World Health Organization reporting system for lung cytopathology-A brief correspondence.

The WHO lung cytopathology reporting system has been published recently and is now a five-tier category system without any subcategorization. WHO reporting system also encourages the application of ancillary diagnostic tests like cell block preparation, immunocytochemistry, and rapid on-site evaluation for better categorization of specimens and further management. This correspondence aims to provide a brief outline of the lung reporting system. Lung cytopathology reporting system use standardized nomenclature and usage of the terminologies harmonizing with the WHO Blue Book, and table and flow diagram may be helpful for the readers.

Utility of C4d Immunohistochemistry as an Adjunct Stain in Diagnostic Renal Pathology of Glomerular Diseases.

C4d is a byproduct of the activation of the classic and lectin complement pathways. Being routinely used as a marker for antibody-mediated rejection, the significance of C4d in native kidney disease is currently being widely studied. We evaluated glomerular and extraglomerular C4d staining in 82 biopsies of proliferative and nonproliferative glomerulonephritis diagnosed in our institution. The staining pattern of C4d was tabulated in various glomerular diseases. All biopsies of membranous nephropathy including membranous lupus nephritis (Class V) and immune complex-mediated membranoproliferative glomerulonephritis (MPGN) consistently showed C4d deposits along glomerular basement membrane mirroring the location of immunoglobulin and complement in these conditions. Conversely, other glomerular diseases like IgA nephropathy, postinfectious glomerulonephritis, focal segmental glomerulosclerosis, minimal change disease, and diabetic nephropathy showed variable mesangial and capillary wall C4d deposits. To summarize, the consistent pattern of C4d staining in membranous nephropathy (primary and secondary)and immune complex-mediated MPGN can be used as a valuable adjunct tool in establishing the diagnosis, especially when immunofluorescence findings are limited by inadequate sampling.C4d reactivity in other glomerular diseases are variable and may not aid as a diagnostic tool in renal biopsy evaluation.

Upcoming World Health Organization system for reporting lymph node cytopathology-A preliminary outline.

Purple book for WHO reporting for lymph node cytopathology - 2023. Lymph node cytopathology reporting system may use standardized nomenclature and usage of the terminologies harmonizing with the WHO Blue Book on hematolymphoid tumors.

Regular resident becomes aggressive enemy: Diagnosed on cytology.

Actinomycosis, an oral cavity commensal, causes cervicofacial infection in patients associated with an immunosuppression state and local mucosal injuries. Bone involvement by this commensal is rare. In the present case, we report a case of left peri mandibular soft tissue, soft to firm, tender swelling in a 39-year-old immunocompetent male diagnosed as Actinomycosis infection on fine needle aspiration cytology (FNAC) and cell block preparation.

Urorectal Septum Malformation Sequence With Retroperitoneal Neuroblastoma: A Case Report of an Unusual Association.

Urorectal septum malformation sequence (URSMS) is an uncommon disease characterized by a failure of the anorectal septum to divide the cloaca and fuse with the cloacal membrane. Complete URSMS is usually lethal in newborn due to severe renal dysfunction and pulmonary hypoplasia. Partial URSMS is compatible with life with a single perineal opening draining a common cloaca with an imperforate anus which amenable to surgical management. Antenatal diagnosis of URSMS is challenging because of multisystem, complex abnormalities involving gastrointestinal, urogenital tract, cardiovascular, and musculoskeletal systems. In this case report, we describe a 15-week male fetus with partial URSMS having a spectrum of multisystem structural anomalies associated with fetal neuroblastoma in retroperitoneal location and adrenal neuroblastoma in situ.

