Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The FOXL2 p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and TERT promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of FOXO1 mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases. Our findings confirmed the high prevalence (99%) of the FOXL2 p.C134W mutation in AGCTs. Secondary truncating FOXL2 mutations were observed in 5% of cases. Two cases with typical AGCT morphology were FOXL2 wild-type, harboring mutations in KRAS or KMT2D instead, suggesting alternative genetic pathways. TERT promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included KMT2D (10%), FOXO1 (7%), CHEK2 (5%), TP53 (3.5%), PIK3CA (3.5%), and AKT1 (3%). Two recurrent, FOXL2-mutated cases also carried DICER1 mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.
- MeSH
- dospělí MeSH
- forkhead box protein O1 * genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * genetika MeSH
- mutace * MeSH
- nádor z folikulárních buněk * genetika patologie MeSH
- nádory vaječníků * genetika patologie MeSH
- prognóza MeSH
- progrese nemoci MeSH
- protein FOXL2 genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- telomerasa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. METHODS: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. RESULTS: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5-10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. CONCLUSION: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- gonadální stromální nádory * patologie diagnóza metabolismus terapie MeSH
- imunohistochemie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * analýza MeSH
- nádory vaječníků * patologie diagnóza metabolismus terapie MeSH
- prognóza MeSH
- stathmin * analýza metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.
Phox2B is a transcription factor responsible for chromaffin cell phenotype. Although it is used routinely for diagnosis of neuroblastoma, previous reports concerning its utility in the diagnosis of neuroendocrine neoplasms have been conflicting. We assessed Phox2b immunoreactivity in different neuroendocrine neoplasms. Tissue microarrays or whole sections of 36 paragangliomas (PGs), 91 well-differentiated neuroendocrine tumours of different organs (WDNETs), 31 neuroendocrine carcinomas (NECs), and 6 olfactory neuroblastomas (ONBs) were stained with Phox2B antibody (EP312) and GATA3. The percentage of positive cells and intensity was analysed using H-score. Phox2B immunoreactivity was seen in 97.2% (35/36) PGs, 11% (10/91) WDNETs, 9.7% (3/31) NECs, and 16.7% (1/6) ONBs. PGs were significantly more often positive (p < 0.001, χ2) than other neuroendocrine tumours, showing highest H-score (mean 144.9, SD ± 75.1) and percentage of positive cells (median 81.3%, IQR 62.5-92.5%). Compared to Phox2B-positive WDNETs, PGs showed significantly higher H-score (median 145 vs 7.5, p < 0.001) and percentage of positive cells (median 82.5% vs 4.5%, p < 0.001). Phox2B positivity was 97.2% sensitive and 89% specific for the diagnosis of PG. GATA3 was 100% sensitive and 88% specific for the diagnosis of PG. When combined, any Phox2B/GATA3 coexpression was 97.1% sensitive and 99.1% specific for the diagnosis of paraganglioma. Widespread Phox2B immunoreactivity is a highly characteristic feature of PGs and it can be used as an additional marker in differential diagnosis of neuroendocrine tumours.
Calcifying pseudoneoplasm of neuroaxis (CAPNON) is a rare lesion of the central nervous system with uncertain histogenesis. We further explored phenotypic spectrum of the entity with respect to possible histogenesis. We collected 5 cases of CAPNONs, performed a detailed morphological assessment, and performed an extensive immunohistochemical analysis (EMA, progesterone receptors, MUC4, SSTR2A, cytokeratin AE1/3, cytokeratin 18, GFAP, neurofilaments, desmin, nestin, synaptophysin, S100 protein, SOX10, CD56, Podoplanin, SATB2, ERG, CD45, and CD163) to elucidate the histogenesis. Furthermore, we performed NGS analysis of one case. The clinical course was benign in all cases. All lesions showed extensively calcified matrix in multilobular arrangement, with a palisade of osteoblast-like cells. Characteristic fibrohyaline matrix was notable in 4/5 cases, while one case was myxoid with rod-like calcifications. Metaplastic lamellar bone was present in 4/5 cases and psammoma bodies were present in 2/5 cases. In 4/5 cases, areas of entrapped glial tissue were present. Expression of EMA was focally present in 3/5 cases, SSTR2A and nestin in 2/5 cases, and progesterone receptor in 2/5 cases in rare cells. We did not observe concomitant expression of EMA, SSTR2A, and progesterone receptor in the same cellular subsets. In one case, NGS showed multiple chromosomal alterations and missense mutation in PIK3CA, attributable to the admixed meningothelial population compatible with meningioma. In another case, biphasic proliferation with myoepithelial phenotype was present. The lesions showed no lineage-specific immunoprofile. Additional pathology was identified in two cases, furthermore suggestive of a possible reactive origin of the lesion.
