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1 Departments of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York
Ave., New York, NY 10021.
2 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer
Center, New York, NY 10021.
3 Present address: Women's Diagnostic and Wellness Center, Nyack Hospital, 160
N. Midland Ave., Nyack, NY 10960.
4 Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY
10021.
Received June 7, 2002;
accepted after revision July 26, 2002.
Address correspondence to A. M. Bach.
Abstract
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MATERIALS AND METHODS. Retrospective review of a radiology database revealed 156 men who had undergone testicular sonography and orchiectomy for testicular cancer. Sonographic abnormalities were correlated with medical records and histopathology. Statistical significance was assessed using Fisher's exact test.
RESULTS. Twenty-three (15%) of 156 patients with prior orchiectomy for testicular cancer had microlithiasis, and 133 (85%) did not have microlithiasis. Four of 23 patients with microlithiasis had masses, and eight had heterogeneous changes. Sonograms of 133 patients without microlithiasis revealed masses in seven and heterogeneous changes in 15 patients. Five patients with microlithiasis and six without microlithiasis underwent a second orchiectomy. Contralateral testicular cancer was confirmed in five (22%) of 23 patients with microlithiasis versus three (2%) of 133 men without microlithiasis. Microlithiasis was present in five (63%) of eight patients with bilateral testicular cancer, and microlithiasis was highly associated with confirmed bilateral testicular cancer (5/23 vs 3/133, odds ratio [OR] = 12.0, p = 0.002). Among the 34 patients who had either testicular masses or heterogeneous changes, microlithiasis had an OR of 4.5 (p = 0.10).
CONCLUSION. In our study, contralateral testicular cancer was significantly associated with intratesticular microlithiasis. Nevertheless, there was not sufficient evidence that intratesticular microlithiasis adds independent diagnostic information for bilateral testicular cancer in the absence of a mass or heterogeneous changes.
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We performed this study in a large cancer referral center to evaluate the association between microlithiasis and contralateral testicular cancer.
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18 years)
were obtained between October 1992 and February 1998. The 156 adult men who
had undergone orchiectomy for histopathologically confirmed testicular cancer
and scrotal sonography after orchiectomy constituted our study population.
Every patient in the study population had a prior orchiectomy for testicular
cancer and had one remaining testis. Patient ages ranged from 19 to 76 years
(mean, 37 years; median, 36 years). Scrotal sonography was ordered by the attending clinician for accepted clinical indications, and sonography was a component of the patient care. Sonography was performed with an Acuson XP using a L7-MHz linear array transducer (Acuson; Mountain View, CA). Color Doppler sonography was used at the discretion of the interpreting sonologist. As the standard practice at our institution, sonograms were obtained by a sonographer, and one of two dedicated radiologists confirmed the findings. For this study, the sonographic findings were determined from the original sonography reports.
Two radiologists retrospectively reviewed the dictated reports and classified the intratesticular abnormalities of the solitary testis as microlithiasis, mass, or heterogeneous changes. The reports were reviewed by one of two radiologists. The presence of microlithiasis is always mentioned in the reports at our institution. Microlithiasis was defined as the presence of at least five pinpoint (<3-mm) hyperechoic foci in one field of view without posterior shadowing [15]. No attempt was made to quantify the microlithiasis. Heterogeneous changes were defined as texture variation, regardless of the size of the testis, with no mass. If a mass and heterogeneity were described in the same patient, then the abnormality was placed into the category of a mass.
The surgical pathology database and medical records were reviewed for every patient. The histopathologic findings of the initial orchiectomy and, if applicable, subsequent orchiectomy were tabulated: benign versus malignant and the type of malignancy were indicated. Diagnosis of testicular cancer was classified into seminoma and nonseminomatous germ cell tumor. The mixed tumors that included seminoma as part of the histologic findings were placed in the nonseminomatous germ cell tumor category.
