Traumatic eosinophilic granuloma of the oral mucosa: a CD30+(Ki-1) lymphoproliferative disorder?

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Oral Oncology, Vol. 33, N o . 5, pp. 375 379, 1997 © 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 1368-8375/97 $ 1 7 . 00 + 0 .0 0

Pergamon PII: S0964-1955 (97)00014-6

Case Report T r a u m a t i c E o s i n o p h i l i c G r a n u l o m a o f the Oral Mucosa: a C D 3 0 + ( K i - 1 ) L y m p h o p r o l i f e r a t i v e Disorder?* G. Ficarra, 1 F. P r i g n a n o 2 a n d P. R o m a g n o l i 3 1Institute of S t o m a t o l o g y ; 2 D e p a r t m e n t of D e r m a t o l o g y II a n d 3Institute of A n a t o m y a n d Histology, U n i v e r s i t y of F l o r e n c e a n d H o s p i t a l of Careggi, F l o r e n c e , Italy

T r a u m a t i c e o s i n o p h i l i c g r a n u l o m a o f t h e o r a l m u c o s a , a l s o k n o w n a s e o s i n o p h i l i c u l c e r , is c o n s i d e r e d to b e a r e a c t i v e l e s i o n of u n k n o w n a e t i o l o g y . It u s u a l l y p r e s e n t s as a t o n g u e u l c e r a n d i n j u r y h a s b e e n considered to play a role in its cause. We present a 72-year-old man who had suffered multiple episodes of recurrent eosinophilic ulcers of the oral mucosa which underwent self-heating. Biopsy specimens (including fresh tissue) were studied with a combination of histology, electron microscopy and immunohistochemistry. A dense cell infiltrate composed of eosinophilis, lymphocytes and large mononuclear cells was constantly shown. Immunostalns showed that the infiltrate was mainly composed of CD3+,CD4+,CDS-T-celIs and CDla+dendritic cells. A p p r o x i m a t e l y 70% of the T - c e l l s expressed CD30 (Ki-1) antigen. On the basis of the clinical behaviour, histology and antigenic f e a t u r e s , it s e e m s r e a s o n a b l e to s u g g e s t t h a t t r a u m a t i c e o s i n o p h i l i c g r a n u l o m a of the o r a l m u c o s a may represent the oral countpart of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. This group of cutaneous lymphomas are indeed characterised by non-aggressive clinical b e h a v i o u r ( s e q u e n t i a l e v o l u t i o n i n u l c e r a t i o n , n e c r o s i s a n d s e l f - r e g r e s s i o n ) a n d e x p r e s s i o n o f CD30 a n t i g e n b y t h e i n f i l t r a t i n g l a r g e T - c e i l s . © 1997 E l s e v i e r S c i e n c e L t d Key words: eosinophilic ulcer, traumatic

granuloma,

cutaneous lymphomas

Oral Oncology, Vol. 33, N o . 5, pp. 3 7 5 - 3 7 9 , 1997

INTRODUCTION Traumatic eosinophilic granuloma (TEG) of the oral mucosa is considered to be a reactive lesion with a benign clinical course. T E G has been known by different terms, including eosinophilic ulcer, eosinophilic granuloma of soft tissue, and traumatic ulcerative granuloma with stromal eosinophilia [1-9]. In infants it has been called Riga-Fede disease [2, 10]. Clinically, it presents as an ulcer on the tongue, gingiva or buccal mucosa that may mimic squamous cell carcinoma. The aetiology of T E G remains obscure, although injury has been considered to play a major role. Microscopically, T E G may resemble a lymphoid neoplasm and Langerhans' cell

disease (idiopathic histiocytosis) [11, 12]. Cases without an obvious traumatic aetiology that show, despite a benign clinical behaviour, some features of histological atypia, have been indicated as atypical histiocytic granuloma [13, 14]. We present a 72-year-old man who has suffered multiple episodes of recurrent T E G of the oral mucosa. We suggest that, on the basis of the clinical behaviour, histology and antigenic features of T E G , it seems reasonable to consider this unusual condition as the oral counterpart of cutaneous CD30+ lymphoproliferative disorders. CASE REPORT

Clinical findings

*Presented in part at the Meeting of the International Association of Oral Pathologists, York, U.K., July 1994. This paper is dedicated to the memory of Dr F. Galeotti, who began the EM analysis of this case and died in 1994. Correspondence to G. Ficarra. Received 8 Nov. 1996; provisionally accepted 21 Nov. 1996; revised manuscript received 21 Feb. 1997.

