- Email: [email protected]
Necrotizing sialometaplasia
oral pathology Editor: LEWIS
R. EVERSOLE,
DDS,
MSD,
MA
Oral Diagnosis, Medicine & Pathology School of Dentistry 53-058 UCLA Health Sciences Center Los Angeles, California 90024
Necrotizing
sialometaplasia
A clinicopathologic
study of-sixty-nine
cases and review
of the literature
Robert B. Brannon, COL. USAF, DC.” Craig B. Fowler, MAJ, USAF, DCb and Kenton S. Hartman, COL, USAF, DC,’ Lackland Air Force Base, Tex. and Washington, D.C. WILFORD
HALL
USAF
MEDICAL
CENTER
AND
ARMED
FORCES
INSTITUTE
OF PATHOLOGY
The clinicopathologic findings in 69 cases of necrotiring sialometaplasia (NS) were analyzed and compared with 115 reported cases of NS in the English-language literature. Data comparing age, sex, race, location, clinical presentation, and possible predisposing factors are summarized. Analysis of the data indicates that NS can occur in a variety of clinical settings and may exhibit a spectrum of histologic features. Recognition of NS, regardless of its clinical or microscopic presentation, is essential to avoid inappropriate or unnecessary treatment for this benign reactive process. (ORAL SURG ORAL MED ORAL PATHOL 1991;72:317-25)
N ecrotizing sialometaplasia (NS) was defined by Abrams et al.’ in 1973 as a reactive necrotizing inflammatory process involving minor salivary glands of the hard palate. Undoubtedly, before the recognition of NS, many patients with this condition had been improperly treated because of its clinical and histologic resemblance to malignancy. Subsequent to this initial report, NS has been described in other oral locations, in major salivary glands, and in the upper respiratory tract. 2* 3 Many cases have now been reported in the literature, documenting its close resemblance to mucoepidermoid carcinoma and squamous cell carcinoma both clinically and histologically. The histologic features of NS as outlined by Abrams et al.’ in their original publication include
The assertions and opinions expressed herein are the private views of the authors and are not to be construed as representing the opinion of the U.S. Air Force or The Department of Defense. “Chairman, Department of Oral Pathology, Wilford Hall USAF Medical Center, Lackland Air Force Base. bAssistant Chairman, Department of Oral Pathology, Wilford Hall USAF Medical Center, Lackland Air Force Base. cAssociate Director, Center for Advanced Pathology, Armed Forces Institute of Pathology, Washington. 7/U/27833
’
lobular (or coagulation) necrosis of glandular acini, extensive squamous metaplasia of ducts, pseudoepitheliomatous hyperplasia of the overlying epithelium, and mucus pooling with an associated granulation tissue and inflammatory response. From the histomorphologic findings, ischemia involving the glandular tissue is probably the underlying cause of NS. However, the nature and pathophysiology of the ischemia remain unclear in many cases. We report the clinicopathologic findings in 69 cases of NS and compare these findings with previously reported cases from the literature, with special emphasis on the factors responsible for or involved in the etiology and pathogenesis of NS. MATERIAL
AND
METHODS
The 69 cases in this study were obtained from the surgical pathology files at the Armed Forces Institute of Pathology (AFIP) and Wilford Hall USAF Medical Center (WHMC). Detailed clinical and historical information was recorded for each patient. The selection of cases as acceptable examples of NS was based on the histologic criteria as set forth by Abrams et al.,’ Gnepp,2 and Hyams et a1.3 for minor salivary glands, major salivary glands, and mucoserous glands of the sinonasal tract, respectively. Histologic confir317
318
Brannon, Fowler,
and Hartman
ORhI
SL RG OR.41
,kfvlED OR.41.
PI\ It101
September
I. Data of patients with NS -- .--.I
Table
Clinical
I 1
datu
AFIP/WHM( study 169 caJe.o
) ,
Table Ill. Site of palatal NS ------._---.-.-_-.Literarure revirk, (I I5 cases)
.SflU/J’
t!nilateral
Age (yr) I .5-75 45.5
Range ,Mean
14-83 46.2
Sex F M/F
ratio
Race White Black Other Not
Table
stated
44 25 1.76:1
76 39 1.95:1
40 ? 0 22
62 14 3 36
AFIPIWHMC srudy (69 cases!
Palate Hard Soft
28
palate palate
7
Junction
9
Palate (NOS) Total (R)
4 48 (69.6)
Other oral sites Lower lip Retromolar area Tongue Buccal mucosa Mucobuccal fold Tonsillar
fossa
Total
Lireralure review (I I5 cases)
2
2 0 0
0
2 1 1
-2
(‘%)
10 (14.5)
-i
(7.0)
Major glands Parotid
6
8
Sublingual
I
0
t (10.1)
I 9 (7.8)
3
2
I 0
0
Submandibular Total (o/c) Other sites Nasal cavity Incisive Maxillary Larynx Total Not
canal sinus
I I
-!?
4 (5.8)
(%)
otherwise
-;i
16 8
3 I2
I 94 -
Table IV. Time interval from first surgery to diagnosis of NS at second surgery I
*References
AFIPIWHMC srudy (25 cases?
Literarure review ( I4 cases I *
6-53
I O-25 21
(days) I8 2. 33. 35. 56. 59. 6 I.
RESULTS AFIPIWHMC
94 (81.7) 2 2
b9
I
did not fulfill the criteria for NS. Four cases from the current study were previously reported.17* 20.29.j2
72 3 16
5 3
Lirerarure review
32
ii
Duration Range Mean
II. Location of NS
Location
X0.5.
Bilateral Midline Not specified Total
M
- .-_ -
.4FIP/WHMC Palarl~
109 I
(3.5)
specitied.
mation of NS was verified in each case. Sections had been stained with hematoxylin and eosin for light microscopic evaluation. A thorough search of the English-language literature revealed 115 acceptable cases of NS.4-64 An additional 13 cases from the literature were eliminated for the purpose of comparison because of limited clinical information or lack of histologic evidence of NS, or because in our opinion the histologic findings
cases
Clinical findings. The ages of the patients ranged from 1.5 to 75 years, with the average being 45.5 years. The majority of the patients were male; the male/female ratio was 1.76: 1. Whites outnumbered blacks by a ratio of approximately 5:l. Data on age, sex, and race are also shown in Table 1. The majority of cases were located on the posterior hard palate; the junction of the hard and soft palate was the second most common site (Table II). About two thirds of the palatal lesions were unilateral; however, bilateral and midline locations were also noted (Table III). Other oral sites of involvement included the lower lip, retromolar area, and tongue. In addition, NS was also found to involve the mucoserous glands of the upper respiratory tract. Seven of the cases occurred in major salivary glands, most commonly the parotid (Table II). Twenty-five cases of NS developed after a surgical procedure, with 14 occurring in the palate, five in the parotid gland, two in the retromolar area, and one each in the sublingual gland, lower lip, tongue, and nasal cavity. For these cases, the time interval from initial surgery to the development and diagnosis of NS ranged from 6 to 53 days, with a mean interval of 18 days (Table IV). Clinically, NS most often presented as a deepseated ulcer; however, a number of cases manifested as a nonulcerated swelling or mass. In addition, the clinical history in four of the ulcerated lesions indi-
Necrotizing
Volume Number
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fable
V. Morphology
and symptoms of NS AFIP/WHMC study (69 cases)
CliniCd
presentation* Morphology Ulcer Mass/swelling Symptoms Pain Numbness Asymptomatic *Specific information with regard not available in every case..
