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Ulcerative eosinophilic granuloma: a report of five new cases
Bnr,.\h Owl end d 1996 The Brltlsh Association ofOral
, 1996, .3l. I I5- I I7 and Maxillofacial Surgeon,
I
I
Ulcerative eosinophilic granuloma: a report of five new cases K. Movassaghi, M. L. Goodman, D. Keith A4assachusrtts General Hospital; Massachusetts Eye und Ear Injirmary; Harvard School qf Dental Medicine, Boston, A4u.ssuchusrtt.s, USA
Hurvmd Medical School,
SUMMAR Y. Five new cases of ulcerative eosinophilic granuloma were diagnosed at the Massachusetts General Hospital between 1982 and 1993. In all cases the site was the tongue. They were unifocal, did not recur, and had a benign course. This report illustrates their benign nature despite the occasional aggressive presentation, and outlines possible aetiology.
from 8 to 46 years. All the lesions were unifocal and limited to the lateral border or the dorsum of the tongue (Fig. 1). There was associated injury in two patients. Of these, one patient reported ‘biting’ and another patient had a history of a recent seizure. The disease presented as an exophytic indurated sessile mass of the tongue. Three patients reported tenderness and three surface ulceration. At the time of biopsy, one patient had clear exudate from the mass. The duration of the lesions from the time of first appearance to complete resolution ranged from 2 weeks to 3 months. All were treated with either conservative excisional biopsy, or incisional biopsy, with spontaneous resolution. There was no history of recurrence and no long term follow-up.
INTRODUCTION
Ulcerative Eosinophilic Granuloma (UEG) is a rare benign disease of the oral mucosa of unknown aetiology. It is not related to eosinophilic granuloma or histiocytosis X and presents as a solitary lesion of the oral cavity, usually the tongue; it does not involve bone and heals spontaneously. Though usually solitary, some cases of multiple lesions have been reported and some have recurred. UEG can occur at any age and there is no sex bias. We know of about 110 reported cases of UEG and it has been given several names.lm5 In infants, it has been called Riga’s disease, Riga-Fede’s disease, sublingual ulcer, sublingual granuloma and reparative lesion of the tongue.3 Other terms include: ulcerated granuloma eosinophilicum diutinum,” traumatic granuloma of tongue,6 eosinophilic granuloma of tongue,’ eosinophilic ulcer of tongue,’ traumatic eosinophilic granuloma,” and ulcerative eosinophilic granuloma of the tongue.’ We prefer the term UEG because it is both concise and descriptive, without making a definitive statement of the aetiology and location in the oral cavity. Here we report five new cases of UEG and emphasize its benign nature, because it is rare and may be mistaken for a cancer or a microbial infection. PATIENTS
Histological features
Histological examination showed a histomorphology similar to those reported by othed a rs. Ulceration was reported in all the cases. Below the ulcerated surface there was inflamed granulation tissue that extended into the submucosa where a more exuberant reactive process was noted (Fig. 2). Eosinophils were scattered, and clustered, at the periphery of the lesion. Plasma cells, mast cells, histiocytes, small vessels, and varying degrees of fibrosis were present in larger quantity. Mitoses were seen occasionally. In the deeper layer, the same cellular infiltrate separated the muscle fasciculi and muscle fibers with varying degrees of degeneration (Fig. 3).
AND METHOD
In this report we present all cases of UEG diagnosed by the pathology department at Massachusetts General Hospital, including five cases between 1982 and 1993. For each case, the medical records were obtained and surgeons contacted for additional information (Table 1).
DISCUSSION
The clinical presentation of UEG as an ulcerated indurated mass can mimic that of cancer or microbial infection; in many of the cases reported, the initial clinical diagnosis was either ‘carcinoma’ or ‘rule out carcinoma’ UEG3 is a clinical entity distinctly different from the eosinophilic granuloma of histiocytosis X. Histiocytosis X is a systemic disease that often
RESULTS Clinical features
One of the main features of UEG was an almost equal male:female ratio. The age distribution ranged 115
116 Table
British Journal of Oral and Maxillofacial 1
Surgery
- Five new cases of ulcerative eosinophilic granuloma
Case no.
