Q U I N T E S S E N C E I N T E R N AT I O N A L
ORAL MEDICINE
Constantino Ledesma-Montes
Review of the literature on necrotizing sialometaplasia and case presentation Constantino Ledesma-Montes, DDS, MSc, PhD 1/Maricela Garcés-Ortíz, DDS, MSc, PhD1/ Juan Francisco Salcido-García, DDS, MSc 2/Florentino Hernández-Flores, DDS, MSc 3 The aim of this article is to report a case of necrotizing sialometaplasia with long-term follow-up. A case of necrotizing sialometaplasia in a 37-year-old man with clinical documentation on the progress during a 2-year follow-up is presented. Data from an extensive review of the literature including clinical, imagenologic, and microscopic features are provided. Information on diagnostic and prognostic factors is offered and comprehensibly discussed. The importance of identification
and diagnosis of this entity during the review of the slides from the first biopsy is stressed and the exclusive performance of an incisional biopsy is debated. The presented clinical photographs reveal the clinical changes of the lesion from the beginning of the lesions up to 2 years follow-up, documenting the complete long-term clinical course and the healing process of this entity. (Quintessence Int 2015;46:67–72; doi: 10.3290/j. qi.a32633)
Key words: necrotizing sialometaplasia, oral squamous cell carcinoma, salivary gland lesions, salivary glands
Necrotizing sialometaplasia (NSM) is an uncommon self-limiting lesion commonly confused with malignant epithelial entities. NSM was first described by Abrams et al in 19731 and in 1974 it was again reported by Dunlap and Barker.2 Afterwards, Brannon et al,3 using data from their own cases and a review of the literature, described extensively its clinicopathologic features. During the following years, this entity has been found in different locations,4-8 and since the Abrams et al first description, the associated etiologic factors of NSM 1
Full-time Professor, Oral Pathology Laboratory, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, México.
2
Full-time Professor, Oral Diagnosis Clinic, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, México.
3
Professor, Oral Surgery Clinic, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, México.
Correspondence: Professor Constantino Ledesma-Montes, Ciprés #169-2, Col. Vergel-Coapa, México, 14320 DF, México. Email: [email protected]
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have been extensively discussed.2,3,8-24 The most accepted theory suggests ischemia as the main etiologic factor. Age range in NSM patients varies from 1.5 years to 83 years with a mean of 46.2 years and an age peak among the fourth and fifth decades.3 Males are more commonly affected, with a male-female ratio of 1.95:1,10 and size varies from 0.5 cm to 4.0 cm.25
CASE REPORT A 37-year-old man was first reviewed in a dental office. He sought advice for the presence of two ulcerated, rapidly growing palatal lesions. The dentist told him that probably it was a malignant lesion, maybe a carcinoma, because the clinical features strongly suggested this diagnosis: sudden apparition, very fast growth, and ulcerated aspect of both lesions. A clinical photograph was taken and the patient made an appointment at the Oral Diagnosis Service of the Facultad de Odontología,
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Fig 1a Two large asymptomatic ulcers in the soft and hard palate are observed.
Fig 1b A hyperplastic squamous epithelium with acantosis, parakeratosis, and a nonkeratinized area is seen. Subepithelial chronic inflammatory reaction is also observed (H&E, 100× magnification).
Fig 1c Photomicrograph showing necrotic glandular tissue (H&E, 200× magnification).
Fig 1d Photomicrograph showing islands of metaplastic keratinized squamous epithelium. Clearly, some of them are ducts with squamous metaplasia (H&E, 200× magnification).
UNAM (México City), in order to obtain a more accurate diagnosis and treatment. The patient attended our institution the next day, and clinical review disclosed the presence of two asymptomatic, well-defined ulcers on the hard and soft palate. They presented slightly elevated and erythematous borders and measured 1.5 × 3.0 cm and 5.6 × 3.8 cm approximately. Thick grayish-white membranes composed of necrotic debris covered the ulcers (Fig 1a), with no bone involvement under palatal pseudomembranes. The patient reported that the lesions suddenly appeared during the previous night without pain or discomfort. He denied tobacco or drug habits, but he did occasionally consume alcohol and reported that no traumatic episodes had occurred recently in the involved area. The patient reported that no preceding
swelling was observed and his clinical history was noncontributory. Panoramic and occlusal radiographs were taken and review of this material confirmed that no bone involvement was present behind the ulcers. A clinical diagnosis of bilateral necrotizing sialometaplasia was made, but differential diagnoses included syphilis and tuberculosis. Under regional anesthesia, an incisional biopsy measuring 2.2 × 2.2 cm was taken from the right ulcer; it was immersed in buffered formalin and sent to the Oral Pathology Laboratory. The surgical field was carefully cleansed and sutured and the patient was discharged with analgesic and antibiotic coverage. In the laboratory, the excised tissue was routinely processed to obtain 5-μm thick, paraffin-embedded, hematoxylineosin (H&E)-stained slides. Microscopic review revealed
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Fig 2a Day 7: Clinical view before elimination of sutures.
Fig 2b Day 15: Some signs of repair are seen.
Fig 2c Day 30: Lesions are decreasing in size.
Fig 2d At 2 months, ulcers are clearly smaller.
Fig 3a Photograph at 4 months: a different clinical picture is seen.
Fig 3b Photograph at 6 months. The left side shows no changes, and at the right side two nodules are observed.
Fig 3c Clinical view at the 1-year follow-up. Slightly irregular cicatrization of the lesions is seen.
