Malignant and in situ subtypes of melanoma are associated with basal and squamous cell carcinoma and its precancerous lesions

Background: Patients with cutaneous malignant melanoma (CMM) are at increased risk of non-melanoma skin cancers (NMSCs) and possibly precancerous lesions. Objectives: To analyse the association between CMM and not only NMSCs but also precursor lesions, actinic keratosis (AK) and Bowen disease (BD). Materials & Methods: The Finnish Cancer Registry data was used to calculate the age-standardized incidence ratio during 2000-2013 for basal (BCC) and squamous (SCC) cell carcinoma in patients with CMM. All tissue material collected from 70,420 subjects during 2000-2013 and reposited in the Biobank of Eastern Finland was used to calculate the age-standardized prevalence of BCC, SCC, BD and AK in CMM patients. Results: In both genders, the age-standardized incidence ratio of BCC and SCC was increased in CMM patients. The age-standardized prevalence of NMSCs and precursor lesions was higher in patients with CMM than in those without CMM, and was higher in CMM patients with immunosuppression (IS) than in those without IS. The association of M-Snomed subtypes, lentigo maligna (LM), melanoma in situ (MIS) and malignant melanoma (MM) with AK and/or BD was stronger than with BCC. LM revealed the highest association with the combination of AKBD-SCC. Male subjects showed a higher age-standardized prevalence of CMM, MM and BCC than females, but the opposite was observed for AK. Conclusion: Melanoma increases the risk of NMSCs, and IS may enhance this risk. Both malignant and in situ subtypes of melanoma associate with not only BCC and SCC, but also precancerous lesions.

Triple collision tumor comprising Merkel cell carcinoma with an unusual immunophenotype, squamous cell carcinoma in situ, and basal cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine cancer which almost always exhibits the cytokeratin (CK)20+/thyroid transcription factor (TTF)-1- immunophenotype. MCC may occur concurrently with squamous cell carcinoma, Bowen disease, and/or basal cell carcinoma (BCC), with some evidence that MCCs which occur in conjunction with other neoplasms exhibit different immunophenotypes compared to pure MCC cases. We present a case of CK20-/TTF-1+ MCC concurrent with Bowen disease and BCC, and discuss possible differences in the pathogenesis of pure vs combined MCC. We also review the literature for this unusual immunophenotype, noting that most cases occur in combined MCC.

Distribution of high-risk α-genus human papillomavirus genotypes impacts cutaneous neoplasms.

BACKGROUND: High-risk α-genus human papillomaviruses (α-HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial. OBJECTIVE: We evaluated the contribution of high-risk α-HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high-risk α-HPV genotypes in these cutaneous tumours. METHODS: HPV genotypes were determined using a commercial PCR-based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α-HPV prevalence and relevant risk factors were analysed. RESULTS: High-risk α-HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high-risk α-HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV-carrying cuSCC patients. Multiple infections with different high-risk α-HPV types were found in 20.5% of HPV-related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high-risk α-HPVs were more frequently found in non-exposed sites rather than in sun-exposed sites of cuSCC. CONCLUSION: Multiple infections, as well as single infection with high-risk α-HPV may link to cuSCC. In spite of the involvement of high-risk α-HPV at high levels in cuSCC and Bowen's disease, no high-risk α-HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV-related cuSCC as a precursor.

Spindle cell squamous cell carcinoma arising in Bowen's disease: Case report and review of the published work.

A 79-year-old Japanese woman presented with an ulcerated, brown-red nodule in the center of a sharply demarcated, tan-brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst-Jadassohn. Small oval nests of bland-appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34ßE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34ßE12 and CK5/6. The MIB-1 index was estimated at approximately 40-50% in both the bland-appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis.

Donovanosis With Bowen Disease.

A 45-year-old farmer presented with ulcers and plaques over his scrotum for the past 4 to 5 years. The condition started as a small lesion on the shaft of the penis, which improved with treatment; however, after 2 to 3 months, papulonodular lesions developed on the scrotum, which increased in size and subsequently broke down to form ulcers. He denied drug abuse but had a history of multiple unprotected sexual exposures. He was prescribed oral antibiotics, which improved the lesions, but he failed to take the antibiotics for more than a week. He also used powders, lotions, and salves (exact nature not known), which did not help and sometimes even burned the skin. After stopping the medicine, he developed new lesions that followed a similar course. Examination revealed nontender ulcers on the scrotum with raised, rolled-out margins and pale red, granulation tissue that bled on touch (Figure 1). In addition, there were nodules with a pinkish red granular surface and scaly erythematous plaques on the scrotum. Regional lymph nodes were not enlarged.

