Epidermodysplasia Verruciformis and Breast Cancer - Casual or Causal?

Sir,

Epidermodysplasia verruciformis (EV) is a rare dermatologic condition that manifests mainly as verrucous cutaneous lesions such as multiple persistent verrucae, pityriasis versicolor-like lesions and other verrucous or 'warty' cutaneous lesions. The immunity deficiency may be either primary, inherited in an autosomal recessive pattern or secondary, observed mainly in HIV-infected, immunocompromised or immunosuppressed individuals.[1] EV is characterised by a decreased immunologic ability to defend against and eradicate certain types of human papillomavirus (HPV), that are innocuous in the general population.[2] We describe for the first time, to our knowledge, a case of EV in relation to breast cancer in which EV lesions resolved after chemotherapy.

A 56-year-old woman presented to our Dermatology Clinic with a 28-year history of cutaneous lesions on her abdomen and lower limbs. She has no other disease and she did not take any medications. In her family history, one of her two brothers had the same findings but with less severe manifestations.

Physical examination revealed multiple brownish-hypopigmented papules scattered on her forehead, abdomen and lower limbs [Figure 1a]. Wood-lamp examination revealed a yellow fluorescence [Figure 1 and c]. Skin biopsy taken from her abdomen showed epidermis acanthosis, and HPV-typing from a paraffin-embedded skin biopsy was positive for HPV-16. Consequently, the patient was diagnosed with EV and she started treatment with acitretin 10 mg once daily. After 2 years' follow-up, the lesions had not improved. Moreover, she was diagnosed with a breast cancer grade 3 in Bloom–Richardson system with oestrogen-receptor-negative, progesterone-receptor-negative and HER2 receptor positive, and was started on neoadjuvant chemotherapy therapy with docetaxel-trastuzumab-pertuzumab each 21 days. After four cycles of treatment, the patient presented a complete tumoral response. Moreover, EV lesions flattened out [Figure 2].

Figure 1

(a) Multiple brownish-hypopigmented macules and papules scattered on lower limbs. (b) Multiple papules scattered on lower limbs with yellow fluorescence using a wood lamp. c) Multiple papules scattered on forehead with yellow fluorescence using a wood lamp

Figure 2

Slight hypopigmented macules on (a) front and (b) lower limbs after chemotherapy

EV is a dermatology condition in which there is widespread and persistent infection with different subtypes of HPV, leading to persistent infection and increased lifetime risk of development of cutaneous dysplasia and malignancy such as squamous cell carcinoma.[3] Nevertheless, the causal relationship between HPV and breast cancer is still controversial. Some molecular pathways regarding the implication of HPV infection being the aetiological factor for breast cancer carcinogenesis have been proposed. Cell surface to surface contact and the exposure of the mammary ducts to the external environment via the nipple-areola complex can provide the entry point for the HPV virus. Some reports suggested a hematogenic or lymphatic transfer of HPV viruses from one organ to another, while other studies indicated that the virus exists in nipple tissues and breast milk, showing that HPV can transfer from the nipple-areola complex to lactiferous ducts.[4] Moreover, the latest meta-analysis between this association showed an increased risk of breast cancer in HPV DNA-positive individuals.[5]

In our patient, the good clinical response of EV lesions to chemotherapy makes this biological association plausible and opens new fields of research on EV treatments. However, a casual clinical improvement could not be dismissed. In conclusion, up to our knowledge, we present for the first time a case of EV in relation to breast cancer with a good clinical response after docetaxel-trastuzumab-pertuzumab chemotherapy.

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Conflicts of interest

There are no conflicts of interest.