Carcinoma Buccal Mucosa:

Anatomy to management

Dr. Ayush Garg

• Anatomy• Epidemiology• Risk Factors• Pre Malignant Lesions• Clinical Features• Pathology• Diagnostic Work Up• Staging• Management• Follow Up

ANATOMY• The buccal mucosa includes the mucosal surfaces of the cheek

and lips from the line of contact of the opposing lips to the pterygomandibular raphe posteriorly.

• This extends to the line of attachment of the mucosa of the upper and lower alveolar ridge superiorly and inferiorly.

• The muscle of the cheek is the buccinator muscle.

• The buccal fat pad is superficial to the fascia covering the buccinator muscle and gives the cheeks a rounded contour.

• Branches of the maxillary and mandibular nerves (cranial nerves V2 and V3) provide sensory innervation to the skin, the cheek, and the mucous membranes lining the cheeks.

• The facial nerve (cranial nerve VII) provides motor innervation to the muscles of the cheeks and lips.

• The lips and cheeks function together as an oral sphincter propelling food into the oral cavity.

• If the facial nerve is paralyzed, food tends to accumulate within the cheek along the affected side so that saliva and food dribble out of the corner of the mouth.

EPIDEMIOLOGY• After carcinoma of the lip, oral tongue, floor of the mouth, and

lower gum, carcinoma of the buccal mucosa is the fifth most common carcinoma of the oral cavity.

• It is the most common carcinoma of the oral cavity in India, Malaysia, and Taiwan.

• It usually occurs in the sixth and seventh decades of life, and is more prevalent in men than in women.

• Tobacco and betel nut chewing appear to play an important role in the cause of these tumors.

• Carcinomas of the buccal mucosa often occur in association with pre-existing leukoplakia and tend to have multiple primary sites and recurrence.

• Excision of the oral leukoplakia may reduce the subsequent development of carcinoma.

• These tumors usually arise in the area adjacent to the lower molars along the occlusal line of the teeth.

RISK FACTORS

PREMALIGNANT LESIONS • Leukoplakia - A chronic white mucosal

macule which cannot be scraped off, cannot be given another specific diagnostic name, and does not disappear with removal of potential etiologic factors (excepting tobacco).

• 4-18% progress to invasive carcinoma

ERYTHROPLAKIA

• Erythroplakia is the clinical diagnostic term - A chronic red mucosal macule which cannot be given another specific diagnostic name and cannot be attributed to traumatic, vascular or inflammatory causes, i.e. it is a diagnosis of exclusion.

• Higher risk of cancer development • (approx 30%)

Oral Sub mucous fibrosis 4.5 – 7.5 % progress to oral cancer

• Clinically, there are three distinct types: exophytic, ulcerative, and verrucous.

• The patient may present with pain or bleeding, trismus, or cervical lymphadenopathy.

• Posterior extension may result in involvement of the lingual or dental nerves, which may cause ear pain.

• Extension behind the pterygomandibular raphe into the pterygoid muscles or into the buccinator and masseter muscles may cause trismus.

Exophytic Ulcerative

Verrucous

• In advanced stages, the tumor may destroy the entire cheek and invade the adjacent bones and the neck. Infection is common and mastication becomes difficult. Death usually occurs as a result of poor nutrition and general debilitation

CLINICAL FEATURES• Non Healing ulcer• Pain• Bleeding• Dysphagia• Referred pain to ear• Hypersalivation• Trismus

Trismus

Classification

ROUTES OF SPREAD• Infiltrating lesions of the buccal mucosa can invade the

buccinator muscle, extend to the buccal fat pad, and invade the subcutaneous tissue.

• Carcinomas of the buccal mucosa frequently spread by direct invasion into the gingivobuccal sulcus, the upper and lower alveolar ridges, the hard palate, the maxilla, and the mandible.

• Lymph node metastasis occurs in approximately 9% to 31% of the patients during the course of the disease.

• The risk of subclinical disease is 16%.

• Distant metastases are rare, as patients often die of uncontrolled local disease before distant metastases are manifested clinically.

