Testicular microlithiasis (TM) is a clinical syndrome characterized by multiple calcifications in the testes. The clinical significance of TM, especially the correlation between TM and tumor and male infertility, has attracted great attention from the medical community. Definition Testicular microcysticercosis was first reported in 1970 by Priebe et al. In 1987, Doherty et al. were the first to describe its sonographic features: “diffusely distributed fine, homogeneous, bright echoes in the testis”. Later, this description was further defined as “randomly distributed high echogenicity of 1 to 2 mm in diameter in the testis”. However, until now, although more detailed descriptions of imaging manifestations are available, a clear and unified definition of TM is still lacking due to the paucity of systematic understanding of TM. Etiology and pathogenesis The etiology of TM is still unclear. It is currently thought to be related to congenital abnormalities of testicular tissue. In addition, TM has been found to be associated with the following intra- and extra-testicular pathologies: male infertility, atrophic testis, testicular dysplasia, testicular tumors, testicular cysts, epididymal or spermatic cysts, testicular epididymitis, testicular or testicular adnexal torsion, testicular syringomyelia, varicocele, AIDS, neurofibromas, Klinefelter’s syndrome, Down’s syndrome, and male hypertension. There is no clear conclusion as to whether TM is a cause or a consequence of these diseases, or whether it is simply a coincidence. In terms of pathogenesis, it is generally believed that the formation of TM is mainly due to degenerative shedding of cells from the varicoceles, which is not completely phagocytosed by the podocytes, and the residual cellular debris collects in the varicoceles, where hydroxyapatite deposits cause calcium deposition and collagen fibrillar-like material accumulates and encapsulates to form microstones. suggested that the formation of microcalculi is divided into two stages: in the first stage, degenerated cells containing solid nuclei and vesicles are deposited in the varicose tubules to form calcium nuclei: in the second stage collagen fibrillar-like tissue encapsulates the calcium nuclei in layers. In contrast, the microlith formation process proposed by Nistal et al. begins with the aggregation of cellular debris in the varicose tubules to form nuclei, followed by the deposition of collagen fibrillar-like tissue around the nuclei and finally calcification. These two processes are inferred to be somewhat different, but both have at their core the formation of deposits of collagenous tissue and calcium salts encircling the detached varicose seminiferous epithelial cells. Epidemiology Most of the current studies on the epidemiology of TM are retrospective and vary due to inconsistent definitions of TM, inconsistent study populations, and differences in ultrasonographic techniques. Deng Chunhua et al. synthesized and analyzed the results of representative large-scale surveys and reported that the incidence of TM ranged from 0.6 to 20% , with a mean of 3.3%. According to foreign reports, the prevalence of TM ranged from 1.5 to 5.6% in the total population, 0.8 to 20.0% in men with low sperm function, and 0.6 to 4.1% in men with complaints of scrotal or testicular discomfort. Although the incidence of TM varies from study to study, there is a growing consensus that the incidence of TM is gradually increasing. Diagnosis There are no obvious clinical signs and symptoms of testicular microstolithiasis, and it is often detected incidentally during ultrasonography. Testicular microcoliths and testicular cancer TM is the only external sign of intra-tubular germ cell tumor (ITGCN). The detection rate of ITGCN by testicular biopsy is much greater in patients with TM than in non-TM patients. The prevalence of ITGCN in infertile male patients with TM has been reported to be approximately 20%, compared to 0.5% in non-TM patients. Therefore, TM has been suggested to be a syndrome of testicular hypoplasia associated with intra-tubular germ cell tumor (ITGCN). Meng Qingxin et al. reported in a comprehensive literature that the incidence of testicular tumors in TM patients ranged from 31% to 46%. it took approximately 6 months to 11 years for TM patients to develop testicular cancer after the diagnosis of TM, calculating a relative increase in risk of approximately 13.2-21.6-fold. Testicular microlithiasis and male infertility The relationship between TM and male infertility has been one of the key concerns of urologists and male surgeons. According to the literature, the incidence of male infertility in TM patients ranges from 17% to 23%, and the incidence of TM in male infertility patients is 1.3% to 3.1%. It is now believed that TM is associated with male infertility and its cause of infertility may mainly affect the quality of semen. among 180 male infertility patients with semen abnormalities, Aizenstein et al. found 5 cases (2.8%, 5/180) with TM, which revealed an early possible association between TM and semen quality abnormalities. thomas et al. reported that the infertility patients with TM had In semen quality, sperm motility and mobility were significantly weaker than those of non-TM patients, and sperm function was correlated with the degree of TM. A domestic study by Li Hongjun et al. on 52 cases of high-grade microcalculosis suggested revealing a certain adverse effect on semen quality. Liu Baoxing et al. reported that testicular volume, sperm density, vitality, viability and serum free testosterone levels were significantly lower in the TM group than in the normal group (P< 0.05), suggesting that TM significantly affects testicular function including spermatogenesis and testosterone secretion function. Regarding the cause of abnormal semen quality caused by TM, it is currently believed that testicular biopsies of infertility patients with TM showed atrophy of the varicocele and the presence of cellular debris in some of the varicocele. Degenerated varicocele affects sperm production, while atrophied varicocele, cellular debris and microliths impede sperm motility, which may contribute to its cause of male infertility. Treatment and follow-up For TM, there is no specific treatment strategy. Tamoxifen (20 mgtid) has been tried abroad for the treatment of infertility caused by TM, but the efficacy is not good. They believe that intracytoplasmic sperm injection technique (ICSI) is currently the best approach for infertility caused by TM. Given the association of TM with testicular cancer and male infertility, a series of follow-up programs should be developed once the disease is diagnosed. Follow-up methods include self-examination, regular physical examination by a urologist, scrotal ultrasound, serum tumor markers, computed tomography (CT) or MRI, testicular biopsy, etc. Regular monthly self-examination of the testes is the cornerstone of any follow-up program. Although it is doubtful whether self-examination is able to detect testicular cancer early, it reduces the delay in TM diagnosis. Ultrasonography is routinely used in selective patients. The use of serum tumor markers, computed tomography (CT) or MRI is not meaningful over-screening for most TM patients and is therefore not recommended. Testicular biopsy, selected in patients with TM and with risk factors for testicular cancer or ITGCN (e.g. bilateral, infertility, undescended testicular atrophy or with a history of contralateral testicular cancer). However, patients should be carefully selected because the biopsy itself is invasive and may cause a range of complications, and the vast majority of TM patients will not develop testicular cancer throughout their lives. It has been proposed abroad that all TM patients should be evaluated for risk factors for ITGCN / testicular cancer, including the presence of bilateral TM, infertility, cryptorchidism, testicular atrophy, or cancer of one testicle. If one or more of these risk factors are present and the patient is younger than 50 years of age, testicular biopsy is strongly recommended. If none of these risk factors are present, or if the patient is older than 50 years (despite the presence of risk factors), or if a pre-existing biopsy is negative, self-examination is the only follow-up recommendation for such patients. Conclusion Testicular microstomia has now become a major interdisciplinary medical topic involving urology, male, gynecology, reproductive medicine, pediatrics, radiology imaging and pathology.The diagnosis of TM relies mainly on ultrasonography. A correlation between TM and testicular cancer has been established and may lead to male infertility by altering semen quality. For TM patients with high risk factors for testicular cancer, testicular biopsy and close follow-up are recommended, while for general patients, only self-examination follow-up is required. There is a lack of definitive treatment for TM, so further exploration and research are warranted.