Introduction
A 45-year-old female who works as a hair stylist presents with a right-sided subcutaneous mass of the lower third of the face. The mass is anterior and inferior to the tragus, overlying the angle of the mandible.
HPI
The mass has been present for more than 20 years with slow progressive enlargement over the past 15 years. The mass is firm but mobile. There is a contour abnormality because the mass measures about 4 cm × 4 cm underneath the skin. Because of her job as a hair stylist, she often wears her hair down to avoid drawing attention to the mass. She has no complaints of pain, numbness, trismus, facial paralysis, or cycles of parotid swelling. She denies any constitutional symptoms, such as weight loss, fevers, chills, or night sweats. She denies the presence of any other masses in the head and neck.
Pleomorphic adenomas, or benign mixed tumors, of the head and neck generally arise from the salivary and lacrimal glands. The major salivary glands include the parotid gland, submandibular gland, and sublingual glands. Minor salivary glands can be found throughout the mucosa of the head and neck. The overwhelming majority of pleomorphic adenomas are found in the parotid gland. Submandibular gland pleomorphic adenomas are uncommon, and those in the sublingual gland are extremely rare. Minor salivary gland pleomorphic adenomas are also very uncommon and account for such tumors in unusual locations, such as the lip, palate, nasal cavity, and the paranasal sinuses.
The clinical history of pleomorphic adenoma is usually benign. It tends to present as a solitary mass. It may have been present for long periods of time with very slow growth. They may be stable in size for years, which may reassure some patients that the tumor is benign. This may result in a delay in care or diagnosis.
Conversely, salivary gland malignancy presents with signs and symptoms of invasion and metastasis. Parotid malignancy may present with a firm, fixed mass; pain; trismus; and sometimes facial nerve paralysis, which is suggestive of locoregional invasion. Malignancies in the sublingual and submandibular glands may present as a firm mass. They may have signs of cranial neuropathy caused by local invasion of the distal lingual and hypoglossal nerves, such as tongue numbness, tongue fasciculations, or tongue paralysis. Salivary ductal invasion may present like a sialolith and sialadenitis with painful swelling with eating. Local invasion of the mandibular, zygomatic, or maxillary periosteum or cortex can immobilize the tumor to the bone. Minor salivary gland tumors may present as an ulcerative or locally invasive mass in the lip, oral cavity, palate, nasal cavity, or paranasal sinuses.
Metastatic cervical lymphadenopathy is a hallmark of malignancy. Pleomorphic adenoma, being a benign process, does not present with associated cervical nodal metastases. Pain, local invasion, and facial nerve paralysis are not typical of a pleomorphic adenoma and should shift suspicion toward malignancy. Pleomorphic adenomas are usually painless, mobile, and the chief complaints tend to be more cosmetic or seeking reassurance of a benign process.
PMHX/PDHX/medications/allergies/SH/FH
The patient has no significant medical history. She takes no medications. She smokes occasionally. She consumes alcohol in social settings only. She has no history of head and neck cancer, head and neck radiation, or other head and neck pathology.
There are no known risk factors for the development of pleomorphic adenomas. Evidence of tobacco use and alcohol abuse being linked to pleomorphic adenomas is not strong. Pleomorphic adenoma is not associated with any familial or genetic syndromes. A prior history of head and neck tumors, particularly pleomorphic adenomas themselves, are of utmost interest in the past medical history. Pleomorphic adenoma is unique in that it is the only benign salivary gland tumor with the potential to convert into a malignant process, known as carcinoma ex-pleomorphic adenoma (CXPA). Thus, a drawn-out course of disease in conjunction with more severe examination and diagnostic workup findings may clue a seasoned diagnostician into suspicion for transformation of a benign tumor into CXPA.
Conversely, in patients with a surgical history of a previous pleomorphic adenoma, a new mass (or masses) in the operative field may suggest a spillage of pleomorphic adenoma cells into adjacent healthy tissues, a devastating complication that will be discussed later. If the capsule of the pleomorphic adenoma is ruptured during surgery, daughter cells spilled into the operative field can give rise to multifocal disease. Treatment of this phenomenon is complicated because these tumors are best treated with surgery. Radiation and chemotherapeutic agents play little role in the management of pleomorphic adenomas. Returning to a scarred operative field increases the risk of complications, including facial nerve paralysis, secondary tumor spillage, and possibly missing microscopic disease, necessitating future visits to the operating room. To complicate matters further, each new focus of pleomorphic adenoma that resulted from spillage also carries a risk of degenerating into CXPA.
Exam
General. The patient is in no distress. She is well developed and well nourished.
Vital Signs. The patient is afebrile. Blood pressure is 118/78, heart rate is 74 bpm, and respirations are 16 breaths per minute.
Face. There is a noticeable right-sided facial mass posterior to the mandible. It measures about 4 cm × 4 cm and mobile. It is soft but firm. There is no fixation to the surrounding tissues. Sensation is grossly intact. She has a House-Brackmann score of 1 of 6. The mass is nontender. There is no associated erythema or warmth.
