Multimodal management of locally advanced rhabdoid tumour of the kidney in an adult

Abstract

Malignant rhabdoid tumours of the kidney (MRTK) are rare paediatric tumours known for their aggressive nature and early metastasis. However, MRTK in adults are even more rare with only a few cases reported in the literature. Herein, we report a case of 65-year-old woman with rapidly progressive left renal mass requiring en-bloc radical nephrectomy, splenectomy and distal pancreatectomy. Histopathology revealed a malignant rhabdoid tumour with characteristic histological and immunohistochemical findings with negative margins. To the best of our knowledge, this is the first reported case of aggressive surgical management of locally advanced MRTK. Despite surgery with curative intent, the patient developed early recurrence and started on tyrosine kinase inhibitor. Unfortunately, the patient expired after 8 months of surgery due to disease progression.

Background

Malignant rhabdoid tumours of the kidney (MRTK) are rare aggressive tumours of paediatric age group and frequently present with early metastasis. There is dearth in literature reporting MRTK in adults. While there are reports available for the management of localised adult MRTK, however, no reports are available on the management of a locally advanced MRTK. Herein, we report a case of rapidly progressive and locally invasive left renal mass requiring radical nephrectomy with en-bloc splenectomy and distal pancreatectomy.

Case presentation

A 65-year-old woman presented with complaints of storage lower urinary tract symptoms (LUTS) for 3 months duration. There was no history of flank pain, haematuria. Also, there were no cough, haemoptysis, breathlessness, jaundice and bone pains. The patient was diabetic, hypertensive and hypothyroid, optimised on oral medications. She had undergone a laparoscopic cholecystectomy 5 years ago. An ultrasonography of the abdomen revealed a left renal mass of 4×4 cm. Further, a contrast-enhanced computed tomography (CECT) showed a 4.8×4.2×4.6 cm heterogeneously enhancing mass in the upper pole of the left kidney. The mass was abutting the spleen and the tail of the pancreas. The renal vein and inferior vena cava were patent (figure 1A, B). She was referred to our tertiary care centre for further management. At the time of presentation, she was asymptomatic and her physical examination did not reveal any abnormality.

Figure 1.

CT images from preoperative and postoperative scenarios depicting tumour characteristics. (A) Initial CT image showing tumour of size 4.8 cm in the left kidney. (B) Initial CT image showing tumour abutting tail of pancreas and splenic hilum with maintained fat planes. (C) CT image within 3 months showing an increase in tumour size. (D) CT image within 3 months showing loss of planes between the tumour, the tail of pancreas and the splenic hilum. (E) Follow-up CT image at 3 months following surgery showing a well-defined cystic lesion in left renal fossa with no enhancing solid component. (F–H) Follow-up CT images at 6 months showing a large ill-defined solid lesion in left renal fossa with ill-defined fat planes.

Investigations

Her routine blood investigations including complete blood counts, renal function test, liver function test and coagulation profile were within normal limits. Her chest X-ray was normal. The CECT was repeated, which showed an increase in the size of the left renal mass as compared with the previous scans done 3 months earlier. In addition, the fat planes with spleen and the tail of the pancreas were lost on the current image. However, the right kidney and rest of the solid organs were normal (figure 1C, D).

Differential diagnosis

The presence of enhancing left renal mass on CECT suggested a working diagnosis of renal cell carcinoma. Involvement of surrounding structures suggested the locally invasive nature of the tumour. Other differential diagnosis included renal lymphoma or infiltrating transitional cell carcinoma. We did not consider a renal mass biopsy in view of absence of distant metastasis. Finally, the characteristics immunohistochemistry confirmed the diagnosis of MRTK.

Treatment

In view of the locally advanced disease, the patient underwent open left radical nephrectomy along with splenectomy and distal pancreatectomy. At the time of surgery, there were no ascites, omental or peritoneal deposits. The liver was cirrhotic, however there were no metastatic deposits. Tumour was densely adherent to the spleen and pancreatic tail, which were removed en-bloc with the renal mass. The estimated blood loss was 800 cc, and she received two units of packed red blood cells. In the immediate postoperative period, she was managed in the intensive care unit. However, the rest of the postoperative course was uneventful and eventually discharged on the fifth postoperative day.

