Contextual role of E2F1 in suppression of melanoma cell motility and invasiveness.

The general transcription factor E2F1 reportedly functions in a protumorigenic manner in several cancer models. We show that the genetic context of cancer cells influence E2F1's role to impede the protumorigenic role. Thirty to fifty percent of melanoma patients carry mutant BRAF with about 90% of mutant BRAF melanomas being V mutation.

Desmosomal defects in acantholytic squamous cell carcinomas.

Background: Acantholytic squamous cell carcinoma (Acantholytic SCC) are epithelial tumors characterized by a loss of cell adhesion between neoplastic keratinocytes. The mechanism underlying loss of cell-cell adhesion in these tumors is not understood.

Methods: A retrospective analysis of acantholytic SCC (n = 17) and conventional SCC (n = 16, controls not showing acantholysis) was conducted using a set of desmosomal and adherens junction protein antibodies.

HLA antigen expression in melanocytic lesions: is acquisition of HLA antigen expression a biomarker of atypical (dysplastic) melanocytes?

Background: Although criteria are established for the histologic diagnosis of atypical nevi (AN), consensus about the criteria in the diagnosis of and in the definition of AN is limited. Moreover, intraobserver and interobserver differences in the application of these criteria for the diagnosis of AN have been observed.

Objective: We sought to determine the usefulness of HLA antigen expression as a biomarker of AN.

Loss of Desmocollin 3 in skin tumor development and progression.

Desmocollin 3 (DSC3) is a desmosomal cadherin that is required for maintaining cell adhesion in the epidermis as demonstrated by the intra-epidermal blistering observed in Dsc3 null skin. Recently, it has been suggested that deregulated expression of DSC3 occurs in certain human tumor types. It is not clear whether DSC3 plays a role in the development or progression of cancers arising in stratified epithelia such as the epidermis.

A mediator of Rho-dependent invasion moonlights as a methionine salvage enzyme.

RhoA controls changes in cell morphology and invasion associated with cancer phenotypes. Cell lines derived from melanoma tumors at varying stages revealed that RhoA is selectively activated in cells of metastatic origin. We describe a functional proteomics strategy to identify proteins regulated by RhoA and report a previously uncharacterized human protein, named "mediator of RhoA-dependent invasion (MRDI)," that is induced in metastatic cells by constitutive RhoA activation and promotes cell invasion.

Imiquimod-induced vitiligo after treatment of nodular basal cell carcinoma.

An 84-year-old male presented with recurrent nodular infiltrative basal cell carcinoma on the left shoulder. The patient was treated with curettage followed by the application of topical imiquimod 5% cream five times a week. The patient discontinued imiquimod after a total of 18 applications because of local inflammation.

Tattoo pigment interpreted as lymph node metastasis in a case of subungual melanoma.

We present a patient with subungual melanoma of the thumb who, during radioisotope-guided selective sentinel lymphadenectomy, was found to have black, hard lymph nodes at multiple axillary node levels. This finding was interpreted intraoperatively as clinical evidence of metastasis and a formal axillary dissection was carried out. Pathological examination of excised nodes failed to demonstrate metastasis but instead showed collections of tattoo pigment.

Human papillomavirus infection and ultraviolet light exposure as epidermoid inclusion cyst risk factors in a patient with epidermodysplasia verruciformis?

Epidermoid inclusion cysts are common lesions with unclear etiology. We sought to examine evidence for human papillomavirus (HPV) infection and ultraviolet light (UV) exposure as risk factors in the formation of epidermoid inclusion cysts. We performed HPV typing of biopsied cysts with polymerase chain reaction for a patient with darkly-pigmented skin, epidermodysplasia verruciformis (EV) and more than 250 photodistributed cysts.

Gastrointestinal melanoma or clear cell sarcoma? Molecular evaluation of 7 cases previously diagnosed as malignant melanoma.

Clear cell sarcoma (CCS) is a rare tumor classically associated with the tendons and aponeuroses of distal extremities of young adults. CCS and malignant melanoma (MM) share immunohistochemical profiles and ultrastructural features, but classic CCS has characteristic morphology with low mitotic activity and minimal pleomorphism. Occasional cases show pleomorphism, high mitotic index, and/or melanin pigmentation, making CCS indistinguishable from MM based on morphology.

Platelet-derived growth factor receptor alpha mutational status and immunohistochemical expression in Merkel cell carcinoma: implications for treatment with imatinib mesylate.

Background: It is not known if Merkel cell carcinomas (MCCs) show mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene similar to a subset of gastrointestinal stromal cell tumors. The purpose of this study was to analyze MCCs for mutations in the PDGFRA gene as well as to analyze those MCCs exhibiting a possible mutation in the PDGFRA gene for immunohistochemical expression of PDGFRA.

