Salivary gland cancer Flashcards

1
Q

What is the incidence of salivary cancers in the United States?

A

∼2,500 cases/yr of salivary cancers (∼5% of all H&N cancers)

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2
Q

What is the sex predilection and median age at presentation for benign vs. malignant tumors?

A

Benign: female > male, 40 yo
Malignant: female = male, 55 yo

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3
Q

What is the most common type of benign tumor of the salivary gland, and where is it most commonly found?

A

Pleomorphic adenoma (65%). It is most commonly found in the parotid glands.

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4
Q

In addition to pleomorphic adenoma, what are some other benign salivary gland tumors?

A

Warthin tumor (papillary cystadenoma lymphomatosum), Godwin tumor (benign lymphoepithelial lesion, associated with Sjögren), and monomorphic adenoma (oncocytoma, basal cell)

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5
Q

What is the most common malignant salivary gland tumor, and where is it most commonly found?

A

Mucoepidermoid carcinoma. It most commonly arises in the parotid (most are low grade, but if the tumor is high grade, it needs to be managed with Sg + LND + adj RT).

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6
Q

How are tumors of the salivary gland separated into low vs. intermediate vs. high grade by histology?

A

Tumors should be assigned a grade by the pathologist. Some tumors are assumed a grade unless specified, though it should always be verified. Acinic cell carcinoma is typically a low-grade tumor. Carcinoma ex-pleomorphic adenoma (CexPA), and salivary ductal carcinomas are almost always high grade. Mucoepidermoid carcinoma must be graded. Adenoid cystic carcinoma (ACC) is often low grade, but rather than grading, pathologists will describe ACC as either tubular, cribriform (low), or solid (high). ACC is
often grouped with high-grade tumors as its propensity for poorly defined borders and neurotropism almost always requires multimodal therapy. The nomenclature for salivary gland tumors is also evolving. Thus, mixed malignant tumors are rarely seen as the majority are CexPA, and most adenocarcinomas seen are aggressive salivary duct carcinoma or low-grade polymorphous adenocarcinoma (most commonly seen in the hard palate).

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7
Q

What is the relationship b/t the gland size and malignant nature of the salivary tumor?

A

Typically, the smaller the gland, the more malignant the tumor.

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8
Q

What is the approximate incidence ratio of benign to malignant tumors in the various salivary glands?

A

Approximate incidence ratios of benign to malignant tumors:

  1. Parotid, ∼75:25
  2. Submandibular gland, ∼50:50
  3. Sublingual gland, ∼10:90
  4. Minor salivary, ∼20:80
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9
Q

What is the most common malignant histology arising in the submandibular gland?

A

ACC is the most common malignant histology of the submandibular gland.

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10
Q

What is the most common malignant histology arising in the minor salivary glands?

A

ACC is the most common malignant histology of the minor salivary glands.

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11
Q

Where are the minor salivary glands found in the H&N?

A

Minor salivary glands are found in the mucosal lining of the aerodigestive tract. Most are in the OC (85%–90%), with the palate (especially the hard palate) being the #1 site. They can be found in all sites of the OC, nasal
cavity, PNS, OPX, and larynx.

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12
Q

What are the risk factors for developing salivary gland tumors?

A

Ionizing RT, personal Hx of tumor, and family Hx

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13
Q

What is the lymphatic drainage predilection of the parotid, submandibular/sublingual, and minor salivary glands?

A

Lymphatic drainage predilection:
Parotid: preauricular, periparotid, and intraparotid, with deep intraparotid nodes draining sequentially along the jugular nodes (levels II–IV)
Submandibular/sublingual: levels I–II nodes, less often levels III and IV
Minor salivary: depends on site of involvement and histology

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14
Q

How does the propensity for LN mets relate to the site of origin of the salivary tumor?

A

The propensity for LN spread is greatest for the minor salivary gland > submandibular/sublingual > parotid gland malignancies.

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15
Q

What is the natural Hx of ACC?

A

ACC is often low grade (cribriform or tubular), but is very locally infiltrative. PNI with skipped lesions and involvement of large nerves is common, as is DM. Recurrence can be very late, though high-grade tumors
(solid type) tend to have a more aggressive course. Nodal mets are uncommon (5%–8%).

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16
Q

What % of pts with ACC ultimately go on to develop lung mets?

A

∼40% of pts with ACC ultimately develop lung mets.

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17
Q

What is the most common presentation of parotid gland tumors?

A

A painless, solitary mass is the most common presentation of parotid gland tumors

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18
Q

For what does a painful growth/mass in the salivary gland predict?

A

It predicts for malignancy or an inflammatory etiology/condition.

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19
Q

What are some other presenting Sx in pts with salivary gland tumors?

A

Pain, facial weakness from CN VII involvement, rapid growth of mass, skin involvement, neck nodes. Sensory changes of the face can occur from involvement of the trigeminal nerve branches (CN V), and dysarthria/ dysphagia can occur from CN XII being affected.

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20
Q

What is the DDx for a parotid mass?

A

Primary tumor, mets, lymphoma, parotitis, sarcoid, cyst, Sjögren syndrome, stone, lipoma, hemangioma

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21
Q

What are the 2 most important factors that predict for nodal mets in salivary gland malignancies?

