Primitive neuroectodermal tumour (PNET) of the renal capsule mimicking solid adrenal tumour

Abstract

Primitive neuroectodermal tumour (PNET) of renal capsule is a rare entity. We report a case of a 17-year-old girl, who presented with symptoms of epigastric and right hypochondrium pain since 1 year. She was afebrile and physical examination revealed a soft, non-tender, firm, bimanually palpable and ballotable mass along right flank. Ultrasound abdomen showed a large heteroechoic mass in right suprarenal region with indistinct planes with upper pole of right kidney. On CT, a large right suprarenal mass was noted with origin likely from right adrenal gland. Surgery was done and intraoperatively, the large mass in right suprarenal region showed involvement of the upper pole of the right kidney. The right adrenal gland was small in size, compressed and displaced by the lesion. Histopathology revealed the mass to be PNET of kidney. We report the relevant imaging findings of the case with review of literature of this entity.

Background

Primitive neuroectodermal tumours (PNETs) arise from neural crest cells and form an important subtype of histological group of small round cell tumours.¹ Extraskeletal PNETs usually present as soft-tissue masses, and PNET genitourinary system is particularly rare.² Few case reports of rare extraskeletal PNETs involving locations like kidney, bladder, prostate, testis, epididymis, ovary and uterus have been described.^3–6 At times it is difficult to differentiate an adrenal neoplasm from a mass arising at the upper pole of kidney.⁷ It is also imperative to differentiate PNET from other common renal neoplasms like renal cell carcinoma (RCC), Wilm’s tumour and so on to initiate appropriate management protocol.⁸ PNETs of kidney usually present in childhood or adolescence, and have higher likelihood of distant metastases with poorer prognosis. Histopathological examination with immunohistochemistry (IHC) form the confirmatory diagnostic tests.^{9 10}

Case presentation

A 17-year-old girl was admitted in our hospital with problems of abdominal pain and distension since 12 months. On further elucidation, she had significant weight loss of about 7 kg over the past 1 year. Physical examination showed a large right flank mass which was firm to hard in consistency and non-tender and showed ballotibility. No significant palpable peripheral lymphadenopathy was present. No associated overlying skin changes were present. Her vital signs were within normal limits.

Investigations

Laboratory findings showed that red blood cell counts, platelet counts and peripheral blood smear were within normal limits. Rest of routine biochemical evaluation did not reveal any abnormality. Serum erythropoietin and haemoglobin levels were normal.

Abdominal ultrasonography (USG) revealed a large heteroechoic mass at right suprarenal region with indistinct planes with upper pole of right kidney. Few small cystic/necrotic areas were seen within. No definite calcification noted on USG. Doppler interrogation showed raised internal vascularity. No significant retroperitoneal adenopathy was seen. There were no focal lesions within liver or any intra-abdominal free fluid.

In view of a right suprarenal mass on USG, of likely adrenal origin, we performed an adrenal protocol CT with CT angiography (CTA) for further characterisation and mapping. CT protocol included an unenhanced phase, contrast-enhanced arterial phase at 20 s after bolus tracking and saline chasing technique, a subsequent venous phase at 60 s post contrast injection and a delayed phase at 15 min post contrast administration. The scan was performed on a 64-slice multidetector CT scanner (Philips Ingenuity, Philips Healthcare, Cleveland, Ohio, USA) with 80 mL of 350 mg/mL of intravenous non-ionic contrast medium (Iohexol: Omnipaque, GE Healthcare, Marlborough, USA) with automated exposure control. Add field of view (FOV), slice thickness.

CT showed a large, heterogeneously hypoenhancing mass with cystic/necrotic components epicentred at right suprarenal region. No foci of calcification or fat was seen within. The right kidney was displaced inferiorly and medially by the mass which showed indistinct fat planes with upper pole of right kidney. No definite renal ‘claw’ was seen. Right adrenal was not visualised separately from mass in the multiplanar planes. Furthermore, there was abutment of inferior surface of liver and inferior vena cava (IVC) with indistinct fat planes with the post wall of IVC. There was no extracompartmental spread to peritoneal cavity and no enlarged locoregional or distant lymph nodes. No secondaries were seen in liver and a CT scan of chest performed subsequently did not show any pulmonary metastases.

A prominent feeder from the right renal artery was seen on CTA (figure 1). No filling defect was seen in the right renal vein or IVC. The delayed scan revealed the lesion showing mass effect on the right upper pole calyces with their inferior displacement (figure 2). The relative and absolute washout patterns were calculated to be 3.5% and 11.1%, respectively.

Figure 1.

(A) CT non-contrast images revealing a heterogenous density right supra renal mass. (B) Contrast-enhanced CT (arterial phase) with maximum intensity projection images in coronal and (C) axial sections showing raised intra and perilesional vascularity of mass with a prominent feeding artery (black arrows in B) arising from right main renal artery. (D) Volume rendered tomography images show displaced right kidney with mass effect on main renal artery.

Figure 2.

