Diagnosis Of Primary Melanoma Research Articles

Abstract 3823: Clinical outcomes of uveal melanoma patients in the emergency department

Abstract Purpose: Uveal melanoma is a rare ocular malignancy that has not been well characterized at a large scale. Specifically, uveal melanoma diagnosis and outcomes in the emergency department (ED) has not been characterized. Methods: The Nationwide Emergency Department Sample was queried from the last quarter of 2015 to 2019 to identify patients with a primary diagnosis of uveal melanoma. Multivariable logistic regression, with patient- and hospital-level characteristics as covariates, was used to identify factors associated with increased risk of inpatient admission. Results: From the last quarter of 2015 to 2019, there were 1,274 ED encounters with a primary diagnosis of uveal melanoma. Most patients were less than 11 years old (43.4%), male (51.1%), or a Medicaid beneficiary (37.8%), and most belonged to a family in the lowest income quartile (32.0%). The median age of these patients was 35 years (IQR: 2-64). Most patients presented to hospitals in the South (53.9%), with a Trauma Level I designation (51.4%), and most to a metropolitan teaching hospital (89.1%). The most common ED outcomes were same-day discharge (61.6%) and admission to the inpatient setting (31.2%). Patients presenting to Trauma Level I hospitals were most likely to be admitted (odds ratio [OR]=2.21; p=0.031). The factors that were most significantly associated with decreased odds of inpatient admission were: patients who were not charged for services (often due to charity) (OR=0.13; p=0.040), Medicaid beneficiaries (OR=0.27; p=0.031), and private insurance beneficiaries (OR=0.34; p=0.047). Among the admitted patients, patients can be discharged to home with self-care (76.2%) or with home-health care (14.9%) or can be transferred to an intermediate-care facility (8.1%). The mean hospital length of stay was 5.7±0.6 days. In-hospital mortality rate for admitted patients was very low (0.8%). Conclusion: Uveal melanoma patient outcomes are closely related to insurance status, indicating socioeconomic factors as a modulator of patient outcomes. Citation Format: Alice A. Beneke, Kamil Taneja, Lauren Ladehoff, Kevin Root, Eric Toloza. Clinical outcomes of uveal melanoma patients in the emergency department [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3823.

Primary malignant melanoma, an atypical presentation in the cervical spine: a case report

BackgroundFew studies have documented the occurrence of melanoma in the cervical spine. Of all malignant melanoma cases, 1% are primary melanoma of the central nervous system, which makes it extremely uncommon and nonspecific. We aim to report a case of the uncommon presentation of primary melanoma in the cervical spine.Case presentationThe patient was a 59-year-old Muganda male who presented with a 2-year history of anterior neck swelling as well as severe pain and a tingling sensation in the left shoulder and arm, which worsened in the recent 6 months. He developed weakness and paresthesia in the upper left arm and progressive gait disturbance of the left leg. A physical examination revealed masses in the left cervical and right submandibular region. Additionally, the upper and lower left extremities revealed hemiparesis and hemihypoesthesia. A magnetic resonance imaging scan showed a hyperintense lesion on TIWI and another hypointense lesion on T2WI, originating from the cervical spine and involving the vertebral bodies and paravertebral soft tissues. The patient underwent surgery, a black tumor was extracted, and histology revealed the tumor to be malignant melanoma. The patient died within 1 month after the diagnosis and surgery.ConclusionThis case is presented to highlight the significance and challenges associated with making a pre- and postoperative diagnosis of primary cervical melanoma with atypical radiological characteristics. Patients with extradural lesions that show hyperintensity on T1-weighted images and hypointensity on T2-weighted images should have spinal melanoma examined as a possible differential diagnosis.

SURG-46. PRIMARY MALIGNANT MELANOMA, AN ATYPICAL PRESENTATION IN THE CERVICAL SPINE

Abstract Few studies have documented the occurrences of melanomas in the cervical spine. one percent of all malignant melanoma cases are primary melanoma of the central nervous system, which is extremely uncommon and nonspecific. We aimed to report a case of uncommon presentation of primary melanoma in the cervical spine. This a 59-year-old, male who presented with a 2-year history of anterior neck swelling, severe pain and tingling sensation in the left shoulder and arm which worsened in the previous 6 months. He developed weakness and paresthesia in the left upper arm and progressive gait disturbance of the left lower limb. Physical examination revealed masses in the left cervical and right submandibular region. There was left upper and lower extremities hemiparesis and hemi hypoesthesia. MRI showed hyperintense lesion on T1WI and hypointense on T2WI originating from the cervical spine and involving the vertebral bodies and paravertebral soft tissues. The patient underwent surgery, a black tumor was extracted, and histology revealed malignant melanoma. This case is presented in order to highlight the significance of and challenges associated with making a preoperative diagnosis of primary cervical melanoma with atypical radiological characteristics. Patients with extradural lesions that show hyperintensity on T1 weighted images and hypo intensity on T2-weighted images should have spinal melanoma examined as a possible differential diagnosis.

