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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., (© 2024. The Author(s).)

Extrapulmonary small cell neuroendocrine carcinoma (EP-SCNC) is a rare malignancy with a poor prognosis. Despite its morphological similarity to lung small cell carcinomas, its oncogenesis remains uncertain. One hundred and seventy-one EP-SCNC were enrolled in a multicenter study, and all tissue samples underwent an immunohistochemical p53 analysis. One hundred twenty-five samples were molecularly analyzed using next-generation sequencing (NGS), comprising DNA and RNA analysis. p53 normal/wild type expression was detected in 68 cases (39.8%), whereas aberrant expression was detected in 103 cases (60.2%). Molecular TP53 alteration was detected in 92 out of 125 tumors (73.6%). The TP53 mutation was shown to be prognostic and associated with shorter overall survival (p = 0.041). The multivariate analysis of p53 and TP53 mutational status found that it impacted overall survival relative to distinct sites of tumor locations (p = 0.004 and p = 0.001, respectively). Age did not influenced survival in the multivariate analysis of p53 and TP53 (p = 0.002; p < 0.001 resp.). Among tumors with paired immunohistochemical and molecular results, 108 exhibited concordance between the immunohistochemical and molecular analysis, whereas 17 were discordant. Accordingly, p53 aberrant expression was tightly associated with a TP53 mutation (p < 0.001). In discordant cases, molecular analysis revealed no alteration in three tumors with p53 overexpression. In contrast, in 14 tumors with wild-type p53 expression, TP53 genetic alteration was detected. Possible causes of discordance are discussed in this manuscript. Furthermore, the incidence of aberrant p53 expression / TP53 molecular alteration was noticeably lower in EP-SCNC than in small-cell lung carcinomas. Therefore, in EP-SCNC, other driver mutations should be sought since personalized therapy can improve patient prognosis., (© 2025. The Author(s).)