Methods: We extracted tumor DNA from nine MCCs, performed polymerase chain reaction amplification of PDGFRA exons 10, 12, 14 and 18, and directly sequenced those gene products for mutations.

Pustulo-ovoid bodies of Milian in granular cell tumors.

Background: Granular cell tumors (GCTs) are benign neural tumors with a distinct histologic appearance on light microscopy, characterized by eosinophilic cytoplasmic granules. Pustulo-ovoid bodies of Milian (POB) are larger granules surrounded by a clear halo. There have been no histologic studies to document their prevalence in GCT.

Merkel cell carcinoma: evaluation of KIT (CD117) expression and failure to demonstrate activating mutations in the C-KIT proto-oncogene - implications for treatment with imatinib mesylate.

Background: Merkel cell carcinomas (MCCs) express the tyrosine kinase receptor KIT. However, it is not known if MCCs have activating mutations in KIT that would make them responsive to treatment with imatinib mesylate. The purpose of this article is to describe the KIT immunohistological staining pattern (CD117) of MCCs and analyze those MCCs for mutations in areas of KIT where mutations are found in gastrointestinal stromal cell tumors.

Granulomatous reaction to titanium alloy: an unusual reaction to ear piercing.

A 68-year-old man presented with 4 firm, flesh-colored, and slightly erythematous nodules located on the superior pole and lobule of each ear. Although reluctant to provide details, it was discovered he had pierced his ears approximately 10 years earlier, and the nodules developed at the sites of the piercings. Keloids were suggested clinically and the lesions were excised.

Kindler syndrome: a new mutation and new diagnostic possibilities.

Background: Kindler syndrome (KS) is a rare genetic disorder that is characterized by blistering in infancy, followed by the onset of poikiloderma and photosensitivity in childhood. The recently elucidated molecular pathogenesis involves mutations in KIND1, a gene encoding the protein kindlin-1, which is involved in the attachment of the actin cytoskeleton to the extracellular matrix in basal keratinocytes.

Observations: We describe a child with the neonatal diagnosis of epidermolysis bullosa simplex who developed poikiloderma and skin fragility at 6 years of age.

Expression of c-kit (CD117) in Spitz nevus and malignant melanoma.

Background: CD117, the receptor for kit-ligand, which is a growth factor for melanocyte migration and proliferation, has shown differential staining in various benign and malignant melanocytic lesions. The purpose of this study is to compare CD117 immunohistological staining in Spitz nevus versus malignant melanoma, to determine whether CD117 can aid in the diagnosis of these two lesions.

Methods: CD-117 immunohistological staining was performed in 22 clinically and pathologically diagnosed pigmented lesions including 9 cases of Spitz nevus, 10 cases of primary MM and 3 cases of metastatic melanoma.

Atypical IgA/IgG pemphigus involving the skin, oral mucosa, and colon in a child: a novel variant of IgA pemphigus?

Immune-mediated blistering diseases are rare in childhood, with the subset of IgA pemphigus being extremely uncommon. A child with a bullous disorder of the oral mucosa, skin, and colon is reported because of the unusual nature of the clinical and laboratory findings. Immunofluorescence studies demonstrated both intercellular epidermal and basement membrane zone deposition of IgA and IgG antibodies, as well as intercellular colonic deposition of IgA antibodies.

Congenital curvilinear palpable hyperpigmentation.

We report two cases of congenital curvilinear palpable hyperpigmentation on the posterior aspect of bilateral legs in male infants. These lesions appeared shortly after birth and mimicked child abuse with looped cord or postinflammatory hyperpigmentation. Histopathologic features showed lentiginous melanocytic hyperplasia.

Completely regressed primary cutaneous malignant melanoma with nodal and/or visceral metastases: a report of 5 cases and assessment of the literature and diagnostic criteria.

Background: Partial regression of primary cutaneous malignant melanoma is not uncommon and may predict a higher likelihood of metastasis and decreased survival. Complete histologic regression of a primary cutaneous melanoma is a rarer occurrence, with only 34 cases reported in the English-language or English language-summarized literature.

Observation: We detail 4 cases of complete histologic regression of primary cutaneous melanoma, discovered at presentation with metastatic disease.

Vulvar clear cells of Toker: precursors of extramammary Paget's disease.

Clear cells of Toker are intraepithelial cells with clear to pale staining cytoplasm and bland cytologic features found with H&E staining in approximately 10% of normal nipples. Toker cells have been hypothesized as a precursor of extramammary Paget's disease (EMPD), although Toker cells have not been identified as a normal component of genital skin. Using immunohistochemistry, we studied 11 vulvectomies for the presence of Toker cells in association with mammary-like glands of the vulva (MLG).