E M E R G E N C Y R O U T E D I A G N O S I S
Spec Care Dentist 36(1) 2016 39
© 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.
Mucoepidermoid carcinoma (MEC) is the most common malignancy of the salivary glands with mean age at diagnosis of 45 years without marked gender differences.1 It most often affects the parotid gland;2 however, MEC may be associated with the submandibular, sublingual, or minor salivary glands. Clinically, MEC typically presents as a nonpainful swelling or mass, however, pain and facial nerve palsy may develop depending on the anatomical location of the tumor.3 All MECs have metastatic poten- tial and the lungs, bones, and liver have all been reported as sites of metastasis.4 Spec Care Dentist 36(1): 39-42, 2016
*Corresponding author e-mail: ets@dental.upenn.edu
1Chief Resident, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania; 2Chair and Professor of Oral Medicine, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania; 3Associate Professor of Oral Medicine, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania.
Milda Chmieliauskaite, DMD, MPH;1 Thomas P. Sollecito, DMD, FDS RCSEd;2 Eric T. Stoopler, DMD, FDS RCSEd, FDS RCSEng3*
DOI: 10.1111/scd.12142
C A S E H I S T O R Y R E P O R T
Emergency route diagnosis of
mucoepidermoid carcinoma initially diagnosed as a temporomandibular disorder
MEC is composed of squamoid cells, mucus-producing cells, and intermediate cells which can have a varied histological presentation.5 Grading of MEC tumors is dependent on a variety of characteristics including necrosis, mitosis, atypical nuclei, and size of cystic component of the tumor.6 Histology and grading of the neoplasm are important in predicting the rate of growth and metastatic potential of the disease.6 Low-grade tumors tend to have a higher mucinous component and have been observed to behave in a more benign fashion, while high-grade tumors consist of poorly differentiated cells and tend to be aggressive with the potential for metastasis.5
The route to diagnosis is an impor- tant factor in determining patient outcomes.7 Emergency route diagnosis of cancer may cause increased anxiety
for the patient due to development of acute symptoms and increase demands on the health-care system by requiring urgent management and the need for out-of-hours personnel.7,8 Biological factors, such as later stage of malignancy at diagnosis and advanced age, contrib- ute to poorer survival of Emergency Department (ED)- presenting patients.9 Delayed definitive diagnosis due to complex symptom presentation can also increase the chances of ED presentation.10
Salivary gland tumors, including MEC, have been previously reported to present with any combination of com- plex symptoms of facial pain, trismus, otalgia, and tinnitus mimicking temporo- mandibular disorders (TMD).11,12 However, it is essential to note that salivary gland tumors with symptoms
A B S T R A C T
Salivary gland malignancy (SGM) can affect both major and minor glands and manifests clinically with various presen- tations. The most common type of SGM is mucoepidermoid carcinoma (MEC), which has been previously reported to be associated with symptomatology associated with temporomandibular dis- orders (TMD). This case report describes a patient with an aggressive form of MEC of the parotid gland that was initially diagnosed as TMD. In addi- tion, the patient's MEC was diagnosed emergently based on development of acute clinical symptomatology. To the best of our knowledge, emergency route diagnosis of MEC affecting the parotid gland has not been previously reported in the literature.
KEY WORDS: emergency route diagnosis, mucoepidermoid carcinoma, temporomandibular disorder
scd12142.indd 39 29/12/15 12:21 PM
40 Spec Care Dentist 36(1) 2016
E M E R G E N C Y R O U T E D I A G N O S I S
Emergency route diagnosis mimicking TMD may also present with
additional signs and symptoms of swell- ing, numbness, or nerve paralysis which should increase suspicion for a malignant process.13 Patients who do not respond to initial therapy or whose symptoms progress disproportionately to the typical course of condition should be further evaluated to rule out other pathologies.11–13
This report presents a case of MEC, initially diagnosed as a TMD that was subsequently diagnosed through referral to an ED as a result of acute symptom onset. To the best of our knowledge, emergency route diagnosis of MEC affecting the parotid gland has not been previously reported in the literature.
Case repor t
A fifty-six-year-old Caucasian female was referred to the Oral Medicine service at the University of Pennsylvania Health System for evaluation of intermittent left facial swelling and pain of at least 5 months’ duration. She described
persistent ache with occasional sharp pain of the left temporomandibular joint (TMJ) that was not affected by jaw function. The patient denied previ- ous trauma to her face, jaw, and TMJ.
Additionally, there was no history of parafunctional habits reported such as bruxism or clenching of the teeth. She was previously evaluated by an otorhi- nolaryngologist and diagnosed with TMD. The patient was treated with a custom occlusal appliance fabricated by her dentist without benefit. Her past medical history was noncontributory and current medications included clindamycin 150 mg and oxycodone–acetaminophen 7.5–325 mg for her current condition.
The patient reported no known drug or food allergies, and her family history was positive for cancer (mother—ovarian cancer, father—neck tumor of unknown origin). Her social history was negative for tobacco, alcohol, and recreational or intravenous drug use. Review of systems was positive for left ear tinnitus and numbness of the left preauricular area.
