The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

Case Records of the Massachusetts General Hospital

TABLE 1. HEMATOLOGIC LABORATORY VALUES.

VARIABLE VALUE

Weekly Clinicopathological Exercises

FOUNDED BY RICHARD C. CABOT

R O B E R T E . S C U L L Y , M. D. , Editor E U G E N E J. M A R K , M. D. , Associate Editor W I L L I A M F. M C N E E L Y , M. D. , Associate Editor J O - A N N E O. S H E P A R D , M. D. , Associate Editor S A L L Y H . E B E L I N G , Assistant Editor S T A C E Y M. E L L E N D E R , Assistant Editor C H R I S T I N E C . P E T E R S , Editorial Staff Case 13-2001

Hematocrit (%) White-cell count (per mm3) Differential count (%) Neutrophils Lymphocytes Monocytes Eosinophils Basophils Platelet count (per mm3) Prothrombin time Partial-thromboplastin time

52.3 7,000 58 31 7 3 1 206,000 Normal Normal

PRESENTATION OF CASE

A 19-year-old man was admitted to the hospital because of headaches and hypertension. The patient had been well until two years earlier, when he began to have episodic mild headaches that resolved spontaneously. Two months before admission, the headaches became much more severe and frequent, occurring almost daily, and were accompanied by throbbing chest pain, sweating, dizziness, palpitations, and a greenish pallor. The episodes occurred during both waking hours and sleep and were often heralded by an epigastric uneasiness that radiated to the head. Four weeks before admission, hypertension was diagnosed. A computed tomographic (CT) scan of the head, obtained without contrast material, showed no abnormalities. Treatment with lisinopril was ineffective. One day before admission, the patients pulse was 87, and his blood pressure was 110/70 mm Hg. An electrocardiogram showed normal findings, with a rate of 63. Thoracic radiographs revealed a paraspinal mass, 6.5 cm in its largest linear dimension, along the right cardiac border, with possible erosion of a rib. During a severe headache, the blood pressure was 235/135 mm Hg, with ventricular bigeminy and profuse sweating. On the day of admission, the patient had another severe headache that was accompanied by moderate chest pain and a blood pressure of 220/ 105 mm Hg. Nitroglycerin was given intravenously, with atenolol and cyclobenzaprine, and the pain decreased. The patient was admitted to this hospital. The patients father had hypertension, which had been discovered when he was in his 50s, and the patients mother had migraines; his siblings were well. He reported that he did not use illicit drugs.

Figure 1. T1-Weighted MRI Scan of the Thoracic Spine Obtained after the Administration of Contrast Material, Showing a RightSided, Paravertebral Mass with Smooth, Sharply Demarcated Borders and Multiple Flow Voids. The mass extends from thoracic vertebrae 7 to 9 and has caused slight scalloping of the adjacent vertebrae.

The temperature was 36.6C, and the respirations were 16. While the patient was supine, the blood pressure was 140/70 mm Hg in the right arm and 120/ 80 mm Hg in the left arm, and the pulse was 72; while he was standing, the systolic blood pressure was 80 mm Hg, and the pulse was 116.

1314 N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org
Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.

CASE RECORDS OF TH E MAS SACH USET TS GENER A L H OSPITA L

On physical examination, the patient appeared well. The carotid upstrokes were bounding. The cardiac apical impulse was prominent. Hematologic laboratory values are shown in Table 1. Blood chemical and enzyme levels were normal except that the phosphorus level was 4.8 mg per deciliter (1.5 mmol per liter). Toxologic testing of a serum sample was negative for more than 100 drugs; no urine specimen was submitted for testing. An electrocardiogram showed a PR interval of 128 msec and nonspecific ST-segment and T-wave abnormalities, with prominent voltage. A magnetic resonance imaging (MRI) examination of the thoracic spine (Fig. 1), performed before and after the injection of gadolinium, revealed a well-demarcated, enhanced paravertebral mass, 8 by 5 by 4 cm, on the right side; multiple flow voids were consistent with the presence of vessels. The mass extended from thoracic vertebrae 7 to 9 and entered the neural foramen of thoracic vertebra 8; there was no extension into the spinal canal. The mass extended to the chest wall but was well demarcated from it. The right lateral margins of the vertebral bodies were slightly scalloped. A CT scan of the abdomen and pelvis, obtained after the oral administration of contrast material, showed no abnormalities. A diagnostic procedure was performed.
DIFFERENTIAL DIAGNOSIS

sion of an adjacent rib by the thoracic mass indicate that the duration of the hypertension may have been longer than the history suggests. I shall first discuss the limited differential diagnosis of the clinical syndrome in this patient, and I shall then discuss the features of pheochromocytoma, which is my diagnosis of the paravertebral mass in this case.
Hyperadrenergic and Hyperadrenergic-like States

