Malignant neoplasms of the oral cavity

Malignant Neoplasms of the Oral Cavity

Dr. Firas Kassab

Malignant

Neoplasms of

the Oral

Cavity

Dr. Firas Kassab


Dr. Firas Kassab

The oral cavity extends from the cutaneous vermilion junction of the lips to the

junction of the hard and soft palate above and to the line of the circumvallate

papillae below.

INCIDENCE

In 2010, there were an estimated 23,880 new cases of oral cavity cancer, leading to

5470 deaths.

BIOLOGIC CHARACTERISTICS

The natural history of oral cavity carcinoma depends on its anatomic site, histologic

type, and stage of the tumor.

STAGING EVALUATION

A physical examination should be performed to determine the location and extent of

the primary tumor and to assess for the possible presence and extent of nodal

involvement.

Computed tomography (CT) scanning will help to determine the extent of the tumor

(particularly, deep invasion), detect bone invasion (CT scanning plus panoramic x-

ray film [Panorex] view), and assess regional lymph nodes. For retromolar trigone

lesions, magnetic resonance imaging (MRI) is useful to assess muscle invasion and

chest radiograph will help to detect pulmonary metastases. The routine use of

positron emission tomography (PET) is not recommended.


Dr. Firas Kassab

PRIMARY THERAPY

For early disease (T1 to early T2 lesions), single-modality surgery or radiotherapy

can achieve excellent local control and survival rates in most oral cavity sites (85%

to 90%). The treatment choice is predicated on function and treatment side effects.

Moderately advanced (large T2 to early T3) lesions are more often treated with

radiotherapy alone or surgery plus irradiation. Moderate rates of local control (60%

to 80%) can be achieved.

LOCALLY ADVANCED DISEASE

For locally advanced disease (large T3 or T4 lesions), combined radiation plus

surgery is indicated in most sites because single-modality disease control is poor

(≤30%). Radiation alone or combined with concomitant chemotherapy likely results

in a lower probability of cure.

For locally recurrent cancers seen after the primary tumor has been treated with

surgery alone, salvage with surgery is appropriate, followed by postoperative

radiotherapy, radiation with or without chemotherapy, or palliative irradiation.

Locally recurrent cancers that occur after definitive irradiation alone or combined

with chemotherapy can be managed with surgical salvage, palliative chemotherapy,

or supportive care.

PALLIATION

Moderate-dose palliative irradiation can be given as 30 Gy in 10 fractions over 2

weeks or 20 Gy in 2 fractions with a 1-week interfraction interval.

The oral cavity consists of the lips, floor of the mouth, oral tongue (the anterior two-

thirds of the tongue), buccal mucosa, upper and lower gingiva, hard palate, and

retromolar trigone. ( Table ) shows the frequency of involvement of various

locations.2 After a general discussion of etiology and epidemiology, issues relative to

the various subsites will be presented separately. A discussion of preradiotherapy

and postradiotherapy dental care is included.

Distribution of Oral Cavity Cancer

http://clinicalgate.com/oral-cavity-cancer/#t0010


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Site Percentage

Lower lip 38

Tongue 22

Floor of mouth 17

Gingiva 6

Palate 6

Retromolar trigone 5

Upper lip 4

Buccal mucosa 2

Etiology and Epidemiology

Oral cavity cancer is predominately a disease of middle-aged men who use tobacco

and alcohol. Approximately 95% of carcinomas appear after age 45 years, with an

average age of 60 years. The use of tobacco in any form is associated with an

increased risk of oral cancer. Some evidence suggests that patients with oral cavity

cancer who continue to smoke during radiation therapy have poorer outcomes. The

risk of tobacco-related cancers of the upper aerodigestive tracts declines among

former smokers after 5 years, and after 10 years of abstention the risk may

approach that of nonsmokers. Although the effects of alcohol and tobacco in

inducing cancers of the upper aerodigestive tract seem to be additive, the risk of

alcohol consumption without tobacco use is unclear. Some studies indicate a slightly

increased risk with alcohol use in the absence of tobacco, whereas others show no

apparent increased risk.

Human papillomavirus (HPV) infection, marijuana smoking, betel quid use, and

drinking the beverage “mate” have also been implicated as causative factors in the

formation of squamous cell carcinomas of the upper aerodigestive tract. In recent


Dr. Firas Kassab

years, oral cancers have increased among relatively young females who have never

consumed alcohol or smoked. The reason for this is unclear.

Smokeless tobacco (snuff) can promote carcinomas of the buccal gingival sulcus,

which are diagnosed most often in older Caucasian women living in the southeastern

United States. Carcinoma of the buccal mucosa is also associated with chewing

tobacco. It is commonly seen in the southeastern United States, with a male to

female ratio of 3 or 4 to 1. Leukoplakia is seen with oral carcinoma in approximately

15% of cases.

Persons with a “Scotch-Irish” complexion (red hair and blue eyes) and/or prolonged

exposure to sunlight are most susceptible to lip carcinoma. In one series, 82% were

previous or present tobacco smokers. Pipe smoking is an alleged risk factor, but this

has not been substantiated by most studies. Lip cancer is often associated with poor

dental hygiene or edentulous patients. Lip trauma and a history of alcohol abuse are

also related factors. Most cases appear after age 40 years, but approximately 10%

occur before age 40 years and a few before age 30 years. This disease is uncommon

in blacks.

Oral Care

A complete dental examination should be performed on all patients, whether dentate

or edentulous, before irradiating any portion of the mandible or maxilla. The

radiation oncologist should inform the patient’s dentist of the anticipated radiation

treatment plan, including dose and location of the radiotherapy (RT) fields. To make

appropriate pretherapy recommendations, the dentist should be familiar with

possible postradiotherapy complications, such as caries and osteoradionecrosis.

