Oral lesions of eosinophilic granuloma

Oral pathology American

Academy

of Oral

Pathology

Donald Kerr, Editor

Oral lesions of eosinophilic granuloma Histologic

and

clinical

considerations

T

he jaws and oral IIIIICOSB are rarely involved with lesions of cosinol~hilic pranuloma. Homever, when this unusual type of pathosis does occur in thv mouth or in bone of the mandible or maxilla, there are invariably prohlcrll~ in diagnosis. The diagnostic problems are related to both clinical and microscopic considerations. The oral manifestations may not be sufficient to arousc suspicion of some underlying pathologic condition rcsponsiblc for dela>-ed healing or for a persist,ent inflammation. Radiographic manifestations seen 011 intraoral or lateral jaw films may be vague or they may resemble pcriapical, pc+odontal, or cystic lesions, so that, a rare lesion such as eosinophilic granulorna ordinarily would not be considered in the differc~ntial diagnosis. Finally, if a biopsy specimen is obtained from the lesion, the microscopic diagnosis may bc missed if the pathologist does not, have some knowledge of the clinical lesions and a suspicion of the possibility of a specific histiocytosis. 111 a mucosal biopsy, the true lesion may be obscured by secondary inflammatory infiltration. This is particularly true in cases where the clinical lesion is an ulcer or a large ulcerated and eroded area. In a biopsy specimen from a bone lesion, the characteristic pathologic change is usually more apl)arcnt. Thcrc is considerable variation in the histologic pattern of eosinophilic granuloma, however, and unless the tissue is ~~11 fixed, wc~ll sectioned, and well stained, the characteristic fratures may not bc cvitlcnt and the initial diagnosis may br! merely tlescriptivc and imprecise. Further biopsy spccimcns ma! rc~cal the tmc Ilatllrc of the lesion. A majority of the cases in our cspcrioncc w‘crc diagnosctl on initial biopsy as chronic iltflammation by compct,cnt pathologists. Rcvicw of this ma613

614

Shklar

et al.

terial often demonstrated the characteristic features of eosinophilic g~rnulorn~~ in given areas of the specimens. Believing that a review of the subject should bc of interest, we shall present some histologic and clinical considerations basc~l llpon Cases in our recent experience. REVIEW

OF THE LITERATURE

The literature contains a number of case reports of cosinophilic granuloma involving the mouth and jaws.‘, 3-‘i*lci In 1959 Blevins and associates,’ reported on 600 cases of histiocytosis X studied at the Mayo Clinic. Oral lesions WL’C found in thirty cases a.nd examined histologically in twenty-seven cases. In this group of twenty-seven, twenty patients were under 8 years of age and onI> three patients were past 30. There were twenty male patients and seven female paticnt,s. The oral manifestations were described as soreness, swelling, necrosis, or ulccbration of the gingivac in twenty-five cases, loose teeth in twenty-one cases, destruction of alveolar bone of the mandible in nineteen cases and of the nlaxilla in fourteen casts, loss of teeth in seventeen cases, cystlike lesions of the mandible in twelve cases, and swelling of the jaws in fire cases. I’:xtriroral involvement was common in this series of cases. Skull lesions occurred in twcnt!. patients; the femur was involved in twelve patients, the ribs in Icn patients, the ilium and pelvis in eight patients, the humerus in five patients, and the clavicles and spine in four patients. Lesions were limited IO the jaws in onI>- five of the twent,y-seven cases. In the past thcrc was a tendency t,o consider cosinophilic granuloma as a unique and specific type of bone lesion. The works of Farber,? Jaffc and Lichtcnstcin,‘o and Lichtenstein,13 developed the concept of a single disease sti\tc ot’ unknown etiology, characterized by thl*ee rnain types of clinical manifcstation. The mildest and most favorable expression of the disease was considerc>d to be represented by lesions of eosinophilic granuloma, where there could hc one or more lesions of bone but no manifestat,ions of ext,raskeletal involvement. The most severe expression of the disease was considered to be represented 1~ lietterclr-Siwe disease, a clinical syndrome in which there were lesions of boric, characterized 1,) skin, mucous membrane, lymph nodes, liver, and lungs-all histiocytic proliferation. The third type was considered to be represent,ed 1)). Hand-Schiiller-Christian disease, a clinical syndrome with skeletal histiocptic Icsions, cxophthalmos, and diabetes insipidus. Only a small minority of rascs show the complete triad. Bone lesions are present in almost all cases, and lesions of the skin, oral mucosa, lungs, lymph nodes, liver, kidney, and spleen may 1~ plwcr1t.

