Myoepithelial neoplasm Dotaz Zobrazit nápovědu
An extremely rare case of epithelial-myoepithelial carcinoma (EMC) of a lobar bronchus in a 47-year-old female is reported. Grossly, the tumor formed a polypoid mass obstructing the bronchial lumen. Microscopically, it was composed of two cellular types--epithelial cells with eosinophilic cytoplasm and clear myoepithelial cells. Numerous tubules formed by an inner epithelial and outer myoepithelial layer were found. Focally, the tumor showed solid growth of clear cells. Prominent hyalinization of the stroma was found. The nature of the cells was confirmed by positive expression of cytokeratins and epithelial membrane antigen in epithelial cells and vimentin and smooth muscle actin in myoepithelial cells. Differential diagnosis of EMC includes a broad spectrum of salivary gland-type tumors. Furthermore, metastases of clear cell carcinoma of the kidney or thyroid, clear cell ("sugar") tumor of the lung, glandular form of carcinoid, bronchioalveolar adenocarcinoma with myoepithelial cells and pulmonary adenosquamous carcinoma with amyloid-like stroma must be distinguished from EMC. The tumor has neither recurred nor metastasised, a fact supporting the current opinion, that EMC is a tumor of low grade malignancy.
- MeSH
- adenokarcinom diagnóza MeSH
- aktiny metabolismus MeSH
- diferenciální diagnóza MeSH
- imunoenzymatické techniky MeSH
- karcinom metabolismus patologie MeSH
- keratiny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin diagnóza MeSH
- nádory plic diagnóza MeSH
- nádory průdušek metabolismus patologie MeSH
- nádory slinných žláz diagnóza MeSH
- nádory štítné žlázy diagnóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- aktiny MeSH
- keratiny MeSH
This study examines the presence of the EWSR1 rearrangement in a variety of clear cell salivary gland carcinomas with myoepithelial differentiation. A total of 94 salivary gland carcinomas with a prominent clear cell component included 51 cases of clear cell myoepithelial carcinomas de novo (CCMC), 21 cases of CCMCs ex pleomorphic adenoma (CCMCexPA), 11 cases of epithelial-myoepithelial carcinoma (EMC), 6 cases of EMC with solid clear cell overgrowth, and 5 cases of hyalinizing clear cell carcinoma of minor salivary glands. In addition, 10 cases of myoepithelial carcinomas devoid of clear cell change and 12 cases of benign myoepithelioma were included as well. All the tumors in this spectrum were reviewed, reclassified, and tested by fluorescence in situ hybridization (FISH) for the EWSR1 rearrangement using the Probe Vysis EWSR1 Break Apart FISH Probe Kit. The EWSR1 rearrangement was detected in 20 of 51 (39%) cases of CCMC, in 5 of 21 (24%) cases of CCMCexPA, in 1 of 11 (9%) cases of EMC, and in 4 of 5 (80%) cases of hyalinizing clear cell carcinoma. The 25 EWSR1-rearranged CCMCs and CCMCexPAs shared similar histomorphology. They were arranged in nodules composed of compact nests of large polyhedral cells with abundant clear cytoplasm. Necrosis, areas of squamous metaplasia, and hyalinization were frequent features. Immunohistochemically, the tumors expressed p63 (96%), cytokeratin CK14 (96%), and S100 protein (88%). MIB1 index varied from 10% to 100%, with most cases in the 20% to 40% range. Clinical follow-up information was available in 21 cases (84%) and ranged from 3 months to 15 years (mean 5.2 y); 4 patients were lost to follow-up. Ten patients are alive with no evidence of recurrent or metastatic disease in the follow-up period from 3 months to 15 years (mean 5 y), 3 patients are alive with recurrent and metastatic disease, and 8 died of disseminated cancer 9 months to 16 years after diagnosis (mean 6 y). Lymph node metastasis appeared in 5 patients within 5 months to 4 years after diagnosis (mean 22 mo), distant metastases were noted in 7 patients with invasion of orbit (2 cases), and in 1 case each metastasis to the neck soft tissues, liver, lungs, mediastinum, and thoracic vertebra was noted. We describe for the first time EWSR1 gene rearrangement in a subset of myoepithelial carcinomas arising in minor and major salivary glands. The EWSR1-rearranged CCMC represents a distinctive aggressive variant composed predominantly of clear cells with frequent necrosis. Most EWSR1-rearranged CCMCs of salivary glands are characterized by poor clinical outcomes.