table
Literature revfew (I I5 cases)
26 18
77 33
15 0 8
52 14 18
to clinical
morphology
and symptoms
3 19
VII. NS associated with another lesion Associated
Site
was
sialometaplasia
AFIP/WHMC study Nasal cavity Hard palate Soft palate Palate Anterior maxilla Parotid Palate Literature review Tonsillar fossa
lesion
Infarcted nasal polyp Infarcted mixed tumor Monomorphic adenoma Salivary gland hyperplasia Incisive canal cyst Infarcted Warthin’s tumor Lymphoproliferative disease Rhabdomyosarcoma5*
VIII. Provisional clinical diagnoses for cases of NS (AFIP/WHMC cases)
Table Table
VI. Possible predisposing ANP/WHMC study
Factors+ Traumatic
injury
6
Dental injection Dentures Alcohol use Smoking URI, allergy Associated lesion
1 8 4 7 6 I
l/R/. Upper respiratory ‘Excluding tRefercnccs $Rrfercnccs
factors of NS Literature review 228.32
1” lot 25 35 114 158
infection.
cases occurring after prior surgical procedure I. 8. I I. 12. 16. 31. 32. 37. 39, 43. 13-15. 17, 18. 21. 35. 41. 50. 64.
catcd that the ulcer was preceded by a nonulcerated swelling. Symptomatic status was known in 23 cases, with 15 described as painful and 8 as asymptomatic (Table V). Possible predisposing factors were recorded for each case (Table VI). Examples of traumatic injury included occlusal trauma, a severe blow to the lip or face, bum injury, and laceration. Only one well-documented case of NS occurred in the area of a prior dental injection, although we suspect from review of our clinical data that dental injection may have been a factor in at least three other cases. Eight patients wore ill-fitting dentures, and 11 had smoking and/or alcohol habits. In six patients NS developed on the palate after an upper respiratory infection. Seven cases of NS were found in association with another lesion (Tables VI and VII). Clinical information with regard to size and duration was provided in 20 and 2 1 cases, respectively. All of these cases were de novo lesions (i.e., they did not occur after a surgical procedure or in association with another lesion). Size of the 20 cases ranged from 0.7 to 5.0 cm; one case was designated only as “large.” The average size was 1.8 cm. Duration of the 21 cases ranged from 4 to 90 days except for one case, which
Clinical
diagnosis
Salivary gland tumor (benign or malignant) Squamous cell CA/CA Ulcer, denture sore Infectious (TB, fungal) NS Midline lethal granuloma/ Wegener’s granulomatosis Palatal abscess (dental) Neoplasm Cyst Nonneoplastic lesion Nasal polyp Incisive canal cyst Foreign body reaction and hypertrophic scar Total CA. Carcinoma;
No. of cases 11
7‘8. tuherculon~s.
was stated to last 180 days. With the exception of this latter case, the average duration was 21.3 days. Radiographic findings were available in four cases from the posterior of the hard palate. No bony involvement was discernible in three cases, whereas one case demonstrated an associated saucerization of the underlying palatal bone. A case involving mucoserous glands in the incisive canal area was characterized by a well-circumscribed radiolucency. Provisional clinical diagnoses are listed in Table VIII, which illustrates that NS was often confused clinically with a benign or malignant tumor, usually a salivary gland neoplasm or squamous cell carcinoma. Histologic features. In the majority of cases, the histopathologic characteristics were the classic features of NS (i.e., acinar necrosis, squamous metaplasia of ducts, pseudoepitheliomatous hyperplasia of surface epithelium, and mucus liberation with an as-
320
Brannon, Fowler, and Hartman
Fig.
1. Ulceratedpalatal mucosawith underlying meta-
plastic salivary ductsand acini. (Hematoxylin-eosinstain; original magnification,X19.8.)
ORAL SURG ORAL
MED ORAL PATHOL September 199 1
Fig. 3. Early lesionof NS with infarcted salivary gland lobuleat left with adjacentinflammation.Normal salivary gland lobule is seenat rig&. (Hematoxylin-eosinstain; original magnification,X99.)
4). However, two cases showed reactive epithelial atypia within the metaplastic squamous islands. These cases were accompanied by a severe acute and chronic inflammatory infiltrate with intraepithelial migration of inflammatory cells. An interesting subjective observation was the occasional presence of partially occluded blood vessels of varying sizes within the immediate vicinity of the NS, regardless of the suspected etiology (Fig. 6). Serous and mucoserous salivary glands, and sinonasal glands, were less likely to show acinar necrosis but frequently showed changes suggestive of acinar atrophy. However, squamous metaplastic involvement of serous and mucoserous glands and ducts was a consistent finding (Figs. 7 and 8). 2. Infarcted lobule of palatal minor salivary gland showingremnantsof acini, squamousmetaplasiaof ducts, andinflammatoryinfiltrate. (Hematoxylin-eosinstain;original magnification,X48.) Fig.
sociated inflammatory response) (Figs. 1 and 2). Our material demonstrated a spectrum of histologic changes depending, in part, on the duration of the lesion. In early lesions, coagulation necrosis of glandular acini predominates, whereas for later lesions, extensive squamous metaplasia and reactive fibrosis dominate the histologic picture (Figs. 3 and 4). In virtually every case where adequate tissue samples were available, preservation of the overall lobular architecture of the involved gland was evident (Fig. 5). In most cases, the squamous nests and islands demonstrated a bland cytologic morphology (Figs. 2 and
Treatment and follow-up. Adequate follow-up information was available on 14 cases. In 12 cases, 11 from the hard and/or soft palate and one from the lower lip, the average healing time was 5.2 weeks. Treatment of these 12 cases consisted of excisional biopsy (6 cases), incisional biopsy (4 cases), and biopsy not otherwise specified (2 cases). In one case involving the mucoserous glands of the sinonasal tract, the patient was free of disease 111 days postoperatively. No evidence of disease was recorded 1 year postoperatively for a patient with palatal NS treated by hemimaxillectomy. In cases where NS was misinterpreted histologically on the initial biopsy, the most frequent diagnoses rendered were mucoepidermoid carcinoma and squamous cell carcinoma (Table IX). As a result, eight patients received unnecessary or inappropriate therapy, ranging from wide excision to total maxillectomy (Table X).
Volume 72 Number 3
Fig. 4. Late lesionof NS with extensivebenign-appearing, squamousmetaplasiaand fibrous proliferation. (Hematoxylin-eosinstain; original magnification,X100.)
Necrotizing
sialometaplasia
321
Fig. 5. Maintenanceof lobular architecture. (Hematoxylin-eosinstain; original magnification,X25.)
Literature cases
Corresponding data for cases of NS obtained from the English-language literature are also presented in Tables I to VII and IX and X. DISCUSSION
This study represents the largest series of cases of NS reported to date. Clinical data from our study is in close agreement with the literature concerning age, sex, and race (Table I). When data from all cases are combined, the average age at diagnosis was 45.9 years. Males outnumbered females by a ratio of 1.9: 1, and whites outnumbered blacks by a ratio of 4.9:1. With regard to location, the majority of cases were found on the posterior of the hard palate; the junction of the hard and soft palate was the second most common site (Table II). Overall, 7 1.1% of palatal lesions were unilateral, 12.0% were bilateral, and 7.7% were located in the midline. Because salivary gland tissue is not normally present directly in the midline of the hard palate, lesions of NS found in this location are most likely due to extension across the midline from a unilateral lesion or coalescence of bilateral lesions. In addition, 10.1% of our cases and 7.8% of the cases from the literature occurred in major salivary glands. The parotid was the most common major gland involved. In all but two of these cases, NS arose after a surgical procedure for a benign or malignant neoplasm. Other oral sites of involvement in our study included the lower lip, retromolar area, and tongue, whereas cases from the literature have also been reported in the lower lips33 54 and retromolar area,52, 57 and buccal mucosa,55~ s6 mucobuccal fold ,28 and ton-
Fig. 6. Metaplastic squamousislandswith atypia and intraepithelialinflammation(arrow]. Note ductal luminain some squamousnests and adjacent blood vessel with narrowed lumen (arrowhead). (Hematoxylin-eosinstain; original magnification,X99.)
sillar fossa. NS involving the mucoserous glands of the upper respiratory tract was found in four of our cases. Cases from the literature have also been reported in the nasal cavity,60> 63 maxillary sinus,6’ and larynx. 62 Excellent discussions and illustrations of NS in these anatomic locations can be found in the publications by Hyams et a1.3 and Hyams.65 Data from this study and from the literature indicate that NS most often presents as a deep-seated ulcer (103 cases). However, 5 1 cases manifested as a nonulcerated swelling or mass. In addition, the clinical history in four of the ulcerated lesions in our study
322
Brannon, Fowler, and Hartman
ORAL
SURC
ORAL
MED
ORAL September
PATHOL 199 I
Fig.
