Evaluation of the follicular patterned thyroid lesions based on the WHO 2022 criteria with an emphasis on the grey-zone lesions.

Follicular-patterned thyroid nodules (FPTN) are classified byWHO-2022 into benign, borderline and malignant categories. There are however, grey-zone lesions that pose a diagnostic challenge due to ambiguity in defining criteria and inter-observer variability. WHO-2022 has enumerated specific diagnostic criteria for these lesions. Accurate categorization of morphologically similar TNs is vital to reduce overtreatment of indolent lesions. In this study, we have reclassified FPTNs according to WHO-2022 criteria, emphasizing on grey-zone lesions. We studied the utility of immunohistochemistry (IHC)-CD56, HBME-1 and CK19 in distinguishing benign from malignant nodules and BRAFV600E IHC to better distinguish the (widely-invasive) encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) from infiltrative FVPTC. Only those cases with dominant nodule having follicular pattern histology were included and re-evaluated for following histopathological features-focality, encapsulation, circumscription, nuclear PTC features, capsular-invasion, angio-invasion, papillae and necrosis. IHC findings for above-mentioned markers were noted. Seventy-nine cases met the inclusion criteria. Amendment of original diagnosis was done in 19 % cases. BRAFV600E IHC was positive in the two cases of infiltrative FVPTC while it was negative in all nine IE (invasive encapsulated) FVPTCs. Diffuse HBME1 was noted in most malignant nodules (61 %) while CD56 was expressed more often in benign lesions (70 %). CK19 was positive in lesions displaying nuclear PTC features (86 %). Using WHO 2022 criteria, we were able to re-classify follicular thyroid lesions with greater confidence. Appropriate IHC panel in adjunct to histology aids in categorizing challenging cases.

Neuroendocrine carcinoma of ovary: Hitherto rare entity in primary ovarian tumors.

Neuroendocrine neoplasms (NEN) of the female genital tract are extremely uncommon. These tumors can be broadly divided into well differentiated (carcinoid) and poorly differentiated NEN (small cell and large cell carcinomas). Occurrence of neuroendocrine carcinomas (NECs) in ovary has rarely been reported. These high-grade malignant tumors have a fulminant clinical course with a short period of survival, even when diagnosed at an early stage. We hereby report two cases of primary neuroendocrine carcinoma of the ovary.

Amelanotic Melanoma: A Great Masquerader.

Malignant melanoma is an aggressive, notorious tumor showing great variability in morphological and immunohistochemical expression, thus commonly leading to an erroneous diagnosis. Within the melanoma group, amelanotic melanoma, with its wide clinical presentations, lack of pigmentation, and varied histological appearances, has taken on a new persona as a master masquerader. Use of immunohistochemistry in the diagnosis of malignant tumors, including melanoma, is primordial and indispensable. However, the problem gets compounded in scenario of aberrant antigenic expression. The present case posed multiple diagnostic challenges in form of atypical clinical presentation, variant morphology, as well as aberrant antigenic expression. Here, we present the case of a 72-year-old male who, upon his initial presentation, was thought to be sarcomatoid anaplastic plasmacytoma, but 5 months later another biopsy from a different site revealed the actual diagnosis of amelanotic melanoma.

Cystic lesions of the adrenal gland.

Cystic lesions of the adrenal glands are relatively uncommon and most of them are clinically silent. Though rarely associated with malignant changes, they may carry clinically detrimental consequences if misdiagnosed. Cystic adrenal lesions exhibit a broad histomorphological spectrum, ranging from pseudocysts, endothelial cysts, epithelial cysts and parasitic cysts. Here we present the case of a young woman with left-sided abdominal pain and contrast-enhanced CT showing a 10.4×7.7×7.8 cm fluid-filled left suprarenal lesion. The patient underwent exploratory laparotomy with cyst excision, and the histopathological examination of the specimen revealed a pseudocyst of the left adrenal gland. Despite being rare, usually benign and asymptomatic, the diagnosis and management of these cystic lesions of the adrenal glands are often unclear. Any functional lesion, potentially malignant lesion or lesion more than 5 cm deserves surgical management, whereas others can be managed conservatively.

Quantification of the Androgen and Estrogen Receptors in the Penile Tissues of Hypospadias in Comparison with Normal Children.

