The Utility of Radiologic Imaging and Full Body Skin Examination in Patients With Melanoma of Unknown Primary.

Although most melanomas have a cutaneous origin, melanomas are rarely discovered without an overt primary site and are found in the metastatic stage. This phenomenon is called melanoma of unknown primary (MUP), which was first recorded in 1963.Melanoma can also rarely present as tumoral melanosis, which has completely regressed. By definition, this does not have viable melanocytes and histologically presents as an infiltration of melanophages and melanin. A 71-year-old female presented for dermatologic evaluation after being found to have melanoma of unknown primary (MUP). The MUP, located in multiple lymph nodes of the left superior and inferior inguinal region, was found on preoperative imaging indicated for surgical management of endometrial carcinoma. After the biopsy, a positron emission tomography-computed tomography (PET-CT) scan was performed to determine the extent of involvement, which noted focal uptake of the left heel of just medial to midline with an SUV max of 2.1. Based on the PET-CT findings, the patient was questioned about the lesion on her heel. She had suspected this was due to friction and stated it had been asymptomatic and present for years. This unique case demonstrates that combined total skin examination and whole-body radiologic imaging (preferably PET-CT) are both critical elements in the evaluation of MUP. Since melanoma of unknown primary is at least American Joint Committee on Cancer (AJCC) 8 Stage III (due to N1 status), imaging is reasonable in these patients.

Incidence and mortality trends of primary cutaneous melanoma: A 50-year Rochester Epidemiologic Project study.

Background: National cancer reporting-based registry data, although robust, lacks granularity for incidence trends. Expert opinion remains conflicted regarding the possibility of melanoma overdiagnosis in the context of rising incidence without a corresponding rise in mortality. Objective: To characterize 10- and 50-year trends in melanoma incidence and mortality. Methods: Multicenter, population-based epidemiologic study utilizing the Rochester Epidemiology Project for Olmsted County, Minnesota residents diagnosed with melanoma from 01/01/1970 to 12/21/2020. Age- and sex-adjusted incidence and disease-specific mortality are calculated. Results: Two thousand three hundred ten primary cutaneous melanomas were identified. Current age- and sex-adjusted incidence rates increased 11.1-fold since 1970s (P < .001). Over the last decade, there is an overall 1.21-fold (P < .002) increase, with a 1.36-fold increase (P < .002) among females and no significant increase among males (1.09-fold increase, P < .329). Melanoma-specific mortality decreased from 26.7% in 1970s to 1.5% in 2010s, with a hazard ratio (HR) reduction of 0.73 (P < .001) per 5-year period. Increased mortality was associated with Breslow thickness (HR 1.35, P < .001), age at diagnosis (HR 1.13, P = .001) left anatomic site (HR 1.98, P = .016), and nodular histogenic subtype (HR 3.08, P < .001). Limitations: Retrospective nature and focused geographic investigation. Conclusion: Melanoma incidence has continued to increase over the past decade, most significantly in females aged 40+. Trend variations among age and sex cohorts suggests external factors beyond overdiagnosis may be responsible. Disease-specific mortality of melanoma continues to decrease over the last 50 years.

Mohs Micrographic Surgery for Invasive Melanoma Allows for Tissue Preservation Compared With Wide Local Excision: A Retrospective Cohort Study.

BACKGROUND: While increasing evidence supports the safety and effectiveness of immunohistochemistry-assisted Mohs micrographic surgery (MMS) for superficially invasive melanoma, there is a paucity of the literature investigating its effect on final defect size. OBJECTIVE: To evaluate the tissue sparing effect of MMS for melanoma. MATERIALS AND METHODS: Three hundred and twenty-eight patients with early-stage (T1a/T1b) cutaneous melanomas treated with MMS from January 2008 to December 2018 were evaluated. Measured defect sizes after Mohs tumor extirpation were compared with anticipated defect size that would result from standard-margin wide local excision (WLE). Average actual versus anticipated defect areas were compared using a paired t-test (95% confidence intervals). RESULTS: The following groups demonstrated a significantly smaller defect area for MMS-treated tumors when compared with anticipated standard-margin WLE defect: All tumors combined (13.8 cm2 vs 10.4 cm2, p < .001), tumors requiring 1 stage (13.6 cm2 vs 10.1 cm2,p < .001), and tumors requiring 2 stages (13.2 cm2 vs 10.5 cm2, p = .004). The majority of patients (83.5%, n = 274) achieved clear margins with 1 stage. CONCLUSION: Immunohistochemistry-assisted MMS for early-stage invasive melanoma is associated with smaller final defect size and overall tissue sparing effect compared with standard WLE margins.

