Clinical Conditions and Lesions Mimicking Salivary Gland DiseasePart 2

The first part of this report began a review of clinical conditions and lesions that mimic salivary gland pathology (Table). Patients were referred to Columbia University’s Salivary Gland Center (SGC) with a mistaken diagnosis of an abnormality associated with their salivary glands and/or saliva. These cases, which were culled from the examination of approximately 6,000 patients, are false-positives. The patients present themselves with a range of subjective complaints and/or objective conditions, which upon close scrutiny prove to be unrelated to salivary pathology.

With the goal of alerting the profession to the patient misrepresentations, a review of these false-positives has been undertaken with the understanding that it is strictly limited only to those conditions examined in the SGC. Because of the numerous and varied entities mimicking salivary gland disease seen in the SGC, this review can only highlight their significant symptomatology and the major means of differential diagnosis. The end result for the informed practitioner will be an improvement in diagnostic skills and the avoidance of needless referrals and therapy.
Part 1 of this review included reviews of somatoform disease, neuromuscular dysfunction, masseteric hypertrophy, lymphadenopathy, and dental etiologies. Part 2 is a continuation of the SGC’s experiences with patients presenting with paraglandular opacities, space infections, proliferating masses of the ramus, and paraglandular soft-tissue pathology as they relate to the misdiagnosis of salivary gland disease.
 
PARAGLANDULAR OPACITIES

Calcifications, when they occur in the region of a salivary gland, can be falsely interpreted to represent salivary stones. Many such patients have been referred with a tentative diagnosis of sialolithiasis. The differentiation of an extraglandular calcification from a sialolith is usually based on the absence of the pain and swelling associated with obstructive sialadenitis factored in with a knowledge of those extraglandular entities that mimic a calcified salivary stone. Problems with the diagnosis develop because asymptomatic stones have been observed. Furthermore, healing following chronic sialadenitis can result in areas of intraglandular dystrophic calcification.
 
Calcified Lymph Node

Figure 1a. Calcified cervical lymph node (arrow). Normal parotid sialogram.

Parotid, submandibular, digastric, and cervical lymph nodes are anatomically situated in close proximity to the parotid and submandibular salivary glands. Healing of such an inflamed lymph node may result in its calcification and may mimic a salivary stone (Figure 1a). Other causes of lymph node calcification include a variety of parasitic infections, tuberculosis, sarcoid, metabolic diseases, and lymphoma.^1,2
The clinician can differentiate a calcified lymph node from a stone if the history and physical examination are considered. Primarily, knowledge of the anatomic location of the lymph nodes and an awareness of any pre-existing inciting situation that can lead to a lymphadenopathy must be part of the evaluation. The absence of the signs and symptoms of sialadenitis suggests that duct stones are not present. Imaging techniques, particularly sialography and the CT scan, are important in differentiating a calcified lymph node from a sialolith. The sialogram will delineate the presence of a calcified lymph node by demonstrating a normal duct pattern (Figure 1a), while the inevitable sialadenitis associated with a stone will reveal a classic irregularity in duct caliber and simultaneously depict the stone’s location. The CT scan is exquisitely sensitive to minute calcifications and will accurately pinpoint their location.³
Calcified lymph nodes do not require interventional therapy. Regardless, consideration should be given to the fact that they may represent active or healed extraoral disorders.
 
Phleboliths

Phleboliths are associated with vascular structures. They represent calcified thrombi, and when they occur in the region of a salivary gland, they can be confused with a sialolith. Although phleboliths are most frequently found in pelvic veins, the next most common site is the head and neck, where phleboliths are associated with the painless, slow-growing intramuscular hemangioma (IMH).⁴ The IMH is believed to have a congenital origin and be dormant for many years, and then—for unknown reasons—expand.⁵ The cervicofacial musculature, typically the masseter and buccinator muscles, is usually involved in head and neck IMH lesions. The purposeless and tortuous IMH vascular channels favor a sluggish vascular flow. Thrombi with calcifications can occur with layering, resulting in lamellations that can be visible radiographically.

Figure 1b. Phleboliths (arrows) present in buccally located intramuscular hemangioma. Parotid sialogram is normal except for some Stensen’s duct displacement.

