|Ahead of print publication
Primary pulmonary epithelial-myoepithelial carcinoma: Report of a rare and under-diagnosed low-grade malignancy
Shivani Sharma1, Aditya Tayal1, Sameer Khatri2, Satyasundar G Mohapatra2, Sambit Kumar Mohanty1
1 Department of Pathology and Laboratory Medicine, CORE Diagnostics, Gurgaon, Haryana, India
2 Department of Oncology, Shanti Mukund Hospital, New Delhi, India
|Date of Submission||01-May-2020|
|Date of Decision||13-Aug-2020|
|Date of Acceptance||02-Nov-2020|
|Date of Web Publication||22-Jun-2022|
Sambit Kumar Mohanty,
406 Udyog Vihar, Phase III, Gurgaon - 12201, Haryana
Source of Support: None, Conflict of Interest: None
Primary epithelial-myoepithelial carcinoma (EMC) is a rare low-grade malignant neoplasm of the lung that originates from the submucosal bronchial glands. It behaves in an indolent fashion, although rare cases with high-grade transformation have been reported. Because of the rarity, optimal therapy for this entity has not been clearly defined. Herein, we report a case of primary pulmonary EMC in a 38-year-old Indian man who had a short history of dyspnea and a computed tomographic (CT) scan revealed a 3 cm diameter homogeneous mass in the lower lobe of the right lung. A CT-guided biopsy revealed a mildly atypical and mitotically quiescent tumor with solid and focal acinar arrangement; foci with biphasic arrangement by inner epithelial and outer myoepithelial cells were identified. The neoplasm revealed cytokeratin (CK) 7 positivity in the epithelial cells, while the myoepithelium expressed smooth muscle actin and p63. The tumor had a low (8%) Ki-67 proliferation index. The neuroendocrine markers, thyroid transcription factor 1, CK5/6, p40, and napsin A were negative. Positron emission tomography-CT was negative for any other mass lesion. The mass was excised with negative margins and the patient was on close follow without any evidence of disease for the past 17 months. A custom made, targeted DNA- and RNA-based 5 gene lung cancer next-generation sequencing panel (Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Ros protocol-oncogene 1 tyrosine kinase (ROS1), B-rapidly accelerated fibrosarcoma family oncogene (BRAF), and mesenchymal epithelial transition molecule (MET)), compatible with the Ion S5 system was performed; however, no mutation was identified. This case depicts awareness about this entity and use of appropriate immunostains, particularly the myoepithelial markers are essential to arrive at a correct diagnosis. Importantly, high-grade transformation, recurrence, and metastases are not very uncommon in EMC, warranting a correct and timely diagnosis for therapeutic decision-making and prognostication of the patient.
Keywords: Low-grade malignancy, primary pulmonary epithelial myoepithelial carcinoma, salivary gland neoplasm
|How to cite this URL:|
Sharma S, Tayal A, Khatri S, Mohapatra SG, Mohanty SK. Primary pulmonary epithelial-myoepithelial carcinoma: Report of a rare and under-diagnosed low-grade malignancy. J Can Res Ther [Epub ahead of print] [cited 2022 Aug 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=347789
| > Introduction|| |
Epithelial-myoepithelial carcinoma (EMC) is a rare malignant tumor that originates from the salivary glands. This tumor displays a biphasic pattern, characterized by a dual cell population, including an inner layer of cuboidal epithelial cells that are peripherally bounded by a layer of myoepithelial cells. EMC accounts for ~ 1% of all salivary gland tumors., Primary pulmonary salivary gland–type tumors (SGTTs) are rare, accounting for 0.1% to 0.2% of all lung tumors. Mucoepidermoid carcinoma (70%) and adenoid cystic carcinoma (23%) are the common SGTT subtypes, while primary pulmonary EMC is a minor SGTT subtype.,,,,,,,,,,,,,,,,, Majority of EMC are located in salivary glands, with few cases reported in the trachea and bronchus.,, While EMC of the salivary glands arise from the intercalated ducts, primary pulmonary EMC appears to originate from the ductal structures of the submucosal bronchial gland, which is one of the lung counterparts to the intercalated duct.,,,,,,,,,,,,,,,,,, It is generally regarded as a low-grade malignant tumor and typically behaves indolently; however, distant metastases and recurrences occasionally occur.,,,,, Some pathologists describe the malignant potential of primary pulmonary EMC as “unproven,” rather than “low-grade malignant.” Due to its rarity and unproven malignant potential, optimal therapy for this entity has not been defined. Herein, we report a case of primary pulmonary EMC in a 38-year-old Indian man.
| > Case Report|| |
The patient, a 38-year-old Indian man presented with dyspnea since 2 months. There were no associated pulmonary or systemic symptoms. There was no personal history of smoking. There was no significant past medical, surgical, or family history.
