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Surgical Pathology Clinics Mar 2021Sclerosing polycystic adenoma (SPA) is the more appropriate name for sclerosing polycystic adenosis. SPA is an uncommon salivary gland lesion with a constellation of... (Review)
Review
Sclerosing polycystic adenoma (SPA) is the more appropriate name for sclerosing polycystic adenosis. SPA is an uncommon salivary gland lesion with a constellation of unusual histologic findings that were originally interpreted as analogous to breast fibrocystic changes. The histologic findings in SPA include fibrosis, cystic alterations, apocrine metaplasia, and proliferations of ducts, acini, and myoepithelial cells in variable proportions. Because of its unusual mixed histology, SPA may be confused with a variety of lesions, ranging from reactive conditions to benign or even malignant neoplasms. The features of SPA are reviewed, with an emphasis on resolving its differential diagnosis.
Topics: Cell Proliferation; Cystadenoma; Cytoplasmic Granules; Diagnosis, Differential; Epithelial Cells; Humans; Immunohistochemistry; Mutation; Phosphatidylinositol 3-Kinases; Prognosis; Salivary Gland Neoplasms; Sclerosis
PubMed: 33526220
DOI: 10.1016/j.path.2020.09.004 -
Journal of Oncology 2022Pulmonary epithelial-myoepithelial carcinoma (P-EMC) is an exceptionally rare subtype of salivary gland lung tumor originating from tracheobronchial glands. P-EMC is a... (Review)
Review
Pulmonary epithelial-myoepithelial carcinoma (P-EMC) is an exceptionally rare subtype of salivary gland lung tumor originating from tracheobronchial glands. P-EMC is a biphasic tumor consisting of an inner layer of epithelial cells and an outer layer of spindle-shaped, clear-cell-like myoepithelial cells. Bronchial obstruction symptom is the main clinical characteristic for P-EMC. Because its clinical and imaging characteristics are highly similar to other types of non-small-cell lung cancer (NSCLC), it is easy to cause missed diagnosis and misdiagnosis. The diagnosis is mainly based on the pathology and immunohistochemistry with an inner layer of epithelial cells immunoreactive for cytokeratin and an outside layer of myoepithelial cells immunoreactive for S100 protein (S-100) and smooth muscle actin (SMA). Therefore, positive for cytokeratin, S-100 and SMA can assist in the diagnosis. Although in general, P-EMC is a low-grade malignant neoplasm, it may occasionally recur and metastasize. The optimal method for P-EMC treatment has not been established, and surgical resection is still the main clinical method. Radiotherapy and chemotherapy have been shown not sensitive for P-EMC treatment, whereas targeted therapy and immunotherapy have not evaluated in clinical practice. This review focuses on the pathological characteristics, molecular characteristics, diagnosis, treatment, and prognosis of P-EMC.
PubMed: 36268279
DOI: 10.1155/2022/4559550 -
Histopathology Jan 2023Myoepithelial cells (MECs) constitute a continuous layer of cells surrounding the breast glands, localised between the epithelial cells (ECs) and the basal membrane.... (Review)
Review
Myoepithelial cells (MECs) constitute a continuous layer of cells surrounding the breast glands, localised between the epithelial cells (ECs) and the basal membrane. MECs play important roles in normal mammary gland as they produce basal membrane and stimulate secretion. During neoplastic transformation, MECs act as a barrier preventing stromal invasion. MECs themselves can undergo a great variety of changes, ranging from hyperplastic to metaplastic, to neoplastic, and giving rise to a wide spectrum of morphological pictures sometimes difficult to interpret on routine diagnoses. Several benign and malignant breast tumours can present features of MECs differentiation. As these latter tumours are quite infrequent, the purpose of the present study is to offer a review of the morphological spectrum of MECs lesions, with correlations to prognosis.
PubMed: 36482278
DOI: 10.1111/his.14826 -
The American Journal of Dermatopathology Jul 2021Eosinophilic hyaline inclusions (EHIs) or globules have been reported in various cutaneous tumors including vascular lesions, myoepithelial neoplasms, and basal cell...
