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CPC#3: Salivary Gland: Primary Mucinous Adenocarcinoma
July 16, 2015
Group 2
SALIENT FEATURES o Intercalated ducts have reserve cells that regenerate
 53-year-old, male acinar tissue and terminal duct system
 3 × 3 cm lump o All epithelium is PSA+
 Location of mass: Right side of neck below the angle of the o Sebaceous glands are attached to ducts, and are
jaw considered part of normal holocrine differentiation
 Originally noted 1 1/2 years prior [holocrine secretions are produced within the cell, then
 Painless and slow growing are released into the lumen after rupture of the plasma
 No associated symptoms membrane], based on the occurrence of salivary tumors
HISTOLOGIC FEATURES OF SUBMANDIBULAR GLAND with sebaceous differentiation
APPROACH TO DIAGNOSIS
 Predominantly serous but also mucinous acini
 3x3 painless & slowly growing lump on right neck below the
angle of mandible  submandibular gland
 Scanner (H&E)
o Unencapsulated well circumscribed lesion, comprised of
- Basophilic cells
- Mucin lakes of varying sizes
DDx:
- Mucinous adenocarcinoma (MAC)
- Mucoepidermoid carcinoma (MEC)
- Mucinous cystadenocarcinoma (MCAC)
- Mucin rich salivary duct carcinoma (mSDC)
- Signet-ring cell adenocarcinoma
- Malignant mixed tumor
- Adenoid cystic carcinoma
 LPO (H&E)
The submandibular gland is a mixed sero-mucous gland. In the o Mucin in contact w/ stroma
mucous portion, the cell nuclei lie flat on the basal membrane, o Cluster of tumor cells in mucus-filled cavities
while the serous portion have round cell nuclei in the lower  Mucinous cystadenoma ruled out
third of the cell. (HE staining) - (-) stroma invasion
 Acini are lined by luminal cells, which are enclosed by  Mucinous cystadenocarcinoma ruled out
myoepithelial cells - (-) mucus-filled lakes of extracellular secretory
material
 HPO (H&E)
o Nests of malignant epithelial cells
- Some having secondary lumen
- Some w/ mucin
o Mucin-filled lakes
- In contact w/ fibrotic stroma
- w/ RBCs
o Tumor cells
- Clear cytoplasm
- Darkly staining nuclei
o (-) Signet rings
 Signet ring cell adenocarcinoma ruled out
 CK 7, CK 20 stain
o CK 7+ / CK 20-
- In salivary gland tumors
- Helps distinguish between
 primary salivary gland neoplasm from metastatic
tumors
 Serous acini
 squamous cell carcinoma
o frequently located at the periphery of mucous acini
- CK 20 not expressed in primary tumors
as crescent-shaped cells (arrow)
 Primary Mucinous Adenocarcinoma
o Dense, basophilic, PAS+ intracytoplasmic secretory
granules containing amylase DIFFERENTIAL DIAGNOSES
o Have central lumen that is rarely visible by H&E ADENOID CYSTIC CARCINOMA (ADCC)
 Mucous acini
o comprise about 10% of acinar tissue
o Larger than serous acini
o Irregular pattern
o Cells have abundant cytoplasm with clear mucin, well-
rounded, basal nuclei, and are arranged around empty
lumina
o Produce acid (positive for Alcian blue and mucicarmine)
and neutral (PAS+) sialomucins
 Myoepithelial cells
o Surround acini and intercalated ducts and mediate
contraction
o Have both epithelial and mesenchymal structures and
functions, and are important in the morphology of most
salivary gland tumors
o Myoepithelial cells surrounding intercalated ducts are  Markedly (+) for Mucicarmine stain
more spindled and have fewer processes than those  Approx 50% of cases are found in the minor salivary glands
surrounding acini  Most common locations: parotid and submandibular glands
 Ducts  Most common malignant tumor in the minor salivary glands
o striated ducts (arrowheads) are more prominent  Also in the nose, sinuses, upper airways, breast, and
o intercalated ducts are shorter than those in the elsewhere
parotid gland.  Slow-growing but highly malignant neoplasm
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SURGICAL PATHOLOGY: Salivary Gland: Primary Mucinous Adenocarcinoma 1.1

