Definition of Carcinoma of Unknown Primary (CUP):
- No obvious identifiable primary site, despite a careful clinical history, physical examination, radiologic imaging, and biochemical or histologic investigations.
- Immunohistochemistry plays a vital role in diagnosis and classification of CUP lesions.
- Most common cases of CUPs --> carcinoma.
- Adenocarcinoma accounts for ~70% cases of CUPS.
- Poorly differentiated carcinoma: 15-20%
- Squamous cell carcinoma 5%
- Neuroendocrine carcinoma 5%
Steps:
1. To find the line of differentiation - lineage markers --> keratins (Pancytokeratin/ CAM 5.2), lymphoid (LCA), melanoma (S100), germ cell (OCT 3/4), and sarcoma markers (Vimentin).
2. To determine the type of CK distribution in the tumor cells - some subsets of CKs are seen in certain tumours.
3. To see if there is coexpression of vimentin.
4. To see if there is expression of supplemental antigens of epithelial or germ cell derivation, that
is, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), or placental alkaline
phosphatase (PLAP).
5. Finally look for expression of cell-specific products, cell-specific structures, and transcription
factors or receptors that are unique identifiers of cell types.
Ref: Dabb's Diagnostic immunohistochemistry
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