title: A case of S-100 negative melanoma: A diagnostic pitfall in the workup of a poorly differentiated metastatic tumor of unknown origin.
abstract: When confronted with a metastatic poorly differentiated tumor of unknown origin, the initial workup includes the standard panel of immunostains to rule out carcinoma, sarcoma, lymphoma, and the greatest mimicker in pathology - malignant melanoma. Although not specific, the S-100 protein is expressed in over 95% of malignant melanomas. Herein, we present a case of multiorgan metastatic malignancy with a dominant hilar and mediastinal mass in a current smoker; clinically, highly suggestive of widespread primary lung cancer. This case was eventually classified as malignant melanoma, despite a significant diagnostic challenge due to lack of prior history, unusual cytomorphology, and S-100 protein negativity. A battery of immunostains was performed and the addition of other melanocytic-associated markers confirmed the melanocytic lineage of the neoplasm. This case highlights the pitfalls in the differential diagnosis of a metastatic tumor of unknown origin by fine needle aspiration cytology due to the significant morphologic overlap of poorly differentiated malignancies. We emphasize that, albeit rare, malignant melanomas can be completely negative for S-100 protein and the use of additional melanocytic-associated markers in the differential workup maybe critical in arriving promptly at a proper diagnosis. We also briefly discuss other currently available immunohistochemical markers that can assist in the identification of the S-100 negative melanoma.
authors.affiliation: Address: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon.
authors.forename: Anna
authors.initials: A
authors.lastname: Biernacka
authors.affiliation: Address: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon; Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Konstantinos D
authors.initials: KD
authors.lastname: Linos
authors.affiliation: Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Department of Pulmonary Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon.
authors.forename: Peter A
authors.initials: PA
authors.lastname: DeLong
authors.affiliation: Address: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon; Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
authors.affiliation: Address: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon; Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Padmanabhan
authors.affiliation: Address: Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon; Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
keywords: Malignant melanoma; S-100; melanocytic-associated markers; poorly differentiated metastatic tumor of unknown origin