CDX2 Expression in Columnar Cell Variant of Papillary Thyroid ...

Anatomic Pathology / CDX2 in Columnar Cell Variant of PTC

CDX2 Expression in Columnar Cell Variant of Papillary Thyroid Carcinoma Miriam L. Enriquez, MD, Zubair W. Baloch, MD, PhD, Kathleen T. Montone, MD, Paul J. Zhang, MD, and Virginia A. LiVolsi, MD Key Words: Columnar cell variant; Thyroid; CDX2; Immunohistochemistry

CME/SAM

DOI: 10.1309/AJCPXE3PUBWVZCGZ

Upon completion of this activity you will be able to: • define the salient features of columnar cell variant of papillary thyroid carcinoma (CCV-PTC). • summarize the utility and limitations of using CDX2 expression by immunohistochemistry to distinguish CCV-PTC from other variants of PTC and from tumors of intestinal origin. • discuss the implications of CDX2 expression in the rare CCV-PTC, as it relates to its peculiar intestinal morphology.

Abstract The columnar cell variant of papillary thyroid carcinoma (CCV-PTC) is a rare subtype of PTC that exhibits morphologic features often described as reminiscent of secretory endometrium or colonic adenomas/adenocarcinomas. CDX2, a nuclear transcription factor, is important for intestinal development. It is normally expressed in intestinal epithelium and is also detected in adenoma and adenocarcinomas of the gastrointestinal tract; however, it has also been reported in tumors of other sites with intestinal-type morphologic features. We evaluated CDX2 expression in CCV-PTC and in a thyroid tissue microarray composed of various benign and malignant thyroid lesions. CDX2 expression was identified in 6 (55%) of 11 cases of CCV-PTC, but not in any other benign and malignant thyroid lesions. We conclude that CDX2 is selectively expressed in CCV-PTC and can be used in distinguishing it from other variants of PTC with overlapping morphologic features.

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Am J Clin Pathol 2012;137:722-726 DOI: 10.1309/AJCPXE3PUBWVZCGZ

The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 836. Exam is located at www.ascp.org/ajcpcme.

The columnar cell variant of papillary thyroid carcinoma (PTC) is a rare but morphologically distinct variant of PTC first described in 1986 by Evans.1 Histologically, this variant is distinguished from conventional PTC by its elongated (“columnar”) cells and prominent nuclear pseudostratification. Although columnar cell carcinomas often display papillary architecture, they infrequently exhibit the classic nuclear features (nuclear clearing, grooves, inclusions) of conventional PTC. Rather, the cytology of this particular PTC variant can resemble columnar epithelia of the endometrium or intestinal tract. Therefore, based solely on the morphologic features, the diagnostic differential for columnar cell variant of PTC can include metastatic adenocarcinoma of these sites. CDX2 is a homeobox gene that encodes an intestine-specific transcription factor and is known to have a critical role in the embryologic development of the gastrointestinal (GI) tract and establishment of the intestinal cell phenotype.2-4 The expression of CDX2 is maintained in neoplastic tissue arising from or related to intestinal cells and is considered somewhat specific for intestinal and colorectal epithelial tumors. In addition to colorectal tumors, occasional CDX2 expression has also been reported in tumors of non-GI origin with mucinous or intestinal morphologic features.5-9 In thyroid, CDX2 expression has been reported in rare cases of PTC in 1 case in a series that did not specify subtype,9 whereas a single report in abstract form has shown rare expression in only 1 of the 10 cases of the columnar cell variant.10 In this study, we evaluated our experience with the expression of CDX2 in the columnar cell variant of PTC and its potential role in the identification of this rare thyroid carcinoma. © American Society for Clinical Pathology

Anatomic Pathology / Original Article

Materials and Methods Case Selection A computerized search of the archival surgical pathology files for 1987 through 2011 at the Hospital of the University of Pennsylvania, Philadelphia, was done (including in-house, outside, and private consultation cases of one of us [V.A.L.]). This search resulted in 12 cases of columnar cell variant of PTC, all of which were located in thyroid. (This case cohort included 3 cases initially reported in an abstract by us.11) The histologic material was rereviewed in all cases to confirm the histologic diagnosis. The histologic criteria for inclusion required that tumor cells display unequivocal features of elongated hyperchromatic nuclei with pseudostratification and supranuclear or subnuclear cytoplasmic vacuoles. Thyroid transcription factor (TTF)-1 and thyroglobulin immunostains were performed in all cases at the time of the initial diagnosis or retrospectively at the time of rereview. Of the 12 cases, 1 was eliminated owing to the lack of sufficient columnar cell morphologic features on rereview. Of the remaining 11 cases, 2 showed focal columnar cell areas (