Diagnosis Of Primary Melanoma Research Articles

Effect of the time interval between melanoma diagnosis and sentinel node biopsy on the size of metastatic tumour deposits in node-positive patients

IntroductionThis study sought to assess whether the interval between diagnostic excision-biopsy of a primary melanoma and definitive wide excision with sentinel node biopsy (SNB) influenced the size of SN metastatic deposits, which might have implications for management and prognosis. MethodsData were collected for (i) a Dutch population-based cohort of patients treated between 2004 and 2014 who underwent SNB within 100 days of complete excision of their primary melanoma and who were SN-positive with known SN metastasis diameter (n = 1027) and (ii) a cohort from a large Australian melanoma treatment centre (n = 541) who presented in the same time period. The effects of SNB timing on the size of SN metastatic deposits were analysed. ResultsDutch patients whose SNB was performed in the second or third months after diagnosis had significantly larger SN metastasis diameters than patients who had their SNB in the first month (median increases of 17% (95%CI -14, 60%, p = 0.211) and 71% (95%CI 15, 119%, p = 0.004), respectively). No significant difference in tumour diameter for early and late SNB was found in the Australian cohort. ConclusionsSN metastasis diameter became progressively greater with SN biopsy in the second and third months after primary melanoma diagnosis in the larger, population-based patient cohort. An increase in metastasis diameter was not observed in the smaller, institutional cohort, possibly due to detection of larger SN metastases by routine pre-operative ultrasound, with fine-needle biopsy confirmation. These patients did not proceed to SNB and were therefore not included in the study.

Prognostic Utility of CpG Island Hypermethylated Phenotype in Early-Stage Invasive Primary Melanomas

In their article in the Journal of Investigative Dermatology, Conway etal. (2021) show the significance of the CpG island methylator phenotype (CIMP) subclass in early-stage invasive primary melanomas, particularly in the lentigo maligna melanoma histological subtype. CIMP melanomas had reduced melanoma-specific survival compared with intermediate and low methylation subtypes. This study emphasizes the importance of epigenomic changes in early-stage primary tumors that are associated with poor prognosis.

Case Report: Differential Genomics and Evolution of a Meningeal Melanoma Treated With Ipilimumab and Nivolumab

Primary melanocytic tumors of the CNS are extremely rare conditions, encompassing different disease processes including meningeal melanoma and meningeal melanocytosis. Its incidence range between 3-5%, with approximately 0.005 cases per 100,000 people. Tumor biological behavior is commonly aggressive, with poor prognosis and very low survivability, and a high recurrence rate, even after disease remission with multimodal treatments. Specific genetic alterations involving gene transcription, alternative splicing, RNA translation, and cell proliferation are usually seen, affecting genes like BRAF, TERT, GNAQ, SF3B1, and EIF1AX. Here we present an interesting case of a 59-year-old male presenting with neurologic symptoms and a further confirmed diagnosis of primary meningeal melanoma. Multiple therapy lines were used, including radiosurgery, immunotherapy, and chemotherapy. The patient developed two relapses and an evolving genetic makeup that confirmed the disease’s clonal origin. We also provide a review of the literature on the genetic basis of primary melanocytic tumors of the CNS.

Melanoma in patients with mycosis fungoides

The development of both malignant neoplasms mycosis fungoides and cutaneous malignant melanoma is a rare condition; nevertheless, the literature describes both cases of the development of mycosis fungoides in patients with a primary diagnosis of melanoma and the detection of cutaneous malignant melanoma in patients with T-cell lymphomas of the skin. The question of the effect of previous therapy for mycosis fungoides on the risk of cutaneous malignant melanoma remains controversial. Currently, the world community is considering a possible pathogenetic relationship between these two oncopathologies. The clinical observations of the development of cutaneous malignant melanoma in 2 patients with mycosis fungoides presented in the article emphasize the importance of a thorough clinical and dermatoscopic examination of all pigmented formations for the timely detection of malignant melanocytic neoplasms, the presence of which radically affects the further choice of treatment tactics for patients.

Melanoma Management during the COVID-19 Pandemic Emergency: A Literature Review and Single-Center Experience.

