Dinesh Pradhan

Uterine Tumors Resembling Ovarian Sex Cord Tumors

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare neoplasms of unknown etiology. Only 67 cases have been reported in the literature, to our knowledge, so far. The neoplasm usually occurs in middle-aged women. Most patients present with abnormal uterine bleeding and/or abdominal pain, along with an enlarged uterus or a palpable uterine mass. There is no specific imaging finding, and the diagnosis is made exclusively on histopathologic examination. A multitude of architectural patterns are described, which include plexiform cords, anastomosing trabeculae, watered-silk, microfollicle, macrofollicle, tubules, retiform, solid cellular islands, and diffuse pattern of growth. The neoplastic cells are usually small with round to ovoid nuclei, nuclear monotony, mild nuclear hyperchromasia, and inconspicuous nucleoli with scant eosinophilic cytoplasm. Nuclear grooves are rare. Mitotic figures are infrequent, and necrosis is mostly absent. This tumor depicts a diverse immunohistochemical profile with expression of sex cord, epithelial, and smooth muscle lineages markers. Sex cord markers, such as inhibin, calretinin, CD99, WT1, and MART-1; epithelial markers, such as pancytokeratin and epithelial membrane antigen; smooth muscle markers, such as smooth muscle actin, desmin, and histone deacetylase 8; and miscellaneous markers, such as CD10, estrogen receptor, progesterone receptor, S100, and CD117, are often coexpressed. Immunoexpression for calretinin and at least for one of the other sex cord markers is required to establish a diagnosis of UTROSCT. Hysterectomy with or without bilateral salpingo-oophorectomy is usually the treatment for UTROSCT. Although most UTROSCTs behave benignly, some do recur, and thus, this entity should be considered as a tumor of low malignant potential. In this review, we discuss the current knowledge on UTROSCT and its clinical relevance.

Sub-typing of renal cell tumours; contribution of ancillary techniques

BackgroundAdult renal epithelial neoplasms are a heterogeneous group with varying prognosis and outcome requiring sub-classification.MethodsCases of renal cell carcinoma (RCC) in a 10 years period were analyzed with regard to the clinical features and histology. Sections were reviewed by four pathologists and the discordant cases were resolved with the help of Hales colloidal iron stain, vimentin, CK 7, and vinculin immunostains and electron microscopy.ResultsAmongst the total of 278 cases, clear cell renal cell carcinoma was the commonest tumor with 74.8% cases, followed by papillary RCC 12.2%, chromophobe RCC 7.9%, oncocytoma 1.8%, and one case of collecting duct RCC. Eight cases were of sarcomatoid renal cell carcinoma. In 28/278 cases, diagnoses varied amongst the four pathologists and the discordance was resolved by Hales colloidal iron stain, CK7 immunostain and electron microscopy. Vimentin and vinculin did not contribute much in differentiating subtypes of renal cell carcinomas. Relative incidence of sub-types of RCCs was compared with other seriesConclusionTo accurately subclassify renal cell carcinomas, simple ancillary techniques would possibly resolve all difficult cases. The relative incidence of sub-types of renal cell carcinoma is relatively consistent the world over. However, in India, RCCs afflict the patients two decades earlier.

Cribriform-morular variant of papillary thyroid carcinoma

Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare morphologic entity. This tumor is usually associated with familial adenomatous polyposis (FAP), but rarely may be sporadic. This neoplasm commonly occurs in young females. The majority of patients present with gradually enlarging painless neck mass. There is no specific imaging finding of CMV-PTC, and the diagnosis is exclusively made on pathologic examination. A multitude of cytologic features of CMV-PTC are described, which includes hypercellularity, cribriform pattern, papillary arrangement of tall columnar cells, morules, spindle cells, clear and ground-glass nuclei, hyaline material, hemosiderin-laden histiocytes, and absence of colloid in the background. CMV-PTC is histologically characterized by the papillary growth of tall columnar cells, cribriform pattern without colloid, spindle cells, squamoid morules, and nuclear clearing. The immunoreactivity for beta-catenin and biotin-positive nuclear clearing may indicate CMV-PTC. Total thyroidectomy for familial or lobectomy for sporadic cases is usually the treatment for CMV-PTC. It carries a better prognosis than the other aggressive variants of papillary thyroid carcinoma. In this review, we discuss the current knowledge on CMV-PTC and its clinical relevance.

