Chianchetti, 2009

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The Laryngoscope
VC 2009 The American Laryngological,
Rhinological and Otological Society, Inc.
Diagnostic Evaluation of Squamous Cell
Carcinoma Metastatic to Cervical Lymph
Nodes From an Unknown Head and Neck
Primary Site
Marco Cianchetti, MD; Anthony A. Mancuso, MD; Robert J. Amdur, MD; John W. Werning, MD;
Jessica Kirwan, MA; Christopher G. Morris, MS; William M. Mendenhall, MD
Objectives/Hypothesis: To discuss our experi-
ence with the diagnostic evaluation in patients with
squamous cell carcinomas (SCCAs) of the head and
neck metastatic to the cervical lymph nodes from an
unknown primary site.
Methods: Between June 1983 and December
2008, 236 patients were evaluated with lymph node
biopsy, computed tomography (CT), and/or magnetic
resonance imaging (MRI) of the head and neck, and
panendoscopy with directed biopsies. Additional
studies included fluorodeoxyglucose–single photon
emission computed tomography (FDG-SPECT) in 26
patients and FDG-positron emission tomography
(FDG-PET) or FDG-PET/CT in 21 patients. Seventy-
nine patients underwent an ipsilateral (72) or bilat-
eral (seven) tonsillectomy.
Results: An occult primary site was detected in
126 patients (53.4%); six patients had two synchro-
nous primary cancers. The most common primary
sites were in the tonsillar fossa (59 patients; 44.7%)
and the base of tongue (58 patients; 43.9%). The pri-
mary site was found in 21 (29.2%) of the 72 patients
with no suspicious findings on physical exam and/or
radiographic evaluation compared with 105 (64.0%) of
164 remaining patients. Tonsillectomy revealed the
primary cancer in 35 (44.3%) of 79 patients. FDG-
SPECT and FDG-PET or FDG-PET/CT was the sole
method of primary site detection in only one patient
(2.1%) of 47 patients.
Conclusions: Diagnostic evaluation should
include a thorough physical examination, CT and/or
MRI of the head and neck, and panendoscopy with
directed biopsies. Unilateral or bilateral tonsillectomy
should be performed on patients with adequate
lymphoid tonsillar tissue. FDG-PET or FDG-PET/CT
should be considered for those with indeterminate
findings on physical examination and/or head and
neck CT and/or MRI if those sites are located outside
of the oropharynx.
Key Words: Diagnosis, squamous cell
carcinoma, lymph node metastasis, head and neck
cancer, unknown primary.
Laryngoscope, 119:2348–2354, 2009
INTRODUCTION
Head and neck cancer patients frequently present
with cervical lymph node metastases. Despite an
adequate diagnostic work-up, the primary tumor cannot
be detected in approximately 2% to 3% of patients.1
Patients are usually males in their 50s.2,3
There are several explanations for a cervical metas-
tasis in the absence of a primary tumor. Small tumors in
particular areas, such as the tonsillar fossa or the base
of tongue, can be easily missed, both on physical and ra-
diographic exams, due to the anatomical complexity of
the region and to the intrinsic limitations of the diagnos-
tic techniques. A small tumor hidden in the crypts of the
lymphoid tissue of the tonsillar fossa and base of tongue
can acquire an early metastatic phenotype and spread
to the regional lymph nodes while remaining
undetectable.4,5
However, there is no general consensus on what
should be included in an optimal diagnostic evaluation.
Thus, we retrospectively reviewed our experience with
patients with cervical lymph node metastases for whom
a conventional work-up (i.e., history, physical exam,
computed tomography [CT] and/or magnetic resonance
imaging [MRI] of the head and neck area) failed to iden-
tify a primary site. The aim of this study was to
evaluate the role and usefulness of panendoscopy,
From the Department of Radiation Oncology (M.C., R.J.A., J.K., C.G.M.,
W.M.M.); the Department of Radiology (A.A.M.), and the Department of
Otolaryngology (J.W.W.), University of Florida College of Medicine,
Gainesville, Florida, U.S.A.
