Medline: 8503017

Seminars in Oncology 20(3): 206-228, 1993.

Pathological evaluation of neoplasms with unknown primary tumor site.

Mackay B, Ordonez NG

Abstract:

Occult primary malignancies represents the eighth most common cancer in the US, but actual incidence may be higher because of a tendency to ascribe a 'best guess' diagnosis without sold proof. Discovery of a metastatic tumor of unknown site of origin leads to a search for the primary involving clinician, radiologist and pathologist. Even at autopsy 16% of primaries may remain unidentified, possibly because they had regressed or are too small to be observed. Imaging studies without definitive focal signs to guide them may be time-consuming, costly and unrewarding. The most cost effective course is to use the extent of metastatic disease, histology of the specimen, and patient performance status as the basis for assignment to treatable subsets. Most adult metastatic tumors are carcinomas, with adenocarcinomas comprising around 50% or more. The most frequent sites are cervical lymph nodes, liver, bones and supraclavicular lymph nodes. Implications of site for potential diagnostic possibilities are discussed for metastatic disease in the head and neck region, brain, axilla, effusions, lung, liver, lymph nodes and bone marrow. Problems of delay in fixing and examining tissue, and the special procedures for dealing with fine needle biopsy specimens are discussed. Light microscopic examination is always the first step and has changed little in recent years. New markers are discussed at length under the headings: epithelial markers, including cytoskeletal proteins keratin and vimentin, epithelial membrane antigen B72.3 Mab, and carcinoembryonic antigen (CEA); neuroendocrine markers, neuron-specific enolase, chromogranins, synaptophysin, neurofilaments, and CD57 antigen; melanoma markers S-100 and HMB-45; soft tissue markers, including myoglobin, beta-enolase, desmin, creatinine phosphokinase-MM, actin, protein Z, fast, slow and heavy-chain myosins, and titin for rhabdomyosarcoma, von Willebrand's factor (FVIII:RAg) and thrombomodulin for angiosarcomas, and CD34 and FVIII:RAg for Kaposi's sarcoma; hematopoietic markers such as L26, MB1 and LN2 for B-cell lymphomas, CD30 (Ki-1) for Hodgkin's disease, and alpha-1-antitrypsin and alpha-1-antichymotrypsin for histiocyte-derived tumors; and genitourinary tumor markers like alpha-fetoprotein and beta-human chorionic gonadotropin for germ cell tumors, PSA for prostate cancer, and URO-2, -3 and -4 for renal cell carcinoma. Electron microscopy has great value, generally for confirmation of tentative diagnoses made by light microscopy, but is only briefly discussed. (251 Refs.)


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