Home
Chapter Home
Jobs
Conferences
Fellowships
Books
Advertisement
Salivary glands
Reviewer: Fatima Aly, M.D., National Cancer Institute (see Reviewers page)
Revised: 8 October 2011, last major update August 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.
Table of contents
Normal: normal anatomy, normal histology, embryology, sebaceous differentiation, saliva
Primary references top Please
refer to these primary references for more detailed discussions and photographs Epithelial/myoepithelial tumors Adenocarcinoma, not otherwise
specified (NOS) Common,
5-10% of salivary gland tumors Mean
58 years old, range 10-93 years Often
fixed to skin or deep tissues; palatal lesions often ulcerated and involve bone Sites: parotid gland, submandibular gland, palate, buccal
mucosa Diagnosis
of exclusion (not metastatic, not another salivary gland carcinoma) Treatment: complete surgical excision Case
reports: 49 year old man with parotid
mass (Archives 2004;128:487) Gross: poorly circumscribed with infiltrative borders;
solid tan cut surface with hemorrhage and necrosis Micro: glandular or ductal differentiation but no features
characteristic of other specific types; small clusters of cuboidal, round or
ovoid cells with distinct borders and abundant cytoplasm; may have clear cell
or oncocytic features; low, intermediate or high grade based on cytomorphic
features Micro
images: cellular
tumor with glandular or ductlike structures, occasional pink cytoplasmic
granules, occasional mucicarmine+ cells; figure
6-smooth muscle actin stains myofibroblasts and stromal cells, not tumor cells DD: polymorphous low grade adenocarcinoma, metastatic
adenocarcinoma, membranous adenoma Formerly
called cylindroma Most
common in submandibular, sublingual or minor salivary glands Also
seen in nose, sinus, upper airway Slow
growing but aggressive; 50% metastasize, often silently to lung or bone;
recurrences are frequent and often late 5 year
survival is 60%, 10 year is 30%, 15 year is 15% Higher
recurrence rates for solid (100%) vs. cribriform (89%) vs. tubular (59%)
patterns 15
year survival rates by pattern are solid (5%), cribriform (26%), tubular (39%) Poorer
prognosis for dedifferentiated, p53+ tumors Better
prognosis for tumors of palate or parotid gland Perineurial
invasion may be due to expression of brain derived neutrotrophic factor (Hum Path 2002;33:933) Treatment: radical surgery regardless of tumor differentiation Gross: small, solid, poorly encapsulated and infiltrative Micro: cribriform, solid or tubular pattern similar to
cylindromas of skin; small bland myoepithelial cells with scant cytoplasm and
dark compact angular nuclei surround pseudoglandular spaces with PAS+ excess
basement membrane material and mucin; peripheral perineurial invasion and small
true glandular lumina; no squamous differentiation; no extensive necrosis Note: presence of pseudoglandular lumina, true glandular
lumina and perineurial invasion is usually required for diagnosis Dedifferentiated
tumors have irregular tumor islands composed of anaplastic cells with abundant
cytoplasm and desmoplastic stroma Grading: tubular and cribriform patterns are considered low
grade/grade 1; 30% to ~70% solid is intermediate grade/grade 2, predominantly
solid is high grade/grade 3. Micro
images: (1) figure
4: A-H&E; B-calponin stains myofibroblasts; (3) various images as
part of case history; (4) classic
tumor with cribriform and tubular structures; (5) low
grade to high grade; (6) H&E,
CK7 and CK20; (7) H&E
and CD117 #1; #2;
#3;
#4 fine
needle aspirate - small
cells with bland nuclear features forming a pseudoglandular space containing a
homogeneous, metachromatically staining hyaline globule #1; #2;
#3:
fig B/C Positive
stains: cells in ducts -
keratin, CEA, alpha-1-antichymotrypsin, S100, CD117/c-kit; cells around
pseudoglandular spaces - S100, actin, variable keratin; dedifferentiated
tumor - S100 Cytogenetics: loss of heterozygosity at 6q23-25 (
t[6;9][q21-24;p13-23] ) EM:
pseudoglandular spaces,
intercellular spaces, abundant basal lamina, true glandular lumina; cells are
intercalated ducts, myoepithelial, secretory and reserve cells DD:
pleomorphic adenoma (not invasive,
no perineurial invasion, has squamous metaplasia and mesenchyme-like areas),
polymorphous low grade adenocarcinoma (very rare in major salivary glands,
bland uniform cells, CD117 weak/negative) References:
AJSP 1999;23:465, Mod Path 2003;16:1224 (CD117
expression). Mod Path
2002;15:687 (CD117/c-kit) Dedifferentiated
tumors Rare
aggressive variant with death usually within 5 years of diagnosis Dedifferentiated
component either poorly differentiated adenocarcinoma or undifferentiated
adenocarcinoma Micro
images: (1) left-classic,
right-dedifferentiated tumor; (2) poorly
differentiated and undifferentiated tumor; (3) HER2,
p53, Rb, Ki-67 References:
Mod Path 2003;16:1265 Rare,
aggressive In
minor (but not major) salivary glands and ducts >90%
males, mean age 58 years (range 32-99 years) Sites: tongue, floor of mouth, nasal cavity, larynx Metastases: in 70-80% even with primaries < 1 cm; variable
histology Treatment: surgical resection with neck dissection 5
year survival: 25% Gross: 2 mm to 1 cm erythroplakic ulcer or indurated
submucosal nodule Micro: adenocarcinoma, squamous cell carcinoma and mixtures
resembling mucoepidermoid carcinoma; may have multifocal carcinoma in situ
involving salivary gland ducts, upward extension of intraductal carcinoma to
involve mucosal epithelium, glassy squamous cells; commonly perineurial
invasion and widespread invasion of submucosa Micro
images: figure
A Positive
stains: mucicarmine, PAS with
diastase, Alcian blue (pH 2.5 and 1.0) DD: mucoepidermoid carcinoma, squamous cell carcinoma,
pseudoglandular squamous cell carcinoma Also
called basaloid carcinoma 1-2%
of salivary gland carcinomas Malignant
counterpart of basal cell adenoma; 23% arise within basal cell adenomas 10-14%
are associated with skin adnexal tumor syndrome Usually
parotid gland, ages 50+ 37%
recur locally, 8% metastasize (solid pattern) to lymph nodes, 4% to lungs;
death from disease in unusual Associated
with dermal cylindromas Treatment: excision with clear margins Micro: low grade malignancy similar to basal cell adenoma
but infiltrative with perineurial invasion and vascular invasion; variable
cytologic atypia and mitotic activity; solid, trabecular, tubular or membranous
patterns; no myxoid matrix Micro
images: (1) various
patterns; (2) H&E
and CD117; (3) figure
A and morphologically similar tumors Positive
stains: p53, HER2, CD117/c-kit DD: adenoid cystic carcinoma (true cribriform
structures, angular and hyperchromatic nuclei or prominent nucleoli, strong
muscle marker staining) Also
called monomorphic adenoma 2% of
benign salivary gland tumors Usually
adults, 2/3 female, mean age 58 years; rarely is congenital and resembles
embryoma Parotid
gland or periparotid lymph nodes Benign;
rarely transforms, more likely if dermal analogue variant Usually
some myoepithelial differentiation using immunostains (Archives 2000;124:401) Treatment: excision Gross: encapsulated, often cystic, relatively small Micro: solid, trabecular or tubular growth of epithelial
cells resembling pleomorphic adenoma but with peripheral palisading; no
histologic evidence of myoepithelial differentiation; fibrous stroma present;
occasionally has acinar cells, squamous whorls or keratinization; no invasion,
no mesenchymal component, no perineurial invasion, no myxoid matrix Micro
images: figure
2-tubular, figure 3-trabecular, figure 4-tubular/trabecular, figure 5-basal
cell adenoma; morphologic
variants; calponin
demonstrating myoepithelial differentiation fine
needle aspirate - A-basal
cell adenoma Positive
stains: ductal cells -keratin,
alpha-1-antichymotrypsin, CEA, S100 (alpha subunit); basaloid cells
- vimentin, actin, S100 (beta subunit) DD: basal cell adenocarcinoma, adenoid cystic carcinoma,
pleomorphic adenoma Dermal
analogue tumor Also
called membranous tumor Uncommon
subtype, usually in parotid gland or intranodal parotid gland Usually
men, mean age 60 years old 25-38%
have cutaneous tumors Occasionally
coexists with multiple dermal cylindromas (Brooke-Spiegler syndrome, autosomal
dominant salivary gland-skin adnexal tumor syndrome) 25-37%
recur, 28% undergo malignant transformation to basaloid adenocarcinoma with
destructive infiltrative growth beyond gland margins and perineurial or
vascular invasion, but not necessarily pleomorphism, necrosis or mitotic
activity Gross: usually unencapsulated, 50% multifocal Micro: jigsaw patterns of epithelial nests surrounded by
deposition of basal lamina, resembling dermal eccrine cylindroma; larger nests
may have cystic change and squamous metaplasia; may have coalescent membrane
droplets within cell nests Micro
images: jigsaw
patterns of basaloid nests; figure
D (H&E and calponin) Cytogenetics: 16q12-13 abnormality (cylindromatosis gene, CYLD) DD: adenoid cystic carcinoma (more cytologic atypia,
hyperchromatic angular nuclei or distinct nucleoli; true cribriform pattern
with basophilic matrix) References: AJSP 2002;26:778 4% of
minor salivary gland tumors Usually
arises from minor salivary glands of upper lip or palate Usually
ages 50+ years Recurrence
is uncommon Gross: often encapsulated, 22% multifocal; tumor may be
received as fragmented specimen Micro: bilayered strands or ribbons of columnar cells with
loose, well vascularized stroma; often basaloid cells or trabecular features;
often cystic change Micro
images: figure
1 (H&E and calponin neg); figure
1 (H&E and calponin neg); branching
canaliculi of columnar cells Positive
stains: S100, focal GFAP Negative
stains: myoepithelial markers (alpha
smooth muscle actin, smooth muscle myosin heavy chain, calponin) DD: adenoid cystic carcinoma (destructive infiltration,
cribriform pattern, strong muscle markers+) Uncommon Mean
age 72 years, range 30-88 years, no gender predominance Clear
cell carcinoma, clear cell epithelial-myoepithelial carcinoma, clear cell
myoepithelial carcinoma, sebaceous carcinoma Also
clear cell variants of acinic cell carcinoma, oncocytoma, mucoepidermoid
carcinoma Also
metastatic renal cell carcinoma or balloon cell melanoma References:
Archives 2002;126:676 Usually
adult women with painless mass in minor salivary glands Treatment: surgical excision with adequate margins; treat
recurrences aggressively Gross: infiltrating, scar-like Micro: trabeculae, cords, islands or nests of monomorphic
clear cells; also cells with eosinophilic and granular cytoplasm; infiltrative
borders; variable atypia; no/rare mitotic figures; no myoepithelial
differentiation Positive
stains: PAS diastase sensitive
(glycogen), cytokeratin (high molecular weight), CEA, EMA Negative
stains: mucin, S100, smooth muscle
actin, calponin, vimentin EM: abundant glycogen, desmosomes, peripheral
tonofilaments, squamoid differentiation, prominent interdigitating microvilli without
actin myofilaments or dense bodies; no lipid, no zymogen granules, no true
ductal lumina DD: myoepithelioma (also positive for glycogen),
sebaceous neoplasms (positive for fat), mucoepidermoid carcinoma (positive for
mucin), acinic cell carcinoma (negative for glycogen, fat and mucin), clear
cell change in oncocytic tumors, metastatic renal cell carcinoma (positive for
RCC, glycogen, vimentin and CD10, negative for high molecular weight
cytokeratin and CEA, abundant lipid but no squamoid differentiation by EM) References:
AJSP 1999;23:1532 Hyalinizing
subtype Nests
of clear cells surrounded by hyalinized bands with foci of myxohyaline stroma Often
affects intraoral salivary glands at base of tongue or palate; also within
nasopharynx and jaw Low
grade malignancies with 15% nodal metastases and possible late recurrence Micro: solid masses, nests, infiltrating cords or single
file clear cells composed of glycogen with mild atypia or eosinophilic
cytoplasm; hyalinized stroma, rare mitotic figures Micro
images: clear
to eosinophilic cytoplasm, EMA+, negative for muscle markers Positive
stains: EMA References: AJSP 1994;18:74 Mean
59 years old, range 20-86 years Often
in major salivary glands, but also in lips, buccal mucosa, palate, tongue,
retromolar area, floor of mouth Usually
indolent, but occasionally recurs locally or metastasizes Gross: cystic masses, 0.4 to 6 cm Micro: invasive, cystic growth pattern, 75% with
conspicuous papillary component; composed of small cuboidal cells, large
cuboidal cells, tall columnar cells or mixture; cyst rupture with hemorrhage
and granulation tissue is common; does not involve the native duct system References:
AJSP 1996;20:1440 Epithelial myoepithelial carcinoma Rare
(less than 0.5% of salivary gland tumors); 80% arise in parotid gland Mean
age 60 years; 60% in women Terminology
may be confusing; also called glycogen rich adenoma (clear cell pattern),
myoepithelioma (spindle cell and plasmacytoid patterns), myoepithelial
carcinoma (if only myoepithelial differentiation and marked cytologic atypia) Low
grade malignancies with frequent local recurrences; previously often considered
to be benign, but with sufficient follow-up, there are rare regional nodal
metastases and distant metastases to lung and kidney In
overtly malignant cases (cytologic atypia and infiltrative), metastases are
found in 47% and 29% die of disease after mean 32 months Case
reports: Case
of Week #54 Gross:
well delineated, firm, infiltration
into adjacent tissue; usually 2-3 cm Micro: low grade with epithelial and myoepithelial
components; often multinodular with partial thick fibrous capsule; most tumor
cells have myoepithelial features with clear cytoplasm or naked nuclei;
focally, there are ducts or tubules with an outer rim of myoepithelial cells
and inner, dark ductal cells with scant eosinophilic cytoplasm and round, bland
nuclei; also islands, nests or sheets of spindle cells, plasmacytoid (hyaline)
cells; may have overt cytologic malignancy, infiltrative growth and perineurial
invasion; often mild nuclear pleomorphism; variable mitotic activity Micro
images: low
power; high
power #1; #2;
AE1-AE3;
S100;
figure
5-clear cells (A: H&E; B: calponin); well
circumscribed, double cell layers, hyalinizing and clear cell patterns Cytology: cellular, with single cells and naked nuclei;
biphasic pattern may not be evident since the clear cells have fragile
cytoplasm and often appear as naked nuclei (Diagn
Cytopathol 2003;28:163) Positive
stains: myoepithelial
component - PAS+, diastase sensitive due to cytoplasmic glycogen; also
S100+, p63+ (Cancer
2005;105:240), smooth
muscle actin+, variable keratin; epithelial component - keratin
and EMA (strong), occasional S100+ Negative
stains: CEA DD: plasmacytoma, skeletal muscle tumors, oncocytoma,
malignant mixed tumor, myoepithelial carcinoma (defined as lacking any
epithelial component, AJSP
2000;24:761),
pleomorphic adenoma (biphasic but
with prominent myxochondroid stroma, myoepithelial cells usually lack
cytoplasmic clearing); other biphasic tumors include adenoid cystic carcinoma
(prominent cribriform pattern) and polymorphous low grade adenocarcinoma
