Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis.

Importance: Perineural invasion (PNI) is an adverse risk feature in cutaneous squamous cell carcinoma (CSCC) that affects patient prognosis and disease management. However, research comparing different PNI patterns on patient outcomes is limited. Objective: To compare 4 assessments of PNI in CSCC, their associations with poor outcomes, and implications for their inclusion in the Brigham and Women's Hospital (BWH) staging system. Design, Setting, and Participants: This retrospective cohort study was performed at a single tertiary care institution and compared 4 PNI assessments: nerve caliber, number of involved nerves per section, PNI maximal depth, and PNI location with respect to tumor. Patients with primary, localized, invasive CSCC with PNI diagnosed between January 1, 2000, and December 31, 2017, were identified via an electronic in-house database. Available pathology slides were secondarily reviewed by study authors. Relevant patient and tumor characteristics and outcomes were abstracted from the medical record. Data analysis was performed between September 6 and October 20, 2022. Main Outcomes and Measures: Risks of recurrence, disease-specific death, and a composite end point (any poor outcome) were calculated via multivariable stepwise Fine and Gray competing-risks regression. Considered revisions to the BWH staging system were assessed via receiver operating characteristic curves and test characteristics. Results: This study included 140 patients with CSCC, with a mean (SD) age of 75.1 (11.2) years. More than half of the patients were men (93 [66.4%]), and most identified as White (132 [94.3%]). Of the 4 PNI assessments studied, only involvement of multiple nerves was associated with poor outcomes. Perineural invasion of 5 or more distinct nerves (extensive PNI [ePNI]) was independently associated with local recurrence (subhazard ratio [SHR], 13.83 [95% CI, 3.50-54.62]; P < .001), disease-specific death (SHR, 6.20 [95% CI, 1.59-24.21]; P = .009), and any poor outcome (SHR, 10.21 [95% CI, 2.88-36.15]; P < .001). A revised BWH staging system with substitution of ePNI for large-caliber PNI resulted in improved area under the curve and test characteristics compared with current BWH staging criteria that use nerve caliber as the measure of PNI. Conclusions and Relevance: The findings of this cohort study suggest that ePNI is the best prognostic measure of PNI. Because ePNI obviated the need for a micrometer and had superior prognostic capacity to nerve caliber in this cohort, ePNI should be considered for inclusion in CSCC tumor staging. Inclusion of ePNI as a high-risk factor in CSCC staging systems may optimize patient selection for primary treatment and adjuvant interventions.

Recommendations for risk stratification of periocular squamous cell carcinoma.

Periocular squamous cell carcinoma is a common cutaneous malignancy with generally favorable outcomes; however, the periocular region is intrinsically a high-risk location, and there exist a subset of lesions with a propensity for poor outcomes. Orbital invasion, intracranial perineural spread, nodal and distant metastasis are feared complications. There are several staging systems for eyelid carcinoma and cutaneous squamous cell carcinoma, but the definition of high-risk lesions remains heterogeneous. It is unclear exactly which lesions can be safely deescalated, and which require nodal evaluation and adjuvant multimodal therapy. We seek to answer these questions by summarizing the literature on clinicopathologic variables, molecular markers, and gene profiling tests in periocular squamous cell carcinoma, with the extrapolation of data from the cutaneous squamous cell carcinoma literature. Standardized pathology reports with information on tumor dimensions, histological subtype and grade, perineural invasion, and lymphovascular invasion should become uniform. Integration with gene expression profiling assessments will individualize and improve the predictive accuracy of risk stratification tools to ultimately inform multidisciplinary decision-making.

Perineural invasion and perineural spread in periocular squamous cell carcinoma.

Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) of the periocular region is a prognostic marker of adverse tumour outcomes. PNI carries a well-established risk of tumour recurrence, regional metastasis and higher likelihood of mortality. This review will explore and stratify the risks conferred by histological PNI parameters. The radiological features of perineural spread (PNS) and the imaging sequences that delineate these findings will also be highlighted. Surgical excision with en face margin control is the preferred technique for achieving histological clearance. Adjuvant radiotherapy improves treatment outcomes in the setting of concomitant high-risk features. For locally advanced or metastatic cutaneous SCC, immunotherapy represents a novel treatment alternative. This review will provide an algorithm for the diagnosis and management of periocular SCC with PNI and PNS.

Epidemiology of cutaneous sebaceous carcinoma.

There has been uncertainty about the demographics and anatomical distribution of cutaneous sebaceous carcinoma. This study aims to investigate these uncertainties by analysing data from various countries. Data were obtained from cancer registries of the United States, England, Norway and Taiwan, and incidence rates were calculated with uniform age-adjustment. sebaceous carcinoma was more commonly reported in males than females in white populations, whereas the inverse was true in Taiwan. Ocular sebaceous carcinoma was more commonly reported in females than males in all populations, despite male predominance in white populations. The majority (approx. 70-90%) occurred on head and neck in Asians and whites. Age-adjusted incidence rate (to the 2000-2025 WHO World Standard Population) ranged from 0.07 to 0.18 per 100 000 person-years and was not higher in Taiwanese than in white populations.

Neoadjuvant vismodegib in the management of locally advanced periocular basal cell carcinoma.

BACKGROUND/OBJECTIVES: Vismodegib, a hedgehog pathway inhibitor, has been used in the management of locally advanced basal cell carcinoma (BCC) not suitable for surgery or radiation therapy. We report our experience using neoadjuvant vismodegib for locally advanced periocular BCC, followed by surgical excision. Our aim was to assess the effect on the extent of surgical excision and histological response. SUBJECTS/METHODS: A retrospective case series of patients treated with neoadjuvant vismodegib, for the management of locally advanced periocular BCC prior to surgical excision, with intraoperative margin control. Patients were treated until a maximum clinical response was seen. The difference between the estimated surgical margins prior to vismodegib and the eventual margins used was compared. Fine (1 mm) vertical sections through the excised tumour were performed to assess the histological response and look for a multifocal tumour. RESULTS: Eight Caucasian patients had neoadjuvant treatment with vismodegib for a median duration of 6 months. Some clinical response was seen in all cases but was only partial in 6/8 patients. Histological evaluation of the excised specimen showed residual BCC in 6/8 cases and thus 2/8 showed complete histological regression. Two cases showed squamous differentiation. Side effects occurred in 7/8 patients all which resolved on cessation of therapy. The mean follow-up was 13.4 ± 5.2 months. CONCLUSIONS: Neoadjuvant treatment of periocular BCC showed a mixed clinical and histological response. Final surgical excision achieved clear margins in all patients with no recurrence at 13 months and a reduction in predicted defect size, but possible squamous differentiation in two cases.

An integrated multidisciplinary team approach to the management of vascular anomalies: challenges and benefits.

BACKGROUND: Vascular anomalies comprise highly variable pathophysiology and commonly pose diagnostic and management dilemmas. Consequently, patients often benefit from input from multiple specialists. This study describes the inception of a multidisciplinary team (MDT) Vascular Anomaly Clinic (VAC) in a tertiary paediatric centre, and the subsequent experience managing this complex patient group. METHODS: This was a retrospective study of paediatric patients (< 18 years old) attending an MDT VAC from its inception in October 2012 until November 2019. Patient demographics, presentation, diagnosis and management were reviewed. RESULTS: One hundred and thirty-three paediatric patients were seen over 7 years with a median age of 9.8 years. Vascular malformations were the most common diagnosis (88%), with venous malformations predominating (27%). The most common symptoms were pain (46%) and swelling (34%). Patients often required ≥ 2 investigations, with Doppler ultrasound (86%) and magnetic-resonance imaging (61%) being most common. Management included surgery (27%), sclerotherapy (26%), compression garments (23%), analgesia (12%), laser (15%), embolisation (5%) and sirolimus (3%). CONCLUSIONS: The complex nature of vascular anomalies and high proportion of patients requiring multi-specialty management justified the establishment of an MDT VAC in our centre. Our experience demonstrates the success of an efficient one-stop MDT environment in the management of these challenging conditions. LEVEL OF EVIDENCE: IV.