Fig 3d Appearance of the lesions after 2 years. Complete cicatrization has taken place.
the presence of hyperplastic stratified squamous epithelium with long rete ridges and pseudoepitheliomatous hyperplasia (Fig 1b). In other areas, an ulcerated zone covered by a fibrino-purulent membrane was identified. The bulk of the lesion was composed of numerous lobules of necrotic mucous-secreting glandular tissue (Fig 1c) with some nidus composed of metaplastic squamous epithelial cells deriving from the ductual epithelium (Fig 1d). No neoplastic changes were observed. Serologic tests discarded syphilis and tuberculosis. One week later, sutures were removed and it was observed that new fibrinoid pseudomembranes covered both ulcers (Fig 2a). At day 15, initial signs of repair were clearly seen. Comparing their size at day 7, both ulcers were slightly smaller and the covering fibrinoid membranes were thinner and almost absent. At this moment and despite the ulcers appearing to be smaller-sized, it was apparent that left side ulcer crossed the middle line increasing its posterior diameter and that right ulcer showed better healing than the left one (Fig 2b). Figure 2c shows that 1 month later, both ulcers clearly decreased in size to approximately
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half of their original size, and missing pseudomembranes were being replaced by a pink, soft, thin, and painful tissue. The right ulcer almost disappeared and in this moment only a small orifice remained. In the clinical review conducted 2 months after the first examination, it was clear that healing of the lesions improved; the left ulcer almost disappeared and the right ulcer was clearly smaller (Fig 2d). Three months from first appointment, a small nodule was observed in place of the left ulcer and a small depression covered with thin epithelium was observed in place of the right ulcer. Four months later, no changes were seen at the left side, but in the right side, two slightly erythematous nodules were found replacing the ulcer (Fig 3a). After 6 months, appearance of the involved areas showed that irregular healing of the lesions occurred (Fig 3b). One year layer it was seen that complete healing was achieved and that only very slight irregularities were observed on the palatal surface (Fig 3c). Two years later, complete cicatrization of the involved tissue was achieved (Fig 3d). The patient presented no new lesions after 12 years’ follow-up.
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DISCUSSION NSM is an uncommon self-limiting lesion commonly confused with malignant epithelial neoplasms. Despite having been recognized by Abrams et al1 in 1973 and with numerous intraoral and extraoral cases reported,1-40 no agreement on the etiology for NSM development has been reached to date. Most authors sustain that some kind of physical-chemical or biological aggressions over the local blood vessels will produce ischemic changes, leading to infarction with posterior necrosis, and that NSM is the ductal proliferation in response to injury.2,8,20,21 Many causes have been suggested as possible etiologic factors including: traumatic, chemical, surgical, and infectious events including alcohol, smoking, and drug abuse.3,10,12-16,22-24 In other instances, some diseases characterized by vascular disturbances have been associated with NSM, supporting the theory that ischemic necrosis is the main etiologic factor.17-19 In 1982, Anneroth and Hansen26 analyzed its histopathogenesis and separated NSM into five microscopic stages: infarction, sequestration, ulceration, reparative stage, and healing. This entity is more frequently found in palate, although it has been also described in other intraoral locations: retromolar area, labial glands, tongue, floor of the mouth, buccal mucosa, mucobuccal fold, sublingual region, and it was also found in parotid and submandibular glands.3,4,8-10 Also, NSM cases were reported in the head and neck area: nasal cavity, maxillary sinus, tonsillar fossa, incisive canal, larynx, trachea, and lymph nodes.3,5,6,9,15,27-31 The most commonly observed clinical feature is a palatal, painful or painless, deep seated ulcer with clean, sharp, and sometimes erythematous or rolled margins, measuring from 1 cm to 3.5 cm. Other symptoms are somewhat variable: fever, chills, malaise, anesthesia, and paresthesia, and rarely NSM is found as a nonulcerative, purulent, diffuse lesion with palpable lymph nodes.3,10,12-14,32 Our case is unique since one of the lesions measured almost 6 cm. The presence of a unique lesion is the most frequent clinical manifestation of NSM, but as it is in the case presented here, sometimes two lesions are present.3,14 Another three
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rare and unique cases have been reported: one with three ulcers, one with multiple palatal ulcerated lesions, and one with metachronous lesions.11,13,32 Also, several cases with one or two palatal asymptomatic, painless, smooth-surfaced nodules of normal color were reported.8,11,14,18,23 Duration of the lesion varies from 3 weeks to 3 months.33 It is well known that almost all studied NSM cases did not display radiographic alterations, but saucerization of the subjacent bone was observed in four reported cases.1,3,11 Some studies of the features of NSM using magnetic resonance (MR) analysis34-36 showed this lesion was hyperintense on T2 and hypointense on T1.34 Lee et al35 reported that under MRI scan, a NSM case associated with an adenoid cystic carcinoma presented a diffuse infiltrating image suggestive of a malignant lesion, and a multislice computed tomographic study showed no bone changes.36 It is essential that the pathologist should receive an adequate biopsy specimen in order to observe all the diagnostic microscopic changes. Under microscopic examination, the lesion is usually covered by hyperplastic squamous stratified epithelium showing elongated epithelial ridges (pseudoepitheliomatous hyperplasia). A very important finding is the acinar necrosis featured by disintegration of the mucus-secreting acinar cells with persistence of the acinar outlines accompanied by spaces filled with mucin, cellular debris, and inflammatory infiltrate of variable intensity composed by polymorphonuclear neutrophilic leukocytes, plasma cells, foamy macrophages, and numerous eosinophils. The most prominent and important diagnostic feature is the presence of ductal squamous metaplasia. It is characterized by a squamous change in the cell lining of the gland ducts. These squamous cells proliferate, and this proliferating lining obliterates the lumen, transforming the ducts into solid masses or nidus of squamous stratified epithelial cells showing eosinophilic cytoplasm with uniform and bland nuclei. It is important to note that mitotic cells are scarce, and of normal appearance with no atypical features. These solid squamous epithelial masses are often observed close to or continuous with the enlarged rete pegs of
