Testicular Microlithiasis: Prevalence andAssociation with Primary TesticularNeoplasm

Howard T. Heller, MD,1 Matthew C. Oliff, MD,1 Peter M. Doubilet, MD, PhD,1 Michael P. O’Leary, MD,2

Carol B. Benson, MD1

1 Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston,MA 021152 Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston,MA 02115

Received 3 May 2013; accepted 31 January 2014

ABSTRACT: Purpose. To assess the prevalence oftesticular microlithiasis and its association with pri-mary testicular neoplasm.

Methods. Evaluated were 6,002 patients under-going scrotal ultrasound at our institution. Datarecorded included age, ultrasound date, presence ofmicrolithiasis, presence of testicular mass on ultra-sound, and pathologic diagnosis for those who hadsubsequent orchiectomy.

Results. Four hundred fifty-six of 6,002 patients(7.6%) demonstrated testicular microlithiasis. Theprevalence increased from 4.6% for those examinedbefore 2001 to 9.02% for those examined since 2001(p < 0.001). The prevalence of primary testicular neo-plasm in patients without microlithiasis was 1.5% (84/5,546), whereas in those with microlithiasis it was12% (53/456) (p < 0.001). The prevalence of pure semi-noma was 39% (33/84) in the nonmicrolithiasis groupwith tumor versus 64% (34/53) in the microlithiasisgroup with tumor (p < 0.001). Germ cell tumors madeup 98% of neoplasms in patients with microlithiasis,but only 85% in patients without microlithiasis (p 5

0.009).Conclusions. Advances in ultrasound technology

have led to an increased detection of testicular micro-lithiasis. We observed an eight-fold increased preva-lence of primary testicular neoplasm in patients withmicrolithiasis than in those without as well as anincreased prevalence of germ cell tumors, particularlypure seminoma. VC 2014 Wiley Periodicals, Inc. J ClinUltrasound 42:423–426, 2014; Published online in

Wiley Online Library (wileyonlinelibrary.com). DOI:10.1002/jcu.22144

Keywords: microlithiasis; testicular neoplasm; germcell tumor; seminoma; ultrasound

The sonographic finding of testicular microli-thiasis (TM) has been the subject of numer-

ous publications over the past two decades.1–16

TM, consisting of small, calcified concretionswithin the seminiferous tubules, was implicatedas being associated with intratubular germ cellneoplasia nearly from the start of the descrip-tion of TM in the literature.1 Many earlyarticles advocated periodic testicular ultrasonicsurveillance of patients with TM to detectmalignancy at an early stage.3–7 One even advo-cated testicular biopsy.8

Although originally thought to be a rareabnormality,1–3 the reported prevalence of sono-graphically detected TM has varied widely,ranging from 0.68% to 18.1%.7–16 With respectto the association between TM and testicularneoplasm, one report from 2001 concluded thatTM is a common abnormality that may not berelated to testicular neoplasm,9 while anotherstudy the same year reported a high associationwith testicular neoplasm.10

The purpose of our study was to examine alarge population of patients over a 17-yearperiod to assess the prevalence of TM and thefrequency of testicular neoplasm in that sub-group. Our goal was also to evaluate whetherthere is an association between specific tumor

Correspondence to: H. T. Heller

VC 2014 Wiley Periodicals, Inc.

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types and TM, and to determine how advancesin ultrasound technology have affected thedetection rate of TM.

PATIENTS AND METHODS

Institutional Review Board approval wasobtained prior to collecting data for this HIPAAcompliant study. The reports of all testicularultrasounds performed on adult patients 17years and older at our institution from Septem-ber 1994 to April 2011 were retrieved retrospec-tively. If a patient had more than oneultrasound during that time period, only thelast study (or the last study prior to any surgi-cal intervention) was included. Any patient whohad a prior history of testicular neoplasm, priororchiectomy (eg, for congenital cryptorchidism),or an absent testicle for any other reason wasexcluded from the study. This led to a studycohort of 6,002 patients. From 1994 throughpart of 2000, examinations were performed onAcuson 128 XP (Acuson, Mountain View, CA)machines using a 7.5-MHz linear array trans-ducer. From the latter part of 2000 through2011, examinations were performed on Acuson

Sequoia (Siemens, Mountain View, CA) systemsusing a 15-MHz linear array transducer.

