Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women.

Smoking has been considering a crucial factor in promoting skin and systemic aging that is associated with the development of a low-level, systemic, chronic inflammation known as "inflammaging" in which monocytes play a pivotal role. Our aim was to investigate the effects of AM3 plus antioxidants vs placebo in the activation status, function of monocytes and cutaneous aging parameters in healthy smoker middle-aged women. A total of 32 women were 1:1 randomly assigned to AM3 plus antioxidants or placebo for three months. Peripheral mononuclear blood cells and cutaneous biopsy were obtained and flow cytometry and immunohistological studies, respectively, were performed before and after the treatment. AM3 plus antioxidants treatment compared with placebo significantly reduced the monocyte production of the proinflammatory interleukin 1 (IL-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) cytokines as well as increased the regulatory IL-10 in middle-aged smoker women. Furthermore, AM3 and antioxidants did not modify ROS production by monocytes and granulocytes but increased their phagocytic activity. The active combination also stimulated a significative increase in reticular dermis depth as well as an increase in the expression of CD117 and CD31. Thus, AM3 and antioxidants treatment reduces the systemic proinflammatory monocyte disturbance of heathy smoker middle-aged women and encourage skin repair mechanisms.

Syringotropic Melanoma: A Diagnostic Challenge With Prognostic Implications.

ABSTRACT: The presence of neoplastic melanocytes within the eccrine apparatus into the reticular dermis and/or subcutaneous tissue is extremely rare. The staging of syringotropic melanomas and their biological behavior are still controversial. We present 6 new cases of syringotropic melanoma and their main histopathologic features; review the previous literature; and discuss about the origin, staging, and prognosis of this rare variant of melanoma.

Pigmented epidermotropic breast cancer metastases: A rare variant with a particularly unusual feature.

Pigmented epidermotropic breast cancer metastases are a rarity, often clinically misdiagnosed as melanocytic lesions. Histopathologically, they show a dermal proliferation of neoplastic metastatic cells that extend to the overlying epidermis in a pattern identical to that seen in primary Paget disease (PD). Differential diagnosis should be established with entities with a similar presentation, such as pigmented mammary PD and malignant melanoma. Immunohistochemistry may be useful for this purpose. We present a new case of pigmented epidermotropic breast cancer metastases with a particularly unusual feature: the absence of dermal infiltration by neoplastic cells, thus considered as pure epidermotropic metastatic involvement.

Cutaneous eruption with reactive endothelial atypia due to emerging targeted cancer therapies: Report of two cases with clinico-pathologic correlation.

Targeted anticancer therapy is being used with greater frequency and dermatologic toxicities are among the most frequent adverse events of these drugs. However, histopathological features of these adverse events are not yet well characterized. We present two cases of clinically different cutaneous toxicities on two patients with hematologic neoplasia. They were treated with different drugs and in both cases medications shared inhibition of PI3K as mechanism of action. The skin biopsy specimen showed endothelial cell atypia with large nuclei and mitotic figures. To the best of our knowledge, no other cases with these striking histopathologic findings have been reported with PI3K inhibitors or other anticancer targeted therapy.

Three additional cases of non-neural granular cell tumor with novel immunohistochemical findings.

BACKGROUND: Non-neural granular cell tumor (NNGCT) is an uncommon neoplasm of controversial histogenesis and its histopathologic differential diagnosis includes, in addition to conventional GCT, other dermal tumors that may exhibit granular cell change. METHODS: Three patients with a diagnosis of NNGCT were identified in the authors' files. Hematoxylin and eosin-stained sections and immunohistochemical studies were performed. RESULTS: Histopathological study of the three lesions showed dermal proliferation of granular cells arranged in thick fascicles between collagen bundles. The lesions showed positivity for Factor XIIIa, CD163, CD68, NKIC3, vimentin, ALK, fascin, and cyclin D1. CONCLUSION: To our knowledge, positivity for cyclin D1 has not been reported to date in NNGCT. In borderline cases, where the diagnosis is unclear despite histopathologic and immunohistochemical findings, positivity for cyclin D1 may favor the diagnosis of NNGCT. Further investigations to assess the differentiation of this rare neoplasm are needed.

Mycosis fungoides progression could be regulated by microRNAs.

Differentiating early mycosis fungoides (MF) from inflammatory dermatitis is a challenge. We compare the differential expression profile of early-stage MF samples and benign inflammatory dermatoses using microRNA (miRNA) arrays. 114 miRNAs were found to be dysregulated between these entities. The seven most differentially expressed miRNAs between these two conditions were further analyzed using RT-PCR in two series comprising 38 samples of early MFs and 18 samples of inflammatory dermatitis. A series of 51 paraffin-embedded samples belonging to paired stages of 16 MF patients was also analyzed. MiRNAs 26a, 222, 181a and 146a were differentially expressed between tumoral and inflammatory conditions. Two of these miRNAs (miRNA-181a and miRNA-146a) were significantly deregulated between early and advanced MF stages. Bioinformatic analysis showed FOXP3 expression to be regulated by these miRNAs. Immunohistochemistry revealed the level of FOXP3 expression to be lower in tumoral MFs than in plaque lesions in paraffin-embedded tissue. A functional study confirmed that both miRNAs diminished FOXP3 expression when overexpressed in CTCL cells. The data presented here suggest that the analysis of a restricted number of miRNAs (26a, 222, 181a and 146a) could be sufficient to differentiate tumoral from reactive conditions. Moreover, these miRNAs seem to be involved in MF progression.

Plaque-Like Pilar Sheath Acanthoma: Histopathologic and Immunohistochemical Study of 3 Unusual Cases.

Pilar sheath acanthoma is an uncommon, benign follicular neoplasm that frequently presents as a solitary lesion. This neoplasm usually appears on the skin around the upper lip of elderly patients. Histopathologically, the neoplasm usually shows a cystic configuration with epithelial lobules resembling to those of the outer root sheath of the hair follicle at the level of the isthmus emanating radially from the cyst wall. We present 3 peculiar cases of a pilar sheath acanthoma showing a plaque-like architecture because the lesions exhibited a horizontal configuration. To our knowledge, there are no previously reported examples of plaque-like pilar sheath acanthoma.

ALK-mutated non-small-cell lung cancer: a new strategy for cancer treatment.

The anaplastic lymphoma kinase (ALK) tyrosine kinase (TK) receptor has emerged recently as a potentially relevant biomarker and therapeutic target in solid and hematologic tumors. A variety of alterations in the ALK gene, such as mutations, overexpression, amplification, translocations, or other structural rearrangements, have been implicated in human cancer tumorigenesis. In this article we review the potential role that ALK may have in lung tumor origin, the methodology to detect the different molecular alterations, and the most important clinical aspects of ALK alterations in NSCLC patients.