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Benign lymphoepithelial lesion of minor salivary gland: report of a case involving the palatal mucosa
Oral Oncology EXTRA (2004) 40, 113–116
http://intl.elsevierhealth.com/journal/ooex
CASE REPORT
Benign lymphoepithelial lesion of minor salivary gland: report of a case involving the palatal mucosa Hamdy Metwalya, Jun Chenga,b, Makoto Suzukia,b, Yoshiyuki Takatac, Chikara Saitohc, Takafumi Hayashid, Takashi Sakua,b,* a
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan b Section of Surgical Pathology, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori Niigata 951-8520, Japan c Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan d Division of Oral and Maxillofacial Radiology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan Received 19 July 2004; accepted 23 July 2004
KEYWORDS
Summary The article describes a rare case of benign lymphoepithelial lesion of the palatal minor salivary gland of a 70-year-old Japanese female patient who suffered from swelling for three months. The serological findings suggested that the patient was affected by Sjo ¨gren’s syndrome, although she had no obvious clinical symptoms. CT examinations revealed the presence of a round soft tissue mass in the posterior right side of the hard palate to the soft palate with slight thinning of the bone cortex of the palate. Histologically, the surgically removed mass was composed of a diffuse infiltration of lymphoid cells in the lamina propriae to the submucosal layer. There were many scattered epi-myoepithelial islands throughout the lymphoid background. The histological finding was consistent with that of benign lymphoepithelial lesion of the major salivary gland. The frequency and incidence of
Benign lymphoepithelial lesion; Minor salivary gland; Sjo ¨gren’s syndrome
* Corresponding author. Address: Division of Oral and Maxillofacial Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan. Tel.: +81 25 227 2832; fax: +81 25 227 0805. E-mail address: [email protected] (T. Saku).
1741-9409/$ - see front matter c 2004 Published by Elsevier Ltd. doi:10.1016/j.ooe.2004.07.001
114
H. Metwaly et al. benign lymphoepithelial lesions in minor salivary glands and their association with Sjo ¨gren’s syndrome were discussed based on 10 cases previously reported in the literature. c 2004 Published by Elsevier Ltd.
Case report The patient was a 70-year-old Japanese female. She had noticed a painless swelling in the right posterior part of her palate for 3 months, and she was referred to our hospital by her dentist. On clinical examination, a soft and painless swelling, measuring 24 mm in diameter, protruded at the right posterior end of the hard palate to the soft palate. The covering mucosa was smooth but a little reddish in color (Fig. 1). Delayed-phase contrasting CT showed a round-shaped well-demarcated nodule with a diffuse and muscle-level density which was cleared up in about four minutes. No bone resorption was observed in the palate (Fig. 2). Laboratory findings showed elevated levels of IgG (2119 mg/ dl), rheumatoid factor (35.5 IU/ml), anti-SS-A (94.4/titer), anti-NA (91.9), anti-EBV IgG (80) and anti-CMV IgG (+). Autoimmune conditions including Sjo ¨gren’s syndrome (SjS) were strongly suspected. However, there were no clinical symptoms such
Figure 1 Clinical feature of palatal swelling by benign lymphoepithelial lesion of minor salivary gland in a 70year-old woman. The lesion was located in the right posterior side of the palate. It appeared as a protruded round-shaped mass (arrows) covered with a smooth and slightly reddish mucosa.
Figure 2 CT image of benign lymphoepithelial lesion of the palate. CT scan with delayed-phase contrasting at 4 min showed a round soft tissue mass located in the posterior right side of the hard palate to the soft palate. The central and peripheral zones of the lesion were rather enhanced in the later stages.
as dry eyes, dry mouth or swelling of major salivary glands. Under a clinical diagnosis of benign tumor, the lesion was surgically removed. Histopathologically, the lesion, located in the lamina propriae to submucosal layer, was well circumscribed and consisted of several compartments separated by fibrous septa. Each compartment was composed of a diffuse and monotonous proliferation of lymphoid cells and scattering eosinophilic epithelial islands (Fig. 3A). The lymphoid cells were mainly mature lymphocytes with B cell predominance and without any monoclonalities (data not shown). The epithelial islands varied in shape and size and some of them contained ductal structures (Fig. 3B). Only at the periphery of the lesion there were remnants of minor salivary gland lobules with atrophic and degenerative changes, which seemed to be due to the extensive lymphocytic infiltrates.
