J6

Cnidtac

Wchasp

S

S

l

p

H

v

©

0

d

Oral Maxillofac Surg9:340-345, 2011

Pattern of Lymphatic Spread FromCarcinoma of the Buccal Mucosa and Its

Implication for Less Than Radical SurgeryManoj Pandey, MS,* Mridula Shukla, DipNB,† and

C.S. Nithya, MDS‡

Purpose: With emerging evidence, focus is shifting to conservative neck procedures aimed at achiev-ing good shoulder function without compromising oncologic safety.

Patients and Methods: Retrospective analysis of 100 consecutive neck dissections for carcinoma of thebuccal mucosa was carried out to evaluate the pattern of lymphatic spread. Pathologic results were correlatedwith clinical/radiologic findings. Survival was calculated with the Kaplan-Meier method and log-rank test.

Results: Only 36 patients were found to harbor metastasis in the lymph nodes on pathologic exami-nation. Most of these were present in levels I and II only. Skip metastasis was not detected in any patient.None of the patients was found to have involvement of level V nodes, whereas 1 patient had involvementof level IV. Thirty-four patients developed recurrences; 3-year disease-free survival was 48%.

Conclusions: Lymphatic spread from carcinoma of the buccal mucosa is low. Involvement of level IVis seen in only 1% of patients. A more conservative approach to the neck in patients with carcinoma ofthe buccal mucosa is recommended.© 2011 American Association of Oral and Maxillofacial Surgeons

J Oral Maxillofac Surg 69:340-345, 2011

ntchpotwmcat

tcpg

P

wsbos

t

onsiderable debate has been generated over theeed for radical neck procedures, with surgeons mov-

ng toward less radical, conservative neck proce-ures.1,2 Much data have been generated on cancer ofhe larynx, oropharynx, and tongue,3-10 but the liter-ture is sparse on node distribution in buccal mucosaancer and its clinical relevance.Buccal mucosa cancer is relatively uncommon in theest but is the most common malignancy in Asian

ountries, where it is associated with tobacco use, alco-ol consumption, and betel nut chewing. Most cases aressociated with submucous fibrosis and have beenhown to have a lesser propensity for lymphatic spread,robably because of fibrosis. This low prevalence of

*Head, Department of Surgical Oncology, Institute of Medical

ciences, Banaras Hindu University, Varanasi, India.

†Senior Resident, Department of Pathology, Institute of Medical

ciences, Banaras Hindu University, Varanasi, India.

‡Consultant, Department of Oral Maxillofacial Surgery, Banga-

oru, India.

Address correspondence and reprint requests to Dr Pandey: De-

artment of Surgical Oncology, Institute of Medical Sciences, Banaras

indu University, Varanasi 221005, India; e-mail: manojpandey@

snl.com

2011 American Association of Oral and Maxillofacial Surgeons

278-2391/11/6902-0005$36.00/0

moi:10.1016/j.joms.2010.02.031

340

eck node metastasis should encourage more conserva-ive neck procedures; however, a paucity of data pre-ludes this. In contrast, the presence of nodal metastasisas been shown to be the single most important inde-endent prognostic factor,11-13 which makes surgeonsvertreat the neck rather than take chances with under-reatment.14,15 Survival is lower than 50% for patientsith node-positive disease, and the neck is the secondost common site of failure after local recurrence of

arcinoma of the buccal mucosa.14,15 This makes anppropriate elective approach to neck nodes essential inhese cases.

The present study retrospectively reviewed the pat-ern of lymphatic spread in 100 consecutive cases ofarcinoma of the buccal mucosa to predict a possibleattern on which to base future management strate-ies of these cases.

atients and Methods

A retrospective analysis of 100 consecutive patientsith carcinoma of the buccal mucosa undergoing

urgical treatment of primary tumors and the necketween January 1997 and February 1999 was carriedut to evaluate the pattern of nodal metastasis andurvival.

