Skin Color Match in Head and Neck Reconstructive Surgery.

OBJECTIVES/HYPOTHESIS: To quantify the degree of color match achieved during microvascular facial reconstruction, and to describe a novel technique for improving reconstructive skin color match. We hypothesize that split-thickness skin grafts (STSG) placed atop de-epithelialized free tissue produces better facial skin color match than free tissue with intact epithelium. STUDY DESIGN: Cross sectional photographic study of reconstructed facial skin color match. METHODS: Sixty-eight adults, who underwent head and neck reconstructive surgery, were divided into six categories based on cutaneous reconstructive technique: cervicofacial flap, radial forearm free flap (RFFF), fibula free flap, anterolateral thigh free flap (ALT), STSG over adiopofascial flap (STAFF), and STSG over myogenous flap (STMF). Averaged color samplings of the reconstructed defect and adjacent normal skin were taken from digital photographs. The color difference was calculated using the delta-E calculation. Blinded expert observers also rated the degree of color match. Nonparametric cohort contrast and correlation statistical analyses were performed. RESULTS: The mean delta-E's and 10-point Likert ratings for the ALT, fibula, RFFF, STAFF, STMF, and cervicofacial flaps were 11.6, 10.0, 7.7, 6.3, 8.8, and 4.7, and 5.1, 6.4, 2.4, 3.2, 2.7, and 1.1, respectively. Likert scale inter-rater correlation was strong, with coefficient = 0.80. CONCLUSIONS: On average, STSG over de-epithelialized myogenous and adipofascial free tissue transfers produced a better color match than the skin paddles of donor sites, with the exception of the radial forearm donor site. Delta-E values obtained from photos correlated well with expert ratings of color match. This reliable technique for quantifying color match may be used in future studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1753-1759, 2022.

NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022.

The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.

The utility of PRAME staining in identifying malignant transformation of melanocytic nevi.

BACKGROUND: PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) staining is used to aid melanoma diagnosis. PRAME expression in nevus-associated melanoma (NAM) has not been evaluated. METHODS: PRAME IHC was applied to cases of NAM; staining for each population of melanocytes (benign and malignant) was graded based on the percentage of labeled cells. No labeling was graded 0, 1% to 25% labeling was 1+, 26% to 50% was 2+, 51% to 75% was 3+, and >76% was 4+. RESULTS: Thirty-six cases were reviewed. Sixty-seven percent (24/36) of melanomas were PRAME positive (4+) while no (0/36) nevi showed 4+ positivity. Eighty-one percent (29/36) of nevi were completely PRAME negative compared to 17% (6/36) of melanomas. In 67% of cases (24/36) PRAME differentiated between benign and malignant melanocyte populations. CONCLUSIONS: We identified a high rate (67%) of differential PRAME staining in adjacent benign and malignant melanocyte populations in NAM. In PRAME positive (4+) melanomas, PRAME differentiates 100% (24/24) of benign and malignant melanocyte populations. When 4+ staining is used as the threshold for positivity, PRAME staining has a sensitivity of 67% (24/36) and a specificity of 100% (36/36). These results support PRAME IHC can assist in distinguishing melanocyte populations in melanoma arising within nevi.

Impact of second-opinion dermatopathology reviews on surgical management of malignant neoplasms.

BACKGROUND: Second-opinion review is linked to error reduction and treatment changes in anatomic pathology. OBJECTIVE: We sought to establish the rate of diagnostic discrepancy identified by second-opinion dermatopathologic review and the effect on surgical treatment. METHODS: Cases referred for treatment of a malignant neoplasm diagnosed by an outside pathologist were reviewed. The external and internal second-opinion dermatopathologic reports were compared. Discordance in diagnosis, subtype, and treatment change owing to second-opinion review was recorded. The referring pathologist's level of dermatopathologic training was also documented. RESULTS: A total of 358 cases were included. Dermatopathologic second-opinion diagnosis was discordant with the outside diagnosis in 37 of 358 cases (10.3%). In 32 of 358 cases (8.9%), second-opinion review resulted in a change in treatment, with 28 of 32 (87.5%) of these changes resulting in cancelled surgery. Dermatologists without dermatopathologic fellowship training had the highest rate of discordant diagnoses compared with pathologists and dermatopathologists. LIMITATIONS: This was a retrospective study at a tertiary care facility. CONCLUSION: Second-opinion dermatopathologic review is associated with identification of discordant diagnoses and a substantial influence on treatment, with both cancellation of surgery and augmented management. Secondary pathologic review should be considered in high-volume surgical practices.

Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution.

Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C+CD301A+ myeloid dendritic cell population in psoriatic epidermis, and IL1ßhiCCL3hiCD14+ monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation.

Biochemistry, Physiology, and Tissue Interactions of Contemporary Biodegradable Injectable Dermal Fillers.

BACKGROUND: Injectable dermal fillers are becoming increasingly popular for soft tissue augmentation and rejuvenation. Most contemporary biodegradable products are derived from hyaluronic acid, calcium hydroxylapatite, or poly-L-lactic acid. Achievement of desired cosmetic outcomes is largely dependent on selection of the optimal injectable product based on the chemical composition, the physiologic interactions with surrounding tissue, product longevity, and a thorough understanding of potential adverse reactions. OBJECTIVE: To review and describe the biochemistry, physiology, and tissue interactions of the most commonly used contemporary biodegradable dermal fillers. METHODS: A thorough review of the literature was performed with additional review of pertinent clinical cases and corresponding histopathology. RESULTS: This article provides a comprehensive review of the biochemistry, physiology, and potential tissue interactions of the most commonly used biodegradable dermal fillers. The underlying biochemical properties of each product and how they contribute to specific physiologic and adverse tissue reactions is described. CONCLUSION: Understanding of the innate differences in the physical properties, and physiologic responses to soft tissue fillers allows clinicians to achieve desired aesthetic outcomes with fewer adverse events.

Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

Basal Cell Skin Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.

Dermatofibrosarcoma protuberans, version 1.2014.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

Merkel cell carcinoma, version 1.2014.

Merkel cell carcinoma is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative nonmelanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The NCCN Guidelines for Merkel Cell Carcinoma provide recommendations on the diagnosis and management of this aggressive disease based on clinical evidence and expert consensus. This version includes revisions regarding the use of PET/CT imaging and the addition of a new section on the principles of pathology to provide guidance on the analysis, interpretation, and reporting of pathology results.

Temporal dissection of tumorigenesis in primary cancers.

Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.

Sclerosing squamous cell carcinoma of the skin, an underemphasized locally aggressive variant: a 20-year experience.

BACKGROUND: Desmoplastic (sclerosing) responses to a variety of neoplasms have been documented but rarely evaluated in association with primary cutaneous squamous cell carcinoma (SCC). We report a distinctive variant of SCC demonstrating an infiltrative growth pattern and stromal desmoplasia. METHODS: Cases were identified through a retrospective review of our dermatopathology and dermatologic surgery databases. After initiation of the study, additional cases were identified prospectively. Neoplasms were scored microscopically for specific histopathologic parameters and reactivity with selected histochemical and immunohistochemical stains. Clinical follow-up data were obtained through a review of medical records or contact with the patient's referring physicians. RESULTS: Seventy-three carcinomas from 72 patients were identified (46 men, 26 women; median age 76, range 45-91). The original pretreatment biopsies were available in 69 of 73 cases. All lesions developed on sun-damaged skin, with the cheek constituting the most common site. The clinical presentation was typically as a sclerotic plaque. All neoplasms extended into the reticular dermis or subcutaneous fat, and perineural invasion was identified in 53 cases (73%). Patients who underwent standard excisional surgery experienced a recurrence rate of 80%; 9% of those treated with micrographic surgery experienced postoperative recurrences. Metastasis or carcinoma-related death was not observed in any patient during the follow-up period (median 36 months). CONCLUSIONS: Our results suggest that desmoplasia is uncommonly found in association with cutaneous SCC but helps define a locally aggressive variant of carcinoma. In light of the infiltrative nature of desmoplastic SCC of the skin and the high incidence of perineural invasion, micrographic surgery is the surgical modality of choice.

Hyperthermic injury to adipocyte cells by selective heating of subcutaneous fat with a novel radiofrequency device: feasibility studies.