Editor’s Note: This Manuscript was accepted for publication June
17, 2009.
Send correspondence to William M. Mendenhall, MD, 2000 SW
Archer Rd., PO Box 100385, Gainesville, FL 32610-0385. E-mail:
mendwm@shands.ufl.edu
DOI: 10.1002/lary.20638
Laryngoscope 119: December 2009 Cianchetti et al.: SCCA Metastases From Unknown Primary Site
2348
tonsillectomy, and metabolic studies, such as fluorodeo-
xyglucose (FDG)-single photon emission computed
tomography (SPECT), FDG-positron emission tomogra-
phy (PET), and PET/CT, as well as describe the
detection rate and most frequent sites of the detected
primary lesions.
MATERIALS AND METHODS
The weekly Head and Neck Conference notes from June
1983 through December 2008 were reviewed to identify patients
who presented with metastatic cervical adenopathy and an
unknown primary site. All patients included in this study had
squamous cell carcinomas (SCCAs) and an upper neck presenta-
tion with the bulk of the metastatic adenopathy in level 2 and/
or level 3. Patients presenting with the bulk of the disease in
the low neck, where it was thought that the primary lesion was
likely below the clavicles, were excluded. Metastases located in
the parotid tail lymph nodes usually originate from cutaneous
SCCAs and were also excluded. Other exclusion criteria were
the following: primary diagnosed before referral to our institu-
tion, primary site detected on physical examination at the
University of Florida, inadequate diagnostic evaluation, cervical
adenopathy secondary to a previously diagnosed primary can-
cer, and prior treatment. For the same period, we searched our
electronic database for patients with T1–T2 SCCAs of the oral
cavity, oropharynx, nasopharynx, hypopharynx, and larynx. All
the charts were then evaluated to detect if the patients had
been referred as an unknown primary SCCA to our institution,
and thus to see if they were eligible for enrollment. All patients
treated for SCCAs from an unknown primary site in the head
and neck were also included.
Patients were enrolled if the diagnostic work-up at the
University of Florida failed to identify a primary tumor. The
conventional work-up included: a complete history and physical
examination, including a head and neck examination by multi-
ple examiners, chest radiography, and CT and/or MRI. Select
patients underwent FDG-SPECT or, in more recent years FDG-
PET, to clarify questionable findings on CT and/or MRI. An
FDG-PET and/or chest CT was also used to detect distant me-
tastases thought to be at high risk, such as those with N3 neck
disease extending below the level of the thyroid notch.
Following the diagnostic evaluation, all patients under-
went panendoscopy with directed biopsies. Patients with
adequate lymphoid tissue in the tonsillar region usually under-
went a unilateral or bilateral tonsillectomy at the discretion of
the attending otolaryngologist.
Two hundred thirty-six patients were deemed eligible for
the analysis. Mean age was 59 years (range, 25–92 years).
Nodal stage according to the American Joint Committee on
Cancer6 is depicted in Table I. Distant pulmonary metastases at
diagnosis were found in two patients (1%) on chest radiography.
Lymph node biopsy procedures included: fine needle aspi-
ration (FNA), 172 patients; incisional biopsy, 24 patients;
excisional biopsy, 70 patients; core needle biopsy, 18 patients;
and neck dissection, one patient. Seven additional patients did
not undergo a procedure to obtain tissue from the metastatic
node and had a histologic diagnosis made at the time of direct
laryngoscopy. Generally, the first attempt was made with FNA;
if this proved to be negative, patients then underwent a core
needle biopsy or an excisional biopsy followed by a neck dissec-
tion if the node was solitary and proved to be pathologically
positive. Incisional biopsies were avoided and usually performed
prior to referral to our institution.7
All patients were evaluated at the Head and Neck Tumor
Conference at the University of Florida by a panel of specialists
including otolaryngologists, radiation oncologists, medical on-
cologists,maxillofacial surgeons, diagnostic radiologists,
pathologists, speech and swallow pathologists, and dental
oncologists.
