Patient education in Mohs surgery: a review and critical evaluation of techniques.

BACKGROUND: Traditional in-person discussion alone is often used for preoperative education in Mohs micrographic surgery (MMS). The appropriate use of more modern education techniques is not well defined in the MMS literature. OBJECTIVE: The authors aim to evaluate patient education techniques for MMS, address education in special populations, and highlight opportunities for improvement. METHODS AND MATERIALS: We performed a PubMed literature search with keywords "Mohs" and "education", "teaching", "understanding", "explanation", "preoperative", or "consent" with no restriction on publication time frame due to literature scarcity. RESULTS: Teledermatology consultation, MMS videos, 3D models, pamphlets/online materials, and shared medical appointments appear to be effective techniques (GRADE B). Analogies are also anecdotally helpful when integrated into traditional verbal education (GRADE C). The role of preoperative educational phone calls is more controversial (GRADE C). CONCLUSION: Regardless of the education technique utilized, no singular technique entirely replaces the traditional in-person discussion. Having access to multiple modalities can be beneficial for patients, allowing them options to choose their preferred method(s) of education. MMS is a difficult topic to conceptualize, and further research into educational techniques is needed to provide clear guidelines for Mohs surgeons.

INTRAVITREAL MELPHALAN FOR TREATMENT OF VITREOUS SEEDING FROM CHOROIDAL MELANOMA.

PURPOSE: To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan. METHODS: Case report. RESULTS: A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 µg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications. CONCLUSION: Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.

UVEAL METASTASIS BASED ON PATIENT AGE IN 1,111 PATIENTS: Comparison of Clinical Features and Outcomes Per Age Category.

PURPOSE: To evaluate clinical features and survival outcomes of uveal metastasis based on patient age. METHODS: Retrospective analysis of all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017. The features and outcomes were analyzed based on patient age classified as children (0-20 years), young adults (21-40 years), middle [aged] adults (41-60 years), older adults (61-80 years) and senior adults (81-100 years). RESULTS: There were 1111 consecutive patients, including children (n = 3, <1%), young adults (n = 77, 7%), middle adults (n = 472, 42%), older adults (n = 509, 46%), and senior adults (n = 50, 4%). At uveal metastasis diagnosis, demographics included mean patient age of 60 years, Caucasian race (88%), and female gender (64%). Compared to the largest cohort (older adults), there were significant differences (age group versus [vs.] older adults) in Caucasian race (senior adult 98% vs. 89%, p = 0.042), male sex (young adults: 22% vs. 43%, p < 0.001) (middle adults: 29% vs. 43%, p < 0.001), unilateral tumor (young adult: 70% vs. 86%, p < 0.001) (middle adult: 79% vs. 86%, p = 0.003) (senior adults: 96% vs. 86%, p = 0.045), and cancer origin in breast (young adults: 51% vs. 32%, p = 0.002) (middle adults: 44% vs 32%, p < 0.001), lung (young adults: 14% vs. 30%, p = 0.004), kidney (young adults: 0% vs. 5%, p = 0.043), prostate (middle adults: 1% vs. 4%, p = 0.001), gastrointestinal tract (senior adults: 8% vs. 2%, p = 0.028), and others (children: 100% vs. 4%, p < 0.001) (young adults: 10% vs. 4%, p = 0.044). Kaplan-Meier survival (children, young, middle, older, and senior adults) at 1 year was 33%, 48%, 60%, 62%, and 76% and at 5 years was 0%, 22%, 29%, 25%, and 40%, respectively, with no difference per age category. The mean overall survival was 17.2 months and children demonstrated hazard ratio (HR) for death at 1 year of 2.1 relative to older adults. CONCLUSION: Uveal metastasis is found in all age groups. Compared to older adults, primary cancer site was more often breast and less likely lung in young and middle adults. Other rare sites were more often seen in children. Survival outcomes at 1 and 5 years were most favorable for senior adults and least favorable for children.

Choroidal amelanotic tumours: clinical differentiation of benign from malignant lesions in 5586 cases.