BACKGROUND AND OBJECTIVE: The main objective of the present study is to demonstrate the feasibility of utilizing a novel non-invasive radiofrequency (RF) device to induce lethal thermal damage to subcutaneous adipose tissue only by establishing a controlled electric field that heats up fat preferentially. STUDY DESIGN/MATERIALS AND METHODS: Adipocyte cells in six-well plates were subjected to hyperthermic conditions: 45, 50, 55, 60, and 65 degrees C during 1, 2, and 3 minutes. Cell viability was assessed 72 hours after exposure. Two groups of abdominoplasty patients were treated with the RF device during and days before their surgical procedure. Temperatures of cutaneous and subcutaneous tissues were measured during treatment (3 minutes) of the first group. The immediate tissue response to heating was assessed by acute histology. The delayed tissue response was assessed by histology analysis of the second group, 4, 9, 10, 17, and 24 days after treatment (22 minutes). A mathematical model was used to estimate treatment temperatures of the second group. The model uses patient-based diagnostic measurements as input and was validated with in vivo clinical temperature measurements. RESULTS: Cell viability dropped from 89% to 20% when temperature increased from 45 to 50 degrees C during 1 minute exposures. Three minutes at 45 degrees C resulted in 40% viability. In vivo, the temperature of adipose tissue at 7-12 mm depth from the surface increased to 50 degrees C while the temperature of cutaneous tissues was <30 degrees C during RF exposure. Acute and longitudinal histology evaluations show normal epidermal and dermal layers. Subcutaneous tissues were also normal acutely. Subcutaneous vascular alterations, starting at day 4, and fat necrosis, starting at day 9, were consistently observed within 4.5-19 mm depth from the skin surface. Subcutaneous tissue temperatures were estimated to be 43-45 degrees C for 15 minutes. CONCLUSIONS: A controlled internal electric field perpendicular to the skin-fat interface is selective in heating up fat and, consequently, has the ability to induce lethal thermal damage to subcutaneous adipose tissues while sparing overlying and underlying tissues. In vitro adipocyte cells are heat sensitive to thermal exposures of 50 and 45 degrees C on the order of minutes, 1 and 3 minutes, respectively. In vivo, 15 minutes thermal exposures to 43-45 degrees C result in a delayed adipocyte cellular death response-in this study, 9 days. The novel RF device presented herein effectively delivers therapeutic thermal exposures to subcutaneous adipose tissues while protecting epidermal and dermal layers.

Radiation therapy for cutaneous squamous cell carcinoma involving the parotid area lymph nodes: dose and volume considerations.

PURPOSE: The intraparotid and periparotid lymph nodes are the most commonly involved when skin cancer of the head and neck metastasizes beyond the primary site. We sought to report the clinical outcome of patients treated with radiation therapy for parotid-area metastases from cutaneous squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: The records of 36 patients treated with radiation therapy for cutaneous squamous cell carcinoma involving the parotid-area lymph nodes were reviewed. All patients had clinically N0 necks and were without evidence of distant disease. Thirty patients (83%) were treated postoperatively after gross total tumor resection. Median dose to the parotid area was 60 Gy (range, 50-72 Gy). Treatment of clinically N0 necks consisted of surgical dissection (7 patients), irradiation (15 patients), and observation (14 patients). RESULTS: The 5-year estimate of local (parotid) control was 86% in patients treated using surgery with postoperative therapy and 47% in patients treated using radiation therapy alone. Three of 4 patients with tumors that relapsed locally after surgery and postoperative radiation received a dose of less than 60 Gy. Elective neck irradiation decreased the incidence of subsequent nodal failures from 50% to 0% and significantly improved neck control (p < 0.001). The 5-year overall survival rate was 63%. CONCLUSIONS: Surgery followed by radiation therapy to doses of at least 60 Gy results in effective local control for patients with parotid area metastasis from cutaneous squamous cell carcinoma. Routine irradiation of the clinically N0 neck is recommended.

Aesthetic analysis of Asian skin.

Attention to restoring healthy and more youthful facial skin complements facial plastic surgery, optimizing cosmetic results. Asian skin has structural and physiologic differences from white skin. These distinctions account for variations in response to ultraviolet light exposure and alternate clinical manifestations of photoaging. The response to cosmetic treatment modalities also differs in patients of darker skin pigmentation, and this needs to be recognized by the cosmetic and laser surgeon. This article reviews the biology of Asian skin and discusses a clinical approach to aesthetic analysis of Asian skin.