PRIMARY SALIVARY GLAND-TYPE NEOPLASMS

Salivary gland-type neoplasms are rare and histologically indistinguishable
from their head/neck counterparts. The World
Health Organization classifies adenoid cystic and mucoepidermoid
carcinoma as salivary gland tumors and pleomorphic
adenoma as adenoma of salivary gland type. These tumors
usually present centrally and the former arise in large airways
(i.e., trachea, carina, or main stem bronchus) from submucosal
tracheobronchial glands. 65 Uncommon presentation, rather
than salivary gland-type morphology, makes the diagnosis of
this neoplastic subtype in the lung challenging. Because these
tumors have equivalents in the head/neck and other organs,
particularly adenoid cystic carcinoma, determining primary
versus metastatic disease can be problematic. Prior clinical history,
location, and multifocal pulmonary disease may favor
metastasis over primary.
Adenoid Cystic Carcinoma Adenoid cystic carcinoma is
rare lung tumor with predisposition for local recurrences and
late distant metastasis 12 typically presenting as a central submucosal
mass, therefore, usually not present on exfoliative cytology
examination. As a result of its uncommonness and location,
adenoid cystic descriptions are relatively more prevalent in the
histological than cytological literature. The cribriform (most
common), tubular, and solid architecture described in surgical
pathology are recapitulated in cytological specimens. The
cellular adequacy is dependent on sampling. The neoplastic cells
are arranged as two-dimensional sheets, cohesive three-dimensional
clusters, and singly. 66 The cells are basaloid appearing,
bland, small, round to oval, and hyperchromatic with scant
cytoplasm. The nuclei have finely distributed hyperchromatic
chromatin and inconspicuous nucleoli. 67 Metachromatic (Diff-
Quik) or light blue (Papanicolaou stain) characteristic hyaline
basement membranelike globules or cylinders are intimately associated
with the cells, yet sharply demarcated from them. 68 The
globules also appear independent of the cellular component 66
and are scant or absent in the solid variant. Intracytoplasmic and
nuclear inclusions, nuclear molding, and dual cell population of
round and spindle cells may occur. 66
Immunohistochemistry The epithelial and myoepithelial
cell phenotype is reflected in the dual immunophenotype. The
tumors express cytokeratin (an epithelial marker) and vimentin,
smooth muscle actin, S-100, and p63, markers associated
with myoepithelial origin.
Differential Diagnosis Reserve cell hyperplasia also has
small cells, but the cells are even smaller than those of adenoid
cystic carcinoma and cuboidal to columnar surfaced by cilia
or terminal bars. The small cells of adenoid cystic carcinoma
solicit a diagnosis of neuroendocrine tumors like carcinoid
and small cell carcinoma. Slightly greater degree of pleomorphism,
hyperchromasia, and coarse chromatin are present in
carcinoid. Small cell carcinoma demonstrates necrosis, brisk
mitotic activity, stippled chromatin, and nuclear molding, although
the latter is described focally in adenoid cystic carcinoma.
66 Ancillary immunohistochemical studies can be highly
useful for differentiating neuroendocrine tumors from adenoid
cystic carcinoma. Extracellular substances such as amyloid 66
and corpora amylacia are alternative potentials for the cylindrical
globules; however, lymphoplasmacytic cells as opposed to
epithelial cells surround amyloid. 66
Mucoepidermoid Carcinoma Mucoepidermoid carcinoma
is a malignant tumor spanning a broad age range but with
a predilection for younger ( 30 years) patients. 12 The tumor is
classified as either low-grade or high-grade and has low metastatic
rate or locally aggressive/metastatic potential, respectively. 69
Histologically, glandular, tubular, and cystic structures with
mucin and bland nuclei predominate in low-grade subtype,
whereas intermediate and squamous areas with pleomorphism
and mitoses largely comprise high-grade tumors. 12
Cytologically, mucoepidermoid carcinoma has three cell
types—mucinous, squamous, and intermediate—occurring
singly or as clusters, with or without associated extracellular
mucin, and necrotic debris. 67 The glandular cells tend to have
eccentrically placed nuclei, sometimes secondary to indentation
by cytoplasmic vacuoles, indistinct cell borders, and delicate
cytoplasm, in contrast to the intermediate/squamous cells
that have denser cytoplasm, centrally located nuclei and sharp
borders. 67 The nuclear:cytoplasmic ratio among the cell types
is variable. 67
Immunohistochemistry Immunohistochemical stains may
be helpful for separating mucoepidermoid carcinoma from
adenocarcinoma. Both are CK7 and CK20 ; TTF-1 is expressed
by adenocarcinoma and CK 5/6 by mucoepidermoid
carcinoma. 70
Differential Diagnosis Failure to recognize the combination
of cell types, may lead to an erroneous diagnosis of either
adenocarcinoma or squamous cell carcinoma. Conversely, appreciation
of the different cells can suggest adenosquamous
carcinoma. The distinction, if it exists, 71 may only be evident
histologically, with identification of an in situ component, exophytic
endobronchial growth, 12 absence of single cell keratination,
21 squamous pearls, 12 transition from low- to high-grade
areas, 69 and central location in mucoepidermoid carcinoma. 17
Pleomorphic Adenoma Pleomorphic adenomas of the
lung are biphasic tumors with epithelial and myoepithelial
components not sufficiently described in cytology, but likely
to have similar traits as in the head and neck tumors. Unlike in
the salivary gland, pulmonary pleomorphic adenomas lack significant
glandular 69 and chondroid areas 12 but have branching
ductules lined by epithelial and myoepithelial cells and periodic
acid-Schiff material on histology. 72 Pleomorphic adenomas
also have fibrillar metachromatic stroma.
Immunohistochemistry All cells stain with pancytokeratin;
however, vimentin, smooth muscle actin, and glial firbrillary
acidic protein is specific for the myoepithelial cells. 12
Differential Diagnosis Like adenoid cystic carcinoma,
pleomorphic adenoma has hyaline material, but it is more
fibrillar, and its transition with the cells is more gradual than
in adenoid cystic caricinoma.