(affects intraoral salivary glands, clear cells do not predominate and are not
associated with ductal cells); clear cell carcinoma (usually affects the minor
salivary glands, unencapsulated, lack epithelial cells and are negative for
myoepithelial markers), metastatic renal cell carcinoma References:
AJSP 2000;24:761, Archives 2002;126:676 Giant cell tumor of salivary glands Very
rare; first reported in 1984 Mean
age 62 years, range 28-92 years; 80% male 87% in
parotid gland; 13% in submandibular gland Uncertain
histogenesis, may be a carcinoma; giant cell component may be neoplastic 50%
associated with carcinoma (usually salivary duct carcinoma or carcinoma ex
pleomorphic adenoma / malignant mixed tumor) 13%
die of disease; more aggressive than giant cell tumor of bone, less aggressive
than undifferentiated carcinoma (48% 5 year survival) Presents
as rapidly enlarging mass Gross: no peripheral mineralized bone shell Micro: evenly distributed osteoclastic giant cells in
background of mononuclear cells; nuclei differ between mononuclear cells and
osteoclastic giant cells (unlike giant cell tumor of bone) Positive
stains: mononuclear cells
- EMA, CEA, androgen receptor, histiocytic markers EM: giant cells are similar to bone osteoclasts;
mononuclear cells have numerous microvilli and some cell junctions but few
lysosomes References: AJSP 2004;28:953 Very
rare (< 0.1% of salivary gland tumors) 2
distinct tumors in same topographic area producing a single clinical and
macroscopic tumor mass Epithelial-myoepithelial
carcinomas are overrepresented in this category Must
sample thoroughly since only one component may be aggressive Mean
age 53-62 years, range 28-81 years Usually
parotid gland Micro
images: epithelial-myoepithelioma
carcinoma and basal cell adenocarcinoma with squamous cell carcinoma component;
various
tumors DD:
collision tumors (distinct masses
that meet), biphasic tumors, recurrent tumor References:
Archives 1999;123:698, Mod Path 2002;15:724 Inflammatory myofibroblastic tumor Also
called inflammatory pseudotumor; formerly called plasma cell granuloma Uncommon,
usually benign behavior, non-neoplastic Case
reports: 70 year old Japanese man
with submandibular gland tumor and autoimmune-like symptoms (Archives 2001;125:1095) Micro: myofibroblasts and chronic inflammatory cells DD: MALT lymphoma Rare
controversial entity (< 20 cases reported), in situ form of salivary duct
carcinoma Mean
age 62 years, range 32-91 years Usually
affects major salivary glands Excellent
prognosis; no metastases or mortality reported; may recur with incomplete
excision as intraductal or invasive tumor May
represent preinvasive phase of some salivary duct carcinomas Recommended
to sample extensively and stain for myoepithelial cells with p63 and actin to
rule out invasion Treatment: total parotidectomy or wide excision to prevent
recurrence / progression Case
reports: 44 year old woman with mass
in buccal mucosa arising from minor salivary glands (AJSP 2004;28:266) Gross: may be multifocal, cystic Micro: unencapsulated but circumscribed intraductal
neoplasm in micropapillary, cribriform, solid, comedo or clinging patterns,
with preservation of myoepithelial cells surrounding intraductal tumor;
resembles breast DCIS; variable atypia, variable mitotic figures, no invasion Micro
images: intraductal
tumors resembling breast DCIS Positive
stains: epithelial cells
- high molecular weight cytokeratin, EMA, S100 (50%), myoepithelial cells
- p63 (nuclear stain), muscle specific actin Negative
stains: ER, PR, p53 Resembles
inverted papilloma of nasal cavity Benign Gross: small submucosal mass Micro: complex invaginations of well differentiated
squamous epithelium with microcysts, mucous cells and columnar cell lining Very
rare, < 10 cases reported Appear
to be derived from salivary ducts undergoing squamous metaplasia Benign;
excision appears to be adequate treatment Gross
images: multicystic
tumor filled with keratin Micro: benign tumor with multicystic spaces lined by
squamous cells with focal solid epithelial nests; parakeratotic and
orthokeratotic keratinization without a granular layer; outer layer has
bud-like protrusions; cells have bland, uniform nuclei and abundant
eosinophilic cytoplasm; occasional normal mitotic figures; focal foreign-body
reaction against keratin; no necrosis, no invasion, no angiolymphatic invasion,
no perineurial invasion, no atypia, no mucous cells Micro
images: squamous
lined cysts filled with keratin Positive
stains: cytokeratin, Ki-67 (outer
basal layer only) Negative
stains: alpha smooth muscle actin,
S100 DD: squamous cell carcinoma, mucoepidermoid carcinoma,
squamous metaplasia in other conditions References: Mod Path
2002;15:1005 Large cell neuroendocrine carcinoma Extremely
rare 2
cases reported in parotid glands in men ages 72 and 73 years (Mod Path 2000;13:554) Aggressive behavior Micro: organoid, solid, trabecular and
rosette-like patterns of large polygonal cells with coarse chromatin and
prominent nucleoli, high mitotic rate, frequent necrosis Micro
images: solid
growth of large tumor cells with prominent nucleoli; organoid
growth, peripheral palisading and rosette-like pattern; neuroendocrine
stains and p53; FNA
with large, loosely cohesive, pleomorphic tumor cells with prominent nucleoli,
Positive
stains:
neuroendocrine markers, cytokeratin, p53, bcl2, epidermal growth factor
receptor, cyclin D1, Ki-67 Negative
stains:
CK20 Molecular: 9p21 abnormalities EM
images:
desmosome-like
junctions and neurosecretory granules DD: undifferentiated carcinoma,
Merkel cell carcinoma (CK20+) Glandular
structures with sertoliform features and adipose tissue May
derive from striated ducts Lymphoepithelioma-like carcinoma Type
of undifferentiated carcinoma common in Eskimos and Chinese, often familial in
these groups Unilateral
mass of parotid gland or submandibular gland of adults Metastases
common to regional lymph nodes; distant metastases to liver, lung, bone Relatively
good outcome Micro: malignant epithelial islands resembling
nonkeratinizing large cell carcinoma and lymphoid tissue with germinal centers;
occasional spindled areas; often perineurial invasion; may have starry sky
pattern Positive
stains: keratin, EBV (often) Also
called carcinoma ex pleomorphic adenoma, carcinosarcoma if malignant
epithelial/myoepithelial and mesenchymal components Rare Usually
malignant transformation of benign pleomorphic adenomas; 2% risk if present
< 5 years, 10% risk if 15 years duration for pleomorphic adenoma Clinically,
have sudden increase in growth, pain or facial paralysis Associated
with surgery or radiation therapy Often
prior history of pleomorphic adenoma is difficult to obtain but necessary for
diagnosis unless benign tumor coexists with malignant tumor Note:
must rule out malignant mixed tumor if a high grade carcinoma of salivary
glands is difficult to classify, by vigorous searching for a benign mixed tumor
(may be 5 mm or less) 50%
survival at 5 years Metastases
to regional lymph nodes, lungs, bone (vertebral column), abdominal organs Prognostic
factors (must thoroughly sample tumor): stage, extent of invasion beyond the capsule (<8 mm is associated
with benign behavior); histologic type and grade of carcinoma, proliferation
index, proportion of carcinoma Case
reports: 47 year old man with
parotid tumor containing pleomorphic adenoma and rhabdomyosarcoma (Archives 2001;125:812), 71 year old man with submandibular tumor with
giant cell component (Archives 2000;124:1559) Gross: widely infiltrative with hemorrhage and necrosis Micro: malignant epithelium, often salivary duct carcinoma,
