Between June 2004 and June 2006, 328 men consented, were examined by ultrasound and included in the data analysis. Of these, 169 were cases, 58 were relatives, and 101 were controls (). Forty-eight TGCT cases had a relative who participated in the study (26 (54.2%) brothers, 7 (14.5%) fathers, 13 (27.1%) sons, 1 (2.1%) maternal uncle and 1 (2.1%) nephew). For 10 relatives, there was no matching case available for analysis. The reasons were: in four relatives, the case had bilateral disease and therefore did not have testes available for ultrasound; in two relatives, the case was deceased; and in four relatives, the case consented to the study but failed to attend the research clinic.
A total of 493 testes in 328 men were examined by ultrasound. Of 169 cases, 162 had only one testis available for ultrasound examination. Four cases had bilateral disease and had undergone a standard total orchidectomy for the first tumour. In two of these cases, the second tumour was diagnosed as CIS at biopsy and both patients were treated without contralateral orchidectomies; ultrasound was performed on the remaining testes. The other two patients with bilateral disease had a contralateral partial orchidectomy and the remaining testicular tissue was examined by ultrasound. Seven cases did not have orchidectomies (five with extragonadal germ cell tumours without clear gonadal primaries and two patients treated for metastatic disease without orchidectomy), both testes were examined by ultrasound in these seven cases. Of 58 relatives, one participant had a history of testicular torsion and orchidectomy; all other relatives had both testes available for analysis. No orchidectomies were reported in the 101 controls (). The mean age of the controls was significantly lower (42) than that of the cases (47) (P=0.0003, t-test) and approached significance with the unaffected relatives (45) (P=0.14, t-test); there was no age difference between the cases and their relatives (P=0.3, t-test).
A total of 173 tumours were reported in the 169 cases as four patients had a second tumour (two seminomas and two CIS). Tumour histology for the first tumour is given in . A total of 41 (24.0%) cases had a documented family history of TGCT. The mean age of diagnosis was 34 years for cases both with and without a family history (). The median time between TGCT diagnosis and research ultrasound was 12 years (range 1–32).
First tumour histology for index TGCT cases
Testicular microlithiasis (
1 microlith in any testis) was more frequent in cases than controls, 62/169 (36.7%) vs
18/101 (17.8%), odds ratio (OR) 3.0 (95% CI 1.6–5.6), age adjusted P
<0.0001. The frequency in unaffected male relatives (20/58, 34.5%) was also higher than that in controls (OR 2.5, 95% CI 1.2–5.4, age adjusted P
=0.02). The proportion of cases and relatives with TM was not significantly different. However, the number of testes available for study in the relative group is double that of the cases. Comparing the testis examined in cases with the same testis in the matched relative, 48 cases had assessable testis of which 18/48 (37.5%) had TM and 11/48 (22.9%) relatives matched testes had TM (P
For the 48 families with a case and a relative, 10 pairs were concordant for the presence of TM, 22 were concordant for the absence of TM and 16 were discordant (P=0.05 for independence) showing that TM diagnosis aggregates in families. To determine if the familial aggregation was likely to be due to shared environmental or shared genetic factors, we evaluated the proportion of brother pairs and other relative pairs in the concordant/discordant TM groups. Of the TM concordant series, 6 were brother pairs (60%); in the discordant set, 11 (69%) were brothers and in the no TM concordant set, 9 (41%) brothers (P=0.22 for equal distribution between brother and other relative pairs).
The frequency of TM in TGCT cases with a family history of TGCT compared with cases with no family history was 18/41 (43.9%) vs 44/128 (34.4%); age adjusted P=0.3. The frequency of TM in men with two or more relatives with TGCT than men with only one affected relative was 11/24 (45.8%) vs 9/34 (26.5%); age adjusted P=0.1 ().
Testicular microlithiasis detected per study group
The frequency of bilateral TM was not different between relatives and controls with TM (8/20 (40.0%) vs 8/18 (44.4%), P=0.8). The severity of TM was greater in cases and relatives than for controls. A total of 83/101 (82%) of controls had no TM, 12 (12%) had LTM and 6 (6%) had CTM. In comparison, 145/227 (64%) of cases and relatives combined had no TM, 39 (17%) had LTM and 43 (19%) had CTM (χ2=12.54, P trend=0.0004).
There was no difference in the distribution of histological types between TGCT cases with and without TM. In cases with TM, 46.7% were diagnosed with a seminoma and 53.2% with non-seminoma; in cases without TM, 44.3% were diagnosed with seminoma and 55.6% with non-seminoma.
Of the four patients with bilateral TGCT and an assessable testis, both patients with biopsy-proven CIS in the contralateral testis showed TM (one LTM and one scant TM). In the two patients who had undergone partial orchidectomy, one had LTM in the remaining portion of the testis and the second had no TM. Of the seven TGCT cases with two assessable testes, bilateral TM was documented in one case, who had a metastatic seminoma treated without orchidectomy (). In the five patients with extragonadal GCT treated without orchidectomies, four had unilateral LTM.
Two tumours were diagnosed in the course of the study. A brother of a TGCT-S case showed bilateral LTM and a lesion that was suspected to be a tumour on ultrasound. Orchidectomy revealed a classical seminoma. The second tumour was diagnosed in an index TGCT-S case. This patient was treated for metastatic disease without orchidectomy 15 years prior to the study and showed no TM on ultrasound but a calcified lesion in the left testis. Orchidectomy revealed a non-seminoma.