7. Parotid gland with intralobular squamousmetaplasia in infarcted lobule. Inflammation and diminutive acini are evident. (Hematoxylin-eosinstain; original magnification, X75.)
Fig. 8. Biopsy of nasal turbinate showing squamous metaplasiaof mucoserousglandsand overlying mucosa. (Hematoxylin-eosinstain; original magnification,~7.5.)
and in 15 from the literature specifically stated that the ulcer was preceded by a nonulcerated swelling. Although bony involvement is not generally described or to be expected in NS, its presence does not preclude such a diagnosis. One case in our series demonstrated saucerization of the underlying palatal bone radiographically. Abrams et al.’ previously described a “faint radiolucency” in two of their seven cases. We are also aware of another case of NS in which “palatal bone destruction” was evident clinically and at surgery (Zunt SL, personal communication). This lesion occurred on the posterior hard palate of a 44-year-old white woman and presented as a painful, red, indurated ulcer of 4 to 5 weeks duration. An incisional biopsy was performed, and the diagnosis of NS was rendered. No further treatment was performed, and the lesion healed completely. Clinical symptoms are variable, but analysis of our cases and those in the literature revealed that painful lesions are more than twice as common as asymptomatic lesions (Table V). This together with other neurologic symptoms such as paresthesia or anesthesia may contribute to the confusion clinically of NS with a malignant neoplasm64 (Table VIII). Most investigators, including Batsakis and Manning,s9 believe that NS arises due to blockage or compromised blood supply to salivary gland lobules, resulting in ischemic necrosis or infarction. However, the nature and pathophysiology of the ischemia has yet to be elucidated in most cases. Arguelles et al6 discussed in detail the possible etiologic factors, which include vascular injury, infection, and physical and chemical trauma. Possible predisposing factors were recorded for cases in our study and in the literature
(Table VI). Examples of traumatic injury in our study included four cases with blows sufficient enough to cause clinically evident damage to blood vessels (three lacerations, one hematoma). In the literature one case of NS occurred in the mucobuccal fold after a blow to the face 2 days previously.** The NS in these cases was likely due to ischemia resulting from direct injury to these vessels. Analysis of our data and that of the literature revealed only two well-documented cases of NS in the area of a prior dental injection,33 both of which occurred on the posterior hard palate. We suspect from review of the clinical data that dental injection may play a larger role than is indicated by these figures, because several patients had received recent dental treatment in the area before the development of NS. A large volume of anesthetic introduced rapidly in the tissue, 66direct injury to a blood vessel from the needle, or prolonged pressure by swelling from anesthestic solution may compromise local blood supply and result in NS6 A total of 18 cases (AFIP/WHMC cases and literature) were associated with dentures (documented as ill-fitting in 11 cases). It is interesting to speculate that undue pressure from an ill-fitting denture might compromise the palatal blood supply enough to result in infarction of minor salivary glands. Interestingly, in 17 patients from this study and from the literature, NS developed on the palate after or in association with an upper respiratory infection or allergy (Table VI). Perhaps the swelling of mucous membranes encountered in upper respiratory infections67 and allergies plays a sole in compromising the vascular supply to the posterior hard and soft palate, nredisnosinn in some cases to NS
Volume Number
72 3
Table
IX.
Necrotizing Cases of NS misinterpreted
Mucoepidermoid CA Squamous cell CA Acinic cell CA Verrucous CA Ductal CA Mucus-producing adenocarcinoma Benign vs malignant* Mixed tumor PEH Mucocele Pyogenic granuloma CA, Carcinoma;
*References TReferences
AFIPIWHMC study (25 cases) 9 6 1 1 1 0 2 2 1 1 1
Table
Literature review (24 cases) 10* lot 0 0 0 13’
initially
AFIPIWHMC study (8 cases)
Treatment Conservative excision Wide excision En bloc excision Partial maxillectomy Maxillectomy Surgery (NOS)
Literature review (13 cases)
2
67. 14,24, 39, 53. 57 56, 10, 19. 33, 54
1 2 1 2
15 160 0 0
0
224v 26
129 0 0 0
PEH, pseudoepitheliomatous hyperplasia. 1, 5, 6, 7, 10, 14, 16, 25, 33, 50. 4, 6, 19, 21. 25, 39, 53, 54, 57,60.
*In two cases from each series, the pathlogists whether the lesion was benign or malignant.
323
X. Cases of NS improperly managed as result of incorrect malignant diagnosis
on initial
biopsy Initial diagnosis
sialometaplasia
could
not determine
NS was found in association with another lesion in seven instances in our study. In these cases, the tumor or cyst itself likely compromised the blood supply to the involved glands, resulting in ischemic necrosis and sialometaplasia. Interestingly, infarction was identified in three of these tumors, further supporting ischemic necrosis as the direct cause of NS (Table VII). Also of note is that one of our cases was associated with lymphoproliferative disease of the hard palate, in which subsequent workup disclosed that the patient had disseminated lymphoma. Paulson et al.$* recently reported a case of NS that was associated with and delayed the diagnosis of a rhabdomyosarcoma in the tonsillar fossa region. In 25 cases from our study and in 14 from the literature (Table IV), NS developed after a surgical procedure for a benign or malignant lesion. The majority of our cases were from the palate, whereas most in the literature involved the parotid gland. The time interval from initial surgery to the development and diagnosis of NS ranged from 6 to 53 days, with a mean interval of 18 days in our series. The mean interval for such cases in the literature was 21 days. These time intervals are roughly 2 weeks longer than in experimental studies by Standish and Shafer6* and subsequently by Englander and Cataldo,6g in which NS was produced in rats by ligating the blood vessels supplying the submandibular and sublingual glands. Interestingly, the average duration from onset to diagnosis for our de novo lesions was also about 21 days. This appears to represent a rough estimate of the time required in human beings for the development of NS. The majority of our cases involving pure mucous glands showed classic NS histologically. However, in
NOS,
Not
otherwise
specified.
