Case of the Month Archives

COM March 2006 Diagnosis

Slightly exophytic yellowish lesion lateral tongue

Can you make the correct diagnosis?

Figure 1

This is a 63-year-old white female who presented with a slightly exophytic, orange-yellow and well demarcated lesion on the right posterior and lateral border of tongue (Fig 1). It was about 1 x 1 cm in size, of one year’s duration and asymptomatic. The surface of this lesion was slightly corrugated to verrucoid in configuration. The patient has a history of lichen planus on the bilateral buccal mucosa (Fig 3), mandibular (Fig 2) and maxillary vestibule, alveolar ridge and lateral tongue (Fig 1). The patient has no history of alcohol or tobacco use. The lesion is asymptomatic but the patient complains of chronic and generalized oral burning sensation interpreted to be due to her chronic lichen planus.

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The lateral border of the tongue is a high-risk location for squamous cell carcinoma. Therefore a lesion on the lateral tongue, even one which is orange-yellow in color as in this case, should be biopsied to rule out SCC. 

Oral squamous cell carcinoma (OSCC) is annually diagnosed in over 30,000 people in the United States and over 570,000 worldwide (1). The five-year survival rate lies between 35% and 50% (2). High mortality persists, and over 8,000 people die of oral cancer each year in the United States alone (2).

Oral SCC occurs predominantly in males over the age of 40 years, with an observed male-to-female occurrence ratio of 2:1 worldwide and 1.4:1 in the USA (1). Excluding the outer lip, the most common sites (in decreasing order) are: ventral and lateral surfaces of tongue (25-50% of cases), floor of mouth (15%), gingiva (12%) and palate (9%). The buccal mucosa and retromolar pad areas (3%) have a relatively low incidence of occurrence (2) unless the patient is a chronic smokeless tobacco user. Oral SCC varies in presentation from deceptively innocent-looking to obviously malig­nant. It may present as a non-healing ulcer, or as red, white or mixed red-and-white lesions. Characteristic signs of oral SCC are a non-healing ulcer, an ulcer with rolled borders, fungation, fixation and induration. Rarely, OSCC may present as an unexplained, asymptomatic lateral neck lymphadenopathy (1, 2). The location, age, risk factors and clinical presentation of this case are typical of OSCC. 

Tongue SCC is the most common type; it is usually found on the lateral and ventral surfaces. Squamous cell carcinoma of the posterior tongue is more aggressive than that of the anterior. 78% of base of tongue carcinomas show early metastasis, especially to regional lymph nodes. 69% of tongue carci­nomas show evidence of metastasis at admission. Oral SCC is most commonly associated with chemically induced mutagenesis, specifically tobacco and alcohol use (3). Human papilloma virus (HPV) has also been found to have a high prevalence in oral cancer, especially in younger patients with no history of tobacco use (4). Prognosis of OSCC is based on the clinical stage and histological classification. Although OSCC is a diagnosis made by histology, surgeons tend to depend exclusively on the TNM classification system for clinical staging and treatment decisions. Histological grading ranges from well to moderately to poorly differentiated. The most important prognostic sign is the presence or absence of metastases at the time of diagnosis.

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Lipoma is a benign neoplasm of mature adipose tissue origin. It is not common in the oral cavity. It is, however, considered to be the most common soft tissue neoplasm on the trunk and extremities. In the latter areas, lipomas are more common in females. In the mouth, lipomas are either of equal gender distribution or are more common in males, with a male-to-female occurrence ratio of nearly 3:1. They tend to occur in adult patients, usually over 40 years of age, with an age range of 9-92 (5). In the mouth, lipomas occur more commonly in the vestibule and buccal mucosa, followed by the lips (especially the lower lip), tongue, palate and floor of mouth. 

Sizes range from a few millimeters to several centimeters in diameter, with an average size of 2cm. Lipomas usually present as single, smooth surfaced, soft, lobulated, painless, yellowish, and sessile nodules. They are usually covered by a thin surface epithelium with visible blood vessels. They are soft and doughy in consistency and can be mistaken for cysts (5-6).

Histologically, lipomas are composed of mature adipose tissue arranged in lobules and surrounded by a thin capsule. The adipocytes show no evidence of atypia and are usually arranged in sheets interspersed with small blood vessels. Several types of benign lipomas are described; some occur in the mouth, especially spindle cell lipoma and fibrolipoma. Less common in the mouth are chondroid lipoma, myxoid lipoma and angiolipoma. Treatment includes conservative surgical removal. Recurrence is rare except in occasional types such as intramuscular lipomas (5-6). The latter may occur in the tongue, but rarely.

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Verruciform xanthoma is a benign condition of unknown etiology and pathogenesis but is favored to be an inflammatory process rather than a neoplasm (7). Viral etiology has been suggested, especially in association with human papilloma virus (8). It has been described in connection with oral lichen planus, which is the case with this patient. It has also been described in association with recessive dystrophic epidermolysis bullosa, graft vs. host disease, congenital hemidysplasia with ichthyosiform erythroderma and limb defect (CHILD) syndrome, and epidermal nevus (9-10). 

VX was first described in the oral cavity by Shafer et al in 1971 (7), and has since been reported in many other areas including the anogenital area and skin (7-10). VX usually presents as a solitary lesion but can also present in multiples. It ranges in diameter from a few millimeters to two centimeters (cm) with an average size of 1cm. However, larger VXs of several cms in size have been described.

