salivary tu prognostic 2009

8/2/2019 Salivary Tu Prognostic 2009

1/7

British Journal of Oral and Maxillofacial Surgery 47 (2009) 587593

Available online at www.sciencedirect.com

Leading article

Prognostic factors in malignant tumours of thesalivary glands

Paul M. Speight a,, A. William Barrett b

a Department of Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Claremont Crescent,

Sheffield S10 2TA, United Kingdomb Department of Histopathology, Queen Victoria Hospital, Holtye Road, East Grinstead, West Sussex RH19 3DZ, United Kingdom

Accepted 27 March 2009

Available online 5 May 2009

Abstract

Salivary gland tumours are a relatively rare group of lesions best managed in specialist centres. We review some of the factors that influence

their prognosis. Clinical stage is the most important, with large malignancies having a poor prognosis regardless of histological grade and

other features such as perineural invasion. Even high grade neoplasms may do well when they are small. A helpful guide to the management

of salivary cancers is the 4 cm rule.

2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Keywords: Head and neck; Salivary gland diseases; Mouth neoplasms; Prognostic factors

Introduction

Salivary gland tumours vary widely in their histological

and clinical features, and are challenging to diagnose and

manage.1 They are uncommon compared with squamous

cell carcinomas (SCCs) of the oral cavity, and have an

overall global incidence of 0.413.5 cases/100,000.2 Most

are benign and the incidence of malignant salivary gland

neoplasms ranges from 0.4 to 2.6 cases/100,000.36 We con-

sider the factors that influence the prognosis of malignant

neoplasms of epithelial origin, which number 24 in the

latest World Health Organization (WHO) classification of

salivary gland tumours.7 In clinical practice, only five sali-

vary gland carcinomas are likely to be encountered withany degree of frequency; mucoepidermoid carcinoma, ade-

noid cystic carcinoma, carcinoma in pleomorphic adenoma,

acinic cell carcinoma and, in the minor glands, polymor-

Corresponding author at: Department of Oral and Maxilofacial Pathol-

ogy, School of Clinical Dentistry, University of Sheffield, Claremont

Crescent, Sheffield S10 2TA, United Kingdom. Tel.: +44 0114 271 7951;

fax: +44 0114 271 7894.

E-mail address: [email protected](P.M. Speight).

phous low grade adenocarcinoma.8 It is likely therefore that

even specialist pathologists and surgeons will be requiredto diagnose and treat salivary gland cancers rarely, with

some being encountered only once or twice in a working

lifetime, if at all. However, many of the prognostic factors

apply to all of them, with histological features providing

additional information in only a few specific entities. In

this review we consider clinical stage, use of histological

grading where it is helpful, and perineural invasion, which

is a characteristic finding in some salivary adenocarcino-

mas.

An overview of prognosis: stage compared with grade

The latest WHO classification of tumour, node, metastasis

(TNM) of salivary gland carcinomas7 is shown in Table 1.

Stage IV is subdivided following the division of T4 into T4a

(resectable tumours invading skin, mandible, ear canal, or

facial nerve), and T4b (unresectable tumours invading the

base of skull, pterygoid plates, or encasing the carotid artery).

Although tumours up to 4 cm are allocated a T grade of T1

(2 cm or less) or T2 (>24cm), any clinical or macroscopic

0266-4356/$ see front matter 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

doi:10.1016/j.bjoms.2009.03.017
mailto:[email protected]://dx.doi.org/10.1016/j.bjoms.2009.03.017http://dx.doi.org/10.1016/j.bjoms.2009.03.017mailto:[email protected]


2/7

588 P.M. Speight, A.W. Barrett / British Journal of Oral and Maxillofacial Surgery 47 (2009) 587593

Table 1

World Health Organization staging of salivary gland carcinomas.7.

Stage Tumour Size Node Metastasis

I 1 2 cm or less 0 0

II 2 24 cm 0 0

III 3


3/7

P.M. Speight, A.W. Barrett / British Journal of Oral and Maxillofacial Surgery 47 (2009) 587593 589

Table 2

Grading of salivary gland adenocarcinomas after Cheuk and Chan13.

Low grade High grade

Polymorphous low grade adenocarcinoma *

Acinar cell carcinoma *

Basal cell adenocarcinoma *

Myoepithelial carcinoma *

Cystadenocarcinomas *Epithelialmyoepithelial carcinoma *

Mucoepidermoid carcinoma * *

Adenoid cystic carcinoma * *

Adenocarcinoma NOS * *

Squamous cell carcinoma * *

Carcinoma ex-pleomorphic adenoma *

Salivary duct carcinoma *

Oncocytic carcinoma *

Undifferentiated carcinomas *

noma is categorised as a low grade tumour,13 or all adenoid

cystic carcinomas are classed as intermediate grade.