mucoserous and serous glands, coagulation necrosis of acini was seldom a prominent feature. Instead, these acini most often demonstrated atrophy, a well-recognized cellular and tissue adaptive response to a diminished vascular s~ppiy.~~ It is apparent from our study that a spectrum of histologic findings exists, ranging from coagulation necrosis of acini in early lesions to squamous metaplasia of ducts and reactive fibrosis in late lesions. Because of this histologic spectrum, the diagnosis of NS frequently requires recognition without the presence of infarctive necrosis of acinar cells. As outlined originally by Abrams et al.’ and more recently by Gnepp,2 helpful criteria in distinguishing NS from a malignant process are (1) maintenance of the overall lobular morphology, (2) the generally bland appearance of the squamous islands or nests, and (3) evidence of residual ductal lumina in one or more of these nests. Occasionally, however, we observed reactive atypia in the squamous islands and nests. In these situations, the overall lobular appearance and the presence of intraepithelial inflammation in the squamous nests are helpful in establishing the correct diagnosis. From this discussion it should be apparent that an adequate biopsy on the part of the surgeon is of paramount importance to ensure accurate histopathologic interpretation of this lesion. Analysis of our cases and those from the literature showed that histopathologic misinterpretation of NS, regardless of its clinical setting, may result in clinical mismanagement. Twenty-one patients from both series received unnecessary or inappropriate therapy, ranging from conservative excision to total maxillectomy (Table X). These procedures were performed as a result of incorrect microscopic interpretations on the initial biopsy. The most frequent misdiagnosis rendered was mucoepidermoid carcinoma or squamous cell carcinoma (Table IX). It is evident that we have included in our series and in the literature review cases of NS that have followed and possibly resulted from prior surgery or trauma, or were associated with another lesion. Some authors are
324
Brannon, Fowler, and Hartman
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SURG ORAL
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September I99 l
not in full agreement that the term necrotizing sialometaplasia should be used for the broad spectrum of histologic patterns and clinical settings such as those which we have outlined. Abrams” has suggested that this term be reserved for those instances where documented spontaneous infarction of gland occurs without previous iatrogenic cause. Because a common etiologic thread exists, that is, vascular compromise with resulting ischemia, regardless of the location or the associated clinical factors, and because of the similarity in histomorphologic characteristics, it is our contention that necrotizing sialometaplasia is a proper designation for the spectrum of histologic changes and clinical settings that have been described for this entity. CONCLUSIONS
Any factor that causes a compromise in blood supply to a minor or major salivary gland or mucoserous gland of the upper respiratory tract may result in NS. NS may occur de novo, after a prior surgical procedure, or in association with another lesion, either benign or malignant. Because of the latter, whenever the diagnosis of NS is made, close follow-up is warranted until healing is complete. The average healing time for our cases and for those in the literature was 5 to 6 weeks. Recognition of the histologic spectrum and the varied clinical settings in which NS can be found is essential, to avoid histopathologic misinterpretation and inappropriate treatment for this benign reactive lesion. Wethank JulieA. Brannon,CardiologyService,WHMC, Lackland Air Force Base,Tex., for assistance in preparing the manuscript,and Mr. Bobby Burnes,Photomicrography Lab, BrooksAir ForceBase,Tex., for technicalexpertisein preparingthe photomicrographs. REFERENCES
1. Abrams AM, Melrose RJ, Howell FV. Necrotizing sialometaplasia: a disease simulating malignancy. Cancer 1973;32: 130-5. 2. Gnepp DR. Warthin’s tumor exhibiting sebaceous differentiation and necrotizing sialometaplasia. Virchows Arch [A] 1981;391:267-73. 3. Hyams VJ, Batsakis JG, Michaels L. Tumors of the upper respiratory tract and ear. In: Hartmann WH, Sobin LH, eds. Atlas of tumor pathology; series 2, fascicle 25. Washington, DC: Armed Forces Institute of Pathology, 1986:109- 11. 4. Wills PI, Fechner RE. Necrotizing sialometaplasia: pathologic quiz case 1. Arch Otolaryngol 1975;101:76-8. 5. Myers EN, Bankaci M, Barnes EL. Necrotizing sialometaplasia: report of case. Arch Otolaryngol 1975;101:628-9. 6. Arguelles MT, Viloria JB Jr, Talens MC, McCrory TP. Necrotizing sialometaplasia. ORAL SURG ORAL MED ORAL PATHOL 1976;42:86-90. 7. Marciani RD, Sabes WR. Necrotizing sialometaplasia: report of three cases. J Oral Surg 1976;34:722-6. 8. Bannayan G, Fox G, Tilson HB. Necrotizing sialometaplasia of the palate. J Oral Surg 1976;34:727-30. 9. Philipsen HP, Petersen JK, Simonsen BH. Necrotizing sia-
lometaplasia: ulcerative or necrotizing stage of leukokeratosis nicotina palati? Int J Oral Surg 1976;5:292-9. 10. Fechner RE. Necrotizing sialometaplasia: a source of confusion with carcinoma of the palate. Am J Clin Pathol 1977: 6713 l5-7. 11. Murphy J, Giunta J, Meyer 1, Robinson K. Necrotizing sialometaplasia. ORAL SURG ORAL MED ORAL PATHOL 1977; 441419-24.
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PATHOL
1979;47:169-72.
18. Raugi GJ, Kessler S. Necrotizing sialometaplasia: a condition simulating malignancy. Arch Dermatol 1979;l 15:329-3 1. 19. Chakravorty RC, Yoneyama T, Makooi C. Necrotizing sialometaplasia of palate, Br J Surg 1979;66:283-4. 20. Brannon RB, Corio RL. Case for diagnosis (necrotizing sialometaplasia, left hard palate). Milit Med 1979;144:295-6, 301. 21. Samit AM, Mashberg A, Greene GW Jr. Necrotizing sialometaplasia. J Oral Surg 1979;37:353-6. 22. Merwin GE, Duckert LG, Pollak K. Necrotizing sialometaplasia of the nasopharynx. Ann Otol 1979;88:348-51. 23. Birkholz H, Minton GA, Yuen YL. Necrotizing sialometaplasia: review of the literature and report of nonulcerative case. J Oral Surg 1979;37:588-92. 24. Williams RF. Necrotizingsialometaplasia after bronchoscopy. J Oral Surg 1979;37:816-8. 25. Dunlap CL, Barker BF. Necrotizing sialometaplasia: report of five additional cases. ORAL SURG ORAL MED ORAL PATHOL 1974;37:722-727.
26. Rye LA, Calhoun NR, Redman RS. Necrotizing sialometaplasia in a patient with Buerger’s disease and Raynaud’s phenomenon. ORAL SURG ORAL MED ORAL PATHOL 1980; 49~233-6. 27. Biedlingmaier JF, Blanchard CL, Masi J. Necrotizing sialometaplasia of the palate and adenocarcinoma of the esophagus. Ear Nose Throat J 1980;59:49-56. 28. Giles AD. Necrotizing sialometaplasia. Br J Oral Surg 1980; 18:45-50. 29. Buller DL. Nodular and ulcerated lesions of the hard palate. J Am Dent Assoc 1980;101:823-4. 30. Stafford RF, Sonis ST, Shklar G. Bilateral necrotizing sialometaplasia: a case report. J Oral Med 198 1;36:28-30. 31. Gavron JP, Ardito JA, Curtis AW. Necrotizing sialometaplasia. Laryngoscope 198 I;91 : I 176-80. 32. Birkholz H, Brownd CL. Necrotizing sialometaplasia: report of an ulcerative case. J Am Dent Assoc 1981;103:48-50. 33. Grillon GL, Lally ET. Necrotizing sialometaplasia: literature review and presentation of five cases.J Oral Surg I98 I ;39:74753. 34. Santis HR, Kabani SP, Roderiques A, Driscoll JM. Necrotizing sialometaplasia: an early, nonulcerative presentation. ORAL SURG ORAL MED
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35. Anneroth G, Hansen LS. Necrotizing sialometaplasia: the relationship of its pathogenesis to its clinical characteristics. Int J Oral Surg 1982;11:283-91. 36. Gavron JP, Shugar MA, Rice DA. Necrotizing sialometaplasia. Am Fam Physician 1983;27:155-7. 37. Gahhos F, Enriquez RE, Bahn SL, Ariyan S. Necrotizing sialometaplasia: report of five cases. Plast Reconstr Surg 1983; 7 1:650-7.
