Clinical Oncology (1992) 4:89-95 © 1992 The Royal College of Radiologists
Clinical Oncology
Original Article The Association of G e r m Cell T u m o u r s of the Testis with Sarcoid-like Processes E. W. Leatham 2, R. Eeles 1, M. Sheppard 2, E. Moskovic 2, M. P. Williams 3, A. Horwich I and D. N. Mitchell 2 1The Royal Marsden Hospital, London and Surrey, 2The Royal Brompton and National Heart Hospital London and 3Freedom Fields Hospital, Plymouth, UK
Abstract. Sarcoid-type pulmonary lymphadenopathy associated with testicular cancer is a rare condition which has been previously reported in only 14 cases. Earlier case reports have failed to distinguish between generalized sarcoidosis as opposed to a local granulomatous reaction to tumour. We describe a further 8 cases of the association and provide strong supportive evidence for systemic sarcoidosis in 5 of our patients. In 3 of our patients with systemic sarcoidosis there was coexisting testicular cancer requiring additional treatment. We therefore advise caution in the interpretation of the clinical and histological findings in these patients, and recommend thorough investigation of all such cases.
Keywords: Germ cell tumour; Granuloma; Kveim test; Sarcoidosis; Teratoma; Testicular cancer
INTRODUCTION
When a patient with a testicular tumour develops para-aortic, hilar or mediastinal lymphadenopathy, the initial assumption made is that the lymphadenopathy is due to malignant disease. Sporadic case reports of 'sarcoidosis' or 'sarcoid-like reactions' occurring in association with testicular malignancy have emphasized the importance of making a histological diagnosis in such circumstances [1-10]. In many of the previously reported cases it has been difficult to conclude whether the association between testicular tumours and pulmonary or mediastinal non-caseating granulomas represents a local granulomatous reaction to tumour cells, a well recognized phenomenon which has been extensively reviewed by Brincker and others [11,12[ or whether there is genuine association between the malignancy and a more generalized or systemic sarcoidosis. We report a series of 9 patients with testicular neoplasia and associated sarcoid-like processes.
Since the distinction between sarcoidosis and a granulomatous cell reaction can be difficult to make on histological grounds alone, we provide as much evidence as possible to support or refute the diagnosis of systemic sarcoidosis.
METHODS We performed a search of index diagnoses of patients attending The Royal Marsden Hospital and The Brompton Hospital from 1976 to 1989. We identified all patients with the combined index diagnoses of 'testicular tumour' and 'sarcoidosis'. For each case, we studied the case records, reviewed all radiographs and CT scans with two radiologists, and reviewed all histology sections and Kveim results with a histopathologist. We also review and tabulate all cases of the association reported in the literature to date.
RESULTS From 1120 patients with germ cell tumours of the testis diagnosed between 1976 and 1989, we found 9 patients with a possible combined diagnosis of sarcoidosis and testicular turnout. We have divided them into three groups for ease of discussion. Patient 5 has been previously reported but is included here because further investigations and follow-up data are of interest. The radiological aspects of some of our cases have been reported elsewhere [13] as part of a case series of conditions which can mimic metastatic teratoma.
Group 1: Sarcoidosis Diagnosed Prior to Tumour Development Patient 1
Correspondence and offprint requests to: Dr R. Eeles, Academic Unit of Radiotherapy and Oncology, The Royal Marsden Hospital, Downs Road, Surrey SM2 5PT, UK.
