Non-functioning retroperitoneal abdominal schwannoma

Abstract

There are less than 150 cases of non-functioning retroperitoneal abdominal schwannoma (NRS) reported. Hormonal assay is crucial in confirming the diagnosis of NRS, as manipulation of a functional retroperitoneal paraganglioma will instigate an abrupt liberation of catecholamines, resulting in devastating consequences. We report the case of 42-year-old woman who presented with headache, night sweats and abdominal discomfort. Cross-sectional imaging demonstrated a retroperitoneal mass adherent to the aorta and inferior vena cava but biochemical testing of blood and urine was negative for metanephrines and normetanephrines. She underwent successful tumour resection via laparotomy, as location increased the complexity and risk of laparoscopic resection.

Background

Non-functioning retroperitoneal abdominal schwannomas (NRS) are asymptomatic due to ample retroperitoneal space that allows the tumour to reach a large size without affecting the adjacent organs.¹ NRS represent 3% of all schwannomas and less than 1% of all retroperitoneal tumours. Ninety per cent of schwannomas are solitary and 4% are associated with neurofibromatosis type 2.^2–4

Most NRS are benign; however, malignant schwannomas may be associated with von Recklinghausen disease.⁵ There are less than 150 cases of NRS reported in the English literature.^6–13 It is essential to perform a pretherapeutic biopsy, even in cases of apparent respectability, and a preoperative biopsy was undertaken in this case, after confirming biochemical inactivity. A preoperative biopsy is contraindicated, if a pheochromocytoma is suspected.

The importance of confirming this diagnosis lies in the fact that preoperative manipulation of a functional or potentially functional retroperitoneal paraganglioma will instigate an abrupt liberation of catecholamines, commanding devastating consequences.¹³

Consent for publication of patient data was obtained according to the principles outlined in the Declaration of Helsinki.

Case presentation

We present the case of a 42-year-old woman, whose chief problems were headache, night sweating, mild abdominal pain and palpitations. Abdominal examination was unremarkable and her abdomen was soft and non-tender. Twenty-four hour urine collection for metanephrine and normetanephrine levels and blood catecholamine studies, including plasma-free metanephrines, were negative.

Investigations

An abdominal pelvic computerised tomographic angiography (CTA) scan delineated a retroperitoneal, para-aortic, retro duodenal solid mass encasing inferior vena cava (IVC) from iliac vein bifurcation to the level of the suprarenal veins (figure 1A–C).

Figure 1.

(A) Computerised tomographic angiography (CTA) non-functioning retroperitoneal abdominal schwannoma (NRS) totally compressing inferior vena cava and pushing it anteriorly and aorta lies to the left. (B) CTA lateral view shows almost total obliteration of the inferior vena cava lumen by external compression by the NRS. (C) CTA’s sagittal view shows almost total obliteration of the inferior vena cava lumen by external compression by the NRS. (D) Magnetic resonance angiography showing the tumour lying posterior to the inferior vena cava and to the right of the aorta.

Magnetic resonance angiography (MRA) documented the same results (figure 1D). MRA of our patient (figure 1D) confirmed the split fat sign (rim of fat surrounding the tumour), the bright rim sign on high T2 signal of the periaortic/IVC mass, with no peritumoral oedema or lobulation and a distinct capsule compressing IVC. The lack of significant enhancement is due to cystic degeneration which correlates with high T2 signal.

The mass measured 55×48×35 mm³ in volume, with rounded, homogenous, necrotic, cystic areas in the centre of the tumour close to the intervertebral foramen (figure 2A, B). A CTA scan with a guided biopsy confirmed no mitotic activity (figure 2).

Figure 2.

(A) Fully excised non-functioning retroperitoneal abdominal schwannoma with intact capsule. (B) Transverse section showing the yellowish necrotic core. (C) A medium power magnification of the tumour, with H&E stain, demonstrating the typical spindle cell morphology of schwannoma. (D) This shows the diffuse positive reaction for S100 in the lesional cells by immunohistochemical staining.

The immunohistochemistry was strongly positive for S100 (figure 2D), a neurogenic marker, with negative markers for leiomyoma including desmin, caldesmon and actin. Gastrointestinal stromal tumour (GIST) assays for Receptor tyrosine kinase (C-KIT) and discovered on GIST 1 (DOG1) were negative. These results increased the likelihood of NRS.

Differential diagnosis

The differential diagnosis from pheochromocytoma, paragangliomas, leiomyosarcoma, lymphoma or retroperitoneal, extragonadal teratomas or seminoma is challenging as imaging studies usually lack specificity for differentiating schwannoma. Schwannoma size and heterogeneous CT appearance are often due to areas of haemorrhage, necrosis and cystic changes. This complicates radiological confirmation without immune-histochemistry.

