Clear cell renal cell carcinoma (CRCC) is well known for its intratumoral heterogeneity. Paneth-like cells (PLC) have been reported in variable organs (i.e., hepatobiliary, genitourinary, and female genital tract). In genitourinary system, it is possible to find PLCs in epididymis, urinary bladder and prostate. The objective of this study was to assess PLC in CRCCs 13 CRCCs with prominent PLC (CRCCPLC) were selected out of 1378 CRCCs in our registry. The tumors were analyzed using morphologic, immunohistochemical, ultrastructural, and molecular genetic methods. CRCCPLCs were mostly of low histologic grade (12/13). Immunohistochemical profile was compatible with classic CRCC. PLC constituted 10 to-70% of the tumor volume (mean 17.7%, median 10%). PLCs did not express neuroendocrine markers (chromogranin, synaptophysin, CD56, INSM-1). Ultrastructurally, PLCs were filled by membrane bounded vesicles of various sizes and were compatible with secretory type of cells. VHL mutation was found in 9/9 cases, and LOH3p was found in 6/8 analyzable cases. Conclusions: PLC morphology can variably be present in "classic" CRCC, even in a substantial proportion. Ultrastructurally, PLCs have all attributes of secretory cells. Preliminary follow up data showed that these tumors may not be associated with aggressive clinical behavior.

• MeSH
• Adult MeSH
• Immunohistochemistry MeSH
• Carcinoma, Renal Cell pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Neoplasms pathology   MeSH
• Paneth Cells pathology   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Paneth-like cells (PLCs) are different from Paneth cells (PCs) and contain Paneth-like granules, which have been reported in non-neoplastic conditions and in neoplasms of various organs. PLCs have been reported in clear cell renal cell carcinoma (CCRCC), but not in non-CCRCC, including acquired cystic disease-associated renal cell carcinoma (ACD-RCC). We analyzed clinicopathological features of 24 acquired cystic disease-associated renal cell carcinoma (ACD-RCC) with PLCs (ACD-RCCP+) and compared with those of 23 ACD-RCCs without PLCs (ACD-RCCP-). Approximately half of ACD-RCCs had PLCs and that almost all kidneys harboring ACD-RCC had cysts with PLCs. The fact that many ACD-RCCs and the cysts had PLCs is further evidence that the cyst with vacuoles and complex architecture might be a precursor lesion for ACD-RCC. The presence of PLCs may provide additional morphologic clue for distinguishing ACD-RCC from PRCC in challenging differential diagnostic workup in acquired cystic disease of the kidney setting.

• MeSH
• Kidney Diseases, Cystic complications   pathology   MeSH
• Cysts pathology   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Carcinoma, Renal Cell diagnosis   pathology   MeSH
• Kidney pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Neoplasms pathology   MeSH
• Oxalates analysis   MeSH
• Paneth Cells pathology   MeSH
• Disease Progression MeSH
• Aged MeSH
• Neoplasm Staging methods   MeSH
• Tumor Necrosis Factor-alpha metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

BACKGROUND: The canonical Wnt signaling pathway controls the continuous renewal of the intestinal epithelium and the specification of epithelial cell lineages. Tcf4, a nuclear mediator of Wnt signaling, is essential for the differentiation and maintenance of Paneth cells in the small intestine. Its deficiency is associated with reduced expression of key α-defensins, highlighting its role in host-microbe interactions. However, the exact function of Tcf4 in specifying the secretory lineage and its contribution to antimicrobial peptide production remain incompletely understood. Remarkably, α-defensin expression has also been detected in human colon adenomas, where aberrant Wnt signaling is a hallmark. This raises important questions: What is the role of these Paneth-like cells in tumor biology, and how does Tcf4 influence their identity and function? METHODS: We investigated cell specification in small intestinal crypts and colon tumors using conditional Tcf7l2 deletion, cell type-specific Cre recombinases, and reporter alleles in mice. Transcriptomic (single-cell and bulk RNA sequencing) and histological analyses were performed and complemented by microbiome profiling, antibiotic treatment, and intestinal organoids to functionally validate the main findings. RESULTS: The inactivation of Tcf4 depletes Paneth cells and antimicrobial peptides, disrupting the gut microbiota balance. In secretory progenitors, loss of Tcf4 shifts differentiation toward goblet cells. In the small intestine, alternative secretory progenitors produce Wnt ligands to support stem cells and epithelial renewal in the absence of Paneth cells. In colon tumors, Paneth-like cells form a tumor cell population, express Wnt ligands, and require Tcf4 for their identity. Loss of Tcf4 redirects their differentiation toward goblet cells. CONCLUSIONS: Tcf4 controls the balance between Paneth and goblet cells and is essential for antimicrobial peptide production in the small intestine. In colon adenomas, Paneth-like tumor cells drive antimicrobial gene expression and provide Wnt3 ligands, which may have implications for cancer therapy.

• MeSH
• alpha-Defensins metabolism   MeSH
• Cell Differentiation MeSH
• Humans MeSH
• Mice MeSH
• Colonic Neoplasms * pathology   genetics   microbiology   metabolism   MeSH
• Organoids metabolism   MeSH
• Paneth Cells metabolism   MeSH
• Goblet Cells metabolism   MeSH
• Wnt Signaling Pathway MeSH
• Gastrointestinal Microbiome * MeSH
• Intestine, Small * metabolism   pathology   microbiology   MeSH
• Transcription Factor 4 * metabolism   genetics   MeSH
• Transcriptome * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Popisovány jsou dvě léze mléčné žlázy s nesmírně vzácnou diferenciací (metaplazií), napodobující acinické buňky serózní slinné žlázy. Jednalo se o ženy ve věku 71 a 40 let; u první jsme rysy podobné acinickému karcinomu nalezli v invazivní komponentě solidního intraduktálního papilokarcinomu, u druhé ženy se jednalo o rozsáhlé změny v rámci běžné intraduktální hyperplazie náhodně zjištěné při exstirpaci fibroadenomu. V obou pozorováních se shodně vyskytovaly hojné epitelie s četnými, v barvení PAS pozitivními, intracytoplazmatickými granuly, která reagovala masivně s protilátkou proti lysozymu a v ultrastruktuře měla jednoznačnou podobu zymogenních granul. Diskutována je diferenciální diagnostika neoplastických proliferací prsu s oxyfilní a granulovanou cytoplazmou a na pozadí literárních faktů a jedinečného nálezu této diferenciace v běžné duktální hyperplazii jsou zvažovány biologické implikace.

