A highly malignant succinate dehydrogenase A‑deficient renal cell carcinoma with bone metastasis misdiagnosed as hereditary leiomyomatosis and renal cell carcinoma: A case report

Abstract

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants of the SDH gene. SDH mutations are associated with an increased risk of developing RCC, although studies describing SDH-deficient RCC are currently limited. The present study reported a case of SDH-deficient RCC with high malignancy and rare bone metastasis. The patient was diagnosed with a right renal mass through B-mode ultrasound imaging and showed a carcinoma embolus in the right renal vein and inferior vena cava through kidney contrast-enhanced computed tomography. A whole-body bone scan showed radionuclide accumulation in the upper end of the left humerus, which indicated possible pathological bone destruction. As a result, surgical resection was performed. The postoperative pathology indicated a high-grade RCC and although the specific classification remained uncertain, hereditary leiomyomatosis and RCC was suspected. Subsequently, a germline mutation of the succinate dehydrogenase complex flavoprotein subunit A gene was identified through high-throughput sequencing (c.1A>G, p. Met1?) and immunohistochemistry demonstrated the loss of succinate dehydrogenase complex flavoprotein subunit B expression. Postoperatively, the patient underwent radiotherapy and targeted therapy. After 6 months of follow-up treatment, there was no indication of recurrence or metastasis on thoracoabdominal CT and whole-body bone scintigraphy. Based on the present report, germline screening should potentially be encouraged in early-onset patients as family history or pathological results may not provide sufficient information for the early, differential diagnosis of SDH-deficient RCC.

Keywords: diagnose; misdiagnosed; renal cell carcinoma; succinate dehydrogenase; succinate dehydrogenase-deficient renal cell carcinoma.

Figure 1.

Ultrasound examination and renal CT scan. (A) A soft tissue mass in the right kidney was found by B-ultrasound during the patient's health check-up. (B) Plain abdominal CT scan showing enlargement of the right kidney, irregular filling of the inferior vena cava and the right renal vein. (C) Contrast-enhanced CT scan showing a mass shadow in the right renal vein; the enhancement of the mass was not obvious compared with the left normal kidney in the arterial stage. (D) An inhomogeneous density shadow was observed in the right renal vein and inferior vena cava in the venous and delayed stage. White arrows indicate tumor and yellow arrows indicate tumor embolus. CT, computed tomography.

Figure 2.

MRI scan showing enlargement of the right kidney with abnormal round signals. (A) A mixed, slightly high T1WI signal, (B) a mixed T2WI signal and (C) an inhomogeneous high DWI signal. (D) The right renal pyelectasis was accompanied by a patchy homogeneous T1 signal and a high T2 signal, while DWI exhibited a high signal. White arrows indicate tumor and yellow arrows indicate tumor embolus. MRI, magnetic resonance imaging; T1WI, T1 weighted image; T2WI, T2 weighted image; DWI, diffusion-weighted imaging.

Figure 3.

Left humerus digital radiography and radioactive whole-body bone imaging. (A) Left shoulder X-ray showed left upper humerus bone discontinuity. Black arrows indicate the site of the fracture. (B) Whole-body bone scan showed radionuclide accumulation at the upper end of the left humerus (Red arrow). (C) A whole-body bone scan demonstrated reduced radionuclide concentration at the upper end of the left humerus three months after surgery.

Figure 4.

Tumor cells exhibiting glandular or tubular arrangement, with abundant cytoplasm, large nuclei and pronounced nuclear pleomorphism (magnification, ×100). (A) Green boxes indicate tumor cells arranged in a papillary pattern and the red oval represents tumor cells arranged in a tubular/cystic pattern. (B) The black oval indicates significant cellular pleomorphism. (C) The yellow arrow indicates characteristic cytoplasmic vacuoles (magnification, ×200). (D) The blue circle denotes lymphocytes expressing SDHB, appearing brownish-red; black arrows indicate cancer cells lacking SDHB expression, appearing gray-blue. SDHB, SDH complex flavoprotein subunit B.

Figure 5.

Immunohistochemistry of renal cancer tissues excised from the patient. (A) Cytokeratin 7 (−), (B) α-methylacyl-coenzyme A racemase (+), (C) E-cadherin (+), (D) CD10 (+), (E) carbonic anhydrase IX (+), (F) Pax-2 (+), (G) CD117 (−), (H) ALK-1A4/1H7 (−), (I) cytokeratin 20 (−), (J) integrase interactor 1 (+), (K) tumor protein 63 (−), (L) GATA binding protein 3 (−), (M) S100 calcium-binding protein P (−), (N) Vimentin (+), (O) octamer-binding transcription factor 4 (−) and (P) CK (+). Scale bar, 40 mm. +, positive; -, negative