A complete physical examination, including mirror and fi-
beroptic examination, was performed on the day of the
consultation in addition to that already done by the single refer-
ring department. The presence of a suggestive, but not
definitive, finding of a possible primary site was recorded.
Radiographic examinations performed by outside institu-
tions were reviewed by the diagnostic radiologist and, if deemed
to be of good quality, were accepted. Otherwise they were
repeated. The radiographic exams that were performed are out-
lined in Table II. A CT scan was obtained significantly more
often than an MRI, reflecting our institutional bias that the for-
mer is more useful to detect an occult primary SCCA. The
presence of a suspicious but not definitive finding of a primary
site on CT and/or MRI was recorded. Patients with negative
biopsies on panendoscopy were sometimes taken back for a sec-
ond and, rarely, a third panendoscopy if findings on the
diagnostic evaluation suggested that a primary site might be
found (Table II).
At least one panendoscopy with biopsies of suspicious
areas and/or a tonsillectomy was performed in all patients. One
panendoscopy and/or a direct laryngoscopy was performed in
170 patients (72.0%); two in 62 patients (26.3%); and three in
TABLE I.
Patient Characteristics.
Characteristic No. of Patients, N¼236 (%)
Sex
Male 205 (85)
Female 31 (13)
Nodal Staging
N1 29 (12.3)
N2a 54 (22.9)
N2b 70 (29.7)
N2c 22 (9.3)
N3 55 (21.2)
Nx 6 (2.5)
TABLE II.
Diagnostic Evaluation.
No. of Patients (%)
CT 227 (96.2)
MRI 27 (11.4)
FDG-SPECT 26 (11.1)
FDG-PET or PET/CT 21 (8.9)
Tonsillectomy
Unilateral 72 (30.5)
Bilateral 7 (3)
Panendoscopy and/or direct laryngoscopy
One 170 (72.0)
Two 62 (26.3)
Three 4 (1.7)
CT ¼ computed tomography; MRI ¼ magnetic resonance imaging;
FDG-SPECT ¼ fluorodeoxyglucose-single photon emission computed to-
mography; FDG-PET ¼ fluorodeoxyglucose-positron emission tomography.
Laryngoscope 119: December 2009 Cianchetti et al.: SCCA Metastases From Unknown Primary Site
2349
four patients (1.7%). These figures include procedures per-
formed at outside institutions. The initial policy, for patients
evaluated up to 1997, was not to repeat an outside panendo-
scopy unless it was thought to be suboptimal or did not sample
suspicious areas. After 1997, patients who did not undergo pan-
endoscopy at the University of Florida were not included in the
study. An ipsilateral tonsillectomy was performed in 72 patients
(30.5%); a bilateral tonsillectomy was performed in seven
patients (3.0%).
Patients were stratified into four groups according to the
findings on physical and radiographic (CT and/or MRI) exams.
The first group included patients with no evidence of a primary
site on physical exam and radiographic evaluation (PEØ/
RADØ). The second group of patients was those with suspicious,
but not definitively positive, findings on physical exam, but not
on radiographic exams (PEþ/RADØ). The third group of
patients were those with suspicious, but not definitively posi-
tive, findings on radiological exams, but not on physical exam
(PEØ/RADþ). The fourth group of patients were those with sus-
picious, but not definitively positive, findings both on physical
and radiographic exams (PEþ/RADþ).
SAS and JMP software provided statistical analysis (SAS
Institute, Cary, NC). A multivariate analysis (MVA) via logistic
regression was performed with the endpoint being detection of
the primary site. The following variables were included in the
MVA: suggestive findings on physical examination, suggestive
findings on CT and/or MRI, suggestive findings on FDG-SPECT,
suggestive findings on FDG-PET or FDG-PET/CT, number of
panendoscopies and/or direct laryngoscopies (1 versus �2), and
tonsillectomy (performed or not performed).
