Penile squamous cell carcinoma (pSCC) is a rare tumour with a variable prognosis. More prognostic markers linked to mutational signatures and the tumour immune microenvironment are needed. A cohort made up of 165 invasive pSCC was retrospectively analysed using formalin-fixed, paraffin-embedded tumour tissue, focusing on tumour mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the number of tumour infiltrating lymphocytes (TILs) expressing cytotoxic T-lymphocyte-associated protein 4 (CTLA4), HPV status determined by p16 immunohistochemistry, and several traditional histopathological variables. High TMB (>10 mut/Mb) was associated with high PD-L1 expression (TPS 50-100%), and HPV-negative status. High PD-L1 expression was linked to HPV negativity, a high number of intratumoural CTLA4+ cells, and brisk lymphocytic infiltrate. High TMB was a significant predictor of shorter overall survival (OS) in both univariate and multivariate analysis when using a median cut-off value of 4.3 mut/Mb, but not when using an arbitrary cut-off of 10 mut/Mb. Low CTLA4+ cell infiltration at the tumour invasion front was a marker of shorter OS and cancer-specific survival in both univariate and multivariate analysis. PD-L1 expression had no significant impact on prognosis. Only two cases were MSI high. The results support the hypothesis of two aetiological pathways in pSCC cancerogenesis: (1) SCC linked to HPV infection characterised by low TMB, less common PD-L1 expression, and a lower number of TILs; and (2) SCC linked to chronic inflammation leading to a high number of acquired mutations (high TMB), HPV negativity, increased neoantigen production (i.e., PD-L1), and high immune cell infiltration.
- MeSH
- antigen CTLA-4 MeSH
- antigeny CD274 metabolismus MeSH
- infekce papilomavirem * komplikace MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory penisu * genetika MeSH
- retrospektivní studie MeSH
- spinocelulární karcinom * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Colorectal cancer (CRC) is a leading global cause of illness and death. There is a need for identification of better prognostic markers beyond traditional clinical variables like grade and stage. Previous research revealed that abnormal expression of cytokeratin 7 (CK7) and loss of the intestinal-specific Special AT-rich sequence-binding protein 2 (SATB2) are linked to poor CRC prognosis. This study aimed to explore these markers' prognostic significance alongside two extraintestinal mucins (MUC5AC, MUC6), claudin 18, and MUC4 in 285 CRC cases using immunohistochemistry on tissue microarrays (TMAs). CK7 expression and SATB2-loss were associated with MUC5AC, MUC6, and claudin 18 positivity. These findings suggest a distinct "non-intestinal" immunohistochemical profile in CRC, often right-sided, SATB2-low, with atypical expression of CK7 and non-colorectal mucins (MUC5AC, MUC6). Strong MUC4 expression negatively impacted cancer-specific survival (hazard ratio = 2.7, p = 0.044). Genetic analysis via next-generation sequencing (NGS) in CK7 + CRCs and those with high MUC4 expression revealed prevalent mutations in TP53, APC, BRAF, KRAS, PIK3CA, FBXW7, and SMAD4, consistent with known CRC mutation patterns. NGS also identified druggable variants in BRAF, PIK3CA, and KRAS. CK7 + tumors showed intriguingly common (31.6%) BRAF V600E mutations corelating with poor prognosis, compared to the frequency described in the literature and databases. Further research on larger cohorts with a non-colorectal immunophenotype and high MUC4 expression is needed.