undifferentiated carcinoma or adenocarcinoma NOS, terminal duct carcinoma or
myoepithelial carcinoma, usually with benign stroma; malignant tumor is
extensively infiltrative with necrosis, perineurial invasion, frequent mitotic
figures, marked nuclear atypia; occasionally benign pleomorphic adenoma is
present with hyalinization and hypocellularity Note:
clinical malignant behavior is associated only with cytologically malignant
foci beyond the capsule of original tumor Less
commonly the stromal component is chondrosarcoma or other malignancy, with no
preexisting benign component and aggressive behavior Micro
images: (1) squamous
cell carcinoma, rhabdomyosarcoma and myoglobin+ sarcomatous component; (2)
resembling
oncocytic papillary adenocarcinoma with osteoclast-like giant cells; (3) salivary duct
carcinoma arising from pleomorphic adenoma Positive
stains: AE1/AE3 (97%), CK7 (94%),
EMA (86%), CEA (75%), vimentin (52%), S100 (29%), p53 (41%), HER2 (30%), B72.3 Cytogenetics: associated with 8q12-13 and 12q13-15 rearrangements References: Hum Path
2001;32:596 Micro: multinodular foci of epithelial islands surrounded
by thick, eosinophilic, hyaline layer; no infiltration of adjacent parenchyma,
nerves, blood vessels Usually
to intraparotid or submandibular lymph nodes Most
common submandibular metastatic tumors are metastatic squamous cell carcinoma
from upper aerodigestive tract or skin, or melanoma to submandibular lymph
nodes Distant
metastases arise from lung, kidney, breast, prostate gland, colon Most
common malignant tumor in salivary glands; most common radiation induced
neoplasm 2/3
occur in parotid gland; also in palate Wide
age range, mean 49 years, range 15-86 years, no gender predominance Low
grade: 15% recur, 5 year survival 90-98%; usually stage I High
grade: 25% recur, 5 year survival 50-56%; deaths usually within first 5 years Note:
significant grading disparity exists between pathologists (AJSP 2001;25:835) AFIP
point system: 2 points if <20%
intracystic component; 2 points if necrosis; 2 points if neural invasion; 3
points if 4+ mitotic figures/10 HPF; 4 points if anaplasia; low grade if total
score is 0-4 points, intermediate grade if 5-6 points, high grade if 7+ points Poor
prognostic factors : older age,
male, submandibular gland, extraglandular extension, vascular invasion,
necrosis, high mitotic rate, high histologic grade Treatment: complete excision, possible radiation therapy Case
reports: 55 year old man with low
grade parotid tumor and dedifferentiation (Hum
Path 2003;34:1068) Gross: low grade - well circumscribed mass
with gray-white, mucin filled cysts Micro: cords, sheets, clusters of mucous, squamous,
intermediate and clear cells; low to high grade, although even high grade
tumors lack marked nuclear atypia, frequent mitotic figures or extensive
necrosis; occasional focal sebaceous cells, oncocytic change, inflammatory
reaction to extravasated mucin or keratin and goblet-type cells; no squamous
cell carcinoma in situ Low
grade: mucinous and intermediate
cells with bland nuclei form glandular spaces High
grade: solid and infiltrative
growth pattern of atypical epidermoid and intermediate cells with cytoplasmic
clearing and small number of mucinous cells; <20% intracystic component Micro
images: figure
3 (A: H&E; B: smooth muscle actin) fine
needle aspirate - low
grade with background mucin, two types of cells with bland nuclear features
(squamoid with dense cytoplasm and glandular with vacuolated cytoplasm) #1;
#2;
high
grade with malignant squamous cells #1; #2;
H&E,
CK7+ and CK20 negative Positive
stains: low grade -
CK7, CK14, antimitochondrial antibodies Cytogenetics: associated with t(11;19)(q14-21;p12-13) EM: mixed luminal epithelial cells and myoepithelial
cells DD: poorly differentiated adenocarcinoma, adenosquamous
carcinoma (has anaplastic nuclear features), necrotizing sialometaplasia,
metastatic carcinoma Oncocytic
variant Oncocytic
tumor cells are 60% or more of neoplasm <10%
of all mucoepidermoid carcinomas Positive
stains: PTAH (granular cytoplasmic
staining), antimitochondrial antibodies References:
AJSP 1999;23:523 Defined
as benign tumor composed only of myoepithelial cells May
have hyalinization and myxoid matrix production See
also epithelial myoepithelial carcinoma
above Also
called oxyphilic adenoma 1-2%
of salivary gland neoplasms Benign
tumor composed of oncocytes Usually
in parotid gland, also submandibular gland Mean
age 60 years; tumors with clear cells are more common in women 20%
associated with radiation therapy or radiation exposure Malignant
if regional nodal or distant metastases, cellular pleomorphism, frequent mitotic
figures or invasion Treatment: local excision; excellent prognosis Case
reports: 79 year old woman with
tumor of deep lobe of parotid gland with oncocytic hyperplasia (Archives 2003;127:e53) Gross: well circumscribed with fibrous capsule, solid,
tan-red-brown, lobulated, often small, may have cystic spaces Gross
images: red-brown
tumor Micro: sheets, trabeculae, acini or follicular patterns of
monotonous large polygonal cells with well defined cell borders, deeply
eosinophilic, granular cytoplasm, small round nuclei; may have clear cell
change, psammoma bodies, tyrosine-rich crystals; no mitotic figures Gross/micro
images: red
brown tumor with central scar, oncocytes packed with mitochondria, oncocytic
metaplasia of ducts Micro
images: fine needle aspirate - A-oncocytoma,
B-acinic cell carcinoma Negative
stains: myoepithelial markers (alpha
smooth muscle actin, smooth muscle myosin heavy chain, calponin) EM: packed with mitochondria with partitions DD: oncocytic metaplasia, oncocytosis Also
called multinodular oncocytoma, multifocal adenomatous oncocytic hyperplasia Benign Micro: either parotid cysts lined by oncocytes or well
defined clusters of oncocytes; oncocytes (oxyphilic cells) are large ductal
epithelial cells with eosinophilic granular cytoplasm EM: numerous mitochondria DD: normal aging (increased oncocytes), Warthin’s tumor,
oncocytoma Also
called malignant oncocytoma Malignant
counterpart of oncocytoma Very
rare Micro: atypia, mitotic figures, infiltrative growth <3%
of parotid tumors; also in oral cavity Called
cystadenocarcinoma if prominent cystic component Poor
prognosis if stromal invasion; similar prognosis to low grade mucoepidermoid
carcinoma if no stromal invasion Gross: often large, with hemorrhage and necrosis Micro: well defined papillary structures, usually mucin, no
squamous or intermediate cell components; may have only focal malignant
component in otherwise benign mucinous cystadenoma DD: mucoepidermoid carcinoma, acinic cell carcinoma,
metastatic carcinoma (thyroid, other) Also
called benign mixed tumor Most
common tumor of salivary glands Often
women in 30’s, but any age Painless,
slow growing tumor 90%
occur in parotid gland (represent 60% of parotid tumors; 50% occur in tail, 25%
in superficial lobe, 25% in deep lobe), 10% in submandibular gland, rare in
sublingual gland; represents 50% of salivary gland tumors of palate Epithelial
and mesenchymal (myxoid, hyaline, chondroid, osseous) cells often arise from
same cell clone (Hum Path 2000;31:498), which may be a myoepithelial or ductal reserve
cell Radiation
exposure increases risk No
difference in behavior based on proportion of various elements Risk
factors for malignant transformation:
submandibular location, older age, larger size, prominent hyalinization,