Clinicopathological features, current status, and progress of primary central nervous system melanoma diagnosis and treatment.

Primary central nervous system (CNS) melanoma is an extremely rare condition, with an incidence rate of 0.01 per 100,000 individuals per year. Despite its rarity, the etiology and pathogenesis of this disease are not yet fully understood. Primary CNS melanoma exhibits highly aggressive biological behavior and presents clinically in a distinct manner from other types of melanomas. It can develop at any age, predominantly affecting the meninges as the primary site, with clinical symptoms varying depending on the neoplasm's location. Due to the lack of specificity in its presentation and the challenging nature of imaging diagnosis, distinguishing primary CNS melanoma from other CNS diseases. The combination of challenges in early detection, heightened tumor aggressiveness, and the obscured location of its origin contribute to an unfavorable prognostic outcome. Furthermore, there has been currently no consensus on a standardized treatment approach for primary CNS melanoma. Despite recent advancements in targeted therapy and immunotherapy for CNS melanoma, patients with primary CNS melanoma have limited treatment options due to their inadequate response to these therapies. Here, we provided a comprehensive summary of the epidemiology, clinical features, molecular pathological manifestations, and available diagnostic and therapeutic approaches of primary CNS melanoma. Additionally, we proposed potential therapeutic strategies for it.

520 Malignant Melanoma: A Rare Primary Bladder Tumour

Abstract A 60-year-old male patient who has been referred by his GP to our ‘one stop hematuria clinic’ due to episodes of visible hematuria for 3 months. The patient is Caucasian, non-smoker, drinking alcohol socially with no related family history of cancer. There is no occupational exposure to any carcinogens. Flexible cystoscopy that showed a dark coloured bladder mass arising from left side of the bladder base. CT urogram that showed evidence of soft tissue lesion in the urinary bladder with upstream mild left hydro-uretero-nephrosis. TURBT was performed carefully. Following complete resection of the tumour lesion, left ureteric orifice became visible. The morphology and immunohistochemistry profile were consistent with malignant melanoma. The presence of in situ component indicated a bladder primary origin rather than metastatic deposit. The case was discussed in our urology Multi-Disciplinary Team (MDT) meeting. Referral for dermatological consultation and radiological correlation were strongly advised in order to exclude any cutaneous or another mucosal primary malignant melanoma. The patient had no suspicious skin lesions. There was no evidence of soft tissue lesions on CT scans. In addition, further PET CT scan failed to show any other malignant lesions except for the bladder. After Histopathologic, dermatologic, and radiologic evidence; the diagnosis of primary urinary bladder malignant melanoma was established. Patient declined radical cystectomy and opted to go for immunotherapy. After completing a course of Nivolumab and Ipilimumab, patient is on a regular follow up cystoscopy with no evidence of recurrence.

Prognostic Significance of Sentinel Lymph Node Status in Thick Primary Melanomas (> 4 mm)

BackgroundThe key prognostic factors for staging patients with primary cutaneous melanoma are Breslow thickness, ulceration, and sentinel lymph node (SLN) status. The multicenter selective lymphadenectomy trial (MSLT-I) verified SLN status as the most important prognostic factor for patients with intermediate-thickness melanoma (Breslow thickness, 1–4 mm). Although most international guidelines recommend SLN biopsy (SLNB) also for patients with thick (> 4 mm, pT4) melanomas, its prognostic role has been questioned. The primary aim of this study was to establish whether SLN status is prognostic in T4 melanoma tumors.MethodsData for all patients with a diagnosis of primary invasive cutaneous melanoma of Breslow thickness greater than 1 mm in Sweden between 2007 and 2020 were retrieved from the Swedish Melanoma Registry, a large prospective population-based registry. A multivariable Cox proportional hazard model for melanoma-specific survival (MSS) was constructed based on Breslow thickness stratified for SLN status.ResultsThe study enrolled 10,491 patients, 1943 of whom had a Breslow thickness greater than 4 mm (pT4). A positive SLN was found for 34% of these pT4 patients. The 5-year MSS was 71%, and the 10-year MSS was 62%. There was a statistically significant difference in MSS between the patients with a positive SLN and those with a negative SLN (hazard ratio of 2.4 (95% confidence interval CI 1.6–3.5) for stage T4a and 2.0 (95% CI 1.6–2.5) for satage T4b.ConclusionSentinel lymph node status gives important prognostic information also for patients with thick (> 4 mm) melanomas, and the authors thus recommend that clinical guidelines be updated to reflect this.