PATHOLOGY• >90 % Squamous cell carcinomas

• Spectrum of diseases from benign lesions like leukoplakia, lichen planus, SMF to verrucous carcinoma to well differentiated squamous carcinoma

• Malignant Minor salivary gland tumors such as Adenoid cystic, Adenocarcinoma, Mucoepidermiod carcinoma (< 10%) are uncommon

• Malignant Melanoma, Lymphoma, Sarcoma occur rarely.

DIAGNOSTIC WORK UP• History & Clinical examination , including head & neck

examination

• Clinical staging

• Assessment of performance & nutritional status

• Investigations for histological diagnosis – Punch Biopsy

Investigations to determine the extent of the disease

• OPG/ Dental examination

• CT Scan / MRI for extent of disease

• USG for N0 neck in select cases

Routine Investigations

• CXR

• Routine blood counts

• Blood chemistry profile

STAGINGT4a-Moderately advanced local disease.• Tumor invades adjacent structures

only (e.g., through cortical bone, [mandible or maxilla] into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face)

T4b-Very advanced local disease.• Tumor invades masticator space,

pterygoid plates, or skull base and/or encases internal carotid artery

• DISTANT METASTASIS (M)• M0-No distant metastasis (no pathologic M0; use clinical

M to complete stage group)• M1-Distant metastasis

GROUP T N M0 Tis N0 M0I T1 N0 M0II T2 N0 M0III T3 N0 M0

T1 N1 M0T2 N1 M0

T3 N1 M0IVA T4a N0 M0

T4a N1 M0T1 N2 M0T2 N2 M0T3 N2 M0T4a N2 M0

IVB Any T N3 M0T4b Any N M0

IVC Any T Any N M1

GROUP T N M 0 Tis N0 M0 I T1 N0 M0 II T2 N0 M0 III T3 N0 M0

T1 N1 M0 T2 N1 M0

T3 N1 M0 IVA T4a N0 M0

T4a N1 M0 T1 N2 M0 T2 N2 M0 T3 N2 M0 T4a N2 M0

IVB Any T N3 M0 T4b Any N M0

IVC Any T Any N M1

PROGNOSTIC FACTORS

Intent of treatment• Stage I – IV A : Curative

• Stage IV B-C : Palliative

The aim of treatment:• Cure• Loco regional control• Preservation of anatomy & function• Reasonable cosmesis• Quality of life

TREATMENT ALGORITHM

T1-2 N0• Excision of primary (preferred) ± unilateral or bilateral selective

neck dissection.

• Neck treatment (dissection or RT) required for lesions >1.5–3 mm thick.

• For +margin only, re-excise if feasible.

• Post-op RT for pT3/T4, close margin, multiple nodes, PNI, and/or LVSI, or level IV–V nodes

• Post-op chemo-RT indicated for +margin, ECE • Alternatively, EBRT ± brachytherapy. Salvage surgery for

residual disease

T3 N0• Excision of primary and unilateral or bilateral selective

neck dissection.

• Reconstruction as indicated.

• For +margin only, reexcise if feasible.

• Post-op RT for all; chemo-RT indicated for +margin, ECE

T4a or N1-3• Excision of primary and ipsilateral comprehensive neck dissection ±

contralateral selective neck dissection, or bilateral neck dissection (for N2c).

• Reconstruction as indicated.

• For +margin only, reexcise if feasible.

• Post-op RT for pT3/T4, close margin, multiple nodes, PNI, and/or LVSI, or level IV–V nodes

• May consider post-op RT for N1 as only risk feature

• Post-op chemo-RT indicated for +margin, ECE

Unresectable• Concomitant chemo-RT (preferred).

• Alternatively, induction chemotherapy followed by chemo-RT, or altered fractionation RT alone if unable to tolerate chemo.

• If primary has < CR, salvage surgery controversial.

• If residual neck mass by CT/MRI or PET at 6–12 weeks, post-RT neck dissection considered

VERRUCOUS CARCINOMA• Perceived risk that the tumor may become more aggressive if it

recurs after RT.

• Many tumors that recur after treatment are biologically more aggressive. Therefore, it is reasonable to treat these lesions with irradiation if surgery is not feasible.

• Wang reported a series of patients with verrucous carcinoma treated with RT; the results were comparable to those for patients treated for squamous cell carcinoma.

