Feocromocitoma Extra Adrenal

7/30/2019 Feocromocitoma Extra Adrenal

1/7

Weekly Clinicopathological Exercises

F O U N D E D B Y R I C H A R D C . C A B O T

ROBERT E. SCULLY

, M.D.,

Editor

E

UGENE

J. M

A RK

, M.D.,

As soc iate Edi tor

W

IL L IA M

F. M

C

N

EELY

, M.D.,

As soc iate Editor

J

O

-A

NN E

O. S

HE PA RD

,

M.D., As soc iate Editor

S

A LL Y

H. E

BELING

, As sis tant Edi tor

S

T A CE Y

M. E

LLENDER

,

As si stant Editor

C

HRIST INE

C. P

E T E RS

, Editorial Staff

Case Records of the Massachusetts General Hospital

1314

N Engl J Med, Vol. 344, No. 17

April 26, 2001

www.nejm.org

The New England Journal of Medicine

Case 13-2001

PRESENTATION OF CASE

A 19-year-old man was admitted to the hospital be-cause of headaches and hypertension.

The patient had been well until two years earlier,when he began to have episodic mild headaches thatresolved spontaneously. Two months before admis-sion, the headaches became much more severe andfrequent, occurring almost daily, and were accompa-nied by throbbing chest pain, sweating, dizziness,palpitations, and a greenish pallor. The episodes oc-curred during both waking hours and sleep and wereoften heralded by an epigastric uneasiness that ra-diated to the head.

Four weeks before admission, hypertension was di-agnosed. A computed tomographic (CT) scan of thehead, obtained without contrast material, showed noabnormalities. Treatment with lisinopril was ineffective.

One day before admission, the patients pulse was87, and his blood pressure was 110/70 mm Hg. Anelectrocardiogram showed normal findings, with arate of 63. Thoracic radiographs revealed a paraspinalmass, 6.5 cm in its largest linear dimension, along theright cardiac border, with possible erosion of a rib.During a severe headache, the blood pressure was235/135 mm Hg, with ventricular bigeminy and pro-fuse sweating. On the day of admission, the patienthad another severe headache that was accompanied bymoderate chest pain and a blood pressure of 220/105 mm Hg. Nitroglycerin was given intravenously,

with atenolol and cyclobenzaprine, and the pain de-creased. The patient was admitted to this hospital.

The patients father had hypertension, which hadbeen discovered when he was in his 50s, and the pa-tients mother had migraines; his siblings were well.He reported that he did not use illicit drugs.

The temperature was 36.6C, and the respirationswere 16. While the patient was supine, the blood pres-sure was 140/70 mm Hg in the right arm and 120/80 mm Hg in the left arm, and the pulse was 72; whilehe was standing, the systolic blood pressure was 80mm Hg, and the pulse was 116.

T

ABLE

1.

H

EMATOLOGIC

L

ABORATORY

V

ALUES

.

V

ARIABLE

V

ALUE

Hematocrit (%) 52.3

White-cell count (per mm

3

) 7,000

Differential count (%)Neutrophils 58Lymphocytes 31Monocytes 7Eosinophils 3Basophils 1

Platelet count (per mm

3

) 206,000

Prothrombin time Normal

Partial-thromboplastin time Normal

Figure 1.

T

1

-Weighted MRI Scan of the Thoracic Spine Obtainedafter the Administration of Contrast Material, Showing a Right-Sided, Paravertebral Mass with Smooth, Sharply DemarcatedBorders and Multiple Flow Voids.

The mass extends from thoracic vertebrae 7 to 9 and has causedslight scalloping of the adjacent vertebrae.

Downloaded from www.nejm.org on October 3, 2008 . Copyright 2001 Massachusetts Medical Society. All rights reserved.


2/7

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL


April 26, 2001

www.nejm.org

1315

On physical examination, the patient appeared well.The carotid upstrokes were bounding. The cardiac api-cal impulse was prominent. Hematologic laboratory

values are shown in Table 1. Blood chemical and en-zyme levels were normal except that the phosphoruslevel was 4.8 mg per deciliter (1.5 mmol per liter).