Diagnostic Performance of Bile Duct Brush Cytology with Risk of Malignancy of Standardized Categories in the Wake of World Health Organization Reporting System for Pancreaticobiliary Cytopathology: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: The WHO Reporting System for Pancreaticobiliary Cytopathology revised the Papanicolaou Society of Cytopathology guidelines in alignment with the WHO classification of digestive system tumors, 5th edition. The current systematic review and meta-analysis have been conducted to accurately assess the performance of bile duct brush cytology and report the risk of malignancy (ROM) of each standard category by following the guidelines of diagnostic test accuracy meta-analysis. METHODS: Medline/Pubmed and Cochrane databases were searched till June 8, 2023, with a strategy that included target site (pancreaticobiliary and related terms), diagnostic method (bile duct brushing and related terms), and keywords for diagnostic performance (for Cochrane database). Inclusion criteria included studies that have assessed bile duct cytology (BDC) for pancreaticobiliary duct stricture with a sample size of over 50, provided cytological diagnoses similar to the WHO system with details to deduce true positives, true negatives, false positives, and false negatives through subsequent final diagnoses (benign vs. malignant). The exclusion criteria were the fewer sample size, assessment through other cytological categories, limited data, and clinical setting. Two authors independently reviewed the result of the search strategy. The quality of the selected articles was assessed by the QUADAS-2 tool. Bivariate random-effects model was used to get the pooled sensitivity and specificity. Heterogeneity across studies was assessed using I-squared statistics, and potential sources were found using meta-regression. Pooled and a range of ROM in each category was analyzed. RESULTS: Thirteen studies were included with 4,398 bile duct brushings. The pooled sensitivity is 0.437 (95% CI: 0.371-0.504), and the pooled specificity is 0.972 (95% CI: 0.943-0.987). The ROM in various categories are as follows: inadequate/nondiagnostic: 23-100% (pooled: 50.15%), benign/negative for malignancy: 22-70% (38%), atypical: 0-95% (66%), suspicious for malignancy: 74-100% (89%), malignant: 91-100% (98%). CONCLUSION: Even with standard cytological categories, the sensitivity of BDC remains low. The review has analyzed and discussed potential causes of heterogeneity that will be helpful for future diagnostic studies.

Solid/trabecular subtype of papillary thyroid carcinoma on cytology with focal differentiated high-grade thyroid carcinoma on histology: a cyto-histologic correlation.

Solid/trabecular subtype of papillary thyroid carcinoma (S/T PTC) is a rare entity that has been shown to have higher tumour recurrence and mortality rates. A definite diagnosis on fine needle aspiration cytology is often not easy. Rather, this entity may be misdiagnosed in cytology due to a lack of widespread features of classic PTC. We present a case of S/T PTC in a 61-year-old female, showing a focus on differentiated high-grade thyroid carcinoma (DHGTC) on histology. We discuss cytological features with the histologic correlation of S/T PTC and briefly discuss the newly introduced entity, DHGTC.

Extragonadal Germ Cell Tumors: A Single Institution Experience with Clinicopathological Correlation.

Background. Extragonadal germ cell tumors (EGCTs) are a rare heterogeneous group of tumors without evidence of primary gonadal germ cell tumors. They account for 2%-5% of overall malignancies. EGCTs are often not clinically suspected, making them challenging for pathologists. In this retrospective observational study, we describe our institutional experience among EGCTs with clinicopathological correlation. Materials and methods. All patients diagnosed as EGCTs from January 2014 to April 2023 were collected. All relevant clinical data and serum markers were retrieved from hospital medical records. Histopathology and immunohistochemistry slides were reviewed. Results. The present study included a total of 56 patients; 34 (60%) men and 22 (40%) women with a men-to-women ratio of 1.5:1. Of them, 1 patient had congenital/neonatal EGCTs, 21 patients had prepubertal EGCTs, and 34 had post-pubertal EGCTs. The common sites included are mediastinum (45%), sacrococcyx (18%), retroperitoneum (14%), and central nervous system (12%). The other rare sites were the vagina, liver, colon, and duodenum. The common germ cell tumor included mature teratoma (34%), mixed germ cell tumor (27%), seminoma/germinoma (12%), pure yolk sac tumor (11%), immature teratoma (9%), mature teratoma with somatic tumor (5%), and embryonal carcinoma (2%). All histological diagnoses of germ cell tumors were confirmed with IHC markers like PLAP, CD117 (KIT), AFP, LIN28, CD30, and ß-hCG. Pre and posttreatment serum tumor marker levels were available in 37 patients. All our treated patients had a decrease or normal tumor marker levels post-therapy. Conclusion. In our study, a heterogeneous group of germ cell tumors was seen. Most of them were seen in post-pubertal adolescents and young adults. Early intervention by platinum-based combination chemotherapy in seminoma and nonseminomatous germ cell tumors has significantly improved the prognosis of malignant EGCTs similar to their germ cell counterparts.