Eosinophilic hyaline inclusions (EHIs) or globules have been reported in various cutaneous tumors including vascular lesions, myoepithelial neoplasms, and basal cell carcinoma. In basal cell carcinoma, the presence of intracytoplasmic inclusions is reportedly associated with myoepithelial differentiation. In this regard, EHI has not been conclusively documented in a cutaneous lesion of genuine squamous cell lineage without aberrant differentiation. In the current case, a biopsy from the right thigh of a 71-year-old male patient demonstrated a relatively well-demarcated intraepidermal squamous lesion featured an admixture of predominantly enlarged keratinocytes harboring distinct eccentric intracytoplasmic EHI and a smaller population of keratinocytes displaying pale cytoplasm. Cytologic atypia, mitotic activity, and inflammatory cells were not identified. The intracytoplasmic EHI stained red with Masson's trichrome and were negative with periodic-acid Schiff with and without diastase. Immunologically, the lesion was strongly and diffusely positive for various cytokeratins but negative for ubiquitin and myoepithelial markers. Only cytokeratin AE1 revealed a differential staining pattern as the suprabasal lesional cells displayed significantly stronger immunoreactivity in comparison with the adjacent normal keratinocytes. Polymerase chain reaction for low-risk and high-risk human papillomavirus was negative. Molecular studies did not reveal any mutations commonly encountered in seborrheic or lichenoid keratoses. As an analogous lesion has not previously reported in the literature, the term hyaline inclusion acanthoma is proposed for this peculiar lesion.
Topics: Acanthoma; Aged; Biomarkers, Tumor; Biopsy; Humans; Hyalin; Immunohistochemistry; Keratinocytes; Male; Skin Neoplasms
PubMed: 33606370
DOI: 10.1097/DAD.0000000000001927 -
Surgical Pathology Clinics Mar 2021Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are uncommon biphasic salivary gland tumors having morphologic similarities to other biphasic salivary... (Review)
Review
Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are uncommon biphasic salivary gland tumors having morphologic similarities to other biphasic salivary gland neoplasms having differentiation toward the intercalated ducts of the salivary gland. Both tumors show mixtures of trabecular, tubular, solid, and membranous solid patterns. BCAC is separated from BCA primarily by the presence of invasion in the former. The diagnosis of BCA and BCAC is best carried out with hematoxylin and eosin-stained sections and careful attention to detail of tumors in the differential diagnosis, including adenoid cystic carcinoma, pleomorphic adenoma, and epithelial myoepithelial carcinoma.
Topics: Adenocarcinoma; Adenoma; Diagnosis, Differential; Epithelial Cells; Humans; Neoplasm Recurrence, Local; Prognosis; Salivary Gland Neoplasms; beta Catenin
PubMed: 33526221
DOI: 10.1016/j.path.2020.09.005 -
International Journal of Oral Science Sep 2023Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity...
Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36 myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36 myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
Topics: Humans; Adenoma, Pleomorphic; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Transcriptome; Myoepithelioma
PubMed: 37679344
DOI: 10.1038/s41368-023-00243-2 -
Seminars in Diagnostic Pathology May 2021The SWI/SNF complexes are major regulators of gene expression and their alterations occur in a large array of cancers both of epithelial and mesenchymal lineages.... (Review)
Review
The SWI/SNF complexes are major regulators of gene expression and their alterations occur in a large array of cancers both of epithelial and mesenchymal lineages. Malignant rhabdoid tumors were the first malignancies linked to deregulation of these complexes with the involvement of SMARCB1 in their development but genetic alterations affect all subunits in other malignancies. In the chest and lung regions, SMARCA4 (BRG1) is the most frequently altered subunit and is involved in the pathogenesis of two subtypes of tumors, including bona fide carcinomas (SMARCA4-deficient non-small cell lung cancers) but also undifferentiated tumors that harbor an undifferentiated phenotype close to those of malignant rhabdoid tumors (SMARCA4-undifferentiated tumors). Although their histogenesis is yet to be fully understood, these tumors are associated with distinct clinical and pathological features even though some overlapping features have been reported in rare cases. SMARCA4 deficiency is easily asserted by immunohistochemistry that show the loss of nuclear expression of the protein in the nuclei of tumor cells. These tumors are commonly associated with high-grade cytological features, rhabdoid cytomorphology, solid architecture and extensive necrosis. The typical immunohistochemical signature of SMARCA4-UT combines co-inactivation of SMARCA2 (BRM) and the overexpression of SOX2 and SALL4. No specific therapeutic strategies have been so far developed for SMARCA4-deficient neoplasms. SMARCB1 subunit is involved in the development of several SMARCB1-deficient sarcomas on top of malignant rhabdoid tumors that may develop in the thorax. Malignant rhabdoid tumors affect mostly children of less than 5y. The differential diagnosis includes epithelioid sarcomas, malignant myoepithelial tumors or myoepithelial carcinomas, extra-skeletal myxoid chondrosarcomas and synovial sarcomas.
