MÊnÍêli JOURNALMaria de Lourdes L. F.Chsutteiíle, Rosana M. Valério,

Cybelle Maria Costa Diniz, Milvia Maria Simões, Silva Enokihara,Nylceo Michalany, Karin Ventura Ferreira, José Antonio Baddini Martinez,

Karine Marques Hassun, Álvaro Nagib Atallah, José Kerbauy

Langerhans celI histiocytosisDisciplina de Hematologia e Hemoterapia, Disciplina de Clínica Médica, Disciplina de Anatomia Patológica,

Disciplina de Dermatologia, Disciplina de Pneumologia - Escola Paulista de Medicina,Universidade Federal de São Paulo - São Paulo, Brazil.

The authors present a rare case 01 Langerhans cell histiocytosis in a 31 year old lemale patient with vulvar, peri-anal and orallesions,diabetes insipidus, pulmonary skin and bone inliltrations. Skin biopsy immunohistochemistry presented positive S100 protein andvimentine, but the diagnosis was done with the demonstration 01 8irbeck granules with eletronic mucroscopy. The treatment wasbased on systemical chemotherapy although vulvar lesion has a bad response to chemotherapy.

UNITERMS: Histiocytosis X, Langerhans cell. Diabetes insipidus.

INTRODUCTION

T he authors present a rare case of Langerhans eellhistioeytosis (LCH) with vulvar, perianal and oralIesions. pulmonary and diabetes insipidus(DI),

skin and bone infiltrations.

CASE REPORT

A 31-year old white woman was admitted to theHospital S. Paulo in April. 1996, due to an uleerated lesion

Address for correspondence:Maria de Lourdes L. F. ChauffailleRua Bo tuca tu, 740 - 3º andarSão Paulo/SP - Brasil - CEP 04023-900

in the vulva that had appeared 1 year previously. She alsoeomplained of eutaneous nodes in the right shoulder andforearm, gengivitis, loosening of the teeth, halitosis,otorrhea, polydipsia, amenorrhea, galaetorrhea and aweight gain of 24 kg in the three previous years, as wellas a spontaneous pneumothorax 10 years earlier. She wasobese, with a 3 em brownish-red papular lesion on lheright shoulder and another of I em on lhe forearm;erythematous plaque in lhe roof of the mouth, wit hsuperior teeth extrusion and loosening. The liver was 5em from the LCM and there was edema ofthe labia majorisand ulcerated vulvar lesion with a granulomatous aspect;and a perianal lesion with the same eharaeteristies.Laboratory exams: Hb= 13.7g/dl; WBC= 6.700/mm3 (siab1%, segmented 56%, eosinophils 5%, basophils 1%,Iymphoeytes 30%, monoeytes 7%); Plalelets=230.000/mm ': SGOT=54( 13), SGPT=60( 14), alkaline phosphatase=340(250), LDH=424(450), urie aeid=7.8 (6.0); thepulmonary funetion had a mixed ventilatory abnormalityand predominanee of a light restrietive pattern;transbronehial biopsy presented unspeeifie infiltrate; waterdeprivation test consistenl with DI and megatest eonsistent

São Paulo Medical Journal/RPM 116(1): 1625-1628, 1998CHAUFFAILLE, M.L.L.F.; VALÉRIO, R.M.; DINIZ, C.M.C.; SIMÕES, M.M.;ENOKIHARA, S.; MICHALANY, N.; FERREIRA, K.V.; MARTINEZ, JAB.; HASSUN,K.M.; ATALLAH, A.N.; KERBAUY, J. - Langerhans cell histiocytosis

162e "

Figure 1 - Immunohistochemistry showing positive 8100 protein.

with panhypopituitarism; chest radiography showedbilateral interstitial infiltrate with mediastinumenlargement; bone scintillography had anomaloushyperconcentration of radioindicator in the distal third ofthe bilateral femur, in the focalleft paranasal area and inthe jaw; computerized tomography (CT) with interstitialmicronodular infiltration, cystic areas in pulmonarparenchyma and interlobular fissure in the rasary; skullmagnetic nuclear resonance with a tumor in theinfundibulo-hypothalamic area; abdominal scan withhepatomegaly and signs of modera te hepatic steatosis.Skin and vulvar lesian biopsies showed Langerhans cellhistiocytosis with pasitive S 100 protein, vimentine andHAM56, and negative LCA, HMB45, Pan B and Pan Tantigens. Electran micrascopy showed the presence ofBirbeck granules.

DISCUSSION

Histiocytoses are disorders characterized by theproliferation of cells from the monocyte-phagocytic series.

There is a great bialogical diversity frorn a benign andindolent pattem to a malignant and fulminant one. It ismore frequent in children with an average age of 2 or 3years old (I). Its incidence is estimated as 0.2 to 0.5 casesper 100,000 children per year in the USA. In adults, theincidence is unknown.

Its etiology is unknown but it is thought it could bea proliferative disorder in response to an antigenic stimulusaf infectious, genetic abnormality, deregulated immuneresponse, or even clanal origino

Hand-Schüller-Christian, Letterer-Siwe andeosinophilic granuloma were the first clinicaldescriptions. Later on, they were named HistiocytosisX, where X stood for etiology unknown. In 1985 theInternational Group of Pathologists and Cliniciansrecommended a new c1assification that was publishedby the Writing Graup of the Histiocyte Society (WG HS)dividing them into: Langerhans cell histiocytosis(LCH), non-Langerhans cell histiocytosis (NLCH) andmalignant histiocytosis. This classification has theadvantage of recognizing the pathognomonic cell.

Clinical presentation may be localized or systematic,invading skin, lungs and bones in adults, and bone marrowand lymphonodes in children.