There is a lifelong risk of impaired healing that can lead to osteoradionecrosis,

especially when teeth are extracted from hypovascularized and hypocellular bone.

Therefore, one objective of the pretherapy oral evaluation is to determine whether

teeth in the proposed irradiated area can be reasonably maintained in a healthy

state for the remainder of the patient’s life.


Dr. Firas Kassab

Medical, dental, and psychosocial issues that affect a person’s future dental health

should be assessed at the pretherapy evaluation. The patient’s compliance,

motivation for daily oral hygiene procedures, dental awareness, and access to dental

care are predictors of dental health. A panoramic radiograph, intraoral radiographs,

and hard and soft tissue examinations should be performed to identify high-risk

dental factors such as deep caries, nonrestorable teeth, root tips, bony pathology,

endodontically treated teeth, periapical and pulpal pathology, and nonfunctional

teeth. Teeth exhibiting periodontal disease should be evaluated to determine their

long-term prognosis. Some prognostic factors for poor periodontal health include

probing depths more than 6 mm, gingival recession, furcation involvement, and

mobility. Because of the numerous reported cases of progression of gingival

recession and periodontal disease after RT, it may be difficult to assess the longevity

of each tooth.

To reduce the future risk of osteoradionecrosis, teeth with high-risk dental factors

should be removed before the patient receives doses of more than 55 Gy. Whether

extraction of teeth with moderate disease is indicated remains controversial. If the

patient has poor resistance to dental disease or an unwillingness to perform routine

dental care or fluoride applications, pretherapy extraction of moderately diseased

teeth may be justified. A healing time of 14 to 21 days is recommended after

extraction, before initiating radiation therapy. Extraction should be accomplished as

atraumatically as possible, with alveoloplasty to remove sharp, bony projections. The

dentist should coordinate dental appointments with the radiation oncologist to

minimize the delay in cancer therapy. However, extraction of healthy teeth does not

reduce the risk of osteoradionecrosis and should be avoided.

Denture adjustments, smoothing edges of sharp teeth, dental cleaning, and oral

hygiene instruction can be accomplished at the pretherapy dental visit. Ill-fitting

dentures that irritate mucosal surfaces should be worn with caution during

radiotherapy. Daily disinfection of dental prostheses is recommended.

Impressions for custom fluoride trays can be made before or within the first 2 weeks

of radiation therapy. Patients who receive radiotherapy to major salivary glands are

at lifelong risk for rampant caries. Daily use of 0.4% stannous fluoride or 1.1%


Dr. Firas Kassab

sodium fluoride gel for 5 minutes, in custom trays, is imperative as long as natural

teeth remain. Patients should be advised to refrain from rinsing, eating, or drinking

for 30 minutes after fluoride application. The dentist and radiation oncologist should

consistently promote proper oral hygiene and use of fluoride throughout the

posttreatment years.

Clinical practice guidelines for the treatment of cancer therapy-induced oral

mucositis have been published. Radiation–induced mucositis cannot be prevented;

however, excellent oral hygiene can reduce the risk of oral infections. Supersoft

toothbrushes and mild toothpastes are available for patients to facilitate proper oral

hygiene during and after RT.

Consultation with the radiation oncologist is required before postirradiation

extraction of teeth or invasive procedures that involve the exposure of irradiated

bone. Preextraction and postextraction hyperbaric oxygen therapy may be indicated

to promote healing of extraction or surgical sites.

Patients should be closely monitored for possible late effects of radiotherapy to

oropharyngeal regions. Trismus, xerostomia, caries, and oral candidiasis can persist

or occur at any time after treatment is completed.

first-echelon nodes in the oral cavity

Two or three submental nodes lie on the mylohyoid muscle in the submental

triangle. This triangle is bounded by the anterior bellies of the digastric muscles and

the hyoid bone.

Six or more submandibular nodes lie on the anterior surface of the submandibular

gland or between the gland and the lower jaw adjacent to the facial artery.

The nodes on the surface of the gland are preglandular nodes; those adjacent to the

facial artery are facial nodes.

They extend upward along the course of the facial artery and are subdivided into

prevascular and retrovascular nodes, depending on their relationship to the facial

artery. With the exception of one or two at the lower border of the jaw, the facial

nodes are small and inconstant.


Dr. Firas Kassab

Lymphatics of the oral cavity

Upper deep jugular nodes located along the upper internal jugular vein, between

the levels of the digastric and omohyoid muscles.

Malignancies of the lips and anterior floor of the mouth as well as adjacent

gingiva and buccal mucosa tend to metastasize to submandibular lymph nodes

first.

Tumors situated more posteriorly in the oral cavity usually metastasize initially to

the upper deep jugular lymph nodes.

As multiple cervical nodes become involved with metastatic disease, spread to

the middle and lower deep jugular nodes occur.


Dr. Firas Kassab

Lips

The lips begin at the

junction of the vermilion

border with the skin and

form the anterior

boundary of the oral

vestibule.

The lip includes only the

vermilion surface, or that

portion of the lip that comes into contact with the opposing lip.

Numerous anastomoses from the lymphatic vessels of the two lip halves are

present near the midline and account for bilateral metastases from tumors that

are close to or cross the midline.

The upper-lip lymphatics drain to preauricular, infraparotid, submandibular, and

submental lymph nodes.

In contrast to the lower lip, only a few of the upper-lip cutaneous lymph trunks

drain to contralateral nodes. No crossing of the midline has been documented for

the mucosal lymphatics of the upper lip.

