The stimulation of vascular endothelial growth factor receptor-2 (VEGFR-2) by tumor-derived VEGF represents a key event in the initiation of angiogenesis. In this work, we report that VEGFR-2 is localized in endothelial caveolae, associated with caveolin-1, and that this complex is rapidly dissociated upon stimulation with VEGF. The kinetics of caveolin-1 dissociation correlated with those of VEGF-dependent VEGFR-2 tyrosine phosphorylation, suggesting that caveolin-1 acts as a negative regulator of VEGF R-2 activity. Interestingly, we observed that in an overexpression system in which VEGFR-2 is constitutively active, caveolin-1 overexpression inhibits VEGFR-2 activity but allows VEGFR-2 to undergo VEGF-dependent activation, suggesting that caveolin-1 can confer ligand dependency to a receptor system. Removal of caveolin and VEGFR-2 from caveolae by cholesterol depletion resulted in an increase in both basal and VEGF-induced phosphorylation of VEGFR-2, but led to the inhibition of VEGF-induced ERK activation and endothelial cell migration, suggesting that localization of VEGFR-2 to these domains is crucial for VEGF-mediated signaling. Dissociation of the VEGFR-2/caveolin-1 complex by VEGF or cyclodextrin led to a PP2-sensitive phosphorylation of caveolin-1 on tyrosine 14, suggesting the participation of Src family kinases in this process. Overall, these results suggest that caveolin-1 plays multiple roles in the VEGF-induced signaling cascade.

Background Patients presenting with a site-specific skin complaint may receive a total body skin examination (TBSE) or a more focused examination. A TBSE may be time-consuming but can potentially detect unsuspected or early stage skin cancers. The purpose of this study was to assess the detection of skin cancers associated with dermatologist-initiated TBSE performed immediately after a focused skin examination on the same patients. Methods The dermatology records of patients with biopsy-proven melanoma, basal cell carcinoma (BCC), or squamous cell carcinoma (SCC) during a 2-year period were reviewed. Generalized linear mixed-effects models were used to estimate the odds of a lesion being identified by a dermatologist (rather than the patient or the patient's primary health care provider). Results A total 1563 biopsy-proven cutaneous malignancies were found on 1010 patients. Of these, 797 cancers (51%) were first identified by a dermatologist on TBSE and 764 (48.9%) by the patient or the referring provider. Among tumors first identified by dermatologists (n = 797), 553 (69%) were BCCs, 220 (28%) were SCCs, and 24 (3%) were melanomas. The mean Breslow depth was 0.53 mm (standard deviation: 0.31 mm) for melanomas found on TBSE versus 1.04 mm (standard deviation: 1.68 mm) if identified by patients or referring providers. BCCs were more likely to be identified by a dermatologist during a TBSE (n = 553 [56%] vs. n = 434 [44%]; odds ratio: 1.79; p < .001). Tumors ultimately diagnosed as SCCs were more often identified by patients or patients’ primary care providers (n = 302 [58%]; odds ratio: 0.56; p < .001). However, 220 otherwise undetected SCCs were found during dermatologist-performed TBSE. Conclusion Dermatologist-performed TBSEs identified numerous cutaneous malignancies that might otherwise have remained undiagnosed. Early detection of melanoma or nonmelanoma skin cancer by TBSEs may spare patients significant morbidity and mortality.

Small tissue biopsies are often difficult to visualize and can be easily lost or mishandled. The authors hypothesized that full epidermal surface coloration of small skin lesions with a sterile skin marker (gentian violet ink) before performing shave biopsy would make small gross specimens easier to identify without impacting microscopic appearance. Live evaluation of 4 inked and 4 noninked gross (2-3 mm) specimens in covered and uncovered formalin-containing jars by 50 consecutive health care personnel demonstrated that inked specimens were significantly (P < 0.001) easier to visualize than noninked specimens. Additionally, a blinded dermatopathologist evaluated 25 inked and 25 noninked specimens microscopically. Utilization of this inking process did not interfere with histopathologic assessment or impede diagnosis. This pilot study describes an easily implementable quality improvement measure that may decrease the rate of loss and mishandling of specimens.

Hemosiderotic dermatofibromas (HDFs) are a rare variant of the relatively common dermatofibroma (DF). HDFs can clinically mimic melanoma as well as other melanocytic lesions and are diagnosed with histopathological examination. Histopathologic diagnosis is not straightforward as there are many DF variants and the features of several variants can often be found in one lesion. These lesions may represent a stage in development from common DF to aneurysmal dermatofibroma (ADF). This possible progression is important to recognize, as ADFs tend to exhibit increased tendency for local recurrence and can also be confused with malignant lesions. We present a case of a 65-year-old presenting with a rare HDF having unique clinical and dermatoscopic findings. Our case underscores the importance of recognizing this rare entity and stresses the importance of remaining mindful of the possible progression to ADF, an entity with increased propensity for recurrence.

BACKGROUND The Mohs histotechnologist (MH) performs tissue preparation, sectioning, and staining, which are critical tasks in ensuring a successful Mohs micrographic surgery (MMS). OBJECTIVE To assess current norms in MH training, practice setting, and utilization of specific histologic techniques. MATERIALS AND METHODS A 16-question survey was created and distributed using Survey Monkey to all members of the American Society for Mohs Histotechnology. RESULTS Response rate was 30%. Most MHs received on-the-job training from other MHs or the Mohs surgeon. Mohs histotechnologists largely performed tasks related to tissue processing while Mohs surgeons generally illustrated the Mohs layer map. Automated routine staining was used in most laboratory tests, and laboratory tests used similar staining techniques. Most respondents worked in private offices verses academic centers. Total staining time was significantly longer at academic medical centers versus private offices (7 vs 5 minutes, p = .01). CONCLUSION These findings provide an updated profile of current laboratory training and tissue preparation techniques at MMS practices across the country. Understanding the roles of the MH in laboratory functioning may help laboratories adopt best practices.