RESULTS
Detection Rate and Primary Site Localization
A primary lesion was identified in 126 patients
(53.4%), with six patients having two synchronous pri-
maries for a total of 132 lesions (Fig. 1). The most
common locations were the tonsillar fossa (44.7%) and
the base of tongue (43.9%) (Table II). Synchronous pri-
mary lesions included: left base of tongue and left
pyriform sinus (one patient), left pyriform sinus and left
tonsillar fossa (one patient), right and left base of tongue
(two patients), right and left tonsillar fossae (one
patient), right tonsillar fossa and left base of tongue (one
patient).
The relationship between patient group and the
likelihood of detecting the primary site is shown in Table
III. The likelihood of primary site detection was signifi-
cantly lower for patients without any evidence of a
primary site on physical exam or radiological exam
(29.2%), when compared to the second (PEØ/RADþ) and
third (PEþ/RADØ) group considered together (61.7%; P
identified in
five cases, three of which had a biopsy-proven primary
site. No primary site was identified in 16 cases; a bi-
opsy-proven primary site was detected in 11 of 16 cases
at panendoscopy. No patient had a biopsy-proven pri-
mary site detected only on FDG-PET or FDG-PET/CT.
Sensitivity was 21.4% (3/14), and specificity was 71.4%
(5/7). The MVA for primary detection revealed that
FDG-PET and FDG-PET/CT did not significantly impact
this endpoint.
Tonsillectomy
The impact of a tonsillectomy on detection of the
primary site is shown in Table VI. One patient was
found to have bilateral tonsillar fossae cancers. There
was no significant difference between the two groups (P
¼ .8921). The MVA revealed that tonsillectomy did not
significantly impact the probability of primary site
detection.
DISCUSSION
Detection Rate and Primary Site Localization
Our data show that the tonsillar fossa and base of
tongue are by far the most common sites found to harbor
an occult tumor. Our experience is likely influenced by
the availability of fiberoptic endoscopy and advances in
diagnostic radiology, such as CT and MRI, which were
available throughout our study period.8 Prior to 1983, it
was more difficult to identify the primary site in some
locations, such as the nasopharynx and hypopharynx.8,9
Additionally, it is likely that, if our study had been con-
ducted in an area where nasopharyngeal carcinoma was
endemic, the incidence of occult nasopharyngeal cancers
would have been higher. Issing and colleagues3 reviewed
their experience for 167 patients evaluated from an
unknown primary cancer from 1979 to 1998. The pri-
mary site was subsequently discovered in 36 (21.5%) of
the 167 patients. The most frequent locations were: ton-
sil, seven patients (19.4%); pyriform sinus, six patients
(16.7%); base of tongue, five patients (13.9%); nasophar-
ynx, four patients (11.1%); and supraglottic larynx, four
patients (11.1%).
CT and/or MR
Muraki et al.10 reported the data from the Univer-
sity of Utah where they found a primary tumor in four
(31%) of 13 patients studied with CT. All of our patients
underwent a CT and/or MRI. Patients with suspicious
findings on a physical exam and/or CT and/or MRI had a
higher probability of primary site detection than those
without suspicious findings. The majority of patients
with suspicious findings had suspicious findings on CT
and/or MRI, primarily the former, rather than on physi-
cal exam. Thus, CT prior to panendoscopy likely
significantly increased the probability of detecting the
primary site.
Tonsillectomy
The tonsillar fossa is often found to harbor occult
primary cancers metastatic to the cervical lymph nodes.
In our series we found this location to be the most prob-
able primary site followed by the base of tongue. Based
on the published data, many authors recommend that
an ipsilateral2,11,12 or bilateral13–15 tonsillectomy be per-
formed as part of the standard diagnostic evaluation for
patients with a head and neck unknown primary tumor.
Righi and Soffermann12 reported on 19 patients
who underwent an ipsilateral tonsillectomy after a thor-
ough physical examination, chest radiography, and CT
scan of the head and neck region; six (32%) of 19 patients
were found to have an occult primary site in the tonsil.
