EPITHELIAL SALIVARY GLANDS MALIGNANCIES

COIMBRA’S PORTUGUESE CANCER INSTITUTE RECENT EXPERIENCE Simoes AM1, Branquinho F2, Cardoso A2, Neves A2, Cruz C2, Pereira H2, Ganho J2, Guimaraes A2

1Centro Hospitalar de Coimbra E.P.E., 2Instituto Português Oncologia Francisco Gentil (IPO FG) de Coimbra

Retrospective study with analysis of

the patients with histological

diagnosis of malignant epithelial

disease of the salivary glands

between 2000 and 2010 treated in

Coimbra’s Portuguese Cancer

Institute. Demographic information,

location, risk factors, complementary

evaluation, treatment modalities,

histological features, follow-up and

failures were analyzed.

Presented 55 cases, aged between

23 and 86 years old, 56% male. 75%

were located at the parotid, 20% in

the submandibular and 5% in minor

salivary glands. Only 2 patients

weren’t submitted to surgical

excision. Most patients were in Stage

II and IV. There were 12 (22%)

adenoid cystic carcinoma, 10 (18%)

mucoepidermoid carcinomas, 10

(18%) adenocarcinomas, 7 (13%)

acinic cell carcinoma and 16 (29%) of

several other entities. 55%

underwent radiation therapy and 18%

chemotherapy. Survival rates at 1

year were 95% and at 5 years 78%.

Failures were observed in 42% (local

and distant).

The analysis of these cases are in

line with the literature, being the

stage of the tumor the principal

prognosis factor in salivary gland

malignancies, even when dealing

with different grade histology entities.

Radiation seems to be an important

option in controlling local disease.

Ana Margarida Simoes

Centro Hospitalar Coimbra E. P. E.

Portugal, Europe

ana.simx@gmail.com

+351962574227

ABSTRACT

The pathology of the salivary glands is essentially

inflammatory and neoplastic.

Tere are multiple and complex histological subtypes with very

different byological behaviors and diagnosis difficulties

relate to the broad morphological spectrum.

Objective

Primer: to perform a comprehensive survey of the primitive

malignant diagnoses of the salivary glands and

characterized them in terms of clinical and biological

behavior.

Secondary: try to draw conclusions on the treatment and

disease control.

79 cases identified, 24 excluded, 55 evaluated.

Ages between 23 and 86 years old;

Mean age 60 yo. Age distribution as Fig. 1.

No gender preference (56% Male; 44% Female).

Time of symptoms determined in 37 cases: mean 13,2 months

with 4 of long time of evolution (14 undetermined).

Location of lesion as Fig. 2.

Associated symptoms: pain - 10 cases (18%); Facial Palsy - 8

parotid cases (20%) and cervical ganglions - 16 cases

(29%).

Exposition to risk factors such as cigarette smoke, radiation,

alcohol consumption, diabetes and immunesuppression :

rarely reported, sporadic cases of diabetes and smokers;

none with former head and neck radiation.Evaluation: ultrasound – 26 cases (47%); CT – 40 (72%);

FNAB – 45 (82%) with 33% of false negatives and 13% of

undetermined.

Histological Types as Fig. 3.

Also classified as: high grade 24 (45%), low grade 16 (30%),

intermediate 8 (15%) and undetermined 5 (10%).

Histologically there were positive ganglions in 18 cases (34%).

Clinical Stage as Fig. 4.

Retrospective Study

Basis: analysis of information contained in the clinical files of patients with salivary gland pathology treated in IPO

FG Coimbra from 2000 to 2010.

Selected those with histological diagnosis (code) of malignant neoplasm of a salivary gland.

Excluded: coding errors, very deficient information (practically nonexistent), inaccessible files.

Statistical analysis of the information – Excell data base 2007.

Used the TNM-classification of the American Joint Committe for Cancer.

All patients submitted to surgical resection, (excepted

the 2 cases staged as IVB - palliation therapy only):

from conservative sialoadenectomy to wider

excisions some with nerve repair and skin or

myocutaneous reconstruction flap.

The association with cervical lymphadenectomy

was performed in 28 patients (53%), being more or

less extended dependent on intraoperative findings,

initial stage, location, or therapeutic decision after

the initial surgery.

Adjunctive therapy with RT:

25 (45%) patients did not perform any type of

radiation.

24 (44%) underwent postoperative RT (including 2

after local recurrence) over salivary gland and / or

neck.

2 (4%) patients had local palliative RT and 7 (13%)

palliative RT for distance metastasis (cranial or

bone).

8 patients (16%) were referred for postoperative RT,

but that was not performed (exceeded optimal date

for various reasons).

The doses ranged from 50.4/28 to 68.4 Gy/38fr,

most often 59.4 Gy/33fr over the loca and neck.

10 patients (18%) had cytotoxic therapy (70%:

Carboplatin + Fluorouracil + Calcium folinate

Protocol) for distant metastasis (6), locally

advanced disease (3) and recurrence (1).

Disease recurrence: from the patients who underwent

surgery, 13 (25%) had local recurrence and 4 (6%)

also had lymph node recurrence.

Distant metastases were observed throughout the

follow-up or as early stage in 15 patients (28%).

The sites were mostly lung metastasis (11 - 73%)

and bone (60-40%) – Fig. 5.

9 patients had locally controlled disease, but

developed distant metastases

5 (56%) were in Stage IV A.

the histological types were varied without

preference for a particular entity.6 (67%) had vascular invasion on histological

examination (3 unspecified)

7 (78%) had invaded surgical margins (2 (22%) safe

margins).

7 (78%) had postoperative RT (only 1 should and did not

had (for extensive M1))

The overall median follow-up of these patients this

evaluation was 49 months.