DR. PAUL R. CONLIN*: This young man presented with paroxysmal hypertension and headaches, and he had a paravertebral mass. I shall not discuss the differential diagnosis of a posterior mediastinal mass, which would be too broad in a patient known to have paroxysmal hypertension with hyperadrenergic symptoms.
General Evaluation of the Patients Hypertension

The onset of hypertension in a 19-year-old man should not always lead to a search for an underlying cause. Indeed, essential hypertension is the most likely diagnosis. However, this patient has clinical manifestations that suggest that the cause is reversible, and a detailed evaluation is warranted. The patients father had hypertension, but his age at its onset suggests that it was essential hypertension. Although essential hypertension is often inherited, it is more likely to develop in middle age than in the teenage years. This patient does not have a family history of an endocrinopathy that would suggest an inherited predisposition to his symptoms. We do not know the exact time of onset of the hypertension. The nonspecific ST-segment and T-wave changes with prominent voltage on the electrocardiogram and the radiologic evidence of possible ero*Chief, Endocrine Section, Veterans Affairs Boston Healthcare System; director, Endocrinology Fellowship Program, EndocrinologyHypertension Division, Brigham and Womens Hospital; assistant professor of medicine, Harvard Medical School all in Boston.

Clinical findings that suggest excessive secretion of catecholamines can occur in several clinical contexts (Table 2). Some patients with essential hypertension, most of whom are young, have palpitations, sweating, tachycardia, and an increased cardiac output, suggesting increased secretion of catecholamines. Only 0.1 percent of patients with presumed essential hypertension, however, are found to have a pheochromocytoma on careful screening. Normotensive persons may experience anxiety attacks that include all the symptoms of excessive catecholamine secretion. Hyperthyroidism may be associated with a hyperkinetic, hyperadrenergic state, characterized by hypertension, palpitations, and sweating, but these manifestations are typically persistent, not paroxysmal. Intracranial lesions, including tumors and subarachnoid bleeding, can cause headaches, hypertension, and increased secretion of catecholamines, but they are accompanied by other neurologic manifestations as well. In rare cases, diencephalic seizures cause paroxysmal hypertension, with symptoms of excessive catecholamine secretion that are often preceded by an aura. This patients epigastric sensation, which heralded his other symptoms, probably did not represent an aura of autonomic epilepsy. Cocaine use, which increases the release and prevents the reuptake of endogenous catecholamines, can cause a marked increase in blood pressure, hyperadrenergic symptoms, and most important, myocardial damage.1 Although toxicologic screening in this patient did not include tests of a urine sample, which would have increased the sensitivity of the screening, the results of serum tests were negative. Finally, baroreflex failure can cause paroxys-

AND

TABLE 2. HYPERADRENERGIC HYPERADRENERGIC-LIKE STATES.

Essential hypertension Anxiety attacks Hyperthyroidism Intracranial lesions Diencephalic seizures Use of drugs (e.g., cocaine) Baroreflex failure Pheochromocytoma (adrenal or extraadrenal)

N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org 1315 Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.

The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

mal swings in blood pressure, accompanied by headache, sweating, and emotional instability.2 This disorder is usually due to damage to head and neck structures, including the glossopharyngeal nerve, resulting in loss of blood-pressure buffering by baroreceptor efferent nerves. There is no evidence of any of those disorders in the present case.
Clinical Features of Pheochromocytoma