16

Boththese neoplasms show histopathological variants that could

be assessed as low, intermediate, or high. Adenocarcinoma

NOS and primary SCC are graded in a similar way to extra

salivary lesions according to the degree of differentiation.

In the case of mucoepidermoid carcinoma, grading was

traditionally based on a subjective assessment of the amount

Fig.1. Mucoepidermoid carcinomaof theparotid.(a) Lowgradelesioncom-

prising scattered cysts with cellular mural thickenings present only focally

(haematoxylin and eosin, original magnification 10) and (b) intermediate

grade tumour where solid islands predominate over the cystic component

(haematoxylin and eosin, original magnification 10).

Table 3

Grading of mucoepidermoid carcinoma using the scheme of Brandwein et

al28.

(A) Histological features

Histological feature Score

Cystic component 4/10 high power fields 3

Prominent atypia 2

Invasion in small nests and islands 2

Lymphatic or vascular invasion 3

Invasion of bone 3

(B) Grading and scoring

Grade Total score

I (low) 0

II (intermediate) 23

III (high) 4+

of cystic change in the tumour, and on features of aggres-

sion or cytological atypia (Fig. 1). More recently, based on

the AFIP experience, Goode et al.23 described a more objec-

tive scheme based on numerical scores given to histological

features, which Brandwein et al.28 modified giving greater

weight to features of invasion (Table 3). The latter group

examined the inter-observer error of the two schemes and

showed that the AFIP scheme tended to downgrade tumours,

which may explain reported cases of aggressive behaviour

in low grade lesions. In the AFIP series, grade 1 lesions

in the major glands metastasised or caused death in 5% of

patients,23

but with the modified grading scheme all grade1 tumours were also stage I and none metastasised.28 All

patients with grade 1 lesions were disease-free at 10 years,

compared with roughly 70% with grade 2 lesions, and less

than 40% with grade 3. The authors claimed that their grad-

ing scheme was better at allocating tumours to more realistic

behavioural groups, but also found stage to be important.

Over 90% of patients with stage I or II tumours were disease-

free at 10 years compared with less than 30% with stage III

or IV disease. This suggests that although grade is important,

stage still seems to be a better indicator of prognosis, a view

shared by the AFIP.10

Polymorphous low grade adenocarcinoma is the only sali-

vary tumour with a name that suggests its clinical behaviour.

In most cases it affects the minor salivary glands and shares

some histological appearances with the benign pleomorphic

adenoma and the more aggressive adenoid cystic carcinoma,

potentially posing a diagnostic problem. Both polymorphous

low grade adenocarcinoma and adenoid cystic carcinoma

may show cribriform morphology and perineural infiltration

(Fig. 2), and distinguishing between the two may be difficult

in a small biopsy specimen. The distinction is important as it

mayaffect treatmentand prognosis. A recentstudy hasshown

that expression of minichromosome maintenance proteins in

these lesions may be a useful discriminatory marker.29 In the


4/7


Fig. 2. Perineural invasion: (a) polymorphous low grade adenocarcinoma.

Between the affected nerves (N) is a cribriform island (C) (haematoxylin

and eosin, original magnification 100) and (b) adenoid cystic carcinoma

of predominantly tubular morphology (haematoxylin and eosin, original

magnification 20).

largest series of polymorphous low grade adenocarcinomas,

which comprised 164 cases,30 98% of patients were either

alive or had died with no evidence of recurrence, over a mean

follow-up period of 115 months. However, despite its name

up to a third of polymorphous low grade adenocarcinomas

recur locally or metastasise to regional lymph nodes. Some

morphological characteristics have been suggested to iden-

tify those tumours that may not, in fact, be low grade. For

example, one study reported a significant relation between a

papillary cystic growth pattern (Fig. 3) and cervical lymph

node metastasis.31 The relation between invaded margins and

local recurrence was also significant, but other clinicopatho-

logical variables, including tumour size, necrosis, mitotic

rate, and bone and perineural invasion had no prognostic sig-

nificance. Unfortunately this introduces another subjective

element, as focal areas of papillary cystic changeare common

in polymorphous low grade adenocarcinoma. Nevertheless, if

papillary cystic change is prominent in a polymorphous low

grade adenocarcinoma we alert the clinical team to the possi-

bility of aggressive behaviour. We have previously discussed

this issue and have suggested that this tumour should not be

designated low grade, but should be called polymorphous

adenocarcinoma.1

Fig.3. Papillarycystic pattern in a polymorphous lowgradeadenocarcinoma

(haematoxylin and eosin, original magnification 100).