Necrotizing
Volume 72 Number 3 38. Chaudhry AP, Yamane GM, Salman L, Salman S, Saxon M, Pierri LK. Necrotizing sialometaplasia of palatal minor salivary glands: a report of two cases. J Oral Med 1985;40:2-6. 39. Mitchell RD. Necrotizing sialometaplasia: case report. Aust Dent J 1985;30:181-4. 40. Kinney RB, Burton CS, Vollmer RT. Necrotizing sialometaplasia: a sheep in wolf’s clothing-healing as a diagnostic test. Arch Dermatol 1986;122:208-10. 41. Rossie KM. A palatal swelling with pain and paresthesia. Ohio Dent J 1985;59:75, 80. 42. Rossie KM, Allen CM, Burns RA. Necrotizing sialometaplasia: a case with metachronous lesions. J Oral Maxillofac Surg 1986;44:1006-8. 43. Lambert PM. Necrotizing sialometaplasia: report of two cases. Spec Care Dentist 1987;7:78-80. 44. Lieberman J, Weinstein M. Necrotizing sialometaplasia. Cutis 1988;41:97. 45. Speechly JA, Field EA, Scott J. Necrotizing sialometaplasia occurring during pregnancy: report of a case. J Oral Maxillofat Surg 1988;46:696-9. 46. Aversa D, Mock D. Necrotizing sialometaplasia. Ontario Dentist 1985;62:17-9. 47. Bhatt AP. Case of the month: necrotizing sialometaplasia [Inside front cover]. J Indian Dent Assoc 1984;56. 48. Mesa M, Schneider L, Clark M. Necrotizing sialometaplasia: a result of ischemia? Report of two casesand review of the literature. Q Nat1 Dent Assoc 1979;38:16-23. 49. Schwartz M, Desormeau L, Hirschfeld J. Necrotizing sialometaplasia. J Dent Quebec 1979;16:11, 13. 50. Toth BB, Chen JJJ. Necrotizing sialometaplasia: a clinical entity for dental awareness. Tex Dent J 1981;99:10-1. 51. Yoshimura Y, Matsuura R, Sugihara T, Matsumoto K. Necrotizing sialometaplasia: report of a case and review of the Japanese literature. J Osaka Univ Dent Sch 1985;25:171-6. 52. Forney SK, Foley JM, Sugg WE Jr, Oatis GW Jr. Necrotizing sialometaplasia of the mandible. ORAL SURG ORAL MED ORAL PATHOL
1977;43:720-6.
53. Matilla A, Flares T, Nogales FF Jr, Galera H. Necrotizing sialometaplasia affecting the minor labial glands. ORAL SURG ORAL MED
ORAL PATHOL
1979;47:161-3.
54. Gad A, Willen H, Willen R, Thorstensson S, Ekman L. Necrotizing sialometaplasia of the lip simulating squamous cell carcinoma. Histopathology 1980;4:11 J-21. 55. Papanayotou PH, Kayavis JG, Epivatianos AA, Trigonidis G. Necrotizing sialometaplasia of the cheek: report of case and review of literature. J Oral Surg 1980;38:538-40. 56. Willen H, Willen R, Ekman L. Necrotizing sialometaplasia of the bucca. Acta Pathol Microbial Stand [A] 1981;89:199-201.
sialometaplasia
325
57. Anneroth G, Bystedt H, Hammarstrom L. Necrotizing sialometaplasia: a malignancy-simulating oral lesion. Swed Dent J 1986;10:53-8. 58. Poulson TC, Greer RO, Ryser RW. Necrotizing sialometaplasia obscuring an underlying malignancy: report of a case. J bra1 Maxillofac Surg 1986;44:570-4. 59. Batsakis JG. Manning JT. Necrotizina sialometanlasia of major salivary glands. J-Laryngol Otol i987;101:982-6. 60. Maisel RH, Johnston WH, Anderson HA, Cantrell RW. Necrotizing sialometaplasia involving the nasal cavity. Laryngoscope 1977;87:429-34. 61. Johnston WH. Necrotizing sialometaplasia involving the mucous glands of the nasal cavity. Hum Path01 1977;8:589-92. 62. Walker GK, Fechner RE, Johns ME, Teja K. Necrotizing sialometaplasia of the larynx secondary to atheromatous embolization. Am J Clin Pathol 1982;77:221-3. 63. Chen KTK. Necrotizing sialometaplasia of the nasal cavity. Am J Otolaryngol 1982;3:444-6. 64. Lamey P-J, Lewis MAO, Crawford DJ, MacDonald DG. Necrotizing sialometaplasia presenting as greater palatine nerve anaesthesia. Int J Oral Maxillofac Surg 1989;18:70-2. 65. Hyams VJ. Pathology of the nose and paranasal sinuses. In: English GM, ed. Otolaryngology; vol 2. Philadelphia: JB Lippincott, 1989:18-9. 66. Mitchell DF, Standish SM. Fast TB. Oral diagnosis/oral medicine. 3rd ed. Philadelphia: Lea & Febiger, 1978:398-9. 67. von Lichtenberg F. Infectious disease. In: Cotran RS, Kumar V, Robbins SL, eds. Robbins pathologic basis of disease. 4th ed. Philadelphia: WB Saunders, 1989:3 15. 68. Standish SM, Shafer WG. Serial histologic effects of rat submaxillary and sublingual salivary gland duct and blood vessel ligation. J Dent Res 1957;36:866-79. 69. Englander A, Cataldo E. Experimental carcinogenesis in duct-artery ligated rat submandibular gland. J Dent Res 1976; 55~229-34. 70. Cotran RS, Kumar V, Robbins SL, eds. Robbins pathologic basis of disease. 4th ed. Philadelphia: WB Saunders, 1989:30, 111. 71. Abrams AM. Necrotizing sialometaplasia of the nasal cavity [Letter]. Otolaryngol Head Neck Surg 1986;94:416.
Reprinf
requests:
Craig B. Fowler, MAJ, USAF, DC Department of Oral Pathology Wilford Hall USAF Medical Center/SGDM Lackland Air Force Base, TX 78236-5300
R. EVERSOLE,
DDS,
MSD,
MA
Oral Diagnosis, Medicine & Pathology School of Dentistry 53-058 UCLA Health Sciences Center Los Angeles, California 90024
Necrotizing
sialometaplasia
A clinicopathologic
study of-sixty-nine
cases and review
of the literature
Robert B. Brannon, COL. USAF, DC.” Craig B. Fowler, MAJ, USAF, DCb and Kenton S. Hartman, COL, USAF, DC,’ Lackland Air Force Base, Tex. and Washington, D.C. WILFORD
HALL
USAF
MEDICAL
CENTER
AND
ARMED
FORCES
INSTITUTE
OF PATHOLOGY
The clinicopathologic findings in 69 cases of necrotiring sialometaplasia (NS) were analyzed and compared with 115 reported cases of NS in the English-language literature. Data comparing age, sex, race, location, clinical presentation, and possible predisposing factors are summarized. Analysis of the data indicates that NS can occur in a variety of clinical settings and may exhibit a spectrum of histologic features. Recognition of NS, regardless of its clinical or microscopic presentation, is essential to avoid inappropriate or unnecessary treatment for this benign reactive process. (ORAL SURG ORAL MED ORAL PATHOL 1991;72:317-25)
N ecrotizing sialometaplasia (NS) was defined by Abrams et al.’ in 1973 as a reactive necrotizing inflammatory process involving minor salivary glands of the hard palate. Undoubtedly, before the recognition of NS, many patients with this condition had been improperly treated because of its clinical and histologic resemblance to malignancy. Subsequent to this initial report, NS has been described in other oral locations, in major salivary glands, and in the upper respiratory tract. 2* 3 Many cases have now been reported in the literature, documenting its close resemblance to mucoepidermoid carcinoma and squamous cell carcinoma both clinically and histologically. The histologic features of NS as outlined by Abrams et al.’ in their original publication include
The assertions and opinions expressed herein are the private views of the authors and are not to be construed as representing the opinion of the U.S. Air Force or The Department of Defense. “Chairman, Department of Oral Pathology, Wilford Hall USAF Medical Center, Lackland Air Force Base. bAssistant Chairman, Department of Oral Pathology, Wilford Hall USAF Medical Center, Lackland Air Force Base. cAssociate Director, Center for Advanced Pathology, Armed Forces Institute of Pathology, Washington. 7/U/27833
’
lobular (or coagulation) necrosis of glandular acini, extensive squamous metaplasia of ducts, pseudoepitheliomatous hyperplasia of the overlying epithelium, and mucus pooling with an associated granulation tissue and inflammatory response. From the histomorphologic findings, ischemia involving the glandular tissue is probably the underlying cause of NS. However, the nature and pathophysiology of the ischemia remain unclear in many cases. We report the clinicopathologic findings in 69 cases of NS and compare these findings with previously reported cases from the literature, with special emphasis on the factors responsible for or involved in the etiology and pathogenesis of NS. MATERIAL
AND
METHODS
The 69 cases in this study were obtained from the surgical pathology files at the Armed Forces Institute of Pathology (AFIP) and Wilford Hall USAF Medical Center (WHMC). Detailed clinical and historical information was recorded for each patient. The selection of cases as acceptable examples of NS was based on the histologic criteria as set forth by Abrams et al.,’ Gnepp,2 and Hyams et a1.3 for minor salivary glands, major salivary glands, and mucoserous glands of the sinonasal tract, respectively. Histologic confir317
318
Brannon, Fowler,
and Hartman
ORhI
SL RG OR.41
,kfvlED OR.41.
