Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of renal neoplasm predominantly affecting younger individuals. It is characterized by germline mutations in SDHx genes, particularly type B. Histologically, SDH-deficient RCC features eosinophilic cytoplasmic cells forming solid nests or microcysts, sometimes entrapping normal tubules. We present three SDH-deficient RCC cases with overlapping morphological features with fumarate hydratase-deficient RCC and TFEB-rearranged RCC, an appearance that has not been previously described. All tumors lacked SDHB expression and harbored pathogenic SDHB mutations, with the germline nature confirmed in two cases. Metastasis developed in two patients. Our case set highlights the diagnostic challenges of molecularly defined renal tumors and expands the morphological spectrum of SDH-deficient RCC with unusual histological features. Clinically, these tumors appear to be aggressive.
- MeSH
- dediferenciace buněk MeSH
- dospělí MeSH
- fumarasa nedostatek genetika MeSH
- karcinom z renálních buněk * genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika analýza MeSH
- nádory ledvin * patologie genetika MeSH
- sukcinátdehydrogenasa * nedostatek genetika MeSH
- transkripční faktory BHLH-Zip genetika MeSH
- zárodečné mutace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
INTRODUCTION: Combined immuno-oncology (IO) regimens are the cornerstone of the current front-line systemic therapy for metastatic renal cell carcinoma (mRCC). Despite the fact that combined IO regimens show high efficacy, they are often accompanied by a wide spectrum of immune-related adverse effects (irAEs). CASE PRESENTATION: We describe a case of rare irAEs manifested as giant cell temporal arteritis (GCA) followed by severe encephalopathy occurring after continuing immunotherapy in a 66-year-old man with mRCC receiving a combination of ipilimumab and nivolumab in the first line of systemic therapy. GCA occurred 4 months after the initiation of IO and responded promptly to the low-dose prednisone therapy. Four months after the continuation of nivolumab maintenance, the patient was hospitalized due to severe irAE encephalopathy which presented as psycho-behavioral abnormalities and progressive cognitive decline. He was treated with high-dose methylprednisolone which led to complete resolution of the symptoms and IO was permanently discontinued. The patient achieved a durable partial response. CONCLUSION: Both GCA and the subsequent encephalopathy in our patient responded well to the corticosteroid therapy, leading to the complete resolution of the symptoms and the patient achieved a durable partial response. Although the risk of severe neurologic irAEs affecting the central nervous system induced by IO re-administration, following previous discontinuation due to irAE, is not well-defined because of their rarity, this case highlights the need for caution, particularly in cases with a history of previous irAE-associated GCA.
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Úvod: Díky mamografickému screeningu a zlepšování diagnostiky karcinomu prsu narůstá také záchyt prekanceróz. Jsou definovány jako morfologické změny mléčné žlázy, u kterých je vyšší pravděpodobnost vzniku karcinomu. Hodnocené prekancerózy jsou atypická duktální hyperplazie (ADH), lobulární karcinom in situ (LCIS) a radiální jizva. Metodika: V období 1. 1. 2018–31. 12. 2022 jsme na Chirurgické klinice FN Plzeň provedli 1 302 plánovaných operací pro onemocnění prsu, z toho 30 operací prekanceróz (2 %). O ADH se jednalo 11×, 8× o LCIS, 11× o radiální jizvu. Průměrný věk pacientek byl ve všech třech skupinách 56 let (27–85). Prekanceróza byla diagnostikována 8× pouze sonograficky, 3× mamograficky a 19× kombinací obou metod. Následně byla vždy doplněna punkční biopsie. Excizi tumoru s peroperační biopsií jsme provedli 28×, 2× mastektomii. Výsledky: V případě ADH z punkční biopsie se peroperačně potvrdila 8× ADH, 2× byl diagnostikován duktální karcinom in situ (ductal carcinoma in situ – DCIS), 1× mucinózní karcinom. U LCIS nebyl peroperační biopsií 4× tumor nalezen, 1× potvrzen LCIS, 1× diagnostikován lobulární invazivní karcinom, 2× provedena mastektomie bez peroperační biopsie. U radiální jizvy 3× diagnostikována ADH, 6× sklerozující adenóza, 1× DCIS, 1× invazivní karcinom. Po definitivním histologickém zpracování vzorků došlo ještě k nárůstu diagnostikovaných karcinomů. U ADH 3× DCIS, 2× DIC, 1× mucinózní karcinom. U LCIS 3× LIC. U radiální jizvy zůstává 1× DCIS a 1× invazivní karcinom. Tedy u 11 pacientek (37 %) byl díky operačnímu řešení diagnostikován karcinom. U žádné pacientky nebyla provedena operace axilárních uzlin. Všech 11 pacientek následně podstoupilo onkologickou léčbu, vždy kombinace radioterapie a hormonální terapie. Všechny pacientky žijí, 10 pacientek je v kompletní remisi onemocnění, u jedné s DCIS došlo po 4 letech k lokální recidivě. Závěr: Chirurgická léčba prekanceróz prsu má smysl, často se vedle prekancerózy skrývá už DCIS, či dokonce invazivní karcinom. Díky operačnímu řešení došlo k odhalení nádorového onemocnění včas.