Simple SummaryCOVID-19 is a highly contagious infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In March 2020, the World Health Organization (WHO) declared that COVID-19 had become a pandemic; since then, several elective clinical and surgical activities have been postponed to reduce the risk of nosocomial infection. This has influenced the diagnosis and management of many diseases, including melanoma. The aim of our literature review was to evaluate whether the management of melanoma has been changed by the outbreak of COVID-19, and if so, what the consequences of these changes are. The main topics in this literature review are the screening of suspicious lesions, diagnosis of primary melanoma, and the management of early-stage and advanced melanomas in the COVID-19 era. We also reported the experience of our dermatological clinic in Turin, one of the most affected areas in Italy.Background: The current COVID-19 pandemic has influenced the modus operandi of all fields of medicine, significantly impacting patients with oncological diseases and multiple comorbidities. Thus, in recent months, the establishment of melanoma management during the emergency has become a major area of interest. In addition to original articles, case reports and specific guidelines for the period have been developed. Purpose: This article aims to evaluate whether melanoma management has been changed by the outbreak of COVID-19, and if so, what the consequences are. We summarized the main issues concerning the screening of suspicious lesions, the diagnosis of primary melanoma, and the management of early-stage and advanced melanomas during the pandemic. Additionally, we report on the experience of our dermatological clinic in northern Italy. Methods: We performed a literature review evaluating articles on melanomas and COVID-19 published in the last two years on PubMed, as well as considering publications by major healthcare organizations. Concerning oncological practice in our center, we collected data on surgical and therapeutic procedures in patients with a melanoma performed during the first months of the pandemic. Conclusions: During the emergency period, the evaluation of suspicious skin lesions was ensured as much as possible. However, the reduced level of access to medical care led to a documented delay in the diagnosis of new melanomas. When detected, the management of early-stage and advanced melanomas was fully guaranteed, whereas the follow-up visits of disease-free patients have been postponed or replaced with a teleconsultation when possible.

1330Is Prognosis Worse for People with Multiple Versus Single Primary Melanoma?

Abstract Background Patients with a primary melanoma may develop more than one in their lifetime. It is unclear whether mortality is worse after diagnosis of multiple primary melanoma (MPM) compared with single primary melanoma (SPM). Methods We analysed data from a population-based cohort of 3,869 patients diagnosed with primary in situ or invasive cutaneous melanoma in New South Wales, Australia in 2006-07 and followed up until 2018 (median 11.9 years) using linked mortality and cancer registry data. We compared overall mortality and melanoma-specific mortality for patients with SPM versus MPM, adjusting for other clinico-pathological prognostic indicators, using Cox proportional hazard models. The primary analysis was based on pathological features from the thickest tumour for MPM patients, however sensitivity analyses were performed using the first and last primary melanoma. Results The cohort consisted of 3,869 patients (2,929 SPM and 940 MPM) and 5,504 melanoma lesions (including 2,575 lesions from MPM patients). The primary multivariable analysis showed MPM was associated with lower mortality from all causes and melanoma compared with SPM with a hazard ratio of 0.62 (95% CI: 0.54-0.71, p < 0.001) and 0.37 (95% CI: 0.32-0.43, p < 0.001) respectively. These findings were also supported by the sensitivity analyses. Conclusions The diagnosis of MPM does not worsen mortality compared to a SPM, in fact it was associated with improved survival. This finding might be related to skin examination behaviours, biological or clinical factors. Key messages MPM patients have a better prognosis than SPM patients.

Melanoma brain metastases in Ireland: surgical and systemic considerations

Background Cerebral metastases is a common complication in patients with melanoma. There is a paucity of information in the Republic of Ireland regarding the factors associated with melanoma brain metastases (MBM). Methods Patients diagnosed with melanoma brain metastases in Ireland were retrospectively identified in Beaumont Hospital between 1999 and 2018. Patient demographics; age at diagnosis of primary melanoma, age at detection of MBM, year of detection of MBM, anatomical location of primary melanoma, BRAF mutation analysis and the number of metastases were investigated. Follow-up data were also derived, including overall survival. Results There has being a 158% increase in the incidence of primary melanoma from 1999 compared to 2016. Over the same time period 128 patients with melanoma brain metastases were diagnosed. There was a significant male predominance (n = 77/128; 60%; p < 0.0001). BRAF mutation and leptomeningeal disease were independent prognostic factors in our cohort with a median survival 8 months and 0.5 months, respectively. Conclusions Male predominance, leptomeningeal disease and BRAF mutation represent important considerations in this population group. The results of this study add to our knowledge concerning outcomes in melanoma brain metastases and may be useful in clinical planning and future treatments.

Increased melanoma recurrence in patients with multiple primary invasive melanomas

To the Editor: Primary melanoma patients have an increased risk of developing other primary melanomas over time, but the influence of multiple primary melanomas on recurrence rates is unknown. Survival was formerly believed to be better in those with multiple primary melanomas,1 but it is now known to be worse with increased melanoma mortality.2 We prospectively assessed the recurrence rates in patients 5 years after the diagnosis of high-risk primary melanoma, comparing patients in whom other primary melanomas developed before or since their index primary melanoma with patients with only the index melanoma.

