Mimics of metastases from testicular tumours

ClinicalRadiology (1990) 41, 395-399

Mimics of Metastases from Testicular Tumours J. F. C. O L L I F F , R. E E L E S * a n d M. P. W I L L I A M S

CRC Radiology Research Group and *The Testicular Tumour Unit, The Royal Marsden Hospital, Downs Road, Sutton, Surrey This paper presents 10 patients with a diagnosis of testicnlar tumour in whom computed tomograpby (CT) at staging or follow-up demonstrated abnormalities which mimic the appearance of metastatic testicular tumour. The entities mimicking metastases were sarcoidosis, mushroom worker's lung, iymphoma and phaeochromocytoma. Representative examples of these lesions are illustrated and features which may enable the radiologist to differentiate them from metastatic testicular tumour are discussed.

lesions diagnosed at another institution as metastases and he was referred for chemotherapy. Marker levels were normal, there was no evidence of mediastinal or abdominal adenopathy and the pulmonary nodules, even on 2 mm thick CT sections, were small, irregular and rather ill-defined (Fig. 4). On close questioning the patient revealed that in his job as a packer, he worked with up to half a ton of fresh mushrooms daily until 12 weeks prior to his presentation with a testicular mass. A Kviem test was negative, serum ACE was normal and a diagnosis of mushroom worker's lung was made. No chemotherapy was given and the patient remains well with an unchanged but abnormal chest radiograph and pulmonary CT scan 2 years later.

LYMPHOMA T h e m a n a g e m e n t o f patients with testicular t u m o u r s places great reliance on r a d i o l o g i c a l investigations a n d serum m a r k e r estimations to d e t e r m i n e the extent o f disease. W h e n s e r u m levels o f a l p h a f e t o p r o t e i n ( A F P ) a n d h u m a n c h o r i o n i c g o n a d o t r o p h i n ( H C G ) are elevated c o n c u r r e n t with a b n o r m a l r a d i o l o g i c a l findings, it is usual to assume t h a t the a b n o r m a l r a d i o l o g y is due to m e t a s t a t i c disease. I f the r a d i o l o g i c a l p a t t e r n is atypical for m e t a s t a t i c testicular t u m o u r then the r a d i o l o g i s t m u s t be alert to the possibility o f c o i n c i d e n t disease, especially if s eru m m a r k e r s are n o t elevated. W e r e p o r t a series o f 10 cases seen in recent years at the R o y a l M a r s d e n H o s p i t a l w h e r e dual p a t h o l o g y was d e m o n s t r a t e d in patients with a p r i m a r y diagnosis o f testicular t u m o u r .

SARCOID T h e clinical details and r a d i o l o g i c a l findings in six patients with sarcoid a n d testicular t u m o u r s are p r esen t ed in T a b l e 1. O n e patient, Case 1, h a d biopsy p r o v e n sarcoid a b d o m i n a l l y m p h a d e n o p a t h y (Fig. 1) in a d d i t i o n to the m o r e typical m e d i a s t i n a l and bilateral hilar l y m p h a d e n o p a t h y exhibited by the r e m a i n i n g five cases. In three patients the e n l a r g e d mediastinal l y m p h n o des were present at the time o f initial staging, whilst in the o t h er three the m e d i a s t i n a l l y m p h a d e n o p a t h y a p p e a r e d be t ween 4 a n d 14 m o n t h s after the p a t ie n t ' s orchidectomy. In one patient, Case 5, the m e d i a s t in a l a n d bilateral hilar n o d e s due to sarcoid (Fig. 2) increased in size whilst the p a t i e n t ' s a b d o m i n a l l y m p h a d e n o p a t h y due to testicular t u m o u r decreased in size on treatment. O n e case o f sarcoid, Case 6, s h o w e d p u l m o n a r y a b n o r m a l i t i e s in plain r a d i o g r a p h y a n d CT. O n C T the s h a d o w i n g was seen to consist o f ill-defined areas o f increased lung density, some c o n t a i n i n g fine n o d u l a r s h a d o w i n g (Fig. 3).

