Treatment of multiple lesions of Bowen's disease and squamous cell carcinoma with topical imiquimod

We observed complete clinical and histopathologic remission of papules, plaques and nodules in two patients with multiple lesions of Bowen's disease and squamous cell carcinoma. Our findings indicate that topical imiquimod is a potentially promising therapeutic approach for the local treatment of early forms of cutaneous neoplasia, such as Bowen's disease and squamous cell carcinoma because it is a non-invasive therapy with a good cosmetic outcome. It may therefore be worthy of consideration in a subgroup of patients who cannot have or do not wish to have surgery.     

A case of multiple Bowen's disease with squamous cell carcinoma of the larynx and adenocarcionoma of the prostate

Bowen's disease, or cutaneous squamous cell carcinoma in situ, has been regarded as a cutaneous marker for internal malignancy. However, the relationship of Bowen's disease to visceral cancers remains controversial. We present a 76-year-old male with multiple lesions of Bowen's disease, who later developed laryngeal cancer and subsequent prostate cancer with distant metastases. Efforts to detect possible common etiologic agents including human papillomavirus and chronic arsenicism revealed no association between Bowen's disease and the internal malignancies. Despite the controversy, we suggest that a conservative cancer workup is ethically indicated in patients with multiple Bowen's disease.     

Focus of tricholemmal differentiation (tricholemmal carcinoma) within Bowen's disease/carcinoma

Bowen's disease (BD)/carcinoma is a type of squamous cell carcinoma of the skin, however, the possibility of adnexal differentiation (the development of sebaceous carcinoma or porocarcinoma) occurring in BD/carcinoma has been suggested. We herein describe a case of BD with superficial invasive carcinoma, which showed a clear cell focus, demonstrating tricholemmal differentiation. This clear cell focus showed the following findings: primarily composed of clear cells, somewhat columnar clear cells aligned in a palisade along a discernible basement membrane, tricholemmal keratinization and glycogen contained within the cells. In addition, the immunohistochemical profile in this clear cell focus, namely, negative staining for cytokeratin (CK)1 and positive staining for CK17 and calretinin in the inner cells of the neoplastic lobule, corresponded to that of the outer root sheath cells. This case suggested that adnexal differentiation can rarely occur within true BD/carcinoma, although adnexal carcinomas are commonly associated with a simple bowenoid change.     

Immunohistochemical characterization of cellular infiltrates in squamous cell carcinoma and Bowen's disease occurring in one patient.

We investigated populations of the infiltrating cells in Bowen's disease (BD) and squamous cell carcinoma (SCC), both of which arose in the same patient, using the Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T lymphocytes were most predominant among infiltrating cells; NK cells, B cells, and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c) T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical results in the present case differed from those of predominant infiltration of h/i T cells and of s/c T cells in three other reports of BD and SCC. These results suggest that the population of the cellular infiltrates may be modulated by the nature of tumors and by the immuno-competent state of the hosts.     

Incomplete efficacy of 5-aminolevulinic acid (5 ALA) photodynamic therapy in the treatment of widespread extramammary Paget's disease

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an effective treatment for several conditions such as Bowen's disease, subsets of basal cell carcinomas and actinic keratosis. Surgical resection is the first-choice therapy for extramammary Paget's disease (EMPD), but extensive resection is highly invasive and recurrences are frequent. We report two cases of genital EMPD treated by PDT with partial efficacy. The first patient, a 78-year-old male, suffered from pubic and scrotal Paget's disease for 6 years despite numerous treatments. The second patient, a 78-year-old female, had vulvar involvement for 2 years that was resistant to multiple treatments. The disease was recurrent and chronic with important pruritus and significant impact on the quality of life. Methyl 5-aminolevulinate was applied for 3 h, and irradiation was applied with red light (630 nm) using a total light dose of 37 J/cm(2) for a period of 10 min. The patients were treated every 2 to 4 weeks for a total of at least three treatments. Both patients experienced a partial transient reduction in their symptoms. One patient had a partial transient remission (< 50% reduction of the involved surface), whereas in the other patient, PDT failed to reduce the surface area of the lesions.     

In‐transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab

A 65‐year‐old Japanese man presented with a dome‐shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin–eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier‐like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in‐transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in‐transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in‐transit recurrence of Merkel cell carcinoma.     

