Suraj S. Venna

Analysis of sentinel lymph node positivity in patients with thin primary melanoma

BACKGROUND A minority of patients with T1 melanoma will have a positive sentinel lymph node (SLN) biopsy (SLNB) finding. Identifying who will develop metastatic disease is important in determining prognosis and treatment. OBJECTIVE We sought to identify clinical and histologic features predictive of a positive SLNB result and determine its prognostic significance in patients with T1 melanoma. METHODS Clinical and histologic parameters were evaluated in 484 patients with T1 melanoma for their ability to predict a positive SLNB result. The impact of various factors on SLN positivity was evaluated. SLN status was examined as a predictor of overall survival. RESULTS In all, 34 patients had a positive SLNB finding. Four factors predicted a higher risk of SLN positivity: age 43 years or younger, Breslow depth 0.8 mm or greater, tumors on the lower extremity and trunk, and tumor-infiltrating lymphocyte level. By multivariate analysis, low tumor-infiltrating lymphocytes (P = .0015) and decreasing age (P = .0058) independently predicted SLN positivity. If 0 to 2 of these factors were present, the rate of a positive SLNB result was 3%; this increased to 15% with 3 factors present and to 30% if all 4 factors were present (P < .002). SLN-positive patients had significantly decreased survival (P = .003), and SLN status was the most powerful predictor of survival (P = .009). LIMITATIONS Our data analysis includes patients from 1994 to 2007 and therefore information on mitotic rate, a recently defined T1b criterion, is not recorded for all patients. CONCLUSIONS Combining clinical and histologic prognostic factors may help identify subgroups of T1 patients at higher risk of SLN positivity. SLN status has significant prognostic impact in patients with thin melanomas.

Inhibition of the elicitation phase of contact hypersensitivity by thymidine dinucleotides is in part mediated by increased expression of interleukin-10 in human keratinocytes

Abstract: The production of immunomodulatory cytokines such as interleukin‐10 (IL‐10) from keratinocytes and other target cells in the skin plays a crucial role in UV‐induced immunosuppression. Substantial evidence supports an association between DNA damage and immunomodulation. It is also known that small DNA fragments such as thymidine dinucleotides (pTpT) can mimic several UV‐induced effects, including inhibition of the induction phase of the contact hypersensitivity response and up‐regulation of tumor necrosis factor‐alpha (TNF‐α). To determine whether pTpT also induces IL‐10 secretion by keratinocytes, and by inference whether IL‐10 production after UV irradiation is a response to DNA damage, we compared the effects of pTpT with those of UV irradiation on primary human keratinocyte cultures. Subconfluent cultures of primary human keratinocytes were treated either with 10 µM or 100 µM pTpT or diluent alone, or exposed to solar‐simulated light (100 J/m2 of UVB) or sham irradiated. An increase in IL‐10 mRNA expression was observed 6–24 h after irradiation and at 24–48 h after treatment with pTpT. Detection of secreted IL‐10 protein coincided with up‐regulation of IL‐10 gene expression at 48 and 72 h as determined by ELISA. Conditioned media from human keratinocytes treated with pTpT, like that from irradiated cells, significantly inhibited lymphocyte proliferation in the allogeneic‐mixed lymphocyte reaction (MLR) assay. To determine whether pTpT mimics the suppressive influence of UVB on the elicitation phase of contact hypersensitivity, believed to result largely from IL‐10 release, we compared the effects of topical application of pTpT with those of UVB irradiation on C57Bl/6 mice sensitized with dinitrofluorobenzene. Sensitized mice treated with pTpT or UVB irradiation showed markedly suppressed elicitation of ear‐swelling responses. These results demonstrate that increased keratinocyte IL‐10 mRNA level and IL‐10 protein release are among the effects of pTpT and support the hypothesis that pTpT treatment triggers many of the biologic effects of UV irradiation by mimicking UV‐induced DNA damage. Finally, regardless of mechanism, the data suggest that topical treatment with pTpT may provide a novel means of suppressing contact hypersensitivity or other lymphocyte‐mediated reactions in skin.

Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement.

IMPORTANCE The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence. OBJECTIVES To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins. EVIDENCE REVIEW The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed. FINDINGS A consensus statement by the PLS of the MPWG following review of the literature, group discussions, and a structured Delphi method consensus. CONCLUSIONS AND RELEVANCE This consensus statement reviews the complexities of management of CAN/DN. A review of the literature and 2 rounds of a structured Delphi consensus resulted in the following recommendations: (1) mildly and moderately DN with clear margins do not need to be reexcised, (2) mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than reexcised, and (3) observation may be a reasonable option for management of moderately DN with positive histologic margins without clinically apparent residual pigmentation; however, more data are needed to make definitive recommendations in this clinical scenario.

Recurrent erythema multiforme triggered by progesterone sensitivity.