Case 8 A 20-year-old man presented with a malignant teratoma of the left testis. As staging showed normal markers and no evidence of metastatic spread, he was managed with regular follow-up. CT one year later showed a 4 x 6 cm soft tissue dense thymic mass. Abdominal CT and serum marker levels were normal. Histological examination of the excised thymus showed nodular sclerosing Hodgkin's disease. The patient was originally treated with mediastinal irradiation, but has subsequently required several courses of chemotherapy for histologically proven relapses of Hodgkin's disease. There is no evidence of metastatic teratoma on follow-up of 6 years.

Case 9 A 48-year-old man presented 18 years ago with a right-sided testicular teratoma. He was treated by orchidectomy and abdominal radiotherapy. Fourteen years later he developed a left-sided seminoma and 6 months after this CT demonstrated enlarged left para-aortic nodes. Aspiration biopsy of a para-aortic node showed clusters of malignant cells thought to be consistent with a diagnosis of metastatic seminoma. He was treated with four courses of carboplatin but CT showed progressive enlargement of the para-aortic nodes. A laparotomy was performed to excise a node. Histology revealed low grade follicular lymphoma. Three years later, he has had one local recurrence of abdominal lymphoma but has no evidence of spread of either of his testicular malignancies.

PHAEOCHROMOCYTOMA

Case 10 A 32-year-old man presented with a right-sided testicular teratoma. At staging his marker levelswere normal, with no evidenceof abdominal lymphadenopathy or pulmonary metastases. CT did, however, show a 2.5 cm mass in the right adrenal gland with a low attenuation centre and rim enhancement on injection of intravenous contrast medium. Specimens were obtained which showed elevated urinary vanilylmandelic acid levels and raised serum metanephrine. Resection of the right adrenal gland confirmed the presence of an asymptomatic phaeochromocytoma. On 3 year follow-up there is no evidence of recurrence of either tumour.

DISCUSSION MUSHROOM

WORKER'S

LUNG

Case 7 A 24-year-old man presented with a right-sided mixed malignant teratoma and seminoma. Staging CT showed multiple small pulmonary Present address and correspondence to: M. P. Williams, Department of Radiology, Freedom Fields Hospital, Plymouth PL4 7JJ.

In recent years the p r o g n o s i s o f patients with testicular t u m o u r s has i m p r o v e d m a r k e d l y , particularly as a result o f the i n t r o d u c t i o n o f p l a t i n u m based c h e m o t h e r a p y regimens. Cure rates o f o v e r 90% are n o w expected in m o s t g r o u p s o f patients with testicular germ cell t u m o u r s ( M R C W o r k i n g P a r t y o n Testicular T u m o u r s , 1985).

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CLINICALRADIOLOGY

Table 1 - Clinical marker and radiological details of six patients with sarcoid and testieular tumours

No

Diagnosis

Age

R M H staging classification (Hendry et al., 1985)

Elevated marker at time of staging

Radiological appearances

Elevated markers at time of diagnosis ofsarcoid

Time from first diagnosis to diagnosis of sarcoidosis

Proof sarcoidosis

1

Seminoma

38

1

AFP

(a) Bilateral hilar lymphadenopathy+ 1 cm mediastinal nodes (b) 2 cm abdominal node

Negative

14 months

Positive Kveim test

Negative

16 months

Bilateral hilar lymphadenopathy Mediastinal nodes 0.5 to 1 cm Bilateral hilar lymphadenopathy Bilateral hilar lymphadenopathy + mediastinal nodes (BHL up whilst abdominal teratoma down) 1 cm right paratracheal nodes x 3 +pulmonary shadowing

Negative

6 months

Negative

4 months

Positive Kveim test, abdominal node aspirate Positive Kveim test, mediastinoscopy Thoracotomy*

Negative

Concurrent

Negative

Concurrent

AFP

Concurrent

2

Terat0ma

32

II

3

Teratoma

52

IV O L2

AFP HCG AFP

4

Teratoma

33

I

neg

5

Teratoma

34

IV B L1

neg

6

Teratoma

26

II B

AFP

Positive Kveim test, thoracotomy Mediastinoscopy and laparotomy

Positive Kveim test, ACE elevated, spontaneous resolution of pulmonary shadowingt

