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BENIGN AND MALIGNANT DISEASE OF THE ORAL CAVITY
Examination
Palpation for cervical lymphadenopathy
•
Systematic oral examination with two dental mirrors
•
Flexible nasoendoscopy
•
Dental examination
•
Initial Investigations
Photographs
•
Incisional biopsy of all suspicious lesions
•
Fine-needle aspiration cytology of suspicious lymphadenopathy
•
Orthopantogram
•
Routine blood values
•
Staging Investigations
Computed tomography (CT) +/− chest CT
•
Magnetic resonance imaging (MRI)
•
Ultrasound (USS) +/− ne needle aspiration cytology (FNA) of lymphadenopathy
•
Positron emission tomography (PET)/PET-CT
•
Surgical Margins
To ensure >5 mm pathological margin post-shrinkage, 1-cm so-tissue and bony mar-
•
gins are standard.
Royal College of Pathologists classify >5 mm as clear, 1–5 mm as close, <1 mm as
•
positive.
Post-operative adjuvant therapy depends on margin status and lymph node
•
involvement.
Surgical Access
Mandibulotomy: Extend neck dissection incision anteriorly and include lip-split pro-
•
cedure. Osteotomy performed anterior to mental foramen to reserve mental nerve
function.
Visor approach with lingual release: Intraoral mucosal incision is made in lingual gin-
•
gival sulcus bilaterally, allowing ‘drop down’ of oral tissues.
Upper cheek ap: Can be a combination of conventional Weber-Ferguson (lip split
•
extending into lateral rhinotomy incision) with subciliary extension (Dienbach
extension) or medial canthal extension (Lynch extension).
Key Points Regarding Tumour Location
Buccal Carcinoma
Commonest site for oral cancer in Southeast Asia.
•
Associated with betel/paan consumption.
•
Good surgical reconstruction to prevent post-operative trismus.
•
Up to 26% of patients have occult nodal metastasis at presentation.
•
Consider selective neck dissection (Levels I–III) if tumour is >4 mm thick.
•
Floor of Mouth Carcinoma
One of the most common sites of oral cancer.
•
Leukoplakia of the oor of mouth has a 1–2.9% annual transformation rate.
•
Anterior lesions may require treatment of both sides of neck.
•
Tendency for cervical metastasis to occur with thinner tumours.
•
348 Head and Neck
BENIGN AND MALIGNANT DISEASE OF THE ORAL CAVITY
Tongue Carcinoma
One of the most common sites of oral cancer.
•
Usually presents at stage I/II disease.
•
Neck dissection should include Levels I–IV because of skip lesions.
•
Reconstruction should maximise function of residual tongue and may involve local or
•
distal pedicled and free aps.
Retromolar Carcinoma
6–7% of oral carcinomas.
•
Frequently presents as stage III/IV disease with extension into adjacent sites.
•
Maxillary Alveolus and Hard Palate
Carcinoma of the maxillary alveolus is three times less common than cancer of the
•
mandibular alveolus.
Carcinoma of the hard palate represents only 1–3% of oral cancers.
•
Palatal carcinoma is associated with reverse smoking.
•
All patients should have dental impressions as part of their workup.
•
Some degree of bone removal is nearly always required.
•
Selective neck dissection is oen required.
•
Mandibular Alveolus
Represents approximately 10% of oral cancers, although the rate is up to 30% in the
•
Japanese population.
94% of tumours invade bone.
•
Alveolar carcinoma is a surgical disease requiring a rim or segmental resection of the
•
mandible.
Management of the Mandible
Bone involvement may be erosion or invasion.
•
MRI, CT, SPECT, and periosteal stripping are complementary in assessing bone
•
involvement.
Bone margins should be dictated by overlying so-tissue margins.
•
Rim resection should be conducted when oncologically acceptable.
•
Lip Reconstruction
Principles of Lip Reconstruction
Nerve supply of reconstructed lip should be preserved if possible, to maintain oral
•
continence.
