Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.

Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinomas (RCC) are difficult to diagnose prospectively. We used immunohistochemistry (IHC) to identify fumarate hydratase (FH)-deficient tumors (defined as FH negative, 2-succinocysteine [2SC] positive) in cases diagnosed as "unclassified RCC, high grade or with papillary pattern," or "papillary RCC type 2," from multiple institutions. A total of 124 tumors (from 118 patients) were evaluated by IHC for FH and 2SC.

Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas.

Dedifferentiated endometrial carcinoma is an aggressive type of endometrial cancer that contains a mix of low-grade endometrioid and undifferentiated carcinoma components. We performed targeted sequencing of eight dedifferentiated carcinomas and identified somatic frameshift/nonsense mutations in SMARCA4, a core ATPase of the switch/sucrose non-fermenting (SWI/SNF) complex, in the undifferentiated components of four tumors. Immunohistochemical analysis confirmed the loss of SMARCA4 in the undifferentiated component of these four SMARCA4-mutated cases, whereas the corresponding low-grade endometrioid component showed retained SMARCA4 expression.

Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.

Mixed endometrial carcinoma refers to a tumor that comprises 2 or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas-11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade ECs (CCC/EC), and 2 mixed CCC and SCs (CCC/SC), using targeted next-generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin.

Eosinophilic, Solid, and Cystic Renal Cell Carcinoma: Clinicopathologic Study of 16 Unique, Sporadic Neoplasms Occurring in Women.

A unique renal neoplasm characterized by eosinophilic cytoplasm and solid and cystic growth was recently reported in patients with tuberous sclerosis complex (TSC). We searched multiple institutional archives and consult files in an attempt to identify a sporadic counterpart. We identified 16 morphologically identical cases, all in women, without clinical features of TSC.

Cystic Renal Oncocytoma and Tubulocystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Comparative Study.

Renal oncocytoma (RO) may present with a tubulocystic growth in 3% to 7% of cases, and in such cases its morphology may significantly overlap with tubulocystic renal cell carcinoma (TCRCC). We compared the morphologic and immunohistochemical characteristics of these tumors, aiming to clarify the differential diagnostic criteria, which facilitate the discrimination of RO from TCRCC. Twenty-four cystic ROs and 15 TCRCCs were selected and analyzed for: architectural growth patterns, stromal features, cytomorphology, ISUP nucleolar grade, necrosis, and mitotic activity.

Diagnosis of Ovarian Carcinoma Histotype Based on Limited Sampling: A Prospective Study Comparing Cytology, Frozen Section, and Core Biopsies to Full Pathologic Examination.

Growing insights into the biological features and molecular underpinnings of ovarian cancer has prompted a shift toward histotype-specific treatments and clinical trials. As a result, the preoperative diagnosis of ovarian carcinomas based on small tissue sampling is rapidly gaining importance. The data on the accuracy of ovarian carcinoma histotype-specific diagnosis based on small tissue samples, however, remains very limited in the literature.

Diagnosis of "Poorly Formed Glands" Gleason Pattern 4 Prostatic Adenocarcinoma on Needle Biopsy: An Interobserver Reproducibility Study Among Urologic Pathologists With Recommendations.

Accurate recognition of Gleason pattern (GP) 4 prostate carcinoma (PCa) on needle biopsy is critical for patient management and prognostication. "Poorly formed glands" are the most common GP4 subpattern. We studied the diagnostic reproducibility and the quantitative threshold of grading GP4 "poorly formed glands" and the criteria to distinguish them from tangentially sectioned GP3 glands.

Urinary bladder xanthoma: a multi-institutional series of 17 cases.

Aims: To present a series of urinary bladder xanthomas and characterize their clinical features and associated pathology.

Methods And Results: We retrieved the clinicopathological data of bladder xanthomas, with and without associated urothelial neoplasms. We identified six isolated bladder xanthomas and 11 arising within or adjacent to urothelial neoplasms.

Incidental nonuterine high-grade serous carcinomas arise in the fallopian tube in most cases: further evidence for the tubal origin of high-grade serous carcinomas.

Most nonuterine high-grade serous carcinomas (HGSCs) in women with hereditary breast and ovarian cancer syndrome, due to germline BRCA1/2 mutation, arise in the fimbria of the fallopian tube. However, the site of origin of sporadic HGSC, which is usually widely disseminated at presentation, is not well established. We sought to characterize cases of HGSC discovered incidentally in patients not known to be at high risk, in order to determine the site distribution and possible origin of sporadic HGSC.

Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients.

Succinate dehydrogenase (SDH)-deficient renal carcinoma has been accepted as a provisional entity in the 2013 International Society of Urological Pathology Vancouver Classification. To further define its morphologic and clinical features, we studied a multi-institutional cohort of 36 SDH-deficient renal carcinomas from 27 patients, including 21 previously unreported cases. We estimate that 0.

Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry.

Aims: To assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility.

Methods And Results: Eight pathologists from four countries (Sweden, Denmark, Norway, and Finland) received an educational lecture on the diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian carcinoma cases were independently reviewed by the participants, who: (i) determined type purely on the basis of histology; (ii) indicated whether they would apply immunohistochemistry in their routine practice; and (iii) determined type after reviewing the staining results.

Testicular hilum and vascular invasion predict advanced clinical stage in nonseminomatous germ cell tumors.

Clinical staging is a critical step in the management of testicular germ cell tumors. Up to one-third of nonseminomatous germ cell tumors of the testis present with metastatic disease (clinical stages II and III). We investigated the predictors of metastatic disease at presentation in a cohort of 148 consecutive nonseminomatous germ cell tumors of the testis, over a 10-year period.

Mesothelioma of tunica vaginalis of "uncertain malignant potential" - an evolving concept: case report and review of the literature.

Mesothelioma of tunica vaginalis is a rare neoplasm, typically demonstrating frankly malignant morphology and aggressive behavior. Rare cases of well-differentiated papillary mesotheliomas have also been reported, which, in contrast, demonstrate indolent behavior. There are, however, cases which do not fit into the well-differentiated or diffuse malignant mesothelioma categories and can be considered mesothelioma of tunica vaginalis of "uncertain malignant potential", which is an emerging diagnostic category.

Interobserver agreement for Polyomavirus nephropathy grading in renal allografts using the working proposal from the 10th Banff Conference on Allograft Pathology.

A classification schema for grading Polyomavirus nephropathy was proposed at the 2009 Banff allograft meeting. The schema included 3 stages of Polyomavirus nephropathy: early (stage A), florid (stage B), and late sclerosing (stage C). Grading categories for histologic viral load levels were also proposed.

Renal oncocytoma revisited: a clinicopathological study of 109 cases with emphasis on problematic diagnostic features.

Aim: To evaluate problematic diagnostic features in renal oncocytoma.

Methods And Results: One hundred and nine cases of oncocytoma were reviewed and the problematic gross and microscopic features recorded. Multifocal and bilateral neoplasms were found in 12 (11%) and five (4.

The impact of the 2005 International Society of Urological Pathology (ISUP) consensus on Gleason grading in contemporary practice.

Aims: To investigate the impact of the 2005 International Society of Urological Pathology (ISUP) Gleason grading consensus in contemporary practice.

Methods And Results: The Gleason scores (GS) were compared in two consecutive patient cohorts with matched biopsies and prostatectomies: (i) 908 patients evaluated before the ISUP consensus (July 2000-June 2004) and (ii) 423 patients evaluated after the ISUP consensus (October 2005-June 2007). All biopsies and prostatectomies were performed and scored in one institution and were sampled and processed identically.

Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens.

We evaluated the usefulness of double immunohistochemical staining for cytokeratin (CK)5/6 and alpha-methylacyl coenzyme A racemase (AMACR) applied sequentially on 1 slide by assessing 223 foci in 110 consecutive prostate specimens. Double-chromogen reaction was used to visualize the antibodies: brown for CK5/6 and red for AMACR. Staining was scored as diffuse, focal, or negative.

How much tissue sampling is required when unsuspected minimal prostate carcinoma is identified on transurethral resection?

Context: When minimal prostate cancer is detected in the initial transurethral resection of the prostate (TURP) sample, it is uncertain how extensively the remaining tissue should be sampled for accurate grading and staging.

Objective: To identify whether additional partial or complete sampling is required to accurately evaluate TURP samples with minimal cancer (stage T1a).

Design: We prospectively examined all TURP samples in our institution during 1 year.

Skeletal muscle-like and rhabdoid cells in uterine leiomyomas.

We describe eight unusual uterine leiomyomas characterized by a component of cells that suggested skeletal muscle differentiation or resembled the rhabdoid cells of extrarenal rhabdoid tumors. All of the tumors were referred because of problems in differential diagnosis, particularly distinction from an epithelioid smooth muscle tumor, a smooth muscle tumor of uncertain malignant potential, or a tumor with skeletal muscle differentiation. The patients were aged 27 to 50 (mean, 38) years, and the presenting clinical features and gross appearance of the tumors were similar to those of typical uterine leiomyomas.

Histologic study of patterns of cervical involvement in FIGO stage II endometrial carcinoma.

The pathology of cervical involvement in endometrial carcinoma has not been fully defined previously. We reviewed the histopathology of 66 hysterectomies of women with stage II endometrial carcinoma. Cervical spread was categorized as macroscopic or microscopic; stage IIA or IIB; direct spread, surface or lymphvascular metastasis; and size, number, and location.