In addition to age and gender, tumor size, grade ofumor, and clinical and pathologic tumor, node, and

etastasis were recorded. The clinical and pathologic

dptemCmwm

dpey

dCpsciamt

R

(wddcdprp

rpnftflcw

pan2

G

C

C

P

P

Po

S

F

Aj

n

PANDEY, SHUKLA, AND NITHYA 341

istribution of the neck nodes was recorded on presetro forma forms and was correlated with the stage ofhe primary tumor. All patients had undergone anvaluation of neck under anesthesia and clinical tu-or, node, and metastasis were modified if indicated.omputed tomographic (CT) evaluation of the pri-ary tumor and neck was carried out in all patientsith T3 and T4 primary tumors and those with tris-us.All patients underwent neck dissection and after

issections levels were separated and sent to theathology department in separately labeled contain-rs. All patients were followed for a minimum of 2ears and any recurrences were recorded.

STATISTICAL ANALYSIS

Frequency tables were prepared for level of nodeistribution and clinical and nodal stage of disease.ross-tabulations were prepared for clinical andathologic tumor and node staging. Sensitivity andpecificity of clinical examination and CT scan werealculated by combining the cross-tabulation resultsnto true and false positive and negative. Survivalnalysis was carried out using the Kaplan-Meierethod and survival was compared using log-rank

Table 1. DISTRIBUTION OF PATIENT AND DISEASECHARACTERISTICS

Variable No. %

enderMale 62 62Female 38 38

linical tumor stagecT1 9 9cT2 32 32cT3 16 16cT4 43 43

linical node stagecN0 38 38cN1 43 43cN2a 5 5cN2b 12 12cN2c 1 1cN3 1 1

athologic tumor stagepT1 14 14pT2 33 33pT3 12 12pT4 41 41

athologic node stagepN0 64 64pN1 19 19pN2a 2 2pN2b 14 14pN2c 1 1

andey, Shukla, and Nithya. Conservative Treatment of Cancerf the Buccal Mucosa. J Oral Maxillofac Surg 2011.

est.Po

esults

Patients’ mean age � SD was 54.9 � 10.5 yearsrange, 28-79 years). There were 62 men and 38omen. At presentation, 43 patients had clinical T4isease, and 32 had cT2, 16 had cT3, and 9 had cT4isease. Of the 100 consecutive cases, 62 were clini-ally node positive, and most of these were cN1isease (Table 1). On pathologic examination, only 36atients were found to have node positivity, and theest were found to have reactive lymph adenopathy;athologic staging is presented in Table 1.

SURGICAL PROCEDURES

Table 2 presents details of the neck dissection andeconstructive procedures that were carried out. Twoatients also underwent contralateral supraomohyoideck dissection; pathologically, these cases wereound to be negative on the contralateral side. Sixty-hree patients had pectoralis major myocutaneousap reconstruction, and 23 required 2 flaps. Primarylosure was done in only 7 patients, and 2 defectsere treated with skin grafts.

SENSITIVITY OFCLINICAL/RADIOLOGIC EXAMINATION

Table 3 presents a cross-tabulation of clinical andathologic node stages. Thirty patients had true neg-tivity, and 28 had true positivity. Percentages of falseegative and false positive results were 54.8% and1%, respectively. Sensitivity of the combined clinical

Table 2. SURGICAL PROCEDURES

Variable No.

urgical procedure on neckRadical neck dissection 15Vein and nerve preserving neck dissection 8Vein preserving neck dissection 66Supraomohyoid neck dissection* 8Muscle-, nerve-, and vein-preserving neck

dissection 2Nerve-preserving modified neck dissection 1

lap reconstructionPMMC 63Temporalis 1PMMC � DP 23Nasolabial 2Sternocleidomastoid 1Tongue 1STG 2Primary closure without flap 7

bbreviations: DP, deltopectoral flap; PMMC, pectoralis ma-or myocutaneous flap; STG, split-thickness skin grafting.