A 39-year-old man had an undifferentiated malignant teratoma (MTU)/seminoma with positive
90 markers (defined as raised /3hCG >2 iu/1 and/or raised AFP >5 iu/1) at orchidectomy. Two years prior to this, the patient had been diagnosed as having systemic sarcoidosis with bilateral hilar lymphadenopathy on a chest radiograph with both lymph node and liver biopsies showing non-caseating granulomas. At the time of orchidectomy the patient's chest radiograph was normal, but an abdominal CT scan showed para-aortic lymphadenopathy. Histology of nodes taken at the time of para-aortic dissection showed non-caseating granulomas with no evidence of tumour. The patient's tumour markers fell to normal after orchidectomy. Five months later, he developed splenomegaly and supraclavicular lymphadenopathy, and his chest radiograph showed mediastinal abnormalities. A C T scan showed two peripheral pulmonary opacities anterior to the heart, there was also right para-aortic lymphadenopathy below the diaphragm. Tumour markers remained normal. The diagnosis of sarcoidosis was made on the basis of the previous history, splenomegaly and a raised serum calcium (corrected serum calcium of 3.16 mmol/1). Prednisolone (40 mg/day orally) reduced the size of the lymphadenopathy and the serum calcium normalized. A supraclavicular lymph node biopsy was then taken because of residual lymphadenopathy. Histology showed non-caseating granulomas only. However, a needle biopsy of one of the pulmonary deposits yielded undifferentiated tumour cells without any evidence of sarcoidosis. The patient was treated with chemotherapy for relapse of malignant teratoma. Follow-up CT scans showed resolution of the pulmonary deposits. The patient has remained well and in clinical remission 28 months from orchidectomy. A further index case was identified of a 26-year-old man who had an intermediate malignant teratoma (MTI) with positive markers at orchidectomy. Sarcoidosis had been diagnosed five years prior to this on the basis of bilateral hilar lyphadenopathy shown on a chest radiograph and a positive Kveim test. The chest radiograph and CT scans of his chest have remained normal to date and the case is not included in further discussion or analysis. Comment. Patient 1 suffered a relapse of malignant teratoma in association with an apparent relapse of systemic sarcoidosis. The cause of the relapse of the sarcoidosis remains speculative but one possible explanation is that the sarcoidosis was reactivated by the tumour cells. There is no obvious reason why relapse of sarcoidosis occurred in one patient and not in the other similar patient. One possibility is that sarcoidosis did not recur in the second patient because there was no relapse of malignant teratoma.
Group 2: Patients Who Had Sarcoid-like Reactions or Systemic Sarcoidosis at the time of Orchidectomy Patient 2
A 27-year-old man had an MTI with positive markers at orchidectomy. A preoperative chest radiograph
E.W. Leatham et al. showed pulmonary shadowing and a CT scan showed patches of ill-defined shadowing in both lung fields with mediastinal and hilar lymphadenopathy. Abdominal computed tomographic scanning showed a mass lying anterior to the inferior vena cava with no para-aortic lymphadenopathy. Two months after orchidectomy, o~-foetoprotein (AFP) levels remained high and there was further progression of the hilar lymphadenopathy on the chest radiograph. Fibre-optic bronchoscopy, transbronchial biopsy and bronchoalveolar lavage were normal. Pulmonary function tests were normal but a serum angiotensin converting enzyme (SACE) level was elevated at 67 nmol/ml/min (normal range 16-52) and a 24-hour urinary calcium excretion estimation was slightly elevated at 7.7 mmols/24 hours (normal range
Clinical Oncology
Original Article The Association of G e r m Cell T u m o u r s of the Testis with Sarcoid-like Processes E. W. Leatham 2, R. Eeles 1, M. Sheppard 2, E. Moskovic 2, M. P. Williams 3, A. Horwich I and D. N. Mitchell 2 1The Royal Marsden Hospital, London and Surrey, 2The Royal Brompton and National Heart Hospital London and 3Freedom Fields Hospital, Plymouth, UK
Abstract. Sarcoid-type pulmonary lymphadenopathy associated with testicular cancer is a rare condition which has been previously reported in only 14 cases. Earlier case reports have failed to distinguish between generalized sarcoidosis as opposed to a local granulomatous reaction to tumour. We describe a further 8 cases of the association and provide strong supportive evidence for systemic sarcoidosis in 5 of our patients. In 3 of our patients with systemic sarcoidosis there was coexisting testicular cancer requiring additional treatment. We therefore advise caution in the interpretation of the clinical and histological findings in these patients, and recommend thorough investigation of all such cases.
Keywords: Germ cell tumour; Granuloma; Kveim test; Sarcoidosis; Teratoma; Testicular cancer
INTRODUCTION
When a patient with a testicular tumour develops para-aortic, hilar or mediastinal lymphadenopathy, the initial assumption made is that the lymphadenopathy is due to malignant disease. Sporadic case reports of 'sarcoidosis' or 'sarcoid-like reactions' occurring in association with testicular malignancy have emphasized the importance of making a histological diagnosis in such circumstances [1-10]. In many of the previously reported cases it has been difficult to conclude whether the association between testicular tumours and pulmonary or mediastinal non-caseating granulomas represents a local granulomatous reaction to tumour cells, a well recognized phenomenon which has been extensively reviewed by Brincker and others [11,12[ or whether there is genuine association between the malignancy and a more generalized or systemic sarcoidosis. We report a series of 9 patients with testicular neoplasia and associated sarcoid-like processes.
Since the distinction between sarcoidosis and a granulomatous cell reaction can be difficult to make on histological grounds alone, we provide as much evidence as possible to support or refute the diagnosis of systemic sarcoidosis.