A

Grade and size are the 2 most important factors that predict for nodal mets: high grade (50%) vs. intermediate/low grade (<10%) and size (>4 cm: 20%
vs. <4 cm: 4%).

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22
Q

What is the typical workup performed for salivary gland tumors?

A

Salivary gland tumor workup: H&P (CNs/nodes), CBC, CMP, CXR, CT/MRI H&N, and FNA Bx

23
Q

How should Bx be obtained for pts who present with a salivary gland mass?

A

Some argue that a salivary gland mass should be removed regardless, so do not Bx. However, FNA should be done (despite an FN rate of 20%), as knowledge of the histology may impact the type of Sg.

24
Q

What is the T-staging breakdown for major salivary gland tumors (AJCC 8th edition)?

A

T1: ≤2 cm no extraparenchymal extension (ST invasion,
clinical/macroscopic)
T2: >2 cm, ≤4 cm, no extraparenchymal extension
T3: >4 cm and/or extraparenchymal extension
T4(a–b): local invasion of adjacent structures (see below)

25
Q

What is the distinction b/t T4a vs. T4b major salivary gland tumors?

A

T4a: usually still resectable; skin, mandible, ear, facial nerve invasion
T4b: usually unresectable; skull base, pterygoid plate, carotid artery encasement

26
Q

What is the clinical nodal staging system used for major salivary gland tumors?

A

The same as most H&N sites (except for NPX and p16+ OPX):
N1: single ipsi, ≤3 cm, ENE(–)
N2a: single ipsi, >3 cm, ≤6 cm, ENE(–)
N2b: multiple ipsi, ≤6 cm, ENE(–)
N2c: any bilat or contralat, ≤6 cm, ENE(–)
N3a: any >6 cm, ENE(–)
N3b: any clinically overt ENE(+)

27
Q

What is the pathologic nodal staging system used for major salivary gland tumors?

A

The same as most H&N sites (except for NPX and p16+ OPX):
N1: single ipsi, ≤3 cm, ENE(–)
N2a: single ipsi/contra ≤3 cm, ENE(+) OR single ipsi >3 cm, ≤6 cm, ENE(–)
N2b: multiple ipsi, ≤6 cm, ENE(–)
N2c: any bilat or contralat, ≤6 cm, ENE(–)
N3a: any >6 cm, ENE(–)
N3b: any ENE(+) besides N2a

28
Q

Per the latest AJCC 8th (2017) edition classification, what are the stage groupings for major salivary gland tumors?

A
Stage I: T1N0
Stage II: T2N0
Stage III: T3N0 or T1–3N1
Stage IVA: T4aN0–1 or T1–4aN2
Stage IVB: T4b any N or any T N3
Stage IVC: M1
29
Q

On what is the staging system for the minor salivary gland tumors based?

A

Staging of the minor salivary gland tumors is based on the site of origin.

30
Q

What are some important prognostic factors in salivary gland tumors?

A

Size, grade, histology, nodal status, and “named” nerve involvement are important prognostic factors.

31
Q

What is the 5-yr OS for stages I–IV cancers of the salivary gland?

A

Stage I: 80%
Stage II: 60%
Stage III: 50%
Stage IV: 30%

32
Q

What is the 5-yr OS of pts who present with facial nerve involvement?

A

The 5-yr OS is 65% with simple invasion and 10% if pts have nerve dysfunction (i.e., if symptomatic).

33
Q

What is the general management paradigm for benign mixed/pleomorphic adenoma of the parotid?

A

Benign mixed/pleomorphic adenoma management paradigm: WLE, or superficial parotid lobectomy → observation (even if +margin or with extraglandular extension)

34
Q

What is the management paradigm for low- to intermediate-grade tumors of the salivary gland?

A

Low- to intermediate-grade salivary gland tumor management paradigm: surgical resection with PORT for close (<2 mm) or +margin, unresectable Dz, pT3–4, PNI, capsule rupture, +nodes, or recurrent Dz

35
Q

What is the management paradigm for high-grade tumors of the salivary gland?

A

High-grade salivary gland tumor management paradigm: surgical resection (facial nerve sparing if possible for parotid tumors), including LND if node+→ PORT

36
Q

What is the role of concurrent CRT for salivary tumors?

A

The level of evidence for CRT is weak. NCCN guidelines (2018) recommend consideration of definitive CRT for T4b Dz or PORT + chemo for pathologic adverse features including intermediate or high grade, inadequate margins, PNI, +LN, and LVI.

37
Q

What is the management paradigm for ACC with pulmonary mets?

A

ACC (cribriform or tubular) with pulmonary mets (typically asymptomatic with low tumor burden) management paradigm: same local therapy as in pts
without mets b/c pulmonary mets have a long natural Hx

38
Q

What is the difference b/t superficial, total, and radical parotidectomy?

A

Superficial: en bloc resection of gland superficial to CN VII
Total: en bloc resection of entire gland with nerve sparing
Radical: en bloc resection of entire gland + CN VII + skin + fascia +/– muscle

39
Q

What are the indications for LND with salivary gland tumors?

