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.

Mohs surgery for female genital Paget's disease: a prospective observational trial.

BACKGROUND: Extramammary Paget's disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy. OBJECTIVE: This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget's disease. STUDY DESIGN: We conducted a prospective observational trial of patients with vulvar or perianal Paget's disease treated with surgical excision guided by Mohs micrographic surgery between 2018 and 2022. The multidisciplinary protocol consisted of office-based scouting biopsies and modified Mohs surgery followed by surgical excision with wound closure under general anesthesia. Modified Mohs surgery cleared peripheral disease margins using a moat technique with cytokeratin 7 staining. Medial disease margins (the clitoris, urethra, vagina, and anus) were assessed using a hybrid of Mohs surgery and intraoperative frozen sections. Surgical and oncologic outcomes were compared with the outcomes of a retrospective cohort of patients who underwent traditional surgical excision. The primary outcome was 3-year recurrence-free survival. RESULTS: Three-year recurrence-free survival was 93.3% for Mohs-guided excision (n=24; 95% confidence interval, 81.5%-100.0%) compared to 65.9% for traditional excision (n=63; 95% confidence interval, 54.2%-80.0%) (P=.04). The maximum diameter of the excisional specimen was similar between groups (median, 11.3 vs 9.5 cm; P=.17), but complex reconstructive procedures were more common with the Mohs-guided approach (66.7% vs 30.2%; P<.01). Peripheral margin clearance was universally achieved with modified Mohs surgery, but positive medial margins were noted in 9 patients. Reasons included intentional organ sparing and poor performance of intraoperative hematoxylin and eosin frozen sections without cytokeratin 7. Grade 3 or higher postoperative complications were rare (0.0% for Mohs-guided excision vs 2.4% for traditional excision; P=.99). CONCLUSION: Margin control with modified Mohs surgery significantly improved short-term recurrence-free survival after surgical excision for female genital Paget's disease. Use on medial anatomic structures (the clitoris, urethra, vagina, and anus) is challenging, and further optimization is needed for margin control in these areas. Mohs-guided surgical excision requires specialized, collaborative care and may be best accomplished at designated referral centers.

Surgical Outcomes of Primary Dermatofibrosarcoma Protuberans: A Retrospective, Multicenter Study.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with a low rate of metastatic disease. Previous series have shown a superiority of Mohs micrographic surgery (MMS) compared with wide local excision (WLE). Likewise, there is paucity of data examining the long-term follow-up of patients. OBJECTIVE: The purpose of the current study was to examine the outcome of surgical treatment of primary DFSP of the trunk and extremities. METHODS: We reviewed 236 patients (115 females, 121 males, mean age 41 ± 15 years) undergoing MMS (n = 81, 34%) or WLE (n = 155, 66%) to treat a primary DFSP. Mean tumor size and follow-up was 4 ± 2 cm and 7 years, respectively. Final margins were negative in 230 (97%) patients. RESULTS: There was no difference (p > 0.05) in patient age, sex, tumor size, negative margin excision, or history of a previous inadvertent excision between patients who underwent WLE and those undergoing MMS. There were two cases of local recurrence and two cases of metastasis, with no difference in the 5-year local recurrence-free survival (98% vs. 99%, p = 0.69) or metastatic-free survival (98% vs. 100%, p= 0.27) between WLE and MMS. CONCLUSION: There was no difference in oncologic outcome comparing MMS with WLE for DFSP outside the head and neck. The goal of treatment for DFSP is to achieve a negative margin, regardless of surgical treatment modalities. A 'less is more' approach to follow-up can likely be taken for patients with completely resected DFSP in easy-to-examine anatomical areas. In these patients, no formal follow-up should be required.

Merkel cell carcinoma of unknown primary: Clinical presentation and outcomes.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion. METHODS: We reviewed 415 patients with biopsy-proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease-free survival, and overall survival. RESULTS: Patients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence-free survival was 59.3% at 5 years. Disease-specific survival was 63.3% at 5 years. CONCLUSION: Patients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

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.