Preservation of muscle-carrying vermilion tissue.
•
Lip tissue should preferentially be used to reconstruct defects.
•
Muscles should be normally oriented if possible.
•
Adjacent tissue, such as cheek, should be considered if the defect is too large.
•
Free-tissue reconstruction is used only if local tissue is insucient.
•
Reconstruction of the Vermilion
Vermilion ap: defects close to the white roll and include advancement or ‘switch’ aps
•
from opposite lip.
Mucosal advancement aps: useful for total vermilionectomy defects.
•
Head and Neck 349
MANAGEMENT OF THE UNKNOWN PRIMARY IN HEAD AND NECK CANCER
Reconstruction of the Upper Lip
Wedge excision: defects up to one third of lip.
•
Cheek ap (e.g. nasolabial) can used for defects up to one half of lip.
•
Abbe-Sabattini ap can be used if commissure is not involved (see Figure 12.17).
•
Total lip reconstruction is rare, but a folded radial forearm ap can be used.
•
Reconstruction of the Lower Lip
Defect up to one third of lip: simple wedge excision
•
Defect between one third and one half of lip:
•
Wedge excision
•
Karapandzic technique: unilateral or bilateral full-thickness mucomusculocuta-
•
neous aps supplied by branches of facial artery (see Figure 12.14)
Johanson’s step technique: square or rectangular segments removed lateral to
•
defect in stepwise fashion (see Diagram 12.16)
Lip switch: Abbe-Sabattini ap or Estlander for commissure reconstruction (see
•
Fig ure 12.18)
Defect greater than one half of lip
•
Freeman modication of Bernard von Burow technique (Figure 12.20)
•
Free tissue transfer
•
Further Reading
1. D’Cruz AK, Vaish R, Kapre N, et a l. Elective versus t herapeutic neck dissection in nodenegative oral cancer. N Engl J Med 2015; 373(6): 521–529. doi:10.1056/NEJMoa1506007
2. Field EA, Longman L, Tyldesley WR. (2003). Tyldesley’s Oral Medicine. Oxford: Oxford
University Press.
3. Stell PM, Maran AGD, Watkinson JC, Gilbert RW. (2012). Stell and Maran’s Textbook
of Head and Neck Surgery and Oncology. London: Hodder Arnold.
68. MANAGEMENT OF THE UNKNOWN PRIMARY IN HEAD
AND NECK CANCER
Introduction
Head and neck squamous cell carcinoma (HNSCC) that presents as carcinoma of
unknown primary (CUP) represents a challenge. Improvements in diagnostic techniques
have enabled the identication of a higher proportion of primary sites in patients presenting with CUP. e most common presentation of CUP in the head and neck is human
papillomavirus (HPV)-associated oropharyngeal carcinoma (HPV + OPSCC). With the
continued increased incidence of HPV+ OPSCC, it is likely that the incidence of CUP will
also increase.
Denition
In the head and neck, the denition of a true unknown or occult primary carcinoma is the
presentation of metastatic neck lymphadenopathy without the development or manifestation of an index primary tumour within a preceding 5-year period. CUP is diagnosed in
a patient when there is proven squamous cell carcinoma (SCC) in one or more cervical
lymph nodes, with an absence of an obvious primary tumour despite rigorous clinical
examination, appropriate imaging, and examination under anaesthesia +/− biopsy.
350 Head and Neck
MANAGEMENT OF THE UNKNOWN PRIMARY IN HEAD AND NECK CANCER
In patients with a true CUP, the primary tumour may never become evident or may remain
undetected on initial presentation, only to later become clinically evident. However, the most
likely primary sites are oen treated by inclusion in radiation elds, such that the primary never
becomes clinically evident. An alternate hypothesis suggests that the primary tumour has been
destroyed by the patient’s immune system aer early metastasis to the cervical lymph nodes.
