Use of Imaging in Cutaneous Squamous Cell Carcinoma to Detect High-Risk Tumor Features, Nodal Metastasis, and Distant Metastasis: A Systematic Review.

BACKGROUND: Imaging has been shown to impact management and disease outcomes in cutaneous squamous cell carcinoma, but the literature on optimal modalities is lacking. OBJECTIVE: To perform a systematic review evaluating the performance of various imaging studies for the detection of perineural spread, bony invasion, nodal metastasis (NM), and distant metastasis in cutaneous squamous cell carcinoma. MATERIALS AND METHODS: Four databases were searched for relevant terms. Articles were included if they presented primary data on 5 or more subjects with cutaneous squamous cell carcinoma who underwent imaging to detect perineural spread, bony involvement, NM, or distant metastasis. RESULTS: Thirty studies and 1,027 subjects were included in the pooled analysis. Magnetic resonance imaging had a 94.9% sensitivity in detecting perineural spread. Computed tomography (CT) demonstrated a sensitivity of 75.7% and specificity of 98.6% in detecting bony invasion. While ultrasound, positron emission tomography-computed tomography, and CT all performed reasonably well in detecting NM, CT demonstrated the highest sensitivity (96.4%) and specificity (100%). Imaging changed management in up to 33% of cases. CONCLUSION: Imaging is useful in high-risk cutaneous squamous cell carcinoma. Magnetic resonance imaging performs best in the detection of perineural spread, and CT is the most accurate modality to detect bony invasion and NM.

Cutaneous Squamous Cell Carcinoma Outcomes in Solid Organ Transplant Recipients: A Matched Retrospective Cohort Study.

BACKGROUND: Solid organ transplant recipients with cutaneous squamous cell carcinoma (CSCC) have an increased risk of poor outcomes. However, a recent study demonstrated that immunosuppression is not an independent risk factor for these poor outcomes after controlling for primary tumor stage. OBJECTIVE: To evaluate whether transplant status is an independent risk factor for poor outcomes in CSCC. MATERIALS AND METHODS: A database of CSCCs treated at an academic center over 10 years was used to perform a retrospective cohort study comparing the risk of poor outcomes (local recurrence, regional and distant metastases, and disease-specific death) in solid organ transplant recipients and controls. Subjects were matched on age, tumor stage, sex, tumor site, and time to poor outcome. RESULTS: There were 316 tumors from 78 transplant patients and 316 tumors from 262 controls. On multivariate analysis, tumor stage and location on the head and neck were predictive of poor outcomes. There was no significant difference in the risk of poor outcomes in the transplant group versus the control group. CONCLUSION: Transplant status was not an independent risk factor for poor squamous cell carcinoma outcomes after controlling for stage, age, sex, site, and time to poor outcome.

Performance of Staging Systems for Non-Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The performance of staging systems in non-head and neck cutaneous squamous cell carcinomas has not been well established. OBJECTIVE: To evaluate the performance of the American Joint Committee on Cancer 8th Edition and Brigham and Women's Hospital staging systems in non-head and neck squamous cell carcinomas. MATERIALS AND METHODS: Eligible tumors were identified and staged from an existing retrospective database. Cumulative incidence function curves of any poor outcome were generated. Distinctiveness, sensitivity, specificity, positive and negative predictive value, and concordance index were calculated. RESULTS: 1,042 primary tumors were included, with 38 resulting in any poor outcome and 16 in any major poor outcome. High-stage tumors represented 2.2% and 3.5% of tumors; these accounted for 10/38 of the poor outcomes (26.3%) and 8/16 of the major poor outcomes (50%). High-stage tumors predicted major poor outcomes with a sensitivity of 0.5 and specificity of 0.99 for the Brigham and Women's Hospital system, and a sensitivity of 0.5 and specificity of 0.97 for the American Joint Committee on Cancer 8th edition system. The concordance index for both was 0.74. CONCLUSION: Current staging systems can be used to predict poor outcomes in cutaneous squamous cell carcinomas off the head and neck.

Use of the Retroauricular Pull-Through Sandwich Flap for Repair of an Extensive Conchal Bowl Defect With Complete Cartilage Loss.

Reconstruction of an extensive conchal bowl defect with notable cartilage loss is challenging due to the unique shape of the concha, the need for adequate structural support, and the lack of adjacent tissue reservoirs. Repair of a full-thickness conchal bowl defect has included 3-stage approaches, such as the anterior pedicled retroauricular flap. For an extensive conchal defect with substantial cartilage loss but intact posterior auricular skin, we recommend consideration of the retroauricular pull-through sandwich flap, which combines a cartilage graft and retroauricular interpolation flap pulled through a posterior auricular incision to resurface the anterior ear.

Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives.