- MeSH
- časové faktory MeSH
- dospělí MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- genová přestavba * MeSH
- hybridizace in situ fluorescenční * MeSH
- imunohistochemie MeSH
- karcinom chemie genetika mortalita sekundární terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- lymfatické metastázy MeSH
- myoepiteliální nádor chemie genetika mortalita sekundární terapie MeSH
- nádorové biomarkery analýza genetika MeSH
- nádory slinných žláz chemie genetika mortalita patologie terapie MeSH
- nekróza MeSH
- pleomorfní adenom chemie genetika mortalita patologie terapie MeSH
- prediktivní hodnota testů MeSH
- přežití po terapii bez příznaků nemoci MeSH
- protein EWS vázající RNA MeSH
- proteiny vázající kalmodulin genetika MeSH
- proteiny vázající RNA genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie 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
- práce podpořená grantem MeSH
- Názvy látek
- EWSR1 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- protein EWS vázající RNA MeSH
- proteiny vázající kalmodulin MeSH
- proteiny vázající RNA 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
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
Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.
- Klíčová slova
- Immunohistochemistry, In situ carcinoma, Microinvasion, Myoepithelium, Reproducibility,
- MeSH
- imunohistochemie metody MeSH
- karcinom patologie MeSH
- laboratorní medicína metody normy MeSH
- lidé MeSH
- metastázy nádorů diagnóza MeSH
- nádorové biomarkery analýza MeSH
- nádory prsu patologie MeSH
- odchylka pozorovatele MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
We report four cases of parotid gland tumours composed predominantly of spindle-shaped myoepithelial cells and mature adipocytes. The central portion of one tumour showed extensive adipose differentiation, whereas in the peripheral parts there were small foci of ductal epithelium arranged in cords and tubules within an abundant myxoid stroma. The other cases were adipose spindle cell myoepitheliomas without an obvious glandular component. Under high-power examination, a transition between modified spindle-shaped myoepithelial cells and adipocytes was observed, and this was confirmed with immunohistochemistry. Ultrastructurally, the modified myoepithelial cells showed intracytoplasmic tonofilaments, bundles of actin microfilaments and lipid droplets. A possible pathogenesis is proposed of true metaplastic transformation of myoepithelial cells to adipocytes. This lesion is important to identify correctly, as inadequate surgery can lead to recurrence.
- MeSH
- cytoplazmatické struktury ultrastruktura MeSH
- diferenciální diagnóza MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metaplazie MeSH
- myoepiteliální nádor chemie patologie chirurgie MeSH
- nádorové biomarkery analýza MeSH
- nádory příušní žlázy chemie patologie chirurgie MeSH
- pleomorfní adenom chemie patologie chirurgie MeSH
- proteiny intermediálních filament analýza MeSH
- senioři MeSH
- tuková tkáň chemie patologie MeSH
- tukové buňky chemie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- nádorové biomarkery MeSH
- proteiny intermediálních filament MeSH
There is described fifty-year-old woman with so called malignant adenomyoepithelioma of the breast. The conventional benign looking adenomyoepithelioma with biphasic tubular pattern continually fused to unequivocal invasive lesion which by immunophenotype turned out to be myoepithelial carcinoma. The 15 months follow up was uneventful. Extensive literature overview and terminology consideration is presented. The paper discusses biologic consequences of this rare breast lesion and its close resemblance to almost identical lesions in the salivary glands and skin adnexa.
- MeSH
- adenomyom patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myoepiteliální nádor patologie MeSH
- nádory prsu patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
Myoepithelial carcinoma of salivary glands is an underrecognized and challenging entity with a broad morphologic spectrum, including an EWSR1-rearranged clear cell variant. Myoepithelial carcinoma is generally aggressive with largely unknown genetic features. A retrospective review of Salivary Gland Tumor Registry in Pilsen searching for the key words "clear cell myoepithelial carcinoma," "hyalinizing clear cell," and "clear cell malignant myoepithelioma" yielded 94 clear cell myoepithelial carcinomas (CCMCs) for molecular analysis of EWSR1 rearrangement using fluorescence in situ hybridization (FISH). Tumors positive for EWSR1 gene rearrangement were tested by next-generation sequencing (NGS) using fusion-detecting panels. NGS results were confirmed by reverse-transcription polymerase chain reaction or by FISH. Twenty-six tumors originally diagnosed as CCMC (26/94, 27.6%) revealed split signals for EWSR1 by FISH. Six of these tumors (6/26, 23%) displayed amplification of the EWSR1 locus. Fifteen cases were analyzable by NGS, whereas 9 were not, and tissue was not available in 2 cases. None of the CCMCs with EWSR1 rearrangements detected by FISH had an EWSR1 fusion transcript. Fusion transcripts were detected in 6 cases (6/15, 40%), including LIFR-PLAG1 and CTNNB1-PLAG1, in 2 cases each, and CHCHD7-PLAG1 and EWSR1-ATF1 fusions were identified in 1 case each. Seven cases, including those with PLAG1 fusion, were positive for PLAG1 rearrangement by FISH, with notable exception of CHCHD7-PLAG1, which is an inversion not detectable by FISH. One single case with EWSR1-ATF1 fusion in NGS showed ATF1 gene rearrangement by FISH and was reclassified as clear cell carcinoma (CCC). In addition, another 4 cases revealed ATF1 rearrangement by FISH and were reclassified as CCC as well. Moreover, 12/68 (17%) CCMCs with intact EWSR1 gene were selected randomly and analyzed by NGS. PLAG1 fusions were found in 5 cases (5/12, 41.6%) with LIFR (2 cases), FGFR1 (2 cases), and CTNNB1 (1 case) as partner genes. Overall, PLAG1 gene rearrangements were detected in 10/38 (26%) tested cases. None of the tumors had SMARCB1 loss by immunohistochemistry as a possible explanation for the EWSR1 abnormalities in FISH. Novel findings in our NGS study suggest that EWSR1-FISH positive CCMC is a gene fusion-driven disease with frequent oncogenic PLAG1 fusions, including LIFR-PLAG1 and CTNNB1-PLAG1 in most cases. Productive EWSR1 fusions are found only in a minority of EWSR1-ATF1-rearranged cases, which were in part reclassifiable as CCCs. Detectable EWSR1-FISH abnormality in CCMCs without gene fusion perhaps represents a passenger mutation with minor or no oncologic effect.