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the superficial epithelium. This finding is suggestive of malignancy and may lead to the common misdiagnosis of squamous cell carcinoma.25 These epithelial nodular masses are present in variable sizes and number, show smooth outlines, and sometimes are complemented with areas of more or less extensive reactive fibrosis. Sometimes, microscopic features of NSM may lead to a diagnostic pitfall of chronic sialadenitis or degenerative age changes. Occasionally, lesions in poorly controlled diabetic patients with mucormycosis may mimic NSM and should not be confused with the so-called sialometaplasia.26,30 Microscopic differential diagnosis should be performed with subacute necrotizing sialadenitis, Sutton disease, syphilis, and tuberculosis.38 The use of immunohistochemistry may help to distinguish mucoepidermoid carcinoma from NSM lesions.33 Lesions with similar microscopic appearance have been reported in non-neoplastic breast parenchyma, bronchial mucosa, lung, and sweat glands,27-30 and there are several reports on malignant and benign tumors associated to NSM lesions,3,6,34,36,39,40 indicating that NSM could develop as a secondary phenomenon. NSM requires no treatment since ulcers or nodular lesions will heal within the following weeks, and it is important to point out that after the initial biopsy for diagnosis, no surgical procedure should be conducted. Recently, 10 mg of intralesional triamcinolone was applied without success,14 and there is general agreement that incisional biopsy is enough and that NSM lesions will resolve spontaneously by secondary intention during the following 3 to 12 weeks.33 Recurrence of NSM is an exceedingly rare event and only one welldocumented case about presentation of new lesions has been reported.7 It is important to recognize NSM in the tissue from the incisional biopsy since several reports of inadequate and excessive treatment such as wide excision, maxillectomy, or hemimaxillectomy7,9,16,20,25 have been published, and unfortunately the final diagnosis of NSM was reached on reappraisal of the original slides or during the examination of the whole operative specimen.2,9
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Sufficient data on long-term follow-up of NSM lesions is not available to date. In this manuscript we present the clinical features observed during the longterm follow-up in a patient. As seen in Fig 2, short-term follow-up of the NSM lesions shows that healing comprises epithelial coverage of the ulcerated area, and replacement of the necrotic tissue occurs with decreasing size of the lesions. Figure 3a shows that 4 months later the ulcers completely disappeared. At the 6-month follow-up, small nodules appeared in place of the ulcers, and 2 years later, remodeling of the zone occurred. The images show that clinical appearance of the affected zone at long-term follow-up corresponded to remodeling and that connective tissue resorption and formation are the main phenomena.
REFERENCES 1. Abrams AM, Melrose RJ, Howell FV. Necrotizing sialometaplasia. A disease simulating malignancy. Cancer 1973;32:130–135. 2. Dunlap LL, Barker BF. Necrotizing sialometaplasia. Oral Surg 1974;37:722–727. 3. Brannon RB, Fowler CB, Hartman KS. Necrotizing sialometaplasia. A clinicopathologic study of sixty-nine cases and review of the literature. Oral Surg Oral Med Oral Pathol 1991;72:317–325. 4. Russo A, Dell’Aquila A, Prota V, Sica GS. Necrotizing sialometaplasia of the submandibular gland. Report of a case. Minerva Stomatol 1998;47:273–277. 5. Ravn T, Trolle W, Kiss K, Balle VH. Adenosquamous carcinoma of the larynx associated with necrotizing sialometaplasia: a diagnostic challenge. Auris Nasus Larynx 2009;36:721–724. 6. Poulson TC, Greer RO Jr, Ryser RW. Necrotizing sialometaplasia obscuring an underlying malignancy: report of a case. J Oral Maxillofac Surg 1986;44:570–574. 7. Arguelles MT, Viloria JB Jr, Talens MC, McCory TP. Necrotizing sialometaplasia. Oral Surg Oral Med Oral Pathol 1976;42:86–90. 8. Lima MA, Rocha LC, Siqueira LMS, Carmo LC, Filho JH. Cystic form of necrotizing sialometaplasia in sublingual salivary gland. Rev Bras Otorrinolaringol 2002;6:276–279. 9. Maisel RH, Johnston WH, Anderson HA, Cantrell RW. Necrotizing sialometaplasia involving the nasal cavity. Laryngoscope 1977;87:429–424. 10. Randhawa T, Varghese I, Shameena P, Sudha S, Nair RG. Necrotizing sialometaplasia of tongue. J Oral Maxillofac Pathol 2009;13:35–37. 11. Imbery TA, Edwards PA. Necrotizing sialometaplasia: literature review and case reports. J Am Dent Assoc 1996;127:1087–1092. 12. Santis HR, Kabani SP, Roderiques A, Driscoll JM. Necrotizing sialometaplasia: an early, nonulcerative presentation. Oral Surg Oral Med Oral Pathol 1982;53:387–390. 13. Speechley JA, Field EA, Scott J. Necrotizing sialometaplasia occurring during pregnancy: report of a case. J Oral Maxillofac Surg 1988;46:696–699. 14. Keogh PV, O’Regan E, Toner M, Flint S. Necrotizing sialometaplasia: an unusual bilateral presentation associated with antecedent anaesthesia and lack of response to intralesional steroids. Case report and review of the literature. Br Dent J 2004;196:79–81. 15. Romagosa V, Bella MR, Truchero C, Moya J. Necrotizing sialometaplasia (adenometaplasia) of the trachea. Histopathology 1992;21:280–282. 16. Batsakis JG, Manning JT. Necrotizing sialometaplasia of major salivary glands. J Laryngol Otol 1987;101:962–966.
