Tumoare fibroasă solitară retroperitoneală cu afectare renală multifactorială

Introduction

Solitary fibrous tumors are a rare type of soft tissue neoplasm of mesenchymal origin, with an incidence of approximately 3.5 cases per million per year⁽¹⁾. 

The median age at diagnosis is 59 years old, with a male predominance, and the predominant site of involvement is the thoracic cavity⁽²⁾.

The characteristic macroscopic appearance is that of a solid lesion with well-defined margins and no calcifications, while the suggestive microscopic pattern consists of a spindle cell proliferation without a specific architectural arrangement. Immunohistochemically, tumor cells are strongly positive for CD34, vimentin and CD99, with Ki-67 expression in approximately 10% of cases, and are negative for Bcl-2, SMA, pan-cytokeratin, S-100 protein and epithelial membrane antigen (EMA)⁽³⁾.

The percentage of solitary fibrous tumors displaying histopathological features suggestive of a benign clinical course appears to be relatively higher⁽⁴⁾. Multiple hypotheses have been proposed regarding histopathological features and malignancy criteria. England et al. suggested that mitotic activity (>4/10 HPF), pleomorphism, tumor size and tumor necrosis are factors associated with an increased risk of local recurrence or metastasis⁽⁵⁾.

Demicco et al. demonstrated a statistically significant association between mitotic activity, age, tumor size and necrosis with the risk of metastasis⁽²⁾. They proposed a risk stratification system based on these criteria, showing that groups classified as intermediate- or high-risk had a statistically significantly higher proportion of distant recurrence compared to the low-risk group, a finding that has also been validated in other studies^(2,6).

The five-year median overall survival is 86% for localized tumors, compared to only 11% for unresectable tumors or those with metastases at the time of diagnosis, with a median survival of 8.4 months⁽⁷⁾.

Surgical resection remains the treatment of choice for localized disease^(7,8). In cases of local recurrence or metastatic disease, radiotherapy and systemic therapy based on anti-VEGF agents and tyrosine kinase inhibitors have been shown to improve survival in several studies⁽⁸⁾.

Retroperitoneal localization of solitary fibrous tumors is extremely rare, accounting for approximately 15% of all solitary fibrous tumors⁽⁹⁾. In this location, tumors more frequently exhibit histopathological features of malignancy, with a higher tendency toward recurrence and metastatic progression.

Renal involvement is a common complication in patients with neoplasms. According to various studies that have histopathologically evaluated the mechanisms of renal impairment, among the most frequently reported causes was drug-induced nephrotoxicity (78%), typically presenting as thrombotic microangiopathy, acute tubular necrosis and interstitial nephritis. This was followed by renal impairment secondary to the neoplasm itself (approximately 8%), occurring via prerenal, postrenal obstructive or paraneoplastic mechanisms, including membranous nephropathy, IgA mesangial deposition nephropathy and minimal change glomerulopathy. Less frequently reported was contrast-induced nephropathy⁽¹⁰⁾.

We report the case of a patient with a voluminous retroperitoneal solitary fibrous tumor presenting with metastases at the time of diagnosis, who subsequently developed rapidly progressive renal failure, among other complications related to the underlying neoplastic disease.

Case presentation

A voluminous lesion was detected on imaging in a 68-year-old female patient, four years prior. The CT scan revealed a large, necrotic, soft-tissue retroperitoneal mass with irregular margins, measuring 87 mm in the transverse dimension, 79 mm anteroposteriorly and 87 mm craniocaudally, primarily located at the splenic hilum, invading the splenic parenchyma along the inferior two-thirds of the visceral surface and incorporating the splenic vascular pedicle, with a filamentous appearance of the splenic artery. Chronic splenic infarction was noted in the inferior one-third of the splenic parenchyma. Additionally, anterior extension involved the caudal region of the pancreas, while the medio-inferior portion engulfed the left adrenal gland and invaded the upper pole of the ipsilateral kidney. Pathologic aorto-renal left-sided lymphadenopathy was present, with necrotic nodes measuring 19×17 mm in the transaxial plane. Thoracic CT scan revealed a 22×20 mm soft-tissue macronodule in the left lower pulmonary lobe. No additional metastatic lesions were noted.

The patient’s medical history at that time included atherosclerosis with coronary artery involvement and ischemic heart disease with reduced ejection fraction and involvement of peripheral arteries consistent with peripheral arterial disease, classified as stage IIb. One notable risk factor was a smoking history, exceeding 40 years. Hematologic and biochemical parameters were within normal limits at the time of diagnosis.