Pathology and Patterns of Spread

The most common neoplasms are moderately to well differentiated squamouscell


Dr. Firas Kassab

carcinomas; approximately 5% are poorly differentiated.26 Basal cell carcinomas

usually arise on the skin above or below the lip and invade the vermilion border,

but rarely arise from the vermilion border. Squamous cell carcinomas start on the

vermilion of the lower lip, and less commonly on the upper lip. The commissure

is rarely the site of origin. Leukoplakia is a common problem on the lower lip and

may precede carcinoma by many years.

Early lesions can initially invade adjacent skin and the orbicularis oris muscle.

Advanced lesions can invade the adjacent commissures of the lip and buccal

mucosa, the skin and wet mucosa of the lip, the adjacent mandible, and

eventually the mental nerve. The incidence of perineural invasion is

approximately 2%. Lymph node involvement at presentation occurs in

approximately 5% to 10% of patients. An additional 5% to 10% of patients with

a clinically negative neck subsequently develop lymph node metastases. The risk

of lymph node involvement increases with depth of invasion, poor differentiation,

larger lesions, invasion of the commissure, and recurrence after prior treatment.

Hendricks and colleagues28 from the Mayo Clinic reported the following incidence

of positive cervical lymph nodes by T stage: T1, 2%; T2, 9%; and T3, 30%. The

overall incidence of adenopathy was 19% when the commissure was involved.

Clinical Manifestations and Staging

Carcinoma of the lip usually presents as a slowly enlarging exophytic lesion with

an elevated border. Occasionally, there is minor bleeding. Erythema of the

adjacent skin may suggest dermal lymphatic invasion. Anesthesia or paresthesia

of the skin indicates perineural invasion.

The American Joint Committee on Cancer (AJCC) staging for lip cancer applies to

lesions arising from the vermilion surface

Oral Cavity Primary Tumor Staging

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor


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Tis Carcinoma in situ

T1 Tumor 2 cm or less in greatest dimension

T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension

T3 Tumor more than 4 cm in greatest dimension

T4 (lip) Tumor invades through cortical bone, inferior alveolar nerve, floor of

mouth, or skin of face (i.e., chin or nose)

T4 (oral cavity) Tumor invades through cortical bone into deep (extrinsic)

muscle of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus

muscles), maxillary sinus, or skin of face

T4b Tumor involves masticator space, pterygoid plate, or skull base and/or

encases internal carotid artery

Early lip cancers rarely require diagnostic imaging. Locally advanced, deeply

infiltrating, or recurrent carcinomas may benefit from a computed tomography

(CT) scan or panoramic x-ray film to evaluate possible bony invasion and regional

nodal spread.

Treatment

Early Lesions (<2 cm)

The majority of these lesions can be surgically excised with primary closure as an

outpatient procedure. Surgery is satisfactory if the lip commissure does not need

to be resected and if the resulting aperture of the oral cavity permits the

insertion of dentures. Postoperative irradiation is recommended for positive

margins or perineural invasion.

Tumors that should be treated with radiotherapy include those involving a

commissure in order to obtain better cosmesis and improved local control. The

uncommon, poorly differentiated lesions are also preferably treated by irradiation

to cover a more generous treatment volume and the first-echelon lymph nodes.

An algorithm for treatment planning is shown in


Dr. Firas Kassab

Moderately Advanced Lesions (2 to 4 cm)

The length of the lower lip is approximately 7 cm. Removal of more than half of

the lower lip with simple closure produces a poor cosmetic and functional result

so that a reconstructive procedure is usually necessary. In these cases,

irradiation has the advantage of a better functional and cosmetic result.

Traditionally, the reconstructed lip may look normal in a photograph but may lack

sensory and motor innervation as well as elasticity. However, there have been

recent improvements in the functional and cosmetic results of various

reconstructive surgical procedures.

Locally Advanced Lesions (> 4 cm)

Large lesions are managed by resection and postoperative irradiation. Erythema

of the skin adjacent to the lesion may indicate dermal lymphatic involvement;

wide-field irradiation is recommended followed by consideration of surgical

resection depending on the response to radiation therapy. Management by


Dr. Firas Kassab

definitive radiotherapy and concomitant chemotherapy is generally preferred in

patients who are not surgical candidates.

T4 Lesions

Cancers that present with bone or nerve involvement are usually treated with a

combination of surgery and EBRT. There are limited data pertaining to the local

control rates after RT or surgery alone, ranging from 0% to 74% ; therefore,

combined treatment is usually recommended.

The postoperative EBRT portals should include the primary site as well as the

regional lymphatics (levels IA, IB, and II). The low neck is usually treated to

doses sufficient for subclinical disease, and doses are frequently higher in

patients with positive nodes. The total dose ranges from 60 to 70 Gy, at 2 Gy per

once-daily fraction to the primary site, depending on the pathologic findings.

Higher doses with altered fractionation schemes (e.g., 74.4 Gy at 1.2 Gy per

fraction twice daily), as well as concomitant chemotherapy, should be considered

in patients with positive margins or other high-risk factors such as extracapsular

extension

Irradiation Techniques

EBRT is usually delivered with either orthovoltage x-rays or electron beam. The

electron beam energy depends on the tumor thickness. Lead shields are placed

behind the lip to limit the dose to the oral cavity and mandible. Orthovoltage

fractionation schedules range from 40 to 45 Gy in 3 to 4 weeks for smaller

lesions, and 50 to 55 Gy in 4 to 6 weeks for moderately advanced lesions. The

dose is increased 10% to 15% for electron beam RT to account for differences in

the relative biological effectiveness. Orthovoltage x-rays are preferred, if

available, because the maximum dose is at the surface and there is less beam

constriction compared with electron beam.