INTRODUCTION: Hypospadias is a common congenital abnormality typified by a proximally placed ectopic urethral meatus along the ventral surface of the penis. Androgen receptor (AR) and estrogen receptor (ER) expression in the hypospadias tissues may be altered in hypospadias. METHODOLOGY: We evaluated by immunohistochemistry the AR and ER expression in 75 tissues from hypospadias repair, and compared this expression to that of tissue from 75 patients undergoing circumcision. We also compared the intensity of AR and ER expression between different severities of hypospadias. RESULTS: AR quantitative grading score decreased with severity of hypospadias, while the ER score increased as the hypospadias worsened, which was statistically significant (p-value <0.05). CONCLUSION: The penile tissue AR expression is decreased and ER expression is increased with increasing severity of hypospadias.

Preliminary Reference Interval for 5-Alpha Reductase in Normal Male Children and Its Association with Hypospadias.

BACKGROUND: 5-alpha reductase (5-AR) enzyme is responsible for conversion of testosterone to dihydrotestosterone (DHT) in humans, which subserves various functions. The aim of the study was to establish a normal reference interval (RI) for blood levels of the enzyme 5-AR. METHODS: We conducted a prospective study on 150 boys, 75 of whom underwent circumcision for various benign conditions or for religious reasons (Group A/controls) and 75 suffering from hypospadias of variable severity (Group B/cases). The plasma levels of 5-AR were measured by enzyme-linked immunosorbent assay (ELISA) in all 150 boys and correlated with the severity of hypospadias. RESULTS: The 5-AR levels in Group A ranged from 14.6 to 17.3 ng/mL. The enzyme levels decreased in value with increasing severity of hypospadias in Group B (P-value <0.01 - statistically significant). The levels of the enzyme in this group ranged from 0.6 ng/mL (in the most severe variety of hypospadias) to 11.5 ng/mL (mild variety of hypospadias). CONCLUSIONS: There is no record of RI values of 5-AR in the literature. The RI of 5-AR needs to be determined by conducting more studies globally. Its levels falls considerably with clinical severity of hypospadias, reinforcing the importance of the enzyme in the development of male external genitalia.

Glomus Tumor of Scrotum and Stomach: Usual Tumor at Unusual Locations.

Glomus tumor is a rare benign neoplasm, accounting for less than 2% of all the soft tissue tumors. Although they can develop in any part of the body, they commonly do so in upper extremities, most commonly in fingers. Here, we report two cases of glomus tumor at rare locations, in order to increase the awareness of this tumor entity in unusual sites. We also highlight the clinicopathological features and differential diagnoses of this tumor.

Obstructing primary squamous cell carcinoma of caecum: A case report.

Squamous cell carcinoma (SCC) of the colon is a rare malignancy and usually a pathological surprise. Clinical presentation is usually very similar to adeno carcinoma variety. We report a case of a 56 year old male with primary SCC of caecum presenting as small bowel obstruction and managed with surgery and adjuvant chemotherapy. It was labelled as primary SCC after extensive search for other primary malignant SCC in body with possible metastasis to caecum. Due to rarity of the disease and lack of literature standardized protocols for neo-adjuvant and adjuvant therapy are not available.

Evaluation of cases of membranoproliferative glomerulonephritis according to newer classification: A retrospective record-based study.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) has traditionally been classified on electron microscopy (EM) into different types based on the location of the immune complexes. Sethi et al. subsequently suggested a more relevant etiology-based and clinically useful classification based on immunofluorescence. METHODS: In this retrospective study, 18 diagnosed cases of MPGN over a one-year period for which direct immunofluorescence (DIF) study results were available, were selected. Cases without archived records of immunofluorescence photographs/reports were excluded. Histological diagnosis of MPGN was confirmed and DIF results were analyzed with reference to antibodies to IgG, IgA, IgM, C3, C1q, kappa, and lambda light chains. RESULTS: Evaluation of cases revealed 8 males and 10 females with age range from 11 to 66 years. Fifteen cases presented with nephrotic syndrome. On evaluation, 88.89% cases (16/18) were immune complex mediated while two (11.11%) were of complement mediated type of MPGN. Among immune complex-mediated cases, a single case of monoclonal gammopathy associated or light chain mediated MPGN was present. CONCLUSION: The classification described by Sethi et al. is easy to use since it relies on DIF instead of EM which is not readily available. Most of the cases were immune complex mediated whereas incidence of complement mediated MPGN, that is, C3 glomerulopathy was low (11.11%). Application of the new classification allows more relevant categorization of cases based on etiology and without the requirement of EM.

Anti-neutrophil cytoplasmic antibody negative crescentic paucimmune glomerulonephritis in a case of scleroderma with systemic lupus erythematosus overlap.

