[Alopecia-keep a cool head]. / Alopezien ­ kühlen Kopf bewahren!

Pathologists often feel discomfort when confronted with scalp biopsies, especially in the case of horizontal sectioning, which is particularly useful in the event of nonscarring alopecia. Apart from a profound knowledge of follicular anatomy, one should be capable of correlating the histologic information with the clinical features of various inflammatory scalp disorders. This review addresses the basic principles of the interpretation of scalp biopsies and discusses the most common forms of scarring and nonscarring alopecia.

[Eruptive epidermoid cysts after imiquimod treatment of recurrent basal cell carcinoma : A case report]. / Eruptive Epidermoidzysten nach Imiquimod-Therapie eines rezidivierenden Basalzellkarzinoms : Ein Fallbericht.

Eruptive epidermoid cysts are a rare adverse event of imiquimod treatment for basal cell carcinoma. Up to date, 8 cases have been described in the literature. We present the case of a 75-year-old Caucasian woman with recurrent basal cell carcinoma on the nose. After multiple excisions and treatment with vismodegib, imiquimod 5% cream was administered 5 times per week over 6 weeks. Two months after the end of treatment, the patient presented with eruptive epidermoid cysts.

Cutaneous Lupus Erythematosus Presenting as Frontal Fibrosing Alopecia: Report of 2 Patients.

Frontal fibrosing alopecia represents a peculiar condition with a quasi-symmetrical, marginal scarring alopecia along the frontal and temporal hairline. The condition has been associated with further histopathologic and/or clinical evidence of lichen planopilaris. Since its emergence with the original report of Kossard in 1994, frontal fibrosing alopecia has been recognized to be associated with a number of comorbidities, including lupus erythematosus. So far, respective case reports and case series have given account of frontal fibrosing alopecia with the histopathologic features of lichen planopilaris associated or overlapping with lupus erythematosus. In contrast, we present cases of histopathologically proven cutaneous lupus erythematosus presenting as frontal fibrosing alopecia with a good response to the respective treatment with oral hydroxychloroquine and/or intralesional triamcinolone acetonide.

Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis.

Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated. Data from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure desmoplastic melanomas were either devoid of mutations (50%) or displayed mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in combination with the exception of a PIK3CA double-mutation lacking established biological relevance. Mixed desmoplastic melanomas on the contrary were frequently mutated (89%), and 67% exhibited activating mutations similar to common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2). Separate analysis of morphologically heterogeneous tumor areas in four mixed desmoplastic malignant melanomas displayed no difference in mutation status and RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal melanomas, were not mutated in our cohort. The RET G691S polymorphism was found in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our findings demonstrate absence of activating driver mutations in pure desmoplastic melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The findings underline the therapeutic dichotomy of mixed versus pure desmoplastic melanoma with regard to activating mutations primarily of the mitogen-activated protein kinase pathway.

Purpuric bullous pemphigoid.

Rare clinical variants of bullous pemphigoid (BP) include vesicular BP, dyshidrosiform BP, pemphigoid nodularis, seborrheic BP, pemphigoid vegetans, localized BP, erythrodermic BP, and juvenile BP. To our knowledge, this is the first report of an unusual case of purpuric BP. We present a case of 85-year-old white man who presented with a 2-week history of blisters and pruritic urticarial lesions all over his body. The diagnosis of purpuric BP was made on the basis of history, clinical presentation, histopathology report, direct and indirect immunofluorescence studies the diagnosis of purpuric BP was made. The reason for the development of palmoplantar purpuric lesions concomitant to ordinary patches and plaques of BP is unknown.

Nail Alterations in Cutaneous T-Cell Lymphoma: A Case Series and Review of Nail Manifestations.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) encompasses a broad range of lymphoproliferative diseases affecting the skin and can be clinically misleading due to its variable presentation. Nail alterations commonly appear in advanced-stage mycosis fungoides and true Sézary syndrome; however, they may be present in any stage of the disease. Although proper recognition of nail involvement in CTCL has both clinical and therapeutic value, specific nail findings have been infrequently described in the current literature. OBSERVATIONS: We describe 4 patients with CTCL who presented with clinically significant nail alterations. The most common findings were nail discoloration, thickening, crumbling, onycholysis, and onychomadesis. Other notable findings included splinter hemorrhages, subungual hyperkeratosis, and anonychia. CONCLUSIONS AND MESSAGE: The described cases illustrate many of the documented nail findings associated with CTCL and emphasize the variable nature of nail manifestations. The presence of specific nail alterations should increase the clinical suspicion of CTCL - especially in patients with concomitant systemic and/or cutaneous manifestations - and early biopsy specimens should be taken for diagnosis. Nail alterations should also be accurately described and monitored in all patients with biopsy-confirmed CTCL to help identify treatment response and detect disease recurrence.

