The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours includes a description of several new entities. In addition, numerous tumor variants were described and new concepts proposed, most of which have been based on recent molecular discoveries. However, there are still some controversial issues that remain to be resolved, and some of them are discussed in this review.
- Klíčová slova
- Carcinosarcoma, Intraductal carcinoma, Intraductal papillary mucinous neoplasms, Mucinous adenocarcinoma, Oncocytic carcinoma, Salivary gland, World health organization classification,
- MeSH
- lidé MeSH
- nádory hlavy a krku * MeSH
- nádory slinných žláz * patologie MeSH
- slinné žlázy patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- New Orleans MeSH
BACKGROUND: Basaloid neoplasms of the sinonasal tract represent a significant group of tumors with histological overlap but often with different etiologies (i.e., viral, genetics), clinical management, and prognostic significance. METHODS: Review. RESULTS: "Basaloid" generally refers to cells with coarse chromatin in round nuclei and sparse cytoplasm, resembling cells of epithelial basal layers or imparting an "immature" appearance. Tumors with this characteristic in the sinonasal tract are represented by a spectrum of benign to high-grade malignant neoplasms, such as adenoid cystic carcinoma, NUT carcinoma, sinonasal undifferentiated carcinoma, SWI/SNF complex-deficient carcinomas, and adamantinoma-like Ewing sarcoma. CONCLUSION: In some instances, histology alone may be sufficient for diagnosis. However, limited biopsy material or fine-needle aspiration specimens may be particularly challenging. Therefore, often other diagnostic procedures, including a combination of histology, immunohistochemistry (IHC), DNA and RNA testing, and molecular genetics are necessary to establish an accurate diagnosis.
- Klíčová slova
- Basaloid neoplasms, Differential diagnosis, Head and neck, Immunohistochemistry, Molecular genetic, Review, Sinonasal tumors,
- MeSH
- Ewingův sarkom * patologie MeSH
- karcinom * patologie MeSH
- lidé MeSH
- nádory sinu maxillaris * patologie MeSH
- paranazální dutiny * patologie MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
GLI1 fusions involving ACTB, MALAT1, PTCH1 and FOXO4 genes have been reported in a subset of malignant mesenchymal tumors with a characteristic nested epithelioid morphology and frequent S100 positivity. Typically, these multilobulated tumors consist of uniform epithelioid cells with bland nuclei and are organized into distinct nests and cords with conspicuously rich vasculature. We herein expand earlier findings by reporting a case of a 34-year-old female with an epithelioid mesenchymal tumor of the palate. The neoplastic cells stained positive for S100 protein and D2-40, whereas multiple other markers were negative. Genetic alterations were investigated by targeted RNA sequencing, and a PTCH1-GLI1 fusion was detected. Epithelioid mesenchymal tumors harboring a PTCH1-GLI1 fusion are vanishingly rare with only three cases reported so far. Due to the unique location in the mucosa of the soft palate adjacent to minor salivary glands, multilobulated growth, nested epithelioid morphology, focal clearing of the cytoplasm, and immunopositivity for S100 protein and D2-40, the differential diagnoses include primary salivary gland epithelial tumors, in particular myoepithelioma and myoepithelial carcinoma. Another differential diagnostic possibility is the ectomesenchymal chondromyxoid tumor. Useful diagnostic clues for tumors with a GLI1 rearrangement include a rich vascular network between the nests of neoplastic cells, tumor tissue bulging into vascular spaces, and absence of SOX10, GFAP and cytokeratin immunopositivity. Identifying areas with features of GLI1-rearranged tumors should trigger subsequent molecular confirmation. This is important for appropriate treatment measures as PTCH1-GLI1 positive mesenchymal epithelioid neoplasms have a propensity for locoregional lymph node and distant lung metastases.
