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The American Journal of Surgical... Jan 2020Pneumocytic adenomyoepithelioma (PAM) was first described in 2007 and was included in the 2015 World Health Organization Classification of lung tumors as a variant of... (Review)
Review
Pneumocytic adenomyoepithelioma (PAM) was first described in 2007 and was included in the 2015 World Health Organization Classification of lung tumors as a variant of epithelial-myoepithelial tumor. This rare pulmonary neoplasm was reported to show both myoepithelial and duct-like components, with the latter exhibiting pneumocytic differentiation with TTF-1 expression. We present an index case and 6 additional retrospectively identified cases of pulmonary tumors with prototypical features of PAM. However, with additional clinicoradiologic, histologic, immunohistochemical and cytogenetic data, we were able to reclassify them as myoepithelial neoplasms-both primary and metastatic-with entrapped exuberantly hyperplastic alveolar structures lined by TTF-1 pneumocytes. We reviewed the available literature related to PAM and myoepithelial tumors. Our cases suggest that the entity referred to as PAM represents interstitial growth of myoepithelial neoplasms enticing marked proliferation of entrapped pneumocytes rather than a distinct biphasic neoplasm with pneumocytic differentiation.
Topics: Adenomyoepithelioma; Aged; Aged, 80 and over; Alveolar Epithelial Cells; Female; Humans; Lung Neoplasms; Male; Middle Aged; Myoepithelioma; Retrospective Studies
PubMed: 31567188
DOI: 10.1097/PAS.0000000000001376 -
Modern Pathology : An Official Journal... Oct 2023Mucoepidermoid carcinoma (MEC) is exceedingly rare in the breast, with <45 cases reported in the literature. Although estrogen receptor/progesterone receptor/human...
Mucoepidermoid carcinoma (MEC) is exceedingly rare in the breast, with <45 cases reported in the literature. Although estrogen receptor/progesterone receptor/human epidermal growth factor 2 triple-negative, MEC is characterized as a special subtype of breast carcinoma with significantly better prognosis than conventional basal-type tumors. Cutaneous hidradenoma (HA) is considered a benign adnexal neoplasm showing histomorphologic overlap with MEC. Rare cases of HA have also been reported in the breast, but these are relatively uncharacterized. In this study, we examined the clinicopathologic, immunohistochemical (IHC), and genetic features of 8 breast HAs, in comparison to 3 mammary MECs. All cases were positive for MAML2 break-apart fluorescence in situ hybridization. Eight cases demonstrated a CRTC1::MAML2 fusion, and one MEC harbored a CRTC3::MAML2 fusion; the latter is a novel finding in the breast. Mutational burden was very low, with only one HA exhibiting a MAP3K1 pathogenic alteration. By IHC, both MEC and HA demonstrated cell type-dependent expression of high- and low-molecular-weight keratins and p63, as well as negative to low-positive estrogen receptor and androgen receptor. Smooth muscle myosin and calponin highlighted an in situ component in the 3 cases of MEC; expression of these myoepithelial markers was negative in HAs. Additional distinguishing characteristics included the growth pattern and tumor architecture, the presence of glandular/luminal cells in HA, and overall higher IHC expression of SOX10, S100 protein, MUC4, and mammaglobin in MEC. Morphologic findings were also compared to a series of 27 cutaneous nonmammary HAs. Mucinous and glandular/luminal cells were identified in significantly more mammary HAs than nonmammary lesions. The findings provide insight into the pathogenesis of MAML2-rearranged neoplasms of the breast, underscore the overlapping genetic features of MEC and HA, and highlight similarities to their extramammary counterparts.
PubMed: 37422157
DOI: 10.1016/j.modpat.2023.100270 -
Journal of Oral Pathology & Medicine :... Feb 2023In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma. (Review)
Review
OBJECTIVES
In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma.
MATERIALS AND METHODS
MEDLINE/PubMed, Scopus, and Embase search was performed with the keywords "myoepithelial carcinoma" "malignant myoepithelioma," and "salivary glands." Primary salivary glands myoepithelial carcinoma that fulfilled the World Health Organization diagnostic criteria were included. The Joanna Briggs Institute tool was used to assess the risk of bias.