By comparison, the grading of adenoid cystic carcinoma

is generally quite straightforward as it depends primarilyon the morphological pattern of the tumour. Three patterns

are recognised, namely cribriform, tubular, and solid, and

tumours are categorised according to the predominant pattern

(Fig.2).13,32,33 The cribriform,multicystic or Swiss-cheese

pattern is the most common and characteristic, and com-

prises 44% of all lesions with the tubular pattern in about

35% and solid in 21%.33,34 Most authorities agree that the

solid adenoid cystic carcinoma is a high grade lesion, and

it has been shown to have a higher rate of proliferation

and greater expression of minichromosome maintenance pro-

teins, which are markers of cell cycle progression.29 Solid

lesions have reported recurrence of up to 100%, comparedwith 5080% for the tubular and cribriform variants.35 In

some reports, no patients with the solid variant survived for

10 years.36

Reports vary about the behaviour of tubular and cribri-

form lesions. Perzin et al.34 reported that the tubular type

have the best outcome with regard to recurrence and sur-

vival, but others found the cribriform pattern to be the

most favourable.35 The AFIP categorise solid adenoid cys-

tic carcinoma as high grade and both the tubular and

cribriform types as intermediate grade.9 At the Memorial

Sloan Kettering Cancer Center adenoid cystic carcinomas

are graded according to the proportion of solid areas.36

Predominantly solid lesions are grade 3 (high), predomi-

nantly cribriform are grade 1 (low), and those with equal

solid and cribriform or tubular areas are grade 2 (intermedi-

ate).

Spiro et al. 19,36,37 generally dismiss the histological fea-

tures of adenoid cystic carcinoma as important predictors of

clinical behaviour, believing clinical factors (notably stage,

large tumour size, and involvement of lymph nodes) to be

more predictive of distant metastasis and ultimate progno-

sis. Grade was a deciding factor for 5-year, but not long

term (1525 years) survival.36 Renehan et al.16 also regard

histological features of little prognostic use. Unfortunately,


5/7


regardless of grade or pattern, all adenoid cystic carcino-

mas have a protracted course and ultimately a poor outcome.

Using the Memorial Sloan Kettering scheme, grade 1 and 2

lesions have similar outcomes at 5 years (roughly 85% sur-

vival), but at 10 years all grades do equally badly, with overall

survival of less than 50%.36 Most adenoid cystic carcinomas

are widely infiltrative at diagnosis, invade bone early, andcharacteristically show perineural infiltration. They typically

recur frequently, and between 35% and 50% develop late

distant metastases, usually to lung or bone, compared with

only 10% with regional lymph node metastases.37,38 These

factors and an unusually slow biological growth result in a

relatively favourable 5-year survival, but poor longer term

outcome.

Age,39 positive surgical margins,4042 lymph node

metastasis,43 and invasion of bone, vasculature, muscle,

or extraglandular structures44 have all been implicated as

adverse findings in some (though by no means all) studies

of adenoid cystic carcinoma. Most reports of this neoplasm

also comment on the importance, or otherwise, of perineuralinfiltration.

Perineural invasion

It is a paradox that perineural infiltration is regarded as a

sinister prognostic indicator, yetit is a characteristic anddiag-

nostically useful feature of both polymorphous low grade

adenocarcinoma and adenoid cystic carcinoma. It may also

occur in any malignant neoplasm, is a feature of 27% of head

and neck SCCs,45 and is a feature of most adenoid cystic

carcinomas (Fig. 2). A review of 35 reports from 1961 to1999 showed that perineural infiltration occurred in roughly

60% of these tumours, though the range was 898%.46 Of

these studies, 25 looked at prognosis and 14 showed that

perineural infiltration was associated with a poor prognosis.

However, in four of these the prognosis was poor only if

major named nerves external to the gland were involved,

or nerves of a minimum diameter. The critical dimension was

0.25 mm or more in one study,47 and between 0.5 and 3.0 mm

in another.48 In the former, invasion of nerves larger than this

critical value correlated with tumour size and advanced clin-

ical stage. Eleven of the 25 studies reported no association

between perineural infiltration and prognosis, but the number

of cases in each series ranged from 21 to 198, and not all of

them had applied statistical tests. A short period of follow-up

could be criticised in others.