Extrapulmonary small cell neuroendocrine carcinoma (EP-SCNC) is a rare malignancy with a poor prognosis. Most patients with EP-SCNC have metastatic disease upon presentation, and their average overall survival (OS) is less than 12 months. Our study aimed to conduct a complex analysis of EP-SCNC. One hundred eighty-one EP-SCNC tissue samples were subjected to a complex analysis. One hundred fifty-five tumors were pure EP-SCNC, whereas 26 were combined tumors. Immunohistochemistry for ASCL1, NEUROD1, YAP1, POU2F3, Rb1, p53, cyclin D1, p16, PTEN, DLL3, PD-L1, CD56, synaptophysin, chromogranin A, and INSM1 was performed, and 128 samples were analyzed molecularly using next-generation sequencing, comprising DNA and RNA analyses. Detailed results on immunohistochemical and molecular analyses were provided for each primary origin of EP-SCNC separately. Median survival for the whole cohort of patients was 8.94 months. Patient age (≥70 years), tumor mutational burden <15, and TP53 and BRCA2 mutations were negative prognostic factors. High expression of ASCL-1 was associated with shorter OS, whereas high expression of YAP1 was associated with longer OS. Patients with genitourinary tumors had significantly better OS than those with gastrointestinal tract EP-SCNC tumors. Rb1 expression loss was detected more often in genitourinary tract SCNCs. In contrast, p16 overexpression was found more often in genitourinary tract SCNCs. POU2F3 expression was detected more often in combined tumors, whereas NEUROD1 was detected more often in pure EP-SCNC. Regarding "druggable markers," DLL3 was expressed in 66% of tumors and PD-L1 in 17.4%. Detailed analyses of different prognostic and predictive markers are needed to better understand EP-SCNC biology and create more personalized therapy to improve patient prognosis., (Copyright © 2025 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the World Health Organization distinguishes between human papillomavirus (HPV)-related and HPV-independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in ≥10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high-grade, lymphatic invasion, programmed death ligand-1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV-associated pSCCs were enriched by EPHA7, ATM, GRIN2A, and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related to adverse clinicopathologic signs, such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination repair pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular pathologic, clinical, and prognostic analysis correlating with prognosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Fungal contamination poses a persistent challenge to industries, particularly in food, healthcare, and clinical sectors, due to the remarkable resilience of fungi in withstanding conventional control methods. In this context, our research delves into the comparative efficacy of UV radiation and non-thermal plasma (NTP) on key foodborne fungal contaminants - Alternaria alternata , Aspergillus niger , Fusarium culmorum , and Fusarium graminearum . The study examined the impact of varying doses of UV radiation on the asexual spores of all mentioned fungal strains. Simultaneously, the study compared the effects of UV radiation and NTP on the metabolic activity of cells after spore germination and their subsequent germination ability. The results revealed that UV-C radiation (254 nm) did not significantly suppress the metabolic activity of cells after spore germination. In contrast, NTP exhibited almost 100% effectiveness on both selected spores and their subsequent germination, except for A. niger . In the case of A. niger , the effectiveness of UV-C and NTP was nearly comparable, showing only a 35% decrease in metabolic activity after 48 hours of germination, while the other strains ( A. alternata , F. culmorum , F. graminearum ) exhibited a reduction of more than 95%. SEM images illustrate the morphological changes in structure of all tested spores after both treatments. This study addresses a crucial gap in existing literature, offering insights into the adaptation possibilities of treated cells and emphasizing the importance of considering exposure duration and nutrient conditions (introduction of fresh medium). The results highlighted the promising antimicrobial potential of NTP, especially for filamentous fungi, paving the way for enhanced sanitation processes with diverse applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal adenocarcinoma is particularly challenging, with limited prospects for cure. As with many other malignant neoplasms, the exploration of microRNAs (miRNAs, miRs) in regulating the biological characteristics of pancreatic cancer is undergoing extensive investigation to enhance tumor diagnostics and unveil the therapeutic possibilities. Herein, we evaluated the expression of miR-21, -96, -148a, -155, -196a, -210, and -217 in UCOGCs and poorly differentiated (grade 3, G3) PDACs. The expression of miR-21, miR-155, and miR-210 in both UCOGCs and G3 PDACs was significantly upregulated compared to the levels in normal tissue, while the levels of miR-148a and miR-217 were downregulated. We did not find any significant differences between cancerous and normal tissues for the expression of miR-96 and miR-196a in G3 PDACs, whereas miR-196a was slightly, but significantly, downregulated in UCOGCs. On the other hand, we have not observed significant differences in the expression of the majority of miRNAs between UCOGC and G3 PDAC, with the exception of miR-155. UCOGC samples demonstrated lower mean levels of miR-155 in comparison with those in G3 PDACs.

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., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In recent years, non-thermal plasma (NTP) has emerged as a promising tool for decontamination and disinfection within the food industry. Given the increasing resistance of microbial biofilms to conventional disinfectants and their adverse environmental effects, this method has significant potential for eliminating biofilm formation or mitigating the metabolic activity of grown biofilms. A comparative study was conducted evaluating the efficacy of UV radiation and NTP in eradicating mature biofilms of four common foodborne filamentous fungal contaminants: Alternaria alternata , Aspergillus niger , Fusarium culmorum , and Fusarium graminearum . The findings reveal that while UV radiation exhibits variable efficacy depending on the duration of exposure and fungal species, NTP induces substantial morphological alterations in biofilms, disrupting hyphae, and reducing extracellular polymeric substance production, particularly in A. alternata and F. culmorum . Notably, scanning electron microscopy analysis demonstrates significant disruption of the hyphae in NTP-treated biofilms, indicating its ability to penetrate the biofilm matrix, which is a promising outcome for biofilm eradication strategies. The use of NTP could offer a more environmentally friendly and potentially more effective alternative to traditional disinfection methods.

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.

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.

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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

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., (© 2022. The Author(s).)

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.