*Two patients underwent contralateral supraomohyoideck dissection as well.

andey, Shukla, and Nithya. Conservative Treatment of Cancerf the Buccal Mucosa. J Oral Maxillofac Surg 2011.

aietpdblp

TiPiis

(tosdtcaswum1n

D

cm

spbota

otlidntrcpbtmmolccpcpbsl

Po

NLLBLLLLBLLLLLBL

A

342 CONSERVATIVE TREATMENT OF CANCER OF THE BUCCAL MUCOSA

nd radiologic examination was 45.16% with a spec-ficity of 21%. The positive predictive value of clinicalxamination combined with CT scan was 22%, andhe negative predictive value was 46.8%. None of theatients with T3 disease and only 2 patients with pT1isease had pathologic node positivity. Equal num-ers of patients with pT2 and pT4 disease showed

ymph node positivity. Surprisingly, 27 patients withT4 tumors showed pathologic node negativity.

NODE DISTRIBUTION AND TOPOGRAPHY

The distribution of nodal levels is presented inable 4. Only 1 patient had clinical level V node

nvolvement, whereas 8 had level IV involvement.athologically, none of the patients was found to have

nvolvement of level V nodes and only 1 patient hadnvolvement of level IV. None of the patients in thistudy group showed a skip metastasis.

RECURRENCES AND SURVIVAL

After a mean follow-up of 14.5 � 10.3 monthsrange, 1-37 months), 34 recurrences/second primaryumors were seen. Of these 6 had local recurrencesnly, and 9 had nodal recurrences; only 1 patienthowed failure locally and in the neck. Five patientseveloped recurrence of surrounding skin. Two pa-ients developed recurrence in the reconstructed mu-osa, whereas 11 developed second primary tumorst sites away from the primary tumor. Four of theecond primary tumors were on the lower alveolus, 2ere on the tongue, and 1 tumor each was on the lip,pper alveolus, soft palate, retromolar trigone, andaxilla. Overall recurrence-free survival was 48% (Fig

, Table 5). Pathologic node stage was the only sig-ificant predictor of recurrence (P � .03; Fig 2).

iscussion

LYMPH NODE POSITIVITY

The present study shows that the positivity per-entage of lymph nodes in cancers of the buccal

Table 3. CROSS-TABULATION OF CLINICAL ANDPATHOLOGIC NECK NODE STAGE

cN/pN pN0 pN1 pN2a pN2b pN2c Total

cN0 30 5 0 3 0 38cN1 26 12 0 5 0 43cN2a 2 1 2 0 0 5cN2b 5 1 0 6 0 12cN2c 1 0 0 0 0 1cN3 0 0 0 0 1 1

andey, Shukla, and Nithya. Conservative Treatment of Cancerf the Buccal Mucosa. J Oral Maxillofac Surg 2011.

ucosa is low at 36%. Similar results have been ob-Po

erved by other investigators who reported positivityercentages from 20% to 40% in carcinoma of theuccal mucosa compared with other subsites in theral cavity.16-18 A higher incidence of lymphatic me-astasis occurs in other subsites of the oral cavity suchs the tongue5,19,20

ORDERLY PROGRESSIONVERSUS SKIPPING OR PEPPERING

Lymphatic drainage from the oral cavity follows anrderly fashion, starting with the first echelon node tohe next, as a simple overflow.5,20 When this order isost and metastasis is found in higher levels withoutnvolvement of the first echelon node or an interme-iary node group, it is called skip metastasis. Carci-oma of the buccal mucosa has been shown to followhe orderly progression, with skipping being veryare. Among all subsites, skipping to level IV nodes isommonly seen in carcinoma of the tongue.20 In theresent study 32 cases had involvement of level Iefore involvement of any other level. Nineteen pa-ients had involvement of level II without involve-ent of level I, and none of the patients had involve-ent of level III, IV, or V nodes without involvement

f level I or II nodes. Clinically, only 1 patient hadevel V nodes and he had nodes in levels I and II. Itan be safely concluded that lymphatic spread fromarcinoma of the buccal mucosa follows an orderlyrogression, and up to 20% of cases of buccal mucosaancer can have level II as the first echelon of lym-hatic spread. This is significant during sentinel nodeiopsy. Larger studies on mixed samples have foundkip metastasis in up to 6% cases; of these 4% were inevel III and only 2% were in level IV.3 Although no

