Vol. 109 No.

1 January 2010

CLINICOPATHOLOGIC CONFERENCE A swelling of the oor of the mouth

Editor: Paul C. Edwards

Eleni Parara, MD, DDS, MSc, MSc,a Panos Christopoulos, DDS, PhD,b Konstantinos Tosios, DDS, PhD,c Irini Paravalou, DDS, MSc,d Christina Vourlakou, DDS, MD, PhD,e Konstantinos Alexandridis, DDS, PhD,f Athens, Greece EVANGELISMOS GENERAL HOSPITAL AND UNIVERSITY OF ATHENS
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:12-16)

CASE PRESENTATION A 69-year-old man was referred to the department of Oral and Maxillofacial Surgery by an ear, nose, and throat surgeon for diagnosis and management of a painless lump on the oor of the mouth, which extended to the submandibular region. The intraoral lesion had been noticed 3 months before consultation. According to the patient, the growth had recently enlarged, interfering with his mastication, but caused no difculty in swallowing or speech. No changes of size or development of intraoral swelling during meal times were reported. The patient was in apparent good health and his medical history was noncontributory. Clinical examination showed a 3 2 cm swelling of the left submandibular area (Fig. 1). It was covered by skin that was normal in both texture and color. Intraorally, elevation of the oor of the mouth was noted,
Hospital Specialist, Oral and Maxillofacial Surgeon, Oral and Maxillofacial Department, Evangelismos General Hospital. b Lecturer, Department of Oral Pathology and Surgery, Dental School, University of Athens; Oral and Maxillofacial Surgeon, Oral and Maxillofacial Department, Evangelismos General Hospital. c Assistant Professor, Department of Oral Pathology and Surgery, Dental School, University of Athens. d Hospital Specialist, Oral and Maxillofacial Surgeon, Department of Oral and Maxillofacial Surgery, Evangelismos General Hospital. e Senior Hospital Specialist, Pathologist, Department of Pathology, Evangelismos General Hospital. f Professor, Department of Oral Pathology and Surgery, Dental School, University of Athens; Oral and Maxillofacial Department, Evangelismos General Hospital. Received for publication Feb 4, 2009; returned for revision Sep 12, 2009; accepted for publication Sep 14, 2009. 1079-2104/$ - see front matter 2010 Published by Mosby, Inc. doi:10.1016/j.tripleo.2009.09.024
a

which was covered by normal mucosa (Fig. 2). On palpation, the nontender mass was soft to rubbery in consistency. Although tongue movement was marginally restricted by the physical presence of the swelling, the mass per se was freely movable anteroposteriorly and medially in relation to the tongue and the bone of the mandible. The patient was totally edentulous and wearing complete acrylic dentures. Normal saliva could be expressed from the left submandibular salivary gland and there was no sign of hypoesthesia or paresthesia of the area corresponding to the ipsilateral lingual nerve. A computerized tomography scan (CT) with enhancement, which had been carried out before consultation, conrmed the existence of a well demarcated dense lesion lying between the mylohyoid and genioglossus muscles (Fig. 3). The lesion was solid, without relation to the mandibular bone. Intravenous contrast medium enhanced the image of the lesion. The remainder of the head and neck scan did not reveal any other pathology or lymph node enlargement. Although it was thought that magnetic resonance imaging could give more precise and accurate information for the diagnosis and management of the lesion, the patient refused any further imaging studies. DIFFERENTIAL DIAGNOSIS The oor of the mouth and submandibular area may be affected by numerous pathologic conditions, which can be broadly classied as developmental, inammatory-obstructive, or neoplastic in origin. Lesions in this area may be present for a prolonged period of time before the patient seeks medical advice, usually as a result of interference with swallowing or speech. The oor of the mouth is the most common intraoral location for developmental lesions of the oral soft tis-

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Fig. 1. Extraoral examination revealed a left submandibular swelling with a diameter of 3 cm. The soft to rubbery swelling was nontender and not rmly attached to overlying skin, the lower jaw, or the tongue.

Fig. 3. Transversal computerized tomography scan with contrast enhancement depicting a well delineated dense lesion of the submandibular triangle.

