Salivary Glands Flashcards
Salivary Glands
- 3 paired major salivary glands:
- Parotid glands
- Submandibular glands
- Sublingual glands
- In addition, there are numerous (600 - 1000) minor salivary glands distributed throughout the submucosa of the upper aerodigestive tract
Parotid gland:
* Largest (weight 15 - 30 g)
* Pyramidal shaped
* Encased in robust parotid fascia
* Branches of the facial nerve traverse the body of the parotid gland to artificially divide the gland into superficial and deep lobes and exit in the form of 5 terminal branches from its anteromedial surface to supply 22 muscles of facial expression
* Stensen duct (~7 cm) is the main excretory duct
* Clinically important as salivary gland tumors can arise in this location
* Responsible for up to 50% of saliva production upon stimulation
* Serous acini –> Dominant component
Submandibular gland:
* Second largest (weight 7 - 15 g)
* Enveloped by a capsule continuous with the superficial layer of the deep cervical fascia
* Wharton duct (~5 cm) is the main excretory duct
* Lingual nerve crosses Wharton duct twice
* Mixed seromucous acini –> serous predominance
Sublingual gland:
* Smallest of the major salivary glands (weight 2 - 4 g)
* Almond shaped and enveloped by loose connective tissue (no discrete capsule)
* There may be multiple minor sublingual ducts, also known as ducts of Rivinus
* Mixed seromucous acini –> mucous predominance
Minor salivary glands:
* Scattered throughout the oral submucosa, with the exception of the gingiva and anterior hard palate
* Not encapsulated and each gland possesses 1 duct draining directly into the oral cavity
* Predominantly mucinous apart from the purely serous von Ebner glands of the dorsal tongue that surround the circumvallate papillae
Sialadenitis
Clinical Features:
* Acute
* Chronic
* Granulomatous
Causative agents:
* Viral –> Paramyxovirus, EBV, coxsackievirus, Flu A, Paraflu
* Bacterial –> Staph aureus, Strep, gram neg
Predisposing conditions:
* Dehydration
* Malnutrition
* Immunosuppression
* Sialolithiasis
Aetiology of Granulomatous subtype:
* Tuberculosis
* Mycosis
* Sarcoidosis
* Duct obstruction
Macro:
* Stone may be present
* Firm to hard
Micro:
* Variable atropic changes
* Fibrosis
* Acute and chronic inflammatory features
* Retained lobular architecture with fibrosis
* Squamous metaplasia
* Chronic sclerosis sialadenitis of submandibular gland –> unilateral, lymphocytic and plasmacytic inflammation encasing ducts
Necrotizing sialometaplasia
- Reactive, self resolving inflammatory condition of the salivary glands
- Classically begins as a swelling that evolves into a crater-like ulceration, which resolves within 3 - 12 weeks
- Most commonly affects the palate
- Necrosis or disruption of salivary acini with squamous metaplasia of ductal structures
- Etiology is thought to be a reaction to trauma or smoking in a setting of vascular compromise / tissue ischemia
- Mimics malignancy both clinically and histopathologically
Micro:
* Squamous metaplasia of ductal structures and acini with preservation of the salivary lobular architecture
* Necrosis / infarction of acini characterized by loss of nuclei and cell borders with or without zones of spilled mucin
* Pseudoepitheliomatous hyperplasia with generally bland cytology or keratinocytic regenerative atypia
* Reactive, myxocollagenous background stroma
* Surface ulceration, granulation tissue and subacute inflammation may be present
* Has been conceptualized by 5 histologic stages of development and evolution: infarction, sequestration, ulceration, repair and healing
Lymphoepithelial sialadenitis
- Part of a heterogeneous group of lesions with a prominent lymphoid component that involves the salivary glands
- Most common cause of diffuse bilateral enlargement of salivary and lacrimal glands
- May be isolated or associated with Sjögren syndrome
- Usually occurs in women
- Affects the parotid (90%) and submandibular gland (10 - 15%) with rare involvement of the minor salivary glands
- Histologically characterized by the lymphoepithelial lesion, which is formed by a proliferation of ductal remnants permeated by lymphocytes