Benign lymphoepithelial lesion of minor salivary gland
Figure 3 Histopathological findings of benign lymphoepithelial lesion of the palate (hematoxylen and eosin staining, A, ·10; B, ·120). A loupe view showed that the lesion, a submucosal nodule, was composed of several compartments separated by connective tissue septa, and each compartment mainly consisted of a diffuse infiltration of lymphoid cells and scattering epi-myoepithelial islands (A). The lymphoid cells were mainly lymphocytes with benign appearance and replaced the salivary parenchyma. Epi-myoepithelial islands varied in shape and size and some of them contained ductal structures (B).
Discussion The incidence of benign lymphoepithelial lesion (BLEL) of minor salivary gland is infrequently reported. It is unknown if minor gland BLEL is associated with SjS or not. To our knowledge, there are only 11 reported cases including our case found in the literature, ten of which (90%) occurred in the palate1–9 and one in the tongue.10 Five cases of the palate (50%) were associated with SjS,1–5 and the tongue case had a simultaneous major salivary gland enlargement, which was diagnosed as Mickulicz’s disease.10 Five cases of the palate including ours (50%) were not associated with apparent SjS or major salivary gland enlargement.6–9 According
115 to available clinical data, the male to female ratio of the patients was 1:4.5, and male patients were younger (mean age 36.5 years) than female patients (65 years) and had both major and minor salivary gland swellings. The enlargement of the major salivary glands is one of the common features of patients with SjS (30–50%), while swellings of minor salivary glands are not usually apparent.3 Parotid glands are most frequently affected, and their swellings occur unilaterally or bilaterally and grow slowly without pain.1–3 Such swellings in the major salivary glands are caused by intense lymphoid cell infiltrations replacing the salivary parenchyma. This lymphoid cell infiltration is associated with hyperplasia and metaplasia of residual duct epithelial cells resulting in formation of so-called epi-myoepithelial islands that characterize the lesion histopathologically. It has also been reported that minor salivary glands have similar histological changes as major glands in about 80% of patients with SjS,3 which are often revealed by lip biopsies and are helpful in diagnosis of SjS without apparent major gland swelling. However, marked swellings or tumor-like masses of minor salivary glands are infrequent. Therefore, few cases of BLEL in the minor salivary gland have been reported. In the present case, the serological finding suggested that the patient suffered from SjS. Although she had silent clinical symptoms or no enlargement of major salivary glands, SjS-specific symptoms were suspected to develop at the future date. As far as we could determine based on the literature, no minor salivary gland swelling has been documented as an earlier onset of SjS symptoms prior to major salivary gland swelling or other symptoms. In our survey of the literature, however, 50% of the cases with solitary minor salivary gland swellings were not recognized as apparent SjS. The solitary onset of minor gland swelling among older female patients, which is in contrast to the simultaneous major gland swelling in younger male patients, may indicate the presence of some female-specific pathogenesis of SjS. Consequently, serological investigations should be necessary for patients with solitary swellings of minor salivary glands to rule out the possibility of early autoimmune conditions, even if they have no other clinical symptoms. The diagnosis of SjS in such early stages has a clinical relevance, because the advent of new biological therapies for these stages may alter the natural history of the disease. Histological findings of the present case showed that the characteristic epi-myoepthelial islands were scattered in the dense lymphoid cell
116 infiltration as seen in benign lymphoepithelial lesions of the major salivary gland. Recently, we revealed that epi-myoepithelial islands are not only composed of epithelial cells and lymphoid cells but also of vascular endothelial cells, which may be a driving force in forming epi-myoepithelial islands by securing blood supplies for epithelial cell proliferation.8,11
References 1. Lancaster JE, Hughes KW. Mikulicz’s disease involving multiple salivary glands: report of a case. Oral Surg Oral Med Oral Pathol 1963;16:1266–9. 2. Cooper JC. Oral swelling in Sjo ¨gren’s syndrome. Br J Oral Surg 1976;14:128–36. 3. Takeda Y, Suzuki A, Kuroda M, Fujioka Y, Takayama K. Minor salivary gland swelling in patient with Sjogren’s syndrome. Acta Pathol Jpn 1987;37:1603–9. 4. Clark MP, Gamble WJ. Mickulicz’s disease of a minor salivary gland. J Oral Surg 1978;36:895–7.
