Primary mucoepidermoid carcinoma of the lung with prominent clear cells David D. Fink, DO, Angela M. Lomas, MD, Anja C. Roden, MD, Prashant C. Shah, MD, and Riyam T. Zreik, MD
Mucoepidermoid carcinoma of the lung is a rare malignancy of salivary gland-type origin. We report a case of a 21-year-old man with a right mainstem bronchus mass composed predominantly of clear cells. This case represents a rare primary pulmonary low-grade mucoepidermoid carcinoma positive for MAML2 rearrangement by fluorescence in situ hybridization with a prominent clear cell component.
a
b
Figure 1 (a) Axial and (b) coronal CT scans of the chest demonstrate a 2.5 cm mass (arrow) within the right main-
P
rimary pulmonary mucoepi- stem bronchus. The tumor was 0.5 cm from the carina and originated from the lateral aspect of the right mainstem dermoid carcinoma (PMEC) bronchus with suspected invasion into the right upper lobe bronchus. is a rare malignant neoplasm representing 0.1% to 0.2% of all primary pulmonary the biopsy was diagnosed as non–small cell carcinoma with carcinomas (1–5). It typically arises in the minor salivary glandclear cell features. type epithelium of the large central airways (2–5). Occasionally, Eight months following initial presentation, a right-sided mucoepidermoid carcinoma (MEC) demonstrates prominent thoracotomy and sleeve right upper lobectomy were performed. cytoplasmic clearing (6–10), and on biopsy, the presence of Gross examination revealed a 2.3 × 2.2 × 1.6 cm well-delineated these clear cells can pose a diagnostic challenge for pathologists. mass protruding into the bronchial lumen. Microscopic exWe present a case of PMEC with prominent clear cells. amination (Figure 2) showed a mass situated in the submucosa of the bronchial wall without invasion into the lung parenCASE DESCRIPTION chyma. In addition to the dominant population of clear cells, A 21-year-old man presented to his primary care physician the tumor had foci of gland formation with mucin, squamoid with a persistent cough producing blood-tinged sputum. The cells, and intermediate cells. There was no increased mitotic initial chest x-ray was unremarkable but over the next 3 months activity or keratinization, but scattered calcifications were apthe patient’s cough continued to worsen, progressing to moderparent. Fluorescence in situ hybridization (FISH) was positive ate hemoptysis. A computed tomography (CT) scan of the chest for MAML2 rearrangement and negative for EWSR1 rearrangerevealed a 2.5 cm mass within the right mainstem bronchus ment (Figure 3). The microscopic features and ancillary tests (Figure 1). Rigid bronchoscopy with biopsy of the mass was supported the diagnosis of low-grade PMEC. performed. The hematoxylin and eosin–stained sections of the The patient tolerated the lobectomy well and was discharged biopsy yielded a neoplasm composed of large epithelioid cells without complications or adjuvant therapy. At 15 months with clear cytoplasm and round-to-oval nuclei with inconspicuous nucleoli. By immunohistochemistry, the tumor cells were From the Departments of Pathology (Fink, Zreik) and Surgery (Shah), Scott & positive for pan keratin, EMA, CK7, and vimentin. The tumor White Medical Center, Temple, Texas; Texas A&M College of Medicine, Temple, cells were negative for PAX8, CD10, RCC, CAIX, HMB45, Texas (Lomas); and the Department of Laboratory Medicine and Pathology, Mayo TTF1, S100, CDX2, inhibin, OCT4, p40, p63, CK5/6, CK20, Clinic, Rochester, Minnesota (Roden). calponin, chromogranin, and synaptophysin. EGFR polymerase Corresponding author: Riyam T. Zreik, MD, Scott & White Medical Center, 2401 chain reaction (PCR) revealed a mutation in exon 18. Based on S. 31st Street, Temple, TX 76508 (e-mail: [email protected]; Twitter handle: @RiyamZreikMD). the available biopsy material and following expert consultation, 322