Age/Sex (years)
Site
Size (cm)
Duration
Injury
Course
Treatment
1
46/F
1.5 x2.0
3 weeks
None
Resolved
2
26/F
1.5 x 1.0
2 days
Biting
Resolved
3
45/M
4 weeks
None
Resolved
Incisional biopsy Incisional biopsy Incisional biopsy
4
8/M
0.4 x 0.5
Not known
History of seizure
Resolved
5
41/M
Lateral tongue Lateral tongue Lateral dorsum tongue Dorsum tongue Lateral tongue
1.6 x 1.2
3 months
None
Resolved
3x 1.5
Fig. 1 - Ulcerative eosinophilic granuloma of the lateral border of tongue. By permission of Dr G. Shklar, Harvard School of Dental Medicine).
Fig. 2 - High power photomicrograph of the tongue lesion showing many eosinophils. (Haematoxylin and eosin stain. Original magnification x 313).
Excisional biopsy Excisional biopsy
Fig. 3 - High power photomicrograph showing mixed inflammatory cells infiltrating into skeletal muscle cells of the tongue which have caused their degeneration. This infiltrate is composed of eosinophils, lymphocytes, macrophages and histiocytes. (Haematoxylin and eosin stain. Original magnification x 313).
presents initially with a lesion in the mouth.’ Such lesions differ clinically from benign lesions of UEG, however, in that they often involve bone and the overlying tissues and tend not to heal. Histologically, they are distinctively characterised by the presence of histiocytic cells with grooved nuclear membranes and Birbeck granules inside the histiocytes as shown in electromicroscopic studies.” The aetiology of UEG remains obscure. Injury has been proposed by some, because the incidence increases at sites that are exposed to damage through mastication or from intraoral appliances. This is further supported experimentally in rats by inducing similar lesions in their tongues by chronic injuries.6 If damaged tissues are the sole cause of tissue eosinophilia, however, one would expect to see UEG more often in the oral cavity. Many have proposed that the damaged tissue in some predisposed individuals leads to ingress of some unknown factors, such as viral particles or toxic agents.293 These substances may subsequently induce the reactive process that involves the interaction between the mast cells and eosinophils that is observed in UEG. Elzay3 suggested that the increased numbers of mast cells and eosinophils in these lesions might interact in similar fashion
Ulcerative
as in bronchial asthma. Recently, EL-Mofty et al. reported 38 new cases of UEG.4 Using immunohistochemical techniques, they showed that the infiltrate was composed predominantly of T-cells and T-cellspecific antigen-presenting cells in addition to the eosinophils and proposed that the pathogenesis of UEG is probably mediated by T-cells4 In a similar study, Regezi et al. showed that T-cells, CD68-positive cells, XIIla-positive cells (the oral counterparts to dermal dendrocytes) and eosinophils are the prominent cell types in UEG.’ Despite all these speculations, the causative factor(s) and pathogenesis are yet to be isolated. The prognosis for UEG is very good though it must be remembered that occasionally the lesion can be aggressive. Total removal of such a lesion may result in loss of partial function, but most cases of UEG have been treated by conservative incisional or excisional biopsy. This usually results in spontaneous healing with occasional reported recurrence.ie4 Because UEG is inflammatory, some authors have also proposed the use of topical or systemic steroids. i2 In summary, UEG is an uncommon disease peculiar to the oral cavity which is of unknown aetiology although injury seems to be a contributing factor. The lesion is usually unifocal, though multifocal lesions and recurrences have been reported. Diagnosis is usually established when the clinical and histological data are correlated. In most cases, the lesions heal spontaneously, so there is no need for more radical surgery. Acknowledgment We thank Dr Thomas Mulvaney, Seldin for allowing us to report
Dr Wayne Colin, their patients.
and Dr Edward
References 1. Doyle JL, Geary W, Bader E. Eosinophilic ulcer. J Oral Maxillofac Surg 1989; 47: 3499352. 2. Tang TT, et al. Ulcerative eosinophilic granulomas of the tongue. Am J Clin Path01 1981; 75: 420-425. 3. Elzay RP. Traumatic ulcerative granuloma with stromal
4.
5.
6. 7. 8. 9.