 Highly recurrent MALIGNANT MIXED TUMOR

 In all age groups, high frequency in middle-aged & older
patients
 No sex predilection, except for a high incidence in women w/
submandibular tumors
 Painful mass
 Facial nerve paralysis may occur d/t perineural invasion
 Macroscopically,
o solid
o well circumscribed but not encapsulated
o firm
o often light tan
 2 main cell types
o Ductal & modified myoepithelial cells
- Hyperchromatic, angular nuclei
- Clear cytoplasm
 Small cells
o dark, compact nuclei
o scant cytoplasm Rule In Rule Out
 Classic form Gross Microscopic
o sieve-like pattern of small malignant, often basaloid cells  53 yr old  Slow growing
 Cells grow in a stroma  Lesion in Parotid Gland  (-) Benign mixed
o usually is prominent  Painless lump tumor areas
o consists of mucopolysaccharides,  (-) Necrosis
 Originally noted 1 1/2
o collagen-like fibers,
years prior
o basal lamina components
Microscopic
 laminin
 Epithelial components
 fibronectin
are malignant
 type IV collagen
 glycosaminoglycans. RULED OUT
 Myoepithelial cells
o flat, spindle-shaped MUCIN-RICH VARIANT
o scanty, indistinct cytoplasm OF SALIVARY DUCT CARCINOMA (mSDC)
o hyperchromatic, angular nuclei
o typically line the pseudocysts in the cribriform areas
 Ductal or luminal cell
o cuboidal or columnar
o broader, eosinophilic cytoplasm
o typically line the true cysts
 Cribriform (glandular) pattern
o most common pattern of arrangement
o created by numerous pseudocysts and some true cysts
scattered in cell islands
o Pseudocysts
 dominate in number
 ‘punched out’ appearance of the cell islands
 contain pools of haematoxyphilic  rare type of salivary duct carcinoma
glycosaminoglycans  predilected to males of 2:1
 furthermore to the glycans, the pseudocysts contain  high occurrence in parotid gland
basal lamina components, and is mucicarmine  has both conventional SDC and mucinous adenocarcinoma-
positive like areas
o True cysts are lined with cuboidal or, occasionally, o in addition to ductal carcinoma cells, clusters of
columnar cells carcinoma cells which float in mucin pools are
 Tubular arrangement present
o well-formed ducts and tubules  mucin lakes not as extensive as in mucinous
o frequently surrounded by a hyaline stroma adenocarcinoma
 Solid type  markedly positive for Mucicarmine stain
o myoepithelial and epithelial cells form solid masses  diagnostic “ductal lesion”
o only few glandular structures and pseudocysts o pleomorphic, epithelioid tumour cells
o strands of stroma between the relatively well- o cribriform growth pattern
demarcated islands of these rather small cells o “Roman bridge” formation
 Identification of both pseudocysts and true glandular lumina o intraductal comedonecrosis
is required to make a diagnosis of adenoid cystic carcinoma  Solid and papillary areas
 Combined patterns of growth are common, whether in the o w/ psammoma bodies
original tumor or in the recurrences o w/ squamous differentiation
RULE IN RULE OUT  Cytologically,
Microscopic Painful mass o abundant, pink cytoplasm
 Presence of pseudocyst o large pleomorphic nuclei
 Pseudocyst lined by Microscopic: o prominent nucleoli
myoepithelial-like cells  No cribiform, tubular, o coarse chromatin
 Pseudocysts have an and solid patterns RULE IN RULE OUT
appearance of having  No true cysts Microscopic Microscopic
been ‘punched out’ of the  Absence of ductal cells  Mucin lakes with islands  (-) ductal epitheloid
cell islands of carcinoma cells tumour cells
 Prominent stroma  (-) cribriform growth
RULED OUT pattern
RULED OUT

MUCINOUS CYSTADENOCARCINOMA

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SURGICAL PATHOLOGY: Salivary Gland: Primary Mucinous Adenocarcinoma 1.1

filled cystic cavities with abundant

extracellular mucin
 Mucus-producing cells arranged in a
papillary pattern projecting into the mucous
pools.
 Tumor cells of irregular shape have a clear
cytoplasm and darkly stained nucleus
 Tumor cells are in direct contact with
stroma
RULED IN