*Residual teratoma excised from lung "~Residual teratoma excised from abdomen

These chemotherapy regimens are toxic, and it is important that treatment should only be instituted for those who need it. Radiology, and in particular CT scanning, plays an important part in the staging and follow-up of patients with testicular tumours (Williams et al., 1987a). CT has been shown to be effective for the detection of abdominal and mediastinal lymphadenopathy and for the detection of metastatic pulmonary nodules (Husband et al., 1981). However, not all radiological abnormalities in patients with testicular tumours, whether shown by CT or plain radiography, are necessarily metastatic and it is important to recognise non-metastatic abnormalities in order to avoid potential overtreatment. Sarcoidosis is a particularly c o m m o n non-malignant cause of both nodular pulmonary shadowing and enlarged lymph nodes which may be confused with metastatic disease. The incidence of sarcoidosis is 19 per 100000 per year (Hillerdal et al., 1984). Fortunately the distribution of lymphadenopathy in sarcoid and in testicular tumours differ. In sarcoid, the classical appearance as shown by chest radiography is of bilateral hilar and right paratracheal lymphadenopathy. CT usually shows multiple small nodes scattered throughout the mediastinum (Fig. 2). In sarcoid, mediastinal lymphadenopathy, with or without pulmonary shadowing, is c o m m o n and abdominal lymphadenopathy is uncommon, although the latter clearly does occur as illustrated by Case 1. In contradistinction, the pattern of nodal enlargement is the opposite in metastatic testicular tumours. The first sites of nodal disease are abdominal with involvement of nodes in the para-aortic regions. Tumours of the left testis classically metastasise to a node or nodes in the left para-aortic chain, just at or below the

level of the left renal vein. Tumours from the right testis typically metastasise to analogous nodes at a more variable level in the right para or precaval regions from the level of the renal veins down to the aortic bifurcation (Chiappa et al., 1966; Ray et al., 1973; D o n o h u e et al., 1982; Dixon et al., 1986). Mediastinal lymphadenopathy m a y be seen as a feature of metastatic testicular tumours, though it is more a feature of chest disease in seminoma than teratoma (Williams et al., 1987b). It is unusual to see mediastinal lymphadenopathy in the absence of either concurrent abdominal metastases or a history of prior treatment for abdominal disease. It is even more unusual to see isolated bilateral hilar lymphadenopathy from testicular turnouts. In a review of the radiological findings of 200 seminoma patients, only two patients out of 30 with metastases to the chest had hilar tymphadenopathy, and in both of these the hilar adenopathy was associated with larger mediastinal nodes (Williams et al., 1987b). The time of appearance of lymphadenopathy or pulm o n a r y shadowing in relation to the time of diagnosis of of testicular tumour may also be of help. In Case 6 described above, the pulmonary shadowing, thought possibly metastatic by his referring hospital, resolved without treatment. In this case the positive Kveim test, elevated angiotensin converting enzyme (ACE) and the spontaneous resolution of the pulmonary shadowing make the 1 cm paratracheal nodes seen at CT more likely due to sarcoid than to metastatic teratoma. When radiological abnormalities appear in patients with testicular tumours, it is vital to assess levels of the serum markers beta H C G and alphafetoprotein. At least one of these markers is elevated in approximately 70% of patients with testicular turnouts at diagnosis and generally if the patient is marker positive at presentation, then

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MIMICS OF METASTASES FROM TESTICULAR TUMOURS

(a)

(a)

(b) Fig. 1 - Detail of C T sections through the upper para-aortic region; (a) shows a 2 cm soft tissue dense node in the interaortico-caval region which four weeks later (b) appeared cystic on a contrast-enhanced study. The node was biopsied revealing epithelioid ceils only with no evidence of malignancy.

