BRIEF REPORTConcurrent Langerhans Cell Histiocytosis and Neuroblastoma

Antje Fischer,1* Lyn Jones,2 and Stephen P. Lowis1

Key words: neuroblastoma; Langerhans cell histiocytosis; diabetes insipidus

Langerhans cell histiocytosis (LCH) and its pathogen-esis are still poorly understood. Abnormalities of the im-mune system involving cytokines and activation of T-lymphocytes and other inflammatory cells have beendocumented. Recently demonstrated monoclonality fa-vors a neoplastic origin rather than a reactive process [1].There have also been several reports of patients withLCH and associated malignancies [2,3]. However, so farthere has been no reported instance of LCH associatedwith neuroblastoma, as was the case of a 2-year-old boywho presented with a 6-week history of polyuria andpolydipsia.

The child had been previously well, and his past andfamily histories were unremarkable. Physical examina-tion revealed a palpable left abdominal mass and a softarea in his frontal bone. Laboratory findings were normalexcept for the water deprivation test, which confirmedthe diagnosis of diabetes insipidus. An abdominal ultra-sound scan showed a large mass anterior to the left kid-ney, which did not cross the midline and contained cal-cification. These findings were confirmed by CT scan(Fig. 1). X-ray films and CT scans of the head showedextensive destruction and meningeal contact of an infil-trating lesion extending bilaterally from the sella turcicato the soft tissues involving the bone of the sinuses andthe middle cranial fossa (Figs. 2 and 3). MIBG scanshowed increased uptake in the abdomen only. Urinaryhomovanillic acid (HVA) and vanillylmandelic acid(VMA) were raised. Bilateral bone marrow aspirates(posterior superior iliac spine) and trephines were clearof disease. The boy underwent left adrenalectomy andbiopsy of the frontal bone lesion. The abdominal tumorwas fully excised and histology confirmed the diagnosisof neuroblastoma. Sampled lymph nodes were free ofdisease. The neuroblastoma was therefore classified asInternational Neuroblastoma Staging System (INSS)stage I. Other prognostic factors (N-myc not amplified,chromosomes 46XY, serum ferritin, neurone-specificenolase, and LDH not significantly elevated) being fa-vorable, no adjuvant treatment was deemed necessary.The histology of the skull lesion revealed Langerhanscell histiocytosis (LCH). MRI scan of the brain con-

firmed the CT scan findings and showed no evidence ofintrinsic brain lesions. The LCH was therefore classifiedas single system disease. In view of the site and extensionof the LCH lesions involving bone and soft tissue in themiddle cranial fossa, it was decided to initiate chemo-therapy according to the LCH 2 protocol. This comprises6 weeks of oral prednisone (40 mg/m2 daily for 4 weeks,then tapering the dose over the following 2 weeks) andweekly vinblastine (6 mg/m2; six doses in total). Reas-sessment after 6 weeks showed no change in distributionor extent of the abnormal soft tissue on the CT scan. The

1Department of Paediatric Oncology, Bristol Royal Hospital for SickChildren, Bristol, England2Department of Radiology, Bristol Royal Hospital for Sick Children,Bristol, England

*Correspondence to: Antje Fischer, Department of Paediatric Oncol-ogy, Bristol Royal Hospital for Sick Children, St. Michael’s Hill,Bristol BS2 8BJ, England.

Received 30 June 1998; Accepted 16 September 1998

Fig. 1. CT scan of the abdomen. Mass anterior to the left kidney(between darts), containing calcification (arrow) and not crossing themidline.

Medical and Pediatric Oncology 32:223–224 (1999)

© 1999 Wiley-Liss, Inc.

diabetes insipidus is controlled with oral desmopressin,which very likely will need to be continued lifelong. Theboy is currently also on a replacement dose of hydrocor-tisone and awaiting formal pituitary function tests.

DISCUSSION

In the literature, the interval between the diagnosis ofLCH and the diagnosis of a malignant lesion is veryvariable, with the diagnosis of a malignancy precedingthe diagnosis of LCH by months or even years or viceversa. In those cases, it is impossible to say whether thesecond disease is at all treatment-related. Most patientsreceived chemotherapy and/or radiotherapy, which inthemselves have oncogenic potential. However, there arestill a number of cases where the diagnosis of LCH andof cancer were made concurrently.

Egeler et al. [3] reviewed a total of 91 cases of LCHassociated with neoplasms. A large group (n4 39) hadassociated malignant lymphoma, another large group (n4 22) had associated leukemia, 12 patients had carci-noma of the lung, and the remaining 18 had a variety ofother solid tumors. The diagnosis of LCH and the ma-

lignant neoplasm were made at the same time in 24(61%) of the lymphoma patients, in 6 (27%) of the leu-kemia patients, in 9 (75%) of the lung carcinoma pa-tients, and in 2 (11%) of those with solid tumours [3]. Inour patient, the diagnosis of neuroblastoma and of LCHwas made at the same time prior to starting any treat-ment. As far as we know this is the first reported case ofLCH and neuroblastoma in the same individual. The un-answered question remains whether these findings arepurely coincidental or whether there is a yet unknowncausative relationship between LCH and malignant pro-cesses.

REFERENCES

1. Lam KY. Langerhans cell histiocytosis (histiocytosis X). PostgradMed J 1997;73:391–394.

2. de Camargo B, Alves AC, Gorender EF, Bianchi A. Associationof malignancy and Langerhans’ cell histiocytosis: report of threecases. Med Pediatr Oncol 1993;21:451–453.

3. Egeler RM, Neglia JP, Pucetti DM, et al. Association of Langer-hans cell histiocytosis with malignant neoplasms. Cancer1993;71:865–873.

Fig. 2. Postintravenous contrast image from a CT scan of the headset on soft tissue windows. Enhancing abnormal soft tissue infiltratesthe superior rectus muscles and frontal sinuses bilaterally. Fig. 3. CT scan of the head with bone window settings. The bony

destruction involves the wall of the left orbit and elements of theanterior and middle cranial fossae.

224 Fischer et al.