Proc (Bayl Univ Med Cent) 2017;30(3):322–324
Most patients present with symptoms of large airway irritation or obstruction including cough, hemoptysis, wheezing, chest pain, and obstructive pneumonia (2–4, 11). PMEC may be missed on chest radiographs; however, CT imaging typically demonstrates a well-defined endobronchial mass (2, 3). PMEC is frequently positron emission tomography avid (3). d c PMEC is composed of varying proportions of mucus-secreting cells, intermediate cells, and epidermoid (or squamoid) cells, lacking keratinization and/or in situ carcinoma of the overlying epithelium (2, 3, 5). The tumor cells display various patterns of growth, including mucin-filled cysts, nests, islands, and tubules or glands (2–4). Occasionally Figure 2. Microscopic examination of the submucosal mass. (a) A well-circumscribed mass composed of a predomi- stromal calcifications with or nant population of clear cells (hematoxylin and eosin [H&E], 40×). (b) The cytologically bland neoplastic cells with without a granulomatous reacample clear cytoplasm and small round nuclei (H&E, 200×). (c) Foci of epidermoid/squamoid cells and rare mucin tion are also observed in areas (H&E, 200×). (d) An increased amount of mucus-secreting cells intermixed with intermediate cells in other areas of of mucous extravasation (3, 11). the neoplasm (H&E, 200×). Immunophenotypically, PMEC is positive for pan cytokeratin, CK7, CK5/6, p63, and p40. S100, following lobectomy, the patient exhibited no recurrence or CEA, and EMA show variable staining. PMEC is negative for metastasis. The patient continued with surveillance bronchosCK20, TTF1, SOX 10, napsin A, androgen receptor, calponin, copy and chest CT scans every 6 months for 5 years. SMA, and smooth muscle myosin heavy chain (3–6, 12). PMEC is associated with a translocation involving CRTC1 DISCUSSION (also known as MECT1) on 19p13 and MAML2 on 11q21 in PMEC is a rare malignant neoplasm typically affecting paat least a subset of cases. Identification of the CRTC1-MAML2 tients
Mucoepidermoid carcinoma of the lung is a rare malignancy of salivary gland-type origin. We report a case of a 21-year-old man with a right mainstem bronchus mass composed predominantly of clear cells. This case represents a rare primary pulmonary low-grade mucoepidermoid carcinoma positive for MAML2 rearrangement by fluorescence in situ hybridization with a prominent clear cell component.
a
b
Figure 1 (a) Axial and (b) coronal CT scans of the chest demonstrate a 2.5 cm mass (arrow) within the right main-
P
rimary pulmonary mucoepi- stem bronchus. The tumor was 0.5 cm from the carina and originated from the lateral aspect of the right mainstem dermoid carcinoma (PMEC) bronchus with suspected invasion into the right upper lobe bronchus. is a rare malignant neoplasm representing 0.1% to 0.2% of all primary pulmonary the biopsy was diagnosed as non–small cell carcinoma with carcinomas (1–5). It typically arises in the minor salivary glandclear cell features. type epithelium of the large central airways (2–5). Occasionally, Eight months following initial presentation, a right-sided mucoepidermoid carcinoma (MEC) demonstrates prominent thoracotomy and sleeve right upper lobectomy were performed. cytoplasmic clearing (6–10), and on biopsy, the presence of Gross examination revealed a 2.3 × 2.2 × 1.6 cm well-delineated these clear cells can pose a diagnostic challenge for pathologists. mass protruding into the bronchial lumen. Microscopic exWe present a case of PMEC with prominent clear cells. amination (Figure 2) showed a mass situated in the submucosa of the bronchial wall without invasion into the lung parenCASE DESCRIPTION chyma. In addition to the dominant population of clear cells, A 21-year-old man presented to his primary care physician the tumor had foci of gland formation with mucin, squamoid with a persistent cough