Download Current controversies in the Management of Malignant Parotid Tumors

Francisco G. Pernas, MD
Faculty Advisor: Susan D. McCammon, MD
Grand Rounds Presentation
The University of Texas Medical Branch
Department of Otolaryngology
February 25, 2011
Outline
Case Presentation
II. Background on Parotid Malignancies
III. Anatomy/Epidemiology
IV. Workup of a patient
V. Types of Malignancies
VI. Areas of Controversy
VII. Conclusions
I.
Case Presentation
H&P
 42-year-old white woman
 16 months prior had undergone resection for
lesion in parotid (described as enucleation by
patient) – Path/Op Report not available
 No further treatment was offered at that time
 Patient presents to ENT
 Complains of regrowth mass in right facial area
Case Presentation
 Weakness
on right side of face
 Pain in region required narcotics
 Denies xerostomia, trismus,
odynophagia, dysphagia, globus
sensation
Case Presentation
PE:
 No suspicious skin lesions
 2.5-cm scar in right pre-auricular region
 2.0-cm non-mobile rubbery mass in the
right parotid gland
 Erythema of surrounding skin
 House-brackman facial nerve- II/VI
 Lymphadenopathy in submandibular
region and anterior triangle of neck
Case Presentation
What to do next?
Case Presentation

Issues:
 Not sure of original path
 Not sure of extent of first surgery
 Facial weakness caused by surgery or tumor
Case Presentation
Discussion:
 Should this patient be offered an FNA?
 Imaging modality?
 Facial N preservation?
 Post-Operative XRT?
Case Presentation

Pt. was scheduled for total
parotidectomy and right selective neck
dissection of lymph node levels I-IV.
Tumors of Salivary Glands
History
RIOLAN 1648: Identified the glandular substance of
parotid
 NIELS STENSON 1660: Identified the parotid duct in
sheep
 THOMAS WARTON 1656 – Identified the submandibular
gland and duct
 HEYFELDER 1825: Avoided the facial nerve after
parotidectomy
 VELPEAU 1830: Identified trunk of facial nerve
 BELL AND VELPEAU: Determined the facial nerve was
responsible for facial animation. Determined facial
sensation was from CN V.

Parotid Gland
Anatomy
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Largest salivary gland
The parotid duct lies on an
imaginary line between the
external nares and the tragus of
the ear.
Boundaries: external auditory
canal, ramus of mandible, &
mastoid process
Gland is encased in a sheath
Stensen’s duct – courses anterior
to masseter muscle, transverses
Buccinator, and exits orally along
maxillary second molar.
Artificial division between the
deep and superficial lobes by
facial nerve.
Parotid Gland
Anatomy – Facial Nerve
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Exits from stylomastoid
foramen
Divides into temporofacial
and cervicofacial
Terminal Branches:
 Temporal/Frontal
 Zygomatico-orbital
 Buccal
 Mandibular
 Cervical
Parotid Gland
Surgical Anatomy – Facial Nerve
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Tympanomastoid suture
Bisects angle between post
belly of digastric and ear canal
Tragal Pointer
 1cm deep and inferior
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Nerve lateral to styloid process
Superficial to retromandibular
vein
Retrograde dissection
Epidemiology
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Malignant salivary gland neoplasms
represent 3-4% of malignant head and
neck disorders
Incidence of 1-2 per 100,000 individuals
Neoplasms arising in the minor salivary
glands have a poorer prognosis than those
primary in the parotids.
20-25% of parotid gland tumors are
malignant
Average age of presentation is 56.6 years
History and Physical
Present with an incidentally noted mass
 Pain
 Nerve palsy, commonly CN VII, but
lingual and hypoglossal nerves may be
affected.
 Presence of lymphadenopathy
 Trismus, numbness, fixation may also
be present

Diagnostic Studies
CT (with contrast)
 Requires contrast and
radiation
 Excellent detail of the tumor
volume
 Useful in evaluating the
parapharyngeal space
 Relation of tumor to
vascular and bony
structures helpful in surgical
planning
 Lymphatic survey
Diagnostic Studies
MRI
 Does not require
iodination or radiation
 Excellent soft tissue
detail
 Superior in defining
the tumor boundaries
 Useful to determine if
nerve involvement
present
T1, low signal
intensity
T2, high signal
intensity
Diagnostic Studies
PET Scan
 Useful in staging and follow-up
 Rule out distant and regional
metastases
 Predicted the nature of the
neoplasm in 69%
 Demonstrated 100% sensitivity
for malignancy
 False-positive rate of 30%
 Role not yet well defined
Diagnostic Studies
Fine-Needle Aspiration
Biopsy
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Efficacy is well
established
Accuracy = 84-97%
Sensitivity = 54-95%
Specificity = 86-100%
Safe, well tolerated
Pleomorphic Adenoma- FNA
Fine-Needle Aspiration Biopsy