Detailed cranial nerve exam II–XII was grossly intact. Extraoral exam did not reveal thyromegaly; however, generalized left facial swelling in the parotid gland region (Figure 1) and a firm 1.5-cm left submandibular lymph node was detected. TMJ examination revealed maximal inter-incisal opening of 35 mm, nontender, bilateral crepitus of the TMJs, and nontender muscles of mastication bilaterally on palpation. Intraoral exam revealed free-flowing saliva from the parotid glands bilaterally when milked.
Masses, lesions, or ulcers of the oral mucosa and gingiva were not detected and dentition appeared stable without gross caries. Differential diagnosis con- sisted of sialadenitis versus salivary gland neoplasm of the left parotid gland. With the exception of nontender, bilateral crepitus of the TMJs, the patient’s symp- toms did not correlate with a diagnosis of TMD. The patient was prescribed cephalexin 500 mg three times daily for 10 days, etodolac 400 mg every 6 hours as needed for pain management, and a magnetic resonance image (MRI) with and without intravenous contrast was ordered to rule out a neoplasm of the left
parotid gland. Prior to obtaining the scheduled MRI, the patient developed acute left facial numbness, increased swelling of the left parotid region accom- panied by left eye nerve palsy. She was advised to report to her local hospital for emergency evaluation.
The MRI was completed emergently and revealed a 2-cm fluid-filled, necrotic left submandibular lymph node and a 4.1×2.4×4.9 cm enhancing mass of the left parotid gland (Figure 2). The patient was urgently referred to the otorhinolar- yngology service and underwent cytologic analysis of the left parotid gland mass via fine-needle aspiration, which was consist- ent with poorly differentiated MEC.
Subsequently, plain film imaging revealed metastases to the mediastinal and hilar lymph nodes, lungs and positron emis- sion tomography (PET-CT) demonstrated metastasis to base of skull (Figure 3).
As a consequence of stage T4aN1M1 parotid gland MEC with symptomatic progressive parenchymal and pleural lung disease, the patient was considered unsuitable for surgical management.
Treatment consisted of radiation to decrease the rate of primary tumor growth in addition to palliative care.
The patient received a total dose of 5,000 cGy in 250 cGy fractions.
Radiation was followed by intermittent chemotherapy; however, the patient experienced rapid disease progression and succumbed to the disease 18 months after MEC diagnosis.
Discussion
Acute symptoms prompting emergency route diagnosis of head and neck cancer is uncommon.8 Variable patterns have been observed in emergency route diag- nosis of cancer based on age, gender, income, and type of cancer, which sug- gests that factors beyond biological qualities of a neoplasm may predict the odds of an emergency route diagnosis.8 Advanced age and low-income status has been associated with emergency head and neck cancer diagnosis, which con- tributes to poor survival prognosis.8,14 Patients with emergency route diagnosis of cancer often have seen primary care Figure 1. Generalized left facial swelling in the
parotid gland region associated with facial nerve palsy.
scd12142.indd 40 29/12/15 12:21 PM
Chmieliauskaite et al. Spec Care Dentist 36(1) 2016 41
E M E R G E N C Y R O U T E D I A G N O S I S
providers prior to their ED presentation, however, complex symptom presentation and lengthy diagnostic testing may delay diagnosis and contribute toward patients seeking emergency care.7 Improving rec- ognition and understanding of the complex clinical presentations of malig- nancies may help prevent emergency route diagnosis.10 A thorough medical history, review of systems, physical examination, and appropriate diagnostic testing are critical for accurate and timely diagnosis of neoplasm. Clinicians should recognize common features that increase suspicion of a neoplasm such as cranial nerve deficits, including numbness or palsy, and palpable lymph nodes.13 The diagnostic work up for neoplasm of the salivary glands may include imaging, such as MRI, CT, and ultrasonography, to determine the location and extent of a tumor.13,15 Further tests include fine-nee- dle aspiration cytology, for histologic interpretation, and PET with or without CT to localize metastases.13
An increased understanding of prog- nostic factors may help patients and clinicians choose treatment to maximize both patient outcomes and quality of life.
Prognostic factors that have been found to be associated with decreased survival in cases of MEC include higher histo- logic grade, older patient age, larger tumor size, extraparenchymal extension, presence of positive lymph nodes, and distant metastasis.6 Advanced techniques can measure levels of membrane-bound mucins, particularly MUC1 and MUC4, whose expression provides insight into disease recurrence and prognosis.16,17 Increased expression and distribution of MUC1 across the membrane of MEC tumor cells may promote tumor growth and survival, however exact mechanisms are not yet known.4,16 MUC4 expression in MEC tumor cells has been associated with decreased recurrence and increased survival, while the exact mechanism of action are still under investigation some speculate that MUC4 may play a role in MEC tumor cell differentiation.16
The National Comprehensive Cancer Network provides guidelines for surgical management of low and high-stage tumors but there are no current Figure 2. Axial MR view of T1-weighted image demonstrating a 4.1 × 2.4 × 4.9 cm enhancing mass
of the left parotid gland consistent with a neoplasm (x).