São Paulo Medical Journal/RPM 116(1): 1625·1628, 1998 CHAUFFAILLE, M.L.L.F.; VALÉRIO, R.M.; DINIZ, C.M.C.; SIMÕES, M.M.;ENOKIHARA, S.; MICHALANY, N.; FERREIRA, K.V.; MARTINEZ, J.A.B.; HASSUN,

K.M.; ATALLAH, A.N.; KERBAUY, J. - Langerhans cel! histiocytosis

1627

Figure 2 - Eleclron microscopy (400x): arrow showing lhe 8irbeck granule.

Skin attack may be the only manifestation of thedisease and may present spontaneous remission, or it mayform part of the involvement of other organs with a worseprognosis. These lesions may precede systematicmanifestations by one year or more. They occur in 30%to 40% of the cases and are very heterogeneous. In theaxillae, inguinal, perianal, neck and retroauricular areas,papules and subcutaneous nodes may ulcerate leading tolesions that are difficult to heal despite treatment. Genitalulcers are more frequent in adults. Localized ordisseminated lesions occur in oral mucosa with plaquesthat tend to ulcerate leading to loss of teeth. These evidentdermal-mucosal presentations were well documented inthis case.

Lung involvement in LCH may be seen isolatedor not (2). l n almost 20% of cases, spontaneouspneumothorax is the first manifestation of the disease.Radiologically, there are diffuse, reticulo-nodularopacities, over multiple cystic images mainly in theupper and mid-lung zones. The chest computerizedtomography scan is superior to X-ray in detecting theseabnormalities as was demonstrated here, since the

"honey comb" abnormalities could be seen. Pulmonaryfunction tests generally show a mixed partem withlower diffusion capacity and hypoxemia that get worsewith exercise (2).

Bone lesion, focal or disseminated, is lytic and maybe curable with curettage, although it can reappear.Gingival infiltration with bone absorption leading to toothfloating is an adult feature of the disease.

Vulvar presentations are rare, but in adults it is morefrequent with around 40 cases related in the literature.Considering the time of evolution for vulvar lesionpresentation, the patients can be classified into 4 groups:genital tract only; lesions subsequently involving multipleorgans; aral ar skin lesions followed by involvernent ofthe genital tract; and DI followed by involvement ofmultiple organs and genital lesions. The third case isapparently the most frequent (3).

The diagnosis was made by lesion biopsy.Histochemistry was positive for Sol 00, CD Ia, HLA-Dr and vimentine, which are generally negative inNLCH. The WGHS considers the presence of Birbeckgranules ar CDla positivity as fundamental criteria for

CHAUFFAILLE, M.l.l.F.; VALÉRIO, R.M.; DINIZ, C.M.C.; SIMÕES, M.M.;ENOKIHARA, S.; MICHALANY, N.; FERREIRA, K.V.; MARTINEZ, J.A.B.; HASSUN,K.M.; ATALLAH, A.N.; KERBAUY, J. - Langerhans cell histiocytosis

São Paulo Medical Journal/RPM 116(1): 1625-1628, 1998

162-B

the diagnosis. In the present case, the definitivediagnosis was made by demonstrating Birbeck granuleswith electron microscopy. UsuaIly, histological aspectsdo not relate to the extension and agressiveness of thedisease and in the initial phase the Langerhans ceIlsand histiocytes may be seen in greater numbers.

It is important to know if the disease is localized ordisseminated, since the involvement of more than oneorgan requires systematic therapy. The treatment in adultsis based in polychemotherapy with etoposide, vinca

alkaloids and glucocorticoid. Poor prognosis factors areadvanced age, disease extent and functional organabnormalities (4). Relapses are common. Vulvar lesionsdo not improve with systematic chemotherapy needinglocal intervention. Radiotherapy, PUVA and intralesionglucocorticoid are also used. This patient received twocycles of etoposide (1Oômg/mvday/J days) and vincristine(2mg/day) every 30 days, without improvement. She wassubmitted to partial vulvectomy and is at present receivingvinblastine IOmg/week/4 months.

RESUMO

Os autores apresentam um caso raro de histiocitose de célula de Langerhans com apresentação lentamente progressiva,lesão vulvar, peri-anal e oral, diabete insipidus, infiltração pulmonar, dérmica e óssea em paciente de 31 anos. Aimunohistoquímica da biopsia de pele foi: proteína 8-100 e vimentina positivas, porém o diagnóstico d.~finitivo foi feito pelademonstração de grânulos de Birbeck à microscopia eletrônica. O tratamento baseia-se em quimioterapia sistêmica e a lesâovulvar tem má resposta à quimioterapia.

REFERENCES

I. Trochtenberg OS, Oessypris EN. Case Report: reversiblehepatornegaly and diabetes mellitus in an adult withdisseminated histiocytosis X. Am J Med Sci 1990;299(3): 179-184.

2. Soler P, Karnbouchner M, Valyere D, Hance AJ. PulmonaryLangerhans cell granulomatosis (histiocytosis X). Annu RevMed 1992:43:105-115.

3. Axiotis CA, Merino MJ, Duray PH. Langerhans cellhistiocytosis of lhe female genital tr act. Cancer 1991;67: 1650·60.

4. Komp O:'!, Perry MC. Introduction: lhe hist iocyt icsyndrornes. Sem in Oncol 1991; 18( I): 1-2.

São Paulo Medical Journal/RPM 116(1): 1625·1628, 1998 CHAUFFAILLE, M.L.L.F.; VALÉRIO, R.M.; DINIZ, C.M.C.; SIMÕES, M.M.;ENOKIHARA, S.; MICHALANY, N.; FERREIRA, KV; MARTINEZ, JAB.; HASSUN,

K.M.; ATALLAH, AN.; KERBAUY, J. - Langerhans cell histiocytosis