Diagnosing carcinoma origin in ultrasound-guided needle biopsies: a context-driven approach anchored in site-specific immunohistochemical markers

BACKGROUND: In small-biopsy carcinomas, tumor-origin assignment often relies on limited tissue, clinical-radiologic context, morphology, and immunohistochemistry. Although site-specific markers are widely used to support tumor-origin assignment, how often such assignment is supported by site-specific-marker-anchored IHC without CK7/CK20 dependence in context-rich, non-CUP/MUO small-biopsy cohorts has been less explicitly addressed. We therefore audited selected small-biopsy carcinomas with a single-site origin assigned at sign-out, to assess how often tumor-origin assignment was supported by site-specific-marker-anchored IHC without CK7/CK20 dependence. METHODS: We reviewed 154 consecutive small biopsies with IHC and analyzed the selected subset of carcinomas in which a single-site origin had been assigned at sign-out. We retrospectively audited the IHC markers used to support tumor-origin assignment, assessing IHC panel sufficiency, site-specific-marker-anchored support without CK7/CK20 dependence, and CK7/CK20 application, theoretical need, and incremental contribution. RESULTS: The selected analytic cohort included 60 carcinomas: 13 primary tumors, 43 metastases, and 4 malignancies of unknown origin submissions. Tumor origin was assigned as breast in 25% (15/60), colorectal in 20% (12/60), lung in 18% (11/60), and liver/hepatocellular carcinoma in 17% (10/60); other origins accounted for 20% (12/60). Overall diagnostic IHC sufficiency was achieved in 95% (57/60). Site-specific markers were applied in all cases. A site-specific-marker-anchored IHC approach was sufficient for tumor-origin assignment in 93% (56/60) of cases. CK7/CK20 was performed in 48% (29/60) of cases, was retrospectively considered theoretically needed in 12% (7/60), and was contributive to final tumor-origin assignment in 2% (1/60). CONCLUSIONS: In this selected, context-rich, non-CUP/MUO small-biopsy cohort, tumor-origin assignment was supported in most cases (56/60, 93%) by site-specific-marker-anchored IHC without CK7/CK20 dependence; CK7/CK20 was selectively needed but showed limited incremental contribution beyond morphology, clinical/imaging context, and site-specific markers. This approach may have practical relevance for tissue-conscious IHC marker selection in small-biopsy workflows, alongside established pre-analytic standards. Further studies are warranted to confirm these findings, assess generalizability in broader biopsy settings, and evaluate diagnostic accuracy against external reference standards.