Giant cell fibroblastoma is a rare locally aggressive tumor of subcutaneous mesenchymal tissue, occurring mostly on the trunk in young individuals with maximal incidence in the first decade of life. Local recurrences of giant cell fibroblastoma are common if marginally excised, however, distant metastases do not occur. Giant cell fibroblastoma was labelled as a juvenile variant of dermatofibrosarcoma protuberans (DFSP) due to quite frequent combination of both lesions, morphological similarities, identical immunoprofile, and shared gene fusion t(17;22) COL1A1-PDGFB. In this paper, we report a case of a young man with a slowly growing subcutaneous tumor in the groin. The tumor was excised and histological examination identified a mesenchymal tumor with variable cellularity, presence of multinucleated giant cells and pleomorphic spindle cells, which lined pseudovascular or angiectoid spaces. The CD34 immunohistochemistry showed strong positivity in all of these cells, whereas ERG was positive only in endothelial cells in true vessels. These findings led to a suspicion on giant cell fibroblastoma. Because of its borderline malignant behaviour and positive surgical margins, the lesion was subsequently reexcised. The molecular analysis identified the transcription product of gene fusion COL1A1-PDGFB and thus, final diagnosis was confirmed. The article includes review of the literature and brief historical overview of giant cell fibroblastoma concept as an unique entity.

Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with a poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 is expressed in preneoplastic lesions, and its expression is maintained in most colorectal cancers (CRC). High TROP2 positivity correlated with lymph node metastases and poor tumor differentiation and was a negative prognostic factor. To investigate the role of TROP2 in intestinal tumors, we analyzed two mouse models with conditional disruption of the adenomatous polyposis coli ( Apc ) tumor-suppressor gene, human adenocarcinoma samples, patient-derived organoids, and TROP2-deficient tumor cells. We found that Trop2 is produced early after Apc inactivation and its expression is associated with the transcription of genes involved in epithelial-mesenchymal transition, the regulation of migration, invasiveness, and extracellular matrix remodeling. A functionally similar group of genes was also enriched in TROP2-positive cells from human CRC samples. To decipher the driving mechanism of TROP2 expression, we analyzed its promoter. In human cells, this promoter was activated by β-catenin and additionally by the Yes1-associated transcriptional regulator (YAP). The regulation of TROP2 expression by active YAP was verified by YAP knockdown in CRC cells. Our results suggest a possible link between aberrantly activated Wnt/β-catenin signaling, YAP, and TROP2 expression.

Penile paraffinoma or sclerosing lipogranuloma is a disease occurring uncommonly in Czechia; a pathologist meets this only rarely. Microscopically, we deal with chronic fibroproductive inflammation localised usually in subcutaneous tissue of the penis. It is caused by previous voluntary injection of liquid paraffin / mineral oil for the purpose of penis circumference augmentation, usually performed by a non-healthcare person or by the patient himself. Human tissues do not have enzymes that can break down synthetic lipids. The application leads, with a variable time lag, to a foreign body giant-cell reaction lasting for years, and often to annoying complications frequently associated with a genital mutilation and sexual dysfunction. The lesion often requires surgical treatment to remove the paraffin substance from the subcutaneous tissue. The surgery does not always lead to satisfying results and the paraffinoma tends to recur. In this article, we describe a case of a man with relapsing paraffinoma, which required excision of subcutis with subsequent plastic surgery with skin graft. During histological examination, lipid droplets were found in dermis and in subcutis, along with xantogranulomatous inflammation. The lipid nature of the material was proven by oil red and Sudan stain. The paper includes clinical and histopathological differential diagnostic consideration, summary of treatment options and relevant literature review.