PI\ It101
September
I. Data of patients with NS -- .--.I
Table
Clinical
I 1
datu
AFIP/WHM( study 169 caJe.o
) ,
Table Ill. Site of palatal NS ------._---.-.-_-.Literarure revirk, (I I5 cases)
.SflU/J’
t!nilateral
Age (yr) I .5-75 45.5
Range ,Mean
14-83 46.2
Sex F M/F
ratio
Race White Black Other Not
Table
stated
44 25 1.76:1
76 39 1.95:1
40 ? 0 22
62 14 3 36
AFIPIWHMC srudy (69 cases!
Palate Hard Soft
28
palate palate
7
Junction
9
Palate (NOS) Total (R)
4 48 (69.6)
Other oral sites Lower lip Retromolar area Tongue Buccal mucosa Mucobuccal fold Tonsillar
fossa
Total
Lireralure review (I I5 cases)
2
2 0 0
0
2 1 1
-2
(‘%)
10 (14.5)
-i
(7.0)
Major glands Parotid
6
8
Sublingual
I
0
t (10.1)
I 9 (7.8)
3
2
I 0
0
Submandibular Total (o/c) Other sites Nasal cavity Incisive Maxillary Larynx Total Not
canal sinus
I I
-!?
4 (5.8)
(%)
otherwise
-;i
16 8
3 I2
I 94 -
Table IV. Time interval from first surgery to diagnosis of NS at second surgery I
*References
AFIPIWHMC srudy (25 cases?
Literarure review ( I4 cases I *
6-53
I O-25 21
(days) I8 2. 33. 35. 56. 59. 6 I.
RESULTS AFIPIWHMC
94 (81.7) 2 2
b9
I
did not fulfill the criteria for NS. Four cases from the current study were previously reported.17* 20.29.j2
72 3 16
5 3
Lirerarure review
32
ii
Duration Range Mean
II. Location of NS
Location
X0.5.
Bilateral Midline Not specified Total
M
- .-_ -
.4FIP/WHMC Palarl~
109 I
(3.5)
specitied.
mation of NS was verified in each case. Sections had been stained with hematoxylin and eosin for light microscopic evaluation. A thorough search of the English-language literature revealed 115 acceptable cases of NS.4-64 An additional 13 cases from the literature were eliminated for the purpose of comparison because of limited clinical information or lack of histologic evidence of NS, or because in our opinion the histologic findings
cases
Clinical findings. The ages of the patients ranged from 1.5 to 75 years, with the average being 45.5 years. The majority of the patients were male; the male/female ratio was 1.76: 1. Whites outnumbered blacks by a ratio of approximately 5:l. Data on age, sex, and race are also shown in Table 1. The majority of cases were located on the posterior hard palate; the junction of the hard and soft palate was the second most common site (Table II). About two thirds of the palatal lesions were unilateral; however, bilateral and midline locations were also noted (Table III). Other oral sites of involvement included the lower lip, retromolar area, and tongue. In addition, NS was also found to involve the mucoserous glands of the upper respiratory tract. Seven of the cases occurred in major salivary glands, most commonly the parotid (Table II). Twenty-five cases of NS developed after a surgical procedure, with 14 occurring in the palate, five in the parotid gland, two in the retromolar area, and one each in the sublingual gland, lower lip, tongue, and nasal cavity. For these cases, the time interval from initial surgery to the development and diagnosis of NS ranged from 6 to 53 days, with a mean interval of 18 days (Table IV). Clinically, NS most often presented as a deepseated ulcer; however, a number of cases manifested as a nonulcerated swelling or mass. In addition, the clinical history in four of the ulcerated lesions indi-
Necrotizing
Volume Number
72 3
fable
V. Morphology
and symptoms of NS AFIP/WHMC study (69 cases)
CliniCd
presentation* Morphology Ulcer Mass/swelling Symptoms Pain Numbness Asymptomatic *Specific information with regard not available in every case..
table
Literature revfew (I I5 cases)
26 18
77 33
15 0 8
52 14 18
to clinical
morphology
and symptoms
3 19
VII. NS associated with another lesion Associated
Site
was
sialometaplasia
AFIP/WHMC study Nasal cavity Hard palate Soft palate Palate Anterior maxilla Parotid Palate Literature review Tonsillar fossa
lesion
Infarcted nasal polyp Infarcted mixed tumor Monomorphic adenoma Salivary gland hyperplasia Incisive canal cyst Infarcted Warthin’s tumor Lymphoproliferative disease Rhabdomyosarcoma5*
VIII. Provisional clinical diagnoses for cases of NS (AFIP/WHMC cases)
Table Table
VI. Possible predisposing ANP/WHMC study
Factors+ Traumatic
injury
6
Dental injection Dentures Alcohol use Smoking URI, allergy Associated lesion
1 8 4 7 6 I
l/R/. Upper respiratory ‘Excluding tRefercnccs $Rrfercnccs
factors of NS Literature review 228.32
1” lot 25 35 114 158
infection.
cases occurring after prior surgical procedure I. 8. I I. 12. 16. 31. 32. 37. 39, 43. 13-15. 17, 18. 21. 35. 41. 50. 64.
catcd that the ulcer was preceded by a nonulcerated swelling. Symptomatic status was known in 23 cases, with 15 described as painful and 8 as asymptomatic (Table V). Possible predisposing factors were recorded for each case (Table VI). Examples of traumatic injury included occlusal trauma, a severe blow to the lip or face, bum injury, and laceration. Only one well-documented case of NS occurred in the area of a prior dental injection, although we suspect from review of our clinical data that dental injection may have been a factor in at least three other cases. Eight patients wore ill-fitting dentures, and 11 had smoking and/or alcohol habits. In six patients NS developed on the palate after an upper respiratory infection. Seven cases of NS were found in association with another lesion (Tables VI and VII). Clinical information with regard to size and duration was provided in 20 and 2 1 cases, respectively. All of these cases were de novo lesions (i.e., they did not occur after a surgical procedure or in association with another lesion). Size of the 20 cases ranged from 0.7 to 5.0 cm; one case was designated only as “large.” The average size was 1.8 cm. Duration of the 21 cases ranged from 4 to 90 days except for one case, which
Clinical
diagnosis
Salivary gland tumor (benign or malignant) Squamous cell CA/CA Ulcer, denture sore Infectious (TB, fungal) NS Midline lethal granuloma/ Wegener’s granulomatosis Palatal abscess (dental) Neoplasm Cyst Nonneoplastic lesion Nasal polyp Incisive canal cyst Foreign body reaction and hypertrophic scar Total CA. Carcinoma;
No. of cases 11
7‘8. tuherculon~s.
was stated to last 180 days. With the exception of this latter case, the average duration was 21.3 days. Radiographic findings were available in four cases from the posterior of the hard palate. No bony involvement was discernible in three cases, whereas one case demonstrated an associated saucerization of the underlying palatal bone. A case involving mucoserous glands in the incisive canal area was characterized by a well-circumscribed radiolucency. Provisional clinical diagnoses are listed in Table VIII, which illustrates that NS was often confused clinically with a benign or malignant tumor, usually a salivary gland neoplasm or squamous cell carcinoma. Histologic features. In the majority of cases, the histopathologic characteristics were the classic features of NS (i.e., acinar necrosis, squamous metaplasia of ducts, pseudoepitheliomatous hyperplasia of surface epithelium, and mucus liberation with an as-
320
Brannon, Fowler, and Hartman
Fig.