WORKING DIAGNOSIS
Mucinous adenocarcinoma of the salivary glands
 histologically identical with breast and colorectal analogues
MUCINOUS CYSTADENOCARCINOMA CASE SLIDE  round or irregular-shaped neoplastic cell nests, clusters and
 slowly growing, painless mass is consistent with the patient’s islands floating in mucus-filled cystic cavities with abundant
extracellular mucin in direct contact with the stroma
manifestation
 cuboidal, columnar or irregular in shape, usually with clear
 patient was on his 50s when he started to notice the mass cytoplasm and dark-stained centrally located nuclei
on his right neck  mitotic figures are rare
o > 70% of cases are seen among >50 years old  tumor cells arranged in solid clusters and tend to form
 65% of cases are found in the salivary gland secondary lumens or incomplete duct-like structures
 size is usually 0.4-6 cm  Mucus-producing cells may arrange in a papillary pattern
o patient’s tumor size was 3x3 cm. projecting into the mucous pools.
 Mucous acinus-like tumour islands may also be present.
 (+)clusters of epithelial cells on both slides
 Both intracytoplasmic and extracellular mucin show positive
 numerous variably-sized cysts filled with mucin staining for periodic acid-Schiff, alcian blue and
o not present on the case slide. mucicarmine.
 Nuclei are bland (evenly colored)
o case slide’s nuclei are atypical
 Cystic spaces are separated by loosely arranged fibrous
stroma.
o case: stroma is in direct contact with the extracellular
mucin
RULE IN RULE OUT
 53 years old Microscopic
 Slowly growing mass  Presence of cystic
 Painless mass configuration
 Right side of neck below  Nuclei typically are
the angle of the jaw uniformly bland
Gross  Loosely arranged fibrous
 3x3 cm lump stroma separating the
Microscopic cystic spaces
 Clusters of mild to
moderate atypical
epithelial cells
H&E Scanner View
 Mucin-containing cysts
RULED OUT  non encapsulated tumor cells and scattered mucin present
within and outside the specimen.
 tumor can be suspected as highly invasive malignant
MUCOEPIDERMOID CARCINOMA
neoplasm due to the absence of a capsule and the presence
of the tumor cells within the large portion of the specimen
extending deep within the neighbor structures.

MUCINOUS ADENOCARCINOMA
RULE IN RULE OUT
 Male
 53 years old H&E LPO
Gross  lobules and the connective tissue septa cannot be
 3 × 3 cm lump on the right side of his neck distinguished due to the massive extracellular mucin in the
below the angle of the jaw that had been stroma.
originally noted 1 1/2 years prior  mucus-producing tumor cells are arranged in a papillary
 Mass is painless and slow growing without pattern that projects into the mucous pools.
any associated symptoms
Microscopic
 Irregular-shaped neoplastic cell nests,
clusters and islands are floating in mucus-