they will be marker positive at relapse. Hence, in patients with known marker positive disease, the appearance of adenopathy with negative serum marker levels argues against the nodes representing recurrence of testicular tumour. This rule is not absolute as different cell lineages may be present in the metastases than predominate in the initial tumour. Thus, a patient with marker positive teratoma may occasionally relapse with marker negative seminoma deposits. If sarcoid co-exists with metastatic disease as it did in three of the cases above, the diagnosis is particularly difficult. In case four, previously reported by O'Connell (O'Connell et al., 1983), nodes involved by biopsyTproven sarcoid, even enlarged after a period of quiescence. Thus simple monitoring of changes in lymph node size may be

(b) Fig. 2 - C T sections through the mediastinum at the level of the top of the aortic arch (a) and at hilar level (b) illustrate the typical appearances of sarcoid. Multiple nodes from 1 to 1.5 cm in diameter are seen in the paratracheal preaortic a n d subcarinal regions with rather larger nodes demonstrated in both hila.

insufficient to assess the status of metastatic disease and histology should be obtained before instituting a change in therapy. Some authors claim that these cases represent not the disease sarcoidosis, but a sarcoid-like reaction to the presence of metastatic testicular tumour (Fossa et al., 1985). Case 7 illustrates a case of non-metastatic nodular pulmonary shadowing. Absence of demonstrable abdominal lymphadenopathy does not rule out pulmonary metastases as up to 20% of patients with metastatic teratoma may show pulmonary lesions without abdominal disease. However, the pattern of pulmonary disease was atypical for metastatic teratoma in that the nodules were all of uniform size and even on thin-section CT, rather ill-defined (Fig, 4). Such an appearance favours an

398

CLINICAL RADIOLOGY

Fig. 3 - CT section through the carina viewed at lung window settings show ill-defined patches of increased lung density, some with a nodular component. These pulmonary shadows which are completely unlike metastatic disease in appearance, were associated with a positive Kveim test and raised levels of angiotensin converting enzyme. They resolved spontaneously before the patient was treated for metastatic abdominal teratoma.

s u b c a r i n a l locations. Less f a v o u r e d b u t nevertheless c o m m o n sites are the low right p a r a t r a c h e a l a n d high left p a r a t r a c h e a l regions (Williams et al., 1987b). T r u e anteri o r m e d i a s t i n a l n o d e i n v o l v e m e n t in the r e g i o n o f the t h y m u s a n d p r e - a o r t i c a r e a is e x c e p t i o n a l l y unusual. Thus w h e n a truly a n t e r i o r m e d i a s t i n a l m a s s arises in a patient with a testicular t u m o u r , an a l t e r n a t i v e e x p l a n a t i o n s h o u l d be sought; t h y m i c h y p e r p l a s i a i f the p a t i e n t has a h i s t o r y o f previous c h e m o t h e r a p y (Kissin et al., 1987) or a second t u r n o u t in a p a t i e n t with n o such history. In Case 9, there were no r a d i o l o g i c a l clues to suggest a n alternative diagnosis to testicular t u m o u r metastasis. T h e d i s t r i b u t i o n o f disease was as w o u l d be expected for a left-sided testicular t u m o u r . The p r i o r h i s t o r y o f irradiat i o n for a c o n t r a l a t e r a l testicular t u m o u r , however, raises the possibility o f a r a d i a t i o n i n d u c e d s e c o n d malignancy. S e c o n d m a l i g n a n c i e s have been r e p o r t e d in patients i r r a d i a t e d for testicular t u m o u r s ( H a y et al., 1984) though the excess m a l i g n a n c i e s in t h a t series consisted largely o f skin t u m o u r s outside the i r r a d i a t e d v o l u m e o r transitional cell c a r c i n o m a s within it. A n excess o f l y m p h o m a o r l e u k a e m i a was n o t r e p o r t e d . I n C a s e 10, the p a t i e n t h a d an ipsilateral a d r e n a l mass at staging with no evidence o f m e t a s t a t i c disease elsewhere. I n a review o f 650 p a t i e n t s with testicular t u m o u r s r e p o r t e d f r o m this i n s t i t u t i o n ( H u s b a n d a n d Bellamy, 1985), o n l y f o u r patients h a d m e t a s t a s e s in the adrenal glands d e m o n s t r a t e d by CT. T w o p a t i e n t s h a d concurrent a b d o m i n a l l y m p h a d e n o p a t h y a n d two h a d extensive m e t a s t a t i c disease elsewhere. A n i s o l a t e d adrenal m e t a s t a s i s was therefore c o n s i d e r e d highly u n l i k e l y in this case a n d b i o c h e m i c a l screening was i n s t i t u t e d which p r o v i d e d evidence o f a n a d r e n a l p h a e o c h r o m o c y t o m a c o n f i r m e d by s u b s e q u e n t surgery. T h e cases described show a wide variety o f radiological a b n o r m a l i t i e s seen in patients with a d i a g n o s i s o f testicular t u m o u r . T h e y serve to illustrate p o t e n t i a l pitfalls in the d i a g n o s i s o f m e t a s t a t i c disease b a s e d o n radiological g r o u n d s alone. I f the p a t t e r n o f m e t a s t a s i s appears u n u s u a l a n d there is no c o n f i r m a t o r y e l e v a t i o n o f serum m a r k e r levels, then the r a d i o l o g i s t m u s t be a w a r e o f the p o s s i b i l i t y o f d u a l p a t h o l o g y . I n such cases it becomes m a n d a t o r y to o b t a i n histological evidence o f m e t a s t a t i c disease in o r d e r to a v o i d o v e r t r e a t m e n t .