Evaluation of panoramic digital images using Panoptiq for frozen section diagnosis

Introduction: Whole slide imaging (WSI) permits intraoperative consultations (frozen sections) to be performed remotely. However, WSI files are large and can be problematic if there are tissue artifacts (e.g., tissue folds) or when slides are scanned without multiplanes (Z-stacks) to permit focusing. The Panoptiq dynamic imaging system allows users to create their own digital files that combine low power panoramic digital images with regions of interest that can be imaged using high power Z-stacks. The aim of this study was to determine the utility of the Panoptiq dynamic imaging system for frozen section telepathology. Materials and Methods: Twenty archival randomly selected genitourinary surgical pathology frozen sectional cases were evaluated using conventional light microscopy (glass slides), panoramic images, and whole slide images. To create panoramic images glass slides were digitized using a Prosilica GT camera (model GT1920C, Allied Vision Technologies) attached to an Olympus B × 45 microscope and Dell Precision Tower 810 computer (Dell). Panoptiq 3 version 3.1.2 software was used for image acquisition and Panoptiq View version 3.1.2 to view images (ViewsIQ, Richmond, BC, Canada). Image acquisition using Panoptiq software involved a pathology resident, who manually created digital maps (×4 objective) and then selected representative regions of interest to generate Z-stacks at higher magnification (×40 objective). Whole slide images were generated using an Aperio XT Scanscope (Leica) and viewed using ImageScope Software (Aperio ePathology, Leica). Three pathologists were asked to render diagnoses and rate image quality (1-10) and their diagnostic confidence (1-10) for each modality. Results: The diagnostic concordance with glass slides was 98.3% for panoramic images and 100% for WSI. Panoptiq images were comparable to the glass slide viewing experience in terms of image quality and diagnostic confidence. Complaints regarding WSI included poor focus near tissue folds and air bubbles. Panoptiq permitted fine focusing of tissue folds and air bubbles. Issues with panoramic images included difficulty interpreting low-resolution ×4 image maps and the presence of tiling artifacts. In some cases, Z-stacked areas of Panoptiq images were limited or not representative of diagnostic regions. The image file size of Panoptiq was more than 14 times smaller than that of WSI files. Conclusions: The Panoptiq imaging system is a novel tool that can be used for frozen section telepathology. Panoramic digital images were easy to generate and navigate, of relatively small file size, and offered a mechanism to overcome focusing problems commonly encountered with WSI of frozen sections. However, the acquisition of representative Panoptiq images was operator dependent with the individual creating files that may impact the final diagnosis.

IgG4-related kidney disease – A review

IgG4-related disease (IgG4-RD) is a recently recognized systemic autoimmune disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive plasma cells in multiple organs. The condition was first described as a disease of the pancreas, and has since been recognized in various organ systems including the kidneys. IgG4 related kidney disease (IgG4-RKD) signifies any form of renal involvement by IgG4-RD. The most common renal involvement by IgG4-RD is tubulointerstitial nephritis. Glomerular disease, in particular membranous glomerulonephritis, may also be seen. Other co-existent glomerular diseases such as IgA nephropathy, membranoproliferative glomerulonephritis, and mesangioproliferative immune complex glomerulonephritis may be identified. IgG4-related plasma cell arteritis has also been noted in the kidney. As with IgG4-RD in general, IgG4 related kidney disease (IgG4-RKD) usually occurs in middle-aged to elderly men. Common findings in IgG4-RKD are plasma cell-rich interstitial inflammatory infiltrate either in a focal or diffuse pattern with increased IgG4+ plasma cells, expansile swirling interstitial fibrosis, high levels of serum IgG and IgG4, hypocomplementemia, high serum IgE levels and/or peripheral blood eosinophilia. By immunofluorescence, most of the cases show IgG4 dominant tubular basement membrane immune complex deposits. Similar to IgG4-RD, IgG4-RKD often shows a rapid response to steroid therapy. In this review, we discuss the current knowledge on IgG4-RKD and its clinical relevance.

Sclerosing angiomatoid nodular transformation of the spleen.