The minimum time of survival in this series was 2 months

and a maximum of 130 months.

The Global Survival Rates were:

1 Year - 42 out of 44 (95%)

5 years - 18 out of 23 (78%)

10 years - 3 out of 8 (38%)

The survival rates were compared in the size of the lesion

(larger and smaller than 4 cm), histological grade (high,

medium and low grade) and clinical stage – results in Fig.

6a, 6b and 6c.

In this series, the most frequent lesion was adenoid cystic

carcinoma and secondary mucoepidermoid carcinoma (MEC)

– in the International literature, MEC represents 30% of all

malignant salivary gland and mimics a pleomorphic adenoma

- local pain, neurological changes and rapid growth suggest

high-grade lesion.

Internationally, there is no prevalence of gender nor obvious

tendency to occur at particular late ages; they are common in

adults, in the 5 th / 6 th decades (rare in children).

With regard to research on possible risk factors, it is our opinion

that the fact of not being actively researched, probably

conditioned the results.

Cytology as a diagnostic method can give important information,

but the results are very dependent on a meticulous

technique, that although easy it is not trivial. In this series

there was a high rate of false negatives, which may be

related to this factor.

Surgery is the treatment of choice for neoplastic salivary

pathology. Alternative therapeutic options are presented as

adjuvants.

Postoperative RT appears to reduce the risk of locoregional

recurrence and slightly increase overall survival by controlling

residual disease.

The different histological types may respond significantly

differently to chemotherapeutic agents (chemotherapy), but

there is no concrete evidence-based recommendations that

support the routine use of adjuvant chemotherapy. Therefore,

generally reserves the use of chemotherapy for palliation of

symptoms due to metastatic or locally recurrent disease, as

seen here also.

The evaluation of survival rates is only indicative due to small

sample size. We can accept that better rates are related to

low histological grade and smaller clinical stage.

In this analysis, tumor stage appears to be the most

important prognostic factor in malignant epithelial

salivary neoplasm. Radiation therapy has an

important role as adjunctive therapy. Relapse rates

are high in the long term and distant metastases

can emerge even with locally controlled disease.

1. Meyers EN, Ferris RL. Salivary Gland Disorders. Springer, 2007

2. McGurk M, Renehan A. Controversies in the management of salivary gland disease. Oxford University

Press, 2001

3. Kokemueller H, Swennen G, Brueggemann N, Brachvogel P et al. Epithelial malignancies of the

salivary glands: clinical experience of a single institution—a review. Int. J. Oral Maxillofac. Surg. 2004;

33: 423–432.

4. Jones AV, Craig GT, Speight PM, Franklin PD. The range and demographics of salivary gland tumours

diagnosed in a UK population. Oral Oncology (2008) 44, 407– 417

5. Bonito N, Broco S, Costa M, Silva R et al. Tumores adenóide císticos das glândulas salivares major –

experiência de um serviço de Oncologia. Revista Portuguesa de ORL e Cirurgia Cervico-Facial Vol 47,

Nº 3 Setembro 2009: 141-144.

CONCLUSIONS

REFERENCES

DISCUSSIONMETHODS AND MATERIALSINTRODUCTION

RESULTS

Adenoid Cystic Ca.23%

Adenocarcinoma18%

MucoepidermoidCa.18%

Acinar Cells Ca.13%

Ex-adenoma Ca.6% Undiferenciated

Ca. 6%

Salivary Duct Ca.4%

Squamous Cell Ca. 4%

Epithelial-Mioepithelial Ca.

4%

Basal Cell Adenocarcinoma

2%

Nerve Sheath Ca. 2%

Other12%

Histological Types Size <4cm >4cm

Survival Rate

1 year

29 out of 31

(94%)

13 out of 13

(100%)Survival Rate

5 years

13 out of16

(81%)

5 out of 7

(71%)Survival Rate

10 years

2 out of 6

(33%)

1 out of 2

(50%)

Grade High 24 (45%) Interm. 8 (15%) Low 16 (30%)

Survival Rate

1 year

19 out f 20

(100%)

7 out of 7

(100%)

12 out of 12

(100%)Survival Rate

5 years

4 out of 8

(50%)

4 out of 5

(80%)

8 out of 8

(100%)Survival Rate

10 years

1 out of 4

(25%)

2 out of 3

(67%)

0 out of 1

(0%)

Stage I II III IV A IV B

Survival Rate

1 year

9 out of 9

(100%)

18 out of 18

(100%)

3 out of 3

(100%)

12 out of 14

(86%)

0 out of 2

(0%)Survival Rate

5 years

2 out of 2

(100%)

10 out of 10

(100%)

2 out of 3

(67%)

4 out of 8

(50%)-

Survival Rate

10 years-

3 out of 4

(75%)

1 out of 2

(50%)

0 out of 2

(0%)-

20%

38%

7%

31%

4%

Clinical Stage

IV B IV A III II I

Figure 4.

Figure 5.

0% 50% 100%

73%40%

27%7%

Distant Metastasis

Liver Skull Bone Lung

0%

10%

20%

30%

40%

50%

0-20 21-40 41-60 61-80 81-100

09%

40%46%

5%

Years

Age DistribuitionFigure 1.

LOCATION Total ♀ ♂ Right Left

Parotid41

(75%)

17

(41%) 24 (59%)

19

(46%)

22

(54%)

Submaxilar11

(20%) 5 (45%) 6 (55%) 5 (45%) 6 (55%)

Sublingual 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

Minor 3 (5%) 2 (66%) 1 (33%)

3

(100%) 0 (0%)

Figure 2.

Figure 3. Figure 6a.

Figure 6b.

Figure 6c.

RESULTS

CONTACT