Immunohistochemical analysis of Bcl-2, nuclear S100A4, MITF and Ki67 for risk stratification of early-stage melanoma - A combined IHC score for melanoma risk stratification.

BACKGROUND AND OBJECTIVES: Overall survival (OS) in patients with early-stage malignant melanoma differs. To date, there are no established prognostic markers. We aimed to contribute to a better understanding of potential prognostic immunohistochemical markers for risk stratification. PATIENTS AND METHODS: 161 surgically resected early-stage malignant melanomas (stage pT1 and pT2) were analyzed for expression of 20 different proteins using immunohistochemistry. The results were correlated with OS. The cohort was randomly split into a discovery and a validation cohort. RESULTS: High Bcl-2 expression, high nuclear S100A4 expression as well as a Ki67 proliferation index of ≥ 20 % were associated with shorter OS. Strong MITF immunoreactivity was a predictor for favorable prognosis. A combination of these four markers resulted in a multi-marker score with significant prognostic value in multivariate survival analysis (HR: 3.704; 95 % CI 1.484 to 9.246; p = 0.005). Furthermore, the score was able to differentiate a low-risk group with excellent OS rates (five-year survival rate: 100 %), an intermediate-risk group (five-year survival rate: 81.8 %) and a high-risk group (five-year survival rate: 52.6 %). The prognostic value was confirmed within the validation cohort. CONCLUSIONS: Combined immunohistochemical analysis of Bcl-2, nuclear S100A4, Ki67 and MITF could contribute to better risk stratification of early-stage malignant melanoma patients.

Livedoid vasculopathy: does hyperhomocysteinaemia play an aetiological role?

BACKGROUND: Livedoid vasculopathy (LV) has been shown to be associated with hypercoagulability. However, relevant genetic and exogenous thrombophilic factors are not fully determined. OBJECTIVES: To evaluate the frequency of hyperhomocysteinaemia (HHCE) and genotypes of hypercoagulative factors in LV patients. MATERIAL AND METHODS: Plasma homocysteine level was measured in 42 LV patients. Polymorphism of MTHFR (677C > T and 1298A > C), PAI1 (-675 5G/4G and -844A > G), and F2 (20210G > A), and the F5 Leiden mutation, as well as biochemical parameters for hypercoagulability, were analysed. RESULTS: Of the LV patients, 62% revealed mild HHCE. Polymorphisms of MTHFR were observed in 75% and 56% and the PAI1 -675 5G/4G polymorphism in 100% and 83% of patients with and without HHCE, respectively. All LV patients with renal failure had mild HHCE. A high level of comorbidity of hypertension (99%) and diabetes type 2 (44%) were noted. CONCLUSION: HHCE seems to play a major pathogenetic role in LV. A high prevalence of further procoagulative factors might support the view that LV is a "complex disease".

[Rickettsiosis - Early skin biopsy is essential because of latency in serological findings]. / Rickettsiose.

BACKGROUND: Global travel increasis practitioner's confrontation with very special infectious diseases, like hemorrhagic viral diseases that are traditionally rare in European countries. Prompt diagnosis and subsequent induction of therapy are essential to prevent high rates of severe and lethal complications. ANAMNESIS: A 59-year-old man complained deterioration of general health after a 3-week vacation to South Africa. He presented fever and hemorrhagic erythema with pustula surrounded by necrotic margin on the right calf. COURSE AND THERAPY: On the second day of inpatient treatment, a papulovesiculous, partly hemorrhagic exanthema appeared. With a tentative diagnosis of Rickettsiosis, we performed specific diagnostics by serology and biopsy. Therapy was initiated with doxycycline (200 mg/d) for 7 days. Under this regimen clinical symptoms healed without consequences. Rickettsioses are ubiquitious zoonoses that are caused by various Rickettsia subtypes. The stay in endemic regions together with signs of fever, reduced general health, eschar and exanthema are suspicious for this disease. Therapy should be initiated immediately in cases of clinical suspicion with a characteristic case history. The seroconversion, which appears later in course, should not give reason for avoiding early skin biopsy due to the potentially fatal course of the disease. Biopsy enables early histological proof of a dermal vasculitic inflammation pattern and PCR analysis before subsequent serological controls and proofs.

Malignant melanoma brain metastases: Treatment results and prognostic factors--a single-center retrospective study.

The brain is one of the most frequent locations of metastasis in malignant melanoma. We aimed to identify prognostic factors for overall survival (OS) and local tumor control (LC) in patients with malignant melanoma metastasized to the brain treated by multimodal therapy. All patients diagnosed with malignant melanoma brain metastases between 1992 and 2011 at a single center were registered (n=100, 65% male, 35% female). OS and LC of individual brain metastases were retrospectively analyzed. Subgroup analyses was performed in patients with multiple brain metastasis (n=35) and LC per lesion (n=72) was evaluated in 37 patients. Median age was 57 (27-81) years. Fifty-three percent of patients had 1-2 brain metastases, 47% had >2 and 71% presented with additional extracranial metastases. Primary treatment included systemic therapy alone (temozolomide/fotemustine, 14%), local therapy (surgery and/or stereotactic radiotherapy, 25%), whole-brain radiotherapy (WBRT, 10%), combined WBRT and systemic therapy (18%), local therapy plus WBRT (5%) and combination of local and systemic therapy (8%). Three percent received a tri-modal therapy (WBRT, local and systemic therapy) and 17% refused treatment. Median follow-up in surviving patients was 32 (4-222) months, median OS in all patients 3.9 months (1-year survival 21.4%). Local therapy (p<0.001), systemic therapy (p=0.002), number of brain metastases and primary therapy including a local therapy (p<0.001) were significantly associated with OS. In the subgroup with multiple brain metastases (n=35), a trend (p=0.058) for improved OS after initial treatment with WBRT plus systemic therapy was noted (median OS 3.8 months) and use of these two modalities over the course of the disease was significantly associated with OS (p=0.007). The best LC per single lesion (n=37) could be achieved by combination of local with systemic therapy (p=0.011). Number of brain metastases, extracranial metastases and use of local therapy are independent prognostic factors in melanoma metastatic to the brain. LC and OS can be improved by combining local with systemic treatment. In patients with multiple brain metastases, WBRT plus systemic therapy provides superior OS.

Flagellate dermatitis after consumption of Shiitake mushrooms.

Flagellate dermatitis occurs in patients who have eaten Shiitake mushrooms. We are reporting on a 55-year-old man, who developed whiplash-striped, severely itching efflorescences on the trunk 3 days after eating Lentinula edodes. Flagellate dermatitis is also known as a cutaneous side effect of bleomycin therapy.