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Association of HPV42 with digital papillary adenocarcinoma and the use of in situ hybridization for its distinction from acral hidradenoma and diagnosis at non-acral sites


Digital papillary adenocarcinoma (DPAC) is a rare tumor of sweat gland origin that preferentially affects the digits and has the potential to metastasize. Its tumor diagnosis can be difficult. Well-differentiated variants of DPAC can be confused with a benign sweat gland tumor, in particular nodular hidradenoma. With the recent detection of HPV42 DNA in DPAC by next-generation sequence analysis, we reasoned that this association could be used for diagnostic purposes. To this end, we performed in situ hybridization for HPV42 on 10 tumors diagnosed as DPAC as well as 30 sweat gland tumors of various histology types, including 8 acral hidradenomas. All DPAC were positive for HPV42. Positive hybridization signals for HPV42 were seen in both primary and metastatic DPACs. All other tumors and normal tissues were negative. This study confirms the association of HPV42 with the tumor cells of DPAC through in situ hybridization. The positive test result in all lesions of DPAC and lack of detection of HPV42 in any of the acral hidradenomas or other sweat gland tumors examined in this series is encouraging for the potential diagnostic utility of the assay. As documented by two scrotal tumors of DPAC, the in situ hybridization test for HPV42 can also help support the rare occurrence of this tumor at a non-acral site.

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Fig. 1: Digital papillary adenocarcinoma from the right 5th finger of a 37-year-old man (Table 1, case 7).
Fig. 2: Digital papillary adenocarcinoma from the right 2nd finger of a 60-year-old man (Table 1, case 3).
Fig. 3: Metastatic digital papillary adenocarcinoma in lymph node.
Fig. 4: Scrotal adenocarcinoma from an 80-year-old man (Table 1, case 9).

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The authors wish to thank Yesenia Gonzalez for her help with the manuscript and the members of the departmental immunohistochemistry laboratory under the supervision of Rene Serette for their help in setting up the in situ hybridization assay.


Research reported in this publication was supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748.

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Authors and Affiliations



K.J.B. performed the study concept and design. K.J.B., C.V., and T.B. performed writing, review, and revision. T.B., G.H., and A.M. contributed pathology material. C.A. and E.A. provided clinical data. All authors read and approved the final paper.

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Correspondence to Klaus J. Busam.

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The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

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The study was conducted under the institutional review board protocols 16–1613, 12–245, and 18–128.

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Vanderbilt, C., Brenn, T., Moy, A.P. et al. Association of HPV42 with digital papillary adenocarcinoma and the use of in situ hybridization for its distinction from acral hidradenoma and diagnosis at non-acral sites. Mod Pathol (2022).

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