Trial Information

Carcinoma of unknown primary (CUP) is defined as biopsy-proven metastasis of an epithelial
malignancy in the absence of an identifiable primary site after complete history and
physical examination, basic laboratory studies, chest X-ray and additional directed studies
indicated by positive findings during the initial work-up. It is characterized by its slow
local development and its high metastatic potential.1,2 Patients with CUP represent 4–10% of
all new cancer patients.3,4 The presenting sites of metastasis identified pathologically,
radiographically or by physical examination were found most frequently in the lymph nodes
(37.1%), followed by the liver, bone, lung, pleura/pleural space, brain, peritoneum, adrenal
and skin. Of the lymph nodes of metastasis, the supraclavicular cervical area is the leading
site (31.3%), followed by the mediastinum, axilla, retroperitonium, and inguina.5 The
incidence of metastatic cervical CUP (MCCUP) varies between 2% and 9% of all head and neck
cancers.6-8 The level of cervical metastatic involvement may give some clue as to the likely
primary site. A submandibular mass (level I) would most commonly be related to a primary in
the oral cavity or skin. Level II nodes, including the jugulodigastric node, may point to a
primary in the oral cavity, oropharynx, or supraglottic larynx. Tumours of the nasopharynx
generally spread to level II or the posterior triangle, as well as retropharyngeal nodes.
Middle and lower jugular nodes (levels III and IV) are more likely related to a laryngeal or
hypopharyngeal cancer. Metastatic disease restricted to the supraclavicular region is often
due to an infraclavicular primary site.9 The prognosis is different according to the
involved lymph node level and possible primary site. Modern cancer management relies heavily
on recognition of the primary tumor; thus the absence of a primary site poses major
diagnostic and therapeutic problems. The patient benefits from identification of the initial
tumor site because postoperative irradiation ports may be reduced and because surveillance
for recurrence may be improved.10 In order to identify the likely primary site of MCCUP and
compare the prognoses of known and unknown primary groups, we report the results according
to the different levels of metastatic cervical lymph nodes.