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Pedunculated soft-tissue mass on the alveolar gingiva
J Oral
MaxillofncSurg
43:1311-1316.1990
Pedunculated Soft-Tissue Mass on the Alveolar Gingiva MARK L. MONSON, DDS,* JOHN POSTGATE, DDS,t ROBERT BOWE, DDS,$ AND THOMAS P. WILLIAMS, DDS§ Case Presentation
tion therapy. His past medical history includes syphilis treated 20 years earlier, a prostate nodule, and peptic ulcer disease. It is not stated if the syphilis had been adequately treated. There is no mention of the duration, character, or treatment provided for the prostate nodule or discussion regarding the duration and status of the patient’s peptic ulcer disease. It is interesting to note that the patient’s medications include indomethacin, 25 mg every 8 hours; codeine, 30 mg every 2 to 4 hours; and Tylenol no. 3 (which contains 1/2grain of codeine) every 4 to 6 hours. Indomethacin, an anti-inflammatory and analgesic agent, is used on occasion for the management of patients with inflammatory conditions, most often arthritidies. As there is no mention of arthritis in the patient’s history, it can be presumed that the patient is receiving indomethacin for relief of pain associated with his lung malignancy despite the fact that it is contraindicated in patients with peptic ulcers. In addition, the patient is receiving approximately 1 grain of codeine also presumably for relief of symptoms associated with his malignancy. The patient admits to a JO pack/yr history of cigarette smoking and moderate alcohol intake although the specific amount consumed is not stated. Clinical examination showed an asymptomatic, erythematous, pedunculated mass of the gingiva lingual to the mandibular left first premolar. Radiographs of that area were negative. The laboratory studies provided were significant for an elevated serum calcium of 12.6 mg/dL and for anemia with a hematocrit of 25.2%. The differential diagnosis for a soft-tissue mass of the gingiva should include developmental, reactive or inflammatory, and neoplastic entities. The location of the mass would exclude consideration of salivary gland lesions or masses arising from striated muscle, as these tissues are not present in this area. However, the clinician should consider masses of epithelial, mesenchymal, and odontogenic origin. It was stated that radiographs of the area are negative; therefore, the origin of the mass is most likely from soft tissue rather than extension from underlying
A 62-year-old black man was seen in the Veterans Administration Hospital Dental Service for construction of partial dentures. The patient was currently hospitalized for tests to determine the etiology of shoulder pain. The test results yielded a diagnosis of left upper lobe pulmonary squamous cell carcinoma. Chest radiographs showed a 10 x 7-cm mass that was deemed inoperable, so the patient was receiving palliative radiation therapy. His past medical history included a prostate nodule, syphilis that was treated 20 years earlier, and peptic ulcer disease. His laboratory examination was significant for a hematocrit of 25.2% and calcium of 12.6 mg/dL. Medications at that time included indomethacin 25 mg orally every 8 hours, codeine 30 mg orally every 2 to 4 hours, and Tylenol no. 3 (McNeil Pharmaceutical, Spring House, PA), one tablet orally every 4 to 6 hours. His social history showed a 40 pack/yr cigarette use and moderate alcohol intake. Routine oral examination showed an asymptomatic 1.O x 0.5 x 0.3-cm erythematous, pedunculated soft-tissue mass on the mandibular alveolar process lingual to the mandibular left first premolar (Fig 1). The patient was unaware of its presence. Radiographic findings were noncontributory. The lesion was excised at its base and submitted for microscopic examination.
Differential Diagnosis This 62-year-old black male has an established diagnosis of inoperable squamous cell carcinoma of the lung for which he is receiving palliative radia-
* Formerly, General Practice Resident, West Los Angeles Veterans Administration; currently, Chief Resident, Oral and Maxillofacial Surgery, Medical University of South Carolina. t Formerly, General Practice Resident, West Los Angeles Veterans Administration; currently, in private practice, Bakersfield, CA. $ Formerly, General Practice Resident, West Los Angeles Veterans Administration; currently, in private practice, Beverly Hills, CA. 8 In private practice, Dubuque, IA. Address correspondence and reprint requests to Dr Monson: VAMC (160), Oral and Maxillofacial Surgery, 16111 Plummer St, Sepulveda, CA 91343. 0 1990 American Association of Oral and Maxillofacial geons 0278-2391190/4812-0011$3.00/O
Sur-
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FIGURE 1. Asymptomatic, pedunculated soft-tissue mass located lingual to the mandibular left first premolar.