The term histiocytosi.~ X was proposed for this diseaseI” on the basis of the fact that the fundamental pathologic change common to all three clinical states was a proliferation of histiocytic cells, either replacing bone and causing radioluccnt lesions or infiltrating skin, mucosa, and a variety of internal organs and resulting in notable morphologic and physiologic alterations. Lichtenstein” has further elaborated upon this concept by presenting a terminology in which the three clinical stat,es arc referred to as histiocytosis localized in bone (eosinophilic granuloma) , mute or nchacute disseminated histiocytosis X (,Lcttercr-

siwe

syndrome),

and

cht~on,ic

disset?Li7Kl.ferl

h,istioc~~tOsiS

,Y

(lI~l~d-Sd~ii~lt~~-

Christian disease). In eosinophilic granuloma the liistiocj?ic proliferation is accompanied bJ large numbers of eosinophil leukocytes. Lichtcnstein” points out that earl?-, rapidly developing lesions of Hand-Schiiller-Christian disease (chronic disscminated histiocytosis X) commonly have the characteristics of eosinophilic granuloma. Furthermore, this is true not only of the bone lesions but also the lesions of the skin, mucosa, lungs, lymph nodes, and other organs. HISTOPATHOLOGY

The microscopic features of eosinophilic granuloma present a reasonably characteristic picture. The initial microscopic impression often suggests chronic inflammation, however, and unless eosinophilic granuloma is suspected clinicall!-, the case may be misdiagnosed on the basis of the initial biopsy specimen. This is particularly true when the oral mucosa or gingiva is biopsied, since the microscopic picture is complicated by the normal infiltration of chronic inflanlmatory cells into this tissue. In our csperience, all cases of eosinophilic granuloma involving the gingiva or alveolar mucosa were originally misdiagnosed as simple chronic inflammation on examination of the initial biopsy specimen. Alan>- lesions of eosinopliilic grannloma involving bone were also misdiagnosed initially, but this occurred less commordy since histiocytosis X was considered in the differential diagnosis of some of these cases because of the appearance of large irregular radiolnccnt areas on the radiographs. Essentially, t,lic lesions of rosinophilic granuloma are composed of two typc5 of cell-the histiocytc and the eosinophil or eosinophil leukocyte. These cells may be more or less evenly distributed throughout the lesion (Fig. 1, D) , with the eosinophils appearing to be sprinkled on a background of histiocytes. There may be very dense accumulations of histioq-tes, so that an epithelioid pattern is suggested on low-power magnification (Fig. 1, A). Eosinophils may be present in rarying numbers within the dense zones of histiocytes. There may be estrernely dcnsc accumulations of cosinophils within a generalized dense aggregation of histioq-tes (Fig. 1, C), or there may be alternating zones where histio@es or eoxinophils appear to predominate (Fig. 1, B). This latter pattern is the one most commonly observed. It has been suggested that the number of cosinophils decreases in older lesions, but wc hart had little opportunity 01 observing tissue from long-standing cases. The oldest lesions in our series were approximately of one year‘s duration, and eosinophils mere plentiful in thcscx tissues. Morphologically, the histiocytes vary considerably, but they rarely appear with the swollen cytoplasm characteristic of the lipoid-laden “foam cells” seen in Hand-Schiiller-Christian disease. The nuclear outline varies from round to spindle-shaped (Fig. 2, A). The eosinophils are easily distinguished bp the obvious eosinophilic granules in the cytoplasm and the deeply staining basophilic nucleus (Fig. 2, B) . The histiocytes often appear with interlacing protoplasmic fibrils (Fig. 2, A). The eosinophil nucleus usually consists of two or three lobes (Fig. 2, B)