- Indolent behavior; however, continued observation is mandatory because of an increased risk for lymphoma development (MALT lymphoma)
Micro:
* Early, extent of inflammation varies with collections of small lymphocytes surrounding intralobular ducts, minimal epitheliotropism, plasma cells not prominent
* Inflammation intensifies, contains lymphoid follicles with germinal center formation and more frequent plasma cells
* As inflammation becomes diffuse, there is partial and then total acinar destruction with the only remaining epithelium being the ducts
* Remnant ducts proliferate and are infiltrated by lymphocytes, forming the lymphoepithelial lesion
* Eosinophilic, hyaline basement membrane-like material may be present among the cells of the lesion
* Overall lobular architecture is maintained
IHC:
* B- and T- cell markers
* Kappa lambda stains on paraffin or frozen tissues
Sjögren syndrome
- Chronic autoimmune disorder of the salivary and lacrimal exocrine glands
- Primary etiological events remain unknown
- Characterized by lymphocytic infiltrates of the affected glands with subsequent dysfunction of these glands and the clinical picture of sicca syndrome
- Considered primary if not associated with other systemic disease or secondary if it occurs in association with another underlying autoimmune condition
- F:M = 9:1
- Bimodal distribution –> Third and fourth decade, Sixth decade
- Positive anti-SSA (Ro) antibodies and anti-SSB (La) antibodies
- ACR / EULAR classification criteria for labial salivary gland biopsy
Micro:
* Focal lymphocytic sialadenitis is the histological hallmark
* 1 or more dense aggregates with 50 or more lymphocytes
* Usually in perivascular or periductal areas
* Other features are nonspecific and include
* Nonspecific chronic sialadenitis and chronic sclerosing sialadenitis
* Mild to diffuse lymphocytic infiltrates
* Progressive atrophy of normal salivary gland acini
* Duct dilatation
* Variable parenchymal fibrosis
* Lymphoepithelial lesions (seen in ~50% of patients with primary Sjögren syndrome
IHC:
* BCL6 highlight germinal center B cells
* CD21 / CD23 can highlight follicular dendritic cells in germinal centers
Lymphoepithelial cyst
- Unilocular cysts that involve the parotid gland
- Frequently but not always HIV related
- Can be associated with autoimmune disease
- May result from cystic dilation of ducts within intraparotid or periparotid lymph node or branchial cleft remnants
- HIV associated lymphoepithelial cyst likely forms due to hyperplasia of intra-salivary gland lymph nodes and associated ductal obstruction
- **Sjögren syndrome **associated lymphoepithelial cysts arise secondary to infiltration of B cells into the ductal epithelium and their expansion within the striated ducts and subsequent basal ductal cell hyperplasia
Micro:
* Most cases show a unilocular cyst with a thin stratified squamous lining
* Simple cyst lined by low stratified squamous epithelium
* Surrounded by polymorphous lymphocytes with prominent germinal centers
Branchial pouch / cleft anomalies
- Slow growing movable mass in the lateral neck, often asymptomatic
- Manifested as inflammatory neck mass or fistula
- Rarely associated with squamous cell carcinoma, but cystic neck masses should be considered to be nodal metastases until proven otherwise (common sites of small primary occult tumors are tonsil, posterior tonsillar pillar, retromolar tongue, nasopharynx)
Micro:
* Stratified squamous or ciliated columnar epithelium lining
* Fibrotic wall with lymphoid follicles resembling lymph node or tonsil
* May be secondarily infected
* Cysts may have sebaceous or mucinous glands
* Occasionally found in thyroid tissue as heterotopic cartilage, thymus or solid cell nests representing ultimobranchial body remnants
Mucocele (Ranula)
- Reactive lesion to mucus extravasation that attracts muciphages without any epithelial lining
- Two types of ranula: Plunging or Cervical
- Typically occurs in the lateral side of the floor of the mouth
- Associated with an excretory duct of the sublingual gland
- Plunging type –> passes around posterior border of mylohyoid or through a hiatus in the muscle
