BIOPSY AND PATHOLOGIC EVALUATION
Diagnosis of metastatic cancer
The initial clinical and pathologic evaluations should focus on identifying a primary site, when possible, and on identifying patients for whom specific treatment is indicated.
Biopsy and Pathologic Evaluation
The diagnosis of metastatic cancer should be confirmed by biopsy of the most accessible metastatic lesion. A fine-needle aspiration is usually sufficient to confirm the diagnosis of metastatic cancer but does not provide adequate material for optimum pathologic evaluation. Therefore, a larger biopsy (surgical or core needle) should be performed if technically feasible.
The initial light microscopic evaluation identifies adenocarcinoma in approximately 60% of patients with cancer of unknown primary site. Other diagnoses obtained by initial light microscopy include poorly differentiated carcinoma (25%), squamous carcinoma (10%), and poorly differentiated neoplasm (inability to distinguish among carcinoma, lymphoma, melanoma, and sarcoma; 5%).
Additional pathologic evaluation is essential in all poorly differentiated tumours. Immunochemical (IHC) stains can usually identify the tumour lineage (e.g., carcinoma vs. lymphoma vs. sarcoma) when the histologic diagnosis is “poorly differentiated neoplasm.” Because more than 50% of these patients have lymphoma, this distinction is important. When the histologic diagnosis is “poorly differentiated carcinoma,” IHC staining sometimes identifies germ cell tumours or neuroendocrine carcinoma.
In patients with adenocarcinoma, it is seldom possible for the pathologist to determine a primary site by light microscopic examination of histology. IHC stains can narrow the diagnostic spectrum, particularly when interpreted in conjunction with clinical features. In several situations, IHC stains are quite specific, including prostate-specific antigen (PSA) for prostate cancer, oestrogen and progesterone receptors for breast cancer, and leukocyte common antigen for non-Hodgkin lymphoma. Other diagnoses suggested by immunoperoxidase staining include neuroendocrine carcinomas, melanomas, and sarcomas.
Occasionally, electron microscopy or analysis for tumour-specific chromosomal abnormalities (i12p in germ cell tumours; t11:22 in Ewing tumour; immunoglobulin gene rearrangements in non-Hodgkin lymphoma) are useful in the evaluation of poorly differentiated tumours if results of other pathologic studies are inconclusive.
Molecular tumour profiling is a new diagnostic method that is in the process of changing the management of patients with cancer of unknown primary origin. Gene expression profiles differ in various normal body tissues, and most cancers retain expression profiles specific to their tissue of origin. Molecular profiling assays can correctly predict the tissue of origin in 85% to 90% of metastatic cancers by detecting tissue-specific gene expression patterns. Although the accuracy of the profiling predictions is more difficult to quantitate in patients with cancer of unknown primary origin (because most primaries never become manifest), current evidence indicates a similar high accuracy rate. Therefore, molecular tumour profiling is a valuable addition to the pathologic evaluation, and is indicated when histologic examination and IHC do not identify a tissue of origin.