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Testicular Microlithiasis: Prospective Analysis of Prevalence and Associated Tumor¹

¹ From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110. From the 2000 RSNA scientific assembly. Received June 29, 2001; revision requested July 24; revision received December 28; accepted January 29, 2002. Address correspondence to W.D.M.

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To evaluate testicular microlithiasis (TM) prospectively with modern state-of-the-art equipment.

MATERIALS AND METHODS: Information concerning indication for examination, presence and degree of TM, presence of testicular tumor, and patient age was prospectively recorded for all patients referred for scrotal ultrasonography between 1996 and 1999. High-frequency linear transducers (7.5 MHz or higher) were used. TM was divided into classic (CTM) and limited (LTM) on the basis of the presence of five or more microliths on one or more images of the testes. Fisher exact tests were used for determining significant differences in proportions.

RESULTS: Data in 1,079 patients were analyzed. The overall prevalence of TM was 18.1% (195 of 1,079). Forty (3.7%) patients had CTM, and 155 (14.4%) had LTM; 15 (1.4%) had tumors visible at US. Tumors were present in three (8%) of 40 patients with CTM (seminoma in two, embryonal cell in one), nine (5.8%) of 155 with LTM (seminoma in six, mixed germ cell in one, Leydig cell in two), and three (0.3%) of 884 with no TM (seminoma in two, other in one). There was no difference between CTM and LTM (P = .72) in the rate of coexisting tumor. There was a significant difference between no TM and CTM or LTM (P .001) in the rate of coexisting tumor. Eighty percent (12 of 15) of patients with tumor at presentation had CTM or LTM.

CONCLUSION: Approximately one of 27 patients had CTM, and one of seven had LTM. Although a majority of patients with testicular tumors had coexistent TM, more than 90% with TM (both CTM and LTM) did not have tumor at presentation.

© RSNA, 2002

Index terms: Scrotum, calculi, 84.81 • Scrotum, US, 84.81 • Testis, calculi, 84.81 • Testis, US, 84.81

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Testicular microliths consist of calcified cores surrounded by concentric layers of collagen fibers located in the lumen of the seminiferous tubules (1). At pathologic examination, they are less than 1 mm in diameter (2). Testicular microlithiasis (TM) is a condition that has traditionally been considered rare, with authors of a recent article (3) describing a prevalence of 0.68%. It is also widely believed that TM is strongly associated with testicular tumors. Authors of earlier articles (4,5) estimated that 30%–40% of patients with TM had testicular tumors. More recent data suggest that the relative risk of testicular tumor in the setting of TM is 21.6-fold, and on the basis of this information, ultrasonographic (US) surveillance for tumor has been described as mandatory (3).

Although data about TM are now fairly abundant, the study results used to determine prevalence and the association with testicular tumors have been retrospective and have, therefore, suffered from the unavoidable biases inherent in retrospective studies. The purpose of our study was to evaluate TM prospectively with modern state-of-the-art equipment.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
All patients referred for scrotal US at our institution between June 1996 and October 1999 were included in the study. Data were accumulated in a prospective manner and included patient age, indication for the examination, presence of TM, and presence of testicular tumor. The study was approved by our human studies committee and included waiver of informed consent. The sonographers performing the examinations and the radiologists interpreting the examination results were aware of the study and were educated about the appearance of TM. All patients underwent scanning by a technologist, and more than 90% underwent scanning by the interpreting radiologist. Eighteen radiologists participated in data collection. All were board certified, with 4–18 years of experience in interpreting scrotal US images.

The radiologist completed a short data sheet immediately after the examination was completed. If TM was present, it was categorized as classic testicular microlithiasis (CTM) if there was at least one image that showed five or more microliths in either or both testes. All patients who had at least one microlith and did not meet criteria for CTM were considered to have limited testicular microlithiasis (LTM). Typical examples of CTM and LTM are shown in Figure 1. If a patient underwent scanning more than once during this period, the results of only the first examination were included in the study.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. (a) Longitudinal US image of the testis shows CTM. More than five microliths (echogenic dots) are scattered diffusely throughout the testis. (b) Longitudinal US image of the testis in a different patient shows LTM. Two microliths (arrows) are in the posterior aspect of the testis.

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. (a) Longitudinal US image of the testis shows CTM. More than five microliths (echogenic dots) are scattered diffusely throughout the testis. (b) Longitudinal US image of the testis in a different patient shows LTM. Two microliths (arrows) are in the posterior aspect of the testis.

	RESULTS

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One thousand seventy-nine patients underwent scanning. Patient age was 15–92 years (mean, 44.4 years). TM was detected in 18.1% (195) of 1,079 patients; 3.7% (40) of 1,079 had CTM, and 14.4% (155) had LTM. The age of patients with CTM was 22–72 years (mean, 41.5 years), and the age of patients with LTM was 17–92 years (mean, 46.1 years). The age of patients without TM was 15–89 years (mean, 44.3 years).