Survival disparities in top five cancers in the United States: A population based study.

e18545 Background: Health inequity is an important field in cancer research and it is vital to determine the underlying etiologies to eliminate health disparities. Health insurance differences in survival outcomes have been reported for patients residing in California and New Jersey. Likewise, we aim to explore the impact of variations in insurance status and demographic factors on survival outcomes in patients with the top five cancers in the United States using a nationwide cancer registry. Methods: Surveillance, Epidemiology, and End Results (SEER) 18 program was queried to identify patients with a primary diagnosis of lung, breast, colorectal, prostate cancer, and melanoma from 2007 to 2016. Patient characteristics included are age (≥20 years), sex, marital status, metropolitan or non- metropolitan residence, insurance status (private vs. Medicaid vs. uninsured), education level, stage at diagnosis, and survivals. Descriptive and survival analyses were performed using Pearson Chi-square, Kaplan-Meier and Cox regression tests. Results: A total of 935,916 patients were included, of which 344,022 (37%) had breast cancer, 209,762 (22%) prostate cancer, 151,553 (16%) colorectal cancer, 151,468 (16%) lung cancer, and 79,111 (8%) melanoma. Most patients were aged &gt; 50 years (76%) and 55% were female. Privately insured accounted for 83% of all patients, 13% had Medicaid and 4% were uninsured. Male gender, married, patients with higher education level, residing in metropolitan areas were more likely to have private insurance (p &lt; 0.001) compared to female gender (84.3% vs. 81.2%), unmarried (90.1% vs. 68.7%), subjects with very low to moderate education level (88.2% vs. 80.8%), and ones residing in non- metropolitan areas (83.4% vs. 76.3%). Patients with private insurance were more likely to be diagnosed at localized stage compared to Medicaid insured and uninsured (59.2% vs. 38.2% and 36.6%; p &lt; 0.001). On bivariate and multivariate analyses across of all five cancers, age &gt; 50 years (HR 2.0; p &lt; 0.001), male gender (HR 1.3; p &lt; 0.001), single (HR 1.3; p &lt; 0.001), Medicaid insurance (HR 1.2; p &lt; 0.001), and uninsured (HR 1.3; p &lt; 0.001) were associated with worse overall survival than age &lt; 50 years, female, unmarried, and privately insured. Conclusions: Along with noticeable survival disparities by insurance status in lung, breast, colorectal, prostate and melanoma, we noted that privately insured patients are more likely to be presented at an earlier stage compared to patients with Medicaid and uninsured. Additionally, elderly age, lower education level, unmarried and low socioeconomic status had a negative impact on survival. Multidisciplinary care team efforts are critical in mitigating these health disparities.

It was just mind blowing to be honest: a qualitative phenomenological study exploring cancer survivor’s experiences of indocyanine green lymphography used to inform lymphedema therapy management

A diagnosis of secondary lymphedema following cancer treatment can necessitate lifelong therapy. Indocyanine green (ICG) lymphography is a technique for visualising lymphatics to enable individualised lymphedema diagnosis, staging and therapy prescription. The participant experience of undergoing the procedure and the impact of imaging findings on lymphedema management is unknown. This study aimed to explore participant's experiences of ICG lymphography to inform cancer-related lymphedema therapy. A qualitative phenomenological study was conducted using semi-structured interviews with 17 adult participants who had undergone ICG lymphography for stage 0 to 2 upper or lower limb secondary cancer-related lymphedema (International Society of Lymphology, Lymphology 53(1):3-10, 2020). Seventeen participants were included in the study ranging in age from 36 to 78years (M = 53.8years), the majority hada primary diagnosis of breast cancer (N = 7) or melanoma (N = 7). Three overarching themes emerged. Firstly, describing the experience of the ICG lymphography procedure. Secondly, the new knowledge explained symptoms and tailored treatment. Participants reflected on how seeing their lymphatic system helped in understanding about their lymphedema symptoms and guided changes towards more individualised lymphedema management. The final themedescribed the internal impact of self-knowledge, which included impacts of the new information on empowerment and motivation to self-manage participant'scondition as well as their feelings. ICG lymphography had beneficial impacts on participant's understanding of their lymphedema symptoms and often led to changes in management, positive outcomes in response to management changes and peace of mind about management plans, leading to feeling more empowered to self-manage their condition.

