Extragenital Human Papillomavirus 16-associated Bowen's Disease.

Sir,

Bowen's disease (BD) is an in situ squamous cell carcinoma (SCC) that may occur with multiple lesions in 10%–20% of cases.[1] Furthermore, histological pagetoid cells type has been reported only in 5% of skin BD biopsy.

We describe a case of a 67-year-old male with multiple erythematous, hyperkeratotic, and ulcerated lesions that occurred 10 years before patient's observation, increasing in size and number over the years. Particularly, the widest lesion is hyperkeratotic and exudative plaque on the trunk, focal ulcerated, sized 11 cm × 8 cm [Figure 1]. Other lesions were observed on the trunk and ears. However, human papillomavirus (HPV)-related lesions were never detected on genitalia and the patient denied chronic ultraviolet and arsenic exposure.

Figure 1

Verrucous hyperkeratotic, exudative plaque on the left side of the trunk

Biopsies from five lesions showed full-thickness epidermis involvement, atypical keratinocytes with large hyperchromatic and pleomorphic nuclei. Several keratinocytes presented vacuolated appearance and perinuclear halo [Figures 2-4]. Immunohistochemical staining showed atypical cells positive for cytokeratins (CKs) 5, 6 and negative for CK 7, carcinoembryonic antigen, epithelial membrane antigen, S100. Cells exhibited intense positivity for p16 (INK4a).

Figure 2

Disorderly maturation of keratinocytes and presence of atypical keratinocytes with perinuclear halos (H and E, ×40)

Figure 4

Atypical keratinocytes with vacuolated appearance (H and E, ×20)

At low magnification, verrucous lesion with marked hyperkeratosis and papillomatosis (H and E, ×10)

Therefore, BD's pagetoid variant diagnosis was made.

DNA was isolated with HPV detection and genotyping; moreover, the L1 gene of HPV and human beta-globin was simultaneously co-amplified [Figure 5]. Furthermore, HPV coinfection 16/18 was detected and confirmed by real-time polymerase chain reaction assay.

Figure 5

Amplification of human papillomavirus L1 gene by real-time polymerase chain reaction: mixed infection of human papillomavirus 16 with human papillomavirus 18

Routine blood tests were normal, and HIV test was negative.

The largest lesion was treated surgically while the others with liquid nitrogen cryotherapy.

HPV infection is one of the risk factors related to BD. Genitalia involvement is often associated with high-risk oncogenic HPV (16, 18, 31, 33) while extragenital lesions are often associated with other subtypes.

HPV 16 has been studied in genital carcinomas, while his role in nongenital SCC is still debated, but probably β-HPVs (Type 2) may be involved.[2]

In literature, a few cases of HPV-associated extragenital BD have been described. Lu et al. evaluated 91 BD patients HPV-negative.[3] Rubben et al. detected six HPV-16 positive cases of 191 lesions[4] that showed genital infection's history suggesting that patients transported by themselves HPV from genitalia to their own hands.

Our patient had multiple extragenital HPV-16 positive lesions, without hands and genitalia involvement or HPV-infection history. It represents a peculiar histological feature with koilocytes such as keratinocytes and perinuclear halo that could be a BD histological pattern related to viral etiology even in the absence of HPV history. Similarly to our case, Sun and Barr[5] described a “papillated BD” HPV negative, with verrucous appearance and koilocyte-like cells. The author speculated low viral load, believing that more sensitive techniques might be necessary to discover HPV.

Our patient is the first case of multiple extragenital BD with histological pagetoid appearance and HPV-16 DNA detection. The differential diagnosis between BD and SCC is sometimes critical; however, fortunately, our case did not show any malignant transformation.

Although in our case we lost the patient after 3 months, BD patients need close follow-up for the SCC risk and HPV research is recommended.

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Nil.

Conflicts of interest

There are no conflicts of interest.