Tumor of the Salivary Glands




(1)
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

 



 

Diana M. Bell






































































Keywords
Salivary glandEpithelial tumorMesenchymal tumorPathologyImmunohistochemistryMolecular genetics



Introduction To Salivary Gland Tumors






Salivary gland tumors are predominantly epithelial (Tables 23.1, 23.2, 23.3, 23.4, 23.5 and 23.6). Mesenchymal tumors most often involve glands by extension rather than arising within the gland. The latter are also found predominantly in children and adolescents. The most commonly encountered tumors in surgical pathology will be highlighted in this chapter. The nonpleomorphic salivary adenomas can be placed under the domain of monomorphic adenoma . These, in turn, can be divided into basaloid and nonbasaloid tumors (Fig. 23.1 and Tables 23.7 and 23.8). There is also an inverse relationship between the site of the affected salivary gland and the frequency of malignancy (Table 23.9)


Table 23.1.
Categorical Classification of Salivary Gland Lesions




















Reactive/developmental

Primary neoplasms

Metastasis

Tumorlike

Benign

Epithelial

Cysts

Malignant

Nonepithelial



Table 23.2.
Tumorlike and Cystic Lesions




































Tumorlike

Cystic lesions

Sialolithiasis

Benign cysts

Sialadenitis

Cystic neoplasms

Sialadenosis

Inflammatory, specific, and nonspecific

Ductal adenoma/hamartoma
 

Oncocytosis

Necrotizing sialometaplasia

Benign lymphoepithelial lesions and Sjögren’s syndrome

Chronic sclerosing sialadenitis of the submandibular gland (Küttner tumor)

Cystic lymphoid hyperplasia in AIDS

Inflammatory pseudotumor

Others: nodular fasciitis, sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease), Wegener granulomatosis



Table 23.3.
Incidence and Location of Nonneoplastic Salivary Gland Cysts (Batsakis and Raymond 1989)




































Type

Site

Frequency (%)

Mucocele

Minor glands

76.0

Salivary duct

Parotid

9.0

Lymphoepithelial

Parotid and oral cavity

7.0

Ranula

Sublingual gland

6.0

Congenital sialectasis

Parotid

1.5

Polycystic (dysgenetic)

Parotid

<1.0



Table 23.4.
Frequency of Retention Mucocele by Site (Modified from S. Seifert)


































Site

Frequency (%)

Lower lip

23.5

Cheek

13.2

Floor of the mouth

12.6

Upper lip

15.4

Palate

8.8

Tongue

4.4

Other areas

16.1

No information

5.9



Table 23.5.
Salivary Gland Neoplasms


































































Benign

Malignant

Epithelial

Mesenchymal

Epithelial

Nonepithelial

Pleomorphic adenoma (benign mixed tumor)

Angioma

Mucoepidermoid carcinoma

Sarcomas

Basal cell adenoma/canalicular adenoma

Sialolipoma

Adenoid cystic carcinoma

Lymphomas

Warthin tumor

Fibrous histiocytoma

Acinic cell carcinoma
 

Oncocytoma

Neurofibroma and neurilemmoma

Terminal duct carcinoma (polymorphous low-grade adenocarcinoma)

Myoepithelioma
 
Epithelial–myoepithelial carcinoma

Sebaceous adenoma

Salivary duct carcinoma

Ductal papilloma

Basal cell adenocarcinoma

Cystadenoma

Sebaceous carcinoma
 
Oncocytic carcinoma

Adenocarcinoma, NOS (not otherwise classified)

Squamous cell carcinoma

Carcinoma ex pleomorphic adenoma

Carcinosarcoma (sarcomatoid carcinoma)

Myoepithelial carcinoma

Undifferentiated carcinoma (small and large cells)

Lymphoepithelioma (undifferentiated carcinoma with lymphoid stroma)



Table 23.6.
Incidence of Primary Epithelial Salivary Gland Neoplasms in Different Sites (%)
















































