Survival outcomes associated with liver-directed therapies in patients with metastatic uveal melanoma.

9590 Background: Metastatic uveal melanoma (mUM) is characterized by a hepatotropic pattern of spread and poor outcomes. Tebentafusp, the only FDA approved therapy, is restricted to patients (pts) with the HLA-A*02:01 genotype. As a result, a variety of liver-directed therapies (LDT) are commonly used for management of hepatic metastases. Methods: Pts with mUM with hepatic metastases who underwent LDT, including radiofrequency ablation, microwave ablation, hepatic metastatectomy, Yttrium-90 radioembolization (SIRT), transarterial chemoembolization (TACE), bland embolization, and immunoembolization (IE), were identified from an institutional database. Data collected included: age, gender, tumor location and size, baseline liver function tests (LFT) and lactate dehydrogenase (LDH), molecular tumor characteristics (where available), type(s) of LDT received, systemic therapies received, and vital status. Time from onset of hepatic metastasis until death (Liver-OS), as well as time from initial diagnosis of primary uveal melanoma until death (Ocular-OS) were calculated. Results: A total of 119 pts were identified. The median age at diagnosis was 53.8 years (range 26-83), 47% were female. At the time of LDT initiation, 33% had bilobar disease and 16% had extrahepatic metastasis. 18% pts had elevated LFTs and 55% had elevated LDH. 72% of pts had M1a disease, 24% had M1b and 4% had M1c disease. 45% of pts received more than one form of LDT. SIRT (31%) was the commonly administered initial LDT, followed closely by IE (26%) and TACE (9%). 86% of pts received systemic therapy including 42% who received immune checkpoint blockade overlapping with LDT. Molecular profiling in 26 pts revealed recurrent mutations in BAP1 (n = 18) and SF3B1 (n = 8). The median ocular-OS across all pts was 71.0 months (95% confidence intervals (CI), 62.8-99.4). The median liver-OS across all pts was 31.8 months (95% CI 25.2-35.3). In pts who received TACE, IE, or SIRT exclusively (n = 44), the median Liver-OS was 15.2 months (95% CI 12.8-NA) for TACE (n = 8), 23.3 months (95% CI 15.8-NA) for SIRT (n = 28), and 28.2 months (95% CI 22.6-NA) for IE (n = 8). Conclusions: Our results provide additional support for the utilization of LDT in pts with mUM, as demonstrated by improved OS compared to historical survival data.

Tolerability and response of palliative radiotherapy in patients receiving tumor-infiltrating lymphocyte therapy.

e14527 Background: Tumor-infiltrating lymphocyte (TIL) therapy is an emerging therapeutic option for patients with metastatic tumors having progressed on multiple lines of systemic therapy. It is unknown how TIL therapy impacts the tolerability and effectiveness of palliative radiotherapy (RT). We herein present a case series of patients having received both TIL therapy and palliative RT along with the associated local responses and toxicity profiles. Methods: A single institution retrospective database review identified patients treated with TIL therapy following progression on ≥2 standard treatment(s) for metastatic disease. Patients were eligible for inclusion if they received palliative radiotherapy treatment within 1 year of TIL delivery as pre- or post-TIL therapy. Patient demographic data was collected and descriptive statistics reported. Radiographic imaging response was assigned in accordance with Response Evaluation Criteria in Solid Tumors (RECIST). Toxicities were graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: Between 2017–2021, a total of 10 patients receiving TIL therapy treated across 12 courses of palliative RT were included for analysis. 8 of 10 patients (80%) had a primary diagnosis of malignant melanoma and 2 (20%) had non-small cell lung cancer. RT was administered to 7 patients pre- and 3 patients post-TIL therapy. Within the pre-TIL cohort, 2 patients received RT between TIL harvest and infusion. Patients received an average total dose of 26 Gy (range, 8-45 Gy). Median patient follow-up after RT was 6 months. Of the patients who received RT prior to TIL therapy, 6 of 9 sites demonstrated at-least stable disease at the site of RT versus 1 of 3 sites receiving post-TIL RT. Across the cohort, 2 patients experienced Grade 1 toxicities associated with RT treatment. No Grade 2+ events were reported. Conclusions: Palliative RT appears to be safe and tolerable when delivered both prior to and post-TIL therapy. RT may be an option for bridging therapy between TIL harvest and infusion. Local response rates to RT were greater in patients receiving RT prior to TIL infusion. Further investigations are warranted to determine the optimal dose, fractionation, and timing of RT when integrating it into future TIL therapy protocols. [Table: see text]