RESULTS
Forty-three studies (71 patients) met the inclusion criteria. The patients showed a mean age of 56.4 ± 19.6 years with no sex predilection. The parotid was the most affected gland (49.3%). The tumor presented as an asymptomatic (65.1%) mass (84%). The most common histological findings were the presence of clear tumor cells (39.7%) and multinodular growth patterns (60.7%). Multivariate analysis showed plasmacytoid cell type (p = 0.010) and solid growth pattern (p = 0.003) were related to decreased disease-free survival. Surgery alone was the most used treatment (53.5%). Patients with a combination of treatments showed a longer disease-free survival (p = 0.049). The 2-year and 5-year overall survival rates were 67.5% and 46.1%, respectively.
CONCLUSION
Salivary gland myoepithelial carcinoma showed no sex predilection, with a higher incidence in the parotid gland. Cell type, growth pattern, and treatment type may be related to a lower disease-free survival. Overall, salivary gland myoepithelial carcinoma presented low recurrence and metastasis rates. Registration and protocol: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022311512).
Topics: Humans; Adult; Middle Aged; Aged; Myoepithelioma; Salivary Gland Neoplasms; Salivary Glands; Disease-Free Survival; Carcinoma
PubMed: 36504414
DOI: 10.1111/jop.13395 -
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 -
Pathology Feb 2022Despite the importance of atypia in diagnosing and classifying breast lesions, the definition of atypia varies depending on the context, with a lack of consistent and... (Review)
Review
Despite the importance of atypia in diagnosing and classifying breast lesions, the definition of atypia varies depending on the context, with a lack of consistent and objective criteria for assessment. Atypia in breast pathology may be cytonuclear and/or architectural with different applications and implications. Cytonuclear atypia is used to assist the distinction of various intraductal epithelial proliferative lesions including usual ductal hyperplasia (UDH) versus atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), and to grade DCIS. In invasive carcinoma, nuclear atypia (i.e., nuclear pleomorphism) is a component of the histological grading system. Stromal cell cytonuclear atypia is one of the key features used to distinguish fibroadenoma from phyllodes tumour (PT) and to classify PT as benign, borderline or malignant. Similarly, cytonuclear atypia is used in the evaluation of myoepithelial cell alterations in the breast. Architectural atypia is used to differentiate flat epithelial atypia (FEA) from ADH or DCIS. In addition to the inherent subjectivity in the interpretation of atypia, which presents as a morphological continuum reflecting a biological spectrum, the lack of standardisation in defining atypia augments diagnostic discordance in breast pathology, with potential implications for patient management. Evidence to date suggests that the traditional criteria used to assess atypia may require modification in the era of digital pathology primary diagnosis. This review aims to provide a comprehensive review of atypia in breast pathology with reference to inconsistencies, challenges and limitations.
Topics: Breast; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Diagnosis, Differential; Female; Fibroadenoma; Humans; Hyperplasia; Neoplasm Grading; Neoplasm Staging; Pathologists; Phyllodes Tumor; Precancerous Conditions; Stromal Cells
PubMed: 34872753
DOI: 10.1016/j.pathol.2021.09.008 -
The American Journal of Dermatopathology Mar 2022The distinction of metastatic carcinomas to the skin (MCS) from cutaneous adnexal carcinomas can pose a significant diagnostic challenge. The differentiation between...
