testicular microlithiasis

4.  Testicular microlithiasis (TML) corresponds to concretions of
hydroxyapatite surrounded by fibrosis located in the seminiferous tubes.
 The first sonographic identification ofTM was described by Doherty in 1987
 They are due to the insufficient capacity of Sertoli cells to phagocyte the
degenerate cells present in the seminiferous tubules.
 They are commonly discovered by ultrasound (US). They are not visible on
Magnetic Resonance Imaging (MRI).

5.  They do not typically affect Leydig cells and the majority of the uninvolved
seminiferous tubules often have abnormal spermatogonia and reduced
luminal diameters.
 Microliths can be seen in the testis as well as in extratesticular structures
such as the lungs and the central nervous system, with genetic factors also
thought to play a role in their development.

6. Definition
 The presence of multiple microintratubular calcifications without any
acoustic shadow in the testicle and is often an incidental finding in US
examinations of the scrotum.
 The microliths do not bring about pain or symptoms and are impalpable.
 TM can be either unilateral or bilateral.

7. Grades
 Three grades are distinguished according to the number ofTML
described by parenchyma per field of view
1. grade 1 (Limited ): 5 to 10
2. grade 2 (Classic ): 10 to 20
3. grade 3 (Diffuse ): with more than 20
Significance
A cluster (a few microliths per
field in a cluster) may be more worrying thanTM
scattered throughout the testis. It may indicate a dysgenic
area in the testis, in which carcinoma in situ
(CIS) may develop

8. Prevalence
 The prevalence ofTM varied in the past data
 In symptomatic adults, it range between 0.6% and 9.0%
 In health population (adults without symptoms) from 2.4% to 5.6%.
 In a group with genetic disorders, the prevalence of TM has been reported
much more higher. In men with Klinefelter syndrome is as high as 17.5%
and 36% in men with Down syndrome

9.  The boys with Down syndrome had higher prevalence of
TML than the general healthy population.
 No case of testicular cancer was recorded among 142 DS
men withTML.
 Only one study found a testicular cancer (Leydig Cell
tumour) in an individual with DS andTML (1/54 = 1.9 %),
and the cancer was diagnosed during the fourth year of
follow-up.
TM and Down syndrome

10.  A congenital disease characterised by
polyostotic fibrous dysplasia, caféau- lait
pigmentation and early puberty.
 Two studies were included concerningTML
and MAS.
 The prevalence ofTML in MAS males was
24.1 % and 62.5 % .
 One testicular cancer (embryonal cell
tumour) was reported among 62 cases of
MAS.
TM and McCune–Albright syndrome

11.  Both appear to have the highest frequencies of TML, ranging from 23 to
63 %.
 The present analysis revealed that in these conditions there seemed to
be no relation between TML and development of testicular cancer.
 This association between TML and chromosomal abnormalities may
indicate TML as part of a degenerative process of the testis.
Males with Down syndrome and McCune–Albright
syndrome Significance

12. Association of testicular microlithiasis with male
infertility
TM association with male infertility is still debated.
Incidence ofTM in a subfertile population is up to 20% .
Reduction in sperm count and sperm motility in a man with microliths is
attributable toTM-related obstruction of seminiferous tubules present in
30 to 60% of patients withTM .
Inflammation and calcification in the seminiferous tubules area bring
about deterioration in sperm quality and cause subinfertility [22].

13. Association of testicular microlithiasis with male
infertility
Thomas et al. reported a relationship between the degree of calcification
and poor sperm function.
TM is associated with worse semen parameters in adult men with infertility.
TM was reported to be more prevalent in patients with spermatogenic
defects such as severe oligospermia and reduced testicular volume .

14. Association of testicular microlithiasis with male
Infertility andTumor
TML and infertility was associated with an approximated sevenfold higher
cancer risk compared to infertile men withoutTML (10.9 vs. 1.6 %)
confirming thatTML, infertility and testicular cancer seem to be
interlinked
TML may be an indicator of a “testicular dysgenesis syndrome”
consisting of infertility, cryptorchidism, CIS and testicular cancer
EUA 2022
The risk for infertility may be higher in patients with microlithiasis and if these patients have any
sign of infertility later, the risk of developing a tumour seems to be higher compared to patients
without microlithiasis and infertility

15. Association of testicular microlithiasis with
testicular cancer
 In the past, there was concern that testicular microlithiasis may increase
the risk of testis cancer. However, more recent data indicates that
testicular microlithiasis does not increase the risk of testis cancer when
there is no solid testis mass and no other risk factors for testis cancer