Cutaneous sebaceous carcinoma.

Cutaneous sebaceous carcinoma occurs almost exclusively on the head and neck and has a significant propensity for recurrence and metastasis. It is easily mistaken for benign conditions, resulting in inappropriate management. Thus, it is important to maintain a high index of suspicion. Despite previous reports, sebaceous carcinoma may occur with similar frequency in Asians and whites. Recent genetic data suggest there are multiple mutational groups of sebaceous carcinoma, paving the way for targeted treatment. After a diagnosis, investigations for staging and for Muir-Torre syndrome should be considered. The available evidence on the treatment options for sebaceous carcinoma is discussed, and specific recommendations for management are made.

Eyelid lesions in general practice.

BACKGROUND: Patients with eyelid lesions often present in the primary healthcare setting. Although most eyelid lumps are benign, accurate diagnosis and early recognition of sinister lesions leads to improved patient outcomes. OBJECTIVE: The aim of this article is to provide an overview of common eyelid lesions presenting to the general practitioner. DISCUSSION: The majority of eyelid lesions are benign, ranging from innocuous cysts (cysts of Moll, Zeis and epidermoid cyst) and chalazion/hordeolum to naevi and papillomas. Key features that should prompt further investigation include gradual enlargement, central ulceration or induration, irregular borders, eyelid margin destruction or loss of lashes, and telangiectasia. The presence of these features should prompt referral to an ophthalmologist for further evaluation.

Propeller flaps in eyelid reconstruction.

PURPOSE: Propeller flaps are island flaps that reach the recipient site through an axial rotation. The flap has a subcutaneous pedicle on which it pivots, thereby resembling a helicopter propeller. We present our series of propeller flaps for the reconstruction of large eyelid defects. METHODS: This is a retrospective review of the clinical case notes of eight patients that underwent tumour excision with reconstruction with a cutaneous propeller flap supplied by a non-perforator orbicularis pedicle between July and December 2016. RESULTS: Propeller flaps were used in the reconstruction of five lower lid defects (size range 19 × 5 mm to 25 × 8 mm), one medial canthus defect (13 mm diameter), one complete upper lid defect (42 × 19 mm diameter) and one lid sparing extenteration defect. The flaps were recruited from nasolabial, lateral canthal, temple or medial upper cheek skin. Post-operatively one case had 'trapdooring' which required flap revision at 4 months and one had persistent oedema that settled without intervention. CONCLUSIONS: The reconstruction of large eyelid defects is challenging in part because of the paucity of locally available skin. Propeller flaps are a paradigm shift in periocular reconstruction in which the subcutaneous pedicle enables the recruitment of large and highly mobile skin flaps from a wide area of regional tissue.

Eyebrow reconstruction.

This is a systematic review of eyebrow reconstruction options, using the PubMed database, as well as dermatology and plastic surgery texts. Eyebrow reconstruction options in various clinical scenarios (small, large, medial, lateral, and total defects) are presented. The goals of eyebrow reconstruction are to provide structural, functional, and aesthetic restoration. A good understanding of various eyebrow reconstruction techniques is essential for plastic, dermatologic, and oculoplastic surgeons.

Perineural Invasion of the Orbit by Neurotropic Nondesmoplastic Melanoma.

The authors report a case of neurotropic nondesmoplastic melanoma involving the ophthalmic division of the trigeminal nerve and the cavernous sinus in a patient with recurrent scalp melanoma. This case highlights the importance of earlier diagnosis of local recurrence of melanoma and the rare association of neurotropic melanoma and orbital metastasis.

Dermatology teaching in Australian Medical Schools.