A 76-year-old caucasian man presented to our Oral Medicine Clinic for the diagnosis and treatment of recurrent, painful ulcers of the oral mucosa. The patient stated that similar lesions had first occurred in 1986 and since then had showed frequent and multiple recurrences. The patient reported suffering for an average of between five and six recurrent ulcerative episodes per year, with lesions mainly located on the dorsum tongue, gingiva and buccal mucosa. At

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that time, a diagnosis of 'eosinophilic granuloma' was m a d e and the lesions were treated by surgical excision. At the first clinical examination in our Clinic (July 1989), the patient presented a round, yellowish nodule, firm to palpation, on the d o r s u m tongue. T h e diameter was approximately 0.8 ram. T h e patient could not recall previous local trauma. Also he did not report a history of any particularly predisposing factors or unusual habit. T h e only concurrent illness was Parkinsons' disease which was treated with L-DOPA. T h e lesion was excised for histopathological examination and the w o u n d healed without complication. After the first examination, the patient continued to develop multiple recurrent episodes, with ulcers occurring mainly on the buccal mucosa and gingiva (Fig. 1a,b). Every single ulcerative episode lasted between 3 and 4 weeks and slowly u n d e r w e n t spontaneous healing. Incisional biopsies were repeated several times and tissues consistently showed features of an eosinophilic granuloma. Lesional tissues obtained from two different ulcerative episodes were also studied (including fresh tissue) with a combination of light microscopy, electron microscopy and immunohistochemistry. At the last follow-up (January 1996) the patient reported m o r e than 30 additional episodes of recurrent ulcers, located mainly on the buccal mucosa, gingiva and d o r s u m of the tongue. T h e appearance of the lesions was followed by spontaneous healing.

(a)

Light microscopy T h r e e specimens from three different ulcerative episodes were examined. Tissues were from ulcers on the tongue, gingiva and buccal mucosa. T h e surface appeared covered with a fibrinopurulent exudate. In each specimen, a dense cell infiltrate extended deep into the submucosa (Fig. 2) and between muscle fibres. Degeneration and loss of muscle fibres was a consistent finding. T h e predominating cells were lymphocytes, eosinophils, and large m o n o n u c l e a r cells with round to ovoid pale staining nuclei (Fig. 3). Granulocytes and plasma cells were present near the surface of the ulcer. In each specimen, the histopathological aspects were consistent with the features of eosinophilic granuloma. Electron microscopy Portions of two specimens were fixed by the K a m o v s k y method, osmicated and e m b e d d e d in E p o n 812. Sections were stained with uranyl acetate and bismuth tartrate and observed in a Siemens Emiskop 1 and 102 transmission electron microscope, at 80 KV. T h e cell types found in infiltrated areas were similar between the two biopsies used for electron microscopical analysis, which derived from samples taken 2 years apart. Only minor quantitative difference were observed in the proportions a m o n g the different cell populations; the percentage reported below were c o m p u t e d from 142 cell sections

Fig. 2. Low p o w e r scan of the b i o p s y s p e c i m e n shows diffuse i n f l a m m a t i o n ( H a e m a t o x y l i n - e o s i n stain; x 25).

(b) Fig. 1. (a) U l c e r a t e d nodule of the u p p e r llp; Co) Painful ulcer o f the upper gingiva.

Fig. 3. At higher magnification the infiltrate appears polym o r p h o u s and contains large m o n o n u c l e a r ceils a d m i x e d with s m a l l e r l y m p h o c y t e s and eosinophils (x 400).

