Up to 50% of patients with uveal melanoma develop metastatic disease with poor prognosis. Regional, mainly liver-directed, therapies may induce limited tumor responses but do not improve overall survival. Response rates of metastatic uveal melanoma (MUM) to systemic chemotherapy are poor. Insights into the molecular biology of MUM recently led to investigation of new drugs. In this study, to compare response rates of systemic treatment for MUM we searched Pubmed/Web of Knowledge databases and ASCO website (1980–2013) for “metastatic/uveal/melanoma” and “melanoma/eye.” Forty studies (one case series, three phase I, five pilot, 22 nonrandomized, and two randomized phase II, one randomized phase III study, data of three expanded access programs, three retrospective studies) with 841 evaluable patients were included in the numeric outcome analysis. Complete or partial remissions were observed in 39/841 patients (overall response rate [ORR] 4.6%; 95% confidence intervals [CI] 3.3–6.3%), no responses were observed in 22/40 studies. Progression-free survival ranged from 1.8 to 7.2, median overall survival from 5.2 to 19.0 months as reported in 21/40 and 26/40 studies, respectively. Best responses were seen for chemoimmunotherapy (ORR 10.3%; 95% CI 4.8–18.7%) though mainly in first-line patients. Immunotherapy with ipilimumab, antiangiogenetic approaches, and kinase inhibitors have not yet proven to be superior to chemotherapy. MEK inhibitors are currently investigated in a phase II trial with promising preliminary data. Despite new insights into genetic and molecular background of MUM, satisfying systemic treatment approaches are currently lacking. Study results of innovative treatment strategies are urgently awaited.Forty clinical studies on metastatic uveal melanoma were reviewed regarding responses to systemic treatments. New insights into genetic and molecular background led to investigation of new substances but promising in vitro data have not yet been translated into satisfying treatment responses; however, preliminary results of ongoing studies are highly encouraging.

Summary Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular neoplasm mainly affecting middle‐aged women. Lesions typically affect the head and neck region. ALHE is considered a distinct disease entity different from Kimura's disease, a benign reactive lymphoid proliferation that is predominantly seen in young Asian men although it can affect all ethnic groups. In contrast to ALHE, Kimura's disease is typically associated with peripheral blood eosinophilia, increased serum IgE and lymphadenopathy. Several case reports suggest an overlap between ALHE and Kimura's disease. We review the current literature and discuss whether AHLE and Kimura's disease might represent two extreme variants of the same disease entity.

BackgroundMerkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment.MethodsTo non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT).ResultsSSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal metastases, 100% for bone, and 67% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13%).ConclusionSSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.

The recently proposed entity of cutaneous follicular helper T (T(FH)) cell lymphoma (CT(FH)CL) harbors distinct clinical and histopathologic features. Here, diagnostic pitfalls are exemplified in a case report and by review of the literature. A 45-year-old patient developed rapidly growing nodules and plaques on upper arms and buttocks, which were initially misdiagnosed as primary cutaneous follicle center B-cell lymphoma (CFCL). Consequently, systemic therapy with rituximab failed and consecutive skin biopsies revealed CT(FH)CL (CD3+CD4+CD10+PD-1+bcl6+ICOS+CXCL13+). Interestingly, the prima vista PD-1-positive and CD10-positive tumor cells lost PD-1 expression in follow-up biopsies while retaining CD10, ICOS and CXCL13 expression. All biopsy specimens displayed an identical clonal T-cell population. Initially, nodules were controlled by local radiotherapy and oral psoralen combined with ultraviolet A (PUVA) therapy. However, disease recurred and progressed rapidly with disseminated nodules. Treatment with bexarotene, methotrexate and polychemotherapy failed to stop disease progression. Finally, modified total skin electron beam radiation resulted in complete remission. Disease stabilized on maintenance therapy with bexarotene in combination with ultraviolet A (UVA) therapy. The case highlights that because of concomitant B-cell stimulation, CT(FH)CL clinicopathologically is prone to be mistaken for CFCL. Importantly, CT(FH)CL might lose PD-1 while retaining CD10 expression in later stages, which may lead to confusion in distinguishing CT(FH)CL from CFCL.

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Regional lymphomatoid papulosis (LyP) accounts for 2-27% of all LyP cases. Several localized dermatoses have been reported in association with Becker's melanosis (BM), e.g. acneiform lesions or lichen planus. Here, we report on regional LyP confined to the area of BM. A 56-year-old man presented with a 1-year history of a steadily increasing number of multiple pruritic red papules developing on the area of BM, which had occurred on his left shoulder during puberty. Histopathological analysis was consistent with regional LyP. Potent topical steroids followed by oral doxycycline did not achieve improvement, while long-term oral bexarotene treatment ameliorated the skin condition. Recently, the proposed entity of ‘persistent agmination of LyP' (PALP) has extended the clinicopathological observations of regional LyP. Since PALP remains controversial, a unifying concept of localized LyP and PALP will be discussed.

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