Five percent of patients with cutaneous squamous cell carcinoma develop locally advanced or metastatic disease that is not amenable to definitive surgical or radiation therapy. Cemiplimab, an antibody against programmed death receptor-1, was approved in the United States for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma in 2018. We performed a literature review on the use of cemiplimab in cutaneous squamous cell carcinoma, with an emphasis on efficacy, safety and tolerability, patient selection, and future directions. Embase and PubMed were searched for relevant terms, and 23 peer-reviewed journal articles presenting primary data on cemiplimab treatment in 5 or more subjects with cutaneous squamous cell carcinoma were included and summarized. Objective response rates in locally advanced and metastatic disease ranged from 42.9% to 50.8% in Phase I/II clinical trials and 32-77% (median 58%) in post-approval observational studies. Phase II trials looking at neoadjuvant use also had favorable response rates. Real-world studies demonstrated cemiplimab efficacy in periorbital tumors, tumors with large caliber perineural invasion, and tumors in solid organ transplant recipients. Cemiplimab was safe and well-tolerated in most patients. While side effects such as fatigue, diarrhea, pruritus, and rash were fairly common, only 9.8% of adverse events required cessation of therapy in phase II trials. Severe adverse events were primarily immune-mediated, including pneumonitis, myocarditis, myositis, and autoimmune hepatitis; the risk of treatment-related death was 3% in clinical trials. Further research on cemiplimab therapy in cutaneous squamous cell carcinoma is needed, and trials are now underway to obtain Phase IV long-term real-world data, further data on adjuvant and neoadjuvant use, and additional data in special populations such as stem cell and solid organ transplant recipients.

Nevus Spilus With Dermatoheliosis: A Histologic Mimicker of Melanoma in Situ at Melanoma Excision Margins.

ABSTRACT: Nevus spilus, or speckled lentiginous nevus, is a relatively common lesion that presents at birth or in early childhood. It consists of a background tan patch, which appears similar to a café au lait macule or lentigo simplex on histology, studded with various types of nevi. Rarely, these nevi can undergo malignant transformation to melanoma. When melanoma develops within a heavily photodamaged nevus spilus, evaluating excision margins may be challenging because the combined histologic features of nevus spilus and severe dermatoheliosis can mimic melanoma in situ. We report a case of an elderly man with extensive sun damage who developed malignant melanoma within an occult nevus spilus, resulting in multiple excisions with false-positive margins.

The role of sentinel lymph node biopsy in extramammary paget disease: a systematic review.

Sentinel lymph node biopsy is increasingly used to detect subclinical nodal metastases in extramammary Paget disease. We performed a comprehensive systematic review of the literature to further explore the role of sentinel lymph node biopsy in extramammary Paget disease. Five databases were searched for relevant terms. Articles were included if they were in English and presented primary data on at least one patient with extramammary Paget disease who underwent sentinel lymph node biopsy in the absence of lymphadenopathy or known metastatic disease. Twenty-eight articles were included, with 366 subjects. Seventy-seven sentinel node biopsies (21.2%) were positive, including 12 in which the primary tumor had microinvasion (15.6%) and 56 with deep invasion (72.7%). Of the positive cases, 11 (14.3%) had no further treatment, 54 (70.1%) underwent nodal dissection, 4 (5.2%) were treated with systemic agents, and 1 (1.3%) had radiation. After a mean follow up of 24 months, 9 subjects with a positive lymph node biopsy experienced nodal recurrence (11.7%), 15 had distant metastases (19.5%), and 13 died of the disease (16.9%). In conclusion, invasive extramammary Paget disease is strongly associated with poor outcomes including nodal metastasis, distant metastasis, and disease specific death. Sentinel lymph node biopsy is a useful tool to screen for subclinical nodal metastases in invasive disease, and can be used to help guide clinical management.

Simulation-based training in dermatologic surgery: a literature review.

Simulation-based training has been shown to increase confidence and improve technical proficiency in surgical trainees. In this review, we describe the methods of simulation-based training currently being utilized in cutaneous surgery education. PubMed and EMBASE were searched for terms related to dermatologic surgery, education, and simulation. Articles published in English from 2013 onward that discussed simulation-based cutaneous surgery training of dermatology, plastic surgery, or otolaryngology resident physicians were included and summarized. Currently utilized simulation modalities in the training of dermatologic surgeons include skin substitutes, cadavers, and technology-based platforms. While each of these modalities have been shown to enhance trainee confidence and/or skill, head-to-head studies comparing their efficacy and usefulness are limited. Dermatologic surgery training, and therefore patient care, may be enhanced by further incorporation of simulation training. However, further studies are needed to clarify the optimal simulation platforms and delivery.

