Ingrid H. Wolf

Germline mutations in BAP1 predispose to melanocytic tumors

Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.

Teledermoscopy - results of a multicentre study on 43 pigmented skin lesions

We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi.

Background  Based on the dermoscopic classification of acquired melanocytic naevi, six different dermoscopic types can be distinguished by morphology (globular, globular‐reticular, globular‐homogeneous, reticular, reticular‐homogeneous, homogeneous) and by pigment distribution (uniform, central hyperpigmentation, central hypopigmentation, peripheral hyperpigmentation, peripheral hypopigmentation, multifocal hyper/hypopigmentation). It has been suggested that most individuals harbour one predominant dermoscopic type among their naevi.

Guidelines on the use of extracorporeal photopheresis

After the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi‐disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease.

Dermoscopy of pigmented lesions of the mucosa and the mucocutaneous junction: results of a multicenter study by the International Dermoscopy Society (IDS).

OBJECTIVE To better characterize the dermoscopic patterns of mucosal lesions in relation to the histopathologic characteristics. DESIGN Retrospective and observational study. SETTING Fourteen referral pigmented lesion clinics in 10 countries. PATIENTS A total of 140 pigmented mucosal lesions (126 benign lesions, 11 melanomas, 2 Bowen disease lesions, and 1 metastasis) from 92 females (66%) and 48 males (34%) were collected from October 2007 through November 2008. MAIN OUTCOME MEASURES Scoring the dermoscopic patterns (dots, globules, or clods, circles, lines, or structureless) and colors (brown, black, blue, gray, red, purple, and white) and correlation with the histopathologic characteristics. RESULTS Based on univariate analysis and 2 diagnostic models, the presence of structureless zones inside the lesions with blue, gray, or white color (the first model) had a 100% sensitivity for melanoma and 92.9% sensitivity for any malignant lesion, and 82.2% and 83.3% specificity for benign lesions in the group with melanoma lesions and the group with malignant lesions, respectively. Based on the colors (blue, gray, or white) only (the second model), the sensitivity for the group with melanoma was 100% and for the group with any malignant lesion was 92.9%, and the specificity was 64.3% and 65.1%, respectively. Patients with malignant lesions were significantly older than patients with benign lesions (mean [SD] ages, 60.1 [22.8] years vs 43.2 [17.3] years, respectively). CONCLUSION The combination of blue, gray, or white color with structureless zones are the strongest indicators when differentiating between benign and malignant mucosal lesions in dermoscopy.

Proliferating pilomatricoma. A histopathologic simulator of matrical carcinoma

We report on 9 patients with pilomatricomas that showed unusual histopathologic features. Our patients were mainly elderly individuals (age range 42 to 88 years; mean age 70.1 years) who presented solitary cutaneous nodules situated on the head and neck (7 neoplasms), upper arm (1 neoplasm), and back (1 neoplasm). All the lesions were treated by simple excision. Follow‐up data available in 7 of the 9 patients (mean follow‐up, 17 months) revealed local recurrences in 1 patient whose lesion recurred 3 times. No lymph node involvement or distant metastases were recorded in any of our cases. Histopathologically, most neoplasms were characterized by a relatively large lesion in the clermis that in some cases showed extension to the subcutis. Each lesion was predominantly composed of a lobular proliferation of basaloid cells in association with adjacent focal areas containing eosinophilic, cornified material with shadow cells. In some cases, relatively large areas of shadow cells were present, whereas, in others only small foci of shadows cells were observed. Cytomorphologically, the basaloid cells showed features of matrical and supramatrical cells of a normal hair follicle and exhibited variable nuclear atypia and mitotic figures. The overall architectural pattern of the neoplasms was different from that of large fully developed stereotypical pilomatricomas that maintain a cystic character with basaloid cells predominantly aligned at the periphery. Based on the histopathologic findings, namely the presence of a large, lobular proliferation of basaloid cells in association with small to large foci of shadow cells, we interpreted these neoplasms to be a distinctive proliferative variant of pilomatricoma and propose the designation “proliferating pilomatricoma.” Proliferating pilomatricomas should be differentiated from the recently described matricoma, basal‐cell carcinoma with matrical differentiation, and matrical carcinoma (pilomatrical carcinoma).

Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: a preliminary study.

Background  Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level.

In vivo confocal scanning laser microscopy of common naevi with globular, homogeneous and reticular pattern in dermoscopy

Background  A systematic examination and comparison of confocal scanning laser microscopy (CSLM) features of benign naevi showing different dermoscopic patterns has never been performed.

Nature of inflammatory infiltrate in superficial cutaneous malignancies during topical imiquimod treatment

Topical imiquimod (IQ) is an effective treatment for genital warts and various malignant tumors of the skin. IQ acts through the Toll-like receptor 7 leading to the production of cytokines and chemokines such as interferons, interleukins, and growth factors. We investigated the composition of the inflammatory cell infiltrate before, during, and after the treatment of 10 superficial cutaneous malignancies (melanoma in situ (n = 4), melanoma metastasis (n = 1), squamous cell carcinoma in situ (n = 4), and basal cell carcinoma (n = 1) with 5% IQ cream. Immunophenotyping revealed in all cases during treatment an increased population of T-lymphocytes positive for CD3, CD4 and CD8, as well as a considerable number of cytotoxic cells (TIA-1+, granzyme B+) and plasmacytoid dendritic cells (CD 123+). These findings further support previous investigations that the antitumor effects of IQ result from an enhanced cytotoxic T-cell mediated immune response and from the recruitment of plasmacytoid dendritic cells to the skin. The population of infiltrative inflammatory cells was similar in all patients irrespective of the type of tumor.

Dermoscopic classification of Clark's nevi (atypical melanocytic nevi)

Clark’s nevi (atypical melanocytic nevi) are acquired melanocytic lesions that are well known clinically by physicians and especially by dermatologists. Clark’s nevi are named for Wallace H. Clark, Jr., who first drew attention to this particular type of nevus in studies of numerous melanocytic nevi in patients with concomitant melanomas.1 This melanocytic nevus, originally designated B-K mole,1 has also been called dysplastic nevus2,3 or atypical mole.4 We prefer to use the nomenclature set forth by Ackerman and Magana-Garcia5 and designate these acquired melanocytic lesions as Clark’s nevi.