Introduction: Thanks to mammographic screening and the improvement of breast cancer diagnostics, the detection of precancers is also increasing. They are defined as morphological changes of the mammary gland which are more likely to cause cancer. The evaluated precancers are atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS) and radial scar. Methodology: In the period 1. 1. 2018–31. 12. 2022, we performed 1,302 planned operations for breast disease at the Surgical Clinic of Teaching Hospital Plzeň, of which 30 (2%) were precancer operations. ADH was confirmed 11×, LCIS 8×, and a radical scar 11×. The average age of the patients in all three groups was 56 years (27–85). Precancer was diagnosed 8× only by sonography, 3× by mammography and 19× by a combination of both methods. Subsequently, a puncture biopsy was always completed. We performed 28 tumor excisions with intraoperative biopsy and 2 mastectomies. Results: In the case of ADH from puncture biopsy, ADH was confirmed intraoperatively 8×, DCIS was diagnosed 2×, and mucinous carcinoma 1×. In LCIS, no tumor was found by intraoperative biopsy 4×, LCIS was confirmed 1×, lobular invasive carcinoma was diagnosed 1×, mastectomy was performed 2× without intraoperative biopsy. In the radial scar, ADH was diagnosed 3×, sclerosing adenosis 6×, DCIS 1×, invasive carcinoma 1×. After the final histological processing of the samples, there was an increase in diagnosed carcinomas. In ADH, DCIS was confirmed 3×, DIC 2×, and mucinous carcinoma 1×. In LCIS, LIC was diagnosed 3×. In the radial scar, DCIS was confirmed 1×, and invasive carcinoma remain 1×. Thus, carcinoma was diagnosed in 11 patients (37%) thanks to the surgical solution. No patient underwent axillary node surgery. All 11 patients subsequently underwent oncological treatment, always a combination of radiotherapy and hormone therapy. All patients are alive, 10 patients are in complete remission of the disease, one with DCIS experienced a local recurrence after 4 years. Conclusion: Surgical treatment of precancers of the breast makes sense, DCIS or even invasive cancer is often hidden in addition to precancer. Thanks to the surgical solution, the cancer was detected in time.
- MeSH
- dospělí MeSH
- intraduktální neinfiltrující karcinom chirurgie diagnostické zobrazování patologie MeSH
- karcinom prsu in situ chirurgie diagnostické zobrazování patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mamografie MeSH
- nádory prsu * chirurgie diagnostické zobrazování patologie MeSH
- prekancerózy * chirurgie diagnostické zobrazování patologie 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
- práce podpořená grantem MeSH
Nefrogenní adenom (NA), dří ve též nefrogenní metaplazie, je raritní benigní lé ze vývodných močových cest. Vznik lé ze je vysvětlová n implantací odloučených rená lní ch tubulární ch epitelií v mí stech poškození urotelu (typicky např . v souvislosti s př edchozí instrumentací močových cest). Klinické symptomy jsou nespecifické a nejčastěji zahrnují hematurii (jak makroskopickou, tak mikroskopickou), polakisurii, bolestivou mikci. Endoskopicky lze tyto lé ze snadno zaměnit za maligní ná dor. Ve zde prezentované m textu jsou př edstaveny dva pří pady NA v močové m měchýř i u dospělých pacientů po transplantaci ledviny, u nichž př i cystoskopické m a radiologické m vyšetř ení ná lez věrně napodoboval uroteliá lní karcinom.
Nephrogenic adenoma (NA), also referred to as nephrogenic metaplasia, is a rare benign lesion affecting the urinary tract. The development of this lesion is attributed to the implantation of isolated renal tubular epithelial cells in areas of damaged transitional epithelium, often associated with prior instrumentation of the urinary tract. Clinical symptoms are nonspecific, commonly manifesting as hematuria (both macroscopic and microscopic), pollakisuria, and painful urination. Notably, during endoscopic examination, these lesions can be easily misinterpreted as malignant tumors. This publication presents two case reports of NA found in the urinary bladder of adult patients after kidney transplantation, the NAs faithfully mimicked urothelial carcinoma during cystoscopic and radiological examination.
