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Subacute necrotizing sialadenitis in the buccal mucosa
J Oral Maxillofac Surg 60:1494-1496, 2002
Subacute Necrotizing Sialadenitis in the Buccal Mucosa Wagner Henriques Castro, DDS, MS,* Se´rgio Neves Drummond, DDS,† and Ricardo Santiago Gomez, DDS, PhD‡ Subacute necrotizing sialadenitis (SANS) is a recently described inflammatory disease of unknown etiology that affects oral minor salivary glands. This lesion generally presents as a localized erythematous palatal papule or nodule with a sudden onset, and it seems to be a self-limiting condition.1-3 The microscopic evaluation of SANS shows a nonulcerated oral mucosa overlying minor salivary glands diffusely infiltrated by acute and chronic inflammatory cells. Atrophy and necrosis of duct and acinar cells are observed. To date, only 3 reports are found in the literature about this condition, and all of the cases reported were localized in the hard and soft palate. The purpose of the present article was to report a case of SANS in the buccal mucosa and to improve the characterization of this new condition. In addition, because the possibility of a viral etiology has been raised concerning the pathogenesis of SANS,1 immunolocalization of early and late cytomegalovirus (CMV) antigens was also investigated.
Discussion
Report of a Case A 30-year-old woman was referred with a painful submucosal nodule on the left buccal mucosa of 1 month’s duration (Fig 1). The medical history was not contributory. With the differential diagnosis of benign mesenchymal or glandular neoplasm, lymphoid hyperplasia, epidermoid cyst, or
Received from the Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. *Lecturer. †Resident. ‡Lecturer and Research Fellow of Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo ´ gico (CNPq). Address correspondence and reprint requests to Dr Gomez: Departmento de Patologia e Cirurgia, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627, Belo Horizonte MG, Brasil; e-mail: [email protected]. ufmg.br © 2002 American Association of Oral and Maxillofacial Surgeons
0278-2391/02/6012-0018$35.00/0 doi:10.1053/joms.2002.36134
mucocele, an excisional biopsy was performed. The histopathologic examination showed a nonulcerated oral mucosa with a submucosal diffuse infiltration of minor salivary glands by a mixed inflammatory infiltrate of lymphocytes, neutrophils, histiocytes, and some eosinophils (Fig 2). The ducts showed atrophy, mild dilatation, or necrosis, and the acinar cells showed early necrosis with involvement by polymorphonuclear neutrophils or mononuclear inflammatory cells (Figs 3, 4). Immunohistochemical investigation was performed for identification of CMV early and late antigens. Briefly, tissue blocks were cut into sections 3 m thick and subjected to the biotin-streptavidin labeling. For microwave antigen retrieval, the slides were subjected to microwave (700 W)/citrate buffer (pH 6.0, 10 mmol/L) pretreatment for 10 minutes (3 ⫻ 5 minutes) and then left to cool for 20 minutes. The primary antibodies used were anti-CMV early antigen (Clone QB1/42, 1:25 dilution; Novocastra, Newcastle upon Tyne, England), and anti-CMV late antigen (Clone QB1/06, 1:25 dilution; Novocastra). Peroxidase was visualized with 3⬘-diaminobenzidine and counterstained with Mayer’s hematoxylin. The results did not show positive immunoreaction for either antigen.
SANS was recently recognized; although only 3 reports that describe it appear in the English-language literature, it may not be a rare lesion. As was pointed out by van der Wal et al,2 the self-limiting nature of the disease may lead to spontaneous healing of the lesion before patient evaluation occurs. All of the cases reported involved the location of the palate, and the present case was the first reported to affect the buccal mucosa. Fowler and Brannon3 showed that patient age ranged from 15 to 45 years, with most cases occurring in the second and third decades. Men were more often affected; a predilection for whites was also noted. The duration of the lesions ranged from 1 day to 4 weeks, but in one case it was reportedly present for 6 years before diagnosis. Although the etiology of SANS has not been established, some clinical and microscopic features appear to favor a traumatic, an infectious, or an allergic etiology. Because none of the cases reported presented with an ulcerated oral mucosa, a traumatic factor
1494
CASTRO, DRUMMOND, AND GOMEZ
1495
FIGURE 3. Histologic section exhibiting infiltration and destruction of minor salivary glands by a mixed inflammatory infiltrate of lymphocytes (left) and neutrophils (right) (hematoxylin and eosin stain, original magnification ⫻100). FIGURE 1. Submucosal nodule presenting as a slight swelling.
seems not to be relevant. An infectious or allergic etiology has also been raised for SANS. According to Fowler and Brannon,3 the close living quarters in some of the cases reported, the association of some cases with upper respiratory infections, the sudden onset, and the peak occurrence in fall and winter support an infectious origin. In addition, Werning et al1 described electron-dense bodies suggestive of viral particles at the ultrastructural investigation. Although macrophages, endothelial cells, fibroblasts, epithelial cells, and salivary glands are the most frequently infected cell types found during CMV disease,4 no immunoreactions for the early and late CMV antigens were found in present case. Although the self-limiting nature of the condition, its rapid course, the erythema, and the microscopic presence of eosinophils may suggest an allergic etiology, further research is necessary to confirm it.