The distinction of metastatic carcinomas to the skin (MCS) from cutaneous adnexal carcinomas can pose a significant diagnostic challenge. The differentiation between (MCS) from a primary cutaneous adnexal tumor is one of the most difficult tasks in the field of dermatopathology, and immunohistochemistry has only been partially helpful in solving this problem. In routine diagnostic surgical pathology, it is essential to identify the myoepithelial cell layer by immunohistochemistry to distinguish between an in situ and invasive breast carcinomas and when establishing the presence of microinvasion. The purpose of this study was to evaluate the role of myoepithelial cell layer expression in difficult cases of cutaneous adnexal carcinomas in which histologically it was challenging to separate them from MCS. We studied 38 adnexal carcinomas and evaluated them for myoepithelial markers to confirm the primary nature of the neoplasm. The used markers to search for myoepithelial cell layer retention included calponin, p63, and smooth muscle actin. Of the 38 cases, we found that 13 cases showed myoepithelial layer retention, confirming the primary cutaneous origin of the neoplastic process. The results of our study suggest that the presence of an identifiable retention of the myoepithelial cell layer in adnexal carcinomas could be a useful adjunct observation in the diagnosis of primary adnexal carcinomas, especially in the clinical setting of a questionable primary adnexal versus metastatic neoplasm.
Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Epithelial Cells; Female; Humans; Male; Middle Aged; Neoplasms, Adnexal and Skin Appendage; Retrospective Studies; Skin Neoplasms
PubMed: 35171883
DOI: 10.1097/DAD.0000000000001844 -
Developmental Cell Jan 2023The development of the mouse salivary gland involves a tip-driven process of branching morphogenesis that takes place in concert with differentiation into acinar,...
The development of the mouse salivary gland involves a tip-driven process of branching morphogenesis that takes place in concert with differentiation into acinar, myoepithelial, and ductal (basal and luminal) sub-lineages. By combining clonal lineage tracing with a three-dimensional (3D) reconstruction of the branched epithelial network and single-cell RNA-seq analysis, we show that in tips, a heterogeneous population of renewing progenitors transition from a Krt14+ multipotent state to unipotent states via two transcriptionally distinct bipotent states, one restricted to the Krt14+ basal and myoepithelial lineage and the other to the Krt8+ acinar and luminal lineage. Using genetic perturbations, we show how the differential expression of Notch signaling correlates with spatial segregation, exits from multipotency, and promotes the Krt8+ lineage, whereas Kras activation promotes proacinar fate. These findings provide a mechanistic basis for how positional cues within growing tips regulate the process of lineage segregation and ductal patterning.
Topics: Mice; Animals; Cell Lineage; Cell Differentiation; Signal Transduction; Stem Cells; Epithelial Cells; Salivary Glands
PubMed: 36693323
DOI: 10.1016/j.devcel.2022.12.009 -
The Journal of Steroid Biochemistry and... May 2020The vitamin D receptor (VDR) and its ligand 1,25(OH)D (1,25D) impact differentiation and exert anti-tumor effects in many tissues, but its role in salivary gland has yet...
The vitamin D receptor (VDR) and its ligand 1,25(OH)D (1,25D) impact differentiation and exert anti-tumor effects in many tissues, but its role in salivary gland has yet to be defined. Using immunohistochemistry (IHC), we have detected strong VDR expression in murine and human salivary gland ducts. Compared to normal gland, VDR protein expression was retained in differentiated human pleomorphic adenoma (PA) but was undetectable in undifferentiated PA and in carcinomas, suggesting deregulation of VDR during salivary cancer progression. To gain insight into the potential role of VDR in salivary cancer, we assessed the effects of vitamin D in vivo and in vitro. Despite the presence of VDR in salivary gland, chronic dietary vitamin D restriction did not alter morphology of the salivary epithelium in C57/Bl6 mice. The localization of VDR in ductal epithelium prompted us to examine the effects of 1,25D in an established cell line (mSGc) derived from normal murine submandibular gland (SMG). This previously characterized cell line consists of multiple stem, progenitor and differentiated cell types as determined by mutually exclusive cellular expression of basal, ductal and myoepithelial markers. We demonstrated VDR expression and regulation of VDR target genes Vdr and Postn by 1,25D in mSGc, indicating functional ligand-mediated transcriptional activity. The effect of VDR signaling on epithelial differentiation markers was assessed by qPCR and IHC in mSGc cells treated with 1,25D. We found that 1,25D reduced mRNA expression of the basal cell progenitor marker keratin 5 (K5) and increased expression of the differentiated ductal cell marker keratin 7 (K7). Further, we found that 1,25D significantly decreased the number of proliferating cells, including proliferating K5 cells. Characterization of cell cycle by Muse cytometry indicated 1,25D treatment decreased cells in S, G, and M phase. The inhibition of K5 cell proliferation by 1,25D is of particular interest because K5 basal cells contribute to a wide variety of salivary tumor types. Our studies suggest that 1,25D alters cancer-relevant progenitor and differentiation markers in the salivary gland.
