Compiled and organized: HadronsBrief analysis of disease types.
Epithelial-myoepithelial carcinoma
At least 65 cases of epithelial-myoepithelial carcinoma of the lungs have been reported in the literature, including one case in a 7-year-old child, but the mean age of the patients is 56 years. A small number of lung epithelial-myoepithelial carcinomas are located within the lung parenchyma, and no bronchial association has been reported in at least five cases.
Epithelial-myoepithelial carcinoma is also composed of two layers of cells, specifically the epithelial cells that form the ducts and the myoepithelial cells that surround the outside, and the latter cytoplasm is often hyaline. Rarely, spindle-shaped and eosinophilic myoepithelial cells can form solid areas within the tumor. Rarely, the myoepithelial component is predominantly and pleomorphic, in which case it is called "myoepithelial anaplasia".Although the prognosis appears to be poor in cases with this anaplastic presentation, the majority of epithelial-myoepithelial carcinomas are indolent.
Similar to adenoid cystic carcinoma, myoepithelial cells in epithelial-myoepithelial carcinoma express SOX10, S100, Calponin, P63, P40, and SMA, while luminal cells express CK7 and CAM52；Epithelial components generally do not express TTF-1, but this is not always the case. CD117 expression can be present in both epithelial and myoepithelial components. The most common mutation in epithelial-myoepithelial carcinoma of the head and neck is HRAS mutation, but it has been reported rarely in primary epithelial-myoepithelial carcinoma of the lung.
Figure 5Epithelial-myoepithelial carcinoma(a) In this case, the tumor is located under the mucosa of the airway, and the arrow shows the mucosa of the respiratory tract;(b) The ductal structure is lined with two layers of cells, and the epithelial cells that form the lumen are cubic, cytoplasmic and eosinophilic, and the cytoplasm of lateral myoepithelial cells is hyaline(c) Immunohistochemistry AE1 AE3 was strongly positive in the epithelial component and weakly positive in the myoepithelial component(d) Myoepithelial cells express p63.
Epithelial-myoepithelial carcinoma should be distinguished from adenoid cystic carcinoma and pleomorphic adenomas. MyB or MyBL1 rearrangement, cribriform structure, and significant invasive growth help determine the tumor in question as adenoid cystic carcinoma rather than epithelial-myoepithelial carcinoma;However, these features are not always present in adenoid cystic carcinoma. Myoepithelial markers, CK, CD117 do not help distinguish between these patients. Compared with pleomorphic adenomas, epithelial-myoepithelial carcinoma generally has more ductal-like structures and generally does not have a myxoid or cartilage myxoid interstitium. Adenomas of mucous glands also have epithelial and myoepithelial components, and TTF-1 is negative, but unlike epithelial-myoepithelial carcinoma, adenomas of mucinous glands are only seen in the proximal airway, and are mostly microcystic with eosinophilic secretions, and there is no solid area formed by myoepithelial hyperplasia.
In a study of 50 cases of lung epithelial-myoepithelial carcinoma, only 2 (4%) died from the disease, which is consistent with the clinical inertity of the tumor.
Myoepitheloma and myoepithelial carcinoma
Primary myoepithelial tumors of the lungs are rare. Only 16 cases of myoepithelial carcinoma of the lungs have been reported in the literature, ranging in age from 24 to 84 years, with a median age of 60 yearsAmong the six cases of pulmonary myoepitheloma reported in the literature, the patients ranged in age from 18 to 60 years, and the median age was 56 years. About half of primary myoepithelial tumors in the lungs are found in the proximal airways.
Myoepithelial cells in myoepithelial tumors are solid, nested, reticulated, beam-like structures with a background of vitreous, muxoid, or cartilaginous myxoid matrix. Cells may be hyaline, plasmacytoid, and spindle-shaped. Tubules or ductal structures may also be formed. The presence of significant cytologic atypia, necrosis, invasive growth, and increased nuclear activity is implied to be myoepithelial carcinoma rather than myoepitheloma. In general, myoepithelial tumors have 1 nucleus of 10 hpf, while myoepithelial carcinoma has 5 to 32 nuclei of 10 hpf. There is a case of myoepithelial carcinoma of the lungs with metastatic lesions in the literature, and the nucleus** is only 2-3 10hpf. It should be noted that the criteria for malignancy of lung myoepithelial tumors are extrapolated from the criteria for salivary gland and soft tissue myoepithelial tumors, while the malignant criteria in salivary glands are capsule invasion and invasive growth, and the malignant criteria for soft tissue myoepithelial tumors are cytological atypical.