- MeSH
- DNA vazebné proteiny genetika MeSH
- dospělí MeSH
- genová přestavba MeSH
- lidé středního věku MeSH
- lidé MeSH
- myoepiteliální nádor genetika MeSH
- nádory slinných žláz genetika MeSH
- onkogenní fúze MeSH
- protein EWS vázající RNA genetika MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- EWSR1 protein, human MeSH Prohlížeč
- PLAG1 protein, human MeSH Prohlížeč
- protein EWS vázající RNA MeSH
Mammary analog secretory carcinoma (MASC) of salivary glands is a recently described neoplasm with favorable outcome. We describe 2 cases of MASC occurring in a 34-year-old female and a 58-year-old male, both presenting with a swelling of upper lip and right parotid gland, measuring 15 and 20mm, respectively. Without adjuvant treatment, both patients have been free of disease for 15 months and 12 months since the operation. Microscopically, both tumors were cystic and showed tubular and cystopapillary architecture. The tumor cells had round to oval nuclei and eosinophilic cytoplasm. Presence of eosinophilic material was evident within cystic spaces. Immunohistochemically, both tumors expressed cytokeratins (CK), CK7, CK8, CK18, epithelial membrane antigen, vimentin, S-100 protein, mammaglobin, and STAT5a (signal transducer and activator of transcription 5a). Interestingly, both tumors showed variable expression of basal/myoepithelial markers. In one case, we observed diffuse expression of calponin and focal expression of p63 whereas expression of CD10 was absent. In the second case, the staining of calponin was negative, but there was focal expression of both p63 and CD10. Both neoplasms harbored the ETV6-NTRK3 fusion transcript as proved by RT-PCR. Although previously reported only rarely, we conclude that MASC may show expression of basal/myoepithelial markers.
- MeSH
- calponiny MeSH
- dospělí MeSH
- fúzní onkogenní proteiny genetika MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- karcinom genetika metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny analýza biosyntéza MeSH
- mikrofilamentové proteiny analýza biosyntéza MeSH
- nádorové biomarkery analýza MeSH
- nádory příušní žlázy genetika metabolismus patologie MeSH
- nádory prsu genetika metabolismus patologie MeSH
- neprilysin analýza biosyntéza MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteiny vázající vápník analýza biosyntéza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CKAP4 protein, human MeSH Prohlížeč
- ETV6-NTRK3 fusion protein, human MeSH Prohlížeč
- fúzní onkogenní proteiny MeSH
- membránové proteiny MeSH
- mikrofilamentové proteiny MeSH
- nádorové biomarkery MeSH
- neprilysin MeSH
- proteiny vázající vápník MeSH
Low-grade cribriform cystadenocarcinoma of salivary glands is a recently described rare tumor with favorable prognosis. This study reports the case of 50-year-old woman with swelling lasting for 9 months in the right parotideomasseteric area. Grossly, the tumor was well circumscribed and dominated by cystic space. Microscopically, the neoplasm consisted of well-demarcated islets, some of them cystically dilated. The architecture of islets varied from solid to cribriform and micropapillary without comedo-type necroses. The tumor cells featured no significant cytologic atypia. Immunohistochemically, luminal cells showed expression of cytokeratins (CK), CK7, CK18, and S100 protein. In addition, immunostains for CK5/6, CK14, p63 protein, and smooth muscle actin displayed a continuous rim of myoepithelial cells around all tumor nests. In contrast, detection of CK20, hormonal receptors (androgen, estrogen, and progesterone), epidermal growth factor receptor and Her-2/neu oncoprotein was negative. The patient is free of disease for 2 years. The relationship between low-grade cribriform cystadenocarcinoma and salivary duct carcinoma is discussed.
- MeSH
- cystadenokarcinom metabolismus patologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory příušní žlázy metabolismus patologie chirurgie MeSH
- nádory slinných žláz patologie MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prognóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové biomarkery MeSH