- Klíčová slova
- Epithelioid soft tissue neoplasm, Hedgehog signaling pathway, Oral cavity, PTCH1-GLI1 gene fusion, S100 protein, Soft palate,
- MeSH
- dospělí MeSH
- lidé MeSH
- myoepiteliální nádor * patologie MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory měkkých tkání * patologie MeSH
- nádory slinných žláz * MeSH
- patro měkké patologie MeSH
- protein Gli1 genetika metabolismus MeSH
- proteiny S100 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- Názvy látek
- GLI1 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- protein Gli1 MeSH
- proteiny S100 MeSH
The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several new entities, including sclerosing polycystic adenoma, keratocystoma, intercalated duct adenoma, and striated duct adenoma among the benign neoplasms; and microsecretory adenocarcinoma and sclerosing microcystic adenocarcinoma as the new malignant entities. The new entry also includes mucinous adenocarcinoma subdivided into papillary, colloid, signet ring, and mixed subtypes with recurrent AKT1 E17K mutations across patterns suggesting that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that may be related to salivary intraductal papillary mucinous neoplasm (IPMN). Importantly, the number of entities in the salivary chapter has been reduced by omitting tumors or lesions if they do not occur exclusively or predominantly in salivary glands, including hemangioma, lipoma, nodular fasciitis and hematolymphoid tumors. They are now discussed in detail elsewhere in the book. Cribriform adenocarcinoma of salivary gland origin (CASG) now represents a distinctive subtype of polymorphous adenocarcinoma (PAC). PAC is defined as a clinically, histologically and molecularly heterogeneous disease group. Whether CASG is a different diagnostic category or a variant of PAC is still controversial. Poorly differentiated carcinomas and oncocytic carcinomas are discussed in the category "Salivary carcinoma not otherwise specified (NOS) and emerging entities". New defining genomic alterations have been characterized in many salivary gland tumors. In particular, they include gene fusions, which have shown to be tightly tumor-type specific, and thus valuable for use in diagnostically challenging cases. The recurrent molecular alterations were included in the definition of mucoepidermoid carcinoma, adenoid cystic carcinoma, secretory carcinoma, polymorphous adenocarcinoma, hyalinizing clear cell carcinoma, mucinous adenocarcinoma, and microsecretory adenocarcinoma.
- Klíčová slova
- Classification, Gene fusion, Neoplasm, Salivary gland, WHO, World Health Organization,
- MeSH
- adenokarcinom * patologie MeSH
- adenom * genetika patologie MeSH
- lidé MeSH
- mucinózní adenokarcinom * MeSH
- nádorové biomarkery genetika MeSH
- nádory slinných žláz * genetika patologie MeSH
- slinné žlázy patologie MeSH
- Světová zdravotnická organizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
Epithelial-myoepithelial carcinoma (EMC) can be a challenging diagnosis due to a lack of obvious invasion and bland cytology. We report an unusual case of a low-grade EMC with prominent fibrous stroma, an extensive solid-oncocytic differentiation and limited areas of morphological clearly identifiable characteristic biphasic (tubular) differentiation, clear cells and PAS-positive secretions/calcifications. Both areas were investigated by next generation sequencing (Oncomine comprehensive assay) and revealed a typical concordant HRAS p.Q61R mutation. An additional heterogeneous ARID1A (p.E672*) terminating mutation with loss of heterozygosity, which could be visualized predominantly in the solid-oncocytic differentiation by immunohistochemical loss of ARID1A protein expression, was found. This is the first case of an EMC of the salivary gland to be described with two separate tumor clones involving concordant HRAS and heterogeneous ARID1A mutations. The latter seem to be a "second hit" and was predominantly found in the solid-oncocytic differentiation, suggesting a potential morpho-molecular association.
- Klíčová slova
- ARID1A, Epithelial myoepithelial carcinoma, HRAS, Heterogeneous, Oncocytic, Salivary gland, Solid,
- MeSH
- DNA vazebné proteiny genetika MeSH
- karcinom genetika patologie MeSH
- lidé MeSH
- mutace MeSH
- myoepiteliální nádor genetika patologie MeSH
- nádory glandulární a epitelové genetika patologie MeSH
- nádory příušní žlázy genetika patologie MeSH
- protoonkogenní proteiny p21(ras) genetika MeSH
- senioři MeSH
- transkripční faktory genetika MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- ARID1A protein, human MeSH Prohlížeč
- DNA vazebné proteiny MeSH
- HRAS protein, human MeSH Prohlížeč
- protoonkogenní proteiny p21(ras) MeSH
- transkripční faktory MeSH
We present a 72 years old male with a left nasal cavity (mammary analogue) secretory carcinoma (SC) which exhibited classical morphological features on light microscopical examination, diffuse strong S100 and mammoglobin positivity on immunohistochemistry, and ETV6-NTRK3 gene fusion on next generation sequencing (NGS) analysis. Unusual features of this tumor are expression of p63 and DOG1 on immunohistochemistry and the atypical junction between Exon 4 of the ETV6 gene and Exon 14 of the NTRK3 gene.
