Multicystic urothelial carcinoma of the bladder with gland-like lumina and with signet-ring cells. A case report

We present the case of 80-year-old male with superficial papillary urothelial carcinoma of the urinary bladder with striking multicystic architecture with a combination of features of urothelial carcinoma with gland-like lumina, with signet-ring cell differentiation and microcystic pattern. However, the tumor shared the morphologic features of several variants of urothelial carcinoma, the most important differential diagnosis covered so-called florid Brunneriosis, cystitis cystica, and primary adenocarcinomas of the urinary bladder

Provizórikus veserákaltípusok a 2016. évi WHO-klasszifikációt követően = Provisional renal cell carcinoma subsets following the 2016 WHO classification

Absztrakt: A vesesejtes carcinoma (RCC) többféle, a veséből kiinduló rosszindulatú daganattípus gyűjtőneve. Az egyes entitások sajátos epidemiológiai, morfológiai, immunhisztokémiai, genetikai és klinikai jellemvonásokkal bírnak. Ezek együttes figyelembevételével került publikálásra 2016-ban a vesedaganatok aktuális WHO-klasszifikációja. Az eltelt három év során újabb, provizórikus RCC-altípusok kerültek leírásra, melyek egyelőre nem képezik részét a hivatalos beosztásnak. Ebben az összefoglalóban ezek az entitások kerülnek részletes áttekintésre. A szerzők bemutatják a következő daganattípusok klinikopatológiai jellegzetességeit: pajzsmirigyszerű follicularis carcinoma, az ALK-transzlokációhoz társult carcinoma, vesesejtes carcinoma prominens simaizomstromával, fumarát-hidratáz-deficiens carcinoma, bifázisos squamoid papillaris carcinoma, eosinophil solid és cysticus carcinoma, atrophiás vesére emlékeztető carcinoma, világossejtes carcinoma óriássejtekkel és emperipolesissel, Warthin-szerű papillaris carcinoma, low-grade oncocytás vesetumor (CD117-negatív, CK7-pozitív), high-grade oncocytás vesetumor, TCEB1-mutáns carcinoma és neuroendokrin vonásokkal rendelkező chromophob carcinoma. Ha a patológus követi az aktuális leletezési protokollokat, akkor ezek az entitások jórészt nem osztályozható RCC-ként kerülnek diagnosztizálásra. A munka meg kívánja ismertetni ezeket az altípusokat a hazai patológus-, onkológus- és urológusközösséggel azért, hogy javuljon a diagnosztikus pontosság, valamint hogy elkezdődhessen az ilyen esetek gyűjtése és további célzott vizsgálata is. Orv Hetil. 2020; 161(3): 83–94. | Abstract: Renal cell carcinoma (RCC) represents a heterogenous group of malignant tumors that originate from the kidney parenchyma. The different entities have their own specific epidemiological, morphological, immunohistochemical, genetic and clinical characteristics. The new WHO classification of renal tumors was published in 2016, and it takes all of these features together into account. Although in the past three years, several emerging subtypes have been described, these are not yet included in the current classification. In this review paper, these entities are summarized in details including the following emerging subsets: thyroid-like follicular carcinoma, ALK rearrangement-associated RCC, renal cell carcinoma with prominent smooth muscle stroma, fumarate hydratase-deficient RCC, biphasic squamoid papillary RCC, eosinophilic solid and cystic RCC, atrophic kidney-like RCC, clear cell RCC with giant cells and emperipolesis, Warthin-like papillary RCC, low-grade oncocytic renal tumor (CD117-negative; CK7-positive), high-grade oncocytic renal tumor, TCEB1-mutated RCC and chromophobe RCC with neuroendocrine features. These entities are mostly diagnosed as RCC unclassified. The aim of this study is to introduce these subsets to the Hungarian pathologists, oncologists and urologists, to prompt diagnostic accuracy and to facilitate a collection along with a consecutive analysis of these cases. Orv Hetil. 2020; 161(3): 83–94

