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Malignant Chemodectoma of the Superior Mediastinum with Elevated Urinary Homovanillic Acid

1974; Elsevier BV; Volume: 66; Issue: 2 Linguagem: Inglês

10.1378/chest.66.2.209

1931-3543

Robert W. Enquist, Douglass C. Tormey, Edwin H. Jenis, Raphael L. Warkel,

Adrenal and Paraganglionic Tumors

A 20-year-old man who presented with a metastatic lesion in his left humerus was found to have a malignant chemodectoma arising in the superior mediastinum. Analysis of urinary phenolic acid excretion revealed a marked increase in homovanillic acid, a slight increase in vanillyl mandelic acid, and normal total metanephrine excretion. The demonstration of secretory granules by electron microscopy suggests that the tumor was responsible for the secretion of catecholamines or catecholamine metabolites. A 20-year-old man who presented with a metastatic lesion in his left humerus was found to have a malignant chemodectoma arising in the superior mediastinum. Analysis of urinary phenolic acid excretion revealed a marked increase in homovanillic acid, a slight increase in vanillyl mandelic acid, and normal total metanephrine excretion. The demonstration of secretory granules by electron microscopy suggests that the tumor was responsible for the secretion of catecholamines or catecholamine metabolites. Chemodectoma is the general term for tumors arising from chemoreceptor tissue. Although the most common site of origin of these tumors is the aortic body, they may also arise in the glomus jugulare, ciliary body, vagal body, mediastinum, retroperitoneum, femoral canal, eye, mandible and ileal mesentery.1Hewit RL Ichinose H Weichert RF et al.Chemodectomas.Surgery. 1972; 71: 275-282PubMed Google Scholar, 2Berk ME Chemodectoma of glomus intravagale; case report and review.Clin Radiol. 1961; 12: 219-226Abstract Full Text PDF Scopus (9) Google Scholar, 3Byrne JJ Carotid body and allied tumors.Am J Surg. 1958; 95: 371-384Abstract Full Text PDF PubMed Scopus (27) Google Scholar Chemodectomas tend to be slow growing, localized tumors. Metastatic lesions are extremely rare.4Fuller AM Brown HA Harrison EG Jr et al.Chemodectoma of the glomus jugulare.Laryngoscope. 1967; 77: 218-238Crossref PubMed Scopus (50) Google Scholar, 5McIlrath DC ReMine WH Carotid-body tumors.Surg Clin N Am. 1963; 43: 1135-1144Crossref PubMed Scopus (14) Google Scholar, 6Fanning JP Woods FM Christian MJ Metastatic carotid body tumor: report of a case with review of the literature.JAMA. 1963; 185: 49-50Crossref Scopus (28) Google Scholar, 7Shamblin WR ReMine WH Sheps SG et al.Carotid body tumor (chemodectoma): Clinicopathologic analysis of 90 cases.Am J Surg. 1971; 122: 732-739Abstract Full Text PDF PubMed Google Scholar A correct diagnosis may be made preoperatively by demonstrating their markedly vascular nature by angiography.8Phillips LA Mediastinal chemodectoma and thoracic aortography.A case report. Clin Radiol. 1963; 14: 129-132Scopus (10) Google Scholar Recent interest in these tumors has been stimulated by demonstration of their ability to secrete catecholamines, notably 1-norepinephrine which may result in a clinical syndrome indistinguishable from that produced by a pheochromocytoma.9Duke WW Boshell BR Soteres P et al.A norephinephrine-secreting glomus jugulare tumor presenting as a pheochromocytoma.Ann Intern Med. 1964; 60: 1040-1047Crossref Google Scholar,10Levit SA Sheldon GS Espinosa RE et al.Catecholamine-secreting paraganglioma of glomus-jugulare region resembling pheochromocytoma.N Engl J Med. 1969; 281: 805-811Crossref PubMed Scopus (84) Google Scholar We present a case in which the urinary homovanillic acid (HVA), a metabolite of catecholamine production, was markedly elevated in a patient with a metastatic malignant chemodectoma. A 20-year-old black man was admitted to Walter Reed Army Medical Center on July 17, 1971 when he sustained a fracture of the left humerus following minimal trauma to the left arm. The patient was otherwise asymptomatic and specifically denied weight loss, fever, night sweats, palpitations, and nervousness. Initial roentgenograms demonstrated a lytic lesion with a fracture in the mid-portion of the shaft of the left humerus.Physical