Testicular microlithiasis and undescended testis
Goede, J.
Citation
Goede, J. (2012, January 19). Testicular microlithiasis and undescended testis. Retrieved from https://hdl.handle.net/1887/18389
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Chapter 1
Clinical aspects of testicular microlithiasis in boys: a review
J Goede WWM Hack
J Pediatr Urol 2011 Aug 18 [Epub ahead of print]
Chapter 1
Abstract
Objective
After reviewing the paediatric literature, we report on the prevalence of testicular microlithiasis and on its relation with benign and malign entities. At the end of this review, we provide a guideline for the management of boys with testicular microlithiasis.
Materials and Methods
The databases searched were Medline, Web of Science, Embase and the Cochrane Library. Data on the rates of testicular microlithiasis were collected and from each study information was extracted on the study population according to country, study design, diagnostic method, type of patient, number of patients, age, associated anomalies, additional diagnostic methods and follow-up information. From the 472 articles, we selected 126 articles as potentially relevant, of which 57 were included.
Results
In asymptomatic boys, the prevalence rate of testicular microlithiasis is 4.2% and in symptomatic referrals it is 1.6%. The development of a testicular malignancy is occasionally reported after diagnosis of testicular microlithiasis. The management of boys with testicular microlithiasis varies widely. Most authors advise regular self-examination and some perform testicular ultrasound and/or screen tumour markers.
Conclusion
The prevalence of testicular microlithiasis in boys varies between 1.1% and 4.2%. For the follow-up, regular self-examination is mostly advised from the age of 15.
Clinical aspects of testicular microlithiasis in boys: a review
Introduction
The use of scrotal ultrasonography (US) has led to increased co-incidental findings of testicular microlithiasis (TM). TM is characterised as multiple foci of less than 3 mm within the seminiferous tubuli. These are found as either diffuse or segmented within the testicular parenchyma. A number of conditions are thought to be associated with TM in both adult and pediatric patients. Physicians have been concerned about the need for follow-up of TM, as it has been associated with testicular malignancies and infertility in adults. In particular, earlier reviews in adults examined the associations of TM with testicular malignancies and management trends in patients with TM.1,2,3 The follow-up in adults ranges from self-examination and annual or biannual US to biopsy, to rule out the actual or future development of testicular malignancies.4 However, in boys the relationship between TM and malignancies has largely been reported only anecdotally, and TM has been associated with several non-malignant conditions. It is not clear whether the same management of TM is recommended in boys as in adults.
For this reason, we reviewed the paediatric literature on TM in order to report on its prevalence, on its relation with benign and malign entities, and on the guidelines presented. At the end of this review, we will present a guideline for the follow-up and management of boys with TM.
Materials and methods
Search strategy
Four electronic databases were searched: Medline, the Cochrane Library, Embase and Web of Science (until December 2010). Searches were performed using key words in different combinations (see Appendix), and languages were restricted to English, German and Dutch. In addition, reference lists of included studies and review articles were screened to identify additional relevant articles.
Selection of studies
We used explicit inclusion and exclusion criteria. Studies were considered eligible for inclusion if they provided data on TM in boys from birth to adolescence. We included both prospective and retrospective, and cross-sectional and longitudinal cohort studies.
Potentially relevant studies were selected by screening the titles and abstracts for relevance. Subsequently, potentially relevant articles were read independently, and studies on TM in boys were selected for inclusion if they met our criteria.
Studies were excluded if the study population consisted of both boys and men and it
Chapter 1
proved impossible to select only the boys. Review articles were not included but were read anyway, as they provided a general overview.
Data extraction
Data were collected regarding the TM rates, and in each study information was extracted about the study population regarding country, study design, diagnostic method, type of patient, number of boys studied, age, associated anomalies, additional diagnostic methods, and follow-up.
Results
As presented in Fig. 1, the search strategies led to the selection by Medline of a total of 198 articles; these were screened by title and abstract. By Embase, 282 articles were selected, of which 183 had not been found by the Medline search. At least 216 articles were selected from Web of Science, and 91 of these had not been found by the searches by Medline and Embase.
After screening the titles and abstracts, 126 of these 472 articles were selected as potentially relevant. Of these 126 articles, eventually 57 were included and 69 excluded.
Of the 69 excluded articles, 9 were editorial comments, 15 were review articles, and 45 proved not relevant for answering our question, even though they had been identified as potentially relevant after screening the titles and abstracts.