Lower Extremity Angiosarcoma: A Life-Threatening Complication of Lymphedema.

ABSTRACT: When angiosarcoma, a rare and aggressive tumor of the soft tissue, develops in the setting of chronic lymphedema, it is referred to as Stewart-Treves syndrome. It is usually seen in chronic lymphedema of the upper limbs postmastectomy. Angiosarcoma developing in the lower limb in the setting of chronic lymphedema is rare and has a poor outcome. The presentation of angiosarcoma can vary, ranging from a bleeding papule to a plaque or a subcutaneous mass, which can later progress to ulceration or necrosis. Treatment for Stewart-Treves syndrome is aggressive because of its poor prognosis and usually requires a multidisciplinary approach of surgery, radiation, and chemotherapy. Several theories have been put forth to explain the mechanism of Stewart-Treves syndrome, but it remains ambiguous. The current literature regarding angiosarcoma developing in the setting of chronic lymphedema in the lower limb is limited to single case reports. Herein, the authors report a series of six cases of biopsy-proven angiosarcoma in the setting of lower extremity lymphedema. Providers should include angiosarcoma in the differential diagnosis of ulcerative or vascular tumors arising in the context of lower extremity lymphedema.

Increasing Incidence and Decreasing Mortality of Melanoma in Elderly Adults: An Epidemiologic Study in Olmsted County, Minnesota.

BACKGROUND AND OBJECTIVE: Primary cutaneous melanoma incidence is increasing in elderly individuals. This population-based cohort examines incidence and mortality rates among adults aged 61 years and older with cutaneous melanoma. MATERIALS AND METHODS: Using the Rochester Epidemiology Project, patients aged 61 years of age or older with a first lifetime diagnosis of cutaneous melanoma between January 1, 1970 and December 31, 2020 were identified. RESULTS: The age- and sex-adjusted incidence rate increased from 16.4 (95% CI, 8.2-24.6) per 100,000 person-years in 1970 to 1979 to 201.5 (95% CI, 185.1-217.8) per 100,000 person-years in 2011 to 2020 (12.3-fold increase). There was a 16.0x increase in males and an 8.5× increase in females. Melanoma incidence has stabilized in males (1.2-fold increase, p = .11) and continues to significantly increase in females (2.7-fold increase, p < .001). Older age at diagnosis was significantly associated with an increased risk of death (HR 1.23 per 5-year increase in age at diagnosis, 95% CI, 1.02-1.47). CONCLUSION: Melanoma incidence continues to increase since 1970. The incidence has risen in elderly females, but has stabilized in males. Mortality has decreased throughout this period.

Association of Lower Extremity Lymphedema and Nonmelanoma Skin Cancers.

OBJECTIVE: To determine whether patients with lymphedema of a lower extremity (LE) had a greater risk of skin cancer than those without lymphedema. PATIENTS AND METHODS: This retrospective cohort study included patients with LE lymphedema examined at Mayo Clinic in Rochester, MN, USA, from January 1, 2000, through December 31, 2020. All patients with the phrase "lower extremity lymphedema" and a diagnostic code for lymphedema present in their electronic health record, as well as their age-, race-, and sex-matched controls without lymphedema, were included in the study. A Kaplan-Meier curve was constructed to examine the time to development of the first skin cancer for the lymphedema cohort and the controls. A Cox proportional hazards regression model was used to calculate hazard ratios. RESULTS: In total, 4437 patients had lymphedema within the study period. Compared with the matched control group, the lymphedema group had a significantly increased risk of skin cancer. For the subset of patients with unilateral lymphedema, the lymphedematous extremity was 2.65 times as likely as the nonlymphedematous LE to have skin cancer, particularly basal cell carcinoma. CONCLUSION: Lower extremity lymphedema appears to be a risk factor for squamous cell carcinoma, basal call carcinoma, and as expected, angiosarcoma. Clinicians caring for patients with LE lymphedema should be aware of this increased risk and monitor at-risk patients accordingly.

Disease-specific survival of malignant melanoma after Mohs micrographic surgery is not impacted by initial margins: A systematic review and meta-analysis.