PURPOSE: To investigate demographics and clinical features of patients with amelanotic choroidal tumours. DESIGN: Retrospective analysis. METHODS: Comparison of demographic and clinical features of various amelanotic choroidal tumours based on stratification by patient age, sex and tumour diameter. Included were all patients with amelanotic choroidal tumours evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA, over a 45-year time period. RESULTS: A total of 5586 amelanotic choroidal tumours in 4638 eyes of 4441 patients were included with a mean age at presentation of 58 years (median 60, range 0.1-100 years). Most patients were white (95%), female (56%) and with unilateral lesion (96%). By comparison, amelanotic melanoma presented at a younger mean age (57 years) compared with metastasis (60 years, p<0.001), nevus (61 years, p<0.001), lymphoma (65 years, p<0.001), sclerochoroidal calcification (70 years, p<0.001) and peripheral exudative haemorrhagic chorioretinopathy (80 years, p<0.001). Melanoma presented at an older mean age compared with osteoma (30 years, p<0.001), granuloma (42 years, p<0.001), haemangioma (49 years, p<0.001) and inflammatory choroidal lesions (49 years, p<0.001). Differences in race and sex were also seen between the various amelanotic choroidal lesions. With few exceptions, amelanotic melanoma had significantly larger basal diameter, greater thickness, more frequent association with subretinal fluid and more often ultrasonographically hollow, compared with other amelanotic choroidal lesions. CONCLUSION: Understanding the demographic and clinical features of amelanotic choroidal melanoma and other amelanotic lesions could lead to an earlier and more accurate diagnosis.

HAND-HELD OPTICAL COHERENCE TOMOGRAPHY MONITORING OF CHEMORESISTANT RETINOBLASTOMA.

PURPOSE: Retinoblastoma (Rb) is a potentially fatal intraocular malignancy in children, and hand-held optical coherence tomography (HH-OCT) can assist in submillimeter detection and monitoring after treatment of Rb. Retinoblastoma located in the macula, or those with chemoresistance, can be among the most difficult to manage. We describe HH-OCT features in a case of chemoresistant macular Rb that eventually responded to plaque radiotherapy after failing intravenous chemotherapy and intraarterial chemotherapy. METHODS: Observational case report. RESULTS: A 15-month-old girl with leukocoria was found to have Group D Rb in the right eye of 6-mm thickness and macular Group B Rb in the left eye of 4-mm thickness. She was treated with 6-monthly cycles of systemic intravenous chemotherapy and focal consolidation therapies to both eyes, with tumor regression in both eyes. However, macular tumor in the left eye demonstrated subsequent recurrence, from regressed thickness of 792 µm on HH-OCT to a dome-shaped hyperreflective retinal mass of >2000 µm thickness. Three cycles of intraarterial chemotherapy were sufficient for tumor regression down to 977 µm thickness on HH-OCT. Six months later, macular tumor in the left eye recurred again to >2000 µm thickness and necessitated plaque radiotherapy using apex dose of 35 Gy over 95.25 hours. Hand-held OCT confirmed rapid tumor regression to 722 µm after plaque treatment and regression remained stable at 6-month follow-up. CONCLUSION: Hand-held OCT was critical in assessment of Rb after failed intravenous chemotherapy and intraarterial chemotherapy and later documenting regression after plaque radiotherapy. Hand-held OCT is vital in providing cross-sectional imaging and measurements of small macular and paramacular Rbs.

Uveal metastasis in 1111 patients: Interval to metastasis and overall survival based on timing of primary cancer diagnosis.

PURPOSE: To evaluate interval between primary cancer diagnosis and uveal metastasis and assess survival outcomes based on whether the primary cancer was diagnosed before or after uveal metastasis. METHODS: In this retrospective analysis, all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017 were included. Features and outcomes based on timing of primary cancer diagnosis, whether before or after diagnosis of uveal metastasis, were assessed. RESULTS: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. Primary cancer was known prior to uveal metastasis in 742 patients (67%) and not known in 369 (33%). Of those not known, the primary cancer was later found in 192 patients (17%) and never found in 177 patients (16%). For those with known primary cancer, mean interval from primary cancer diagnosis to uveal metastasis was 5.2 years with differences in primary sites of gastrointestinal (2.1 years, p = 0.003), lung (2.2 years, p < 0.001), breast (6.5 years, p < 0.001), and thyroid (13 years, p < 0.001). By Kaplan-Meier analysis, the 5-year overall survival showed no difference between patients with primary cancer found before (28%) vs after (20%) vs never found (33%), relative to uveal metastasis. CONCLUSION: Of 1111 patients with uveal metastasis, early-onset uveal metastases were found with lung and gastrointestinal tract cancers, whereas late-onset metastases were found with breast and thyroid cancers. Overall survival did not vary on whether the primary tumor was diagnosed before, after, or never found, relative to uveal metastasis.