Rare Case Report of Primary Gastric Melanoma

Gastric melanomas are usually metastatic, and primary is almost rare entity.&#x0D; Present case is a rare malignant melanoma of the gastric region with barely reported cases in the literature. A 65 year old male presented with pain abdomen and melena He was evaluated with relevant investigation. UGI endoscopy and PETCT shows large polypoidal irregular gastric mass in the proximal curvature extending upto gastroesophageal junction. Endoscopic biopsy a ulcero-infiltrating tumour, Individual cells are large, round, having moderately pleomorphic, hyperchromatic nuclei with prominent eosinophilic nucleoli and moderate eosinophilic cytoplasm. Immunohistochemistry of S100 and HMB45 was positive and negative for CK7 and CK20.&#x0D; Early diagnosis of primary gastric melanoma allows for better prognosis of the patient from the right intervention.

Role of vitamin D serum levels in prevention of primary and recurrent melanoma

Patients afflicted with melanoma show lower vitamin D serum levels (VDSL) than the healthy population. This hypothesis agrees with its well-known antiproliferative features. An observational study was carried out to collect VDSL in patients suffering from melanoma. Our aim was to identify a potential connection between low VDSL and the risk to incur melanoma. Furthermore, we studied the association between VDSL at the diagnosis of melanoma and other germane prognostic factors. The population held in regard was composed of 154 patients with a diagnosis of melanoma between 2016 and 2019. These patients were retrospectively collected from our follow-up storage. We compared VDSL to clinical and pathological parameters (age, sex, tumour location, Breslow’s depth, Clark’s level, histological subtype, ulceration, et aliqua). Moreover, we recruited a control group with negative melanoma history. Mean and median of VDSL were significantly lower in the melanoma group. Instead, we found a negative association between melanoma and VDSL > 30 ng/L (OR 0.11; p < 0.0001). No correlation between VDSL and both Breslow’s depth and Clark’s level was discovered, but the VDSL comparison between thin (depth ≤ 1 mm) and thick tumours (depth > 1 mm) revealed a statistically significant difference (21.1 ± 8.2 ng/L vs 17.8 ± 8.1; p = 0.01). Moreover, VDSL were significantly lower in melanomas with mitotic rate ≥ 1/mm2 (22.1 ± 8.3 ng/L; p < 0007). Nevertheless, no connection was found between VDSL and both ulceration and positive sentinel nodes (p = 0.76; p = 0.74). Besides, our study revealed no association between VDSL and histological subtype (p = 0.161). Lower VDSL correlate with thick and high mitotic rate tumours. Future prospective studies would investigate if appropriate upkeep of suitable VDSL can decrease the risk of primary and recurrent melanoma diagnosis.

Late melanoma metastases in stomach and small bowel: a case report

Background: Primary cutaneous malignant melanoma with gastric metastases is a rare phenomenon, which usually occurs within one year from the time of the primary tumor diagnosis. In this case, the diagnosis of primary melanoma was 8 years prior to gastric metastases diagnosis. Case Presentation: 75-year-old male with a history of malignant melanoma presented with ferropenic anemia was found to have metastases to the stomach, detected on endoscopy. A Palliative Subtotal Gastrectomy was performed because of recurrent gastrointestinal bleeding. After surgery, the patient was referred to our oncology clinic for chemotherapy. Conclusion: Surgical intervention offered symptomatic relief while attempting to prolong the patient’s survival. Most publications on this topic are limited to single case-reports given the low frequency of gastric lesions in patients with primary cutaneous melanoma. This case report contributes to the understanding of this rare phenomenon while reaffirms that Metastatic Melanoma in the stomach should be suspected in any patient with a previous history of Melanoma.

Locoregional Therapies for the Treatment of Uveal Melanoma Hepatic Metastases.

Uveal melanoma is the most common primary intraocular malignant tumor in adults. Approximately 50% of patients develop metastatic disease of which greater than 90% of patients develop hepatic metastases. Following the development of liver tumors, overall survival is dismal with hepatic failure being the cause of death in nearly all cases. To prolong survival for patients with metastatic uveal melanoma, controlling the growth of hepatic tumors is essential. This article will discuss imaging surveillance following the diagnosis of primary uveal melanoma; locoregional therapies used to control the growth of hepatic metastases including chemoembolization, immunoembolization, radioembolization, percutaneous hepatic perfusion, and thermal ablation; as well as currently available systemic treatment options for metastatic uveal melanoma.

Photoacoustic tomography for assessment and quantification of cutaneous and metastatic malignant melanoma - A systematic review.