Background: During Mohs surgery for melanoma, evidence has demonstrated that many surgeons opt for smaller initial margins than traditionally recommended (0.5 cm for in situ and 1 cm for invasive). Literature regarding surgical outcomes based on initial margin is sparse. Objective: To determine differences in disease-specific survival of melanoma after Mohs micrographic surgery for varied initial surgical margins. Methods: A literature search was conducted on February 14, 2022, from MEDLINE via PubMed (1946-present), Embase (1974-present), Central (1991-present), and Scopus (1960-present). The primary outcome was disease-specific mortality. Results: Nineteen studies were included for final analysis. The overall disease-specific mortality rate of melanoma in all included studies was 0.5% (CI, 0.1-0.8; P, .010). Disease-specific mortality for 1 to 5, 5, and 6 to 10 mm categories were 0.4% (CI, 0.0-0.9; P, .074), 0.7% (CI, 0.2-1.3; P, .2-1.3), and 0.4% (CI, -0.9 to 1.8; P, .524), respectively. None of the variances across initial margin categories were statistically significant. Limitations: Early-stage melanomas have low overall mortality rates. In our associated article, initial margins of 5 to 10 mm were shown to have the lowest rates of local recurrence. Conclusions: In this systematic review and meta-analysis, melanoma-specific mortality was not significantly impacted by the initial surgical margin taken during Mohs micrographic surgery.

Increasing Incidence and Decreasing Mortality of Cutaneous Melanoma in Middle-Aged Adults: An Epidemiologic Study in Olmsted County, Minnesota.

OBJECTIVE: To identify changes in the incidence and mortality of cutaneous melanoma in the fastest-growing segment of the US population, middle-aged adults. PATIENTS AND METHODS: Using the Rochester Epidemiology Project, patients aged 40 to 60 years with a first lifetime diagnosis of cutaneous melanoma between January 1, 1970, and December 31, 2020, while a resident of Olmsted County, Minnesota, were identified. RESULTS: A total of 858 patients with a primary cutaneous first-time melanoma were identified. The overall age- and sex-adjusted incidence rate increased from 8.6 (95% CI, 3.9 to 13.3) per 100,000 person-years in 1970-1979 to 99.1 (95% CI, 89.5 to 108.7) per 100,000 person-years in 2011-2020 (11.6-fold increase). There was a 52.1-fold increase in women and a 6.3-fold increase in men between these 2 periods. In recent years (2005-2009 vs 2015-2020), the incidence has stabilized in men (1.01-fold increase; P=.96) and continues to significantly increase in women (1.5-fold increase; P=.002). Among 659 patients with invasive melanoma, 43 deaths were due to melanoma, and male sex was significantly associated with an increased risk of death (hazard ratio, 2.95; 95% CI, 1.45 to 6.00). A more recent diagnosis of melanoma was significantly associated with a decreased risk of death due to melanoma (hazard ratio, 0.66 per 5-year increase in calendar year of diagnosis; 95% CI, 0.59 to 0.75). CONCLUSION: Melanoma incidence has significantly increased since 1970. During the past 15 years, the incidence has continued to rise in middle-aged women (approximately 50% rise in incidence) but has stabilized in men. Mortality decreased in a linear fashion throughout this time.

Spatial heterogeneity of global forest aboveground carbon stocks and fluxes constrained by spaceborne lidar data and mechanistic modeling.

Forest carbon is a large and uncertain component of the global carbon cycle. An important source of complexity is the spatial heterogeneity of vegetation vertical structure and extent, which results from variations in climate, soils, and disturbances and influences both contemporary carbon stocks and fluxes. Recent advances in remote sensing and ecosystem modeling have the potential to significantly improve the characterization of vegetation structure and its resulting influence on carbon. Here, we used novel remote sensing observations of tree canopy height collected by two NASA spaceborne lidar missions, Global Ecosystem Dynamics Investigation and ICE, Cloud, and Land Elevation Satellite 2, together with a newly developed global Ecosystem Demography model (v3.0) to characterize the spatial heterogeneity of global forest structure and quantify the corresponding implications for forest carbon stocks and fluxes. Multiple-scale evaluations suggested favorable results relative to other estimates including field inventory, remote sensing-based products, and national statistics. However, this approach utilized several orders of magnitude more data (3.77 billion lidar samples) on vegetation structure than used previously and enabled a qualitative increase in the spatial resolution of model estimates achievable (0.25° to 0.01°). At this resolution, process-based models are now able to capture detailed spatial patterns of forest structure previously unattainable, including patterns of natural and anthropogenic disturbance and recovery. Through the novel integration of new remote sensing data and ecosystem modeling, this study bridges the gap between existing empirically based remote sensing approaches and process-based modeling approaches. This study more generally demonstrates the promising value of spaceborne lidar observations for advancing carbon modeling at a global scale.

