Christian L. Baum

Staging for Cutaneous Squamous Cell Carcinoma as a Predictor of Sentinel Lymph Node Biopsy Results: Meta-analysis of American Joint Committee on Cancer Criteria and a Proposed Alternative System

IMPORTANCE The appropriate clinical setting for the application of sentinel lymph node biopsy (SLNB) in the management of cutaneous squamous cell carcinoma (cSCC) is not well characterized. Numerous case reports and case series examine SLNB findings in patients who were considered to have high-risk cSCC, but no randomized clinical trials have been performed. OBJECTIVE To analyze which stages in the American Joint Committee on Cancer (AJCC) criteria and a recently proposed alternative staging system are most closely associated with positive SLNB findings in nonanogenital cSCC. DESIGN, SETTING, AND PARTICIPANTS Medical literature review and case data extraction from private and institutional practices to identify patients with nonanogenital cSCC who underwent SLNB. Patients were eligible if sufficient tumor characteristics were available to classify tumors according to AJCC staging criteria and a proposed alternative staging system. One hundred thirty patients had sufficient data for AJCC staging, whereas 117 had sufficient data for the alternative system. EXPOSURE Nonanogenital cSCC and SLNB. MAIN OUTCOMES AND MEASURES Positive SLNB findings by cSCC stage, quantified as the number and percentage of positive nodes. RESULTS A positive SLN was identified in 12.3% of all patients. All cSCCs with positive SLNs were greater than 2 cm in diameter. The AJCC criteria identifed positive SLNB findings in 0 of 9 T1 lesions (0%), 13 of 116 T2 lesions (11.2%), and 3 of 5 T4 lesions (60.0%). No T3 lesions were identified. The alternative staging system identified positive SNLB findings in 0 of 9 T1 lesions (0%), 6 of 85 T2a lesions (7.1%), 5 of 17 T2b lesions (29.4%), and 3 of 6 T3 lesions (50.0%). Rates of positive SLNB findings in patients with T2b lesions were statistically higher than those with T2a lesions (P = .02, Fisher exact test) in the alternative staging system. CONCLUSIONS AND RELEVANCE Our findings suggest that most cSCCs associated with positive SLNB findings occur in T2 lesions (in both staging systems) that are greater than 2 cm in diameter. The alternative staging system appears to more precisely delineate high-risk lesions in the T2b category that may warrant consideration of SLNB. Future prospective studies are necessary to validate the relationship between tumor stage and positive SLNB findings and to identify the optimal staging system.

Risk Factors for Cutaneous Squamous Cell Carcinoma Recurrence, Metastasis, and Disease-Specific Death: A Systematic Review and Meta-analysis.

IMPORTANCE To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically. OBJECTIVE To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC. DATA SOURCES Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each databases inception to May 14, 2015. STUDY SELECTION Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC. DATA EXTRACTION AND SYNTHESIS Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. MAIN OUTCOMES AND MEASURES A priori outcomes were recurrence, metastasis, and DSD. RESULTS Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2 mm (risk ratio [RR], 9.64; 95% CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95% CI, 4.17-13.88), Breslow thickness exceeding 6 mm (RR, 7.13; 95% CI, 3.04-16.72), perineural invasion (RR, 4.30; 95% CI, 2.80-6.60), diameter exceeding 20 mm (RR, 3.22; 95% CI, 1.91-5.45), location on the temple (RR, 3.20; 95% CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95% CI, 1.72-4.14). Significant risk factors for metastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95% CI, 3.59-34.97), Breslow thickness exceeding 2 mm (RR, 10.76; 95% CI, 2.55-45.31), Breslow thickness exceeding 6 mm (RR, 6.93; 95% CI, 4.02-11.94), diameter exceeding 20 mm (RR, 6.15; 95% CI, 3.56-10.65), poor differentiation (RR, 4.98; 95% CI, 3.30-7.49), perineural invasion (RR, 2.95; 95% CI, 2.31-3.75), immunosuppression (RR, 1.59; 95% CI, 1.07-2.37), and location on the temple (RR, 2.82; 95% CI, 1.72-4.63), ear (RR, 2.33; 95% CI, 1.67-3.23), or lip (RR, 2.28; 95% CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20 mm (RR, 19.10; 95% CI, 5.80-62.95), poor differentiation (RR, 5.65; 95% CI, 1.76-18.20), location on the ear (RR, 4.67; 95% CI, 1.28-17.12) or lip (RR, 4.55; 95% CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95% CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95% CI, 3.10-5.32). Evidence quality was considered low to moderate. CONCLUSIONS AND RELEVANCE Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20 mm is associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.