Each patient was classified as “TM” or “non-TM” by reviewing the sonographic report.According to our departmental protocol, a testic-ular scan is reported as showing TM if thereare five or more calcifications in one or bothtestes on at least one image11 (Figure 1). BothTM and non-TM groups were subdivided byage: under 30, 30–39, and 40 and above. Theprevalence of TM in our population was catego-rized by examination date range: 1994–2000and 2001–2011 to take into account equipmentimprovements over time and to reflect a majorinstitutional equipment upgrade between thetwo time periods.

Patients in our study population with testicu-lar tumors or masses on ultrasound were identi-fied, and in these patients the pathology reportswere obtained and reviewed. The tumors wereclassified by cell type as pure seminoma, embry-onal cell, Leydig cell, Sertoli cell, Sertoli-Leydigcell, nonseminomatous germ cell, granulosa cell,and teratoma (Figure 2).

FIGURE 1. Testicular microlithiasis in a 37-year-old asymptomatic

man. Sagittal (A) and transverse (B) images of the testicle. There are

five or more microcalcifications (1-2 mm each) per image, the defini-

tion of classic testicular microlithiasis.FIGURE 2. Testicular neoplasm in association with testicular microli-

thiasis. (A) Mixed germ cell tumor in a 24-year-old man. (B) Pure

seminoma in a 31-year-old man.

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We compared the rate of tumor in the TMgroup to the control (non-TM) group andassessed tumor type to see if the distributionwas different in the TM and non-TM groups. v2

and Fisher exact tests were performed to evalu-ate statistical significance.

RESULTS

Among our 6,002 cases, 456 had TM and theremaining 5,546 did not, for an overall preva-lence of TM of 7.6% (Table 1). The mean age ofpatients with TM was 41.3 years, similar to themean age of 41.4 years in the non-TM group.Over time, the prevalence increased from 4.6%(88/1926) during 1994–2000 (the years weemployed the Acuson 128 XP scanner) to 9.0%(368/4076) during 2001–2011 (when we used theSequoia scanner) (p < 0.001, v2).

A total of 137 of our 6,002 patients (2.3%)were shown to have pathology-proven testicularneoplasia. The prevalence was the same in boththe 1994–2000 and the 2001–2011 time periods.Tumor prevalence varied by age group (p <0.001, v2) and was highest in the 30–39-yeargroup: 4.1% in this group versus 2.2% for thoseunder 30 and 1.3% at 40 years and above. Noprimary testicular neoplasm was seen in anypatient above age 62. The prevalence of tumorwas approximately eight times as high in theTM group as in the non-TM group: 53/456(11.6%) in the former group and 84/5,546 (1.5%)in the latter group (p < 0.001, v2) (Table 1).

Of the TM patients with primary neoplasm,34 of 53 (64%) had pure seminoma comparedwith 33 of 84 (39%) in the non-TM group (p <0.001, v2) (Table 2). Among patients with neo-plasms, 52 of 53 (98%) were germ cell tumors inthe TM group, compared with 71 of 84 (85%) inthe non-TM group (p 5 0.009).