Diagnosis and treatment of primary urethral melanoma with regional lymphatic metastasis in an elderly woman: a case report and review of available therapies

BackgroundMucosal melanomas account for 17% of melanomas, and less than 1% affect the urogenital tract. Primary urethral melanoma is extremely rare; less than 200 cases have been reported so far since it was first described. The clinical presentation is usually delayed, and the prognosis is generally poor.Case presentation.An 86-year-old female was referred to urology due to the presence of a three-month-old violaceous mass in the urethral meatus protruding through the vagina. On physical examination, a pedunculated, hyperpigmented, friable, and tender lesion was seen in the urethral meatus bulging between the labia minora. After initial diagnostic studies, the patient was taken to surgical resection of the lesion. The pathology report identified the lesion as a malignant melanoma of the urethra, and staging studies revealed regional lymph node metastases. After discussing the treatment options with the patient, palliative therapy with nivolumab was started. In follow-up at 26 months, the patient had evidence of extensive lymph node involvement, but a conserved performance status and no visceral metastases.ConclusionPrimary melanoma of the female urethra is an uncommon disease with a poor prognosis. Despite the deficiency in literature regarding its management, it is important to consider patient expectations and preferences when treating this rare disease.

Surgical Resection of Pulmonary Metastases from Melanoma in Oligometastatic Patients: Results from a Multicentric Study in the Era of Immunoncology and Targeted Therapy.

In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed.

Study protocol for a randomised controlled trial to evaluate the use of melanoma surveillance photography to the Improve early detection of MelanomA in ultra-hiGh and high-risk patiEnts (the IMAGE trial)

IntroductionMelanoma surveillance photography (MSP) is a comprehensive surveillance method that comprises two- or three-dimensional total body photography with tagged digital dermoscopy, performed at prescribed intervals. It has the potential to reduce unnecessary biopsies and enhance early detection of melanoma, but it is not yet standard care for all high-risk patients in Australia. This protocol describes a randomised controlled trial (RCT) designed to evaluate the clinical impact and cost-effectiveness of using MSP for the surveillance of individuals at ultra-high or high risk of melanoma from a health system perspective.Methods and designThis is a registry-based, unblinded, multi-site, parallel-arm RCT that will be conducted over 3 years. We aim to recruit 580 participants from three Australian states: Victoria, New South Wales and Queensland, via state cancer registries or direct referral from clinicians. Eligible participants within 24 months of a primary cutaneous melanoma diagnosis will be randomised 1:1 to receive either MSP in addition to their routine clinical surveillance (intervention group) or routine clinical surveillance without MSP (control group). Most participants will continue surveillance with their usual care provider, and the frequency of follow-up visits in both groups will depend on the stage of their primary melanoma and risk factors. The primary outcome measure of the study is the number of unnecessary biopsies (i.e. false positives, being cases where a lesion is biopsied due to suspected melanoma on clinical examination, either with or without MSP, but the resulting histopathology finding is negative for melanoma). Secondary outcomes include the evaluation of health economic outcomes, quality of life and patient acceptability. Two sub-studies will explore the benefit of MSP in high-risk patients prior to a melanoma diagnosis and the diagnostic performance of MSP in the teledermatology setting compared to the en face clinical setting.DiscussionThis trial will determine the clinical efficacy, cost-effectiveness and affordability of MSP to facilitate policy decision-making at the national and local levels, across primary and specialist care.Trial registrationClinicalTrials.gov NCT04385732. Registered on May 13, 2020.

