Oral Surgery

Multifocal Langerhans cell histiocytosis of the jaws: a case reportJohnson David Gnanasekhar* / Mahmoud Sayed Ahmad** / RachpaUi Raja Reddy***

Langerhans cell histiocytosis is an uncommon disease that includes a spectrum of disor-ders in which there is an abnormal proliferation of Langerhans cells. This articledescribes a case of a benign form ofmultifocal Langerhans cell histiocytosis of themaxilla and mandible. The patient was followed for a period of 2'A years, duringwhich time there was spontaneous remission of some of the lesions.(Quintessence lnt 1991:22:559-564.)

Introduction

Histiocytosis X (HX) is an uncommon disease char-acterized by abnormal proliferation of histiocytes,which replace bone or infiltrate mucosa, epidermis, orinternal organs.' This disease is divided into three clin-ical entities: Letterer-Siwe disease (LS), Hand-Schül-ler-Christian disease (HSC), and eosinophilic granu-loma (EGJ. This most widely used classification hascome under increasing criticism because it fails to em-phasize transitions among the vanous entities, anddocs not eorrelatc well with the histologie findings andprognosis." Some opponents are even reluctant to ac-cept EG as part of HX, '̂'' while others suggest thatHX be separated into two categories, one composedof LS alone, and one composed of HSC and EG.̂Because the prohferating cells in HX are Langerhanscells {LC), HX has been renamed as Langerhans cellhisîiocytosis (LCH).* It is also currently recommendedthat LCH be classified into acute disseminated hisfio-cytosis, chronic progressive histiocytosis, and benignlocalized bistiocytosis.'

Acute disseminated histiocytosis (or LS) is the mostaggressive variant of LCH. Tt mainly affects childrenunder the age of 3 years, and the condition is almostalways fatal because of widespread, rapid involvementof the skeletal and extraskeletai tissues. Chronic pro-gressive histiocytosis (or HSC) is the chronic form ofLCH. in which there are also skeletal and extraskeletailesions. It involves a triad of disorders: diahetes insi-pidus, resulting from a lack of antidiuretic hormonecaused by infiltration of histiocytes into the posteriorpituitary; exophthalmus, caused by the infiltration ofthe wall of the orbit; and other bone lesions. All tbreedisorders of chronic progressive histioeytosis are gen-erally not present in the same patient. Benign loealizedhistiocytosis (or hG) is the most passive variant ofLCH and accounts for 50% to 60% of all cases ofLCH.̂ It is usually found in young adults and is char-acterized by one, but occasionally by more than one,osteolytic lesion with or without accompanying softfissue le.sions.

This article presents a case ofmultifocal benign his-tiocytosis of the maxilla and mandible. No treatmentwas given to this patient; bowever, there was sponta-neous remission of some of the lesions.

* Periodontist, Dental Department. Al-Adan Hospital; PO Bos25878, 13119 Safat, Kuwait,

*" Consultant Pathologist. Al-Adan Hospital; PO Box 5022,13051 Safat, Kuwait,

-** Registrar, Department of Radiology, Ai-Adan Hospital;PO Box 46881, 64019 Fahaheel, Kuwait,

Because postal service to Kuwait has been suspended, the authorswere unable to review proof of this article.

Case report

In December 1987 a 30-year-old man came to the peri-odontics elinie at Al-Adan Hospital, Kuwait, com-plaining of pain in both jaws, bleeding gingiva, andmobile teeth. He had suffered from bleeding gingivafor several years, and his dentist had extracted a fewteeth and provided periodontai care. The patient'spast medical history revealed nothing relevant.

Quintessence International Volume 22, Number 7/1991 559

Oral Surgery

Intraoral examination revealed a granulomatous-appearing lesion on the left side of the palate adjacentto the molars (Fig 1). A similar lesion, but with a littlemore edema, was present on the gingiva on the lingualside of the mandibular anterior teeth (Fig 2), Deepperiodontal pockets were present around all the mo-lars and adjacent to the granulomatous lesions. Allthe remaining molars except the maxillary right firstmolar showed grade III mobility,

A panoramic radiograph showed a weil-demarcatedradiolucent area on the right side of the mandiblemesial to the second molar and a punched-out roundlesion on the left side of the mandible near the apexof the first molar (Fig 3}, There was also extensivealveolar bone loss around the left maxillary molars.Lateral oblique views of the mandible after the ex-traction of the right second molar showed a large ra-diolucent lesion on the body of the mandible (Fig 4),

The patient's blood count and biochemistry werewithin normal limits. All the molars except the max-illary right first molar were extracted.

Biopsy specimens were taken from the intraosseouslesion on the right side of the mandible, from thegranulomatous lesion on the gingiva behind the man-dibular anterior teeth, and from the palate adjacentto the extracted left maxillary molars. Histology of allthe biopsy specimens showed infiltration of the boneand submucosa by sheets of mononuclear cells withan ill-defmed cell membrane, a faint eosinophilic cy-toplasm, and a lobulated nucleus, Infiammatory cellsand a few eosinophils were also present (Figs 5 and6), These histologie features were consistent with adiagnosis of benign histiocytosis,

A complete skeletal radiographie survey, includinglateral oblique and occlusal views, did not reveal anyother lesions apart from the jaw lesions.

After the diagnosis, the patient was lost to followup.In February 1990. the patient returned, and stated thatafter the extracfions and biopsy, the pain from the jawshad been reduced considerably and that he felt therewas no need for further treatment.

Clinical examination showed complete resolution ofthe granulomatous lesions in the palate (Fig 7) andthe lesion behind the mandibular anterior teeth (Fig8), A complete skeletal radiographie survey revealedno new lesions. Lateral oblique radiographs showedsome bone fill of the lesion on the right side of themandible {Fig 9),

The patient experienced dull pain of the left side ofthe mandible, but he refused to undergo any treatmentfor the remaining lesions.

Discussion

All three types of LCH have radiographie and histo-logie similarities, but their dinical features and naturalhistory are different,"* Only a total evaluation of chti-ical manifestations, including the site of the lesion,extent of involvement, histologie findings, and history,allows LCH to be categorized into its subtypes.

The occurrence of LCH as oral lesions is well doc-umented."*"̂ " From these reports it appears that os-seous defects are a prominent feature in most cases,and these can develop in the maxilla, mandible, andpalate. The most commonly involved site is the man-dible,'"'-" especially along the posterior alveolarridge.' ' Soft tissue lesions may appear over the affectedbone. Gingival lesions can appear markedly enlargedand reddened,'^ or ulcerated and granulomatous."'*Dull pain is a usual symptom of the d i sea se, ̂ ''•̂ ' whilespontaneous bleeding from gingival lesions has alsobeen reported."'" Severe periodontal disease may besimulated by the jaw lesions because there is destruc-tion of alveolar bone and tooth mobihty, in additionto the gingival lesions.̂ "'̂ '̂̂ ''

Radiographie features of LCH may be apparentabout 6 weeks after the onset of the first symptoms.-'Involvement of the skuh and other flat bones in LCHappear as punched-out, osteolytic lesions. In the max-illa and mandible, the disease may appear as periap-ical lesions,^' or as advanced periodontal disease withsevere loss of alveolar bone.-" In general, LCH in bonemanifests itself as a well-demarcated, round or ovalcystic radiolucency with no peripheral bone conden-sation.̂ ^

Langerhans cell histiocytosis is characterized byproliferation of histiocytes mixed with inflammatorycells.-^ Two separate sets of histiocytes have been iden-tified in LCH: the Langerhans cells, which are consid-ered to be the proliferating cells, and macrophages,which are probably reactive phagocytes.^' Langerhanscells are a subpopulation of the mononuclear phag-ocytic system. They are derived from the bone marrowand migrate into the tissues.̂ * They are normally pres-ent in epidermis and in buccal and other surface mu-cosa where they fix antigens and present them to theT-lymphocytes.*' Infiamed gingiva has 5 times as manyLangerhans cells as normal gingiva from the samepatient.-'* Following antigenic stimulation by dentalplaque, the Langerhans cells migrate to the gingivapossibly enhancing immunologie surveillance. But thecause of proliferation of Langerhans cells in LCH isunknown. Theories to explain the prohferation in-

560 Quintessence International Volume 22, Number 7/1991

Oral Surgery

Fig 1 Granulomatous lesion on the left side ot the palate.

K 1̂ '^ JL

1Fig 2 Similar granuiomatous lesion on the gingiva on thelingual side of the mandibular anterior teeth.

Fig 3 Panoramic radiograph shows a well-demarcated ra-diolucent lesion on the right side of the mandible and apunched-out round lesion on the left side ot the mandiblenear the apex of the first molar.