increased mitotic rate (if present, sample tumor more thoroughly) Treatment: wide local excision (25% recur with enucleation, 4%
with adequate parotidectomy) Recurrences
are usually within 18 months, but also up to 50 years later; after surgery for
recurrent tumor, 25% recur again Gross: well-demarcated, partially encapsulated, gray-white
myxoid, rubbery mass with solid cut surface, often 6 cm or less, tumor
extensions into adjacent tissue may be subtle Gross
images: white
tumor with myxoid cut surface Micro: not as well circumscribed as may grossly appear,
with tongue like protrusions into surrounding salivary gland; thick capsule if
present in deep parotid lobe; biphasic population of epithelial and mesenchymal
cells; epithelial cells are glandular or occasionally squamous; may be spindled
or oval, have large hyperchromatic nuclei; have myoepithelial basal layer or
overlying pseudoepitheliomatous hyperplasia or be very cellular; stroma is
myxoid, hyaline, chondroid, rarely adipose tissue or osseous; occasional
angiolymphatic invasion; mucin often present; may have adenoid cystic pattern;
no mitotic figures, no necrosis Micro
images: figure
2A-cellular pleomorphic adenoma fine
needle aspirate - bland
epithelial cells and fibrillar, metachromatically staining stroma #1; #2;
#3 Micro
images: fine needle aspirate -
pleomorphic
adenoma #1; #2 Positive
stains: ductal component
- keratin (CK19, CK14), EMA, CEA, alpha-1-antitrypsin,
alpha-1-antichymotrypsin, GCDFP-15, PSA (50%), PAP (50%), myoepithelial
component - keratin, actin, myosin, other smooth muscle proteins, S100
(particularly in cartilaginous areas), GFAP Negative
stains: amylase, p53 Cytology: clusters of benign epithelial cells with blue myxoid
matrix and tyrosine-rich crystals Cytogenetics: normal or rearrangements of 8q12 or 12q14-15 EM: features of epithelial and mesenchymal cells Benign
metastasizing mixed tumors Rare,
<50 cases reported Late
metastasis (6-52 years) after tumor excision to lymph nodes, lung, bone, skin,
spinal cord or kidney with benign morphology in original and metastatic tumor Associated
with prior local recurrence and occasionally with immunosuppression Metastasis
thought to occur via vascular channels due to tumor fragmentation or seeding at
surgery 22%
mortality Case
reports: 53 year old woman with
solitary kidney mass and subsequent parotid mixed malignant tumor (AJSP 2000;24:1159), 37 year old man with spinal cord compression after
submandibular tumor (Archives 2003;127:887) Micro
images: spinal
cord tumor (MRI and H&E) Polymorphous low grade
adenocarcinoma Also
called terminal duct carcinoma, lobular carcinoma, low grade papillary
adenocarcinoma Usually
palate; second most common tumor at this location after adenoid cystic
carcinoma In
major salivary glands is usually associated with pleomorphic adenoma Median
age 54 years, range 22-71 years, 2/3 women 12-30%
recur, nodal metastases in 10-15%, 10% have distant metastases or tumor related
death (AJSP 2000;24:1319) Protracted
clinical course; 9-17% recur locally, 9% metastasize to regional lymph nodes,
rarely metastasizes to lung, transforms to high grade tumor or causes death More
than focal papillary growth is associated with cervical lymph node metastases Positive
or unknown surgical margins are associated with local recurrence Treatment: conservative wide excision Micro:
nonencapsulated but often well
circumscribed tumor with diverse (polymorphous) growth patterns (tubular,
cribriform, focally papillary, solid, fascicular, microcystic, single file,
pseudoadenoid cystic [without true lumens], strand-like, mixed); infiltrative
borders as small islands and tubules; mucoid and hyaline stroma; cells have
only mild atypia with uniform, bland nuclei, but with perineurial invasion
common around small nerves; no/rare mitotic figures, rare tumor necrosis Micro
images: (1) figure
2 (A: H&E, B: calponin negative); (2) low
grade cytologic features; (3) polymorphous
patterns #1; #2;
(5) Figures
a-c: H&E, CK7 and CK20; (6) H&E
and CD117 Positive
stains: S100, EMA, keratin, focal
GFAP, focal muscle specific actin, focal CEA Negative
stains: myoepithelial markers (alpha
smooth muscle actin, smooth muscle myosin heavy chain, calponin), CD117 (may be
weak) DD: pleomorphic adenoma (circumscribed, no perineurial
invasion, although both may extend focally into adjacent minor salivary
glands), basal cell adenoma, adenoid cystic carcinoma (bilayered tubules,
nuclear atypia, muscle markers+), cystadenocarcinoma (also has papillary
areas), metastatic lobular breast carcinoma (image,
Archives 2000;124:157) References: AJSP 1988;12:461
(stains), AJSP
1984;8:367, Mod Path
2002;15:687 (CD117/c-kit) Uncommon;
usually elderly, 75% males Usually
parotid gland, also submandibular gland High
grade tumors are aggressive with frequent metastases to regional lymph nodes
and distant sites, 70% mortality May
arise from pleomorphic adenoma or polymorphous low grade adenocarcinoma or de
novo Aggressive,
60% have nodal or distant metastases; commonly tumor infiltration into soft
tissue at diagnosis >60%
die from tumor, usually within 5 years Poor
prognostic factors: > 3 cm,
metastases, small intraductal component Treatment: excision with regional lymph node sampling and
radiation therapy; possibly prostate cancer-like hormonal therapy Gross: white-tan masses with solid or cystic cut surface
or necrosis Micro: resembles breast carcinoma subtypes, both high grade
(papillary, sarcomatoid, colloid) or low grade (cribriform with Roman-bridge
structures, see also below), with in situ and invasive components; cells have
eosinophilic cytoplasm, marked nuclear pleomorphism with vesicular nuclei,
prominent nucleoli; frequent perineurial and vascular invasion, fibrous and
hyalinized stroma, mitotic figures; may have dystrophic calcification Micro
images: 1-cribriform
pattern, 2-oncocyte-like cells, 3-infiltrating in cords, 4-perineurial invasion;
figure
7; patterns;
H&E,
CK7 and CK20; H&E
and PPAR gamma expression Positive
stains: keratin, EMA, CEA, B72.3,
androgen receptors (>90%), PPAR gamma (80%), GCDFP-15 (especially
intraductal component), PSA (60%), PAP (20%), 50% HER2 Negative
stains: ER, PR (80% negative), S100,
myoepithelial markers DD: metastatic carcinoma, polymorphous low grade
carcinoma, mucoepidermoid carcinoma References: AJSP 2000;24:579,
Hum Path 2000;31:208
(sarcomatoid), Mod
Path 2003;16:1218 (PPAR gamma expression) Colloid
carcinoma (mucin rich) variant of salivary duct carcinoma Very
rare; poor outcome May
represent extreme variation of a common occurrence of extracellular mucin Micro: large extracellular mucin lakes containing clusters
and single tumor cells Positive
stains: keratin (CK7), EMA, androgen
receptors, GCDFP-15, CEA, MUC2, MUC5B, MUC6, variable HER2 overexpression Negative
stains: CK20, S100, myoepithelial
markers, ER, PR, MUC5AC, MUC7 References: AJSP 2003;27:1070 Low
grade salivary duct carcinoma Rare
(<1% of salivary gland carcinomas), first reported in 1996 Median
64 years Usually
parotid gland May be
entirely intraductal or locally invasive Excellent
prognosis Treatment: surgery Gross: unencapsulated Micro: single to multiple dominant cysts accompanied by
adjacent intraductal proliferation; cysts lined by small, multilayered, bland
ductal cells with fine chromatin and small nucleoli; smaller ductal structures
have variable proliferating ductal epithelium with cribriform, micropapillary
or solid patterns resembling ADH or low grade DCIS of breast; may have
indistinct cytoplasm membranes, apocrine-type cytoplasmic microvacuoles;
