Medical and Pediatric Oncology 12: 144-147 (1984)

Rebound Thymic Hyperplasia in a Child With Cancer

B.A. Bell, MD, D.W. Esseltine, MD, and E.M. AZOUZ, MD

A case of biopsy-proven thymic hyperplasia is described in a child with group I paratesti- cular rhabdosarcoma while on chernother- apy. Other cases of children with cancer re- ported with this phenomenon are reviewed.

Tissue diagnosis is important to differentiate metastatic tumor and to rule out second ma- lignances in these patients. The initial evalua- tions are facilitated by CT scanning of the chest and upper extremity venography.

Key words: thymus, thymic hyperplasia, rhabdosarcoma

INTRODUCTION

Benign thymic hyperplasia [ 1-31 has been described i n several clinical situations such as after cardiovascular surgery [4], following the stress of severe burns, after the cessation of oral corticosteroids [5] , and in endocrin- ological disorders like hyperthyroidism [6], Addison’s disease, and acromegaly.

The phenomenon of rebound or regeneration of thymic tissue has been reported in only a few patients with tumors 17-91. Attempts are being made to assess nonin- vasive approaches to the diagnosis of the cancer patient who is found to have mediastinal widening on chest x- ray.

The following case adds to the reports of thymic hyperplasia associated with malignancies and highlights the management problems that accompany the incidental finding of mediastinal widening in a child undergoing chemotherapy.

CASE REPORT

A 2 !h-year-old boy presented with a 1-month history of a slowly enlarging left testicle. A firm 4 X 6 cm left scrota1 mass was present on examination. The complete blood count was normal and the absolute lymphocyte count 4.5 X lO’/liter. The bone marrow aspiration was normal and showed 45% mature lymphocytes. A bone marrow biopsy and cerebrospinal fluid examination were normal. A full radiological investigation for metastatic tumor was negative.

A left inguinal orchidectomy and ipsilateral retroperi- toneal lymphadenectomy were performed for complete gross tumor removal. The pathological diagnosis was paratesticular embryonal rhabdosarcoma with spermatic cord involvement. No lymph node metastases were found.

The patient was treated with vincristine and actino- mycin-D according to the Intergroup Rhabdomyosar- coma Study I1 for group I disease. No radiation was given.

Ten months after diagnosis, the chest x-ray was nor- mal (Fig. 1). At 12 months a routine chest x-ray revealed enlargement of the superior mediastinum (Fig. 2). A computed tomography (CT) scan of the chest (Fig. 3) showed a predominantly left-sided upper mediastinal mass extending posteriorly to the region of the esopha- gus. It was of soft tissue density with no visible serous fluid, fat, or calcium content. The lungs were normal. A venogram of the mediastinum was normal.

At thoracotomy, the thymus was enlarged to twice its normal size. The right lobe, weighing 28 g, was re- moved. The pathological diagnosis was thymic hyperpla- sia in an otherwise normal thymus.

The patient resumed chemotherapy and completed the original protocol requirements. He has been off treatment for over 1 year and remains well. The chest x-ray and CT scan were normal at just over 3 years from diagnosis.

DISCUSSION

Paratesticular rhabdosarcoma spreads by involvement of regional lymph nodes first, but may also hematoge- nously seed to distant sites, including lungs and bones [ 101. Rhabdosarcoma rarely metastasizes to the media- stinum. Curnes et al [ l l] described a case of a boy with

From the Departments of Pediatrics (Hematology) (B.A.B., D.W.E.) and Radiology (E.M.A.), McGill University, and the Montreal Chil- dren’s Hospital, Montreal, Canada.

Address reprint requests to Dr D.W. Esseltine, Service of Hematol- ogy, Montreal Children’s Hospital, 2300 Tupper Street, Montreal, Quebec, Canada H3H 1 P3.

0 1984 Alan R. Liss, Inc.

Rebound Thymic Hyperplasia in a Child 145

Fig. 1. Normal plain radiography of the chest at 10 months after diagnosis. widened superior mediastinum.

Fig. 2. Chest radiograph done at 12 months after diagnosis shows

paratesticular rhabdosarcoma who had an anterior me- diastinal mass along with pulmonary and bone marrow metastases. The mediastinal mass responded to chemo- therapy. In our patient, mediastinal widening was noted on a surveillance chest radiograph done nearly 12 months after diagnosis of early stage paratesticular rhabdosar- coma while the patient was on chemotherapy. It was necessary to differentiate tumor metastasis from the be- nign condition, thymic hyperplasia.