Sclerosing Angiomatoid Nodular Transformation (SANT) of the spleen is a rare benign lesion of the spleen with unknown etiology. SANT is classically considered to be a female-predominant disease, with most of the patients in the 30- to 60-year age group. Most lesions are found incidentally on imaging. Although SANT has specific imaging findings, the differential diagnosis from other splenic tumors or malignant lesions is very difficult. Histopathologically, these tumors reveal multiple confluent angiomatoid nodules; these nodules are surrounded by concentric collagen fibers exhibiting an inflammatory and myofibroblastic response and are accompanied by numerous erythrocytes and siderophages. The nodules are populated by endothelial cells, phenotypically recapitulating normal splenic vasculature, such as sinusoids, capillaries, and small veins. Nuclear atypia is minimal, mitotic figures are extremely rare, and necrosis is consistently absent. This lesion has a unique immunohistochemical profile characterized by CD34(-)CD31(+)CD8(+) sinusoids, CD34(+)CD31(+)CD8(-) capillaries, and CD34(-)CD31(+)CD8(-) small veins. CD68 is positive in macrophages. Splenectomy is a useful and effective technique for the management of SANT. SANT patients have a good prognosis, with no recurrence after splenectomy. In this review, we discuss the current knowledge of SANT of the spleen and its clinical relevance.

Clinical significance of atypical glandular cells in Pap tests: An analysis of more than 3000 cases at a large academic women's center.

The interpretation of atypical glandular cells (AGC) in Papanicolaou (Pap) tests and screening for glandular neoplasia remain challenging.

Uterine angioleiomyoma: A rare variant of uterine leiomyoma - A case report and literature review

Uterine angioleiomyoma (AL) is an extremely rare variant of leiomyoma and only 15 cases have been reported till date. Herein we present a case of AL of the uterus in a 39-year-old multiparous female with polymenorrhagia and pain abdomen. A pelvic ultrasonogram showed a large heterogeneously hypoechoic intramural nodule in the posterior myometrium. The patient underwent a total abdominal hysterectomy. Histological examination of the nodule revealed a moderately cellular spindle cell tumor composed of interlacing fascicles of spindle to plump cells swirling around the thick walled vessels. No hypercellularity, pleomorphism, mitotic figures, or necrosis was identified. The spindle to plump cells showed strong and diffuse immunoreactivity for smooth muscle actin, desmin and progesterone receptor, focal and weak positivity for CD10 and estrogen receptor and were negative for CD34 and HMB-45. The Ki-67 labeling index was low (1%). A diagnosis of AL was offered. The patient is on follow up for over 10 months and is asymptomatic.

Mediastinal mixed germ cell tumor in an infertile male with Klinefelter syndrome:A case report and literature review

Klinefelter syndrome (KS) is a well-documented abnormality of the sex chromosome, with an incidence of 1 in 600 newborn males. It is characterized by a 47, XXY or a mosaic karyotype, hypergonadotrophic hypogonadism, infertility, reduced body hair, gynecomastia, and tall stature. Different neoplasms such as breast, testicular, and lymphoreticular malignancies may occur in 1% to 2% of the cases with KS. Herein we describe a case of mediastinal mixed germ cell tumor (GCT) in a 40-year-old male with KS. Interestingly, this case also had mitral valve prolapse, and an incidental papillary microcarcinoma of the thyroid gland. In view of the presence of pulmonary nodules, antemortem differential diagnoses considered were mycobacterial infection, lymphoma, thymic carcinoma, and a primary/metastatic neoplasm of the lung. As GCT was not considered, the serum markers of a GCT were not performed. The diagnosis of this rare mediastinal mixed GCT with KS was made at autopsy.

Next-generation sequencing-based molecular characterization of primary urinary bladder adenocarcinoma

Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes. Genomic profiles of 25 HGUCs and 25 colorectal adenocarcinomas using next-generation sequencing of 50 genes were compared with primary bladder adenocarcinoma. Genomic profiles were visualized using JavaScript library D3.js. A striking finding was the distinct lack of genomic alterations across the 51 genes assessed in mucinous subtype of primary bladder adenocarcinoma. Eleven of 15 primary bladder adenocarcinoma harbored at least one genomic alteration in TP53, KRAS, PIK3CA, CTNNB1, APC, TERT, FBXW7, IDH2 and RB1, many of which are novel findings and of potential therapeutic significance. CTNNB1 and APC mutations were restricted to enteric subtype only. While genomic alterations of primary bladder adenocarcinoma showed substantial overlap with colorectal adenocarcinoma, FGFR3 and HRAS mutations and APC, CTNNB1 and IDH2 alterations were mutually exclusive between primary bladder adenocarcinoma and high-grade urothelial carcinoma. These alterations affecting the MAP kinase, PI3K/Akt, Wnt, IDH (metabolic) and Tp53/Rb1 signaling pathways may provide the opportunity for defining targeted therapeutic approaches.