Topics: Biomarkers, Tumor; Carcinoma; DNA Helicases; Humans; Immunohistochemistry; Lung Neoplasms; Nuclear Proteins; Rhabdoid Tumor; Sarcoma; Transcription Factors
PubMed: 33451916
DOI: 10.1053/j.semdp.2020.12.002 -
PloS One 2022The salivary gland can be permanently impaired by radiation treatment for head and neck cancers. Efforts at tissue regeneration have focused on saliva-producing acinar...
The salivary gland can be permanently impaired by radiation treatment for head and neck cancers. Efforts at tissue regeneration have focused on saliva-producing acinar cells. However, myoepithelial cells are also critical to gland function, but mechanisms that regulate their differentiation are poorly defined. To study myoepithelial differentiation, we employed mSG-PAC1 murine salivary gland epithelial cells. We demonstrate that mSG-PAC1 spheroids exhibit phenotypic plasticity between pro-acinar and myoepithelial cell fates. Increased expression of pro-acinar/acinar or myoepithelial RNAs was identified from spheroids cultured under different media conditions by microarray followed by gene-set enrichment analysis. Spheroids cultured with different medium components expressed proteins typical of either acinar or myoepithelial cells, as detected by immunocytochemistry. We demonstrate that the pattern of TAZ expression in the epithelial compartment of the differentiating murine salivary gland correlates with the expression of the myoepithelial marker alpha-SMA, as is the case for TAZ expression in mSG-PAC1 spheroids. Our analysis also indicates that YAP/TAZ target genes are upregulated together with myoepithelial markers. Importantly, siRNA targeting of TAZ expression in mSG-PAC1 spheroids diminished the expression of myoepithelial markers. Our results in this in vitro cell model implicate TAZ signaling in myoepithelial differentiation.
Topics: Animals; Mice; Acinar Cells; Cell Differentiation; Epithelial Cells; Salivary Glands
PubMed: 35617216
DOI: 10.1371/journal.pone.0268668 -
The American Journal of Surgical... Sep 2022Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the...
Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis.
Topics: Adenoma, Pleomorphic; Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; Skin Neoplasms
PubMed: 35354162
DOI: 10.1097/PAS.0000000000001896 -
Journal of Cellular Physiology Aug 2019The epithelial cell adhesion molecule (EpCAM) is a Type I transmembrane superficial glycoprotein antigen that is expressed on the surface of basolateral membrane of... (Review)
Review
The epithelial cell adhesion molecule (EpCAM) is a Type I transmembrane superficial glycoprotein antigen that is expressed on the surface of basolateral membrane of multiple epithelial cells with some exceptions such as epidermal keratinocytes, hepatocytes, thymic cortical epithelial cells, squamous stratified epithelial cells, and myoepithelial cells that do not express the molecule. The molecule plays a pivotal role in the structural integrity, adhesion of the epithelial tissues and their interaction with the underlying layers. EpCAM prevents claudin-7 and claudin-1 molecules from degradation, thereby, decreasing the number of tight junctions and cellular interconnections, and promoting the cells toward carcinogenic transformation. Moreover, the mutations in the EpCAM gene lead to congenital tufting enteropathy, severe intestinal epithelium homeostasis disorders, and Lynch and Lynch syndrome. Overexpression of EpCAM on stem cells of some cancers and the presence of this molecule on circulating tumor cells (CTCs) makes it a promising candidate for cancer diagnosis as well as tracing and isolation of CTCs.
Topics: Animals; Biomarkers, Tumor; Cell Adhesion; Epithelial Cell Adhesion Molecule; Gene Expression Regulation; Humans; Protein Conformation; Signal Transduction
PubMed: 30628064
DOI: 10.1002/jcp.28132