Paraganglioma retroperitoneal no funcional: reporte de un caso en la Fundación Cardioinfantil, Bogotá, Colombia / Retroperitoneal non-functional paraganglioma: report of a case from the Cardioinfantil Foundation, Bogotá, Colombia

Los paragangliomas son tumores derivados de las células cromafines de la cresta neural y por ello tienen la capacidad de secretar catecolaminas, hormonas y péptidos; al ser tumores extraadrenales del sistema nervioso central se los puede encontrar en la base del cráneo, el cuello, el tórax y el abdomen; se clasifican en funcionales y no funcionales. En este artículo se describe un paciente de sexo masculino que cursó inicialmente con dolor inespecífico en el hipocondrio derecho; con base en los estudios imaginológicos iniciales se sospechó la presencia de un neuroblastoma, pero no fue posible diferenciarlo de un paraganglioma, un ganglioneuroblastoma o un neurofibroblastoma. Se lo intervino quirúrgicamente y el estudio patológico del espécimen reveló áreas hemorrágicas extensas, compatibles con un paraganglioma extraadrenal no funcional. Estos tumores son infrecuentes, de localización diversa y de tratamiento quirúrgico difícil.

Paragangliomas are tumors derived from chromaffin cells from the neural crest. They are able to secrete catecholamines, hormones and peptides. They can be found in the skull base, neck, thorax and abdomen, and may be functional or not-functional. We report the case of a male patient with non-specific pain in the right hypochondrium. Based on the initial imaginological studies a neuroblastoma was suspected, but it not possible to differentiate it from a paraganglioma, a ganglioneuroblastoma or a neurofibroblastoma. The pathological study of the surgical specimen revealed extensive hemorrhagic areas, consistent with a non-functional extra-adrenal paraganglioma. This is an infrequent neoplasia with difficult surgical treatment.

A case of bilateral multiple pulmonary chondroma: necessity of follow-up for Carney's triad.

We report a case of pulmonary bilateral multiple chondromas that were possibly an initial clinical presentation of Carney's triad. A 56-year-old Japanese non-smoking asymptomatic woman was admitted to the hospital for further examination of small, multiple, bilateral nodules in the lungs. Although chest radiological findings suggested that the nodules were possibly metastatic pulmonary tumors, the malignant origin was not detected. During diagnostic video-assisted thoracic surgery, wedge resections including the nodules were performed. Since pathological examination showed nodules were surrounded by fibrous and eosinophilic stroma, we diagnose the nodules as chondromas. These chondromas were possibly components of Carney's triad, because each nodule had a thin fibrous pseudocapsule and did not have an entrapped epithelium and fat. Some patients die of Carney's triad because of malignant alteration of lesions. Therefore, the patients with Carney's triad should be taken a medical check periodically. This patient was scheduled to undergo the check-up for several years.

A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney-Stratakis dyad.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchyme neoplasms of the gastrointestinal tract. Gain-of-function somatic mutations of the KIT or PDGFRA genes represent the most prevalent molecular alterations in GISTs. In Carney-Stratakis dyad, patients portray germline mutations of the succinate dehydrogenase subunits B (SDHB), C (SDHC) and D (SDHD) and develop multifocal GISTs and multicentric paragangliomas (PGLs). We herein report a novel germline SDHB mutation (c.T282A--Ile44Asn) occurring in a 26 years-old patient diagnosed with a spindle cell intermediate risk GIST that did not present KIT/PDGFRA/BRAF gene mutations. Further analyses revealed loss of the wild-type SDHB allele and complete loss of SDHB expression in the tumor tissue. After genetic screening of other family members, we detected in the patient's mother a SDHB mutation without any clinical/laboratorial evidence of GIST or PGL. Altogether, our findings (germline SDHB mutation with absence of PGL in the index case and of GIST and/or PGL in his mother) raise the possibility that this familiar setting corresponds to an incomplete phenotype of the Carney-Stratakis dyad.

Pathological mechanisms and parent-of-origin effects in hereditary paraganglioma/pheochromocytoma (PGL/PCC).

Paragangliomas/pheochromocytomas (PGL/PCC) are tumors of the paraganglia. They can occur sporadically, as one sign in a hereditary (tumor) syndrome or as the only manifestation in hereditary PGL/PCC. To date, five forms of hereditary PGL/PCC have been described. They are inherited as autosomal dominant traits and are caused by mutations in genes required for structure and function of complex II of the respiratory chain (succinate-ubiquinone oxidoreductase, succinate dehydrogenase, SDH). Mutations in genes encoding the small subunits of SDH, i.e., SDHD and SDHC, cause PGL1 and PGL3. Mutations in the large subunit genes SDHB, SDHA (currently only one case), and in SDHAF2 cause PGL4, 5, and 2, respectively. This article gives an overview of PGL/PCC in the context of the anatomy and function of paraganglia. It describes SDH, the genes encoding SDH, and provides information on genetic mechanisms in hereditary PGL/PCC. A model is proposed to explain exclusive paternal inheritance and loss of the maternal (putatively imprinted) allele as a prerequisite for tumor formation in PGLs 1 and 2.