(A) and (B) Axial and sagittal contrast-enhanced CT (venous phase) showing large right supra renal mass showing heterogenous enhancement with central necrosis abutting the posterior wall of inferior vena cava with loss of fat planes (arrow in A). Absence of claw sign with blunt edges (arrow head in B) of right kidney. (C) Coronal delayed phase and (D) volume rendered images of delayed phase showing inferiorly compressed upper pole calyces by the right supra renal mass.

The lesion showed signs of being extrarenal in origin: negative beak sign, negative embedded organ sign, positive phantom sign in form of absent right adrenal gland and prominent feeding artery sign. The endocrinological workup with plasma and urinary metanephrines was negative for pheochromocytoma. Serum cortisol levels were not raised.

Differential diagnosis

As the retroperitoneal signs were in favour of an adrenal lesion on imaging, our first differential diagnosis was adrenal cortical carcinoma, with less likely possibility of high-grade lymphoma or adrenal secondaries with remote possibility of exophytic renal capsular sarcoma in view of young age of the patient and exophytic RCC.

Treatment

A decision was made to excise the tumour with consent for intraoperative nephrectomy as per intraoperative findings. In view of high vascularity of lesion, a preoperative angioembolisation was planned. Digital subtraction angiography showed prominent feeders from upper pole branch of main right renal artery. These were embolised with gel foam mixed with iodinated non-ionic contrast. Intraoperatively, a large necrotic mass epicentred at right suprarenal region was seen with infiltration of right renal upper pole and with involvement of posterior wall of IVC. Intraoperatively, right adrenal gland could not be localised separately. However, intraoperative frozen section revealed it to be a mass of renal origin. Right nephrectomy with adrenalectomy was performed with partial IVC wall resection.

Outcome and follow-up

On gross pathological examination, the mass was seen infiltrating the renal parenchyma and right adrenal gland was small, thinned out and pushed posterosuperiorly (figure 3). Histopathology with IHC staining showed a large round blue cell tumour with infiltration of the capsule of the right kidney. Tumour was seen localised to the renal capsule, confined within the perinephric fat between renal capsule and adrenal gland. The renal sinus and pelvis were free of tumour. The posterior wall of IVC showed infiltration by the mass till the adventitia. The right adrenal gland was free from tumour cells. Resected subcentimetric locoregional lymph nodes were reactive. The cells were positive for CD99 and vimentin and negative for desmin, myogenin, PanCK (cytokeratin), neuron-specific enolase (NSE) and synaptophysin. The histopathological examination with IHC markers suggested PNET (figure 4A, B). In view of imaging findings and gross pathological examination, the likely origin of the tumour is thought to be renal capsule.

Figure 3.

(A) Photograph of gross specimen showing tumour contained within the capsule of renal fascia. (B) Cut open specimen showing grey and brown, centrally necrotic mass infiltrating the upper pole of kidney.

Figure 4.

Microscopic staining showed that the tumour comprised small round to ovoid cells disposed in sheets and rosettes. The cells showed high nucleocytoplasmic ratio, hyperchromatic nuclei and scant cytoplasm (H&E staining; original magnification ×200 in A, B, C). (B) Photomicrograph shows that the tumour cells (*) can be seen separate from renal parenchyma with intervening renal capsule (black arrows). (C) The adrenal gland parenchyma (black arrowhead) can be seen separately, free from tumour cells. (D) Immunohistochemistry showing expression of CD99 marker in tumour cells (immunostaining with CD99; original magnification ×200).

The patient withstood the surgery well and was discharged at 10 days post procedure. She has been referred to medical oncology for appropriate adjuvant chemotherapy.

Discussion

Peripheral PNETs were recognised as subgroup of ‘small round cell neoplasms’ in 1918 by Arthur Purdy Stout.¹¹ Peripheral PNETs have a low incidence rate, contributing to only 1% of all sarcomas.¹² Renal PNETs presenting at a young age tend to show an aggressive spread. A mild male predominance is seen. In a study by Thyavihally et al, it was seen that most lesions (63%) were localised to kidney. Surgical excision is the treatment of choice which has shown long-term survival benefits.¹³

Certain named radiological signs help in localisation of tumour and help in determining the organ of origin especially in the retroperitoneal lesions. They include (1) beak sign—mass deforms the edges of its organ of origin into a beak shape; hence it is called positive beak sign. When an adjacent organ shows dull edges with the mass, it means that the mass compresses the organ but does not arise from and is called negative beak sign; (2) phantom (invisible) organ sign—a large mass arising from a small organ makes the small organ undetectable; (3) embedded organ sign—mass compresses the adjacent plastic organs like IVC and bowel into a crescent shape; and (4) prominent feeding artery sign-hypervascular tumours cause enlargement of the tumour supplying vessel, which gives a clue to identifying the organ of origin of the mass.¹⁴ In our case, the lesion showed negative beak sign with kidney, negative embedded organ sign (compression of IVC) and phantom organ sign as right adrenal was not seen separately despite multiplanar reconstruction views. Hence, in our patient, it was initially thought to be of adrenal origin. On histopathology, the tumour showed localisation to renal capsule. Thus, we have tried to show that in cases of tumours arising from renal capsule these retroperitoneal signs may not be very sensitive in detecting the exact localisation of the tumour and may show false-negative features. However, in younger children presenting with large exophytic renal mass, we must think of renal capsular PNET as a differential.