Fig. 2. Intraoral photograph showing ipsilateral elevation of the oor of the mouth. The swelling was covered by normal mucosa and was freely movable anteroposteriorly and medially.

sues, particularly dermoid cysts, branchial cleft cysts, heterotopic gastrointestinal cysts, and thyroglossal duct cysts.1-3 Dermoid cysts are considered to be a variation of teratomas and are thought to arise from entrapment of epithelial remnants during closure of the branchial arches or as a result of trauma.4,5 Almost one-fth of the dermoid cysts that occur in the head and neck area are located on the oor of the mouth,1,4 where they may cause tongue elevation, submental protrusion, or both.4,5 They are predominantly seen in young persons, presenting as soft to rubbery swellings in the midline or laterally.1 Branchial cleft cysts are developmental anomalies which arise from incomplete closure of branchial arches.1,2,4 They usually appear in relatively young patients as uctuant swellings located anteriorly

to the sternocleidomastoid muscle.1,6,7 Heterotopic gastrointestinal cysts are choristomas of head and neck and mostly affect the sublingual area or the oor of the mouth. They appear to have a male preponderance and are usually lined with gastric mucosa.3 Thyroglossal duct cysts arise from remnants of the embryonic thyroid.1,2,4 They typically present in the midline in close contact to the hyoid bone, often producing a characteristic movement during swallowing,3 which was not seen in the present patient. In most cases, a uctuant or soft swelling is evident in the neck region, although some lesions may appear intraorally1,2 and cause dysphagia.4 Half of the patients are younger than 20 years at the time of diagnosis.1 Developmental lesions present a relatively silent course before causing any symptoms, as with the present patient. However, this patients age made the probability of such an entity less likely. Additionally, the CT ndings were suggestive of a solid rather than a cystic lesion. Congenital lesions, such as vascular malformation or lymphangioma (cystic hygroma), are generally included in the differential diagnosis of neck masses extending to the oor of the mouth. Both lesions are most commonly seen in childhood, with 90% of lymphangiomas of the head and neck diagnosed by the age of 2 years.5 They demonstrate a variety of clinical

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features, ranging from small varicosities to large bluish or red masses that may reach large dimensions and cause disgurement.1,2 Nevertheless, such lesions are not likely to initially present in an older patient and were not compatible with the CT images of our case. Infections and inammatory lesions of perioral tissues may also present as a swelling of the submandibular area extending to the oor of the mouth.1,2 Acute infections, such as Ludwig angina, cellulitis, submandibular, or sublingual space infections, which may derive from an odontogenic focus of infection, osteomyelitis, or trauma, were not considered in the differential diagnosis, because of the chronic nature of the condition. In addition, fever, malaise, and pain would normally accompany the clinical presentation of an acute infection, and tenderness to palpation and xed or uctuant overlying skin would be apparent in the clinical examination. Another entity which should be considered is lymphadenitis of different causes. Submandibular lymph nodes may commonly be affected by cat-scratch disease, tuberculosis (scrofula), or actinomycosis.1,8 The present patients noncontributory past medical history, the CT ndings, and the absence of any skin sinuses, precluded these entities from our clinical differential diagnosis. Additionally, lymphadenitis typically does not produce this degree of intraoral swelling. Salivary gland lesions are commonly seen intraorally and in the submandibular triangle.2 The ranula is located exclusively on the oor of the mouth. It is considered to be a mucus retention cyst of the sublingual gland4,5 or a mucous extravasation phenomenon of either the major salivary glands or the minor sublingual salivary glands.1 It appears as an enlargement of normal to bluish color, varying from a uctuant process to a lesion of soft consistency, depending on the thickness of the overlying tissues. Children and young adults are more frequently affected, and a history of repetitive rupture and recurrence is a common nding. Plunging ranula is a variation of the ranula, produced by dissection of extravasated mucin through the mylohyoid muscle.1,5 It appears as a lump in the submandibular neck area, with or without intraoral signs.1,5 Although ranulas appear well dened and unilocular on CT imaging,9 they are characteristically hypodense. Inammatory disorders of the salivary glands merited consideration in the differential diagnosis of the present lesion. Acute sialadenitis of the submandibular gland usually presents with swelling associated with meals and pain and purulent discharge from the Wharton duct,1,2,4 and chronic sialadenitis runs a prolonged course of remissions and exacerbations. Both conditions are more frequent in the sixth decade of life and present no gender predilection.4 Moreover, both conditions usually involve a number of predisposing factors,