Mixed germ cell sex cord-stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical square off quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff(PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to that seen in the germ cells of spermatocytic seminomas. Immunohisto-chemically, the germ cells of MGSCTs in one case reacted positively with antibody to AE1-AE3 by paranuclear dotlike or rodlike positivity. All three testicular MGSCTs had a negative reaction with the rest of antibodies, including placental alkaline phosphatase (PLAP), OCT4, and c-kit protein. Ovarian MGSCT in our series differed from the testicular lesions in both the germ cell component and the sex cord component. The germ cells in all four ovarian cases had cytomorphological and immuno-histochemical features identical to those in classical seminomas/dysgerminomas. They possessed the typical square off quality of the nuclei, which were much more blastic, with more mitoses compared with the testicular tumors in our series, and they were PLAP (4/4), OCT4 (4/4) and c-kit protein (3/4) positive immunohisto-chemically. The cytoplasm of the germ cells in ovarian neoplasms contained PAS positive glycogen. Germ cells in one ovarian MGSCTs showed amplification of l2p. All other germ cells were negative for amplification of 12p. All five successfully analyzed cases showed no mutation in all studied exons and exon-intron junctions in c-kit and PDFGRA genes

Low-grade sarcoma in classical seminoma - the first case reported

A 30-year-old male with no previous history of neoplastic disease presented with a 5 cm large testicular tumor. Routine histopathological examination and immunohistochemical investigation showed a classical seminoma with a contiguous 8 mm large nodule. The nodule was separated from the tunica albuginea by tubuli semi-niferi showing intratesticular germ cell neoplasi not otherwise specified (NOS). The nodule was composed of spindle cells with low-grade nuclear atypia, nuclear and cytoplasmic S100 protein immunoreactivity in 15% of the cells and a proliferative activity of up to 20%. No other germ cell tumor components were found. To the best of our knowledge, we herein present the first tumor of a pure classical seminoma with an associated low-grade sarcomatous component.Natl Univ Hlth Syst, Dept Pathol, Singapore 119074, SingaporeCharles Univ Prague, Med Fac Hosp, Sikls Dept Pathol, Plzen, Czech RepublicFed Univ Sao Paolo, EPM UNIFESP, Dept Pathol, Sao Paulo, BrazilBiopticka Lab Sro, Plzen, Czech RepublicFed Univ Sao Paolo, EPM UNIFESP, Dept Pathol, Sao Paulo, BrazilWeb of Scienc

Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer

Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others. Papillary RCC type 2 is now known to include likely several different molecular entities, such as fumarate hydratase (FH) deficient RCC. In MIT family translocation RCC, an increasing number of gene fusions are now described. Some TFE3 fusion partners, such as NONO, GRIPAP1, RBMX, and RBM10 may show a deceptive FISH result due to the proximity of the genes on the same chromosome. FH and succinate dehydrogenase (SDH) deficient RCC have implications for patient counseling due to heritable syndromes and the aggressiveness of FH-deficient RCC. Immunohistochemistry is increasingly available and helpful for recognizing both. Emerging tumor types with strong evidence for distinct diagnostic entities include eosinophilic solid and cystic RCC and TFEB / VEGFA / 6p21 amplified RCC. Other emerging entities that are less clearly understood include TCEB1 mutated RCC, RCC with ALK rearrangement, renal neoplasms with mutations of TSC2 or MTOR, and RCC with fibromuscular stroma. In metastatic RCC, the role of molecular studies is not entirely defined at present, although there may be an increasing role for genomic analysis related to specific therapy pathways, such as for tyrosine kinase or MTOR inhibitors

TERT gene fusions characterize a subset of metastatic Leydig cell tumors

Objective: Metastatic Leydig cell tumors (LCT) are rare, difficult to treat malignancies without known underlying molecular-genetic events. An index case of metastatic LCT showed an LDLR-TERT gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs. Patients and Methods: Twenty-nine LCT (27 male and 2 female patients) were profiled using NGS and immunohistochemistry. Results: TERT gene fusions were detected only in testicular metastatic Leydig cell tumors, in three of seven successfully analyzed cases (RMST:TERT, LDLR:TERT and B4GALT5:TERT). TOP1 and CCND3 amplifications were identified in the case with a B4GALT5:TERT fusion. A TP53 mutation was detected in one metastatic tumor without a TERT fusion. Five primary (four testicular and one ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed BAP1 mutation and copy number amplifications affecting the NPM1, PCM1 and SS18 genes. At the protein level, 4/7 metastatic and 6/10 primary testicular LCTs over-expressed TOP1. Androgen receptor (AR) was overexpressed in 10/13 primary testicular tumors and 2/5 metastatic testicular LCT (without detectable ARv7 mRNA or ARv7 protein). Only one metastatic testicular LCT exhibited high TMB while all tested cases were MSI stable and did not express PD-L1. Conclusions: Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic Leydig cell tumors. TOP1 and AR may guide decisions on chemo- and/or hormone therapy for selected individual patients.Qatar National Librar

Mixed epithelial and stromal tumor of the kidney with cervical and intestinal differentiation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47519/1/428_2005_Article_1269.pd