Fig. 2. A, Lou=power pllotorlli(~rogr;tllll of oral l(3ion of oosinophilic gr:111111m11. Nott Eosinophils :\I’(’ wat dt~nsc: mass of histiocytes at lvft, suggestive of au c~pithclioicl pattwu. tcwd throughout. (Hematoxyliu and cosin stain. Magnificat~ion, xl00 ; reduwd lh .‘i B, Low-power photomicrograpl~ of oral lesion of eosinophilic: granuloma wi tll pat tern 0 i alternating zones in whirh histioc’ytcs or cosinophils pmlominatct. ~Hcmmtos~lin :trl~i oosiu stain. Magnification, x100; wducctl IA.) C, Oral lesion of c~osinophilic granuloma with it ydtturn of dcnw histiocjtica infiltration (Hmmtoxylin and cosin stain. Magnificaand extremely dense accumulations of cosinophils. tion, x80; reduced %.) I>, Mandibular lesion of eosinophilic granuloma characterized by an even distribut,ion of histiocytes and cosinophils. (Hematoxplin and eosin stain. Magnikation, xl 00 : rwlurcii IA .)

l)tlt c~osinophils with a sin& sm111nuclear mass arc not unusual. The rosino1~l~ils am distinguished 1)~ the c~ytoplasmic granules rather than the nuclear pattern. and the cytoplasmic granules appear bright d only if the hcmatosylin and cosin staining technique is proprrly pc~rforwed. If the wsin is washed out, the striking nature of t,he microscopic pictuw is lost and the general impression is one of inflammation. In lesions of mucosa there arc diagnostic problems which must be considered. ( :ingival or mucous membrane involvement with eosinol~hilic grwnuloma is often vharacterizcd hy areas of ulceration. In these zones a dt~nse infiltration of

neutrophil polymorphonuclear leukocytes, lymphocytes, and plasma cells is superimposed on the histiocyte-cosinophil background, and the diagnostic landmarks are obscured. Even in these inst,ances, however, there may be dense clusters of eosinophils at the margins of the ulcers and deeper in the underlying corium (Fig. 3, B).

The eosinophilic granuloma of mucosa tends to be an cspanding as well as a locally infiltrative lesion. The mucosa overlyin, 0’ the eosinophilic granuloma is thin, and the rete pegs are flattened (Fig. 3, 11) as pressure is exerted upward by the developing histiocytic lesion. This feature is more characteristic of the growth of a benign tumor than an inflammatory lesion. The thin cpithelium may demonstrate areas of degeneration. CLINICAL

AND

RADIOGRAPHIC

MANIFESTATIONS

The oral manifestations of eosinophilic granuloma are nonspecific. There may be a tumorlike mass or an ulcer of the oral mucosa covering alveolar bone that does not heal normally. Oral manifestations ma>- not be present in cases of eosinophilic granuloma of the jaws but, when prcwnt, the lesions are usually in close relation to alveolar bone. Lesions of cosinophilic granuloma may first be suspected bccansc of a mobile tooth, with almormal healing of the alveolar socket following extraction. In all these instances the initial biopsy or surgical specimen may not readily rcvcal the prwcncc of eosinophilic gwnuloina, since the superimposed inflammntoqpictmae ma\- olw~wc the underlying lesions. Several biopsy p~occdurcs may bc necessary bot’orc a final diagnosis is possible. Xicroscopic diagnosis is usually I’acilitatcd if the clinician suspects eosinophilic granuloma and stews the histopathologist in this direction. Xucosnl lesions are rarely prcscnt without coesistclnt lesions of the mandible or maxilla. Therefore, it is essential that adcquatc radiographic studies be made as early as possible in the diagnostic routine. The maxillary or mandibular radiolucent areas may be small and close to the surface (Fig. 4)) or they may involrc large areas of the jaws. The radiographic lesions of eosinophilic granuloma tend to present sharp margins and arc usually well circumscribed. Lesions of other bones are possible in cosinophilic grannloma, and a radiographic series is always necessary for a definitive diagnosis of the condition and the extent of involvement. Lesions of cosinophilic granuloma without oral manifestations may be suggested by any large circumscribed radioluccnt awa of the mandible or maxilla or b!- a series of smaller but sharply dcfincd radiolucencies. A biopsy of eosinophilic granuloma of bone is usually of diagnostic value, as superimposed inflammatory lesions are not as common as in oral mucosal inrolrement. We have recently studied six casrs of eosinophilic grannloma of the oral mucosa and jaws. In all these cases, diagnosis was effect cd by biopsy studies of oral and jaw lesions, but in several cases more than one biopsy was rcquirccl. A case of this type is included. CASE REPORT A SO-Fear-old white man canoe to the Oral Surgery Hcr~ice of Boston City Hospital on Aug. 18, 1961, with R complaint of poor healing following extraction of teeth. The teeth Imtl Imn extracted Iwause of pyorrhra approxinmtclv one -car before, and healing had l)rogressc’(l slowly and imperfectly. Ucntures were eonstructcd and sulwxprntly relined, l3ut lhc tit was 1wor ant1 the tissues \rcw wtl nntl painful. Tht patient hat1 cspcricncccl :L gradual xcigllt loss 0VPr tile pst Sererd weclis 1Wc~auscof the sownoss in llis lnouth and an inability to cat lnwpwl~. ITe evils refcrwtl lly llis tlrntist. to tllc> Oral Burg(lry Clinic for cvaluati(ju, diagnosis, and tllerxpJ-.