H. Metwaly et al. 5. Kemker BJ, Dayal VS, DeMay RM. Sjogren’s syndrome presenting with minor salivary gland mass. J Otolaryngol 1998;27:298–300. 6. Cruickshank HA. Benign lymphoepithelial salivary lesion to be distinguished from adenolymphoma. J Clin Pathol 1965; 18:391–400. 7. Marker P. A case of benign lymphoepithelial lesion of the hard palate. Int J Oral Surg 1983;12:348–54. 8. Saku T, Okabe H. Immunohistochemical and ultrastructural demonstration of epi-myoepithelial islands of autoimmune sialadenitis in man. Arch Oral Biol 1984;29: 687–9. 9. Toida M, Ichihara H, Fujitsuka H, Tatematsu N. Isolated lymphoepithelial lesion of the palate: report of a case and review of the literature. J Oral Maxillofac Surg 2001;59: 1101–3. 10. Bhaskar SN, Bernier JL. Mikulicz’s disease, clinical features, histology, and histogenesis. Report of 73 cases. Oral Surg Oral Med Oral Pathol 1960;13:1387–99. 11. Metwaly H, Cheng J, Ida-Yonemotchi H, Ohshiro K, Jen KY, et al. Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion). Virchows Arch 2003;443:17–27.
http://intl.elsevierhealth.com/journal/ooex
CASE REPORT
Benign lymphoepithelial lesion of minor salivary gland: report of a case involving the palatal mucosa Hamdy Metwalya, Jun Chenga,b, Makoto Suzukia,b, Yoshiyuki Takatac, Chikara Saitohc, Takafumi Hayashid, Takashi Sakua,b,* a
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan b Section of Surgical Pathology, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori Niigata 951-8520, Japan c Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan d Division of Oral and Maxillofacial Radiology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan Received 19 July 2004; accepted 23 July 2004
KEYWORDS
Summary The article describes a rare case of benign lymphoepithelial lesion of the palatal minor salivary gland of a 70-year-old Japanese female patient who suffered from swelling for three months. The serological findings suggested that the patient was affected by Sjo ¨gren’s syndrome, although she had no obvious clinical symptoms. CT examinations revealed the presence of a round soft tissue mass in the posterior right side of the hard palate to the soft palate with slight thinning of the bone cortex of the palate. Histologically, the surgically removed mass was composed of a diffuse infiltration of lymphoid cells in the lamina propriae to the submucosal layer. There were many scattered epi-myoepithelial islands throughout the lymphoid background. The histological finding was consistent with that of benign lymphoepithelial lesion of the major salivary gland. The frequency and incidence of
Benign lymphoepithelial lesion; Minor salivary gland; Sjo ¨gren’s syndrome
* Corresponding author. Address: Division of Oral and Maxillofacial Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan. Tel.: +81 25 227 2832; fax: +81 25 227 0805. E-mail address: [email protected] (T. Saku).
1741-9409/$ - see front matter c 2004 Published by Elsevier Ltd. doi:10.1016/j.ooe.2004.07.001
114
H. Metwaly et al. benign lymphoepithelial lesions in minor salivary glands and their association with Sjo ¨gren’s syndrome were discussed based on 10 cases previously reported in the literature. c 2004 Published by Elsevier Ltd.
