Pathogenic alterations, namely, fusions and amplifications, of the GLI1 gene have been identified in various mesenchymal tumors, including pericytoma with t(7;12), plexiform fibromyxoma, gastroblastoma, and other malignant mesenchymal neoplasms arising in the soft tissues, as well as in various visceral organs. However, only three cases of GLI1-rearranged renal tumors have been reported to date, comprising two low-grade spindle cell tumors with GLI1::FOXO4 fusion along with one GLI1-rearranged case with an unknown fusion partner. In this study, we analyzed three cases with GLI1::FOXO4 fusion and overlapping morphology. One of the cases was reported previously, but an extended clinical and immunohistochemical information is provided. The studied cases occurred in 2 female and 1 male patients aged 35, 55, and 62 years (mean 51 years). All three tumors affected the renal parenchyma and grew as unencapsulated but well-circumscribed solid masses containing occasional entrapped and dilated renal tubules. The tumor cells were organized in cords, nests, or fascicles, had a round to spindled shape, and exhibited only mild nuclear atypia and minimal mitotic activity. They had a sparse eosinophilic to clear cytoplasm and were embedded in myxocollagenous stroma. Immunohistochemically, all cases expressed GLI1 (albeit with variable intensity) and harbored GLI1::FOXO4 fusion. All three patients were treated solely by complete surgical excision. Case 1 was alive with unknown disease status, case 2 was alive without evidence of disease, and case 3 died of unrelated causes. Our study doubles the number of reported cases with GLI1::FOXO4 fusion. The so far absolute predilection of this fusion for renal tumors, coupled with the absence of reports of other GLI1 fusions in tumors of the kidney, might indicate the potential existence of a distinct renal subtype with morphological features similar to other GLI1-altered tumors. All four reported cases had an uneventful follow-up which, together with their low-grade morphological features, suggests that these tumors might have a favorable prognosis.

• MeSH
• Adult MeSH
• Forkhead Transcription Factors * genetics   MeSH
• Gene Rearrangement * MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor * genetics   analysis   MeSH
• Kidney Neoplasms * genetics   pathology   MeSH
• Zinc Finger Protein GLI1 * genetics   MeSH
• Cell Cycle Proteins * genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Malignant glomus tumors are rare tumors of pericytic origin with a propensity to develop in the upper gastrointestinal tract. Hereby we demonstrate a tumor of a 20-year-old man, who presented with dysphagia and an exophytic esophageal mass. Histologic examination of the resected mass revealed a multinodular tumor in the esophageal wall composed of epithelioid cells showing nesting and monomorphic atypia, staghorn vessels and scanty stroma. Immunohistochemically, the neoplastic cells were positive for SMA, and H-caldesmon, while desmin was negative. Collagen IV and laminin decorated a dense intercellular basal membrane meshwork. RNA-sequencing using TruSight RNA Pan-Cancer Panel revealed a CARMN::NOTCH2 fusion, that is a recurrent, frequently described and so far specific genetic alteration in glomus tumors. In spite of the adjuvant chemotherapy regimens, the patient died of disseminated metastatic disease 2 years after the diagnosis. Our patient presentation and the previous reports in the literature highlight the frequently aggressive behavior of glomus tumors arising in the esophagus.

• MeSH
• Esophagus pathology   surgery   diagnostic imaging   MeSH
• Fatal Outcome MeSH
• Oncogene Proteins, Fusion * genetics   MeSH
• Glomus Tumor * genetics   pathology   diagnosis   MeSH
• Humans MeSH
• Young Adult MeSH
• Biomarkers, Tumor genetics   analysis   MeSH
• Esophageal Neoplasms * pathology   genetics   diagnosis   MeSH
• Receptor, Notch2 * genetics   MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10-15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients.