Toxologic testing of a serum sample was negative formore than 100 drugs; no urine specimen was sub-mitted for testing. An electrocardiogram showed aPR interval of 128 msec and nonspecific ST-segmentand T-wave abnormalities, with prominent voltage.

A magnetic resonance imaging (MRI) examination ofthe thoracic spine (Fig. 1), performed before and afterthe injection of gadolinium, revealed a well-demarcat-ed, enhanced paravertebral mass, 8 by 5 by 4 cm, onthe right side; multiple flow voids were consistent withthe presence of vessels. The mass extended from tho-racic vertebrae 7 to 9 and entered the neural foramenof thoracic vertebra 8; there was no extension intothe spinal canal. The mass extended to the chest wall

but was well demarcated from it. The right lateral mar-gins of the vertebral bodies were slightly scalloped.

A CT scan of the abdomen and pelvis, obtained afterthe oral administration of contrast material, showedno abnormalities.

A diagnostic procedure was performed.

DIFFERENTIAL DIAGNOSIS

D

R

. P

AUL

R. C

ONLIN

*: This young man present-ed with paroxysmal hypertension and headaches, andhe had a paravertebral mass. I shall not discuss thedifferential diagnosis of a posterior mediastinal mass,

which would be too broad in a patient known tohave paroxysmal hypertension with hyperadrenergic

symptoms.

General Evaluation of the Patients Hypertension

The onset of hypertension in a 19-year-old manshould not always lead to a search for an underlyingcause. Indeed, essential hypertension is the most like-ly diagnosis. However, this patient has clinical man-ifestations that suggest that the cause is reversible, anda detailed evaluation is warranted.

The patients father had hypertension, but his ageat its onset suggests that it was essential hypertension.

Although essential hypertension is often inherited, itis more likely to develop in middle age than in theteenage years. This patient does not have a family his-

tory of an endocrinopathy that would suggest an in-herited predisposition to his symptoms.

We do not know the exact time of onset of the hy-pertension. The nonspecific ST-segment and T-wavechanges with prominent voltage on the electrocar-diogram and the radiologic evidence of possible ero-

sion of an adjacent rib by the thoracic mass indicatethat the duration of the hypertension may have beenlonger than the history suggests.

I shall first discuss the limited differential diagnosisof the clinical syndrome in this patient, and I shall thendiscuss the features of pheochromocytoma, which is

my diagnosis of the paravertebral mass in this case.

Hyperadrenergic and Hyperadrenergic-like States

Clinical findings that suggest excessive secretion ofcatecholamines 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, suggest-ing increased secretion of catecholamines. Only 0.1percent of patients with presumed essential hyper-tension, however, are found to have a pheochromo-cytoma on careful screening. Normotensive personsmay experience anxiety attacks that include all thesymptoms of excessive catecholamine secretion. Hy-

perthyroidism may be associated with a hyperkinetic,hyperadrenergic state, characterized by hypertension,palpitations, and sweating, but these manifestationsare typically persistent, not paroxysmal. Intracraniallesions, including tumors and subarachnoid bleeding,can cause headaches, hypertension, and increased se-cretion of catecholamines, but they are accompaniedby other neurologic manifestations as well. In rarecases, diencephalic seizures cause paroxysmal hyper-tension, with symptoms of excessive catecholamine se-cretion that are often preceded by an aura. This pa-tients epigastric sensation, which heralded his othersymptoms, probably did not represent an aura of au-tonomic epilepsy. Cocaine use, which increases the

release and prevents the reuptake of endogenous cat-echolamines, can cause a marked increase in bloodpressure, hyperadrenergic symptoms, and most im-portant, myocardial damage.

1

Although toxicologicscreening in this patient did not include tests of aurine sample, which would have increased the sensi-tivity of the screening, the results of serum tests werenegative. Finally, baroreflex failure can cause paroxys-

*Chief, Endocrine Section, Veterans Affairs Boston Healthcare System;director, Endocrinology Fellowship Program, EndocrinologyHyperten-sion Division, Brigham and Womens Hospital; assistant professor of med-icine, Harvard Medical School all in Boston.

T

ABLE

2.

H

YPERADRENERGIC

AND

H

YPERADRENERGIC

-

LIKE

S

TATES

.