Uveal Metastasis Based on Patient Sex in 2214 Tumors of 1111 Patients. A Comparison of Female Versus Male Clinical Features and Outcomes.

BACKGROUND: Lacking in previous studies on uveal metastasis is a robust statistical comparison of patient demographics, tumor features, and overall survival based on patient sex. OBJECTIVE: The aim of this study was to evaluate demographics, clinical features, and overall survival of patients with uveal metastasis based on sex. METHOD: This is a retrospective analysis. All patients were evaluated on the Ocular Oncology Service, Wills Eye Hospital, PA between January 1, 1974 and June 1, 2017. RESULTS: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. A comparison (female versus male) revealed differences across several demographic and clinical features including, among others, mean age at metastasis diagnosis (58 vs 63 years, P < 0.001), bilateral disease (21% vs 11%, P < 0.001), and mean number of metastases per eye (1.8 vs 1.6 tumors per eye, P = 0.04). There were differences in overall mean survival (20 vs 13 months, P = 0.03) and 5-year survival (Kaplan-Meier estimate) (31% vs 21%, P < 0.001). CONCLUSIONS: There are demographic, clinical, and survival differences when patients with uveal metastases are compared by sex. Understanding these differences can aid the clinician in better anticipating patient outcomes.

A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis.

A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis. Patients were randomly assigned to receive placebo, apremilast 30 mg twice daily (APR30), or apremilast 40 mg twice daily (APR40) for 12 weeks. During weeks 12-24, all patients received APR30 or APR40. A biopsy substudy evaluated atopic dermatitis-related biomarkers. Among 185 randomly assigned intent-to-treat patients at week 12, a dose-response relationship was observed; APR40 (n = 63), but not APR30 (n = 58), led to statistically significant improvements (vs. placebo, n = 64) in Eczema Area and Severity Index (mean [standard deviation] percent change from baseline = -31.6% [44.6] vs. -11.0% [71.2], P < 0.04; primary endpoint). mRNA expression of T helper type 17/T helper type 22-related markers (IL-17A, IL-22, and S100A7/A8; P < 0.05) showed the highest reductions with APR40, with minimal changes in other immune axes. Safety with APR30 was largely consistent with apremilast's known profile (common adverse events: nausea, diarrhea, headache, and nasopharyngitis). With APR40, adverse events were more frequent, and cellulitis occurred (n = 6). An independent safety monitoring committee discontinued the APR40 dosage. APR40 showed modest efficacy and decreased atopic dermatitis-related biomarkers in moderate to severe atopic dermatitis patients. Adverse events, including cellulitis, were more frequent with APR40, which was discontinued during the trial. Clinical Trial Registration Number: NCT02087943 (clinicaltrials.gov).

Philadelphia Telemedicine Glaucoma Detection and Follow-up Study: Ocular Findings at Two Health Centers.

Blindness from glaucoma can be prevented by early detection and treatment. Telemedicine improves access to treatment in high-risk populations that face barriers to receiving adequate ophthalmic care. We used a practice-based telemedicine screening model at two health centers. Telemedicine imaging of the fundus and optic nerve, followed by a complete eye exam at the same location for participants with abnormal findings, unreadable images, or ocular hypertension (OHTN), was performed. A total of 182 participants were screened, of whom 108 qualified for a complete eye exam. Of these, 62 (34.1%) had abnormal images, 12 (6.6%) had OHTN, and 34 (18.7%) had unreadable images. Eighty-nine of the 108 (82%) returned for the complete eye exam. Predominantly, participants were African American with glaucoma suspect and cataract. Screening location was an important factor for follow-up. Assessment of the fundus and optic disc using telemedicine resulted in early detection of glaucoma and other ocular pathology.

Uveal Metastasis: Clinical Features and Survival Outcome of 2214 Tumors in 1111 Patients Based on Primary Tumor Origin.