Because the cervicofacial IMH can be in close relation to the salivary glands, its persistent painless swelling can mimic a salivary neoplasm. To add to the confusion, a phlebolith within the IMH can be interpreted to represent a sialolith (Figure 1b). The difference lies in the fact that sialolithiasis causes the symptomatology of obstructive sialadenitis.
The radiologic hallmark of a phlebolith is its lamellated concentric ring appearance, while a sialolith tends to be evenly opaque. Phlebo-liths are usually multiple, while sialoliths tend to occur singly. Phleboliths are distributed in a randomized pattern, while sialoliths, particularly when several are present, trace the anatomic pathway of the involved duct.
The therapeutic approach to the IMH and its phleboliths is dependent on many factors. Patient age, rapidity of growth, size, location, and cosmetics all must be considered. Radiotherapy, sclerosing agents, lasers, cryotherapy, embolization, and no treatment have been advocated, but surgical excision remains the method of choice.⁴
 
Stylohyoid Ligament Ossification (Eagle’s Syndrome)

Figure 1c. Submandibular swelling (arrow) caused by elongated styloid process and ossification of stylohyoid ligament (Eagle’s syndrome).	Figure 1d. Lateral radiograph of patient in Figure 1c demonstrates ossification of stylohyoid ligament (arrows).

Ossification of the stylohyoid ligament (SHL)^6,7 can result in a persistent swelling in the submandibular area and serve as the reason for patient referral (Figure 1c). Palpation will indicate a firm, nonmovable, and painless mass just anterior and medial to a normal submandibular salivary gland. A CT scan or radiograph will clearly demonstrate an elongated styloid process with ossification of the entire SHL (Figure 1d). The fullness in the submandibular region that clinically mimics sialadenopathy is a result of the rigid extension of the styloid process and the ossified SHL.
A diagnosis is usually made during routine imaging studies, and no treatment is necessary. Occasionally pain may develop, particularly when turning or extending the head. In such cases, surgical intervention may be indicated.
 
Tonsillolith

Figure 1e. Panoramic radiograph reveals tonsillolith (arrows).	Figure 1f. Intraoral view of tonsillolith (arrow).

The surface contour of the glossopalatine tonsil is interrupted by numerous crypts, and saliva can accumulate and stagnate in the depth of these crypts. Both debris, which can serve as an available nidus, and the salivary stagnation favoring physico-chemical precipitation of salts, can cause the occasional development of a calcified body, the tonsillolith in a tonsillar crypt.^8,9
When a tonsillolith is present, the standard dental panoramic film superimposes its opacity on the anterior-inferior portion of the parotid (Figure 1e) or even imitates a submandibular stone. Dif-ferentiation from a salivary stone is best achieved when the clinical symptoms—pain and swelling associated with eating—are absent. Close examination of the tonsil usually reveals the presence of the hard, yellowish object (Figure 1f). Obviously, the CT scan and other radiologic techniques will accurately locate the calcified body.
Tonsilloliths should be removed. They can readily be enucleated intraorally via a curetting approach.
 
Other Opacities

Figure 1g. Extravasated nonhydrolysable dye following attempted parotid sialogram 1 year previously.

A variety of other opaque bodies have been observed in the area of the salivary glands. Oil-based sialographic dyes were used in the past. Occasionally during the process of introducing this dye, the duct was perforated, and the dye entered the soft tissues close to the gland that was being investigated (Figure 1g). Because oil-based dyes do not lose opacity and are relatively resistant to normal physiologic removal, opaque pools of dye will be noted for many years. Radiographically, the dye’s opacity is more intense than the opacity of a calcified mass. Misdiagnoses have occurred, and patients have been referred for sialolith evaluation. With the advent of the new hy-drolysable dyes, with their rapid loss of opacity, this problem has disappeared.
Acne is a common facial problem, and healing is often accompanied by calcification.^9,10 Confusion with parotid stones may occur if the acne involves the skin overlying the parotid gland. Parasitic lesions with calcification,⁹ arterial wall calcification, myositis ossifications, calcinosis cutis,^11,12 and metallic fragments represent other facial opacities that can add to the diagnostic dilemma.
 
FASCIAL SPACE INFECTIONS

Fasciae are continuous layers of connective tissue that sheath, bind together, and support internal structures. Fascial spaces are potential areas between the planes of fascia. The loose connective tissue that binds the planes together can be altered by bacteria, and a fascial space infection will then be established.¹³
Anatomically, space infections and their swellings in the region of a salivary gland can mimic salivary gland disease. Patients with swellings from a space infection have been referred with diagnoses of glandular swellings. As previously stated, milking of the gland will produce a clear saliva if the gland is not involved, while a cloudy return suggesting the presence of pus will be observed when the salivary gland is directly involved in the infectious process. Imaging with a CT scan or MRI is a key factor in identifying the involved fascial space.
Space infections will usually respond to standard therapy. Treatment includes antibiotics, evacuation of pus by incising and draining the infected area, and removal of the causative agent, which often is a tooth.
 