Included studies
Of the 126 studies selected, we identified 57 studies in which TM in boys was described:
15 studies were prospective, 10 were retrospective and 32 were case reports. Of these 57 included studies, 13 reported on the prevalence of TM in boys, 9 prospectively and 4 retrospectively. Eight studies investigated both men and boys; in two of these studies it was impossible to detect how many boys were included. Twelve studies documented the prevalence in a group of boys with different symptoms and one in asymptomatic boys;
the latter was a prospective study. Table 1 gives an overview of the included studies and relevant characteristics.
Prevalence
The prevalence in asymptomatic boys was determined in one (prospective) ultrasound study, which documented a rate of 4.2%.5 The prevalence in boys referred for various scrotal complaints was determined in three studies (all retrospective) and varied between 1.1% and 2.0%.6,7,8 Cumulatively, TM was found in 27 of the 1671 boys studied, which
Clinical aspects of testicular microlithiasis in boys: a review
indicates an average prevalence of 1.6% in these symptomatic boys. The prevalence of TM in boys with undescended testes was determined in two prospective studies with a cumulative prevalence rate of 3.5%.9,10
The relationship between TM and ethnic background was analyzed in one prospective ultrasound study in healthy boys and in one study in boys with undescended testis.
However, only a few non-whites were included; therefore, the TM rate according to ethnic background could not be assessed. As far as we could ascertain, no studies had been performed on the frequency of TM in boys with retractile testis, varicocele or hydrocele.
Association with benign anomalies
There are a number of reported associated conditions with TM, the majority of which are case reports. In boys, TM is commonly reported in association with a benign anomaly of the testis, such as hydrocele6,11,12, varicocele13, undescended testis9,10,14-18, Figure 1
Flow-chart of the selection of studies on boys with testicular microlithiasis.
Figure 1
Excluded: 224 duplicates
Excluded:
• 45 not relevant
• 15 reviews
• 9 editorial comments
Chapter 1
testicular asymmetry19-21, testicular pain22-26, torsion of the testis27,28 and torsion of the appendix of the testis.29,30 Moreover, TM has been associated with several chromosomal abnormalities. Vachon et al. studied 92 patients of 0-29 years old with Down syndrome and found a prevalence rate of 29% compared to 7% in controls.31 Wasniewska et al.
reported a prevalence of 6 out of 10 boys in a study of patients with McCune-Albright Syndrome32 The association with McCune-Albright Syndrome was also reported in two case reports.33,34 Bercovitch et al. investigated 12 patients with pseudoxanthoma elasticum and found TM in 9 patients, 2 of whom were boys.35 Pourbagher et al.
described the cases of three brothers with TM who were also diagnosed with Fragile X syndrome.36 TM was also reported in otherwise healthy siblings by Goede et al.
and Thomas et al..10,12 Other syndromes associated with TM are Cornelia de Lange syndrome29 and Peutz-Jeghers syndrome.7 Other benign anomalies associated with TM include mumps37, urethroperineal fistula38, retro-iliac ureter39, hypogonadotropic hypogonadism14,40 and β –thallassemia.41,42
Association with testicular malignancies
In analyzing the association between TM and testicular malignancies, it is important to differentiate between the development of a tumor in patients with pre-existing TM and the co-existence of TM and testis tumor. Three studies reported on the development of a testicular malignancy in boys after TM was diagnosed: a yolk sac tumor in an otherwise healthy 17-year-old boy, a mixed germ cell tumor in a 9-year-old boy with precocious pseudo puberty, and a mixed germ cell tumor in a 16-year-old boy.11,43,44
The co-existence of TM and testicular tumor was described in one retrospective study and in five case reports. Backus et al. reported on 42 patients with TM, only three of
Abbreviations Prosp Prospective Retrosp Retrospective US Ultrasound LH Luteinizing Hormone FSH Follicle Stimulating Hormone αFP Alpha-fetoprotein
β-HCG Beta-Human chorionic gonadotropin MGCT Mixed Germ Cell Tumor
TGCT Testicular Germ Cell Tumor ALL Acute Lymphatic Leukemia LDH Lactate dehydrogenase Table 1
Characteristics of the 57 included studies on boys with testicular microlithiasis.
