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.

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For decades students have struggled to understand the complexities of acid‐base balance. Facts must be learned, but more importantly concepts must be mastered. To complicate this issue, the student must appreciate the interactions between respiratory physiology, renal physiology, and the complexities involved in acid dissociation and buffering capability. The Davenport diagram provides a graphic representation of the Henderson‐Hasselbalch equation giving students a visual tool useful in understanding these complex interactions. One of the least understood components of this graph is the buffer line. The slope of the buffer line is determined by the amount of fixed buffers in the body which can decrease the extent to which new hydrogen ions alter pH. A rapid decrease in ventilation adds additional CO2 and produces acute respiratory acidosis. As can be seen on the ordinate of the Davenport diagram, the bicarbonate ion concentration can easily increase 3–4mEq/l. As this occurs, an equal amount of hydrogen ion is also produced. If it was not for the presence of fixed buffers, this would result in plasma pH≈3. The current teaching approach employs the van't Hoff Equation and the accepted rate of CO2 production in a normal individual. Using these values, it can be demonstrated that the amount of bicarbonate ions produced by reduced respiration is capable of increasing plasma bicarbonate ion by 3–4 mEq/l in several minutes. This increase in bicarbonate is independent of renal function.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.