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Detection of MYB Alterations and Other Immunohistochemical Markers in Primary Cutaneous Adenoid Cystic Carcinoma

North, Jeffrey P. MD*; McCalmont, Timothy H. MD*; Fehr, André PhD; van Zante, Annemieke MD, PhD; Stenman, Göran DMD, PhD; LeBoit, Philip E. MD*

The American Journal of Surgical Pathology: October 2015 - Volume 39 - Issue 10 - p 1347–1356
doi: 10.1097/PAS.0000000000000463
Original Articles
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Adenoid cystic carcinoma (ACC) can arise in several organs, and prognosis is highly dependent on the primary tumor site. Primary cutaneous ACC has an excellent prognosis compared with salivary or lacrimal ACC. Activation of MYB by gene fusion or other mechanisms has been found in salivary, breast, and lacrimal ACCs but has not been described in cutaneous ACC. We analyzed the histopathologic and immunohistochemical features of 19 primary cutaneous ACCs, 2 periorbital ACCs, and 12 salivary gland ACCs and assessed for MYB activation in primary cutaneous ACC by immunohistochemistry and molecular methods. The presence of perineural invasion differed significantly among ACCs of various sites (83% salivary, 50% eyelid, 11% skin, P=0.0002). Over 90% of all ACCs were grade 1 or 2 and exhibited diffuse (>50%) positivity with CD117, SOX-10, and smooth muscle actin immunostains. CK15 and vimentin showed diffuse positivity in 36% and 57% of cutaneous ACCs, respectively, and were negative or only focally positive in all salivary ACCs (P=0.04 and 0.002). Six of the 11 cutaneous and periorbital ACCs tested with reverse transcriptase polymerase chain reaction and/or fluorescence in situ hybridization had MYB rearrangements including 2 cases that expressed MYB-NFIB fusion transcripts. Diffuse expression of MYB protein assessed by immunostaining was present in 8 of 9 cutaneous ACCs, including cases both with and without MYB rearrangements. These results indicate that cutaneous ACCs possess the same types of MYB alterations as ACCs of other anatomic sites. Vimentin and CK15 appear to have some discriminatory value in differentiating between primary cutaneous and salivary gland ACCs.

Departments of *Dermatology and Pathology

Pathology, University of California San Francisco, San Francisco, CA

Department of Pathology, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden

Conflicts of Interest and Source of Funding: Parts of this study was supported by grants from the Swedish Cancer Society and BioCARE—a National Strategic Research Program at the University of Gothenburg. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Jeffrey P. North, MD, Department of Dermatopathology, University of California San Francisco, 1701 Divisadero St. Room 280, San Francisco, CA 94115 (e-mail: jeffreypaulnorth@gmail.com).

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