Incidence
e universal availability of cross-sectional imaging and standardized diagnostic protocols
has reduced the incidence of CUP in HNSCC signicantly. e incidence reported in the
current literature is around 5% of HNSCC. It is increasingly recognized that high-risk (HR)
HPV-related HNSCC tends to present with regional disease and a clinically unrecognised
primary focus, and most patients presenting with CUP will likely have a primary site in the
oropharynx.
Nomenclature
Recent changes to the TNM staging system published in the 8th edition of the American Joint
Committee on Cancer (AJCC) Cancer Staging Manual included changes to CUP staging.
A T0 category is no longer assigned to p16– OPSCC and other non-HR HPV cancers (e.g.
larynx, oral cavity, and hypopharynx). is is because, in these tumours, an exact primary site is by denition unable to be established. In contrast, cytology specimens from an
enlarged lymph node in which the presence of metastatic carcinoma is conrmed can be
tested for HPV and Epstein-Barr virus (EBV) status, which safely allows the primary site to
be determined as either oropharynx or nasopharynx, respectively. erefore, classication
systems for p16+ OPSCC and nasopharyngeal cancer maintain T0 categories.
Evaluation and Diagnosis
Clinical Assessment
Patients presenting with metastatic lymphadenopathy with an occult primary should
undergo a structured diagnostic workup, as recommended by evidence-based guidelines.
History: A thorough history is essential. Social history, such as smoking and alcohol
•
consumption, or a history of multiple sexual partners and orogenital contact, may
supply clues to the location of the primary tumour.
Clinical Examination: e site of the node is an indicator of the primary site.
•
Nomograms based on epidemiological data and lymph node distribution have been
created to help predict the primary site. Fibreoptic nasopharyngolaryngoscopy should
be performed, with special attention to sites where a small primary focus may be
missed (e.g. nasopharynx, base of tongue (BOT), infrahyoid epiglottis, and piriform
sinus). Novel endoscopic techniques, such as narrow-band imaging (NBI), have shown
some utility in the clinic setting, being able to identify neoplastic tissue at an earlier
stage than conventional endoscopy.
Imaging: Cross-sectional imaging, such as multiplanar computed tomography (CT)
•
and/or magnetic resonance imaging (MRI) and uorodeoxyglucose (FDG) positron
emission tomography (FDG-PET) CT should be performed prior to an assessment
under general anaesthesia.
Examination under anaesthesia: If the primary site is not identied with imaging, t hen
•
the patient should undergo panendoscopy under a general anaesthetic, with biopsies
of the nasopharynx and BOT as well as tonsillectomy. Using this protocol, most CUP
cases turn out to be oropharyngeal primaries (either tonsillar or BOT).
Endoscopic Biopsy of the Nasopharynx
Blind biopsies of the nasopharynx oen provide a poor yield of primary site diagnosis. It is
therefore recommended that biopsies from this site should be guided using rigid endoscopes,
especially where abnormalities have been noted on imaging.
Head and Neck 351
MANAGEMENT OF THE UNKNOWN PRIMARY IN HEAD AND NECK CANCER
Figure 68.1 Photomicrograph showing immunohistochemistry of a lymph node from a patient
with metastatic HNSCC of unknown primary suggesting a tonsil origin. (a) Positivity to p16 in the
tonsil (b) identied malignant cells in the tonsil.
Bilateral Tonsillectomy
In the HR HPV era, there is greater recognition that tumours can be multifocal at presentation and that the primary may reside in the contralateral tonsil in up to 10% of cases, providing a basis for bilateral tonsillectomy (Figure 68.1). Furthermore, bilateral tonsillectomy could
reduce the need for bilateral irradiation to the neck, thus leading to reduced morbidity. Where
patients have undergone previous tonsillectomy but have tonsillar remnants, the excised remnants should be sent for analysis because primary tumours may be found in them.
