High risk HPV strain linked to ruxolitinib associated sebaceous neoplasms: IJDVL study

Ruxolitinib is a JAK1/2 inhibitor approved for hematologial conditions in adults. Its use in dermatology is rising, especially in dermatoses like atopic dermatitis, vitiligo, psoriasis and alopecia areata.² Cutaneous malignancies have been reported with its use.

A 57‑year‑old male with myelofibrosis, maintained on ruxolitinib over the past year presented with complaints of 2 growing nodules on the scalp of 5 & 2 months duration respectively. Histopathology from nodule showed papillomatous epidermal proliferations with koilocytic changes and mounds of parakeratosis admixed with hemorrhage at the top of the papillae, simulating the diagnosis of verruca vulgaris. Immunoreactivity to the androgen receptor and epithelial membrane antigen confirmed its sebaceous nature. The bigger lesion with more than 50% germ cells was diagnosed as sebaceoma and the smaller one with mature sebocytes as sebaceous adenoma.

Analysis was done for the 30 high and low risk HPV subtypes by 2 step polymerase chain reaction (EUROArray HPV detection kit, EUROIMMUN AG, Germany). HPV 66 strain was detected in both lesions.

Sebaceous carcinomas can harbor TP53 or RB1 mutations or are HPV driven. Two main viral proteins, E6 and E7 inhibit two tumor suppressor proteins TP53 and Rb. This explains sebaceous carcinomas in cases negative for the driving mutations (p53 and Rb) but positive for human papillomavirus infections.

HPV‑associated sebaceous tumors differ from others in that they-

• Are more likely to occur in younger individuals
• are less aggressive
• Rarely display worrisome histological phenotypes
• Warrant less aggressive postoperative surveillance

In conclusion sebaceous tumors can occur in patients on ruxolitinib; HPV can be a major cause in them which should be looked for as HPV associated sebaceous tumors have different behaviour than the others.

Source-

1. Hamie L, Bardawil T, Khalifeh I. High‑risk human papillomavirus in ruxolitinib‑associated sebaceous neoplasms. Indian J Dermatol Venereol Leprol 2021;87:404-8.
2. Tegtmeyer K, Ravi M, Zhao J, Maloney NJ, Lio PA. Off-label Studies on the Use of Ruxolitinib in Dermatology. Dermatitis. 2021 May-Jun 01;32(3):164-172. doi: 10.1097/DER.0000000000000658. PMID: 33443378.