Rates of Upstaging, Between Diagnosis and Surgery, and Clinical Management of Metastatic Cutaneous Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC. OBJECTIVE: The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC. MATERIALS AND METHODS: This was a retrospective, case-control, single institution, multi-center study. Univariate analysis was used. RESULTS: Sixty-eight subjects (34 metastatic & 34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p < .001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p < .001). CONCLUSION: Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Outcomes of Sentinel Lymph Node Biopsy for Primary Cutaneous Squamous Cell Carcinoma of the Head and Neck.

BACKGROUND: Limited data exist on sentinel lymph node biopsy (SLNB) for cutaneous squamous cell carcinoma (cSCC) of the head and neck. OBJECTIVE: To review the results of SLNB for patients with cSCC of the head and neck at the authors' institution. MATERIALS AND METHODS: A retrospective review was completed for patients who underwent SLNB for cSCC of the head and neck over 19 years. Patient demographics, immune status, tumor stage, total patients with positive SLNB, local recurrence, nodal recurrence, in-transit metastasis, and disease-specific death were recorded. RESULTS: Sixty patients underwent lymphoscintigraphy, and an SLN was identified in 58 patients. The mean follow-up was 3.2 years (range, 15 days-16 years). Four patients (6.9%) had a positive SLNB. All were Brigham and Women's Hospital (BWH) stage T2b tumors. Three of these patients were immunosuppressed, 3 patients underwent neck dissection, and 2 patients received adjuvant radiation. None developed local or regional recurrence. Of the 53 patients with a negative SLNB, there were 4 local recurrences, 2 in-transit metastases, and no nodal recurrences. CONCLUSION: Immunosuppressed patients with tumors BWH stage T2b or greater may be a reasonable cohort to focus future prospective studies on the utility of SLNB in cSCC of the head and neck.

Systematic Review of Technical Variations for Mohs Micrographic Surgery for Melanoma.

BACKGROUND: Mohs micrographic surgery (MMS) for cutaneous melanoma is becoming more prevalent, but surgical technique varies. OBJECTIVE: To define variations in published techniques for MMS for melanoma. METHODS AND MATERIALS: A systematic review was performed of PubMed, EMBASE, and Scopus databases to identify all articles describing surgical techniques for MMS for melanoma. Technical details were recorded for the preoperative, intraoperative, and postoperative phases of MMS. RESULTS: Twenty-four articles were included. Mohs surgeons vary in how they assess clinical margins, how wide a margin they excise on the first MMS layer, and how they process tissue to determine tumor stage and margin clearance during MMS for melanoma. CONCLUSION: Mohs micrographic surgery for melanoma is performed with varied surgical techniques. To establish best practices, additional research is necessary to determine how different techniques affect outcomes.

Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia.

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. OBJECTIVE: To evaluate the association of factors associated with SCC risk. METHODS: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). LIMITATIONS: The sample size decreases when combining all risk factors in a single model. CONCLUSION: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.

Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma.

BACKGROUND: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease. OBJECTIVE: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease. METHODS: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome. RESULTS: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P = .0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95% confidence interval 0.21-0.84; P = .0113). LIMITATIONS: This is a multicenter but single institution study of a white population. CONCLUSION: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.

Nasal Valve Insufficiency in Dermatologic Surgery.

BACKGROUND: Few publications have addressed nasal valve (NV) insufficiency as a complication of Mohs micrographic surgery. OBJECTIVE: To comprehensively review the literature and further characterize the causes, prevalence, evaluation, and management of NV insufficiency as it relates to cutaneous oncology. MATERIALS AND METHODS: A PubMed search was completed to identify articles related to the NV in the context of Mohs micrographic surgery, cutaneous oncology, and reconstruction. RESULTS: Nasal valve insufficiency may occur during tumor removal and/or reconstruction. Defect size larger than 1 cm; location on the ala, sidewall, or alar crease; lack of structural support; and poorly planned flaps are the main risk factors for NV insufficiency. Several surgical techniques have been described to avoid and correct this complication. CONCLUSION: Nasal valve insufficiency may be an underrecognized and underreported complication of Mohs micrographic surgery. Nasal valve insufficiency may be identified with relatively simple tests. Knowledge of NV anatomy and preoperative function assessment is essential. Recognition of this potential complication and awareness of its prevention and management may decrease morbidity in patients undergoing cutaneous surgery.