lipofuscin-like pigment; may have definite stromal invasion, transition between
low grade and high grade areas; rarely goblet cells or oncocytoid cells;
no/rare mitotic figures or necrosis Positive
stains: S100, calponin
(myoepithelial cells lining cystic spaces) Negative
stains: HER2 DD: papillocystic variant of acinic cell carcinoma
(smaller vacuoles, S100 negative, zymogen granules by EM), cystadenocarcinoma
(no resemblance to breast ADH or DCIS, usually widely invasive) References:
AJSP 2004;28:1040
Also
called intraductal papilloma, intraductal papillary tumor Very
rare Benign;
usually in minor salivary glands Case
reports: benign
sublingual tumor and microinvasive intraductal parotid tumor (Archives 2000;124:291) Micro: papillary proliferations of bland
cuboidal/columnar epithelial cells with fibrovascular cores Micro
images: (1) intraductal
papillary proliferation #1; #2;
(3) papillary,
tubular and solid patterns; (4) microinvasion;
(5) smooth
muscle actin demonstrates lack of invasion DD: papillary cystadenoma, papillary
cystadenocarcinoma, papillary-cystic variant of acinic cell carcinoma, salivary
duct carcinoma, polymorphous low grade adenocarcinoma, metastatic papillary
thyroid carcinoma Sebaceous adenoma / lymphadenoma Benign
tumors with predominantly sebaceous component Sebaceous
lymphadenoma if prominent lymphoid stroma Rare,
benign tumor with nests and islands of bland epithelium composed in part of
sebaceous elements, in a prominent lymphoid stroma (lymphadenoma) Over
90% occur in or near the parotid gland May arise from salivary duct inclusions within parotid lymph node,
similar to Warthin’s tumor (AJCP
1980;74:683) Usually
diagnosed prior to excision (Acta
Otorhinolaryngol Ital 2007;27:144) Case
reports: Case of the
Week #103, Archives 2005;129:e171, University of Pittsburgh Case of
Month Treatment: excision is curative, no recurrences, rare malignant
transformation (Eur
Arch Otorhinolaryngol 2006;263:940) Gross:
solid or cystic, well circumscribed,
tan-yellow mass, up to 3 cm, with variable encapsulation Gross
images: large
nodule, small nodule on left is oncocytoma Micro: nests and islands of benign squamous cells, often
lining a cyst; epithelial nests have focal sebaceous differentiation;
background is prominent lymphoid infiltrate, often with germinal centers; may
be associated foreign body reaction, collections of histiocytes, oncocytic
change Micro
images: large
nodule #1; #2;
small
nodule #1; #2;
#3
Cytology: mixed population of large and small lymphocytes,
plasma cells and occasional tingible body macrophages; 3 dimensional, cohesive
aggregates of epithelial cells, often with cytoplasmic vacuoles characteristic
of sebaceous differentiation, surrounded by layers of basaloid cells (Acta
Cytol 2004;48:551) Cytology
images: Diff
Quik touch prep DD: normal sebaceous glands (present in
10% of parotid glands but no mass), Warthin’s tumor Warthin’s tumor (prominent
cysts and lymphoid stroma, cysts have bilayered oncocytic epithelium), low
grade mucoepidermoid carcinoma (epithelial islands, ducts and cysts tend to be
haphazardly distributed with variable shapes and sizes; usually infiltration of
connective tissue or parenchyma; cells have some atypia, cells are mucin+) Rare
benign tumor of salivary gland origin Usually
hard palate or parotid gland of men over 40 years Gross: well circumscribed, round/oval, papillary tumor of
mucosal surface Micro: biphasic, with well differentiated papillary
hyperplastic squamous epithelium covering ductal component of cleftlike cystic
spaces lined by cuboidal or columnar epithelium with occasional goblet cells;
variable oncocytes and squamous metaplasia Positive
stains: squamous epithelium
- CK7, AE1-AE3, CEA, EMA; ductal structures - CK7,
AE1-AE3, CAM 5.2, CEA, EMA, S100 Negative
stains: CK20, GFAP, desmin, muscle
specific actin EM: oncocyte is predominant cell; contains numerous
mitochondria, parallel filaments within cell cytoplasm attached by desmosomes (Archives 1986;110:523) DD: Warthin’s tumor, papillary syringocystadenoma References:
Archives 2001;125:1595 Signet ring cell adenocarcinoma Rare
subtype of adenocarcinoma (2% of primary minor salivary gland malignancies) Slow
growing with favorable outcome, based on limited data Micro: non-circumscribed tumor composed of bland, mucin
containing signet ring cells that invade in narrow parallel strands, with
scattered small nests or individually infiltrating cells; often perineurial
invasion; minimal ductal differentiation; no solid, cribriform or papillary
components; no angiolymphatic invasion Positive
stains: CAM 5.2, smooth muscle
actin, GFAP, p63 Negative
stains: calponin DD: mucoepidermoid carcinoma, polymorphous low grade
adenocarcinoma, colloid (mucinous) carcinoma References: AJSP 2004;28:89 Rare;
aggressive; pure or with squamous cell carcinoma or adenocarcinoma 2% of
parotid gland carcinomas, 4% of minor salivary gland malignancies Usually
age 50+ but also < 30 years Either
neuroendocrine (Merkel cell or pulmonary varieties) or ductal types Micro: resemble lung tumors with solid areas of small
spindled to ovoid cells with minimal cytoplasm, hyperchromatic nuclei with fine
chromatin, indistinct nuclei; high mitotic activity, geographic necrosis; often
a better differentiated carcinoma is present; rarely squamous or ductal
differentiation; does not arise from surface epithelium but may involve it
secondarily Positive
stains: keratin (punctuate
perinuclear), CK20 (75%, paranuclear dotlike pattern), EMA, at least one
neuroendocrine marker (chromogranin, synaptophysin, CD57/Leu7, neuron specific
enolase) Micro
images: tumor
with better differentiated component; figure
C EM: variable dense core secretory granules DD: adenoid cystic carcinoma-solid variant (focal
cribriform architecture, myoepithelial differentiation, no neuroendocrine
differentiation); lymphoma (CD45+, keratin-), melanoma (S100+, HMB45+,
vimentin+, CK-), large cell undifferentiated carcinoma (cells > 30 microns,
moderate N/C ratio, coarse chromatin, prominent nucleoli), metastatic squamous
cell carcinoma References:
Mod Path 1990;3:631, Mod Path 2002;15:264, AJSP 2004;28:762 True
salivary gland primaries of squamous cell carcinoma are very rare Most
tumors of parotid gland are metastases to intraparotid lymph nodes from
primaries in oral cavity, upper aerodigestive tract or skin May
represent malignant component of malignant mixed tumor or high grade
mucoepidermoid carcinoma Rapid
growth with infiltration of surrounding structures, regardless of origin 50% 5
year survival Treatment: radical surgery, radiation therapy Gross: large, poorly encapsulated mass Micro
images: (1) H&E,
CK7 neg/weak and CK20 neg; (2) C:basaloid-H&E;
D:CD117; (3) figure
B-basaloid squamous cell-figure B; (4) 2-keratinization
and pseudoglandular features; 3-in situ carcinoma; 4-mucicarmine+ tonsillar
metastases References: Archives
2001;125:740 Also
called papillary cystadenoma lymphomatosum papilliferum, adenolymphoma Almost
always in parotid gland; represents 10% of parotid gland tumors Occasionally
in oral cavity, larynx, cervical lymph nodes (Auris Nasus Larynx
2004;31:293) Usually
male smokers age 40+ years Arises
from incorporation of lymphoid tissue in parotids or induction of cystic and
oncocytic changes by inflammatory infiltrate; non-neoplastic (Hum Path 2000;31:1377) 70% of
bilateral salivary gland tumors are Warthin’s tumors Rarely
transforms to lymphoma, adenocarcinoma, mucoepidermoid carcinoma, squamous cell
carcinoma, oxyphilic carcinoma or Merkel cell carcinoma Case
