Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma

Abstract

Pulmonary mucoepidermoid carcinoma is an uncommon but distinctive manifestation of mucoepidermoid carcinoma. Pulmonary mucoepidermoid carcinoma occurs in adults and children and can cause diagnostic problems, especially in small biopsies. Few studies have characterized the histologic and immunophenotypic features of pulmonary mucoepidermoid carcinoma. t(11;19)(q21;p13) is considered disease-defining for mucoepidermoid carcinoma; its significance in pulmonary mucoepidermoid carcinoma warrants further study. Forty three pulmonary mucoepidermoid carcinomas were re-reviewed and graded according to the Brandwein grading system for mucoepidermoid carcinoma. Four cases were excluded because of a split opinion between pathology report and re-review. These cases were negative for MAML2 rearrangement by FISH. TTF-1, napsin A, p40 and p63 immunostains were scored: 0 (negative), 1 (1-25% tumor cells), 2 (26-50%), 3 (51-75%) or 4 (>75%). FISH to detect MAML2 rearrangement used a MAML2-11q21 break-apart probe. Thirty nine pulmonary mucoepidermoid carcinoma (4 low, 30 intermediate, 5 high grade) contained mucous, epidermoid and intermediate cells and lacked keratinization and in situ carcinoma of the overlying epithelium. All cases with available gross description (n=22) had a central/endo- or peribronchial location. All 25 cases tested for immunohistochemistry were positive (scores 1-4) for p63; 23 also expressed p40. In six cases, the p63 score was higher than p40. TTF-1 and napsin were uniformly negative in all 25 cases. MAML2 rearrangement was identified by FISH in each of the 24 cases tested (3 low, 19 intermediate, 2 high grade). Clinical history was available in 29 patients (15 men) (median age, 48 years) with follow-up in 24 (median, 8.4 years). Five patients died of unrelated causes; one developed metastatic pulmonary mucoepidermoid carcinoma. In conclusion, features helpful in distinguishing pulmonary mucoepidermoid carcinoma from other lung cancers include its central/endo- or peribronchial location together with the presence of mucous cells, p63 expression, lack of keratinization and MAML2 rearrangement. TTF-1 and napsin are typically not expressed.

Primary Mucoepidermoid Carcinoma of the Lung with Prominent Clear Cells

“…Identifi cation of the CRTC1-MAML2 fusion gene is now considered to be pathognomonic for this entity, and the fusion gene can be detected by real-time PCR or FISH in both low-grade and high-grade MEC (3,5,7,8,13,14). Recent studies of PMEC demonstrate MAML2 rearrangement in 60% to 100% of tested cases (5,15,16) detected by FISH or real-time PCR. Additionally, there are documented reports of EGFR mutations in PMEC with involvement of exon 18 (L861Q) (3,17).…”

“…S100, CEA, and EMA show variable staining. PMEC is negative for CK20, TTF1, SOX 10, napsin A, androgen receptor, calponin, SMA, and smooth muscle myosin heavy chain (3)(4)(5)(6)12).…”

“…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). Th e tumor cells display various patterns of growth, including mucin-filled cysts, nests, islands, and tubules or glands (2-4).…”

“…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. P rimary pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignant neoplasm representing 0.1% to 0.2% of all primary pulmonary carcinomas (1)(2)(3)(4)(5). It typically arises in the minor salivary glandtype epithelium of the large central airways (2)(3)(4)(5).…”

“…P rimary pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignant neoplasm representing 0.1% to 0.2% of all primary pulmonary carcinomas (1)(2)(3)(4)(5). It typically arises in the minor salivary glandtype epithelium of the large central airways (2)(3)(4)(5). Occasionally, mucoepidermoid carcinoma (MEC) demonstrates prominent cytoplasmic clearing (6)(7)(8)(9)(10), and on biopsy, the presence of these clear cells can pose a diagnostic challenge for pathologists.…”