Clinical History
A 55-year-old man, originally from Haiti, presented to the ENT
clinic with a two-month history of an enlarging left parotid mass. A 3.0 cm firm, tender mass, which
appeared to be fixed to skin, was palpated. There was mild left facial weakness and patient denied
weight loss. An FNA was performed (Figures A,B,C).
Case 2 - Figure A - Hypercellular aspirate. Cluster of undifferentiated epithelial cells with scant cytoplasm (Diff-Quik stain, high power).
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Case 2 - Figure B - Aspirate shows clusters of undifferentiated epithelial cells with scant Cytoplasm, finely stippled nuclear chromatin, and vague acinar formation (Papanicolaou stain, high power).
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Case 2 - Figure C - Some epithelial cells are associated with globular hyaline membrane-like material (Papanicolaou stain, high power).
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Cytologic Findings
Aspirates were obtained from the left parotid gland
mass. Direct smears stained with Papanicolaou and Diff-Quik stains were hypercellular and consisted of
numerous small to medium-sized neoplastic epithelial cells, which arranged in clusters, sheets, and few
acinar arrays. Chromatin pattern ranged from stippled to mildly granular and mitoses were occasionally
seen. Tumor cells contained scant to none cytoplasm. Presence of basement membrane-type material was
scarce to none, although some neoplastic cell groups, particularly on Papanicolaou-stained smears,
appeared to be surrounded by globular hyaline membrane-like material. The background exhibited rare
serous acinar parotid gland cells.
Histology and Clinical Follow-up
Because of presence of mild left facial weakness
the patient underwent magnetic resonance imaging (MRI) and in addition to the left parotid tumor mass he
was found to have a 1.5 cm enhancing mass lesion of unknown etiology in the right temporal area, which
was located posterior and superior to the coronoid process of the mandible just deep to the zygomatic
arch. Patient was brought to the operating room and forceps biopsies were obtained from the right
temporal mass. The specimen was received fresh and consisted of multiple fragments of yellow-red soft
tissue measuring in aggregate 1.0 x 1.0 x 0.4 cm. Touch preparations revealed large numbers of small to
medium-sized neoplastic cells having scant cytoplasm, which exhibited an organoid pattern with occasional
rosette-like arrangements. Nuclear pseudoinclusions were rarely observed. Histologic examination
revealed small neoplastic cells forming pseudo-rosettes and invading the skeletal muscle tissue. Rare
mitotic figures and focal areas of necrosis were present. The tumor cells were strongly immunoreactive
with chromogranin and synaptophysin, focally reactive with cytokeratin (AE1/3) and CAM 5.2, and
non-reactive with smooth muscle actin, CK20, and S100 protein immunostains.
Chest radiographs showed infiltrates of the right middle lobe with questionable atelectasis. Computed
tomography (CT) of the thorax with intravenous contrast confirmed the atelectasis and revealed 3.3 x 2.2
cm right hilar adenopathy, likely metastasis, while on abdominal CT suspicious large hypodense lesions
with central necrosis were found in the liver and there was a 1.2 cm metastatic lymph node posterior to
the spleen. Clinical history indicated that this patient was a smoker until 10 years prior to the
current presentation.
Patient received radiation therapy of his left parotid tumor mass for palliation of pain and
chemotherapy for his systemic disease.
Discussion
The cytological diagnosis of the left parotid gland mass was: suspicious for malignancy, favor
undifferentiated variant of adenoid cystic carcinoma.
Due to the finding of a new lesion in the right temporal area on follow-up MRI testing an incisional
biopsy was performed on this mass and the surgical pathology diagnosis was:
metastatic high-grade neuroendocrine carcinoma invading skeletal muscle
tissue. Further imaging studies demonstrated infiltrates of the right middle lobe with
ipsilateral hilar lymphadenopathy, as well as suspicious liver masses and an enlarged retro-splenic lymph
node.
This case illustrates an uncommon example of neuroendocrine (small-cell) carcinoma of the lung
presenting through its metastasis to the salivary gland in the context of a rapidly growing parotid gland
mass with no systemic or pulmonary symptoms and no previous history of malignancy. An enlarging parotid
gland mass lesion in a middle-aged patient most likely represents a primary neoplasm, of which the most
common on the major salivary glands are benign mixed tumors. The fact that this patient presented with a
rapidly enlarging mass fixed to the skin, in addition to tenderness and mild ipsilateral facial weakness,
suggested a primary salivary gland malignancy. Aspirates revealed a monotonous population of small to
medium-sized epithelial cells organized into clusters, sheets, and acinar arrangements. This cytologic
presentation on aspirates from major salivary gland mass lesions, along with the associated clinical
findings described, is highly indicative of adenoid cystic carcinoma, particularly the undifferentiated
(or solid) variant. Presence of globular hyaline membrane-like material intimately associated with
occasional clusters of neoplastic cells on the aspirates provided additional base to suggest adenoid
cystic carcinoma.