SURGERY• Used as single modality in early disease (Stage I & II )

• Combined with post operative adjuvant radiotherapy in advanced disease(Stage III & IV)

• Wide excision of tumor in all dimensions with adequate margins & appropriate neck dissection essential for locoregional control of disease

ADVANTAGES OF SURGERY• Treatment time is shorter.

• The risk of immediate and late radiation sequel are avoided.

• Irradiation is reserved for recurrence, which may not be resectable.

• Pathological assessment, accurate staging.

Disadvantage: functional & cosmetic impairment, increased morbidity when bilateral neck is addressed.

• Modified neck dissection is sufficient treatment for the ipsilateral neck for patients with N1 without PNI.

• Radiation therapy is added for

• N1 with PNI/LVI• N2,N3 stages, for control of contra lateral subclinical disease• For invasion through the capsule of the node,• For multiple positive nodes

NECK DISSECTION

• RND : superficial & deep cervical fascia with its enclosed LN (level I-V) is removed in continuity of SCM, omohyoid muscle, internal & external jugular veins, spinal accessory N & submandibular gland

• MND : is finding more acceptance & preference to RND in managing N0 neck because of severe morbidity related to RND such as, shoulder dysfunction, poor cosmesis, facial edema (level I-V LN)

• SOHND : least morbid, provides most satisfactory sampling of the LN at the level I, II, III which are greatest risk

• Extended SOHND : level I-IV LN dissection

NCCN GUIDELINES FOR NECK TREATMENT

MANDIBULECTOMY• Marginal mandibulectomy: partial-thickness (marginal) mandibular

resection • Segmental Mandibulectomy

For small lesions with minimal bone invasion, a short section of mandible is removed in continuity with the tumor (e.g., removal of the mandible from the angle to the mental foramen).

• Hemimandibulectomy- Removal of the mandible symphysis to the condyle on one side.

- Major cosmetic and functional loss - Reconstruction is performed with a composite osteomyocutaneous flap

MARGINAL MANDIBULECTOMY SEGMENTAL MANDIBULECTOMY

HPE REPORTGross pathology1. Morphology2. Location & extent of the tumor / lesion3. Tumor dimensions 4. Distance from various margins of excision5. Nodal dissection

Microscopy1. Histologic type2. Grade3. Extent of disease including depth of infiltration4. Perineural invasion5. Extracapsular Spread6. Lymphovascular Invasion7. Bone / Cartilage / Skin / Soft tissue involvement8. Margins of excision, submucosal spread, In – situ changes9. Nodal status – no. & size of nodes, perinodal extension &

level of nodes 10. Status of cut margins

Miscellaneous features1. In RND/ MND status of internal jugular vein2. Presence of predisposing factors - leukoplakia, SMF3. Dysplasia/ in situ elements

• Unresectable Disease

Primary disease• Adequate surgical clearance is not achievable• Extensive Infra Temporal Fossa involvement • Extensive involvement of base skull • Extensive soft tissue disease – skin edema / ulceration

Nodal disease• Clinically fixed nodes• Infiltration of Internal / Common carotid artery• Extensive infiltration of prevertebral muscles

IRRADIATION

• Better functional and cosmetic outcome

• Elective irradiation of the lymph nodes can be included with little added morbidity, whereas the surgeon must either observe the neck or proceed with an elective neck dissection (sometimes bilateral depending on the primary site),

• The surgical salvage of irradiation failure is probably more likely than the salvage of a surgical failure.

• The risk of postoperative complications is avoided

INDICATIONS OF POST OP RT Primary:• Advanced primary – T3 or T4• Close or positive margins of excision• Depth of invasion • High grade tumor• LVI & PNI

Nodes:• Bulky nodal disease N2/N3• Extra nodal extension• Multiple level involvement

INDICATIONS OF POST OP CHEMO RT• Extracapsular nodal involvement

• Positive Surgical Margin

RADIOTHERAPY BORDERS

• T3 and T4 lesions

• Patients with significant tumor extension toward the midline are treated with parallel opposed fields weighted 3 : 2 toward the side of the lesion.