Opponents argument:
 Doesn’t change management
○ Often surgery regardless of reported
diagnosis
 Obscuring final pathologic diagnosis
 Frequency of “inadequate” sampling,
requires multiple biopsies, prolongs course
until definitive treatment, increases cost
Fine-Needle Aspiration Biopsy

Proponent’s argument:
 Important to distinguish benign vs. malignant
nature of neoplasm
 Preoperative patient counseling
 Surgical planning
 Differentiate between neoplastic and nonneoplastic processes
○ Avoid surgery in a number of patients
Risk Factors for
Primary Salivary Malignancy
Increased risk:
 Radiation exposure
 Full-mouth dental x-rays
 Rubber industry
 Nickel compound/alloy
 Hair dye
 Silica dust
 Kerosene cooking fuels
 Vegetables preserved in salt
Decreased risk:
 High intake liver
 High intake dark yellow vegetables
Histologic Types
Mucoepidermoid Carcinoma
34%
Adenoid Cystic Carcinoma
22%
Adenocarcinoma
18%
Carcinoma ex pleomorphic adenoma
13%
Acinic cell carcinoma
7%
Squamous cell carcinoma
4%
Mucoepidermoid Carcinoma
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Most common type
80-90% occur in the parotid gland
Female to male ratio of 4:1
Highest prevalence in 5th decade of life
Characterized histologically by a mixed population
of cell, mucin-producing cells, epithelial cells, and
intermediate cells.
Stain positive with Mucicarmine stain
Classified as low, intermediate, high grade based
on clinical behavior and tumor differentiation.
Mucoepidermoid Carcinoma
Low-grade tumors have a higher
proportion of mucous cells to epidermoid
cells.
 High-grade mucoepidermoid carcinomas
have a higher proportion of epidermoid
cells  difficult to differentiate from
scca.

Mucoepidermoid Carcinoma
Characterized by islands having
squamous cells as well as clear cells
containing mucin and intermediate
cells.
Mucicarmine stain
Mucoepidermoid Carcinoma
Survival rates:
5 yr.
survival
15 yr.
survival
Low
Grade
70%
50%
High
Grade
47%
25%
Adenoid Cystic Carcinoma
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More common in submandibular, sublingual and
in minor salivary glands
Presents equally frequent in women and men
Asymptomatic mass
Clinical course is indolent and protracted
Perineural spread, including discontinuous
spreading can occur along a nerve in 80%
Therefore adjuvant radiation to regional named
nerves is recommended
Lymphatic spread is uncommon
Adenoid Cystic Carcinoma

Microscopically, adenoid cystic
carcinoma has a basaloid epithelium
arranged in cylindric formations in an
eosinophilic hyaline stroma.
Adenoid Cystic Carcinoma
Subtype
%
Characteristics
Swiss cheese pattern
Cribiform 44% of vacuolated area
(best prognosis)
Tubular
Cords & nests of
35%
malignant cells
Solid
Solid sheets of cells
21%
(worst prognosis)
Cribiform subtype
Adenocarcinoma
Aggressive behavior
25-60% nodal metastases
50% recur locally
Originates from excretory or striated ducts.
Histologically identified by mucicarmine stain for
mucus & negative keratin stain
 Polymorphous low-grade adenocarcinoma is a
more benign subtype
 Prognosis: 5 yr survival is 25-70%
 Poor prognostic indicators: advanced stage,
infiltrative growth pattern, abnormal DNA
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Carcinoma Ex-Pleomorphic adenoma
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75% occur in parotid gland
Arise from/in pleomorphic adenomas (a benign
mixed tumor)
Associated with a rapid change in size of a
previously stable tumor.
Histologically: mixture of epithelial and
mesenchymal cells
Malignant component is purely epithelial
Classified as high grade
Prognosis: if treated prior to invasion, good.
5 yr. survival is <10%.
Carcinoma Ex-Pleomorphic adenoma