VX is most commonly described in patients in the fifth and sixth decade of life with a 2:1 predilection for occurrence in females (7-9). VX of the scrotal area is described mostly in older Japanese males with a wide age range. It is rare in children in general. It is usually asymptomatic and does not have a specific clinical presentation. However, when presenting as yellowish or orange-like in color, it can be clinically diagnostic. This was the case in this patient; the orange-yellow color with a warty surface is clinically diagnostic of VX. It can occur anywhere in the mouth, but the gingiva and the alveolar ridge constitute 50% of all cases, followed by the palate. The tongue is a rare location for VX (7-8). 

The histology in this case is characteristic of VX in that the epithelium is usually papillary with evenly aligned rete pegs. The papillary projections are short and extend slightly above the surface. The projections have deep clefts filled with keratin. The projections are supported by connective tissue papillae which are densely packed with large cells with foamy cytoplasm referred to as xanthoma cells. The latter are usually in the connective tissue papillae, but can extend into the surface epithelium and into the connective tissue below the superficial papillae. The xanthoma cells are believed to be of monocyte-macrophage lineage (8-10). Inflammatory cells and microabscesses can be present within the epithelium as well as the connective tissue. 


A small 4 mm punch biopsy was performed under local anesthesia. Since the diagnosis was rendered as benign with no potential for transformation, the patient elected not to remove the remaining lesion (Fig 4).


  1. Examinations for oral cancer – United States. MMWR. Morb.MortalWkly Rep. 43:198 (1992). 
  2. Bundgaard T, S Bentzen, et al. Histopathologic, stereologic, Epidemiologic, and clinical parameters in the prognostic evaluation of squamous cell carcinoma of the oral cavity. Head & Neck. 18:142-152 (1996).
  3. Barasch A, DE Morse, et al. Smoking, gender, and age as risk factors for site-specific intraoral squamous cell carcinoma. Cancer 73:509-513 (1994).
  4. Syrjanen SM, KJ Syrjanen et al. Human papillomavirus (HPV) DNA sequences in oral precancerous lesions and squamous cell carcinoma demonstrated by in situ hybridization. J Oral Pathol. 17:273 (1988).
  5. Furlong MA, Fanburg-Smith JC, Childers EL. Lipoma of the oral and maxillofacial region: Site and subclassification of 125 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Oct;98(4):441-50
  6. Shafer WG. Verruciform xanthoma. Oral Surg Oral Med Oral Pathol. 1971;31:784-789.
  7. Khaskhely NM, Uezato H, Kamiyama T, et al. Association of human papilloma virus type 6 with a verruciform xanthoma. Am J Dermatopathol. 2000;22:447-452.
  8. Philipsen HP, Reichart PA, Takata T, Ogawa I. Verruciform xanthoma–biological profile of 282 oral lesions based on a literature survey with nine new cases from Japan. Oral Oncol. 2003 Jun;39(4):325-36.
  9. Polonowita AD, Firth NA, Rich AM. Verruciform xanthoma and concomitant lichen planus of the oral mucosa. A report of three cases. Int J Oral Maxillofac Surg. 1999 Feb;28(1):62-6.
  10. Xue JL, Fan MW, Wang SZ, Chen XM, Li Y. A clinicopathological study of 14 cases of oral granular cell tumor
  11. Brannon RB, Anand PM. Oral granular cell tumors: an analysis of 10 new pediatric and adolescent cases and a review of the literature. J Clin Pediatr Dent. 2004;29(1):69-74.

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This is a benign neoplasm of uncertain histogenesis first described by Abrikossoff in 1926 (11-12). It has been called by a number of names, including myoblastoma, a name which implies muscle origin. This implication was based on the H & E histology in about 70% of cases in which the granular cells are closely associated with the skeletal muscle fibers. A small percentage of these tumors are also found in close association with nerve fibers, implying their origin from the neural crest. The immunohistochemistry markers support the origin of this tumor from the neural crest and not from muscle, hence the name change to granular cell tumor (11).

The tongue is the most common site of occurrence of this tumor; almost one third of cases occur in the tongue. Skin is another common site, but this lesion is known to occur in a variety of sites and tends to be benign in most cases. A malignant form is described, but is rare.

In the mouth, the buccal mucosa is second to the tongue in site predilection, and the lesion is more common in females than males (2:1 ratio). It tends to occur in adults over 30 years of age but it has also been described in children average age 14.5 with a range of 3-19 (12). In children it is 3:1 females and 50% occurrence in the tongue (12). It is usually asymptomatic and can be of a long-term duration ranging from months to years. The dorsal-lateral tongue is a common location and in about 80% of cases, it is superficial and submucosal. The color ranges from pink or white with a keratotic surface to yellow-orange. A newborn counterpart is described and is known as congenital epulis of the newborn; it is believed to be a separate entity with different cell origin (11-12). 

Histologically, granular cell tumor is composed of strands and fascicles of large cells with distinct cell borders containing abundant granular cytoplasm. The nuclei are small and round to oval and are eccentrically located. These cells are at times intimately related to surrounding skeletal muscle fibers and at times to nerve. The lesion can be well demarcated and confined or infiltrative. The overlying epithelium can be normal in thickness or can show psuedoepitheliomatous hyperplasia (PEH) (11-12). The latter, when extensive in rare cases, can be mistaken for well differentiated squamous cell carcinoma, especially if the biopsy is superficial. 

The tumor cells are positive with S-100 protein and neuron specific enolase (NSE) indicating a neural crest origin. Treatment includes conservative surgical excision. Recurrence is extremely rare.