Diagnosis of primary biliary melanoma with distinct imaging features: a case report and literature review

Primary biliary melanoma arises from proliferating melanocytes in the mucosal surface of the bile duct and is extremely rare. Since the vast majority of biliary melanomas represent metastases of cutaneous origin, accurate preoperative diagnosis of melanoma and exclusion of other primary sources are vital in cases involving primary lesions. Although melanomas with pigmented cells have typical signal characteristics, obtaining a non-invasive pre-treatment diagnosis remains difficult, due to their low incidence. Here, the case of a 61-year-old male Asian patient who presented with upper quadrant abdominal pain, swelling and jaundice for 2 weeks, and who was diagnosed with primary biliary melanoma following extensive preoperative blood analyses, computed tomography (CT) and magnetic resonance imaging (MRI), is described. Post-resection immunohistochemistry confirmed the diagnosis and the patient received six chemotherapy cycles of temozolomide and cisplatin, however, progression of multiple liver metastases was observed at the 18-month follow-up CT. The patient continued with pembrolizumab and died 17 months later. The present case of primary biliary melanoma is the first reported diagnosis based on typical MRI features and the exhaustive exclusion of a separate primary origin.

A CT-Based Radiomics Nomogram Model for Differentiating Primary Malignant Melanoma of the Esophagus from Esophageal Squamous Cell Carcinoma.

The diagnosis of primary malignant melanoma of the esophagus (PMME) before treatment is essential for clinical decision-making. However, PMME may be misdiagnosed as esophageal squamous cell carcinoma (ESCC) sometimes. This research is aimed at devising a radiomics nomogram model of CT for distinguishing PMME from ESCC. In this retrospective analysis, 122 individuals with proven pathologically PMME (n = 28) and ESCC (n = 94) were registered from our hospital. PyRadiomics was applied to derive radiomics features from plain and enhanced CT images after resampling image into an isotropic resolution of 0.625 × 0.625 × 0.625 mm3. The diagnostic efficiency of the model was evaluated by an independent validation group. For the purpose of differentiation between PMME and ESCC, a radiomics model was constructed using 5 radiomics features obtained from nonenhanced CT and 4 radiomics features derived from enhanced CT. A radiomics model including multiple radiomics features showed excellent discrimination efficiency with AUCs of 0.975 and 0.906 in the primary and validation cohorts, respectively. Then, a radiomics nomogram model was developed. The decision curve analysis has shown remarkable performance of this nomogram model for distinguishing PMME from ESCC. The proposed radiomics nomogram model based on CT could be used for distinguishing PMME from ESCC. Moreover, this model also contributed to helping clinicians determine an appropriate treatment strategy for esophageal neoplasms.

Clinical Impact and Accuracy of Shave Biopsy for Initial Diagnosis of Cutaneous Melanoma

IntroductionEffective treatment of malignant melanomas is dependent upon accurate histopathological staging of preoperative biopsy specimens. While narrow excision is the gold standard for melanoma diagnosis, superficial shave biopsies have become the preferred method by dermatologists but may transect the lesion and result in inaccurate Breslow thickness assessment. This is a retrospective cohort study evaluating an initial method of biopsy for diagnosis of cutaneous melanoma and indication for reoperation based on inaccurate initial T-staging. MethodsWe retrospectively analyzed consecutive patients referred to the Medical College of Wisconsin, a tertiary cancer center, with a diagnosis of primary cutaneous melanoma. Adult patients seen between 2015 and 2018 were included. Fisher's exact test was used to assess the association between method of initial biopsy and need for unplanned reoperation. ResultsThree hundred twenty three patients with cutaneous melanoma from the head and neck (H&N, n = 101, 31%), trunk (n = 90, 15%), upper extremity (n = 84, 26%), and lower extremity (n = 48, 28%) were analyzed. Median Breslow thickness was 0.54 mm (interquartile range = 0.65). Shave biopsy was the method of initial biopsy in 244 (76%), excision in 23 (7%), and punch biopsy in 56 (17%). Thirty nine (33%) shave biopsies had a positive deep margin, as did seven (23%) punch biopsies and 0 excisional biopsies. Residual melanoma at definitive excision was found in 131 (42.5%) of all surgical specimens: 95 (40.6%) shave biopsy patients, 32 (60.4%) punch biopsy patients, and four (19.0%) excision biopsy patients. Recommendations for excision margin or sentinel lymph node biopsy changed in 15 (6%) shave biopsy patients and five (9%) punch biopsy patients. ConclusionsShave biopsy is the most frequent method of diagnosis of cutaneous melanoma in the modern era. While shave and punch biopsies may underestimate true T-stage, there was no difference in need for reoperation due to T-upstaging based on initial biopsy type, supporting current diagnostic practices. Partial biopsies can thus be used to guide appropriate treatment and definitive wide local excision when adjusting for understaging.