reports: tumor of nasopharynx (Case of the
Week #112) Treatment: surgical excision; 2% recur after resection Gross: encapsulated, lobulated, pale gray surface,
multicystic with mucinous/serous secretion, 10-15% multifocal/bilateral; 2-5
cm; may be fixed to overlying skin; may undergo hemorrhagic infarction,
particularly after fine needle aspiration Gross
images: well-demarcated
gray-yellow tumor Warthin’s tumor (continued) Micro: double layer of epithelial cells resting on dense
lymphoid stroma with variable germinal centers; cystic spaces narrowed by
polypoid projections of lymphoepithelial elements; surface palisading of
oncocytic columnar cells with underlying discontinuous basal cells; occasional
features are cilia, squamous metaplasia associated with infarct-like necrosis,
mast cells, dendritic cells, mucin secreting cells, sebaceous cells; very
rarely signet ring cells; no myoepithelial component Micro
images: figure
1A nasopharyngeal
tumor - #1;
#2;
#3 multilocular
papillary cystadenoma: #1; #2; #3; #4; #5 Positive
stains: keratin (CK7, CK 8/18,
CK19), mitochondrial markers; focal CEA Negative
stains: amylase, vimentin, desmin Molecular: not clonal (Hum
Path 2000; 31:1377, Mod Path 2005;18:964), although cases with coexisting mucoepidermoid
carcinoma are associated with t(11;19) and the CRTC1/MAML2 fusion transcript (Genes Chromosomes Cancer
2008;47:309) EM: oncocytes are stuffed with mitochondria with cup
shapes or concentric-ring forms but no partitions Lymphomas 3% of
salivary gland neoplasms Mean
age 63 years Primary
lymphomas may arise from intraparotid lymph node or within parotid or
submandibular gland Unilateral
masses, often diffuse large B cell lymphoma, follicular lymphoma, MALT or
SLL/CLL Increased
risk with autoimmune disease 3% of
tumors of major salivary glands Indolent,
excellent prognosis Most
common lymphoma of salivary glands Often
associated with Sjogren’s syndrome or benign lymphoepithelial lesion, perhaps
due to chronic antigenic stimulation May
arise post-transplantation (AJSP 2000;24:100) Case
report arising in chronic sclerosing sialadenitis / Kuttner’s tumor (AJSP 2001;25:1546) Diagnosis: monoclonality by immunohistochemistry or flow
cytometry or monocytoid infiltrates in regional lymph nodes; monoclonality in
lymphoid infiltrates by PCR is insufficient for diagnosis Micro: monocytoid cells surround ducts Micro images: figure
F (monocytoid cells surround ducts) Positive
stains: CD19, CD20, CD22 Negative
stains: CD5 (usually), CD10,
bcl-1/cyclin D1 Molecular: t(11;18)(q21;q21) is specific; encodes c-IAP2-MLT
fusion protein Very
rare Often
EBV+ Case
reports: 42 year old man with AIDS
and parotid gland tumor with NK/T cell phenotype (Archives 2002;126:738) Micro
images: tumor
cells with large vesicular nuclei and prominent nucleoli, CD3+, UCHL-1+,
TIA-1+, EBER+ by ISH Sarcomas Extremely
rare in salivary glands, usually parotid (primary or secondary) or
submandibular gland (primary) Often
have relatively good outcome Micro: usually spindled cells with solid or vasoformative
growth pattern, often epithelioid Micro
images: (1) high
grade submandibular tumor; (2) metastatic
high grade tumor to parotid; (3) Factor
VIIIraq+, CD31+ and CD34+ References:
Mod Path 2003;16:263 Desmoplastic small round cell tumor Case
reports: parotid gland of 22 year
old man (Hum Path 1999;30:430) Positive
stains: cytokeratin, desmin,
neuron-specific enolase Molecular: EWS-WT1 fusion transcript Also
called juvenile hemangioma Most
common salivary gland tumor of infants/children; often girls Often
congenital, involves parotid gland Not
malignant; 70-95% regress spontaneously by age 7 years May be
associated with Kasabach-Merritt syndrome Fine
needle aspiration may be useful for diagnosis (Archives 2001;125:1340) Treatment: delay excision in hope of spontaneous regression Gross: diffuse soft mass uninvolved with overlying skin Micro: anastomosing thin walled capillaries growing between
salivary ducts and acini; variable mitotic figures Cytology: spindle shaped cells in sheets and clusters in
bloody background; cell block shows ductal structures trapped in sheets of
spindle cells Cytology
images: hypercellular
clusters of bland spindle cells surrounding ductal structures in cell block,
factor VIII+, CD34+ Positive
stains: CD34 and factor VIII Rare
in oral cavity or salivary gland region Median
age (oral/salivary gland) is 51 years, range 30-70 years; no childhood cases No
gender predominance Better
prognosis than at other sites; no metastases or deaths due to disease Treatment: complete excision and careful follow-up Gross: mean 4.2 cm (1.5-6.0 cm) Micro: usually well differentiated, myxoid or
dedifferentiated; increased numbers of lipoblasts are present Micro
images: well
differentiated liposarcomas; parotid
myxoid liposarcoma References:
Mod Path 2002;15:1020 <75
cases reported Most
frequent salivary gland sarcomas are rhabdomyosarcoma and malignant fibrous
histiosarcoma Diagnosis
of exclusion (no primary lesion elsewhere) Case
reports: 53 year old with parotid
tumor (Archives 2002;126:849) Gross
images: pink
tan soft tumor Micro
images: malignant
tumor cells surround residual parotid ducts/acini, normal cells but not tumor
are AE1-AE3+; tumor
and metaplastic bone, EM shows multinucleated tumor with rough endoplasmic
reticulum DD: spindle cell carcinoma, malignant mixed tumor Other tumors Also
called sialoblastoma Very
rare; diagnosed at or shortly after birth Cellular
epithelial parotid tumor in infants with embryonal or blastomatous appearance May
recur locally or involve regional lymph nodes Case
reports: 21 month old with 1-2 cm
mass in parotid gland with increasing anaplasia over time (AJSP 1999;23:342) Micro:
ductules and solid organoid nests of
basaloid cells with fine chromatin and cuboidal epithelial cells; variable
necrosis, variable mitotic activity, variable nuclear atypia, no perineurial
invasion Positive
stains: cytokeratin (ductal
structures), S100 DD: teratoma Cases
associated with surgical trauma may have features of traumatic neuroma Case
reports: 74 year old man with right
submandibular lesion but no prior trauma (Archives
2001;125:1000) Micro:
large eosinophilic cells with
granular cytoplasm and small central nuclei Micro
images: granular
cells near nerve fascicles (arrows), S100+ Positive
stains: PAS, S100, CD68,
alpha-1-antitrypsin Rarely
involves parotid gland Case
reports: 47 year old man with
spindle cell lipoma of parotid gland diagnosed by fine needle aspiration (Archives 2001;125:820) Micro
images: spindle cell lipoma-fine needle aspirate - bland
spindle cells with myxoid change and fat, CD34 Diffuse
deposition of adipose tissue throughout parotid gland with overall enlargement
of parotid but no distinct mass Associated
with diabetes, cirrhosis, alcoholism, malnutrition, hormonal abnormalities May be
preceded by sialadenosis (acinar cell hypertrophy, interstitial edema, ductal
atrophy) Unusual Median
age 66 years, range 30-84 years Usually
represents metastatic disease from head and neck Poor
prognosis; rare patients have prolonged survival after surgery Gross: often multiple nodules Micro: sheets of cells with abundant eosinophilic cytoplasm
and prominent nucleoli; often spindle cell regions, angiolymphatic invasion Micro
images: various
melanomas References:
Archives 2000;124:1780 Also
called sinus histiocytosis with massive lymphadenopathy Rarely
presents as salivary gland involvement without significant lymphadenopathy Unknown
origin, but associated with immunologic abnormalities Usually