The reason for the examination was pain in 48.1% (519) of 1,079 patients, palpable mass in 24.9% (269), scrotal enlargement in 20.4% (220), infertility in 4.8% (52), history of tumor in 2.9% (31), and various other reasons in 11.2% (121). Several patients had more than one reason for the examination so that the numbers total more than 1,079.

Fourteen patients had pathologically documented testicular tumors. All were identified at the time of initial US. One 79-year-old patient had an intratesticular lesion that was consistent with a tumor clinically and at US but never had pathologic confirmation. He died after US without follow-up. The prevalence of testicular tumor in this patient population was 1.4% (15) of 1,079. Eighty percent (12) of 15 patients who had tumor at presentation had CTM or LTM.

Eight percent (three) of 40 patients with CTM had tumors (seminoma in two, embryonal cell in one) (Fig 2). Of patients with LTM, 5.8% (nine) of 155 had tumors (seminoma in six, mixed germ cell in one, Leydig cell in two) (Fig 3). Of patients without TM, 0.3% (three) of 884 had tumors (seminoma in two, tumor not evaluated pathologically in one). When CTM was compared with LTM (three of 40 vs nine of 155), there was no difference in the rate of coexisting tumor (P = .72). When CTM was compared with no TM (three of 40 vs three of 884), there was a significant difference in the rate of coexisting tumor (P = .001). When LTM was compared with no TM (nine of 155 vs three of 884), there was a significant difference in the rate of coexisting tumor (P < .001).

View larger version (149K): [in this window] [in a new window] [Download PPT slide]   Figure 2. CTM with associated tumor (T). Longitudinal US image shows a hypoechoic mass pathologically proved to be a seminoma. Multiple (more than five) microliths are scattered throughout the testicular parenchyma (upper left quarter of image).

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. LTM with associated tumor. (a) Longitudinal US image of the testis shows a hypoechoic mass pathologically proved to be a mixed germ cell tumor (T). A single microlith (arrow) is in the upper pole of the testis. (b) Longitudinal US image obtained through a different portion of the testis shows two additional microliths (arrows). No image showed five or more microliths.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. LTM with associated tumor. (a) Longitudinal US image of the testis shows a hypoechoic mass pathologically proved to be a mixed germ cell tumor (T). A single microlith (arrow) is in the upper pole of the testis. (b) Longitudinal US image obtained through a different portion of the testis shows two additional microliths (arrows). No image showed five or more microliths.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

Part of the incentive for investigating TM is the reported association with testicular tumor. By using mammographic techniques, Ikinger et al (10) found that 74% of patients with tumors had microcalcifications, whereas only 8% of testicular specimens with benign conditions had microcalcifications. Patel et al (11) reported tumors in three of the four cases they detected with US between 1984 and 1991. Hobarth et al (12) found tumors coexisting with TM in 44% (seven) of 16 cases. In a larger series, Backus et al (4) confirmed an association between tumors and TM detected with US. They found that 40% (17) of 42 cases of TM were associated with a coexistent tumor. In a subsequent review of the literature published in 1996, Miller et al (5) found that 30% (26 of 86) of cases were associated with tumor. This high association rate has prompted multiple authors (3,4,5,11–17) to recommend periodic US follow-up in patients with TM without detectable tumor.

The rationale for serial US surveillance has been supported by the results of several case reports in which the development of testicular tumors was documented in patients with previously identified uncomplicated TM (13–17). Authors of two of the case reports describe patients who had what appeared to be LTM (13,15), and the authors of another case report describe a case that barely met the criteria for CTM (16), yet all the patients developed testicular tumors. These alarming statistics, and the possibility that the arbitrary definition of CTM may exclude patients with LTM who are still at risk, stimulated our current analysis.

In our prospective study, only three (0.3%) of 884 patients without TM had testicular tumor. On the other hand, three (8%) of 40 patients with CTM had coexistent tumor. The significant difference in patients with and those without TM emphasizes that TM and tumors are linked in some way. However, it seems clear from our prospective data that the previously reported risk of 30%–40% that was based on retrospective data (4,5) actually represents a four- to fivefold overestimation of the risk of tumor in patients with CTM. Perhaps just as important is the fact that the previously published literature has excluded LTM from the analysis, yet our data show a 5.8% (nine of 155) rate of tumor coexisting with LTM. There was no statistically significant difference between CTM and LTM with respect to the rate of coexisting tumors.

We believe that the difference between our results and previous results is related primarily to study design. Retrospective studies of testicular scans are unlikely to miss testicular tumors. This is related to the fact that technologists performing testicular US are well trained to look for testicular tumors and to image tumors when they are present. Likewise, radiologists interpreting scans are well aware of the appearance and importance of testicular tumors and are likely to report tumors when they are identified. Therefore, retrospective reviews of US images, or word searches of US reports, will lead to identification of a majority of testicular tumors.