PURPOSE: The purpose of this study is to evaluate patients with uveal metastasis based on primary tumor site. METHODS: Retrospective analysis from Wills Eye Hospital, Philadelphia, PA, USA, for uveal metastasis clinical features and outcomes based on the primary tumor site. RESULTS: There were 2214 uveal metastases diagnosed in 1111 consecutive patients. The demographics included mean age of 60 years (median 61 years), Caucasian race (88%), and female gender (64%). The tumor was unilateral (82%) and primary site was established before uveal metastasis (67%). The primary tumor originated in the breast (37%), lung (26%), kidney (4%), gastrointestinal (GI) tract (4%), cutaneous melanoma (2%), lung carcinoid (2%), prostate (2%), thyroid (1%), pancreas (1%), other sites (3%), and unknown (16%). Comparative analysis of the 5 most common primary sites (breast, lung, kidney, GI tract, and cutaneous melanoma), revealed metastasis at mean age (57, 62, 66, 61, 59 years), as unilateral tumor (74%, 86%, 85%, 93%, 85%), with mean number of metastasis/eye (1.9, 1.7, 1.0, 1.1, 2.0), and in females (99%, 46%, 26%, 25%, 30%). Choroidal metastases measured mean base (9.3, 10.2, 9.1, 11.0, 7.3 mm), mean thickness (2.4, 3.6, 4.4, 4.0, 2.9 mm), and demonstrated predominant color yellow (94%, 91%, 56%, 97%, 36%). Of the 769 patients with documented follow-up, mean patient survival was poor (22.2, 11.5, 8.6, 12.4, 11.4 months) and Kaplan-Meier analysis revealed 3-year survival (33%, 19%, 0%, 14%, 21%) and 5-year survival (24%, 13%, 0%, 14%, 21%). The worst survival was found in patients with pancreatic metastasis (mean 4.2 months) and best survival with lung carcinoid (92% at 5 years). CONCLUSION: In a tertiary referral service, uveal metastasis originates from cancer in the breast, lung, kidney, GI tract, cutaneous melanoma, or others. Overall prognosis is poor with 5-year survival at 23% and worst survival with pancreatic metastasis whereas best survival with lung carcinoid metastasis.

Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial.

BACKGROUND: Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems. OBJECTIVE: To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD). METHODS: A total of 104 ambulatory patients with mild to moderate AD were enrolled in this randomized, double-blind, vehicle-controlled trial between December 2015 and September 2016. VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was applied twice daily for 28 days. Pretreatment and posttreatment skin biopsy specimens were obtained from a subset of 33 patients. Changes in SCORing of Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global Assessment, and tissue biomarkers (by real-time polymerase chain reaction and immunostaining) were evaluated. RESULTS: Topical VTP-38543 was safe and well tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of epidermal barrier differentiation (loricrin and filaggrin, P = .02) and lipid (adenosine triphosphate-binding cassette subfamily G member 1 and sterol regulatory element binding protein 1c, P < .01) measures and reduced epidermal hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 nonsignificantly suppressed cellular infiltrates and down-regulated mRNA expression of several TH17/TH22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and innate immunity (interleukin 6) markers. CONCLUSION: Topical VTP-38543 is safe and well tolerated. Its application led to improvement in barrier differentiation and lipids. Longer-term studies are needed to clarify whether a barrier-based approach can induce meaningful suppression of immune abnormalities. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02655679.

The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins.

Beyond classic "allergic"/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-ß) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis. Consistent with skin expression, AD serum showed up-regulation of Th2 (IL-13, CCL17, eotaxin-1/CCL11, CCL13, CCL4, IL-10), Th1 (CXCL10, CXCL11) and Th1/Th17/Th22 (IL-12/IL-23p40) responses. Surprisingly, some markers of atherosclerosis (fractalkine/CX3CL1, CCL8, M-CSF, HGF), T-cell development/activation (CD40L, IL-7, CCL25, IL-2RB, IL-15RA, CD6) and angiogenesis (VEGF-A) were significantly increased only in AD. Multiple inflammatory pathways showed stronger enrichment in AD than psoriasis. Several atherosclerosis mediators in serum (e.g. E-selectin, PI3/elafin, CCL7, IL-16) correlated with SCORAD, but not BMI. Also, AD inflammatory mediators (e.g. MMP12, IL-12/IL-23p40, CXCL9, CCL22, PI3/Elafin) correlated between blood and lesional as well as non-lesional skin. Overall, the AD blood signature was largely different compared to psoriasis, with dysregulation of inflammatory and cardiovascular risk markers, strongly supporting its systemic nature beyond atopic/allergic association.

Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is an autosomal dominant, tumor predisposing disorder usuallycaused by germline mutations in mismatch repair (MMR) genes. A subset of HNPCC, Muir-Torre Syndrome (MTS) also involves MMR gene defects and is generally accepted as a variant of HNPCC. MTS is typicallycharacterized by at least one visceral malignancy and one cutaneous neoplasm of sebaceous differentiation, with or without keratoacanthomas. In either version of the disorder, nonfunctional MMR systems lead tothe loss of genomic integrity, marked commonly by mismatches in repetitive DNA sequences, resulting in microsatellite instabilities. Deleterious nucleotide alterations ultimately drive the process of tumorigenesis in both HNPCC and MTS. The following article reviews the epidemiology, genetics, clinical presentation, and management of HNPCC and its MTS variant.