Table 4. DISTRIBUTION OF NECK NODES

Node Groups Clinical Pathologic

egative 38 64evel I alone 5 16evel II alone 12 4/L level I 1 2evels I and II 10 9evels I and III 1 0evels II and III 3 1evels II and IV 1 0/L level I with I/L level II 4 1evels I, II, and III 10 2evels I, II, and IV 1 1evels I, II, and V 1 0evels II, III, and IV 2 0evels I, II, III, and IV 2 0/L level I with I/L levels II and III 6 0evels II, III, IV, and V 1 0

bbreviations: B/L, bilateral; I/L, ipsilateral.

andey, Shukla, and Nithya. Conservative Treatment of Cancerf the Buccal Mucosa. J Oral Maxillofac Surg 2011.

aotslhf

tlrtss

iTthcaiwrsgrt

tsfFtt56tf

ntvyc

P of the B

OP

P

G

Po

PANDEY, SHUKLA, AND NITHYA 343

ttempt was made in this study to look at the locationf the tumor in the buccal mucosa, one can assumehat the lesions located anteriorly near the commis-ure might have spread to level I, whereas lesionsocated posteriorly near the retromolar trigone mightave spread first to level II; this could be an area foruture study.

SENSITIVITY OFCLINICAL/RADIOLOGIC EXAMINATIONS

The sensitivity and specificity of clinical examina-ion of the neck are very low, and there are severalimiting factors, such as a short neck and previousadiotherapy. Attempts have been made to augmenthis with the addition of examination under anesthe-ia and various radiologic techniques, such as ultra-ound, computed tomography, magnetic resonance

FIGURE 1. Overall recurrence-free s

andey, Shukla, and Nithya. Conservative Treatment of Cancer

Table 5. SURVIVAL (PERCENTAGE)

1 yr 2 yr 3 yr P Value

verall survival 67.7 57.5 48athologic nodes .03N0 75.3 63.5 57.1N1 48.9 40.7 0.0N2 59.2 59.2 59.2

athologic tumor stage .71T1 74.5 74.5 49.7T2 57.4 57.4 43T3 61.3 46 46T4 74.6 54.9 54.9

ender .63Male 67.9 53.3 42.7Female 67.7 59.6 51.1

pandey, Shukla, and Nithya. Conservative Treatment of Cancerf the Buccal Mucosa. J Oral Maxillofac Surg 2011.

maging, and positron emission tomography.10,21-23

he reported sensitivity and specificity vary from cen-er to center and from patient cohort to patient co-ort. We calculated the sensitivity and specificity oflinical nodal positivity by combining the clinical ex-mination with CT findings of the neck. The sensitiv-ty was found to be 46% with a specificity of 21%,

hich is lower than that reported in previous se-ies.2,21,22,24 The reason for this could be the inclu-ion of patients with irradiated primary tumors under-oing salvage surgery in this group, where theadiation changes could have hampered interpreta-ion of the CT findings.