BACKGROUND/OBJECTIVES: Although skin disease and skin cancers cause significant morbidity and mortality in Australia, limited time is dedicated to dermatology teaching in most medical courses. The aim of this study was to define the current state of dermatology teaching in Australian medical schools with a view to developing a national core curriculum for dermatology. METHODS: An electronic questionnaire was circulated to the dermatology teaching leads and relevant medical program coordinators of the 18 medical schools in Australia. RESULTS: Replies were received from 17 medical schools. Dermatology was included as part of the core curriculum in 15 schools. Time set aside for dermatology teaching varied, as reflected by the number of lectures delivered (0-21, mean 5, median 3) and minimum clinics attended (0-10, mean 1.2, median 0). Only four medical schools had a compulsory clinical attachment in dermatology. Furthermore, satisfying requirements in dermatology was mentioned in the university examination regulations in only six schools. Certain core learning outcomes were addressed in most schools, including the structure and function of the skin, common conditions such as atopic dermatitis and psoriasis and cutaneous malignancies. However, there were important omissions, ranging from common problems like dermatophyte infections and drug reactions to the recognition of dermatological emergencies. CONCLUSIONS: These results are a compelling impetus to improve current standards of dermatology teaching, learning and assessment. The introduction of a national core curriculum would provide guidelines for dermatology teaching in medical schools, enabling the more effective utilisation of available time for key learning outcomes.

In-Transit Metastasis From Squamous Cell Carcinoma.

BACKGROUND: In-transit metastasis from cutaneous squamous cell carcinoma (SCC) is an uncommon form of metastasis through lymphatics and occurs more commonly in immunosuppressed patients. OBJECTIVE: To identify cases of in-transit SCC and determine patient characteristics, tumor features, management, and prognosis. METHODS AND MATERIALS: A multicenter case series treated by Australian and New Zealand clinicians. RESULTS: In 31 patients, median age was 72 years (range 52-99) and 68% were immunocompetent. Tumors occurred on the head and neck in 94% of cases, with 71% of all tumors occurring on the scalp, forehead, or temple. The median time to presentation with in-transit SCC from treatment of the initial tumor was 5 months. Management included surgery (94%), radiotherapy (77%), chemotherapy (10%), and reduction of immunosuppression (3%). Median follow-up was 12 months. Overall survival at 3 and 5 years were 27% and 13%, respectively. CONCLUSION: In-transit metastases are described in 31 patients, of whom the majority was immunocompetent. The scalp, forehead, and temple were the most common sites. New clinical and histological diagnostic criteria are proposed. Prognosis was poor with 5-year survival of 13%. Recommended management is a combination of surgery and adjuvant radiotherapy. Reduction of any iatrogenic immunosuppression should be considered.

Scalp Basal Cell Carcinoma: Review of 2,202 Cases.

BACKGROUND: Increases in the incidence of basal cell carcinoma (BCC) in women, younger age groups and in aggressive scalp subtypes in younger women have been reported. OBJECTIVE: To describe lesion and patient characteristics in scalp BCC. MATERIALS AND METHODS: Retrospective audit of scalp BCCs from 3 pathology laboratories in Adelaide, South Australia, January 2009-December 2013. RESULTS: Scalp BCC was 2.6% of all BCC. Of 2,202 patients with scalp BCC, 62% were male and 78% were >60 years. Histologic subtypes included nodular (55%), mixed (30%), and superficial (8%). The concordance between biopsy and excision was 83% for division into nonaggressive and aggressive subtypes. The incomplete excision rate was 16%. Aggressive subtypes were larger and had perineural invasion (PNI) in 8.5% and incomplete excision in 26%. CONCLUSION: Basal cell carcinoma on the scalp was less common. Men and the elderly had the majority of cases, with no predilection for women, including aggressive histologic subtypes in younger women. Aggressive subtypes were associated with increased size, incomplete excision, and PNI. A preliminary biopsy assisted division into aggressive and nonaggressive histologic subtypes. Incomplete excision rates were higher and increased in aggressive histologic subtypes and PNI. Mohs surgery or wider margins are suggested in these cases.