Radiofrequency ablation (RFA) is a routinely used, safe, and effective method for the tissue destruction. Often, in case of its application in malignant conditions, the extent of tissue destruction is insufficient due to the size of the target lesion, as well as due to the risk of heat-induced damage to the surrounding organs. Nevertheless, there are conditions requiring superficial precise-depth ablation with preservation of deeper layers. These are represented, for example, by mucosal resurfacing in case of Barrett's esophagus or treatment of recurrent mucosal bleeding in case of chronic radiation proctitis. Recently, new indications for intraluminal RFA use emerged, especially in the pancreatobiliary tract. In the case of intraductal use of RFA (e.g., biliary and pancreatic tract), there are currently available rigid and needle tip catheters. An expandable balloon-based RFA catheter suitable for use in such small-diameter tubular organs could be of benefit due to possible increase of contact between the probe and the target tissue; however, to prevent excessive tissue damage, a compatible generator suitable for low-impedance catheter/tissue is essential. This project aimed to develop a radiofrequency ablation generator and bipolar balloon-based catheter optimized for the application in the conditions of low-impedance tissue and (micro)endoluminal environment. Subsequent evaluation of biological effect in vivo was performed using duodenal mucosa in Wistar rat representing conditions of endoluminal radiofrequency ablation of low-impedance tissue. Experiments confirming the safety and feasibility of RFA with our prototype devices were conducted., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Jana Nociarova et al.)

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is usually CK7 - and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan-Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years, P = 0.007) and 5-year survival (29.4% vs. 64.6%, P = 0.0221) in CK7 + tumors compared to CK7 - tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years, P = 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years, P = 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years, P < 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic., (© 2021. The Author(s).)

Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan-Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson's chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa ( p = 0.014), and they occurred more often in female patients and vice versa ( p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided ( p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors ( p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage ( p = 0) and right sided localization ( p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC.

Giant cell myocarditis (GCM) is a rare inflammatory disease of the heart that often affects younger patients. The clinical course is typically rapid with fulminant congestive heart failure. Prognosis is poor; the proper diagnosis is often rendered at the autopsy. Herein, we present a prototypical case of this rare type of myocarditis, affecting a 44-year-old previously healthy woman who was referred to the intensive care department due to an acute onset cardiac arrest followed by resuscitation. The heart ultrasound and imaging examinations revealed a severe dysfunction and dilatation of both ventricles, without any significant finding in the coronary arteries. Twelve days after the initial presentation, the patient died due to congestive heart failure refractory to intensive therapy. The post-mortem histology of the heart revealed multiple small necrotic foci in the myocardium in both ventricles, with dense inflammatory infiltration with abundant multinucleated giant histiocytes, in line with a diagnosis of GCM. The natural history, pathophysiology, and histological differential diagnosis is discussed, together with review of the relevant literature including uncommon and emerging units.

Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC ( p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively ( p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hrudka, Prouzová, Mydlíková, Jedličková, Holešta, Whitley and Havlůj.)

Undifferentiated or anaplastic thyroid carcinoma (ATC) is rare and one of the most aggressive human malignancies. The tumor is usually voluminous and fast-growing and mostly affects older women. The most common sites of distant metastases are the lungs, brain, and bones. Herein, we describe the case of a 66-year-old woman with a history of bilateral breast carcinoma and ATC, who presented with an acute abdomen and subsequently died. At autopsy, an isolated metastasis of ATC in the small intestine leading to bowel perforation was found. Moreover, there was adenocarcinoma in the descending colon. The review of extra-abdominal malignancies metastasizing to bowel and coincidence of breast and thyroid carcinoma is included., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © 2021 The Author(s).)

