[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.

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.

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.

In vivo analysis of solar lentigines by reflectance confocal microscopy before and after Q-switched ruby laser treatment.

Solar lentigines are benign lesions usually found on sun-damaged skin. We investigated twelve cases of solar lentigines through dermoscopy and reflectance confocal microscopy, performed before, and 30 min and 10 days after, a single treatment with a Q-switched ruby laser. At baseline, all lesions showed characteristic features of solar lentigines in reflectance confocal microscopy analysis: regular honeycomb patterns, edged dermal papillae and cord-like rete ridges at the dermoepidermal junction. Thirty minutes post-laser treatment, blurred epidermal intercellular connections, dark structureless areas of different sizes and shapes in the lower epidermal layers, and hyporeflective dermal papillae, reflecting epidermal and dermal oedema, were observed. Ten days post-treatment highly reflective round-to polygonal areas and aggregated granules, representing extracellular melanin, were detected in all epidermal layers featuring regular honeycomb patterns. Reflectance confocal microscopy can be used to visualise dynamic skin processes, allowing non-invasive in vivo follow-up of skin lesions after treatment.

Intralymphatic histiocytosis. A clinicopathologic study of 16 cases.

Intralymphatic histiocytosis is a rare condition characterized by the presence of dilated lymphatic vessels containing aggregates of mononuclear histiocytes (macrophages) within their lumina. The phenomenon seems to occur almost exclusively within the reticular dermis. Although its pathogenesis remains uncertain, there has been speculation about the possible relationship between intralymphatic histiocytosis and intravascular reactive angioendotheliomatosis. In addition, several examples historically have been associated with rheumatoid arthritis. We describe our experience with 16 cases of intralymphatic histiocytosis. Clinically, the lesions were located predominantly on the upper and lower limbs, and they consisted of asymptomatic and poorly demarcated erythematous plaques and livedo reticularis-like lesions. They were characterized histopathologically by dilated vascular structures involving the reticular dermis. Some of these dilated vessels had empty lumina, whereas others contained variable number of mononuclear histiocytes. An inflammatory response of variable intensity from case to case was also present in the adjacent dermis. The dilated vessels exhibited thin walls with irregular shapes, and a single discontinuous layer of flat endothelial cells lined their lumina. Immunohistochemically, the endothelial cells lining the dilated lumina expressed immunoreactivity for CD31, CD34, podoplanin, D2-40, Lyve-1, and Prox-1, which confirmed their nature as lymphatic endothelial cells. Intralymphatic mononuclear histiocytes expressed CD68 (PGM1), although some cases also had variable immunoexpression for myeloperoxidase, CD31, and podoplanin. In the 4 cases that employed double immunohistochemistry, with podoplanin + CD68 (PGM1) or with Lyve-1 + CD68 (PGM1), each marker highlighted their specific target cells unequivocally; the endothelial cells expressed podoplanin or Lyve-1 immunoreactivity, and intralymphatic histiocytes showed CD68 (PGM1) immunoexpression. Our findings expand on the previously described morphologic and immunohistochemical features of intravascular histiocytosis. We also discuss the possible relationship between intralymphatic histiocytosis and the so-called reactive intravascular angioendotheliomatosis.

New diagnostic methods in dermatopathology: in vivo reflectance confocal microscopy.

Reflectance confocal microscopy is a new non-invasive imaging technique which enables the visualization of upper skin layers in-vivo at quasi-histological resolution. Skin changes seen in confocal microscopy in Porokeratosis Mibelli and scabies infection are described in the following two cases.

The morphologic spectrum of primary cutaneous anaplastic large T-cell lymphoma: a histopathologic study on 66 biopsy specimens from 47 patients with report of rare variants.

BACKGROUND: Primary cutaneous anaplastic large T-cell lymphoma (PCALCL) is a well-defined entity with prognostic differences from the nodal counterpart [nodal anaplastic large cell lymphoma (NALCL)]. Several histological variants of NALCL have been characterized (common, lymphohistiocytic and small cell). However, studies on morphological variants of PCALCLs are lacking. METHODS: We analyzed retrospectively the clinicopathologic features of 66 biopsies from 47 patients (M : F = 27 : 20; median age: 53 years; mean age: 51.8 years; range: 14-82) with PCALCL, in order to better characterize the spectrum of this unusual neoplasm. RESULTS: The 'common variant' was the most frequent (40.4%). In contrast to NALCL, in PCALCL, marked reactive infiltrates are more commonly present. In fact, 26 cases were classified as 'inflammatory type' (15 cases) and 'lymphohistiocytic' (11 cases). Concerning the predominant cell morphology, large anaplastic cells (33%) were almost as frequent as large pleomorphic (36%) and small to medium-sized cells (26%). We reported for the first time in the skin 2 rare cases with the predominance of large cells with a 'signet-ring'-like appearance. Epidermotropism and presence of eosinophils were found in a proportion of cases in all PCALCL variants. CONCLUSIONS: PCALCL is characterized by variable histopathological presentations and a broad cytomorphologic spectrum.