Case Report: Malignant Primary Sellar Paraganglioma With Unusual Genetic and Imaging Features

Abstract

BackgroundParaganglioma occurs rarely in the sellar/parasellar region. Here, we report a patient with malignant paraganglioma with primary sellar location with unusual genetic and imaging features.Case PresentationA 31-year-old male presented with mild hypertension, headache, nausea, and vomiting. A sellar/parasellar tumor mass was revealed by magnetic resonance imaging (MRI), while an endocrine work-up found partial hypopituitarism, suggesting that it was a non-functioning pituitary tumor. Antihypertensive therapy and hormone replacement were initiated. Tumor reduction was achieved with transsphenoidal neurosurgery. However, histological diagnosis was not possible due to extensive tissue necrosis. After 4 years of stable disease, the residual tumor showed re-growth requiring gamma knife radiosurgery. Four years after the radiosurgery, MRI showed a significant tumor progression leading to a second neurosurgery. This time, pathological and immunohistochemical findings revealed paraganglioma. Plasma levels of metanephrine and normetanephrine were normal. A gene sequencing panel performed on DNA extracted from blood excluded germline mutations in 17 susceptibility genes. The patient developed new tumor masses in the neck, and the third surgery was performed. Immunohistochemistry demonstrated lack of ATRX (alpha thalassemia/mental retardation syndrome X-linked) protein in tumor cells, indicating an ATRX gene mutation. Molecular genetic analysis performed on tumor DNA revealed a combination of ATRX and TP53 gene abnormalities; this was not previously reported in paraganglioma. MRI and 68Ga-DOTANOC PET/CT revealed the full extent of the disease. Therapy with somatostatin LAR and 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) was initiated.ConclusionAlthough rare, paraganglioma should be considered in the differential diagnosis of sellar/parasellar tumor lesions, even in the absence of typical imaging features. ATRX gene mutation in paraganglioma is an early predictor of malignant behavior and a potential novel therapeutic marker when pharmacological therapy targeting mutated ATRX becomes available.

Unusually large paraganglioma complicated with successive catecholamine crises: A case report and review of the literature

“…Based on the presence or absence of typical clinical signs, retroperitoneal paragangliomas can be classified into three categories: non-functional, sub-clinical, and functional types. Patients with functional paragangliomas that overproduce catecholamines may experience the classic triad symptom including tachycardia, headache, and diaphoresis ( 6 – 10 ). In contrast, those with non-functional retro-peritoneal paragangliomas are often diagnosed incidentally or manifest as compressive symptoms such as abdominal pain that may be associated with nausea, vomiting, abdominal distension, weight loss, or even paralytic ileus ( 8 , 11 , 12 ).…”

The Effects of Peptide Receptor Radionuclide Therapy on the Neoplastic and Normal Pituitary

“…DOTANOC shows a very high affinity for SSTR2 and low affinity for SSTR3 and SSTR5, whereas DOTATATE only binds to SSTR2; thus, the main target of PRRT with radiolabelled somatostatin analogues is represented by SSTR2 [5,7]. PRRT has been successfully used to treat NETs due to their high expression levels of SSTR2 [8][9][10], but PRRT may also be effective for other cancers, such as primary brain tumours [5], paragangliomas [11][12][13][14], or thyroid cancer [15][16][17][18].…”

“…Brain tumours may express high levels of SSTRs, in particular meningiomas (90% of them express SSTR2) [5,[23][24][25], but also astrocytomas and gliomas [5,[26][27][28][29], making such tumours amenable to PRRT. PRRT has also been effective for treating paragangliomas, with disease control rates of 67-80% [12,13], including a malignant primary sellar paraganglioma case [11]. Additionally, PRRT has been used with variable efficacy for medullary and nonmedullary thyroid cancer [15][16][17][18].…”