A biopsy specimen was obtained under ultrasound guidance for histopathological examination, and the immunohistochemical profile was suggestive of a solitary fibrous tumor. The immunohistochemical profile demonstrated that Pan CK (clone AE1/AE3), DOG1 (clone DOG1 1), S100 (clone ZR115) and SMA (clone HHF35) were negative in tumor cells. Vimentin (VIM, clone SP20) was positive in tumor cells. Ki67 (clone MIB1) showed a nuclear positivity index of 30%. CD34 (clone QBE~d/10) and STAT6 (clone YE361) exhibited loss of expression in tumor cells. Risk stratification was performed according to the Demicco criteria, and the tumor was classified as intermediate risk⁽²⁾.

Considering the local and distant extent of the tumor burden, the patient was not considered a candidate for surgical therapy, and a treatment strategy consisting of systemic chemotherapy followed by radiotherapy was initiated.

The patient underwent 12 monthly cycles of systemic chemotherapy with doxorubicin and ifosfamide, administered at weight-adjusted doses. The treatment required postponement on two occasions due to hematologic toxicity, as evidenced by altered laboratory parameters.

During follow-up, the patient received palliative external radiotherapy to the primary tumor site, administered sequentially at yearly intervals, as follows: initially 39 Gy in 13 fractions, subsequently 55 Gy in five fractions, and in 2025 an additional course of radiotherapy was delivered to a total dose of 45 Gy in 30 fractions.

After eight cycles of chemotherapy and radiotherapy with 39 Gy/13 fractions, the imaging demonstrated persistence of the large retroperitoneal soft-tissue mass. At the thoracic level, a new 6-7 mm peribronchovascular nodule was identified in the anterobasal segment of the right lower lobe, along with dimensional regression of a previously described pulmonary macronodule located in the lateral-basal segment of the left lower lobe.

The patient was monitored through periodic oncologic follow-up evaluations, initially maintaining stable disease, with no clinical, radiological or biochemical evidence of tumor progression or organ involvement related to the underlying neoplastic condition. Tumor markers, as well as hematologic and biochemical parameters, remained stable throughout follow-up. Renal function had remained stable.

However, 1.5 years after completion of chemotherapy and three months after the last course of targeted radiotherapy, CT scan demonstrated tumor growth with approximately 1 cm larger in diameter, consistent with disease progression. The degree of invasion into adjacent tissues and organs has progressed. The dimensions around the renal hilum appear slightly increased, and the lymph node conglomerate located below the left renal hilum, measuring 54×42 mm, was enlarged. The thin fatty plane separating the tumor from the descending aorta was no longer visible. No new pulmonary nodules or secondary hepatic or osseous lesions were observed, and no additional superficial or deep lymphadenopathy was noted.

At the time of imaging, renal function was compromised, with no anterior uremic retention solutes being documented. Consequently, the CT scan was performed without intravenous contrast to avoid nephrotoxicity.

The patient developed progressive azotemia, with a serum creatinine of 2.9 mg/dL initially, which increased over the next five months to 4.87 mg/dL, corresponding to a severely reduced estimated glomerular filtration rate (eGFR) of 9 mL/min/1.73 m², and consistent with rapidly progressive renal function deterioration. Urinalysis revealed leukocyturia exceeding hematuria, with both isomorphic and dysmorphic red blood cells, and proteinuria with an albumin-to-creatinine ratio (ACR) of 700 mg/g. Renal ultrasound demonstrated reduced kidney size, suggestive of chronic kidney disease.

Multiple mechanisms of renal involvement are considered in this oncologic patient; however, a definitive diagnosis would have required a kidney biopsy, which was deemed unnecessary given the prolonged course of azotemic retention and the ultrasound appearance of the kidneys, suggestive of advanced chronic kidney disease, incompatible with the possibility of renal function recovery. The patient is managed with a low-sodium diet and conservative therapy appropriate for end-stage renal disease. She is followed periodically by nephrology for the potential initiation of renal replacement therapy.

Clinically, the patient accused diffuse abdominal pain, nausea and vomiting. The patient also stated marked weight loss over the last weeks, but the general status remained stable, with moderate normocytic, normochromic anemia, interpreted primarily as secondary to the underlying renal pathology, and she received treatment with erythropoiesis-stimulating agents (ESAs). Regarding the neoplastic disease, the oncologic assessment committee recommended the initiation of treatment with pazopanib, for which there were no contraindications in this patient. Renal disfunction did not constitute a contraindication, and proteinuria was minimal. The overall prognosis remains guarded.

Discussion

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm characterized by an unpredictable clinical course, with a subset of cases demonstrating aggressive behavior, including the risk of local recurrence and distant metastasis. Intraabdominal SFTs tend to present with larger tumor size and at older ages, and are associated with a higher risk profile at diagnosis compared to SFTs arising in other anatomical locations⁽²⁾.