Dr. Firas Kassab

An appositional field with a margin of 1 to 1.5 cm is sufficient for most small to

moderately advanced lesions if orthovoltage irradiation is used. The field borders

are determined by bimanual palpation. Because of beam constriction, 2- to 2.5-

cm margins are necessary if an electron beam is employed. A lead shield is used

to collimate the beam at the skin/lip surface.

Brachytherapy may be used as the sole treatment or in conjunction with EBRT.

Implantation is usually performed under local anesthesia using Ir sources and a

single-plane plastic tube technique. The sources are arranged horizontally 10 to

12 mm apart with crossing sources on the lateral aspects of the implant. Three to

five horizontal sources are used depending on the size of the lesion. The

advantage of the plastic tube technique is that the volume of the implant is more

easily adapted to the extent of the tumor and the commissure is readily included,

if necessary. Alternatively, cesium needles mounted in a nylon bar may be

employed .

The sources are spaced 1 cm apart and the dose is specified 0.5 cm from the

plane of the implant. A gauze roll is placed between the lip and gum to increase

the distance between the radioactive sources and the alveolar ridge. The

recommended dose is 60 to 70 Gy at a dose rate of 0.4 to 0.5 Gy per hour for an

implant alone. Large infiltrative lesions may be first treated with EBRT, 30 Gy at

2.5 Gy per fraction to shrink the tumor, followed by an interstitial brachytherapy


Dr. Firas Kassab

boost to deliver an additional 35 to 40 Gy. Treatment of lip cancer with high-

dose-rate interstitial needles is advocated by some.

T3 and T4 Tumors

Low-volume T3 cancers may be treated with primary irradiation, preferably

combining EBRT to the primary lesion and neck followed by a brachytherapy boost.

EBRT is administered with parallel opposed fields, including the lip lesion and the

level I and II lymph nodes .

A cork is placed in the mouth to displace the maxilla and upper lip and reduce the

volume of normal tissue included in the fields. A separate anterior field is used to

treat the level III and IV lymph nodes with a tapered midline block over the larynx.

The supraclavicular lymph nodes are at low risk and are not included in the fields.

Both sides of the neck are treated with irradiation because it is unlikely that T3 and

T4 primary lesions would be well lateralized.


Dr. Firas Kassab

The junction between the parallel opposed fields and the low-neck field is at the

thyroid notch. The dose fractionation schedule used varies from 38.4 Gy at 1.6 Gy

twice daily to 50 Gy at 2 Gy per fraction once daily, followed by a brachytherapy

boost. Low-energy photons such as 4-MV or 6-MV beams are recommended.

High-volume T3 and T4 cancers are unlikely to be cured with RT alone and are

better treated with surgery and postoperative irradiation. EBRT fields are similar to

those used to treat patients with irradiation alone. A petroleum jelly gauze bolus is

placed over incisions to ensure that the surface dose is adequate. The fields are

extended to the skull base along the course of the third division of the fifth cranial

nerve if perineural invasion is present. The dose depends on the surgical margins:

negative (R0), 60 Gy; microscopically positive (R1), 66 Gy; and gross residual

disease (R2), 70 Gy. Patients are treated once daily at 2 Gy per fraction, 5 days a

week, in a continuous course.

Complications

After RT, there is gradual atrophy of the irradiated tissues. The irradiated lip must be

protected from sun exposure by use of hats and ultraviolet protectants. Because the

anterior teeth and gingiva are protected by lead shields when radiation is given by

EBRT, radiation caries, bone exposure, and osteoradionecrosis are uncommon.

Floor of the mouth

The floor of the mouth is a crescent-shaped region of mucosa overlying the

mylohyoid and hyoglossus muscles, extending from the inner aspect of the lower

alveolar ridge to the underside of the anterior two thirds of the tongue.

Posteriorly, the floor of the mouth is continuous with the base of the anterior

tonsillar pillar, and anteriorly the frenulum of the tongue divides it into two sides.

On either side of the frenulum is the sublingual caruncle, marking the orifices of the

submandibular duct.


Dr. Firas Kassab

Posterolaterally from the orifices is a rounded ridge called the sublingual fold, which

overlies the upper border of the sublingual salivary glands.

The paired mylohyoid muscles constitute a muscular diaphragm and provide the

structural support of the anterior floor of the mouth.

They arise from the mylohyoid lines of the mandible and insert into the hyoid bone.

Their borders unite in the midline as a median raphe that extends from the

symphysis of the mandible to the hyoid bone

The hyoglossus muscle partly supports the extreme posterior floor of the mouth;

it is a flat, quadrilateral muscle extending upward into the tongue from the body and

greater horn of the hyoid, partly above and partly behind the mylohyoid muscle.

An important point of surgical anatomy is that the lingual nerve, submandibular

duct, sublingual gland, and twelfth cranial (hypoglossal) nerve lie lateral to the

hyoglossus muscle, whereas the lingual artery runs deep (medial) to it.

Medially, the space between the mylohyoid muscle and the mucosa of the floor of

the mouth contains the three extrinsic muscles of the tongue: the hyoglossus,

genioglossus, and the styloglossus.

Laterally, this space contains the sublingual gland, the submandibular gland duct,

the lingual nerve, and branches of the lingual artery.

The lingual artery and vein supply the floor of the mouth.

The artery arises from the external carotid and enters the oral cavity deep to the

hyoglossus muscle.

After giving rise to the dorsal lingual artery, which supplies the base of the tongue,

the lingual artery terminates in the sublingual and deep lingual arteries, which

supply the floor of the mouth.