Essential hypertension

Anxiety attacks

Hyperthyroidism

Intracranial lesions

Diencephalic seizures

Use of drugs (e.g., cocaine)

Baroreflex failure

Pheochromocytoma (adrenalor extraadrenal)



3/7

1316


April 26, 2001

www.nejm.org


mal swings in blood pressure, accompanied by head-ache, sweating, and emotional instability.

2

This dis-order is usually due to damage to head and neckstructures, including the glossopharyngeal nerve, re-sulting in loss of blood-pressure buffering by baro-receptor 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 ofsymptoms attributable to periodic increases in the se-cretion of catecholamines. In a patient with hyperten-sion, the usual triad of headaches, palpitations, andsweating strongly suggests the presence of pheochro-mocytoma. Less frequent symptoms are pallor, nau-sea, abdominal and chest pain, and tremor.

The symptoms are often mild initially but subse-quently increase in frequency and duration. Ninetypercent of patients with pheochromocytoma have hy-pertension, which is sustained in two thirds of them

and intermittent in the remainder. About half of thepatients with persistent hypertension also have parox-

ysmal symptoms. Thus, overall, paroxysms are presentin about two thirds of patients with pheochromocy-toma.

3

The paroxysms last for a few minutes to a few hoursand are often spontaneous. Emotional stress does notinduce attacks. Triggers include abdominal pressure,

which may increase catecholamine secretion by thetumor, and a sudden drop in blood pressure, such asmay occur during the induction of general anesthesia.Drugs can also precipitate a hypertensive crisis, includ-ing drugs that lower blood pressure, thereby stimulat-ing catecholamine secretion by the tumor; those that

block neuronal uptake of catecholamines, such as tri-cyclic antidepressants; and other substances thoughtto alter catecholamine secretion by the tumor, such asglucagon, opiates, and metoclopramide. Treatment ofparoxysms with b

-adrenergicreceptor antagonistsintensifies the hypertension, presumably by abolish-ing the vasodilating effects ofb

2

-adrenergicrecep-tor stimulation while the excessive catecholamines arestimulating vasoconstricting a

1

-adrenergic receptors.This patient was given atenolol, but it does not appearto have affected his blood pressure.

Most pheochromocytomas secrete catecholaminescontinuously, with episodes of increased secretion. Inrare cases, the secretion is only episodic and is linkedto the onset of symptoms. Even in patients with a sus-tained elevation of catecholamine levels, the bloodpressure is not always markedly elevated and may evenbe normal, probably because of hemodynamic alter-ations caused by the excessive secretion of catechol-amines. These changes include an increase in periph-eral vascular resistance and a reduction in sympatheticreflexes caused by the down-regulation of sympatheticreceptors, and they are manifested as orthostatic hy-potension, hypovolemia, and occasionally an increased

hematocrit, which is thought to be due to the reducedplasma volume. These manifestations of hemodynam-ic changes were present in this patient. In addition, an-gina, arrhythmias, and even acute myocardial infarc-tion may occur during paroxysmal increases in bloodpressure in patients without coronary artery disease.

Base-line electrocardiographic changes, including non-specific ST-segment and T-wave changes and voltagechanges associated with left ventricular hypertrophy,may be present. In rare cases, cardiomyopathy withcongestive heart failure develops, which is thoughtto be due to catecholamine-induced focal myocardialnecrosis.

Another frequent clinical manifestation of pheo-chromocytoma is hyperglycemia, which is due to theinhibition of insulin secretion and the stimulation ofhepatic glucose output by catecholamines. Ectopicproduction of parathyroid hormonerelated peptideby the tumor may cause hypercalcemia; the calciumlevel often returns to normal after the tumor has been

removed.

4

Pheochromocytoma may be a componentof type IIA or IIB multiple endocrine neoplasia ormay be associated with neurofibromatosis or von Hip-pelLindau disease. This patient had a normal calci-um level, however, and he did not have a family his-tory of any of these syndromes.