Tongue Base Biopsies
Blind biopsies of the BOT are oen unsatisfactory because occult carcinomas rarely arise
from the mucosal surface and are oen deeper. BOT mucosectomy, a procedure that has
developed with the advent of robotic techniques (which oer superior manoeuvrability and
access), allows sampling of the entire BOT mucosa and is able to identify a primary site in
over 50% of patients who are PET negative and have no tonsil primary (Figures 68.2 and
68.3). Interestingly, around 10% can have contralateral foci. However, the morbidity of this
procedure cannot be underestimated, with the risk of bleeding, need for tube feeding, and
the potential for pharyngeal stenosis.
Pet Scanning
FDG-PET CT scanning is now a key modality in the evaluation of the unknown primary.
It provides anatomical localisation of the avid lesion. A negative PET CT result does not
eliminate the requirement for panendoscopy and multiple-site biopsies. FDG-PET CT is only
Figure 68.2 (a) Robotic tongue base mucosectomy in progress and (b) completed procedure.
352 Head and Neck
MANAGEMENT OF THE UNKNOWN PRIMARY IN HEAD AND NECK CANCER
Figure 68.3 Bilateral tonsillectomy and robotic tongue base mucosectomy specimen oriented
and mounted for pathological examination.
useful if it is performed before anaesthesia and biopsy, because the post-biopsy inammatory response may increase the uptake of FDG, causing a false-positive result (Figure 68.4).
Studies have determined the sensitivity and specicity of PET scanning in identifying the
primary site in CUP to be as high as 92%.
Nice Recommendations
e National Institute for Health and Clinical Excellence (NICE) made the following recommendations for patients with a neck lump thought to arise from a head and neck cancer.
e recommendations are summarised in an algorithm in Figure 68.5. Ultrasound-guided
ne-needle aspiration cytology (FNAC) or core biopsy, with a cytopathologist or a biomedical scientist present to assess the adequacy of the cytology sample, may help streamline the
diagnostic process. Similarly, an FDG-PET scan can be carried out as the rst investigation
to detect the primary site.
Figure 68.4 FDG-PET CT scan demonstrating tracer uptake in the right oropharynx in a patient
presenting with metastatic SCC of the right neck.
Head and Neck 353
MANAGEMENT OF THE UNKNOWN PRIMARY IN HEAD AND NECK CANCER
Consider
reassessment
with narrow
band imaging
endoscopy at
any stage prior
to biopsy
If FNAC and core
biopsy do not indicate
cancer, but index of clinical
suspicion remains high,
consider open biopsy as an
oncological procedure,
i.e. a selective neck
dissection.
Primary site seen
Diagnostic biopsy
Comprehensive ENT examination shows no primary site
Patient presenting
with neck node
Fine-needle aspiration cytology (FNAC)
conrms squamous cell cancer
Consider core biopsy to assess
HPV and EBV status
Conventional imaging (CT/MRI)
shows no primary site
18
FDG-PET-CT
imaging
Detection of primary
tumour site in ≈50%
If EBV positive, targeted
nasopharynx biopsy
No primary site seen
Panendoscopy and
bilateral tonsillectomy,
tongue base
mucosectomy
Figure 68.5 Suggested algorithm for the management of the unknown primary.
Clinical Management
In the absence of high-level evidence, the optimal management of CUP continues to generate
debate. CUP management can be organized into the treatment of early disease (N1 with no
extracapsular spread) and advanced disease (extracapsular spread, N2 and N3; Table 68.1). In
early disease, single-modality therapy can be considered, either in the form of neck dissection (ND) alone without adjuvant treatment and a ‘watch and wait’ approach to the primary,
or radiotherapy (RT) alone in patients who pose a high surgical risk. Advanced cases require
combined modality therapy.