Periorbital reconstructive techniques following Mohs micrographic surgery or excisions: a systematic review.

There are many articles in the literature on periorbital reconstruction after Mohs micrographic surgery (MMS) or surgical excision, however, the literature lacks a comprehensive systematic review of these reports. We performed a systematic review of published data on periorbital defect reconstruction to identify trends in the literature. A comprehensive search of eight databases was performed. To be included in the study, articles had to be published in English between 2005 and 2020 and contain repair data for MMS or excision defects in the periorbital region. Studies with less than four patients, literature or systematic reviews, and abstract-only publications were excluded. Data extracted from eligible articles included the authors' medical specialties, study design, subject number and demographics, defect characteristics, procedure type, reconstructive methods, complications, outcome measures, and method of outcome assessment. 53 studies met the inclusion criteria. The first and last authors' specialties were ophthalmology (47%), plastic and reconstructive surgery (23%), dermatology (13%), otolaryngology (4%), or were multi-specialty collaborations (13%). Only 5 of the studies were prospective. Defects were located on the lower eyelid (55%), medial canthus (31%), upper eyelid (8%), lateral canthus (4%), or a combination of these sites (2%). Reconstructive methods were reported for 3678 cases and included linear repair (18%), advancement flap (8%), rotation flap (5%), transposition flap (3%), island pedicle flap (1%), unspecified local skin flap (21%), skin graft (23%), secondary intention (4%), tarsoconjunctival flap (3%), and combined reconstruction techniques (13%). Thirty-three of 53 articles specified the periorbital subunit for each reconstructive technique that was employed. Among these 33 articles which allowed for correlation between defect location and reconstructive technique, the most utilized repair method for lower eyelid defects was local skin flap. Defects on the upper eyelid or medial canthus were most frequently repaired with a skin graft. Forty articles commented on cosmetic outcomes, however, only 3 of these articles utilized a defined grading system, objective measurements, or independent reviewers to assess the cosmetic outcomes. The methods of reconstruction in this review were diverse, however, local skin flaps and grafts were the most utilized techniques. In future reports, increased reporting of reconstructive technique by defect location as well as increased use of standardized assessments of aesthetic outcomes can help strengthen this body of literature.

Mohs micrographic surgery for verrucous carcinoma: a review of the literature.

Verrucous carcinoma is a rare, low grade variant of squamous cell carcinoma that rarely metastasizes but tends to display aggressive local behavior. Wide local excision is the most common treatment, but has high rates of local recurrence, ranging from 19 to 75% in the literature. The cases of verrucous carcinoma treated with Mohs micrographic surgery in the literature, as well as a previously unpublished case is summarized. PubMed was searched for terms related to verrucous carcinoma and Mohs micrographic surgery, and articles reporting cases of verrucous carcinoma treated with Mohs were reviewed and summarized. A previously unpublished case treated at our institution was also reported. Thirty-eight cases of verrucous carcinoma treated with Mohs surgery were analyzed. The average age of patients was 52.1, and 50% were male. The most common sites were the foot (47%) and the anogenital region (34%). Lesion duration ranged from 0.17 to 40 years with a mean of 4.8 years, and tumor diameter ranged from 1 to 10 cm with a mean of 4.6 cm. The local recurrence rate following Mohs was 16%, with nodal metastasis occurring in 3% and no cases of distant metastasis. As verrucous carcinoma demonstrates locally aggressive behavior and a high risk of local recurrence, Mohs micrographic surgery should be considered as first line treatment. Further research directly comparing wide local excision to Mohs surgery is needed.

Clinical practicality of reporting cutaneous squamous cell carcinoma risk factors at the time of Mohs surgery.

Multiple high-risk factors have been associated with poor outcomes in cutaneous squamous cell carcinoma, including immunosuppression, poor differentiation, depth, diameter, and perineural invasion. While many of these are included in major staging systems, their measurement and reporting vary considerably in clinical practice. We performed a survey study of fellowship-trained Mohs surgeons to explore their attitudes and practices related to recording squamous cell carcinoma high-risk factors and staging information at the time of Mohs. An anonymous Qualtrics survey of 25 questions was distributed to the American College of Mohs Surgery membership listserv. There were 107 complete surveys (response rate 7.1%), with over 95% of subjects from the United States. Fifty-five percent had been practicing 10 years or less, 28% between 11 and 20 years, and the remainder greater than 20 years. Fifty-seven percent were in private or group practices, and 43% were in academia. Nearly all respondents consistently report tumor recurrence (100%), location (100%), immunosuppression (94%), and diameter (93%). Only 70% grade differentiation for every squamous cell carcinoma case. Sixty-six percent of participants consistently record anatomic depth, while only 2% always or almost always record Breslow depth. Although 96% of respondents almost always or always record perineural invasion, only 34% consistently record nerve diameter. Forty-three percent reported that they never or rarely stage cutaneous squamous cell carcinomas, whereas 43% often, almost always, or always stage. In conclusion, certain high-risk factors, such as differentiation, Breslow depth, and stage, are recorded inconsistently by Mohs surgeons. Several participants commented that they prefer to send a central debulk to dermatopathology to assess staging parameters in all tumors with high-risk features. While this strategy may be useful in some practice settings, Mohs surgeons possess the skills necessary to perform a central debulk analysis themselves at the time of Mohs. Whether performed at the time of Mohs or by dermatopathology, assessing high-risk features and accurately staging cutaneous squamous cell carcinoma is paramount to detecting tumors at higher risk of poor outcomes.