Treatment

Following multidisciplinary team discussion and consensus, the patient consented for an exploratory laparotomy. Through a midline incision, the posterior peritoneum was incised, ligament of Trietz was cut and the duodenum was mobilised. The tumour was resected caudally to cranially. The solid tumour was peeled from the distal aorta first towards the IVC caudally until the distal end of the tumour was lifted, then the tumour was followed towards the left renal vein until entirely excised.

The tumour was adherent to the IVC and aorta with strong fibrotic adhesions, so a combination of surgical titanium clips, sharp dissection and a LigaSure device (Medtronic, Santa Rosa, California, USA) were used in order to secure several feeding vessels originating from the retroperitoneum and draining from the tumour into the IVC. The tumour, together with the intact capsule, was resected curatively (figure 3A–C). We performed total retroperitoneal adenectomy. The abdomen was closed in layers. The patient was discharged home on the fourth postoperative day.

Figure 3.

(A) Non-functioning retroperitoneal abdominal schwannoma (NRS) compressing the inferior vena cava. (B) NRS compressing the inferior vena cava with right ovarian vein transversing anteriorly and the aorta lying posteriorly. (C) Excision of the whole tumour with intact capsule.

The tumour weighed 61 g and was fully encapsulated. Slicing showed yellow grey cut face with frequent degenerative and necrotic changes, with focal haemorrhage, which could explain the bouts of severe abdominal pain. The tumour was formed predominately of spindle cells in intervening fascicles with eosinophilic cytoplasm in a collagenous compact stroma. There were Antoni A tissue in hypercellular areas and Antoni B tissue in hypocellular areas.

The tumour was traversed by hyalinised vessels with infiltration of macrophages and lymphoid aggregates with a small segment of a nerve at the periphery. An immunohistochemical panel for schwannoma confirmed positive diffuse S100 (figure 1D) antibodies with focal positivity of broad-spectrum cytokeratin marker AE1/3 confirming the diagnosis. There were negative results for desmin, smooth muscle actin, cluster of differentiation 117 (CD 117) and DOG1. All lymph nodes were negative for mitotic activity or GIST with no evidence of C-KIT and DOG1.

The morphological findings, overall histopathologic assessment and the immunohistochemical staining profile, were consistent with a benign peripheral nerve schwannoma with marked regressive changes. All symptoms from the preoperative stage were not present postoperatively.

Outcome and follow-up

None of the signs and symptoms observed preoperatively was present postoperatively and there has been no report of recurrence at 1 year. We recommended lifelong follow-up with abdominal pelvic ultrasound.

Discussion

The diagnosis of non-functional retroperitoneal paraganglioma is an arduous task that renders the surgery more challenging. Our case highlights the importance of including extra-adrenal paraganglioma in the differential diagnosis of retroperitoneal tumours. Retroperitoneal schwannomas¹⁴ are rare but adrenal gland schwannomas are the rarest and are realised serendipitously. Most of them are discovered as a non-secreting mass in asymptomatic patients. Adrenal incidentalomas¹⁵ are mostly cortical adenomas, carcinomas or medullary lesions like pheochromocytoma, neuroblastoma and ganglioneuroma, and all may be diagnosed preoperatively by immune-histochemistry.

Currently, there is no way to predict metastatic risk definitively. As recurrence and metastasis are common, lifelong follow-up is required.¹⁶ The most common site of sympathetic paragangliomas is in the organ of Zuckerkandl at the aortic bifurcation, consistent with the distribution of paraganglia first characterised in the human fetus by Zuckerkandl in 1901^{17 18} The median age of diagnosis for retroperitoneal paragangliomas is 37–43 years and the incidence is similar between men and women.¹⁹

Nakashima et al²⁰ categorised schwannomas into two groups: Antoni type-A tissue with a compact cellular region in a palisade or turbinate pattern and Antoni type-B tissue with a loose, hypocellular and myxoid region with a microcystic space that is composed of myxoid and degenerated tissue with fewer cells and a gelatinous substance.

Both pathologies were identified in our case. NRS has an inadequate response to chemo or radiotherapy, and surgery is the gold standard with complete tumour excision, inclusive of the capsule, pseudocapsule with the neovascularisation zone and retroperitoneal adenectomy.² Surgery is the optimal treatment provided that it is complete, with survival rates of 75% and 45% at 5 and 10 years, respectively.²¹

A genetic predisposition, with RNA deletion or mutation, will increase the risk of paraganglioma. Associated conditions include multiple endocrine neoplasia type 2 syndrome, von Hippel-Lindau syndrome, neurofibromatosis type 1, hereditary paraganglioma syndrome, Carney-Stratakis dyad of paraganglioma and GIST or Carney triad of paraganglioma, GIST, pulmonary chondroma and gene mutations of the subunits of succinate dehydrogenase.^{22 23}

Ji et al¹³ identified that the functional tumour presents at a smaller size of 2.5–3 cm. He reviewed 34 cases and described tumours that were located in the para-aortic plexus or mesenteric artery region, to the left side and posterior to the IVC, originating from the para-aortic plexus or from the intervertebral foramen, and they were most probably schwannomas.