Data on the significance of histological perineuralinvasion

is therefore equivocal. Some studies report it as significant

on univariate, but not on multivariate analysis.22,49,50 How-

ever, two studies have found it to be an independent factor

in prognosis,42,51 and it is a means by which the tumour can

grow along a plane of low tissue resistance. Even anatomical

barriers can be breached since all are pierced by neurovascu-

lar bundles. It is particularly important when it occurs outside

the main tumour mass, or causes clinical manifestations.

As implied by the prognostic index described above,24,27

clinical evidence of nerve invasion is a poor prognostic indi-

cator. Such evidence may become manifest as paralysis,

paraesthesia, deafness, diplopia, pain or tic. A review of

18 series reported between 1961 and 1999 suggested that

clinical signs and symptoms of the involvement of nerves

occurred in about 25% of patients with adenoid cystic car-cinoma. However, the range was 286% for tumours at all

sites and 957% of those affecting the parotid gland.46 Paral-

ysis of the facial nerve is an important predictor of lymph

node metastasis,52 and the gravity of VIIth nerve palsy was

emphasised by Eneroth,53 who reviewed 378 parotid ade-

nocarcinomas. While only 46 presented with this symptom,

77% of them developed metastasis and 98% died. In contrast,

of the 332 patients with no evidence of involvement of the

facial nerve there was metastasis in 27% and 33% died of

their disease.

Summary and Conclusions

The potential prognostic indicators in salivary gland can-

cers are stage, histological type and grade, involvement of

nerves, site, age, gender, and status of surgical margins. In

most studies stage and clinical evidence of nerve invasion

are independent factors deemed to be of the greatest prog-

nostic importance. Histological grade is a helpful guide in

some neoplasms, and specific histological features may pro-

vide additional clues about unfavourable behaviour. T1 and

T2 tumours less than 4 cm in size generally do well regard-

less of histological grade or any other features, and this rulehas proved to be a useful clinical guide to behaviour and

outcome.

References

1. Speight PM, Barrett AW. Salivary gland tumours. Oral Dis

2002;8:22940.

2. Ellis GL, Auclair PL. Classification of salivary gland neoplasms. In:

Ellis GL, Auclair PL, Gnepp DR, editors. Surgical pathology of the

salivary glands. Philadelphia: Saunders; 1991. p. 12934.

3. Ostman J, Anneroth G, Gustafsson H, Tavelin B. Malignant salivary

gland tumours in Sweden 19601989an epidemiological study. OralOncol 1997;33:16976.

4. Pinkston JA, Cole P. Incidence rates of salivary gland tumors:

results from a population-based study. Otolaryngol Head Neck Surg

1999;120:83440.

5. Sun EC, Curtis R, Melbye M, Goeder JJ. Salivary gland cancer

in the United States. Cancer Epidemiol Biomarkers Prev 1999;8:

1095100.

6. Koivunen P, Suutala L, Schorsch I, Jokinenk K, Alho OP. Malig-

nant epithelial salivary gland tumors in northern Finland: incidence

and clinical characteristics. Eur Arch Otorhinolaryngol 2002;259:

1469.

7. Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health

Organization classification of tumors: pathology and genetics of head

and neck tumors. Lyon IARC Press; 2005.


6/7


8. Jones AV, Craig GT, Speight PM, Franklin CD. The range and demo-

graphics of salivary gland tumours diagnosed in a UK population. Oral

Oncol 2008;44:40717.

9. Ellis GL, Auclair PL. Salivary gland neoplasms: general considerations.

In: Ellis GL, Auclair PL, Gnepp DR, editors. Surgical pathology of the

salivary glands. Philadelphia: Saunders; 1991. p. 13564.

10. Ellis GL, Auclair PL. Atlas of tumor pathology. In: Tumors of the sali-

vary glands. Series 3, Fascicle 17. Washington, DC: Armed Forces

Institute of Pathology; 1996.

11. Spiro RH. Salivary neoplasms: overview of a 35-year experience with

2807 patients. Head Neck Surg 1986;8:17784.

12. Spiro RH, Thaler HT, Hicks WF, Kher UA, Huvos AH, Strong EW. The

importance of clinical staging of minor salivary gland carcinoma. Am J

Surg 1991;162:3306.

13. Cheuk W, Chan JKC. Salivary gland tumours. In: Fletcher CDM, edi-

tor. Diagnostic histopathology of tumors. 3rd ed. London: Churchill

Livingstone; 2007. p. 239325.

