and an antibody response to L1 HPV proteins. HPV 16 and HPV 18 (high-risk genotype) cause cervical cancer and squamous cell carcinoma (tonsils, larynx, anus, vulva and penis) whereas HPV 6 and HPV 11 (low-risk genotype) cause warts and condylomas. Conventional treatments for HPV infection involve topical drugs (podophyllotoxin, imiquimod, retinoid acid derivatives) and, in case of failure, CO2 laser ablation. The two HPV vaccines, the bivalent vaccine (Cervarix, Glaxo Smith Kline) and the quadrivalent vaccine (Gardasil, Sanofi Aventis MerckSharp&Dome) remain the only preventive measure against most HPV-related diseases. Several immunodeficiencies (epidermodysplasia verruciformis, WHIM syndrome, SCID, CVID, HIV, etc.) result in severe HPV. 1,2 In the immunocompromised, treatment and cure of HPV may represent a complex and challenging task.The identification of a high-risk HPV genotype in our patient prompted us to investigate the potential effect of the quadrivalent vaccine (HPV 6/11/16/18 subtypes). Our observation of a complete remission of plantar warts after the second dose with absence of genital response is intriguing.To our knowledge, the treatment with HPV vaccine of a few anecdotal cases with recalcitrant warts and condylomas has produced ambiguous results. 3-6 Although spontaneous regression of warts may occur, a role for HPV vaccination in the immunocompromised is undefined. A thorough analysis of HPV innate and adaptive immune response will help guide a prudent answer to this unexpected dual response. Yet, prospective randomized multicentre clinical trials are warranted to investigate whether HPV vaccines can treat common warts and/or prolong their progression time with significant advances on the immune mechanisms that control HPV infection and potential impact on the quality of life of our patients.

Cancer immunotherapy has highlighted the clinical relevance of enhancing anti-tumor response of CD8+ T cells in several cancer types. Little is known, however, about the involvement of the immune system in extramammary Paget’s disease (EMPD). We examined the cytotoxicity and the effector functions of CD8+ T cells using paired samples of peripheral blood and tumors by flow cytometry. Expression levels of perforin, granzyme B, IFN-g, TNF-a, and IL-2 in CD8+ tumor-infiltrating lymphocytes (TILs) were significantly lower than those in CD8+ T cells of peripheral blood. Significantly higher expression of PD-1 was found in CD8+TILs than in CD8+ T cells of peripheral blood. A high number of CD8+ cells was significantly associated with poor overall survival (OS) adjusted with age, sex, and clinical stage (hazard ratio [HR] = 5.03, P = 0.045, 95% confidence interval [CI] 1.03–24.4). On the other hand, the number of PD-1+ cells was not associated with OS or disease-free survival (DFS). Moreover, we found that tumor cells produced immunosuppressive molecule indoleamine 2,3-dyoxygenae (IDO). In conclusion, CD8+ TILs displayed an exhausted phenotype in EMPD. IDO expression seemed more relevant in inducing CD8 exhaustion than PD-1 upregulation or PD-L1 expression by immune cells. Restoring the effector functions of CD8+ TILs could be an effective treatment strategy for advanced EMPD.

Syringocystadenocarcinoma papilliferum (SCACP) is a very rare cutaneous adnexal neoplasm. SCACP presents histologic variability, and it is difficult to establish the diagnosis from a punch biopsy. SCACP has an overall configuration similar to that of syringocystadenoma papilliferum (SCAP). When we diagnose SCACP, the histologic features of SCAP can be contributing and immunohistochemical staining is useful. Our case shows the histologic variability of SCACP and the pitfalls of a punch biopsy for the diagnosis of SCACP.

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Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti–programmed death ligand‐1 (PD‐L1) is a well‐studied biomarker for response to anti–programmed death‐1 PD‐1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3‐dioxygenase (IDO) is correlated to a response to anti–CTLA‐4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti–PD‐1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD‐L1 expression with response to anti–PD‐1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti–PD‐1 antibody from the perspective of IDO and PD‐L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression‐free survival (HR = 0.33, 95% CI = 0.13‐0.81, P = 0.016), whereas PD‐L1 expression on tumors was not associated with progression‐free survival. Significantly lower expression of IDO in tumors was found in non–responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti–PD‐1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.