Clinical:
* Simple type –> painless mass in the floor of the mouth
* Plunging type –> neck swelling, CT/MRI –> extension of lesion in submandibular space (tail sign)
Macro:
* Small, dome-shaped swelling of mucosa
* 0.2 to 1cm
* Consistancy is soft and fluctuant
Micro:
* Cyst
* Mucin surrounded by fibroconnective tissue/granulation tissue
* Frequent histiocytes
* Devoid of epithelial lining
* Thrombi and blood-filled vessels
Pleomorphic adenoma
- Triphasic salivary gland tumors with ductal cells, myoepithelial cells and stromal component
- Most common salivary gland neoplasm
- Prior radiation increases the risk of developing pleomorphic adenoma
- Slow growing, painless, well circumscribed mass involving salivary gland
Prognostic:
* Benign tumor
* Surgical resection with negative margin is considered curative
* Enucleation is associated with 15 - 25% risk of local recurrence
* Recurrences are usually within 18 months but can be up to 50 years later
* Risk of malignant transformation is ~5%
* Risk factors for malignant transformation: multiple recurrences, submandibular location, older age, larger size, prominent hyalinization, increased mitotic rate (if present, sample tumor more thoroughly), radiation exposure
Macro:
* Primary tumor: well demarcated, bosselated gray-white myxoid mass
* Recurrent tumor: numerous myxoid to fibrotic nodules of various size, giving a shotgun bullet appearance
Micro:
* Typically has 3 components:
* Epithelial (ductal) component forming the inner layer of cysts and tubules
* Myoepithelial cells as the outer layer of cysts and tubules and scattered within the myxoid stroma
* Stromal component is typically myxoid, chondroid or myxochondroid
* It can also be hyalinized or fibrotic
* Metaplastic changes may be seen, e.g. adipose metaplasia, osseous metaplasia, squamous metaplasia (sometimes with keratinization), sebaceous metaplasia and mucinous metaplasia
* Other features that may be seen in pleomorphic adenoma include:
* Tyrosine crystal: dense amorphous eosinophilic floret shaped crystal
* Increased cellularity: so called cellular pleomorphic adenoma
* Increased mitotic activity
* Myoepithelial rich area or tumor
Molecular:
* PLAG1 fusion (chromosome 8q12) or
* HMGA2 fusion (chromosome 12q14-15)
IHC:
* Ductal (epithelial) cells are typically positive for cytokeratins (e.g. AE1 / AE3, CAM5.2 and CK7)
* Myoepithelial cells are positive for GFAP, S100, SOX10, actin - alpha smooth muscle, calponin, p40 and p63
* PLAG1 and HMGA2 can be used as surrogate immunohistochemical markers for underlying PLAG1 or HMGA2 fusion
Warthin tumor
- Benign salivary gland tumor that is composed of oncocytic epithelial cells lining papillary and cystic structures in a lymphoid stroma
- Second most frequent benign tumor of the parotid gland (after pleomorphic adenoma)
- Infarcted / metaplastic subtype may occur following FNA biopsy
- Almost exclusively involves the parotid gland, especially the inferior pole and periparotid lymph nodes
- Strong link to cigarette smoking (especially when bilateral)
- Other suggested risk factors include radiation exposure in atomic bomb survivors and autoimmune diseases (especially thyroiditis)
- Glucose avid on PET and often incidentally detected during PET work up
Macro:
* Most are well circumscribed oval masses, 20 - 50 mm in diameter
* Solid areas and multiple cysts with papillary projections are apparent on the cut surface
Micro:
* Varying proportions of papillary cystic structures lined by bilayered oncocytic epithelial cells
* Surrounded by a lymphoid stroma including germinal centers
* Epithelial component is comprised of inner columnar and outer cuboidal cells
* Limited foci of squamous, mucous, ciliated and sebaceous cells can be present
* Infarcted / metaplastic subtype
* Bilayered epithelium is replaced by squamous metaplastic epithelium with no atypia
* Mucinous metaplasia may also be present
* Biopsy site reaction may be present with necrosis, squamous metaplasia and a stromal reaction (including granuloma formation)
Molecular:
* Absent MAML2 fusion (positive in mucoepidermoid carcinoma)