Imaging studies intended for further evaluation of the left parotid gland neoplasm revealed the
presence of another mass lesion that was located in the right temporal area. Open biopsy of this lesion
revealed high-grade neuroendocrine carcinoma invading the skeletal muscle consistent with metastasis,
which was supported by consistent immunohistochemical staining. Additional imaging revealed evidence of
a primary pulmonary source for this right temporal malignancy with obvious metastatic disease to
ipsilateral hilar lymph nodes, liver, and retro-splenic lymph node. Although immunostains for
neuroendocrine markers were not performed on the aspirates from the left parotid gland mass,
retrospective morphologic comparison with the incisional biopsy material from the right temporal area
-which included touch preparations- afforded the conclusion that both biopsies represented the same
neoplasm and the left parotid gland mass indeed was a metastasis from a primary small cell carcinoma of
pulmonary origin.
Frequency of Benign versus Malignant Primary Salivary Gland Neoplasms
Pleomorphic adenoma (mixed tumor) and variants constitutes the most common (75%) primary neoplasm
arising in the salivary glands, whereas mucoepidermoid carcinoma is considered as the most common parotid
gland malignancy and adenoid cystic carcinoma as the most common primary malignant tumor arising in all
salivary glands other than the parotid.
However, at the Armed Forces Institute of Pathology (AFIP) adenoid cystic carcinoma accounts for up to
55% of malignancies arising in the parotid glands.
Metastatic Malignancy in Major Salivary Glands
The overwhelming majority of malignant tumors affecting the major salivary glands are primary.
Metastatic neoplasms constitute approximately 10% of all malignancies affecting the major salivary glands
–excluding lymphoma- at the AFIP. Of these 80% are metastases from primary tumors of the head and neck
region and 20% originate in infra-clavicular sites. The most common infra-clavicular sites that produce
metastases to the major salivary glands are lung, kidney, and breast. In 80-90% of the cases metastasis
to the major salivary glands occur in the parotid with the remainder occurring in the submandibular
gland. Most head and neck carcinomas and melanomas reach the parotid gland via lymphatic spread, while
infra-clavicular malignancies use the hematogenous route to metastasize into the salivary glands.
Differential Diagnosis of Small-cell Malignancies in the Parotid Gland
Adenoid cystic carcinoma (ACC) accounts for the great majority of malignant salivary gland
tumors presenting with small cell morphology, especially the undifferentiated or solid variant of ACC,
which lacks the classic cribiform appearance of most ACC. In the major salivary glands this neoplasm is
slow growing and usually fixed to the overlying skin or deeper tissues. Due to its high propensity to
invade nerves ACC commonly presents with tenderness, pain, and facial nerve paralysis. The index case
shared a similar clinical presentation and exhibited small cell undifferentiated cytomorphology.
Cellular mixed tumor (monomorphic adenoma) and polymorphous low-grade adenocarcinoma
(PLGA) are other primary salivary gland neoplasms that share morphologic resemblance with ACC. However,
PLGA can be practically excluded from the differential diagnosis of the index parotid gland tumor case
since PLGA occurs almost exclusively in the minor salivary glands of the palate. Differentiation of
solid variant of ACC from monomorphic adenoma can be quite challenging and is often impossible on the
basis of cytology alone. Nuclear atypia and presence of necrosis or nucleoli favor ACC over cellular
mixed tumor.
Lymphomas present with a monomorphic population of cells in a single-cell distribution with
virtually absent cell clusters. If required immunostains can further assist in the differentiation of
lymphoid from epithelial neoplasms.
Small cell undifferentiated carcinoma primary to the salivary glands is a rare neoplasm whose
morphology and immunohistochemical appearances are indistinguishable from those of small cell carcinoma
of the lung. Establishing morphologic similarity between a salivary gland tumor and a small cell
carcinoma at another site constitutes strong evidence of metastastic disease rather than primary salivary
gland carcinoma. Moreover, primary salivary gland small cell carcinoma is much less common than
metastasis from a pulmonary lesion.
Our index case, as well as other previous experiences in the literature, indicates that some
metastatic carcinomas present in the salivary glands without a previous history of malignancy.
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