Despite some suggestions that SANS may be a spectrum of necrotizing sialometaplasia, the histopathologic examination of both conditions shows key differences.3 In SANS, inflammation seems to be the earliest event and happens before acinar necrosis. In necrotizing sialometaplasia, the acinar necrosis induced by ischemia is the earliest event, followed by mucus liberation and inflammatory response. Although lobular acinar necrosis, fibrosis, and squamous metaplasia are observed in necrotizing sialometaplasia, only focal acinar necrosis, no squamous metaplasia, and significant fibrosis are observed on SANS. In addition, although SANS is almost always a nonulcerated lesion, necrotizing sialometaplasia generally presents as a deep ulcerative lesion. In conclusion, SANS is a nonspecific inflammatory condition of oral minor salivary glands. Additional studies are necessary to further delineate the etiology, clinical and histologic presentations, and evolution of this new condition.
FIGURE 2. Histologic section showing a diffuse inflammation of salivary glands with a relative loss of acini (hematoxylin and eosin stain, original magnification ⫻25).
FIGURE 4. Histologic section showing ducts with mild dilatation and atrophy surrounded by sheets of mononuclear inflammatory cells (hematoxylin and eosin stain, original magnification x400).
1496
References 1. Werning JT, Mooney JW: Subacute necrotizing sialadenitis. Oral Surg Oral Med Oral Pathol 70:756, 1990 2. Van der Wal JE, Kraaijenhagen HA, Van der Waal I: Subacute necrotising sialadenitis: A new entity? Br J Oral Maxillofac Surg 33:302, 1995
3. Fowler CB, Brannon RB: Subacute necrotizing sialadenitis: Report of 7 cases and a review of the literature. Oral Surg Oral Med Oral Pathol 89:600, 2000 4. So ¨ derberg-Naucle´ r C, Nelson JY. Human cytomegalovirus latency and reactivation: A delicate balance between the virus and its host’s immune system. Intervirology 42:314, 1999
Subacute Necrotizing Sialadenitis in the Buccal Mucosa Wagner Henriques Castro, DDS, MS,* Se´rgio Neves Drummond, DDS,† and Ricardo Santiago Gomez, DDS, PhD‡ Subacute necrotizing sialadenitis (SANS) is a recently described inflammatory disease of unknown etiology that affects oral minor salivary glands. This lesion generally presents as a localized erythematous palatal papule or nodule with a sudden onset, and it seems to be a self-limiting condition.1-3 The microscopic evaluation of SANS shows a nonulcerated oral mucosa overlying minor salivary glands diffusely infiltrated by acute and chronic inflammatory cells. Atrophy and necrosis of duct and acinar cells are observed. To date, only 3 reports are found in the literature about this condition, and all of the cases reported were localized in the hard and soft palate. The purpose of the present article was to report a case of SANS in the buccal mucosa and to improve the characterization of this new condition. In addition, because the possibility of a viral etiology has been raised concerning the pathogenesis of SANS,1 immunolocalization of early and late cytomegalovirus (CMV) antigens was also investigated.
Discussion
Report of a Case A 30-year-old woman was referred with a painful submucosal nodule on the left buccal mucosa of 1 month’s duration (Fig 1). The medical history was not contributory. With the differential diagnosis of benign mesenchymal or glandular neoplasm, lymphoid hyperplasia, epidermoid cyst, or
Received from the Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. *Lecturer. †Resident. ‡Lecturer and Research Fellow of Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo ´ gico (CNPq). Address correspondence and reprint requests to Dr Gomez: Departmento de Patologia e Cirurgia, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627, Belo Horizonte MG, Brasil; e-mail: [email protected]. ufmg.br © 2002 American Association of Oral and Maxillofacial Surgeons
0278-2391/02/6012-0018$35.00/0 doi:10.1053/joms.2002.36134
mucocele, an excisional biopsy was performed. The histopathologic examination showed a nonulcerated oral mucosa with a submucosal diffuse infiltration of minor salivary glands by a mixed inflammatory infiltrate of lymphocytes, neutrophils, histiocytes, and some eosinophils (Fig 2). The ducts showed atrophy, mild dilatation, or necrosis, and the acinar cells showed early necrosis with involvement by polymorphonuclear neutrophils or mononuclear inflammatory cells (Figs 3, 4). Immunohistochemical investigation was performed for identification of CMV early and late antigens. Briefly, tissue blocks were cut into sections 3 m thick and subjected to the biotin-streptavidin labeling. For microwave antigen retrieval, the slides were subjected to microwave (700 W)/citrate buffer (pH 6.0, 10 mmol/L) pretreatment for 10 minutes (3 ⫻ 5 minutes) and then left to cool for 20 minutes. The primary antibodies used were anti-CMV early antigen (Clone QB1/42, 1:25 dilution; Novocastra, Newcastle upon Tyne, England), and anti-CMV late antigen (Clone QB1/06, 1:25 dilution; Novocastra). Peroxidase was visualized with 3⬘-diaminobenzidine and counterstained with Mayer’s hematoxylin. The results did not show positive immunoreaction for either antigen.