Spectrum of cervicovaginal Pap smears in newly established tertiary care medical institute.

Objectives: We undertook this study to find out the spectrum of the cervical smear pattern along with the clinical profiles of patients who underwent cervical Papanicolaou (Pap) smear evaluation in our newly started tertiary care center. We also tried to find the possible clinical cause for unsatisfactory smears and factors for epithelial cell abnormality. Material and Methods: The present study was a retrospective observational study. Pap smears cases with their clinical findings mentioned on the requisition form and cytopathology observations were retrieved from the archives of the department of pathology. Fisher's exact test was used for statistical analysis. Results: Five hundred and ninety-four cases were included in the study. The most common age group was 36- 40 years. White discharge per vaginum was the most common clinical presentation. The negative for squamous intraepithelial lesions or malignancy was the most common interpretation (86.87%). Cervical erosion had statistically significant associations with unsatisfactory smears, while bacterial vaginosis had with satisfactory smears. Epithelial cell abnormality was seen in 4.62% patients. We observed a statistically significant association of cervical mucoid discharge, and inflammation with "no epithelial cell abnormality" cases, while postmenopausal bleeding was associated with "epithelial cell abnormality" cases. Conclusion: In the presence of clinical factors like cervical erosion, which may affect the quality of Pap smear, proper sampling techniques are to be used by health-care providers. The careful evaluation of Pap smears, especially in cases of cervical mucoid discharge, postmenopausal bleeding, and inflammatory smears is required to ensure that epithelial cell abnormalities are not overlooked.

A Comprehensive Review of the Newest World Health Organization (WHO) Cytopathology Reporting Systems.

World Health Organization cytopathology reporting system systems have proposed for the pancreatobiliary tract, lung, lymph node, and soft tissue aligned with the updates in the World Health Organization classification of Tumor series. Among them, the pancreatobiliary tract and lung specimen reporting system have been published recently and are now a 7-tier and 5-tier category system, respectively, without any subcategorization. World Health Organization reporting systems also encourage the application of ancillary diagnostic tests like cell block preparation, immunocytochemistry, and rapid on-site evaluation for better categorization of specimens and further management, especially in indeterminate (atypical and suspicious for malignancy) and malignant cytology categories. In this brief review, we aim to provide a brief outline of both the systems and their clinical risk-based management strategies.

Primary Pediatric Yolk Sac Tumor of Liver With Lung Metastasis: An Unusual Presentation With Diagnosis Aided by LIN28 Immunohistochemistry.

Yolk sac tumor is a malignant germ cell tumor, which typically occurs in the gonads with elevated serum alpha-fetoprotein (AFP). Among extragonadal sites, the liver is an uncommon location for primary pediatric yolk sac tumors. Other common hepatic tumors in this age group presenting with elevated serum AFP like hepatoblastoma and hepatocellular carcinoma must be differentiated from yolk sac tumors for initiating appropriate treatment and accurate prognostication. Lung metastasis with refractoriness to chemotherapy is an extraordinary presentation that has never been documented in the literature. We report our experience with a 2-year-old female child initially misdiagnosed as hepatoblastoma. It was found that LIN28 positivity by immunohistochemistry aided in confirmation of the histopathological diagnosis of primary yolk sac tumor of the liver.

Insufficient/inadequate category in breast cytology: Are the standardized guidelines of rapid on-site evaluation available to reduce its rate?

In 2017, the International Academy of Cytology announced a five-tier reporting system for breast fine-needle aspiration biopsy (FNAB) cytopathology. We observed the insufficient/inadequate cases rate varied from 2.05% to 39.89%, with a risk of malignancy varying from 0% to 60.87%. This wide range of variation poses a significant number of patients at risk due to delay in management. Some authors describe rapid on-site evaluation (ROSE) as a tool to reduce its rate. In this preliminary review, we also observed that there were no uniform guidelines available for ROSE to reduce the insufficient/inadequate category rate. We expect that cytopathologists will construct some uniform guidelines for ROSE in the future, which may help to reduce the rate of category 1.

Cytology of micropapillary mucinous carcinoma: A case report of a clinically and genetically distinct breast carcinoma variant.