Diagnosis

Parotid

Submandibular

Sublingual

Minor

Benign

 Pleomorphic adenoma

63.3

59.5

0

42.9

 Adenolymphoma

14.0

0.8

0

0

 Monomorphic adenoma

8.0

2.3

14.0

11.0

Malignant

 Mucoepidermoid carcinoma

1.5

1.6

0

8.9

 Acinic cell carcinoma

2.5

0.4

0

1.8

 Adenoid cystic carcinoma

2.0

16.8

28.6

13.1

 Adenocarcinoma (NOS)

2.6

5.0

14.2

12.2

 Squamous carcinoma

1.1

1.9

0

1.2

 Undifferentiated carcinoma

1.8

3.9

14.2

2.1

 Carcinoma ex PA

3.2

7.8

28.6

7.1


A145302_4_En_23_Fig1_HTML.jpg


Fig. 23.1.
Ductal adenoma.


A145302_4_En_23_Fig2_HTML.jpg


Fig. 23.2.
Necrotizing sialometaplasia.



Table 23.7.
Types of Monomorphic Adenomas
























Basal

Nonbasal

Tubulotrabecular

Warthin tumor

Solid

Oncocytoma

Canalicular

Sebaceous lymphadenoma

Dermal analog

Sebaceous adenoma

Ductal adenoma (Fig. 23.1)



Table 23.8.
Differential Characteristics Between Basal Adenomas and Canalicular Adenoma
















































































Feature

Basal adenoma

Other types

Canalicular

Sex

 Female/male

1:10

1:1

1.7:1

Age (years)

 Range

34–74

1–83

34–88

 Mean

58.1

58.6

65.1

 Synchronous

37.7%

0

0

 Dermal lesions
     

Site (%)

 Parotid

86.2

90.1

1.6

 Submandibular

6.8

4.9

0

 Upper lip

0

1.9

87.2

 Other minor site

6.8

0

24.7

Multicentricity

48%

0.9

24.0

Recurrences

24%

0

0

Malignant transformation

28%

3.9%

0


Modified from Eveson and Cawson 1985



Table 23.9.
Frequency of Epithelial Malignancy in Different Salivary Gland Sites

























Site

Malignant (%)

Parotid

14.7

Submandibular

37.0

Sublingual

85.7

Minor

46.1

Unknown

?

 


Tumorlike And Cystic Lesions



Tumorlike Lesions (See Table 23.2)



Sialolithiasis






Predominantly in the submandibular gland

 



Undulant and tender swelling

 



Parotid: less frequent and difficult to diagnose clinically

 


Microscopic



Dilated ducts

 



Squamous metaplasia

 



Acinar atrophy and inflammation

 


Sialadenitis






Acute and chronic nonspecific inflammation

 



Bacterial: Staphylococcus aureus



  • Viral: cytomegalovirus, paramyxovirus, Epstein–Barr virus, para- and influenza viruses, and coxsackievirus

 



Granulomatous



  • Obstructive sialadenopathy





    Ruptured mucoceles

     



    Extravasated mucin

     


  • Infectious





    Mycobacterial, cat scratch disease, tularemia, fungal, toxoplasmosis, and others

     


  • Sarcoidosis


  • Associated with systemic disease





    Wegener granulomatosis, Crohn disease, and others

     


  • Associated with salivary gland tumor





    Acinic cell carcinoma

     



    Mucoepidermoid carcinoma

     



    Warthin tumor

     



    Lymphoepithelial lesions

     


  • Foreign body granulomas





    Iatrogenic (sialography)

     

 


Sialadenosis






Hypertrophy and hyperplasia of acini

 



Associated with systemic and neural disorders

 



Presents as bilateral painless and recurrent swelling

 



Etiology: neurogenic, metabolic, or hormonal

 


Necrotizing Sialometaplasia (Fig. 23.2)




Clinical



Benign self-limiting reactive inflammatory process

 



Sites: palate, 81.7%; other oral sites, 7.0%; major glands, 7.8%; and other, 3.5%

 



Age: 40–60 years

 



More men than women

 



Uncertain etiology, possible vascular infarction

 


Macroscopic



Mucosal site, ulceration, and painful swelling

 



Nonulcerated: one-third of lesions

 



Microscopic (Fig. 23.2 )



Lobular distribution

 



Central ductal squamous metaplasia

 



Peripheral necrotic and inflamed acini

 


A145302_4_En_23_Fig3_HTML.jpg


Fig. 23.3.
Oncocytosis/oncocytic hyperplasia.