Leiomyosarcoma of the skin: Clinical, histopathologic, and prognostic factors that influence outcomes

BACKGROUND Superficial leiomyosarcoma (LMS) is a rare tumor with important clinical, pathologic, and treatment features. Previous LMS studies have included few patients, included minimal follow-up, and typically combined the superficial and subfascial (deep) forms. OBJECTIVE We sought to characterize clinical features, effectiveness of treatment approaches, and long-term outcomes for LMS stratified by depth of invasion. METHODS In all, 71 cases of primary superficial LMS, 48 dermal and 23 subcutaneous (mean follow-up of 8 years), were examined and clinical, histopathologic, and treatment factors reported. RESULTS Tumor size and subcutaneous classification correlated with greater likelihood of metastasis and death at 5 years. When superficial LMS metastasizes, other skin sites are the most common distant location. Treatment with wide local excision with minimum 1-cm margins showed statistically lower rates of recurrences and metastasis compared with excision with narrow surgical margins. Fourteen cases of Mohs micrographic surgery had no recurrences or metastases. Five cases of dermal LMS metastasized, 2 of which resulted in death. LIMITATIONS This study is a retrospective review of a relatively small number of patients. CONCLUSION LMS can metastasize and warrants surgical intervention and long-term follow-up. Wide local excision, and Mohs micrographic surgery in particular, appear to provide the best management approach for definitive treatment.

Increased incidence and recurrence rates of nonmelanoma skin cancer in patients with non-Hodgkin lymphoma: A Rochester Epidemiology Project population-based study in Minnesota

BACKGROUND Cutaneous malignancy is associated with worse outcomes in patients with chronic lymphocytic leukemia (CLL). OBJECTIVE We sought to identify the incidence and recurrence rate of nonmelanoma skin cancer (NMSC) in patients with non-Hodgkin lymphoma (NHL). METHODS NMSC incidence was calculated and Cox proportional hazards models were used to evaluate associations with risk of recurrence for patients with NHL between 1976 and 2005 who were in the Rochester Epidemiology Project research infrastructure. RESULTS We identified 282 patients with CLL or small lymphocytic lymphoma and 435 with non-CLL NHL. The incidence of basal cell carcinoma and squamous cell carcinoma was 1829.3 (95% confidence interval [CI] 1306.7-2491.1) and 2224.9 (95% CI 1645.9-2941.6), respectively, in patients with CLL. The cumulative recurrence rate at 8 years after treatment with Mohs micrographic surgery was 8.3% (95% CI 0.0%-22.7%) for basal cell carcinoma and 13.4% (95% CI 0.0%-25.5%) for squamous cell carcinoma in patients with CLL. LIMITATIONS This was a retrospective cohort study. CONCLUSIONS After Mohs micrographic surgery and standard excision of NMSC, patients with NHL had a skin cancer recurrence rate that was higher than expected. Careful treatment and monitoring of patients with NHL and NMSC are warranted.

Incidence and Trends of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma: A Population-Based Study in Olmsted County, Minnesota, 2000 to 2010

Objective: To determine population‐based incidence estimates of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Patients and Methods: We reviewed the medical records of a population‐based cohort diagnosed with nonmelanoma skin cancer between January 2, 2000, and December 31, 2010. The age‐ and sex‐adjusted incidence rates were calculated and compared with estimates from previous periods. Results: The age‐adjusted BCC incidence (cases per 100,000 person‐years) was 360.0 (95% CI, 342.5‐377.4) in men and 292.9 (95% CI, 278.6‐307.1) in women. The age‐adjusted cSCC incidence (cases per 100,000 person‐years) was 207.5 (95% CI, 193.9‐221.1) in men and 128.8 (95% CI, 119.4‐138.2) in women. From years 1976 to 1984 to years 2000 to 2010, the age‐ and sex‐adjusted incidence (cases per 100,000 person‐years) of BCC increased from 222.0 (95% CI, 204.5‐239.5) to 321.2 (95% CI, 310.3‐332.2) and that of cSCC from 61.8 (95% CI, 52.3‐71.4) to 162.5 (95% CI, 154.6‐170.3). Over time, the anatomical distribution of BCC shifted from the head and neck to the torso and that of cSCC shifted from the head and neck to the extremities. Conclusion: The incidences of BCC and cSCC are increasing, with a disproportionate increase in cSCC relative to BCC. There is also a disproportionate increase in the incidence of both tumors in women, as well as a shift of anatomical distributions.