Treatment is surgical
resection with facial
nerve preservation,
neck dissection for
nodal disease, and
adjuvant
radiotherapy.
Ductal structures (D) are randomly
scattered and lined by cuboidal or
columnar epithelium which usually
surrounded by myoepithelial cells
(M). Islands of well-differentiated
squamous cells with keratin (S) are
seen.
Acinic Cell Carcinoma
80-90% occur in parotid gland
Presents in 5th decade of life
Higher incidence in women
Low-grade malignancy
Two cell types: serous acinar cells (explains
parotid gland preference) & clear-cytoplasm cells
 Four histologic types: Solid, microcystic,
papillary, & follicular
 Prognosis at 5, 10 & 15 yrs is 78%, 63%, 44%
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Acinic cell carcinoma
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Round cells with
abundant
granular, blue
cytoplasm
Squamous Cell Carcinoma
Existence of true primary SCC of salivary glands
debated
 Present in elderly males
 Commonly present in advanced stage
 20% facial paralysis
 40-70% nodal metastases
 15-20% distant metastases
 Must distinguish from mucoepidermoid carcinoma with
immunohistochemical staining for mucin.
 Must exclude extension from skin primary or mucosal
primary
 Neck dissection is indicated
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Metastases to Parotid Gland
Lymph Nodes
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Less than 10% of malignant
salivary disorders are
metastases from other sites
Most are lymphatic
metastases from skin cancer
of face, ear, scalp.
Most commonly SCC or
Melanoma.
Elective superficial
parotidectomy and neck
dissection should be
performed for primary
melanoma of intermediate
depth (1.5-4mm) located
within periparotid drainage
area.
TNM Staging
T1 Tumor less than 2cm
 T2 Tumor between 2cm and 4cm
 T3 Tumor greater than 4cm and/or
extraparenchymal extension
 T4a Moderately advanced disease,
invades skin, mandible, ear or facial n.
 T4b Very advanced disease, invades
skull base, pterygoids or encases
carotid

Areas of Controversy
FNA
 PET-CT usefulness
 Preferred modality of imaging.
 Radiotherapy for unresectable tumors
 Facial nerve preservation
 LN Dissection

FNA
Remove cells by aspiration
 Not able to visualize structure of tissue
 George Papanicolaou (1883–1962) is
generally credited with the rediscovery
of cytopathologic examination
 Extracts diagnostic information from the
appearance of individual cells and cell
clusters.
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FNA
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Among H&N sites, the parotid gland has
the highest FNA inaccuracy rates:
 Sheer number of number and diversity of
salivary gland tumors.
 Relatively uncommon – cytopathologist
experience limited.
 Distinct tumor types often share some
overlapping morphologic features.
 Some parotid carcinomas appear very bland
and nonthreatening at cellular level.
FNA

Should reliably:
 Distinguish benign from malignant
 Identify lymphoma
 Cutaneous malignancy
Fine needle aspirationcytology in the management of a
parotid mass: A two centre retrospective study
K. Balakrishnan et. al

6 yr study, N= 132
52 (46%) aspirates were suggestive of
the final diagnosis
 35 (31%) were non-diagnostic
 15 (13%) were sampling errors
 11 (10%) FNAC results were misleading.
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Fine needle aspirationcytology in the management of a
parotid mass: A two centre retrospective study
K. Balakrishnan et. al
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Sensitivity of FNAC in detecting
malignant disease was 79% (95% CI 6197%)

Specificity of 84% (95% CI 73-95%)

Positive predictive value of 68% (95% CI
48-88%)
Fine needle aspirationcytology in the management of a
parotid mass: A two centre retrospective study
K. Balakrishnan et. al

Concluded:
 Majority of neoplasms are benign and FNAC
appears better at predicting benign than
malignant disease.
 Correctly identifying pleomorphic adenoma
as a benign tumour was 92%.
 FNA did not reliably predict/dx lymphoma,
but may have avoided radical parotidectomy.
Value of the cytological diagnosis in
the treatment of parotid tumors.
Jafari et. al.

6yr interval, N=110
concordance b/w cyto & histo was
observed in 82.1% of cases
 benign or malignant concordance of the
tumors reached 92 percent.

Value of the cytological diagnosis in
the treatment of parotid tumors.
Jafari et. al.
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Sensitivity of FNAC in detecting
malignant disease was 67%
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Specificity of 96%
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PPV was 80% and NPV was 93%.
Value of the cytological diagnosis in
the treatment of parotid tumors.
Jafari et. al.
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Concluded:
 In the majority of parotid tumors, there was a
good correlation between the FNA
cytological diagnosis and the
histopathological results
 FNA provides an adjuvant tool in the
strategic and surgical approach of a parotid
tumor:
○ wider resection of parotid gland
○ cervical neck dissection
Value of Fine Needle Aspiration Biopsy of Salivary
Gland Masses in Clinical Decision-Making
Heller et. al.
Complications of FNAB appear to be
rare.
 No sign of tumor implantation by FNA.
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FNA resulted in a change in the clinical
approach to 35% of the patients.
 Surgery avoided in 27%
 Lesser procedure performed in 8%
PET
Inflammatory lesions, warthin’s and
pleomorphic adenomas can have
increased FDG uptake.
Accuracy was 53%.
 False-positive rate was 55% when the
cut-off value for SUV was set at 3.5.