Laboratory Diagnosis of Pheochromocytoma

The diagnosis of pheochromocytoma is establishedby demonstrating increased levels of catecholaminesor catecholamine metabolites, typically in urine sam-ples but also sometimes in plasma samples. The mostreliable tests are measurements of free catecholamines,metanephrines, or vanillylmandelic acid in a 24-hour

urine specimen. The last measurement is less sensitivethan the other two. Diagnostic accuracy is improvedby measuring at least two of the three substances. Tu-mors that secrete catecholamines continuously can bedetected by tests of randomly collected urine samples,but the sensitivity is increased if the urine is collectedduring or soon after a hypertensive crisis, when thelevels of catecholamines and their metabolites are typ-ically at least three times as high as normal. Recentlyingested substances may occasionally cause false neg-ative or positive results, especially in the case of vanill-

ylmandelic acid.Plasma catecholamine measurements have a sensi-

tivity of more than 90 percent and a specificity of 95percent for the diagnosis of pheochromocytoma.

5

Care must be used in obtaining the plasma samples,however, since the level of endogenous catecholaminescan be increased by stress and by the procedure ofdrawing blood. In a recently reported study of pa-tients with familial pheochromocytoma, measurementsof plasma normetanephrine and metanephrine had asensitivity of 97 percent and a specificity of 96 per-cent.

6

Suppressive tests (e.g., with the use of clonidine)



4/7



April 26, 2001

www.nejm.org

1317

or provocative tests (e.g., with the use of glucagon)are rarely necessary to establish the diagnosis of phe-ochromocytoma. Since provocative tests may inducea hypertensive crisis, they should be reserved for pa-tients who probably have a pheochromocytoma butin whom the diagnosis cannot be confirmed with sim-

ple biochemical testing.

Localization of the Tumor

Ninety percent of pheochromocytomas arise fromthe adrenal gland. However, of those that are extra-adrenal, 98 percent are found in the abdomen. Themost common extraadrenal sites in the abdomen arethe organ of Zuckerkandl, sympathetic ganglia, andthe urinary bladder. Thoracic tumors may arise in thesympathetic ganglia in the posterior mediastinum,along the aorta or the heart. In rare cases, the tumordevelops in the carotid body.

Since most pheochromocytomas involve the adrenalgland, the abdomen should be the first area evaluated

by imaging, but only after a biochemical diagnosis hasbeen made. In up to 5 percent of abdominal imagingstudies, an adrenal mass is found, but in most casesit is an incidental adenoma unrelated to the patientssymptoms. Either CT or MRI scanning can detecttumors as small as 0.5 cm in diameter. An advantageof MRI is that the pheochromocytoma appears as abright mass on a T

2

-weighted image.

7

Occasionally,despite a biochemical diagnosis, imaging techniques donot reveal a pheochromocytoma. In such cases, scan-ning with [

131

I]metaiodobenzylguanidine may be use-ful,

8

since it is concentrated in pheochromocytomas.Recent experience with the use of radiolabeled octre-otide shows promise as a diagnostic procedure.

9

Treatment of Pheochromocytoma

Once a pheochromocytoma has been diagnosed onthe basis of biochemical tests, the patient should betreated with agents that block catecholamine receptors

while the evaluation proceeds. The most widely usedagent is phenoxybenzamine, a nonspecific a

-adrener-gicreceptor antagonist. The definitive treatment issurgical excision of the pheochromocytoma. It may betempting to perform a fine-needle aspiration biopsyof the mass preoperatively, but it should be avoided,particularly if the patient has not been receiving treat-ment with an a

-adrenergicreceptor antagonist, be-cause needle biopsy can itself provoke the secretion ofcatecholamines, resulting in a hypertensive crisis.

10

The diagnostic procedure in this case was probablythe measurement of urine catecholamines and meta-nephrines, followed by resection of the tumor.

D

R

. L

AURA

P. W

OLSKO

: I obtained the additionalinformation that the patients paroxysms were precip-itated by exertion and postural changes, and also thathis symptoms had been aggravated by the administra-tion of morphine at another hospital before his admis-sion to this hospital. The diagnosis of pheochromocy-

toma was strongly suggested by the clinical findings,and we proceeded to control the blood pressure with

a

-adrenergicreceptor blockade while awaiting the re-sults of urine and blood tests. The urinary norepineph-rine level was 20 times the normal value, and the met-anephrine and vanillylmandelic acid levels were also

markedly elevated. The plasma norepinephrine levelwas nine times as high as the normal level, and thedopamine level was four times as high. Epinephrinelevels were undetectable, however, in both ur ine andblood specimens.