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17. Buller DL. Nodular and ulcerated lesions of the hard palate. J Am Dent Assoc 1980;101:823–824. 18. Lynch DP, Crago CA, Martinez MG Jr. Necrotizing sialometaplasia. A review of the literature and report of two additional cases. Oral Surg Oral Med Oral Pathol 1979;47:63–69. 19. Mandel L, Kaynar A, DeChiara S. Necrotizing sialometaplasia in a patient with sickle-cell anemia. J Oral Maxillofac Surg 1991;49:757–759. 20. Johnston WH. Necrotizing sialometaplasia involving the mucous glands of the nasal cavity. Hum Pathol 1977;8:589–592. 21. Suckiel JM, Davis WH, Patakas BM, Kaminishi RM. Early and late manifestations of necrotizing sialometaplasia. J Oral Surg 1978;36:902–905. 22. Solomon LW, Merzianu M, Sullivan M, Rigual NR. Necrotizing sialometaplasia associated with bulimia: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:39–42. 23. Prabhakaran VC, Flora RS, Kendall C. Pressure-induced necrotizing sialometaplasia of the parotid gland. Histopathology 2005;48:464–465. 24. Fava M, Cherubini K, Yurgel L, Salum F, Figueiredo MA. Necrotizing sialometaplasia of the palate in a cocaine-using patient. A case report. Minerva Stomatol 2008;57:199–202. 25. Grillon GL, Lally ET. Necrotizing sialometaplasia: literature review and presentation of five cases. J Oral Surg 1981;39:747–753. 26. Anneroth G, Hansen LS. Necrotizing sialometaplasia. The relationship of its pathogenesis to its clinical characteristics. Int J Oral Surg 1982;11:283–291. 27. Goldman RL, Klein HZ. Proliferative sialometaplasia arising in an intraparotid lymph node. Am J Clin Pathol 1986;86:116–119. 28. Hurt MA, Díaz-Arias AA, Rosenholtz MJ, Havey AD, Stephenson HE Jr. Posttraumatic lobular squamous metaplasia of breast. An unusual pseudocarcinomatous metaplasia resembling squamous (necrotizing) sialometaplasia of the salivary gland. Mod Pathol 1988;1:385–390.
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29. Pagni F, Zàrate AF, Urbanski SJ. Necrotizing sialometaplasia of bronchial mucosa. Int J Surg Pathol 2010;18:64–65. 30. Zschoch H. Mucus gland infarct with squamous epithelial metaplasia in the lung. A rare site of so-called necrotizing sialometaplasia. Pathologe 1992;13:45–48. 31. King DT, Barr RJ. Syringometaplasia: mucinous and squamous variants. J Cutan Pathol 1979;6:284–291. 32. Rossie KM, Allen CM, Burns RA. Necrotizing sialometaplasia: a case with metachronous lesions. J Oral Maxillofac Surg 1986;44:1006–1008. 33. Rizkalla H, Toner M. Necrotizing sialometaplasia versus invasive carcinoma of the head and neck: the use of myoepithelial markers and keratin subtypes as an adjunct to diagnosis. Histopathology 2007;51:184–189. 34. Farina D, Gavazzi E, Avigo C, Borghesi A, Maroldi R. Case report. MRI findings of necrotizing sialometaplasia. Br J Radiol 2008;81:173–175. 35. Lee DJ, Ahn HK, Koh ES, Rho YS, Chu HR. Necrotizing sialometaplasia accompanied by adenoid cystic carcinoma on the soft palate. Clin Exp Otorhinolaryngol 2009;2:48–51. 36. Suomalainen A, Törnwall J, Hagström J. CT findings of necrotizing sialometaplasia. Dentomaxillofacial Radiol 2012;41:529–532. 37. Gnepp DR. Warthin tumor exhibiting sebaceous differentiation and necrotizing sialometaplasia. Virchows Arch A Pathol Anat Histol 1981;391:267–273. 38. Libero-Femopase F, Hernandez SL, Gendelman H, Criscuolo MI, de Blanc SAL. Sialometaplasia necrotizante: Presentación de cinco casos. Clínicos. Med Oral Patol Oral Cir Bucal 2004;9:304–308. 39. Wenig BM. Necrotizing sialometaplasia of the larynx. A report of two cases and a review of the literature. Am J Clin Pathol 1995;103:609–613. 40. Franchi A, Gallo O, Santucci M. Pathologic quiz case 1. Necrotizing sialometaplasia obscuring recurrent well-differentiated squamous cell carcinoma of the maxillary sinus. Arch Otolaryngol Head Neck Surg 1995;121:584–586.