A retrospective review of literature showed that radiological findings seen in retroperitoneal PNETs were similar to our case. They usually present as a large mass with areas of necrosis, heterogeneous enhancement on contrast imaging with more aggressive lesions showing features of vascular invasion and metastasis. Thus, a large renal PNET with extensive necrosis would closely mimic a cystic RCC.¹⁵ Few imaging features have been described in literature by Lee et al which are help in differentiating PNET versus RCC.¹⁶ Renal PNET showed multiple irregular septum like structures within both the necrotic and solid areas of the tumour, which microscopically corresponded to intertumoral nodules separated by fibrovascular septae composed of small round cells.¹⁶ Large RCCs generally show central necrosis with or without haemorrhagic areas whereas a large renal PNET shows multifocal or diffuse areas of haemorrhage or necrosis. Renal PNETs tend to be hypoenhancing as compared with renal parenchyma, whereas the commoner clear cell variants of RCC tend to be hyperenhancing lesions. PNETs tend to be more aggressive as compared with RCC in terms of vascular invasion. RCC and Wilm’s tumour show foci of calcification whereas very few PNETs show calcific foci within.¹⁷ However, despite described differences in imaging pattern, there is usually a diagnostic dilemma that remains in differentiating a large RCC versus a renal PNET on imaging. Intraoperative frozen sections play a key role in identifying the organ of origin of a large tumour, especially located at the upper pole of the kidney where the possibility of renal or adrenal tumour cannot be delineated clearly.¹²

Microscopically renal PNET shows proliferation of small round cells in nests and rosettes diffusely infiltrating the renal parenchyma. In our case, the small round to oval tumour cells was seen separate from the renal parenchyma with intervening layer of renal capsule. The renal capsule was infiltrated by the tumour cells (figure 4C, D). An appropriately selected IHC panel has a key role in differentiating renal PNET from other small round cell tumours of the kidney like rhabdomyosarcoma, neuroblastoma, clear cell sarcoma, desmoplastic small round cell tumour, carcinoid tumour, nephroblastoma and Ewing’s sarcoma. The presence of macrophage inhibitory cytokine (MIC-2) gene product known also as CD99, 12E7, E2, 013 and HBA71, strongly suggests PNET. PNET cells express vimentin, NSE and CD99. Thus, a positive reaction to CD99 is a strong clue to diagnosis of PNET.^{18 19} In our case, the tumour cells were positive for CD99 and vimentin on IHC.

A 5-year survival rate of 70% with localised disease and 40% with metastatic disease is seen in renal PNET. Initial treatment comprises radical nephrectomy and radiation therapy for local disease control, followed by chemotherapy.²⁰

Due to biological similarity of renal PNET with Ewing’s sarcoma, a similar chemotherapy regimen is followed for both. Despite aggressive treatment with combination of surgery, chemotherapy and radiotherapy, the prognosis remains poor with overall 5-year survival rates reported at 45%–55%.¹³

Radiation therapy is useful in treating patients with non-resectable margins or positive margins/residual disease.

As our case had a confined mass which was amenable to resection with no locoregional lymph nodal spread, surgery was the treatment of choice, but as the mass showed infiltration of the posterior wall of IVC, radical nephrectomy was done with negative margins on histopathology. Patient has been sent for adjuvant chemotherapy.

In conclusion, renal PNETs are rare and tend to be locally aggressive, invariably presenting with features of vascular invasion. If these lesions arise from upper pole of kidney with likely capsule origin, they may give a false impression of adrenal origin; hence, they must be included in differentials of renal masses in adolescent age group of patients. IHC is the mainstay to confirming the diagnosis of PNET; an aggressive multimodality treatment is recommended to manage these tumours.

Patient’s perspective.

I am the child’s father. My daughter always complained of pain along with distention of abdomen. She had lost her appetite in the last 1 year. We came to the hospital to show as she had no relief despite taking medication at a local doctor near our home town. Here we were shocked when we found out that she had a tumour in her right kidney. The doctors ran multiple tests along with ultrasound and CT scan. I was told that she would need a surgery. I was told that if need arises, they may have to remove her right kidney along with the tumour. She underwent the scheduled surgery and was kept in post-operative ICU care at hospital. She was shifted to ward on the second day post surgery. The doctors told me that the tumour was large in size and was successfully removed, however they told me that the right kidney had to be removed as the tumour was closely attached to it. They also advised that she could carry on with life as the left kidney would compensate for the body functions. We were happy that the operation was successful. She started taking oral meals after 2 days of surgery. We have been told that although the tumour has been removed, we will have to take her for chemotherapy sessions after being discharged from here. Am just happy that my daughter has fought this disease with bravery and that we had such a cooperative staff and such strong doctor support.

Learning points.

• In a young patient with renal mass, renal primitive neuroectodermal tumour should be considered among differentials.

• Not all renal neoplasms are renal cell carcinoma.

• The retroperitoneal localising signs for renal versus non-renal lesions can be false negative in cases of exophytic renal tumours.