Anatomic Pathology / CDX2 SEPARATES MUCINOUS BRONCHIOLOALVEOLAR FROM METASTATIC MUCINOUS COLORECTAL CARCINOMA Usefulness of Cdx2 in Separating Mucinous Bronchioloalveolar Adenocarcinoma of the Lung From Metastatic Mucinous Colorectal Adenocarcinoma

We studied the diagnostic value of Cdx2 to distinguish mucinous bronchioloalveolar carcinoma from mucinous colorectal adenocarcinoma metastatic to the lung. We retrieved 92 via the hospital computer system, including 30 mucinous bronchioloalveolar carcinomas, 32 nonmucinous bronchioloalveolar carcinomas, and 30 mucinous colorectal adenocarcinomas metastatic to the lung. All cases were confirmed by clinical history and surgical resection with occasional immunohistochemical studies. Cases were stained with antibodies against Cdx2, thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7, and CK20. Bronchioloalveolar carcinoma, mucinous type, showed positive staining for Cdx2, TTF-1, CK7, and CK20 in 0 (0%), 5 (17%), 30 (100%), and 18 (60%) of 30 cases, respectively; nonmucinous tumors were positive in 0 (0%), 30 (94%), 32 (100%), and 0 (0%) of 32 cases, respectively. For colorectal adenocarcinoma, the positive staining for Cdx-2, TTF-1, CK7, and CK20 was 29 (97%), 0 (0%), 7 (23%), and 29 (97%) of 30 cases, respectively. Our results demonstrated Cdx2 as a sensitive and specific marker for differentiating metastatic colorectal adenocarcinoma from mucinous bronchioloalveolar adenocarcinoma. Because the lung is a common site for primary and metastatic adenocarcinomas, defining the origin of a carcinoma in a patient with a pulmonary nodule occasionally can be a diagnostic dilemma. The differentiation between primary and metastatic pulmonary adenocarcinoma is crucial for therapeutic and prognostic purposes.1 Metastatic lesions can be treated by wedge resection in contrast with lobectomy, which is recommended for primary tumors.2 In addition, lung metastases from colorectal carcinomas can be resected with improved survival or even cure.2,3 Identifying the characteristic histologic features of colorectal adenocarcinoma, such as dirty necrosis and elongated and pencil-like nuclei, might be difficult in small biopsy specimens; these features also can be seen in pulmonary adenocarcinoma.4,5 In addition, bronchioloalveolar carcinoma can manifest as multiple lung nodules similar to cancer metastatic to the lung, while metastatic colorectal carcinoma can line the alveolar walls in a lepidic pattern mimicking primary mucinous bronchioloalveolar carcinoma.6 Immunohistochemical markers serve an important role in the differential diagnosis between primary and metastatic lung lesions. Among the markers used to identify primary lung tumors are thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7, and CK20.7-9 Several reports have shown that the predominant CK profile of lung adenocarcinoma (CK7+/CK20–) is distinctly different from that of colonic adenocarcinoma (CK7–/CK20+).10,11 However, both colorectal adenocarcinoma and mucinous bronchioloalveolar carcinoma are reported to be CK7+/CK20+ and TTF-1–.12-15 Because of these immunophenotypic similarities, the differentiation between mucinous bronchioloalveolar carcinoma and metastatic mucinous colorectal carcinoma can be a challenge. Am J Clin Pathol 2004;122:421-427 421 421 DOI: 10.1309/UMF715KRG2V198YD 421 © American Society for Clinical Pathology Saad et al / CDX2 SEPARATES MUCINOUS BRONCHIOLOALVEOLAR FROM METASTATIC MUCINOUS COLORECTAL CARCINOMA Cdx2, a member of Cdx homeobox genes, is a nuclear transcription factor that has an essential role as a regulatory protein for proliferation and differentiation of intestinal epithelial cells in fetal and adult tissues.16 Cdx2 is expressed specifically in colonic and small intestinal mucosa and has been implicated in disorders involving abnormal intestinal differentiation and neoplasia.17,18 The use of Cdx2 as an immunohistochemical marker has been described recently in studies of human gastric and colonic cancer.19-21 In the present study, we evaluated the immunohistochemical expression of Cdx2 in a series of mucinous bronchioloalveolar carcinomas and metastatic mucinous colorectal adenocarcinomas to determine whether Cdx2 expression is a reliable marker to identify the colorectal origin of a lung metastasis. We also examined the distribution of TTF-1, CK7, and CK20 staining in mucinous and nonmucinous bronchioloalveolar carcinomas to study their patterns of reactivity. Materials and Methods