IO. 1 I. 12.
eosinophilic
granuloma-a
report
of five new cases
117
eosinophilia ( Riga-Fede’s disease and traumatic eosinophilic granulbma). Oral Surg 1983; 55: 497-506. EL-Moftv SK. Swanson PE. Wick MR. Miller AS. Eosinophilic ulcer of the oral mucosa. Oral Surg Oral Med Oral Path01 1993; 75: 7 16622. Regezi JA. Zarbo RJ. Daniels TE, Greenspan JS. Oral traumatic granuloma. Oral Surg Oral Med Oral Patho175: 7233727. Bhaskar SN. Lilly GE. Traumatic granuloma of the tongue (human and experimental ). Oral Surg 1964; 18: 206- 218. Shapiro L, Juhlin EA. Eosinophilic ulcer of the tongue. Dermatologica 1970; 140: 242- 250. Welborn JF. Eosinophilic granuloma of the tongue: report of a case. J Oral Surg 1966; 24: 176-179. Hjorting-Hansen E, Schmidt H. Ulcerated granuloma eosinophilicum diutinum of the tongue. Acta Derm Venereol (Stockh) 1961: 41: 2355239. Tornes K. Bang G. Traumatic eosinophilic granuloma of the gingiva. Oral Surg 1974; 38: 99- 102. Nezelof C. Histiocytosis X: a histological and histogenetic study. Perspect Pediatr Pathol 1979; 5: 153- 178. Sklavounou A, Laskaris G. Eosinophilic ulcer of oral mucosa. Oral Surg Oral Med Oral Pathol 1984: 58: 43 I
The Authors Kiumars Movassaghi DMD Oral and Maxillofacial Surgery Resident Massachusetts General Hospital Boston MA lJSA Max L. Goodman MD Director of Otolaryngology Pathology Massachusetts Eye and Ear Infirmary Associate Professor of Pathology Harvard Medical School Boston MA USA David Keith BDS, FDSRCS, DMD Associate Professor of Oral and Maxillofacial Surgery Harvard School of Dental Medicine Visiting oral and maxillofacial surgeon at Massachusetts General Hospital Chief of oral and maxillofacial surgery at Harvard Community Health Plan Boston MA USA Correspondence Movassaghi, Massachusetts
and requests for offprints to Kiumars Department of Oral and Maxiltofdciat Surgery. General Hospital, Boston. MA 02114, USA
Paper received 1 February Accepted IO June 1994
1994
, 1996, .3l. I I5- I I7 and Maxillofacial Surgeon,
I
I
Ulcerative eosinophilic granuloma: a report of five new cases K. Movassaghi, M. L. Goodman, D. Keith A4assachusrtts General Hospital; Massachusetts Eye und Ear Injirmary; Harvard School qf Dental Medicine, Boston, A4u.ssuchusrtt.s, USA
Hurvmd Medical School,
SUMMAR Y. Five new cases of ulcerative eosinophilic granuloma were diagnosed at the Massachusetts General Hospital between 1982 and 1993. In all cases the site was the tongue. They were unifocal, did not recur, and had a benign course. This report illustrates their benign nature despite the occasional aggressive presentation, and outlines possible aetiology.
from 8 to 46 years. All the lesions were unifocal and limited to the lateral border or the dorsum of the tongue (Fig. 1). There was associated injury in two patients. Of these, one patient reported ‘biting’ and another patient had a history of a recent seizure. The disease presented as an exophytic indurated sessile mass of the tongue. Three patients reported tenderness and three surface ulceration. At the time of biopsy, one patient had clear exudate from the mass. The duration of the lesions from the time of first appearance to complete resolution ranged from 2 weeks to 3 months. All were treated with either conservative excisional biopsy, or incisional biopsy, with spontaneous resolution. There was no history of recurrence and no long term follow-up.