VOLUME 46 • NUMBER 1 • JANUARY 2015
ORAL MEDICINE
Constantino Ledesma-Montes
Review of the literature on necrotizing sialometaplasia and case presentation Constantino Ledesma-Montes, DDS, MSc, PhD 1/Maricela Garcés-Ortíz, DDS, MSc, PhD1/ Juan Francisco Salcido-García, DDS, MSc 2/Florentino Hernández-Flores, DDS, MSc 3 The aim of this article is to report a case of necrotizing sialometaplasia with long-term follow-up. A case of necrotizing sialometaplasia in a 37-year-old man with clinical documentation on the progress during a 2-year follow-up is presented. Data from an extensive review of the literature including clinical, imagenologic, and microscopic features are provided. Information on diagnostic and prognostic factors is offered and comprehensibly discussed. The importance of identification
and diagnosis of this entity during the review of the slides from the first biopsy is stressed and the exclusive performance of an incisional biopsy is debated. The presented clinical photographs reveal the clinical changes of the lesion from the beginning of the lesions up to 2 years follow-up, documenting the complete long-term clinical course and the healing process of this entity. (Quintessence Int 2015;46:67–72; doi: 10.3290/j. qi.a32633)
Key words: necrotizing sialometaplasia, oral squamous cell carcinoma, salivary gland lesions, salivary glands
Necrotizing sialometaplasia (NSM) is an uncommon self-limiting lesion commonly confused with malignant epithelial entities. NSM was first described by Abrams et al in 19731 and in 1974 it was again reported by Dunlap and Barker.2 Afterwards, Brannon et al,3 using data from their own cases and a review of the literature, described extensively its clinicopathologic features. During the following years, this entity has been found in different locations,4-8 and since the Abrams et al first description, the associated etiologic factors of NSM 1
Full-time Professor, Oral Pathology Laboratory, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, México.
2
Full-time Professor, Oral Diagnosis Clinic, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, México.
3
Professor, Oral Surgery Clinic, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, México.
Correspondence: Professor Constantino Ledesma-Montes, Ciprés #169-2, Col. Vergel-Coapa, México, 14320 DF, México. Email: [email protected]
VOLUME 46 • NUMBER 1 • JANUARY 2015
have been extensively discussed.2,3,8-24 The most accepted theory suggests ischemia as the main etiologic factor. Age range in NSM patients varies from 1.5 years to 83 years with a mean of 46.2 years and an age peak among the fourth and fifth decades.3 Males are more commonly affected, with a male-female ratio of 1.95:1,10 and size varies from 0.5 cm to 4.0 cm.25
CASE REPORT A 37-year-old man was first reviewed in a dental office. He sought advice for the presence of two ulcerated, rapidly growing palatal lesions. The dentist told him that probably it was a malignant lesion, maybe a carcinoma, because the clinical features strongly suggested this diagnosis: sudden apparition, very fast growth, and ulcerated aspect of both lesions. A clinical photograph was taken and the patient made an appointment at the Oral Diagnosis Service of the Facultad de Odontología,
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Fig 1a Two large asymptomatic ulcers in the soft and hard palate are observed.
Fig 1b A hyperplastic squamous epithelium with acantosis, parakeratosis, and a nonkeratinized area is seen. Subepithelial chronic inflammatory reaction is also observed (H&E, 100× magnification).
Fig 1c Photomicrograph showing necrotic glandular tissue (H&E, 200× magnification).
Fig 1d Photomicrograph showing islands of metaplastic keratinized squamous epithelium. Clearly, some of them are ducts with squamous metaplasia (H&E, 200× magnification).
UNAM (México City), in order to obtain a more accurate diagnosis and treatment. The patient attended our institution the next day, and clinical review disclosed the presence of two asymptomatic, well-defined ulcers on the hard and soft palate. They presented slightly elevated and erythematous borders and measured 1.5 × 3.0 cm and 5.6 × 3.8 cm approximately. Thick grayish-white membranes composed of necrotic debris covered the ulcers (Fig 1a), with no bone involvement under palatal pseudomembranes. The patient reported that the lesions suddenly appeared during the previous night without pain or discomfort. He denied tobacco or drug habits, but he did occasionally consume alcohol and reported that no traumatic episodes had occurred recently in the involved area. The patient reported that no preceding
swelling was observed and his clinical history was noncontributory. Panoramic and occlusal radiographs were taken and review of this material confirmed that no bone involvement was present behind the ulcers. A clinical diagnosis of bilateral necrotizing sialometaplasia was made, but differential diagnoses included syphilis and tuberculosis. Under regional anesthesia, an incisional biopsy measuring 2.2 × 2.2 cm was taken from the right ulcer; it was immersed in buffered formalin and sent to the Oral Pathology Laboratory. The surgical field was carefully cleansed and sutured and the patient was discharged with analgesic and antibiotic coverage. In the laboratory, the excised tissue was routinely processed to obtain 5-μm thick, paraffin-embedded, hematoxylineosin (H&E)-stained slides. Microscopic review revealed
68
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Fig 2a Day 7: Clinical view before elimination of sutures.
Fig 2b Day 15: Some signs of repair are seen.
Fig 2c Day 30: Lesions are decreasing in size.
Fig 2d At 2 months, ulcers are clearly smaller.
Fig 3a Photograph at 4 months: a different clinical picture is seen.
Fig 3b Photograph at 6 months. The left side shows no changes, and at the right side two nodules are observed.