Photoacoustic tomography (PAT) is an emerging noninvasive imaging technique combining high sensitivity optical absorption contrast, such as melanin, with high-resolution ultrasound for deep tissue imaging. The ability of PAT to provide real-time images of skin structures at depth has been studied for diagnosis of primary and metastatic malignant melanoma (MM). To provide an overview of the rapidly expanding clinical use of PAT for determination of melanoma thickness and architecture, visualization of metastases in lymph nodes and detection of circulating melanoma cells. Medline, PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Library were searched for papers using PAT to assess cutaneous malignant melanoma and melanoma metastases in humans or human specimens. The research resulted in 14 articles which met the search criteria. Results from current studies suggest that PAT is a promising tool for assessing both primary and metastatic malignant melanoma in the clinic. The potential of PAT to noninvasively visualize tumour boundaries, as well as assist in the evaluation of metastatic status, could facilitate more effective treatment, resulting in better clearance and reducing the need for additional biopsies. However, larger and methodologically sound studies are warranted.

Venous Thromboembolism Incidence and Impact on Survival in Patients with Brain Metastases

Background: Patients with brain metastases are considered especially high risk for venous thromboembolism (VTE). The incidence of VTE following a diagnosis of brain metastases and the impact of VTE on overall survival among patients with brain metastases have not been well characterized. Methods: Using the linked Surveillance, Epidemiology and End Results (SEER) and Medicare databases between 2008-2015, we identified all patients ≥66 years with a primary diagnosis of lung, renal cell, breast cancer or melanoma and brain metastases (ICD-9-CM 198.3 present anytime in Medicare claims). Patients were required to have continuous Medicare part A and B enrollment from 12 months before and 12 months after diagnosis or until death. The primary outcome was incidence of VTE (deep vein thrombosis or pulmonary embolism or both) in the 12- months following a diagnosis of brain metastases. Patients with a VTE diagnosis prior to brain metastases were excluded. Incidence rates were calculated as VTE events per 100 patient years. Tumor specific multivariable Cox proportional hazards model adjusting for age, sex, race, time from primary cancer diagnosis to brain metastasis, comorbidities and VTE as a time varying covariate was used to assess the association of VTE and 12-month overall survival following a diagnosis of brain metastasis. Results: Among 154,918 individuals with a primary cancer diagnosis of interest, 21,623 (14.0%) had a brain metastasis diagnosis. Majority of patients with brain metastases had a primary diagnosis of lung cancer (N=19,141 (88.5%)), followed by melanoma (N=1,607 (7.4%)), renal cell cancer (N=576 (2.7%)) and breast cancer (299 (1.4%)). The baseline characteristics are highlighted in Table 1. Among these patients, VTE was diagnosed in 3,432 (15.9%). In the year following a diagnosis of brain metastasis, the incidence of VTE per 100 patient-years was highest among those with a diagnosis of renal cell cancer (19.4), followed by breast (16.3), lung (16.0) and melanoma (12.5). The median time to VTE from a diagnosis of brain metastasis is 1 month (IQR 0-3 months) and the cumulative incidence of VTE stratified by tumor type and accounting for the competing risk of death over 12 months is illustrated in Figure 1.The median overall survival following a diagnosis of brain metastasis was 2.7 months (95% CI 2.1-3.1 months). In a multivariable Cox proportional hazards model, a diagnosis of VTE following brain metastasis was associated with increased risk of death in patients with lung cancer (HR 1.23 (95% CI 1.18-1.28)), renal cell cancer (HR 1.36 (95% CI 1.06-1.75)) and melanoma (HR 1.32 (95% CI 1.12-1.55)), but not breast cancer (HR 1.16 (95% CI 0.80-1.69)). Conclusions: This large real-world retrospective cohort analysis demonstrates and quantifies the high tumor specific incidences of VTE among individuals with brain metastases. The VTE incidence rates observed are comparable to metastatic pancreatic cancer and highest in the initial 3 months following a diagnosis of brain metastasis. Furthermore, a diagnosis of VTE is associated with a reduced 12-month overall survival in this patient population. We are mindful to highlight the inherent limitations of claims data in identifying clinical events such as brain metastases and VTE, thus possible misclassification and selection biases should be considered when interpreting these findings. However, considering the complexity of managing VTE in this high-risk patient population and the high thrombotic burden demonstrated, these findings warrant further prospective validation. Disclosures Key: Takeda: Research Funding; Grifols: Research Funding; Uniqure: Consultancy; Novo Nordisk: Other: Chair of Grants Committee. Lund:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; AbbVie: Research Funding.