Fig 4 Lateral oblique view ot the right mandible shows thelarge lesion in the body of the mandible.

Fig 5 Histologie analysis of the lesion shows the gingivalmucosa and diffuse cellular infiltrate of the submucosa.[Original magnification >Í63.)

Fig 6 Higher magnification of the submucosal infiltrateshows the mononuclear ceils. (Original magnificationX 400.)

Quintessence International Volume 33, Number 7/1991 561

Oral Surgery

Fig 7 Compiete resolution of the palatai lesion 2 yearsafter the extraction of the teeth adjacent to the iesion.

Fig 8 Complete resolution ot the gingival lesion in themandible 2 years after the patient was first examined.

Fig 9 Lateral obiique view of the right mandible showssome bone fill of the iesion.

elude the belief that it is a response to an as yet uni-dentified antigen," an immunologie abnormality re-sulting from suppressor cell deficiency,'" a defectiveinteraction between Langerhans cells and T-cells," andthat the Langerhans cells in LCH are abnormal,-*-'-

Langerhans cells are identified by the presence ofBirbeck granules," which are visible only with theelectron microscope.''' Langerhans cells have on theirsurfaee the T-6 antigens'^ and within their cytopla,smthe S-100 protein.'* Demonstration of these markersby various staining methods are also used to identifythe Langerhans cells,-' In the absence of an electronmicroscope, and, in some difficult cases, detection ofS-100 protein is used to diagnose LCH,"''* Radio-nuclide studies (bone scans) are generally considereda sensitive indicator of the presence of lesions in bone.In LCH, bone scanning may show increased activity

at the site of the lesion,"-'*" However, recent studiesshow that radiographie bone surveys are more effec-tive than is bone scanning in detecting IX^H lesions,'*'̂ 'In a study of 20 bone scans, seven were found to hecompletely normal in patients with extensive radi-ographie evidence of the disease.'' Another studyfound that skeletal radiographs were three times aseffective as bone scans in detecting LCH lesions.'"

There is a close relationship between age of the pa-tient and the extent of LCH, and the disease has anaggressive course in younger patients,^" Solitary bonelesions have a favorable prognosis, but with the in-volvement of additional organ systems, the prognosisbecomes less favorable. In LCH, there is a correlationbetween the mortality rate and the number of organsystems involved in the disease."*""' Adult-onset LCHoften takes the form of benign histiocytosis of the

562 Quintessence international Volume 22, Number 7/1991

Oral Surgery

bone."" In general, the prognosis for adult patientswith benign localized histiocytosis is good, and thepresence of additional bone iesions or subsequent gen-erahzed disease is rare,"''^ Prognosis tnay beeome un-favorable if additional organs become involvcd."

Treatment of LCH can be separated into manage-ment of local symptomafic lesions by means of sur-gical curettage and/or radiation and treatment of thesystemic disease by chemotherapy. It has been sug-gested that surgieal curettage may not completely re-move all histiocytic infiltration into the tissues andthat radiation may be préféra ble.''- However, a reviewof 114 patients with LCH with oral involvementshowed that patients who had radiation therapy alonehad the highest rate of recurrence. '" Surgical curettageis considered the treatment of choice, and radiationtherapy is indicated for lesions in surgically inacces-sible sites'" and for lesions that recur after .surgery.'''Althotigh there are reports of patients who received1000 rads or more of radiation,''"'" the recommendeddose of radiation is under 1000 rads per lesion.""'Higher doses do not appear to be more effective andpresent potential hazards, such as growth retardationand secondary mahgnancy.'

Even when surgical curettage is combined with ra-diation therapy, the lesion may occasionally becomeresistant and disseminate.''^ In such cases, and in pe-diatric patients, chemotherapy may be preferable he-cause of poor success and potential damage to dentalfollicles from radiation."^ However, adverse reactionsto cytotoxic drugs are numerous,'" and their use in thetreatment of locahzed LCH of the bone may not bejustified.

Complete resolution of solitary benign histioeytosisfollowing injection of methyl prednisolone into thelesion has been recently reported.^ Although this is anisolated case, but considering the complications andthe lasting effects of other treatment modes, injectionof methyl prednisolone may be included as anotheroptional local treatment. Local treatment, such as cu-rettage and radiation, does not have any influence onthe formation of new lesions in other sites or on thegeneral course of the disease.'