Keyes et al. reported an accuracy of
69%
 False-positive rate of 30% for
differentiation of benign and malignant
masses using PET.
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PET identified all 26 lesions:
 All 12 malignant lesions
 Correct categorization in only 69% of cases.
 Thus, it was not as good as the more
conventional diagnostic methods, their
correct categorizations being 85% (clinical),
87% (CT/MRI), and 78% (FNAB) in the
same patients.
(*)The lesion contains high intensity area relative to CSF and that area
shows partial enhancement (yes) and no enhancement (no).
MRI vs CT
N=40 with a parotid mass
 CT vs MRI
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Concluded:
 MRI better at distinguishing intrinsic vs
extrinsic
 Inaccuracy rate of both MRI and CT was the
same regarding the tumor infiltration
 MRI 3x more expensive than CT
 CT and MRI are morphologically equivalent
studies and have the same diagnostic
potential in parotid tumors
MRI – Perineural Spread
Better at determining perineural spread
than CT
 Criteria:
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 Replacement of nerve with tumor
 Enhancement of gad
 Increase in size of nerve
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More sensitive and specific.
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MRI was better in
determining cisternal
segment and
cavernous sinus
CT and MR imaging
were virtually
identical in
demonstrating
penineural tumor
below the skull base
T1 weighed MRI before and after GAD
is the study of choice if perineural
spread is suspected.
 Fat suppression also beneficial around
skull base.
 Generally, MRI indicated when nerve
involvement suspected.

Post-Operative XRT
166 Patients
 34 yrs experience at MDA
 Excluded patients with macroscopic
disease
 Patients radiated to treat suspected
microscopic disease
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Results:
 9% local recurrence
 10yr local control rates – 90%
 Facial nerve sacrifice and ND were associated
with local failure
Concluded

Recommended postop XRT for:
 High-grade histology
 Recurrent disease
 Inadequate surgical margins
 Perineural invasion
 Extension of disease beyond the gland
 Nodal disease
Facial Nerve
Should the facial nerve be sacrificed
to achieve clear surgical margins?
Traditional management as been to preserve
facial nerve whenever possible.
 1992 study of parotid adenoid cystic
carcinomas by Casler and Conley called into
question the customary surgical approach of
preserving the facial nerve.
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Casler and Conley:
 32 patient with nerve sacrifice
 Normal pre-op function
 Higher 15-yr survival rate (60%) than in
those patients in which nerve was
preserved.
 But did not reach statistical significance
Retrospective chart review
 Adenoid cystic from 1966-2007
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Concluded:
 Selective sacrifice when nerve impaired or where
tumor margins compromised seems to improve
local control and survival.
 QOL significantly affected.
 Pre-op FNA and CT extremely useful in
counseling patients.
 Patients managed w XRT better local control.
Role of Neck Dissection
Traditionally surgery for primary site
with XRT to neck for clinically
negative neck in parotid malignancy
Literature Review
 39 total publications from 1997-2007

83% (out of 871 patients) were staged
N0 by palpation and radiology
 23% of ELND identified pathologic
nodes
 Elective treatment by either (selective)
neck dissection or radiotherapy is,
therefore, widely practiced.
 Regional recurrences are only 5% after
aggressive therapy.

Predictive Factors in N0 Neck
High tumor grade
 Facial paralysis
 Older age (>54y/o)
 Perilymphatic invasion
 Extraparotid extension
 T3 or T4 disease
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Caveats:
 Most important factor is tumor grade
however this is usually unknown prior
pre-operatively

Still controversial how to treat N0 neck
Conclusions
Parotid carcinoma accounts for 3-4% of
H&N cancers
 FNA important in counseling patient

 Especially when FN is involved
 Keep in mind variety of morphologies
(benign and malignant)
CT generally useful
 MRI more useful when perineural
spread

Conclusions

PET may play a role but not initially
 False positive in inflammatory process
 Can not reliably distinguish benign from
malignant process
Post-Operative XRT indicated when
facial nerve is involved or in clinically
positive neck
 Elective neck dissection maybe
indicated in certain circumstances