Fig 3c Clinical view at the 1-year follow-up. Slightly irregular cicatrization of the lesions is seen.
Fig 3d Appearance of the lesions after 2 years. Complete cicatrization has taken place.
the presence of hyperplastic stratified squamous epithelium with long rete ridges and pseudoepitheliomatous hyperplasia (Fig 1b). In other areas, an ulcerated zone covered by a fibrino-purulent membrane was identified. The bulk of the lesion was composed of numerous lobules of necrotic mucous-secreting glandular tissue (Fig 1c) with some nidus composed of metaplastic squamous epithelial cells deriving from the ductual epithelium (Fig 1d). No neoplastic changes were observed. Serologic tests discarded syphilis and tuberculosis. One week later, sutures were removed and it was observed that new fibrinoid pseudomembranes covered both ulcers (Fig 2a). At day 15, initial signs of repair were clearly seen. Comparing their size at day 7, both ulcers were slightly smaller and the covering fibrinoid membranes were thinner and almost absent. At this moment and despite the ulcers appearing to be smaller-sized, it was apparent that left side ulcer crossed the middle line increasing its posterior diameter and that right ulcer showed better healing than the left one (Fig 2b). Figure 2c shows that 1 month later, both ulcers clearly decreased in size to approximately
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half of their original size, and missing pseudomembranes were being replaced by a pink, soft, thin, and painful tissue. The right ulcer almost disappeared and in this moment only a small orifice remained. In the clinical review conducted 2 months after the first examination, it was clear that healing of the lesions improved; the left ulcer almost disappeared and the right ulcer was clearly smaller (Fig 2d). Three months from first appointment, a small nodule was observed in place of the left ulcer and a small depression covered with thin epithelium was observed in place of the right ulcer. Four months later, no changes were seen at the left side, but in the right side, two slightly erythematous nodules were found replacing the ulcer (Fig 3a). After 6 months, appearance of the involved areas showed that irregular healing of the lesions occurred (Fig 3b). One year layer it was seen that complete healing was achieved and that only very slight irregularities were observed on the palatal surface (Fig 3c). Two years later, complete cicatrization of the involved tissue was achieved (Fig 3d). The patient presented no new lesions after 12 years’ follow-up.
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DISCUSSION NSM is an uncommon self-limiting lesion commonly confused with malignant epithelial neoplasms. Despite having been recognized by Abrams et al1 in 1973 and with numerous intraoral and extraoral cases reported,1-40 no agreement on the etiology for NSM development has been reached to date. Most authors sustain that some kind of physical-chemical or biological aggressions over the local blood vessels will produce ischemic changes, leading to infarction with posterior necrosis, and that NSM is the ductal proliferation in response to injury.2,8,20,21 Many causes have been suggested as possible etiologic factors including: traumatic, chemical, surgical, and infectious events including alcohol, smoking, and drug abuse.3,10,12-16,22-24 In other instances, some diseases characterized by vascular disturbances have been associated with NSM, supporting the theory that ischemic necrosis is the main etiologic factor.17-19 In 1982, Anneroth and Hansen26 analyzed its histopathogenesis and separated NSM into five microscopic stages: infarction, sequestration, ulceration, reparative stage, and healing. This entity is more frequently found in palate, although it has been also described in other intraoral locations: retromolar area, labial glands, tongue, floor of the mouth, buccal mucosa, mucobuccal fold, sublingual region, and it was also found in parotid and submandibular glands.3,4,8-10 Also, NSM cases were reported in the head and neck area: nasal cavity, maxillary sinus, tonsillar fossa, incisive canal, larynx, trachea, and lymph nodes.3,5,6,9,15,27-31 The most commonly observed clinical feature is a palatal, painful or painless, deep seated ulcer with clean, sharp, and sometimes erythematous or rolled margins, measuring from 1 cm to 3.5 cm. Other symptoms are somewhat variable: fever, chills, malaise, anesthesia, and paresthesia, and rarely NSM is found as a nonulcerative, purulent, diffuse lesion with palpable lymph nodes.3,10,12-14,32 Our case is unique since one of the lesions measured almost 6 cm. The presence of a unique lesion is the most frequent clinical manifestation of NSM, but as it is in the case presented here, sometimes two lesions are present.3,14 Another three
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rare and unique cases have been reported: one with three ulcers, one with multiple palatal ulcerated lesions, and one with metachronous lesions.11,13,32 Also, several cases with one or two palatal asymptomatic, painless, smooth-surfaced nodules of normal color were reported.8,11,14,18,23 Duration of the lesion varies from 3 weeks to 3 months.33 It is well known that almost all studied NSM cases did not display radiographic alterations, but saucerization of the subjacent bone was observed in four reported cases.1,3,11 Some studies of the features of NSM using magnetic resonance (MR) analysis34-36 showed this lesion was hyperintense on T2 and hypointense on T1.34 Lee et al35 reported that under MRI scan, a NSM case associated with an adenoid cystic carcinoma presented a diffuse infiltrating image suggestive of a malignant lesion, and a multislice computed tomographic study showed no bone changes.36 It is essential that the pathologist should receive an adequate biopsy specimen in order to observe all the diagnostic microscopic changes. Under microscopic examination, the lesion is usually covered by hyperplastic squamous stratified epithelium showing elongated epithelial ridges (pseudoepitheliomatous hyperplasia). A very important finding is the acinar necrosis featured by disintegration of the mucus-secreting acinar cells with persistence of the acinar outlines accompanied by spaces filled with mucin, cellular debris, and inflammatory infiltrate of variable intensity composed by polymorphonuclear neutrophilic leukocytes, plasma cells, foamy macrophages, and numerous eosinophils. The most prominent and important diagnostic feature is the presence of ductal squamous metaplasia. It is characterized by a squamous change in the cell lining of the gland ducts. These squamous cells proliferate, and this proliferating lining obliterates the lumen, transforming the ducts into solid masses or nidus of squamous stratified epithelial cells showing eosinophilic cytoplasm with uniform and bland nuclei. It is important to note that mitotic cells are scarce, and of normal appearance with no atypical features. These solid squamous epithelial masses are often observed close to or continuous with the enlarged rete pegs of