- MeSH
- dospělí MeSH
- fenotyp MeSH
- fosfatidylinositol-3-kinasy třídy I genetika metabolismus MeSH
- imunohistochemie * MeSH
- keratin-7 metabolismus genetika MeSH
- kolorektální nádory * genetika patologie metabolismus mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mucin 4 genetika metabolismus MeSH
- mucin 5AC genetika metabolismus MeSH
- mucin 6 genetika metabolismus MeSH
- mutace MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- prognóza MeSH
- protoonkogenní proteiny B-Raf genetika MeSH
- protoonkogenní proteiny p21(ras) genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktory MeSH
- vazebné proteiny DNA v oblastech připojení k matrix * genetika metabolismus MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Karcinom pankreatu patří mezi poměrně časté maligní nádory se stoupající incidencí i mortalitou, protože nádor je obvykle diagnostikován v pokročilém stadiu a má obecně špatnou prognózu, pouze 5 % nemocných žije 5 let od stanovení diagnózy. Zásadním faktorem ovlivňujícím prognózu je stadium onemocnění v době diagnózy, přičemž u lokalizovaných nádorů žije 3 roky od diagnózy 25 % nemocných, u generalizovaných pouze 1 %. Radikální chirurgické odstranění nádoru (parciální či totální pankreatektomie) je klíčovým parametrem prodlužujícím přežití, téma je tedy pro chirurgickou obec vysoce relevantní. Statistiky o karcinomu pankreatu zpracovávají ve své většině duktální adenokarcinom, který je v pankreatu nejčastějším a prognosticky nejméně příznivým maligním nádorem pankreatu. Toto přehledové sdělení se zaměřuje právě na duktální adenokarcinom, jeho varianty a prekancerózy. Článek shrnuje informace z poslední WHO klasifikace z roku 2019, která vyšla 11 let od předchozího vydání. V této nové WHO klasifikaci došlo v oblasti duktálního adenokarcinomu oproti staršímu spíše k minoritním změnám, přičemž vymezení vzácných variant duktálního adenokarcinomu má své opodstatnění na základě genetické i morfologické příbuznosti a na základě klinické relevance, kdy se jednotlivé subtypy zásadně liší prognózou. Článek obsahuje i popis a definiční vymezení makroskopických i mikroskopických prekurzorů duktálního adenokarcinomu. Genetické a imunohistochemické diferenciálně diagnostické aspekty jsou pojednány stručně, neboť jsou relevantní spíš pro patologa než pro chirurga.
Pancreatic carcinoma is a relatively common malignant tumor with increasing incidence and mortality. The tumor is usually diagnosed at an advanced stage and generally has a poor prognosis, with only 5% of patients surviving 5 years from the time of diagnosis. The stage of the disease at the time of diagnosis is a crucial factor for the prognosis; 25% of patients with localized tumors survive 3 years from diagnosis, compared to only 1% of those with generalized tumors. Radical surgical removal of the tumor (partial or total pancreatectomy) is a key factor in improving survival. Therefore, the topic is highly relevant to surgeons. Statistics on pancreatic carcinoma mainly focus on ductal adenocarcinoma, which is the most common and least favorable malignant tumor of the pancreas. This review focuses on ductal adenocarcinoma, its variants, and precancerous lesions. The article summarizes information from the latest WHO classification of 2019, which was released 11 years after the previous edition. Compared to the previous version, this new WHO classification introduced rather minor changes in the field of ductal adenocarcinoma. The delineation of rare variants of ductal adenocarcinoma is justified based on genetic and morphological similarities and clinical relevance, as individual subtypes significantly differ in prognosis. The article also includes a description of macroscopic and microscopic precursors of ductal adenocarcinoma and their definitions. Genetic and immunohistochemical differential diagnostic aspects are briefly discussed, as these are more relevant to pathologists than to surgeons.
- MeSH
- barvicí látky terapeutické užití MeSH
- diferenciální diagnóza MeSH
- duktální karcinom slinivky břišní * chirurgie diagnóza klasifikace patologie MeSH
- histologické techniky metody MeSH
- lidé MeSH
- nádory slinivky břišní * chirurgie diagnóza klasifikace patologie MeSH
- prekancerózy chirurgie diagnóza klasifikace patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare malignancy regarded as a subvariant of pancreatic ductal carcinoma (PDAC) characterized by variable prognosis. UCOGC shows a strikingly similar spectrum of oncogenic DNA mutations to PDAC. In the current work, we analyzed the landscape of somatic mutations in a set of 13 UCOGC cases via next-generation sequencing (NGS). We detected a spectrum of pathogenic or likely pathogenic mutations similar to those observed in PDAC following previously published results (10 KRAS, 9 TP53, 4 CDKN2A, and 1 SMAD4, CIC, GNAS, APC, ATM, NF1, FBXW7, ATR, and FGFR3). Our results support the theory that UCOGC is a variant of PDAC, despite its unique morphology; however, a UCOGC-specific genomic signature as well as predictive markers remain mainly unknown. Programmed death ligand 1 (PD-L1) status remains an important predictive marker based on previous studies.