DISCUSSION

TM is characterized by small calcifications inthe seminiferous tubules of the testicle, visiblesonographically as tiny bright echoes scatteredthroughout the testicular parenchyma. Sincethe early 1990s, an association between TM andgerm cell neoplasia has been suggested, withthe increased risk of tumor reported to be ashigh as 20 times the risk in patients withoutTM.7,8,13 Our retrospective study, evaluatingone of the largest patient cohorts on this topic,demonstrates a significantly increased preva-lence of tumor in men with TM. Our eight-foldhigher prevalence is similar to a 2007 study,13

and midrange among the various other studiesthat report prevalence rates.7,8,10,15 Our studyhas also shown that tumors in patients with

TABLE 1

Prevalence of TM and Tumor by Examination Date Range and Age Group

All Patients TM Patients Non-TM Patients

No. No. (%) with Tumor No. No. (%) with Tumor No. No. (%) with Tumor Prevalence of TM

Date range

1994–2000 1,926 44 (2.3%) 88 16 (18.2%) 1,838 28 (1.5%) 4.6%*

2001–2011 4,076 93 (2.3%) 368 37 (10.1%) 3,708 56 (1.5%) 9.0%*

Age group

<30 1,371 30 (2.2%)† 97 13 (13.4%) 1,274 17 (1.3%) 7.1%

30–39 1,641 67 (4.1%)† 164 26 (15.6%) 1,477 41 (2.8%) 10.0%

401 2,990 40 (1.3%)† 195 14 (7.2%) 2,795 26 (0.9%) 6.5%

Total 6,002 137 (2.3%) 456 53 (11.6%)‡ 5,546 84 (1.5%)‡ 7.6%

Abbreviation: TM, testicular microlithiasis.

*p < 0.001 (v2), comparing prevalence of TM in the two date ranges.†p < 0.001 (v2), comparing prevalence of tumor in the three age groups.‡p < 0.001 (v2), comparing prevalence of tumor in patients with and without TM.

TABLE 2

Tumor Breakdown by Subtype in TM and Non-TM Groups

Tumor TypeTM Patients

No. (%)Non-TM Patients

No. (%)

Germ cell

Embryonal 2 (4%) 2 (2%)

NSGCT 13 (24%) 36 (43%)

Seminoma 34 (64%)* 33 (39%)*

Teratoma 3 (6%) 0 (0)

Subtotal 52 (98%)† 71 (85%)†

Non-germ cell

Leydig 1 (2%) 8 (10%)

Sertoli 0 (0) 3 (4%)

Sertoli-Leydig 0 (0) 1 (1%)

Granulosa 0 (0) 1 (1%)

Subtotal 1 (2%) 13 (15%)

Total 53 84

Abbreviations: NSGCT, nonseminomatous germ cell tumor (mixed

type); TM, testicular microlithiasis.

*p < 0.001 (v2), comparing seminoma versus all other tumor types

in TM and non-TM patients.†p 5 0.009 (Fisher exact test), comparing germ cell versus non-

germ cell tumors in TM and non-TM patients.

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VOL. 42, NO. 7, SEPTEMBER 2014 425

TM are disproportionately germ cell tumors,particularly pure seminomas, compared withthe non-TM population, an observation that, toour knowledge, has not been previouslydescribed.

Our study found that the detection rate ofTM has increased over time. This is likely dueto improvements in ultrasound technology,including higher frequency transducers thatprovide greater resolution, because the exami-nation date ranges in our study were brokendown into before and after a department-wideequipment upgrade. Newer, higher resolutionequipment is better able to visualize smallstructures, such as tiny testicular calcifications.

Our study, because it is not a longitudinal one,has not shown how likely a man with TM is todevelop testicular neoplasm. Another limitationof our study is that our population consists ofpatients who are either symptomatic or haveanother clinical indication for referral to ourultrasound facility. It is likely that this referralbias falsely increased the overall incidence of tes-ticular neoplasm, but it is unlikely to affect thecomparison of testicular tumors in patients withTM compared with those without TM. Thus, wecan be confident that the association we foundbetween TM and testicular tumor is valid.

In conclusion, we found that TM is detectedmore frequently with modern, high-resolutionequipment than with earlier scanners and isassociated with an eight-fold increase in testicu-lar neoplasia. Primary testicular tumors thatdevelop in patients with TM are disproportion-ately likely to be germ cell tumors, particularlypure seminoma.

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