Micropapillary mucinous carcinoma (MPMC) is an uncommon histopathological variant of breast cancer accounting for approximately one-fifth of all mucinous breast carcinomas. In contrast to pure mucinous carcinoma, MPMC tends to affect younger women and is associated with decreased progression-free survival, higher nuclear grade, lymphovascular invasion, lymph node metastasis, and positive HER2 status. Typically MPMC histology shows micropapillary architecture with "hobnailing" of cells and reverse polarity. Very few publications document the cytomorphological findings of MPMC. We report a case of MPMC that was suspected in fine needle aspiration cytology (FNAC) and confirmed at histopathology.

Lethal Restrictive Dermopathy with ZMPSTE24 Mutation.

Lethal restrictive dermopathy is genodermatoses associated with lamin protein defects resulting in connective tissue abnormalities of skin, musculoskeletal, and adipose tissue. We report one such case with a mutation in the ZMPSTE24 gene which is involved in lamin protein synthesis, resulting in fetal akinesia or hypokinesia deformation sequence. Early recognition in the perinatal period of distinctive clinical and skin histological features followed by molecular diagnosis enabled genetic counseling for the affected family.

BK polyomavirus and urothelial carcinoma: Experience at a tertiary care centre in India with review of literature.

INTRODUCTION: BK polyomavirus is ubiquitous and remains dormant in the urothelial tract, reactivating and replicating in the immunocompromised state especially in the setting of post-renal transplantation where it is believed to be directly oncogenic based on recent reports. Its oncogenic role in the immunocompetent host is controversial. This study aimed to investigate the association of BK polyomavirus in Urothelial Carcinoma. MATERIAL AND METHODS: Patients with suspected urothelial carcinoma (UC) admitted under Department of Urology over a period of one year were recruited and transuretheral bladder tumor (TURBT) resection was performed, along with sampling of cystoscopically normal-appearing urothelium away from the tumor. In addition, cystectomy specimens with UC were included, with sampling of grossly normal-appearing urothelium away from the tumor. Immunohistochemistry (IHC) for SV40 T-Antigen and chromogenic in situ hybridization (CISH) using BK polyomavirus specific probe was performed on the paired samples (tumor and normal). RESULTS: Twenty-three TURBT and 14 cystectomy specimens were assessed. None of the cases showed evidence of BK polyomavirus infection in tumor or in surrounding mucosa by IHC. CISH performed in ten cases were also found to be negative. In comparison, one post-renal transplant urothelial carcinoma in our experience showed diffuse SV40 staining. CONCLUSIONS: This study suggests that BK polyomavirus infection is not associated with urothelial malignancy in the immunocompetent setting unlike in the immunocompromised setting where it should always be investigated for.

Glomerular C4d Staining Does Not Exclude a C3 Glomerulopathy.

INTRODUCTION: C4d, an early product in the classical/lectin complement pathway has shown potential in the evaluation of C3 glomerulopathy where its absence would support an alternative pathway abnormality. As autoimmune/genetic complement testing is not readily available to most parts of the world, glomerular C4d staining may serve as a useful additional step toward the diagnosis. METHODS: To test this hypothesis, C4d staining was performed on a large cohort of C3 glomerulopathy. Archival cases from 2011 to 2017 were reviewed and immunohistochemistry for C4d was performed, scored (scale of 0 to 3+), and correlated with the immunofluorescence and ultrastructural findings. Paraffin immunofluorescence was performed in cases of "discordant C4d" to unmask Igs. RESULTS: Twenty-seven cases of dense deposit disease (DDD) and 14 cases of C3 glomerulonephritis (C3GN) were retrieved. C4d demonstrated a range of staining intensities with negative/traces in only 22% of DDD and 64% of C3GN. Lower-intensity C4d staining (1 to 2+) was mostly concordant with similar amounts of Igs/C1q. Discordant 3+ staining was noted in approximately 50% of cases of DDD and 20% of cases of C3GN. Among them, paraffin immunofluorescence unmasked polyclonal Igs in 2 of 5 cases of DDD and 1 of 3 cases of C3GN. CONCLUSION: This observational study suggests that the presence of glomerular C4d should not exclude a C3 glomerulopathy. In lower intensities, it appears to represent overlying classical/lectin pathway activation with concordant Ig/C1q deposits. A subset of cases, however, displays intense and discordant C4d staining, which raises the possibility of an associated lectin pathway abnormality, a potential future area of study.