• The low neck is treated with an anterior field with a 6-MV X-Ray beam to 50 Gy in 25 fractions once daily

3D CRT TARGET VOLUMES

RT DOSE• Doses of 66-70 Gy in 1.8-2-Gy per fraction is given over 6.5-7

weeks

• Phase 1- 44 Gy is given over 4.5 weeks

• Phase 2-26 Gy is given over 2.5 weeks

• A LAN is often used, treated to either 50 Gy in 2-Gy fractions or 50.4 Gy in 1.8-Gy fractions.

ROLE OF IMRT

PASSPORT Trial: Numbers not enough to establish non- inferiority

Conventional Radiotherapy

IMRT

2 year PFS 80% 78%

Estimated 2 year OS

76% 78%

IMRT TARGET VOLUMES• GTV

Gross tumor on imaging studies

• CTV• High risk: GTV• Intermediate risk: areas with high likelihood of nodal

disease or tumor spread• Low risk: elective nodal treatment

• PTVCTV plus 3–5 mm

DOSE RECOMMENDATION• A total dose of 66–70 Gy in 30–33 fractions using

simultaneous integrated boost (SIB) technique with 7–14 coplanar fields can be used according to the shape of PTV:

• High-risk PTV: 70 Gy to high-risk CTV

• Intermediate-risk PTV: 59.4 Gy

• Low-risk elective PTV: 50–54 Gy

PRESCRIPTION FOR HEAD & NECK IMRT• 95 % prescription dose to cover 98% of high dose PTV• Prescription dose to cover at least 91% of high dose PTV• 95% dose to cover at least 95% of low risk PTV• Avoid hotspots > 107%• Parotid• PRV Spine• Mandible

BRACHYTHERAPY• Accessible lesions• Small (preferably < 3cm ) tumors• Well defined borders• Lesion away from bone• Superficial lesions

• Tumors of the anterior two thirds of the buccal mucosa without involvement of gingiva are ideally suited for brachytherapy alone.

• Interstitial implants with iridium wires or seeds in nylon ribbons can be considered for treatment of early, small lesions that have not invaded the buccogingival sulcus, the gingiva, or bone.

• Usually a minimum tumor dose of 60 to 70 Gy in 5 to 8 days is delivered through a single-plane or double-plane implant on the thickness of the lesion.

• The buccal mucosa tolerates high-dose RT with a low risk of late complications.

• Trismus may develop if the muscles of mastication receive high doses of irradiation.

CHEMOTHERAPY

• Cisplatin - Used in NACT (T4b and N3 cases)

- Used in CTRT

FOLLOW UP

THANK YOU

Table 1. Re-irradiation for Head and Neck cancer (various sites)

Author Year Site Treatment Radiotherapy Outcome Adverse reaction Bleeding †Prognostic factors

(Institute) (Pt No.) [Median preRT dose / RT interval (M)] RR/ 2yOS/ 2yLC/ MST

Conventional 6De Crevoisier 1998 Various rec/2nd (1) Conv. RT 27 (1) RT 65Gy (1) RR 41% / 2y OS 25% / 5y OS 6% / MST 10M Acute G4< 13% 5 /169 (2.9%) Small volume irradiation favorable

(Gustave-Roussy) (169) [65Gy/ 40M] (2) Conv. RT+CTX 106 (2) Voks protocol: HU+5-FU+RT60Gy (2) RR 48%/ 2yOS 24%/ 5yOS 14%/ MST 10M Severe 29%

(3) HfxRT+CTX 36 (3) MMC, 5-FU+1.5 Gy/bid 60Gy (3) RR 63%/ 2y OS 10%/ 5y OS 0%/ MST 11M G2-3 fibrosis 41%, mucosal necrosis 21%,

Higher RT dose favorable16Ohizumi 2002 Various rec Conv. RT, HfxRT± CTX 53Gy RR64%/ 2y OS 10% Acute severe 2/44 (4.5%) none Overlapping RT field 40 cc < favorable

(Tokai Univ) (44) [62.1Gy (mean) / 13.5M] Late severe 5 (11%), laryngeal edema etc. NPC, OPC, kkk favorable