METHODS We performed a search of index diagnoses of patients attending The Royal Marsden Hospital and The Brompton Hospital from 1976 to 1989. We identified all patients with the combined index diagnoses of 'testicular tumour' and 'sarcoidosis'. For each case, we studied the case records, reviewed all radiographs and CT scans with two radiologists, and reviewed all histology sections and Kveim results with a histopathologist. We also review and tabulate all cases of the association reported in the literature to date.
RESULTS From 1120 patients with germ cell tumours of the testis diagnosed between 1976 and 1989, we found 9 patients with a possible combined diagnosis of sarcoidosis and testicular turnout. We have divided them into three groups for ease of discussion. Patient 5 has been previously reported but is included here because further investigations and follow-up data are of interest. The radiological aspects of some of our cases have been reported elsewhere [13] as part of a case series of conditions which can mimic metastatic teratoma.
Group 1: Sarcoidosis Diagnosed Prior to Tumour Development Patient 1
Correspondence and offprint requests to: Dr R. Eeles, Academic Unit of Radiotherapy and Oncology, The Royal Marsden Hospital, Downs Road, Surrey SM2 5PT, UK.
A 39-year-old man had an undifferentiated malignant teratoma (MTU)/seminoma with positive
90 markers (defined as raised /3hCG >2 iu/1 and/or raised AFP >5 iu/1) at orchidectomy. Two years prior to this, the patient had been diagnosed as having systemic sarcoidosis with bilateral hilar lymphadenopathy on a chest radiograph with both lymph node and liver biopsies showing non-caseating granulomas. At the time of orchidectomy the patient's chest radiograph was normal, but an abdominal CT scan showed para-aortic lymphadenopathy. Histology of nodes taken at the time of para-aortic dissection showed non-caseating granulomas with no evidence of tumour. The patient's tumour markers fell to normal after orchidectomy. Five months later, he developed splenomegaly and supraclavicular lymphadenopathy, and his chest radiograph showed mediastinal abnormalities. A C T scan showed two peripheral pulmonary opacities anterior to the heart, there was also right para-aortic lymphadenopathy below the diaphragm. Tumour markers remained normal. The diagnosis of sarcoidosis was made on the basis of the previous history, splenomegaly and a raised serum calcium (corrected serum calcium of 3.16 mmol/1). Prednisolone (40 mg/day orally) reduced the size of the lymphadenopathy and the serum calcium normalized. A supraclavicular lymph node biopsy was then taken because of residual lymphadenopathy. Histology showed non-caseating granulomas only. However, a needle biopsy of one of the pulmonary deposits yielded undifferentiated tumour cells without any evidence of sarcoidosis. The patient was treated with chemotherapy for relapse of malignant teratoma. Follow-up CT scans showed resolution of the pulmonary deposits. The patient has remained well and in clinical remission 28 months from orchidectomy. A further index case was identified of a 26-year-old man who had an intermediate malignant teratoma (MTI) with positive markers at orchidectomy. Sarcoidosis had been diagnosed five years prior to this on the basis of bilateral hilar lyphadenopathy shown on a chest radiograph and a positive Kveim test. The chest radiograph and CT scans of his chest have remained normal to date and the case is not included in further discussion or analysis. Comment. Patient 1 suffered a relapse of malignant teratoma in association with an apparent relapse of systemic sarcoidosis. The cause of the relapse of the sarcoidosis remains speculative but one possible explanation is that the sarcoidosis was reactivated by the tumour cells. There is no obvious reason why relapse of sarcoidosis occurred in one patient and not in the other similar patient. One possibility is that sarcoidosis did not recur in the second patient because there was no relapse of malignant teratoma.
Group 2: Patients Who Had Sarcoid-like Reactions or Systemic Sarcoidosis at the time of Orchidectomy Patient 2
A 27-year-old man had an MTI with positive markers at orchidectomy. A preoperative chest radiograph
E.W. Leatham et al. showed pulmonary shadowing and a CT scan showed patches of ill-defined shadowing in both lung fields with mediastinal and hilar lymphadenopathy. Abdominal computed tomographic scanning showed a mass lying anterior to the inferior vena cava with no para-aortic lymphadenopathy. Two months after orchidectomy, o~-foetoprotein (AFP) levels remained high and there was further progression of the hilar lymphadenopathy on the chest radiograph. Fibre-optic bronchoscopy, transbronchial biopsy and bronchoalveolar lavage were normal. Pulmonary function tests were normal but a serum angiotensin converting enzyme (SACE) level was elevated at 67 nmol/ml/min (normal range 16-52) and a 24-hour urinary calcium excretion estimation was slightly elevated at 7.7 mmols/24 hours (normal range