S1774 Primary Anorectal Malignant Melanoma: Rare and Fatal

INTRODUCTION: We present an uncommon diagnosis of primary anorectal malignant melanoma (ARMM) in a patient with anemia and altered bowel habits. Primary ARMM accounts for less than 4% of anorectal malignancies and less than 1.5% of all melanomas. ARMM can often go undiagnosed, which is detrimental to patients due to its aggressive nature. CASE DESCRIPTION/METHODS: 63 y.o. African American male with a history of ascending colon resection for colon adenocarcinoma 8 years prior was referred for change in bowel habits and nausea with eating. He had worsening intermittent constipation, but denied melena or blood in his stool. He had nausea 45 minutes after eating but no vomiting. He denied recent weight loss. His last colonoscopy was a year after colon resection. The ileocolonic anastomosis was at 70 cm from anal verge, there was a 3 mm hyperplastic polyp in the sigmoid and repeat colonoscopy was recommended in a year. Physical exam was negative for skin hyperpigmentation, moles or lesions. Abdominal exam was negative for tenderness, guarding or rebound. Labs showed normocytic anemia, Hgb 8.1 g/dl from 12 g/dl the year prior. Digital rectal exam revealed a firm immobile mass, 3 cm from anal verge. Colonoscopy showed a fungating, ulcerated, non-obstructing 3 cm mass in the rectum. Biopsies were done with cold forceps for histology. Pathology noted the mass had brownish pigmentation and extensive necrosis, consistent with malignant melanoma. Immunohistochemical staining was positive for S-100, HMB-45, Melan-A and SOX-10 supporting the diagnosis. A diagnosis of primary anorectal malignant melanoma was made as patient had no evidence of cutaneous or ocular melanoma. PET scan showed metastasis to a large pelvic lymph node so patient was not a surgical candidate. Oncology started patient on immunotherapy with ipilmumab and nivolumab. DISCUSSION: Primary ARMM is a rare malignancy, especially in African Americans such as our patient, with a poor prognosis. As with our case, presenting symptoms can be unspecific such as anemia. Often patients with ARMM present with rectal bleeding that is attributed to hemorrhoids and endoscopic intervention is not pursued. This is detrimental as it causes a delay in diagnosis. Our patient’s mass was pigmented, but in 29% of cases the mass may be amelanotic resulting in misdiagnosis. Treatment is abdominoperineal resection if there is no evidence of metastasis. Our case highlights the importance of recognizing primary ARMM as a cause of rectal bleeding in patients with an anorectal mass.Figure 1.: Retroflexed view in the rectum revealing the pigmented, ulcerated, non-obstructing 3 cm mass at 3 cm from anal verge.Figure 2.: The mass is composed of melanoma cells that formed irregular nests and cords, and manifested enlarged and hyperchromatic nuclei with irregular nuclear contours and prominent nucleoli. The pigments were finely granular and brownish. (H&E, x200).Figure 3.: Immunohistochemistry demonstrated the tumor cells to be positive for S-100 (Fig. A, cytoplasmic stain, fast red; X100), HMB-45 (Fig. B, cytoplasmic stain, fast red; X100) and SOX-10 (Fig. D, nuclear stain, fast red; X100). They were negative for expression of pan-cytokeratin, the brown granules in the background are melanin pigments (Fig.C, AE1/3, lack of cytoplasmic stain, DAB; X100).

S2223 Dead End in the Small Bowel: Rare Case of Small Bowel Melanoma Presenting as Melena

INTRODUCTION: Malignant melanoma accounts for only 1% of all malignant tumors of the small bowel. The majority are usually metastatic from the skin eye or anorectum. Less than 50 cases of truly primary small bowel melanomas have been described in literature with overt bleeding as a presenting complaint even rarer. We present such a case of an elderly man with middle gastrointestinal bleeding who was found to have unresectable small bowel melanoma on device assisted enteroscopy. CASE DESCRIPTION/METHODS: An 80-year-old man with stage IV Chronic kidney disease presented to the hospital with a few months of dark tarry stools and symptomatic iron deficiency anemia refractory to iron supplementation needing up to 7 transfusions. He did not endorse Non-steroidal anti-inflammatory drug use. An esophagoduodenoscopy and colonoscopy at an outside facility was unremarkable. Video capsule endoscopy showed hematin in the the proximal jejunum with a possible ulcer more distally. A single balloon enteroscopy revealed a 10 mm cratered jejunal ulcer with slight pigmentation in the base (Figure 1). This was biopsied. Pathology revealed malignant melanoma with BRAF V600E mutation. Subsequent positron emission tomography (PET) showed a 6 cm small bowel mass compatible with primary site and metastatic lesions in the mesentery, perihepatic and subdiaphragmatic region (Figure 2). Following tumor board discussion, he was referred for palliative radiotherapy. DISCUSSION: Primary mucosal melanoma most commonly arises from the anal canal (31.4%), rectum (22.2%) and oropharynx (33%). Only 2.3% of cases have been reported from the small bowel. Presence of melanocytes has not yet been demonstrated in the small intestine, and the origin of primary melanoma of the small intestine remains unknown. Blecker et al. suggested a strict criteria for the diagnosis of primary intestinal melanoma: no evidence of concurrent cutaneous lesions, absence of extraintestinal metastatic spread of melanoma, and presence of intramucosal lesions in the overlying intestinal epithelium. This form of melanoma is more aggressive and associated with worse prognosis. Other factors of poor prognosis include lymph node involvement, advanced age and failure to undertake surgical resection (which remains the primary treatment option). Our case highlights the importance of keeping a broad differential in patients presenting with middle GI bleeding and aggressively pursuing tissue diagnosis in such cases.Figure 1.: Proximal Jejunum ulcer.Figure 2.: PET scan image with metastatic melanoma.