• MeSH
• Cytokines metabolism   immunology   MeSH
• Endometriosis * immunology   therapy   pathology   etiology   MeSH
• Endometrium immunology   pathology   MeSH
• Humans MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

PURPOSE: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting. EXPERIMENTAL DESIGN: Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphologic features could serve as a potential marker for OS in the neoadjuvant setting. RESULTS: Excellent correlation between the trained network and pathologists was obtained for the quantification of necrosis content (R2 = 0.899; r = 0.949; P < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). The morphology-based supervised approach predicted OS; P = 0.0028, HR = 2.43 (1.10-5.38). The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS [log-2 hazard ratio (lg2 HR); -2.366; -1.164; -1.175; 95% confidence interval, (-2.996 to -0.514)]. Viable/partially viable tumor and fat necrosis were associated with worse OS [lg2 HR; 1.287; 0.822; 0.828; 95% confidence interval, (0.38-1.974)]. CONCLUSIONS: Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphologic biomarkers specific to the necrotic and tumor regions, which could serve as predictors.

• MeSH
• Deep Learning MeSH
• Child MeSH
• Adult MeSH
• Kaplan-Meier Estimate MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Bone Neoplasms * mortality   pathology   MeSH
• Necrosis * MeSH
• Neoadjuvant Therapy * methods   MeSH
• Neural Networks, Computer * MeSH
• Osteosarcoma * mortality   pathology   therapy   MeSH
• Prognosis MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Two benign adenomatous lesions are commonly recognized within the sinonasal tract, namely respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH). We present 10 hitherto unrecognized benign polypoid nasal and sinonasal tumoriform lesions having in average 3.6 cm in largest dimension, which are histogenetically related to SH and REAH. In addition to typical structures of REAH and SH, these lesions contained an additional characteristic and slightly atypical adenomatous component, which we termed atypical sinonasal glands arising in SH (ASGSH). ASGSH often produced deep red colored secretion with peripheral clearing similar to that seen in thyroid follicles. In contrast to SH, ASGSH was endowed by both secretory and myoepithelial layers and had mostly angulated shapes with snout-like protrusions into the lumens. Both layers were formed by an irregular, disorganized, and often incomplete cell lining, which had slightly atypical cytological features without mitoses. In 3 cases, ASGSHs revealed sebaceous differentiation, and in 3 cases the stroma produced a well-differentiated cartilage. Neoplastic nature of ASGSH was supported by finding of various mutations as revealed by next generation sequencing in five cases. In two cases each, we found identical mutations in BRAF gene (Val600Glu), and RET gene (Arg912Trp), respectively and in one case FAT1 gene alteration (Pro1665Leu).

• MeSH
• Adenoma pathology   genetics   MeSH
• Adult MeSH
• Hamartoma * pathology   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Nose Neoplasms pathology   genetics   MeSH
• Paranasal Sinus Neoplasms pathology   genetics   MeSH
• Respiratory Mucosa pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Classification MeSH
• Neoplasms diagnosis   MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• patologie
• onkologie

Acral fibrochondromyxoid tumor (AFCMT) is a recently described likely benign mesenchymal neoplasm arising in the distal extremities with distinctive histologic features and a recurrent THBS1::ADGRF5 fusion. We studied an additional 37 cases of AFCMT and expanded on the so-far reported clinicopathologic and molecular findings. Tumors occurred in 21 females and 16 males, ranging in age from 17 to 78 years (median age: 47), and solely involved the hands (24/37, 65%) or feet (13/37, 35%). Histologic examination revealed well-delineated uni- or multinodular tumors with prominent vasculature-rich septa and bland, chondrocyte-like tumor cells set within abundant chondromyxoid stroma. Immunohistochemical studies showed that tumor cells were positive for CD34 (25/27; 93%) and ERG (27/27; 100%), whereas negative for S100 protein (0/31). Molecular analysis revealed evidence of a THBS1::ADGRF5 fusion in 17 of 19 (89%) successfully tested tumors. Clinical follow-up was available in 8 cases (median: 97 months), with multiple local recurrences in 1 case at 276, 312, and 360 months. We conclude that AFCMT is a distinct entity with reproducible morphologic, immunohistochemical, and molecular genetic features that should be differentiated from other similar appearing acral mesenchymal neoplasms.