Acknowledgements. The authors would like to acknowledge the generosity of the Cancer Research Campaign and the Daniel Marks Fund for funding of two of the authors, J.O. and M.P.W. respectively. Our thanks for the careful preparation of this manuscript to Mrs Dorothy Mears and Miss Jan Gadd.

Fig. 4 - CT section obtained with 2 mm collimation viewed at lung window settings shows multiple irregular ill-defined nodules. These nodules were distributed uniformly throughout the whole of both lungs in a patient whose occupation involved regular exposure to large quantities of fresh mushrooms. The lesions have persisted unchanged for over two years.

REFERENCES

interstitial lung disease r a t h e r t h a n metastases. In this case, o n l y close q u e s t i o n i n g b y the r a d i o l o g i s t revealed the relevant o c c u p a t i o n a l h i s t o r y a n d saved the p a t i e n t unnecessary c h e m o t h e r a p y . Cases :8 a n d 9 describe p a t i e n t s w h o d e v e l o p e d lymp h o m a ' w h i l s t o n surveillance for testicular t u m o u r s . Case 8 has been d e s c r i b e d p r e v i o u s l y (Leslie et al., 1986). H e r e the clue t h a t the m e d i a s t i n a l m a s s d i d n o t represent m e t a s t a t i c testicular t u m o u r is in its a n t e r i o r location. F a v o u r e d sites o f n o d a l disease in m e t a s t a t i c testicular t u m o u r are the p o s t e r ! o r m e d i a s t i n a l a n d

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MIMICS OF METASTASES FROM TESTICULAR TUMOURS Hendry, WF, Goldstraw, P & Peckham, MJ (1985). Excision of residual masses after chemotherapy for metastases from non-seminomatous germ cell tumours of the testis. In Germ Cell Tumours1I, Jones, WG, Milford Ward, A & Anderson, CK (eds). Pergamon Press, Oxford, pp. 409 418. Hillerdal, G, Nou, E, Osterman, K & Schmekel, B (1984). Sarcoidosis: epidemiology and prognosis. American Review of Respiratory Disease, 130, 29-32. Husband, JE & Bellamy, EA (1985). Unusual thoracoabdominal sites of metastases in testicular tumors. American Journalof Roentgenology, 145, 1165-1171. Husband, JE, Macdonald, JS & Peckham, MJ (1981). Computed tomography in testieular disease: a review. Journal of the Royal Society of Medicine, 74, 441-447. Kissin, CM, Husband, JE, Nicholas, D & Eversman W (1987). Benign thymic enlargement in adults after chemotherapy: CT demonstration. Radiology, 163, 67-70. Leslie, MD, Brada, M & Peckham, MJ (1986). Hodgkin's disease during surveillance of Stage 1 testicular teratoma. The British Journal of Radiology, 59, 1230-1231.

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