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Genitourinary Imaging |
1 From the Departments of Radiology (A.M.B., O.H., C.S.G., H.H.Y., L.E.H.), Epidemiology and Biostatistics (W.S., H.T.), and Urology (J.S.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021. From the 1999 RSNA scientific assembly. Received September 25, 2000; revision requested November 4; revision received December 20; accepted January 16, 2001. Address correspondence to A.M.B. (e-mail: bacha@mskcc.org).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Testicular sonograms obtained in 528 men were retrospectively reviewed to identify patients with US findings suggestive of microlithiasis, intratesticular masses, and intratesticular heterogeneous changes. The association of US findings with medical records and with histopathologic findings that were available in 95 patients was evaluated. Statistical analysis was performed to determine the relationship of testicular cancer, intratesticular mass, and microlithiasis.
RESULTS: Forty-eight (9%) of the 528 patients had microlithiasis; 13 of these (27%) had testicular cancers. Of the 480 patients without microlithiasis, 38 (8%) had testicular cancer. Ninety patients had an intratesticular mass, of whom 23 (26%) had microlithiasis. Forty-three (12 with microlithiasis) patients with a mass had testicular cancer, 43 (10 with microlithiasis) had benign findings or nontesticular malignant histopathologic findings, and four (one with microlithiasis) had no pathologic findings.
CONCLUSION: Intratesticular microlithiasis is highly associated with confirmed testicular cancer, as well as with US evidence of testicular mass.
Index terms: Testis, calculi, 847.8172 • Testis, neoplasms, 847.31, 847.32, 847.33 • Testis, US, 847.1298
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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In an autopsy series, Renshaw (2) found that the laminated calcifications may be seen in as many as 50% of cryptorchid testes, 40% of testes with germ cell tumors (specifically embryonal carcinomas) and regressed germ cell tumors, and 4% of otherwise normal testes. These calcifications may result from the accumulation of cellular debris in the seminiferous tubules, followed by the deposition of concentric rings of glycoprotein (3).
Testicular microlithiasis has been associated with Klinefelter syndrome, male pseudohermaphroditism, Down syndrome, subfertility, infertility, cryptorchism, hypogonadism, and pulmonary microlithiasis (4,5). Several authors (4,6–10) have also reported the association of testicular microlithiasis with testicular cancer. Testicular cancer has been reported (6) to be present in as many as 75% of patients with testicular microlithiasis. Many of the previous studies, however, were limited by technique and small patient populations. In one study (10), a mammographic technique was used in imaging the testes, and in another study (11), a sector scanner was used. We performed this study to determine the prevalence of testicular microlithiasis in patients who were referred for scrotal US at a large cancer referral center and to evaluate the association between microlithiasis and testicular cancer.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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18 years old) were obtained at our institution between October 1992 and February 1998. A total of 168 patients who underwent prior testicular surgery were excluded from the analysis. The remaining 528 patients underwent 635 scrotal US examinations and constitute the study group. Patients were aged 18–87 years (mean age, 45 years; median age, 41 years). Our institutional review board does not require its approval and patient informed consent for review of medical records. Scrotal US was performed (Acuson XP machine; Acuson, Mountain View, Calif) by using a L7-MHz linear-array transducer. Color Doppler US was performed at the discretion of the interpreting sonologist (A.M.B., L.E.H.). As a standard practice at our institution, US was performed by a sonographer, and one of two designated sonologists confirmed the findings. For this study, US findings were determined from the original US reports.
Three sonologists (A.M.B, O.H., C.S.G.) retrospectively reviewed the reports of the initial scrotal US examinations performed during the study period. Each of the three sonologists independently reviewed a subgroup of the reports. The patients were assigned to two groups on the basis of the presence of microlithiasis. Microlithiasis was defined as the presence of at least five pinpoint (<3-mm) hyperechoic foci in one field of view, without posterior shadowing (1) (Fig 1). No attempt was made to quantify the microlithiasis. Findings of an intratesticular mass and heterogeneous changes were also recorded. Heterogeneous changes were defined as a texture variation regardless of the size of the testis. If mass and heterogeneity were described in the same patient, the abnormality was categorized as a mass.
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At our institution, histopathologic reports may indicate the presence of microlithiasis, but the microlithiasis is not further classified according to the two subtypes described earlier. The pathologic reports do not routinely indicate the presence of microlithiasis; therefore, the diagnosis of microlithiasis is based solely on US findings. In cases in which patients had a mass but no histopathologic abnormalities, the benign or malignant nature of the US-depicted mass was determined by means of a clinical explanation. The patient with a normal testicular sonogram was classified as having no testicular cancer.