Neck. There is no palpable lymphadenopathy on either side of the neck.
Intraoral. There is no trismus. The patient has healthy dentition. The parotid duct and the submandibular duct are patent without any signs of inflammation or induration. Tongue movement and sensation are unremarkable. There are no floor or mouth, buccal, palatal, or pharyngeal lesions of concern.
Neurologic. The patient is alert and oriented. Her cranial nerve examination is unremarkable. There is no facial nerve weakness. Sensation is intact throughout the trigeminal nerve distribution.
A pleomorphic adenoma typically presents as a painless mass in the superficial lobe of the parotid or submandibular gland. The examination findings are usually benign. There is no associated pain or tenderness. The mass is generally mobile without evidence of spread or invasion. There is no evidence of perineural invasion resulting in cranial nerve palsy, such as a facial nerve paralysis. Cranial nerve palsies, pain, trismus, tumor fixation, and cervical adenopathy are signs of a malignant process, and they are not typical of a treatment-naïve pleomorphic adenoma. Deep lobe parotid tumors may not be present on clinical examination. If sizeable, they may be visible or palpable on the neck examination or may create a mass effect on the pharynx on transoral examination. Typically, deep lobe and parapharyngeal space masses are found incidentally on imaging.
Imaging
A noncontrast computed tomography (CT) scan was ordered by the patient’s primary care physician along with a referral to a head and neck surgeon. The patient’s CT scan showed a right-sided parotid mass. Without contrast, it had a similar appearance to the parotid parenchyma ( Fig. 40.1 ). Subsequent magnetic resonance imaging (MRI) was ordered by the head and neck surgeon. The MRI showed a 3.2-cm × 2.3-cm × 3.3-cm well-circumscribed, heterogeneously enhancing, partially cystic superficial right parotid mass. An incidental left deep lobe parotid mass was identified as well, measuring 1.6 cm × 1.2 cm × 1.3 cm. There was no associated pathologic lymph node enlargement. There was symmetric enhancement of the facial nerves on MRI.
On imaging, pleomorphic adenomas appear as well-circumscribed masses, often with bosselated borders. On ultrasonography, pleomorphic adenomas are hypoechoic solid masses with internal cystic foci. On CT scan, they typically enhance with contrast. On MRI, pleomorphic adenomas present as well-circumscribed masses. They may be homogenous when they are small. Larger tumors may be more complex with a more heterogeneous composition. On T1-weighted imaging, they present as a hypointense solid mass ( Fig. 40.2 ). On T2-weighted imaging, they may be hyperintense with decreased signal intensity along the capsule of the tumor ( Fig. 40.3 ). Contrasted T2-weighted images of smaller tumors may show homogeneous enhancement. However, as the tumors get larger, inhomogenous enhancement may be more pronounced ( Fig. 40.4 ).
Ultrasonography, CT, and MRI are the most common modalities used in evaluating salivary gland pathology. CT and MRI are frequently used as complementary studies. CT scans are an excellent objective modality that are accurately used by seasoned clinicians for both creating a clinical impression and for surgery planning. MRI is a powerful complementary study because of its superiority in evaluating salivary gland soft tissue.
Ultrasonography is an excellent, low-cost imaging study that is useful as an initial first study. However, its objectivity can be lacking when performed by a third party. Ultrasonography is most useful as a guided study for fine-needle aspiration (FNA) biopsy. FNA biopsy under ultrasound guidance is best performed by an experienced clinician. For tumors in the superficial parotid lobe, the tail of parotid, and the submandibular gland, ultrasound-guided FNA is usually feasible. However, for tumors in difficult-to-reach spaces in the neck, such as the deep lobe of the parotid, parapharyngeal space, or masticator space, CT-guided FNA is generally preferred. Analysis of the biopsy is best performed by an experienced pathologist who can provide diagnostic information to help guide treatment.
Labs
No routine laboratory tests are specific for the diagnosis of a pleomorphic adenoma or any other salivary gland tumor. However, laboratory tests may be used to evaluate for other causes of facial masses or swelling. A complete blood cell count may be obtained to evaluate for leukocytosis caused by an infectious process. Viral markers may be helpful in evaluating for viral causes of parotid swelling, such as mumps. An HIV test may slant the differential diagnosis toward a lymphoepithelial cyst.
Rheumatologic testing such as antinuclear antibody, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) may be suggestive of an autoimmune process. ESR and CRP are markers that may also be elevated in infectious processes. In Sjögren’s syndrome, there may be elevation of markers SS-Ro and SS-La. The diagnosis of Sjögren’s syndrome is left to the clinical judgment of a rheumatologist. Parotid swelling can occur in sarcoidosis, in which angiotensin-converting enzyme and vitamin D levels may be elevated. In cases of systemic autoimmune disease, bilateral or symmetric involvement portends a more benign process. In the case of our patient, a unilateral salivary gland process is less likely to favor a rheumatologic condition.
