Hypertrophic osteoarthropathy in a child with nasopharyngeal carcinoma

Abstract

We report a 13-year-old boy with nasopharyngeal carcinoma, skull metastases and hypertrophic osteoarthropathy. Although the metastases and the primary tumour responded well to chemotherapy, hypertrophic osteoarthropathy persisted during follow-up. [PUBLICATION ABSTRACT]

Pediatr Radiol (2000) 30: 570572 Springer-Verlag 2000

Ali VaranTezer KutlukFigen B. Demirkazk Canan Akyz Mnevver Bykpamuku

Hypertrophic osteoarthropathy in a child with nasopharyngeal carcinoma

Received: 24 February 1999 Accepted: 5 January 2000

A. Varan T. Kutluk ()) C. Akyz M. Bykpamuku Department of Paediatric Oncology, Institute of Oncology, Hacettepe University, 06100 Ankara, Turkey

F. B. Demirkazk Department of Radiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Abstract We report a 13-year-old boy with nasopharyngeal carcinoma, skull metastases and hyper-trophic osteoarthropathy. Although the metastases and the primary tumour responded well to chemotherapy, hypertrophic osteoarthropathy persisted during follow-up.

Introduction

Hypertrophic osteoarthropathy (HOA) is a rare condition characterized by periosteal reactions of long bones. It is usually associated with pulmonary, cardiac or hepatic disease. HOA is rarely reported in children with malignant disease, although it is relatively more common in adults [1]. Patients with osteosarcoma, Hodgkin's disease, thymic carcinoma and lung tumours are reported to present with HOA [14]. It is associated with pulmonary metastases or decreased oxygen concentration. Hypertrophic osteoarthropathy without pulmonary metastases in nasopharyngeal carcinoma is exceptional [1, 58]. We describe a child with systemic metastases without lung metastases. The metastatic lesions regressed during treatment, although HOA persisted. Most authors have reported that HOA regresses with treatment [1, 4, 6].

Case report

A 13-year-old boy was admitted to our hospital with frontal swelling, swelling in the left cervical region and pain in the extremities. He had 5 6-cm lymphadenopathy in the left superior cervical region, a 5 4-cm mass in the right frontal region and a 4 4-cm mass in the right parietal region. There was no finger clubbing. Physical examination was otherwise normal. The skeletal survey revealed multiple lytic lesions in the frontal and parietal bones and 7th, 10th and 11th ribs. There were diffuse, symmetrical, diaphyseal periosteal reactions on the humeri, radii, tibiae, femora and fibulae (Fig. 1). Bone scintigraphy showed increased uptake along the cortical margins of long bones. MRI demonstrated a nasopharyngeal mass invading the parapharyngeal spaces on both sides, the right cavernous sinus and pterygopalatine fossa (Fig. 2). This mass also invaded the dura. In addition, metastatic lesions in the parietal and frontal bones were detected (Fig. 3). Histological examination of a cervical lymph node biopsy showed undifferentiated metastatic carcinoma.

He was treated with 5-fluorouracil, cisplatinum, methotrexate and leucovorin rescue. Radiotherapy was administered to the nasopharyngeal mass. After 6 months, the nasopharyngeal and cranial metastases regressed almost completely, but the periosteal reactions remained unchanged. One year later, vertebral metastases developed while HOA persisted. The patient died with progressive disease 3 months later.

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b c

Fig. 1ac Diffuse periosteal new bone (arrows) on both legs and arms. a Right humerus and radius, b both femora and c both tibiae and fibulae

Discussion

In the course of malignant diseases, HOA is very rare [1, 5, 8]. It is reported in association with Hodgkin's disease, thymic carcinoma, osteosarcoma and lung, kidney and stomach carcinomas [14]. In children, 12 % of those with HOA have a neoplastic disease while in adults the figure is 92 % [9]. This syndrome is commonly encountered in patients with lung metastases or decreased lung capacity due to a mediastinal mass. Staalman and Umans [1] reviewed the literature and

documented nasopharyngeal carcinoma in 11 of 25 children with HOA. Ladeb et al. [7] identified 29 patients with nasopharyngeal carcinoma and HOA in the literature, but 25 of them had mediastinal or lung involvement.

Although the pathophysiology of HOA is still unknown, some authors stress its association with hormone-secreting tumours [4, 10]. Uchisako et al. [10] reported a patient with lung cancer and HOA in whom ectopic growth hormone caused a periosteal reaction. We were unable to measure growth hormone levels in our patient. Vagal impulses may also cause HOA. Diner[11] reported that vagotomy relieved bone pain in a patient with HOA. Miyachi et al. [12] described a patient with HOA, cryoglobulinaemia and nasopharyngeal carcinoma. They proposed a causal relationship between

Fig. 2 Axial T1-weighted MRI after Gd-DTPA demonstrates a nasopharyngeal mass invading both pterygopalatine fossae (arrow)

Fig. 3 Coronal T1-weighted MRI demonstrates a right parietal region metastasis

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References1. Staalman CR, Umans U (1993) Hyper-trophic osteoarthropathy in childhood malignancy. Med Pediatr Oncol 21: 676679

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3. Ilhan I, Kutluk T, Ggs S, et al (1994) Hypertrophic pulmonary osteoarthropathy in a child with thymic carcinoma: an unusual presentation in childhood. Med Pediatr Oncol 23: 140143

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(1997) Hypertrophic osteoarthropathy and intrathoracic Hodgkin disease of childhood. Med Pediatr Oncol 29: 578581

immunocomplexes and HOA. Many intrathoracic conditions such as tumours, nonspecific infections, cystic fibrosis and tuberculosis can be responsible for this situation. We believe that HOA is a paraneoplastic syndrome associated with nasopharyngeal carcinoma.

The differential diagnosis of HOA and bone metastases is critical. The diffuse, widespread periosteal proliferation on the shafts of long bones was typical of HOA in this patient with painful extremities. There were no lytic lesions in the long bones, but the lateral skull X-ray demonstrated lytic metastases, confirmed by MRI and bone scintigraphy. Bone scintigraphy also showed typical increased cortical uptake in the long bones giving an appearance called the `parallel tract sign' [10].

Hypertrophic osteoarthropathy can develop at the beginning of the disease or during treatment. Late-onset lesions have worse prognosis because they often accompany progressive disease [1, 4]. In our case, nasopharyngeal carcinoma and HOA were detected si-

multaneously. The prognosis of HOA with nasopharyngeal carcinoma is poor [1, 4], although survival with other tumours may differ. Morgan et al. [13] reported 28 cases of HOA in a series of 164 patients with lung cancer; survival was not affected after 2 years' follow-up. HOA with nasopharyngeal carcinoma is very rare and most cases are associated with pulmonary metastases [1, 8].

Most authors report that patients with non-resolving HOA after chemotherapy have a worse prognosis. If treatment is successful, HOA will resolve. While our patient's primary nasopharyngeal tumour and cranial metastases responded to treatment, periosteal reactions along the long bones did not resolve. One year later, vertebral metastases occurred while HOA persisted and the patient died with progressive disease after a further 3 months. Persistence of HOA, as in our patient, might be indicative of poor prognosis. We suggest that more intensive regimens should be used in the treatment of children with disseminated tumour and HOA.

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