Successful Treatment of Relapsing Bowen's Disease with Ingenol Mebutate: The Use of Dermoscopy to Monitor the Therapeutic Response.

Ingenol mebutate (IM) has recently been approved for the topical treatment of actinic keratoses. It appears to have a dual mechanism of action: rapid necrosis after gel application and a subsequent immune-mediated response, which targets any residual dysplastic epidermal cells. We report the successful treatment of a woman, who had been relapsing into Bowen's disease (BD) on her right forefinger for 8 years. During her clinical history, she had received an allogeneic, HLA-identical stem cell transplant for myeloproliferative syndrome with a JAK2V617F mutation and lobectomy of the pulmonary right lower lobe for adenocarcinoma. We used dermoscopy to monitor the therapeutic response of BD. We discuss IM gel as a possible therapeutic option for BD.

Human papillomavirus infection and p16 expression in the immunocompetent patients with extragenital/extraungual Bowen's disease.

BACKGROUND: The role of human papillomaviruses (HPV) in the development of squamous cell carcinoma (SCC) has been established for anogenital lesions but still remains controversial for carcinomas in other sites. The aim of this study was to determine the α-HPV and ß-HPV prevalence and their association with p16 expression, sun exposure, and clinicopathological findings in patients with Bowen's disease (BD). METHODS: One hundred sixty nine skin biopsy specimens from 157 immunocompetent patients with extragenital/extraungual BD were examined for HPV status and p16 expression. The presence of koilocyte-like changes, solar elastosis and papillomatosis was recorded for each specimen. RESULTS: BD was diagnosed more often in potentially sun-exposed sites with prevalence 73.6 % and a remarkable predilection for the head and neck region. High risk α-HPV or ß-HPV were detected in 34.7 % of lesions and ß-HPV infections dominated over α-HPV. Higher prevalence of koilocyte-like changes and papillomatosis was found in HPV-positive specimens but it was not statistically significant. The expression of p16 was detected in 79.8 % of lesions and displayed no correlation with the HPV status. HPV-positivity tended to be detected more often in sun-protected sites. Dual infections by α-HPV/ß-HPV genera and mixed α-HPV infections were not detected, while 37.5 % of ß-HPV positive specimens were infected by two or more ß-HPV genotypes. HPV 9 was significantly associated with mixed ß-HPV infections. CONCLUSIONS: HPV may play an etiological role at least in some SCC in situ arising in extragenital sites. Sunprotected sites may be more dependent on HPV-mediated co-carcinogenesis than sun exposed areas. The presence of the p16-expression, papillomatosis or koilocyte-like change is not a reliable marker of HPV infection in SCC in situ.

Co-existence of porokeratosis variants concurrent with Bowen's disease: two rare cases report.

Coexisting variants of porokeratosis rarely occurs. Disseminated superficial porokeratosis (DSP) is characterized by multiple uniform small annular papules distributed all over body. DSP commonly coexist with linear porokeratosis (LP), but it is uncommon for DSP to coexist with porokeratosis of Mibelli (PM). PM presents with central atrophic erythematous plaques and thread-like elevated border. It occurs mainly on extremities. Although malignant transformation can be found in the porokeratosis, there is still no report case of coexisting variants of porokeratosis concurrent with Bowen's disease. The clinical and histopathologic finding of rare coexisting variants of porokeratosis (PM and DSP) concurrent with squamous dysplasia is described.

Pigmented Bowen's disease of the penis and scrotum in a patient with AIDS.

Patients with HIV have higher risk of developing squamous cell carcinoma of the skin given the increased risk of HPV infection, which alters cell proliferation and apoptosis [1]. Pigmented Bowen's disease is an uncommon form of squamous cell carcinoma in-situ characterized by pigmented lesions that can clinically mimic superficial spreading melanoma, pigmented basal cell carcinoma, melanocytic nevus, Bowenoid papulosis, and seborrheic keratosis.