- Klíčová slova
- ETV6-NTRK3 fusion protein, human, Immunohistochemistry, Mammary analogue secretory carcinoma, Nasal cavity,
- MeSH
- anoctamin 1 biosyntéza MeSH
- exony genetika MeSH
- fúzní onkogenní proteiny genetika MeSH
- lidé MeSH
- membránové proteiny biosyntéza MeSH
- nádorové biomarkery analýza MeSH
- nádorové proteiny biosyntéza MeSH
- nádory nosu genetika patologie MeSH
- nosní dutina patologie MeSH
- sekreční karcinom mamárního typu genetika patologie MeSH
- sekvenční analýza DNA MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- ANO1 protein, human MeSH Prohlížeč
- anoctamin 1 MeSH
- CKAP4 protein, human MeSH Prohlížeč
- ETV6-NTRK3 fusion protein, human MeSH Prohlížeč
- fúzní onkogenní proteiny MeSH
- membránové proteiny MeSH
- nádorové biomarkery MeSH
- nádorové proteiny MeSH
Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms most commonly spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. Multiple familial trichoepithelioma (MFT) is a phenotypic variant of the disease characterized by the development of numerous trichoepitheliomas (cribriform trichoblastoma) only. Malignant tumors arise in association with preexisting benign cutaneous neoplasms in about 5-10% of the patients . Apart from the skin, major and minor salivary glands have been rarely involved in BSS patients. Extremely rare is the occurrence of breast tumors (cylindroma). The gene implicated in the pathogenesis of the disease is the CYLD gene, a tumor suppressor gene located on chromosome 16q12-q13. Germline CYLD mutations are detected in about 80-85% of patients with the classical BSS phenotype and in about 40-50% of the individuals with the MFT phenotype using a PCR based approach with analysis of exonic sequences and exon-intron junctions of the CYLD gene. There appears to be no genotype-phenotype correlations with respect to the severity of the disease, the possibility of malignant transformation, and development of extracutaneous lesions.
- Klíčová slova
- Brooke-Spiegler syndrome, CYLD gene, Cylindroma, Spiradenoma, Trichoepithelioma,
- MeSH
- dědičné nádorové syndromy * genetika patologie MeSH
- deubikvitinizační enzym CYLD MeSH
- fenotyp MeSH
- genotyp MeSH
- lidé MeSH
- nádorové supresorové proteiny genetika MeSH
- nádory kůže * genetika patologie MeSH
- zárodečné mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- CYLD protein, human MeSH Prohlížeč
- deubikvitinizační enzym CYLD MeSH
- nádorové supresorové proteiny MeSH
Angioleiomyoma (ALM; synonyms: angiomyoma, vascular leiomyoma) is an uncommon benign tumor of skin and subcutaneous tissue. Most arise in the extremities (90 %). Head and neck ALMs are uncommon (~10 % of all ALMs) and those arising beneath the sinonasal tract mucosa are very rare (<1 %) with 38 cases reported so far. We herein analyzed 16 cases identified from our routine and consultation files. Patients included seven females and nine males aged 25-82 years (mean 58; median 62). Symptoms were intermittent nasal obstruction, sinusitis, recurrent epistaxis, and a slow-growing mass. Fifteen lesions originated within different regions of the nasal cavity and one lesion was detected incidentally in an ethmoid sinus sample. Size range was 6-25 mm (mean 11). Histologically, all lesions were well circumscribed but non-encapsulated and most (12/16) were of the compact solid type superficially mimicking conventional leiomyoma but contained numerous compressed muscular veins. The remainder were of venous (2) and cavernous (2) type. Variable amounts of mature fat were observed in four cases (25 %). Atypia, necrosis, and mitotic activity were absent. Immunohistochemistry showed consistent expression of smooth muscle actin (12/12), h-caldesmon (9/9), muscle-specific actin (4/4), variable expression of desmin (11/14) and CD56 (4/6), and absence of HMB45 expression (0/11). The covering mucosa was ulcerated in 6 cases and showed squamous metaplasia in one case. There were no recurrences after local excision. Submucosal sinonasal ALMs are rare benign tumors similar to their reported cutaneous counterparts with frequent adipocytic differentiation. They should be distinguished from renal-type angiomyolipoma. Simple excision is curative.