US findings were correlated with hospital pathologic findings and findings from the medical record database. The associations of intratesticular microlithiasis, confirmed testicular cancer, and intratesticular mass were assessed with a 
2 test or the Fisher exact test. The association of intratesticular microlithiasis and confirmed testicular cancer, by adjusting for testicular mass, was assessed with the Cochran-Mantel-Haenszel test. All statistical analyses were performed with SAS software (SAS Institute, Cary, NC). A P value of less than .05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients without Histopathologic Abnormalities
Histopathologic data were not available in 433 patients. Three hundred sixty-seven patients had a normal scrotal US finding. An intratesticular mass was present in 20 patients: two with and 18 without microlithiasis. Of those patients with a mass at US and no histopathologic correlation, six had a mass that was considered benign at US (see the following); three (one of whom had microlithiasis) had an extensive metastatic germ cell tumor, with the testicular abnormality thought to represent the primary cancer; three had testicular abnormalities that were resolved at follow-up; and four had testicular abnormalities that were thought to be due to lymphoma in two, leukemia in one, and multiple myeloma in one. In four patients, orchiectomy was recommended, but the patients (one of whom had microlithiasis) were lost to follow-up. Forty-six patients had heterogeneous changes.
Six patients had an intratesticular mass that was thought to be benign at US. One patient had a history of trauma, and the abnormality was most consistent with hematoma. In one patient, the abnormality was an echogenic peripheral lesion and was considered to be a scar. In one patient, the mass was believed to be characteristic of an epidermoid cyst. It was not proved, and no follow-up was available. In three patients, the abnormality was subcapsular and triangular and most consistent with an infarct.
Correlation of US and Histopathologic Findings and Medical Records
In our study population of 528 patients, 51 patients had testicular cancer (Table 2). Testicular cancer was present in 13 of 48 patients with intratesticular microlithiasis, compared with 38 of 480 patients without microlithiasis. Microlithiasis was present in 13 (25%) of the patients with testicular cancer. IGCN was present in 37 patients: eight (17%) of 48 patients with microlithiasis and 29 (6%) of 480 patients without microlithiasis, all of whom had testicular cancer.
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Correlation of Intratesticular Microlithiasis and Testicular Cancer
In the current study, there was a strong association between testicular cancer (yes vs uncertain vs no) and the presence of testicular microlithiasis (yes vs no) (P < .001, Fisher exact test) (Table 2). Microlithiasis was more than three times as frequent in patients with testicular cancer (25%) as in patients without testicular cancer (7%). There was also a strong correlation between testicular mass (yes vs no) and the presence of microlithiasis (P < .001, 2 test) (Table 2). The presence of microlithiasis was more than four times as frequent in patients with a testicular mass (25%) as in patients without a testicular mass (6%). When adjustment for testicular mass was made, there was no significant association between testicular cancer and the presence of testicular microlithiasis (P = .26, Cochran-Mantel-Haenszel test) (Table 4). In patients with a testicular mass, the prevalence of microlithiasis was nearly identical to that of patients with testicular cancer (28%), patients with unknown status (26%), and patients with no testicular cancer (23%). In patients without a testicular mass and with or without other US abnormalities, the prevalence of microlithiasis decreased in all three groups (13% in patients with testicular cancer, 11% in patients with unknown status, and 5% in patients with no testicular cancer).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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We found a 25% incidence of microlithiasis in patients with testicular neoplasm versus 7% in those without a primary testicular tumor. An association with cancer has been reported by a number of authors (4,6–10). Ikinger et al (10), using a mammographic technique, also found a higher incidence of microlithiasis in cancerous testes compared with that of benign testes. Microlithiasis was present in 32 (74%) of 43 testes with a tumor versus eight (16%) of 49 testes without a tumor. Comparison of our data with that of Ikinger et al was limited by differences in the sample size and the use of a mammographic rather than a US technique.
Backus et al (8) and Hobarth et al (11), respectively, reported that 17 (40%) of 42 and five (45%) of 11 patients with microlithiasis had associated intratesticular germ cell tumors. Janzen et al (7) and Patel et al (6), respectively, reported that two (18%) of 11 patients at US and three (75%) of four patients had associated testicular germ cell tumor in the presence of microlithiasis. Roberts and Loughran (12) reported that a patient with bilateral testicular seminomas was also found to have testicular microlithiasis at US.
To our knowledge, our series of 48 adult patients with microlithiasis detected at US is the largest series accumulated from one institution. In 1996, Miller et al (13) published a review article that compiled from the literature and from their institution 86 patients with testicular microlithiasis. Testicular cancer was present in 25 (29%) of 86 patients. That study included pediatric patients, and their patients were aged 10 months to 65 years (mean age, 22.3 years). Our study was limited to adults.