620

Shklur

rt trl

OH, ()..\I. k 0.1’. \I:t,v. 1962

Past

medical

history

Tllc family uc,gatire.

Radiographic

ant1 swial

histories

were noncontril)utory.

Tlw rrl~&val

history

\vas wscntially

examination

ridge. Tlw \\‘cbll-tlrfint~d supwfic*ial radiolucent areas wrre sren in the lrft mandibular mamlil~ular csanal was prominwt, and the trnl~wulation was normal (Fig. 4, 13). The rigbt mandi Mar awa appeared essentially normal (Fig. 4, I) ) Intraoral radiographs revealrxl considerable drstruetion of bone in the antwior arca of the mandible. The superior hordrr of tllc mantiihle presented irregular areas of resorption, nitb tbv lesions appearing to invade tllcx mandible from the surfare (Fig. 4, C) . Tbr surrounding hone appeared dense and tinvly trabwulated. The maxilla showed gwwralizcvl hone loss in tlrc, maxillary ridge, most estclnsivt, in tllc tulwrosity region. Hoentgenograpllir findings in tlw skull we’re within normal limits. .\ m&astatic how scriw was nc~g;ttiw. laboratory

Course

tests

and

management

Biopsy spwimcvls takrn on August 22 from tilt: mandibular and maxillary ridges rttwalrd acwte and cllronic inflammation. Tile patirnt was plawd on eonsrrrativc llonw c’arr, utilizing moutlt rinses and not wearing the dentures. Tlwre was d&nit,, improvwwnt, but some arcas of ulwration remained. Further hiopsics performed on Rcptemher 18 1~1 to a tliagnosis of acwtc and chronic inflammation. On October 9 the lwions in the mandilrl~~ UWY~ (*urctted, and tllo soft brown-gray material was submitted for micsroscopic examination. *.I diagnosis of vosinopbilic granuloma was madr. Slow healing was encountered, but it was complrtt~ 18 days following the surgical proredurt. On October 16 a similar prowdure was performrct on tllcb maxilla, again with wry slow healing. A radiation treatment dose of 2,00() I’ was giwn to tllc maxilla and ma.ndihle. Gradual healing of tissues occurrptl. The final (lpfects in tbc mandibular and maxillary ridges revealed tlw extent of the lesions. Tb
DISCUSSION

\Vitlr ~losc~l~wopcmtion htwwn c~linician and llistopatlwlogist, 01~1 lesions ol’ cwsinopllili~ g~nulonw c~~lcl h dfvvtivcly dia~noscd upon initial biopsy. The diagnosis of eosinopliilic grxnulonia depcntls upon cai*eful clinical and undiographic evaluation, with microscopic correlation.

622

Xhklav ct al.

