Abstract
Background: Testicular microlithiasis is said to be characterized by calcific concretions within the seminiferous tubules. There have been reports suggesting a link between testicular microlithiasis and testicular dysfunction and tumors.
Methods: In this study, we assessed subjects with varicoceles detected by using testicular ultrasound, and evaluated the cases of testicular microlithiasis in terms of age, seminalysis findings, and endocrinological parameters (testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL)). The subjects comprised 224 patients with varicoceles diagnosed by using testicular ultrasound, who attended this institution as outpatients between January 1998 and August 2000.
Results: Testicular microlithiasis was detected in 15 out of 224 subjects (6.7%), bilateral in all cases. No significant differences were seen between the group with testicular microlithiasis and the group without testicular microlithiasis, in terms of age, seminalysis findings, and/or endocrinological parameters (testosterone, FSH, LH, prolactin). The incidence of testicular microlithiasis in outpatients undergoing testicular ultrasound varies between reports, but is of the order of 0.6–2.0%.
Conclusion: In this study, we found a high proportion of testicular microlithiasis at 6.7%, strongly suggesting a link with male infertility. (Reprod Med Biol 2002; 1: 75–79)
Keywords: male infertility, testicular microlithiasis, varicocele
INTRODUCTION
TESTICULAR MICROLITHIASIS IS a rare condition that accompanies a variety of clinical conditions, including male infertility. Characteristic of testicular microlithiasis on testicular ultrasound are multiple small punctate shadows with a high echo signal, diffusely scattered throughout the testicular parenchyma. Histologically, these findings are said to correspond to laminated calcium deposits within the seminiferous tubules.
Testicular microlithiasis is reported to be seen in association with such conditions as germ cell neoplasia, Klinefelter's syndrome, cryptorchidism and alveolar microlithiasis. 1 , 2 The incidence of testicular microlithiasis is reported to be particularly high in testicular tumors. 3 However, the clinical characteristics and etiological mechanisms of testicular microlithiasis have yet to be elucidated.
There have been a number of reports concerning the incidence of testicular microlithiasis in patients with male infertility, but almost none concerning the incidence in patients with varicoceles. In this study, we addressed this lack. Apart from determining the incidence of testicular microlithiasis in subjects with varicoceles, we divided our subjects into a group with testicular microlithiasis and a group without testicular microlithiasis, and compared the two groups in terms of age, seminalysis findings, and/or endocrinological parameters (testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL)).
MATERIALS AND METHODS
WE DETERMINED THE incidence of testicular microlithiasis in 224 subjects with varicoceles that were detected on a testicular ultrasound, who attended the Omori Hospital Reproduction Center, affiliated with the Toho University School of Medicine, between January 1998 and August 2000.
The ultrasound machine used was a Toshiba SSA‐380 A (Toshiba, Tokyo, Japan), with an electric linear type 8.0 MHz probe (Toshiba). Varicoceles were diagnosed on palpitation at rest and during the Valsalva maneuver, supine and standing positions, by using color Doppler ultrasonography, and by measurement of the scrotal surface temperature.
The diagnosis of testicular microlithiasis was made on testicular ultrasound if one or more high echo signal punctate shadows were seen per field of view. Less than five high echo signal punctate shadows per field of view was classified as limited testicular microlithiasis (LTM) (Fig. 1), whereas five or more high echo signal punctate shadows per field of view was classified as classic testicular microlithiasis (CTM; Fig. 2; Bennett et al. 4 ). The degree of microlithiasis in the left and right testes was compared, and the more extensive side was used for evaluation.
Figure 1.
A testicular ultrasound image of less than five calcifications field of view, which corresponds to limited testicular microlithiasis (LTM).
Figure 2.
A testicular ultrasound image of more than 100 calcifications per field of view (countless calcifications), which corresponds to classic testicular microlithiasis (CTM). Testicular microlithiasis is bilateral in this case.
Samples of sperm for seminal analysis were produced after at least 5 days abstinence, by masturbation in the semen collection rooms at this institution. The parameters tested included semen volume, sperm count, motility and morphology, and were determined in accordance with the WHO guidelines. 5
The endocrinological parameters measured were testosterone, FSH, LH and PRL. Measurements were performed at the Special reference laboratories, by using radioimmunoassay (RIA).
statview version 4.5 software (HULINKS, Tokyo, Japan) was used to conduct statistical analysis. The Mann–Whitney U ‐test was used to test the data. Subjects with varicoceles were assessed by using testicular ultrasound, and the cases of testicular microlithiasis were evaluated in terms of age, seminalysis findings (semen volume, sperm count, motility and morphology), and endocrinological parameters (testosterone, FSH, LH, PRL).