Figure 3. Axial positron emission tomography (PET/CT) view demonstrating increased uptake of radiotracer by the neoplasm.
scd12142.indd 41 29/12/15 12:21 PM
42 Spec Care Dentist 36(1) 2016
E M E R G E N C Y R O U T E D I A G N O S I S
Emergency route diagnosis guidelines for the surgical management
of intermediate-grade disease.18
Treatment is frequently limited in cases of emergency diagnosis, due to the late stage at presentation, and often is limited to palliative care.14 In the case of MEC treatment, there is no established chemo- therapy protocol and attempts to use chemotherapy have had poor results.19
This case highlights acute symptom onset of a high-grade parotid gland MEC diagnosed via the emergency route. Due to the poorly differentiated nature of the tumor and advanced stage of disease at the time of diagnosis, the patient’s sur- vival rate was poor. Earlier detection of the MEC might have led to a more favorable prognosis due to decreased tumor size, risk of metastases, and possi- ble additional therapeutic options. In addition, this patient was initially diag- nosed with TMD and was treated for this condition without benefit. It is important for clinicians to understand these disease processes and appreciate clinical signs and symptoms of these disorders to ensure appropriate patient evaluation and management in a timely manner for optimal treatment outcomes.
References
1. Coca-Pelaz A, Rodrigo JP, Triantafyllou A, et al. Salivary mucoepidermoid carcinoma revisited. Eur Arch Otorhinolaryngol 2015;4:799-819.
2. Ghosh-Laskar S, Murthy V, Wadasadawala T, et al. Mucoepidermoid carcinoma of the parotid gland: factors affecting outcome.
Head Neck 2011;33:497-503.
3. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. 2nd ed.
New York, NY: Saunders; 2008.
4. Liu S, Ruan M, Li S, Wang L, Yang W.
Increased expression of muc1 predicts poor survival in salivary gland mucoepidermoid carcinoma. J Craniomaxillofac Surg 2014;42:1891-6.
5. Yamazaki K, Ohta H, Shodo R, Matsuyama H, Takahashi S. Clinicopathologic features of mucoepidermoid carcinoma. J Laryngol Otol 2014;128:91-5.
6. Chen M, Roman SA, Sosa JA, Judson BL.
Histologic grade as prognostic indicator for mucoepidermoid carcinoma: a population- level analysis of 2400 patients. Head Neck 2014;36:158-63.
7. Mithcell E. The role of primary care in cancer diagnosis via emergency presenta- tion; qualitative synthesis of significant event reports. Br J Cancer 2015;112:S50-6.
8. Abel GA, Shelton J, Johnson S, Elliss- Brookes L, Lyratzopoulos G. Cancer-specific variation in emergency presentation by sex, age and deprivation across 27 common and rarer cancers. Br J Cancer 2015;112:
S129-36.
9. McPhail S. Emergency presentation of cancer and short-term mortality. Br J Cancer 2013;8:2027-34.
10. Keeble S, Abel GA, Saunders CL, et al.
Variation in promptness of presentation among 10,297 patients subsequently diag- nosed with one of 18 cancers: evidence from a national audit of cancer diagnosis in primary care. Int J Cancer 2014;5:1220-8.
11. Marchese N, Witterick I, Freeman BV.
Symptoms resembling temporomandibular joint disorder ca-used by a pleomorphic adenoma. J Can Dent Assoc 2013;79:d15.
12. Grosskopf CC, Kuperstein AS, O’Malley BW Jr., Sollecito TP. Parapharyngeal space tumors: another consideration for otalgia and temporomandibular disorders. Head Neck 2013;35:E153-6.
13. Vander Poorten V, Bradley PJ, Takes RP, Rinaldo A, Woolgar JA, Ferlito A. Diagnosis and management of parotid carcinoma with a special focus on recent advances in molec- ular biology. Head Neck 2012;34:429-40.
14. Savage P, Sharkey R, Kua T, et al. Clinical characteristics and outcomes for patients with an emergency presentation of malig- nancy: a 15 month audit of patient level data. Cancer Epidemiol 2015;39:86-90.
15. Davachi B, Imanimoghaddam M, Majidi MR, et al. The efficacy of magnetic resonance imaging and color Doppler ultrasonography in diagnosis of salivary gland tumors. J Dent Res Dent Clin Dent Prospects 2014;8:246-51.
16. Mohamed F. Recent advances in mucin immunohistochemistry in salivary gland tumors and head and neck squamous cell carcinoma. Oral Oncol 2011;47:797-803.
17. Siyi L, Shengwen L, Min R, Wenjun Y, Lizheng W, Chenping Z. Increased expres- sion of MUC-1 has close relation with patient survivor in high-grade salivary gland mucoepidermoid carcinoma. J Oral Pathol Med 2014;43:579-84.
18. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology head and neck cancers version 2. National Comprehensive Cancer Network Website. http://oralcancerfoundation.org/
treatment/pdf/head-and-neck.pdf. Updated May 29, 2013. Accessed January 31, 2015.
19. Laurie SA, Licitra L. Systemic therapy in pal- liative management of advanced salivary gland cancers. J Clin Oncol 2006;24:2673-8.
scd12142.indd 42 29/12/15 12:21 PM
