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BioMed Central
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BMC Urology
Open Access
Research article
Surveillance of testicular microlithiasis?: Results of an UK based
national questionnaire survey
Subramanian Ravichandran*
1,4
, Richard Smith
2
, Philip A Cornford
3
and
Mark VP Fordham
3
Address:
1
Specialist Registrar in Urology, University Hospital Aintree, Liverpool, L9 7AL, UK,
2
SHO in Urology, Royal Liverpool University
Hospital, Prescot Road, Liverpool, UK,
3
Consultant Urologist, Royal Liverpool University Hospital, Prescot Road, Liverpool, UK and
4
17, Milfield,
Neston, Cheshire, CH64 3TF, UK
Email: Subramanian Ravichandran* - chintuappu@aol.com; Richard Smith - richsmith@doctors.net.uk;
Philip A Cornford - Philip.conford@rlbuht.nhs.uk; Mark VP Fordham - Mark.Fordham@rlbuht.nhs.uk
* Corresponding author
Abstract
Background: The association of testicular microlithiasis with testicular tumour and the need for
follow-up remain largely unclear.
Methods: We conducted a national questionnaire survey involving consultant BAUS members
(BAUS is the official national organisation (like the AUA in USA) of the practising urologists in the
UK and Ireland), to provide a snapshot of current attitudes towards investigation and surveillance
of patients with testicular microlithiasis.
Results: Of the 464 questionnaires sent to the BAUS membership, 263(57%) were returned. 251
returns (12 were incomplete) were analysed, of whom 173(69%) do and 78(31%) do not follow-up
testicular microlithiasis. Of the 173 who do follow-up, 119(69%) follow-up all patients while
54(31%) follow-up only a selected group of patients. 172 of 173 use ultra sound scan while 27(16%)
check tumour makers. 10(6%) arrange ultrasound scan every six months, 151(88%) annually while
10(6%) at longer intervals. 66(38%) intend to follow-up these patients for life while, 80(47%) until
55 years of age and 26(15%) for up to 5 years. 173(68.9%) believe testicular microlithiasis is
associated with CIS in < 1%, 53(21%) think it is between 1&10% while 7(3%) believe it is > 10%.
109(43%) believe those patients who develop a tumour, will have survival benefit with follow-up
while 142(57%) do not. Interestingly, 66(38%) who follow-up these patients do not think there is
a survival benefit.
Conclusion: There is significant variability in how patients with testicular microlithiasis are
followed-up. However a majority of consultant urologists nationally, believe surveillance of this
patient group confers no survival benefit. There is a clear need to clarify this issue in order to
recommend a coherent surveillance policy.
Background
Ever since Doherty et al [1] described testicular microlith-
iasis on ultrasound scan in the late 80 s, the interest in this
subject had been on the increase. However despite an
Published: 15 March 2006
BMC Urology2006, 6:8 doi:10.1186/1471-2490-6-8
Received: 04 October 2005
Accepted: 15 March 2006
This article is available from: http://www.biomedcentral.com/1471-2490/6/8
© 2006Ravichandran et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0
),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BMC Urology 2006, 6:8 http://www.biomedcentral.com/1471-2490/6/8
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association of testicular microlithiasis with testicular
tumour [2-8] its aetiological role and the need for follow-
up have remained largely unclear. The incidence of micro-
lithiasis detection has increased with the development of
more sensitive ultrasound transducers in the recent past
and this has in turn increased patient anxiety in addition
to the NHS workload. The cost of on going radiological
surveillance of this patient group could also be phenome-
nal. A recent prospective follow-up study of patients with
incidentally diagnosed testicular microlithiasis by Ray-
mond A Costabile [9,10], shows no link between inciden-
tally diagnosed testicular microlithiasis on ultrasound
and testicular tumour. However the importance of testic-
ular microlithiasis in patients with a high risk of develop-
ing testicular tumour such as cryptorchidism, small
atrophic testis, sub-fertile men and testicular tumour in
the contra lateral testis is not clear and needs further eval-
uation [12,13]. With conflicting evidence for the rationale
of routinely following patients with incidentally diag-
nosed testicular microlithiasis [9-11] we conducted a
national survey to provide a snapshot of current attitudes
towards investigation and surveillance of this patient
group in the United Kingdom.