Patients with pheochromocytoma have a variety of symptoms attributable to periodic increases in the secretion of catecholamines. In a patient with hypertension, the usual triad of headaches, palpitations, and sweating strongly suggests the presence of pheochromocytoma. Less frequent symptoms are pallor, nausea, abdominal and chest pain, and tremor. The symptoms are often mild initially but subsequently increase in frequency and duration. Ninety percent of patients with pheochromocytoma have hypertension, which is sustained in two thirds of them and intermittent in the remainder. About half of the patients with persistent hypertension also have paroxysmal symptoms. Thus, overall, paroxysms are present in about two thirds of patients with pheochromocytoma.3 The paroxysms last for a few minutes to a few hours and are often spontaneous. Emotional stress does not induce attacks. Triggers include abdominal pressure, which may increase catecholamine secretion by the tumor, and a sudden drop in blood pressure, such as may occur during the induction of general anesthesia. Drugs can also precipitate a hypertensive crisis, including drugs that lower blood pressure, thereby stimulating catecholamine secretion by the tumor; those that block neuronal uptake of catecholamines, such as tricyclic antidepressants; and other substances thought to alter catecholamine secretion by the tumor, such as glucagon, opiates, and metoclopramide. Treatment of paroxysms with b-adrenergicreceptor antagonists intensifies the hypertension, presumably by abolishing the vasodilating effects of b 2-adrenergicreceptor stimulation while the excessive catecholamines are stimulating vasoconstricting a1-adrenergic receptors. This patient was given atenolol, but it does not appear to have affected his blood pressure. Most pheochromocytomas secrete catecholamines continuously, with episodes of increased secretion. In rare cases, the secretion is only episodic and is linked to the onset of symptoms. Even in patients with a sustained elevation of catecholamine levels, the blood pressure is not always markedly elevated and may even be normal, probably because of hemodynamic alterations caused by the excessive secretion of catecholamines. These changes include an increase in peripheral vascular resistance and a reduction in sympathetic reflexes caused by the down-regulation of sympathetic receptors, and they are manifested as orthostatic hypotension, hypovolemia, and occasionally an increased

hematocrit, which is thought to be due to the reduced plasma volume. These manifestations of hemodynamic changes were present in this patient. In addition, angina, arrhythmias, and even acute myocardial infarction may occur during paroxysmal increases in blood pressure in patients without coronary artery disease. Base-line electrocardiographic changes, including nonspecific ST-segment and T-wave changes and voltage changes associated with left ventricular hypertrophy, may be present. In rare cases, cardiomyopathy with congestive heart failure develops, which is thought to be due to catecholamine-induced focal myocardial necrosis. Another frequent clinical manifestation of pheochromocytoma is hyperglycemia, which is due to the inhibition of insulin secretion and the stimulation of hepatic glucose output by catecholamines. Ectopic production of parathyroid hormonerelated peptide by the tumor may cause hypercalcemia; the calcium level often returns to normal after the tumor has been removed.4 Pheochromocytoma may be a component of type IIA or IIB multiple endocrine neoplasia or may be associated with neurofibromatosis or von HippelLindau disease. This patient had a normal calcium level, however, and he did not have a family history of any of these syndromes.
Laboratory Diagnosis of Pheochromocytoma

The diagnosis of pheochromocytoma is established by demonstrating increased levels of catecholamines or catecholamine metabolites, typically in urine samples but also sometimes in plasma samples. The most reliable tests are measurements of free catecholamines, metanephrines, or vanillylmandelic acid in a 24-hour urine specimen. The last measurement is less sensitive than the other two. Diagnostic accuracy is improved by measuring at least two of the three substances. Tumors that secrete catecholamines continuously can be detected by tests of randomly collected urine samples, but the sensitivity is increased if the urine is collected during or soon after a hypertensive crisis, when the levels of catecholamines and their metabolites are typically at least three times as high as normal. Recently ingested substances may occasionally cause false negative or positive results, especially in the case of vanillylmandelic acid. Plasma catecholamine measurements have a sensitivity of more than 90 percent and a specificity of 95 percent for the diagnosis of pheochromocytoma.5 Care must be used in obtaining the plasma samples, however, since the level of endogenous catecholamines can be increased by stress and by the procedure of drawing blood. In a recently reported study of patients with familial pheochromocytoma, measurements of plasma normetanephrine and metanephrine had a sensitivity of 97 percent and a specificity of 96 percent.6 Suppressive tests (e.g., with the use of clonidine)

1316 N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org
Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.

CASE RECORDS OF TH E MAS SACH USET TS GENER A L H OSPITA L

or provocative tests (e.g., with the use of glucagon) are rarely necessary to establish the diagnosis of pheochromocytoma. Since provocative tests may induce a hypertensive crisis, they should be reserved for patients who probably have a pheochromocytoma but in whom the diagnosis cannot be confirmed with simple biochemical testing.
Localization of the Tumor