14. Spiro RH. Factors affecting survival in salivary gland cancers. In:

McGurk M, Renehan A, editors. Controversies in the management

of salivary gland disease. Oxford: Oxford University Press; 2001. p.

14350.

15. Armstrong JG, Harrison LB, Spiro RH, Fass DE, Strong EW, Fuks ZY.

Malignant tumors of major salivary gland origin. A matched-pair analy-

sis of the role of combined surgery and postoperative radiotherapy.Arch

Otolaryngol Head Neck Surg 1990;116:2903.

16. Renehan AG, Gleave EN, Slevin NJ, McGurk M. Clinico-pathological

and treatment-related factors influencing survival in parotid cancer. Br

J Cancer1999;80:1296300.

17. Vander Poorten VL, Balm AJ, Hilgers FJ, Tan IB, Keus RB, Hart AA.

Stage as major long term outcome predictor in minor salivary gland

carcinoma. Cancer 2000;89:1195204.

18. Slevin N, Frankenthaler R. The role of radiotherapy in the management

of salivary gland cancer. In: McGurk M, Renehan A, editors. Contro-

versies in the management of salivary gland disease. Oxford: Oxford

University Press; 2001. p. 16372.

19. Spiro RH, Huvos AG. Stage means more than grade in adenoid cystic

carcinoma. Am J Surg 1992;164:6238.

20. Plambeck K, Friedrich RE, Schmelzle R. Mucoepidermoid carcinomaof salivarygland origin: classification,clinicalpathological correlation,

treatment results and long-term follow-up in 55 patients. J Craniomax-

illofac Surg 1996;24:1339.

21. McGurk M. Management of salivary gland cancer: clinically or patho-

logically based? Overview. In: McGurk M, Renehan A, editors.

Controversies in the management of salivary gland disease . Oxford:

Oxford University Press; 2001. p. 15561.

22. Frankenthaler RA, Luna MA, Lee SS, et al. Prognostic vari-

ables in parotid gland cancer. Arch Otolaryngol Head Neck Surg

1991;117:12516.

23. Goode RK, Auclair PL, Ellis GL. Mucoepidermoid carcinoma of the

major salivaryglands: clinical and histopathologic analysis of 234 cases

with evaluation of grading criteria. Cancer 1998;82:121724.

24. Vander Poorten VL, Balm AJ, Hilgers FJ, et al. The development

of a prognostic score for patients with parotid carcinoma. Cancer1999;85:205767.

25. Vander Poorten VL, Balm AJ, Hilgers FJ, et al. Prognostic factors

for long term results of the treatment of patients with malignant sub-

mandibular gland tumors. Cancer1999;85:225564.

26. Bell RB, Dierks EJ, Homer L, Potter BE. Management and outcome of

patients with malignant salivary gland tumors. J Oral Maxillofac Surg

2005;63:91728.

27. Vander Poorten VL, Hart AA, van der Laan BF, et al. Prognostic index

for patients withparotid carcinoma: externalvalidation using the nation-

wide 19851994 Dutch Head and Neck Oncology Cooperative Group

database. Cancer2003;97:145363.

28. Brandwein MS, Ivanov K, Wallace DI, et al. Mucoepidermoid carci-

noma: a clinicopathologic study of 80 patients with special reference to

histological grading. Am J Surg Pathol 2001;25:83545.

29. Vargas PA, Cheng Y, Barrett AW, Craig GT, Speight PM. Expression

of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland

tumours. J Oral Pathol Med2008;37:30918.

30. Castle JT, Thompson LD, Frommelt RA, Wenig BM, Kessler HP. Poly-

morphous low grade adenocarcinoma: a clinicopathologic study of 164

cases. Cancer1999;86:20719.

31. EvansHL, LunaMA. Polymorphouslow grade adenocarcinoma: a study

of40 caseswith long-termfollowup andan evaluationof theimportance

of papillary areas. Am J Surg Pathol 2000;24:131928.

32. Batsakis JG, Luna MA, el-Naggar A. Histopathologic grading of sali-

vary gland neoplasms. III. Adenoid cystic carcinomas. Ann Otol Rhinol

Laryngol 1990;99:10079.

33. TomichCE. Adenoid cystic carcinoma. In:Ellis GL,Auclair PL, Gnepp

DR, editors. Surgical pathology of the salivary glands. Philadelphia:

Saunders; 1991. p. 33349.

34. Perzin KH, Gullane P, Clairmont AC. Adenoidcystic carcinomasarising

in salivary glands:a correlationof histologic features andclinicalcourse.