Methods
A standardised questionnaire was sent to the 464 consult-
ants on the British Association of Urological Surgeons
(BAUS) register. BAUS is the official national organisation
(like the AUA in USA) of the practising urologists in the
UK and Ireland. The questionnaire aimed to record indi-
vidual consultants' preferred practice for managing
patients in whom a finding of testicular microlithiasis is
made.
Participants were asked initially whether they chose to
routinely follow-up these patients and, if so, how this was
achieved:
• All patients or a selected group only
• Intended duration of follow-up (life-long/up to 55 yrs of
age/<5 yrs)
• Surveillance modality used (Clinical examination/ultra-
sound/tumour markers/Biopsy)
• Frequency of follow-up ultrasonography if utilised
Participants were also asked to record their opinion with
regard to whether they felt a survival advantage was con-
ferred for those who go on to develop a testicular malig-
nancy by surveillance of this microlithiasis group. In
addition, the participants' perceptions of the degree of
association between microlithiasis and testicular carci-
noma-in-situ were also requested.
Results
Of the 464 questionnaires sent out, 263 (57%) were
returned of which 12 were inadequately completed. A
total of 251 were therefore analysed.
173 (69%) of the responding participants routinely
choose to follow-up patients with testicular microlithiasis
while 78 (31%) do not. Of those who do, 119 (69%)
decide to follow-up all patients while 54 (31%) only do
so for a selected patient group.
Of the 173 participants who do follow-up microlithiasis,
all but one consultant used ultrasonography in addition
to clinical examination as part of their surveillance. This
lone consultant uses annual clinical examination as his
preferred method of follow-up. While 10 (6%) of the par-
ticipating consultants arrange ultrasound scan on a 6
monthly basis, a vast majority of them 151 (88%) do it
annually. A further 10 (6%) scan patients at more
extended intervals.
27 (16%) consultants request tumour markers in addition
to ultrasound scan, while 10 (6%) would consider biopsy
in selected group of patients.
With regard to the duration of follow-up these patients,
66 (38%) of the positive responders would follow-up
their patients for life, while 80 (47%) would follow them
up until they were 55 yrs of age. 26 (15%) would dis-
charge their patients after 5 yrs of surveillance.
Based on their understanding of the current literature 173
(69%) participants believe testicular microlithiasis is asso-
ciated with carcinoma-in-situ in less than 1% of patients.
53 (21%) felt this figure to be between 1–10% while 7
(3%) believe it to be greater than 10%.
109 (43%) participants believe that surveillance does con-
fer a survival benefit for microlithiasis patients who go on
to develop testicular malignancy while 142 (57%) do not.
Interestingly, 66 (38%) responders who do choose to fol-
low-up this patient group do not think there is a survival
benefit.
Discussion
Microlithiasis in the testis can be histological or radiolog-
ical microcalification. They are not essentially the same
entity. Of interest to the urologist however is the radiolog-
ically detected micolithiasis.
Oiye was the first to describe intratesticular calicifications
in 6 of 192 testicles in autopsy specimens as early as1928
[14]. This report was followed a year later by Blumensaat,
who reported similar intratubular bodies in postmortem
specimens [15]. He felt they were degenerated spermato-
BMC Urology 2006, 6:8 http://www.biomedcentral.com/1471-2490/6/8
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gonia displaced into the lumen of the seminiferous
tubules. Later Bigger and Mc Adams using various histo-
chemical techniques found that the laminated eosi-
nophilic material was a glycoprotein derived from intra
tubular secretions, which later calcified [16]. But it was
not until 1961 that Azzopardi & Mostofi [17] from the
Armed forces institute of Pathology in Washington
described the two different types of intra-testicular calcifi-
cation and their associated pathology. They reported the
more commonly found rounded laminated intra tubular
calicifications associated with cryptorchid testis, adenom-
atous or inflammatory pathology. They then reported the
amorphous haematoxylin staining calcific bodies in
dilated seminiferous tubules found in 13 of 17 patients
with wide spread chorio-carcinoma. Histo-chemical
methods showed them to consist of phospholipid, pro-
tein debris, DNA and calcium phosphate. These calcifica-
tions were seen in close association with malignant
neoplastic cells.