Safety of Oral Midazolam as a Perioperative Anxiolytic for Outpatient Dermatologic Procedures.

BACKGROUND: Perioperative anxiety can negatively impact patient satisfaction and can complicate outpatient dermatologic procedures. OBJECTIVE: Evaluate adverse events associated with oral midazolam as a perioperative anxiolytic during dermatologic surgery and assess whether an enhanced monitoring approach is associated with an increased detection rate. MATERIALS AND METHODS: Five hundred cases (250 before and after change in monitoring) where patients were administered oral midazolam between July 2015 and May 2017 were retrospectively reviewed. The number of procedures, type of procedures, dose in milligrams, number of doses, major and minor adverse events, and vital signs were recorded. RESULTS: The difference in number of treatment sites, types of procedures, and total dose administered was not significant. There were minor but significant differences in the mean change in blood pressure, heart rate, respiratory rate, and Richmond Agitation and Sedation Scale score before and after the procedure but not oxygen saturation. These vital sign changes were not clinically significant. There were zero major adverse events in both groups. There were 2 patients who became transiently hypoxic. CONCLUSION: Oral midazolam administration was not associated with major adverse events including in the more intensively monitored group. This supports its use as an anxiolytic for outpatient dermatologic procedures.

Management of local or regional non-nodal disease.

Some melanomas develop a striking avidity for lymphatic spread. In spite of multiple recurrences, patients can remain years without visceral metastasis. There is clearly a biologic reason for this lymphotrophic pattern of growth and dissemination, which we have yet to uncover. In-transit metastases have widely diverse clinical presentations and can be a stubborn disease to cure. As a result, a host of treatments exist that should be tailored to the individual patient.

Comparison of tumor staging systems for cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) are at increased risk for poor outcomes as a result of cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: To compare the relative effectiveness of tumor staging systems for CSCC in a well-defined cohort of patients with CLL. METHODS: This retrospective outcomes study included 454 CSCC tumors among 161 patients with underlying CLL who were evaluated at a single academic medical center. Each tumor was staged according to Brigham and Women's Hospital (BWH), Union for International Cancer Control eighth edition (UICC8), and American Joint Committee on Cancer seventh edition (AJCC7) and eighth edition (AJCC8) criteria. We compared the effectiveness of tumor risk stratification according to each system. RESULTS: The BWH tumor staging system demonstrated superior risk stratification relative to the AJCC7 criteria (C-index, 0.725 vs 0.615; P = .036) and trended toward improved stratification relative to the AJCC8 (C-index, 0.796 vs 0.732; P = .214) and UICC8 (C-index, 0.725 vs 0.636; P = .096) staging systems. LIMITATIONS: Our study must be interpreted in the context of its retrospective design and relatively small number of adverse outcomes available for statistical analysis. CONCLUSIONS: The BWH system outperformed the AJCC7 criteria and trended toward superior risk stratification relative to both the AJCC8 and UICC8 criteria.

Opioid prescribing for acute postoperative pain after cutaneous surgery.

BACKGROUND: Little information is available to predict which patients require opioid analgesia following cutaneous surgery. When opioids are indicated, information regarding the optimal opioid agent selection and dosage is lacking. OBJECTIVE: To make recommendations for opioid prescription after cutaneous surgery. METHODS: A PubMed literature search was conducted to review the available literature. Recommendations are presented on the basis of available evidence and the opinion of the authors. RESULTS: Most patients undergoing cutaneous surgery do not require opioid analgesia. For those who do, the duration of pain warranting opioid analgesia is generally less than 36 hours. Opioid refill requests warrant a follow-up visit to ascertain the cause of ongoing pain after excisional procedures. LIMITATIONS: The recommendations are not based on prospective randomized trials. CONCLUSIONS: The presented recommendations for opioid prescription practice are derived from available evidence, recommendations, and expert opinion.

The prognostic value of inositol polyphosphate 5-phosphatase in cutaneous squamous cell carcinoma.