examination revealed a temperature of 36.6°C, a blood pressure of 120/72 mm Hg and a pulse rate of 88 per minute. The trachea was deviated to the right. Bilateral supraclavicular masses were palpable. Bruits were audible over both carotid arteries, and a grade 2/6 systolic murmur was heard at the left sternal border. With the exception of the left humerus, there was no other bone tenderness.The white blood cell count was 8,000 per cubic millimeter with a normal differential. The hematocrit was 33 percent, platelet count was 367,000 per cubic millimeter, reticulocyte count was 0.6 percent and erythrocyte sedimentation rate was 55 per hour. The serum electrolytes, BUN, creatinine, calcium, phosphorus, protein electrophoresis, thyroid function tests and urinalysis were normal. A serum sample for carcinoembryonic antigen was negative.The chest roentgenogram revealed a superior mediastinal mass extending into the left hemithorax (Fig 1). The trachea was shifted to the right and lytic expansile lesions were noted in the fifth and ninth ribs on the right and the fifth and sixth ribs on the left. A metastatic bone series revealed additional lytic lesions involving the skull, right femur, right radius and humerus, ileum, pubic bones and several vertebrae. An aortic angiogram revealed an extremely vascular mass 10 cm in diameter (Fig 2). Laminograms of the superior mediastinum demonstrated a soft tissue mass displacing both carotid arteries to the right; there was no calcium apparent in the mass. An intravenous pyelogram and brain, liver-spleen and thyroid scans were normal.Examination of tissue obtained from an open biopsy of the ninth rib revealed the marrow spaces to be replaced by alveolar collections (“zellballen”) of polygonal cells surrounded by vascular fibrous septae. The cells had a homogenous, pale eosinophilic cytoplasm with round or oval nuclei. The nucleoplasm was vesicular with chromatin clumping at the nuclear membrane. Most of the cells contained from one to three small eosinophilic nucleoli. Mitoses were not prominent. Special stains failed to demonstrate argentaffin granules.A closed needle biopsy of the right ileum was processed for electron microscopy. The metastatic tumor was found to be composed of polygonal cells with interdigitating cytoplasmic processes. In contrast to their light microscopic appearance, many nuclei were irregularly shaped with deep cytoplasmic indentations and occasional central cytoplasmic invaginations. Many nuclei contained multiple nucleoli. The distribution of nuclear chromatin was quite variable; it was either peripherally dispersed against the nuclear membrane or uniformly distributed throughout the nucleoplasm.Endocrine-type secretory granules were present in the cytoplasm of many cells. The number of secretory granules varied from a few to many per cell. They were round or oval in shape and measured 100 to 200 μ in maximum diameter. The granules contained a homogenous electron-dense core separated from a distinct limiting membrane by a narrow zone of peripheral electron-lucency. The cytoplasm of the neoplastic cells contained abundant, normal appearing mitochondria. Golgi apparatus, smooth and rough endoplasmic reticulum, free ribosomes, polyribosomes, lipid bodies, and myelin figures were occasionally observed in the cytoplasm.Because of the secretory potential of this tumor, measurements were made of the urinary excretion of catecholamine catabolites utilizing previously described methods.11Armstrong MD McMillan A Shaw RNF Methoxy-4-hydroxy-D-mandelic acid, a urinary metabolite of norepinephrine.Biochim Biophys Acta. 1957; 25: 422-423Crossref PubMed Scopus (98) Google Scholar, 12Armstrong MD Shaw KNF Wall F The phenolic acids of human urine; paper chromotography of phenolic acids.J Biol Chem. 1956; 218: 293-303PubMed Google Scholar, 13Gitlow SE Mendlowitz M Wilk EK et al.Excretion of catecholamine catabolites by normal children.J Lab Clin Med. 1968; 72: 612-620PubMed Google Scholar The initial 24-hour urine specimen revealed the following: vanillyl mandelic acid (VMA) 5.0 μg per milligram of urinary creatinine (normal 0.2 to 3.5), total metanephrines (normetanephrines+metanephrines) 1.3 μg per milligram of urinary