Rural health disparities in melanoma staging and prognostic outcomes in Iowa

To the Editor: Melanoma is currently the fifth most common cancer in men and the sixth most common cancer in women, with 91,000 estimated new cases of melanoma and 9300 deaths in the United States in 2018. Presentation at a higher stage and higher mortality rates for multiple cancers1Hashibe M. Kirchhoff A.C. Kepka D. et al.Disparities in cancer survival and incidence by metropolitan versus rural residence in Utah.Cancer Med. 2018; 7: 1490-1497Crossref PubMed Scopus (26) Google Scholar have been found to be comparatively higher in numerous studies of rural populations. Geographic location strongly influences health care education, access to care, and outcomes.2Fennell K.M. Martin K. Wilson C.J. Trenerry C. Sharplin G. Dollman J. Barriers to seeking help for skin cancer detection in rural Australia.J Clin Med. 2017; 6: 19Crossref Scopus (9) Google Scholar Influential factors may include sociodemographic barriers such as access to finances, distance from providers, home environment, and patient cultural background. Of the US population, 14% to 19% (46.2-59 million people) live in rural areas,3Blake K.D. Moss J.L. Gaysynsky A. Srinivasan S. Croyle R.T. Making the case for investment in rural cancer control: an analysis of rural cancer incidence, mortality, and funding trends.Cancer Epidemiol Biomarkers Prev. 2017; 26: 992-997Crossref PubMed Scopus (110) Google Scholar representing a significant area for targeting and improving health care quality. We sought to assess whether disparities existed in stage at diagnosis and mortality between rural and metropolitan patients with melanoma and took advantage of our status as a state with 36% rural residents.4Iowa State Data CenterIowa quick facts.https://www.iowadatacenter.org/quickfactsDate: 2018Google Scholar We accessed the deidentified Surveillance, Epidemiology, and End Results Program of the National Cancer Institute public use data set for patients in the state of Iowa (Iowa Cancer Registry). Categories available included age, race, sex, marital status, stage at diagnosis (Breslow depth), treatment type, vital status, and site of melanoma. All patients with a first-time diagnosis of nonocular primary cutaneous melanoma between 1996 and 2015 were included. Location was categorized as rural or metropolitan by using the US Office of Management and Budget definition of metropolitan areas as urbanized areas with 50,000 or more people5Parker T. Rural-urban continuum codes. US Department of Agriculture Economic Research Service.https://www.ers.usda.gov/data-products/rural-urban-continuum-codes.aspxGoogle Scholar and all other areas as rural. Multivariate statistical analysis was performed to assess whether geographic location was associated with metastatic disease or increased mortality. We identified 12,991 diagnosed patients who met these criteria during the 20-year period, of whom 6829 (52.6%) were in metropolitan areas and 6162 (47.4%) were in rural areas. A total of 8550 (65.8%) patients were alive, and 4441 (34.2%) were deceased. The mean age in rural areas was 61 years, and in metropolitan areas it was 58 years. Living in rural areas was associated with decreased odds of being an ethnic minority (odds ratio, 0.36; P < .01; 95% CI, 0.21-0.62). Multivariate analysis of the full population indicated that patients with metastatic disease had increased odds (odds ratio, 1.13; P = .01; 95% CI, 1.03-1.24) of being located in rural areas of Iowa compared to those diagnosed with nonmetastatic disease (Table I). Those diagnosed in rural areas also had increased all-cause mortality when compared to those diagnosed in metropolitan areas (hazard ratio, 1.26; P < .01; 95% CI, 1.19-1.34) (Table II).Table IModeling the probability of a patient living in a rural area: Multivariate resultsCovariateLevelNRural/metropolitanOdds ratio95% CIP valueRaceOther4280.360.21-0.62<.01White12,563———SexFemale59260.940.88-1.01.11Male7065———StageMetastatic19671.131.03-1.24.01Nonmetastatic11,024———SiteNot specified4450.850.70-1.04.12Trunk/limbs96060.840.78-0.92<.01Head/neck2940———Marital statusDivorced/separated/widowed18461.121.01-1.24.03Single12770.730.65-0.82<.01Married7986———SurgeryYes12,2481.140.98-1.33.08No734———ChemotherapyYes150.980.35-2.69.96No12,726———RadiationYes4001.180.97-1.45.10No12,587———Hormone therapyYes150.970.35-2.68.95No12,975———Breslow depth (mm)Stage II (0.77-1.50)19851.040.93-1.15.52Stage III (1.51-2.25)7081.050.90-1.23.52Stage IV (2.26-3.0)4131.100.90-1.34.37Stage V (3.0 or more)9921.221.06-1.40<.01Stage I (0.75 or less)4527———Age12,9911.011.01-1.01<.01Bolded text indicates that statistical significance was noted.CI, Confidence interval. Open table in a new tab Table IIOverall survival on full population: Multivariate overall survivalCovariateLevelNSurvivalHazard ratio95% CIP valueRaceOther4270.080.05-0.14<.01White12,494———SexFemale58880.550.52-0.59<.01Male7033———SiteNot specified4452.882.55-3.25<.01Trunk/limbs95530.470.44-0.51<.01Head/neck2923———StageDistant/regional19623.993.74-4.26<.01Localized10,959———Rural/metropolitanRural61351.261.19-1.34<.01Metropolitan6786———Marital statusDivorced/separated/widowed18362.081.93-2.23<.01Single12700.770.68-0.86<.01Married7942———SurgeryYes12,1790.340.31-0.38<.01No733———ChemotherapyYes156.663.87-11.49<.01No12,656———RadiationYes4005.624.99-6.33<.01No12,517———HormoneYes153.341.80-6.21<.01No12,905———Breslow depth (mm)Stage II (0.77-1.50)19821.181.05-1.33<.01Stage III (1.51-2.25)7082.141.86-2.47<.01Stage IV (2.26-3.0)4123.232.76-3.77<.01Stage V (3.0 or more)9894.954.46-5.51<.01Stage I (0.75 or less)4517———Age12,9211.071.07-1.07<.01Bolded text indicates that statistical significance was noted.CI, Confidence interval. Open table in a new tab Bolded text indicates that statistical significance was noted. CI, Confidence interval. Bolded text indicates that statistical significance was noted. CI, Confidence interval. Here, we report the correlation between location of diagnosis and stage at diagnosis and all-cause mortality. Limitations include that the Surveillance, Epidemiology, and End Results data set reports only all-cause mortality. Furthermore, only location of diagnosis was reported; hence, it cannot be definitively said whether patients lived in metropolitan or rural areas. Early staging and treatment of melanoma are crucial to prevent further future morbidity and mortality and to decrease costs. Disparities seen in rural populations may indicate the need for greater focus in these areas.