Ninety percent of pheochromocytomas arise from the adrenal gland. However, of those that are extraadrenal, 98 percent are found in the abdomen. The most common extraadrenal sites in the abdomen are the organ of Zuckerkandl, sympathetic ganglia, and the urinary bladder. Thoracic tumors may arise in the sympathetic ganglia in the posterior mediastinum, along the aorta or the heart. In rare cases, the tumor develops in the carotid body. Since most pheochromocytomas involve the adrenal gland, the abdomen should be the first area evaluated by imaging, but only after a biochemical diagnosis has been made. In up to 5 percent of abdominal imaging studies, an adrenal mass is found, but in most cases it is an incidental adenoma unrelated to the patients symptoms. Either CT or MRI scanning can detect tumors as small as 0.5 cm in diameter. An advantage of MRI is that the pheochromocytoma appears as a bright mass on a T2-weighted image.7 Occasionally, despite a biochemical diagnosis, imaging techniques do not reveal a pheochromocytoma. In such cases, scanning with [131I]metaiodobenzylguanidine may be useful,8 since it is concentrated in pheochromocytomas. Recent experience with the use of radiolabeled octreotide shows promise as a diagnostic procedure.9
Treatment of Pheochromocytoma

toma was strongly suggested by the clinical findings, and we proceeded to control the blood pressure with a-adrenergicreceptor blockade while awaiting the results of urine and blood tests. The urinary norepinephrine level was 20 times the normal value, and the metanephrine and vanillylmandelic acid levels were also markedly elevated. The plasma norepinephrine level was nine times as high as the normal level, and the dopamine level was four times as high. Epinephrine levels were undetectable, however, in both urine and blood specimens. DR. JOHN C. WAIN: The imaging studies indicated that the tumor was an isolated lesion, as it is in 90 percent of cases. We explored the patients thorax and found a well-circumscribed tumor attached to portions of four ribs, which we excised en bloc with the tumor. The tumor was highly vascular, which is characteristic of pheochromocytomas, and numerous transfusions were required.
CLINICAL DIAGNOSIS

Extraadrenal pheochromocytoma.
DR. PAUL R. CONLINS DIAGNOSIS

Extraadrenal pheochromocytoma.
PATHOLOGICAL DISCUSSION

Once a pheochromocytoma has been diagnosed on the basis of biochemical tests, the patient should be treated with agents that block catecholamine receptors while the evaluation proceeds. The most widely used agent is phenoxybenzamine, a nonspecific a-adrenergicreceptor antagonist. The definitive treatment is surgical excision of the pheochromocytoma. It may be tempting to perform a fine-needle aspiration biopsy of the mass preoperatively, but it should be avoided, particularly if the patient has not been receiving treatment with an a-adrenergicreceptor antagonist, because needle biopsy can itself provoke the secretion of catecholamines, resulting in a hypertensive crisis.10 The diagnostic procedure in this case was probably the measurement of urine catecholamines and metanephrines, followed by resection of the tumor. DR. LAURA P. WOLSKO: I obtained the additional information that the patients paroxysms were precipitated by exertion and postural changes, and also that his symptoms had been aggravated by the administration of morphine at another hospital before his admission to this hospital. The diagnosis of pheochromocy-

DR. WILLIAM C. FAQUIN: The resected specimen consisted of a lobulated mass, 6.5 cm in diameter, with an attached portion of the lateral chest wall, including four ribs. Sectioning of the mass revealed wellcircumscribed, tan, focally hemorrhagic tissue (Fig. 2). Microscopical examination showed a tumor composed largely of nests, or Zellballen, of round-to-polygonal chief cells separated by a prominent sinusoidal vasculature (Fig. 3). These cells were characterized by abundant pale, finely granular, eosinophilic cytoplasm and central round-to-oval vesicular nuclei containing small nucleoli. Although occasional cells had atypical nuclei, mitotic activity and necrosis were absent. Scattered stellate sustentacular cells were present, mostly in the periphery of the nests. The chief cells were generally strongly positive for chromogranin A (Fig. 4), synaptophysin, and neuron-specific enolase and negative for keratin on immunohistochemical staining, indicating their neuroendocrine nature. The sustentacular cells were generally positive for S-100 protein (Fig. 5). Ultrastructural examination of a chief cell showed that it contained numerous intracytoplasmic, electrondense, membrane-bound granules, 100 to 300 nm in diameter (Fig. 6). Some of the granules had an eccentric core and a prominent halo, which is consistent with the presence of norepinephrine, whereas others had an inconspicuous halo, which is consistent with the presence of epinephrine, although there was no laboratory evidence that the tumor was secreting epinephrine. The pathological findings in this case are charac-

N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org 1317 Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.