A branch of the mandibular nerve (V3) supplies the mylohyoid muscle.

Branches of the lingual nerve provide sensory innervation to the floor of the mouth.

The lymph vessels of the floor of the mouth spring from an extensive submucosal

plexus that forms two discrete systems: a superficial mucosa and a deep collecting.

The superficial system has crossing afferent lymphatic vessels in the anterior floor of

the mouth, where no definite midline exists. These channels drain into the ipsilateral

and contralateral preglandular lymph nodes.


Dr. Firas Kassab

The deep collecting system drains into the ipsilateral preglandular nodes.

Only the most anterior collecting vessels of the deep system cross the midline.

Lymph channels from the posterior portion of the floor of the mouth drain directly

into the jugulodigastric and jugulocarotid nodes.

Malignant tumors of the floor of the mouth usually occur anteriorly near the midline

and spread to such contiguous structures as the root of the tongue and the

mandible.

Tumors near the orifice of the submandibular duct frequently track along the duct.

Tumors may also extend far along the lingual nerve.

As cancer encroaches on the lingual cortex of the mandible, it extends downward

through the mylohyoid into the submandibular space to involve the submandibular

gland and occasionally the subcutaneous tissues and skin.

The tongue is no barrier to the spread of cancer from the anterior floor of the

mouth.

The tumor frequently invades the anterior musculature of the tongue and tracks

inferiorly as far as the hyoid bone and, in rare instances, into the prelaryngeal space.

Pathology and Patterns of Spread

Most floor of mouth neoplasms are squamous cell carcinomas; most are moderately

differentiated. Adenoid cystic and mucoepidermoid carcinomas arise from the minor

salivary glands and account for 2% to 3% of floor of mouth malignant tumors.

Most floor of mouth carcinomas are located in the anterior midline adjacent to

Wharton’s ducts. Extension toward the gingiva and periosteum occurs early and

frequently.

Small to moderate-size (stage T1 and T2) lesions are associated with metastases to

the ipsilateral regional lymph nodes in 15% to 38% of cases, depending on the size

and depth of invasion of the primary tumor.


Dr. Firas Kassab

Floor of Mouth Carcinomas: Correlation of Primary Tumor Thickness with Neck

FailureThickness (mm) T1N0 T2N0

0.1 to 1.5 1/38 (3%) 0/19

1.6 to 3.5 1/5 (20%) 3/7 (43%)

≥3.6 7/11 (64%) 2/4 (50%)

shows the distribution of clinically positive neck nodes at diagnosis and depicts

the distribution of pathologically positive nodes after elective neck dissection in

patients with carcinoma of the floor of the mouth.64 The incidence of positive

lymph nodes was 19% for those with T1 or T2 lesions and 26% for patients with

T3 or T4 cancers.

Carcinoma of the floor of the mouth.


Dr. Firas Kassab

The distribution of involved neck nodes in the N0 neck

Clinical Manifestations, Patient Evaluation, and Staging

Floor of mouth carcinomas usually present as slightly elevated mucosal lesions

with well-defined borders. A background of leukoplakia may be present. The

lesions are often diagnosed by a dentist or physician during a routine physical

examination.

T1 and T2 tumors may be noted initially when the patient feels a lump in the

floor of the mouth with the tip of the tongue. Advanced lesions tend to produce

pain, bleeding, foul breath, loose teeth, and change in speech as the result of

fixation of the tongue.


Dr. Firas Kassab

Bimanual palpation is necessary to accurately determine the extent of induration

and degree of fixation to the periosteum. Extensive lesions may exhibit invasion

into the soft tissues of the neck or skin.

The AJCC staging system is based on tumor size and invasion of adjacent

structures such as bone or soft tissue of the neck. Radiographic studies may

facilitate staging with reference to (1) the status of the mandible and teeth,

(2) the deep extent of the tumor,

(3) the evaluation of the regional lymph

nodes. CT scans should be obtained in essentially all patients. The mandible may

be evaluated by panoramic x-ray films, dental films, and CT scanning. Magnetic

resonance imaging (MRI) is useful to evaluate marrow space invasion and

perineural involvement.

The role of PET scanning as part of the initial staging workup for oral cavity

cancers has not gained widespread acceptance. It may, however, be useful in

early detection of recurrences and in prediction of which patients may benefit

from elective neck dissection after chemoradiation.

Treatment

Early Lesions (T1 and Superficial T2)

Surgery and radiation therapy produce equal cure rates for T1 and superficial T2

lesions. The risk of irradiation-induced bone and soft tissue necrosis is significant.

Therefore, surgery is usually the treatment of choice. The neck is also treated

with an elective neck dissection,70 although some advocate observation of the

neck in select patients with clinically negative nodes (cN0).


Dr. Firas Kassab

Treatment algorithm for de novo floor of mouth cancer. *Treat neck with neck

dissection or radiotherapy in any patient with a primary lesion that is more than

1.5 mm thick.60 † Concomitant chemotherapy may be used.

Sentinel lymph node biopsy is being investigated for possible use in oral cavity

cancers. However, a recent study showed that this procedure was less sensitive

for floor of mouth cancers (80%) compared with other oral sites (100%).

Some patients present after excisional biopsy of the primary tumor. If the

margins are either close or involved and there is no evidence of visible or

palpable residual tumor, an interstitial implant alone to the primary site is a good

alternative provided that the depth of invasion is less than 1.5 mm. Re-excision

may not be feasible, because the surgeon does not know exactly what to

remove. An additional advantage of RT is the ability to treat a larger area.

