Improving survival in metastatic carcinoma of unknown origin Malcolm L. Brigden, MD Nevin Murray , MD PREVIEW When the primary tumor site cannot be identified in patients with metasta - tic carcinoma, the survival rate is discouragingly low. In such cases , recog - nition of subgroups of patients who have a better chance of long-term sur- vival is critical. In this article , Drs Brigden and Murray present a detailed approach to diagnosis and management. M etastatic carcinoma fr om an unknown primary site has acquired the follow- ing definition: histologically docume nted cancer with no pri- mary site appare nt after ( 1) care- ful clinical history taking and (2) ph ys ical examination that includes pelvic and rectal inspec- tion and c hest fi lms. 1 " 3 This cir- cumstance accounts for about 3% to 5% of all newly diagnos ed cancers in North Amer ica. Me- dian survival time is less than 6 mo nths, and 85% of pa tients are dead within a year 2 (figure 1 ). However, 5% to 10% of pa tients may be lon g- term survivors. 3 Despite dismal survival stati s- tics for these patie nts taken as a whole, recent studies have em- ph as i zed that metastatic carci- noma of unknown ori gin repre- se nts a heterogeneous group of clinical prese ntations with vary - ing prog noses. The strategy that has evolved is to individualize treatme nt op tions by a tte mpting to id ent ify subgroups of patients who may benefit from different types of therapy that have proved effective (table 1). Pathologic diagnosis Direct communication with a pathologist is essential in the manageme nt of patie nts with metastatic carcinoma from an unknown primary site. Fine- needle aspiration biopsies are inadequate for appropriate patho- logic examination; indeed, the common es t reason for a nonspe- cific pa th ologic diagn os is is a sma ll , inadequate bi opsy. The use of monoclonal antibody tech- niqu es on paraffin-embedded tiss ue can unequivocally confirm th e diagnos is of lymphoma, sar- coma, neuroendocrine tumors, germ ce ll tumors, melanoma, and o ther lesions. Howeve r, in up to 30% of cases, the results of spe- VOL 105 I NO 5 I MAY 1, 1999 I POSTGRADUATE MEDICI NE I METASTATIC CANCER cial staining may be inconclusive. 4 Available cytogenetic studies may be helpful. For instance, an abnorma li ty of chromosome 12 h as rece ntly been a consiste nt finding in poorly differe nti ated germ cell tumors. 5 Pathologic review separates va ri ous subtyp es of carcinoma of unknown origin. These subtypes include adenocarcinoma ( 60%), undifferentiated or poorly differ- e ntiated carcinomas (30%), squa- mous cell carcinoma (6 %), and neuroendocrine tumors (2%). 6 Well-differentiated adenocarci- noma from an unknown primary site mos t often occurs in li ver, lung, or bone, whereas squamous cell carcinoma from an unknown primary site is almost always found in cervi ca l, supraclavicular, or inguinal lymph node s. For pa- tients with we ll-differe nti ated adenocarcinoma or squamous cell carcinoma, consideration of the clinical setting and judicious use of immunocytochemical tech- niqu es may help identify a treat- able cancer. 4 Neuroendocrine tumors are a diverse group that includes carci- noid tumors, islet cell tumors, neuroblastoma, small-ce ll carci- noma of the lung, and extrapul- monary sma ll -ce ll carcinoma. 7 continued 63