Characteristics of Sebaceous Carcinoma and Early Outcomes of Treatment Using Mohs Micrographic Surgery Versus Wide Local Excision: An Update of the Mayo Clinic Experience Over the Past 2 Decades

BACKGROUND Sebaceous carcinoma (SC) is a rare cutaneous neoplasm. OBJECTIVE To characterize SC and treatment approaches and outcomes. METHODS and MATERIALS We retrospectively reviewed records of patients with SC from 1992 through 2012. Recurrence‐free survival was estimated and compared between groups. RESULTS We identified 52 patients with SC (39, 75.0% male). Mean age ± standard deviation at diagnosis was 72.7 ± 10.8. Forty‐nine patients (94.2%) were white. Twenty‐one (of 29 with known status) had a diagnosis of Muir‐Torre syndrome. Six had multiple primary SCs (total of 73 SCs in 52 patients). The most common locations for SC were the back (20.5%), cheek (13.7%), nose (11.0%), and eye (9.6%). Treatment was recorded for 70 SCs; 35 (50.0%) were treated using Mohs micrographic surgery (MMS) and 26 (37.1%) using wide local excision (WLE). Of the 45 patients (66 SCs) with clinical follow‐up, three (6.7% of patients; 4.8% of SCs) had documented recurrence. CONCLUSION MMS and WLE are effective treatments for SC. Further research is warranted to determine whether one treatment is more efficacious than the other.

Tumor-induced osteomalacia resulting from primary cutaneous phosphaturic mesenchymal tumor: a case and review of the medical literature.

Tumor-induced osteomalacia, also known as oncogenic osteomalacia, is a rare paraneoplastic condition frequently associated with a distinct mesenchymal neoplasm, namely phosphaturic mesenchymal tumor, mixed connective tissue variant (hereafter, phosphaturic mesenchymal tumor). Although this neoplasm type has been reported in various anatomic locations, primary cutaneous involvement is exceptionally rare. Treatment involves complete surgical removal. Because of the locally infiltrative nature of the tumor, surgical margin control may be challenging. We describe a case of phosphaturic mesenchymal tumor that mimicked dermatofibrosarcoma protuberans and that was treated successfully with Mohs micrographic surgery. Furthermore, we review the clinicopathologic features of all cases of primary cutaneous phosphaturic mesenchymal tumor that have been described in the medical literature. A 40-year-old man presented with a 4-year history of progressive pain in his legs, lower back, and ribs. The patient denied any family history of the heritable forms of osteomalacia. Laboratory tests revealed an elevated total alkaline phosphatase level, low phosphorous level, and elevated fibroblast growth factor 23 level. Imaging studies showed multiple stress fractures involving the ribs and pelvis, and a bone density scan found a Z-score in the osteoporosis range. Findings were unremarkable on an F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) test. A clinical diagnosis of acquired hypophosphatemic osteomalacia was rendered by his endocrinologist, and the patient was referred to dermatology for a 2.0 × 1.7-cm subcutaneous nodule on the left shoulder. An excisional biopsy was performed and submitted with a clinical impression of an epidermal cyst. On scanning microscopy, the lesion demonstrated a predominantly dermal-based tumor invading the subcutis. The tumor was composed of a dense population of spindle-shaped cells with dark, but uniform, nuclei arranged in a honeycomb growth pattern within the subcutaneous tissue, reminiscent of that seen in dermatofibrosarcoma protuberans (Figure 1). Frequent small deposits of acellular, partially calcified basophilic matrix and scattered osteoclast-type multinucleated giant cells were also identified (Figure 2). The lesional

Rare Presentations of Primary Melanoma and Special Populations: A Systematic Review

A subset of patients with melanoma present in rare and unique clinical circumstances requiring specific considerations with respect to diagnostic and therapeutic interventions. Herein, we present our review of patients with: (1) primary mucosal melanoma of the head and neck, gastrointestinal, and genitourinary tracts; (2) primary melanoma of the eye; (3) desmoplastic melanoma; (4) subungual melanoma; (5) melanoma in special populations: children, nonwhites, as well as a discussion of familial melanoma.

Guidelines of care for the management of basal cell carcinoma

Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed.

Mohs micrographic surgery in the treatment of trichilemmal carcinoma: The Mayo Clinic experience

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