Lapeyre et al.2 evaluated 87 patients between 1969
and 1992; an ipsilateral tonsillectomy was performed as
a part of the diagnostic evaluation. The primary site was
found in the tonsil in 23 (26%) of 87 patients.
TABLE V.
Detection of the Primary Pite by FDG-PET or FDG-PET/CT.
Patient Group
FDG-PET
Negative;
No. Primary
Detected/No.
Patients (%)
FDG-PET
Positive;
No. Primary
Detected/No.
Patients (%)
PEØ/RADØ 3/4 No data
PEþ and/or RADþ 8/12 3/5
Total 11/16 (68.8) 3/5 (60)
FDG-PET ¼ fluorodeoxyglucose-positron emission tomography; CT
¼ computed tomography; PEØ ¼ physical exam negative; RADØ ¼ radio-
logical exam negative; PEþ ¼ physical exam suspicious, not definitively
positive; RADþ ¼ radiological exams (computed tomography and/or mag-
netic resonance imaging) suspicious, not definitively positive.
TABLE VI.
Detection of the Primary Site on Tonsillectomy.
Patient Group
No. of Patients With
Pathologically Proven Site in
Tonsillar Fossa/No. Patients
Having Tonsillectomy (%)
PEØ/RADØ* 9/22 (41.1)
PEþ and/or RADþ* 26/57 (45.6)
Total 35/79 (44.3)
*Radiographic evaluation ¼ computed tomography (CT) and/mag-
netic resonance imaging with or without fluorodeoxyglucose-single photon
emission computed tomography or fluorodeoxyglucose-positron emission
tomography (FDG-PET) or FDG-PET/CT.
PEØ ¼ physical exam negative; RADØ ¼ radiological exam negative;
PEþ ¼ physical exam suspicious, not definitively positive; RADþ ¼ radio-
logical exams (computed tomography and/or magnetic resonance imaging)
suspicious, not definitively positive.
Laryngoscope 119: December 2009 Cianchetti et al.: SCCA Metastases From Unknown Primary Site
2351
McQuon et al.15 evaluated the efficacy of a routine
tonsillectomy in the diagnostic work-up of patients with
carcinoma from an unknown primary site. Thirty-seven
patients were subjected to panendoscopy after a com-
plete physical examination and radiological evaluation
revealed no clear evidence of a primary tumor. Thirty-
six of 37 patients had multiple biopsies; ipsilateral ton-
sillectomy was done in seven cases, and a bilateral
tonsillectomy was performed in 16 cases. Tonsillectomy
yielded a diagnosis of cancer in nine (39%) of 23 cases,
whereas none of the biopsies obtained from other sites
showed cancer. One patient with bilateral tonsillar carci-
nomas was identified. Remarkably, only 13% of the
tonsillar biopsies were positive for carcinoma, pointing
out the need for complete removal of the tonsillar tissue.
They concluded that routine bilateral tonsillectomy
should be performed in the work-up of these patients.
Koch et al.13 reported 41 patients who underwent
panendoscopy and biopsies, including a tonsillectomy,
between 1996 and 1999. Of these, 16 (39%) had cancer
of the tonsil; in two cases the tumor was located contra-
lateral to the metastatic lymph node, and in two others
the cancers were bilateral. Because four (9.8%) of
41 patients had a contralateral or bilateral cancer(s), the
authors recommended bilateral tonsillectomy for all
patients as part of the diagnostic evaluation for patients
with an unknown primary.
Kothari et al.14 performed a bilateral tonsillectomy
on 22 patients after a work-up, including MRI and FDG-
PET, failed to reveal MRI findings suggestive of a pri-
mary lesion. Bilateral tonsillar carcinomas were detected
in five patients (23%); three of them had FDG-PET find-
ings indicative of disease only on the same side of the
positive lymph node. The authors recommended that, if
there is no evidence of a primary site on physical and ra-
diographic exams, a bilateral tonsillectomy be performed
routinely.
