Deep Shave Removal of Suspected Basal Cell Carcinoma: A Prospective Study.

BACKGROUND: Diagnosis and treatment of basal cell carcinoma (BCC) in the same visit by shave removal may decrease health care spending and promote patient satisfaction. OBJECTIVE: To prospectively evaluate deep shave removal of lesions clinically suspicious for low-risk BCC on the trunk or extremities in immunocompetent patients. MATERIALS AND METHODS: Deep shave removal with the intent to remove the entire tumor was performed from January 2015 to June 2016, and patients were followed prospectively for clinical evidence of tumor recurrence. RESULTS: Seventy-seven lesions were removed from 51 patients, including 29 (37%) superficial and nodular BCCs, 27 (35%) superficial BCCs, 16 (21%) nodular BCCs, and 5 (6%) non-BCCs. Fifteen BCCs (21%) had positive residual margins after deep shave removal, which was significantly more likely to occur in nodular compared with superficial BCCs (odds ratio = 7.8, 95% confidence interval = 1.4-43), and underwent re-excision. Fourteen specimens initially reported to have negative margins after deep shave underwent resectioning, which revealed positive margins in 4 specimens (28.6%). No BCCs have recurred clinically after an average follow-up of 50 months (SE 3.2). CONCLUSION: Consider deep shave removal for low-risk BCCs on the trunk or extremities in immunocompetent patients hoping to avoid a second treatment visit.

Histopathologic Spectrum of Morphea.

ABSTRACT: Morphea is an autoimmune skin disease with protean clinical manifestations. Histologic features are similarly variable, and skin biopsies may be nondiagnostic. A single-institution retrospective cohort study was conducted. Morphea patients who had a biopsy in 2005-2015 were included, and a histopathological review was conducted by 2 pathologists. There were 51 biopsy specimens from 40 subjects. The most common histologic features were dermal sclerosis (90%), dermal thickening (78%), collagen homogenization (86%), a superficial and deep infiltrate (76%), a moderate-abundant inflammatory infiltrate (73%), and periadnexal fat loss/decreased skin appendages (71%). Twenty-four specimens were not diagnostic of morphea. In these specimens, the main clues to diagnosis included the presence of dermal sclerosis (79%), subtle collagen homogenization (75%), dermal thickening (58%), moderate-to-abundant plasma cells (50%), and perineural inflammation (50%). There were no statistically significant differences between active and inactive lesions, nor untreated and treated lesions. The histopathologic features of morphea are variable and a high proportion of biopsies are not diagnostic. Clinicians and pathologists should have a high degree of suspicion to correctly make the diagnosis of morphea.

Intermediate heparan sulfate binding during HPV-16 infection in HaCaTs.

Human papillomavirus (HPV) is the most prevalent sexually transmitted disease in the United States and can cause cancer with persistent infection. The most common cancer caused by HPV is cervical carcinoma with an average of 12,000 cases reported every year in the United States. Worldwide, over 500,000 cases of cervical cancer are reported yearly with over 250,000 deaths attributed to the disease. Although much is known about the serious health risks associated with HPV infection, there is still much to be discovered about how HPV binds and enters target cells. Understanding is required on how HPV infections will lead to strategies and therapies for reducing the number of infections and HPV-related diseases, including cancers. The HPV viral particle is composed of 2 viral proteins, L1 and L2. Data suggest that binding of the viral capsid to cells is dependent on the L1 protein. We hypothesize that this initial binding to a heparan sulfate is composed of 2 independent events: the first results in a structural change that exposes a hidden portion of the L1 protein leading to a second binding event on the heparan sulfate. Our experiments tested if this "hidden" portion of L1 is necessary for infection and explored the nature of this binding. We generated a peptide with the sequence of the "hidden" portion of L1. Infection of HaCaT cells in the presence of this peptide is highly reduced. Our results suggest that the binding of the L1 C-terminal domain is dependent on amino acid sequence and is necessary for infection.

Dynasore inhibits removal of wild-type and DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) from the plasma membrane.

Dynasore, a small molecule inhibitor of dynamin, was used to probe the role of dynamin in the endocytosis of wild-type and mutant CFTR (cystic fibrosis transmembrane conductance regulator). Internalization of both wild-type and 'temperature-corrected' DeltaF508 CFTR was markedly inhibited by a short exposure to dynasore, implicating dynamin as a key element in the endocytic internalization of both wild-type and mutant CFTR. The inhibitory effect of dynasore was readily reversible upon washout of dynasore from the growth media. Corr-4 ({2-(5-chloro-2-methoxy-phenylamino)-4'-methyl-[4,5']-bithiazolyl-2'-yl}-phenyl-methanonone), a pharmacological corrector of DeltaF508 CFTR biosynthesis, caused a marked increase in the cell surface expression of mutant CFTR. Co-incubation of DeltaF508 CFTR expressing cells with Corr-4 and dynasore caused a significantly greater level of cell surface CFTR than that observed in the presence of Corr-4 alone. These results argue that inhibiting the endocytic internalization of mutant CFTR provides a novel therapeutic target for augmenting the benefits of small molecule correctors of mutant CFTR biosynthesis.