Author, yearCountryStudy designDiagnostic method Kind of patientsNumber of patients AgeAssociated anomalies Additional diagnostics Follow-upFollow-up method Tumor during follow-up (boys)
Author, yearCountryStudy designDiagnostic methodKind of patientsNumber of patientsAgeAssociated anomaliesAdditional diagnosticsFollow-upFollow-up methodTumor during follow-up (boys) Akar T et al. 1997TurkeyCase reportUSHypogonadism1 (1)15 yrs----- Alaee A et al. 2007IranCase reportUSβ-thalessemia major1 (1)10 yrs----- Amodio JB et al. 2004 USAProsp.USPoly-orchidism3 (1)14-28 yrs----- Arrigo T et al. 2006 ItalyCase reportUS + histologyPrecocious pseudopuberty1 (1)6 yrsHydroceleLH,FSH, testosterone, αFP, β-HCG 3 yrsUSMGCT Backus ML et al. 1994 USARetrosp.USVarious scrotal complaints42 (3)14-70 yrsTGCT (n= 17) , testicular infarct (n=1)
---- Bercovitch RS et al. 2005 USARetrosp. + Prosp.USPseudoxanthoma elasticum9 (2)13-56 yrs----- Blau H et al. 2002 IsraelProsp.USCystic Fybrosis12 (12)2-12 yrs----- Bober E et al. 2007 TurkeyCase reportUSTesticular enlargement1 (1)7.5 yrs-LH,FSH, testosterone, αFP, β-HCG 3 yrsUS, Self- examination, FSH, LH
- Brown SM et al. 1990 USAProsp.USSpermatic cord torsion5 (5)2-12 daysHemorrhagic infarctionNuclear scintigraphy--- Campagnoli MF et al. 2006 ItalyCase reportUS + histologyFamilial tumoral calcinosis1 (1)14 yrsOligazoospermiaBiopsy--- Urine culture, US, αFP, β-HCGAFP, β-HCG Coley BD. 2005 USACase reportUSScrotal pain1 (1)8 yrs--4 yrsUS- Cortes D et al. 2003DenmarkProsp.USUndescended testis13 (13)0.5-7.9 yrsInguinal hernia---- Dagash H et al. 2007 UKRetrosp.USScrotal pain, undescended testis ,hydrocele, testicular enlargement
623 (623)7-15 yrs--Max 5,5 yrs (mean 2.9)US- Daneman A et al. 2007CanadaCase reportUSMcCune-Albright syndrome1 (1)14 yrs----- Dell’Áqua A et al. 1999ItalyProsp.USScrotal trauma, undescended testis, varicocele
6 (6)3-12 yrs-----
10 yrs-1 yr-Chan PT et al. 1998CanadaCase reportUSMumps1 (1)
Author, yearCountryStudy designDiagnostic method Kind of patientsNumber of patients AgeAssociated anomalies Additional diagnostics Follow-upFollow-up method Tumor during follow-up (boys)
Author, yearCountryStudy designDiagnostic method Kind of patientsNumber of patients AgeAssociated anomalies Additional diagnostics Follow-upFollow-up method
Tumor during follow-up (boys) Demirel S et al. 1997
TurkeyCase reportUSMultiple Leiomyomas
1 (1)15 yrsEmpty sella turcicaMultiple blood/hormone profiles and radiological images, Karyotype.