INTRODUCTION
Ulcerative Eosinophilic Granuloma (UEG) is a rare benign disease of the oral mucosa of unknown aetiology. It is not related to eosinophilic granuloma or histiocytosis X and presents as a solitary lesion of the oral cavity, usually the tongue; it does not involve bone and heals spontaneously. Though usually solitary, some cases of multiple lesions have been reported and some have recurred. UEG can occur at any age and there is no sex bias. We know of about 110 reported cases of UEG and it has been given several names.lm5 In infants, it has been called Riga’s disease, Riga-Fede’s disease, sublingual ulcer, sublingual granuloma and reparative lesion of the tongue.3 Other terms include: ulcerated granuloma eosinophilicum diutinum,” traumatic granuloma of tongue,6 eosinophilic granuloma of tongue,’ eosinophilic ulcer of tongue,’ traumatic eosinophilic granuloma,” and ulcerative eosinophilic granuloma of the tongue.’ We prefer the term UEG because it is both concise and descriptive, without making a definitive statement of the aetiology and location in the oral cavity. Here we report five new cases of UEG and emphasize its benign nature, because it is rare and may be mistaken for a cancer or a microbial infection. PATIENTS
Histological features
Histological examination showed a histomorphology similar to those reported by othed a rs. Ulceration was reported in all the cases. Below the ulcerated surface there was inflamed granulation tissue that extended into the submucosa where a more exuberant reactive process was noted (Fig. 2). Eosinophils were scattered, and clustered, at the periphery of the lesion. Plasma cells, mast cells, histiocytes, small vessels, and varying degrees of fibrosis were present in larger quantity. Mitoses were seen occasionally. In the deeper layer, the same cellular infiltrate separated the muscle fasciculi and muscle fibers with varying degrees of degeneration (Fig. 3).
AND METHOD
In this report we present all cases of UEG diagnosed by the pathology department at Massachusetts General Hospital, including five cases between 1982 and 1993. For each case, the medical records were obtained and surgeons contacted for additional information (Table 1).
DISCUSSION
The clinical presentation of UEG as an ulcerated indurated mass can mimic that of cancer or microbial infection; in many of the cases reported, the initial clinical diagnosis was either ‘carcinoma’ or ‘rule out carcinoma’ UEG3 is a clinical entity distinctly different from the eosinophilic granuloma of histiocytosis X. Histiocytosis X is a systemic disease that often
RESULTS Clinical features
One of the main features of UEG was an almost equal male:female ratio. The age distribution ranged 115
116 Table
British Journal of Oral and Maxillofacial 1
Surgery
- Five new cases of ulcerative eosinophilic granuloma
Case no.
Age/Sex (years)
Site
Size (cm)
Duration
Injury
Course
Treatment
1
46/F
1.5 x2.0
3 weeks
None
Resolved
2
26/F
1.5 x 1.0
2 days
Biting
Resolved
3
45/M
4 weeks
None
Resolved
Incisional biopsy Incisional biopsy Incisional biopsy
4
8/M
0.4 x 0.5
Not known
History of seizure
Resolved
5
41/M
Lateral tongue Lateral tongue Lateral dorsum tongue Dorsum tongue Lateral tongue
1.6 x 1.2
3 months
None
Resolved
3x 1.5
Fig. 1 - Ulcerative eosinophilic granuloma of the lateral border of tongue. By permission of Dr G. Shklar, Harvard School of Dental Medicine).
Fig. 2 - High power photomicrograph of the tongue lesion showing many eosinophils. (Haematoxylin and eosin stain. Original magnification x 313).
Excisional biopsy Excisional biopsy
Fig. 3 - High power photomicrograph showing mixed inflammatory cells infiltrating into skeletal muscle cells of the tongue which have caused their degeneration. This infiltrate is composed of eosinophils, lymphocytes, macrophages and histiocytes. (Haematoxylin and eosin stain. Original magnification x 313).
