Table 2:

Broad Tumor Classes with Associated Screening Markers

Broad Tumor Class	Screening Markers	When to Consider	Confirmatory Markers
Carcinoma	Broad-spectrum keratin (e.g., AE1/AE3, OSCAR); EMA, EpCAM (i.e., MOC-31, Ber-EP4), Claudin-4	Always	See additional sections of this review
Hematolymphoid	CD45	Always; “triple-negative” neoplasm	CD45-negative lymphoma: panel to include CD43, CD79a, MUM1, ALK, CD30
Melanoma	SOX10 or S-100	Always	Melan A, HMB-45, tyrosinase
Sarcoma	None	Spindle cell morphology; tumor in mediastinum, retroperitoneum, or somatic soft tissue	Unclassified malignant neoplasm in the mediastinum, retroperitoneum, paratestis: MDM2/CDK4 (dedifferentiated liposarcoma) Epithelioid neoplasm defying typing: ERG (angiosarcoma), INI1 (epithelioid sarcoma)
Germ cell	SALL4 or PLAP	Tumor in the mediastinum, retroperitoneum, or gonads; “triple-negative” neoplasm; keratin-positive neoplasm defying typing/site of origin assignment	Seminoma: OCT4, KIT, D2-40 Embryonal carcinoma: OCT4, CD30 Yolk sac tumor: AFP, glypican-3 Trophoblastic tumors: β-HCG, GATA-3, inhibin, PD-L1
Mesothelioma	None (diagnostic consideration in keratin-positive tumors)	Tumor in the pleura or peritoneum	Diagnostic markers: calretinin, WT-1, D2-40, CK5/6, BAP1 (loss)
Pheochromocytoma/paraganglioma	None	Epithelioid morphology; “triple-negative” malignant neoplasm; general neuroendocrine marker-expressing tumor defying site of origin assignment	GATA-3, PHOX2B, tyrosine hydroxylase