Differential Clinicopathological Features in Spontaneous Regression of Melanomas and Melanocytic Naevi.

The aim of this study was to determine the clinical, histological and/or immunohistochemical features that enable differential diagnosis of regression of melanocytic naevi from regression of melanomas. All melanocytic neoplasms with histologically-confirmed regression diagnosed in our hospital between 2002 and 2009 were reviewed retrospectively. Lamellar and delicate fibrosis were associated with melanocytic naevi (p <0.0001 and p = 0.021, respectively). Compact fibrosis, high vessel density and higher number of granzyme B+ lymphocytes were associated with malignant melanoma (p = 0.011, p = 0.005 and p = 0.013, respectively). Density of inflammatory infiltrate (p = 0.016), vascular proliferation (p = 0.005), epidermal atrophy (p = 0.009), rate of apoptosis (p = 0.046) and granzyme B immunoreactivity (p = 0.013) was more common in severe-dysplastic naevi and melanomas than in the remaining melanocytic naevi. Logistic regression demonstrates that 5 variables (age, lamellar fibrosis, melanophages, vessel density, and granzyme B immunostaining) would serve to classify appropriately 87% of melanomas among melanocytic lesions with complete regression.

Histiocytosis with mixed cell populations.

Langerhans cell histiocytosis (LCH) and juvenile xanthogranuloma (JXG) are thought to originate from a common stem cell precursor, with divergent differentiation under different microenvironmental conditions. We describe an exceptional case of multiple cutaneous lesions in a 10-year-old boy, in which the coexistence of both LCH and JXG cell populations is found in every single lesion. The presence of Birbeck granules and CD207 (langerin) immunostaining in the LCH component would argue against the diagnosis of indeterminate cell histiocytosis (ICH). This unique case gives additional support to the hypothesis of a potentially common histogenesis for LCH and JXG.

Parvovirus B19-Associated Microvesicular Eruption.

We report on a 3-year-old girl with a microvesicular generalized rash in whom primary infection by parvovirus B19 was demonstrated by seroconversion. To our knowledge, this is the first instance of an eruption arising from parvovirus B19 with this peculiar clinical pattern.

Deregulation of glyceraldehyde-3-phosphate dehydrogenase expression during tumor progression of human cutaneous melanoma.

BACKGROUND/AIM: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a highly abundant housekeeping gene. GAPDH overexpression has been reported in diverse types of human cancers including cutaneous melanoma. Our goal was to quantify GAPDH mRNA and protein expression in the whole spectrum of primary and metastatic melanomas in the search for a specific role for this ubiquitous molecule during tumor progression. MATERIALS AND METHODS: Intratumoral GAPDH mRNA expression was quantified by real-time PCR in 71 cases, including 29 primary melanomas and 42 metastatic cases. Relative expression levels in thin (≤1 mm) and thick (>1 mm) primary tumors and 'in-transit', lymph node and distant metastases were compared. Similarly, protein expression was investigated by means of immunohistochemistry. Specific exons of GAPDH were analyzed by DNA sequencing. RESULTS: GAPDH mRNA expression was significantly up-regulated in thick melanomas when compared to primary thin melanomas. Similar differences were also encountered between metastatic melanomas when compared to lymph-node metastatic melanomas. Interestingly, GAPDH protein immunoexpression was higher in thick melanomas and distant metastases than in thin tumors and lymph node metastases, respectively. However, no specific point-mutations in GAPDH-specific exons were found in any patient. CONCLUSION: Deregulation of GAPDH during melanoma progression was demonstrated in our series by mRNA and protein expression studies.

Spontaneous regression of multiple melanocytic nevi after melanoma: report of 3 cases.

Complete spontaneous regression of multiple melanocytic nevi after melanoma is an extremely rare phenomenon. We report 3 cases of patients with a history of melanoma that showed regression of almost all melanocytic nevi over time. One of the patients had 2 simultaneous primary cutaneous melanomas without metastasis. In the other 2 patients, regression of the melanocytic nevi was seen after the development of metastasis in lymph nodes. These patients had spontaneously developed an efficient immune response against melanocytes, and they would represent paradigmatic examples of the spontaneous immune responses in melanoma patients. Better understanding of the mechanisms involved in the complete regression of melanocytic lesions would lead to a better selection of melanoma patients for immunotherapy.

Complete regression of a melanocytic nevus under intense pulsed light therapy for axillary hair removal in a cosmetic center.

Intense pulsed light (IPL) therapy using noncoherent broad-spectrum light has been reported to be effective for hair removal, and also for treating superficial pigmented lesions like ephelides and solar lentigines. We report complete regression of a pigmented melanocytic nevus, histologically confirmed, after hair removal treatment with IPL. The use of lasers and IPL is a common procedure used by dermatologists and even other professions for the treatment of cosmetically troubling skin conditions. The main advantage of such treatment is a reduction of surgical scars, thus producing a favorable cosmetic outcome, but a major limitation is that histopathologic diagnosis is not usually obtained prior to treatment. Such devices should be carefully used in patients with potentially dangerous melanocytic lesions. We also review the recent literature regarding inadequate treatment of melanocytic lesions with lasers.

CCL27-CCR10 and CXCL12-CXCR4 chemokine ligand-receptor mRNA expression ratio: new predictive factors of tumor progression in cutaneous malignant melanoma.

CXCR4, CCR7 and CCR10 chemokine receptors are known to be involved in melanoma metastasis. Our goal was to compare the relative intratumoral mRNA expression of these receptors with that of their corresponding chemokine ligands, CXCL12, CCL19, CCL21, and CCL27 across the full spectrum of human melanoma progression: thin and thick primary melanomas, as well as "in transit", lymph node, and distant metastases. Expression was quantified by real-time RT-PCR in 103 melanoma samples: 51 primary tumors and 52 metastases. Particular emphasis was focused on chemokine ligand-receptor expression ratios. Immunohistochemistry was performed to identify the cell types expressing these molecules. CXCL12-CXCR4 and CCL27-CCR10 ratios were higher in thin than in thick primary melanomas, and all four chemokine-receptor ratios were higher in primary tumors than in melanoma metastases. CCL27-CCR10 and CXCL12-CXCR4 expression ratios in primary tumors were inversely associated with the development of distant metastases, and improved the predictive value of tumor thickness for distant metastasis, which is important since chemokine ligand-receptor ratios are not affected by the endogenous gene employed for normalizing mRNA expression. Both receptor and ligand immunolabeling were detected in neoplastic cells suggesting autocrine mechanisms. Our results support the concept that low CCL27/CCR10 and CXCL12/CXCR4 intratumoral mRNA ratios are associated with melanoma progression, and in combination with Breslow thickness, are the best predictive factors for the development of distant metastases in primary cutaneous melanoma.

Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy.

To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non-alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease.