We report two sets of brothers with the diagnosis of syringocoele, raising the possibility of genetic implications in its development.
Authors: Dr Handoo Rhee, Urology Registrar, Mater Children’s Hospital, Raymond Terrace,South Brisbane, QLD 4101
Dr David Winkle, Consultant Urologist, Mater Children’s Hospital, Raymond Terrace, South Brisbane, QLD 4101
Corresponding Author: Dr Handoo Rhee, Urology Registrar, Mater Children’s Hospital, Raymond Terrace,South Brisbane, QLD 4101Corresponding author. +61 407766382E-mail address: [email protected]
Syringocoele of Cowper’s gland is a rare congenital abnormality that can cause obstructive or irritative symptoms. There have been many hypotheses in the past regarding the embryogenesis and aetiology of the condition. However, due to its rarity, there have been few clues to proceed with further investigation. We report two sets of brothers with the diagnosis of syringocoele, raising the possibility of genetic implications in its development. A literature search has been performed to provide evidence for this theory’s plausibility.
Syringocoele of Cowper’s gland is a rare congenital abnormality that can present as an obstructive or an irritative condition in the paediatric population. Cowper described bulbourethral glands in 1705 as “two small glands, placed on each side of the urethra, a little above the bulb of its cavernous body”. The ducts cohere in the mid bulbar urethra, and their dilatation was first recognized as a syringocoele by Fenwick in 1896, and classified by Maizel in 1983.[3-4] Typically diagnosed in male infants and children, it is a relatively uncommon condition.
We present two sets of brothers with voiding difficulties and later diagnosed as having syringocoele, which raises the possibility of hereditary components in its embryogenesis and aetiology.
The older brother presented with post micturition dribbleing at age of 12. The symptom was initially described at the age of 6. At the time of cystourethroscopy, Type III Cowper’s duct syringocoele was identified and deroofed (Figure 1).
Figure 1. Cystourethroscopy of older brother 1. (a) Urethral sphincter. (b) Type III syringocoele. (c,d) Endoscopic deroofing of the lesion.
Eight years later, his younger brother aged 14 at the time was diagnosed with the same condition. He was also increasingly suffering from post void dribbling. Ascending urethrogram demonstrated a filling defect in the bulbar urethra on the inferior aspect, representing a syringocoele (Figure 2).
Figure 2. Retrograde urethrogram of untreated Cowper’s syringocoele
This was again marsupialized endoscopically with a good result.
These brothers were both diagnosed with Type III syringocoele during cystoscopies to treat cystine stones. Both had been diagnosed with cystinuria requiring approximately 200 procedures altogether including open pyelolithotomy, percutaneous nephrolithotomy and lasertripsy. Both patients eventually required treatment for their syringocoeles to alleviate developing symptoms.
Cowper’s gland cyst or syringocoele is a rare condition that is well documented and classified. Unfortunately, its embryogenesis and aetiology are not well understood. We performed extensive literature search via PubMed, Ovid, Sciencedirect, Google Scholar and Elsevier databases to find 43 case reports since 1983 when Maizel described and classified the lesion. The collected case reports described 149 patients in total.
History of Understanding Syringocoele
Many investigators have attempted to delineate the aetiology of syringocoele. Lebowitz (1978), together with Fenwick’s description in 1896, stated that the cystic development in the bulbourethral duct was due to stenoses of the ductal orifice(s) from urethritis or other inflammatory disease.  However, due to the lack of convincing evidence, the focus turned to a congenital aetiology as more patients presented from a very early age without the history of infections or instrumentation. Cook (1961) hypothesised that the cysts in the glands were more common when there is anomalous development of the ducts, such as when the paired Cowper’s ducts have joined to form a single distal duct.  So far, there have been no reports to develop the hypothesis.
Associations of Syringocoele
Syringocoele has been described with other conditions, although without any consistency. Some of the conditions associated with syringocoele include urethral diverticulum, anterior urethral valves, posterior urethral valves, ureterocoele, acontractile bladder and Cobb’s collar. [7-11] Recently Lo described syringocoele in a 5 week old boy with posterior urethral valves, and bilateral small simple single system ureterocoeles. In this report, we described a pair of brothers both with cystinuria and syringocoele. There are no other reports of such association.
Syringocoele in Animals
In an attempt to explain the aetiology of our serendipitous findings, the literature search was extended to include experimental animals. Kiupel et al (2000) described an extremely high incidence of syringocoele in certain inbred mice colonies. The article described the necropsy report of particular mice strains (SJL/J and RBF/DnJ), where cystic bulbourethral glands were found in 83.8% of mice, without other significant abnormalities.  A high incidence of bulbourethral gland cysts and ductal dilatations were also found in certain strains of bulls and sheep (up to 26%). [13-14] Some have implicated the oestrogenic effects of particular clover pastures in development of low fertility and high incidence of syringocoeles in wethers. In Western Australia, the subterranean clover content of pastures is strictly monitored to maintain fertility and well being of animals. 
Transforming growth factor and the bulbourethral gland
The bulbourethral gland is often studied in isolation to demonstrate the effects of various agents on androgen dependent development. Observing the ultrastructural features of the human bulbourethral glands demonstrate complex parenchyma made up of secretory tubules and alveoli lined by mucoid cells and excretory duct systems, supported by stroma and smooth muscle cells.  These are the result of complex interactions between dihydrotestosterone, mesonephric duct and urogenital sinus, which triggers epithelial-mesenchymal reactions.
Transforming growth factor (TGF) beta is an agent that appears to aid epithelial-mesenchymal interactions in many organs including the prostate and Cowper’s glands. TGF-Beta related mutations have been associated with disturbances in the regulations of immunity, cancer, heart disease, Marfan’s syndrome, and Loeys-Dietz syndrome. 
Dunker and Aumuller in 2002  described development of cystic dilatation of Cowper’s gland in mutant mice with a deletion of transforming growth factor beta subtype 2 gene. They postulated that the hyperplasia of Cowper’s gland epithelium and cystic dilatation is the result of disturbance in epithelial-stromal interactions secondary to reduced TGF-Beta subtype 2 level in heterozygous mutants and eventual decrease in apoptosis of these cells. However, given the in-utero mortality associated with homogenous TGF-Beta subtype 2 mutation, and its roles in a variety of cells, it is unlikely to be the entire cause for the development of isolated syringocoele without other medical conditions. [19-21]
Cystinuria is an autosomal recessive disorder of cystine and dibasic amino acid transporters found in the kidneys and small intestine. SLC3A1 and SLC7A9 are gene mutations that cause different types of cystinuria. Cystinuria is not known to cause hormonal or stromal-epithelial interaction abnormalities. During the literature search, no articles that links mutations in TGF and cystinuria could be found.
Syringocoele appears to develop in a variety of environments across different species. The literature search has provided us with some clues to the future directions in understanding the aetiology of syringocoele. They include genetic mutations that affect stromal-epithelial interactions with or without the effects of disturbances in hormone balance and amino acid transporting pathways.
Historically, there has been significant interest in understanding the aetiology of syringocoele. Due to the rarity of the reports, there have been little clues to direct research. Although these cases are not proof enough to firmly associate genetic implications on the development of syringocoele, the report does provide some clues for future research.
1. Campobasso P, Schieven E, Fernandes EC. Cowper’s syringocoele: an analysis of 15 consecutive cases. Arch Disease Child. 1996; 75: 71-73.
2. Cowper W: Two new glands near the prostate glands, with their excretory ducts, lately discover’d. The Philosophical Transactions and Collections, London 3: 194, 1705.
3. Fenwick EH. Retention cysts of Cowper’s glands as a cause of chronic gleet, spasmodic stricture, organic stricture, extravasation of urine and of so-called “false passages” in the bulbous urethra. Br Med J. 1896; 1:4.
4. Maizels M, Stephens FD, King LR, et al. Cowper’s syringocoele: a classification of dilatations of Cowper’s gland duct based upon clinical characteristics of 8 boys. J Urol. 1983; 19: 129: 111-114.
5. Colodny AH, Lebowitz RL. Lesions of Cowper’s ducts and glands in infants and children. J Urol. 1978; 11:4:321-325.
6. Cook FE, Shaw JL. Cystic anomalies of the ducts of Cowper’s glands. J Urol. 1961; 85:659.
7. Salas RJ, Corominas CI. Diverticulum of the anterior urethra or syringocoele of the Cowper glands. Anal Esp Ped. 1989; 31:6:605-6.
8. Lo A, Upadhyay V, Teele R. Syringocoele of the bulbourethral duct with additional lower genitor-urinary anomalies. Pediatr Radiol. 2011; 41: 1201-1204.
9. Turker Koksal I, Erdogru T, Usta M, Ates M, Baykara M. Unexpected presentation of syringocele: Acontractile bladder. Urol Intern. 2003; 71:2:222-3.
10. Mutlu N, Culha M, Mutlu B, Acar O, Turkan S, Gokalp A. Cobb’s collar and syringocoele with stone. Intern J Clin Prac. 1998; 52:5:352-3.
11. McLellan DL, Gaston MV, Diamond DA, Lebowitz RL, Mandell J, Atala A et al. Anterior urethral valves and diverticula in children: a result of ruptured Cowpers duct cyst? Brit J Urol Intern. 2004; 94: 375-378.
12. Kiupel M, Brown K, Sundberg J. Bulbourethral gland abnormalities in inbred laboratory mice. J Exp Anim Sci. 2000; 40: 178-188.
13. Campero C, Ladds P, Thomas A. Pathological findings in the bulbourethral glands of bulls. 1988. Austr. Vet. J. 65: 241-244.
14. McEntee K, 1990. Reproductive pathology of Domestic Mammals. Academic Press, Inc., San Diego.
15. Department of Agriculture. Farmnote No 41/2005 [newsletter]. Keith Croker et al; Government of Western Australia; 2007.
16. Riva A, Usai E, Cossu M, et al. Ultrastructure of human bulbourethral glands and of their main excretory ducts. Arch Androl. 1990; 24: 177-184.
17. Carlson B. Human Embryology and Developmental Biology, 4th Edition. Philadelphia, Pennsylvania: Mosby/Elsevier, 2009.
18. Dunker N, Aumuller G. Transforming growth factor-beta 2 heterozygous mutant mice exhibit Cowper’s gland hyperplasia and cystic dilations of the gland ducts (Cowper’s syringocoeles). J Anat. 2003. 201: 173-183.
19. Sims Lucas S, Caroona G, Dowling J, et al. Augmented and accelerated nephrogenesis in TGF-beta2 heterozygous mutant mice. Pediatr Res. 2008; 63:6:607-12.
20. Dunker N, Krieglstein K. Targeted mutations of transforming growth factor-beta genes reveal important roles in mouse development and adult homeostasis. Eur J Biochem. 2000; 267: 6982-6988.
21. Sanford LP, Ormsby I, Gittenberger-de Groot A, et al. TGF Beta 2 knockout mice have multiple developmental defects that are non-overlapping with other TGF beta knockout phenotypes. Dev. 1997; 127; 2659-2670.
Date added to bjui.org: 23/01/2012