Secretory carcinoma (SC) is a relatively recently described salivary gland adenocarcinoma characterized by ETV6-NTRK3 gene fusion and, in most cases, indolent clinical behavior. Morphologically, the tumor shows a glandular architecture and the presence of monophasic tumor cells with vacuolated cytoplasm, low-grade nuclear atypia, and mucin production, with possibly a tubular, papillary, or cystic arrangement. In this article, we describe a case of a 52-year old man with SC involving a neck lymph node clinically manifesting as a slowly growing cystic neck mass without recent proof of the primary tumor, but with a history of a parotid gland "cystadenopapilloma," which had been removed 35 years prior. A fine-needle aspiration biopsy revealed a diagnosis of SC. Subsequent histopathological examination after lymph node dissection confirmed the diagnosis. The tumor showed typical features of SC, including immunohistochemical positivity for NTRK and NTRK3 gene rearrangement, detected using in situ hybridization. We discuss that the tumor may be a late metastasis occurring 35 years after resection of undiagnosed salivary SC or a primary SC arising from heterotopic salivary tissue within a lymph node. Differential diagnostic considerations and review of relevant literature are included., (© 2020 Wiley Periodicals LLC.)

Malignant melanoma is commonly known for its high probability of metastasizing to distant organs. Metastases to gastrointestinal tract are well documented, but resulting jaundice is only scarcely seen. We present a case of histologically verified metastasis of amelanotic melanoma to the head of pancreas infiltrating the common bile duct and consequently causing obstructive jaundice which constituted its first clinical manifestation. Multidisciplinary approach is essential in patients with malignant melanoma since early detection of the melanoma or its metastases may improve patients' clinical outcome, especially owing to the use of targeted biological treatment without any delay.

Pancreatic carcinoma remains one of the leading cancer-related causes of death worldwide and is generally characterized by a dismal prognosis and limited potential for oncologic treatment. A rare subvariant of pancreatic cancer, undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), has an unpredictable prognosis according to many previous studies, with unexpectedly long survival in individual cases. In this study, we collected, retrospectively, 13 cases of well-documented UCOGCs and performed immunohistochemistry focused on the expression of the programmed death-ligand 1 (PD-L1) and several other potential therapeutic and predictive markers (PanTRK, p53, MSH2, PMS2, and the number of tumor-infiltrating lymphocytes), to explore their correlation with the follow-up of the patients. As a control group, we examined 24 cases of conventional pancreatic ductal adenocarcinoma (PDAC). In our results, PanTRK was negative in all 24 cases. P53 did not show any significant differences between UCOGCs and PDACs, and the entire cohort was MSH2, MLH1, PMS2, and MSH6 positive. Significant differences were present in the analysis of PD-L1: UCOGCs were found to express PD-L1 significantly more frequently and have a higher number of tumor-infiltrating lymphocytes than PDAC. The expression of PD-L1 was related to significantly shorter survival in patients with UCOGC and in the entire cohort. Patients with PD-L1 negative UCOGCs displayed surprisingly long survival in comparison to PD-L1 positive UCOGCs and PDACs (both PD-L1+ and PD-L1-). We compared our results with previously published data, and, after statistical analysis, we were able to identify PD-L1 as an effective prognostic marker of UCOGC and suggest a strong need for a clinical trial of immune checkpoint immunotherapy in patients with advanced PD-L1 positive UCOGC.

Adenoid cystic carcinoma (ACC) is one of the most common salivary gland malignancies. In rare cases, ACC undergoes high-grade transformation, which is associated with poor prognosis, in contrast to relatively long survival in the conventional ACC. Conventional ACC is characterized by typical histopathology showing glandular arrangement with sharply demarcated lumina, the tumor cells have sparse cytoplasm and angulated hyperchromatic nuclei. ACCs undergoing high-grade transformation lack these morphological features. In this paper we present a case of 46 years old female patient presenting with locally advanced tumor of the parotid gland and neck lymphadenopathy, coming for surgery. A suspect lymph node was sent to freeze section histology. Large non-cohesive cells with vesicular nuclei and prominent nucleoli along with well persevered lymph node architecture were seen in the frozen slide. This finding lead to suspicion of a lymphoma, the surgery finished in the extent of superficial parotidectomy and selective neck dissection of regions II-IV. Subsequent histopathological examination of formalin-fixed lymph node proofed epithelial nature of the atypical cells by p63 positivity. In the parotid gland resection specimen, an ACC with high-grade component was indentified. The high-grade ACC shared cell morphology with the lymph node metastasis. 17 from 20 lymph neck nodes contained metastases of high-grade ACC. Interestingly, there was strong CD117 expression in the high-grade ACC, whereas the conventional part was fully negative. To the best of our knowledge, the high-grade ACC of the parotid gland was reported only in 10 cases in the medical literature.

