Primary renal embryonal rhabdomyosarcoma in an adult patient

Abstract

Adult renal rhabdomyosarcoma (RMS) is a rare and aggressive entity with a paucity of data and reports in the literature. As a result, treatment guidelines for this malignancy are not well-established. Herein, we present the diagnosis, management and clinical course of a 39-year-old patient diagnosed with primary renal embryonal RMS (ERMS) following radical nephrectomy. We also review the existing literature on primary renal ERMS.

Background

Sarcomas represent only 1%–3% of primary renal tumours.¹ Of these, rhabdomyosarcoma (RMS), an aggressive tumour that arises from muscle progenitor cells, accounts for a very small number of sarcomas in the adult population. RMS can be classified into four subtypes: alveolar, embryonal, spindle-cell and pleomorphic.² While an estimated 25% of embryonal RMS (ERMS) cases in adolescents involve the genitourinary system, there are only a few genitourinary RMS cases reported in the adult literature.³ Our thus case adds to the limited amount of data on this disease.

These tumours are known to present late and behave aggressively in adults, with the majority of cases being metastatic at presentation.² Radiographically, primary renal RMS has characteristics similar to renal cell carcinoma with no predictive features on CT imaging. Thus, definitive diagnosis is dependent on postoperative immunohistochemical analysis after surgery.^{3 4} Grignon et al first established criteria necessary to make the diagnosis of primary sarcoma of the kidney. Three criteria are suggested for establishing this diagnosis: (1) metastatic sarcoma to the kidney must be ruled out, (2) the tumour should arise from the renal pelvis, and (3) a sarcomatoid variant of renal cell carcinoma must be ruled out.⁵ Today, immunohistochemistry can aid in the diagnosis, with myogenin and MyoD1, two regulatory proteins expressed in skeletal muscle, being markers that are specific for RMS.⁶ On diagnosis, the current standard for treatment is radical nephrectomy. However, given the aggressive nature of this tumour in the adult population, the use of adjuvant chemotherapy is often warranted.

Case presentation

We present the case of a 39-year-old woman with a 3-month history of epigastric pain and intermittent nausea and vomiting. Medical history was unremarkable with the exception of occupational exposure to dry cleaning solvents, and physical examination was unremarkable aside from moderate hypertension. Urinalysis revealed trace leucocyte esterase and trace blood. CT scan of the abdomen and pelvis demonstrated a 14.0×13.0×15.1 cm retroperitoneal mass arising from the lower pole of the right kidney (figures 1 and 2), suggestive of renal cell carcinoma, transitional cell carcinoma, or renal sarcoma. Subsequent MRI was suggestive of renal sarcoma or primary retroperitoneal sarcoma. MRI also demonstrated severe right hydronephrosis and retroperitoneal adenopathy, with displacement of the inferior vena cava, pancreas and duodenum by the mass. Metastatic workup was negative.

Figure 1.

CT abdomen/pelvis with intravenous contrast (axial view) demonstrates a large right renal mass that occupies most of the right hemi-abdomen.

Figure 2.

CT abdomen/pelvis with intravenous contrast (coronal view) demonstrates a large right renal mass that occupies most of the right hemi-abdomen.

Investigations

On pathological examination, the tumour was 18×15×10 cm, light tan, with no areas of haemorrhage or necrosis, and was located in the lower pole of the kidney with extension into the renal hilum (figure 3). There was no involvement of the renal capsule and no lymphovascular invasion. Ureteral and vascular margins at the hilar resection site were negative for tumour. One interaortocaval lymph node was positive for metastatic sarcoma.

Figure 3.

(A) Gross image of renal tumour (red arrow); (B, C) H&E sections of renal tumour; (D) H&E section of metastatic tumour in lymph node; (E, G) immunostain for myogenin in tumour cells in kidney and lymph node, respectively; (F, H) immunostain for desmin in tumour cells in kidney and lymph node, respectively.

Karyotyping revealed multiple numerical and structural aberrations consistent with sarcoma including deletion of chromosome six and loss of chromosome 21. The tumour cells stained positive for desmin, smooth muscle actin and myogenin (figure 3E, F). Cells from the lymph node showed a similar staining pattern (figure 3H, G). On final pathology, the tumour was classified as stage III, T2b, N1, M0, primary renal ERMS.

