Primary mucinous (so-called colloid) carcinomas of the lung - A clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression

Herein we describe the clinicopathologic and immunohistochemical features of 13 primary mucinous (colloid) carcinomas (MCs) of the lung, an uncommon and controversial tumor. The patients, 7 males and 6 females, ranged in age from 50 to 79 years (mean, 64.5 years). All the tumors presented as a peripheral solitary nodule with gelatinous cut-surface and well circumscribed but lacking a complete fibrous wall. The size ranged from 1 to 5.5 cm. Microscopically, they consisted of neoplastic elements floating in large mucin pools and focally lining the alveolar spaces. Eleven cases were predominantly composed of tall, columnar goblet cells (goblet cell-type MC), while 2 consisted of signet-ring tumor cells (signet-ring cell-type MC). Five tumors were incidentally discovered by chest radiographs, while the others were symptomatic. All patients underwent complete surgical resection (six lobectomies and seven wedge resections). Postoperative chemotherapy was performed in 3 cases. Overall, the median follow-up was 26 months (mean 33 months; range 9-95 months). All patients with goblet cell-type MC were alive and well, while the 2 patients with signet-ring cell-type MC died of disease. Immunohistochemically, all the 11 goblet cell-type MCs were strongly stained with CDX-2 and MUC2, 8 reacted with TTF-1, 6 with cytokeratin 20 (CK20), 9 with cytokeratin 7 (CK7), and 2 with MUC-5AC. Conversely, the two signet-ring cell-type MCs were stained with TTF-1, CK7, and MUC5AC but were negative for CDX-2, MUC2, and CK20. Surfactant apoprotein-A (SP-A) was positive in four goblet cell-type and one signet-ring cell-type MC. When compared with 10 mucinous bronchioloalveolar carcinomas (m-BAC), the latter reacted with CK7, CK20, MUC5AC, TTF-1, SP-A, CDX-2, and MUC2 in 100%, 90%, 100%, 30%, 10%, 0%, and 0% of the cases, respectively. In summary, MC of the lung represents an entity with two distinct clinicopathologic and immunophenotypic variants: 1) the goblet cell-type, presenting a more indolent clinical behavior and frequently co-expressing markers of intestinal and pulmonary differentiation; and 2) the more aggressive signet-ring cell-type, which retains only markers of pulmonary origin. On morphologic and immunohistochemical grounds, MCs are easily distinguishable from m-BAC. Since goblet cell-type MC strongly stains with CDX2, MUC2, and CK20, differential diagnosis with metastatic colorectal carcinoma is very challenging and requires appropriate clinical correlation.