Peritoneal mesothelioma presenting as a skin nodule.

Mesothelioma is a malignancy of the pleura, pericardium and peritoneum that is rarely seen in cutaneous biopsies. We present a case of a 75-year-old man with significant occupational exposure to asbestos who developed peritoneal mesothelioma that presented as a skin nodule in an old appendectomy scar. The patient presented with a complaint of increased hardness along his appendectomy scar. Physical examination revealed an anterior abdominal wall mass overlying the appendectomy scar, which was subsequently biopsied. Histologic examination of the abdominal wall mass revealed an infiltrating epithelioid and papillary neoplasm within the dermis and subcutaneous tissue. Immunohistochemical stains showed immunoreactivity for cytokeratin (CK) 7, CK 5/6, calretinin and vimentin. CK 20, monoclonal carcinoembryonic antigen, prostate-specific antigen and prostate-specific acid phosphatase were negative. The profile supported the diagnosis of mesothelioma. Cutaneous presentation of mesothelioma is rare but should be considered in the differential diagnosis of patients with significant asbestos exposure.

HPV16 and BPV1 infection can be blocked by the dynamin inhibitor dynasore.

The initial entry of papillomaviruses into their target cells has been shown to occur by clathrin-mediated endocytosis and caveolae-mediated endocytosis. These mechanisms entail the formation of nascent-coated vesicles at the plasma membrane. Such coated vesicles, clathrin or caveolin, form and pinch-off in a controlled mechanism that involves several proteins including dynamin. Dynamin is a GTPase that forms a dynamin ring at the stem connecting the nascent vesicle to the plasma membrane. In a still not fully characterized mechanism, dynamin's contraction and twisting results in the scission of the vesicle. In an effort to better characterize the role and molecular mechanisms of dynamin's function, researchers have identified dynasore, a dynamin GTPase inhibitor that prevents the scission of dynamin-dependent endocytic vesicles. Here, we have tested if infection by pseudovirus corresponding to the oncogenic human papillomavirus type 16 and bovine papillomavirus type 1 can be blocked by dynasore. We present data demonstrating that dynasore can block infection of human papillomavirus type 16 and bovine papillomavirus type 1 pseudovirions in a dose- and time-dependent manner with equal efficiency. Presently, there is no available therapy that can block infection by a wide range of papillomavirus regardless of species or genotypes. Targeting dynamin may lead to the rational design of drug able to prevent infection by papillomaviruses, and by other infectious agents dependent on this protein for initial internalization into target cells. Whether such an approach will prove successful needs further investigation.

HPV16 infection of HaCaTs is dependent on ß4 integrin, and α6 integrin processing.

Our understanding of human papillomavirus (HPV) is still evolving. To further study the field, our laboratory has focused on determining the role of integrins in the initial steps of viral endocytosis into HaCaT cells. Our and others' previous findings have shown that α6 is necessary for infection. Here we show that α3 and ß1 were dispensable, and we identified integrin α6ß4 complex as necessary for infection in HaCaTs. ß4 knock down resulted in a significant decrease in HPV16 PsV infection and perhaps most importantly resulted in defective post-translational α6 processing. We showed that the unprocessed α6 does not localize to the cell surface. We propose that the α6ß4 complex is necessary for the formation of an endocytic complex that results in the signaling transduction events necessary for initial endocytosis.

Usage of heparan sulfate, integrins, and FAK in HPV16 infection.

Human papillomavirus type 16 (HPV16) is the major causative agent of cervical cancer. Studies regarding the early binding and signaling molecules that play a significant role in infection are still lacking. The current study analyzes the role of heparan sulfate, integrins, and the signaling molecule FAK in HPV16 infection of human adult keratinocytes cell line (HaCaTs). Our data demonstrate that infection requires the binding of viral particles to heparan sulfate followed by activation of focal adhesion kinase through an integrin. Infections were reduced in the presence of the FAK inhibitor, TAE226. TAE226 was observed to inhibit viral entry to the early endosome a known infectious route. These findings suggest that FAK can serve as a novel target for antiviral therapy.