Intraneural pseudocyst (so-called ganglion) in an unusual retroperitoneal periadnexal location?
© Adamek et al.; licensee BioMed Central Ltd. 2014
Received: 10 June 2014
Accepted: 7 July 2014
Published: 20 July 2014
A case of an unusual unilocular cystic lesion of diameter 7 cm located retroperitoneally in the pelvis in close connection to the right adnexa of a 61 year-old woman is presented. Macroscopically, the lesion had a smooth outer and inner surface and was filled with translucent fluid. Histological examination revealed a fibrous and hyalinized wall which lacked a specific lining. Numerous nerve bundles in the cyst wall constituted the most conspicuous element of its histology possibly with some contribution of perineurial and/or mesothelial components. The morphology and immunohistochemistry speak for an intraneural pseudocyst sometimes called intraneural ganglion cyst which is rare in this location.
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KeywordsPseudocyst Adnexa Immunohistochemistry Intraneural ganglion cyst Ganglion cyst involving peripheral nerves (GCPN)
Intraneural ganglion cysts or alternatively ganglion cysts involving peripheral nerves - GCPNs - (another synonym is intraneural pseudocyst) are rare disorders and present as unilocular cysts filled with translucent mucin . Clinical features of these lesions typically include motor weakness, sensory changes or pain due to compression of the affected nerve . Intraneural ganglion cysts affect most frequently the peroneal nerve but the involvement of other nerves of the upper and lower extremities as well as the obturator nerve have also been reported [2, 3]. There had been lots of controversies over their pathogenesis until Spinner et al. suggested in 2003 in the now well accepted “unifying theory”, that an articular connection with the cyst and synovial fluid pushing its way through the nerve following the way of least resistance is the basic mechanism of cyst formation . For every so far reported case of an intraneural ganglion cyst, the articular connection theoretically could be identified . Here, an intraneural ganglion cyst located in the retroperitoneum in the vicinity of the right adnexa with no identifiable connection to a joint is reported. The presentation is enriched with a broadened discussion on the possible origins, differential diagnosis, and on histological contributors to the structure of its wall.
Differential diagnoses considered during the process of arriving at the diagnosis listed with their main histological characteristics, typical location, and basic references
Main histological characteristics
Intraneural ganglion cyst
Fibrous-walled, distorted nerve fascicles in the wall, non-epithelial lining
Proximity to joints in upper and lower extremities, common peroneal nerve
Haphazard bundles of regenerated axons, unencapsulated, nerve fibers within fibrous tissue
Stump of a transsected nerve, along the course of a traumatized nerve
Multiple variably sized cystic spaces, lymphoid endothelial lining, fibrocollagenous stroma
Various, including the ovary
Peripheral nerves, frequently with arachnoidal membrane component
Nerve roots of the lower spinal cord
Lining of cuboidal or flattened mesothelial cells, fibrovascular stroma
Fibrotic cyst wall, typically with remnants of endometrium and hemosiderin deposits, but occasionally without neither endometrial epithelium nor stroma (what justifies the term “hemorrhagic cyst of undetermined origin”)
Any site in abdomen and pelvis
other cystic lesions like: Pseudocystic metastasis of neuroendocrine tumor
Thick wall resembling the primary tumor, floating neoplastic cells, a blood-filled core, thin fibrous septa
Most frequently in the liver and regional lymph nodes
Regarding evident numerous nerve bundles in the wall of the cyst, the diagnosis of an intraneural ganglion cyst was initially favored. Intraneural ganglion cysts are unilocular cysts usually filled with translucent mucin and cause motor weakness and sensory changes or pain due to compression of the affected nerve [1, 2]. Although intraneural ganglion cysts usually arise in the vicinity of joints, cysts in the pelvic region involving the obturator nerve with a connection to the hip joint have been reported [3, 11]. In the presented case, a relation to the obturator nerve might explain the pathogenesis of the lesion in accordance with the articular theory . Although not in the direct vicinity of the hip joint, intraneural ganglion cysts in the pelvic region can affect nerves which give rise to articular branches, including the sciatic, quadratus femoris, superior gluteal, obturator and femoral nerves . However, a relation of the cyst either to the genital or to the femoral branch of the genitofemoral nerve might be more probable in the presented case. Although we don’t think that the cyst was related to the obturator nerve, one cannot exclude some atypical anatomical distribution of the nerves in the investigated case.
Haphazard and tortuous nerve bundles (Figure 2C) theoretically may also suggest associations with a form of a posttraumatic neuroma (in this case one may speculate of a “pseudocystic” form of it, Table 1).
Positivity for EMA – a reliable marker of perineurium  – may speak in favor of a perineurial cyst, which is frequently named Tarlov cyst (Table 1). Tarlov cysts typically occur in relation to intervertebral joints. However, they are reported in other locations including the pelvic region, where they mimic adnexal masses . On the other hand, positivity for D2-40 arises the possibility that the cyst could be related to lymphatics . Cystic forms of lymphangiomas (Table 1) were reported in the pelvic region . When involving the ovary, lymphangiomas present as adnexal masses consisting of solid and cystic areas and can cause lower abdominal pain . However, the positive immunostaining for both EMA and D2-40 in a similar expression pattern (Figure 2E and F) may in turn suggest a mesothelial character of the lesion  (mesothelial cyst, Table 1). Mesothelial cysts were also reported in this region . Nevertheless, EMA and D2-40 positivity was not present in the very inner surface of the lesion but deeper within its wall.
Alternatively, one has to remember that there is a small chance for another extremely rare cystic form of a tumor, for example pseudocystic metastases of non-functioning gastro-entero-pancreatic neuroendocrine tumors (NETs) as reported by Fiori et al. . Noteworthy is that also cystic metastases to the ovary with clinically overt primary tumors are common .
One should also not forget the possibility of a form of endometriotic cysts which not infrequently are devoid of any remnants of endometrium. However, typically they show evidences of previous hemorrhages (deposits of hemosiderin and/or siderophages). Such cysts deserve the term “hemorrhagic cysts of undetermined origin” . In the presented case, not a single siderophage, nor any trace of hemosiderin that could suggest an endometriotic origin of the cyst were found.
Last but not least, one may speculate upon an intraneural, un-specific inflammatory process of pathogenesis. Although we have not found any evidences of an active inflammatory reaction (like lymphocytes etc.) one cannot exclude that some parts of S-100 immunopositivity may be due to the presence of dendritic cells, which are involved in autoimmune inflammatory processes within the nerve (autoimmune neuritis for instance) . We may also hypothesize that an autoimmune inflammatory process terminated long ago could have lead to a cyst formation by creating osmotic pressure within the nerve. The same osmotic factor is probably also involved in synovial fluid pathogenesis of an intraneural cyst (ganglion) where synovium permeating the nerve bundle not only causes expansion of the nerve by pure hydrodynamic pressure but also acts by forming an osmotic force.Considering all aforementioned facts in the presented case, we think that there is no convincing evidence to attribute the lesion neither to perineurial nor lymphatic nor mesothelial origin. A development of the cyst inside the nerve seems to be especially convincing (Figure 2C and D) which makes the term “intraneural ganglion cyst” most suitable. However, immunopositivity for EMA and D2-40 in the presented case may suggest that there might be a contribution of perineurial and/or mesothelial elements to the structure of such pseudocysts located adjacent to the pelvic wall.
Lastly, one cannot help remarking that though it is very hard to find a more benign and innocuous lesion in human pathology in whichever site of the body as the cyst described here, even such a “simple” lesion demands cautious differential diagnosis. Moreover, a clinician, especially a gynecologist, being aware of the existence of lesions like reported here may be much more convincing trying to dispel any worries of a patient if confronted with a similar case.
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
D.A. (MD, PhD) is a specialist in pathomorphology and neuropathology and now at the position of Chair of Pathomorphology and Head of the Department of Neuropathology, Medical College, Jagiellonian University, Krakow (Poland). He is also a lecturer of pathology in the Faculty of Medicine of the Jagiellonian University.
C.J. (B.Sc.) is a student of biomedicine (master) at the Julius-Maximilians-University of Wuerzburg (Germany) doing an internship at the Chair of Pathomorphology, Jagiellonian University.
M.H. (MD) is a postgraduate/intern in pathomorphology at the Chair of Pathomorphology, Jagiellonian University.
R.J. (MD, PhD) is a specialist in Gynecology and Obstetrics and Gynecology and Oncology, Jagiellonian University. He is also a lecturer in Gynecology at the Medical Faculty of the Jagiellonian University.
B.G. (MD) is a postgraduate/intern at Gynecology and a junior assistant.
Ganglion cyst involving peripheral nerves
Epithelial membrane antigen
Gastro-entero-pancreatic neuroendocrine tumor.
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