Dermatofibrosarcoma protuberans is a quite rare local aggressive tumor of dermis and subcutis, revealing characteristic morphology and chromosomal translocation (17; 22)(q21;q13) with gene fusion COL1A1-PDGFB. The tumour almost never metastasizes and complete excision signs an excellent prognosis. Approximately in 10% of cases, dermatofibrosarcoma undergoes a fibrosarcomatous transformation associated with metastatic disease and worse prognosis. In this paper, we refer a case of a male patient with subcutaneous tumor in back region, in which the small biopsy lead to diagnosis of a spindle cell sarcoma. However, only the histopathological examination of the entire tumor in the material from the radical surgery detected the dermatofibrosarcoma protuberans with fibrosarcomatous transformation. Both components of the tumor showed the characteristic genetic alteration. Identification of fibrosarcomatous component within the DFSP matters in prognosis. Distinction between fibrosarcoma arising within the dermatofibrosarcoma protuberans and fibrosarcoma arising de novo is of therapeutic consequence: the patients with metastatic or inoperable DFSP with fibrosarcomatous transformation may profit form imatinib treatment.

Background: Squamous cell carcinoma is the most common malignant tumor of the uterine cervix with a well-documented link to infection with human papillomaviruses (HPV). According to a recent classification, there are several morphological variants of cervical squamous carcinoma, without reference to sarcomatoid squamous cell carcinoma, which is well described in other organs., Case Presentation: In this paper, we describe an extremely rare case of a 77-year-old woman with primary malignant cervical tumor displaying biphasic histomorphology with an epithelioid and sarcomatoid part; the latter was immunohistochemistry positive for cytokeratin and vimentin. The association with a high-grade squamous intraepithelial lesion and molecular proof of HPV33 infection in the tumor tissue supported our diagnosis of carcinoma with partial sarcomatoid differentiation., Conclusion: We report a rare case of a primary cervical epithelial tumor with a partial sarcomatoid phenotype, an unequivocal HPV infection, and an associated precancerous lesion in the cervical mucosa. This is the first description of an HPV33 infection underlying a biphasic epithelioid-sarcomatous tumor of the uterine cervix. The terminology overlap between sarcomatoid carcinoma and carcinosarcoma is also discussed.

Intramyocardial dissection or intramyocardial dissecting hematoma is uncommon complication either of myocardial infarction or severe thoracic injury. Intramyocardial dissecting hematoma is caused by intersecting bleeding between the layers of myocardial fibers. In contrast to cardiac rupture, the myocardial wall maintains its integrity. In this paper, we present a case of patient suffering with ischemic heart disease, reporting worsening chest pain and dyspnea 2 months after autovenous graft bypass surgery. The coronary angiography revealed severe stenosis of the autovenous graft, which was treated by stent implantation. Three hours after intervention, the patient showed signs of cardiogenic shock with clinical suspicion of heart tamponade because of ventricular wall rupture. The patient died despite the surgical drainage of the hematoma and blood transfusions. In the necropsy, the large intramyocardial dissecting hematoma in the very superficial layer of the left ventricular myocardium was found, accompanied with very small extent of necrotic myocardium in the neighborhood of the intramyocardial dissecting hematoma. The prevailing majority of the left ventricle thickness was vital. The lack of developed transmural infarction in our case leads us to hypothesis that the increased intravascular pressure during the reperfusion is the main contributor to the intramyocardial dissecting hematoma development, together with reduced biomechanical resistance of the capillaries affected by chronic ischemia., (Copyright © 2019 Elsevier Inc. All rights reserved.)