RESULTS
TESTICULAR MICROLITHIASIS WAS detected in 15 out of 224 subjects (6.7%) with varicoceles (Table 1). Testicular microlithiasis was bilateral in all subjects. There were four cases of LTM, with less than five calcifications per field of view, and 11 cases of CTM, with five or more calcifications per field of view.
Table 1.
Fifteen cases of testicular microlithiasis (testicular microlithiasis, seminalysis, endocrinological tests)†
| Name | Age (years) | TM (rt. testis) | TM (lt. testis) | Volume (mL) | Count (10 × 6/mL) | Motility (%) | Morphology | Testosterone (ng/dL) | FSH (mIU/mL) | LH (mIU/mL) | PRL (ng/mL) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| KT | 34 | 15 | 10 | 8.5 | 85 | 60 | 95 | 603 | 4.6 | 3.4 | 12 |
| HK | 36 | 4 | 4 | 2.2 | 18 | 33 | 56 | 560 | 9 | 4.2 | 7.2 |
| MS | 38 | 6 | 4 | 2 | 89 | 64 | 63 | 375 | 8.7 | 2.8 | 9.5 |
| NM | 46 | 100 | 100 | 1.5 | 87 | 3.5 | 90 | 522 | 10 | 5.2 | 10 |
| SK | 36 | 12 | 3 | 6 | 43 | 8 | 89 | 353 | 6.8 | 3 | 14.4 |
| OT | 28 | 100 | 100 | 2.4 | 8 | 35 | 80 | 284 | 10 | 2.8 | 1.9 |
| HM | 30 | 2 | 2 | 4.4 | 79 | 40 | 90 | 444 | 3.1 | 4 | 2.9 |
| IK | 37 | 100 | 100 | 3 | 70 | 35 | 75 | 346 | 7.7 | 3 | 2.1 |
| MM | 34 | 4 | 5 | 0.8 | 0.94 | 5 | 21 | 521 | 2.5 | 3.1 | 7.2 |
| MT | 38 | 5 | 2 | 1.9 | 95 | 7 | 71 | 514 | 27 | 8.5 | 3.6 |
| UT | 34 | 100 | 100 | 2.4 | 18 | 40 | 80 | 626 | 14 | 6.9 | 6.4 |
| IN | 34 | 3 | 1 | 3.4 | 67 | 40 | 51 | 196 | 7.3 | 3.1 | 33.1 |
| OK | 31 | 5 | 3 | 3.2 | 66 | 35 | 72 | 672 | 5.1 | 5.3 | 19.4 |
| YE | 36 | 100 | 100 | 4.9 | 47 | 45 | 95 | 470 | 17.4 | 6.5 | 18 |
| IJ | 28 | 4 | 4 | 7.5 | 4 | 40 | 85 | 359 | 13.5 | 5 | 16.1 |
Count, sperm count; FSH, follicle stimulating hormone; LH, luteinizing hormone; lt., left; PRL, prolactin; rt., right; TM, testicular microlithiasis on one ultrasonographic image; Volume, sperm volume; †Shows the degree of testicular microlithiasis and the results of seminalysis and endocrinological testing in the 15 cases of testicular microlithiasis out of 224 subjects with varicoceles.
Of the 15 subjects with testicular microlithiasis, six underwent high ligation of the left testicular vein, and left testicular biopsy. Calcification was confirmed histologically in only one subject (Fig. 3), but could not be detected in the remaining five subjects.
Figure 3.
A histological specimen of testicular microlithiasis (H&E stain, original magnification ×400).
The group with testicular microlithiasis and the group without testicular microlithiasis were compared for age by using the Mann–Whitney U‐test, but no significant difference was detected (Table 2).
Table 2.
Comparison of the group with testicular microlithiasis (15 subjects) and the group without (209 subjects)
| P | ||
|---|---|---|
| Age | 0.76 | |
| Sperm function | Sperm volume | 0.75 |
| Sperm count | 0.09 | |
| Motility | 0.59 | |
| Morphology | 0.94 | |
| Hormone analysis | Testosterone | 0.94 |
| Follicle stimulating hormone | 0.21 | |
| Luteinizing hormone | 0.11 | |
| Prolactin | 0.80 |
Mann–Whitney's U‐test was used with a level of significance of P = 0.05.
Seminalysis results for the 15 subjects with testicular microlithiasis are shown in Table 1. The group with testicular microlithiasis and the group without testicular microlithiasis were compared for semen volume, sperm count, motility, and morphology by using the Mann–Whitney U‐test, but no significant differences were detected (Table 2).
The results of hormone estimations for the 15 subjects with testicular microlithiasis are shown in Table 1. The baseline levels were 270–1070 ng/mL for testosterone, 2.9–8.2 mIU/mL for FSH, 1.8–5.2 mIU/mL for LH, and 1.5–9.7 ng/mL for PRL.