O.S., O.hi. & O.P. May, 1966

REFERENCES

1. Bailey, J. W., and Freis, E. I).: Eosinophilic Granuloma of Bone, J. Am. Ilent. A. 31: 91, 1944. 2. Blevins, C.! Dahlin, D. C., Lovestedt, S. A., and Kennedy, R. L. J.: Oral and Dental Manifest trons of Histiocytosis X, ORAL SURG., ORAL MED. & ORAL PATH. 12: 473, 1959. 3. Brunner, %I.: Bosinophilic Granuloma of Mouth, Pharynx, and Nasal Passages, ORAT, SURG., ORAL MED. & ORAL PATH. 4: 623, 1951. 4. Conran, W. R.: Eosinophilic Granuloma of Mandible, J. Oral Surg. 6: 261, 1948. 5. Cox, M. E. : Eosinophilic Granuloma, Am. J. Orthodontics & Oral Surg. 32: 569-578, 1946. do granulomatose histio6. Dechaume, M., Chaput, A., and Held, A. J.: Trois observations cyto-Cosinophile des maxillaires, Rev. st,omatol. 61): 70, 1949. or Eosinophilic Granuloma of Boric, Am. J. Path. 7. Farber, 8.: The Nature of Solitary 17: 625. 1941. Granuloma Diagnosed by Gingival Biopsy, J. 8. Grupe, k., and Orban, B.: Eosinophilic Periodont. 21: 21. 1950. Bone Granuloma With Regard 9. Holst, G.,, Husted,‘E., and Pindborg, J. J.: On Eosinophilic to Localization in Jaws and Relations to General Histiocytosis, Aeta odont. scandinav. 10: 148, 1953. 10. Jaffe, H. L., and Liehtenstein, L.: Eosinophilic Granuloma of Bone; a Condition Affecting One, Several, or Many Bones, But Apparently Limited to the Skeleton, and Representing the Mildest Clinical Expression of the Peculiar Inflammatory Histiocytosis Also Underlying Letterer-&we Disease and Schiiller-Christian Disease, Arch. Path. 37: 99, 1944. 11. Kaufman, M.: Eosinophilic Granuloma of Bone, J. Oral Surg. 9: 273, 1951. 12. Kruger, G. O., Prickman, L. E., and Pugh, D. Q.: So-Called Eosinophilic Granuloma, ORAL SURG., ORAL MED. & ORAL PATH. 2: 770, 1949. 13. Lichtenstein, L. : Histiocytosis X; Integration of Eosinophilic Granuloma of Bone, “Letterer-Siwe Disease,” and “Schiiller-Christian Disease” as Related Manifestations of a Single Nosoloaic Entitv. Arch. Path. 56: X4. 1953. 14. Lichtenstein, I?.: Histi&ytosis X (Eosinophilic Granuloma of Bone, Letterer-Siwe Disease, and Schiiller-Christian Disease) ; Further Observations of Pathological and Clinical Jniportance, J. Bone 8; Joint Surg. 46-A: 76, 1964. 15. Mezl and Skorpil: Le granulome paradontaire histioeosinophilc, Paradentologie 2: 1, 1947. 16. Nesbitt, A.: Eosinophilic Granuloma of Maxilla and Mandihle, Proc. Roy. Sot. Med. 48: 990, 1955. 17. Oberman, II. A.: Idiopathic Histiocytosis; a Clinicopathologic Study of 40 Cases and Review of the Literature on Eosinophilic Granuloma of Bone, Hand-Schiiller-Christian Disease and Letterer-Siwc Disease, Pediatrics 28: 307, 1955. 18. Pinkus, H., Copps, L. A., Custer, S., and Epstein, 8.: Reticulogranuloma; Report of a Case of Rcticulosis of Skin and Oral Mucosa Under the Clinical Picture of Hand-SchiillcrChristian Disease, Am. J. Dis. Child. 77: 503, 1949. 19. Ross, I. F., Brown, G. N., and Conrad. 8. C.: Chronic Disseminated Histiocvtosis X (HandRchiiller-Christian’ Type) With Oral’ Mucosal Lesions, ORAL SURG., ORA;, MED. & ORAL PATH. 9: 529. 1956. 20. Salman, I., and Darlington, C. G.: Eosinophilic Granuloma, Am. J. Orthodontics & Oral Surg. 31: 89, 1945. 21. Schroff, J.: Eosinophilic Granuloma of Bone, ORAL ST-KG., ORAL MED. & ORAL PATH. 1: 256, 1948. 22. Sleeoer. E. L.: Eosinonhilic Granuloma of Bone, ORAL SURG.. ORAL MED. & ORAL PATH. I 4: &IS,’ 1951. 23. Thoma, K. H.: Eosinophilic Granuloma With Reports of One Case Involving First the Mandible, Later Other Bones, and Being Accompanied hy Diabetes Tnsipidus, Am. J. Orthodontics & Oral Surg. 29: 641, 1943.