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the superficial epithelium. This finding is suggestive of malignancy and may lead to the common misdiagnosis of squamous cell carcinoma.25 These epithelial nodular masses are present in variable sizes and number, show smooth outlines, and sometimes are complemented with areas of more or less extensive reactive fibrosis. Sometimes, microscopic features of NSM may lead to a diagnostic pitfall of chronic sialadenitis or degenerative age changes. Occasionally, lesions in poorly controlled diabetic patients with mucormycosis may mimic NSM and should not be confused with the so-called sialometaplasia.26,30 Microscopic differential diagnosis should be performed with subacute necrotizing sialadenitis, Sutton disease, syphilis, and tuberculosis.38 The use of immunohistochemistry may help to distinguish mucoepidermoid carcinoma from NSM lesions.33 Lesions with similar microscopic appearance have been reported in non-neoplastic breast parenchyma, bronchial mucosa, lung, and sweat glands,27-30 and there are several reports on malignant and benign tumors associated to NSM lesions,3,6,34,36,39,40 indicating that NSM could develop as a secondary phenomenon. NSM requires no treatment since ulcers or nodular lesions will heal within the following weeks, and it is important to point out that after the initial biopsy for diagnosis, no surgical procedure should be conducted. Recently, 10 mg of intralesional triamcinolone was applied without success,14 and there is general agreement that incisional biopsy is enough and that NSM lesions will resolve spontaneously by secondary intention during the following 3 to 12 weeks.33 Recurrence of NSM is an exceedingly rare event and only one welldocumented case about presentation of new lesions has been reported.7 It is important to recognize NSM in the tissue from the incisional biopsy since several reports of inadequate and excessive treatment such as wide excision, maxillectomy, or hemimaxillectomy7,9,16,20,25 have been published, and unfortunately the final diagnosis of NSM was reached on reappraisal of the original slides or during the examination of the whole operative specimen.2,9
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Sufficient data on long-term follow-up of NSM lesions is not available to date. In this manuscript we present the clinical features observed during the longterm follow-up in a patient. As seen in Fig 2, short-term follow-up of the NSM lesions shows that healing comprises epithelial coverage of the ulcerated area, and replacement of the necrotic tissue occurs with decreasing size of the lesions. Figure 3a shows that 4 months later the ulcers completely disappeared. At the 6-month follow-up, small nodules appeared in place of the ulcers, and 2 years later, remodeling of the zone occurred. The images show that clinical appearance of the affected zone at long-term follow-up corresponded to remodeling and that connective tissue resorption and formation are the main phenomena.
REFERENCES 1. Abrams AM, Melrose RJ, Howell FV. Necrotizing sialometaplasia. A disease simulating malignancy. Cancer 1973;32:130–135. 2. Dunlap LL, Barker BF. Necrotizing sialometaplasia. Oral Surg 1974;37:722–727. 3. Brannon RB, Fowler CB, Hartman KS. Necrotizing sialometaplasia. A clinicopathologic study of sixty-nine cases and review of the literature. Oral Surg Oral Med Oral Pathol 1991;72:317–325. 4. Russo A, Dell’Aquila A, Prota V, Sica GS. Necrotizing sialometaplasia of the submandibular gland. Report of a case. Minerva Stomatol 1998;47:273–277. 5. Ravn T, Trolle W, Kiss K, Balle VH. Adenosquamous carcinoma of the larynx associated with necrotizing sialometaplasia: a diagnostic challenge. Auris Nasus Larynx 2009;36:721–724. 6. Poulson TC, Greer RO Jr, Ryser RW. Necrotizing sialometaplasia obscuring an underlying malignancy: report of a case. J Oral Maxillofac Surg 1986;44:570–574. 7. Arguelles MT, Viloria JB Jr, Talens MC, McCory TP. Necrotizing sialometaplasia. Oral Surg Oral Med Oral Pathol 1976;42:86–90. 8. Lima MA, Rocha LC, Siqueira LMS, Carmo LC, Filho JH. Cystic form of necrotizing sialometaplasia in sublingual salivary gland. Rev Bras Otorrinolaringol 2002;6:276–279. 9. Maisel RH, Johnston WH, Anderson HA, Cantrell RW. Necrotizing sialometaplasia involving the nasal cavity. Laryngoscope 1977;87:429–424. 10. Randhawa T, Varghese I, Shameena P, Sudha S, Nair RG. Necrotizing sialometaplasia of tongue. J Oral Maxillofac Pathol 2009;13:35–37. 11. Imbery TA, Edwards PA. Necrotizing sialometaplasia: literature review and case reports. J Am Dent Assoc 1996;127:1087–1092. 12. Santis HR, Kabani SP, Roderiques A, Driscoll JM. Necrotizing sialometaplasia: an early, nonulcerative presentation. Oral Surg Oral Med Oral Pathol 1982;53:387–390. 13. Speechley JA, Field EA, Scott J. Necrotizing sialometaplasia occurring during pregnancy: report of a case. J Oral Maxillofac Surg 1988;46:696–699. 14. Keogh PV, O’Regan E, Toner M, Flint S. Necrotizing sialometaplasia: an unusual bilateral presentation associated with antecedent anaesthesia and lack of response to intralesional steroids. Case report and review of the literature. Br Dent J 2004;196:79–81. 15. Romagosa V, Bella MR, Truchero C, Moya J. Necrotizing sialometaplasia (adenometaplasia) of the trachea. Histopathology 1992;21:280–282. 16. Batsakis JG, Manning JT. Necrotizing sialometaplasia of major salivary glands. J Laryngol Otol 1987;101:962–966.