- Klíčová slova
- Angioleiomyoma, Angiomyolipoma, Angiomyoma, Nasal, PEComa, Sinonasal tract, Vascular leiomyoma,
- MeSH
- angiomyom patologie MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory nosu patologie MeSH
- nádory vedlejších dutin nosních patologie MeSH
- senioři nad 80 let MeSH
- senioři 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
- přehledy MeSH
- Názvy látek
- nádorové biomarkery MeSH
Cribriform adenocarcinoma of the tongue and minor salivary glands (CATMSG) is a tumor occurring mostly, but not exclusively, in the base of the tongue. Other locations are minor salivary glands of the oral cavity. Histopathologically, CATMSG resembles papillary carcinoma of the thyroid gland. It usually reveals a solid growth devoid of colloid, and eosinophilic material present in follicular areas is rather pale in contrast to metastatic foci seen in papillary thyroid carcinoma that shows typical deeply eosinophilic colloid with "moth-eaten peripheries" and cystic configuration. In addition, giant multinucleated cells are not observed in CATMSG and psammoma bodies are found only exceptionally. Unlike papillary thyroid carcinoma, CATMSG is composed of hybrid secretory-myoepithelial cells. Most importantly, CATMSG is consistently negative with both thyroglobulin and TTF-1. CATMSG is a distinct tumor entity that also differs from polymorphous low-grade adenocarcinoma by location, cytology, histological architecture, and behavior, with frequent metastases at the time of presentation. Paradoxically, early metastatic disease seen in most cases of CATMSG is associated with an indolent behavior. It makes CATMSG a unique neoplasm among all low-grade salivary gland tumors.
- MeSH
- adenokarcinom genetika metabolismus patologie MeSH
- imunohistochemie MeSH
- lidé MeSH
- malé slinné žlázy metabolismus patologie MeSH
- nádorové biomarkery analýza MeSH
- nádory jazyka genetika metabolismus patologie MeSH
- nádory slinných žláz genetika metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nádorové biomarkery MeSH
Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor with ETV6 translocation. Akin to secretory breast cancer, MASC expresses S-100 protein, mammaglobin, vimentin, and harbors a t(12;15) (p13;q25) translocation which leads to ETV6-NTRK3 fusion product. Histologically, MASC displays a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogeneous or bubbly secretions. Colloid-like secretory material stains positive for periodic acid-Schiff (PAS) with and without diastase and for Alcian blue. The cells of MASC are devoid of PAS-positive secretory zymogen granules. These features help to exclude the most important differential diagnostic considerations, namely acinic cell carcinoma, low-grade cribriform cystadenocarcinoma, cystadenocarcinoma (not otherwise specified), and low-grade mucoepidermoid carcinoma. To date the presence of the ETV6-NTRK3 fusion gene has not been demonstrated in any other salivary gland tumor than MASC. It is likely that MASC is more common than currently recognized and with further studies, the clinical need for molecular studies of the ETV6-NTRK3 fusion may diminish. However, molecular testing is recommended at this time to arrive at the diagnosis of MASC.
- MeSH
- acinární karcinom diagnóza MeSH
- cystadenokarcinom diagnóza MeSH
- diferenciální diagnóza MeSH
- fúzní onkogenní proteiny genetika MeSH
- imunohistochemie MeSH
- karcinom genetika MeSH
- lidé MeSH
- mukoepidermoidní karcinom diagnóza MeSH
- nádorové biomarkery analýza MeSH
- nádory prsu genetika MeSH
- nádory slinných žláz diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ETV6-NTRK3 fusion protein, human MeSH Prohlížeč
- fúzní onkogenní proteiny MeSH
- nádorové biomarkery MeSH