such as sialolithiasis, chronic illness, hospitalization, or medications, all of which may be associated with xerostomia. Especially regarding drug-induced xerostomia, it is worth mentioning that the geriatric population is more susceptible, because the risk increases with the number of drugs taken.1,2,10 Although in most cases of sialadenitis the infection is bacterial, viral causes, i.e., cytomegalovirus or paramyxovirus, are also not uncommon. The present patient presented no such risk factors and reported no previous episodes of swelling in the area. The size and asymptomatic nature of the swelling would argue against an inammatory salivary gland origin. However, a Kuttner tumor, a subset of chronic sclerosing sialadenitis, can achieve considerable size and was included in the clinical differential diagnosis.11 Sialosis is often related to disorders such as diabetes, acromegaly, hypothyroidism, alcoholism, or general undernourishment.1 Medications affecting the autonomous nervous system, such as antihypertensive or psychotropic drugs, are also associated with sialosis.1 Benign lymphoepithelial lesions commonly occur as part of Sjgren syndrome.1 Although the lesion affects mostly the parotid glands, involvement of the submandibular glands may be seen. Pleomorphic adenoma and monomorphic adenoma are usually included in the differential diagnosis of painless and slowly growing intraoral masses. However, salivary gland neoplasms of the oor of the mouth are more often malignant than benign.4 The present patients age conforms to the higher incidence of salivary gland neoplasms.1,4,12 However, the posterior hard palate/soft palate is the site of predilection for minor salivary gland tumors.2,4 The most common malignant neoplasms of salivary glands are the mucoepidermoid carcinoma and the adenoid cystic carcinoma.1 Acinic cell carcinoma is also seen, especially in older patients.2 Nevertheless, in the case of a malignant neoplasm, the growth is often xed to adjacent structures. Adenoid cystic carcinoma also frequently invades neighboring nerves, resulting in hypoesthesia of the lingual nerve. Another possible cause of a cervical swelling is lymphoma, both Hodgkin and non-Hodgkin.13,14 Although more common in children and young adults, lymphoma may present in older patients as well.13,15 The 3-month course of asymptomatic growth, the lack of neurologic signs or evidence of attachment to surrounding structures, and the soft consistency directed the differential diagnosis toward a benign tumor. Furthermore, the normal appearance of the overlying mucosa is suggestive of a benign tumor of mesenchymal origin, such as lipoma, neurilemmoma, or leiomyoma, or of salivary gland origin.1,2 Lipoma is quite rare in the oral cavity. The buccal mucosa is the site of predilection, with 50% of the cases, but the oor of the

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Fig. 4. Histologic examination revealed a lesion consisting of large polygonal cells with eosinophilic to clear cytoplasm (hematoxylin and eosin stain, original magnication 200).

Fig. 5. Higher power histologic examination shows crossstriations (arrow) in lesional cells (hematoxylin and eosin stain, original magnication 400).

mouth may also be involved. It typically presents as a slowly enlarging mass covered by normal appearing mucosa of yellowish hue. Middle-aged persons are more prone to develop lipomas, and no gender predilection has been reported.1,2 The CT imaging of a lipoma is that of a hypodense nonenhancing lesion, in contrast to the present case. Malignant soft tissue tumors were considered to be a remote possibility. Rapid growth, lack of circumscription, xation to adjacent structures, and ulceration of the overlying mucosa1,12 are common features of malignancy that were not noted in the present patient. MANAGEMENT AND DIAGNOSIS With the provisional diagnosis of a benign soft tissue tumor, an incisional biopsy under local anesthesia was planned. During the initial incision and identication of Wharton duct, it became apparent that the growth was encapsulated and clearly separated from nearby structures, allowing for the excision of the lesion in toto. The surgical specimen, consisting of a brown encapsulated lobulated tumor measuring 3.0 1.5 cm, was xed in 10% buffered formalin and processed for routine histopathologic examination. Hematoxylin and eosinstained sections showed a benign lesion encapsulated by brous connective tissue. The lesion consisted of large polygonal cells with eosinophilic to clear cytoplasm (Fig. 4), several presenting with discrete crossstriations (Fig. 5). No nuclear or cellular pleomorphism or mitoses were seen. The cells stained red with Masson trichrome, and were immunohistochemically reactive for desmin and myoglobin. The nal diagnosis was adult rhabdomyoma. The patients postsurgical recovery was uneventful, without salivary gland obstruction or lingual hypoes-