--- Drut R. 2003 ArgentinaCase reportUSYolk sac tumor1 (1)2 yrs-αFP, CT--- Drut R et al. 2002
ArgentinaProsp.HistologyALL, ITGCN, undescended testis, torsion appendage testes 11 (11)3-15 yrsCornelia de Lange syndrome
Biopsy--- Erdeve SS et al. 2006
TurkeyCase reportUSMcCune-Albright syndrome 1 (1)5 yrs----- Estaun JE et al. 2001
SpainCase reportUSUrethroperineal fistula 1 (1)5 yrs--2 yrsUS- Furness PD et al. 1998
USARetrosp.USVarious scrotal complaints 26 (?)0.5-21 yrs-αFP, β-HCG (n=15), Biopsy (n=9) Max 7 yrsUS, Self- examination
- US, Self- examination Goede J et al. 2009
NetherlandsProsp.USAsymptomatic694 (694)0.5-18 yrs----- Goede J et al. 2008 NetherlandsCase reportUSPseudoxanthoma elasticum 1 (1)9 yrsUndescended testis -7 yrsUS- Goede J et al. 2010
NetherlandsProsp.USUndescended testis501 (501)0-18 yrs----- Horowitz MB et al. 1997 USACase reportUSBenign cystic teratoma
1 (1)4 yrs--1 yrUS- αFP, β-HCG, LDH Jaramillo D et al. 1989
USACase reportUSTorsion testis1 (1)14 yrsInfarction of the testis Biopsy, Karyotype, X-ray chest --- Kent E et al. 2007
USACase reportUSScrotal pain1 (1)15 yrs-----
15 yrs----Howard RG et al.1998
Hong KongCase reportUSMediastinal germ cell tumor
1 (1)
22 (?)8-63 yrs-Biopsy (n=2),Max 9 yrs-Ganem JP et al. 1999
USAProsp.US + histology Various scrotal complaints
Author, yearCountryStudy designDiagnostic method Kind of patientsNumber of patients AgeAssociated anomalies Additional diagnostics Follow-upFollow-up method
Tumor during follow-up (boys) Kocaoglu M et al. 2007
TurkeyCase reportUSRetro iliac ureter1 (1)13 yrsUndescended testis, cerebral palsy, epilepsy
---- Kocaoglu M et al. 2005
TurkeyRetrosp.USVarious scrotal complaints, Failure to thrive 9 (9)3-16 yrs-Abdominopelvic US, X-ray chest Max 1 yrUS- Kwan DJ et al. 1995
USACase reportUSTorsion appendix testis 1 (1)8 yrsReactive flegmoneαFP, β-HCG, urinalysis UnknownUS, Self- examination - Leman J et al. 2000
UKCase reportUSMultiple lentigines1 (1)17 yrs----- US, AFP, β-HCG αFP, β-HCG, MRI Miller FN et al. 2007 UKRetrosp.USSymptomatic refferals
198 (198)Unknown----- Metabolic, endocrinological tests, Spermiogram, Biopsy Nistal M et al. 2004
SpainRetrosp.HistologyRete testis tumor 8 (1)4 yrsRenal agenesia, imperforate anus ---- Nistal M et al. 1995
SpainRetrosp.HistologyUndescended testis, Dwarfism, hypogoadotropic hypogonadism 15 (7)4-14 yrs----- Nistal M et al. 1992
SpainRetrosp.HistologyTesticular torsion109 (?)15 yrsAnoxic lesions---- Nistal M et al.1979 SpainCase reportHistologyUndescended testis2 (2)6 yrs----- Nokes SR et al. 1994
?Case reportUSScrotal pain1 (1)17 yrs----- Pinto K et al. 2004 USACase reportUSScrotal pain1 (1)14 yrsPseudoxanthoma elasticum αFP, β-HCG1 yrUS, AFP, b- HCG,Self- examination
-
14 yrs----Moran JM et al. 1993
SpainCase reportUSTesticular enlargement
1 (1)
1 (1)16 yrs----
17 yrs-αFP, β-HCG6 yrsYolk sac tumor Meyer MA et al. 2010
USACase reportUSExtragonadal germ cell tumor
McEniff et al. 1995 USACase reportUSTesticular enlargement
1 (1)
Author, yearCountryStudy designDiagnostic method Kind of patientsNumber of patients AgeAssociated anomalies Additional diagnostics Follow-upFollow-up method Tumor during follow-up (boys)
Author, yearCountryStudy designDiagnostic method Kind of patientsNumber of patients AgeAssociated anomalies Additional diagnostics Follow-upFollow-up method
Tumor during follow-up (boys) Pourbagher MA et al. 2005
TurkeyCase reportUSAbdominal pain3 (1)13-21 yrsFragile X syndrome
αFP, β-HCG--- X-ray chest, abdomen and vertebrae, Karyotype Riebel T et al. 2000
GermanyProsp.USUndescended testis68 (68)3-13 yrs----- Slaughenhoupt B et al. 2009 USACase reportUSScrotal wall edema1 (1)11 yrs-αFP, β-HCG5 yrsSelf- examination, US Metastatic Germ Cell Tumor Tahlan A et al. 2005
IndiaCase reportHistologyUndescended testis1 (1)5 yrsAtrophic testis--- Thomas D et al. 2008 GreeceCase reportUSHydrocele2 (2)5-6 yrsUndescended testis (n =1)
Full blood count, Metabolic + edocrinolgical tests, αFP, b- HCG, Karyotype, Urinalysis, X-ray chest 1.6 yrsSelf- examination, US
- Toh ST et al. 2000
IndiaCase reportUSUndescended testis1 (1)15 yrsMGCT---- 92 (?) Down, 0-29 yrs Down, 200 (200) controls
0-18 yrs controls Vegni-Talluri M et al. 1980
ItalyProsp.HistologyUndescended testis30 (30)Unknown ----- Wasniewska M et al. 2006 ItalyProsp.USMcCune-Albright Syndrome 10 (10)0.5-17 yrs----- Wasniewska M et al. 2004
ItalyProsp.USMcCune-Albright Syndrome 8 (6)5-21 yrs----- Weinberg AG et al. 1973
USACase reportX-ray + histology β- thallasemia major1 (1)6 yrs-X-ray of testes siblings, Serum calcium + phosforus, Karyotype.