presents initially with a lesion in the mouth.’ Such lesions differ clinically from benign lesions of UEG, however, in that they often involve bone and the overlying tissues and tend not to heal. Histologically, they are distinctively characterised by the presence of histiocytic cells with grooved nuclear membranes and Birbeck granules inside the histiocytes as shown in electromicroscopic studies.” The aetiology of UEG remains obscure. Injury has been proposed by some, because the incidence increases at sites that are exposed to damage through mastication or from intraoral appliances. This is further supported experimentally in rats by inducing similar lesions in their tongues by chronic injuries.6 If damaged tissues are the sole cause of tissue eosinophilia, however, one would expect to see UEG more often in the oral cavity. Many have proposed that the damaged tissue in some predisposed individuals leads to ingress of some unknown factors, such as viral particles or toxic agents.293 These substances may subsequently induce the reactive process that involves the interaction between the mast cells and eosinophils that is observed in UEG. Elzay3 suggested that the increased numbers of mast cells and eosinophils in these lesions might interact in similar fashion
Ulcerative
as in bronchial asthma. Recently, EL-Mofty et al. reported 38 new cases of UEG.4 Using immunohistochemical techniques, they showed that the infiltrate was composed predominantly of T-cells and T-cellspecific antigen-presenting cells in addition to the eosinophils and proposed that the pathogenesis of UEG is probably mediated by T-cells4 In a similar study, Regezi et al. showed that T-cells, CD68-positive cells, XIIla-positive cells (the oral counterparts to dermal dendrocytes) and eosinophils are the prominent cell types in UEG.’ Despite all these speculations, the causative factor(s) and pathogenesis are yet to be isolated. The prognosis for UEG is very good though it must be remembered that occasionally the lesion can be aggressive. Total removal of such a lesion may result in loss of partial function, but most cases of UEG have been treated by conservative incisional or excisional biopsy. This usually results in spontaneous healing with occasional reported recurrence.ie4 Because UEG is inflammatory, some authors have also proposed the use of topical or systemic steroids. i2 In summary, UEG is an uncommon disease peculiar to the oral cavity which is of unknown aetiology although injury seems to be a contributing factor. The lesion is usually unifocal, though multifocal lesions and recurrences have been reported. Diagnosis is usually established when the clinical and histological data are correlated. In most cases, the lesions heal spontaneously, so there is no need for more radical surgery. Acknowledgment We thank Dr Thomas Mulvaney, Seldin for allowing us to report
Dr Wayne Colin, their patients.
and Dr Edward
References 1. Doyle JL, Geary W, Bader E. Eosinophilic ulcer. J Oral Maxillofac Surg 1989; 47: 3499352. 2. Tang TT, et al. Ulcerative eosinophilic granulomas of the tongue. Am J Clin Path01 1981; 75: 420-425. 3. Elzay RP. Traumatic ulcerative granuloma with stromal
4.
5.
6. 7. 8. 9.
IO. 1 I. 12.
eosinophilic
granuloma-a
report
of five new cases
117
eosinophilia ( Riga-Fede’s disease and traumatic eosinophilic granulbma). Oral Surg 1983; 55: 497-506. EL-Moftv SK. Swanson PE. Wick MR. Miller AS. Eosinophilic ulcer of the oral mucosa. Oral Surg Oral Med Oral Path01 1993; 75: 7 16622. Regezi JA. Zarbo RJ. Daniels TE, Greenspan JS. Oral traumatic granuloma. Oral Surg Oral Med Oral Patho175: 7233727. Bhaskar SN. Lilly GE. Traumatic granuloma of the tongue (human and experimental ). Oral Surg 1964; 18: 206- 218. Shapiro L, Juhlin EA. Eosinophilic ulcer of the tongue. Dermatologica 1970; 140: 242- 250. Welborn JF. Eosinophilic granuloma of the tongue: report of a case. J Oral Surg 1966; 24: 176-179. Hjorting-Hansen E, Schmidt H. Ulcerated granuloma eosinophilicum diutinum of the tongue. Acta Derm Venereol (Stockh) 1961: 41: 2355239. Tornes K. Bang G. Traumatic eosinophilic granuloma of the gingiva. Oral Surg 1974; 38: 99- 102. Nezelof C. Histiocytosis X: a histological and histogenetic study. Perspect Pediatr Pathol 1979; 5: 153- 178. Sklavounou A, Laskaris G. Eosinophilic ulcer of oral mucosa. Oral Surg Oral Med Oral Pathol 1984: 58: 43 I
The Authors Kiumars Movassaghi DMD Oral and Maxillofacial Surgery Resident Massachusetts General Hospital Boston MA lJSA Max L. Goodman MD Director of Otolaryngology Pathology Massachusetts Eye and Ear Infirmary Associate Professor of Pathology Harvard Medical School Boston MA USA David Keith BDS, FDSRCS, DMD Associate Professor of Oral and Maxillofacial Surgery Harvard School of Dental Medicine Visiting oral and maxillofacial surgeon at Massachusetts General Hospital Chief of oral and maxillofacial surgery at Harvard Community Health Plan Boston MA USA Correspondence Movassaghi, Massachusetts
and requests for offprints to Kiumars Department of Oral and Maxiltofdciat Surgery. General Hospital, Boston. MA 02114, USA
Paper received 1 February Accepted IO June 1994
1994