Submasseteric Abscess

The submasseteric abscess is a space infection whose diagnosis frequently eludes the clinician. The submasseteric space, a subdivision of the masticator space, represents a potential space between the laterally positioned thick masseter muscle and the medially located mandibular ramus.^14,15 The most frequent cause of pus in the submasseteric space is infection tracking backward from an infected mandibular second or third molar.^13,15,16

Figure 2a. The swelling of the patient’s right parotid area is caused by a submasseteric abscess.	Figure 2b. Axial CT scan. Right submasseteric abscess (arrows) in patient seen in Figure 2a. Note enlargement of right masseter muscle (M) resulting from myositis.

The bulk of the parotid gland—the superficial lobe—rests on the posterior lateral surface of the masseter muscle. Consequently, the visible swelling caused by the submasseteric abscess imitates a parotid swelling (Figure 2a). The ability to differentiate between a submasseteric abscess and parotitis rests on several observations. Because the masseter muscle functions as the lateral limiting wall of a submasseteric abscess, a myositis with trismus will develop. Trismus is not a prominent feature of a parotitis. Furthermore, a parotitis will usually identify itself with increased pain and swelling during eating. Additionally, saliva as it exists from the parotid duct orifice will be clear in quality, testifying to the presence of a normal parotid gland. The CT scan or MRI has proven to be extremely valuable in recognizing submasseteric infections (Figure 2b).¹⁷
 
Submandibular and Sublingual Space Infections

The floor of the mouth and the suprahyoid region of the neck are closely related and represent an anatomic entity. This complex can be divided into 3 spaces.¹³ The submandibular space is that region of the neck that contains the submandibular salivary gland. The sublingual space, containing the sublingual salivary gland, is limited inferiorly by the mylohyoid muscle, anteriorly and laterally by the mandibular body, and superiorly by the oral mucosa. The submental space is suprahyoid in location, bordered superiorly by the mylohyoid muscle, and encompasses the anatomic outline of the submental triangle.

Figure 2c. Sublingual abscess secondary to infected mandibular molars.	Figure 2d. Extension of sublingual abscess (in patient seen in Figure 2c) to the submandibular space.

Infection of the subman-dibular space usually originates from an infected mandibular molar with pus moving inferiorly to the vicinity of the submandibular gland (Figures 2c and 2d). A cursory oral inspection usually identifies the responsible tooth, eliminates a salivary gland etiology, and is substantiated when saliva exiting from the associated Wharton’s duct is ob-served to be normal. The fact that accentuated swelling and pain does not occur with meals is further evidence of the presence of a normal submandibular gland.
The sublingual space, resting on the oral aspect of the mylohyoid muscle, contains the sublingual salivary gland. Infection from a mandibular tooth apex situated superior to the internal oblique line can move lingually above the mylohyoid muscle to involve the sublingual space. The SGC has seen several patients who developed a cellulitis of this space secondary to an infected tooth. The edema and swelling can be extensive and simulate an intraoral ranula. Differentiation rests in recognition of the infected tooth and its inflammatory symptomatology, while the cyst-like intraoral ranula is essentially asymptomatic except for its physical presence.
 
PROLIFERATING RAMUS MASS

Figure 3a. Parotid area swelling caused by aggressive keratocyst in mandibular ramus.	Figure 3b. Coronal CT scan of patient in Figure 3a. Note almost complete destruction of right mandibular ramus by the keratocyst with swelling of facial soft tissues.

A proliferative lesion in the ramus of the mandible can perforate through the lateral cortical plate. When this occurs, the lesion will displace in a lateral direction the masseter muscle and the overlying superficial parotid lobe with its duct. Clinically, the resulting facial swelling may appear to be a parotid gland swelling. The offending ramus pathology may be cystic or neoplastic. Odontogenic keratocysts (Figures 3a and 3b) and ameloblastomas can be the source of the problem. Occasionally, the proliferating mass in the ramus is a secondary manifestation of a primary malignant lesion located elsewhere. An osteoblastic tendency exists in malignancies involving the prostate, breast, thyroid, and even the lung. With the growth of the metastasis in the ramus, lateral extension with facial swelling can be expected. Two patients seen by the SGC were in this category. Both had breast metastases to the ramus with facial swellings that initially were thought to be parotid in origin.
The clinical diagnosis is facilitated when a parotid sialadenitis can be ruled out by the presence of normal clear saliva and the absence of sporadic swellings. The history of a long-standing, slowly growing mass points to a benign neoplasm but does not void the presence of a parotid malignancy, either primary or metastatic. Although fine needle aspiration (FNA) biopsy is helpful, a presurgical diagnosis is facilitated with a CT scan or MRI. Final diagnosis awaits histologic examination.
 
PARAGLANDULAR SOFT-TISSUE PATHOLOGY

In addition to adjacent bone, the salivary glands are positioned near a variety of anatomic soft-tissue structures. The cells from these tissues, as well as embryological remnants in this region, can proliferate and give rise to a great diversity of pathologic entities located in close proximity to the salivary glands.
 