Differential Diagnosis



Squamous carcinoma



  • Infiltrative, keratinization, cellular features of malignancy


  • Lacks lobular preservation

 



Mucoepidermoid carcinoma



  • Mucinous cells, infiltrative intermediate cells, and cystic formations

 


Oncocytic Hyperplasia of Ductal and Acinar Structure (Fig. 23.3)






Unilateral or bilateral enlargement

 



Preservations of lobular architecture

 



Old age

 


Lymphoepithelial Lesions




Clinical



Idiopathic, autoimmune disease, HIV infection

 



Localized, systemic

 



Older women

 



Recurrent painful swelling

 



Epimyoepithelial islands

 



Microscopic (Fig. 23.4 )



Focal periductal lymphoreticular proliferation

 



Partial or total obliteration of the acinar structure

 



Epimyoepithelial islands

 



Marked lymphoreticular infiltrate with germinal centers

 



Hyaline-like material deposits

 


A145302_4_En_23_Fig4_HTML.jpg


Fig. 23.4.
Lymphoepithelial lesion.


Sjögren Syndrome




Clinical



Associated with



  • Keratoconjunctivitis sicca


  • Xerostomia


  • Connective tissue disease

 



Assessed by labial minor salivary gland biopsy



  • Focus score: number of inflammatory foci/4 mm of the gland (focus is defined as ≥50 lymphocytes)


  • High incidence of non-Hodgkin lymphoma in women


  • Nonlymphoid malignancy, low frequency

 


Differential Diagnosis



Lymphoepithelial carcinoma

 



Lymphoma (MALT)



  • Both tumors may arise in this setting

 


Küttner Tumor (Chronic Sclerosing Sialadenitis of the Submandibular Gland)






Unilateral

 



Lymphoplasmacytic periductal infiltrate with fibrosis

 



Clinically tumorlike

 


Cystic Lymphoid Hyperplasia (HIV+ Subjects) (Fig. 23.5)




A145302_4_En_23_Fig5_HTML.jpg


Fig. 23.5.
Cystic lymphoid hyperplasia .



Clinical



HIV-infected patients

 



Nodular or diffuse enlargement of salivary glands

 



Unknown pathogenesis

 



(p24) Antigen infection

 


Microscopic



Glandular atrophy

 



Intense lymphocytic proliferation with follicular hyperplasia

 



Cystic formation with epithelial lining from ductal inclusion

 



Epimyoepithelial islands

 


Inflammatory Pseudotumors




Clinical



Firm, nodular swelling in the parotid

 


Microscopic



Myofibroblastic proliferation and chronic inflammatory cells

 


Immunohistochemistry



SMA, MSA, and CD68+

 


Salivary Gland Cysts (See Tables 23.3 and 23.4)



Benign Cysts of the Salivary Gland: An Overview






Congenital cyst – rare (2%) (Fig. 23.6)

A145302_4_En_23_Fig6_HTML.jpg


Fig. 23.6.
Congenital cyst.

 



Secondary acquired, pseudocysts

 



Most secondary pseudocysts are mucocele

 



Parotid duct cyst (11%), lymphoepithelial cyst (7%), and ranula (5%)

 


Cystic Neoplasms






Cystic mucoepidermoid carcinoma

 



Warthin tumor

 



Cystadenocarcinoma

 



Sebaceous lymphadenoma

 


Inflammatory, Specific, and Nonspecific




Dysgenetic Cysts



Polycystic dysgenetic lesions (Fig. 23.7)

A145302_4_En_23_Fig7_HTML.jpg


Fig. 23.7.
Dysgenetic polycystic lesion.