IHC:
* All epithelial cells are positive for pancytokeratin
* CK7, CK8 / CK18 and EMA are positive in luminal (or inner) epithelial cells
* p63 and p40 show heterogenous nuclear staining of the basal cells
* Lymphoid cells are positive for: B cell markers (CD20) and T cell markers (CD3, CD4, CD8)
+
Myoepithelioma
- Rare, benign tumor composed almost exclusively of myoepithelial cells
- Epithelial component should be less than 5% (some consider even focal epithelial differentiation sufficient to label the tumor as pleomorphic adenoma)
- Monomorphic histology and rare or absent ductal structures in myoepithelioma differentiate it from pleomorphic adenoma
- 1% of salivary gland tumors
- More common in parotid (40%) and minor salivary gland (21%)
- Usual age of presentation is 40 - 50 years (range: 9 - 85 years)
- No sex predilection
- Slow growing, painless, well circumscribed mass
- Recurs locally if incomplete removal
- Clear cell variant may have unpredictable clinical course despite being histologically benig
Macro:
* Up to 5 cm; encapsulated, may have cystic change
* Absence of grossly myxoid or chondroid areas
* Solid, tan or yellow-tan glistening cut surface
* Usually encapsulated in parotid gland and no capsule for those in minor salivary glands
Micro:
* Types:
* Spindled
* Epithelioid
* Plasmacytoid
* Clear
* Oncocytic cells
* Most tumors are composed of a single cell type but combinations may occur
Molecular:
* Clear cell myoepithelial carcinoma can have EWSR1 rearrangement
* NTF3-PLAG1
* FBXO32-PLAG1
* GEM-PLAG1 fusions have been detected in oncocytic myoepithelioma
* Detection of PLAG1 rearrangement by cytogenetics or other methods can be helpful
Oncocytoma
- Benign tumor composed of oncocytes (mitochondria-rich cells)
- Usually parotid gland mass, also submandibular gland or minor salivary glands
- Mean age 60 years
- 20% associated with radiation therapy or radiation exposure
- Rarely bilateral, multiple
- Rarely synchronous with Warthin tumor or carcinoma ex pleomorphic adenoma
- May occur in trisomy 7 or in BHD syndrome
Macro:
* Well circumscribed with fibrous capsule
* Solid
* May have cystic spaces
* Tan-red-brown
* Lobulated
* Often small
Micro:
* Eosinophilic or clear cell (glycogen) with sheets, trabeculae, acini or follicular patterns
* Monotonous large polygonal cells with well defined cell borders, deeply eosinophilic, granular cytoplasm, small round nuclei
* Vascular stroma
* May have clear cell change
* Background of oncocytic nodular hyperplasia
* Psammoma bodies
* Tyrosine rich crystals
* No mitotic figures
* No elastosis
IHC:
* PTAH, CK5 / 6, CK8 / 18, CK10 / 13, EMA, Ki67, p63
* Also antimitochondrial antibody, CK7+ / CK20-
* High viral load of high risk HPV
Basal cell adenoma
- Benign salivary tumor composed of nests and cords of small basaloid cells with inner ductal epithelial cells
- Solitary or part of turban tumor, Brooke-Spiegler syndrome
- Rarely transforms into malignancy; more likely if membranous type (4% malignant transformation)
- Most commonly involves parotid gland (70%)
Macro:
* Small (mostly < 5 cm), round or oval, encapsulated nodule
* Membranous subtype often nonencapsulated, multicentric and multilobular
* Usually brownish appearance; typically uniform and solid, without necrosis; can be cystic
Micro:
Types of tumor cells:
* Basaloid cells with basal cells or myoepithelial phenotype
* Luminal cells
* Fibrocellular stroma can be present
4 histologic patterns: mixture of at least 2 patterns is common
- Solid pattern: most common, basaloid cells are present in the form of solid masses which may show peripheral palisading
- Trabecular pattern: narrow or broad trabeculae which may get interconnected with each other creating a reticular pattern
- Tubular pattern: numerous tubules consisting of a central lumen and an outer single layer or double layered lining of cuboidal and basaloid cells is seen; the lumen often contains an eosinophilic secretion / mucin which is PAS positive
- Membranous types: histologically identical to dermal cylindroma, eosinophilic hyaline membranes separating cell nests; BCA with greater than 50% membranous pattern should be designated as membranous type