A computed tomographic (CT) scan revealed a well-circumscribed and homogeneous mass in the lower lobe of the right lung (apical segment abutting the major fissure) that measured 3 cm in maximum dimension [Figure 1].
|Figure 1: A computed tomographic scan revealed a well-circumscribed and homogeneous mass in the lower lobe of the right lung (apical segment abutting the major fissure) that measured 3 cm in maximum dimension|
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A CT-guided biopsy was performed. The sections revealed a mildly atypical and mitotically quiescent tumor with solid and focal acinar arrangement; foci with biphasic arrangement by inner epithelial and outer myoepithelial cells were identified. A few discrete tubules and duct-like structures were seen. The tumor cells are round to polygonal with moderate clear to eosinophilic cytoplasm, round enlarged vesicular nuclei, and small nucleoli. Some cells are smaller in size with hyperchromatic nuclei and scant cytoplasm. No necrosis was identified [Figure 2]a and [Figure 2]b.
|Figure 2: Primary pulmonary epithelial-myoepithelial carcinoma. (a) The tumor with glandular arrangement (Hematoxylin and eosin stain ×10); (b) Solid pattern of arrangement of the tumor cells (Hematoxylin and eosin stain ×10); (c) Diffuse expression of smooth muscle actin in the tumor (smooth muscle actin immunoperoxidase stain ×10); (d) Diffuse nuclear p63 positivity in the tumor (p63 immunoperoxidase stain ×10); (e) Diffuse cytokeratin 7 expression in the tumor (CK7 immunoperoxidase stain ×10); (f) Low Ki-67 proliferation index (MIB-1 immunoperoxidase stain ×10)|
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A battery of immunohistochemical (IHC) stains, including pancytokeratin (CK), smooth muscle actin (SMA), p63, S100, CK7, thyroid transcription factor (TTF)-1, CK5/6, p40, napsin A, and Ki-67 were performed. The clones used with names of the commercial vendors, dilutions, antigen retrieval methods, incubation time for the primary antibodies, and the localization techniques are summarized in the [Table 1]. Appropriate positive and negative controls were performed with each antibody. The extent of tumor staining results was recorded in semi-quantitative fashion as estimated percentage of lesional cells immunoreactive with the antibodies. 0: No staining, 1+: 1%–25% of immunoreactive lesional cells, 2+: 26%–50% of immunoreactive lesional cells, and 3+: 51%–100% of the immunoreactive lesional cells. The intensity of staining was recorded as weak, moderate, and strong. For S100, p63, TTF1, and p4p0 nuclear immunoreactivity was considered positive while a cytoplasmic and/or membranous staining was considered positive for SMA, CK, CK7, and CK5/6, napsinA. The results were expressed in a semi-quantitative manner as estimated percentage of tumor cells immunoreactive with the antibodies. A Ki-67 proliferation index (% positivity in 100 cells counted) was ascertained for each case.
|Table 1: The details of clones used with names of the commercial vendors, dilutions, antigen retrieval methods, incubation time for the primary antibodies, and the localization techniques are summarized|
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The neoplasm revealed CK and CK7 positivity in the epithelial cells, while the myoepithelium expressed SMA and p63 [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f. The tumor had a low (8%) Ki-67 proliferation index. The neuroendocrine markers, TTF1, CK5/6, p40, and napsin A were negative. A diagnosis of primary pulmonary EMC was rendered. Positron emission tomography-CT was negative for any other mass lesion. The mass was excised with negative margins and the patient was on close follow without any evidence of disease for the past 17 months.
The DNA- and RNA-based 5 hot-spot gene non-small cell lung carcinoma (particularly for adenocarcinoma) panel, an amplicon-based panel that was designed using the Ion Ampliseq Designer Tool (ThermoFischer Scientific). This next generation sequencing panel was designed to detect hot-spot mutations, including single nucleotide variants, small indels (insertions/deletions) in the ALK, BRAF, EGFR, and MET genes, and fusions in ALK and ROS1 genes clinically relevant to solid tumors in a single sequencing run. The panel covered 220 loci (hot-spots) in the ALK, BRAF, EGFR, and MET genes and 73 fusion targets in the ALK and ROS1 genes and was based on the Ion Torrent™ S5 NGS platform. We used the above-mentioned molecular test in this case on the paraffin tissue block material. No mutation was observed.
| > Discussion|| |
The tracheobronchial submucosal glands are the pulmonary counterpart of the minor salivary gland system. The bronchial submucosal gland neoplasms are rare and they share morphologic and IHC features of their salivary gland counterpart.