Case report The patient was a 70-year-old Japanese female. She had noticed a painless swelling in the right posterior part of her palate for 3 months, and she was referred to our hospital by her dentist. On clinical examination, a soft and painless swelling, measuring 24 mm in diameter, protruded at the right posterior end of the hard palate to the soft palate. The covering mucosa was smooth but a little reddish in color (Fig. 1). Delayed-phase contrasting CT showed a round-shaped well-demarcated nodule with a diffuse and muscle-level density which was cleared up in about four minutes. No bone resorption was observed in the palate (Fig. 2). Laboratory findings showed elevated levels of IgG (2119 mg/ dl), rheumatoid factor (35.5 IU/ml), anti-SS-A (94.4/titer), anti-NA (91.9), anti-EBV IgG (80) and anti-CMV IgG (+). Autoimmune conditions including Sjo ¨gren’s syndrome (SjS) were strongly suspected. However, there were no clinical symptoms such
Figure 1 Clinical feature of palatal swelling by benign lymphoepithelial lesion of minor salivary gland in a 70year-old woman. The lesion was located in the right posterior side of the palate. It appeared as a protruded round-shaped mass (arrows) covered with a smooth and slightly reddish mucosa.
Figure 2 CT image of benign lymphoepithelial lesion of the palate. CT scan with delayed-phase contrasting at 4 min showed a round soft tissue mass located in the posterior right side of the hard palate to the soft palate. The central and peripheral zones of the lesion were rather enhanced in the later stages.
as dry eyes, dry mouth or swelling of major salivary glands. Under a clinical diagnosis of benign tumor, the lesion was surgically removed. Histopathologically, the lesion, located in the lamina propriae to submucosal layer, was well circumscribed and consisted of several compartments separated by fibrous septa. Each compartment was composed of a diffuse and monotonous proliferation of lymphoid cells and scattering eosinophilic epithelial islands (Fig. 3A). The lymphoid cells were mainly mature lymphocytes with B cell predominance and without any monoclonalities (data not shown). The epithelial islands varied in shape and size and some of them contained ductal structures (Fig. 3B). Only at the periphery of the lesion there were remnants of minor salivary gland lobules with atrophic and degenerative changes, which seemed to be due to the extensive lymphocytic infiltrates.
Benign lymphoepithelial lesion of minor salivary gland
Figure 3 Histopathological findings of benign lymphoepithelial lesion of the palate (hematoxylen and eosin staining, A, ·10; B, ·120). A loupe view showed that the lesion, a submucosal nodule, was composed of several compartments separated by connective tissue septa, and each compartment mainly consisted of a diffuse infiltration of lymphoid cells and scattering epi-myoepithelial islands (A). The lymphoid cells were mainly lymphocytes with benign appearance and replaced the salivary parenchyma. Epi-myoepithelial islands varied in shape and size and some of them contained ductal structures (B).