- Cyst formation is common and can be a main histopathologic feature of basal cell adenoma
- Occasionally has acinar cells, squamous whorls or keratinization
- No invasion, no perineurial invasion, no chondromyxoid matrix
Molecular:
* CTNNB1 mutations are common in BCA, especially those with tubular or tubulotrabecular patterns
* CYLD1 mutations and loss in sporadic and Brooke-Spiegler syndrome associated basal cell adenoma
IHC:
* Ductal cells: keratin, alpha-1-antichymotrypsin, CEA, EMA, CD117
* Basaloid cells: vimentin, actin, calponin, S100, p63, GFAP
* Spindle cell in the stroma is positive for S100, negative for p63
* Can be positive for BCL2 and nuclear beta catenin
Canalicular adenoma
- Monotonous, benign epithelial neoplasm; no basal / myoepithelial layer
- Most frequently located in the minor salivary glands (upper lip)
- May be multifocal
- Treatment by surgical resection
Micro:
* Tumors may be single or multifocal
* Bilayered strands or ribbons or anastomosing cords or branching tubules
* Canalicular to cystic spaces between the cell strands; trabecular features
* Lack of an outer layer of myoepithelial cells
* Beading pattern, club ended cords
* May infiltrate capsule and show extracapsular tumor islands (including in the normal salivary gland / multiple tumors)
* Often cystic change
IHC:
* Pancytokeratin
* CK7
* S100
* SOX10
* KIT (CD117)
Adenoid cystic carcinoma
- A carcinoma of primary salivary gland or minor salivary gland
- Biphasic ductal and myoepithelial differentiation, tubular / cribriform / solid architecture
- Most commonly affected site is the parotid gland
- May present with facial nerve paralysis
- Characterized by a propensity of perineural invasion, high frequency of local and distant recurrence and poor long term prognosis
Macro:
* Infiltrative ill defined firm mass
Micro:
* Biphasic salivary gland tumor, composed of ductal and myoepithelial cells
* Myoepithelial cells have dark angulated nuclei and scanty cytoplasm, giving a basaloid appearance
* Tubular, cribriform and solid architecture
* Tubular pattern contains simple tubules composed of inner ductal and outer myoepithelial cells
* Cribriform pattern is composed of predominantly myoepithelial cells with myxoid or hyalinized globules. Scattered ductal elements may be seen within the cribriform area
* Solid pattern is solid nests composed of sheets of basaloid cells
* Perineural invasion is frequent
* High grade transformation can be seen in a small number of cases, defined as:
* comedo type tumor necrosis
* frequent mitoses (often > 10 per 10 high power fields)
* marked nuclear atypia
* high grade transformation is associated with high risk of lymph node metastasis, distant metastasis and disease related death
Molecular:
* 60 - 90% have characteristic and diagnostic fusion involving MYB, MYBL1 or NFIB gene, the most common being t(6,9) MYB-NFIB fusion
IHC:
* Ductal component is typically positive for CK7 and CAM 5.2
* Myoepithelial component is positive for myoepithelial markers, e.g. SMA, S100, calponin, p40, p63, GFAP and cytokeratins
* Other positive stains: c-KIT (CD117)
Acinic cell carcinoma
- Malignant epithelial neoplasm of the salivary glands characterized by serous acinar cell differentiation (cytoplasmic zymogen granules) in at least some of the neoplastic cells
- Parotid gland is the most common site
Macro:
* Tumor dimensions range from < 1 cm to 13 cm (85% of the lesions are < 3 cm)
* Well circumscribed, soft rubbery, tan-yellow to pink mass with homogeneous cut surface
* Ususally single, but can be multiple or bilateral
* Cystic change and hemorrhage may occur
Micro:
Multiple cell types are noted:
* serous acinar
* intercalated ductal
* vacuolated
* nonspecific glandular
* Clear cells
- Acinar cells are large and polyhedral, with basophilic granular cytoplasm and eccentric nuclei
- Cytoplasmic diastase resistant positive periodic acid-Schiff (PAS) reaction may be focal
Variety of morphologic patterns:
* solid
* microcystic
* papillary cystic
* follicular
* Prominent lymphoid infiltrate may be present
* Mitosis