Primary pulmonary EMC is a rare SGTT (7%) of the lung.,,,,,,,,,,,,,,,,, The typical morphologic patterns reported in EMC are those with tubules, glands, and solid areas. Papillary architecture has also been described in rare instances. EMCs occur in patients aged from 30 years to 70 years with a mean age of 50 years. There is no gender predilection. No association with smoking has been reported. The common symptoms include dyspnea, cough, hemoptysis, and obstructive features. The patients may be completely asymptomatic, if the lesion is small and peripheral in location. On imaging, they either present as masses or exophytic intrabronchial growth, sometimes completely obstructing the bronchial lumina.,,,,,,,,,,,,,,,,, Rarely cavitary lesion can be seen. Primary pulmonary EMC tends to be located in the central region of the lung, rather than in the periphery. Since bronchial glands are located in the central airway, it may explain the tumor's propensity to arise in central lung regions., Grossly, these tumors are not encapsulated but are well-delineated. In the present case, the patient, a nonsmoker with dyspnea who had a slightly eccentric solid and well-circumscribed right lung mass with the typical morphologic and IHC prolife of primary pulmonary EMC [Table 2],,,,,,,,,,,,,,,.
|Table 2: Details of the cases of primary pulmonary epithelial-myoepithelial carcinoma cases reported till date in the literature|
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The differential diagnoses of primary pulmonary EMC include adenocarcinoma, adenosquamous carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, pleomorphic adenoma, myoepithelial tumors, clear cell (sugar) tumor, primary and metastatic clear cell and papillary carcinomas, and metastases from a salivary gland neoplasm.,,,,,,,,,,,,,,,,,,, EMC differs from adenocarcinoma in having a low Ki67 index with usual negativity for pneumocyte marker(s), such as TTF1 and napsin A. Squamous component is seen in adenosquamous carcinoma which is absent in EMC. Moreover, degree of cytologic atypia, necrosis, and immunoprofile differentiate an EMC from adeno or adenosquamous carcinoma. EMC can be distinguished from pleomorphic adenomas by the absence of myxoid or chondromyxoid stroma. Adenoid cystic carcinoma with a tubular pattern and its peripheral myoepithelial cell layer may be confused with EMC; however, adenoid cystic carcinoma has a characteristic cribriform growth pattern with perineural invasion. Myoepithelial neoplasms lack the dual cell population. Clear cell tumor of the lung usually occurs at the peripherally and has a sinusoidal vascular pattern. The cells are large and polygonal with glycogen-rich clear cytoplasm. In contrast to EMC, clear cell tumor of the lung is a monophasic tumor, and the cells have a CK-/HMB-45+ phenotype. Primary and metastatic clear cell and papillary carcinomas may pose a diagnostic dilemma. The presence of a biphasic pattern and immunopositivity for myoepithelial markers aids in exclusion of these tumors from an EMC. A metastatic salivary gland EMC to the lung should always be excluded. Our patient had no such history in the past nor did he have any parotid, sublingual, or submandibular mass.
Primary pulmonary EMC is generally regarded as a low-grade malignant tumor and typically behaves in an indolent fashion; however, a few cases of high-grade pulmonary EMC that presented with metastasis in the regional lymph nodes, bone, and chest wall have been reported. Some pathologists describe the malignant potential as “unproven,” rather than “low-grade malignant.” Because of its rarity and unproven malignant potential, optimal therapy has not been defined. It appears that lobectomy or pneumonectomy and sometimes sleeve resection may be the treatment of choice.,,,,,,,,,,,,,,,,,
In essence, primary pulmonary EMC is a rare and usually low-grade malignant neoplasm of the lung lacking any specific molecular signature and needs to be differentiated from its mormophologic mimics. Awareness of this entity is essential for the practicing pathologists as high-grade transformation, recurrence, and metastases are not very uncommon, warranting a correct and timely diagnosis for therapeutic decision-making and prognostication of the patient.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]