Renal Involvement in scleroderma is a known problem and the manifestations are well described. Renal involvement in systemic lupus erythematosus (SLE) is also well known. However, in scleroderma and SLE overlap syndrome, the renal findings may vary being a combination of features of immune complex mediated glomerulonephritis as well as thrombotic microangiopathy. We report a case in which the renal manifestation in such a situation was of a focal necrotising pauci-immune glomerulonephritis with crescents, anti-neutrophil cytoplasmic antibody negative. To the best of our knowledge, such manifestations have not been described before. Renal dysfunction in a normotensive setting in such a case should direct one towards evaluation for other causes and should prompt a kidney biopsy. This would be valuable in delineating the pathological process in the kidney and would help in guiding therapy.

Oxford classification of IgA nephropathy and C4d deposition; correlation and its implication.

Introduction: IgA nephropathy (IgAN) is well known to be the most common form of primary glomerulonephritis throughout the world. The histopathological changes are wide and varied as brought out by the various classification systems like the Haas and Oxford systems. C4d is a well-known biomarker of the complement cascade and has recently been implicated in certain native renal diseases. We attempted to characterize C4d deposition in IgAN and correlate this with histopathology by the Oxford classification system. Patients and Methods: This retrospective study included renal biopsies of 15 cases of IgAN diagnosed on histopathology and immunofluorescence over a period of 2 years. Demographic parameters of age and sex were reviewed. The Oxford classification system was applied to score the cases and immunohistochemistry for C4d was done on all cases to characterize staining pattern and intensity and was correlated with Oxford classification. Results: On histological examination, the cases showed various combinations of lesions ranging from M0E0S0T0 to M1E1S1T1. C4d deposition was found to be occurring mainly in mesangial location (12/15 cases, 80%). Forty percent cases showed C4d deposition in the glomerular capillary walls in a segmental fashion and 26.67% showed global pattern. Other patterns of deposition were arteriolar (53.33%), in peritubular capillaries (26.67%) and in tubular epithelium (20%). Conclusion: On comparing the various patterns of deposition of C4d with the four variables of the Oxford classification system, we found that segmental and global deposition of C4d correlated best with endocapillary proliferation.

Immuno-histological assessment of sub-clinical acute and borderline rejection in renal allograft recipients: Data from a transplant center in India.

This single-center study was carried out on living related and unrelated renal transplant recipients (RTRs) to evaluate the usefulness of surveillance biopsies in monitoring stable renal allografts using immuno-histological markers for immune-activation. This is a prospective, longitudinal study. Protocol biopsies of 60 RTRs with stable graft function were evaluated at three, six and 12 months post-transplant. Immuno-histological evaluation was carried out using immune-activation markers (perforins, granzyme and interleukin-2R), phenotypic markers (CD-3 and CD-20), viral markers and C4d. The demographic and clinical profile was recorded for each patient. All cases of acute sub-clinical rejection (SCR) were treated and borderline SCR cases were followed-up without treatment. SCR at three and six months post-transplant was evident in 16.7% and 3.7% of RTRs, respectively. Positive statistical association of SCR was seen with HLA-DR mismatches, whereas patients receiving induction therapy and tacrolimus-based immunosuppression exhibited a lower incidence of SCR. T cell phenotype with persistent expression of immune-activation markers exhibited positive statistical association with interstitial fibrosis and tubular atrophy at 12-month follow-up biopsy. The mean creatinine levels were significantly lower in the protocol biopsy group than the non-protocol biopsy group. No significant difference was found between the mean creatinine levels of the SCR group after treatment and the non-SCR cases within the protocol biopsy group. Early treatment of sub-clinical acute rejection leads to better functional outcomes. However, persistent immune-activation is associated with chronicity and may have implications on long-term graft survival.

A case of reticulate acropigmentation of kitamura: dowling degos disease overlap with unusual clinical manifestations.

Reticulate hyperpigmentary disorders are a group of rare genetic pigmentary abnormalities which includes reticulate acropigmentation of Kitamura (RAPK), Dowling-Degos disease (DD), reticulate acropigmentation of Dohi (RAPD), Haber's syndrome, and Galli-Galli disease. A 25-year-old male presented with asymptomatic dark-colored lesions on his hands and feet with light-colored skin lesions involving the trunk since three years. Dermatological examination revealed hyperpigmented macules in a reticulate pattern involving the dorsa of the hands and feet, front and sides of the neck, axillae, periorbital region, and groin. Multiple pits were present over both palms, with breaks in dermatoglyphics. He also had multiple nonacne facial scars predominantly on the nose and malar areas. The patient had overlapping features of RAPK and DDD. In addition, he also had hypopigmented macules and acneiform facial scars. Such an overlap of features of reticulate pigmentation has not been previously reported in the literature.

Evaluation of fascin-1 expression as a marker of invasion in urothelial carcinomas.