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SURGICAL PATHOLOGY: Salivary Gland: Primary Mucinous Adenocarcinoma
 extracellular mucin was seen predominantly and with the
serous cells being invaded by it.
 mucin was found within the tumor cells.
 mucin was seen to surround and suspend the clusters of
these tumor cells.
 individual tumor cells from these clusters are shaped
irregularly with clear cytoplasm and darkly stained nuclei.
 these tumor cells are also noted in direct contact with the
stroma of the specimen slide which is a characteristic found
in mucinous adenocarcinomas
Mucicarmine
 Upon staining with mucicarmine, mounted specimen was
noted to be positive.
 Mucicarmine staining technique that involves the use of
chloride and mucine to detect the presence of mucin and
mucin-secreting adenocarcinomas.
 confirmed that the tumor was a mucin-producing neoplasm
and the mounted specimen contains mucins.
Cytokeratin 7
Cytokeratin 20
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 Immunohistochemical staining for CK 7 and 20 revealed only
CK 7 positivity.
 This confirmed that the tumor was salivary gland in origin
and ruled out the possibility that it was a cause of any other
metastatic carcinomas.
 Thus, the confirmations established from mucicarmine
staining, CK 7, and CK 20, the tumor was considered to be a
primary mucinous adenocarcinoma.
PRIMARY MUCINOUS ADENOCARCINOMA
 malignant tumor composed of epithelial clusters with large
pools of extracellular mucin (WHO).
 Primary mucinous adenocarcinoma of the salivary glands is
an extremely rare neoplasm.
 Only 21 cases with major or minor salivary gland
involvement have been reported to date (Ide, et al., 2009)
 more common in the intraoral minor salivary glands
 Approx 2:1 predilection for the minor over major glands.
 most frequently affected sites
o minor salivary glands of the palate and the sublingual
glands > submandibular glands and the lower lip > the
parotid glands
o also arise in the stomach, lower gastrointestinal tract and
lacrimal glands
 in 42 to 86 years old (mean 66.6 years)
 male to female ratio of 10:8
 Most frequent presenting symptom: painless mass of 4
weeks to 11 years duration.
 Intraoral tumors may be ulcerated and range in size from 0.5
to 7.6 cm in diameter, mostly 2-4 cm.
 Prognosis varies with location, histological type and grade
 The clinical stage of the disease is the most prognostic
factor.
EXPECTED GROSS FINDINGS
 Tumour is firm, nodular and ill defined. The cut surface is
greyish white, containing many cystic cavities with gelatinous
contents.
DIAGNOSTIC WORKUP
 MRI
o most sensitive study to determine soft-tissue extension
and involvement of adjacent structures.
 Imaging studies lack the specificity for differentiating benign
and malignant neoplasms.
 FNA
o frequently aids diagnosis of salivary gland tumors.
o can provide an accurate preoperative diagnosis in 70%
to 80% of cases.
 Surgical excision
o confirms final histopathologic diagnosis
STAGING
T GROUPS FOR MAJOR SALIVARY GLAND CANCERES
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 or nerve (except T4a and
T4b)
 Microscopic evidence alone does not constitute
extraparenchymal extension
N GROUPS FOR MAJOR SALIVARY GLAND CANCERES
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 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
N2  N2a: Metastasis in a single ipsilateral lymph node,
more than 3 cm but not more than 6 cm in greatest
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dimension  perineural invasion

 N2b: Metastasis in multiple ipsilateral lymph  direct invasion of regional structures
nodes, none more than 6 cm in greatest dimension  regional metastasis
 N2c: Metastasis in bilateral or contralateral lymph  high-grade histology
nodes, none more than 6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in
greatest dimension

M GROUPS FOR MAJOR SALIVARY GLAND CANCERES

M0 No distant metastasis
M1 Distant metastasis.
MX Cannot be assessed

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

PROGNOSIS
 MAC of the salivary glands is a rare entity, it is difficult to
compare the behavior of them to a similar tumor in a
different location.
 high propensity for local recurrence and significant risk for
lymph node metastases.
o high chance of having recurrence and metastasis
especially on advance stages of cancer.

Stage 5-year Relative Survival Rate

I 91%
II 75%
III 65%
IV 39%

TREATMENT
SURGERY
 primary treatment of salivary malignancies
 In the case, basic surgical principles include the en bloc
removal of the involved gland with preservation of all nerves
unless directly invaded by tumor.
 In most cases, the cancer and some or all of the surrounding
salivary gland will be removed.
 Nearby areas of soft tissue may be removed as well.
 If the cancer is high grade (more likely to grow and spread
quickly) or if it has already spread to lymph nodes, the
surgeon will usually remove lymph nodes from the same
side of the neck in an operation called a neck dissection.
 Cervical lymph node dissection
o Salivary gland cancers sometimes spread to lymph
nodes in the neck (cervical lymph nodes)
o may be done if:
 Lymph nodes in the neck are enlarged (as felt by
physical exam or seen on a CT or MRI scan)
 PET scan suggests the lymph nodes may contain
cancer
 cancer is high grade or has other features that
mean it has a high risk of spreading.
RADIATION THERAPY
Maybe used:
 as the main treatment (alone or with chemotherapy) for
some salivary gland cancers that can’t be removed by
surgery because of the size or location of the tumor, or if a
person can’t have (or doesn’t want) surgery.
 After surgery (alone or with chemotherapy) to try to kill any
cancer cells that might have been left behind, if the cancer
has a higher chance coming back.
 In people with advanced salivary gland cancer to help with
symptoms such as pain, bleeding, or trouble swallowing
External beam radiation therapy
 used most often to treat salivary gland cancer
Postoperative radiation treatment
 plays an important role in the treatment of salivary
malignancies
Indications for radiation therapy:
 presence of extraglandular disease

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