The present case involves a retroperitoneal solitary fibrous tumor with pulmonary metastases, associated with a poor prognosis. Very few cases have been documented, and, consequently, no consensus has been reached regarding optimal therapy. Surgical treatment is not considered a standard of care at this stage. Local tumor extension further worsens prognosis due to invasion of adjacent vascular structures and abdominal organs. The role of radiotherapy remains controversial; however, one study has reported limited efficacy in retroperitoneal SFTs⁽⁴⁾. Current literature supports the use of systemic therapy, particularly tyrosine kinase inhibitors (TKIs) and antiangiogenic agents, which have demonstrated superior disease control rates compared to conventional chemotherapy^(8,11). In the present case, the patient received standard chemotherapy with alkylating agents and anthracyclines, under which she exhibited a stable course in terms of primary tumor parameters over a period of three years.

Renal involvement in patients with neoplastic disease is a frequent phenomenon. Studies report drug-induced nephrotoxicity as the most common cause of renal dysfunction, predominantly manifesting as thrombotic microangiopathy, acute tubular necrosis and acute interstitial nephritis. Paraneoplastic glomerulonephritis associated with malignancies most commonly includes IgA nephropathy, membranous nephropathy and minimal change disease, but also amyloidosis. The invasion of the urinary tract can result in obstructive nephropathy in approximately 4% of cases, while prerenal acute kidney injury has been reported in 8% of cases^(10,12).

The reported median serum creatinine at the time of diagnosis was 2.58 mg/dL, with a median proteinuria of 700 mg/g creatinine-to-albumin ratio (ACR)⁽¹²⁾. The manifestation of renal impairment in this patient aligns with findings described in the existing literature.

Ultrasonographic evaluation revealed bilaterally reduced kidney size, suggestive of long-standing chronic kidney disease. Given the patient’s history of systemic atherosclerosis, vascular nephropathy with acute kidney injury precipitated by prerenal mechanisms cannot be excluded in a patient with intermittent nausea and vomiting. It is noteworthy that imaging at the time of diagnosis indicated minimal invasion of the renal parenchyma at the upper pole, a finding that remained stable for a prolonged period without alterations in laboratory parameters suggestive of renal dysfunction. However, subsequent tumor involvement of the renal vascular pedicle, as well as compression of the renal vascular pedicle by a large lymph node conglomerate coincided temporally with the onset of azotemic retention, and it cannot be excluded as a contributing factor in a patient with multiple potential causes of renal insufficiency, including chronic hypoperfusion.

Although interstitial nephritis is among the most common renal manifestations in oncologic patients, targeted chemotherapy was discontinued more than one year ago, rendering this etiology unlikely, as are acute tubular necrosis and chemotherapy-induced thrombotic microangiopathy.

In light of the rapid decline in renal function, a more probable alternative diagnosis is glomerulonephritis with extracapillary proliferation. IgA nephropathy is suggested by urinalysis demonstrating microscopic hematuria. Although urinalysis showed persistent microscopic hematuria with isomorphic and dysmorphic red blood cells, the diagnosis cannot be confirmed without renal biopsy.

Glomerulopathies associated with neoplastic disea­ses, such as membranous nephropathy, minimal change disease, membranoproliferative glomerulonephritis or amyloidosis, most frequently present with nephrotic syndrome and generalized edema, which appears unlikely in the present patient, giving the low-grade proteinuria.

The absence of ureterohydronephrosis excludes the possibility of obstructive nephropathy.

Irrespective of the underlying etiology, the recovery of renal function is considered unattainable, and the management remains conservative until the initiation of renal replacement therapy. Chronic kidney disease additionally exerts an additional negative impact on the patient’s overall prognosis.

Conclusions

Retroperitoneal solitary fibrous tumors (SFTs) constitute a rare neoplastic entity with a poor prognosis, particularly in the metastatic setting. These tumors more frequently involve adjacent organs, making surgical resection technically difficult, or possible only at the cost of excising affected structures, thereby further compromising the prognosis. The therapeutic approach is not standardized, and additional studies are needed to establish optimal treatment strategies. Renal impairment is common in oncologic patients, complicating therapy administration or impacting overall survival, particularly when hemodialysis is required. Accordingly, the careful assessment of renal function through evaluation of uremic retention solutes and urinalysis is essential for patient management.   

Corresponding author: Corina-Daniela Ene E-mail: corina.ene@spcaroldavila.ro

Conflict of interest: none declared.

Financial support: none declared.

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