Described are two epithelial lesions of the breast displaying extremely rare, widespread acinic cell-like differentiation (metaplasia). Two women, 70 and 40-year-old, one with invasive ductal papillocarcinoma, the other one with conventional intraductal hyperplasia without atypia, both demonstrated massive diffuse, PAS positive, granular eosinophilic transformation of the cell cytoplasm. This unusual cell appearance closely simulated acinar cells in normal serous salivary gland/acinic cell carcinoma or Paneth cells. Both extensive expression of lysozyme and finding of numerous zymogen granules ultrastructurally confirmed the acinic cell-like fenotype. Discussed is differential diagnosis of the breast neoplasm containing overt eosinophilic and granular cytoplasm. Reviewing literature and comparing our unique finding of unusual salivary-type differentiation in conventional ductal hyperplasia of the breast, biologic implications are considered.

• MeSH
• Carcinoma, Acinar Cell pathology   MeSH
• Carcinoma, Ductal, Breast pathology   MeSH
• Humans MeSH
• Breast Neoplasms pathology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• Keywords
• střevní bariéra,
• MeSH
• Acute Disease MeSH
• Dysbiosis MeSH
• Enteral Nutrition adverse effects   MeSH
• Immune System immunology   MeSH
• Cathelicidins physiology   immunology   MeSH
• Humans MeSH
• Enterocolitis, Necrotizing * etiology   immunology   physiopathology   MeSH
• Infant, Premature MeSH
• Infant, Low Birth Weight MeSH
• Infant, Newborn MeSH
• Paneth Cells physiology   immunology   MeSH
• Risk Factors MeSH
• Gastrointestinal Microbiome * immunology   MeSH
• Intestinal Mucosa * physiology   immunology   growth & development   MeSH
• Digestive System Physiological Phenomena immunology   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• Publication type
• Handbook MeSH

• NML Publication type
• publikace WHO

• MeSH
• International Classification of Diseases MeSH
• Kidney Neoplasms genetics   pathology   MeSH
• Genital Neoplasms, Male genetics   pathology   MeSH
• Prostatic Neoplasms genetics   pathology   MeSH
• Urologic Neoplasms genetics   pathology   MeSH
• Publication type
• Handbook MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• urologie
• andrologie
• onkologie
• NML Publication type
• publikace WHO

The classification of salivary gland tumors is ever-evolving with new variants of tumors being described every year. Next-generation sequencing panels have helped to prove and disprove prior assumptions about tumors' relationships to one another, and have helped refine this classification. Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and occurs at all major and minor salivary gland and seromucous gland sites. Most AdCC are predominantly myoepithelial and basaloid with variable cribriform, tubular, and solid growth. The luminal tubular elements are often less conspicuous. AdCC has largely been characterized by canonical MYB fusions, with MYB::NFIB and rarer MYBL1::NFIB. Anecdotal cases of AdCC, mostly in nonmajor salivary gland sites, have been noted to have unusual patterns, including squamous differentiation and macrocystic growth. Recently, this has led to the recognition of a subtype termed "metatypical adenoid cystic carcinoma." Another unusual histology that we have seen with a wide range of architecture, is striking tubular hypereosinophilia. The hypereosinophilia and luminal cell prominence is in stark contrast to the vast majority of AdCC that are basaloid and myoepithelial predominant. A total of 16 cases with tubular hypereosinophilia were collected, forming morular, solid, micropapillary, and glomeruloid growth, and occasionally having rhabdoid or Paneth-like cells. They were subjected to molecular profiling demonstrating canonical MYB::NFIB (5 cases) and MYBL1::NFIB (2 cases), as well as noncanonical EWSR1::MYB (2 cases) and FUS::MYB (1 case). The remaining 6 cases had either no fusion (3 cases) or failed sequencing (3 cases). All cases were present in nonmajor salivary gland sites, with seromucous glands being the most common. These include sinonasal tract (7 cases), laryngotracheal (2 cases), external auditory canal (2 cases), nasopharynx (1 case), base of tongue (2 cases), palate (1 case), and floor of mouth (1 case). A tissue microarray of 102 conventional AdCC, including many in major salivary gland sites was examined for EWSR1 and FUS by fluorescence in situ hybridization and showed that these novel fusions were isolated to this histology and nonmajor salivary gland location. In summary, complex and striking tubular hypereosinophilia and diverse architectures are present within the spectrum of AdCC, particularly in seromucous gland sites, and may show variant EWSR1/FUS::MYB fusions.

• MeSH
• Carcinoma, Adenoid Cystic * genetics   pathology   MeSH
• Eosinophilia * MeSH
• Oncogene Proteins, Fusion genetics   MeSH
• In Situ Hybridization, Fluorescence MeSH
• Humans MeSH
• Salivary Gland Neoplasms * genetics   pathology   MeSH
• RNA-Binding Protein EWS genetics   MeSH
• RNA-Binding Protein FUS MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH