Sentinel lymph nodes (SLNs), being the first nodes to receive lymph from a primary tumour and the preferential site of initial tumour metastases, are intensively exposed to the bioactive products of tumour cells and other associated cells. This makes them ideal for studies of the factors that determine selective tissue susceptibility to metastases. We postulate that tumour-induced immune modulation of SLNs facilitates lymph-node metastases by inhibiting the generation of tumour-specific cytotoxic T cells that are active against tumour cells of primary and metastatic melanomas. Immune modulation of the lymph nodes can be reversed by granulocyte/macrophage colony-stimulating factor (GM-CSF), a finding that has implications for the future therapy of lymph-node metastases.

Down-regulation of the immune system facilitates tumor progression at different stages of cutaneous melanoma. Sentinel nodes, the first lymph nodes on lymphatics draining directly from a primary melanoma are immune down-regulated by tumor-generated immune-suppressive cytokines including interleukin-10. To better understand the kinetics of sentinel node suppression, we investigated interleukin-10 expression by melanoma cells and tumor-associated macrophages and lymphocytes at different stages of primary melanoma evolution. We used reverse transcriptase in situ polymerase chain reaction to identify cellular sources of interleukin-10 mRNA in 39 melanomas. Interleukin-10 mRNA was identified in tumor cells of 2/6 melanomas in situ (33%), 17/21 invasive melanomas (81%) and 11/12 metastatic melanomas (92%). Higher interleukin-10 expression correlates with tumor progression, with differences between melanoma in situ, invasive melanoma and metastatic melanoma. In primary melanomas, the interleukin-10 mRNA content of tumor cells correlates with Clark level. There was significantly more interleukin-10 mRNA in vertical growth phase melanoma cells than in radial growth phase cells. In a logistic regression model, moderate to high interleukin-10 mRNA expression by tumor cells was significantly associated with vertical growth phase melanoma. Interleukin-10 mRNA was detected in melanoma-associated macrophages and lymphocytes. In invasive melanomas, the interleukin-10 mRNA reactivity of macrophages declined as Clark level increased. Alterations of immunity by interleukin-10 derived from melanoma cells and melanoma-associated macrophages and lymphocytes potentially facilitate evolution of the primary melanoma and render regional lymph nodes susceptible to metastases.

Background Angiosarcomas are malignant mesenchymal neoplasms, including sarcomas of presumptive vascular endothelial origin and sarcomas of probable lymphatic origin. It is, however, often difficult to determine whether they are from blood vascular or lymphatic endothelium. The majority of angiosarcomas are thought to originate from vascular endothelia and spread via bloodstream to lung, but lymphatic metastases can occur. Methods We investigated immunohistochemical expression of vascular endothelial growth factors (VEGF‐A, VEGF‐C) and their receptors (VEGFR‐1, VEGFR‐2, VEGFR‐3) in a series of 34 angiosarcomas. Results VEGF‐A was expressed by 32/34 (94%), VEGF‐C by 4/34 (12%), VEGFR‐1 by 32/34 (94%), VEGFR‐2 by 22/34 (65%), and VEGFR‐3 by 27/34 (79%). Patients who expressed low or no VEGFR‐2 showed a significantly unfavorable prognosis by log‐rank test (P = 0.010) and multivariate analysis (hazard ratio, 5.16; 95% CI, 1.40–19.04; P = 0.014). VEGFR‐1 and VEGFR‐3 were not significantly associated with patients' prognosis. Conclusions VEGF‐A and VEGFR‐1 were detected in diverse subtypes of angiosarcomas. In cooperation, VEGF‐A and VEGF‐C are likely to be involved in the development of angiosarcoma associated with lymphedema. VEGF‐C expression may cause susceptibility to lymphatic metastasis through tumor lymphangiogenesis. Angiosarcoma of the scalp, which is traditionally considered as a true hemangiosarcoma, may include some cases of lymphatic origin. J. Surg. Oncol. 2008;97:74–81. © 2007 Wiley‐Liss, Inc.

p53 mutation is one of the major results of ultraviolet (UV) radiation. UV photoproducts of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (64PPs) also play an important role in skin cancer development. Atypical fibroxanthoma (AFX), which mimics malignant fibrous histiocytoma (MFH) histologically, occurs in the sun-exposed skin of the elderly, and therefore, an association with UV has long been suspected. Eighteen fibrohistiocytic skin lesions comprising AFX (n = 7), storiform-pleomorphic type MFH centered in the subcutis (superficial MFH; S-MFH; n = 4) and benign fibrous histiocytoma (BFH; n = 7) were used for immunohistochemical and molecular analysis. Eight cases of deep MFH (D-MFH) were also analyzed for UV photoproduct expression for the purposes of comparison. Immunohistochemically, the CPD scores of AFX (3.6 +/- 0.4) were significantly higher than those of S-MFH (1.3 +/- 0.8), D-MFH (0.8 +/- 0.5), or BHF (1.4 +/- 0.7); however, the 64PP scores were extremely low in all these tumors (AFX, 0.1 +/- 0.1; S-MFH, 0.0 +/- 0.0; D-MFH, 0.0 +/- 0.0; and BHF, 0.0 +/- 0.0). AFX, S-MFH, and BFH showed immunoexpression for p53 (2/7, 2/4, and 0/7), respectively. p53 mutations were detected in AFX (4/6; 67%) and S-MFH (1/4; 25%), but not in BFH (0/5; 0%) using polymerase chain reaction-single-strand conformation polymorphism, and all of the mutations in AFX were either C-T transitions or at dipyrimidine sites. In conclusion, AFX and S-MFH are both similar fibrohistocytic lesions; however, AFX has high immunoreactivity for CPDs compared with S-MFH, D-MFH, or BFH. These data suggest that CPDs may play an important role in the pathogenesis of AFX.

Acquired generalized hypohidrosis/anhidrosis is a rare condition of unknown pathogenesis, while idiopathic cholinergic urticaria is relatively common. We report the case of a 19-year-old male with cholinergic urticaria and acquired generalized hypohidrosis, and review previously published similar cases of this association.