• MeSH
• Adult MeSH
• In Situ Hybridization, Fluorescence MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Biomarkers, Tumor * genetics   analysis   MeSH
• Soft Tissue Neoplasms genetics   pathology   MeSH
• Foot pathology   MeSH
• Hand pathology   MeSH
• Aged MeSH
• Thrombospondin 1 genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Karcinom pankreatu je nádorové onemocnění se špatnou prognózou, které představuje třetí nejčastější příčinu úmrtí na zhoubný nádor ve vyspělých zemích a jehož incidence a mortalita dle predikcí nadále významným způsobem porostou. Téměř 80 % pacientů je diagnostikováno s pokročilým onemocněním a je tudíž odkázáno na paliativní protinádorovou léčbu s limitovanou účinností. Avšak i u 10-20 % nemocných s lokalizovaným karcinomem pankreatu, kteří úspěšně absolvovali radikální resekci a následnou adjuvantní chemoterapii, obvykle dojde k relapsu do 2-3 let od operace. Příčiny lze hledat v pozdním stanovení diagnózy, v komplikované anatomické lokalizaci, ve výrazné nádorové heterogenitě znesnadňující testování nových léčiv a v neposlední řadě i v přítomnosti denzního nádorového stromatu znesnadňujícího přístup jak cytostatik, tak i cílených léčiv do nádorové tkáně. V tomto sdělení uvádíme souhrn aktuálních možností diagnostiky a léčby lokalizovaných i pokročilých forem karcinomu pankreatu včetně možností molekulární diagnostiky a cílené léčby podskupin.

Pancreatic ductal adenocarcinoma is a cancer disease with a very poor prognosis, which poses the third-leading cause of cancer-related deaths and whose incidence and mortality have been predicted to increase significantly in the upcoming years. Almost 80% of patients are diagnosed with advanced unresectable disease and therefore rely on palliative anticancer treatment with limited efficacy. However, even in case of 10-20 % of patients who have successfully undergone radical surgical resection of the localized disease and subsequent adjuvant chemotherapy, the vast majority will relapse within 2-3 years of surgery. The reasons can be found in late diagnosis due to the prolonged clinically asymptomatic course of the disease, complicated anatomical localization, significant tumor heterogeneity, which makes it difficult to test new drugs and, last but not least, in the presence of dense tumor stroma, that complicates the access of cytostatics and targeted drugs into the tumor tissue. Here we present a summary of current treatment options of localized and advanced pancreatic cancer, including molecular diagnostics and targeted treatment of small patients subgroups.

• MeSH
• Molecular Targeted Therapy * methods   MeSH
• Drug Therapy methods   MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Pathology, Molecular methods   MeSH
• Pancreatic Neoplasms * diagnosis   drug therapy   pathology   MeSH
• Pancreatectomy methods   MeSH
• Check Tag
• Humans MeSH