BACKGROUND: Prognostication and therapeutic evaluation of urothelial carcinomas significantly depends on the depth of invasion. The assessment of invasion on routine histopathological sections may be difficult in some cases. Fascin is an actin-bundling protein involved in tumor cell migration with enhanced expression associated with invasive tumors. The data available on fascin-1 expression in urothelial carcinoma however is limited. To characterize fascin-1 expression in urothelial neoplasms and its correlation with invasiveness in urothelial carcinomas. METHODS: A descriptive study design wherein fascin-1 immunoreactivity was studied in 126 urothelial neoplasms using monoclonal antibody against fascin by immunohistochemistry. 52/126 (41.26%) were low grade carcinomas (48/52 stage pTa and 4/52 stage pT1), 46/126 (36.5%) high grade carcinomas (13/46 stage pTa, 8/46 stage pT1 and 25/46 stage pT2), 02/126 carcinoma-in-situ, 03/126 papilloma, 12/126 papillary urothelial neoplasm of uncertain malignant potential and 11/126 were other variants of urothelial carcinomas. Fascin-1 cytoplasmic immunoreactivity was assessed semiquantitatively in terms of extent, intensity and a combined immunoreactivity score. Correlation between immunoreactivity scores and invasiveness was evaluated using Pearson's chi-square (χ2) and Nonparametric Spearman rho (ρ) correlation coefficient two tailed. RESULTS: The scores for intensity, extent and combined immunoreactivity were significantly higher in invasive carcinomas. In addition, strong staining was observed exclusively in invasive carcinomas. None of the pTa tumors demonstrated intense staining, including those categorized as high grade carcinomas. CONCLUSION: Fascin-1 overexpression may be used as a marker in urothelial carcinomas where it is morphologically difficult to determine the status of invasion.

Unusual case of pulmonary renal syndrome with autopsy findings.

Scleroderma renal crises (SRC) is a serious complication of systemic sclerosis whose prognosis remains serious despite management with angiotensin-converting enzyme inhibitors, antihypertensives and dialysis. Pulmonary renal syndrome (PRS), characterised by diffuse alveolar hemorrhage (DAH) and SRC, is rare and carries a grave prognosis. This case report discusses the clinicopathological features of a 43-year-old male presenting with severe hypertension and rapidly progressive renal failure who subsequently developed DAH and died. The clinical course, exhaustive investigative work-up and autopsy findings led to a diagnosis of diffuse systemic sclerosis with PRS subcategorized into PRS with thrombotic microangiopathy. The index case came without a prior diagnosis of systemic sclerosis, thereby posing a serious diagnostic challenge and management issues.

BK polyoma viral infection in renal allograft recipients.

BACKGROUND: BK polyoma viral nephropathy (BKVAN) has emerged as a significant cause of renal allograft loss. The literature on BK viral infection from India is scarce. The study was therefore undertaken to evaluate impact of BK polyoma viral (BKV) infection on renal allograft recipients in Indian scenario from a service renal transplantation centre. METHODS: Renal allograft recipients who underwent graft biopsy formed the part of this descriptive cross-sectional study group. The clinicopathological profile of the patients was analysed. The diagnostic modalities employed were histopathology, immunohistochemistry using antibody for Simian virus 40 large T antigen along with real time quantification of the BK viral DNA load in the urine and the serum. RESULTS: One hundred forty seven renal allograft recipients were evaluated. 73.47 percent (108/147) patients presented with graft dysfunction and rest were protocol biopsies. There were 53 cases of rejection related diagnosis, 8 cases of graft pyelonephritis, 64 cases showed normal histology and rest exhibited miscellaneous causes. Nineteen percent (28/147) cases were positive for BKV DNA (viruria 26/147, 17.6% and viraemia 8/147, 5.44%. 3.4 percent (5/147) exhibited histological and immunohistochemical evidence of BKVAN. Nuclear enlargement, smudging and intranuclear inclusions along with plasma cell rich interstitial nephritis were important features observed on histopathology. Concomitant acute rejection was seen in 4/5 cases of BKVAN. All cases of BKVAN exhibited viraemia (> 2500 copies/mL), though cut-off values could not be defined statistically due to small sample size. Positive statistical correlation was observed between use of anti-thymocyte globulin (induction therapy and/or treatment of steroid resistant rejection, Pearson ×(2) value 6.9, P=0.008) and rejection episodes (Pearson ×(2) value 9.8, P = 0.007) with BKV infection. CONCLUSION: BK polyoma nephropathy should be added to the list of differential diagnosis considered for a renal allograft dysfunction. Renal biopsy remains the gold standard for diagnosis supplemented by non-invasive molecular techniques for screening and monitoring of BKV infection.