About half of cases of thoracic myoepithelial tumors, both benign and malignant, have EWSR1 rearrangements and, rarely, FUS rearrangementsIts fusion ligands include PBX1, ZNF444, and KLF17;In contrast, the fusion ligand for EWSR1 in vitreous clear cell carcinoma is ATF1 or CREM. These are similar to rearrangements in myoepithelial tumors of soft tissues and other internal organs.
Among the 3 cases of myoepithelial carcinoma without EWSR1 fusion, 2 cases were found to have no expression of INI1 by immunohistochemical testingOne of them had a striated muscle-like morphology and was a background and epithelioid cell of the mucinoid interstitium. It has been found that the incidence of loss of immunohistochemical ini1 expression in soft tissue myoepithelial carcinoma in children is % (9 22), respectivelyHowever, this feature is not seen in myoepitheloma. PLAG1 rearrangements are common in primary myoepithelial carcinomas of the salivary glands, including de novo and in pleomorphic adenomas, but there does not appear to be PLAG1 rearrangements in soft tissue myoepithelial tumors, and no such rearrangements have been reported in pulmonary myoepithelial tumors.
TTF-1 is expressed in trapped or reactive alveolar cells in myoepithelial tumors, and it is important to distinguish it from neoplastic TTF-1-negative epithelial components, the presence of which may indicate other salivary gland tumors (eg, epithelial-myoepithelial carcinoma, adenoid cystic carcinoma, pleomorphic adenoma) other than myoepithelial tumors. In the 2021 edition of the World Health Organization classification, the term "pneumocytic adenomyoepithelioma" is no longer recommended to describe myoepithelial tumors with a TTF-1-positive epithelial component, as this component is likely to be trapped hyperplastic alveolar epithelium. Myoepithelial tumors may also have a squamous nest or mulberry body that appears suddenly, and should not be mistaken for evidence of squamous cell carcinoma;Immunohistochemistry S100 and SMA are positive to help rule out squamous cell carcinoma.
For 10 cases of lung myoepithelial carcinoma, the median follow-up time was 14The five-month study found that four patients died from the disease, with a median survival time of 125 months;Two patients were still alive with metastatic disease, and four were disease-free and healthy.
Vitreous clear cell carcinoma
At present, there are only 18 cases of vitreous clear cell carcinoma of the lung reported in the literature, all of which are seen in **, ranging in age from 33 to 64 years, and all of them are related to ** airway.
The tumor is characterized by a cord-like, beam-like, nest-like structure with cells that are small to medium-epithelial, cytoplasmic, hyaline, or eosinophilic, with a background of vitreous fibrosis or vitreous myxoid interstitium. Mucoceles may be present, possibly due to obstruction and mucus retention.
Vitreous clear cell carcinoma immunohistochemically expresses p40 and p63, but the absence of squamous cell morphology and mucinous cells are helpful in differentiating squamous cell carcinoma from mucinous epidermoid carcinoma, respectively. Vitrified clear cell carcinoma does not express other myoepithelial markers, nor does it express TTF-1, Napsin A, neuroendocrine markers, CD117.
Similar to vitreous clear cell carcinoma of the head and neck, all vitreous clear cell carcinomas of the lung that were tested had EWSR1 gene rearrangements. Of the 9 cases in which rearrangement ligands were identified, 8 were ATF1 and one was CREM. EWSR1::ATF1 fusions are also seen in clear cell sarcoma, hemangiomatoid fibrohistiocytoma, angiosarcoma, and primary myxoid sarcoma of the lung, but these diseases are generally morphologically indistinguishable from vitroid clear cell carcinoma. EWSR1::ATF1 fusions have also been seen in soft tissue myoepithelial tumors, but according to the authors of this article, this fusion has not been reported in primary myoepithelial tumors of the lungs.
Figure 6Vitreous clear cell carcinoma(a) Tumor cells are nested and beam-shaped, with vitreous fibrosis in the background;(b) Many tumor cells are hyaline cytoplasm and some are eosinophilic cytoplasm;(c) Tumor cells expressing p40;(D, E) Partial tumor cells surrounding the mucus component (arrows, Figure E shows mucus card red staining);(f) Break probe FISH detection confirms EWSR1 rearrangement.
Similar to vitreous clear cell carcinoma of the salivary gland, vitreous clear cell carcinoma of the lungs is also an indolent biological behavior, and no deaths from the disease have been reported in the literature.
To be continued
Previous review: primary salivary gland tumor in the lung of the pathological glandular glandular gland (1).
Pathological primary salivary gland tumor in the lung of the glandular gland (2).