16. Association of testicular microlithiasis with
testicular cancer According to EUA and AUA
 Testicular microlithiasis without a concomitant solid testis mass
testicular microlithiasis in men
with no solid testis mass and no
risk factors for testis c.
testicular microlithiasis (but no solid testis
mass) and at least one risk for testis
cancer
annual follow-up with
Ultrasound is conterversal and monthly self-
examination should be
advised
does not require further
evaluation
Role of
testicular
biopsy

17. Role of testicular biopsy in patient withTM and risk factors
 In patients at risk to develop testicular cancer, observation versus
testicular biopsy is debatable.
 At present, testicular biopsy remains the gold standard to detect ITGCN
 The early biopsy allows treating early these patients with radiotherapy
therefore avoiding orchiectomy and the risk of subsequent chemotherapy.
However, such an approach could alter definitively spermatogenesis and
has no impact on overall survival.

18. Role of testicular biopsy in patient withTM and risk factors
 When biopsy is indicated for fertility purposes in patients with testicular
microlithiasis, a search for ITGCN should be systematically performed.
 Observation versus testicular biopsy is also debatable in patients
previously treated by orchiectomy for a testicular cancer and harboring
microlithiasis in the contralateral testis

19. Role of testicular biopsy in patient withTM and risk factors
 Due to the low incidence of a contralateral tumor, even in cases of
testicular microlithiasis, there is no indication for contralateral testicular
biopsy in prepubertal boys (EUA 2022).
 While in Adult an individualized approach based on the age of the
patient,the presence of concurrent features of testicular dysgenesis
syndrome, the fertility of the couple, the desire of paternity and the
ultrasound pattern (bilateral and clusteredvs. unilateral and limited) is
recommended

20. A diagram explaining the link between different feature of dysgenetic testis and testicular
cancer.

21. A decision tree for patients having testicular microlithiasis.

22. Association of testicular microlithiasis with
testicular cancer
Testicular microlithiasis with a concomitant solid testis mass-these
patients are assumed to have testis malignancy
surgical exploration with testicular
biopsy or orchiectomy should be
considered An ultrasonography of a 16-year-old male
with testicular cancer and multiple
Classic testicular microlithiasis
and accompanying lobulated
seminoma .

23.  Data in the literature are sparse, and cancer subtypes were inconsistently
reported.
 Recently, it was suggested that there might be a positive association between
TML and seminoma, and a negative association betweenTML and embryonal
cell carcinoma.This was confirmed in our review, in which seminoma accounted
for 36 % of cancer cases reported withTML compared to 1 % for embryonal
carcinoma .
 There appears to be no association betweenTML, age and tumour size
Association of testicular microlithiasis and cancer
subtypes

24. Summary and Our Recommendations When Testicular Microlithiasis
Is Noted
The management of TM detected on ultrasound can be divided into four
categories.
First,TM in the presence of a
mass is irrelevant.The mass
trumps all. “Most masses in
the testicle are assumed to
represent testicular cancer
until proven otherwise”
Second, the patient can be
reassured that if the patient is
at low risk forTC,
the risk ofTC developing in
the setting of isolatedTM,
although not precisely known,
is extremely small (with the
worst estimate of risk being 1
in 100 cases).
Third, and of most importance,
the patient should be educated
about the need for regular
monthly testicular self-
examination.
Finally, the risk of
TC should be stratified on the basis of
other
Risk factors , and follow-up ultrasound
examination should be reserved for high-
risk
patients.

25. Take-home massage
 This association betweenTML and chromosomal abnormalities may indicateTML as part
of a degenerative process of the testis.
 TML and infertility was associated with an approximated sevenfold higher cancer risk
compared to infertile men withoutTML (10.9 vs. 1.6 %).
 In the absence of risk factors, the occurrence of testicular cancer in patients withTML is
similar to the risk of the general population.
 TM at risk to develop testicular cancer, observation versus testicular biopsy is debatable.
 Most masses in the testicle are assumed to represent testicular cancer until proven
otherwise”

26. 1. Winter, T. C., et al. (2016). "Testicular Microlithiasis: What Should You Recommend?"
AJR Am J Roentgenol 206(6): 1164-1169.
2. Leblanc, L., et al. (2018). "Testicular microlithiasis and testicular tumor: a review of
the literature." Basic Clin Androl 28: 8.
3. Pedersen, M. R., et al. (2019). "Association between risk factors and testicular
microlithiasis." Acta Radiol Open 8(9): 2058460119870297.
4. Aoun, F., et al. (2019). "Testicular microlithiasis: Systematic review and Clinical
guidelines." Prog Urol 29(10): 465-473.
5. EUA 2022
REFERENCE