Cappel, Mark A.

SummaryShiitake dermatitis is a rare cutaneous reaction to lentinan, a polysaccharide component in the cell walls of shiitake mushrooms (Lentinula edodes). Herein, we systematically review the case report and case series English‐language literature on shiitake dermatitis, which refers to a total of 50 patients (38 males, 12 females; mean age: 44.58 years). The majority of cases occurred after the consumption of raw mushrooms, whereas 22% of cases were caused by the eating of lightly or undercooked mushrooms. The most common clinical presentations, localized symptoms, and systemic findings include linear flagellated dermatitis (98%), pruritus (78%), and fever, diarrhea, and mucosal ulcers, respectively. The diagnosis of this entity continues to be based on clinical findings as laboratory abnormalities, and the findings of skin biopsies and patch/prick tests are nonspecific and inconsistent. The condition is self‐limiting, resolving in approximately 12.5 d without treatment. Based on the included case reports, it appears that medical treatment may slightly shorten the course of disease (to 9–11 d, varying by therapy) but should be considered on an individual patient basis. However, the treatment of symptoms, reassurance, and the avoidance of re‐exposure are sufficient treatment recommendations for this condition.

Checkpoint blockade inhibitors have revolutionized the treatment of metastatic melanoma. Despite the success of these agents in improving the overall survival of patients with metastatic melanoma, not all patients achieve clinical benefit, leaving room for improvement. The presence of cutaneous metastases in patients with metastatic melanoma provides the unique opportunity to treat the cutaneous lesions with a local modality while simultaneously treating systemic disease with systemic therapy. Herein, we describe the treatment of two patients with both in-transit and metastatic melanoma with the combination of the topical toll-like receptor 7 agonist imiquimod with systemic ipilimumab. Both patients appeared to have progressed and developed new cutaneous and systemic metastases while on single agent ipilimumab only to respond when started on topical imiquimod. Both patients tolerated the combination of imiquimod and ipilimumab without serious adverse events, and both patients had excellent clinical responses. These cases provide a proof of principle of the possibility of the combination of toll-like receptor 7 agonists with immune checkpoint blockade inhibitors.

Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

Abstract Therapies that activate the immune system through blocking the binding of programmed death ligand 1 (PD-L1) present on tumors and PD-1 (programmed death 1) present on activated immune cells are revolutionizing the care for patients with cancer. These therapies work by inhibiting negative regulators of the immune system, thereby decreasing a tumor's ability to evade the immune system. The side effects of anti–PD-1/PD-L1 therapies are generally mild and as expected are related to autoimmune reactions. Two of the most common side effects of anti–PD-1/PD-L1 therapies are rash and pruritus occurring in approximately 20% of patients. Although the rash is generally recognized to be immune mediated, the exact mechanisms of the rash remain unclear. Herein, we report three cases of lichenoid dermatitis in three patients treated with MK-3475 (anti–PD-1) that were characterized with marked T-cell infiltrates with few PD-1–positive cells. The rashes in all three patients were relatively mild, allowing treatment to continue despite the rashes. Cancer Immunol Res; 3(1); 18–22. ©2014 AACR.

AbstractBackgroundBasosquamous carcinoma (BSC) and metatypical basal cell carcinoma (MBCC) are uncommon tumors poorly defined in the literature. Available studies suggest these tumors carry a greater risk of recurrence and metastases than basal cell carcinomas (BCCs) and, in some studies, squamous cell carcinomas. Formal treatment recommendations are not fully established.ObjectiveTo analyze BSC and MBCC separately, evaluate whether they are distinct tumor subtypes, and analyze Mohs micrographic surgery (MMS) efficacy for BSC and MBCC.MethodsRetrospective review of medical records and histologic specimens was conducted for 293 patients with 303 biopsy‐proven BSCs or MBCCs treated with MMS between 1996 and 2004. In total, 32 BSCs and 128 MBCCs were identified. Surgical and follow‐up data were analyzed.ResultsKaplan–Meier estimates of recurrence‐free survival after MMS were 100% at one year for both tumor subtypes and were 100% for BSC and 93.8% for MBCC at 5 years. Initial mean sizes were 1.5 cm for BSC and 1.3 cm for MBCC. Approximately 7% represented recurrent tumors at surgery. Of six patients with recurrences, none had known metastatic disease.LimitationsLimitations include retrospective design, analysis of only head and neck sites, and small sample sizes.ConclusionBSC and MBCC showed no significant distinguishing characteristics to separate them into two BCC subtypes. Reported recurrence rates for BSC and MBCC are 12–45% with wide local excision; estimated recurrence rates are 4.1% with MMS. Our study showed recurrence‐free survival of 95.1% at five years. Hence, MMS is effective in treating these BCC subtypes.

AbstractBackgroundVirtual microscopy is increasingly being used in dermatopathology educational settings.ObjectiveThe objective is to evaluate diagnostic accuracy and attitudes between virtual microscopy and traditional glass slide microscopy among dermatology residents.MethodsA 48‐question dermatopathology examination was administered to 35 dermatology residents at three different dermatology residency training sites during the 2011–2012 academic year with half (n = 24) of the questions using the gold standard of glass slide microscopy and half (n = 24) using whole, scanned virtual slides. Correct number of questions using glass slides and virtual slides was evaluated. Participants were surveyed regarding previous experience with digital slide imaging; quality, ease of use, and speed of slide review; and overall microscopy preferences.ResultsOverall, diagnostic accuracy was better with glass slides than virtual slides (p = 0.01). However, no statistically significant difference was found in diagnostic accuracy of first‐year trainees (p > 0.99) or trainees with exposure to virtual microscopy greater than two times per month (p = 0.27). There was no overall personal preference for glass slide vs. virtual microscopy.LimitationsDifferent cases and questions were used for glass slides and virtual microscopy.ConclusionsDiagnostic accuracy with virtual microscopy is dependent on year of residency training and prior experience with virtual microscopy.

AbstractScreening for the Muir‐Torre variant of Lynch Syndrome (LS) using Mismatch Repair (MMR) gene immunohistochemistry (IHC) on sebaceous neoplasms (SNs) is technically feasible. To date, research into the clinical utility of MMR IHC for this indication is limited. We conducted a retrospective chart review of 90 patients with MMR IHC completed on at least one SN from January 2005 to May 2010. SNs included were adenomas, epitheliomas, carcinomas and basal and squamous cell carcinomas with sebaceous differentiation. Of the 90 patients, 13 (14 %) had genetically confirmed or fulfilled clinical criteria for a diagnosis of MTS and 51 patients (57 %) presented with an abnormal MMR IHC result (loss of one or more MMR proteins) on at least one SN. Abnormal IHC had a sensitivity of 85 %, specificity of 48 %, positive predictive value (PPV) of 22 % and negative predictive value (NPV) of 95 % when evaluating for MTS. When personal or family history of colorectal cancer (≥2 family members with a history of colorectal cancer) was taken into consideration, ignoring IHC results, sensitivity was 92 %, specificity was 99 %, PPV was 92 % and NPV was 99 %. MMR IHC on SNs when used to screen for MTS has poor diagnostic utility. We recommend that MMR IHC not be performed routinely on SNs when the patient does not have either personal or family history of colorectal cancer.