FACTORS AFFECTING NODE POSITIVITY

Efforts have been made to determine the factorshat may affect node positivity. Tumor thickness,tage of primary tumor, and grade of tumor have beenound to be associated with node positivity.17,25,26

ukano et al25 reported that tumor thickness is one ofhe most significant predictors of lymph node metas-asis; tumors thinner than 5 mm are found in only.9%, whereas tumors thicker than 5 mm are found in4%. A wait-and-watch policy has been advocated forhin lesions, and elective neck dissection is an optionor thick lesions.27

EFFECT ON SURVIVAL

Numerous studies have shown that the presence ofeck metastasis is the single most important prognos-ic indicator in carcinoma of the buccal mucosa. Sur-ival has been reported to decrease to below 50% at 5ears in the presence of neck nodes.28,29 This de-rease is greater if it is associated with other poor

in carcinoma of the buccal mucosa.

uccal Mucosa. J Oral Maxillofac Surg 2011.

urvival

rognotic factors. The addition of elective neck dis-

sirtahislns

tototitcs

R

1

1

1

1

1

1

1

1

1

1

2

P of the B

344 CONSERVATIVE TREATMENT OF CANCER OF THE BUCCAL MUCOSA

ection has been reported to increase survival by 11%n patients with head and neck cancer.30 The failureate in the neck with N0 tumor is 5%, which increaseso 15% to 25% in the presence of nodes, despite theddition of adjuvant radiotherapy.18 The failure rate isigher in India.23 In this study, too, lymph node pos-

tivity was found to be the single factor affectingurvival, with disease-free survival being significantlyower in node-positive cases compared with node-egative cases (P � .03); none of the other factorstudied was found to be significant.

In conclusion, lymphatic spread from carcinoma ofhe buccal mucosa was low and was seen in aboutne third of patients. No patient showed skip metas-asis, and involvement of level IV was seen in only 1%f patients. Based on these results, a more conserva-ive approach to spare the neck with levels IV and Vnvolvement in patients with clinical N0 carcinoma ofhe buccal mucosa is recommended. In patients withlinically N� disease, a level V–sparing dissectionhould be adequate.

eferences1. Ferlito A, Silver CE, Rinaldo A: Neck dissection: Present and

future? Eur Arch Otorhinolaryngol 265:621, 20082. Kowalski LP, Sanabria A: Elective neck dissection in oral carci-

noma: A critical review of the evidence. Acta OtorhinolaryngolItal 27:113, 2007

3. Lodder WL, Sewnaik A, den Bakker MA, et al: Selective neckdissection for N0 and N1 oral cavity and oropharyngeal cancer:Are skip metastases a real danger? Clin Otolaryngol 33:450, 2008

4. Rapoport A, Ortellado DK, Amar A, et al: Radical versus supra-omohyoid neck dissection in the treatment of squamous cellcarcinoma of the inferior level of the mouth. Braz J Otorhino-laryngol 73:641, 2007

FIGURE 2. Recurrence-free s

andey, Shukla, and Nithya. Conservative Treatment of Cancer

5. Woolgar JA: The topography of cervical lymph node metastasesrevisited: The histological findings in 526 sides of neck dissec-

tion from 439 previously untreated patients. Int J OralMaxillofac Surg 36:219, 2007

6. De Zinis LO, Bolzoni A, Piazza C, Nicolai P: Prevalence andlocalization of nodal metastases in squamous cell carcinoma ofthe oral cavity: Role and extension of neck dissection. Eur ArchOtorhinolaryngol 263:1131, 2006

7. Lim YC, Koo BS, Lee JS, et al: Distributions of cervical lymphnode metastases in oropharyngeal carcinoma: Therapeutic im-plications for the N0 neck. Laryngoscope 116:1148, 2006

8. Tao L, Lefevre M, Callard P, et al: Reappraisal of metastaticlymph node topography in head and neck squamous cell car-cinomas. Otolaryngol Head Neck Surg 135:445, 2006

9. Jose J, Coatesworth AP, MacLennan K: Cervical metastases inupper aerodigestive tract squamous cell carcinoma: His-topathologic analysis and reporting. Head Neck 25:194, 2003

0. Nithya C, Pandey M, Naik B, et al: Patterns of cervical metas-tasis from carcinoma of the oral tongue. World J Surg Oncol1:10, 2003

1. Layland MK, Sessions DG, Lenox J: The influence of lymphnode metastasis in the treatment of squamous cell carcinoma ofthe oral cavity, oropharynx, larynx, and hypopharynx: N0versus N�. Laryngoscope 115:629, 2005

