To the Editor: Bowen disease (BD) is an in situ squamous cell carcinoma (SCC) characterized by well-demarcated scaly plaques. BD is usually solitary, but multiple lesions may also develop. Although BD of the hands and feet has been shown to be strongly linked with human papillomavirus (HPV) infection,1,2 cases associated with HPV-18 or HPV-45 are rare, and coinfection with both HPV types has not been reported. Here, we report a case of invasive SCC and numerous BD lesions on the hands and foot with HPV-18 and HPV-45 infections. A 72-year-old woman was referred to our department with invasive SCC of the right index finger. She had noticed multiple plaques and nodules on the palms and fingers 7 years before her visit to our hospital. The lesions had been treated with cryotherapy and oral etretinate but had gradually increased in size and number. From 6 months before the visit, a nodule of the right index finger had rapidly grown, and a biopsy specimen revealed invasive SCC. She had a 10-year medical history of primary macroglobulinemia, along with its associated Evans syndrome, which had been previously treated with several medicines including fludarabine, rituximab, and eltrombopag olamine for 7 years, leading to remission. After the remission, eltrombopag olamine has been maintained, but no relapses of anemia or reduced platelets had occurred since then, although her blood IgM had been slightly higher than the normal level. Physical examination revealed an erosive tumor on the right index finger and numerous keratotic plaques and nodules on the palm and fingers of both hands and the right foot (Figs. 1A–C). The keratotic plaques and nodules were suspected to be BD. Computed tomography (CT) revealed no lesions suggestive of metastases, and amputation of the right index finger and wide resections of the other keratotic lesions (32 in total) were performed (Figs. 1D, E). Histologically, the tumor showed numerous nests composed of atypical keratinocytes, which invaded into the subcutaneous tissue (Figs. 2A, B). The surrounding epidermis also showed atypical keratinocyte proliferation with hyperchromatic and clumped nuclei (Fig. 2C), suggesting invasive SCC developing from BD. All the other lesions were also diagnosed as BD. The surgical margins were negative. HPV genotyping using the PCR-rSSO method revealed the presence of HPV-18 and HPV-45 in the lesions (Fig. 2D). Three months after the surgery, multiple small plaques had recurred, but frequent cryotherapy was shown to be diminishing the lesions at the 3-month follow-up. CT 6 months after the surgery revealed enlarged lymph nodes in the left cervical region, which histologically showed relapse of the primary macroglobulinemia. Patient has provided informed consent for publication of the case.FIGURE 1.: A, B, An erosive tumor on the right index finger and numerous keratotic plaques and nodules on the palm and fingers of both hands. C, Keratotic plaques and nodules on the right foot. D, E, Amputation of the right index finger and wide resections of the other keratotic lesions were performed. The black lines indicate the resection lines for the lesions.FIGURE2.: A, B, The tumor of the right index finger revealed numerous nests composed of atypical keratinocytes with invasion into the dermis and subcutaneous tissue (hematoxylin and eosin [H&E], ×40 [a], ×400 [b]). C, The surrounding epidermis of the tumor also showed atypical keratinocyte proliferation with hyperchromatic and clumped nuclei (HE, ×200). D, HPV genotyping using the PCR-rSSO method revealing the presence of HPV-18 and HPV-45 in the lesions.HPV is a well-known risk factor for many cancers, especially cervical cancer. Some high-risk mucosal HPV types, such as HPV-16 and HPV-73, are frequently detected in BD of the hands and feet, and autoinoculation of mucosal HPV from the genitalia is suggested to be the cause.2,3 Although HPV-18 and HPV-45, detected in our case, are also high-risk mucosal HPV types and are frequently detected in cervical cancer,4 BD cases of the hands or feet with HPV-18 or HPV-45 infection are rare, and coinfection with both of the HPV types, as in our case, have not been reported, suggesting low susceptibility to HPV-18 and HPV-45 infections in these regions.5 Multiple BD lesions are rare and sometimes associated with immunologic dysfunction, although cases of such numerous lesions of 30 or more, as in our case, have not been reported.6–8 Our patient also had a history of primary macroglobulinemia and Evans syndrome, which may be associated with immunologic dysfunction.9,10 Therefore, although the precise mechanism remains unclear, the potential immunologic dysfunction associated with these disorders might have been involved in the development of such numerous BD lesions through impaired immune response to the tumors and promotion of the rare types of oncogenic HPV infection.
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Open Access
Jan 4, 2022
Tomo Shimizu + 8