bone. As the radiographs were negative, it can be assumed that there is no carious or periodontal involvement of the teeth in this location. It may also be presumed that the mass has been present for a considerable period of time, for if it was of short duration, it is likely that the patient would have been aware of it. However, it should be stated that in view of the relative lack of oral hygiene noted from the clinical photograph, it appears that the patient is not oral-health conscious. The clinician should also consider whether the erythematous appearance of the mass is from inflammatory involvement of surface epithelium or characteristic of the underlying connective tissue. Close examination of the mass from the clinical photograph suggests that the surface is not entirely smooth, but, rather, has a cobblestone appearance in areas. With these thoughts in mind, consideration of various entities should begin with developmental processes that occur on the gingiva. The gingival cyst may present as an exophytic mass; however, the surface epithelium is usually blanched or normal in color and those cysts are not pedunculated. Although not excludable, the gingival cyst is unlikely. The calcifying odontogenic cyst, although classified as a cyst of odontogenic epithelium, is thought by some investigators to be an odontogenic neoplasm. Although they most often occur as an intraosseous lesion of the jaws, 25% to 35% occur on the gingiva as an exophytic mass without osseous involvement. Therefore, although not usually pedunculated, the calcifying odontogenic cyst cannot be excluded from the differential diagnosis. Lesions of vascular origin, such as the hemangioma and vascular malformation, should also be considered. It has not been stated if the mass was compressible or blanched with pressure, characteristics of both hemangiomas and vascular malformations. They may occur in any location within the oral cav-
PEDUNCULATED
MASS ON ALVEOLAR
GINGIVA
ity and have an erythematous appearance. Although the hemangioma is congenital, it may not become apparent until childhood and then may persist. Persistence without involution is characteristic of the vascular malformation. Therefore, the hemangioma and vascular malformation should be included in the differential diagnosis. The lymphangioma, also thought to be congenital, occurs as an exophytic mass. Usually it is not well circumscribed, except for the variant referred to as lymphangioma circumscripta. Therefore, except for this variant, lymphangioma is unlikely. As the patient has not been aware of the mass and the radiographs are noncontributory, the clinician may make the assumption that reactive or inflammatory diseases as a result of pulpal necrosis can be excluded. Reactive lesions of nonodontogenic origin that may be considered include the condyloma acuminatum. The condyloma acuminatum may occur on the gingiva as a soft, pedunculated exophytic mass. Although they initially occur as a group of nodules, they may coalesce to form a single mass. Thought to be a result of infection by human papillomavirus subtype 6 and 11, it may have either a cobblestone or cauliflower appearance as a result of epithelial proliferation. Therefore, it cannot be excluded from the differential diagnosis. The pyogenic granuloma should also be considered in the differential diagnosis. Poor oral hygiene has been implicated as an etiologic factor for this reactive lesion. Because this patient’s lesion has an exophytic, erythematous, pedunculated appearance, the pyogenic granuloma should be considered. The peripheral giant cell granuloma is also a painless, exophytic, hemorrhagic, pedunculated mass that occurs on the gingiva and should be included in the differential diagnosis. The fibroma, most often thought to be reactive and not neoplastic, may involve the gingiva. Although smooth-surfaced and not usually hemorrhagic, it cannot be excluded from the differential diagnosis, but is unlikely. Condyloma latum, a manifestation of secondary syphilis, can be excluded from the differential based on the length of time elapsed since the patient’s infection. The mass does not have characteristics of a gumma and therefore tertiary syphilis also would be unlikely. Malignant and benign neoplastic processes may involve the gingiva and should be included in the differential diagnosis. With the presumption that the mass has been present for a long time, benign neoplasms should be strongly considered. However, the history of advanced squamous cell carcinoma of the lung and a prostate nodule mandates that metastatic lesions not be ignored as a possibility. Metastasis to the soft tissues of the oral cavity
MONSON
ET AL
is rare. If a metastasis to gingiva had occurred, the clinician should expect to see tissue breakdown and ulceration associated with rapid growth. Therefore, although unlikely due to the location and lack of ulceration, metastatic lesions from lung or prostate cannot be excluded. A plasmacytoma also may involve the gingiva as an exophytic, hemorrhagic mass and, therefore, it too cannot be excluded. The clinician should also consider benign neoplasms that occur on the gingiva. Benign neoplasms arising from surface epithelium normally have a cauliflower or papillary appearance. Because this mass does not have such an appearance, benign neoplasms of epithelial origin can be excluded. However, benign neoplasms of mesenchymal origin should be considered. The granular cell tumor most often occurs on the tongue, but may involve gingiva. Thought to be of neural origin, supported by the demonstration of S-100 protein within the granules, it presents as an asymptomatic exophytic mass. The schwannoma derived from proliferation of Schwann cells may also involve the gingiva, presenting as a solitary exophytic mass. The neurofibroma also may occur as a solitary exophytic mass in the gingiva. Although entities of neural origin cannot be specifically excluded from the differential diagnosis, they present as submucosal masses that are not pedunculated or erythematous and, therefore, are unlikely considerations. The myxoma, although rare within the oral cavity, may involve gingiva and has been reported to occur at any age. It is also an unlikely consideration because myxomas usually are not erythematous, pedunculated, or cobblestoned. The leiomyoma may occur at any age and involve gingiva, but is quite rare. It presents as a submucosal mass that is not erythematous. However, a variant, the vascular leiomyoma, has a prominent vascular component with an erythematous, exophytic appearance and should be considered in the differential diagnosis. Benign neoplasms of odontogenic origin should be included in the differential diagnosis. For the sake of discussion, the peripheral odontogenic fibroma and peripheral ossifying fibroma will be considered together. Thought to originate from the periodontal ligament, both entities occur on the gingiva, usually adjacent to teeth. The peripheral odontogenic fibroma in distinction to the peripheral ossifying fibroma is rare; however, both may have an exophytic hemorrhagic appearance. They may be firm or soft to palpation dependent on the degree of calcification within the mass. Although this patient’s mass does not involve the free gingival margin, the peripheral odontogenic fibroma and peripheral ossifying fibroma cannot be specifically excluded from the differential diagnosis.
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The peripheral ameloblastoma, a soft-tissue variant of ameloblastoma, occurs in an older age range than the intraosseous ameloblastoma. It occurs on the gingiva as an exophytic mass. Thought to arise from surface epithelium or remnants of dental lamina, it may have a cobblestone appearance and, therefore, should be included within the differential diagnosis. The calcifying epithelial odontogenic tumor and adenomatoid odontogenic tumor have been reported to occur as solitary soft-tissue masses without osseous involvement. Both entities involve gingiva and, although rare, cannot be specifically excluded from consideration. Development of a differential diagnosis would not be complete without discussion of the other significant findings of the history, and physical and laboratory examinations. The patient had an elevated serum calcium of 12.6 mg/dL and, therefore, a differential diagnosis of hypercalcemia should be considered. Hypercalcemia may occur from excessive secretion of serum parathormone, as in primary hyperparathyroidism, or from disease states not associated with elevated serum parathormone. Aside from hyperparathyroidism, other causes of hypercalcemia are malignancy, both hematologic and nonhematologic; granulomatous diseases such as sarcoidosis; endocrine disorders such as thyrotoxicosis or acute adrenal insufftciency; familial hypocalcuric hypercalcemia; excessive ingestion of calcium, vitamin A, or vitamin D; extensive skeletal immobilization; and idiopathic hypercalcemia of infancy. The presence of hypercalcemia is established when at least three measures of serum calcium are elevated. The clinician should determine the cause for hypercalcemia based upon the history, physical examination, and adjunctive laboratory studies. A long-standing illness with a history of nephrolithiasis, but no weight loss, suggests primary hyperparathyroidism. A disease of short duration with weight loss, but without nephrolithiasis, suggests a cause other than hyperparathyroidism for the hypercalcemia. Patients with malignant disease may have hypercalcemia of short duration without a history of nephrolithiasis. The history provided for this patient does not suggest endocrine abnormalities, excessive ingestion of calcium or vitamin A or D, or familial disease. The patient does have a history of peptic ulcer, which is often associated with primary hyperparathyroidism. However, in view of the patient’s diagnosis of squamous cell carcinoma of the lung, hypercalcemia of malignancy should be strongly considered. It is thought that hypercalcemia associated with malignancy occurs, not as a result of widespread metastatic disease with skeletal involvement, but from production of osteolytic humoral factors that include parathormonelike sub-
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stances, prostaglandins, and lymphokines such as osteoclast activating factor. Hypercalcemia is common in patients with lung cancer. It has been reported to occur in 12% of all cases, but in 23% of cases of squamous cell carcinoma of the lung. Hypercalcemia from nonhematologic malignancies is caused by secretion of humoral factors that stimulate osteoclast activity. In contrast, hematologic malignancies such as multiple myeloma produce hypercalcemia as a result of extensive bone destruction. Although it is likely that this patient’s hypercalcemic state is a result of lung cancer, primary hyperparathyroidism and multiple myeloma cannot be excluded. Therefore, in addition to the history and physical examination, a radioimmunoassay for parathyroid hormone and serum electrophoresis should be performed to rule out these two conditions. Therapy should be directed towards reduction of the serum calcium as the hypercalcemia could be life-threatening. Treatment includes parenteral hydration, forced diuresis, reduction of dietary calcium, and careful monitoring of serum calcium and electrolytes. The patient also presents with anemia, having a hematocrit of 25.2%. There are several factors to be considered in the workup of this patient’s anemia. He is taking indomethacin, a nonsteroidal antiinflammatory drug contraindicated in patients with peptic ulcers. Patients receiving indomethacin have been reported to have perforation of ulcers of the gastrointestinal tract with occult blood loss progressing to the development of anemia. Red cell indices and testing of the stool for occult blood would provide valuable information. An additional cause of anemia in this patient might be alcoholic cirrhosis, folate or pyroxidine deficiency, hemolysis, and toxicity of ethanol upon the bone marrow. Although the amount of alcohol consumed by the patient was not stated, that determination, along with the laboratory evaluation, would assist in the diagnosis. Anemia is also a frequent finding in patients with lung cancer. Such patients may have an autoimmune hemolytic anemia or a microangiopathic hemolytic anemia manifested by fragmented erythrocytes. Disseminated intravascular coagulation may also occur in patients with lung malignancy; however, most often it is subclinical without overt bleeding. These entities should be considered as possible causes of this patient’s anemia. The case presentation stated that the past medical history included a prostate nodule; however, the duration, character, and treatment provided, if any, were not discussed. It is presumed that the patient was tested to rule out carcinoma of the prostate. Symptoms associated with prostatic cancer may be absent or can include hematuria, lymphadenopathy,
PEDUNCULATED MASS ON ALVEOLAR GINGIVA
and edema of the legs. Rectal examination should be performed to ascertain if an indurated nodule can be palpated within the substance of the gland. The diagnosis is then confirmed by microscopic examination of a specimen obtained by needle biopsy. The patient’s past medical history also included syphilis treated 20 years earlier. Although it may be presumed to have been adequately treated, the venereal disease research laboratories (VDRL) test should be performed as a screening examination. If there is a question regarding the presence of syphilis despite a negative VDRL, the patient can be treated with penicillin if no allergy exists. In summary, the differential diagnosis for this patient’s gingival mass should include developmental, reactive, and neoplastic processes. Strong consideration should be given to the following lesions: condyloma acuminatum, pyogenic granuloma, peripheral giant cell granuloma, metastasis presumably from lung or possibly from prostate, plasmacytoma, vascular leiomyoma, peripheral ameloblastoma, peripheral odontogenic fibroma, hemangioma or vascular malformation (particularly if the mass blanches upon compression). Although there are other entities not specifically excluded from the differential diagnosis, these lesions are thought to most likely represent the diagnosis. Ultimately, confirmation of the diagnosis will occur following excision and microscopic examination of the mass. In addition, the patient should be tested for hypercalcemia as detailed previously. Although primary hyperparathyroidism and muitiple myeloma cannot be ruled out, the hypercalcemia is probably secondary to epidermoid carcinoma of the lung. The patient should also be evaluated for anemia. It is most likely a result of gastrointestinal blood loss, alcoholic cirrhosis, or associated with a paraneoplastic syndrome. The administration of indomethacin should also be evaluated. Further information should be obtained regarding the prostate nodule, presence of syphilis, and peptic ulcer disease. SUBSEQUENT
COURSE
The specimen was fixed in formalin and stained by routine hematoxylin and eosin (Figs 2 to 4). Examination of the sections showed the mass to consist of a submucosal proliferation of cells contiguous with a hyperplastic overlying epithelium. The submucosal proliferation was composed of islands, sheets, and cords of epithelial cells. The outermost layer consisted of palisading columnar basaloid cells. These surrounded squamous cells with abundant pink cytoplasm and large ovoid pale staining nuclei. Occasional areas of spongiosis were noted; however, no stellate reticular areas were noted. Mitoses were not prominent. The intervening stroma consisted of loose fibrous connective tissue of moderate vascularity. The
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MONSON ET AL
FIGURE 2. Photomicrograph showing islands of tumor cells consisting of an outer layer of palisaded basaloid cells surrounding an inner core of mature squamous cells. The intervening fibrous stroma is dense (hematoxyhn-eosin stain, original magnification X 100).
overlying epithelium showed normal maturation with several areas of basal cell proliferation that blended into the submucosal neoplasm. The deep margin of the specimen contained tumor cells. Based on the histopathologic tindings, a diagnosis of peripheral ameloblastoma was made. After receipt of the pathology report, the patient was treated with a local supraperiosteal stripping of the biopsy site. There was no evidence of neoplasm noted in the histologic examination of the submitted specimen. The surgical site healed without complication. The patient subsequently died 4 months after admission of causes related to his pulmonary carcinoma. There was no evidence of recurrence of the peripheral ameloblastoma.
Discussion The peripheral ameloblastoma is a rare odontogenie tumor of the soft tissues covering the tooth-
FIGURE 4. Higher-power photomicrograph showing that despite a high degree of cellularity, the mitotic rate is low (hematoxylin-eosin stain, original magnification X400).
bearing surfaces of the jaws.lY2 Although it shares the histologic characteristics common to intraosseous ameloblastoma, this variant lacks its locally destructive and persistent qualities.3 It is interesting to note that the basal cell carcinoma of the gingiva is histologically identical to the peripheral ameloblastoma and considered by most to be the same lesion.3-6 The lesion appears as an epulis measuring up to 5 cm.7 The lingual gingiva of the mandible is the preferred site.3.8 Radiographic examination is usually normal. In a few instances, superficial “cupping or saucerization” of bone has been reported. This is generally felt to be due to resorption rather than invasion“3; however, Balfour has reported a case in which he believed invasion of underlying bone had occurred.’ The lesion has been reported in patients ranging in age from 23 to 92 years, with a mean of 51. Whites are affected most commonly, with males showing a slight predilection.3 There have been two sources postulated as the origin of the peripheral ameloblastoma: the dental lamina and the surface epithelium.
FIGURE 3. Photomicrograph of tumor islands showing prominent “reverse polarization” of the nuclei of the outermost basaloid cells (hematoxylin-eosin stain, original magnification x 150).
1,2*7,10-12
The treatment of this lesion, simple excision, is often confounded by the ominious connotation the term ameloblastoma implies in the mind of the surgeon. Treatment in the past has ranged from simple excision to en bloc resection.3*9 The problem of overly aggressive treatment of peripheral ameloblastoma prompted a move for a change in terminology’3; however, despite its lack of local destructiveness and persistence, the lesion’s histologic characteristics are undeniably ameloblastoma. The current treatment of choice is conservative supraperiosteal surgical excision with adequate disease-free margins.3*7,‘0,14 Recurrences are infrequent and probably reflect inadequate surgical
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margins. ’ Periodic follow-up examinations ommended .
are rec-
Summary A case of peripheral ameloblastoma, a rare intraoral neoplasm, has been presented. The lesion appears most commonly as a mass on the mandibular lingual gingiva of patients in their fifth and sixth decades of life. The peripheral ameloblastoma does not share the aggressive nature of the intraosseous variant. The lesion has been overtreated in the past and warrants only a local supraperiosteal excision. References 1. Gardner D: Peripheral ameloblastoma. Cancer 39:1625, 1977 2. Wesley R, Bominski E, Mix&zS: Peripheral ameloblastoma: Report of case and review of the literature. J Oral Surg 35:670, 1977 3. Moskow B, Baden E: The peripheral ameloblastoma of the gingiva. J Periodontol 53:736, 1982 4. Waldron CA: Comments on Peters, R.A. et al. Basal cell
5. 6.
7.
8.
9. 10. 11. 12. 13. 14.
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GINGIVA
carcinoma of the oral cavity: Report of a case. J Oral Surg 30:63, 1972 Simpson H: Basal cell carcinoma and peripheral ameloblastoma. Oral Surg 38:233, 1974 Yasuchika K, Shigeru U: Peripheral ameloblastoma resembling a papilloma: Report of case. J Oral Maxillofac Surg 44~737, 1986 Woo S, Williams J, Sciubba J, et al: Peripheral ameloblastoma of the buccal mucosa: Case report and review of the English literature. Oral Surg Oral Med Oral Path01 63:78, 1987 Horowitz I, Hirshberg A, Dayan D: Peripheral ameloblastoma: A clinical dilemma in gingival lesions. J Clin Periodontol 14:366, 1987 Balfour R, Loscalzo L, Sulka M: Multicentric peripheral ameloblastoma. J Oral Surg 31:535, 1973 Bonn G, DeBoom G: Multilocular radiolucent area of the posterior mandible. J Am Dent Assoc 116:393. 1988 Frankel K, Smith 3, Frankel L: Soft tissue ameloblastoma in a 92 year old woman. Arch Otolaryngol 103:499, 1977 Shafer H, Hine M, Levy B: A Textbook of Oral Pathology fed 4). Philadelphia, Saunders, 1983, p 276 Richardson J, Greer R: Ameloblastoma of mucosal origin. Arch Otolaryngol 100: 174, 1974 Gardner D, Pecak M: The treatment of ameloblastoma based on pathologic and anatomic principles. Cancer 46:2514. 1980
MaxillofncSurg
43:1311-1316.1990
Pedunculated Soft-Tissue Mass on the Alveolar Gingiva MARK L. MONSON, DDS,* JOHN POSTGATE, DDS,t ROBERT BOWE, DDS,$ AND THOMAS P. WILLIAMS, DDS§ Case Presentation
tion therapy. His past medical history includes syphilis treated 20 years earlier, a prostate nodule, and peptic ulcer disease. It is not stated if the syphilis had been adequately treated. There is no mention of the duration, character, or treatment provided for the prostate nodule or discussion regarding the duration and status of the patient’s peptic ulcer disease. It is interesting to note that the patient’s medications include indomethacin, 25 mg every 8 hours; codeine, 30 mg every 2 to 4 hours; and Tylenol no. 3 (which contains 1/2grain of codeine) every 4 to 6 hours. Indomethacin, an anti-inflammatory and analgesic agent, is used on occasion for the management of patients with inflammatory conditions, most often arthritidies. As there is no mention of arthritis in the patient’s history, it can be presumed that the patient is receiving indomethacin for relief of pain associated with his lung malignancy despite the fact that it is contraindicated in patients with peptic ulcers. In addition, the patient is receiving approximately 1 grain of codeine also presumably for relief of symptoms associated with his malignancy. The patient admits to a JO pack/yr history of cigarette smoking and moderate alcohol intake although the specific amount consumed is not stated. Clinical examination showed an asymptomatic, erythematous, pedunculated mass of the gingiva lingual to the mandibular left first premolar. Radiographs of that area were negative. The laboratory studies provided were significant for an elevated serum calcium of 12.6 mg/dL and for anemia with a hematocrit of 25.2%. The differential diagnosis for a soft-tissue mass of the gingiva should include developmental, reactive or inflammatory, and neoplastic entities. The location of the mass would exclude consideration of salivary gland lesions or masses arising from striated muscle, as these tissues are not present in this area. However, the clinician should consider masses of epithelial, mesenchymal, and odontogenic origin. It was stated that radiographs of the area are negative; therefore, the origin of the mass is most likely from soft tissue rather than extension from underlying
A 62-year-old black man was seen in the Veterans Administration Hospital Dental Service for construction of partial dentures. The patient was currently hospitalized for tests to determine the etiology of shoulder pain. The test results yielded a diagnosis of left upper lobe pulmonary squamous cell carcinoma. Chest radiographs showed a 10 x 7-cm mass that was deemed inoperable, so the patient was receiving palliative radiation therapy. His past medical history included a prostate nodule, syphilis that was treated 20 years earlier, and peptic ulcer disease. His laboratory examination was significant for a hematocrit of 25.2% and calcium of 12.6 mg/dL. Medications at that time included indomethacin 25 mg orally every 8 hours, codeine 30 mg orally every 2 to 4 hours, and Tylenol no. 3 (McNeil Pharmaceutical, Spring House, PA), one tablet orally every 4 to 6 hours. His social history showed a 40 pack/yr cigarette use and moderate alcohol intake. Routine oral examination showed an asymptomatic 1.O x 0.5 x 0.3-cm erythematous, pedunculated soft-tissue mass on the mandibular alveolar process lingual to the mandibular left first premolar (Fig 1). The patient was unaware of its presence. Radiographic findings were noncontributory. The lesion was excised at its base and submitted for microscopic examination.
Differential Diagnosis This 62-year-old black male has an established diagnosis of inoperable squamous cell carcinoma of the lung for which he is receiving palliative radia-
* Formerly, General Practice Resident, West Los Angeles Veterans Administration; currently, Chief Resident, Oral and Maxillofacial Surgery, Medical University of South Carolina. t Formerly, General Practice Resident, West Los Angeles Veterans Administration; currently, in private practice, Bakersfield, CA. $ Formerly, General Practice Resident, West Los Angeles Veterans Administration; currently, in private practice, Beverly Hills, CA. 8 In private practice, Dubuque, IA. Address correspondence and reprint requests to Dr Monson: VAMC (160), Oral and Maxillofacial Surgery, 16111 Plummer St, Sepulveda, CA 91343. 0 1990 American Association of Oral and Maxillofacial geons 0278-2391190/4812-0011$3.00/O
Sur-
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FIGURE 1. Asymptomatic, pedunculated soft-tissue mass located lingual to the mandibular left first premolar.
bone. As the radiographs were negative, it can be assumed that there is no carious or periodontal involvement of the teeth in this location. It may also be presumed that the mass has been present for a considerable period of time, for if it was of short duration, it is likely that the patient would have been aware of it. However, it should be stated that in view of the relative lack of oral hygiene noted from the clinical photograph, it appears that the patient is not oral-health conscious. The clinician should also consider whether the erythematous appearance of the mass is from inflammatory involvement of surface epithelium or characteristic of the underlying connective tissue. Close examination of the mass from the clinical photograph suggests that the surface is not entirely smooth, but, rather, has a cobblestone appearance in areas. With these thoughts in mind, consideration of various entities should begin with developmental processes that occur on the gingiva. The gingival cyst may present as an exophytic mass; however, the surface epithelium is usually blanched or normal in color and those cysts are not pedunculated. Although not excludable, the gingival cyst is unlikely. The calcifying odontogenic cyst, although classified as a cyst of odontogenic epithelium, is thought by some investigators to be an odontogenic neoplasm. Although they most often occur as an intraosseous lesion of the jaws, 25% to 35% occur on the gingiva as an exophytic mass without osseous involvement. Therefore, although not usually pedunculated, the calcifying odontogenic cyst cannot be excluded from the differential diagnosis. Lesions of vascular origin, such as the hemangioma and vascular malformation, should also be considered. It has not been stated if the mass was compressible or blanched with pressure, characteristics of both hemangiomas and vascular malformations. They may occur in any location within the oral cav-
PEDUNCULATED
MASS ON ALVEOLAR
GINGIVA
ity and have an erythematous appearance. Although the hemangioma is congenital, it may not become apparent until childhood and then may persist. Persistence without involution is characteristic of the vascular malformation. Therefore, the hemangioma and vascular malformation should be included in the differential diagnosis. The lymphangioma, also thought to be congenital, occurs as an exophytic mass. Usually it is not well circumscribed, except for the variant referred to as lymphangioma circumscripta. Therefore, except for this variant, lymphangioma is unlikely. As the patient has not been aware of the mass and the radiographs are noncontributory, the clinician may make the assumption that reactive or inflammatory diseases as a result of pulpal necrosis can be excluded. Reactive lesions of nonodontogenic origin that may be considered include the condyloma acuminatum. The condyloma acuminatum may occur on the gingiva as a soft, pedunculated exophytic mass. Although they initially occur as a group of nodules, they may coalesce to form a single mass. Thought to be a result of infection by human papillomavirus subtype 6 and 11, it may have either a cobblestone or cauliflower appearance as a result of epithelial proliferation. Therefore, it cannot be excluded from the differential diagnosis. The pyogenic granuloma should also be considered in the differential diagnosis. Poor oral hygiene has been implicated as an etiologic factor for this reactive lesion. Because this patient’s lesion has an exophytic, erythematous, pedunculated appearance, the pyogenic granuloma should be considered. The peripheral giant cell granuloma is also a painless, exophytic, hemorrhagic, pedunculated mass that occurs on the gingiva and should be included in the differential diagnosis. The fibroma, most often thought to be reactive and not neoplastic, may involve the gingiva. Although smooth-surfaced and not usually hemorrhagic, it cannot be excluded from the differential diagnosis, but is unlikely. Condyloma latum, a manifestation of secondary syphilis, can be excluded from the differential based on the length of time elapsed since the patient’s infection. The mass does not have characteristics of a gumma and therefore tertiary syphilis also would be unlikely. Malignant and benign neoplastic processes may involve the gingiva and should be included in the differential diagnosis. With the presumption that the mass has been present for a long time, benign neoplasms should be strongly considered. However, the history of advanced squamous cell carcinoma of the lung and a prostate nodule mandates that metastatic lesions not be ignored as a possibility. Metastasis to the soft tissues of the oral cavity
MONSON
ET AL
is rare. If a metastasis to gingiva had occurred, the clinician should expect to see tissue breakdown and ulceration associated with rapid growth. Therefore, although unlikely due to the location and lack of ulceration, metastatic lesions from lung or prostate cannot be excluded. A plasmacytoma also may involve the gingiva as an exophytic, hemorrhagic mass and, therefore, it too cannot be excluded. The clinician should also consider benign neoplasms that occur on the gingiva. Benign neoplasms arising from surface epithelium normally have a cauliflower or papillary appearance. Because this mass does not have such an appearance, benign neoplasms of epithelial origin can be excluded. However, benign neoplasms of mesenchymal origin should be considered. The granular cell tumor most often occurs on the tongue, but may involve gingiva. Thought to be of neural origin, supported by the demonstration of S-100 protein within the granules, it presents as an asymptomatic exophytic mass. The schwannoma derived from proliferation of Schwann cells may also involve the gingiva, presenting as a solitary exophytic mass. The neurofibroma also may occur as a solitary exophytic mass in the gingiva. Although entities of neural origin cannot be specifically excluded from the differential diagnosis, they present as submucosal masses that are not pedunculated or erythematous and, therefore, are unlikely considerations. The myxoma, although rare within the oral cavity, may involve gingiva and has been reported to occur at any age. It is also an unlikely consideration because myxomas usually are not erythematous, pedunculated, or cobblestoned. The leiomyoma may occur at any age and involve gingiva, but is quite rare. It presents as a submucosal mass that is not erythematous. However, a variant, the vascular leiomyoma, has a prominent vascular component with an erythematous, exophytic appearance and should be considered in the differential diagnosis. Benign neoplasms of odontogenic origin should be included in the differential diagnosis. For the sake of discussion, the peripheral odontogenic fibroma and peripheral ossifying fibroma will be considered together. Thought to originate from the periodontal ligament, both entities occur on the gingiva, usually adjacent to teeth. The peripheral odontogenic fibroma in distinction to the peripheral ossifying fibroma is rare; however, both may have an exophytic hemorrhagic appearance. They may be firm or soft to palpation dependent on the degree of calcification within the mass. Although this patient’s mass does not involve the free gingival margin, the peripheral odontogenic fibroma and peripheral ossifying fibroma cannot be specifically excluded from the differential diagnosis.
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The peripheral ameloblastoma, a soft-tissue variant of ameloblastoma, occurs in an older age range than the intraosseous ameloblastoma. It occurs on the gingiva as an exophytic mass. Thought to arise from surface epithelium or remnants of dental lamina, it may have a cobblestone appearance and, therefore, should be included within the differential diagnosis. The calcifying epithelial odontogenic tumor and adenomatoid odontogenic tumor have been reported to occur as solitary soft-tissue masses without osseous involvement. Both entities involve gingiva and, although rare, cannot be specifically excluded from consideration. Development of a differential diagnosis would not be complete without discussion of the other significant findings of the history, and physical and laboratory examinations. The patient had an elevated serum calcium of 12.6 mg/dL and, therefore, a differential diagnosis of hypercalcemia should be considered. Hypercalcemia may occur from excessive secretion of serum parathormone, as in primary hyperparathyroidism, or from disease states not associated with elevated serum parathormone. Aside from hyperparathyroidism, other causes of hypercalcemia are malignancy, both hematologic and nonhematologic; granulomatous diseases such as sarcoidosis; endocrine disorders such as thyrotoxicosis or acute adrenal insufftciency; familial hypocalcuric hypercalcemia; excessive ingestion of calcium, vitamin A, or vitamin D; extensive skeletal immobilization; and idiopathic hypercalcemia of infancy. The presence of hypercalcemia is established when at least three measures of serum calcium are elevated. The clinician should determine the cause for hypercalcemia based upon the history, physical examination, and adjunctive laboratory studies. A long-standing illness with a history of nephrolithiasis, but no weight loss, suggests primary hyperparathyroidism. A disease of short duration with weight loss, but without nephrolithiasis, suggests a cause other than hyperparathyroidism for the hypercalcemia. Patients with malignant disease may have hypercalcemia of short duration without a history of nephrolithiasis. The history provided for this patient does not suggest endocrine abnormalities, excessive ingestion of calcium or vitamin A or D, or familial disease. The patient does have a history of peptic ulcer, which is often associated with primary hyperparathyroidism. However, in view of the patient’s diagnosis of squamous cell carcinoma of the lung, hypercalcemia of malignancy should be strongly considered. It is thought that hypercalcemia associated with malignancy occurs, not as a result of widespread metastatic disease with skeletal involvement, but from production of osteolytic humoral factors that include parathormonelike sub-
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stances, prostaglandins, and lymphokines such as osteoclast activating factor. Hypercalcemia is common in patients with lung cancer. It has been reported to occur in 12% of all cases, but in 23% of cases of squamous cell carcinoma of the lung. Hypercalcemia from nonhematologic malignancies is caused by secretion of humoral factors that stimulate osteoclast activity. In contrast, hematologic malignancies such as multiple myeloma produce hypercalcemia as a result of extensive bone destruction. Although it is likely that this patient’s hypercalcemic state is a result of lung cancer, primary hyperparathyroidism and multiple myeloma cannot be excluded. Therefore, in addition to the history and physical examination, a radioimmunoassay for parathyroid hormone and serum electrophoresis should be performed to rule out these two conditions. Therapy should be directed towards reduction of the serum calcium as the hypercalcemia could be life-threatening. Treatment includes parenteral hydration, forced diuresis, reduction of dietary calcium, and careful monitoring of serum calcium and electrolytes. The patient also presents with anemia, having a hematocrit of 25.2%. There are several factors to be considered in the workup of this patient’s anemia. He is taking indomethacin, a nonsteroidal antiinflammatory drug contraindicated in patients with peptic ulcers. Patients receiving indomethacin have been reported to have perforation of ulcers of the gastrointestinal tract with occult blood loss progressing to the development of anemia. Red cell indices and testing of the stool for occult blood would provide valuable information. An additional cause of anemia in this patient might be alcoholic cirrhosis, folate or pyroxidine deficiency, hemolysis, and toxicity of ethanol upon the bone marrow. Although the amount of alcohol consumed by the patient was not stated, that determination, along with the laboratory evaluation, would assist in the diagnosis. Anemia is also a frequent finding in patients with lung cancer. Such patients may have an autoimmune hemolytic anemia or a microangiopathic hemolytic anemia manifested by fragmented erythrocytes. Disseminated intravascular coagulation may also occur in patients with lung malignancy; however, most often it is subclinical without overt bleeding. These entities should be considered as possible causes of this patient’s anemia. The case presentation stated that the past medical history included a prostate nodule; however, the duration, character, and treatment provided, if any, were not discussed. It is presumed that the patient was tested to rule out carcinoma of the prostate. Symptoms associated with prostatic cancer may be absent or can include hematuria, lymphadenopathy,
PEDUNCULATED MASS ON ALVEOLAR GINGIVA
and edema of the legs. Rectal examination should be performed to ascertain if an indurated nodule can be palpated within the substance of the gland. The diagnosis is then confirmed by microscopic examination of a specimen obtained by needle biopsy. The patient’s past medical history also included syphilis treated 20 years earlier. Although it may be presumed to have been adequately treated, the venereal disease research laboratories (VDRL) test should be performed as a screening examination. If there is a question regarding the presence of syphilis despite a negative VDRL, the patient can be treated with penicillin if no allergy exists. In summary, the differential diagnosis for this patient’s gingival mass should include developmental, reactive, and neoplastic processes. Strong consideration should be given to the following lesions: condyloma acuminatum, pyogenic granuloma, peripheral giant cell granuloma, metastasis presumably from lung or possibly from prostate, plasmacytoma, vascular leiomyoma, peripheral ameloblastoma, peripheral odontogenic fibroma, hemangioma or vascular malformation (particularly if the mass blanches upon compression). Although there are other entities not specifically excluded from the differential diagnosis, these lesions are thought to most likely represent the diagnosis. Ultimately, confirmation of the diagnosis will occur following excision and microscopic examination of the mass. In addition, the patient should be tested for hypercalcemia as detailed previously. Although primary hyperparathyroidism and muitiple myeloma cannot be ruled out, the hypercalcemia is probably secondary to epidermoid carcinoma of the lung. The patient should also be evaluated for anemia. It is most likely a result of gastrointestinal blood loss, alcoholic cirrhosis, or associated with a paraneoplastic syndrome. The administration of indomethacin should also be evaluated. Further information should be obtained regarding the prostate nodule, presence of syphilis, and peptic ulcer disease. SUBSEQUENT
COURSE
The specimen was fixed in formalin and stained by routine hematoxylin and eosin (Figs 2 to 4). Examination of the sections showed the mass to consist of a submucosal proliferation of cells contiguous with a hyperplastic overlying epithelium. The submucosal proliferation was composed of islands, sheets, and cords of epithelial cells. The outermost layer consisted of palisading columnar basaloid cells. These surrounded squamous cells with abundant pink cytoplasm and large ovoid pale staining nuclei. Occasional areas of spongiosis were noted; however, no stellate reticular areas were noted. Mitoses were not prominent. The intervening stroma consisted of loose fibrous connective tissue of moderate vascularity. The
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FIGURE 2. Photomicrograph showing islands of tumor cells consisting of an outer layer of palisaded basaloid cells surrounding an inner core of mature squamous cells. The intervening fibrous stroma is dense (hematoxyhn-eosin stain, original magnification X 100).
overlying epithelium showed normal maturation with several areas of basal cell proliferation that blended into the submucosal neoplasm. The deep margin of the specimen contained tumor cells. Based on the histopathologic tindings, a diagnosis of peripheral ameloblastoma was made. After receipt of the pathology report, the patient was treated with a local supraperiosteal stripping of the biopsy site. There was no evidence of neoplasm noted in the histologic examination of the submitted specimen. The surgical site healed without complication. The patient subsequently died 4 months after admission of causes related to his pulmonary carcinoma. There was no evidence of recurrence of the peripheral ameloblastoma.
Discussion The peripheral ameloblastoma is a rare odontogenie tumor of the soft tissues covering the tooth-
FIGURE 4. Higher-power photomicrograph showing that despite a high degree of cellularity, the mitotic rate is low (hematoxylin-eosin stain, original magnification X400).
bearing surfaces of the jaws.lY2 Although it shares the histologic characteristics common to intraosseous ameloblastoma, this variant lacks its locally destructive and persistent qualities.3 It is interesting to note that the basal cell carcinoma of the gingiva is histologically identical to the peripheral ameloblastoma and considered by most to be the same lesion.3-6 The lesion appears as an epulis measuring up to 5 cm.7 The lingual gingiva of the mandible is the preferred site.3.8 Radiographic examination is usually normal. In a few instances, superficial “cupping or saucerization” of bone has been reported. This is generally felt to be due to resorption rather than invasion“3; however, Balfour has reported a case in which he believed invasion of underlying bone had occurred.’ The lesion has been reported in patients ranging in age from 23 to 92 years, with a mean of 51. Whites are affected most commonly, with males showing a slight predilection.3 There have been two sources postulated as the origin of the peripheral ameloblastoma: the dental lamina and the surface epithelium.
FIGURE 3. Photomicrograph of tumor islands showing prominent “reverse polarization” of the nuclei of the outermost basaloid cells (hematoxylin-eosin stain, original magnification x 150).
1,2*7,10-12
The treatment of this lesion, simple excision, is often confounded by the ominious connotation the term ameloblastoma implies in the mind of the surgeon. Treatment in the past has ranged from simple excision to en bloc resection.3*9 The problem of overly aggressive treatment of peripheral ameloblastoma prompted a move for a change in terminology’3; however, despite its lack of local destructiveness and persistence, the lesion’s histologic characteristics are undeniably ameloblastoma. The current treatment of choice is conservative supraperiosteal surgical excision with adequate disease-free margins.3*7,‘0,14 Recurrences are infrequent and probably reflect inadequate surgical
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margins. ’ Periodic follow-up examinations ommended .
are rec-
Summary A case of peripheral ameloblastoma, a rare intraoral neoplasm, has been presented. The lesion appears most commonly as a mass on the mandibular lingual gingiva of patients in their fifth and sixth decades of life. The peripheral ameloblastoma does not share the aggressive nature of the intraosseous variant. The lesion has been overtreated in the past and warrants only a local supraperiosteal excision. References 1. Gardner D: Peripheral ameloblastoma. Cancer 39:1625, 1977 2. Wesley R, Bominski E, Mix&zS: Peripheral ameloblastoma: Report of case and review of the literature. J Oral Surg 35:670, 1977 3. Moskow B, Baden E: The peripheral ameloblastoma of the gingiva. J Periodontol 53:736, 1982 4. Waldron CA: Comments on Peters, R.A. et al. Basal cell
5. 6.
7.
8.
9. 10. 11. 12. 13. 14.
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carcinoma of the oral cavity: Report of a case. J Oral Surg 30:63, 1972 Simpson H: Basal cell carcinoma and peripheral ameloblastoma. Oral Surg 38:233, 1974 Yasuchika K, Shigeru U: Peripheral ameloblastoma resembling a papilloma: Report of case. J Oral Maxillofac Surg 44~737, 1986 Woo S, Williams J, Sciubba J, et al: Peripheral ameloblastoma of the buccal mucosa: Case report and review of the English literature. Oral Surg Oral Med Oral Path01 63:78, 1987 Horowitz I, Hirshberg A, Dayan D: Peripheral ameloblastoma: A clinical dilemma in gingival lesions. J Clin Periodontol 14:366, 1987 Balfour R, Loscalzo L, Sulka M: Multicentric peripheral ameloblastoma. J Oral Surg 31:535, 1973 Bonn G, DeBoom G: Multilocular radiolucent area of the posterior mandible. J Am Dent Assoc 116:393. 1988 Frankel K, Smith 3, Frankel L: Soft tissue ameloblastoma in a 92 year old woman. Arch Otolaryngol 103:499, 1977 Shafer H, Hine M, Levy B: A Textbook of Oral Pathology fed 4). Philadelphia, Saunders, 1983, p 276 Richardson J, Greer R: Ameloblastoma of mucosal origin. Arch Otolaryngol 100: 174, 1974 Gardner D, Pecak M: The treatment of ameloblastoma based on pathologic and anatomic principles. Cancer 46:2514. 1980