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17. Buller DL. Nodular and ulcerated lesions of the hard palate. J Am Dent Assoc 1980;101:823–824. 18. Lynch DP, Crago CA, Martinez MG Jr. Necrotizing sialometaplasia. A review of the literature and report of two additional cases. Oral Surg Oral Med Oral Pathol 1979;47:63–69. 19. Mandel L, Kaynar A, DeChiara S. Necrotizing sialometaplasia in a patient with sickle-cell anemia. J Oral Maxillofac Surg 1991;49:757–759. 20. Johnston WH. Necrotizing sialometaplasia involving the mucous glands of the nasal cavity. Hum Pathol 1977;8:589–592. 21. Suckiel JM, Davis WH, Patakas BM, Kaminishi RM. Early and late manifestations of necrotizing sialometaplasia. J Oral Surg 1978;36:902–905. 22. Solomon LW, Merzianu M, Sullivan M, Rigual NR. Necrotizing sialometaplasia associated with bulimia: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:39–42. 23. Prabhakaran VC, Flora RS, Kendall C. Pressure-induced necrotizing sialometaplasia of the parotid gland. Histopathology 2005;48:464–465. 24. Fava M, Cherubini K, Yurgel L, Salum F, Figueiredo MA. Necrotizing sialometaplasia of the palate in a cocaine-using patient. A case report. Minerva Stomatol 2008;57:199–202. 25. Grillon GL, Lally ET. Necrotizing sialometaplasia: literature review and presentation of five cases. J Oral Surg 1981;39:747–753. 26. Anneroth G, Hansen LS. Necrotizing sialometaplasia. The relationship of its pathogenesis to its clinical characteristics. Int J Oral Surg 1982;11:283–291. 27. Goldman RL, Klein HZ. Proliferative sialometaplasia arising in an intraparotid lymph node. Am J Clin Pathol 1986;86:116–119. 28. Hurt MA, Díaz-Arias AA, Rosenholtz MJ, Havey AD, Stephenson HE Jr. Posttraumatic lobular squamous metaplasia of breast. An unusual pseudocarcinomatous metaplasia resembling squamous (necrotizing) sialometaplasia of the salivary gland. Mod Pathol 1988;1:385–390.
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29. Pagni F, Zàrate AF, Urbanski SJ. Necrotizing sialometaplasia of bronchial mucosa. Int J Surg Pathol 2010;18:64–65. 30. Zschoch H. Mucus gland infarct with squamous epithelial metaplasia in the lung. A rare site of so-called necrotizing sialometaplasia. Pathologe 1992;13:45–48. 31. King DT, Barr RJ. Syringometaplasia: mucinous and squamous variants. J Cutan Pathol 1979;6:284–291. 32. Rossie KM, Allen CM, Burns RA. Necrotizing sialometaplasia: a case with metachronous lesions. J Oral Maxillofac Surg 1986;44:1006–1008. 33. Rizkalla H, Toner M. Necrotizing sialometaplasia versus invasive carcinoma of the head and neck: the use of myoepithelial markers and keratin subtypes as an adjunct to diagnosis. Histopathology 2007;51:184–189. 34. Farina D, Gavazzi E, Avigo C, Borghesi A, Maroldi R. Case report. MRI findings of necrotizing sialometaplasia. Br J Radiol 2008;81:173–175. 35. Lee DJ, Ahn HK, Koh ES, Rho YS, Chu HR. Necrotizing sialometaplasia accompanied by adenoid cystic carcinoma on the soft palate. Clin Exp Otorhinolaryngol 2009;2:48–51. 36. Suomalainen A, Törnwall J, Hagström J. CT findings of necrotizing sialometaplasia. Dentomaxillofacial Radiol 2012;41:529–532. 37. Gnepp DR. Warthin tumor exhibiting sebaceous differentiation and necrotizing sialometaplasia. Virchows Arch A Pathol Anat Histol 1981;391:267–273. 38. Libero-Femopase F, Hernandez SL, Gendelman H, Criscuolo MI, de Blanc SAL. Sialometaplasia necrotizante: Presentación de cinco casos. Clínicos. Med Oral Patol Oral Cir Bucal 2004;9:304–308. 39. Wenig BM. Necrotizing sialometaplasia of the larynx. A report of two cases and a review of the literature. Am J Clin Pathol 1995;103:609–613. 40. Franchi A, Gallo O, Santucci M. Pathologic quiz case 1. Necrotizing sialometaplasia obscuring recurrent well-differentiated squamous cell carcinoma of the maxillary sinus. Arch Otolaryngol Head Neck Surg 1995;121:584–586.
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