* Necrosis and significant pleomorphism usually absent
Proposed grading system:
* Low to intermediate grade: mitotic count < 5/10 HPF and no necrosis
* High grade: mitotic count ≥ 5/10 HPF or necrosis
Molecular:
* NR4A3, leading to NR4A3 IHC overexpression
* Loss of function mutations of CDKN2A / CDKN2B gene are associated with high grade histology and distant metastasis
IHC:
Pancytokeratins, EMA and CEA
DOG1: intense positivity
SOX10
PASD –> highlights resistant granules
Secretory carcinoma
- redominantly (76%) occurs in parotid, minor salivary glands of oral cavity and submandibular gland
- Mean age 40s
- Low-grade behaviour
Macro:
* Generally well circumscribed unencapsulated lesions, solid or cystic
* Size range 6 - 30 mm, Tumors as large as 70 mm have been reported
Micro:
* Circumscribed or infiltrative edge
* Lobulated architecture
Growth patterns:
* macrocystic
* microcystic
* solid
* tubular
* follicular
* papillary cystic patterns
- Occasional lymphovascular invasion and perineural invasion are seen
- Colloid like secretions
Molecular:
* Recurrent translocation t(12;15)(p13;q24), resulting in fusion of ETV6 on chromosome 12 and NTRK3 on chromosome 15
* Alternate fusion partners have been identified, including ETV6-RET and ETV6-MET
IHC:
* CK7: 100% sensitive, nonspecific when compared with acinic cell carcinoma
* GATA3: 100% sensitive; useful to distinguish from histologic mimic acinic cell carcinoma
* S100: 100% sensitive, 67% specific when compared with acinic cell carcinoma
* SOX10: 100% sensitive
MUC4: 91% sensitivity, 100% specificity
Mammaglobin
Polymorphous adenocarcinoma
- Polymorphous adenocarcinoma is an indolent salivary gland carcinoma characterized by cytologic uniformity and architectural diversity
- Predominantly affecting minor salivary glands, in particular the hard and soft palate
- F:M = ~2:1
- Commonly presents with palpable mass –> can erode underlying bone
Macro:
* Typically presents as a submucosal white to beige, firm, lobulated nodule or mass with infiltrative border
* Ranges 1 to 5cm
Micro:
Diagnostic criteria:
* Cytologic uniformity: the tumor is composed entirely of one type of tumor cells characterized by monotonous pale nuclei with marked chromatin clearing resembling that of papillary thyroid carcinoma
* Architectural diversity: showing highly variable architectural patterns of different proportions, including single filing arrangement, trabecular, tubular, reticular, papillary, solid and cribriform pattern
* Targetoid arrangement and streaming of tumor cells and nests around nerves and vessels are common
* Perineurial invasion is frequent, being seen in 60 - 75% of cases
* Uncommon histologic features include: microcalcification, oncocytic changes, mucocytes and high grade transformation (defined as marked nuclear atypia, prominent mitotic activity and tumor necrosis)
Molecular:
* 73 - 89% harbor PRKD1 E710D hotspot mutation
* 6 - 11% contain fusions involving PRKD1, PRKD2 or PRKD3 genes, with the fusion partners being ARID1A or DDX3X
IHC:
S100, CK7 and SOX10: diffusely and strongly positive
p63: variably positive (78 - 100%)
Mucoepidermoid carcinoma
- Malignant epithelial neoplasm
- Characterized by mucous, intermediate and epidermoid cells, with columnar, clear cell or oncocytoid features
- Most common malignant salivary gland neoplasm in both adults and children
- Prognosis influenced by tumor stage, tumor site, surgical margins
- Occurs in major and minor salivary glands (predominance of major > minor) —> Major: parotid > submandibular > sublingual
- Increased risk after exposure to radiation
- May be associated with Warthin tumour
Macro:
* Incompletely encapsulated or unencapsulated
* Well circumscribed
* Low grade: often cystic
* High grade: often solid, necrotic, tan-pink
Micro:
* Composed of varying proportions of mucous, epidermoid, and intermediate-type cells
* Neoplastic cells –> columnar and have foamy cytoplasm –> may resemble goblet cells or clear cells
* Clear cells may be a minor component –> mainly due to glycogen and less often to mucin
* Architecture is cystic ot papillary cystic with lumens filled with mucin.