Melanoma and COVID-19: A narrative review focused on treatment.

Melanoma is the most severe form of skin cancer and its incidence has increased over the past few decades. COVID-19 pandemic affected the diagnosis and management of many diseases including melanoma. In this study, we aimed to provide a review focused on the diagnosis and management of melanoma in the era of COVID-19. A comprehensive search was conducted on PubMed, Web of Science, and Google Scholar databases using the keywords "melanoma," "coronavirus," "COVID 19," and "SARS-CoV-2." The relevant guidelines published by the European Society for Medical Oncology and the National Comprehensive Cancer Network were also included. The current guidelines recommend that surgical interventions for new diagnosis of invasive primary melanoma, patients with postoperative complications, wide resection and sentinel lymph node biopsy for newly diagnosed T3-T4 melanoma, and planned surgical procedures for patients in neo-adjuvant trials should be prioritized. Surgical treatment of T3/T4 melanomas should be prioritized over T1/T2 melanomas except for any melanoma in which large clinical residual lesion is visible. Adjuvant therapies can be postponed for up to 12 weeks depending on the local center circumstances. PD-1 inhibitor monotherapy is recommended for patients starting immunologic therapy. Combination immunotherapy is still considered suitable for patients with higher-risk disease. Encorafenib and binimetinib should be prioritized for patients requiring BRAF-targeted therapy due to the lower chance of symptoms mimicking COVID-19 infection.