Moderately Advanced Lesions (Large T2 and Exophytic T3)

Infiltrative lesions with fixation or tethering to inner tables of the mandible are

best treated by excision with resection of the periosteum with or without a rim of


Dr. Firas Kassab

mandible. Postoperative RT is indicated for patients with close (≤5 mm) or

positive margins, perineural invasion, and/or lymphatic space invasion.

One common indication for adjuvant RT is the inability of the surgeon to obtain

adequate margins of resection, because this often leads to local recurrence,

even if immediate re-excision is performed. Jacobs and associates and Laramore

and colleagues reported a large intergroup study where adjuvant postoperative

EBRT (60 Gy) was administered for locally advanced cancers. They found that

the relapse rate was 11% in patients with satisfactory margins and 26% in those

with unsatisfactory margins. Unsatisfactory margins tend to reflect a higher

residual tumor burden; therefore it may be prudent to deliver a higher dose of

postoperative RT. At the University of Florida, patients with involved margins

receive hyperfractionated irradiation to increase the dose given to the primary

site while minimizing the potential late morbidity.

Locally Advanced Lesions (Endophytic T3 and T4)

Patients with locally advanced floor of mouth cancers are treated with surgery

followed by postoperative RT. In some cases, preoperative irradiation can be

used for unresectable tumors. Patients with extensive tongue invasion with

fixation or extension into the soft tissues of the neck, as well as those with

massive neck disease, can be treated with palliative RT (30 Gy in 10 fractions or

20 Gy in 2 fractions with a 1-week interfraction interval).

Concomitant Postoperative Chemoradiation

The issue of whether concomitant chemotherapy is beneficial when administered

with postoperative irradiation for head and neck cancer was recently addressed

by two randomized trials (RTOG 9501 and EORTC 22931). Each of these showed


Dr. Firas Kassab

an improvement in locoregional control and DFS when cisplatin (100 mg/m2) was

given on days 1, 22, and 43 of the EBRT regimen. Severe acute effects are seen

more frequently with chemoradiation compared with postoperative RT alone

Irradiation Techniques

Because of the proximity of the gingival ridge, which is vulnerable to high-dose

irradiation-induced soft tissue injury or osteoradionecrosis, the floor of the mouth

has a lower radiation therapy tolerance than other portions of the oral cavity.

Therefore preirradiation and postirradiation oral care is critical.

T1 and T2 Cancers

Patients with superficial (≤4 mm thick), well-differentiated squamous cell

carcinomas of the floor of the mouth may be treated either with brachytherapy

alone or, when accessible, with intraoral cone irradiation. Brachytherapy is not

feasible if the tumor abuts or extends onto the mandibular alveolar ridge because

of the risk of bone exposure. Brachytherapy may be performed with either rigid

cesium needles mounted in a customized template or with iridium using the

plastic tube technique. The rigid needles are preferable because although the

needles are active, the implant can be accomplished rapidly because the needles

are mounted in a rigid template . An additional advantage of this technique is

that the geometry of the implant is optimal and dosimetry can be obtained

before the implant. The vertical needles are spaced approximately 1 cm apart

with a crosser to ensure an adequate surface dose. The implant is anchored in

place by a suture placed through the submentum into the floor of the mouth.


Dr. Firas Kassab

Custom-made implant device for T1 to T2 cancers of the floor of the mouth. Note the single crossing needle

through the center of the device (arrowheads). The device is now machined from nylon. Cesium needles

have replaced the radium needles.


Dr. Firas Kassab

Intraoral cone irradiation is administered with either orthovoltage x rays or electrons.

Orthovoltage x rays are preferred because there is less beam constriction and the

surface dose is higher. Before each treatment, it is necessary for the radiation

oncologist to verify the position of the tumor relative to the intraoral cone. Because

a small volume of tissue is included in the intraoral cone field, the dose per fraction

may be increased to 2.5 to 3 Gy once daily.

Cancers thicker than 4 mm and those that are poorly differentiated have an

increased risk of subclinical disease in the regional nodes. The first-echelon nodes

for the floor of the mouth are the level I and II nodes. EBRT is delivered with either

4-MV or 6-MV x-rays using parallel opposed fields that encompass the primary tumor

as well as the first-echelon nodes. An intraoral stent is placed in the mouth to

displace the maxilla and upper lip out of the fields

The EBRT fields are treated to 46 Gy in 23 fractions once daily or 38.4 Gy at 1.6

Gy per fraction twice daily. Brachytherapy follows the EBRT if that is the

technique selected to boost the tumor. If intraoral cone radiation therapy is

selected to boost the tumor, it precedes the EBRT so the extent of the tumor can

be optimally defined and because it may be difficult to place the cone after EBRT

because of patient discomfort. The total dose ranges from 65 to 70 Gy.


Dr. Firas Kassab

Buccal mucosa

The buccal mucosa includes the entire membrane lining of the interior surface of

the cheek and lips, from the opposing lip’s line of contact to the

pterygomandibular raphe posteriorly and to the line of attachment of the alveolar

ridge mucosa above and below.

The buccal mucosa forms the lateral wall of the oral vestibule.

The buccinator muscle is the lateral muscular wall of the oral cavity and, along

with the orbicular mouth muscle, helps to determine oral competence.

It extends from the superior constrictor of the pharynx and blends with orbicular

muscle fibers in the upper and lower lips.

Tumors of the buccal mucosa may extend laterally through the buccinator muscle

to involve the buccal fat pad posteriorly or subcutaneous tissues and skin of the

cheek.

The buccal branch of CN VII is the motor supply to the buccinator muscle.

It runs in the same direction as the buccal branch of CN V (V3), which provides

sensory innervation to the cheek.