In the workup of any solitary or unilateral mass, the clinical suspicion should be for a neoplastic process until proven otherwise. Biopsy and histopathologic analysis are imperative in the diagnostic workup. For easy-to-access tumors in the lip, oral cavity, or nasal cavity, biopsy under direct or indirect visualization is feasible. For tumors in the parotid gland, submandibular gland, or other deep neck space, image-guided (ultrasound or CT) FNA of the solid portion of the mass is often diagnostic. Aspirate of the cystic portion of a salivary tumor may yield fluid that may be suggestive of a disease process but is generally insufficient for diagnosis of a neoplastic process. For example, aspirate demonstrating a brownish fluid may be suggestive of a Warthin tumor. Yellow-green mucopurulent material may be suggestive of a first branchial cleft cyst. Saliva aspirated from a cystic mass may suggest a sialocele.
Our patient declined a biopsy, electing to move forward with excision of the mass.
Differential
The differential diagnosis for pleomorphic adenoma of the parotid gland includes other benign lesions, primarily a Warthin tumor or, less commonly, an oncocytoma. Lymphoepithelial cysts are a consideration in patients who are immunocompromised. Less common tumors include solitary fibrous tumor, which is a tumor of mesenchymal origin. Other benign considerations include sialocele and first branchial cleft cyst. A sialocele is usually considered in the setting of trauma or recent surgery. A branchial cleft cyst is a congenital epithelial cyst, and first branchial cleft cysts are exclusively found between the ear and the submandibular gland.
Regarding salivary gland malignancies, slow-growing processes, such as an adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma, are on the differential. More rapidly progressing tumors include poorly differentiated mucoepidermoid carcinoma, CXPA, squamous cell carcinoma metastasis from a separate primary cutaneous or mucosal site, and primary squamous cell carcinoma of the salivary gland. Less commonly, a hematologic malignancy such as a lymphoma may present as a solid tumor of the major salivary glands.
Salivary gland abscess is an infectious consideration in the presence of an acute onset and rapidly progressing sepsis, including fever, erythema, and pain. For unvaccinated measles, mumps, rubella patients with exposure in endemic areas, mumps is a consideration. An autoimmune process may be more chronic and systemic manifestations. Patients with Sjögren’s syndrome may have dry eyes. Pediatric patients may have swelling of their parotid glands in recurrent parotitis in children.
For tumors in the parapharyngeal space, prestyloid tumors favor salivary gland origin, most commonly pleomorphic adenoma. Poststyloid parapharyngeal space tumors tend to favor paragangliomas and nerve sheath tumors. For tumors of the palate, a polymorphous low-grade adenocarcinoma and necrotizing salivary metaplasia are other considerations.
Assessment
A unilateral salivary gland mass is considered malignancy until proven otherwise. Imaging is useful in assessment and surgery planning of salivary gland masses but is generally nondiagnostic. The presence of bilateral tumors, deep lobe tumors, or prestyloid parapharyngeal space tumors may favor a benign process. Imaging suggesting extracapsular spread, increased facial or lingual nerve enhancement, asymmetric widening of skull base foramina, and cervical nodal metastases favor a malignant process. Nonetheless, the diagnosis requires tissue. The diagnosis is established with biopsy via FNA, core needle, or excisional surgical biopsy.
For pleomorphic adenoma, FNA can provide high diagnostic accuracy (89.5%–96.2%). Microscopically, pleomorphic adenoma has variable appearance. In fact, the diverse morphology of the tumor is where the “pleomorphism” or benign “mixed” tumor moniker is derived. Aspirate smears show a mix of bland ductal polygonal epithelial cells, spindle-shaped myoepithelial cells, and a fibrillary myxochondroid stroma. The stromal component comprises at least 25% of lesion material. Stroma is metachromatic on Romanowsky stains. Myoepithelioma and basal cell adenoma cytologically represent pleomorphic adenoma but are rarer. Nonetheless, they are on the cytologic differential diagnosis for pleomorphic adenoma.
Grossly, pleomorphic adenomas appear as solitary, well-circumscribed masses. There is usually an avascular areolar plane between the mass and the surrounding parenchyma. When possible, it is best to keep a margin around the tumor. The color of the tumor varies from white-tan to blue-gray. On core biopsy or excisional biopsy, they demonstrate pleomorphism and variable proportions of ductal to myoepithelial cells in a background of stromal elements ( eFigs. 40.5 to 40.8 ). There are epithelial and mesenchymal elements. Epithelial elements may include ducts, tubules, solid sheets, and ribbons. The mesenchymal component may appear myxoid, hyalinized, or cartilaginous. Myoepithelial cells may appear as spindle cells. When present, plasmacytoid cells are characteristic of mixed tumors because they are never found in any other salivary gland tumors. Encapsulation under a microscope is seen as a pseudocapsule, which may appear smooth or as fingerlike projections, or pseudopodia. These projections are thought to contribute to the pathophysiology of recurrence.