* Often have pools of extravasated mucin in surrouinding tissue
Molecular:
* t(11;19)(q14-21;p12-13) with CRTC1(MECT1)-MAML2 fusion
* Present in 80% of mucoepidermoid carcinoma
* Low to intermediate grade (78%), high grade (84%)
* Detected by fluorescence in situ hybridization (FISH) or RT-PCR
IHC:
* Pancytokeratin, CK5/6, p63, p40, EMA, CK7, CK14
* Membrane bound mucins: MUC1, MUC2, MUC4, MUC5AC and MUC5B
* Mucocytes: mucin positive for mucicarmine and PASD (diastase resistant) stains
Grading
Armed Forces Institute of Pathology (AFIP) grading scheme (quantitative)
* Criteria:
Intracystic component less than 20% (2)
Neural invasion (2)
Necrosis (3)
4 or more mitoses (3)
Anaplasia (4)
- Grade:
Low grade (0 - 4)
Intermediate grade (5 - 6)
High grade (7 or more)
Brandwein et al. grading scheme (quantitative)
- Criteria:
Intracystic component less than 25% (2)
Tumor front invades in small nests and islands (2)
Pronounced nuclear atypia (2)
Lymphovascular invasion (3)
Bony invasion (3)
4 or more mitoses (3)
Perineural invasion (3)
Necrosis (3) - Grade:
Low grade (0)
Intermediate grade (2 - 3)
High grade (4 or more)
Modified Healy grading system (qualitative)
Memorial Sloan Kettering Cancer Center (MSKCC) grading system (qualitative)
Epithelial myoepithelial carcinoma
- Rare primary salivary gland neoplasm
- Biphasic neoplasm with a combination of both epithelial and myoepithelial elements
- Major salivary glands –> Most common parotid (70%), submandibular (12%)
- Minor salivary glands –> Palate and upper aerodigestive tract
- Subset may be associated with preexisting pleomorphic adenoma
- Slow growing, painless mass
- Usually unilateral
- Rarely presents with facial nerve palsy and lymphadenopathy, may indicate high grade transformation
- Generally good prognosis
- Poorer prognosis associated with minor salivary gland location, large tumor (> 4 cm), high proliferation index, margin status, high grade transformation
Macro:
* Lobulated, may be partially encapsulated
* Firm gray-tan rubbery mass
* Cystic change seen in up to 30%
Micro:
* Bilayered arrangement of small luminal cells with eosinophilic cytoplasm and outer myoepithelial cells with clear cytoplasm rich in glycogen (diastase sensitive PAS+)
* A few morphologic types may be seen, depending on the proportion of epithelial and myoepithelial cells present:
* Classic
* Epithelial dominant
* Myoepithelial dominant
* Tubular, glandular, solid growth patterns
* Papillary and cystic areas may also be present
* Basement membrane-like hyalinized matrix may be present
* Myoepithelial component can often be spindled or have clear cells
* Ductal cells relatively large, polygonal to spindle-shaped cells. clear cytoplasm. eccentrically locasted nuceli. Atypia usually mild.