Melanocortin 1 receptor variants and their association with phenotypic characteristics and sporadic multiple primary melanomas in a cohort of 402 Spanish subjects.

The melanocortin 1 receptor (MC1R) gene is considered to be a major determinant of the risk of melanoma. The role of MC1R polymorphisms as predisposing factors for the development of a second primary melanoma is not well established. The present study analyses the characteristics from subjects with certain MC1R variants without any other genetic predisposition, as well as the risk of second primary melanoma associated with these variants. We performed a prospective longitudinal single-centre study based on follow-up information of 402 patients diagnosed with cutaneous melanoma. MC1R gene was sequenced in all subjects. High-risk variants were defined as those previously associated with melanoma (V60L, V92M, I155T, R160W, R163Q and D294H). 253 (63%) patients had at least one predisposing variant. These individuals had higher proportion of red/blonde hair, multiple primary melanomas and first melanoma diagnosis under the age of 60. Second primary melanomas were detected in 28 (3.8%) subjects. Having more than 25 melanocytic nevi was associated significantly to the development of second primary melanomas. A higher proportion of individuals carrying at least one predisposing MC1R variant develop a second melanoma, although statistical significance was not reached. Therefore, some MC1R polymorphisms might determine clinical and histological differences between patients with cutaneous melanoma and may represent a risk factor for second primary melanoma, although more studies are needed.

Incidence of different types of cancer in the follow-up period after primary diagnosis and treatment of melanoma. Single-centre 4-year follow-up on a population of 709 patients.

Follow-up plays a key role in melanoma management, especially in the first years after diagnosis. During this period it is crucial to assess possible recurrence, progression of the disease or treatment complications. An important aspect is also the possibility of formation of new primary foci or other skin cancers. To assess the coincidence of skin lesions and cancers among the melanoma patients. Patients treated in the Comprehensive Cancer Centre between 2019 and 2022 were retrospectively analysed for occurrence of skin lesions diagnosed during the follow-up, and confirmed by biopsy. The lesions considered included skin cancers, dysplastic nevus and actinic keratosis. In 100 (14%) out of 709 enrolled patients, 184 lesions were diagnosed. In 7 patients it was melanoma, in 49 BCC, and in 16 SCC. Dysplastic nevus and actinic keratosis were excised in 28 and 14 patients, respectively. More than one site of the skin lesion was observed in 39 patients, and more than one type of the lesion in 13 patients. Patients with lesions were on average 8.6 years older (p < 0.001), had less advanced tumours (p = 0.010), and primary melanoma was more often located on the head and neck (p = 0.056). Among melanoma patients, particular attention must be paid to, apart from early detection of melanoma recurrence and progression, the occurrence of new primary foci or independent skin cancers.

Primary early diagnosis of skin melanoma after individual training of doctors

Primary early diagnosis of skin melanoma after individual training of doctors

Risk Factors Associated With First and Second Primary Melanomas in a High-Incidence Population