FDG-PET and PET/CT
Dong et al.16 performed a meta-analysis of the liter-
ature to evaluate the diagnostic accuracy of FDG-PET
and FDG-PET/CT to detect the primary tumor in
patients presenting with an unknown primary site. A
total of 28 studies were found after researching various
electronic databases. Although their analysis included
all sites of disease, they obtained separate data from 13
studies for patients with cervical metastases. All of the
studies had to have a histologic diagnosis of a primary
site and/or adequate follow-up. They reported a pooled
sensitivity, specificity, and log diagnostic ratio, respec-
tively, of 0.81 (95% confidence interval [CI]: 0.73–0.88),
0.82 (95% CI: 0.76–0.87), and 3.11 (95% CI: 2.35–3.87).
The area (� standard error) under the symmetrical sum-
mary receiver-operating characteristic (SROC) curve, a
global measure of test accuracy,17,18 was 0.889 (�0.028).
The false-positive rate (false positives as a percentage of
all positive tests) was 28.6% for uptake in the base of
the tongue, which was higher than for all other sites,
including those outside of thehead and neck. FDG-PET
exhibited a lower sensitivity with respect to the tumors
in the base of the tongue and tonsil, 68.2 and 76.7%,
respectively. For the comparison between FDG-PET and
FDG-PET/CT, the authors confirmed data from previous
studies (including all primary sites) indicating that the
latter had a higher sensitivity and specificity. They ana-
lyzed seven studies of FDG-PET/CT that provided data
on the location of the primary site: tonsil 6.9%, base of
tongue 9.8%, and pharynx 13.7%. False-positive rates
were 41.6%, 16.7%, and 12.5%, respectively; and sensi-
tivities were 87.5%, 83.3%, and 87.5%, respectively.
Rusthoven et al.19 performed a literature review to
assess the role of FDG-PET in detecting the origin of
cervical metastases from unknown primaries. Sixteen
studies were identified and included data from 302
patients. The primary site was identified in 74 patients
(24.5%). The same detection rate was found when con-
sidering studies in which both CT and/or MRI and
panendoscopy were included in the conventional work-
up. Sensitivity, specificity, and accuracy rates were
88.3%, 74.9%, and 78.8%, respectively. The locations of
the primary sites were: below the clavicles, 27 patients
(24.3%); tonsils, 20 patients (18.0%); hypopharynx,
11 patients (9.9%); nasopharynx, eight patients (7.2%);
oropharynx, seven patients (6.3%); larynx, six patients
(5.4%); and oral cavity/other head and neck sites, five
patients (4.5%). There were 47 false positives and 13
false negatives. The false-positive rates were: tonsillar
fossa, 39.3%; and base of tongue, 21.4%. This sensitivity
rate was 81.5% for the base of tongue cancers versus
90.5% of all other sites.
Johansen et al.20 performed a prospective non-
randomized study to assess the value of FDG-PET in the
management of patients with an unknown head and
neck primary cancer. FDG-PET was done prior to panen-
doscopy in 19 patients and after the procedure in
41 patients. Areas of increased uptake were further
investigated to confirm a potential primary site via other
radiographic exams for sites in the chest or abdomen, or
with examination under anesthesia for sites in the head
and neck. Altogether, 33 potential sites of disease were
found in 30 patients; of these, 22 were above the
clavicles and 11 were below. After a conclusive investiga-
tion, a head and neck primary site was detected in 11
(50%) of 22 patients and distant metastases below the
clavicles were found in six (55%) of 11 patients. Two
patients had two synchronous primary tumors. The
detection rate of a primary cancer was 37% (7/19) for the
prepanendoscopy group and 27% (11/41) for the postpa-
nendoscopy group (P ¼ .43). The sensitivity, specificity,
and positive predictive values were 86%, 69%, and 60%,
respectively. The negative predictive value was 90%. The
authors recommended the use of FDG-PET prior to pan-
endoscopy to detect the primary site.