Cancer 1978;42:26582.

35. Nascimento AG, Amaral AL, Prado LA, Kligerman J, Silveira TR.

Adenoid cystic carcinoma of salivary glands: a study of 61 cases with

clinicopathologic correlation. Cancer 1986;57:3129.

36. Spiro RH. The controversial adenoid cystic carcinoma. Is this cancer

curable and where does it fail? In: McGurk M, Renehan A, editors.

Controversies in the management of salivary gland disease . Oxford:

Oxford University Press; 2001. p. 20711.

37. Spiro RH. Distant metastasis in adenoid cystic carcinoma of salivary

origin. Am J Surg 1997;174:4958.

38. Matsuba HM, Spector GJ, Thawley SE, Simpson JR, Mauney M, Pikul

FJ. Adenoid cystic salivary gland carcinoma. A histopathologic review

of treatment failure patterns. Cancer 1986;57:51924.

39. da Cruz Perez DE, de Abreu Alves F, Nobuko Nishimoto I, de Almeida

OP, Kowalski LP. Prognostic factors in head and neck adenoid cystic

carcinoma. Oral Oncol 2006;42:13946.

40. GardenAS, Weber RS,Morrison WH,AngKK, PetersLJ. Theinfluence

of positive margins and nerve invasion in adenoid cystic carcinoma of

the head and neck treated with surgery and radiation. Int J Radiat Oncol

Biol Phys 1995;32:61926.

41. Kokemueller H, Eckardt A, Brachvogel P, HausamenJE. Adenoid cysticcarcinoma of the head and necka 20 years experience. Int J Oral

Maxillofac Surg 2004;33:2531.

42. Chen AM, Bucci MK, Weinberg V, et al. Adenoid cystic carcinoma

of the head and neck treated by surgery with or without postoperative

radiation therapy: prognostic features of recurrence. Int J Radiat Oncol

Biol Phys 2006;66:1529.

43. Jones AS, Hamilton JW, Rowley H, Husband D, Helliwell TR.

Adenoid cystic carcinoma of the head and neck. Clin Otolaryngol

1997;22:43443.

44. Huang M, Ma DQ, Sun K, Yu G, Guo C, Gao F. Factors influencing

survival rate in adenoid cystic carcinoma of the salivary glands. Int J

Oral Maxillofac Surg 1997;26:4359.

45. Soo KC, Carter RL, OBrien CJ, Barr L, Bliss JM, Shaw HJ. Prognostic

implications of perineural spread in squamous carcinomas of the head

and neck. Laryngoscope 1986;96:11458.46. Barrett AW, Speight PM. The controversial adenoid cystic carcinoma.

The implications of histological grade and perineural invasion. In:

McGurk M, Renehan A, editors. Controversies in the management

of salivary gland disease. Oxford: Oxford University Press; 2001.

p. 2117.

47. Luna MA, el-Naggar A, Batsakis JG, Weber RS, Garnsey LA, Goepfert

H. Flow cytometric DNA content of adenoid cystic carcinoma of sub-

mandibular gland.Arch OtolaryngolHead Neck Surg 1990;116:12916.

48. Eibling DE, Johnson JT, McCoy Jr JP, et al. Flow cytometric evaluation

of adenoid cystic carcinoma: correlation with histologic subtype and

survival. Am J Surg 1991;162:36772.

49. Beckhardt RN, Weber RS, Zane R, et al. Minor salivary gland tumors of

the palate: clinical and pathologic correlates of outcome. Laryngoscope

1995;105:115560.


7/7


50. Pohar S, Gay H, Rosenbaum P, et al. Malignant parotid tumors: presen-

tation, clinical/pathologic prognostic factors, and treatment outcomes.

Int J Radiat Oncol Biol Phys 2005;61:1128.

51. Mendenhall WM, Morris CG, Amdur RJ, Werning JW, Hinerman RW,

Villaret DB. Radiotherapy alone or combined with surgery for ade-

noid cystic carcinoma of the head and neck. Head Neck 2004;26:

15462.

52. Frankenthaler RA, Byers RM, Luna MA, Callender DL, Wolf P,

Goepfert H. Predicting occult lymph node metastasis in parotid cancer.

Arch Otolaryngol Head Neck Surg 1993;119:51720.

53. Eneroth CM. Facial nerve paralysis. A criterionof malignancy in parotid

tumors. Arch Otolaryngol 1972;95:3004.

salivary tu prognostic 2009

Documents