Surgical Management of the Neck
Traditionally, most units favour ND up front, followed by either RT or chemoradiotherapy
(CRT) as indicated. Selective neck dissection (SND) is a valid option for patients with N2a
and N2b disease, because the risk of metastases in Levels I and V is low in patients with CUP
unless they present with N3 disease. Surgery allows adequate pathological staging of the neck
Table 68.1 Treatment recommendations from ENT-UK Multidisciplinary Treatment Guidelines (2016)
Stage Surgery Radiotherapy Chemotherapy
T0N1M0 (No ECS) SND or MRND (modied
radical ND)
T0N1M0 (ECS) SND or MRND Yes, to neck Should be considered
T0N2M0 SND or MRND Yes: ipsilateral, but
T0N3M0 MRND or RND Yes: ipsilateral, but
354 Head and Neck
No, unless for mucosal
sites
contralateral should be
considered
contralateral should be
considered
No
Should be considered
Should be considered
MANAGEMENT OF THE UNKNOWN PRIMARY IN HEAD AND NECK CANCER
and therefore tailoring of onward treatment. Performing surgery in a non-irradiated neck is
also advantageous in minimising morbidity. However, this approach could potentially cause
a treatment delay if any unexpected surgical complications occur. Primary RT or CRT will
reduce the need for surgery but may render surgery dicult and with an increased risk of
complications.
However, recent randomized trials have reported that PET-CT-guided active surveillance
following radical CRT showed similar survival outcomes to up-front ND followed by CRT
and led to considerably fewer NDs, fewer complications, and lower costs. Although this was
in the setting of the known primary, the data are robust enough to warrant a re-examination
of the current approach using primary surgery in CUP.
Branchial Cyst Carcinoma
The evidence for the existence of branchial cyst or branchiogenic carcinoma is tenuous.
Many patients with CUP may present with a cystic lateral neck mass. There is enough
evidence to recommend that all patients over 35 years old with lateral cystic masses
must be presumed to have cancer until proven otherwise, and therefore they should be
entered into a CUP investigation protocol even if the initial FNAC is not suggestive of
metastatic SCC.
RT to the Neck and the Putative Primary Site
e recommended RT elds remain controversial, with some centres oering unilateral
radiation to the neck and ipsilateral likely primary sites, while others propose bilateral neck
treatment and ‘total mucosal irradiation’.
Bilatera l neck irradiation tends to give better local control a nd disease-free survival than unilateral treatment, but the improvement in overall survival is not always seen. Unfortunately,
bilateral irradiation is associated with increased morbidity in terms of pain, xerostomia, and
long-term dysphagia with increased feeding tube dependence.
Intensity-modulated radiotherapy (IMRT) with bilateral neck radiation has the potential for
reduced acute and late toxicity and a signicant reduction in morbidity. IMRT is currently
the standard of care for head and neck cancers in several countries.
Recommended Treatments
cT0N1M0 without ENE (extranodal extension): single-modality treatment either with
•
SND or involved eld RT alone
pT1N0M0 with ENE: post-operative RT if ENE is identied
•
T0N2M0 and T0N3M0: primary CRT followed by PET-CT guided surveillance or
•
combined modality treatment, ND followed by RT or CRT
Treatment Outcomes
Most series show improved overall and disease-free survival with combined modality treatment. Survival results are dependent upon the N category at presentation, with an expected
5-year survival of 70–100% for N1 cancers, 30–60% for N3, and 52–75% for all stages of
HNSCC with unknown primary site.
Patterns of Failure
e pattern of failure largely depends on the initial treatment protocol. If RT is used, disease recurrence is usually in the neck and distant metastases. FDG-PET CT scan is probably the best method for detection and diagnosis of recurrences. Distant metastases oen
occur within a year of treatment completion and are most oen in the lung. e incidence of
recurrence in the potential primary site is extremely variable, and mainly occurs in patients
treated with surgery alone.
Head and Neck 355
METASTATIC NEC K DISE ASE
KEY POINTS
• CUP in HNSCC is an increasingly rare entity and accounts for fewer than 5% of cases.
• The diagnostic workup should include history, examination, cross-sectional imaging,
and examination under anaesthesia as well as biopsies.
• Treatment of CUP should be based on the stage of the disease process, with a single
modality used for early-stage disease and a combined modality used for patients with
advanced disease.
• The survival outcomes are generally good for early and late-stage disease.