Diffuse microcalcification in the testis on a plain X ray
film was first reported by Priebe & Garret in a 4 year old
boy with an otherwise normal testicle in 1970 [18]. But it
was not until the mid 80 s when Doherty et al using a 10-
MHz transducer first described ultra sonically detected tes-
ticular microlithiasis [1]. Ever since, the interest in this
entity has increased, with several case reports and retro-
spective studies reporting an association with testicular
cancer [2-8]. However these studies were either isolated
case reports or retrospective studies in selected group of
patients.
In one series of 263 sub-fertile men, 20% were found to
have microlithiasis [12]. In the same study 20% of the
men with bilateral microlithiasis were found to have CIS.
Interestingly there was no association of CIS with unilat-
eral microlithiasis in this study group. In another series of
patients with testicular germ cell tumour Skakkabaek
found a significant association of contra-lateral testicular
microlithiasis and CIS [13]. Clearly in the high-risk group
(described earlier) there seems be a significant association
of testicular microlithiasis and CIS, which needs to be
clarified with further longitudinal studies.
In an ultrasound screening study involving 1504 men
between 18 to 35 years from the US army officer corps,
Peterson & Costabile R A. [9] found the prevalence of tes-
ticular microlithiasis to be 5.6%. In this study African
Americans were found to have a higher prevalence of 14%
as opposed to whites who had a prevalence of 4%. How-
ever the incidence of testicular tumour is higher in whites
than African Americans. Analysis of the geographical dis-
tribution of these cases showed a negative correlation
with the incidence of testicular tumour in the United
States. Interestingly there was an association with STD in
the regions where testicular microlithiasis had a higher
prevalence in this study. In their follow-up report after
more than 4 years presented at the AUA meeting in 2004
at San Francisco, USA, they have not had a single case of
testicular tumour in their study subjects with testicular
microlithiasis.
Our survey confirms that many urologists tend to follow
this patient group for a considerable period of time. How-
ever there seems to be a considerable variation in the sur-
veillance policy. This is likely to have an enormous
bearing on the cost conscious NHS practice in future. The
estimated cost in the United States to follow-up all
patients with microlithiasis between 18-to 35 years old
are about 18-billion dollars per year [10]. It is also known
from many studies that there is an average delay of 3–6
months between noticing a testicular lump and seeking
medical advice without significantly affecting cure. With
the cure rate for testicular cancer exceeding 90%, it is
debatable whether an earlier ultrasound diagnosis will
have any effect on the outcome than self examination.
With the emerging evidence it seems safe not to routinely
follow-up patients who are incidentally diagnosed with
testicular microilithiasis [9-11]. They should however be
advised to continue testicular self-examination. The
importance of testicular microlithiasis in the high-risk
groups is not clear and needs further evidence. Until such
time it would be logical to follow-up all patients in the
high risk group.
We do acknowledge that the response rate to our ques-
tionnaire survey has been moderate, with only 57%
returns. This has a small chance of bias towards urologists
actively following microlithiasis returning the question-
naire, than those who are not keen on following them.
However this is more likely to be due to the fact that the
questionnaire was sent during school term holidays,
when many urologists tend to be on annual leave. The
returns were also fairly evenly distributed throughout the
UK.
Conclusion
Our survey highlights a significant variation in how
patients with testicular microlithiasis are followed-up in
the UK. The majority of consultants nationally believe sur-
veillance of this patient group confers no survival benefit.
However significant proportions of them continue to fol-
low-up these patients. There is an urgent need to clarify
this issue in order to recommend a coherent surveillance
policy.
Competing interests
The author(s) declare that they have no competing inter-
ests.
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Authors' contributions
SR designed the Questionnaire, conducted the survey,
analysed the results and also wrote the paper. RS helped
in computing and analysing the data. PAC and MVPF
helped in the design of the questionnaire and overall
guidance.
References
1. Doherty FJ, Mullins TL, Sant GR, Drinkwater MA, Ucci AA Jr: Testic-
ular microlithiasis: A unique sonographic appearance. J Ultra-
sound Med 1987, 6(7):389-92.
2. Winter TC 3rd, Zunkel DE, Mack LA: Testicular carcinoma in a
patient with previously demonstrated testicular microlithia-
sis. J Urol 1996, 155(2):648.
3. Miller RL, Wissman R, White S, Ragosin R: Testicular microlithia-
sis: a benign condition with a malignant association. J Clin
Ultrasound 1996, 24(4):197-202.
4. Kaveggia FF, Strassman MJ, Apfelbach GL, Hatch JL, Wirtanen GW:
Diffuse testicular microlithiasis associated with intratubular
germ cell neoplasia and seminoma. Urology 1996, 48(5):794-6.
5. Parra BL, Venable DD, Gonzalez E, Eastham JA: Testicular micro-
lithiasis as a predictor of intratubular germ cell neoplasia.
Urology 1996, 48(5):797-9.
6. Berger A, Brabrand K: Testicular microlithiasis a possibly pre-
malignant condition: Report of five cases and a review of the
literature. Acta Radiol 1998, 39(5):583-6.
7. Cast JE, Nelson WM, Early AS, Biyani S, Cooksey G, Warnock NG,
Breen DJ: Testicular microlithiasis: prevalence and tumor risk
in a population referred for scrotal sonography. AJR Am J
Roentgeno 2000, 175(6):1703-6.
8. Backus ML, Mack LA, Middleton WD, King BF, Winter TC 3rd, True
LD: Testicular microlithiasis: imaging appearances and path-
ologic correlation. Radiology 1994, 192(3):781-5.
9. Peterson AC, Bauman JM, Light DE, McMann LP, Costabile RA: The
prevalence of testicular microlithiasis in an asymptomatic
population of men 18 to 35 years old. J Urol 2001,
166(6):2061-4.
10. Costabile RA: How worrisome is testicular microlithiasis?
State of the art lecture The AUA-2004 meeting at San Francisco .
11. Rashid HH, Cos LR, Weinberg E, Messing EM: Testicular micro-
lithiasis: a review and its association with testicular cancer.
Urol Oncol 2004, 22(4):285-9.
12. De Gouveia Brazao CA, Pierik FH, Oosterhuis JW, Dohle GR, Looi-
jenga LH, Weber RF: Bilateral testicular microlithiasis predicts
the presence of the precursor of testicular germ cell tumors
in subfertile men. J Urol 2004, 171(1):158-60.
13. Holm M, Hoei-Hansen CE, Rajpert-De Meyts E, Skakkebaek NE:
Increased risk of carcinoma in situ in patients with testicular
germ cell cancer with ultrasonic microlithiasis in the contral-
ateral testicle. J Uro 2003, 170(4 Pt 1):1163-7.
14. Oiye T: Uber anscheinend noch nicht beschriebene Steinchen
in den menschlichen Hoden. Beiter. Path Anat 1928, 80:479.
15. Blummensaat C: Ubereinen neuen Befund in Knabenhoden.
Virchows Arch Path Anat 1929, 273:51.
16. Bieger RC, Passarge E, Mcadams AJ: Testicular intratubular bod-
ies. J Clin Endocr 1965, 25:1340.
17. Azzopardi JG, Mostofi FK, Theiss EA: Lesions of testes observed
in certain patients with widespread choriocarcinoma and
related tumors. The significance and genesis of hematoxylin-
staining bodies in the human testis. Am J Pathol 1961, 38:207-25.
18. Priebe CJ Jr, Garret R: Testicular calcification in a 4-year-old
boy. Pediatrics 1970, 46(5):785-8.
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