IGCN (referred to in the older literature as carcinoma in situ) is considered to be a precancerous lesion. In our study, all 36 patients with IGCN had cancer. There were 28 patients without microlithiasis and eight patients with microlithiasis. The prevalence of IGCN in the general population has been reported to be 0.3% (14). Except for spermatocytic seminomas, all types of testicular germ cell tumors are thought to be preceded by IGCN (15). After 7 years of observation, invasive growth was seen in 70% of men with IGCN. An association of IGCN with microlithiasis has also been described (8,9,16–18) in the literature.
Backus et al (8) reported that five patients with IGCN in their series of 42 patients had microlithiasis and that one patient also had a neoplasm. Parra et al (16) described a patient with a left testicular mass at US and microlithiasis in the right testis. The patient underwent left radical orchiectomy, and pathologic examination revealed a mixed germ cell tumor. Biopsy of the right testis revealed multiple intratubular calcific concretion, which correspond to the microlithiasis and multiple foci of IGCN.
Kragel et al (9) also reported a case of microlithiasis and IGCN. Berthelsen and Skaddebaek (17) performed routine biopsy of the contralateral testis in men undergoing radical orchiectomy for testicular cancer. They found that 13 (5.2%) of 250 biopsies revealed histologic evidence of IGCN. Skakkebaek et al (18) demonstrated that the IGCN in 50% of patients progresses to carcinoma in 5 years. On the basis of this finding, they recommend routine biopsy of the contralateral testis in all men undergoing radical orchiectomy for testicular cancer. Intratubular germ cell tumor has no specific US findings and is diagnosed at histopathologic examination.
The subsequent development of testicular neoplasm after US detection of testicular microlithiasis has been described. Frush et al (19) described findings in a 25-year-old man who underwent an initial US examination that demonstrated scattered microlithiasis in the left testis and no microlithiasis in the right testis. He returned 1 year 4 months later, and a left testicular mass was discovered. In the previously normal right testis, a few foci of microlithiasis were now scattered. The patient underwent left radical orchiectomy, and a germ cell tumor was diagnosed. Images acquired for staging revealed left paraortic adenopathy, which was a metastatic germ cell tumor. In 1995, McEniff et al (20) reported that, because of the risk of tumor development, they perform annual US in all patients with testicular microlithiasis. They described a case in which a malignant yolk sac tumor of the testis was discovered during a routine fourth annual US, performed in a pediatric patient who was followed up for testicular microlithiasis. Winter et al (21) reported the development of a testicular cancer in a 24-year-old patient 3 years after the documentation of testicular microlithiasis in that gonad.
Interestingly, Furness et al (22) described findings in 26 patients (age range, 6 months to 21 years; mean age, 12 years) with testicular microlithiasis. Follow-up of these patients demonstrated that at 1 month to 7 years (mean, 27.6 months) no testicular tumor had developed. As discussed by the authors, follow-up may have been too short. Bieger et al (4) described findings in a child with testicular microlithiasis who developed testicular cancer 6 years after the diagnosis was made.
We recognize some inherent limitations in our study. First, it was a retrospective study. In addition, only the US reports were reviewed, and therefore, the distribution and extent of the microlithiasis could not be included in the study. Testicular microlithiasis is usually symmetric and bilateral; however, considerable variation can be seen (8). Backus et al (8) did not demonstrate any correlation between the presence of tumor and the number or distribution of microlithiasis in 11 patients with a tumor. It is important to emphasize that we are a cancer referral center, and our study population may not be representative of those in the general population with microlithiasis.
Numerous authors have recommended follow-up scanning at frequent intervals and monitoring of serum tumor markers in patients with testicular microlithiasis (6–8,13,22,23). They believe that it should not be considered a benign finding. To our knowledge, there is no generally accepted protocol in dealing with these patients.
In conclusion, we found that intratesticular microlithiasis is highly associated with confirmed testicular cancer as well as with US evidence of a testicular mass. By controlling for testicular mass, testicular microlithiasis does not independently aid in the prediction of testicular cancer at the time of initial diagnosis. Therefore, on the basis of these findings, testicular microlithiasis does not appear to add independent diagnostic information for testicular cancer. Since, to our knowledge, a long-term, large-scale, prospective study has not yet been performed, we do not know the risk of cancer developing later in patients with microlithiasis in otherwise normal testes. Some follow-up is probably still appropriate for these patients.
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, A.M.B.; study concepts and design, A.M.B.; literature research, A.M.B.; clinical studies, A.M.B., O.H., C.S.G., L.E.H.; data acquisition, A.M.B., O.H., C.S.G., H.H.Y.; data analysis/interpretation, A.M.B., W.S., H.T., H.H.Y.; statistical analysis, A.M.B., H.H.Y., W.S., H.T.; manuscript preparation, A.M.B.; manuscript definition of intellectual content, editing, revision/review, and final version approval, all authors.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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