PMC9709202_01
Chronological computed tomography of the perivascular epithelioid cell tumor. (A) The primary tumor was identified as right kidney mass. (B) Metastases were identified in the right abdominal cavity 10 months after resection of the primary tumor. (C, D) Shrinkage of the abdominal cavity tumor was identified 3 months (C) and 6 months (D) after the initiation of anti-VEGFR TKI treatment, respectively. (E, F) Continuous shrinkage of the abdominal cavity tumor and appearance of new metastases in gallbladder fossa was identified 15 months after the initiation of anti-VEGFR TKI treatment. (G, H) New, widespread metastases were identified in the abdomen and pelvis 15 months after the initiation of the MTOR inhibitor everolimus treatment.
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The computed tomography (CT) scan later performed in Shanxi Cancer Hospital showed right kidney mass of 8.2 x 7.1 cm indicative of kidney cancer ( Figure 1A ).Radical right nephrectomy was immediately performed under general anesthesia. New CT scan revealed multiple nodules in the right abdominal cavity and lateral peritoneum and extraperitoneum, as well as the right side of the liver border, along with psoas muscle involvement and slightly enlarged retroperitoneal lymph nodes, indicative of metastasis ( Figure 1B ). Overall the inhibitor appeared effective, leading to tumor shrinkage as revealed by follow-up CT scans ( Figures 1C, D ). New CT scan showed a new gallbladder fossa mass, while previously identified nodules in the right abdominal cavity and lateral peritoneum and extraperitoneum became smaller ( Figures 1E, F ). However, the follow-up CT scan after another 15 months manifested progression with extensive metastases in the abdomen and pelvis ( Figures 1G, H ).
Pathological and immunohistochemistry features of the primary perivascular epithelioid cell tumor resected right kidney. (A) Hematoxylin-eosin staining of resection specimen. (B-F) Immunohistochemistry of select tumor markers: HMB45 (B), SDHB (C), MLANA (D), TFE3 (E), and Ki-67 (F).
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Pathology microscopy revealed atypical cells with large nucleus and abundant, pink-stained cytoplasm ( Figure 2A ). The nuclei appeared in vacuoles, with easily identifiable nucleoli showing mitotic characteristics ( Figure 2A ). Cells appeared in nests and sheets with abundant interstitial blood vessels, and were accompanied by necrosis in certain areas ( Figure 2A ). TFE3 (weak positive), and negative for AE1/AE3, vimentin, MME, and CA9 ( Figures 2B-E  and data not shown). Ki-67 labeling index in the tumor cells was 15% ( Figure 2F ). The pathological findings supported the diagnosis of malignant PEComa.
Pathological and immunohistochemistry features of the perivascular epithelioid cell tumor metastases. (A-D) hematoxylin-eosin staining (A) and imunohistochemistry of HMB45 (B), MLANA (C), and Ki-67 (D) of the biopsy specimen of the pelvis metastases identified 10 months after the resection of the primary tumor. (E-H) hematoxylin-eosin staining (E) and imunohistochemistry of HMB45 (F), MLANA (G), and Ki-67 (H) of the biopsy specimen of the gallbladder fossa metastases identified 15 months after pelvis manifestation and the initiation of anti-VEGFR TKI treatment.
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The pathology showed that most of the tissues were necrotic, with a few degenerated cells bearing large nucleus ( Figure 3A ). Immunohistochemical stains showed tumor cells positive for HMB45 and TFE3, and negative for AE1/AE3, vimentin, MLANA, PAX8, S100, SMA ( Figures 3B, C  and data not shown). Ki-67 labeling index in the tumor cells was 40% ( Figure 3D ). The pathology identified irregular cells with deviated nuclei ( Figure 3E ). KIT and S100 (partially), and negative for AE1/AE3, MME and calponin ( Figures 3F, G  and data not shown). Ki-67 labeling index in the tumor cells was 80% ( Figure 3H ).
Patient treatment timeline. DFS, disease-free survival, PFS, progression-free survival. *Apatinib was started at 500 mg qd for 3 months and then increased to 750 mg qd for 10 days, but changed back to 500 mg qd due to the side effect at the high dosage (high blood pressure and nose bleeding).
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The disease progression and the responses to the evolving treatment is summarized in  Figure 4 .