TREATMENT

A right radical nephrectomy and retroperitoneal lymph node dissection were performed within weeks of the initial imaging studies. Intraoperatively, the inferior vena cava was found to be densely adherent to the tumour and the kidney was adherent to the liver, diaphragm and pleura. After successful removal of the kidney, a retroperitoneal lymphadenectomy was performed. The patient tolerated the procedure well with no complications and the tumour was completely excised. She was discharged 1 week later without event.

After recovery, adjuvant therapy was initiated with irinotecan and vincristine, followed by cyclophosphamide and radiotherapy. This treatment regimen was based on a phase II clinical trial in children with metastatic ERMS showing success with irinotecan in combination with vincristine and radiotherapy.⁷

Outcome and follow-up

Although the patient was without evidence of disease on imaging in the 6 months following surgery, at 9 months after surgery the patient developed metastatic disease with involvement of multiple bones requiring radiation to the thoracic and lumbar spine. Slightly less than 1 year from time of surgery, the patient presented to the emergency department with drooping of the eyelid and blurred vision. MRI demonstrated rapidly progressive sarcoma involving the skull bones with compression of the optic nerve and thoracic spine. Palliative care was initiated and the patient passed away within 2 weeks of presentation to the emergency department.

Discussion

RMS of the genitourinary system typically affects children ages 2–6 years, however, it most often originates from the bladder or pelvic organs.⁸ Renal RMS is an extremely rare entity in the adult population. Fang et al reported the existence of 11 cases in adults in their 2014 report which assessed the available English literature.⁹ We found two additional cases in the English-literature that occurred after the publication of Fang’s article. In 2016, Lin et al reported an 18 year old patient discovered to have a pleomorphic-type primary renal RMS.⁹ Furthermore, in 2017, Farzad Allameh and colleagues published a case report of a 33-year-old woman who presented with gross haematuria and was later found to have the botryoid variant of RMS as a primary tumour of the kidney.⁴

In 2012, Fanous et al described a 37-year-old woman with primary renal ERMS.² She presented with a 6-month history of fatigue, right flank pain, weight loss and gross haematuria. On CT of the abdomen, a large heterogeneous 16 cm mass was seen replacing the right kidney. After right radical nephrectomy, pathology demonstrated tissue that expressed myogenin and focally expressed MyoD. This patient was not started on adjuvant therapy and remained disease-free at 4 months postoperatively.

Kaabneh et al described in 2014 a 22-year-old woman with a botyroid-type of RMS originating from the renal pelvis.¹⁰ This patient presented with a 3-week history of left flank pain. Imaging was remarkable for a mass in the renal pelvis however, biopsy was inconclusive. Pathology after nephroureterectomy revealed tissue that stained positive for desmin, MyoD1 and actin. There was no evidence of metastasis at time of diagnosis and adjuvant therapy was not initiated. After 1 year, she remained free of disease. In this report, the authors suggest a role for nephroureterectomy and subsequent surveillance to spare young patients from immediate chemotherapy regimens.

Fang et al presented a 26-year-old woman with primary renal ERMS who presented with a 2-day history of right flank pain and gross haematuria. CT scan showed a 5.4×4.3 cm mass involving the right upper pole of the kidney. Metastatic work-up was negative. The patient underwent a right radical nephrectomy and the tumour was noted to be invading the hilum and local vessels with sparing of the renal capsule and ureter. This patient was administered adjuvant vincristine, actinomycin D and cyclophosphamide in conjunction with radiotherapy. In this report, the patient was without evidence of recurrence 4 months after initial diagnosis with longer follow-up not provided.

Learning points.

• Primary renal rhabdomyosarcoma (RMS), an aggressive tumour arising from muscle progenitor cells, is an extremely rare neoplasm in the adult population.

• Patients may present with symptoms similar to those of renal cell carcinoma including flank pain, gross haematuria, fatigue and weight loss.

• Cross-sectional imaging is useful to determine disease burden but is not sufficient for diagnosis which is made via histopathological analysis and immunochemistry of the surgical specimen.

• Radical nephrectomy is the established surgical therapy, however, radical nephroureterectomy has also been utilised for these cases. Adjuvant chemotherapy and radiotherapy are often warranted.

• Primary renal RMS can recur rapidly and aggressively after successful resection and adjuvant therapies.