SANS was recently recognized; although only 3 reports that describe it appear in the English-language literature, it may not be a rare lesion. As was pointed out by van der Wal et al,2 the self-limiting nature of the disease may lead to spontaneous healing of the lesion before patient evaluation occurs. All of the cases reported involved the location of the palate, and the present case was the first reported to affect the buccal mucosa. Fowler and Brannon3 showed that patient age ranged from 15 to 45 years, with most cases occurring in the second and third decades. Men were more often affected; a predilection for whites was also noted. The duration of the lesions ranged from 1 day to 4 weeks, but in one case it was reportedly present for 6 years before diagnosis. Although the etiology of SANS has not been established, some clinical and microscopic features appear to favor a traumatic, an infectious, or an allergic etiology. Because none of the cases reported presented with an ulcerated oral mucosa, a traumatic factor
1494
CASTRO, DRUMMOND, AND GOMEZ
1495
FIGURE 3. Histologic section exhibiting infiltration and destruction of minor salivary glands by a mixed inflammatory infiltrate of lymphocytes (left) and neutrophils (right) (hematoxylin and eosin stain, original magnification ⫻100). FIGURE 1. Submucosal nodule presenting as a slight swelling.
seems not to be relevant. An infectious or allergic etiology has also been raised for SANS. According to Fowler and Brannon,3 the close living quarters in some of the cases reported, the association of some cases with upper respiratory infections, the sudden onset, and the peak occurrence in fall and winter support an infectious origin. In addition, Werning et al1 described electron-dense bodies suggestive of viral particles at the ultrastructural investigation. Although macrophages, endothelial cells, fibroblasts, epithelial cells, and salivary glands are the most frequently infected cell types found during CMV disease,4 no immunoreactions for the early and late CMV antigens were found in present case. Although the self-limiting nature of the condition, its rapid course, the erythema, and the microscopic presence of eosinophils may suggest an allergic etiology, further research is necessary to confirm it.
Despite some suggestions that SANS may be a spectrum of necrotizing sialometaplasia, the histopathologic examination of both conditions shows key differences.3 In SANS, inflammation seems to be the earliest event and happens before acinar necrosis. In necrotizing sialometaplasia, the acinar necrosis induced by ischemia is the earliest event, followed by mucus liberation and inflammatory response. Although lobular acinar necrosis, fibrosis, and squamous metaplasia are observed in necrotizing sialometaplasia, only focal acinar necrosis, no squamous metaplasia, and significant fibrosis are observed on SANS. In addition, although SANS is almost always a nonulcerated lesion, necrotizing sialometaplasia generally presents as a deep ulcerative lesion. In conclusion, SANS is a nonspecific inflammatory condition of oral minor salivary glands. Additional studies are necessary to further delineate the etiology, clinical and histologic presentations, and evolution of this new condition.
FIGURE 2. Histologic section showing a diffuse inflammation of salivary glands with a relative loss of acini (hematoxylin and eosin stain, original magnification ⫻25).
FIGURE 4. Histologic section showing ducts with mild dilatation and atrophy surrounded by sheets of mononuclear inflammatory cells (hematoxylin and eosin stain, original magnification x400).
1496
References 1. Werning JT, Mooney JW: Subacute necrotizing sialadenitis. Oral Surg Oral Med Oral Pathol 70:756, 1990 2. Van der Wal JE, Kraaijenhagen HA, Van der Waal I: Subacute necrotising sialadenitis: A new entity? Br J Oral Maxillofac Surg 33:302, 1995
3. Fowler CB, Brannon RB: Subacute necrotizing sialadenitis: Report of 7 cases and a review of the literature. Oral Surg Oral Med Oral Pathol 89:600, 2000 4. So ¨ derberg-Naucle´ r C, Nelson JY. Human cytomegalovirus latency and reactivation: A delicate balance between the virus and its host’s immune system. Intervirology 42:314, 1999