Outcome and follow-up

The histopathological examination revealed sheets of discrete intermediate to large-sized rhabdoid cells with prominent nucleoli. The tumour was invading the renal sinus. It was also extending up to the renal capsule and involving the perinephric fat. There was also focal invasion into the splenic hilum and the pancreatic parenchyma. However, the resected margins were free of tumour (figure 2A–C). Immunohistochemical analysis revealed that the tumour cells were strongly positive for pan-cytokeratin with retained integrase interactor 1 (INI-1) nuclear protein expression while negative for CK7, desmin, myogenin and P40 suggesting a diagnosis of MRTK (figure 2D–H). The pathological stage was pT4NxM0.

Figure 2.

Photomicrographs of the renal tumour mass showing diffuse sheets of discrete cells (A; He ×40). These cells on higher magnification showing rhabdoid morphology with an eccentric nucleus and vesicular nucleus with prominent nucleoli (B and C; He ×400). The tumour cells are immunonegative for Alpha-methylacyl-CoA racemase (AMACR) (D). Immunopositivity for vimentin (E; diffuse and strong), pan-cytokeratin (F; patchy and strong). Immunostain for INI-1 was retained (G). The tumour cells were immunonegative for desmin (H). INI-1, integrase interactor 1.

At 3 months follow-up, the patient was asymptomatic. The follow-up CECT showed a well-defined loculated cystic collection of about 54×32×65 mm in the left renal fossa. There was no solid enhancing component or lymph nodal enlargement (figure 1E). The patient did not give any history of fever and was kept on observation. However, the follow-up CECT at 6 months revealed a 12×12×9 cm large lobulated heterogeneously enhancing mass in the operative bed suggestive of local recurrence of the tumour (figure F–H). The patient was started on sorafenib 400 mg two times per day. At the time of last follow-up, the patient was asymptomatic and tolerated sorafenib. While awaiting the next follow-up, the patient succumbed to the disease 2 months later.

Discussion

MRTK is a rare tumour of the paediatric age group, comprising about 1.8% of all malignant renal tumours. Its incidence is even rarer in adults with only a few reported cases in the literature.¹ Beckwith and Palmer previously described MRTK as a rhabdomyo-sarcomatoid variant of Wilms tumour as the cells resembled rhabdomyoblasts. However, further studies with ultrastructural analysis failed to demonstrate any myogenic differentiation.^{2 3}

To the best of our knowledge, only eight cases have been reported on adult MRTK and we will discuss a brief review of literature with our present case. In our review of literature, age at presentation ranged from 32 to 79 years with no known sex predilection. Common presenting symptoms were flank pain, abdominal distension, fatigability and weight loss. Two (25%) patients had pulmonary symptoms, while one (12.5%) had haematuria at the time of initial presentation. Incidental renal mass was detected in one case (12.5%). This neoplasm has a left-side predominance (75%) with only two reported cases of right kidney involvement.^{2 4–10} MRTK are aggressive tumours with 62.5% patients presented in advanced stage. Lung was the most common site of metastasis (37.5% of cases).^{4 5 9} In the present case, an incidental left renal mass was detected while evaluating for LUTS. The tumour progressed in size, found invading the spleen and the distal pancreas within 3 months of initial imaging suggesting an aggressive nature.

Complete surgical removal with adequate negative margins is the key to successful outcome. The characteristic histopathology findings include sheets of non-cohesive tumour cells with eosinophilic, fibrillar cytoplasmic inclusions, along with eccentric nuclei and prominent nucleoli. It’s striking immunohistochemical features of positive vimentin and negative desmin and myoglobin suggest mesenchymal origin. Pan-cytokeratin positivity is variable. In our case, the tumour cells were strongly positive for pan-cytokeratin with retained INI-1 nuclear protein expression. INI staining differentiates pure rhabdoid tumours from composite renal tumours with secondary rhabdoid differentiation.² It was hypothesised that there is no single cell of origin for MRTK, but multiple cell lineages. This results from congenital or acquired mutations in INI-1 gene.² Deletion or mutation of Chromosomal 22q11.2 leads to mutation in INI-1 tumour suppressor gene, which is implicated in renal and extrarenal malignant rhabdoid tumours, and these studies have firmly established MRT as a distinct entity.¹¹ Loss of INI-1 protein nuclear expression can also differentiate between pure rhabdoid tumour and rhabdoid transformation of clear-cell, papillary, chromophobe renal cell carcinoma and transitional cell carcinoma.^{2 12}