Discussion The incidence of benign lymphoepithelial lesion (BLEL) of minor salivary gland is infrequently reported. It is unknown if minor gland BLEL is associated with SjS or not. To our knowledge, there are only 11 reported cases including our case found in the literature, ten of which (90%) occurred in the palate1–9 and one in the tongue.10 Five cases of the palate (50%) were associated with SjS,1–5 and the tongue case had a simultaneous major salivary gland enlargement, which was diagnosed as Mickulicz’s disease.10 Five cases of the palate including ours (50%) were not associated with apparent SjS or major salivary gland enlargement.6–9 According
115 to available clinical data, the male to female ratio of the patients was 1:4.5, and male patients were younger (mean age 36.5 years) than female patients (65 years) and had both major and minor salivary gland swellings. The enlargement of the major salivary glands is one of the common features of patients with SjS (30–50%), while swellings of minor salivary glands are not usually apparent.3 Parotid glands are most frequently affected, and their swellings occur unilaterally or bilaterally and grow slowly without pain.1–3 Such swellings in the major salivary glands are caused by intense lymphoid cell infiltrations replacing the salivary parenchyma. This lymphoid cell infiltration is associated with hyperplasia and metaplasia of residual duct epithelial cells resulting in formation of so-called epi-myoepithelial islands that characterize the lesion histopathologically. It has also been reported that minor salivary glands have similar histological changes as major glands in about 80% of patients with SjS,3 which are often revealed by lip biopsies and are helpful in diagnosis of SjS without apparent major gland swelling. However, marked swellings or tumor-like masses of minor salivary glands are infrequent. Therefore, few cases of BLEL in the minor salivary gland have been reported. In the present case, the serological finding suggested that the patient suffered from SjS. Although she had silent clinical symptoms or no enlargement of major salivary glands, SjS-specific symptoms were suspected to develop at the future date. As far as we could determine based on the literature, no minor salivary gland swelling has been documented as an earlier onset of SjS symptoms prior to major salivary gland swelling or other symptoms. In our survey of the literature, however, 50% of the cases with solitary minor salivary gland swellings were not recognized as apparent SjS. The solitary onset of minor gland swelling among older female patients, which is in contrast to the simultaneous major gland swelling in younger male patients, may indicate the presence of some female-specific pathogenesis of SjS. Consequently, serological investigations should be necessary for patients with solitary swellings of minor salivary glands to rule out the possibility of early autoimmune conditions, even if they have no other clinical symptoms. The diagnosis of SjS in such early stages has a clinical relevance, because the advent of new biological therapies for these stages may alter the natural history of the disease. Histological findings of the present case showed that the characteristic epi-myoepthelial islands were scattered in the dense lymphoid cell
116 infiltration as seen in benign lymphoepithelial lesions of the major salivary gland. Recently, we revealed that epi-myoepithelial islands are not only composed of epithelial cells and lymphoid cells but also of vascular endothelial cells, which may be a driving force in forming epi-myoepithelial islands by securing blood supplies for epithelial cell proliferation.8,11
References 1. Lancaster JE, Hughes KW. Mikulicz’s disease involving multiple salivary glands: report of a case. Oral Surg Oral Med Oral Pathol 1963;16:1266–9. 2. Cooper JC. Oral swelling in Sjo ¨gren’s syndrome. Br J Oral Surg 1976;14:128–36. 3. Takeda Y, Suzuki A, Kuroda M, Fujioka Y, Takayama K. Minor salivary gland swelling in patient with Sjogren’s syndrome. Acta Pathol Jpn 1987;37:1603–9. 4. Clark MP, Gamble WJ. Mickulicz’s disease of a minor salivary gland. J Oral Surg 1978;36:895–7.
H. Metwaly et al. 5. Kemker BJ, Dayal VS, DeMay RM. Sjogren’s syndrome presenting with minor salivary gland mass. J Otolaryngol 1998;27:298–300. 6. Cruickshank HA. Benign lymphoepithelial salivary lesion to be distinguished from adenolymphoma. J Clin Pathol 1965; 18:391–400. 7. Marker P. A case of benign lymphoepithelial lesion of the hard palate. Int J Oral Surg 1983;12:348–54. 8. Saku T, Okabe H. Immunohistochemical and ultrastructural demonstration of epi-myoepithelial islands of autoimmune sialadenitis in man. Arch Oral Biol 1984;29: 687–9. 9. Toida M, Ichihara H, Fujitsuka H, Tatematsu N. Isolated lymphoepithelial lesion of the palate: report of a case and review of the literature. J Oral Maxillofac Surg 2001;59: 1101–3. 10. Bhaskar SN, Bernier JL. Mikulicz’s disease, clinical features, histology, and histogenesis. Report of 73 cases. Oral Surg Oral Med Oral Pathol 1960;13:1387–99. 11. Metwaly H, Cheng J, Ida-Yonemotchi H, Ohshiro K, Jen KY, et al. Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion). Virchows Arch 2003;443:17–27.