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

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.

Head and Neck Malignant Paragangliomas: Experience from a Single Institution

Objectives: To summarize the clinicopathological and genetic features of malignant paragangliomas in head and neck cancer and to explore the appropriate treatment options for this rare lesion. Methods: Six patients harboring head and neck malignant paraganglioma from Beijing Tongren Hospital were retrospectively reviewed. The clinicopathological characteristics, gene mutations, and prognosis of these patients were analyzed. Results: Of these 6 patients, 3 were male and 3 were female; 4 patients harbored malignant carotid body tumors, and two had malignant vagal paragangliomas. Three patients had cervical lymph node metastasis, two presented with lung and bone metastasis, and 1 had lung and liver metastasis. Of the 6 patients, four underwent surgical resection, and the other two patients denied surgery and instead received chemotherapy with paclitaxel, ifosfamide, and dacarbazine. These 2 patients with vagal paraganglioma received postoperative radiotherapy. All 6 patients are still alive at the present time, with a median follow-up time of 66 months. Positive Ki-67 expression in tumor tissue ranged from 1% to 40%. Genetic mutations in SDHD, SDHB, ATR, and MAP3K13 were identified in 4 patients. Conclusions: After comprehensive treatment, head and neck malignant paraganglioma can attain a favorable prognosis. Genetic mutations are commonly detected in patients with malignant paragangliomas. This study also identified mutations in ATR and MAP3K13 in these patients.

Metastatic Malignant Paraganglioma Presenting as a Neck Mass Treated with Radiolabeled Somatostatin Analog

Paragangliomas are rare neuroendocrine tumors that arise from chromaffin-containing tissue. Surgical resection and/or radiation are used for locoregional disease, and reduction of tumor burden with systemic therapy is reserved for metastatic disease. Iobenguane I-131, somatostatin analog (octreotide), and Sunitinib are noncytotoxic options for treatment, while cyclophosphamide, vincristine, and dacarbazine (CVD) and temozolomide are often used as initial chemotherapy options as studies have shown that they offer some tumor response. However, there are no randomized clinical trials demonstrating prolonged survival with the use of chemotherapeutics in metastatic cases. Investigation of alternative therapies that provide survival benefit is thus necessary. We present a case of a 69-year-old female with metastatic malignant paraganglioma presenting as a left parapharyngeal neck mass, which metastasized after surgery, requiring radiation therapy for bony metastasis who was treated with a radioisotope somatostatin analog for disease progression.

Clinical and Morphological Analysis of Adrenal Glands Pathology in Kharkiv Region (according to Archival Material for the Period 2015-2019)

The adrenal glands play an important role in the functioning of the human body. There are more opportunities for early tumors detection of these endocrine glands thanks to modern diagnostic procedures, but the problem is very relevant. Morphological investigation is the basis for differentiating adrenocortical adenoma from carcinoma. Material and methods. The article presents the clinical and morphological features of the adrenal glands pathology in Kharkiv region in the period 2015-2019 by analyzing the archival histological material of 77 patients who were operated in hospitals of the State Institution "Institute of General and Emergency Surgery named after V. T. Zaitsev of National Academy of Medical Sciences of Ukraine" and "V. Danilevsky Institute for Endocrine Pathology Problems of the National Academy of Medical Sciences of Ukraine". Results and discussion. The study established that in 2015 there were 18 cases (including 8 malignant tumors), in 2016 – 16 cases (2 cases with bilateral damage, 1 malignant tumor), in 2017 – 12 cases, in 2018 – 20 cases, in 2019 – 11 cases. All tumors were benign in the last 3 years of the study. We calculated that 48.6 years was the average age of patients with this localization tumor processes (20-75 years). Women suffered more often than men (61.03% and 38.97%, respectively). Both adrenal glands had pathological changes in 2 people. The left gland is most often affected. The vast majority of the formations in 2015-2019 were benign (88.61%). Adrenocortical adenomas (45 cases, mostly clear cell variant, leftward, in women) and mature pheochromocytomas (13 cases, uncomplexed variant, leftward, in men), adrenal cysts (6 cases, more often on the right, in men, with a dense fibrous capsule), hyperplasia of the cortical, cerebral or both layers (4 cases), ganglioneuroma of the adrenal medulla (1 case) and a combination of pheochromocytoma with two adrenocorticosteromas (1 case) were among them. Conclusion. Malignant tumors were represented by malignant corticosteromas (5 cases out of 9, leftward, various sizes, with secondary changes in tumor tissue), malignant pheochromocytomas (3 cases out of 9, right, different size) and malignant paraganglioma (1 case). The larger size of the tumor did not always correlate with the nature of the process