Local-regional recurrence of sporadic or syndromic abdominal extra-adrenal paraganglioma: incidence, characteristics, and outcome.

BACKGROUND: Operative excision of abdominal extra-adrenal paragangliomas (EAPs) does not preclude the late development of local-regional recurrence. We describe the incidence, characteristics, and outcome of this rarely reported feature. METHODS: Retrospective analysis of local-regional recurrence that occurred during follow-up of 51 consecutive patients operated for a sporadic (n = 26) or hereditary (n = 25) EAP. RESULTS: Seven patients with a sporadic or syndromic EAP (n = 4: von Hippel-Lindau syndrome and SDHB, SDHC, and SDHD gene mutations) underwent reoperation for a local-regional recurrence after a median time of 46 months (interquartile range [IQR], 16-100). The Kaplan-Meier estimated incidence of local-regional recurrence (+/- standard error of the mean) reached 15% +/- 7% at 5 years and 23% +/- 9% after 10 years. Recurrent EAPs were all secreting and 38% provoked clinical symptoms. New lesions were smaller than the primary EAP (P = .01) and more often associated with lymph node metastases (43% vs 4%, P = .01). Operative excision seemed complete in 5 patients. Clinical remission was maintained in 4 patients after a median follow-up of 57 months (IQR, 22-102). CONCLUSION: Local-regional recurrence of sporadic and syndromic EAPs is frequent and may be delayed beyond 10 years, requiring lifelong follow-up after the initial operation. When technically feasible, operative excision can lead to prolonged remission.

Paragangliomas: etiology, presentation, and management.

Paragangliomas are catecholamine-secreting tumors arising from the chromaffin cells of the sympathetic ganglia, and are known as extra-adrenal pheochromocytomas. These tumors commonly present with episodic hypertension, tachycardia, headache, and diaphoresis, and can be either benign or malignant. Diagnosis is made by serum and urine analysis for catecholamines and metanephrines, and confirmed with imaging studies including computed tomography scanning, magnetic resonance imaging, or 123-I metaiodobenzylguanidine imaging. Although the majority of paragangliomas are sporadic, a growing percentage of cases are found to be part of a familial genetic syndrome. Genetic testing should be offered to patients diagnosed with paraganglioma, particularly in patients who are young, have multiple tumors, or have a family history of malignancy. Management of paraganglioma is predicated on surgical resection, and careful perioperative management with alpha- and beta-adrenergic blockade is imperative for optimal outcomes. The majority of these tumors are benign, but for patients with malignant disease, chemotherapy, and radiation therapy may provide modest benefit. Long-term follow-up is essential, as paragangliomas can recur many years after initial diagnosis. Ongoing research into the genetic underpinnings of this tumor may allow for more targeted molecular therapies in the future.

Chemodectomas: review and report of nine cases.

We have reviewed the broad spectrum of disease caused by chemodectomas. This spectrum extends from the benign to the aggressively malignant with many graduations in-between. Our analyses included cases from the literature and nine new cases seen over the past twenty-five years. Surgery as the primary and most definitive form of therapy, is recommended if feasible, with total excision as the goal, in both benign and malignant histologies. An excellent outcome is to be expected in benign cases. At present, no predictor exists to foretell the behavior of malignant lesions, which can range from the aggressive to the slowly progressive. Both radiotherapy and chemotherapy have been tried in malignant cases. No consistent good result has occurred from the use of either. The future will hopefully bring us more effective therapy.

Chronic hypoxia and chemodectomas in bovines at high altitudes.

A severe degree of hyperplasia of the chief cells occurs in bovine carotid bodies at high altitudes, compared to sea level. As a result, the carotid body from an animal at high altitudes is significantly heavier and larger than the carotid body from an animal at sea level (P less than .001). In eight of 20 (40%) animals at high altitudes, the hyperplastic reaction had progressed to form chemodectomas. The findings suggest that neoplasia can result from chronic stimulation by a biologically essential environmental factor (atmospheric PO2) that acts pharmacologically on the target tissues (chief cells of the carotid body).

The effect of combined chronic hypoxia and N-ethyl-N-nitrosourea on the carotid bodies of rats.

We measured the carotid body volume of rats treated with chronic hypoxia alone and chronic hypoxia together with a single neonatal injection of N-ethyl-N-nitrosourea (10 mg/kg). All the animals so treated showed enlargement of their carotid bodies, but no carotid body chemodectomas occurred.