Mediastinal widening is first identified on the routine chest x-ray, but a more sensitive differentiation of me- diastinal structures is obtained with CT of the chest along with venography.

Rapid widening of the superior mediastinum in this patient’s age group may be due to lymphadenopathy, thymic enlargement, dermoid cyst, or lipoma. Venous ectasia was ruled out because a bilateral upper extremity and mediastinal venogram was normal [ 121. There was no history of trauma or heart surgery, so a mediastinal hematoma was unlikely.

CT is a noninvasive method of defining mediastinal mass lesions [13,14]. It provides axial imaging with ac- curate localization of the mass, its size, exact anatomical relationship, and internal composition. The use of intra- venous iodinated contrast material differentiates between vascular and other structures. The attenuation value of a mediastinal mass may permit a more definitive diagnosis than was possible with other radiographic tools. In our CT study (Fig. 3), the “mass” was not of fat density (as would be seen with lipoma or mediastinal fat accumula-

Fig. 3. C T of the chest confirms the superior mediastinal widening or mass.

tion), and there was no calcification or ossification (such as with dermoid cysts, teratomas, and venous angiomas). There was no evidence of either tracheal or esophageal compression, making a malignant tumor much less likely.

Gallium (Ga-67) citrate localizes frequently to the thymus in children with leukemia and lymphoma, more frequently than the 11-15% prevalence reported in a

146 Bell, Esseltine, and AZOUZ

TABLE I. Thymic Hyperplasia in Children With Cancer

Case Reference

7.8

8 8

8

8 8

8

9

This report

Age (years)

3

2.6 9 8/12

5 4/12

4 3/12 4 5/12

1.9

18

2 112

Sex

M

F M

F

M F

F

F

M

Tumor type; chemotherapy

Wilms; vincristine ALL Osteosarcoma

Teratocarcinoma; vincristine, actinomycin-D, cyclophosphamide Lymphoma Lymphoma

Wilms; vincristine, actinomycin-D Hodg k i n

Rhabdosarcoma: vincristine,

Detection mediastinal mass from

time of diagnosis (months)

12

> 39 17

5

On or off chemo

Off (9 mo)

Off Off

(1 mo) On

30 On 10 Off

10 On (1 mo)

11 Off

10 On (7 mo)

Treatment

Biopsy

Biopsy Observation

Observation

Observation Prednisone

Prednisone

Biopsy

Biopsy

actinomycin-D

control group [ 151. It is found with either tumor invasion or thymic regeneration after chemotherapy. Donahue et a1 1151 suggest that patients with an abnormal chest x- ray, CT scan of the mediastinum, and abnormal thymic localization of Ga-67 should have tissue confirmation of the diagnosis by surgical biopsy. However, if only one of these studies is abnormal, and the child is clinically well, then close observation may be sufficient. Others [3] have suggested the use of a prednisone trial, once leuke- mia and lymphoma have been excluded, to shrink the thymic mass and so justify a period of observation with- out the need for surgical biopsy. This may be a logical step in avoiding surgical excision, as long as a predni- sone-sensitive tumor has been ruled out.

We found that the CT and venography were helpful in narrowing the diagnostic possibilities but we could not

that our patient had lymphocytosis at diagnosis and was on cycles of chemotherapy given every 12 weeks. Like other patients reported, he had no evidence of disease recurrence. Except for the case of Shin and Ho [9], enough clinical details are not given to reinforce the speculations that thymic hyperplasia is associated with bolstered cell-mediated immunity and a good prognosis for the cancer patient.

As more cases of thymic hyperplasia are described and followed for a long period of time, it will be impor- tant to see how often patients with this type of presenta- tion have active neoplastic disease. The cases described to date have all been in remission. Thymic rebound may in fact indicate a good prognosis and recovery of immune function after chemotherapy or viral infections.

- - fully exclude recurrent tumor or a second malignancy. Our patient did not have a Ga-67 scan.

There have been only a few reported cases of thymic hyperplasia in children with cancer, and these are sum-

We thank Mrs. Johanne Therrien for typing the manuscript.

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