Malassezia‐derived aryl hydrocarbon receptor ligands enhance the CCL20/Th17/soluble CD163 pathogenic axis in extra‐mammary Paget's disease

Malassezia yeast play a role in the pathogenesis of chronic dermatitis, especially in apocrine areas, by polarizing the local immunologic background to a Th2/Th17 state through aryl hydrocarbon receptor (AhR)‐dependent pathways. Extra‐mammary Paget's disease (EMPD) is an adenocarcinoma of apocrine origin, and except for cases associated with Malassezia yeast and their metabolites, the lesions typically develop in areas not exposed to environmental material. The purpose of this study was to investigate (a) the immunomodulatory effects of Malassezia metabolites on normal human keratinocytes (NHKCs), focusing on interleukin (IL)‐17 and related cytokines/chemokines (IL‐23, IL‐36γ, CCL20), (b) the expression of these factors in lesion‐affected skin in EMPD and (c) the activation of tumor‐associated macrophages (TAMs) by these factors. Malassezia metabolites augmented the expression of cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), CCL20 and IL‐36γ mRNA in NHKCs in vitro. In lesion‐affected skin of patients with EMPD, epidermal keratinocytes expressed CYP1A1 and CCL20. In addition, Paget cells expressed CCL20 and IL‐23. IL‐17–producing cells were distributed adjacent to Paget cells. Compared to healthy donors, patients with EMPD exhibited significantly increased serum levels of soluble (s)CD163, CXCL5, CXCL10 and CCL20. In addition, serum levels of sCD163 decreased significantly following tumor resection. Our study demonstrates a possible mechanism for the development of EMPD involving AhR‐mediated signalling by epidermal keratinocytes and RANKL‐induced recruitment of Th17 cells and TAMs.     

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by pulsed dye laser and blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

Background

Squamous cell carcinoma (SCC) is the second most common cutaneous malignancy, after basal cell carcinoma (BCC). Photodynamic therapy (PDT) involves converting a photosensitizer to reactive oxygen intermediates, which preferentially bind to hyperproliferative tissue. The most commonly used photosensitizers are methyl aminolevulinate and aminolevulinic acid (ALA). Presently, ALA-PDT is approved in the US and Canada for the treatment of actinic keratoses on the face, scalp, and upper extremities.

Aims

This cohort study evaluated the safety, tolerability, and efficacy of aminolevulinic acid, pulsed dye laser, and photodynamic therapy (ALA-PDL-PDT) for treatment of facial cutaneous squamous cell carcinoma in situ (isSCC).

Methods

Twenty adult patients with biopsy-confirmed isSCC on the face were recruited. Only lesions 0.4–1.3 cm in diameter were included. Patients underwent two treatments with ALA-PDL-PDT spaced 30 days apart. The isSCC lesion was then excised 4–6 weeks following the second treatment for histopathological assessment.

Results

No residual isSCC was detected in 17/20 (85%) patients. Two of the patients with residual isSCC had skip lesions present that explained the treatment failure. Excluding the patients with skip lesions, the posttreatment histological clearance rate was 17/18 (94%). Minimal side effects were reported.

Limitations

Our study was limited by small sample size and lack of long-term recurrence data.

Conclusions

The ALA-PDL-PDT protocol is a safe and well-tolerated treatment option for isSCC on the face, providing excellent cosmetic and functional results.     

Serum cytokeratin 19 fragment 21‐1 is a useful tumor marker for the assessment of extramammary Paget's disease

Cytokeratin 19 fragment 21‐1 (CYFRA 21‐1) has been used as a tumor marker for several malignancies. However, to date, no studies have assessed whether CYFRA 21‐1 could be a useful marker for extramammary Paget's disease (EMPD). The present study aimed to evaluate the significance of CYFRA 21‐1 as a serum tumor marker for EMPD progression. Concentrations of serum CYFRA 21‐1 and carcinoembryonic antigen (CEA) in 13 cases of EMPD were measured prior to undergoing treatment at Sapporo Medical University Hospital from January 2014 to May 2016. Four of the 13 patients had lymph node metastases at diagnosis, but none had distant metastases. Immunohistochemistry indicated that all 13 primary tumors and four metastatic tumors in lymph nodes were positive for cytokeratin 19. Although none of the 13 patients showed high serum CEA levels, six patients (46.2%) had elevated serum CYFRA 21‐1. Furthermore, CYFRA 21‐1 was reduced in association with post‐treatment tumor reduction in all six patients. Among these six patients, four developed recurrence and metastasis during the follow‐up period. CYFRA 21‐1 was re‐elevated in all four of these patients; however, serum CEA was elevated only in the patient with distant metastasis. These results suggest that CYFRA 21‐1 is more sensitive compared with CEA, and can be useful as a tumor marker for evaluating tumor progression and treatment efficacy in patients with EMPD.     

5% fluorouracil chemowraps in the management of widespread lower leg solar keratoses and squamous cell carcinoma

Elderly patients with extensive hypertrophic solar keratoses and squamous cell carcinoma on the lower legs can pose significant management challenges. Typically these patients require surgical treatment which is complicated by comorbidities and poor background lower leg skin. 5% fluorouracil chemowraps provides a useful alternative technique for the management of diffuse hypertrophic solar keratoses and as an adjuvant, and in some situations as a palliative treatment, for squamous cell carcinomas on the lower legs.