Local Recurrence Rates of Malignant Melanoma After Mohs Micrographic Surgery Are Lowest With 5- to 10-mm Initial Margins: A Systematic Review and Meta-Analysis.

BACKGROUND: Current consensus guidelines have discouraged the use of sub-0.5-cm (in situ) and sub-1-cm (invasive) margins when performing Mohs micrographic surgery (Mohs) for melanoma, with minimal evidence to guide this recommendation. OBJECTIVE: To compare melanoma local recurrence rates after Mohs based on initial margin size. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted with search terms including Mohs micrographic surgery, surgical margin, recurrent disease, and melanoma. RESULTS: Forty-three studies were included. The 5- to 10-mm margin category had a statistically significant lower local recurrence compared with 1- to 5-mm and 5-mm categories. Recurrence for 1- to 5-mm, 5-mm, 5- to 10-mm, and 10-mm categories were 2.3% (CI 0.8-3.5, p < .001), 1.4% (CI 0.6-2.2, p < .001), 0.3% (CI 0.2-0.5, p < .001), and 6.1% (CI -6.7 - 18.8, p = .349), respectively. Number of stages for 1 to 5, 5, 5 to 10, and 10-mm categories were 1.8, 1.8, 1.6, and 1.6, respectively. There was no statistically significant difference between the groups (p = .694). CONCLUSION: Five- to 10-mm margins were associated with the lowest local recurrence rates. A 5- to 10-mm initial margin should be considered where other factors (tumor characteristics, anatomical or functional considerations) allow.

Local Recurrence Rates of Extramammary Paget Disease Are Lower After Mohs Micrographic Surgery Compared With Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Extramammary Paget disease (EMPD) is a rare, slow growing neoplasm that presents most commonly in the anogenital region of older adults. OBJECTIVE: To analyze the difference in local recurrence rates of EMPD in patients treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic review of the literature and meta-analysis were performed. Inclusion criteria were adults greater than 18 years of age with a diagnosis of EMPD who have undergone surgical intervention and had follow-up data. Studies were independently reviewed by 2 coinvestigators with discrepancies resolved by the principal investigator. RESULTS: Twenty-seven studies met the inclusion criteria. Patients had a 2.67 times higher chance of local recurrence after WLE than MMS (95% confidence interval [CI]:1.47, 4.85; p = .001). Meta-analysis of single-arm studies revealed a 7.3% local recurrence rate after MMS (95% CI: 0.039, 0.107; p < .001) versus a 26.3% recurrence rate after WLE (95% CI: 0.149, 0.376; p < .001). After excluding recurrent tumors, the odds ratio for recurrence in WLE versus MMS was 2.3 (95% CI: 0.285, 18.43, p = .435). CONCLUSION: There is a clinically and statistically increased risk of local recurrence of EMPD after WLE compared with MMS.

Risk Factors for Canalicular Injury After Mohs Micrographic Surgery.

BACKGROUND: There is a paucity of literature describing risk factors for canalicular injury (CI) during periocular Mohs micrographic surgery (Mohs). OBJECTIVE: This study aimed to determine factors associated with CI after Mohs. This information may inform patient counseling and surgical planning. MATERIALS AND METHODS: This case-control study compared subjects with canalicular injury after Mohs with subjects requiring ophthalmologic Mohs repair without canalicular injury. All subjects who had CI after Mohs were included in the control group. CI from other causes were excluded. RESULTS: Basal cell carcinoma was the most common etiologic tumor (p < .00001). Canalicular injury was associated with infiltrative, morpheaform, and/or micronodular-type basal cell carcinoma. Initial tumor location involving the medial canthus was not statistically different between cases and controls (32% vs 17%, p = .22). Having a final defect involving the medial canthus region was more likely in cases versus controls (55% vs 26%, p = .01952). CONCLUSION: Although most final defects involved the medial canthal region, a substantial number of tumors resulting in CI did not initially seem to involve the medial canthus. Surgeons cannot rely simply on anatomical location when assessing risk for CI, and anticipation of need for canalicular reconstruction is challenging.