Repair of auricular defects following Mohs micrographic surgery or excision: a systematic review of the literature.

Repair of auricular defects following tumor removal can be challenging. Many techniques have been described, but the literature lacks a comprehensive review of these methods. To perform a systematic review to compile and describe methods of reconstruction for post-surgical defects on the ears, eight databases were searched using terms related to ear anatomy, Mohs and excisions, and repair methods. Articles were eligible for inclusion if they contained repair data for ear defects following Mohs or excision for at least 4 subjects and were published in English between 2004 and 2019. Two reviewers screened all abstracts, and then evaluated the remaining full text articles to determine eligibility. The authors' specialties, study design, subject information, tumor and defect characteristics, procedure, repair methods, outcomes, and complications were then extracted. Most articles were written by dermatologic surgeons (66.7%). Repair methods included wedge excisions (19 cases), second intention healing (376), linear closures (294), purse strings (4), locoregional flaps (221), and grafts (2003). Most studies were small observational case series or cohort studies that lacked clear outcome measures. The available evidence on this topic is low quality. Further research utilizing improved study designs and standardized outcome measures is needed.

Nasal reconstructive techniques following Mohs surgery or excisions: a systematic review.

Numerous reconstructive techniques for nasal defects following skin cancer removal have been described; however, the literature lacks a comprehensive systematic review. Our objective was to systematically review nasal reconstruction methods after tumor removal, correlate the use of specific techniques to the nasal subunits involved, assess the quality of the available evidence, and set the stage for future research on this topic. Eight databases were searched for studies published in English from January 2004 to December 2018 containing repair data for nasal defects following Mohs or excision for four or more subjects. Recorded data included author specialties, study design, subject number, demographics, defect characteristics, procedure type, reconstructive methods, outcome measures, and complications. One-hundred and eleven studies were included. Study types included case series (73%), observational cohort studies (25%), and clinical trials (2%). Most authors were dermatologic surgeons (61%). Resection was most commonly performed via Mohs (82%). Flaps (42%), linear closures (28%) and grafts (25%) were most utilized for reconstruction. In Zones I and II, transposition flaps were the most common followed by advancement flaps. In Zone III, full thickness skin grafts were the most common repair. Most studies were case series or small cohort studies, representing low level evidence. Flaps are the most common method described in the literature for nasal reconstruction. The overall quality of the evidence available on this topic is low.

Learning Experiences in LGBT Health During Dermatology Residency.

Approximately 4.5% of adults in the United States identify as members of the lesbian, gay, bisexual, transgender (LGBT) community, and this population has a variety of health care disparities. Dermatologists have the potential to greatly impact the health of this community, but learning experiences in dermatology residency are lacking. In this study, we investigated LGBT education in dermatologic residency from the residents' perspective and assessed preparedness of dermatology residents to care for this community. An online survey was distributed to current US dermatology residents through program coordinator and program director listserves and postings on dermatology social media groups. Descriptive statistics and a Kruskal-Wallis rank test were used for analysis. There were 114 respondents. This study demonstrated that many dermatology residents are not effectively taught LGBT health topics and feel unprepared to treat this community. Most dermatology residents desired increased training. Further research is needed to determine the best strategies for increasing LGBT learning experiences in dermatology residency programs.

Natural Killer Cell Recognition and Control of Epithelial Cancers.

ABSTRACT: Natural killer (NK) cells possess an innate ability to recognize cancer and are key mediators of cytotoxic efficacy for anticancer antibodies. Recent advances in the ability to generate, qualify, and safely infuse NK cells have led to a wide variety of clinical trials in oncology. Although their efficacy is best established for liquid cancers, their potential application in solid cancers has received increased attention. Here, we provide general background across a disparate group of exemplary solid tumors for which there is evidence for an NK cell role, discuss NK cell recognition motifs specific to each and murine and human studies of each that are supportive of NK cell adoptive immunotherapy, and end with special considerations relevant to the solid tumor microenvironment.