Localized insulin-derived amyloidosis (LIDA) is a rare local complication of subcutaneous insulin application occurring in patients with diabetes type 1 and 2. A 45-year-old woman with an 11-year history of insulin-dependent diabetes mellitus type 1 underwent a mini-abdominoplasty and excision of a long-standing palpable mass in left hypogastric subcutaneous tissue in the area of long-term insulin application. Histopathological examination revealed insulin amyloidosis as a substrate of the mass lesion. Several months after surgery, there was a transient improvement in previously poor diabetes compensation. In addition to local allergic reactions, abscess formation, scarring, lipoatrophy/dystrophy, and lipohypertrophy, LIDA broadens the differential diagnostic spectrum of local insulin injection complications. LIDA has been described as a cause of poor glycemia compensation, probably due to the conversion of soluble insulin into insoluble amyloid fibrils, which prevents insulin from circulating in the blood and regulating glucose blood concentration. Improvement in diabetes compensation has been described in several reports, including our case. LIDA is a rare local complication of subcutaneous insulin application; accurate diagnosis and treatment have clinical consequences. Immunohistochemical or immunofluorescence distinction from other amyloid types is highly recommended.
- Publikační typ
- kazuistiky MeSH
Penile squamous cell carcinoma (pSCC) is a rare malignancy with a slowly increasing incidence and variable prognosis. Regional lymph node involvement signifies poor prognosis but represents a late sign, and more prognostic markers for effective patient risk stratification are urgently needed. In this retrospective study, 152 tumour samples with formalin-fixed, paraffin-embedded tissue were analysed for traditional pathological variables, tumour budding, p53, p16, and mismatch repair proteins (MMR) immunohistochemistry. The density of tumour lymphocytic infiltrate was also determined, using subjective evaluation by two pathologists (brisk/non-brisk/absent) and also using the immunoscore method, which categorised the cohort into five immunoscore groups according to the number of CD3+ and CD8+ T-cells in both the tumour centre and tumour invasion front. Only one case (0.6%) was MMR-deficient. Tumour budding count ≥5 tumour buds/20× power field and non-brisk/absent lymphocytic infiltrate were significant negative predictors of both the overall survival (OS) and cancer-specific survival (CSS), whereas a low immunoscore was a significant marker of shorter OS but not CSS. Advanced pT stage (3+4) was a significant marker of shorter CSS but not OS. In the multivariate analysis, high-grade budding was a significant parameter if adjusted for the patient's age and associated variables, except for the pN stage. The lymphocytic infiltrate retained its prognostic significance if adjusted for age and associated variables. The negative prognostic significance of the previously described parameters (lymphatic, venous, and perineural invasion, regional lymph node metastasis, and p53 mutated profile) were confirmed in our study. Grade, histological subtype, and HPV status (as determined by p16 immunohistochemistry) showed, surprisingly, little or no prognostic significance.
