Siegfried Werchau

Merkel cell carcinoma induces lymphatic microvessel formation

BACKGROUND Merkel cell carcinoma (MCC) is a rare, highly malignant neuroendocrine tumor of the skin characterized by frequent lymphatic metastasis. OBJECTIVE We sought to identify lymphovascular anatomy and expression profiles of lymphangiogenic cytokines to give an opinion on lymphangiogenesis in MCC. METHODS We studied lymphatic microanatomy and lymphangiogenic cytokines in 27 MCC by immunohistology or immunofluorescence (D2-40, lymphatic vessel endothelial hyaluronan receptor [LYVE-1], vascular endothelial growth factor [VEGF] receptor-3, VEGF-C, VEGF-D, Ki67/MiB-1, CD68/PG-M1, CD68/KP1, CD163), Merkel cell polyomavirus-specific polymerase chain reaction, and coanalysis with clinical and histologic data. RESULTS We found a more than 3-fold increase in the mean density of absolute numbers of small lymphatic capillaries (diameter <10 μm) and a more than 8-fold increase in the median ratio of the number of small to large lymphatics (<10/≥10 μm) paratumorally compared with intraindividual controls. VEGF-C(+)CD68(+) CD163(+) cells (interpreted as M2 macrophages) could be identified as an important potentially lymphangiogenesis-inducing cell type. LIMITATIONS Partially lacking follow-up data limited the analysis of the prognostic impact. CONCLUSIONS Our findings strongly indicate lymphangiogenesis in MCC driven by VEGF-C(+)CD68(+) CD163(+) M2 macrophages.

Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus: analysis using tissue microarray

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease. Different pathogenetic mechanisms, including the accumulation of apoptotic keratinocytes in CLE, have been reported. Therefore, we investigated whether CLE and other inflammatory skin diseases differ with regard to the epidermal expression of molecules that are crucial for the initiation and regulation of apoptosis. In this study, 241 skin biopsies from patients with CLE, psoriasis (PSO), lichen planus (LP) and healthy controls (HCs) were analysed immunohistochemically using the tissue microarray (TMA) technique. The TUNEL assay and anti‐activated caspase‐3 antibodies revealed a significant increase of apoptotic keratinocytes in CLE lesions compared with HCs. Furthermore, we detected a significant increase in the epidermal expression of CD95 in CLE specimens compared with PSO, LP and HCs. These data suggest that the accumulation of apoptotic keratinocytes in CLE might be due to the increased epidermal expression of CD95, resulting in increased activity of the extrinsic apoptotic pathway in the disease.

Generalized interstitial granuloma annulare – response to adalimumab

Background  Cause and pathogenesis of granuloma annulare are poorly understood. A foreign‐body granuloma formation induced by an unknown inciting antigen is suspected. Generalized forms often coincides with recalcitrant progression and frustrated experimental therapies.

Keratitis-Ichthyosis-Deafness Syndrome: Response to Alitretinoin and Review of Literature

to 75% of patients achieving a psoriasis area severity index of 75 by week 12. Ustekinumab was well tolerated in initial clinical studies, with very few serious adverse events (0.8% to 1.4%). However, concerns persist regarding long-term susceptibility to infection and malignancy. Patients with congenital deficiency of IL-12 have increased risk of severe infections with intracellular pathogens such as mycobacteria and salmonella. Thus far, no increased infection risk has been shown in patients treated with ustekinumab compared with controls. In addition, animal studies have demonstrated antitumor activity of IL-12 against murine tumors, including melanoma. Although these studies raise the concern for the potential malignancy in patients treated with ustekinumab, it is reassuring that patients with congenital deficits of IL-12 do not have increased rates of malignancy. Though ustekinumab appears to be an efficacious medication for the treatment of psoriasis, long-term follow-up will be required to monitor safety.

Solitary, well-circumscribed, depressed palmar lesion.

ANSWER Circumscribed acral hypokeratosis. Circumscribed acral hypokeratosis (CAH) is a rare idiopathic dermatosis that was first described in 2002. CAH typically affects the thenar or hypothenar eminences of middle-aged to elderly women. The soles are less frequently involved. The clinical presentation usually consists of solitary, asymptomatic, and well-circumscribed patches of depressed skin with a scaly border. Nevertheless, there are cases with multiple lesions and even reports about congenital CAH. Lesions often are long-standing and patients are not clear about the initial presentation. The etiology of CAH remains unclear. Different etiologic hypothesis are reported, including epidermal malformation, infection with human papillomavirus, and repeated minor trauma. Recently, Akaska et al described an abnormal keratin expression in the affected areas. Histology is decisive in diagnosing CAH. Lesions show a depressed epidermis with a sharply demarcated thinned area of stratum corneum that appears to have been punched out from the surrounding thick compact orthokeratin. Lesions are not erosive in that the epidermis is depressed but not absent. The thickness of the granular layer is variable. Some lesions show a normal granular layer, whereas others reveal central hypogranulosis. Atypical keratinocytes and cornoid lamellae are absent. Sometimes the blood vessels in the dermal papillae are dilated. The clinical differential diagnosis of CAH includes Bowen disease, squamous cell carcinoma, basal cell carcinoma, porokeratosis of Mibelli, and traumatic skin erosions. The majority of cases show a benign clinical behavior. Nevertheless, Kanitakis et al reported a case of CAH that underwent premalignant transformation and hypothesized that the absent stratum corneum rendered the underlying epidermis susceptible to photocarcinogenesis. Given this report, patients suffering from CAH might benefit from treatment of the lesions to prevent malignant transformation. Proper treatment is controversial. Different case reports describe topical application of calcipotriol, steroids, and retinoids with variable results. Furthermore, cryotherapy, photodynamic therapy, and complete excision are reported as therapeutic options. In summary, it is still unclear which therapeutic option is consistently effective and whether treatment of CAH is necessary at all, especially because a case of CAH with spontaneous regression has been reported and lesions are generally asymptomatic.

Solitary, well-circumscribed depressed palmar lesion: challenge.

CASE REPORT A 72-year-old white woman, otherwise healthy, presented with a 5-year history of a solitary, sharply marginated flat-based patch of depressed skin on her left thenar eminence (Fig. 1). The lesion was neither painful nor pruritic, and the patient denied any history of trauma. The remaining integument and the oral mucosa revealed no abnormal findings. A punch biopsy was performed and the histopathologic examination showed thick stratum corneum at the periphery and an abrupt step-down in the cornified layer centrally. The zone of hypokeratosis included compact orthokeratin atop thin zones of parakeratosis. Neither cornoid lamellae nor fungal hyphae were present (Fig. 2).