- Klíčová slova
- nefrogenní adenom,
- MeSH
- diagnostické techniky urologické MeSH
- endoskopie metody MeSH
- hematurie etiologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- močové ústrojí patologie MeSH
- nádory močového měchýře * diagnóza klasifikace MeSH
- senioři MeSH
- transplantace ledvin MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in patients with hereditary leiomyomatosis and renal cell carcinoma syndrome or that some seminomas may occur in Lynch syndrome patients. Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.
- MeSH
- dědičné nádorové syndromy * patologie genetika MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- nádory mužských pohlavních orgánů patologie genetika MeSH
- testikulární nádory * genetika patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
a-Methylacyl coenzyme A racemase (AMACR) is traditionally considered to be a marker of papillary renal cell carcinoma. However, AMACR expression can be seen in other renal tumors. The aim of this study was to investigate AMACR immunoreactivity within the spectrum of clear cell renal cell neoplasms. Fifty-three clear cell renal epithelial tumors were used in assembling the following four cohorts: low grade (LG) clear cell renal cell carcinoma (CCRCC), high grade (HG) CCRCC, CCRCC with cystic changes, and multilocular cystic renal neoplasm of low malignant potential (MCRNLMP). Representative blocks were stained for AMACR, using two different clones (SP52 and OV-TL12/30). There were at least some AMACR immunoreactivity in 77.8 % and 68.9 % of CCRCCs (using SP52 and OV-TL12/30 clone, respectively). Moderate to strong positivity, or positivity in more than one third of the tumor (even weak in intensity) was detected in 46.7 % of CCRCCs using SP52 and in 48.9 % of CCRCC using OV-TL12/30 clone. The highest AMACR reactivity was observed in HG CCRCC (60 % by SP52 and 66.7 % by OV-TL12/30). Strong and diffuse AMACR positivity was detected in 8.9 % of all CCRCCs. AMACR immunoreactivity in MCRNLMP was 37.5 % (SP52 clone) and 25 % (OV-TL12/30 clone). We demonstrated relatively high expression rate of AMACR in CCRCC, while very variable in intensity and distribution. This finding may have diagnostic implications especially in limited samples (i.e., core biopsies), as AMACR positivity does not exclude the diagnosis of CCRCC.
- MeSH
- imunohistochemie metody MeSH
- karcinom z renálních buněk * patologie metabolismus diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * metabolismus MeSH
- nádory ledvin * patologie metabolismus diagnóza MeSH
- racemasy a epimerasy * metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Papillary renal neoplasm with reversed polarity (PRNRP) is a recently described rare renal neoplasm. Traditionally, it was considered a variant of papillary renal cell carcinoma (PRCC). However, several studies reported significant differences between PRNRP and PRCC in terms of clinical, morphological, immunohistochemical and molecular features. Nonetheless, PRNRP remains a poorly understood entity. We used microarray analysis to elucidate the non-coding RNA (ncRNA) and gene expression profiles of 10 PRNRP cases and compared them with other renal neoplasms. Unsupervised cluster analysis showed that PRNRP had distinct expression profiles from either clear cell renal cell carcinoma (ccRCC) or PRCC cases at the level of ncRNA but were less distinct at the level of gene expression. An integrated omic approach determined miRNA:gene interactions that distinguished PRNRP from PRCC and we validated 10 differentially expressed miRNAs and six genes by quantitative RT-PCR. We found that levels of the miRNAs, miR-148a, miR-375 and miR-429, were up-regulated in PRNRP cases compared to ccRCC and PRCC. miRNA target genes, including KRAS and VEGFA oncogenes, and CXCL8, which regulates VEGFA, were also differentially expressed between renal neoplasms. Gene set enrichment analysis (GSEA) determined different activation of metabolic pathways between PRNRP and PRCC cases. Overall, this study is by far the largest molecular study of PRNRP cases and the first to investigate either ncRNA expression or their gene expression by microarray assays.
- MeSH
- dospělí MeSH
- karcinom z renálních buněk * genetika patologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory ledvin * genetika patologie metabolismus MeSH
- nekódující RNA * genetika MeSH
- papilární karcinom patologie genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