Other morphological variants
* Oncocytic
Usually presents in older patients
- Apocrine
Positive for androgen receptor and GCDFP-15
IHC:
* Ductal: AE1 / AE3 (100%), EMA (100%), DOG1 (53% apical)
* Myoepithelial: p63 (100%), smooth muscle actin (83%), calponin (64%), DOG1 (53% membranous), CK5/6, p40, SMMHC
* Both: S100 (49 - 95%), SOX10
Salivary duct carcinoma
- High grade salivary gland malignancy
- Histology is similar to invasive ductal carcinoma of the breast (specifically luminal androgen receptor [AR]+ subtype)
- In situ areas frequently have comedo necrosis
- Nearly all cases (> 90%) are AR positive
- Poor prognosis
- Most commonly affects the parotid gland
- Other sites include the submandibular gland and minor salivary glands
Macro:
* Mean gross greatest dimension is 3.2 cm and ranges from 0.5 - 9 cm
* Tumors typically have ill defined borders but may appear well circumscribed
* Cut surface is heterogeneous and can show gross evidence of necrosis
* Regional lymphadenopathy is common
Micro:
* Invasive tumor cells with ample eosinophilic (oncocytic) cytoplasm forming cords, nests and cribriform glands in a desmoplastic stroma
* In situ component frequently shows central necrosis
* Roman bridges
* Comedo necrosis
* Perineural and perivascular invasion
* Lymph node mets common
Molecular:
PLAG1, HMGA2, PIK3CA, HRAS, TP53, ERBB2, BRAF alterations may be present
IHC:
* Nearly all are positive for AR (> 90%)
* GATA3
* AE1 / AE3, CK7, 34βE12 and EMA
* Most (~80%) are positive for GCDFP-15
* PSA positive in ~57%
* HER2 (3+) in 10 - 35%
* Mucicarmine in mucin rich variant
Carcinoma ex pleomorphic adenoma
- Epithelial or myoepithelial malignancy developing from primary or recurrent pleomorphic adenoma
- Most commonly parotid gland
- Identification of both malignant and benign components is essential for diagnosis
- In cases where the benign component has been obliterated by carcinoma, a history of pleomorphic adenoma at the site must be documented
- 5% of pleomorphic adenomas undergo malignant transformation, with the highest risk associated with recurrent or longstanding pleomorphic adenoma
- Typical clinical presentation is a longstanding palpable mass in the parotid region that has undergone recent rapid growth
- Main predictors of outcome are patient age, tumor diameter, degree of capsule invasion, histological subtype of malignant component and lymph node or distant metastases
Macro:
* Gross appearance depends on the proportion of pleomorphic adenoma to carcinoma
* If pleomorphic adenoma is the dominant component, it may appear circumscribed and gray, glistening or white
* If pleomorphic adenoma is not apparent, it may be a poorly circumscribed irregular infiltrative mass involving adjacent structures
* Malignant component can show necrosis or hemorrhage
Micro:
Must have either:
* Microscopic confirmation of both benign and malignant components or
* Microscopic diagnosis of carcinoma (see below) and previously documented pleomorphic adenoma at the site
* Stratification based on extent of capsule invasion:
* Intracapsular: good prognosis
* Minimally invasive: generally considered as < 1.5 mm
* Widely invasive: ≥ 1.5 mm
* Carcinomatous component may be salivary duct carcinoma, myoepithelial carcinoma or epithelial myoepithelial carcinoma
* If adenocarcinoma –> Often high grade
* If myoepithelial carcinoma –> often low grade
* Mixture of subtypes may also occur
Markers
S100
* Polymorphous adenocarcinoma
* Mammary analogue secretory carcinoma
* Low grade cribriform cystadenocarcinoma
SOX10
* Polymorphous adenocarcinoma
* Mammary analogue secretory carcinoma
* Acinic cell carcinoma
* Low grade cribriform cystadenocarcinoma
* Adenoid cystic carcinoma
Androgen Receptor
* Salivary duct carcinoma