The patients were divided into two groups on the basis of the presence or absence of microlithiasis in the solitary testis. On the basis of the sonographic findings, each of these two groups was further divided into three subgroups: intratesticular mass, heterogeneous changes, and normal findings. If the patient had only microlithiasis and no other findings, they were placed into the normal category. Sonographic findings were correlated with medical record database and histopathology when available.
Statistical analysis was performed using Fisher's exact test to determine the association between intratesticular microlithiasis, intratesticular mass, heterogeneous changes, and contralateral testicular cancer. The proportion of repeated sonograms during the study period between patients who did or did not have a second testicular cancer was compared using the chi-square test. The distribution of age and the time interval from the date of prior pathology to the first sonogram at our institution in these two groups were studied using a t test or Wilcoxon's rank sum test, respectively. All statistical analyses were performed with SAS software (Cary, NC). A p value of less than 0.05 was considered to be statistically significant.
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Seven of 133 patients without microlithiasis had masses (Fig. 2), and 15 patients had heterogeneous changes (Fig. 3). Six patients underwent orchiectomy because of masses (n = 5) or heterogeneous changes (n = 1). Three of these patients, all of whom had masses, had a second testicular neoplasm. Two additional patients with sonographically evident intratesticular masses and no microlithiasis did not have surgery. One patient had stable findings on sonography for 3 years, and sonographic findings were considered consistent with an infarct. The other patient with a peripheral 5-mm hypoechoic intratesticular mass refused surgery, and the mass has remained stable for 6 years.
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A second testicular carcinoma was found in the remaining testis of eight (5%) of 156 men with prior orchiectomy for testicular carcinoma, and five (63%) of the eight testicular carcinomas were in men with intratesticular microlithiasis. Sonographically evident intratesticular masses were present in seven (88%) of the eight patients with bilateral testicular cancer, and one patient had heterogeneous changes.
Histopathologic findings in the five patients with bilateral testicular cancer and microlithiasis included bilateral seminomas (n = 3), bilateral nonseminomatous germ cell tumor (n = 1), and initial nonseminomatous germ cell tumor with a seminoma in the opposite gonad (n = 1). Of the three patients without testicular microlithiasis who had bilateral testicular cancer, one patient had bilateral seminomas, and two patients had nonseminomatous germ cell tumor originally and subsequently developed seminoma in the contralateral testis. The histopathology reports did not mention microlithiasis.
Of the patient population studied, the presence of microlithiasis was highly associated with confirmed bilateral testicular cancer in five of 23 patients with microlithiasis versus three of 133 patients without microlithiasis (p = 0.002; OR = 12.0). Microlithiasis was also associated with sonographic evidence of heterogeneous changes (8/23 vs 15/133, p = 0.008) and marginally associated with sonographic evidence of a mass (4/23 vs 7/133, p = 0.06). As expected, the presence of intratesticular mass was an ultimate independent predictor for confirmed testicular cancer (7/11 vs 1/145, p < 0.00000001; OR = 252). When attention was restricted to patients who had masses or heterogeneous changes, microlithiasis was no longer significantly associated with testicular cancer (5/12 vs 3/22, p = 0.10; OR = 4.5) (Table 1).
Of the eight patients who had bilateral testicular cancer, one sonogram had been obtained in six, and two sonograms had been obtained in two patients (25%) before the current surgery. In 148 patients who had prior testicular cancer alone, one sonogram had been obtained in 117, and two sonograms had been obtained in 31 patients (21%) during the study period. The proportion of patients who had repeated sonograms was not different (p = 0.68, chi-square test) in these two groups. The median time from prior pathologic date to the first sonogram at our institution was 20.4 months (range, 3-138 months) and 36.5 months (range, 0.3-348 months) in patients who had bilateral or unilateral testicular cancer, respectively. The distributions of the time intervals were not significantly different (p = 0.36) between these two groups.
Review of the medical records revealed that two of the patients had synchronous testicular cancers (the second cancer was suspected because of an abnormal finding seen on the sonogram before the initial orchiectomy), and the remainder of the cancers were metachronous. The time between the two surgeries for the patients with bilateral testicular cancer was 5, 6, 9, 15, 34, 75, 88, and 138 months (median, 24.5 months; mean, 46.3 months). In those without microlithiasis, the time between the two surgeries was 5, 9, and 88 months. In the group with microlithiasis and bilateral testicular cancer, the time between the two surgeries was 6, 15, 34, 75, and 138 months.