Roh et al.21 evaluated the role of combined FDG-
PET/CT in 44 patients; all patients had a CT and PET/
CT prior to panendoscopy and a guided biopsy of the
tonsils, base of tongue, nasopharynx, and other suspi-
cious sites. Patients with histologies other than SCCA
were included, as were those with low-neck presenta-
tions. The primary tumor was found in 16 patients
(35.4%): nine were in the tonsil, two in the nasopharynx,
Laryngoscope 119: December 2009 Cianchetti et al.: SCCA Metastases From Unknown Primary Site
2352
two in the base of tongue, and one each in the hypophar-
ynx, oral cavity, and thyroid gland. Pathological foci
were detected at FDG-PET/CT in 19 cases, of which 14
were true positive. There were five patients with false-
positive findings: one each in the tonsil, hypopharynx,
palate, parotid, and submandibular gland. Sensitivity
and specificity rates for FDG-PET/CT were 87.5% and
82.1%, respectively; and for CT they were 43.7% and
89.3%, respectively. Sensitivity was superior for FDG-
PET/CT (P ¼ .016), whereas specificity was similar. Posi-
tive and negative predictive values for FDG-PET/CT
were 73.7% and 92.0%, respectively; accuracy was
84.1%. The authors recommended FDG-PET/CT for
primary site detection, accurate nodal staging, and
detection of distant metastases.
Our experience with FDG-PET and FDG-PET/CT
has been less favorable. None of the 21 patients in our
series had the primary site detected solely on these stud-
ies. Both studies have a relatively high false-positive
rate in the base of tongue and tonsils, which were the
two most likely sites for the occult primary cancer in our
experience. Thus, the incremental benefit of FDG-PET
and FDG-PET/CT over physical examination and CT/
MRI is, in our opinion, limited.
Biologic Studies
Detection of the Epstein-Barr virus in the lymph
node biopsy is useful to detect nasopharyngeal carci-
noma in the areas where the disease is endemic.22,23
Otherwise, its value is likely limited.
There is clear evidence of the role of high-risk
human papillomavirus in the pathogenesis of head and
neck carcinoma, particularly for oropharyngeal cancer,24
and its detection in the biopsy specimen can be a reliable
tool to identify a primary site in the oropharynx.25
CONCLUSION
Approximately two thirds of patients with suspicious
findings on physical and/or radiographic examinations
will have the primary site detected versus approximately
30% for the remainder. In our experience, FDG-PET and
FDG-PET/CT are unlikely to improve the probability of
detection of the unknown primary. It is possible that,
when expertise in CT and/or MRI is less developed, these
studies may be more useful.
The tonsillar fossa and base of tongue are the two
most common primary sites. Panendoscopy, with ipsilat-
eral tonsillectomy and directed biopsies, remains a
mainstay of the diagnostic evaluation. A second panen-
doscopy should be performed only if a suspicious site
was not adequately biopsied at the first procedure.
Patients presenting with disease primarily in the
low-neck and/or supraclavicular lymph nodes, and those
with histologies other than SCCA, likely have a primary
site below the clavicles.
Our current approach to patients presenting with a
likely squamous cell carcinoma in the upper neck (levels
II and/or III) with an unknown primary site is to obtain
an FNA to establish a histologic diagnosis. If the FNA is
nondiagnostic, it is either repeated, or a core needle bi-
opsy is obtained. Open biopsies are avoided unless
absolutely necessary because of the risk of contaminat-
ing the neck and adversely impacting the patients
prognosis. Patients undergo a CT of the head and neck
and a chest radiograph. MRI and/or PET scan is
obtained to further evaluate equivocal findings observed
on the CT and/or physical examination. Patients with a
solitary node without obvious extracapsular extension
may be taken for an open biopsy and, if positive on fro-
zen section, undergo a neck dissection. Patients are then
taken for direct laryngoscopy and directed biopsies of
the tonsillar fossae, base of tongue, nasopharynx, and
any other area thought to be suspicious on the work-up
prior to the procedure or at the time of examination
under anesthesia. A unilateral or, less often, bilateral
tonsillectomy is performed if adequate lymphoid tissue
resided in the tonsil(s) to warrant the procedure.
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