The group with testicular microlithiasis and the group without testicular microlithiasis were compared for testosterone, FSH, LH, and PRL levels by using the Mann–Whitney U‐test, but no significant differences were detected (Table 2).
DISCUSSION
THE CAUSE AND etiological mechanism for testicular microlithiasis are unclear. One theory suggests that, although degenerated cells within the seminiferous tubules normally undergo phagocytosis and excretion by Sertoli cells, for some reason they are not excreted, but accumulate within the seminiferous tubules. 6 Testicular microlithiasis is a rare condition, where calcifications develop within the seminiferous tubules, thought to be caused by secondary cell degeneration. The calcifications seen within the seminiferous tubules histologically and ultrasonographically are considered to be concentric‐laminated rings formed by the gradual deposition of glycoproteins and calcium. 2
Testicular microlithiasis is seen in association with a variety of conditions, including testicular maldescent, male infertility, Klinefelter's syndrome, pulmonary alveolar microlithiasis, and testicular neoplasia. The incidence of testicular microlithiasis is said to be particularly high in patients with germ cell tumors and seminomas. Renshaw reported finding testicular microlithiasis in 41 out of 82 (50%) patients with germ cell tumors. 7
We surveyed the literature concerning testicular microlithiasis. The incidence of testicular microlithiasis varies in subjects undergoing testicular ultrasound as outpatients, with reports of incidences of 0.6, 8 0.68, 9 0.8 10 and 2%. 11 Reported incidences of testicular microlithiasis in patients with male infertility are 0.9, 12 1.4 13 and 6.7%, 14 thus showing higher incidences in this population. Maeda et al. reported seven cases of testicular microlithiasis out of 200 testicular specimens (56 orchidectomy specimens, 144 testicular biopsy specimens) examined histologically; an incidence of 3.5%. 15 Of the seven cases of testicular microlithiasis, germ cell tumors were also present in four specimens (57.1%). Testicular microlithiasis was detected in three out of 122 testicular biopsy specimens (2.5%) from patients with male infertility.
In the present study, we performed a left testicular biopsy on six of the 15 subjects with testicular microlithiasis, but testicular microlithiasis could be confirmed in only one case. This mismatch between the ultrasonographical and histological findings is thought to be because of the fact that, although the testes can be examined completely using ultrasound, tissue is only taken from one part of the testicle in a biopsy.
At present, there are no clear standards for the diagnosis, degree, or classification of testicular microlithiasis. Backus et al. defined more than five calcifications per field of view on testicular ultrasound as testicular microlithiasis. 1 Bennett et al. classify five or more calcifications per field of view on testicular ultrasound as CTM, and less than five calcifications per field of view on testicular ultrasound as LTM. 4 They reported 39 cases of CTM and 65 of LTM out of 104 cases of testicular microlithiasis. The cases of CTM are at high risk to develop testicular tumors. Even cases of less than five calcifications per field of view, not included in the definition of testicular microlithiasis by Backus et al., 1 do suggest a risk of progression to malignancy. Our 15 cases of testicular microlithiasis consisted of 11 cases of CTM and four of LTM. No obvious conclusions can be made because of the small number of cases used, but our results, which indicate more CTM and less LTM in subjects with varicoceles, contradict those from the findings of Bennett et al. 4
Thomas et al. performed a testicular ultrasound on 159 male infertility patients, and found testicular microlithiasis in 10 (6.2%) subjects. 14 Of these, five (3.1%) met the criteria of Backus et al. (more than five calcifications per field of view on testicular ultrasound), and the remaining five cases were described as ‘a minor degree of calcification’. They further reported that varicoceles were present in 58 out of 159 subjects with male infertility (36.5%), and in six out of 10 subjects with testicular microlithiasis (60%).
The present study was limited to subjects with varicoceles, and testicular microlithiasis was detected in 15 out of 224 (6.7%) patients. This incidence is higher than those seen in other studies, where testicular ultrasound was performed on subjects with male infertility. Varicoceles were also present in association with testicular microlithiasis in a relatively high incidence in the study by Thomas et al., 14 indicating some sort of relationship between the two conditions, although the reason for this is unclear. In the subjects with varicoceles in the present study, we compared the group with testicular microlithiasis and the group without testicular microlithiasis in terms of age, seminalysis parameters (semen volume, sperm count, motility and morphology), and endocrinological parameters (testosterone, FSH, LH, PRL), but no significant differences were seen. No clear effect on seminalysis or endocrinological parameters from testicular microlithiasis was apparent in our study.
Testicular microlithiasis is, however, said to possess significant premalignant potential. Ganem et al. 11 suggest that, at the very least, patients with testicular microlithiasis should be followed up with testicular ultrasound one to two times per year, as well as with physical examination and measurement of tumor markers.
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