An increasing number of people develop more than 1 primary melanoma, yet to date, no population-based prospective cohort studies have reported on risk factors for developing first vs second primary melanomas. To compare the clinical characteristics of first and second melanomas and then to estimate the relative risks of developing 1 vs multiple melanomas associated with demographic, phenotypic, sun exposure, and genetic factors. This population-based prospective cohort study included men and women aged 40 to 69 years recruited in 2011 and followed up until December 2018 in Queensland, Australia. Data analysis was performed from February to July 2022. Self-reported information about demographic, phenotypic, and sun exposure measures captured using a survey completed at baseline, and polygenic risk score for melanoma. Incident first or second primary melanoma diagnosis, and histologic and clinical characteristics thereof. The Wei-Lin-Weissfeld model for recurrent events was used to estimate the association of each factor with the risks of first and second primary melanoma. A total of 38 845 patients (mean [SD] age at baseline, 56.1 [8.2] years; 17 775 men and 21 070 women) were included in the study. During a median follow-up period of 7.4 years, 1212 (3.1%) participants had a single primary melanoma diagnosis, and 245 (0.6%) had a second primary melanoma diagnosis. Second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (ie, ≤1 mm) than first melanomas. Having many moles at age 21 years (self-reported using visual scoring tool) was more strongly associated with second (hazard ratio [HR], 6.36; 95% CI, 3.77-10.75) than first primary melanoma (HR, 3.46; 95% CI, 2.72-4.40) (P value for difference between the HRs = .01). A high genetic predisposition (ie, polygenic risk score in tertile 3) was also more strongly associated with second (HR, 3.28; 95% CI, 2.06-5.23) than first melanoma (HR, 2.06; 95% CI, 1.71-2.49; P = .03). Second melanomas were more strongly associated with a history of multiple skin cancer excisions (HR, 2.63; 95% CI, 1.80-3.83) than first melanomas (HR, 1.86; 95% CI, 1.61-2.16; P = .05). For all other phenotypic characteristics and sun exposure measures, similarly elevated associations with first vs second melanomas were observed. Findings of this cohort study suggest that within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanomas.

Melanoma surgery-An update.

Cutaneous melanoma is the major cause of mortality from all skin cancers. The treatment has been revolutionized in recent years by introduction of immunotherapy and targeted therapy for melanoma patients Stages III and IV. Therefore, the role of surgery in melanoma treatment needs to be redefined. In this narrative review, we will focus on surgery for diagnosis, treatment of primary tumor, and metastases in the era of new and effective medical treatment options. Neoadjuvant therapy is currently investigated in several trials. Surgery for treatment-resistant metastases is another field of interest. In conclusion, surgery remains a cornerstone for diagnosis and treatment of primary melanoma. Therapeutic lymphadenectomy has lost importance while surgery in sentinel lymph node diagnostics and metastasectomy are useful in a tailored individual approach of combined treatments. There is a trend to less invasive surgical procedures.