A

A clinically+ neck. LND is often done for high-grade and large tumors, but in the clinically negative neck, if the pt is to get PORT, the role of LND is questionable.

40
Q

What are the indications for PORT in the management of salivary gland cancers?

A

Adj RT is indicated for the following: high grade (regardless of margin), close/+ margin, pT3–T4 Dz, PNI, capsule rupture, tumor spillage, ECE, N2–N3 Dz, unresectable tumor/gross residual Dz, and recurrent tumor

41
Q

For which cN0 salivary gland tumors, by histology, does elective nodal RT significantly reduce the incidence of nodal relapse?

A

Elective nodal RT is more likely to reduce the incidence of nodal relapse in pts with squamous, undifferentiated, or adenocarcinoma histologies. (Chen AM et al., IJROBP 2007)

42
Q

When should bilat neck coverage with RT be considered for salivary gland neoplasms?

A

Tx of the ipsi neck should be adequate for major salivary gland cancers. Bilat nodal Tx is considered for high-grade minor salivary gland cancers affecting
midline structures.

43
Q

What are some ways to deliver RT/set up the RT fields in the Tx of parotid gland tumors?

A

RT delivery and set up of RT fields:

  1. AP/PA wedge pairs (120-degree hinge angle) but difficult setup, exit through OC
  2. Sup/Inf wedge pair (with 90-degree couch kick), avoids exit through OC but exits through brain
  3. Single direct field with mixed energy beam (80% 15 MeV electron: 20% 6 MV photon) with bolus, electron portal 1 cm larger than the photon field b/c of IDL constriction with depth, higher dose to bone, keep contralat parotid at <30 Gy
  4. IMRT (most commonly utilized nowadays)
44
Q

What are the PORT doses used in the management of salivary gland tumors?

A

60 Gy for –margin, 66 Gy for close/+margin, 70 Gy for gross residual, and 50–56 Gy to a low-risk neck

45
Q

What RT techniques can be used in the management of the ipsi neck?

A

RT techniques for the ipsi neck:

  1. Single lat appositional electron field
  2. Mixed electron–photon beam technique
  3. Half beam block technique
  4. IMRT (most commonly utilized nowadays)
46
Q

What key retrospective data demonstrated the importance of adding PORT for stages III–IV and high-grade salivary gland tumors?

A
MSKCC data (Armstrong JG et al., Arch Otolaryngol Head Neck Surg 1990; Harrison L et al., J Surg Oncol 1990) showed improved LC and survival. SEER data (Mahmood U et al., Arch Otolaryngol Head Neck Surg
2011) also showed improved survival.
47
Q

What is the largest retrospective study demonstrating the benefit of adj RT for malignant salivary gland neoplasms?

A

Dutch NWHHT study (Terhaard CHJ et al., IJROBP 2005): 498 pts. Adj RT significantly improved LC in pts with T3–T4 Dz, a close margin, incomplete resection, bony invasion, and PNI.

48
Q

What is the best RT modality for managing unresectable salivary gland tumors?

A

Neutrons (sup LC, with photons showing LC of 25% for inoperable cases). If no access to neutrons, some advocate concurrent CRT

49
Q

When is surgical resection alone adequate in the management of recurrent salivary gland tumors?

A

If tumors are of low/intermediate grade, <3 cm, and there are no other risk features, then Sg alone may suffice.

50
Q

What is Frey syndrome, and from what does it result?

A

Auriculotemporal nerve syndrome (gustatory sweating or redness and sweating on the cheek area when the pt eats, sees, or thinks about or talks about certain kinds of food). It is a postop complication of parotidectomy.

51
Q

What is 1st bite syndrome, and from what does it result?

A

First bite syndrome is a rare complication of Sg involving the infratemporal fossa, parapharyngeal space or removal of the deep lobe of the parotid gland.
It is characterized by facial pain after the 1st bite of each meal which usually subsides after subsequent bites. It is believed to be caused by autonomic dysfunction of salivary myoepithelial cells.

52
Q

What are some possible Tx sequelae from RT for parotid cancers?

A

The main concerning sequelae are related to the ear. Acute effects include otitis externa or media with mild hearing loss. Late effects include dry cerumen, otitis media, and hearing loss. ORN of the temporal bone (parotid cancer) is uncommon as is mandibular ORN. Since Tx is mostly unilat, xerostomia is mild.

53
Q

Above which RT doses can salivary gland function be compromised, resulting in xerostomia?

A

The parotid is the most sensitive gland d/t a large component of serous glands which are highly radiosensitive. There is no dose threshold. Min doses to
effect parotid function start at ∼14 Gy. Based on older data, mean doses of 26–30 Gy are still used as planning goals with IMRT, although doses as high as 40 Gy can still allow some recovery. The doses that result in damage to other salivary glands have not been well studied

54
Q

What is the general follow-up for pts with salivary gland neoplasms?

A

Per 2018 NCCN guidelines, H&P (q1–3 mos for yr 1, q2–6 mos for yr 2, q4–8 mos for yrs 3–5, and q12 mos thereafter), chest imaging if clinically indicated, and TSH q6–12 mos if neck RT