A case of seminoma-associated orbitopathy

Case Reports

A case of seminoma-associated orbitopathy Michael Guiney, FRACP, FRACR" Christopher Buckley, FRACS, FRACO, FRCS t Nicolas Radford, FRACPS Gerard Joyce, FRACSS

Testicular cancer is a relatively uncommon malignancy accounting for only 1% of all malignancy in men. Seminoma, the most common histologic subgroup, accounts for 40% of testicular cancers. Graves orbitopathy, associated with thyroid dysfunction, is the single most common cause of exophthalmos, bilateral and often asymmetric. Chemosis, exophthalmos, limitation of extraocular muscle movement causing diplopia, and enlarged extraocular muscles seen on C T scan are the classic signs. The simultaneous occurrence of Graves-type orbitopathy and testicular seminoma has only been reported in three previous cases. We report a fourth case. Case report A 34-year-old man presented with a three-week history of having noted a change in size and texture of his left testicle. At approximately the same time, he noted redness and irritation of the left eye. He was diagnosed as having a testicular tumour and a radical left inguinal orchidectomy was performed on the 7 May 1993. Pathological examination revealed a 50 x 30 mm tumour in the testicle. The histology revealed pure seminoma of the classic type with extensive granulomatous reaction and fibrosis. The epididymis and spermatic cord were not involved and the resection was considered complete. During the interval between orchidectomy and commencement of radiotherapy, his left eye symptoms worsened and he developed diplopia. An

ophthalmological consultation was obtained. His vision was normal in both eyes when corrected for his myopia. He was noted to have left axial proptosis, restriction of abduction and elevation of the left eye and chemosis medially overlying an enlarged medial rectus muscle which was visible through the conjunctiva. A CT scan of the orbits performed on 25 May 1993 revealed enlargement of the left medial, left and right inferior r e d and both superior oblique muscles. The tendon of the left medial rectus muscle was also enlarged, which was the part of the muscle that could be seen beneath the conjunctiva. Bilateral exophthalmos was also noted (Figures 1, 2). There was no evidence of an intraorbital mass, excluding a metastasis from the testicular seminoma. There was no clinical evidence of thyrotoxicosis. The thyroid gland was not enlarged, there was no thyroid acropachy or pretibial myxoedema. Thyroid function tests performed on 31 May 1993 revealed a normal serum free T4 level of 14.1 (normal range, 10.0 to 20.0 pmollL) and ultra sensitive TSH of 1.5 (normal range, 0.3 to 5.0). Tests for antithyroglobulin, antimicrosome and TSH receptor antibodies were negative. The patient was then given 60 mg of prednisolone daily. He was referred to the East Melbourne Radiation Oncology Centre for adjuvant irradiation to the para-aortic and pelvic lymph nodes. Preoperative tumour markers (alphafetoprotein, beta human chorionic gonadotrophin [HCG]) were within the

*Radiation and Medical Oncologist, East Melbourne Radiation Oncology Centre, 132 Grey Street, East Melbourne 3002, Victoria. +Consultant Ophthalmologist, Monash Medical Centre. $Consultant Physician, St Vincent's Hospital, Melbourne. $Consultant Urologist, Department of Urology, St Vincent's Hospital, Melbourne. Reprints: Dr M Guiney. A case of seminoma-associated orbitopathy

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Figure 1 Axial C T image of orbits.

Figure 2 Coronal C T image of orbits.

normal range. A chest x-ray was normal, and C T scan of the abdomen and pelvis noted two 1.0 cm lymph nodes in the left para-aortic region just inferior to the renal hilum, the significance of which was unclear. He received 30 Gy in 20 fractions of irradiation to the para-aortic and iliac lymph nodes via anterior and posterior fields. His radiotherapy was completed on 5 July 1993. Over the next two months his eye symptoms and signs steadily abated. Prednisolone was gradually reduced and ceased in September 1993. A repeat CT scan of the abdomen and pelvis performed in November 1993 was normal. The previously enlarged para-aortic lymph nodes were not detectable. The patient refused to have a repeat C T scan of the orbits following resolution of the eye signs and symptoms. Twenty-four months after completing radiotherapy and 22 months after ceasing prednisolone, there is no evidence of recurrence of his eye symptoms and signs. There is no evidence of recurrent seminoma and his alphafetoprotein and betaHCG levels remain within the normal range.