The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

Figure 2. Resected Specimen Showing a Well-Circumscribed, Tan, Focally Hemorrhagic Tumor Adherent to Adjacent Ribs. Figure 4. Neoplastic Chief Cells Stained Brown for Chromogranin A (Immunoperoxidase Staining, 200).

Figure 3. Neoplastic Chief Cells Arranged in Nests (Zellballen) (Arrows) Delineated by Delicate, Fibrovascular Septa (Hematoxylin and Eosin, 500).

Figure 5. Spindle-Shaped Sustentacular Cells Scattered at the Periphery of Nests of Chief Cells and Stained Brown for S-100 Protein (Immunoperoxidase Staining, 500).

teristic of a paraganglioma. The term used for this type of tumor varies. Clinicians often refer to it as a pheochromocytoma, regardless of its location, if it is associated with the clinical syndrome characteristic of that tumor. Pathologists, however, usually reserve the term for an adrenal medullary tumor of chromaffin

cells and call any extraadrenal tumor a paraganglioma, regardless of whether or not it has the clinical and laboratory features of the adrenal tumor. Extraadrenal paragangliomas are tumors of the autonomic nervous system composed of cells derived from the primitive neural crest.11,12 These tumors ac-

1318 N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org
Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.

CASE RECORDS OF TH E MAS SACH USET TS GENER A L H OSPITA L

DR. FAQUIN: There is no proven correlation between the size of the tumor and its malignant or benign nature. DR. WAIN: In the immediate postoperative period, the patient had a very large volume requirement ascribable to his diminished plasma volume before surgery and ongoing a-adrenergicreceptor blockade. It took 72 hours for his hemodynamic status to become stable without the use of various suppressants and fluid supplementation. His blood pressure is now normal, his symptoms have disappeared, and the results of laboratory tests have become normal.
ANATOMICAL DIAGNOSIS

Paraganglioma (pheochromocytoma) of the posterior mediastinum.

REFERENCES
1. Hollander JE. The management of cocaine-associated myocardial ischemia. N Engl J Med 1995;333:1267-72. 2. Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R , Robertson RM. The diagnosis and treatment of baroreflex failure. N Engl J Med 1993;329:1449-55. 3. van Heerden JA, Sheps SG, Hamberger B, Sheedy PF, Poston JG, ReMine WH. Pheochromocytoma: current status and changing trends. Surgery 1982;91:367-73. 4. Stewart AF, Hoecker JL, Mallette LE, Segre GV, Amatruda TT, Vignery A. Hypercalcemia in pheochromocytoma: evidence for a novel mechanism. Ann Intern Med 1985;102:776-9. 5. Gifford RW, Manger WM, Bravo EL. Pheochromocytoma. Endocrinol Metab Clin North Am 1994;23:387-404. 6. Eisenhofer G, Lenders JWM, Linehan WM, Walther MM, Goldstein DS, Keiser HR. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von HippelLindau disease and multiple endocrine neoplasia type 2. N Engl J Med 1999;340:1872-9. 7. Doppman JL, Reinig JW, Dwyer AJ, et al. Differentiation of adrenal masses by magnetic resonance imaging. Surgery 1987;102:1018-26. 8. Nguyen HH, Proye CAG, Carnaille B, Combemale F, Pattou FN, Huglo D. Tumour size: the only predictive factor for 131I MIBG uptake in phaeochromocytoma and paraganglioma. Aust N Z J Surg 1999;69: 350-3. 9. van der Harst E, de Herder WW, Bruining HA, et al. [123I]Metaiodobenzylguanidine and [111In]octreotide uptake in benign and malignant pheochromocytomas. J Clin Endocrinol Metab 2001;86:685-93. 10. Chimori K, Miyazaki S, Nakajima T, Miura K. Preoperative management of pheochromocytoma with the calcium-antagonist nifedipine. Clin Ther 1985;7:372-9. 11. The sympathoadrenal neuroendocrine system. In: Lack EE. Pathology of adrenal and extra-adrenal paraganglia. Vol. 29 of Major problems in pathology. Philadelphia: W.B. Saunders, 1994:186-219. 12. Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma. J Urol 1992;147:1-10. 13. Odze R , Begin LR. Malignant paraganglioma of the posterior mediastinum: a case report and review of the literature. Cancer 1990;65:5649. 14. Gallivan MV, Chun B, Rowden G, Lack EE. Intrathoracic paravertebral malignant paraganglioma. Arch Pathol Lab Med 1980;104:4651. 15. Olson JL, Salyer WR. Mediastinal paragangliomas (aortic body tumor): a report of four cases and review of the literature. Cancer 1978;41: 2405-12. 16. Noorda RJP, Wuisman PIJ, Kummer AJ, Winters HAH, Rauwerda JA, Egeler-Peerdeman SM. Nonfunctioning malignant paraganglioma of the posterior mediastinum with spinal cord compression: a case report. Spine 1996;21:1703-9. 17. Kliewer KE, Cochran AJ. A review of the histology, ultrastructure, immunohistology, and molecular biology of extra-adrenal paragangliomas. Arch Pathol Lab Med 1989;113:1209-18. [Erratum, Arch Pathol Lab Med 1990;114:308.] 18. Kliewer KE, Wen DR , Cancilla PA, Cochran AJ. Paragangliomas: assessment of prognosis by histologic, immunohistochemical, and ultrastructural techniques. Hum Pathol 1989;20:29-39.