producing blood-tinged sputum. The cells, and intermediate cells. There was no increased mitotic initial chest x-ray was unremarkable but over the next 3 months activity or keratinization, but scattered calcifications were apthe patient’s cough continued to worsen, progressing to moderparent. Fluorescence in situ hybridization (FISH) was positive ate hemoptysis. A computed tomography (CT) scan of the chest for MAML2 rearrangement and negative for EWSR1 rearrangerevealed a 2.5 cm mass within the right mainstem bronchus ment (Figure 3). The microscopic features and ancillary tests (Figure 1). Rigid bronchoscopy with biopsy of the mass was supported the diagnosis of low-grade PMEC. performed. The hematoxylin and eosin–stained sections of the The patient tolerated the lobectomy well and was discharged biopsy yielded a neoplasm composed of large epithelioid cells without complications or adjuvant therapy. At 15 months with clear cytoplasm and round-to-oval nuclei with inconspicuous nucleoli. By immunohistochemistry, the tumor cells were From the Departments of Pathology (Fink, Zreik) and Surgery (Shah), Scott & positive for pan keratin, EMA, CK7, and vimentin. The tumor White Medical Center, Temple, Texas; Texas A&M College of Medicine, Temple, cells were negative for PAX8, CD10, RCC, CAIX, HMB45, Texas (Lomas); and the Department of Laboratory Medicine and Pathology, Mayo TTF1, S100, CDX2, inhibin, OCT4, p40, p63, CK5/6, CK20, Clinic, Rochester, Minnesota (Roden). calponin, chromogranin, and synaptophysin. EGFR polymerase Corresponding author: Riyam T. Zreik, MD, Scott & White Medical Center, 2401 chain reaction (PCR) revealed a mutation in exon 18. Based on S. 31st Street, Temple, TX 76508 (e-mail: [email protected]; Twitter handle: @RiyamZreikMD). the available biopsy material and following expert consultation, 322
Proc (Bayl Univ Med Cent) 2017;30(3):322–324
Most patients present with symptoms of large airway irritation or obstruction including cough, hemoptysis, wheezing, chest pain, and obstructive pneumonia (2–4, 11). PMEC may be missed on chest radiographs; however, CT imaging typically demonstrates a well-defined endobronchial mass (2, 3). PMEC is frequently positron emission tomography avid (3). d c PMEC is composed of varying proportions of mucus-secreting cells, intermediate cells, and epidermoid (or squamoid) cells, lacking keratinization and/or in situ carcinoma of the overlying epithelium (2, 3, 5). The tumor cells display various patterns of growth, including mucin-filled cysts, nests, islands, and tubules or glands (2–4). Occasionally Figure 2. Microscopic examination of the submucosal mass. (a) A well-circumscribed mass composed of a predomi- stromal calcifications with or nant population of clear cells (hematoxylin and eosin [H&E], 40×). (b) The cytologically bland neoplastic cells with without a granulomatous reacample clear cytoplasm and small round nuclei (H&E, 200×). (c) Foci of epidermoid/squamoid cells and rare mucin tion are also observed in areas (H&E, 200×). (d) An increased amount of mucus-secreting cells intermixed with intermediate cells in other areas of of mucous extravasation (3, 11). the neoplasm (H&E, 200×). Immunophenotypically, PMEC is positive for pan cytokeratin, CK7, CK5/6, p63, and p40. S100, following lobectomy, the patient exhibited no recurrence or CEA, and EMA show variable staining. PMEC is negative for metastasis. The patient continued with surveillance bronchosCK20, TTF1, SOX 10, napsin A, androgen receptor, calponin, copy and chest CT scans every 6 months for 5 years. SMA, and smooth muscle myosin heavy chain (3–6, 12). PMEC is associated with a translocation involving CRTC1 DISCUSSION (also known as MECT1) on 19p13 and MAML2 on 11q21 in PMEC is a rare malignant neoplasm typically affecting paat least a subset of cases. Identification of the CRTC1-MAML2 tients