On the other hand, technologists performing testicular US have only recently been trained to recognize and look for TM. Because of this, it is possible to have cases of isolated TM (ie, TM without associated tumor) that have not been documented with images. In addition, radiologists have also only recently recognized and understood the implications for detecting isolated TM, so cases that are documented with images may not be reported. Thus, cases of isolated TM easily could be missed with word searches of reports and also with retrospective reviews of scans. The overall result is to identify nearly all cases of TM associated with tumors but to miss cases of isolated TM, and this difference leads to an overestimation of the rate of coexistent tumor in patients with TM.

In our study, everyone involved with performing the examinations and interpreting the results was aware of the study and actively participated in collecting the data at the time of the examination. Additionally, radiologists participated in performing scanning in a majority of patients. Therefore, it is much less likely that patients with TM were missed in this study than in studies performed in a less controlled retrospective manner.

Another factor that likely plays a role is the way that TM and tumors are detected. Tumors are most often detected by means of palpation and are then confirmed with US. The ability to palpate a tumor has not changed in the past 10 years. On the other hand, TM is detected only with US. Improvements in high-resolution transducers and signal-processing techniques have occurred steadily since the first reports of TM and have made detection of TM easier.

Our data indicate a higher prevalence of TM than that reported in most previous studies. Hobarth et al (18) reported a prevalence of 0.6% in a group of 1,710 scrotal US images collected prior to 1992. Although in this study TM was not quantitated as CTM or LTM, it is likely that all of the cases were CTM. We detected CTM in 3.7% (40) of 1,079 patients, which is approximately six times the rate previously reported. Interestingly, a recent analysis (3) prior to ours showed a prevalence of 0.7% among 4,819 patients. In this study, patients with TM or testicular tumors were identified retrospectively with a computerized word search. Since these patients underwent scanning during a similar time span and with equipment of similar quality as ours, the difference in results is almost certainly related to limitations in retrospective studies.

An inherent limitation of our study and of all previous studies of TM prevalence is related to the patient population. All of the patients in our study were referred for scrotal US because they were clinically suspected of having scrotal disease. This introduces a bias that undoubtedly exaggerates the prevalence of TM over what would be expected in a randomly selected group of men. This problem is illustrated in the results of a recent retrospective study (19) of TM that showed a prevalence of 9%. Although the indications for the scans were not reported, this study was performed at a tertiary cancer referral center, and it is likely that there was a bias toward cancer patients. In our study, 25% of the patients underwent scanning to evaluate a palpable mass, and 3% had a history of a tumor. We believe that our referrals for scrotal US reflect a broad spectrum of clinical indications that is probably similar to that which can be expected in most radiology practices. Since only patients with signs or symptoms of scrotal disease undergo scanning, the prevalence of TM in this group of patients is relevant.

The risk of testicular tumor could also be measured by means of following up a cohort of patients who have TM but present initially without a tumor. Although we did not perform long-term US follow-up in this investigation, we previously performed a longitudinal study in 72 patients with CTM or LTM (20). In this study, we detected no development of tumors during an average of 42 months of US follow-up. On the basis of these results, we suggested that annual physical examination and periodic self-examination may substitute for regular US follow-up in patients with isolated TM. Our current prospective results indicate that TM is less ominous than had been previously suspected, and they lend support to a less aggressive form of surveillance.

In conclusion, we believe that retrospective studies performed in the past have led to underestimation of the prevalence of TM and overestimation of the risk of coexisting tumor. We estimate that CTM will be detected in approximately one of every 27 patients and that LTM will be detected in approximately one of every seven patients referred for scrotal US. Although the risk of coexisting tumors is clearly increased in patients with CTM or LTM, it is estimated to be in the 5%–10% range rather than in the 30%–40% range, as previously reported.

	ACKNOWLEDGMENTS

 
We thank Charles Hildebolt, PhD, for statistical analysis and Shadi Sedaghi, BS, for data entry, organization, and analysis.

	FOOTNOTES

 
Abbreviations: CTM = classic TM, LTM = limited TM, TM = testicular microlithiasis

Author contributions: Guarantor of integrity of entire study, W.D.M.; study concepts, W.D.M., S.A.T.; study design, W.D.M.; literature research, W.D.M., S.A.T.; clinical studies, W.D.M., S.A.T.; data acquisition, W.D.M., S.A.T.; data analysis/interpretation, W.D.M., C.S.S.; statistical analysis, W.D.M., C.S.S.; manuscript preparation, W.D.M.; manuscript definition of intellectual content, W.D.M., S.A.T.; manuscript editing, revision/review, and final version approval, W.D.M., S.A.T., C.S.S.

	REFERENCES

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This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: 2242011137v1 224/2/425    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Middleton, W. D. Articles by Santillan, C. S. Search for Related Content PubMed PubMed Citation Articles by Middleton, W. D. Articles by Santillan, C. S.