Determining the underlying etiology of recurrent erythema multiforme (EM) can be a difficult endeavor. Although infection with herpes simplex virus (HSV) has been implicated in some cases, the precise trigger of a given patients recurrent EM often remains elusive. We discuss the case of a woman with a recurrent blistering eruption that was clinically and histopathologically consistent with EM. An investigation into the etiology of the patients EM suggested that HSV was not the causative factor but instead pointed toward a hormonal influence that we interpret as autoimmune progesterone dermatitis (APD). This case is presented to highlight the importance of considering hormonal triggers in women with recurrent EM that consistently flares during the luteal phase of the menstrual cycle, the point at which serum progesterone levels peak. A brief review of the literature regarding the diagnosis, histopathology, etiology and treatment of APD is further provided.

Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome treated with a combination of isotretinoin and pamidronate.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a clinically heterogeneous entity, encompassing a variety of debilitating conditions that have in common inflammation of the skeletal system and skin. To date, there is a paucity of documented efficacious treatment options. We report a 48-year-old man with skeletal and cutaneous signs and symptoms who improved dramatically after treatment with a combination of isotretinoin and pamidronate. This report provides an alternative treatment regimen for SAPHO that addresses the possible underlying pathophysiology of this likely underdiagnosed syndrome.

Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Forces 2016 Draft Recommendation Statement on skin cancer screening.

Management Strategies of Academic Pigmented Lesion Clinic Directors in the United States

of patients had a good response and 15% had an excellent response. There was a statistically significant difference between the groups (P 1⁄4 .024) with regard to satisfaction, with 40% of patients in group 3 expressing excellent satisfaction (Table I). Different treatment options for vitiligo, acting either on proliferation of melanocytes or suppression of immune response, have been used. Recent procedures, including needling, have shown acceptable degrees of repigmentation in limited types of vitiligo. In a comparison of the results of needling plus a topical steroid with NB-UVB and an examination of the additional value of a using combination of both modalities in acrofacial vitiligo, needling yielded a good-to-excellent response in 45% of cases, whereas combining needling with NB-UVB raised that percentage to 70%. The overall incidence of side effects was minimal, except for pain, which can be minimized by using topical anesthetics before sessions. In conclusion, the addition of needling to NB-UVB is a reasonable combination therapy for patients with resistant vitiligo and is well tolerated.

Asymptomatic Longitudinal Pachyxanthonychia of the Fingernail

A 62-year-old white female without prior history of skin cancer presented with an asymptomatic white streak on her right fourth fingernail of 3 months’ duration. On examination, a 3-mm white to yellow longitudinal nail plate thickening with ridging and transverse overcurvature was noted ( Fig. 1 ). Dermoscopy revealed longitudinal white streaks and several proximal and distal splinter hemorrhages ( Fig. 2 ). Proximal nail matrix biopsy revealed a fibroepithelial tumor consisting of digitate projections of typical but reduplicated nail matrix epithelium with fibrovascular cores ( Fig. 3 ). The fibrovascular stroma was superficially cellular but relatively hypocellular and fibrotic deeply. Immunohistochemistry showed strong CD34 staining of the fibrovascular component ( Fig. 4 ). What is your diagnosis? Received: December 15, 2016 Accepted: January 4, 2017 Published online: January 26, 2017

Antitumor and Anti–Hepatitis C Viral Response After Administration of the Anti–Programmed Death 1 Antibody Pembrolizumab

INTRODUCTION Antibodies that block programmed death 1 (PD-1) receptor and its ligand, PD-L1, have showndurable responses in multiple cancer types. PD-1 has been shown to be upregulated in hepatitis C virus (HCV) –specific CD8 cells. This suggests that anti–PD-1 therapy may be a therapeutic target in patients with HCV infection. However, patients with chronic hepatitis are usually excluded from clinical trials. Herein, we report a case in which PD-1 antibody was administered to treat metastatic Merkel cell carcinoma (MCC) in a patient with untreated chronic HCV infection. Treatment resulted in a rapid antitumor response as well as a rapid decline in HCV RNA without apparent hepatocellular injury, which suggested that not only can anti–PD-1 therapy induce antitumor immune responses, but that it may also restore antiviral T-cell function and overcome viral immune escape.

Poorly differentiated squamous cell carcinoma arising within a lesion of discoid lupus erythematosus in an African-American woman

The incidence of skin cancer is rare in African Americans; however, there are several reports of patients with depigmented or hypopigmented lesions on sun-exposed areas, such as the scalp, who are at increased risk for squamous cell carcinoma (SCC). Decrease in melanin, immunosuppressive therapy, frequent ultraviolet exposure, human papillomavirus infection, chronic scarring, and inflammatory processes are factors associated with the development of SCC in black patients.1 We present a rare case of a 55-year-old African-American woman who had SCC within a discoid lupus erythematosus (DLE) lesion.