Faculty Bibliography

Neutrophilic eccrine hidradenitis typically manifests as erythematous plaques on the face, trunk, or extremities. This eruption has been associated with numerous factors, but most commonly is seen with chemotherapy, particularly cytarabine. We report a 73-year-old woman with acute myelogenous leukemia who developed rapidly expansive neutrophilic eccrine hidradenitis mimicking facial cellulitis only after a course of cytarabine was followed by granulocyte-colony stimulating factor. Prompt diagnosis is imperative to prevent prolonged antimicrobial therapy

BACKGROUND: Overexpression of Neutral Endopeptidase (NEP) has been reported in metastatic carcinomas, implicating NEP in tumor progression and suggesting a role for NEP inhibitors in its treatment. We investigated the role of NEP expression in the clinical progression of cutaneous melanoma. METHODS: We screened 7 melanoma cell lines for NEP protein expression. NEP-specific siRNA was transfected into the lines to examine the role of gene transcription in NEP expression. Immunohistochemistry was done for 93 specimens and correlated with clinicopathologic parameters. Thirty-seven metastatic melanoma specimens were examined for NEP transcript expression using Affymetrix GeneChips. In a subset of 25 specimens for which both transcript and protein expression was available, expression ratios were used to identify genes that co-express with NEP in GeneChip analysis. RESULTS: NEP was overexpressed in 4/7 human melanoma cell lines, and siRNA knock-down of NEP transcripts led to downregulation of its protein expression. NEP protein overexpression was significantly more common in metastatic versus primary tumors (P = 0.002). Twelve of 37 (32%) metastatic tumors had increased NEP transcript expression, and an association was observed between NEP transcript upregulation and protein overexpression (P < 0.0001). Thirty-eight genes were found to significantly co-express with NEP (p < 0.005). Thirty-three genes positively correlated with NEP, including genes involved in the MAP kinase pathway, antigen processing and presentation, apoptosis, and WNT signaling pathway, and 5 genes negatively correlated with NEP, including genes of focal adhesion and the notch signaling pathways. CONCLUSION: NEP overexpression, which seems to be largely driven by increased transcription, is rare in primary melanoma and occurs late in melanoma progression. Functional studies are needed to better understand the mechanisms of NEP regulation in melanoma

BACKGROUND: The color, architecture, symmetry, and homogeneity (CASH) algorithm for dermoscopy includes a feature not used in prior algorithms, namely, architecture. Architectural order/disorder is derived from current concepts regarding the biology of benign versus malignant melanocytic neoplasms. OBJECTIVE: We sought to evaluate the accuracy of the CASH algorithm. METHODS: A total CASH score (TCS) was calculated for dermoscopic images of 325 melanocytic neoplasms. Sensitivity, specificity, diagnostic accuracy, and receiver operating characteristic curve analyses were performed by comparing the TCS with the histopathologic diagnoses for all lesions. RESULTS: The mean TCS was 12.28 for melanoma, 7.62 for dysplastic nevi, and 5.24 for nondysplastic nevi. These differences were statistically significant (P < .001). A TCS of 8 or more yielded a sensitivity of 98% and specificity of 68% for the diagnosis of melanoma. LIMITATIONS: This is a single-evaluator pilot study. Additional studies are needed to verify the CASH algorithm. CONCLUSIONS: The CASH algorithm can distinguish melanoma from melanocytic nevi with sensitivity and specificity comparable with other algorithms. Further study is warranted to determine its intraobserver and interobserver correlations

'Fat fingers' are thick digitate linear, curvilinear, branched, or oval/circular dermoscopic structures typically seen in seborrheic keratoses where they represent the gyri of their cerebriform surfaces. Their recognition is very useful in the diagnosis of these lesions, especially when the classic features (eg, milia, comedo-like openings) are absent. Histologically and by confocal microscopy the 'fat finger' gyri are accentuated by pigmented keratin filling the sulci. 'Fat fingers' must be differentiated from other linear structures such as 'network-like structures'; branched streaks; network; globules; pigmented ovoid-nests; and streaks/pseudopods seen in different melanocytic and non-melanocytic lesions

BACKGROUND: Function of the retinoblastoma tumor suppressor protein (pRB) may be compromised at a genetic level by gene loss or mutation or at a post-translational level by hyperphosphorylation. In this study, we examined adult soft tissue sarcomas (ASTS) to determine if alterations of pRB were associated with distinct patterns of pRB expression and clinical outcome. DESIGN: We investigated 86 ASTS patients using monoclonal antibodies that distinguish between hyperphosphorylated and underphosphorylated pRB products. We also used microsatellite analysis to investigate the genetic status of the RB locus. We correlated pRB alterations with proliferative activity, and with clinicopathological outcomes. RESULTS: Altered patterns of pRB expression are common in ASTS occurring in 84% of cases, and it is significantly associated with proliferative activity (p<0.001). Patients whose tumors either lack expression of pRB, or express hyperphosphorylated forms of pRB, have poor survivals compared to patients whose tumors exhibit a normal, underphosphorylated pattern of pRB expression (p=0.03). In addition, 63% of cases lacking expression of pRB showed loss-of-heterozygosity at the locus. CONCLUSIONS: Inactivation of pRB is common in adult STS, which may be due to either gene loss or post-translational modification, namely hyper-phosphorylation. Both mechanisms are associated with tumor cell proliferation and poor survival