BackgroundMelanoma has a wide range of histologic variants and cytomorphologic features that make its diagnosis challenging. Melanoma can also rarely have neuroendocrine markers adding further diagnostic uncertainty particularly given that unrelated tumor types, such as prostate cancer, can also display focal neuroendocrine differentiations.Case presentationOur patient is a 74-year-old Caucasian man found to have a lung mass. Initial biopsy revealed typical microscopic morphology and neuroendocrine differentiation consistent with small cell carcinoma. Despite standard chemoradiation treatment, the patient continued to progress with new metastasis in the brain, liver and bone. Subsequent chest wall biopsy revealed golden-brown pigment associated with melanin. Further tumor immunohistochemistry revealed extensive neuroendocrine differentiation with CD56, synaptophysin, and INSM1, as well as strong immunoreactivity for melanocyte markers including SOX10, S100, PRAME, and MITF, consistent with metastatic melanoma with neuroendocrine differentiation. Genomic testing revealed increased tumor mutational burden and alterations in NF1, BRAF, CDKN2A/B, TERT. The patient was transitioned to checkpoint inhibitor therapy with nivolumab and ipilimumab and had resolution of his intracranial mass and decrease in size of other metastatic lesions.ConclusionOften the combination of anatomic findings such as a lung mass, typical microscopic morphology, and confirmation of neuroendocrine differentiation correctly identifies a patient with small cell carcinoma. However, in a patient who fails to respond to treatment, a broader immunohistochemical workup along with molecular testing with additional tissue may be warranted.

Introduction Pancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous disease often diagnosed with synchronous metastatic disease involving the liver. Tumors with extra‐abdominal spread that bypass the liver are thought to represent a unique molecular subgroup and those with isolated pulmonary metastatic disease are thought to have a more favorable clinical phenotype. Method We conducted a retrospective review of patients with pathologically confirmed PDAC treated between the years 2007 and 2020 at a Scripps Health hospital. The final study sample (N = 205) included patients with isolated pulmonary metastasis (IL), isolated liver metastasis or synchronous liver and lung metastasis (LL), or metastasis to any site other than the liver or lung (NLL). Primary endpoint was overall survival (OS). Progression‐free survival (PFS) and recurrence‐free survival (RFS) were analyzed as secondary endpoints. Each survival outcome was analyzed using Cox proportional hazards tests. Results No statistically significant differences were seen between the three groups in OS, PFS, or RFS. Median OS for the IL group was 561 days, 341 days for the LL group, and 441 days for the NLL group. Median RFS was 748 days for the IL group, 574 days for the LL group, and 545 days for the NLL group. Median PFS was 307 for the IL group, 236 for the LL group, and 265 for the NLL group. When comparing only the IL and LL groups, a statistically significant difference in OS was seen favoring the IL group (HR1.59 LL vs IL [ref], CI 1.04–2.41, p = 0.031) Conclusion Though statistically significant differences in survival outcomes were not seen in our population, there was a trend toward improved survival for patients with isolated lung metastases. When comparing only the IL to LL group, statistically significant overall survival favoring the IL group was seen. These findings highlight a potential prognostic indicator of metastatic PDAC.

e16257 Background: Pancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous disease often diagnosed with synchronous metastatic disease involving the liver. Tumors with extra-abdominal spread that bypass the liver are thought to represent a unique molecular subgroup of the disease. Specifically, those with isolated pulmonary metastatic disease are thought to have a more favorable clinical phenotype. We sought to retrospectively investigate whether patients with isolated pulmonary metastases had improved survival compared to those with disease involving the liver. Methods: We conducted a retrospective review of patients with pathologically confirmed PDAC treated between the years 2010 and 2020 at a Scripps Health hospital. The final study sample included only patients with pulmonary and/or liver primary metastases (N = 175). Analyses were conducted on subgroups defined by metastatic sites of disease in the liver only, lung only and combined liver+lung. Primary and secondary outcome analyses compared isolated lung versus liver/liver+lung. Primary endpoint was overall survival (OS), defined as from the date of diagnosis to date of death or most recent follow up. Progression free survival (PFS) was also analyzed as a secondary endpoint and defined as from the date of diagnosis to date of radiographic progression. Each survival outcome was analyzed using Cox Proportional Hazards tests. Results: No statistically significant differences were seen in OS (HR 0.67, CI 0.44–1.03; p= 0.069) or PFS (HR 1.05, CI 0.68–1.65; p= 0.816) between patients with primary lung metastases compared to those with either liver or liver+lung metastases (reported as hazard ratios of liver/liver+lung relative to lung only). However, a trend towards improved OS was seen for patients with isolated lung metastasis and the kaplan-meier curve for OS showed improved survival for these patients at 3 years, with crossing of the survival curves around 5 years from time of diagnosis. Conclusions: There appears to be a unique clinical phenotype in patients with PDAC presenting with isolated pulmonary disease. Though there was not a statistically significant difference in OS and PFS seen in our population, there was a trend towards improved overall survival compared to those with hepatic involvement. These findings highlight a potential prognostic indicator of metastatic PDAC and further subgroup analysis will help characterize clinical variations that may lead to these differences in tumor biology.[Table: see text]