying information from multiple sources. The early sections of the review focus on anatomy and morphology in disease diagnosis. The latter parts highlight how molecular profiling and genomic sequencing enhanced classification and treatment. The integration of whole-slide imaging and artificial intelligence is examined in different dimensions-workflow transformation and computational enhancement. The concept of "Precision Diagnostic Pathology" is highlighted, where the pathologist serves as a clinical integrator. The goal is to combine multiple data sources-morphology, immunophenotyping, molecular and genomic data, including clinical information, radiology, and evidence-based guidelines, into unified, actionable reports. The article briefly addresses trainees' concerns about the future of pathology in the age of AI, emphasizing that technology is expected to enhance pathologists' work as integrative physicians rather than replace them. Precision Diagnostics in support of Precision Medicine requires integrating multimodal data types, with the pathologist's expertise essential for effective personalized care.
ABSTRACT:Renal cell carcinoma (RCC) is a notorious tumor, known for its unpredictable metastatic behavior; however, metastasis to the testis remains exceptionally rare. We report an unusual case of incidentally detected testicular metastasis from renal cell carcinoma in a patient who was undergoing treatment for coexistent prostatic adenocarcinoma. A 70-year-old man presented with lower urinary tract symptoms and hematuria and was diagnosed with high-grade prostatic adenocarcinoma, for which transurethral resection of the prostate and bilateral orchidectomy were performed. Histopathological examination of the orchidectomy specimen unexpectedly revealed metastatic RCC. On reviewing prior medical records, a history of left radical nephrectomy for clear cell RCC 7 years earlier was noted, confirming a late and isolated ipsilateral testicular metastasis. Subsequent imaging did not demonstrate disease at any other site. This case highlights the remarkable latency and unpredictable metastatic potential of RCC and emphasizes the importance of careful histopathological evaluation of specimens removed for unrelated primary malignancies.
Gastroblastoma is a malignant epithelial tumor of the stomach, which is primarily diagnosed based on its biphasic histomorphology and the demonstration of its characteristic molecular fusion gene, MALAT1-GLI1. Variability in the histomorphology has not been studied so far owing to its rarity. With very few cases reported in the literature, its long-term course is not entirely understood, with most of the cases treated based on its stage.
OBJECTIVE:Depending on cell context, aberrant expression of Notch-1 and Notch-3 can employ either tumor suppressive or oncogenic roles. However, their roles in oral squamous cell carcinoma (OSCC) remain unclear, particularly in Indian population due to lack of availability of data from India. Therefore, we sought to explore the roles of Notch-1 and Notch-3 in OSCC and to investigate their influence on the disease outcome of patients. MATERIALS AND METHOD:Protein expression of Notch-1 and Notch-3 were localized immunohistochemically in 120 pre-therapeutic OSCC patients and assessed for their roles in disease outcomes. RESULTS:Protein expressions of Notch-1 and Notch-3 were detected in 54% and 61% of patients, respectively. Notch-1 was found to be significantly negatively associated with tumor size ( P = 0.009), nodal status ( P = 0.045), and disease stage ( P = 0.003). Contradictorily, the expression of Notch-3 was found to be positively correlated with tumor size ( P = 0.003), nodal status ( P = 0.012), and disease stage ( P = 0.001). In a Cox multivariate analysis, Notch-1 ( P = 0.037) acts as an independent favorable prognosticator for disease-free survival (DFS). For overall survival (OS), Notch-3 ( P = 0.006) remained an unfavorable prognostic parameter for predicting worse OS. CONCLUSION:Notch-1 and Notch-3 are useful prognosticators; however, Notch-1 acts as a tumor suppressor, whereas, Notch-3 acts as an oncogene correlating with aggressive phenotype. Therefore, it is very important to study both markers for OSCC patients to add prognostic information and thereby help guide therapeutic decisions.
Malignant gastrointestinal neuroectodermal tumor (MGNET) is a rare and highly aggressive malignancy originating in the gastrointestinal tract. It resembles various gastrointestinal mesenchymal tumors in appearance and microscopic morphology. While typical immunohistochemistry aids diagnosis, abnormal immunophenotypes can complicate it. We report a case of MGNET in the transverse colon in a 37-year-old man. Immunohistochemical results showed DOG1 positivity and S100 negativity, mimicking CD117-negative/DOG1-positive gastrointestinal stromal tumors (GIST). Fluorescence in situ hybridization (FISH) revealed EWSR1 gene rearrangement, and next-generation sequencing (NGS)-based RNA fusion gene detection identified EWSR1::ATF1 fusion, supporting the diagnosis of MGNET. We will discuss the abnormal immunophenotype and differential diagnosis of MGNET, reviewing relevant literature.
ABSTRACT:Prostate cancer is the second most common cancer in men, with bone metastases in advanced cases, commonly involving the spine. Pleomorphic giant cell carcinoma (PGCC) is a rare and aggressive variant of prostate cancer. We present a 71-year-old male with a history of prostate adenocarcinoma, treated with prostatectomy, radiotherapy and androgen blockade, who developed progressive lower back pain and bilateral leg weakness. Imaging showed spinal metastases at L5-S1 and D6-D7, with spinal cord compression. Biopsy revealed a metastatic high-grade, poorly differentiated tumor, consistent with PGCC. The patient received palliative radiotherapy and supportive care. This case underscores the confounding morphology and aggressive nature of PGCC, and the need for tailored management in metastatic prostate cancer.
