Testicular Microlithiasis

Description

Testicular microlithiasis, the deposition of calcium phosphate microliths within the seminiferous tubules, has a population prevalence of 0.6 to 9% (Kim et al., 2003). Middleton et al. (2002) found that it was associated with a majority of primary testicular malignancies. Miller and Sidhu (2002) found that it was present in 1% of male idiopathic infertility cases.

Clinical Features

Coffey et al. (2007) analyzed the frequency of testicular microlithiasis (TM) in 169 patients with testicular germ cell tumor (TGCT; 273300), 58 relatives, and 101 controls, and found that TM was more frequent in cases than controls (age-adjusted p less than 0.0001) and in unaffected male relatives than controls (age-adjusted p = 0.02). TGCT cases and matched relative pairs showed greater concordance for TM than would be expected by chance alone (p = 0.05). Coffey et al. (2007) concluded that TM is a familial risk factor for TGCT and that it is likely that there exists a genetic susceptibility to TM that also predisposes to TGCT. They suggested that TM is an alternate manifestation of a TGCT susceptibility allele.

Korde et al. (2008) performed testicular ultrasound in 48 men with familial testicular cancer from 31 families with at least 2 cases of TGCT, and in 33 of their unaffected male relatives. Testicular microlithiasis (TM) was more frequent in the contralateral testicles of men with a history of TGCT than in unaffected men (48% vs 24%; p = 0.04). The association appeared stronger for men with 5 or more microliths than for those with less than 5 microliths. Testicular microlithiases were bilateral in 6 (87%) of 7 unaffected men in whom they were detected. Among affected men, TM was not associated with histology, age at diagnosis, or cancer treatment. Korde et al. (2008) noted that TM was more prevalent among unaffected family members in this study (24%) than previously described in the general population (0.6 to 9%), and that it appeared to cluster in certain families. The findings suggested both a familial predisposition to TM and an association between TM and TGCT.

Molecular Genetics

Because the SLC34A2 gene (604217), which is mutant in cases of pulmonary alveolar microlithiasis (265100), is expressed also in the testis, Corut et al. (2006) searched for mutations of this gene in subjects with testicular microlithiasis. In 2 of the 15 subjects studied, they identified 2 rare variants, 1 synonymous and the other noncoding, that they suggested may be associated with the condition. The authors noted that further studies were needed to determine whether these variants had any effect on expression of the gene or on its protein product.