Vřetenobuněčný / pleomorfní lipom je poměrně vzácný mezenchymální nádor vyskytující se nejčastěji v podkožní tukové tkáni šíje a zad u starších mužů řazený mezi adipocytické nádory. Mikroskopicky nacházíme dobře ohraničený tumor sestávající z vřetenitých buněk v myxoidním stromatu s v různém množství zastoupenou adultní tukovou tkání, charakteristická jsou vmezeřená kolagenní vlákna a žírné buňky ve stromatu. Imunohistochemicky je pravidlem pozitivita CD34. Nádor je řazen do rodiny lézí s delecí chromozomu 13 a/nebo 16 se ztrátou tumor supresorového genu RB1. Součástí této jednotky je i několik histologických variant včetně raritní “fat-poor” neboli “nízkotučné”, kde jsou tukové buňky v minimálním množství nebo úplně chybí. V této práci referujeme případ staršího muže s objemným tumorem šíje, který byl na základě histologického vyšetření, pozitivity CD34 a výpadku exprese Rb1 diagnostikován jako vřetenobuněčný lipom se znaky myxoidní a “fat-poor” varianty. Diagnózu podpořil následný molekulární průkaz delece RB1. Článek diskutuje poměrně širokou problematiku diferenciální diagnostiky vřetenobuněčných myxoidních CD34+ mezenchymálních tumorů.
Spindle cell / pleomorphic lipoma is a relatively rare mesenchymal adipocytic tumor occurring typically in subcutaneous fat tissue in the posterior neck region in middle aged and elderly male. Microscopically, the tumor is usually well-circumscribed consisting of spindle shaped cells with myxoid stroma and variable amount of adult fat tissue. Entrapped collagen fibers and mast cells are constant finding. The lesion is characterized by positive CD34 immunohistochemistry. The tumor belongs to a family with chromosomes 13 and/or 16 deletion and loss of tumor suppressor gene RB1. Several histological variants including “fat-poor” spindle cell lipoma with minimal or absent fat cells may rarely occur. In this article we report a case of elderly man with a voluminous posterior neck tumor diagnosed as a fat-poor spindle cell lipoma based on histological examination, CD34-positivity and loss of Rb1 expression shown by immunohistochemistry. The diagnosis was confirmed by a molecular proof of RB1 deletion. The paper discusses a wide differential diagnosis of spindle cell myxoid CD34+ mesenchymal tumors.
- Klíčová slova
- nízkotučná varianta,
- MeSH
- genetické techniky MeSH
- histologické techniky MeSH
- krk patologie MeSH
- lidé MeSH
- lipom * diagnóza genetika patologie MeSH
- senioři nad 80 let MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
Cholangiocelulární karcinom je relativně vzácný maligní nádor vycházející z biliárních epitelií, který může vznikat v intra- i extrahepatálních žlučovodech, ve žlučníku a ve Vaterské ampule. Tento přehledový článek se věnuje problematice cholangiocelulárního karcinomu z pohledu histopatologa. Kromě shrnutí základních morfologických, imunohistochemických a molekulárně genetických charakteristik jednotlivých typů cholangiokarcinomu a prekancerózních lézí se zaměřuje na problematiku peroperačních biopsií a na změny v aktuálním 8. vydání TNM klasifikace. Součástí sdělení je makroskopická i mikroskopická obrazová dokumentace z naší praxe a přehled recentní literatury.
Cholangiocarcinoma is a relatively rare malignant tumor arising from the biliary epithelium of the intra- and extrahepatic bile ducts, the gallbladder, and the ampulla of Vater. This review article presents cholangiocarcinoma from the routine histopathological point of view. In addition to an overview of basic morphological, immunohistochemical, and molecular genetic characteristics of cholangiocarcinoma subtypes and precancerous lesions, the article is focused on intraoperative biopsies and on changes in the 8th edition of the TNM classification. Macroscopic and microscopic photo documentation and a review of recent literature are included.
- MeSH
- cholangiokarcinom patologie MeSH
- lidé MeSH
- nádory žlučových cest * chirurgie patologie MeSH
- žlučové cesty extrahepatické patologie MeSH
- žlučové cesty intrahepatální patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.
- MeSH
- antigeny CD274 genetika metabolismus MeSH
- keratin-7 genetika MeSH
- kolorektální nádory * patologie MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- prognóza MeSH
- transkripční faktory genetika MeSH
- vazebné proteiny DNA v oblastech připojení k matrix * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