Figure 6. Electron Micrograph of a Chief Cell Containing Intracytoplasmic, Electron-Dense, Neurosecretory Granules (Arrows). The chief cell is adjacent to spindle-shaped sustentacular cells. The bar represents 1.4 mm.

count for only 0.3 percent of all mediastinal neoplasms.13-16 About one third of them are located in the posterior mediastinum. They are functional in 35 to 50 percent of cases, are aggressive in less than 15 percent of cases, and are generally smaller and less often multicentric than anterior mediastinal tumors.13-16 There are no generally accepted histologic criteria for distinguishing benign from malignant paragangliomas, since features such as nuclear atypia, mitoses, and capsular or vascular invasion are seen in both types of tumor. Data from at least two groups of investigators, however, suggest that the number of sustentacular cells is smaller in malignant tumors than in benign tumors.17-19 The operative finding of invasion and the detection of metastasis, most often to the lymph nodes, lung, liver, or bone, remain the most reliable indicators of malignancy.12,13,17,20,21 DR. MILTON E. SKELLY: Is the size of the tumor a prognostic factor?

N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org 1319 Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.

The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

19. Bird DJB, Seiler MW. Aorticopulmonary paraganglioma (aortic body tumor): report of a case. Ultrastruct Pathol 1991;15:475-9. 20. Glenner GG, Grimley PM. Tumors of the extra-adrenal paraganglion system (including chemoreceptors). Atlas of tumor pathology. 2nd series. Fascicle 9. Washington, D.C.: Armed Forces Institute of Pathology, 1974. 21. Capella C, Riva C, Cornaggia M, Chiaravalli AM, Frigerio B, Solcia E.

Histopathology, cytology and cytochemistry of pheochromocytomas and paragangliomas including chemodectomas. Pathol Res Pract 1988;183: 176-87. Copyright 2001 Massachusetts Medical Society.

35-MILLIMETER SLIDES FOR THE CASE RECORDS Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a medical teaching exercise or reference material is eligible to receive 35-mm slides, with identifying legends, of the pertinent x-ray films, electrocardiograms, gross specimens, and photomicrographs of each case. The slides are 2 in. by 2 in., for use with a standard 35-mm projector. These slides, which illustrate the current cases in the Journal, are mailed from the Department of Pathology to correspond to the week of publication and may be retained by the subscriber. Each year approximately 250 slides from 40 cases are sent to each subscriber. The cost of the subscription is $450 per year. Application forms for the current subscription year, which began in January, may be obtained from Lantern Slides Service, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 (telephone [617] 726-2974). Slides from individual cases may be obtained at a cost of $35 per case.

1320 N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org
Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.