  • Rare


  • Mainly in the parotid


  • Multiple cysts lined by simple epithelial lining


  • Female predominance


  • Delayed clinical manifestation


  • Bilateral


  • Fluctuating, nontender parotid swelling


  • Diagnosis: sialogram, spare main salivary duct


  • Surgical excision for diagnosis and treatment


  • Etiology: most likely developmental

 



Sclerosing polycystic adenosis (Figs. 23.8 and 23.9)

A145302_4_En_23_Fig8_HTML.jpg


Fig. 23.8.
Sclerosing polycystic adenosis.


A145302_4_En_23_Fig9_HTML.jpg


Fig. 23.9.
Sclerosing polycystic adenosis.




  • Resemblance of fibrocystic disease of the breast in its diversity


  • Preservation of lobular architecture


  • Duct ectasia, with or without epithelial hyperplasia, apocrine-like metaplasia


  • Occasional collagenous spherulosis


  • Uncapsulated but often demarcated, limitation of nodules from adjacent salivary tissue


  • Differential diagnosis: dysgenetic polycystic parotid gland, obstructive sialadenitis


  • Surgical excision for diagnosis and treatment


  • Etiology: unclear, pseudoneoplastic benign entity versus neoplastic

 



Cyst of the submandibular gland



  • Benign cyst lined by flattened epithelium


  • Etiology: duct segmentation

 


Secondary Cysts



Salivary duct cyst



  • Mainly in the parotid


  • 10% of all nonneoplastic cysts


  • More than two-thirds male in the second decade of life


  • Multilayered, cuboidal epithelial lining


  • Occasional oncocytic and squamous metaplastic changes


  • Cystic contents, spheroliths or crystalline precipitate


  • Pathogenesis: ductal obstruction

 



Lymphoepithelial cyst



  • Locations: parotid, intraparotid lymph nodes, and floor of the mouth


  • Lining: flattened or multilayered epithelium surrounded by lymphocytes and lymphoid follicles


  • Sebaceous glands and goblet cells may be present


  • Pathogenesis: displacement of epithelium into lymphoid tissue or proliferation of bronchial pouch epithelium


  • Related to benign lymphoepithelial lesions, chronic myoepithelial sialadenitis, and HIV-related cystic lymphoid hyperplasia

 



Mucoceles, Retention, and Extravasation (Ranula) (Fig. 23.10 )



Retention mucocele



  • Less common, 15%


  • Older age, >20 years


  • Site: minor salivary glands


  • Cyst lined by flat, cuboidal, or multilayered epithelium surrounded by thick fibrous capsule


  • Pathogenesis: obstruction

 



Extravasation



  • Most common, 85%


  • Sites: lip, cheek, and floor of the mouth


  • More in men (60%)


  • Peak incidence: second decade


  • Initially ill-defined mucus lakes, followed by granuloma formation and muciphages, finally mucin-filled pseudocysts (no epithelial lining)

 


A145302_4_En_23_Fig10_HTML.jpg


Fig. 23.10.
Subepithelial encapsulated mucin leakage (ranulas).


Benign Cystic Lesions of the Neck






Thyroglossal duct cyst



  • Midline, two-thirds below the hyoid bone, one-third off midline, anteromedial to carotid artery and jugular vein

 



Branchial cleft cyst



  • Lateral neck, unrelated to hyoid, majority near angle of mandible; if small, anterior to sternomastoid and lateral to carotid artery and internal jugular vein

 



Parathyroid cyst



  • 95% near inferior thyroid margin, off midline; anterior to carotid artery and internal jugular vein

 



Cervical thymic cyst



  • Off midline, low neck, anterior to carotid artery and internal jugular vein

 



Cystic hygroma

 



Dermoid cyst



  • Near midline, usually in the upper neck


  • Benign teratoma


  • Usually near the thyroid gland

 



Cervical ranula



  • Off midline and suprahyoid in submental and submandibular triangle

 


Benign Tumors (See Tables 23.5 And 23.6)



Epithelial



Pleomorphic Adenoma (Mixed Tumor)




Clinical



Comprised of 55–70% of all salivary neoplasms

 