2. Moor JW, Jose J, Johnston C, et al: Upper aerodigestive tract squa-mous cell carcinoma: Distribution of extracapsular spread and softtissue deposits in the neck. Acta Otolaryngol 124:97, 2004

3. Tankere F, Camproux A, Barry B, et al: Prognostic value oflymph node involvement in oral cancers: A study of 137 cases.Laryngoscope 110:2061, 2000

4. Iype EM, Pandey M, Mathew A, et al: Oral cancer amongpatients under the age of 35 years. J Postgrad Med 47:171, 2001

5. Iype EM, Pandey M, Mathew A, et al: Squamous cell cancer ofthe buccal mucosa in young adults. Br J Oral Maxillofac Surg42:185, 2004

6. Shah JP, Candela FC, Poddar AK: The patterns of cervicallymph node metastases from squamous carcinoma of the oralcavity. Cancer 66:109, 1990

7. Shear M, Hawkins DM, Farr HW: The prediction of lymph nodemetastases from oral squamous carcinoma. Cancer 37:1901, 1976

8. Spiro JD, Spiro RH, Shah JP, et al: Critical assessment of su-praomohyoid neck dissection. Am J Surg 156:286, 1988

9. Chiesa F, Mauri S, Grana C, et al: Is there a role for sentinelnode biopsy in early N0 tongue tumors? Surgery 128:16, 2000

0. Woolgar JA: Histological distribution of cervical lymph nodemetastases from intraoral/oropharyngeal squamous cell carci-

by presence of neck nodes.

uccal Mucosa. J Oral Maxillofac Surg 2011.

urvival

nomas. Br J Oral Maxillofac Surg 37:175, 1999

2

2

2

2

2

2

2

2

2

3

PANDEY, SHUKLA, AND NITHYA 345

1. Ng SH, Yen TC, Liao CT, et al: 18F-FDG PET and CT/MRI inoral cavity squamous cell carcinoma: A prospective study of124 patients with histologic correlation. J Nucl Med 46:1136, 2005

2. Stuckensen T, Kovacs AF, Adams S, et al: Staging of the neck inpatients with oral cavity squamous cell carcinomas: A prospec-tive comparison of PET, ultrasound, CT and MRI. J Craniomax-illofac Surg 28:319, 2000

3. Mishra RC, Parida G, Mishra TK, et al: Tumour thickness andrelationship to locoregional failure in cancer of the buccalmucosa. Eur J Surg Oncol 25:186, 1999

4. Woolgar JA, Vaughan ED, Scott J, et al: Pathological findings inclinically false-negative and false-positive neck dissections for oralcarcinoma. Ann R Coll Surg Engl 76:237, 1994

5. Fukano H, Matsuura H, Hasegawa Y, et al: Depth of invasion asa predictive factor for cervical lymph node metastasis in tongue

carcinoma. Head Neck 19:205, 1997

6. Woolgar JA, Beirne JC, Vaughan ED, et al: Correlation of his-topathologic findings with clinical and radiologic assessmentsof cervical lymph-node metastases in oral cancer. Int J OralMaxillofac Surg 24:30, 1995

7. Persky MS, Lagmay VM: Treatment of the clinically negativeneck in oral squamous cell carcinoma. Laryngoscope 109:1160,1999

8. Kalnins IK, Leonard AG, Sako K, et al: Correlation betweenprognosis and degree of lymph node involvement in carcinomaof the oral cavity. Am J Surg 134:450, 1977

9. Woolgar JA, Rogers S, West CR, et al: Survival and patterns ofrecurrence in 200 oral cancer patients treated by radical sur-gery and neck dissection. Oral Oncol 35:257, 1999

0. Cunningham MJ, Johnson JT, Myers EN, et al: Cervical lymphnode metastasis after local excision of early squamous cell

carcinoma of the oral cavity. Am J Surg 152:361, 1986