In patients with multiple lesions, the different le-sions may heal simultaneously or at different rates.''*Even with a combination of radiation and chemo-therapy, bone eroded by LCH has been reported toregenerate."'" After radiation, or with spontaneoushealing, the lesions in tlat bones disappear completely.In long bones, new bone formation on the periostealside has been clearly observed.-^ The natural behavior

of benign localized histiocytosis is the gradual regres-sion of the eosinophils followed by fihrosis and callousformation.'' This may explain the rare spontaneousrecovery that has been reported in all types ofLCH."'-"

In our patient, there was spontaneous remission ofthe palatal lesion and the gitigival lesion of the man-dible. In the osseous lesions of the mandible, somebone fill was ohserved.

LCH may recur many years after complete resolu-tion.'^ It has been suggested that physical and radi-ographie examinations be carried out at 3-month in-tervals during the first year after completion of ther-apy. If the patient remains free of disease, the intervalbetween examinations can be prolonged." Youngerpatients are more likely to develop new lesions, andshould therefore be examined at regular intervals forseveral years.

References

t. Glick D, Gutman D, Laufer D, et al; Histiocytosis X: reportof Iwo cases. Oral Health 1979;69:35-38.

2 Bokkerink JPM, de Vaan GAM: Histiocytosis X. Eur J Pediatrl9S0;135:129-t46,

3. Lieberman PH, Jones CR, Dargeon HWK, et at: A reappraisalof eosinophilic granuloma of bone, Hand-Schul 1er-Christiansyndrome and Letterer-Siwe syndrome. Meilieine 1969;48:375-400.

4. Daneshbod K, Kissane JM: Idiopatbic differentiated histiocy-tosis. Am J Clin Pathoi 197S;70:38]-389.

5. Cline MJ, Golde DW: A review and réévaluation of the histio-cytic disorders. Am J Med 1973;55:49-60.

6. Anonsen CK, Donaldson SS: Langcrhans cell histiocytosis ofthe head and neck. Laryngoscope 1987;97:537-542.

7. Robbins SL, Kumar V: Basic Pathology. Philadelphia, WBSaunders Co. 1987. pp 402^03,

8. Jones LR, Toth BB, Cangir A: Treatment for solitary eosino-philic granuloma of the mandible by steroid injection. / OralMa.\illofae Surg 19 8 9;47:306-309.

9 Danesbbod K, Kissane JM: Histiocytosis: the prognosis ofpolyostotic eosinophilic granuloma. Am J Ciin Pathoi 1975; 65:601-611.

to. Hartman KS: Histiocytosis X: a review of It4 cases with oralinvolvement. Orai Surg Orai Med Orai Pathoi i980;49:38-54.

11. Jones OJ, Pillsbnry HC: HisUocytosis X of the head and neck.Laryngoscope 1984;94:1031-1035,

t2, Krutchoff DJ, Jones CR: Multifocal eosinophilic granuloma: aclinical pathological conference, J Oral Pathoi 1989;13:472-4SS.

13. Zuendal MT, Bowers DF, Kramer RN: Recurrent histiocytosisX with mandibular lesions. Orai Surg Orai Med Orai Pathot1984;58:420-423,

14. Maclntyre DR, Canty AJ, Pell GM: Multifocal eosinophilicgranuloma presenting in the mandible. Br Dent J 1985;159:338-340.

Quintessence International Volume 32, Number 7/1991 563

Oral Surgery

15. Whitche^'hitcher BL. Webb DJ; Treatment of recurrent eosinophilicSranuloma of the mandible following radiation therapy. / OridMaxillofac Surg 1986; 44; 556-570.

16. Moorthy AP; Eosinophilic granuloma manifesting as periodon-tai problems. Br Dent J 1986;161;66-67.

17. Boltomley WK, Gabriel SA. Corio RL, et al: Histiocytosis X;report of an oral soft tissue lesion without bony involvement.Oral Surg Oral Med Oral Pathol 1987;6J;228-231.

18. Finney DS. Rees TD. Wright JM, et al; Solitary eosinophilicgranuloma (Histiocytosis X) of tbe gingiva. J Periodomol

Shaw L, Glenwright HD; Histiocylosis X; an oral diagnosticproblem. J Clin Periudomol I988;15;M2-315.

Artii Z, Gorsky M, Raviv M: PeriodoQtai manifestations ofadult onset of Histiocytosis X. J Periodomol ]989;60;57-55.

Berry DH. Becton DL; Natural bistory of histiocytosis X. Hem-atol Oncoi Clin North Am 1987J;23-34.