---
--Max 5 yrsUSLeydig cell tumor (n=1)
Vachon L et al. 2006
USAProsp.USDown-syndrome
1 (1)4 yrs-2 yrsUnknown-Priebe CJ et al. 1970
USACase reportX-ray+ Histology
Hernia inguinalis
Author, yearCountryStudy designDiagnostic method Kind of patientsNumber of patients AgeAssociated anomalies Additional diagnostics Follow-upFollow-up method Tumor during follow-up (boys)
Clinical aspects of testicular microlithiasis in boys: a review
whom were under the age of 19 years. In 17 of these patients, a germ cell neoplasm was observed.45 Drut described two additional cases of a testicular tumor associated with TM: a yolk sac tumor in a 2-year-old boy, and a 16-year-old boy with bilateral intratubular germ cell neoplasia.29,46 Two other authors also reported on the co-existence of TM and a germ cell tumor; one of these cases was also diagnosed with cryptorchidism.47,48 Finally, Nistal et al. reported on a 4-year-old boy with left renal agenesia and imperforate anus who presented with a rete testis tumor.49
Additional diagnostics
Diagnostic methods in evaluating patients with TM included tumor markers (α-fetoprotein and β-chorionic gonadotropin), hormone assays and radiological images such as testicular ultrasound, X-rays and MRI. Also, karyotyping and biopsies were reported (see Table 1). In almost all studies, testicular ultrasound was performed as a diagnostic method, and in 23 of the studies some form of additional diagnostics was performed. In 13 of these 23 studies tumor markers were determined, and 8 studies performed some form of additional radiological method other than US of the testes, such as X-ray of the chest (in 4 studies). In 5 studies, a biopsy was performed of at least one of the testes with TM. In all of the studies, the results of these additional diagnostic methods were within normal range. A detailed survey of the additional diagnostics is given in Table 1.
Follow-up
In the 54 studies in boys, 17 authors describe different forms of follow-up, including self- examination, testicular ultrasound, and screening tumor markers and/or hormone profiles.
The follow-up period varies between 1 month and 9 years. All 17 authors recommend physical examination and annual or biannual follow-up by ultrasound; 4 also advised determining tumor markers serially in addition to ultrasound. In the three case studies reporting on the development of testicular malignancies in boys already known with TM, the tumor developed after 3-6 years. In all these studies, follow-up examination comprised US in addition to physical examination; in one study, tumor markers were routinely screened. Table 1 provides detailed information on the kinds of follow-up carried out in the 17 studies.
Discussion
Nowadays US of the testis is used more frequently and modern US machines make TM easier to detect; as a result, TM is increasingly being detected. TM prevalence has frequently been investigated in adult men, but is only occasionally reported in boys. The reported TM prevalence rate in asymptomatic boys is 4.2%, whereas in symptomatic
Chapter 1
referrals a cumulative rate of 1.6% is reported. The TM rate in boys with undescended testes shows a cumulative prevalence of 3.5%. These rates indicate that TM does not occur more frequently in symptomatic boys than in asymptomatic boys.
Segmented TM may be more prevalent in patients with testicular germ cell tumor (TGCT);
therefore, it must be differentiated from diffuse TM.45 A distinction has also been made between limited and classical microlithiasis; this distinction is based on the number of microliths observed per view. Classical TM refers to the presence of five or more echogenic foci in one or both testes, whereas limited TM is defined as fewer than five foci. The grading of TM according to the number of microliths does not predict tumor development.50,51
The appearance of TM in siblings suggests a co-incidental finding, since there are only two reports which described TM in brothers. Also, it is likely that in some patients TM is related to an underlying abnormality, for example in patients with pseudoxanthoma elasticum.