creatinine (normal 0.02 to 2.2) and homovanillic acid 100.0 μg per milligram of urinary creatinine (normal 1.0 to 5.0).Both humeri were irradiated to a total dose of 5000 rads over 35 days; no direct radiographic change was observed. Two chemotherapeutic regimens were completed with no apparent change in the lesions or alterations in the urinary excretion of HVA.FIGURE 2Aortic angiogram (subtraction film) demonstrating tumor blush. See text for description.View Large Image Figure ViewerDownload (PPT) Metastatic chemodectomas are exceedingly rare. Fuller and co-workers4Fuller AM Brown HA Harrison EG Jr et al.Chemodectoma of the glomus jugulare.Laryngoscope. 1967; 77: 218-238Crossref PubMed Scopus (50) Google Scholar reported 72 glomus jugulare tumors and McIlrath and associates5McIlrath DC ReMine WH Carotid-body tumors.Surg Clin N Am. 1963; 43: 1135-1144Crossref PubMed Scopus (14) Google Scholar reported 64 carotid body tumors in which no metastases were found. Monro14Monroe RS Natural history of carotid body tumors and their diagnosis and treatment with a report of five cases.Br J Surg. 1950; 37: 445-453Crossref PubMed Scopus (40) Google Scholar reviewed 179 cases of carotid body tumors and found only three with evidence of hematogenous spread. In 1973, Fanning and colleagues,6Fanning JP Woods FM Christian MJ Metastatic carotid body tumor: report of a case with review of the literature.JAMA. 1963; 185: 49-50Crossref Scopus (28) Google Scholar reviewed the literature and found 25 cases of chemodectomas with hematogenous and lymphatic metastases. Visceral metastases were present in 14 of the cases while metastases to regional lymph nodes occurred in 13 cases. In 1969, Brown and co-workers15Brown JW Burton RC Dahlin DC Chemodectoma with skeletal metastasis: report of two cases.Mayo Clin Proc. 1967; 42: 551-555PubMed Google Scholar reported two cases of chemodectomas metastatic to bone and found seven additional cases in the English literature. The secretory potential of chemodectomas has been suggested by the demonstration of intracellular secretory granules by electronmicroscopic examination.16Kawabata I Duvall AJ Paparella MM Ultrastructure of the glomus jugulare tumor.Arch Klin exp Ohr Nas Kehlkopf heilk. 1969; 195: 97-103Crossref PubMed Scopus (9) Google Scholar, 17Capella C Solcia E Optical and electron microscopical study of cytoplasmic granules in human carotid body, carotid body tumors and glomus jugulare tumors.Virchows Arch Abt B Zellpath. 1971; 7: 37-53Google Scholar In addition, Levit and co-workers10Levit SA Sheldon GS Espinosa RE et al.Catecholamine-secreting paraganglioma of glomus-jugulare region resembling pheochromocytoma.N Engl J Med. 1969; 281: 805-811Crossref PubMed Scopus (84) Google Scholar reported a norepinephrine secreting chemodectoma in the neck of a 24 year-old man and reviewed six previously reported cases in which elevated catecholamine excretion or clinical symptoms or both compatible with pheochromocytoma were present. The marked elevation of HVA excretion demonstrated in our case further substantiates the secretory potential of these tumors and suggests that measurement of catecholamine or catecholamine metabolite excretion may be a useful diagnostic test even in those patients who do not have symptoms usually associated with catecholamine secreting tumors. Accurate preoperative diagnosis of a chemodectoma may be extremely important in assuring optimal surgical management of such patients. Since these lesions tend to be extremely vascular, significant hemorrhage may occur at the time of surgery. In addition manipulation of a catecholamine secreting tumor may result in extreme hemodynamic instability during the operative procedure. These complications can be minimized by proper preoperative management if the correct diagnosis is suspected. We wish to express our gratitude to Dr. Stanley E. Gitlow at Mount Sinai School of Medicine, New York, for the urinary catecholamine analysis, to Dr. Gustavo Reynoso at Roswell Park Memorial Institute, Buffalo, New York, for the carcinoembryonic antigen determinations; and Drs. Johannes Blom ana Michael E. Whitcomb, LTC, MC at Walter Reed Army Medical Center, Washington, DC, for reviewing the manuscript.