Topics: Animals; Calcitriol; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Gene Expression Regulation, Developmental; Homeostasis; Humans; Mice; Receptors, Calcitriol; Salivary Gland Neoplasms; Salivary Glands; Signal Transduction; Vitamin D
PubMed: 31958633
DOI: 10.1016/j.jsbmb.2020.105600 -
Frontiers in Cell and Developmental... 2021Myoepithelial and luminal cells synergistically expand in the mammary gland during pregnancy, and this process is precisely governed by hormone-related signaling...
Myoepithelial and luminal cells synergistically expand in the mammary gland during pregnancy, and this process is precisely governed by hormone-related signaling pathways. The bone morphogenetic protein (BMP) signaling pathway is now known to play crucial roles in all organ systems. However, the functions of BMP signaling in the mammary gland remain unclear. Here, we found that BMPR1a is upregulated by hormone-induced Sp1 at pregnancy. Using a doxycycline (Dox)-inducible BMPR1a conditional knockout mouse model, we demonstrated that loss of BMPR1a in myoepithelium results in compromised myoepithelial integrity, reduced mammary stem cells and precocious alveolar differentiation during pregnancy. Mechanistically, BMPR1a regulates the expression of p63 and Slug, two key regulators of myoepithelial maintenance, through pSmad1/5-Smad4 complexes, and consequently activate P-cadherin during pregnancy. Furthermore, we observed that loss of BMPR1a in myoepithelium results in the upregulation of a secreted protein Spp1 that could account for the precocious alveolar differentiation in luminal layer, suggesting a defective basal-to-luminal paracrine signaling mechanism. Collectively, these findings identify a novel role of BMP signaling in maintaining the identity of myoepithelial cells and suppressing precocious alveolar formation.
PubMed: 34336839
DOI: 10.3389/fcell.2021.691050 -
Cancer Cell International Dec 2022Over the past decades, luminal epithelial cell lineage has gained considerable attraction as the functionally milk-secreting units and as the most fruitful acreage for... (Review)
Review
Over the past decades, luminal epithelial cell lineage has gained considerable attraction as the functionally milk-secreting units and as the most fruitful acreage for breast cancer launching. Recognition of the effective involvement of the myoepithelial cells in mammary gland development and in hampering tumorigenesis has renewed the interest in investigating the biological roles of this second main mammary lineage. The human breast is made up of an extensively branching ductal system intervening by copious lobular units. The ductal system is coated by a chain of luminal epithelial cells (LECs) situated on a layer of myoepithelial cells (MECs) and encompassed by a distinguished basement membrane. Ductal contractility during lactation is a well-known function delivered by the MECs however this is not the only assignment mediated by these cellular populations. It has been well appreciated that the MECs exhibit a natural paracrine power in defeating cancer development and advancement. MECs were found to express numerous proteinase inhibitors, anti-angiogenic factors, and tumour suppressors proteins. Additionally, MECs contributed effectively to maintaining the right luminal cells' polarization and further separating them from the adjacent stroma by making an integrated fence. Indeed, disruption of the MECs layer was reported to facilitate the invasion of the cancer cells to the surrounding stroma. Nonetheless, MECs were also found to exhibit cancer-promoting effects and provoke tumour invasion and dissemination by displaying distinct cancer chemokines. Herein in this review, we aimed to address the roles delivered by MECs in breast cancer progression and decipher the molecular mechanisms regulating proper MECs' physiology, integrity, and terminal differentiation.
PubMed: 36510219
DOI: 10.1186/s12935-022-02829-y