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

Vanderbilt, Chad; Brenn, Thomas; Moy, Andrea P.; Harloe, Gordon; Ariyan, Charlotte E.; Athanasian, Edward A.; Busam, Klaus J.

doi:10.1038/s41379-022-01094-8

Cited by 19 publications

(33 citation statements)

References 24 publications

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“…Of the 10 cases of DPAc reviewed, all were positive for HPV-42, although all 8 of the hidradenoma cases were negative. 4 Our case report further supports this association. Although the pathogenesis of this association is unknown, the observation of positive in situ hybridization signals in only tumor cells, as opposed to the overlying epidermis, suggests that HPV-42 may be the primary etiologic factor in the development of DPAc.…”

Section: Discussionsupporting

confidence: 84%

“…However, one report observed an association of recurrent DPAc and HPV-58–positive invasive squamous cell carcinoma with HPV-73–positive squamous cell carcinoma in situ on the collateral digits. 5 In conclusion, our case report in combination with the study by Vanderbilt et al 4 demonstrates the need for further investigation into the association between DPAc and HPV-42.…”

Section: Discussionsupporting

confidence: 56%

“…Although in most cases this diagnostic dilemma can be resolved by knowledge of DPAc, careful evaluation of histologic features (presence or lack of papillary structures) and immunohistochemistry and additional studies to more definitively separate DPAc from its mimickers is needed. Interestingly, a recent study by Vanderbilt et al 4 discusses a novel association of HPV-42 with DPAc. They explored the diagnostic utility of HPV-42 in situ hybridization.…”

Section: Discussionmentioning

confidence: 99%

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Human papillomavirus 42–associated digital papillary adenocarcinoma

Cascardo¹,

Cornell²,

Moesch³

2023

JAAD Case Reports

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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Human papillomavirus 42–associated digital papillary adenocarcinoma

Cascardo¹,

Cornell²,

Moesch³

2023

JAAD Case Reports

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“…42 Recently, a study reported low-risk HPV subtype 42 (HPV42) to be positive in 10/10 cases of DPA, including three cases with lymph node metastasis, suggesting that HPV42 is associated with DPA. 19 Importantly, none of the tumors harbored a BRAF V600E mutation identified by NGS, and all cases had a low TMB. 43 These findings are concordant with our study, wherein we found four DPA with BRAF-WT that were reactive with a low-risk HPV ISH probe that included HPV42.…”

Section: Discussionmentioning

confidence: 90%

“…17,18 A recent study reported HPV42 in 10/10 DPAs, including three cases with lymph node metastasis. 19 The aim of this study is to determine whether BRAF V600E mutation and HPV infection represent mutually exclusive alternative pathogenic pathways in tumorigenesis of DPA.…”

mentioning

confidence: 99%

Two distinct pathogenic pathways of digital papillary adenocarcinoma — BRAF mutation or low‐risk HPV infection

et al. 2023

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Digital papillary adenocarcinoma (DPA) is a rare neoplasm that can exhibit local recurrence and distant metastasis. We present a series of eight cases of DPA showing two distinct clinical presentations, morphologies, immunophenotypes, and molecular features.Four cases were characterized by painless, slow-growing nodules located on the digits.The lesions were small, well-defined, and confined in the dermis. Histopathologically, these tumors were composed of glandular structures lined by cuboidal epithelium with luminal papillary infoldings. Only rare mitotic figures and minimal squamoid differentiation were present, and cellular necrosis was absent. All four cases were positive for the BRAF V600E immunohistochemistry but negative for p16, low-risk and high-risk HPV in situ hybridization (ISH). In contrast, the remaining four cases were characterized by painful, rapidly growing masses on the digits. These four lesions were located in the deep dermis and consisted of a solid, tightly packed papillary architecture lined by atypical epithelioid cells with inconspicuous nucleoli. Cellular necrosis, numerous mitotic figures, and prominent squamoid differentiation were seen. All cases were negative for the BRAF V600E IHC. However, they showed strong, patchy to diffuse reactivity for p16 and were positive for low-risk HPV ISH and negative for high-risk HPV ISH. Our findings suggest that the current classification of DPA encompasses tumors that show two discrete pathogenic pathways -BRAF mutation or low-risk HPV infection. DPAs with low-risk HPV infection exhibit aggressive clinical features, high-grade morphology, marked squamoid differentiation, and wild-type BRAF. DPAs with BRAF V600E have less aggressive clinical features, low-grade morphologic findings, mild to absent squamoid differentiation, and negative HPV infection.

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