Letter to the Editor
Normotensive pheochromocytoma associated with ganglioneuroma
Feocromocitoma normotensivo asociado a ganglioneuroma
Gabriela Mintegui
, Beatriz Mendoza, Carolina Guarneri
Corresponding author
Clinics Hospital, School of Medicine, UdelaR, Montevideo, Uruguay
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(B) Macroscopy of the adrenal tumor: a sector of the remaining compressed adrenal is visualized (arrow). (C) Histopathological findings (hematoxylin and eosin staining), microscopic examination of pheochromocytoma. Tumor cells show eosinophilic cytoplasm, without evident cellular or nuclear atypia, separated by fine connective tracts.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pheochromocytoma is a catecholamine-secreting tumor of the adrenal medulla that causes arterial hypertension (HT) and increased morbidity. It can be associated with an embryologically linked neurogenic tumor (compound pheochromocytoma), forming a mixed endocrine-neuroblastic tumor (ganglioneuroma in 80% of cases) and represents 1–3% of pheochromocytomas. It is more frequent in adults between 40 and 60 years of age and they are usually larger tumors than conventional pheochromocytomas, ranging between 4 and 6<span class="elsevierStyleHsp" style=""></span>cm.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Only 5–15% of pheochromocytomas are normotensive within adrenal incidentalomas and occur mainly in large cystic tumors.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The frequency of incidentally discovered normotensive pheochromocytoma increased due to better availability and accessibility of imaging procedures.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Thirty-five years old woman with no notable history who consulted for pain in the right hemiabdomen and hypogastrium, without symptoms of peritoneal irritation. Abdominal ultrasound showed a complex image in relation to the upper pole of the left kidney, septate, with vascularization, measuring 92<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>72<span class="elsevierStyleHsp" style=""></span>mm. The CT scan, a well-defined, mixed, predominantly cystic, rounded left adrenal tumor, enhanced with contrast, 85<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>90<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>72<span class="elsevierStyleHsp" style=""></span>mm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). MR left SR tumor of 10<span class="elsevierStyleHsp" style=""></span>cm, well defined; it contacts the upper renal pole, to which it displaces, and the pancreas, without infiltration elements. In summary: voluminous SR lesion with characteristics of a benign nature. The patient did not present with hypertension, headaches, tachycardia or piloerection. A basic paraclinical was requested that was normal and metanephrines in urine that were 8300<span class="elsevierStyleHsp" style=""></span>μg/24<span class="elsevierStyleHsp" style=""></span>h (normal value [VN] 80–130); normetanephrines: 1878<span class="elsevierStyleHsp" style=""></span>μg/24<span class="elsevierStyleHsp" style=""></span>h (VN 111–419); total metanephrines 10<span class="elsevierStyleHsp" style=""></span>178<span class="elsevierStyleHsp" style=""></span>μg/24<span class="elsevierStyleHsp" style=""></span>h (VN 149–535). Preparation prior to surgery with oral α-adrenergic blocker (terazosin 2.5<span class="elsevierStyleHsp" style=""></span>mg/day) and diet with 5<span class="elsevierStyleHsp" style=""></span>g of sodium per day. Blood pressure monitoring did not show paroxysmal hypertension or hypotension. He did not have tachycardia, so he did not receive ß-blockers. He underwent a left adrenalectomy in open surgery. He did not present hemodynamic instability during it. The histopathological characteristics of the 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>cm nodule tumor, with multilocular cystic cavity, the largest of 5.5<span class="elsevierStyleHsp" style=""></span>cm with thin and smooth walls, with serohematic content. Remnant of the adrenal gland of 2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>cm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Microscopy: adrenal parenchyma showing substitution by well-defined, encapsulated proliferation of ganglioneuroma-like cells (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). Immunohistochemistry: the tumor cells were positive for chromogranin A, synaptophysin, with a cytoplasmic granular pattern in S100 sustainable cells, enolase in tumor cells and a schwann component, CD34 in vascular structures, neurofilaments in neuronal cells of the ganglioneuroma component. They were negative for steroidogenic factor 1. Ki 67 shows proliferative activity that in sectors reaches 2% of the activity. The final diagnosis: ganglioneuroma-associated pheochromocytoma (compound pheochromocytoma). During the evolution, the patient continued to be normotensive and metanephrines and normetanephrines were normal 3 months after surgery.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The classic triad of symptoms in patients with pheochromocytoma comprises episodic headache, sweating, and tachycardia. About half have paroxysmal hypertension; most of the rest have primary hypertension (formerly called “essential” hypertension) or normotension. The explanation in the absence of hypertension and the circulating levels of catecholamines may involve several mechanisms such as (1) the “down-regulation” of receptors, that is, the decrease in the sensitivity of adrenergic receptors to catecholamines; (2) individual differences in sensitivity of vessels to catecholamines; (3) adaptive response with decreased blood volume, secondary to sustained vasoconstriction; (4) secretion of products with vasodilator action by the tumor, which would modify the response of the vessels to catecholamines (nitric oxide, natriuretic peptide, among others).<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3,4</span></a> Pheochromocytoma exceptionally has a malignant behavior and its cystic variant is usually even rarer. This tumor usually does not present the typical clinical, radiological, and laboratory characteristics but is accompanied by nonspecific abdominal symptoms.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> The poor prognosis and/or malignancy factors for this type of tumor are the same as those for conventional pheochromocytomas, such as necrosis, vascular invasion, and high mitotic index. The long-term prognosis of patients after resection of normotensive pheochromocytoma remains uncertain.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Cystic and compound pheochromocytomas are rare neoplasms, mostly incidental findings, and with HT. This case shows a rare variant that, despite presenting very high levels of catecholamines, did not cause symptoms in the patient at any time of her clinical course.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 875 "Ancho" => 2917 "Tamanyo" => 396373 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Computed tomography, showing the left adrenal tumor (red circle), mixed, predominantly cystic, with septa in its interior that enhance with contrast. (B) Macroscopy of the adrenal tumor: a sector of the remaining compressed adrenal is visualized (arrow). (C) Histopathological findings (hematoxylin and eosin staining), microscopic examination of pheochromocytoma. Tumor cells show eosinophilic cytoplasm, without evident cellular or nuclear atypia, separated by fine connective tracts.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Young WF, Nieman LK, Martin KA. Clinical presentation and diagnosis of pheochromocytoma. Up to date [accessed 30.11.20]" ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:2 [ 0 => null 1 => null ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Normotensive pheochromocytoma: institutional experience" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Agarwal" 1 => "S. Gupta" 2 => "A.K. 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