CTA can demonstrate a close relationship between the NRS and the intervertebral foramen, which confirms the diagnosis, but absence of this relationship does not exclude schwannoma.⁶ In our case, the heterogeneous NRS correlated with the histopathology and partly pronounced regressive changes. In our patient, although the tumour was in close contact with the aorta and IVC, the resection was complete. The proximity of the tumour to the aorta and vena cava increased the potential complexity of laparoscopic resection and the risk of bleeding.⁶ When lesions are amassed within the adventitia of these vessels, the risk of vessel injury, and the fatal consequences thereof, dictates an approach which allows for rapid vessel control. Preoperative cross-sectional imaging demonstrated an inflammatory fibrous mass involving the lesion and both great vessels, with no discernible surgical plane between the lesion and vessels. Laparoscopic techniques have been very successful in experienced hands, especially when cross-sectional imaging demonstrates a clear lack of infiltration into the surrounding tissues, thereby rendering enucleation and full tumour removal likely.^{24 25} Cross-sectional imaging did not provide this surety in the current reported case, rather it demonstrated likely inflammatory response involving the tumour and great vessel adventitia. Safe laparoscopic and robotic excision of retroperitoneal schwannoma have been described.^{26 27} With increasing experience and expertise, these approaches may become safer for complex lesions and reduce morbidity associated with the procedure. According to the expertise of the team and in view of the size of the lesion, and the appearance of inflammatory tissue on preoperative imaging that encased the lesion and the large vessels, this lesion was excised via laparotomy. The patient was recovered without complication and was discharged on the fourth postoperative day.

Schwannomas demonstrate typical MRI features of T1 iso-to-hypointensity and T2 hyperintensity. The target sign consists of intermediate T2 signal centrally due to the fibrous tissues, with high T2 signal peripherally due to myxoid tissues. The fascicular sign signifies multiple ring-like structures, consistent with fascicular bundles similar in cross-section to normal nerves.²⁸ The fascicular sign was not evident in our study, like in most schwannomas which are retroperitoneal, however the target sign was present.

Features that favour malignant transformation include ill-defined margins and larger size more than 5 cm, however our case was more than 6 cm, but proved to be benign on immune-histochemistry. An ominous sign for a neurogenic neoplasm is muscle atrophy within the nerve distribution which was absent in our patient. However, distinguishing benign schwannomas from malignant soft-tissue tumours on MRI is challenging and often not possible.²⁹

Despite studies of pleomorphism, mitotic activity or vascular invasion of the tumour, the evolution is unpredictable. The prognosis is dependent on the expression of neuropeptides protein S100, which is abundant in the highly vascular appearance of sustentacular cell protein.³⁰

Approximately 20%–42% of extra-adrenal sympathetic paragangliomas metastasise. Sites of metastasis include lymph nodes, and that is why we performed retroperitoneal adenectomy. Metastatic lesions have a poor prognosis, with a reported 5-year survival rate of 36%.^{31 32}

NRS is an uncommon entity, and the diagnosis is a challenge, since clinical examination, imaging and morphological properties are commonly undefined. Large non-secreting well-encapsulated heterogeneous tumours must be biopsied percutaneously once biochemical inactivity is confirmed.

We must have a high index of suspicion if a retroperitoneal tumour is closely adjacent to a neural structure in imaging studies.⁹ Complete surgical excision is the gold standard, and incomplete excision is the most common cause of recurrence. We recommend lifelong follow-up.

Learning points.

• Ample retroperitoneal space allows non-functioning retroperitoneal abdominal schwannoma (NRS) to reach a large size without affecting the adjacent organs.

• Biopsy is an essential prerequisite, after excluding a pheochromocytoma by hormonal assay, as a functional retroperitoneal paraganglioma will instigate an abrupt liberation of catecholamines if a biopsy is taken and will result in devastating consequences.

• NRS has an inadequate response to chemo or radiotherapy, and so complete tumour excision, inclusive of the capsule, pseudocapsule with the neovascularisation zone and retroperitoneal adenectomy, is necessary.

• The prognosis is dependent on the expression of neuropeptides protein S100.

• Incomplete excision is the most common cause of recurrence and lifelong follow-up is mandatory.