long clinical course with exacerbations and remissions and eventual complete
remission Case
reports: 48 year old with systemic
lupus erythematosus and parotid gland involvement (Archives 2001;125:1348) Micro: histiocytic proliferation with emperipolesis in
background of plasma cells and lymphocytes with eventually effacement of organ
and formation of fibrous bands Micro
images: emperipolesis,
histiocytic proliferation, S100+ Positive
stains: S100 DD: sinus histiocytosis, metastatic carcinoma, melanoma
(also phagocytose hematopoietic cells) May
arise from facial nerve and present as salivary gland tumor Gross: encapsulated Micro: resembles schwannoma elsewhere Uncommon First
described in 2001 Wide
age range Parotid
gland, hard and soft palate cases Benign
behavior, no recurrences reported Case
reports: Case of the
Week #49 Gross: well circumscribed, resemble lipoma Gross
images: well
circumscribed tumor, bisected
tumor Micro: mature adipose tissue mixed with acinar, ductal,
basal and myoepithelial cells of normal salivary gland; also duct ectasia with
fibrosis, prominent lymphoid infiltrates with nodular aggregates in the stroma Micro
images: from Case of the Week #49 - peripheral
lipomatous tissue with central salivary gland elements, lipoma
like areas, acini
and dilated ducts #1, #2,
#3,
ducts
with fibrosis of wall infiltrated by lymphocytes #1, #2 Miscellaneous Major salivary gland tumors only (parotid,
submandibular, sublingual glands) Tumors arising in minor salivary glands are staged
according to anatomic site of origin Primary tumor (T) TX:
Primary tumor cannot be assessed T0: No
evidence of primary tumor T1: Tumor
2 cm or less in greatest dimension without extraparenchymal extension* T2: Tumor
more than 2 cm but not more than 4 cm in greatest dimension without
extraparenchymal extension* T3: Tumor
more than 4 cm in greatest dimension or tumor having extraparenchymal
extension* T4a:
Moderately advanced disease; tumor invades skin, mandible, ear canal or facial
nerve T4b: Very
advanced disease; tumor invades skull base or pterygoid plates or encases
carotid artery * Note:
extraparenchymal extension is clinical or macroscopic evidence of invasion of soft
tissues. Microscopic evidence alone does not constitute extraparenchymal
extension for classification purposes. Regional lymph nodes (N) NX:
Regional lymph nodes cannot be assessed N0: No
regional lymph node metastasis N1:
Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension N2:
Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than
6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more
than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes,
none more than 6 cm in greatest dimension N2a:
Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than
6 cm in greatest dimension N2b:
Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest
dimension N2c:
Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in
greatest dimension N3:
Metastasis in a lymph node more than 6 cm in greatest dimension Distant metastasis (M) M0: No
distant metastasis M1:
Distant metastasis Stage grouping I :
T1 N0 M0 II :
T2 N0 M0 III :
T3 N0 M0 or T1-3 N1 M0 IVA :
T4a N0-1 M0 or T1-T4a N2 M0 IVB :
Any T N3 M0 or T4b any N M0 IVC :
Any T any N M1 At
least one section per 1 cm of tumor for large tumors, including tumor center
and periphery Submit
entire tumor if can do so in 5 sections or less Submit
resection margins Save
intervening levels on biopsies for special stains For
neck dissections, should have 6 or more lymph nodes if selective dissection and
10 or more if modified radical neck dissection Useful
to determine extent of surgery needed, particularly for parotid tumors Most
common error is to diagnose mucoepidermoid carcinomas as benign Rapid, reliable, safe FNA
> 90% sensitive, but may induce necrotic and reparative changes in tumor,
particularly oncocytic tumors Induces numerous histologic changes, including
hemorrhage, multinucleated giant cells and inflammation, granulation tissue and
fibrosis, squamous cell metaplasia, infarction and necrosis, subepithelial
stromal hyalinization; occasionally cholesterol clefts, pseudoxanthomatous
reaction, pseudocapsular invasion, microcystic degeneration Core
biopsy not recommended as tumor may implant along needle tract Recommended to initially classify as normal
tissue/inflammation, pleomorphic adenoma, Warthin’s tumor, cyst, small cell
epithelial lesion, large cell epithelial lesion (low grade or high grade),
spindle cell lesion (low grade or high grade) Diagnostic difficulties: extensive squamous metaplasia may resemble squamous
cell carcinoma or mucoepidermoid carcinoma; basal cell adenoma may resemble
adenoid cystic carcinoma (solid type); oncocytic proliferations may resemble
acinic cell carcinoma Micro images: central
necrosis, squamous metaplasia; squamous
metaplasia, giant cell reaction Micro images: (1) A-basal
cell adenoma, B/C-adenoid cystic carcinoma; (2) benign
duct obstructive lesion; (3) oncocytoma
and acinic cell carcinoma References: Archives
2000;124:87, Mod Path
2002;15:342 Tumor
histologic type and pattern Anatomic
site of origin Tumor
size Tumor
histologic grade (for mucoepidermoid carcinoma, adenocarcinoma NOS, malignant
mixed tumor, adenoid cystic carcinoma) Tumor
extension to adjacent structures Status
of resection margins Vascular
invasion Perineural
invasion Lymph
nodes: for each level, number obtained, number involved by tumor, size of nodal
metastases, presence of extracapsular spread End of Salivary
gland chapter
Developmental disorders: heterotopia, polycystic disease
Inflammation: diffuse infiltrative lymphocytosis syndrome, Kimura’s disease, Mikulicz’s disease, necrotizing sialometaplasia, sialadenitis, sialolithiasis, Sjogren’s syndrome, xerostomia
Non-neoplastic tumors/tumor-like conditions: adenomatoid hyperplasia, adenomatous ductal hyperplasia of major salivary glands, amyloidosis, benign lymphoepithelial cyst, choristoma, epidermoid cyst, lymphoid hyperplasia, radiation effect
Epithelial/myoepithelial tumors: general, classification, acinic cell carcinoma, adenocarcinoma NOS, adenoid cystic carcinoma, adenosquamous carcinom, basal cell adenocarcinoma, basal cell adenoma, canalicular adenoma, clear cell tumors, clear cell carcinoma, cystadenocarcinoma, epithelial myoepithelial carcinoma, giant cell tumor, hybrid carcinomas, inflammatory myofibroblastic tumor, intraductal carcinoma, inverted ductal papilloma, keratocytoma, large cell neuroendocrine carcinoma, lipoadenoma, lymphoepithelioma-like carcinoma, malignant mixed tumor, membranous adenoma, metastases, mucoepidermoid carcinoma, myoepithelioma, oncocytoma, oncocytosis, oxyphilic carcinoma, papillary adenocarcinom, pleomorphic adenoma, polymorphous low grade adenocarcinoma, salivary duct carcinoma, salivary duct papilloma, sebaceous adenoma/lymphadenoma, sialadenoma papilliferum, signet ring adenocarcinoma, small cell carcinoma, squamous cell carcinoma, Warthin’s tumor
Lymphomas: lymphoma-general, MALT lymphoma,, T cell lymphoma
Sarcomas: angiosarcoma, desmoplastic small round cell tumor, hemangioendothelioma, liposarcoma, undifferentiated sarcoma
Other tumors: embryoma, granular cell, lipoma, lipomatosis, melanoma, Rosai-Dorfman disease, schwannoma, sialolipoma
Miscellaneous: TNM staging, grossing, frozen section, fine needle aspiration, features to report
AJCC
Cancer Staging Manual (7th ed)
American Journal of Surgical Pathology
Archives of Pathology and Laboratory
Medicine
Human Pathology
Modern Pathology
Johns Hopkins cytopathology tutorial
Adenoid cystic carcinoma
