Testicular microlithiasis as a familial risk factor for testicular germ cell tumour

Abstract

Testicular microlithiasis (TM) is characterised by small intratesticular calcifications, which can be visualised by ultrasound. Men with testicular germ cell tumour (TGCT) have a higher frequency of TM than men without TGCT. To clarify the association between TGCT and TM and to investigate the relationship between TGCT susceptibility and TM, we recruited TGCT patients with and without family history of TGCT, unaffected male relatives and healthy male controls from the UK. Testicular ultrasound data were analysed from 328 men. Testicular microlithiasis was more frequent in TGCT cases than controls (36.7 vs 17.8%, age adjusted Po0.0001) and in unaffected male relatives than controls (34.5 vs 17.8%, age adjusted P ¼ 0.02). Testicular germ cell tumour case and matched relative pairs showed greater concordance for TM than would be expected by chance (P ¼ 0.05). We show that TM is present at a higher frequency in relatives of TGCT cases than expected by chance indicating that TM is a familial risk factor for TGCT. Although the familiality of TM could be due to shared exposures, it is likely that there exists a genetic susceptibility to TM that also predisposes to TGCT. We suggest that TM is an alternative manifestation of a TGCT susceptibility allele. (Forman et al, 1992;Westergaard et al, 1996;Heimdal et al, 1996a;Sonneveld et al, 1999;Hemminki and Li, 2004), a previously diagnosed germ cell tumour (Osterlind et al, 1991;Wanderas et al, 1997), a history of undescended testis (Brown et al, 1987;Swerdlow et al, 1997), infertility (Petersen et al, 1998;Moller and Skakkebaek, 1999;Jacobsen et al, 2001;Richiardi et al, 2004), atrophy (Harland et al, 1998), and gonadal dysgenesis (Verp and Simpson, 1987). In a proportion of cases (B2%), a first-degree family member is also affected with the disease (Forman et al, 1992). The relative risk to a brother of a TGCT case is 8 -10 (Forman et al, 1992;Heimdal et al, 1996b;Hemminki and Li, 2004), which is higher than for most other cancer types that rarely exceed four (Dong and Hemminki, 2001) and suggests that predisposition genes are important in this disease. However, despite intensive efforts, susceptibility genes are yet to be identified (Crockford et al, 2006). Testicular microlithiasis (TM), the presence of multiple small deposits of calcium within the testis, shows characteristic sonographic findings of multiple, intratesticular, nonshadowing echogenic foci. Since the original description of ultrasounddetected TM (Doherty et al, 1987), a number of studies have reported an association between TGCT and TM (Backus et al, 1994;Miller et al, 1996Miller et al, , 2006Cast et al, 2000;Bach et al, 2001;Bennett et al, 2001;Derogee et al, 2001;Middleton et al, 2002;Sakamoto et al, 2006). All the studies report ultrasound findings for men investigated for a suspect testicular pathology (infertility, hydrocele, varicocele or suspected tumour) and compare the rate of TM in men found to have TGCT with those that have other diagnoses, including normal testes. The studies have shown a hig...

Imaging of the scrotum: role of MRI

“…MRI is no doubt valuable for the study and characterisation of small, nonpalpable testicular lesions, as it provides the information required for preoperative planning. Although there is no consensus on the significance of testicular microlithiasis, the prevailing view is that it is a precancerous condition [14][15][16][17][18].…”

“…La RM è certamente metodica di ausilio nello studio delle piccole lesioni non palpabili del testicolo e nella loro caratterizzazione, potendo fornire dati utili all'urologo nella pianificazione preoperatoria. In letteratura si trovano opinioni discordanti sul significato della MT, tuttavia prevalgono le tesi che attribuiscono alla MT il ruolo di condizione precancerosa [14][15][16][17][18].…”

Prevalence of small testicular hyperechogenic foci in subgroups of 382 non‐vasectomized, azoospermic men: a retrospective cohort study

“…Similar to this study, Coffey et al . (2007) has classified THF according to: none, a limited, a scant, a moderate, or too numerous THF to count. Middleton et al .…”

“…Thus, a mixed germ cell tumor developed 64 months after the initial screening study (DeCastro et al ., 2008). Therefore, THF is suggested not to be an etiological factor in TGCN – but rather a marker or a familial risk factor increasing the risk of TGCN (Coffey et al ., 2007) particularly in men with other risk factors, for example cryptorchidism (Goede et al ., 2010). …”

“…Coffey et al . (2007) found THF aggregated in families, not only in men with testicular neoplasia but also in unaffected male relatives. On this background, they suggest a common genetic susceptibility to THF and testicular neoplasia rather than considering THF as etiological factor for neoplasia.…”