INCIDENCE OF POSTCHECKPOINT INHIBITOR SARCOIDOSIS: A SINGLE-CENTER OBSERVATIONAL STUDY

SESSION TITLE: Late Breaking Diffuse Lung Disease PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: The purpose of this study is to determine the incidence of sarcoidosis in cancer patients following treatment with immune checkpoint inhibitors and assess whether checkpoint inhibitor related sarcoidosis has a protective effect on cancer recurrence.METHODS: We examined consecutive patients who received immune checkpoint inhibitor therapy (ICI) between 2013 and 2020 at a tertiary medical center in Columbus, Ohio. All cases were reviewed by board-certified pulmonologists on the study team and attribution of sarcoidosis was determined by the presence of non-necrotizing granulomas on tissue biopsy and the lack of an alternate diagnosis (cancer progression, infection). Patient demographics, cancer diagnosis, ICI agent, time from ICI therapy to diagnosis of sarcoid, relapse or progression of cancer after diagnosis of sarcoid were recorded.RESULTS: Between 2013 and 2020, 8 post-checkpoint inhibitor sarcoidosis cases were identified from a total of 2,964 patients. The incidence of sarcoidosis following initiation of ICI therapy was 0.27%. The average time from ICI therapy to diagnosis of sarcoid was 487 days (range 101-1335 days), while the average number of ICI infusions received was 26 (5-75 doses). Melanoma was the most common primary cancer for post-ICI sarcoidosis with 6 cases (incidence of 1.16%, 6/518). Lung cancer was the primary cancer for 2 cases (incidence of 0.19%, 2/1075). All eight patients had pulmonary involvement in their sarcoidosis, one had skin involvement, and one had liver/GI involvement. Four patients had progression of their cancer after starting ICI and three died. One patient who had progression on ICI did not have any further progression after diagnosis of sarcoid. None of the patients received sarcoid-directed treatment.CONCLUSIONS: We demonstrate here that the incidence of sarcoidosis following ICI therapy is greater than the general population, which suggests ICI increases risk for sarcoidosis. This increased incidence is especially pronounced in patients with a primary diagnosis of melanoma. However, the incidence of sarcoidosis in lung cancers may be underrepresented because new or progressive lymphadenopathy in these patients may be less likely to be re-biopsied.CLINICAL IMPLICATIONS: Sarcoidosis is an underrecognized side effect of ICI, though its clinical significance on cancer prognosis is not clear. Cancer patients on ICI with progressive lymphadenopathy may not be from disease progression, and biopsy should be considered to rule out a sarcoid-like response, especially in melanoma patients who appear to have a higher incidence of post-treatment sarcoidosis. Further investigation will be needed to determine 1). Effects of sarcoidosis on cancer recurrence in a larger cohort that underwent sarcoid-directed therapies and 2). Whether treatment of post-checkpoint inhibitor sarcoidosis impacts cancer recurrence.DISCLOSURES:Collaboration via BARDA grant funding relationship with Beckman Coulter, Inc. Please note: 9/19/2019-8/31/2014 by Elliott Crouser, value=Grant/Research SupportRemoved 06/06/2022 by Elliott CrouserGrant recipient relationship with aTyr Pharmaceutical Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/ResearchGrant recipient relationship with Xentria Pharmaceutical Please note: 2021-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/Research SupportBoard Member relationship with Foundation for Sarcoidosis Research Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=No financial supportNo relevant relationships by Robert EasterlingNo relevant relationships by Kevin HoNo relevant relationships by Arindam Singha SESSION TITLE: Late Breaking Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: The purpose of this study is to determine the incidence of sarcoidosis in cancer patients following treatment with immune checkpoint inhibitors and assess whether checkpoint inhibitor related sarcoidosis has a protective effect on cancer recurrence. METHODS: We examined consecutive patients who received immune checkpoint inhibitor therapy (ICI) between 2013 and 2020 at a tertiary medical center in Columbus, Ohio. All cases were reviewed by board-certified pulmonologists on the study team and attribution of sarcoidosis was determined by the presence of non-necrotizing granulomas on tissue biopsy and the lack of an alternate diagnosis (cancer progression, infection). Patient demographics, cancer diagnosis, ICI agent, time from ICI therapy to diagnosis of sarcoid, relapse or progression of cancer after diagnosis of sarcoid were recorded. RESULTS: Between 2013 and 2020, 8 post-checkpoint inhibitor sarcoidosis cases were identified from a total of 2,964 patients. The incidence of sarcoidosis following initiation of ICI therapy was 0.27%. The average time from ICI therapy to diagnosis of sarcoid was 487 days (range 101-1335 days), while the average number of ICI infusions received was 26 (5-75 doses). Melanoma was the most common primary cancer for post-ICI sarcoidosis with 6 cases (incidence of 1.16%, 6/518). Lung cancer was the primary cancer for 2 cases (incidence of 0.19%, 2/1075). All eight patients had pulmonary involvement in their sarcoidosis, one had skin involvement, and one had liver/GI involvement. Four patients had progression of their cancer after starting ICI and three died. One patient who had progression on ICI did not have any further progression after diagnosis of sarcoid. None of the patients received sarcoid-directed treatment. CONCLUSIONS: We demonstrate here that the incidence of sarcoidosis following ICI therapy is greater than the general population, which suggests ICI increases risk for sarcoidosis. This increased incidence is especially pronounced in patients with a primary diagnosis of melanoma. However, the incidence of sarcoidosis in lung cancers may be underrepresented because new or progressive lymphadenopathy in these patients may be less likely to be re-biopsied. CLINICAL IMPLICATIONS: Sarcoidosis is an underrecognized side effect of ICI, though its clinical significance on cancer prognosis is not clear. Cancer patients on ICI with progressive lymphadenopathy may not be from disease progression, and biopsy should be considered to rule out a sarcoid-like response, especially in melanoma patients who appear to have a higher incidence of post-treatment sarcoidosis. Further investigation will be needed to determine 1). Effects of sarcoidosis on cancer recurrence in a larger cohort that underwent sarcoid-directed therapies and 2). Whether treatment of post-checkpoint inhibitor sarcoidosis impacts cancer recurrence. DISCLOSURES: Collaboration via BARDA grant funding relationship with Beckman Coulter, Inc. Please note: 9/19/2019-8/31/2014 by Elliott Crouser, value=Grant/Research Support Removed 06/06/2022 by Elliott Crouser Grant recipient relationship with aTyr Pharmaceutical Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/Research Grant recipient relationship with Xentria Pharmaceutical Please note: 2021-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/Research Support Board Member relationship with Foundation for Sarcoidosis Research Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=No financial support No relevant relationships by Robert Easterling No relevant relationships by Kevin Ho No relevant relationships by Arindam Singha