High expression of FOXP3 in primary melanoma is associated with tumour progression.

BACKGROUND The antitumour immune response plays an important role in the prognosis of melanoma. High numbers of circulating regulatory T cells have been associated with rapid disease progression. OBJECTIVES To assess the influence of forkhead box protein (FOXP)3, CD1a and langerin expression on the prognosis of primary melanoma. METHODS We analysed 185 primary melanomas by immunohistochemical staining for expression of the regulatory T-cell marker FOXP3 and the dendritic cell markers langerin and CD1a, and correlated marker expression with clinical outcome. RESULTS Disease-free survival and overall survival were significantly longer in patients expressing low levels of FOXP3 in the primary melanoma, whereas they were associated with high expression of CD1a. The negative prognostic value of FOXP3 expression was independent of the Breslow tumour thickness. Langerin expression did not correlate with the clinical outcome. CONCLUSIONS High expression of FOXP3 in the primary melanoma may be used as an additional independent prognostic marker for early tumour progression in patients with melanoma.

[Primary malignant melanoma of the parotid gland: a case report and review of the literature]

Malignant melanomas (MMs) of the parotid gland are relatively uncommon. They occur almost invariably as metastases from a primary tumour located in the region of the scalp or the mucous membranes of the nose, paranasal sinuses, or throat. Primary MMs arising in the parotid gland are extremely rare. It is assumed that they originate in the glandular tissue or in intraglandular lymph nodes. We present a case report and review of the literature on the diagnosis, treatment, and prognosis of intraparotid malignant melanoma. Diagnosis is based primarily on B-scan ultrasonography and fine-needle aspiration cytology. Patients with a cytological diagnosis of MM are further evaluated by magnetic resonance imaging and positron emission tomography and receive a thorough ear-nose-throat and dermatological examination. The treatment of choice is total parotidectomy and selective neck dissection. The effectiveness of adjuvant treatments such as radiotherapy, chemotherapy, or immunotherapy remains controversial. Patients with primary MMs of the parotid gland appear to have a better prognosis than those with parotid metastases from melanomas of the skin or mucous membranes.

Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D2-40 and MITF1 in Primary Cutaneous Melanoma.

BACKGROUND Lymphovascular invasion (LVI) is associated with adverse outcomes in primary cutaneous melanoma (PCM). Detection of LVI by hematoxylin and eosin staining alone is 0%-6%, but targeting lymphovascular structures increases the detection rate. OBJECTIVE To examine the prognostic significance of LVI detected by immunostaining for D2-40 and microphthalmia-associated transcription factor 1 (MITF1) in PCM. METHODS The authors retrospectively analyzed 120 PCM samples. We compared the LVI detection rates of immunostaining for D2-40 only (22%), double staining for D2-40 and MITF1 (38%), and hematoxylin and eosin, and examined the association of LVI with clinicopathologic variables and clinical outcomes. RESULTS Immunolabeling with both methods significantly increased the LVI detection rate. Double staining for D2-40 and MITF1 as well as D2-40-detected LVI was significantly associated with increased Breslow thickness, number of mitoses, and sentinel lymph node (SLN) metastasis. D2-40-detected LVI was also associated with ulceration. Although the difference was not significant, double staining for D2-40 and MITF1 allowed for easier detection of LVI than D2-40 alone. LIMITATIONS This study was conducted in a tertiary referral institution; therefore, a referral bias cannot be excluded. CONCLUSIONS Immunolabeling increased detection of LVI in PCM. Because LVI is a positive predictive marker for SLN metastasis, the authors propose using anti-D2-40 and anti-MITF1 in the evaluation of LVI in patients with PCM with a certain risk of SLN metastasis.

Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07

The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical trials with temozolomide plus bevacizumab therapy in metastatic melanoma patients are ongoing, although the predictive value of the MGMT promoter methylation status in this setting remains unclear. We assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of metastatic melanoma patients treated with first-line temozolomide and bevacizumab from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In addition, the MGMT expression levels were also analyzed by MGMT immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with response rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in solid tumors) (p<0.05) with a trend to prolonged median progression-free survival (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein expression patterns with heterogeneous and homogeneous nuclear MGMT expression were identified. Negative MGMT expression levels were associated with overall disease stabilization CR+PR+SD versus PD (p=0.05). There was only a poor correlation between MGMT methylation and lack of MGMT expression. A significant proportion of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may be a promising predictive marker for temozolomide therapy in metastatic melanoma patients. Larger sample sizes may help to validate significant differences in survival type endpoints.

Primary perivascular epithelioid cell tumor of the liver not related to hepatic ligaments: hepatic PEComa as an emerging entity

Primary perivascular epithelioid cell tumor (PEComa) of the liver is a very rare example of an emerging family of hepatic PEC tumors. Only few cases have been described so far. We report the case of a large but benign hepatic PEComa in a 53-year-old man without signs of tuberous sclerosis. In contrast to recently described PEC-derived liver tumors in children and young adults, this neoplasm was not related to the hepatic ligaments but had developed deeply within the liver substance. The neoplastic cells displayed the complete phenotype typical for PEComas, i.e. reactivity for several melanoma markers and for smooth muscle actin. The unique relationship of myoid tumor cells to the adventitia of blood vessels prompted us, in comparison with published findings obtained with angiomyolipomas, to comment on the possible origin of the still enigmatic perivascular epithelioid cells.

Excision of fascia in melanoma thicker than 2 mm: no evidence for improved clinical outcome.

BACKGROUND Lack of evidence-based data causes significant variation among surgeons concerning the depth of wide excision for primary cutaneous melanomas. OBJECTIVES To evaluate the clinical effect of excision of the deep fascia in melanomas thicker than 2 mm on patient outcome. METHODS We performed a retrospective cohort review (1996-2012) of patients with melanomas thicker than 2 mm. Included patients underwent excision with a 1-cm margin. Data collected included the patients' sex, age, tumour location, tumour type, Breslow depth and presence of ulceration. Local recurrences, locoregional and distant metastases, and disease-free and overall survival were compared between the fascia-excised and the fascia-preserved groups. RESULTS Out of 2182 patients with malignant melanomas, 213 melanomas thicker than 2 mm, with a median follow-up of 1547 days, were included. The mean age of the patients was 62·6 years and the mean Breslow depth was 4·2 mm. Analysis of data for death attributable to melanoma (P = 0·72), local recurrence (P = 0·71), and locoregional (P = 0·87) and distant metastases (P = 0·34) were not significantly different between the study groups. Furthermore, Kaplan-Meier and Cox regression analysis of both groups showed no evidence of significant difference regarding disease-free [P = 0·35; hazard ratio (HR) 1·25; 95% confidence interval (CI) 0·79-1·97] and overall survival (P = 0·63; HR 1·18; 95% CI 0·61-2·27). CONCLUSIONS We believe that excision of the deep fascia does not improve the outcome of melanomas thicker than 2 mm.