thesia. Further management included endoscopy of the larynx and pharynx to exclude multifocal type of rhabdomyoma.16 The patients stomach, prostate, and heart were investigated with ultrasonography. Moreover, the patient had no features associated with tuberous sclerosis, such as childhood seizures, hypomelanotic macules, facial angiobromas, or bone cysts.17 At the time of writing, the patient had been under regular follow-up for 2 years and remained free of recurrence or new lesion. DISCUSSION Rhabdomyomas are rare benign tumors originating from striated muscle18,19 and classied as cardiac and extracardiac.18 Cardiac rhabdomyomas affect the myocardial bers and produce a diffuse distortion of the heart muscle. They are generally considered hamartomas rather than true neoplastic lesions and are usually associated with tuberous sclerosis.17,18 The number of extracardiac rhabdomyomas reported in the literature exceeds 160 cases, since the rst report in 1897.16,19,20 Extracardiac rhabdomyomas are of 3 types: adult, fetal, and genital. The majority of extracardiac rhabdomyomas are of the adult type and occur in the head and neck.5,16,19 The fetal type, also occurring more commonly in the head and neck region, is considered to be a developmental abnormality.19,21 The adult type usually presents at a mean age of 50 years with a male preponderance of 4:1.16,20 The genital type, in contrast, is a solitary lesion that occurs more commonly in women.20,22 On microscopic examination, the fetal rhabdomyoma is composed of slightly differentiated polygonal cells admixed with spindle-shaped cells.23 This type is typ-

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12. Munir N, Bradley PJ. Diagnosis and management of neoplastic lesions of the submandibular triangle. Oral Oncol 2008;44: 251-60. 13. Rockacy J, Viozzi CF, Zent CS. Mantle cell lymphoma presenting as a slowly enlarging lesion of the oor of the mouth in a healthy 72-year-old female: report of a case. J Oral Maxillofacial Surg 2007;65:333-7. 14. Vaughan ED. Primary tumors of the neck. In: Booth PW, Schendel SA, Hausamen, JE, editors. Maxillofacial surgery. 2nd ed. Edinburgh: Churchill Livingstone; 2007. p. 461-74. 15. Epstein JB, Epstein JD, Le ND, Gorsky M. Characteristics of oral and paraoral malignant lymphoma: a population-based review of 361 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:519-25. 16. Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK, Hyams VJ. Adult rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study. Hum Pathol 1993; 24:608-17. 17. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet 2008;372:657-68. 18. Cleveland DB, Chen S, Allen CM, Ahing SI, Svirsky JA. Adult rhabdomyomaa light microscopic, ultrastructural, virologic, and immunologic analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1994;77:147-53. 19. Liess BD, Zitsch RP, III Lane R, Bickel JT. Multifocal adult rhabdomyoma: a case report and literature review. Am J Otol 2005;26:214-7. 20. Veziroglu F, Uckan S, Senguven B. Adult type rhabdomyoma in a child. Oral Oncol Extra 2006;42:213-6. 21. Reid CO, Smith CJ. Rhabdomyoma of the oor of the mouth: a new case and review of recently reported intra-oral rhabdomyomas. Br J Oral Maxillofac Surg 1985;23:284-91. 22. Davies B, Noha P, Smaldone MC, Ranganathan S, Docimoa SG. Paratesticular rhabdomyoma in a young adult: case study and review of the literature. J Pediatr Surg 2007;42:E5-E7. 23. Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Human Pathol 1993;24: 754-65. 24. Favia G, Lo Muzio L, Serpico R, Maiorano E. Rhabdomyoma of the head and neck: clinicopathologic features of two cases. Head Neck 2003;23:700-4. 25. Garcia-Ruiz JA, Sanchez-Aniceto G, De La Mata-Pages R, Gonzalez-Rex JA, Ballestin Carcavilla C. Submandibular rhabdomyoma: a case report. Br J Oral Maxillofac Surg 1991; 29:123-6. 26. Koutsimpelas D, Weber A, Lippert BM, Mann WJ. Multifocal adult rhabdomyoma of the head and neck: a case report and literature review. Auris Nasus Larynx 2008;35:313-7. 27. Neville BW, McConnel FM. Multifocal adult rhabdomyoma: report of a case and review of the literature. Arch Otolaryngol 1981;107:175-8. 28. Valdez TA, Desai U, Volk MS. Recurrent fetal rhabdomyoma of the head and neck. Int J Pediatr Otorhinolaryngol 2006;70: 1115-8. Reprint requests: Eleni Parara 16, Koimiseos Theotokou st 151 24 Athens Greece [email protected]