More in females in the fourth decade

 



Painless, slow-growing mass

 



In the parotid: 90% superficial lobe, 10% deep lobe

 


Macroscopic



Well-defined lobulated mass

 



Multifocal in 0.5% of cases

 



Variegated appearance, cartilaginous

 



Microscopic (Figs. 23.11 , 23.12 , 23.13 and 23.14 )



Biphasic epithelial and mesenchymal elements

 



Epithelial cells



  • Tubules, nests, ribbons, and files with occasional squamous, oncocytic, or sebaceous differentiation

 



Myoepithelial cells



  • Spindle or plasmacytoid cells

 



Stroma



  • Mucoid, myxoid, hyaline, or chondroid


  • Rarely adipose tissue and bone

 



Crystals



  • Tyrosine-calcium oxalate , collagenous spherules

 


A145302_4_En_23_Fig11_HTML.jpg


Fig. 23.11.
Pleomorphic adenoma cartilaginous and ductal components.


A145302_4_En_23_Fig12_HTML.jpg


Fig. 23.12.
Pleomorphic adenoma (myxoid stroma).


A145302_4_En_23_Fig13_HTML.jpg


Fig. 23.13.
Pleomorphic adenoma (squamous differentiation).


A145302_4_En_23_Fig14_HTML.jpg


Fig. 23.14.
Pleomorphic adenoma with crystals.


Immunohistochemistry



Generally noncontributory

 



S-100 protein and smooth muscle actin (SMA)+in stroma and myoepithelial cells

 


Cytogenetics and Molecular Genetics



Alteration, rearrangements, and LOH at 8q21 and 12q 14–15 regions

 


Differential Diagnosis



Adenoid cystic carcinoma



  • Lacks mesenchymal elements; clear demarcation between collagenous, epithelial, and mucoid materials


  • Propensity for perineural invasion

 



Myoepithelioma



  • Lacks ductal and mesenchymal elements

 



Terminal duct carcinoma



  • Variegated epithelial patterns


  • Lacks mesenchymal features

 


Recurrent Mixed Tumor



Histologically similar to original tumor

 



Multiple nodules

 



Extension to surrounding tissue

 


Myoepithelioma




Clinical



Uncommon, 1.5% of all salivary tumors

 



2.2–5.7% of all benign tumors

 



Male to female ratio, 1:1

 



Most common sites: palate and parotid

 


Macroscopic



Well-demarcated mass

 



Tan, homogenous, and solid

 



Microscopic (Figs. 23.15 and 23.16 )



Comprised of >90% myoepithelial cells

 



Cellular, mucoid, or hyalinized stroma may be present

 



Lacks ductal differentiation

 



Cell types: spindle, plasmacytoid, epithelioid, and clear cells

 


A145302_4_En_23_Fig15_HTML.jpg


Fig. 23.15.
Myoepithelioma (organoid pattern).


A145302_4_En_23_Fig16_HTML.jpg


Fig. 23.16.
Myoepithelioma (spindle cell).


Immunohistochemistry



Keratin (CK14)+, SMA+, S-100 protein+

 


Electron Microscopy



Microfilaments, 50–100 Å in size

 



Pinocytic vesicles

 


Differential Diagnosis



Spindle cell myoepithelioma



  • Leiomyoma, nerve sheath tumors, synovial sarcoma, nodular fasciitis


  • Keratin immunoreactivity excludes mesenchymal tumors

 



Plasmacytoid myoepithelioma



  • Plasmacytoma, positive for monoclonal light chain reaction and negative keratin−

 



Clear cell myoepithelioma



  • Metastatic renal cell carcinoma : vascular, cellular atypia, hemorrhage, history of RCC


  • Myoepithelial carcinoma : cellular atypia, infiltrative growth

 


Oncocytoma




Clinical



Rare, 1% of all salivary tumors

 



Women slightly more than men

 



Bilaterality, in 7% of cases

 



Main presentation, swelling

 


Macroscopic



Solitary, encapsulated

 



Reddish brown, smooth, and homogenous cut surface

 



Microscopic (Fig. 23.17 )



Large polygonal eosinophilic cells with central round nuclei

 



Cord, ribbon, and acinar formation

 



Focal mucinous or squamous metaplasia may be present

 



Clear cell variant (clear cell oncocytoma)

 



Oncocytic hyperplasia may occasionally be found at periphery

 


A145302_4_En_23_Fig17_HTML.jpg


Fig. 23.17.
Oncocytoma.