BACKGROUND: Inositol polyphosphate 5-phosphatase (INPP5A) has been shown to play a role in development and progression of cutaneous squamous cell carcinoma (cSCC). The goal of the current study was to explore the prognostic value of INPP5A expression in cSCC. METHODS: A total of 189 cases of actinic keratosis and SCC in 174 patients were identified; clinical and outcome data were abstracted, histopathology was rereviewed, and immunohistochemical staining and interpretation was performed for INPP5A. RESULTS: The majority of tumors (89.4%) had an INPP5A score of 2 or 3. No patients had complete loss of INPP5A. Tumors with an INPP5A score of 1 were more likely to be intermediate- to high-risk tumors (Brigham and Women's Hospital stage ≥T2a 85.0% vs 23.7% [P < .0001]) characterized by a larger diameter (2.4 cm vs 1.3 cm [P = .0004]), moderate-to-poor differentiation (86.7% vs 17.6% [P < .0001]), and perineural invasion (37.5% vs 5.3%, [P < .0001]). An INPP5A score of 1 was associated with a worse 3-year survival (a rate of 42.3% [hazard ratio, 2.81, P = .0006]) and a local metastasis rate of 48.0% (hazard ratio, 4.71; P < .0001). CONCLUSIONS: Low INPP5A scores are predictive of aggressive tumors and may be a useful adjunct to guide clinical management of cSCC.

Squamous Cell Carcinoma in Perineal, Perianal, and Gluteal Hidradenitis Suppurativa: Experience in 12 Patients.

BACKGROUND: Few reports describe squamous cell carcinoma (SCC) arising in hidradenitis suppurativa (HS). OBJECTIVE: The 2 objectives were (1) to describe the clinical characteristics, pathologic findings, and postoperative outcomes of SCC in HS and (2) to assess whether human papillomavirus (HPV) is involved in the pathogenesis. MATERIALS AND METHODS: Cases of SCC in HS were identified through institutional medical records (1976-2013) and the Rochester Epidemiology Project. Tumor specimens were assessed for HPV DNA/RNA with in situ hybridization. RESULTS: Twelve patients were identified (11 Caucasians and 9 men). All SCCs involved gluteal, perianal, or perineal skin; 1 patient had, in addition, involvement of the vagina. Surgical excision was performed on all 12 patients, 4 of whom had a colostomy. Mean duration of HS before SCC development was 28.5 years (range, 15-53 years). Mean follow-up was 4.3 years after surgical excision. Seven of 12 patients followed had postoperative SCC recurrence. Squamous cell carcinoma caused death despite wide surgical excision in these 7 patients. Of the remaining 5 patients, 4 are unknown and 1 who did not recur had an in situ SCC (Bowen disease carcinoma). Squamous cell carcinoma was not associated with high-risk or low-risk HPV. CONCLUSION: Invasive SCC arising in HS carries a high risk of death.

Patient-Centered Outcomes for Skin Cancer Management: Utilization of a Patient Delphi Process to Identify Important Treatment Themes.

BACKGROUND: Patient-reported outcomes are critical to research directed at maximizing patient benefit. The outcomes patients consider most relevant in the treatment of skin cancer have not been directly investigated. OBJECTIVE: To develop a ranked list of outcomes deemed most important by patients with skin cancer through a proctored Delphi process. METHODS: Twenty-one patients with a history of skin cancer volunteered to participate in the patient summit. The patient members participated in a guided discussion to generate a long list of potentially relevant outcomes. The list was then condensed and ranked through 2 rounds of a proctored Delphi process. RESULTS: Patients were diverse in their skin cancer histories and complexities, ages, and states of residence. Twelve themes were rated as highly important by 70% or more of participants. Most of these themes related to patient education and the collaborative nature of the physician-patient relationship. Fear of recurrence and cosmetic outcome were also highly rated. Limitations include a preponderance of older patients and patients from the midwest and northeast. CONCLUSION: Patients with skin cancer overwhelmingly prioritize a shared decision-making process, in which they are actively engaged and value detailed education regarding their disease. This should inform future research directed at skin cancer treatment and current physician-patient interactions.