Lymphoepithelial Cyst (Intraoral)

Figure 4. Lymphoepithelial cyst (arrows) overlying Wharton’s duct in mouth floor.

Surprisingly, several patients have been referred to the SGC for the removal of a submandibular sialolith because of a visible yellowish nodular mouth floor lesion that in reality was a lymphoepithelial cyst. These cysts most commonly occur in the mouth floor of adults and are movable, well-circumscribed, painless, and rarely measure more than a few millimeters in diameter (Figure 4). When these cysts occur in the anterior mouth floor, visual examination along with palpation can result in the erroneous diagnosis of a submandibular sialolith.
These cysts are now generally accepted to develop as a result of obstruction and modest proliferation of the epithelium that lines the crypts located within aggregates of oral lymphoid tissue.^18,19 They are not to be confused with the parotid lymphoepithelial cysts associated with HIV disease.
Patients with a lymphoepithelial cyst in the floor of the mouth will not reveal the classic obstructive history associated with a stone, nor will calcifications along the course of the submandibular duct be noted radiographically. The size and location of the lymphoepithelial cyst allow for a simple surgical excision.
 
Branchial Cleft Cyst

It is generally accepted that the branchial cleft cyst (BCC) is derived from remnants of the ectodermally lined cervical sinus.²⁰ The embryologic first and second branchial arches grow caudally and meet a mesodermal outgrowth from the fifth arch. In the process, the third and fourth arches with their adjacent clefts become recessed in a deep ectodermal pit—the cervical sinus.²⁰ With further fetal development, the cervical sinus becomes obliterated, but its remnants are thought to give rise to the BCC.

Figure 5a. Branchial cleft cyst in region of submandibular triangle.	Figure 5b. Axial CT scan of branchial cyst (C) along anterior border of sternocleidomastoid muscle (M) with some anterior displacement of the right submandibular salivary gland (G). Courtesy of Dr. John Silver.

The BCC manifests along the anterior border of the entire length of the sternocleidomastoid muscle (SCM), but it is most frequently present at the junction of the muscle’s upper and middle third, where the BCC becomes evident posteriorly and slightly inferior to the mandibular angle^21,22 (Figures 5a and 5b). Patients with a BCC arising in the region of the submandibular triangle can be mistakenly diagnosed with pathology related to the submandibular salivary gland.
As can be expected with a cystic mass, the BCC has a circumscribed ovoid outline and is soft in consistency and painless. It varies in size and occurs in young adults of either sex. Fistulae may exist and may open externally on the cervicofacial area or internally into the pharynx.
Histologically, the BCC is usually lined by stratified squamous epithelium. This lining rests on connective tissue with a prominent lymphoid infiltrate that may contain germinal centers.²³ The lymphoidal tissue can become involved in an adjacent infectious process, and this may serve as the stimulus for the cystic proliferation.²³
The BCC that occurs in the submandibular triangle area can easily be palpated. Palpation and the absence of clinical inflammation may suggest a cyst, but its exact nature cannot be defined. A FNA biopsy can reveal the pathognomonic cystic fluid and epithelial and lymphocytic cells.²⁴ Substantiation demands imaging studies, specifically the CT scan or MRI. Obviously, final diagnosis awaits the therapeutic approach of surgical excision and histologic examination.
 
Other Entities

The SGC has encountered other soft-tissue paraglandular entities that initially appear to be salivary gland swellings. One such entity was a well-circumscribed lateral dermoid cyst whose clinical presence in the submandibular triangle was the source of confusion. The classic finding of sebaceous glands and hair follicles within the wall of the surgically excised cyst confirmed the diagnosis. These dermoid cysts probably originate from proliferation of trapped ectoderm in the midline of the mouth floor. The cyst may then shift laterally and enter the submandibular area.^25-29

Figure 6. Axial CT scan. Lymphangioma (arrow) left parotid (P) masseteric (M) area.

Another unusual extra-glandular condition, which is characterized by a gross painless swelling of long duration superficially superimposed upon the anterior paro-tid surface, has been seen. An extraparotid lymphangioma (Figure 6) was diagnosed only after the clinical evaluation and imaging findings were buttressed by the histologic examination of the excised lesion. Lymphangiomas are believed to originate from a failure of the primitive lymph sac to connect to the venous system, with subsequent lymph accumulation and endothelial proliferation.^30,31
 
CONCLUSION

The experiences of the SGC with both these common and uncommon conditions highlight the need for a full range of diagnostic procedures when evaluating suspected salivary gland disease. It is only when all the diagnostic data, specifically clinical findings, imaging via the CT scan and MRI, and microscopic findings have been collated that the correct diagnosis, be it a true disorder of the salivary gland or a disorder that mimics a glandular morbidity, can be made.

References

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