of recurrent tumour or eye disease. The histology of the tumour was predominantly seminomatous with occasional microscopic nests of choriocarcinomatous elements. The second case was reported in 1974 by Leyson.2 This patient had mediastinal seminoma associated with bilateral exophthalmos and gynaecomastia. This patient died before receiving any therapy. The third case was reported in 1978 by Taylor et al. This 57-year-old man presented with chemosis, bilateral proptosis, impaired visual acuity and marked ~phthalmoplegia.~There was no evidence of hyperthyroidism and he was given 80 mg of prednisolone daily. He responded to steroid medication, but two attempts in three months to reduce the dose of prednisolone resulted in recurrence of his eye disease. Three months after presentation he was diagnosed as having a pure seminoma of the left testis (betaHCG level was zero) and orchidectomy was performed. His steroid medication was rapidly tapered with no recurrence of his orbitopathy with four years of follow-up. Our case presented in the more typical age range for seminoma while the other cases were in their sixth decade. The cases reported by Taylor et al.3 and Mann' showed rapid improvement in the eye signs following orchidectomy. In our case, the eye signs persisted and even worsened following orchidectomy and did not resolve until retroperitoneal nodal irradiation was completed. This would suggest that there was metastatic disease in the retroperitoneal lymph nodes. The fact that the two

Discussion The association of exophthalmos with seminoma has only been reported in three other The first report, by Mann in 1967,' was that of a 58-year-old man who had symptoms and signs consistent with Graves orbitopathy four weeks prior to presentation. He had noted a mass in the left testicle for 12 months before presentation. Following orchidectomy, his eye signs improved dramatically. With five years of follow-up, there was no evidence 336

Australian and New Zealand Journal of Ophthalmology 1995; 23(4)

1.O cm lymph nodes in the left para-aortic region noted on the C T scan before radiotherapy were not present on a repeat CT scan performed four months after irradiation would support this. Hence it would appear that the orbitopathy can be sustained by metastatic disease alone, without the need for the primary tumour to be in situ. Seminoma-associatedorbitopathy can arise across the entire clinical spectrum of seminoma. In the report by Mann,’ although the tumour was predominantly seminoma, microscopic foci of choriocarcinoma was noted. The cases reported by Taylor et a1.’ and L e y ~ o n as , ~ well as ours, were pure seminoma. Thus the phenomenon of orbitopathy can occur in mixed germ cell tumours as well as pure seminomas. Mann’s case had elevated levels of gonadotrophin hormone prior to orchidectomy, which remained elevated postoperatively for five years without evidence of tumour recurrence. The preoperative HCG level was normal in the case reported by Taylor et el. and in the current case. Thus an elevated HCG level is not a prerequisite for the development of orbitopathy. The orbitopathy can also arise in association with extragonadal seminoma, as in the case of Leyson where the tumour arose in the media~tinum.~ The orbitopathy associated with Graves disease usually runs a more protracted course independent of the underlying hyperthyroid state. It is not unusual in cases of orbitopathy associated with Graves disease to have residual exophthalmos and ophthalmoplegia even after the disease activity has

A case of seminoma-associated orbitopathy

ceased. However, it would appear that the orbitopathy associated with seminoma resolves completely once the underlying turnour has been eradicated. Tendinous involvement, although recognised in Graves orbitopathy, is rare and involvement of the superior oblique muscles is uncommon. The presence of these features in a case of orbitopathy may be clues to a possible association with ~ e m i n o m a . ~ In our case and that reported by Taylor et al., antibody studies were negative and thyroid function tests normal. In cases of euthyroid and antibody-negative orbitopathy, investigations for testicular and extragonadal seminoma should be performed routinely as seminoma is a curable malignancy and its treatment results in resolution of the orbitopathy. The orbitopathy fulfils the criteria of a paraneoplastic syndrome associated with seminoma, though the underlying mechanism is currently unknown. It is hoped that as the association between the two conditions is now well documented, future cases will be recognised earlier and investigation during the disease process may lead to the elucidation of the underlying link between the two conditions.

References 1. Mann AS. Bilateral exophthalrnos in seminoma. J Clin Endocrinol 1967;27:1500-3. 2. Leyson JFJ. Mediastinal seminoma associated with exophthalmos and gynaecomastia. Urology 1974;111:366-9. 3. Taylor JB, Solomon DH, Leaven RE, Ehrlich RM. Exophthalmos in seminoma. Regression with steroids and orchidectomy. JAMA 1978;240:860- 1. 4. Rootman J, ed. Diseases ofthe orbit. Philadelphia: J P Lippincott, 1988.

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