- MeSH
- kalcinóza * patologie MeSH
- lidé MeSH
- meningeální nádory * MeSH
- meningeom * MeSH
- nestin MeSH
- receptory progesteronu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Radiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports. MATERIALS AND METHODS: All patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated. RESULTS: Data of 53 patients were analyzed. The median age at diagnosis was 72 (range 44-89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36-172) months. The median radiation dose was 57.6 (range 34-66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3-66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period. CONCLUSION: The present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.
- MeSH
- adjuvantní radioterapie * škodlivé účinky MeSH
- dospělí MeSH
- hemangiosarkom * radioterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mastektomie MeSH
- nádory prsu * radioterapie MeSH
- nádory vyvolané zářením * epidemiologie MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- segmentální mastektomie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Úvod: Fyloidní nádory prsu jsou vzácnými a velice zvláštními typy mamárních neoplazií. Jsou charakterizovány svou bifázičností, tedy přítomností stromální a epitelové komponenty. Malignita je určena stupněm stromální diferenciace. Koexistence maligní epitelové složky je velmi vzácný, leč v literatuře již popsaný jev. Dosud byly popsány řádově desítky případů simultánního výskytu fyloidního tumoru a epiteliální neoplazie. Biologická podstata tohoto procesu je dosud neobjasněným a kontroverzním tématem. Kazuistika: Prezentujeme kazuistiku pacientky s náhle se zvětšujícím ložiskem v prsu, dle první chirurgické resekce byla stanovena diagnóza high grade maligního fyloidního nádoru s fibrosarkomovou diferenciací, stromálním přerůstáním a utlačením epitelové komponenty. V časně vzniklé rezistenci v jizvě již byla vyslovena diagnóza triple negativního invazivního nízce diferencovaného karcinomu prsu s velmi vysokou proliferační aktivitou, nastala tedy malignizace epiteliální složky nádoru. U pacientky došlo ještě k druhé časné recidivě, nakonec byla provedena i disekce axily s negativním nálezem v lymfatických uzlinách. Pacienta podstoupila komplexní adjuvantní chemoterapii a radioterapii, nyní je 3 roky bez průkazu recidivy nádoru. Závěr: Koexistence fyloidního nádoru a karcinomu prsu je velmi vzácná. Uvádíme dosud první publikovaný případ, který dokumentuje následný vývoj invazivního nízce diferencovaného duktálního karcinomu bezprostředně po resekci high grade fyloidního tumoru. Léčba a prognóza je určena charakteristikou maligní karcinomové složky.
Introduction: Phyllodes tumors of the breast are rare and very distinct types of mammary neoplasms. They are characterized by their biphasicity, i.e. the presence of stromal and epithelial components at the same time. Malignancy is determined by the degree of stromal differentiation. The coexistence of the malignant epithelial component is a very rare phenomenon. Dozens of cases of simultaneous phyllodes tumor and epithelial malignancy have been reported so far. Nevertheless, the biological nature of this process is still an unexplained and a controversial topic. Case report: In this paper, we present a case of a patient with a suddenly enlarging lesion in the breast. According to the first surgical resection, a diagnosis of high-grade malignant phyllodes tumor was made with fibrosarcoma differentiation, stromal overgrowth and suppression of the epithelial component. Examination of scar resistence in early postoperative period revealed a triple-negative invasive low-differentiated breast carcinoma with very high proliferative activity, thus malignization of the epithelial component of the tumor occurred. Shortly, a diagnosis of second recurrence was made, treatment included axillary lymph node dissection (ALND) with a negative histological findings. The patient underwent complex adjuvant chemotherapy and radiotherapy and remained disease free 3 years after the surgery. Conclusion: Coexistence of phyllodes tumor and the breast carcinoma is very rare. The article describes the first published case, which documents the subsequent development of invasive low-differentiated ductal carcinoma immediately after resection of high-grade phyllodes tumor. Treatment and prognosis are generally determined by the characteristics of the carcinomatous component.
- MeSH
- adjuvantní chemoterapie metody MeSH
- cystosarcoma phyllodes diagnóza terapie MeSH
- duktální karcinom prsu diagnóza terapie MeSH
- histologické techniky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mamografie metody MeSH
- nádory prsu * diagnóza terapie MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- radikální mastektomie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Úvod: Cílem naší práce je prezentovat dosavadní výsledky a zkušenosti s metodou E.P.Si.T. (endoscopicpilonidal sinus treatment) v léčbě sinus pilonidalis. Metody: Výkon je prováděn za použití speciálního endoskopu, tzv. fistuloskopu. V první fázi operace zjišťujeme rozsah a hledáme všechny trakty sinu. Ve druhé fázi je celý komplex ošetřen pomocí grasperu, kartáčku a elektrody zevnitř. Výsledky: Na našem pracovišti bylo od prosince 2018 do září 2019 provedeno 21 operací. V souboru převažují muži v poměru 6:1. Průměrný věk pacientů byl 27 let. V 18 případech došlo ke zhojení. U dvou pacientů se nález primárně nezahojil, jeden se vytratil z dispenzarizace. Závěr: Dle prvních zkušeností a výsledků se metoda E.P.Si.T. ukazuje jako velmi dobrá k ošetřování pilonidálního sinu. V porovnání s otevřenými výkony se výrazně zkrátila délka hospitalizace, nutnost podávání analgetik a antibiotik. Došlo ke zkrácení doby rekonvalescence, k urychlení návratu do běžného života. Velikost souboru a doba pooperační dispenzarizace nám v tuto chvíli ještě nedovolují se k přesným výsledkům vyjádřit statisticky.