T r a u m a t i c Eosinophilic G r a n u l o m a of the Oral M u c o s a

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Table 1. Monoclonal antibodies used in this study Antigen (cluster designation)

Source

Specificity

HLA-DR CDla CD2 CD3 CD4 CD8 CD14

BD ODS CC ODS CC ODS DP

CD30

DP

CD36 CD68

ODS DP

MHC class II antigens Langerhans cells and related cells E-rosette receptor Mature T-cells Helper/inducer T-cells Suppressor/cytotoxic T-cells Monocytes, macrophages immature dendritic cells Activation/early differentiation antigen Dendritic macrophages Macrophages

BD: Becton Dickinson, Mountain View, California, U.S.A.; DP: Dakopatts, Gostrup, Denmark; ODS: Ortho Diagnostic Systems, Raritan, New Jersey, USA; CC: Coulter Clone, Leicester, U.K.

Fig. 4. Infiltrate in a lesion o f the gingiva, consisting o f m o n o c y t e - m a c r o p h a g e (M), l y m p h o c y t e s (L), and eosinophils (E) (EM, ×4500).

containing the nucleus of both biopsies used for this analysis. M o s t cells appeared to be leucocytes, i.e. non-lymphocyte m o n o n u c l e a r cells (54%), lymphocytes (20%), eosinophilis (7%) and neutrophilis (2%) (Fig. 4); further cells in these areas were fibroblasts (7%) and cells which could not be ascribed to a definite type on the basis of electron microscopy (10%). Each cell in the infiltrate contacted several other cells, of the same and different types, over wide areas. A m o n g non-lymphocyte m o n o n u c l e a r cells, some were relatively small, with few and short cytoplasmic projections and few organelles, which included some m e m b r a n e - b o u n d , electron-dense bodies interpreted as residual bodies. Other cells were large, had a cytoplasm extending into broad and long dendrites and were rich in organelles, especially rough endoplasmic reticulum Golgi, endocytic vesicles close to the plasma m e m b r a n a and residual bodies, which were n u m e r o u s and distributed all over the cytoplasm. F u r t h e r cells had cytoplasmic features intermediate between those described above. T h e nucleous of all non-lymphocyte m o n o n u c l e a r cells had some indentations, a peripheral, unevenly thick rim of condensed chromatin and pale chromatin in the centre. Because of the overall morphology and constant presence of residual bodies, all these cells were interpreted as of m o n o cytes-macrophage lineage. Birbeck granules, although carefully searched for, were never seen; however, serial sections were not prepared. Lymphocytes and granulocytes appeared to have a normal structure u n d e r any respect.

some cases have established that T E G is characterised by a m i x e d cellular infiltrate which shows a p r e d o m i n a n c e of eosinophils, T-lymphocytes, CD68-positive cells and XIIIapositive cells, the most prevalent cell type in T E G [7, 8]. Regezi et al. [8] reported that the peculiar, large m o n o n u c lear, pseudoneoplastic infiltrate consists primarily of macrophage, dendrocytes, and occasional S-100-positive cells. In our case, immunostains showed that the infiltrate was mainly c o m p o s e d of C D 3 + , C D 4 + , and C D 8 - T-cells associated with C D l a + d e n d r i t i c cells. In addition, approximately 70% o f th e T-cells expressed C D 3 0 (Ki-1) antigen. A discrepancy has been found between the expression of C D l a antigen (a marker of Langerhans cells) and the electron microscopical features of infiltrating m o n o n u c l e a r cells. T h e s e lacked any features of Langerhans lineage, such as richness in s m o o t h vesicles and tubules in the interior of the cytoplasm (not only close to the cell m e m b r a n e ) and virtual absence of residual bodies, not to say of Birbeck granules. T h e richness in residual bodies of these cells hints to active phagocytosis and a macrophage phenotype. This discrepancy might be a consequence of incorrect terminal differentiation of dendritic cells in the infiltrate [15-17]; it cannot be stated at present whether it can play a pivotal role in the infiltration of lymphocytes and eosinophils or, on the contrary can follow abnormal stimulation by C D 3 0 + infiltrating lymphocytes.