Further Reading
Mackenzie K, Watson M, Jankowska P, et al. Investigation and management of the unknown
primary with metastatic neck disease: United Kingdom National Multidisciplinary
Guidelines. J Laryngol Otol 2016; 130: S170–S175.
Mehanna H, McConkey CC, Rahman JK, et al. PET-NECK: a multicentre randomised Phase
III non-inferiority trial comparing a positron emission tomography-computerised
tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell
head and neck cancer. Health Technol Assess 2017; 21: 1–122.
Paleri V, Roland NJ. Head and neck cancer: United Kingdom national multidisciplinary
guidelines. J Laryngol Otol 2016; 130: S1–S224.
69. METASTATIC NECK DISEASE
e most important prognostic factor in head and neck squamous cell cancer (HNSCC) is
the presence or absence, level, and size of metastatic neck disease. Patients with lymph node
involvement in HNSCC have a signicantly reduced chance of survival compared to those
who have no lymph node metastases.
Elective removal of regional lymph nodes serves as a staging procedure to ascertain whether
metastatic disease is present and to identify high-risk patients who might benet from systemic adjuvant therapy; it is not expected to diminish the metastatic potential.
Neck Levels
Currently, six neck levels representing the sites of rst-echelon nodes within the head and
neck are recognised (Figure 69.1).
Neck Dissection Terminology
e terminology of the Committee for Neck Dissection Classication of the American Head
and Neck Society is used (Table 69.1 and Figure 69.2).
However, division of SND into named subtypes has been superseded by recommendations that the levels or sublevels removed during SND be precisely stated in the operative
notes.
Region-Specic Lymphatic Drainage
In a landmark study of 1,155 patients with previously untreated HNSCC published by
Lindberg in 1972,
1
the topographical distribution of clinically evident cervical metastases
was set out. is identied distinct patterns of spread to the neck based on the primary site
356 Head and Neck
METASTATIC NEC K DISE ASE
Figure 69.1 The lymph node levels of the neck.
Table 69.1 Classication of neck dissection techniques
Radical neck dissection
(RND)
Modied radical neck
dissection (MRND)
Selective neck dissection
(SND)
Extended radical neck
dissection (ERND)
Removal of Levels I–V, accessory nerve, internal jugular vein,
and sternocleidomastoid (SCM)
Removal of Levels I–V dissected; preservation of one or more of the
accessory nerve, internal jugular vein, or SCM (types I, II, III, respectively)
Preservation of one or more levels of lymph nodes
Removal of one or more additional lymphatic and/or non-lymphatic
structures(s) relative to a radical neck dissection, e.g. Level VII,
retropharyngeal lymph nodes, hypoglossal nerve
(Table 69.2). Histological proof of this concept was produced in 1990 by Shah in a series of
1,119 neck dissections.
Metastatic Behaviour in the Previously Treated Neck
Surgery and radiotherapy signicantly disrupt the natural lymphatic drainage of the head
and neck. us, the patterns of drainage described above will not be applicable to disease
recurrence following treatment.
Occult Nodal Disease
e term occult disease is used to describe the presence of metastases in the neck nodes that
cannot be clinically or radiologically identied. ese are most commonly from a primary
in the oropharynx.
Cystic Neck Metastases
Cystic neck metastases are usually of oropharyngeal origin, with the most common sites
being the tonsil or tongue base. Human papillomavirus (HPV)-related tumours are more
oen associated with cystic metastases than HPV-negative tumours.
Prognostic Nodal Features
Prognostic nodal features are summarised in Box 69.1. In a study of 1,330 patients, Lefebvre
et al. demonstrated that irrespective of T category, extra-nodal extension (ENE), three or
more positive nodes and positive Level IV nodes doubled the risk of regional recurrence and
trebled the risk of distant metastases.
3
Clinical Staging
e joint UICC and AJCC classications for regional cervical lymphadenopathy have had
substantial changes made to them in the 8th edition (see Chapter 61).
Head and Neck 357
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