The patients who had bilateral testicular cancer were relatively younger than those who had prior testicular cancer alone (p = 0.06). All eight patients who had a second testicular cancer were 40 years old or younger (mean, 33 years; range, 26-40 years). In 148 patients who did not have a second testicular cancer, one third were older than 40 years old (range, 1-76 years; mean, 37 years).
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Although bilateral testicular carcinoma was associated with microlithiasis, there was not sufficient evidence that microlithiasis added independent diagnostic information to the presence of a mass or heterogeneous change. Therefore, surgery should not be performed for microlithiasis alone in an otherwise normal-appearing testis. Most patients underwent the second orchiectomy for sonographically evident mass in the remaining testis. Although either mass or testicular heterogeneous changes may be suggestive of malignancy, testicular carcinoma more frequently presents as a mass. In a previous study of sonographic findings in men after orchiectomy for testicular carcinoma, 67% of testicular masses and 27% heterogeneous changes proved to be testicular carcinoma [14].
We did not have access to all the sonograms obtained before the initial orchiectomy. Many of those orchiectomies were performed at other institutions. We do not know if there was microlithiasis in the testis with the initial neoplasm or if microlithiasis was present in the opposite testis at that time.
Several authors have reported the association of testicular microlithiasis with testicular cancer [3,4,5,6,7,8,9,10,11]. The 15% incidence of microlithiasis in patients with testicular cancer found in our study is lower than that in previous reports that have shown microlithiasis in 18-75% of men with testicular cancer [3,4,5,6,7,8,9,10,11]. Ikinger et al. [9], using mammography, found microlithiasis in 32 (74%) of the 43 testes with tumor versus eight (16%) of 49 testes without tumor. Comparison of our data with that study is limited by differences in imaging techniques (mammography vs sonography) used to detect microlithiasis.
Discrepancies in the frequency of microlithiasis in men with testicular tumors may also be related to variation in patient population. In a prior study of 528 scrotal sonograms, we found a 25% incidence of microlithiasis in men with testicular cancer [5], similar to the 29% frequency reported by Miller et. al. [18] in a review of 86 patients with microlithiasis. Backus et al. [7] and Hobarth et al. [10] reported that from 40% (17/42) to 45% (5/11), respectively, of patients with microlithiasis had associated intratesticular germ cell tumors. Sonographic findings in two (18%) of 11 patients reported by Janzen et al. [6] and in three (75%) of four patients reported by Patel et al. [4] showed associated testicular germ cell tumor in the presence of microlithiasis.
We recognize some inherent limitations in our study. It is a retrospective study, and only the sonography reports were reviewed. This study represents our experience in patients who have been referred for testicular sonography after orchiectomy, and we realize that findings at a tertiary care cancer center may not be representative of the general population. Also, the true frequency of bilateral testicular cancer may be underestimated in this study because the time interval between the initial orchiectomy and sonography may have been too short. Another limitation of this study is that testicular microlithiasis may be more readily identified with our newer technology and improved transducer quality. This however should be a finding that affects both groups and should not have a skewed effect on the statistical analysis.
Yearly screening with scrotal sonography of patients between 20 and 50 years old with microlithiasis has been suggested [19]. Others recommend, for all patients, an initial CT of the chest and abdomen when the microlithiasis is discovered and then follow-up with periodic (every 6-12 months) scrotal sonography [18]. All our patients who had bilateral testicular cancer were 40 years or younger. Therefore, we believe that clinical and sonographic follow-ups are even more important in that subgroup of patients who are young (< 40 years old) and have current sonographic findings of microlithiasis and have had prior orchiectomy for testicular cancer. In conclusion, we found an increased incidence of bilateral testicular cancer in patients with intratesticular microlithiasis.
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