18Salama 2006 Various rec/2nd rec 66： 2nd 49 Micro lesion 60Gy/Macro lesion 66-70Gｙ 3y OS 22%/ 3y LRC 33%/ MST 11M 21 G4< (18%) 6 /115 (5.2%) 2nd (vs. rec) favorable

(Chicago Univ) (115) [67.5Gy/NA] Conv. RT, HfxRT± CTX Conv. RT 2Gy/day or Hfx RT 1.5Gy x 2/day Lethal 19 (16.5%) Carotid blow-out 5 > 1Y interval / CTX(GEM etc) favorable

inOP49/ OP49 inOp 2yOS 11% vs. OP 2yOS 39% OP (vs. inOP) favorable

19Spencer 2006 Various rec/2nd HfxRT + CTX 60Gy 2y OS 15.2%/ 5y OS 3.8%/ MST8.8M Acute G4 17.7%, G5 7.6% 1 (1%) > 1Y interval favorable

(RTOG96-10) (81) [55-65Gy / 24M] HU +5-FU 1.5 Gy/bid x 5d other weekx4 Lethal 6/81(7%) on treatment

10Langer 2007 Various rec/2nd HfxRT + CTX 60Gy 2y OS 25.9%/ MST12M Acute G4< 28% 2/81 (2.4%)

(RTOG99-11) (105) [65.4Gy/ 39.6M] cisplatin+paclitaxel+GCSF 1.5 Gy/bid x 5d other weekx4 Lethal 8 (acute 5, late 3)

22McDonald 2011 Various rec/2nd Various Various Various 1.8-2Gy QD or 1.2Gy bid bleeding 1.3%-1.8% 41/1554 (2.6%) 76% fatal

(Review) (1554) 1.5 Gy bid or delayed accelerating HfxRT bleeding 4.5%

IMRT20Sulman 2009 Various rec CTX 26 60Gy 2y OS 58%/ 2y LRC 64% Severe 15 (20%) none Younger favorable

(MDAC) (74) [60Gy/ 46M] platinum based Death 1 (unknown cause) Male favorable

23Popovtzer 2009 Various rec/2nd HfxRT ± CTX 68Gy 2y OS 40%/ 2y LC 27% Acute G3 26, G4 11 2/66 (3%) Almost recurrence occurred

(Michigan Univ) (66) [64Gy/ 37M] CTX 47 (cisplatin etc.) 1.25Gybidx6wks (1wk interval in midway) Late G3 < 19 (29%) surgically salvaged inside irradiated area

24Duprez F 2009 Various rec/2nd OP19 69Gy 2yOS 35%/ 2y LCR 48%/ MST13.4M Acute G3< 26 (31%) 2/84 (2.3%) T4, short interval, HPC unfavorable

(Belgium) (84) [61Gy/ 49.5M] CTX17 (cisplatin etc.) Late G3 < 11 (14%)

25Biagioli 2007 Various rec CTX 60Gy/30fr, each other week RR76%/ 2y OS 48.7% Acute G3< 32% 1/41 (2.5%)

(Miami) (41) [60Gy/ 25M] Cisplatin or CBDCA Late 6

26Lee 2007 Various rec IMRT 74, nonIMRT 31 59.4Gy RR50%/ 2yOS 37%/ 2yLRPFS 42%/ MST15M Acute G3-4 23% none NPC favorable

(MSK) (105) [62Gy/ 38M] 71% CTX Late G3-4 15 % (severe 11%) > 50Gy favorable

Abbreviations: MSK; Memorial Sloan-Kettering Cancer Center, MDAC; MD Anderson Cancer Center, rec; recurrence, 2nd; second primary, LC; local control, OS; overall survival, RR; response rate, DSS: disease-specific survival, LRC: locoregional control, MST; median survival time

NA; not available, OP; surgery, inOP; inoperative case, QD; once a day, bid; twice a day

RT; radiotherapy, Conv. RT; conventional fractionated radiation, HfxRT; hyperfractionated radiation, CTX; Chemotherapy, HU; Hydroxyurea, 5-FU; 5 fluorouracil, CBDCA.; Carboplatin, GEM; Gemcitabine

†prognostic factors for overall survival if otherwise stated