ically more cellular than the adult type and often has a myxoid stroma. Lesions with pleomorphic characteristics and increased mitotic activity can rarely be mistaken for rhabdomyosarcomas.23 The adult type presents a simpler structure compared with the fetal subtype, with large ovoid or polygonal cells with granular eosinophilic cytoplasm. Some cells present a vacuolated cytoplasm due to the accumulation of glycogen.16,23,24 There are usually a large number of blood vessels, scant stroma, and a well dened capsule.18 Routine hematoxylin and eosin histologic features are usually sufciently characteristic. Immunohistochemical markers of skeletal muscle differentiation, such as desmin, myoglobin, and muscle-specic actin, may occasionally be of value in conrming the diagnosis.16,25 The treatment of choice for rhabdomyoma is surgical excision. Multifocal presentation26,27 and local recurrence16,28 are possible, mandating long-term follow-up, especially for lobulated tumors or tumors showing invasive growths.16,20 Recurrence is usually associated with inadequate resection and not locally aggressive biologic behavior.16,24,28
The authors express their gratitude to Dr. D. Rontogianni, Head of the Pathology Department of Evangelismos General Hospital, Athens, Greece, for permission to take pictures of the tissue specimen. REFERENCES
1. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. 2nd edition. Philadelphia: Saunders; 2002. 2. Regezi JA, Sciubba J. Oral pathology, clinical-pathologic correlations. 2nd edition. Philadelphia: Saunders; 1993. 3. Smith JE, Wren MK, Richardson MS, White DR. Colonic duplication in the submandibular region of the neck. Int J Pediat Otorhinolaryngol Extra 2009;4:17-20. 4. Lian TS. Benign tumors and tumor-like lesions of the oral cavity. In: Flint P, Haughey B, Robbins KT, Thomas JR, editors Cummings otolaryngology: head and neck surgery. 4th ed. Philadelphia: Mosby; 2005. p. 1574-7. 5. Beil CM, Keberle M. Oral and oropharyngeal tumors. Eur J Radiol 2008;66:448-59. 6. Glosser JW, Pires CA, Feinberg SE. Branchial cleft or cervical lymphoepithelial cysts. Etiology and management. J Am Dent Assoc 2003;134:81-6. 7. Tosios K, Rallis G, Vallianatou D, Vlachodimitropoulos D. Yellow-white tumor on the oor of the mouth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:701-4. 8. Philbert RF, Kim AK, Chung DP. Cervical tuberculosis (scrofula): a case report. J Oral Maxillofac Surg 2004;62:94-7. 9. Mosier KM. Nononcologic imaging of the oral cavity and jaws. Otolaryngol Clin North Am 2008;41:103-37. 10. Scully C. Drug effects on salivary glands: dry mouth. Oral Dis 2003;9:165-76. 11. Huang C, Damrose E, Bhuta S, Abemayor E. Kuttner tumor (chronic sclerosing sialadenitis). Am J Otolaryngol 2002;23: 394-7.