A case of a composite pheochromocytoma with a spindle cell sarcoma exhibiting aggressive behavior

Vasiliki Venetsanaki; Maria Sfakiotaki; Mickey J. M. Kuo; Eleni-Konstantina Syntzanaki; Amalia Sertedaki; Labrini Papanastasiou; Athanasios Fountas; Georgios Zografos; Mayank Patel; Theodosia Choreftaki; Georgios Kyriakopoulos; Karel Pacak; Paraskevi Xekouki

doi:10.1530/endoabs.99.P5

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Endocrine Abstracts (2024) 99 P5 | DOI: 10.1530/endoabs.99.P5

ECE2024 Poster Presentations Adrenal and Cardiovascular Endocrinology (95 abstracts)

A case of a composite pheochromocytoma with a spindle cell sarcoma exhibiting aggressive behavior

Vasiliki Venetsanaki ¹ , Maria Sfakiotaki ¹ , Mickey J. M. Kuo ^2,3 , Eleni-Konstantina Syntzanaki ¹ , Amalia Sertedaki ⁴ , Labrini Papanastasiou ⁵ , Athanasios Fountas ⁵ , Georgios Zografos ⁶ , Mayank Patel ^3,7 , Theodosia Choreftaki ⁸ , Georgios Kyriakopoulos ⁹ , Karel Pacak ³ & Paraskevi Xekouki ¹

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¹University General Hospital of Heraklion, Department of Endocrinology, Metabolism and Diabetes, Heraklion, Greece; ²National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch, Bethesda, Maryland, United States; ³National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Medical Neuroendocrinology, Bethesda, Maryland, United States; ⁴‘Agia Sophia’ Children’s Hospital, Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens, Greece; ⁵‘Georgios Gennimatas’ General Hospital, Endocrinology, Metabolism and Diabetes Center, Athens, Greece; ⁶‘Georgios Gennimatas’ General Hospital, Third Department of Surgery, Athens, Greece; ⁷National Cancer Institute, Center for Cancer Research, Laboratory of Pathology, Bethesda, Maryland, United States; ⁸‘Georgios Gennimatas’ General Hospital, Department of Pathology, Athens, Greece; ⁹‘Evangelismos’ General Hospital, Department of Pathology, Athens, Greece

Introduction: Pheochromocytomas (PHEOs) are rare catecholamine-producing tumors with metastatic potential. Composite PHEOs are rare (3% of adrenal tumors) including components other than adrenal chromaffin cells. We report a case of a rare composite neoplasm with a very rapid disease progression.

Case report: A 57-year-old male was referred to the Endocrinology Department for investigation of a retroperitoneal mass. He presented with nonspecific symptoms and mild hypertension. Computed tomography (CT) of the abdomen revealed a left-sided 14.5×12×14 cm mass with cystic, necrotic and hemorrhagic features. Investigation revealed elevated levels of 24-hour urinary metanephrine [690 μg/24 h (44–261)], normetanephrine [3471 μg/24 h (128–484)] and dopamine [998 μg/24 h (60–440)] and serum chromogranin A (CgA) [>9000 ng/ml (10–110)] suggestive of a PHEO. The ¹²³I-MIBG scintigraphy showed increased uptake in the left adrenal, multiple skeletal sites and the liver. He underwent left adrenalectomy and nephrectomy. The initial pathology report revealed a poorly differentiated PHEO (PASS score 17) composed of a high-grade spindle cell component and an epithelioid cell component. There was focal staining of CgA and Synaptophysin in the areas of better differentiation, while Ki-67 index was high (75%). Extensive necrosis and marked mitotic activity (>30 mitoses/HPF) were also observed. Postoperative 24 h urinary metanephrines decreased significantly although CgA levels remained high and CT scans showed disease progression with multiple liver and bone metastases. Treatment with cyclophosphamide, vincristine, dacarbazine (CVD) and concurrent radiation of left femoral metastasis was decided but after 3 CVD cycles further disease progression was noted. The patient died 6 months after diagnosis due to hepatic failure. Pathology review at the National Institutes of Health (NIH) concluded that this was a sarcomatoid, malignant spindle cell neoplasm immediately associated and commingled with a differentiated PHEO. Immunohistochemistry (IHC) was positive for CgA, S100, and Synaptophysin in the PHEO component. The partially retained expression of H3K27me3 on IHC did not support the possibility of a malignant peripheral nerve sheath tumor (MPNST). Exome sequencing was negative for germline pathogenic variants in genes associated with PHEO; Next generation sequencing performed on tumor tissue detected pathogenic (likely homozygous) deep deletions in NF1, CDKN2A, and CDKN2B.

Conclusion: Composite PHEOs are very rare and their clinical course depends on their components. MPNST is a rare component of composite PHEO with dismal prognosis. In our case, histology and genetic variants indicated spindle cell sarcoma with no clear evidence of a neurogenic origin. Alternatively, this could represent a PHEO which partially dedifferentiated to a sarcomatoid neoplasm.