Immunohistochemistry



AMA (antimitochondrial antibody)

 


Electron Microscopy



Large accumulation of mitochondria with lamellar structure

 



Occasionally large glycogen particles

 


Special Stains



Phosphotungstic acid hematoxylin (PTAH)+ stain

 


Differential Diagnosis



Conventional oncocytoma



  • Pleomorphic adenoma with oncocytic metaplasia: features of pleomorphic adenoma


  • Mucoepidermoid carcinoma: PTAH–, mucinous, intermediate, and squamous differentiation


  • Acinic cell carcinoma: acinar differentiation, PTAH–, granules


  • Oncocytosis and oncocytic hyperplasia: diffuse, lacks fibrous encapsulation, retains architecture

 



Clear cell oncocytoma



  • Epimyoepithelial carcinoma: dual cellular differentiation (myoepithelial and ductal)


  • Metastatic renal cell carcinoma: high vascularity, history of renal cell carcinoma

 


Warthin Tumor (Adenolymphoma)




Clinical



Second most common benign tumor

 



Superficial, slow-growing mass

 



Exclusively the parotid, 2–15% of all parotid tumors

 



Bilaterality not uncommon

 



Male to female ratio, 8:1

 


Macroscopic



Well circumscribed and cystic

 



Brownish, creamy materials

 



Microscopic (Fig. 23.18 )



Oncocytic epithelial lined spaces with occasional papillary formation

 



Lymphoid stroma, with germinal centers

 



Occasional goblet, squamous, and sebaceous cells

 


A145302_4_En_23_Fig18_HTML.jpg


Fig. 23.18.
Warthin tumor oncocytic ductal proliferation with lymphoid stroma.


Immunohistochemistry



Noncontributory

 


Electron Microscopy



Enlarged mitochondria in oncocytes

 


Cytogenetics



Structural alteration in chromosome 7

 



A subset of WT t(11;19)

 


Differential Diagnosis



Oncocytoma (in stroma-deficient Warthin tumor)



  • Lacks cystic formation

 



Sebaceous adenoma, squamous carcinoma, and mucoepidermoid carcinoma



  • Lack lymphoid stroma


  • Minimal oncocytic features

 


Sebaceous Lymphadenoma




Clinical



Rare, 0.1% of all adenomas

 



The parotid is the most common site

 



Male to female ratio, 1:1

 



Painless mass

 


Macroscopic



Circumscribed and encapsulated mass

 



Microscopic (Fig. 23.19 )



Solid sebaceous or cystic nests and metaplastic ducts in lymphoid stroma

 



Giant cell reaction to extravasated cystic content

 


A145302_4_En_23_Fig19_HTML.jpg


Fig. 23.19.
Sebaceous lymphadenoma.


Sebaceous Adenoma




Clinical



Rare, 0.1% of all salivary gland tumors

 



Males slightly more than females

 



Parotid, submandibular, and oral cavity glands are the most common sites

 


Macroscopic



Solid, gray, well-circumscribed mass

 


Microscopic



Benign irregular sebaceous cellular nests in lymphoid stroma

 



Large cystic formation

 


Basal Cell Adenoma (see Table 23.7)




Clinical



1–3% of all major salivary gland tumors

 



Mostly in women

 



The parotid is the most common site

 



May present within the cervical lymph node

 


Macroscopic



Encapsulated, round, or oval mass

 



Grayish or white homogenous cut surface

 



Average size 2 cm

 



Occasional cystic formation

 



Microscopic (Figs. 23.20 and 23.21 )



Trabecular, solid , mixed, and membranous cellular patterns

 

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Sep 21, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Tumor of the Salivary Glands

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