Follicular malignant melanoma: primary follicular or folliculotropic?

Follicular malignant melanoma (FMM) is a rare variant of melanoma arising on sun-damaged skin of elderly patients. It is characterized histopathologically by a prominent involvement of 1 or 2 adjacent hair follicles. The authors report 3 new cases of FMM (M:F = 2:1; age range, 23-67 years; median age, 50 years) located on the scalp, cheek, and upper back. Complete effacement of the hair follicle, replaced by neoplastic melanocytes, was observed in 1 case. The interfollicular epidermis and adventitial dermis were involved in all 3 cases. Our series shows that FMM is not restricted to elderly patients but may arise also in young individuals without association with chronic sun damage. FMM should be distinguished from folliculotropic metastases of melanoma and from atypical melanocytic nevi. Although the histopathological features and the term FMM may suggest a derivation from melanocytes of the hair follicle, the exact origin of neoplastic cells is yet unclear, and at least some of these cases may represent folliculotropic examples of primary epidermal malignant melanoma.

Alopecia universalis associated with cutaneous T cell lymphoma.

BACKGROUND: Alopecia areata-like hair loss may occur in the context of cutaneous T cell lymphoma (CTCL) and can very rarely evolve to alopecia universalis-like presentation. The dermoscopic findings of CTCL-related alopecia have not been described. METHODS: Two patients with alopecia areata universalis-like hair loss occurring in the context of preexisting, pathology-proven CTCL are presented. RESULTS: Clinical examination showed subtotal scalp alopecia with sparse fine hair or total scalp alopecia with loss of eyebrows, eyelashes and body hair. On dermoscopy there was follicular or diffuse scaling, reduced number of follicular openings with broken hairs, short hairs or keratotic filiform spicules. Pathology confirmed the diagnosis of CTCL-related alopecia. One patient had almost complete hair regrowth after treatment. CONCLUSION: CTCL-related alopecia universalis is a rare non-scarring form of hair loss which simulates alopecia areata universalis. We provide clues to distinguish both based on clinical, dermoscopic and pathologic findings.

In vivo reflectance confocal microscopy assessment of the therapeutic follow-up of cutaneous T-cell lymphomas causing scalp alopecia.

Cutaneous T-cell lymphomas involving the scalp and determining scarring alopecias are difficult to be followed up during treatment because of the peculiar anatomical site of onset. In vivo reflectance confocal microscopy has already been reported to be useful for cutaneous T-cell lymphoma evaluation and for therapeutic follow-up in inflammatory skin conditions. We describe a case of a 26-year-old man affected by cutaneous T-cell lymphoma affecting the scalp in which reflectance confocal microscopy demonstrated to be useful for in vivo evaluation of the therapeutic response to topical and systemic treatment.

Mutations in POGLUT1, encoding protein O-glucosyltransferase 1, cause autosomal-dominant Dowling-Degos disease.

Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation. We previously identified loss-of-function mutations in KRT5 but were only able to detect pathogenic mutations in fewer than half of our subjects. To identify additional causes of DDD, we performed exome sequencing in five unrelated affected individuals without mutations in KRT5. Data analysis identified three heterozygous mutations from these individuals, all within the same gene. These mutations, namely c.11G>A (p.Trp4*), c.652C>T (p.Arg218*), and c.798-2A>C, are within POGLUT1, which encodes protein O-glucosyltransferase 1. Further screening of unexplained cases for POGLUT1 identified six additional mutations, as well as two of the above described mutations. Immunohistochemistry of skin biopsies of affected individuals with POGLUT1 mutations showed significantly weaker POGLUT1 staining in comparison to healthy controls with strong localization of POGLUT1 in the upper parts of the epidermis. Immunoblot analysis revealed that translation of either wild-type (WT) POGLUT1 or of the protein carrying the p.Arg279Trp substitution led to the expected size of about 50 kDa, whereas the c.652C>T (p.Arg218*) mutation led to translation of a truncated protein of about 30 kDa. Immunofluorescence analysis identified a colocalization of the WT protein with the endoplasmic reticulum and a notable aggregating pattern for the truncated protein. Recently, mutations in POFUT1, which encodes protein O-fucosyltransferase 1, were also reported to be responsible for DDD. Interestingly, both POGLUT1 and POFUT1 are essential regulators of Notch activity. Our results furthermore emphasize the important role of the Notch pathway in pigmentation and keratinocyte morphology.

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests.

Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis.