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Exophytic gingival mass in a geriatric patient
CLINICOPATHOLOGIC CONFERENCE
Editor: Steven D. Vincent
Exophytic gingival mass in a geriatric patient Denis P. Lynch, DDS, PhD, a Tom O. Conlon, DDS, b Gary R. Maxwell, DMD, MS, c and Felix Martinez, MD, d Memphis, Tenn., and Spokane, Wash. UNIVERSITYOF TENNESSEE
CLINICAL PRESENTATION An 86-year-old woman otherwise in good health was seen for a chief complaint of a "roughened area" in the left anterior maxilla, followed by asymptomatic gingival enlargement, of 3 weeks duration (Fig. 1). A moderately well-circumscribed radiolucency was found extending from the maxillary left central incisor to the maxillary left premolar area (Fig. 2). The margin of the radiolucency was not sclerotic, and the central portion of the lesion exhibited decreased trabeculation without obvious lytic areas. The patient's medical history, drug history, and systems review were all noncontributory. A previously noted elevated sedimentation rate was felt to be nonspecific and not indicative of any underlying systemic disease. The gingival mass and underlying radiolucency were the only significant findings. No tooth mobility or cervical lymphadenopathy was noted. The initial clinical impression was either a pyogenic granuloma or a peripheral giant cell granuloma. A superficial incisional biopsy was performed. Microscopically, there appeared to be a lichenoid infiltrate without evidence of atypia, and a diagnosis of lichen planus was rendered. The clinical presentation was felt to be incompatible with lichen planus; however, the diagnosis was confirmed with the pathologist. The lesion continued to enlarge, and approximately 1 month later the lesion was rebiopsied by way of a wide local excision, at which time significant bone destruction was noted.
DIFFERENTIAL DIAGNOSIS Inflammatory and reactive hyperplasias most commonly affect the gingiva and are often responsible for This paper was presented in part at the Annual Meeting of the American Academy of Oral and MaxillofacialPathology;Colorado Springs, Colorado,May 6-9, 1995. aprofessor of Biologic and Diagnostic Sciences, College of Dentistry, and Professorof Medicine, College of Medicine. bprivatepracticeperiodontist, Spokane,Washington. cprivate practice oral and maxillofacial surgeon, Spokane, Washington. dprivate practicepathologist, Spokane,Washington. Received for publication Sept. 2, 1997; accepted for publication Sept. 2~ 1997. Copyright © 1998 by Mosby,Inc. 1079-2104/98/$5.00 + 0 7/14/85922
Fig. 1. At initial presentation, tumor mass was confined to labial gingiva from maxillary left first incisor through maxillary left canine. Mucosa is dusky brown in color with an irregular but non-ulcerated surface.
localized gingival enlargements. Pyogenic granulomas are one of the most frequently reported inflammatory hyperplasias in the oral cavity, often occurring secondary to chronic irritation. They most commonly affect the anterior gingiva, with an increased incidence in females. Peripheral giant cell granulomas are more common in the mandible than in the maxilla and usually occur in the premolar region. They are also more common in females and tend to resorb underlying alveolar bone. Peripheral ossifying fibromas are most commonly found in the anterior maxilla, arising from the interdental papillae. 1 Primary gingival malignancies are uncommon. Squamous cell carcinoma of the gingiva is the most commonly reported primary gingival malignancy; however, primary gingival verrucous carcinoma, malignant mesenchymal lesions, and reticuloendothelial tumors have all been described. 2 Metastatic lesions should also be considered in the differential diagnosis of blastomatoid lesions of the gingiva. The most corm-non primary sites of metastatic oral disease are the breast, lung, kidney, bone, colon, and thyroid; however, most metastases are to the jaws rather than to the soft tissues. When oral soft tissue metastases do occur, the gingiva and alveolar mucosa account for 5
6 Lynch et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
January 1998
Fig. 2. Radiolucency extends from maxillary left first incisor through maxillary left first premolar. Borders are regular and well circumscribed. Decreased trabeculation is noted centrally, without obvious lytic areas, and the teeth are not mobile. most sites. The most common primary malignancy that metastasizes to the gingiva is lung cancer, usually in older adults, with a significant male predominance)
Fig. 3. A, Atypical cellular infiltrate is composed of sheets of large, immature myeloblasts, and myelocytes. Nuclei are acentric and hyperchromatic with multiple nucleoli. (Hematoxylin-eosin, original magnification x160) B, Cytoplasmic myeloperoxidase is strongly positive in granulocytic sarcomas and responsible for transitory greenish discoloration of cut fresh tissue sections. (Myeloperoxidase, original magnification x160)
DIAGNOSIS
The excisional biopsy specimen revealed sheets of atypical cells with high nuclear-to-cytoplasmic ratios and granular-appearing cytoplasm (Fig. 3, A). The cytoplasm of the cellular infiltrate stained strongly positive for the presence of myeloperoxidase (Fig. 3, B). The final diagnosis was granulocytic sarcoma (chloroma). MANAGEMENT
The patient received local radiation therapy (3000 cGy) and experienced complete resolution of the lesion (Fig. 4); subsequent hematologic findings were consistently normal and bone marrow biopsies unremarkable. Twenty-eight months later, the patient manifested raspy breathing, and a slight cough, but she was otherwise in good health; cardiopulmonary and abdominal findings were negative. There was no palpable hepatomegaly, splenomegaly, or lymphadenopathy. A pulmonary corn-
puted tomography scan revealed a small mass in the left upper lobe bronchus, which was examined by fiberoptic bronchoscopy. The endobronchial biopsy confirmed the clinical suspicion of an endobronchial lymphoma of B-cell origin, i.e., a "MALToma". The patient began to undergo treatment with chemotherapy, which consisted of cyclophosphamide, prednisone, and vincristine. One month after the diagnosis of her lymphoma, leukocytosis (26,000/mm 3) with abundant myeloblasts developed in the patient. The diagnosis of acute myelogenous leukemia was confirmed with DNA flow cytometry. One week later she complained of lethargy, malaise, and weight loss due to decreased appetite; however, she indicated that there had been no nausea, vomiting, or other gastrointestinal symptoms. At that time she was febrile (100.3 ° F) and her leukocyte count had risen to 129,000/mm3; the leukocytes were primarily blast forms. The hemoglobin value was 9.8 mg/ml,
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 85, Number 1
Lynch et al. 7
and her platelet count was 86,000/ram 3. She was admitted for b l o o d transfusions and c h e m o t h e r a p y with hydroxyurea; however, she did not respond to treatment and died several weeks after admission.
DISCUSSION Granulocytic sarcomas were first described by Burns in 1811. King coined the term "chloroma" in 1853, on account of tile rapidly fading, grayish-green color of cut sections of the tumor, secondary to exposure of cytoplasmic m y e l o p e r o x i d a s e to the air. The association between granulocytic sarcomas and acute myelocytic leukemia was first recognized by yon Recklinghausen in 1855. The term granulocytic sarcoma, first proposed by Rappaport in 1966, is preferred to the term chloroma, inasmuch as the lesions frequently do not exhibit the characteristic color change on sectioning. A granulocytic sarcoma occurs in any one of three clinical settings: (1) in association with acute myelogenous leukemia; (2) as a predecessor to acute myelogenous leukemia; and (3) in association with other leukemic processes. 4 Nearly 5% of patients with myelogenous leukemia experience the development of one or more granulocytic sarcomas in association with their disease. Aleukemic patients with granulocytic sarcomas have normal hematologic, lymphoid, and bone marrow findings for up to 4 years; however, granulocytic sarcomas are associated with a poor overall long-term prognosis, especiaUy when they occur in patients who are aleukemic and and who have chronic m y e l o g e n o u s leukemia. 5 Granulocytic sarcomas occur over a large age range in both genders; however, they are more prevalent in males and young to middle-aged adults. Up to 40% of granulocytic sarcomas involve the head and neck, especially the cranium and orbit, with a predilection for periosteal and ligamentous involvement. Oral lesions are rare, the present case being the fifteenth reported in the literature. Twelve of the cases have been summarized by de Vincente Rodriguez et al., 6 Eisenberg et al.,7 and Saleh et al. s The histopathologic features o f granulocytic sarcomas are frequently not diagnostic, and the lesion may initially be misdiagnosed as a lymphoma. Characteristically, the large, immature myeloblasts and myelocytes contain hyperchromatic, acentric nuclei with multiple nucleoli. C y t o p l a s m i c granules are frequently noted with Wright-Giemsa staining; however, Auer rods are uncommon. Positive naphthol ASD-chloroacetateesterase staining of cytoplasmic esterase can be used to rule out a m o n o c y t i c histogenesis. L y s o z y m e , detectable by immunoperoxidase, is not present in the lymphocytic cell series. Finally, the presence of cyto-
Fig. 4. After radiation therapy, patient is in excellent oral health with only residual postsurgical gingival recession. plasmic myeloperoxidase is strongly positive in granulocytic sarcomas and can be demonstrated with Sudan black B staining, peroxidase, or diaminobenzidine reactions. In the absence of other signs of disease, granulocytic sarcomas are treated primarily with radiation therapy, and the initial response rate is very favorable. Patients who do not respond to radiation therapy or who have other manifestations of disease are treated with a variety of chemotherapeutic agent protocols. Unfortunately, the overall survival rate for patients with granulocytic sarcomas is poor. Of the 15 reported cases of oral granulocytic sarcoma, only 4 of the patients have survived more than 3 years. REFERENCES 1. Bouquot JE, Gundlach KKH. Oral exophytic lesions in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986;62:284-91. 2. Heller AN. Squamous cell carcinoma of the gingiva: a review. N Y State Dent J 1994;60:31-3. 3. Hirshberg A, Buchner A. Metastatic tumours to the oral region: an overview.Eur J Cancer B Oral Oncol 1995;31B:355-60. 4. Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 1981;48:1426-37. 5. Krause JR, Granulocytic sarcoma preceeding acute leukemia: a report of six cases. Cancer 1979;44:1017-21. 6. de Vincente Rodriguez JC, Arranz JS, Fresno Forcelledo M. Isolated granulocytic sarcoma: report of a case in the oral cavity. J Oral Maxillofac Surg 1990;48:748-52. 7. Eisenberg E, Peters ES, Krutchkoff DJ. Granulocytic sarcoma (chloroma) of the gingiva: report of a case. J Oral Maxillofac Surg 1991;49:1346-50. 8. SalehMN, Rodu B, Prchal JT, de Leon ER. Acute myelofibrosis and multiple chloromas of the mandible and skin. Int J Oral Maxillofac Surg 1987;16:108-11.
Reprint requests: Denis R Lynch, DDS, PhD College of Dentistry University of Tennessee 875 Union Ave. Memphis, TN 38163
Editor: Steven D. Vincent
Exophytic gingival mass in a geriatric patient Denis P. Lynch, DDS, PhD, a Tom O. Conlon, DDS, b Gary R. Maxwell, DMD, MS, c and Felix Martinez, MD, d Memphis, Tenn., and Spokane, Wash. UNIVERSITYOF TENNESSEE
CLINICAL PRESENTATION An 86-year-old woman otherwise in good health was seen for a chief complaint of a "roughened area" in the left anterior maxilla, followed by asymptomatic gingival enlargement, of 3 weeks duration (Fig. 1). A moderately well-circumscribed radiolucency was found extending from the maxillary left central incisor to the maxillary left premolar area (Fig. 2). The margin of the radiolucency was not sclerotic, and the central portion of the lesion exhibited decreased trabeculation without obvious lytic areas. The patient's medical history, drug history, and systems review were all noncontributory. A previously noted elevated sedimentation rate was felt to be nonspecific and not indicative of any underlying systemic disease. The gingival mass and underlying radiolucency were the only significant findings. No tooth mobility or cervical lymphadenopathy was noted. The initial clinical impression was either a pyogenic granuloma or a peripheral giant cell granuloma. A superficial incisional biopsy was performed. Microscopically, there appeared to be a lichenoid infiltrate without evidence of atypia, and a diagnosis of lichen planus was rendered. The clinical presentation was felt to be incompatible with lichen planus; however, the diagnosis was confirmed with the pathologist. The lesion continued to enlarge, and approximately 1 month later the lesion was rebiopsied by way of a wide local excision, at which time significant bone destruction was noted.
DIFFERENTIAL DIAGNOSIS Inflammatory and reactive hyperplasias most commonly affect the gingiva and are often responsible for This paper was presented in part at the Annual Meeting of the American Academy of Oral and MaxillofacialPathology;Colorado Springs, Colorado,May 6-9, 1995. aprofessor of Biologic and Diagnostic Sciences, College of Dentistry, and Professorof Medicine, College of Medicine. bprivatepracticeperiodontist, Spokane,Washington. cprivate practice oral and maxillofacial surgeon, Spokane, Washington. dprivate practicepathologist, Spokane,Washington. Received for publication Sept. 2, 1997; accepted for publication Sept. 2~ 1997. Copyright © 1998 by Mosby,Inc. 1079-2104/98/$5.00 + 0 7/14/85922
Fig. 1. At initial presentation, tumor mass was confined to labial gingiva from maxillary left first incisor through maxillary left canine. Mucosa is dusky brown in color with an irregular but non-ulcerated surface.
localized gingival enlargements. Pyogenic granulomas are one of the most frequently reported inflammatory hyperplasias in the oral cavity, often occurring secondary to chronic irritation. They most commonly affect the anterior gingiva, with an increased incidence in females. Peripheral giant cell granulomas are more common in the mandible than in the maxilla and usually occur in the premolar region. They are also more common in females and tend to resorb underlying alveolar bone. Peripheral ossifying fibromas are most commonly found in the anterior maxilla, arising from the interdental papillae. 1 Primary gingival malignancies are uncommon. Squamous cell carcinoma of the gingiva is the most commonly reported primary gingival malignancy; however, primary gingival verrucous carcinoma, malignant mesenchymal lesions, and reticuloendothelial tumors have all been described. 2 Metastatic lesions should also be considered in the differential diagnosis of blastomatoid lesions of the gingiva. The most corm-non primary sites of metastatic oral disease are the breast, lung, kidney, bone, colon, and thyroid; however, most metastases are to the jaws rather than to the soft tissues. When oral soft tissue metastases do occur, the gingiva and alveolar mucosa account for 5
6 Lynch et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
January 1998
Fig. 2. Radiolucency extends from maxillary left first incisor through maxillary left first premolar. Borders are regular and well circumscribed. Decreased trabeculation is noted centrally, without obvious lytic areas, and the teeth are not mobile. most sites. The most common primary malignancy that metastasizes to the gingiva is lung cancer, usually in older adults, with a significant male predominance)
Fig. 3. A, Atypical cellular infiltrate is composed of sheets of large, immature myeloblasts, and myelocytes. Nuclei are acentric and hyperchromatic with multiple nucleoli. (Hematoxylin-eosin, original magnification x160) B, Cytoplasmic myeloperoxidase is strongly positive in granulocytic sarcomas and responsible for transitory greenish discoloration of cut fresh tissue sections. (Myeloperoxidase, original magnification x160)
DIAGNOSIS
The excisional biopsy specimen revealed sheets of atypical cells with high nuclear-to-cytoplasmic ratios and granular-appearing cytoplasm (Fig. 3, A). The cytoplasm of the cellular infiltrate stained strongly positive for the presence of myeloperoxidase (Fig. 3, B). The final diagnosis was granulocytic sarcoma (chloroma). MANAGEMENT
The patient received local radiation therapy (3000 cGy) and experienced complete resolution of the lesion (Fig. 4); subsequent hematologic findings were consistently normal and bone marrow biopsies unremarkable. Twenty-eight months later, the patient manifested raspy breathing, and a slight cough, but she was otherwise in good health; cardiopulmonary and abdominal findings were negative. There was no palpable hepatomegaly, splenomegaly, or lymphadenopathy. A pulmonary corn-
puted tomography scan revealed a small mass in the left upper lobe bronchus, which was examined by fiberoptic bronchoscopy. The endobronchial biopsy confirmed the clinical suspicion of an endobronchial lymphoma of B-cell origin, i.e., a "MALToma". The patient began to undergo treatment with chemotherapy, which consisted of cyclophosphamide, prednisone, and vincristine. One month after the diagnosis of her lymphoma, leukocytosis (26,000/mm 3) with abundant myeloblasts developed in the patient. The diagnosis of acute myelogenous leukemia was confirmed with DNA flow cytometry. One week later she complained of lethargy, malaise, and weight loss due to decreased appetite; however, she indicated that there had been no nausea, vomiting, or other gastrointestinal symptoms. At that time she was febrile (100.3 ° F) and her leukocyte count had risen to 129,000/mm3; the leukocytes were primarily blast forms. The hemoglobin value was 9.8 mg/ml,
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 85, Number 1
Lynch et al. 7
and her platelet count was 86,000/ram 3. She was admitted for b l o o d transfusions and c h e m o t h e r a p y with hydroxyurea; however, she did not respond to treatment and died several weeks after admission.
