Strickland-Marmol, Leah B.

Abstract Context. —Brain metastases of adenocarcinoma of unknown primary pose a diagnostic dilemma to the surgical pathologist. Although the most common source in these cases is the lung, determining a primary source is difficult on routinely stained slides. Immunohistochemical stain panels including differential cytokeratins, hormone receptors, and breast-specific proteins are commonly used in these cases. Recently, attention has turned to tissue-specific transcription factors, such as thyroid transcription factor 1 (TTF-1) and Cdx2, in the appraisal of metastatic adenocarcinomas. Objective. —To characterize the previously unpublished immunohistochemical expression of the relatively new tissue-specific transcription factor Cdx2 in metastatic adenocarcinomas to the brain. Design. —We reviewed the surgical pathology files of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla, and retrieved 38 consecutive cases of metastatic adenocarcinoma (22 pulmonary, 10 breast, 6 gastrointestinal [2 esophagus/gastroesophageal junction, 4 colorectal]) to the brain with confirmation of the primary site by chart review and histologic evaluation. Sections were immunohistochemically stained with antibodies to TTF-1, Cdx2, and cytokeratins 7 and 20 by standard methods. Results. —Specificities and positive predictive values for Cdx2 and TTF-1 equaled 100% for metastatic gastrointestinal and pulmonary adenocarcinomas, respectively. The negative predictive value of Cdx2 was also very high at 97%. Conclusions. —Cdx2 is a specific and valuable tool for the surgical pathologist when faced with the common problem of metastatic adenocarcinoma of unknown primary. In conjunction with TTF-1, cytokeratin 7, and cytokeratin 20, Cdx2 can accurately differentiate the most common sources of metastatic adenocarcinoma to the brain.

Metastases to the brain may be the first presentation of systemic malignancy in 3–10% of new patients and thus pose a diagnostic challenge. While lung is the most common source, other frequent sites of origin include the GI tract and breast. The histologic appearance of metastatic adenocarcinoma often does not lend itself to identification of the primary source. In many cases immunohistochemical studies (IHC) to define these lesions may provide a reliable result, thus limiting the time and expense incurred by various clinical investigations. We have examined the IHC expression of cytokeratins 7 and 20, thyroid transcription factor ‐1 (TTF‐1) and the relatively new tissue specific transcription factor CDX2 in metastatic adenocarcinomas to the brain. 38 consecutive cases of metastatic adenocarcinoma (22 pulmonary, 10 breast, 6 gastrointestinal (2 esophagus/GE junction, 4 colorectal) to the brain were retrieved through a search of the surgical pathology files of the H. Lee Moffitt Cancer Center, Tampa, Florida. Confirmation of the primary site was obtained by chart review and histologic evaluation. Sections were immunohistochemically reacted with antibodies to TTF‐1, CDX2, and Cytokeratins 7 and 20 (CK7 and CK20) by standard methods. Specificities and positive predictive values for CDX2 and TTF‐1 equaled 100% for metastatic gastrointestinal and pulmonary adenocarcinomas, respectively. The negative predictive value of CDX2 was also very high at 97%. Our studies confirm that in conjunction with TTF‐1, CK7 and CK20, CDX2 can accurately differentiate the most common sources of metastatic adenocarcinoma from an unknown primary site to the brain.