The infraorbital (V2) and mental (V3) nerves provide additional sensory

innervation to the anterior buccal mucosa.

Lymphatics of the buccal mucosa arise from a submucosal capillary network and

drain to lymph nodes located in the submental and submandibular triangles.

Upper and lower alveolar ridges

The alveolar ridges include the alveolar processes of the mandible and maxilla

and their mucosal covering that, in the case of the lower alveolar ridge, extends

from the line of attachment of mucosa in the buccal gutter to the line of free

mucosa in the floor of the mouth.

Posteriorly, the lower alveolar ridge’s mucosa extends to the ascending ramus of

the mandible.


Dr. Firas Kassab

The upper alveolar ridge’s mucosa extends from the line of attachment of

mucosa in the upper buccal gutter to the junction of the hard palate.

Its posterior margin is the upper end of the pterygopalatine arch. Malignancies of

the upper gingiva readily invade underlying bone and may extend upward into

the floor of the nasal cavity or into the maxillary antrum.

Lateral spread will result in involvement of the upper buccal sulcus and buccal

mucosa. Medial extension will involve the hard palate.

The maxillary nerve (V2) provides innervation to the teeth of the upper jaw

through the posterosuperior and anterosuperior alveolar nerves.

Different sensory branches of the maxillary nerve innervate the lingual and labial

gingiva of the upper alveolus.

The greater palatine nerve supplies the lingual side of the alveolus behind the

premaxilla.

The nasopalatine nerve supplies the lingual gingiva of the premaxilla; two

different branches of the maxillary nerve innervate the labial surface of the upper

alveolar gingiva.

The posterosuperior alveolar nerve, which descends on the infratemporal surface

of the maxilla, supplies the gingiva posterior to the premaxilla.

Branches of the infraorbital nerve supply the labial gingiva.

The mandibular nerve (V3) innervates the teeth and gingiva of the lower jaw.

The teeth are also innervated by the inferior alveolar nerve, which enters the

mandibular foramen and runs the length of the mandible in the mandibular canal

to exit the mental foramen.

Malignancies arising on the alveolus may infiltrate bone and reach the

mandibular canal, where the tumor may follow the mandible along the nerve

toward the skull base or through the mental foramen and into the skin of the

lower lip and chin.


Dr. Firas Kassab

In edentulous persons the alveolar bone is absorbed, and the mandibular canal

may be only a few millimeters from the mandible’s upper margin, providing for

early access of the tumor into the mandible’s medullary portion.

Branches of the lingual nerve supply the entire lingual gingiva of the lower

alveolus.

The buccal nerve (V3) supplies the labial surface behind the canine tooth; the

mental nerve supplies the surface in front of the canines.

The posterosuperior alveolar artery and vein provide the blood supply to the

upper alveolus. The greater palatine artery and vein also contribute to the lingual

aspect. The inferior alveolar artery and vein primarily supply the lower alveolus.

Lymphatics of the buccal aspect of the upper and lower alveolar ridges drain to

submental and submandibular lymph nodes.

Lymphatics from the lingual aspect of the upper and lower gingiva pass chiefly to

upper deep jugular and lateral retropharyngeal lymph nodes.

Some channels may drain to lymph nodes adjacent to the tail of the parotid

gland (subparotid). Lymphatics from the lingual surface of the lower alveolus also

may end in submandibular nodes.

Retromolar trigone

The retromolar trigone is the attached gingiva overlying the ascending ramus of

the mandible.

The distal surface of the last lower molar forms the base of this triangular area,

and its apex terminates at the maxillary tuberosity.

The upward extension of the oblique line of the mandible to the coronoid process

forms the triangle’s lateral side, and a line connecting the distal lingual cusp of

the last molar and the coronoid process forms the medial side.

The triangle’s base is continuous laterally with the gingivobuccal sulcus and

medially with the gingivolingual sulcus.

The triangle’s lateral side is continuous with the buccal mucosa, and the medial

side blends into the anterior tonsillar pillars.


Dr. Firas Kassab

The mucosa adheres closely to the underlying bone in the region of the

retromolar trigone, and malignant tumors arising in this area may readily

infiltrate the mandible.

The inferior alveolar nerve enters the mandibular foramen at a point just

posterior to the midpoint of the trigone’s medial side and may be affected by

neoplasm early in the course of disease.

Nerve twigs from the ninth cranial (glossopharyngeal) nerve and branches of the

lesser palatine nerve (V2) provide sensory innervation to the retromolar triangle.

The contribution of CN IX accounts for the referred ear pain that may be

observed in patients with cancer arising in this region

Hard palate

The hard palate is a semilunar area consisting of mucous membranes covering

the horizontal laminae of the palatine bones.

The upper alveolar ridge partly surrounds the hard palate, which extends from

the inner surface of the superior alveolar ridge to the posterior edge of the

palatine bone.

Each palatine bone is somewhat L-shaped.

The palate’s horizontal lamina meets the other side’s lamina in the midline,

forming the secondary palate, and the perpendicular lamina runs upward,

forming the posterolateral wall of the nasal passage.

The fusion of the palatine processes of the two maxillae, known as the primary

palate, forms the bony palate in front of the palatine bone’s horizontal laminae.

The primary palate is part of the premaxilla, or the bone that bears the incisor

teeth. Its union with the posterior portion of the hard palate is marked in the

midline by the incisive fossa.

Two or more foramina are located posterolaterally on either side near the

junction of the hard and soft palate.


Dr. Firas Kassab

The larger is the greater palatine foramen, and behind this are one or two lesser

palatine foramina.