1. Ulceratedpalatal mucosawith underlying meta-
plastic salivary ductsand acini. (Hematoxylin-eosinstain; original magnification,X19.8.)
ORAL SURG ORAL
MED ORAL PATHOL September 199 1
Fig. 3. Early lesionof NS with infarcted salivary gland lobuleat left with adjacentinflammation.Normal salivary gland lobule is seenat rig&. (Hematoxylin-eosinstain; original magnification,X99.)
4). However, two cases showed reactive epithelial atypia within the metaplastic squamous islands. These cases were accompanied by a severe acute and chronic inflammatory infiltrate with intraepithelial migration of inflammatory cells. An interesting subjective observation was the occasional presence of partially occluded blood vessels of varying sizes within the immediate vicinity of the NS, regardless of the suspected etiology (Fig. 6). Serous and mucoserous salivary glands, and sinonasal glands, were less likely to show acinar necrosis but frequently showed changes suggestive of acinar atrophy. However, squamous metaplastic involvement of serous and mucoserous glands and ducts was a consistent finding (Figs. 7 and 8). 2. Infarcted lobule of palatal minor salivary gland showingremnantsof acini, squamousmetaplasiaof ducts, andinflammatoryinfiltrate. (Hematoxylin-eosinstain;original magnification,X48.) Fig.
sociated inflammatory response) (Figs. 1 and 2). Our material demonstrated a spectrum of histologic changes depending, in part, on the duration of the lesion. In early lesions, coagulation necrosis of glandular acini predominates, whereas for later lesions, extensive squamous metaplasia and reactive fibrosis dominate the histologic picture (Figs. 3 and 4). In virtually every case where adequate tissue samples were available, preservation of the overall lobular architecture of the involved gland was evident (Fig. 5). In most cases, the squamous nests and islands demonstrated a bland cytologic morphology (Figs. 2 and
Treatment and follow-up. Adequate follow-up information was available on 14 cases. In 12 cases, 11 from the hard and/or soft palate and one from the lower lip, the average healing time was 5.2 weeks. Treatment of these 12 cases consisted of excisional biopsy (6 cases), incisional biopsy (4 cases), and biopsy not otherwise specified (2 cases). In one case involving the mucoserous glands of the sinonasal tract, the patient was free of disease 111 days postoperatively. No evidence of disease was recorded 1 year postoperatively for a patient with palatal NS treated by hemimaxillectomy. In cases where NS was misinterpreted histologically on the initial biopsy, the most frequent diagnoses rendered were mucoepidermoid carcinoma and squamous cell carcinoma (Table IX). As a result, eight patients received unnecessary or inappropriate therapy, ranging from wide excision to total maxillectomy (Table X).
Volume 72 Number 3
Fig. 4. Late lesionof NS with extensivebenign-appearing, squamousmetaplasiaand fibrous proliferation. (Hematoxylin-eosinstain; original magnification,X100.)
Necrotizing
sialometaplasia
321
Fig. 5. Maintenanceof lobular architecture. (Hematoxylin-eosinstain; original magnification,X25.)
Literature cases
Corresponding data for cases of NS obtained from the English-language literature are also presented in Tables I to VII and IX and X. DISCUSSION
This study represents the largest series of cases of NS reported to date. Clinical data from our study is in close agreement with the literature concerning age, sex, and race (Table I). When data from all cases are combined, the average age at diagnosis was 45.9 years. Males outnumbered females by a ratio of 1.9: 1, and whites outnumbered blacks by a ratio of 4.9:1. With regard to location, the majority of cases were found on the posterior of the hard palate; the junction of the hard and soft palate was the second most common site (Table II). Overall, 7 1.1% of palatal lesions were unilateral, 12.0% were bilateral, and 7.7% were located in the midline. Because salivary gland tissue is not normally present directly in the midline of the hard palate, lesions of NS found in this location are most likely due to extension across the midline from a unilateral lesion or coalescence of bilateral lesions. In addition, 10.1% of our cases and 7.8% of the cases from the literature occurred in major salivary glands. The parotid was the most common major gland involved. In all but two of these cases, NS arose after a surgical procedure for a benign or malignant neoplasm. Other oral sites of involvement in our study included the lower lip, retromolar area, and tongue, whereas cases from the literature have also been reported in the lower lips33 54 and retromolar area,52, 57 and buccal mucosa,55~ s6 mucobuccal fold ,28 and ton-
Fig. 6. Metaplastic squamousislandswith atypia and intraepithelialinflammation(arrow]. Note ductal luminain some squamousnests and adjacent blood vessel with narrowed lumen (arrowhead). (Hematoxylin-eosinstain; original magnification,X99.)
sillar fossa. NS involving the mucoserous glands of the upper respiratory tract was found in four of our cases. Cases from the literature have also been reported in the nasal cavity,60> 63 maxillary sinus,6’ and larynx. 62 Excellent discussions and illustrations of NS in these anatomic locations can be found in the publications by Hyams et a1.3 and Hyams.65 Data from this study and from the literature indicate that NS most often presents as a deep-seated ulcer (103 cases). However, 5 1 cases manifested as a nonulcerated swelling or mass. In addition, the clinical history in four of the ulcerated lesions in our study
322
Brannon, Fowler, and Hartman
ORAL
SURC
ORAL
MED
ORAL September
PATHOL 199 I
Fig.
7. Parotid gland with intralobular squamousmetaplasia in infarcted lobule. Inflammation and diminutive acini are evident. (Hematoxylin-eosinstain; original magnification, X75.)
Fig. 8. Biopsy of nasal turbinate showing squamous metaplasiaof mucoserousglandsand overlying mucosa. (Hematoxylin-eosinstain; original magnification,~7.5.)