DISCUSSION Granulocytic sarcomas were first described by Burns in 1811. King coined the term "chloroma" in 1853, on account of tile rapidly fading, grayish-green color of cut sections of the tumor, secondary to exposure of cytoplasmic m y e l o p e r o x i d a s e to the air. The association between granulocytic sarcomas and acute myelocytic leukemia was first recognized by yon Recklinghausen in 1855. The term granulocytic sarcoma, first proposed by Rappaport in 1966, is preferred to the term chloroma, inasmuch as the lesions frequently do not exhibit the characteristic color change on sectioning. A granulocytic sarcoma occurs in any one of three clinical settings: (1) in association with acute myelogenous leukemia; (2) as a predecessor to acute myelogenous leukemia; and (3) in association with other leukemic processes. 4 Nearly 5% of patients with myelogenous leukemia experience the development of one or more granulocytic sarcomas in association with their disease. Aleukemic patients with granulocytic sarcomas have normal hematologic, lymphoid, and bone marrow findings for up to 4 years; however, granulocytic sarcomas are associated with a poor overall long-term prognosis, especiaUy when they occur in patients who are aleukemic and and who have chronic m y e l o g e n o u s leukemia. 5 Granulocytic sarcomas occur over a large age range in both genders; however, they are more prevalent in males and young to middle-aged adults. Up to 40% of granulocytic sarcomas involve the head and neck, especially the cranium and orbit, with a predilection for periosteal and ligamentous involvement. Oral lesions are rare, the present case being the fifteenth reported in the literature. Twelve of the cases have been summarized by de Vincente Rodriguez et al., 6 Eisenberg et al.,7 and Saleh et al. s The histopathologic features o f granulocytic sarcomas are frequently not diagnostic, and the lesion may initially be misdiagnosed as a lymphoma. Characteristically, the large, immature myeloblasts and myelocytes contain hyperchromatic, acentric nuclei with multiple nucleoli. C y t o p l a s m i c granules are frequently noted with Wright-Giemsa staining; however, Auer rods are uncommon. Positive naphthol ASD-chloroacetateesterase staining of cytoplasmic esterase can be used to rule out a m o n o c y t i c histogenesis. L y s o z y m e , detectable by immunoperoxidase, is not present in the lymphocytic cell series. Finally, the presence of cyto-
Fig. 4. After radiation therapy, patient is in excellent oral health with only residual postsurgical gingival recession. plasmic myeloperoxidase is strongly positive in granulocytic sarcomas and can be demonstrated with Sudan black B staining, peroxidase, or diaminobenzidine reactions. In the absence of other signs of disease, granulocytic sarcomas are treated primarily with radiation therapy, and the initial response rate is very favorable. Patients who do not respond to radiation therapy or who have other manifestations of disease are treated with a variety of chemotherapeutic agent protocols. Unfortunately, the overall survival rate for patients with granulocytic sarcomas is poor. Of the 15 reported cases of oral granulocytic sarcoma, only 4 of the patients have survived more than 3 years. REFERENCES 1. Bouquot JE, Gundlach KKH. Oral exophytic lesions in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986;62:284-91. 2. Heller AN. Squamous cell carcinoma of the gingiva: a review. N Y State Dent J 1994;60:31-3. 3. Hirshberg A, Buchner A. Metastatic tumours to the oral region: an overview.Eur J Cancer B Oral Oncol 1995;31B:355-60. 4. Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 1981;48:1426-37. 5. Krause JR, Granulocytic sarcoma preceeding acute leukemia: a report of six cases. Cancer 1979;44:1017-21. 6. de Vincente Rodriguez JC, Arranz JS, Fresno Forcelledo M. Isolated granulocytic sarcoma: report of a case in the oral cavity. J Oral Maxillofac Surg 1990;48:748-52. 7. Eisenberg E, Peters ES, Krutchkoff DJ. Granulocytic sarcoma (chloroma) of the gingiva: report of a case. J Oral Maxillofac Surg 1991;49:1346-50. 8. SalehMN, Rodu B, Prchal JT, de Leon ER. Acute myelofibrosis and multiple chloromas of the mandible and skin. Int J Oral Maxillofac Surg 1987;16:108-11.
Reprint requests: Denis R Lynch, DDS, PhD College of Dentistry University of Tennessee 875 Union Ave. Memphis, TN 38163