Solitární fibrózní tumor je poměrně vzácný měkkotkáňový fibroblastický nádor, tvořící přibližně 2 % nádorů měkkých tkání. Primárně byl popsán jako nádor pleurální dutiny, nicméně až 70 % případů se vyskytuje extrapleurálně téměř v jakékoliv anatomické lokalizaci, z toho důvodu může být jeho diagnostika obtížná. Pokud je na tuto diagnózu pomýšleno, je v současnosti k dispozici protilátka STAT6, která vykazuje vysokou senzitivitu i specificitu. V této práci popisujeme případ 72-leté pacientky, několik let dispenzarizované a léčené ambulantním endokrinologem pro polynodózní eufunkční strumu. Z důvodu kompletní nodózní přestavby levého laloku štítné žlázy a sonografickému nálezu několika menších uzlů v pravém laloku štítné žlázy, byla pacientce doporučena totální thyroidektomie. Operace byla provedena na ORL oddělení Nemocnice Jindřichův Hradec. Materiál z operace byl následně zaslán k histopatologickému vyšetření. V pravém laloku štítné žlázy bylo mikroskopicky zastiženo několik hyperplastických koloidních uzlů a drobný onkocytární adenom. V levém laloku bylo na řezu zastižené nepřesně ohraničené, šedobělavé ložisko velikosti 2 x 1,8 x 1,5 cm. Mikroskopicky šlo o nepřesně ohraničený nádor, tvořený vřetenitými buňkami v ložiskově hyalinizovaném stromatu. V imunohistochemickém vyšetření nádorové buňky reagovaly pozitivně s protilátkou CD34, negativní reakce byla s protilátkami proti thyreoglobulinu, širokospektrým cytokeratinům (CK AE1/AE3) a S100 proteinu. Další imunohistochemická vyšetření (Bcl2, CD99, STAT6) s pozitivním výsledkem byla doplněna konzultačně na vyšším pracovišti. Na základě morfologie a výsledků provedených imunohistochemických vyšetření byl nádor hodnocen jako solitární fibrózní tumor štítné žlázy. V této lokalizaci se jedná o poměrně neobvyklý nález, dle literárních údajů bylo popsáno pouze několik desítek případů.

Solitary fibrous tumour is a relatively rare soft tissue fibroblastic tumour, accounting for approximately 2% of soft tissue tumours. It has been described primarily as a tumour of the pleural cavity; however, up to 70% of cases occur elsewhere, in any anatomical location, which can make diagnosis difficult. If this is the diagnosis being considered, the STAT6 antibody is currently available with high sensitivity and specificity. In this paper we describe the case of a 72-year-old female patient, followed up and treated by an outpatient endocrinologist for a multinodular euthyroid goitre for several years. Due to complete nodular remodelling of the left lobe of the thyroid gland and sonographic findings of several small nodules in the right lobe of the thyroid gland, total thyroidectomy was recommended to the patient. The operation was performed at the ENT department in Jindřichův Hradec Hospital. Material from the operation was subsequently sent for histopathological examination. Several hyperplastic colloid nodules and a small oncocytic adenoma were detected microscopically in the right lobe of the thyroid gland. In the left lobe, an imprecisely delineated, greyish-white lesion measuring 2 x 1.8 x 1.5 cm was observed on the section. Microscopically, the tumour consisted of spindle-shaped cells in a focally hyalinised stroma. In the immunohistochemical examination, tumour cells reacted positively with the CD34 antibody, and negatively with antibodies against thyroglobulin, cytokeratins (CK AE1/AE3) and S100 protein. Further immunohistochemical examinations (Bcl2, CD99, STAT6) with positive results were supplemented upon consultation at a higher facility. Based on morphology and the results of the immunohistochemical examinations, the tumour was diagnosed as a solitary fibrous tumour of the thyroid gland. This is a relatively unusual finding in this location; according to literature, only a few dozen cases have been described.

• MeSH
• Immunohistochemistry methods   MeSH
• Humans MeSH
• Thyroid Neoplasms * surgery   diagnosis   MeSH
• Aged MeSH
• Solitary Fibrous Tumors * surgery   diagnosis   MeSH
• STAT6 Transcription Factor analysis   MeSH
• Thyroidectomy methods   MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Endopeptidases MeSH
• Neoplasm Invasiveness pathology   MeSH
• Humans MeSH
• Membrane Proteins metabolism   MeSH
• Adenocarcinoma, Mucinous * pathology   mortality   metabolism   MeSH
• Biomarkers, Tumor * metabolism   analysis   MeSH
• Ovarian Neoplasms * pathology   mortality   MeSH
• Serine Endopeptidases metabolism   MeSH
• Thrombospondins metabolism   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Editorial MeSH