The exact pathogenesis of TM remains unclear, although it is thought to be the result of the degeneration of cells in the seminiferous tubules in which hydroxyapatite deposits develop, surrounded by concentric layers. The origin of TM is presumably related to Sertoli cell dysfunction.52 TM has been associated with various chromosomal abnormalities including Down syndrome, fragile X syndrome and Klinefelter’s syndrome and may be an indication of a degenerative process of the testis. In boys with Down syndrome, TM may be an indication of infertility because nearly all of these boys are infertile due to decreased spermatogenesis.53 In contrast, the formation of microliths in patients with pseudoxanthoma elasticum may be caused by dystrophic mineralization in the testis parenchyma, a process found in elastic tissue in other parts of the body, including the skin and arteries.54
In adults, a number of studies have shown an association between TM and infertility and testicular malignancy.1-3,55 The development of TGCT following diagnosis of TM has been described incidentally in adults.56-58 Follow-up of boys with TM is widely advocated to make early detection of TGCT possible. A questionnaire among UK urologists showed that 69% percent advise some kind of follow-up.4 Follow-up schemes consist of self- examination in combination with physical examination by a specialist, US examinations at different intervals, monitoring of tumor markers, or biopsy.4 Recently, a new algorithm has been proposed for the follow-up of adults with TM.59 Although there is insufficient evidence to produce such an algorithm in boys, regular self-examination from the age of 15 years has to be the cornerstone of any follow-up scheme.
Nearly all follow-up schemes in boys comprise US examinations, although such examinations are controversial; after all, early detection of testicular tumor by US will not change the strategy of testicular cancer, which has an extremely high cure rate regardless of stage. Therefore, US appears not to be cost-effective and should not be standard procedure in the follow-up of boys with TM. Screening tumor markers
Clinical aspects of testicular microlithiasis in boys: a review
or other types of screening are not widely used in boys. Screening tumor markers in asymptomatic men with classical TM appears normal and likewise seems unnecessary.60 Unfortunately, other than US there are no valuable data available regarding the screening for TM in boys. As a result, we do not recommend any of these methods in the follow- up of boys with TM. Until further data are available, we advise three-monthly testicular self-examination in boys with TM, from the age of 15, since testicular malignancies can occur from this age onward. If there is testicular pain, testicular enlargement or Down- syndrome, we recommend regular follow-up by US. Table 1 shows the follow-up schemes of the included studies and the development of malignancies during follow-up.
A limitation of this study is that we determined cumulative percentages for TM prevalence in different groups of boys. These cumulative prevalence rates should be interpreted with caution due to the methodological differences between the studies. For example, there is no uniform definition of TM and the US machines used variable resolutions.
Conclusion
The reported prevalence rate of TM in asymptomatic boys is 4.2%, whereas in symptomatic referrals it varies between 1.1% and 2.8%. A number of conditions are associated with TM; however, most of these have been found in case reports.
Furthermore, it is likely that in some patients TM is related to an underlying abnormality.
The development of TGCT following the diagnosis of TM is reported occasionally. Only US is recommended for the evaluation of patients with TM. We do not recommend any additional diagnostic methods such as screening tumor markers, hormone assays, karyotyping, biopsies and radiological images such as X-rays and MRI.
For the follow-up of boys with TM, we advise regular self-examination from the age of 15.
If there is testicular pain, testicular enlargement or Down syndrome, regular follow-up by US is additionally recommended.
Appendix
Search 1
Testicular microlithiasis OR testicular calcification OR testicular calcifications OR testicular lithiasis OR testicular calculi OR intratesticular microlithiasis OR intratesticular calcification OR intratesticular calcifications OR intratesticular lithiasis OR intratesticular calculi OR scrotal microlithiasis OR scrotal calcification OR scrotal lithiasis OR scrotal calculi
Chapter 1
Search 2
Child*[tw] OR schoolchild*[tw] OR infan*[tw] OR adolescen*[tw] OR pediatri*[tw] OR paediatr*[tw] OR boy[tw] OR boys[tw] OR boyhood[tw] OR youth[tw] OR youths[tw]
OR toddler*[tw] OR teen[tw] OR teens[tw] OR teenager*[tw] OR puberty[tw] OR preschool*[tw]
Limits
English, German, Dutch
Clinical aspects of testicular microlithiasis in boys: a review
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