Cutaneous Adverse Events in Chronic Hepatitis C Patients Treated With New Direct-Acting Antivirals: A Systematic Review and Meta-Analysis.

BACKGROUND: Direct-acting antivirals (DAAs) are known to present with additional dermatological events over pegylated-interferon/ribavirin (Peg-IFN/RBV). OBJECTIVE: A systematic review and meta-analysis was conducted to assess the incidence/risk of cutaneous adverse events (AEs) for simeprevir, sofosbuvir, ABT450/r-ombitasvir, dasabuvir, ledipasvir, daclatasvir, and asunaprevir. METHODS: The databases searched included PubMed, Clinicaltrials.gov, and Clinicaloptions.com. Data on telaprevir and boceprevir were obtained from a previous study. RESULTS: The incidences of cutaneous AEs were 34.3% (95% CI 18.4%-54.8%) for the old DAAs + Peg-IFN/RBV, 22.0% (95% CI 17.9%-26.8%) for the new DAAs + Peg-IFN/RBV, 9.8% (95% CI 8.6%-11.2%) for the DAAs + RBV, and 3.8% (95% CI 2.4%-6.1%) for DAAs only. Simeprevir + Peg-IFN/RBV was associated with an increased relative risk over Peg-IFN/RBV; RR = 1.319 (95% CI 1.026-1.697). CONCLUSION: Dermatological events are still an important issue for many of the new DAAs. Appropriate monitoring, management, and patient education are needed to minimize AEs and achieve HCV cure.

Sebaceus and Becker's Nevus: Overview of Their Presentation, Pathogenesis, Associations, and Treatment.

Nevus sebaceus (NS) and Becker's nevus (BN) are two variants of epidermal nevi. NS clinically presents as a yellowish-orange, hairless plaque on the scalp, face, or neck, while BN presents as a tan-to-brown hyperpigmented, sometimes hypertrichotic, plaque typically on the chest and shoulder. Histologically, NS displays mature or nearly mature sebaceus glands as well as acanthosis and fibroplasia of the papillary dermis. BN shows variable papillomatosis, acanthosis, and hyperkeratosis, with hyperpigmentation of the basal/suprabasal layer. While the genetic basis of NS is thought to be due to post-zygotic mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS)/Kristen rat sarcoma viral oncogene homolog (KRAS) genes, the genetic basis of BN is relatively unknown and is implicated with paradominant inheritance. In some patients, NS and BN can each be associated with additional cutaneous and extra-cutaneous anomalies, ranging from benign or malignant tumors to multiple organ irregularities. Due to the wide range of possible associations, treatment for NS and BN is devised on a case-by-case basis. In this article, we review the features, etiology, and diagnosis/management of NS and BN, with a focus on associations. We also report a patient who concomitantly presents with both lesions.

Leiomyoma cutis: a focused review on presentation, management, and association with malignancy.

Cutaneous leiomyomas (CLs) are rare, sporadic, or inherited tumors of smooth muscle origin associated with various disorders. Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the primary tumor predisposition syndrome associated with inherited CLs, affecting 180 families worldwide, with significant mortality. CLs are subdivided into piloleiomyomas, genital leiomyomas, and angioleiomyomas based on their smooth muscle of origin, as well as their clinicopathologic features. Piloleiomyomas, derived from arrector pili muscle, are solitary or multiple firm papulonodules located typically on the extremities and trunk; genital leiomyomas, derived from dartoic, vulvar, or mammary smooth muscle, are solitary papulonodules or pedunculated papules located on the scrotum, vulva, or nipple; and angioleiomyomas, which include solid, cavernous, or venous subtypes, are derived from the tunica media of small arteries and veins and typically present on the extremities. Partial/excisional biopsy is required for diagnosing all CLs. Histology shows interlacing fascicles of spindle cells with moderate amounts of eosinophilic cytoplasm and a blunt-ended, elongated nucleus with perinuclear halos. Surgical excision is curative for CLs, with other management options including medical or destructive therapy; active surveillance is advised to monitor HLRCC-associated neoplasms, with pharmacological therapies under active research.