These foramina represent the lower end of the pterygopalatine canal, through

which nerves and vessels are conducted from the pterygopalatine fossa to supply

the hard and soft palate.

The foramina provide access for tumor spread into the pterygopalatine fossa and

regions of the skull base.

Likewise, the incisive fossa and canal provide a pathway for tumor extension into

the nasal cavity.

The hard palate receives its vascular supply from the greater palatine artery and

vein, which are terminal branches of the sphenopalatine vessels.

They gain access to the palate through the greater palatine foramen.

The greater palatine nerve supplies the secondary palate and exits the foramen.

The nasopalatine nerve, a branch of the maxillary nerve (V2) that descends

through the incisive canal from the nasal passage, innervates the primary palate.

Lymphatics of the hard palate are sparse compared with other sites in the oral

cavity.

Drainage is similar to that of the lingual surface of the upper alveolus. Most of

the lymphatics drain into upper deep jugular (subdigastric) or lateral

retropharyngeal nodes.

Lymph channels draining the primary palate may terminate in the prevascular

and retrovascular group of submandibular nodes.

Anterior two thirds of the tongue

The anterior two thirds of the tongue, known as the oral tongue, are considered

part of the oral cavity.

The oral tongue is the freely mobile portion of the tongue that extends anteriorly

from the line of the circumvallate papillae to the root.


Dr. Firas Kassab

The root of the tongue is the undersurface at its junction with the floor of the

mouth.

The oral tongue consists of four anatomic regions: the tip, the lateral borders,

the dorsum, and the undersurface (nonvillous surface).

The base of the tongue is that portion posterior to the circumvallate papillae and

is considered a structure of the oropharynx.

Three extrinsic and three intrinsic muscles on each side compose the tongue.

The extrinsic muscles are the genioglossus, hyoglossus, and styloglossus; these

move the tongue body and alter its shape.

The intrinsic muscles are the inferior lingual, vertical, and transverse; these alter

the shape of the tongue during deglutition and speech.

The tongue has a relatively avascular midline marked by a median fibrous

septum that is attached to the hyoid bone and does not reach the dorsum.

The lingual artery alone provides the arterial supply to the tongue.

It arises from the external carotid artery at the level of the greater horn of the

hyoid and runs forward immediately adjacent to the middle pharyngeal

constrictor, which separates it from the mucosa of the pharynx.

The lingual artery runs deep to the hyoglossus muscle, giving arise to two dorsal

lingual arteries and a single sublingual artery, and continues as the deep artery

to supply the anterior two thirds of the tongue.

Its only anastomosis is with its fellow artery at the tip of the tongue.

Small companion veins accompany the lingual artery. The chief vein of the

tongue, however, is the deep vein, which follows the hyoglossus and is then

joined by the companion veins to form the lingual vein, which ends in the internal

jugular vein.

CN XII runs forward between the submandibular gland and the hyoglossus

muscle well below the lingual nerve.


Dr. Firas Kassab

As it crosses the hyoglossus, the nerve innervates the three extrinsic muscles of

the tongue; at the anterior border of this muscle it plunges into the tongue to

supply the intrinsic muscles.

The sensory nerve supply of the oral tongue is the lingual branch of the

mandibular nerve (V3).

The chorda tympani, a branch of CN VII, travels with the lingual nerve and

provides the sensation of taste.

The posterior third of the tongue (tongue base) has a different origin than the

oral tongue and is supplied by CN IX and the superior laryngeal nerve. Both of

these nerves provide sensation and taste to the tongue base.

Lymphatics of the tongue arise from an extensive submucosal plexus, and all

vessels drain ultimately into the deep jugular lymph nodes between the levels of

the digastric and omohyoid muscles.

The nearer the tip of the tongue the lymphatics arise, the lower is the first-

echelon node; and the farther posterior, the higher the node.

Lymphatic collecting channels of the tongue are the anterior (apex), lateral

(marginal), central, and posterior groups.

Vessels from the apex pierce the mylohyoid muscle and partly drain to first-

echelon submental nodes.

The lateral or marginal trunks partly pierce the mylohyoid to end in

submandibular nodes.

The remaining trunks drain on either side of the hyoglossus muscle to deep

jugular nodes.

The central trunks descend in or near the septum of the tongue and follow the

lingual artery to the deep jugular nodes. Lymph channels from the tongue base

pass through the pharyngeal wall laterally below the tonsil to reach principally

the jugulodigastric nodes.

Cancer of the tongue frequently metastasizes bilaterally, primarily because of the

rich lymphatics in the submucosal plexus, which freely communicate across the

midline.


Dr. Firas Kassab

In addition, collecting lymphatic trunks from the apex, central, and posterior

groups have many collecting channels that cross over to terminate in

contralateral lymph nodes.

Malignancies of the tongue frequently grow to considerable size before producing

symptoms.

The relatively loose connective tissues separating the intrinsic musculature

provide little barrier to the advance of cancer.

Symptoms do not occur until the tumor has grown to a size that interferes with

movement, producing dysfunction of speech and deglutition, or when the tumor

has involved the lingual nerve, producing pain.

Cancer of the tongue or the floor of the mouth involving the lingual nerve causes

pain that is typically referred to the ipsilateral ear.

The lingual nerve is a branch of the mandibular nerve (V3) that also provides

sensation to the external auditory meatus, tympanic membrane, and

temporomandibular joint through the auriculotemporal nerve.

Likewise, cancer of the tongue base may also produce referred ear pain because

CN IX provides sensory innervation to the middle ear.

Malignant neoplasms of the oral cavity

Health & Medicine

Transcript of Malignant neoplasms of the oral cavity