[Moderate to high-risk primary malignant solitary fibrous tumor of the kidney: a clinicopathological and molecular analysis of five cases].

Objective: To explore the clinicopathological features, immunophenotype, molecular characteristics, and prognosis of primary malignant solitary fibrous tumor (MSFT) of the kidney. Methods: The clinicopathological data of four renal MSFT cases diagnosed at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China and one case at the Ningbo Clinical Pathology Diagnostic Center, Ningbo, China between 2015 and 2025 were collected. The clinical features, histomorphology, and immunohistochemical characteristics were analyzed. Fluorescence in situ hybridization (FISH) and RNA-based next-generation sequencing were performed. Follow-up and review of relevant literature were conducted. Results: Among the five patients, three were male and two were female, aged 70(61,71) years. The tumors were all found during routine physical examinations. Four cases (cases 1, 3, 4, and 5) occurred in the left kidney, and one case (case 2) first occurred in the left kidney and recurred in the right kidney 5 years later. Four cases had a single lesion with a maximum diameter of 6.0-19.0 cm, and one case (case 5) had 2 lesions with maximum diameters of 2.0 cm and 4.0 cm, respectively. Histologically, three cases (cases 1, 2, and 5) were de novo MSFT, one case (case 5) was morphologically similar to synovial sarcoma with spindle cells arranged densely in bundles, one case (case 1) had sheets of epithelioid tumor cells, and one case (case 2) had alternating myxoid and spindle cell areas, with sparse tumor cells in the myxoid areas and dense tumor cells in the spindle cell areas. Two cases (cases 3 and 4) were classic solitary fibrous tumor (SFT) with dedifferentiation, and the dedifferentiated components were high-grade undifferentiated sarcoma. In the typical SFT areas, tumor cells were alternately dense and sparse, with collagenized areas and rare mitotic figures, while branching or hemangiopericytoma-like structures were also present. In the dedifferentiated areas, tumor cells were spindle-shaped or epithelioid with conspicuous nucleoli. Necrosis was seen in all three de novo MSFT cases (cases 1, 2, and 5) and one dedifferentiated case (case 4). The mitotic figures in three de novo SFT cases and two dedifferentiated areas were 4 to 10 per 10 HPF. No heterologous differentiation was found in any of the five cases. According to the Demicco risk classification, four cases were of moderate risk, and one case (case 4) was of high risk. Four cases showed diffuse expression of STAT6, while one case (case 3) showed partial expression. CD34 was diffusely positive in 3 cases, partially positive in one case (case 4) and negative in one case (case 1). Only one of the 5 cases expressed CKpan which was focally positive. PAX8, desmin, BCOR, S-100 protein, Melan A and HMB45 were all negative. H3k27Me3 expression was retained. FISH showed no SYT (SS18, 18q11) rearrangements in two cases (cases 4 and 5), and no MDM2 amplification in one case (case 5). RNA sequencing in four cases detected NAB2::STAT6 gene fusion, all of which were NAB2ex6::STAT6ex16 fusion subtypes. Follow-up data were available for four cases, with the follow-up period of 11-30 months. Among the 4 cases, one case had liver metastasis 3 months after surgery, and one case of left renal MSFT (moderate risk) had right renal recurrence 5 years after surgery. The other two had no recurrence or metastasis. Conclusions: Renal MSFT with moderate to high-risk is rare, shows a wide morphological spectrum and needs to be differentiated from various tumors. Extensive sampling, careful morphological observation, immunohistochemical staining and molecular detection of NAB2::STAT6 fusion are helpful for the diagnosis. It appears to have aggressive biological behaviors.