Immunohistochemistry Sections were prepared from snap frozen tissue, cryosectioned, air dried, fixed in cold acetone and i m m u n o l a b e l l e d according to the alkaline phosphatase-anti-alkaline (APMP) phosphatase technique. T h e m o n o c l o n a l antibodies used as primary antibodies are listed in T a b l e 1. Immunostains showed that the infiltrate was mainly c o m posed of C D 3 + , C D 4 + , C D 8 T-cells, associated with C D l a+dendritic cells. Approximately 70% of T-cells expressed the C D 3 0 (ki-1) antigen, as shown by both Ki-1 and BerH 2 antibodies (Fig. 5). DISCUSSION T h e histogenesis of T E G is currently a matter of debate. I m m u n o h i s t o c h e m i c a l studies of the cellular infiltrate of

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T h e C D 3 0 antigen, which is recognised by the m o n o c l o n a l antibodies Ki-1 and Ber-H2, is expressed in H o d g k i n ' s disease ( H D ) , in highly activated B- and T-cells and in certain large cell l y m p h o m a s of b o t h T - and B-cell origin [18-25]. T h e s e C D 3 0 (Ki-1)-positive lymphomas may also affect the skin showing a complex clinicopathologic and i m m u n o h i s t o chemical s p e c t r u m [23]. Willemze and Belljaards [24] have a t t e m p t e d to classify these disorders into three major groups consisting of: (a) primary cutaneous C D 3 0 + , large cell lymphomas (anaplastic and non-anaplastic), l y m p h o m a t o i d papulosis, various intermediate ill-defined conditions and exceptional cases of primary cutaneous H D ; (b) cutaneous C D 3 0 + l y m p h o m a resulting from another type of l y m p h o m a of the skin (mycosis fungoides); and (c) secondary cutaneous involvement of a primary non-cutaneous C D 3 0 + large cell l y m p h o m a or of H D . Primary cutaneous C D 3 0 + l a r g e cell l y m p h o m a s (group (a)) occurs mainly in adults. At the first clinical presentation, most patients show solitary skin papulonodular and/or plaque-like lesions, sometimes coalescing in larger ulcerated t u m o u r masses. Only few patients (about 10%) have lesions spread to more than one anatomic area, and often these n u n o u r s undergo self-regression. This type of cutaneous l y m p h o m a has a non-aggressive clinical behaviour and favourable prognosis, with a 4-year survival rate of 90%. Radiotherapy is usually very effective and the treatment of choice [24, 25]. Histologically, these l y m p h o m a s show a dense infiltrate of large C D 3 0 + t u m o u r cells, which assume a cohesive growth pattern forming large clusters or nodules. A variable n u m b e r of inflammatory cells, mainly eosinophils, small lymphocytes and macrophages are generally found at the periphery of these clusters. Immunostains demonstrate that most of these primary cutaneous C D 3 0 + lymphomas are of T-cell origin [26, 27]. A disease that is considered as part of the clinical and histological s p e c t r u m of primary cutaneous C D 3 0 + lymphomas is l y m p h o m a t o i d papulosis [24, 28]. T h i s is a distinct entity, which manifests as recurring, self-healing crops of necrotic papules and displays a cytologically malignant infiltrate. Histologically, it is characterised by the presence of variable numbers of C D 3 0 + large, atypical, Reed-Sternberg-like cells ( type A) and/or C D 3 0 + atypical cerebriform m o n o n u c l e a r cells (type B) similar to those in mycosis fungoides [28]. It is interesting to note that our case displays a great similarity to those reported u n d e r the term of atypical histiocytic granuloma by Eversole et al. [13]. This lesion is currently interpreted as a reactive proliferation formed of histiocytes, which show intense p l e o m o r p h i s m and n u m e r o u s mitotic figures, and variable n u m b e r s of lymphocytes and eosinophilic cells. T h e s e lesions do not appear to be associated with systemic disease and heal spontaneously despite their worrisome microscopic appearance. T h e possible expression of C D 3 0 by the cells of so-called atypical histiocytic granuloma has not yet been tested. Because of either the clinical or microscopic similarities between T E G and atypical histiocytic granuloma, these entities may represent a spectrum of the same disease [9]. Recently, Rosenberg et al. [29] reported 2 patients with primary extranodal C D 3 0 + n o n - H o d g k i n ' s lymphomas of the oral m u c o s a which mimicked multifocal T E G and periodontitis. O n the basis of the clinical behaviour histology and antigenic features of our case, the interpretation of T E G as a histiocytic disorder is worth discussion. Alternatively, it