Duncan WK. Post AC. McCoy BP; Eosinophilic granuloma.Oral Surg Oral Med Oral Pathot 1988;65;736-741.Sigala JL, Silverman S, Brody HS. et al: Dental involvement inhistiocytosis. Orat Surg Oral Med Oral Pathol 1972;33;42^7,Sbafer WG, Hine MK. Levy BM; A Textbook of Oral Piithologr.Philadelphia, WB Saunders Co. 1983, pp 634 637.

Ennis JT, Whitehouse G, Ross FGM. et al; The radiology ofthe bone changes in histiccytosis X. Ctin Radio! 1973;24;212-220.Beckstead JH, Wood GS, Turner RR: Histiocytosis X cells andLangerhans cells: enzyme histochemical and lmmunologicalsimilarities. Hum Fathol 1984;15;826-833.Elema JD, Briggs JEA; Langerhans cells and macrophages ineosinophilic granuloma. Cancer 19S4;54:2174~21S1.

Leikin SL; Immunology of histiocytosis X. Hematot Oncol ClinNorth Am 1987;1:49-61.DiFranco CF, Toto PD. Rowden G, et al: Identification ofLangerhans cells in human gingival epithelium. J Periodontot1985;56:48-54.Osband ME, Lipton JM, Lavin P: Histiocylosis X. New Eng! JMed 1981;3Ü4:146-153.Tbomas JA, Janosy G, Cbilosi M, et al: Combined immuno-logical and histochemical analysis of skin and lymphnode lesionsin histiocytosis X. J Ctin Pathol 1982;35;327-Î37.Osband ME, Pochedly C: Histiocytosis X: an overview. HematotOncot Ctin North Am 1987;l;l-7.

33. Birbeck MSC, Breathnacb AS, Everall JP; An electron micro-scopic study of basal melanocytic and level clear cells (Langer-bans cells) in Vitilogo. J Invest Dermotol 1961;37;51-63.

34. Friedm;in PS: The immunology of Langerhans cells. ImmunolToday I981;2124-I28.

35. Muipby GF, Bhan AK, Bagot M; A new immunologie markerfor human Langerbans cells. New Engl J Med 1981;304;791-792.

36. Nakajima T, Watanabe S, Sato Y, et al; An immunopcn^xidasestudy of S-100 protein distribution in normal and neoplastictissues. Am J Surg Pattwl 19K2;6;715-727,

37. Kilüne B, RasKid RH: Eosinopbilic granuloma in the mandible.A case report, Jordan Dent J 1987;7:4-8.

38. Parker BR, Pinckney L, Etenbanas E; Relative efficacy of ra-diographie radionuclide bone surveys in the detection of theskeletal lesions of Histiocytosis X. Radiology 198U;134:377-388.

39. Siddiqui AR, Tashjiau JH, Lazarus: Nuclear medicine studiesin evaluation of skeletal lesions with bistiocytosis X, Radiology1981;140;787-789.

40. Lahey ME: Histiocytosis X; comparison of three treatment reg-imens. J Fediatr 1975;78;179-183.

41. Lucaya J: Histiocytosis X. .4m J Dis Child 1971;121;289-295.

42. Geiser CF; The histiocytosis syndromes, Pediatr Ann i979;8:54-64.

43. Smith DG, Nesbit ME, D'Angio GJ. et al: Histiocytosis X; roleof radiation tberapy in management with special reference todose levels employed. Radiology 1973;106;419-422,

44. West WO; Velban as treatment for disseminated eosinophilicgranuloma of bone, J Bone Joint Surg 1984;66;1I28.

45. Chase CD. Eversole LR. Hall HD: Histiocytosis X with jawinvolvement. J Oral Surg 1974;32.494-502.

46. Womer RB. Raney RB, D'Angio GJ: Healing rates of treatedand untreated bone lesions in bistiocytosis X, Pediatr1985;76:285-288,

47. Wolfson SL, Botero F, Hurwitz S, et al: Pure histiocytosis X.Cancer 1981;48:2236-2238,

48. Broadbent V, Davies EG, Heaf D, et al: Spontaneous remissionof multisystem histiocytosis X, Lancet 1984;l;253-254.

49. Moore AT, Pritchard J, Taylor DSI: Histiocytosis X: an ophthal-mological review. Br J Ophthalmot 1985;69;7-14. •

564 Quintessence International Volume 22, Number 7/1991