and in 15 from the literature specifically stated that the ulcer was preceded by a nonulcerated swelling. Although bony involvement is not generally described or to be expected in NS, its presence does not preclude such a diagnosis. One case in our series demonstrated saucerization of the underlying palatal bone radiographically. Abrams et al.’ previously described a “faint radiolucency” in two of their seven cases. We are also aware of another case of NS in which “palatal bone destruction” was evident clinically and at surgery (Zunt SL, personal communication). This lesion occurred on the posterior hard palate of a 44-year-old white woman and presented as a painful, red, indurated ulcer of 4 to 5 weeks duration. An incisional biopsy was performed, and the diagnosis of NS was rendered. No further treatment was performed, and the lesion healed completely. Clinical symptoms are variable, but analysis of our cases and those in the literature revealed that painful lesions are more than twice as common as asymptomatic lesions (Table V). This together with other neurologic symptoms such as paresthesia or anesthesia may contribute to the confusion clinically of NS with a malignant neoplasm64 (Table VIII). Most investigators, including Batsakis and Manning,s9 believe that NS arises due to blockage or compromised blood supply to salivary gland lobules, resulting in ischemic necrosis or infarction. However, the nature and pathophysiology of the ischemia has yet to be elucidated in most cases. Arguelles et al6 discussed in detail the possible etiologic factors, which include vascular injury, infection, and physical and chemical trauma. Possible predisposing factors were recorded for cases in our study and in the literature
(Table VI). Examples of traumatic injury in our study included four cases with blows sufficient enough to cause clinically evident damage to blood vessels (three lacerations, one hematoma). In the literature one case of NS occurred in the mucobuccal fold after a blow to the face 2 days previously.** The NS in these cases was likely due to ischemia resulting from direct injury to these vessels. Analysis of our data and that of the literature revealed only two well-documented cases of NS in the area of a prior dental injection,33 both of which occurred on the posterior hard palate. We suspect from review of the clinical data that dental injection may play a larger role than is indicated by these figures, because several patients had received recent dental treatment in the area before the development of NS. A large volume of anesthetic introduced rapidly in the tissue, 66direct injury to a blood vessel from the needle, or prolonged pressure by swelling from anesthestic solution may compromise local blood supply and result in NS6 A total of 18 cases (AFIP/WHMC cases and literature) were associated with dentures (documented as ill-fitting in 11 cases). It is interesting to speculate that undue pressure from an ill-fitting denture might compromise the palatal blood supply enough to result in infarction of minor salivary glands. Interestingly, in 17 patients from this study and from the literature, NS developed on the palate after or in association with an upper respiratory infection or allergy (Table VI). Perhaps the swelling of mucous membranes encountered in upper respiratory infections67 and allergies plays a sole in compromising the vascular supply to the posterior hard and soft palate, nredisnosinn in some cases to NS
Volume Number
72 3
Table
IX.
Necrotizing Cases of NS misinterpreted
Mucoepidermoid CA Squamous cell CA Acinic cell CA Verrucous CA Ductal CA Mucus-producing adenocarcinoma Benign vs malignant* Mixed tumor PEH Mucocele Pyogenic granuloma CA, Carcinoma;
*References TReferences
AFIPIWHMC study (25 cases) 9 6 1 1 1 0 2 2 1 1 1
Table
Literature review (24 cases) 10* lot 0 0 0 13’
initially
AFIPIWHMC study (8 cases)
Treatment Conservative excision Wide excision En bloc excision Partial maxillectomy Maxillectomy Surgery (NOS)
Literature review (13 cases)
2
67. 14,24, 39, 53. 57 56, 10, 19. 33, 54
1 2 1 2
15 160 0 0
0
224v 26
129 0 0 0
PEH, pseudoepitheliomatous hyperplasia. 1, 5, 6, 7, 10, 14, 16, 25, 33, 50. 4, 6, 19, 21. 25, 39, 53, 54, 57,60.
*In two cases from each series, the pathlogists whether the lesion was benign or malignant.
323
X. Cases of NS improperly managed as result of incorrect malignant diagnosis
on initial
biopsy Initial diagnosis
sialometaplasia
could
not determine
NS was found in association with another lesion in seven instances in our study. In these cases, the tumor or cyst itself likely compromised the blood supply to the involved glands, resulting in ischemic necrosis and sialometaplasia. Interestingly, infarction was identified in three of these tumors, further supporting ischemic necrosis as the direct cause of NS (Table VII). Also of note is that one of our cases was associated with lymphoproliferative disease of the hard palate, in which subsequent workup disclosed that the patient had disseminated lymphoma. Paulson et al.$* recently reported a case of NS that was associated with and delayed the diagnosis of a rhabdomyosarcoma in the tonsillar fossa region. In 25 cases from our study and in 14 from the literature (Table IV), NS developed after a surgical procedure for a benign or malignant lesion. The majority of our cases were from the palate, whereas most in the literature involved the parotid gland. The time interval from initial surgery to the development and diagnosis of NS ranged from 6 to 53 days, with a mean interval of 18 days in our series. The mean interval for such cases in the literature was 21 days. These time intervals are roughly 2 weeks longer than in experimental studies by Standish and Shafer6* and subsequently by Englander and Cataldo,6g in which NS was produced in rats by ligating the blood vessels supplying the submandibular and sublingual glands. Interestingly, the average duration from onset to diagnosis for our de novo lesions was also about 21 days. This appears to represent a rough estimate of the time required in human beings for the development of NS. The majority of our cases involving pure mucous glands showed classic NS histologically. However, in
NOS,
Not
otherwise
specified.
mucoserous and serous glands, coagulation necrosis of acini was seldom a prominent feature. Instead, these acini most often demonstrated atrophy, a well-recognized cellular and tissue adaptive response to a diminished vascular s~ppiy.~~ It is apparent from our study that a spectrum of histologic findings exists, ranging from coagulation necrosis of acini in early lesions to squamous metaplasia of ducts and reactive fibrosis in late lesions. Because of this histologic spectrum, the diagnosis of NS frequently requires recognition without the presence of infarctive necrosis of acinar cells. As outlined originally by Abrams et al.’ and more recently by Gnepp,2 helpful criteria in distinguishing NS from a malignant process are (1) maintenance of the overall lobular morphology, (2) the generally bland appearance of the squamous islands or nests, and (3) evidence of residual ductal lumina in one or more of these nests. Occasionally, however, we observed reactive atypia in the squamous islands and nests. In these situations, the overall lobular appearance and the presence of intraepithelial inflammation in the squamous nests are helpful in establishing the correct diagnosis. From this discussion it should be apparent that an adequate biopsy on the part of the surgeon is of paramount importance to ensure accurate histopathologic interpretation of this lesion. Analysis of our cases and those from the literature showed that histopathologic misinterpretation of NS, regardless of its clinical setting, may result in clinical mismanagement. Twenty-one patients from both series received unnecessary or inappropriate therapy, ranging from conservative excision to total maxillectomy (Table X). These procedures were performed as a result of incorrect microscopic interpretations on the initial biopsy. The most frequent misdiagnosis rendered was mucoepidermoid carcinoma or squamous cell carcinoma (Table IX). It is evident that we have included in our series and in the literature review cases of NS that have followed and possibly resulted from prior surgery or trauma, or were associated with another lesion. Some authors are
324
Brannon, Fowler, and Hartman
ORAL
SURG ORAL
MED ORAL
PATHOL
September I99 l
not in full agreement that the term necrotizing sialometaplasia should be used for the broad spectrum of histologic patterns and clinical settings such as those which we have outlined. Abrams” has suggested that this term be reserved for those instances where documented spontaneous infarction of gland occurs without previous iatrogenic cause. Because a common etiologic thread exists, that is, vascular compromise with resulting ischemia, regardless of the location or the associated clinical factors, and because of the similarity in histomorphologic characteristics, it is our contention that necrotizing sialometaplasia is a proper designation for the spectrum of histologic changes and clinical settings that have been described for this entity. CONCLUSIONS
Any factor that causes a compromise in blood supply to a minor or major salivary gland or mucoserous gland of the upper respiratory tract may result in NS. NS may occur de novo, after a prior surgical procedure, or in association with another lesion, either benign or malignant. Because of the latter, whenever the diagnosis of NS is made, close follow-up is warranted until healing is complete. The average healing time for our cases and for those in the literature was 5 to 6 weeks. Recognition of the histologic spectrum and the varied clinical settings in which NS can be found is essential, to avoid histopathologic misinterpretation and inappropriate treatment for this benign reactive lesion. Wethank JulieA. Brannon,CardiologyService,WHMC, Lackland Air Force Base,Tex., for assistance in preparing the manuscript,and Mr. Bobby Burnes,Photomicrography Lab, BrooksAir ForceBase,Tex., for technicalexpertisein preparingthe photomicrographs. REFERENCES
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Reprinf
requests:
Craig B. Fowler, MAJ, USAF, DC Department of Oral Pathology Wilford Hall USAF Medical Center/SGDM Lackland Air Force Base, TX 78236-5300