seems reasonable to suggest that T E G of the oral mucosa may represent the oral counterpart of cutaneous CD30+lymphoproliferative disorders (Group A according to Willemze and Beljaards [24]. This distinctive subtype of cutaneous l y m p h o m a is indeed characterised by non-aggressive clinical behaviour (sequential evolution in ulceration, necrosis and self-regression) and expression of C D 3 0 antigen by the infiltrating large T-cells. 1. Bhaskar, S. N. and Lilly, G. E., Traumatic granuloma of the tongue (human and experimental). Oral Surgery, Oral Medicine, Oral Pathology, 1964, 18, 206-218. 2. Elzay, R. P., Traumatic ulcerative granuloma with stromal eosinophilia (Riga-Fede disease and traumatic eosinophilic granuloma). Oral Surgery, Oral Medicine, Oral Pathology, 1983, 55, 497-506. 3. Sklavounou, A. and Laskaris, G., Eosinophilic ulcer of the oral mucosa. Oral Surgery, Oral Medicine, Oral Pathology, 1984, 58, 431-436. 4. Tang, T. T., Glicklich, M., Hodach, A. E., Oechler, H. W. and McCreadie, S. R., Ulcerative eosinophilic grantdoma of the tongue. A light and electron-microscopy study. American Journal of Clinical Pathology, 1981, 75, 420425. 5. Doyle, J. L., Geary, W. and Baden, E., Eosinophilic ulcer. Journal of Oral Maxillofacial Surgery, 1989, 47, 349-352. 6. Lombardi, T., Kuffer, R. and Samson, J., Eosinophilic ulceration of the oral mucosa. A case report. International Journal of Oral Maxillofacial Surgery, 1993, 22, 366-367. 7. EI-Mofty, S. K., Swanson, P. E., Wick, M. R. and Miller, A. S., Eosinophilic ulcer of the oral mucosa. Report of 38 new cases with immunohistochemical observations. Oral Surgery, Oral Medicine, Oral Pathology, 1993, 75, 716-722. 8. Regezi, J. A., Zarbo, R. J., Daniels, T. E. and Greenspan, J. S., Oral traumatic granuloma. Characterization of the cellular infiltrate. Oral Surgery, Oral Medicine, Oral Pathology, 1993, 75, 723727. 9. Mezei, M. M., Tron, V. A., Stewart, W. D. and Rivers, J. K., Eosinophilic ulcer of the oral mucosa. Journal of the American Academy of Dermatology, 1995, 33, 734-740. 10. Eichenfield, L., Honig, P. and Nelson, L., Traumatic granuloma of the tongue (Riga-Fede): association with familial dysautonomia. Journal of Pediatrics, 1990, 116, 742-744. 11. Godfrey, R. M. and Sloan, P., Traumatic (eosinophilic) granuloma of oral soft tissues: a report of two cases with pseudo-lymphomatous features. British Journal of Oral Maxillofacial Surgery, 1985, 23, 351-354. 12. Rongioletti, F. and Nunzi, E., Traumatic eosinophilic ulcer of the oral mucosa. Cuds, 1989, 43, 357-359. 13. Eversole, L. R., Leider, A. S., Jacobson, P. L. and Kidd, P. M., Atypical histiocytic granuloma. Cancer, 1985, 55, 1722-1729. 14. De Vincente-Rodriquez, J. C., Santos-Oiler, J. M., JunqueraGutierrez, L. M. and Lopez-Arranz, J. S., Atypical histiocytic granuloma of the tongue: case report. British Journal of Oral Maxillofacial, 1991, 29, 350-352. 15. Pimpinelli, N., Romagnoli, P., Bosi, A., et al., Dendritic cells in the skin after allogenic bone marrow transplantation: immunohistochemical and electron microscopic monitoring. European Journal of Dermatology, 1993, 4, 310-317. 16. Mori, M., Pimpinelli, N., Romagnoli, P., Bernacchi, E., Fabbri, P. and Giarmotti, B., Dendritic cells in cutaneous lupus erythematous: a hint to the pathogenesis of lesions. Histopathology, 1994, 24, 311-321. 17. Priguano, F., Mori, M., Bacci, S., Pimpinelli, N., Romagnoli, P., Morphologic and antigenic features of dendritic cells in immunemediated dermatoses: a hypothesis of differentiation. In Dentritic Cells in Fundamental and Clinical Immunology, eds J. Banchereau and D. Schmidt. Plenum, New York, 1995, pp. 125-128. 18. Schawb, U., Stein, H., Gerdes, J. et al., Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin disease and a subset of normal lymphoid cells. Nature, 1982, 299, 65-67. 19. Stein H., Mason, D. Y., Gerdes, J., et al., The expression of Hodgkin-associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Stenberg cells and histiocytic