Essential features for pathologic diagnosis of MRTK include histological features showing rhabdoid features and immunohistochemistry suggesting absence of INI-1 protein nuclear expression. Electron microscopic demonstration of cytoplasmic intermediate filaments in whorls or swirls provides additional support for the diagnosis.²

Surgery is considered to be the best mode of therapy in feasible cases. To the best of our knowledge, no guidelines are available for the management of advanced MRTK. However, we followed EAU guidelines on management of renal cell cancer in the management of this patient.¹³ There is paucity of data on effect of adjuvant treatment in patients with MRTK. Few researchers have tried immunotherapy and chemotherapy in the advanced stage, but with mixed results. Ebbinghaus et al was the first to show objective antitumour response to low-dose IL-2 in a case of metastatic adult MRTK.⁹ Koos et al found a consistent expression of tyrosine kinase expression c-Abl in rhabdoid tumour cell lines. They showed treatment with tyrosine kinase inhibitor imatinib resulted in reduced cellular growth.¹⁴ In a clinical set-up, Kapoor et al showed the efficacy of sorafenib in an adult with advanced MRTK reporting a stable disease at 1 year follow-up.¹⁵ We started our patient on sorafenib following the local recurrence, but she had disease progression and could not survive the disease. Immunotherapy has shown some benefit in the treatment of malignant rhabdoid tumours of other body organs. In one of such reports, pemborlizumab had shown a significant reduction in tumour load in thoracic malignant rhabdoid tumours. Reason of its response is still under investigations.¹⁶ Detailed evaluation of human and mice rhabdoid tumours, including immunohistochemistry, RNA sequencing and DNA methylation studies,¹⁷ showed a high degree of tumour infiltration by T cells and cells of myeloid lineage. T-cell receptor and single cell RNA sequencing revealed the heterogeneity of these cells and potential targetable receptor and development of CD8+ T cell, suggesting a tumour-specific response.¹⁷ Immune checkpoint inhibitor therapy in an experimental rhabdoid tumour model induced effective immune response and remarkable regression of tumour.¹⁶ Initial reports suggest a potential therapeutic role of immunotherapy in systemic treatment of rhabdoid tumours, as their immunohistochemical profile is encouraging.^{9 16 17}

Differential diagnosis includes rhabdoid differentiation of renal cell cancer¹⁸ and rhabdoid differentiation of transitional cell cancer.¹⁹ Rarely metastasis to the kidney may also mimic primary renal malignancies.²⁰ The present case is unique from previous reports in the surgical approach used. In contrast to previous reports, we did en-bloc removal of the left kidney along with the spleen and distal pancreas to achieve R0 resection. Despite negative margins in the final histopathology, the patient developed local recurrence within 6 months duration and died from the disease at 8 months follow-up. This suggests the aggressive nature of the tumour. In general, MRTK is associated with poor prognosis and high mortality, as a majority of them have metastasis at the time of initial presentation. Lacunae exist in the natural history and ideal treatment protocol of adult MRTK. Further larger case series with long-term follow-up is needed to clarify such queries.

Learning points.

• Adult malignant rhabdoid tumours of the kidney is an extremely rare and aggressive renal tumour with a propensity for early recurrence.

• The characteristic immunohistopathological findings may aid in reaching the diagnosis.

• Aggressive surgical approach including en-bloc removal of surrounding structures can be considered in achieving negative surgical margins.

• Early recurrences are common despite complete removal and the adjuvant therapy protocols are still lacking.

• Despite aggressive management, prognosis appears to be poorer compared with other renal cell cancers.

• Even in absence of metastases up front use of Tyrosine kinase inhibitors (TKI) in locally advanced MRTK may be tried to improve survival.