D

R

. J

OHN

C. W

AIN

: The imaging studies indicat-ed that the tumor was an isolated lesion, as it is in 90percent of cases. We explored the patients thorax andfound a well-circumscribed tumor attached to por-tions of four ribs, which we excised en bloc with thetumor. The tumor was highly vascular, which is char-acteristic of pheochromocytomas, and numerous trans-fusions were required.

CLINICAL DIAGNOSIS

Extraadrenal pheochromocytoma.

DR. PAUL R. CONLINS DIAGNOSIS

Extraadrenal pheochromocytoma.

PATHOLOGICAL DISCUSSION

D

R

. W

ILLIAM

C. F

AQUIN

: The resected specimenconsisted of a lobulated mass, 6.5 cm in diameter,

with an attached portion of the lateral chest wall, in-cluding four ribs. Sectioning of the mass revealed well-circumscribed, tan, focally hemorrhagic tissue (Fig. 2).Microscopical examination showed a tumor composedlargely of nests, or Zellballen,

of round-to-polygonal

chief cells separated by a prominent sinusoidal vascu-lature (Fig. 3). These cells were characterized by abun-dant pale, finely granular, eosinophilic cytoplasm andcentral round-to-oval vesicular nuclei containing smallnucleoli. Although occasional cells had atypical nuclei,mitotic activity and necrosis were absent. Scatteredstellate sustentacular cells were present, mostly in theperiphery of the nests. The chief cells were generallystrongly positive for chromogranin A (Fig. 4), syn-aptophysin, and neuron-specific enolase and negativefor keratin on immunohistochemical staining, indicat-ing their neuroendocrine nature. The sustentacularcells were generally positive for S-100 protein (Fig. 5).Ultrastructural examination of a chief cell showedthat it contained numerous intracytoplasmic, electron-dense, membrane-bound granules, 100 to 300 nm indiameter (Fig. 6). Some of the granules had an eccen-tric core and a prominent halo, which is consistent

with the presence of norepinephrine, whereas othershad an inconspicuous halo, which is consistent withthe presence of epinephrine, although there was nolaboratory evidence that the tumor was secreting ep-inephrine.

The pathological findings in this case are charac-



5/7

1318


April 26, 2001

www.nejm.org


teristic of a paraganglioma. The term used for this typeof tumor varies. Clinicians often refer to it as a phe-ochromocytoma, regardless of its location, if it is as-sociated with the clinical syndrome characteristic ofthat tumor. Pathologists, however, usually reserve theterm 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 lab-oratory features of the adrenal tumor.

Extraadrenal paragangliomas are tumors of the au-tonomic nervous system composed of cells derivedfrom the primitive neural crest.

11,12

These tumors ac-

Figure 3.

Neoplastic Chief Cells Arranged in Nests (

Zellballen

)(Arrows) Delineated by Delicate, Fibrovascular Septa (Hema-toxylin and Eosin, 500).

Figure 4.

Neoplastic Chief Cells Stained Brown for Chromo-granin A (Immunoperoxidase Staining, 200).

Figure 5.

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

Figure 2.

Resected Specimen Showing a Well-Circumscribed,Tan, Focally Hemorrhagic Tumor Adherent to Adjacent Ribs.



6/7



April 26, 2001

www.nejm.org

1319

count for only 0.3 percent of all mediastinal neo-plasms.

13-16

About one third of them are located inthe posterior mediastinum. They are functional in 35to 50 percent of cases, are aggressive in less than 15percent of cases, and are generally smaller and less of-ten multicentric than anterior mediastinal tumors.

13-16

There are no generally accepted histologic criteriafor distinguishing benign from malignant paragangli-omas, since features such as nuclear atypia, mitoses,and capsular or vascular invasion are seen in both typesof tumor. Data from at least two groups of investi-gators, however, suggest that the number of susten-tacular cells is smaller in malignant tumors than inbenign tumors.

17-19

The operative finding of invasionand the detection of metastasis, most often to thelymph nodes, lung, liver, or bone, remain the mostreliable indicators of malignancy.