T r a u m a t i c Eosinophilic G r a n u l o m a o f the Oral M u c o s a

20. 21. 22. 23. 24.

25.

malignancies are derived from activated lymphoid tissue. Blood, 1985, 66, 848-858. Kadin, M. E., Sako, D., Bediner, N., et al., Childhood Ki-1 lymphoma presenting with skin lesions and peripheral lymphadenopathy. Blood, 1986, 68, 1042-1049. Agnarsson, B. A. and Kadin, M. E., Ki-1 positive large cell lymphoma: a morphologic and immunologic study of 19 cases. American Journal of Surgical Pathology, 1988, 12, 264-274. Chott, A., Kaserer, K., Augustin, I., et al., Ki-1 positive large cell lumphoma: a clinicopathologic study of 41 cases. American Journal of Surgical Pathology, 1990, 14, 439-448 Greer, J. P., Kinney, M. C. Collins, R. D., et al., Clinical features of 31 patients with Ki- 1 anaplastic lage cell lymphoma. Journal of Clinical Oncology, 1991, 9, 539-547. Willemze, R. and Belljaards, R. C., Spectrum of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment. Journal of the American Academy of Dermatology, 1993, 28, 973-980. Pimpinelli, N., Santucci, M. and Giannotti, B., Cutaneous lymphoma: a clinically relevant classification. International Journal of Dermatology, 1993, 32, 695-700.

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26. Gianotti, R., Alessi, E., Caicchini, S., et al., Primary cutaneous pleomorphic T-cell lymphoma expressing CD30 antigen. American ffournal of Dermatopathology, 1991, 13, 503-508. 27. Belljaards, R. C., Kaudewitz, P., Berti, E., et al., Primary cutaneous large cell lymphoma with favorable prognosis: a European multicenter study on 47 patients. Cancer, 1993, 71, 2097-2104. 28. Karp, D. L. and Horn, T. D., Lymphomatoid papulosis. Journal of the American Academy of Dermatology, 1994, 30, 379-395. 29. Rosenberg, A., Biesma, D. H., Sie-Go, D. M. D. and Slootweg, P. J., Primary extranodal CD30-positive T-cell non-Hodgkin's lymphoma of the oral mucosa. Report of two cases. International Journal of Oral Maxillofacial Surgery, 1996, 25, 57-59.

A c k n o w l e d g e m e n t s - - T h i s research was supported in part by the Italian Ministry of Universities and Regione Toscana (as part of the 3rd Project of finalised health research). The authors would like to thank Professor Marco Santucci and Dr Nicola Pimpinelli from the University of Florence for their helpful suggestions.

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