Introduction: The aim of our article is to present the results and experience with the method E.P.Si.T. – endoscopic pilonidal sinus treatment. Methods: The operation is performed using a special endoscope – fistuloscope. In the first phase, we determine the extent and look for all the sinus tracts. In the second phase, the whole complex is treated with a grasper, a brush and an electrode from the inside. Results: A total of 21 operations were performed at our department from December 2018 through September 2019. In our sample, men predominated 6:1. Mean age of the patients was 27 years. Complete healing was achieved in 18 patients. Two patients were not healed primarily. One patient was lost to follow-up.Conclusion: According to the first experience and results, the E.P.Si.T. seems to be a very good method for treating pilonidal sinus. Compared to open procedures, the length of hospitalization, the need for analgesics and antibiotics were significantly reduced. The period of convalescence was shortened and the return to normal life was faster. The size of the cohort and the duration of post-operative follow-up do not allow us yet to statistically evaluate the results.
- Klíčová slova
- fistuloskop,
- MeSH
- endoskopie metody MeSH
- lidé MeSH
- miniinvazivní chirurgické výkony metody MeSH
- pilonidální sinus * chirurgie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Mezi nejčastější příčiny maligní axilární lymfadenopatie patří sekundární postižení karcinomem prsu, maligním melanomem či hematoonkologickým onemocněním. V literatuře jsou dále raritně popisovány axilární metastázy s primárním nádorem plic, gastrointestinálního traktu, ovaria/varlete či hypofaryngu. Diferenciální diagnostiku opíráme hlavně o výsledek histologického vyšetření, dále mamologické, kožní, endoskopické, plicní a ORL vyšetření a často ji řešíme v rámci multioborové komise. Uvádíme kazuistiku 86leté ženy s četnými kožními projevy trupu ve smyslu spinocelulárních karcinomů in situ avšak s výraznou lymfadenopatií v axile, kde byl patologem popsán dlaždicobuněčný karcinom. Výše uvedená vyšetření nevedla k odhalení primárního tumoru. Po čtyřech měsících pacientka sama přichází pro krvácení z vaginy. Onkochirurgem byl nalezen tumor vulvy, který byl následně gynekologem a patologem uzavřen jako dlaždicobuněčný karcinom. Jednalo se o primární origo axilární lymfadenopatie, která byla jediným projevem onemocnění. Solitární metastázy vaginy či vulvy v axilárních uzlinách nejsou v odborných článcích evidovány.
The most common causes of malignant axillary lymphadenopathy include secondary impairment of the breast cancer, malignant melanoma and haemato-oncological disease. Descriptions of axial metastases with primary tumours of the lungs, gastrointestinal tract, ovaria and/or testicle or hypopharynx are rarely found in medical literature. To determine a differential diagnosis, we focus mainly on results from histological examinations and from other examinations such as mammological, dermatological, endoscopic, pulmonary or ENT. Multi-disciplinary commissions usually come out with such diagnoses very often. We present in our paper the case history of an 86-year-old female with numerous thoracic skin manifestations to the spinal cellular carcinomas in situ and with a distinctive lymphadenopathy in her axilla, where the described pathogen was a squamous cell carcinoma. All the above-mentioned examinations have not led to any revealing of the primary tumour. After four months the patient came complaining of vaginal bleeding. The oncological surgeon discovered a vulvar tumour, which was subsequently confirmed also by the gynaecologist. Furthermore, the pathologists concluded with the squamous cell carcinoma diagnosis as being a primary origin axillary lymphadenopathy which was an unusual only symptom of the disease. The solitary vaginal or vulvar metastases in axillary nodes have of yet to be recorded in any medical article.
- MeSH
- axila patologie MeSH
- Bowenova nemoc chirurgie diagnóza patologie MeSH
- děložní krvácení etiologie MeSH
- fatální výsledek MeSH
- gastrointestinální krvácení etiologie MeSH
- histologické techniky MeSH
- kožní manifestace MeSH
- lidé MeSH
- lokální recidiva nádoru diagnóza MeSH
- lymfadenopatie * chirurgie diagnostické zobrazování etiologie patologie MeSH
- metastázy nádorů diagnóza MeSH
- nádory vulvy * chirurgie diagnóza epidemiologie patologie terapie MeSH
- odmítnutí terapie pacientem MeSH
- senioři nad 80 let MeSH
- spinocelulární karcinom chirurgie diagnóza patologie terapie MeSH
- ultrasonografie MeSH
- vulvektomie MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