12,13,17,20,21

D

R. M ILTON E. SKELLY: Is the size of the tumora prognostic factor?

DR. FAQUIN: There is no proven correlation be-tween the size of the tumor and its malignant or be-nign nature.

DR. WAIN: In the immediate postoperative period,the patient had a very large volume requirement as-cribable to his diminished plasma volume before sur-

gery and ongoing a-adrenergicreceptor blockade. Ittook 72 hours for his hemodynamic status to becomestable without the use of various suppressants and flu-id supplementation. His blood pressure is now normal,his symptoms have disappeared, and the results of lab-oratory tests have become normal.

ANATOMICAL DIAGNOSIS

Paraganglioma (pheochromocytoma) of the poste-rior mediastinum.

REFERENCES

1. Hollander JE. The management of cocaine-associated myocardial ische-mia. N Engl J Med 1995;333:1267-72.

2. Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Gar-cia 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, Re-Mine WH. Pheochromocytoma: current status and changing trends. Sur-gery 1982;91:367-73.4. Stewart AF, Hoecker JL, Mallette LE, Segre GV, Amatruda TT, VigneryA. Hypercalcemia in pheochromocytoma: evidence for a novel mechanism.Ann Intern Med 1985;102:776-9.5. Gifford RW, Manger WM, Bravo EL. Pheochromocytoma. EndocrinolMetab Clin North Am 1994;23:387-404.6. Eisenhofer G, Lenders JWM, Linehan WM, Walther MM, GoldsteinDS, Keiser HR. Plasma normetanephrine and metanephrine for detectingpheochromocytoma in von HippelLindau disease and multiple endocrineneoplasia type 2. N Engl J Med 1999;340:1872-9.7. Doppman JL, Reinig JW, Dwyer AJ, et al. Differentiation of adrenalmasses 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]Metaiodo-benzylguanidine and [111In]octreotide uptake in benign and malignantpheochromocytomas. J Clin Endocrinol Metab 2001;86:685-93.10. Chimori K, Miyazaki S, Nakajima T, Miura K. Preoperative manage-ment of pheochromocytoma with the calcium-antagonist nifedipine. ClinTher 1985;7:372-9.11. The sympathoadrenal neuroendocrine system. In: Lack EE. Pathologyof adrenal and extra-adrenal paraganglia. Vol. 29 of Major problems in pa-thology. Philadelphia: W.B. Saunders, 1994:186-219.12. Whalen RK , Althausen AF, Daniels GH. Extra-adrenal pheochromo-cytoma. J Urol 1992;147:1-10.13. Odze R, Begin LR. Malignant paraganglioma of the posterior medi-astinum: a case report and review of the literature. Cancer 1990;65:564-9.14. Gallivan MV, Chun B, Rowden G, Lack EE. Intrathoracic paraver-tebral malignant paraganglioma. Arch Pathol Lab Med 1980;104:46-51.

15. Olson JL, Salyer WR. Mediastinal paragangliomas (aortic body tu-mor): a report of four cases and review of the literature. Cancer 1978;41:2405-12.16. Noorda RJP, Wuisman PIJ, Kummer AJ, Winters HAH, R auwerda JA,Egeler-Peerdeman SM. Nonfunctioning malignant paraganglioma of theposterior mediastinum with spinal cord compression: a case report. Spine1996;21:1703-9.17. Kliewer KE, Cochran AJ. A review of the histology, ultrastructure, im-munohistology, and molecular biology of extra-adrenal paragangliomas.Arch Pathol Lab Med 1989;113:1209-18. [Erratum, Arch Pathol Lab Med1990;114:308.]18. Kliewer KE, Wen DR, Cancilla PA, Cochran AJ. Paragangliomas: as-sessment of prognosis by histologic, immunohistochemical, and ultrastruc-tural techniques. Hum Pathol 1989;20:29-39.

Figure 6. Electron Micrograph of a Chief Cell Containing Intra-

cytoplasmic, Electron-Dense, Neurosecretory Granules (Arrows).

The chief cell is adjacent to spindle-shaped sustentacular cells.The bar represents 1.4 mm.



7/7

1320 N Engl J Med, Vol. 344, No. 17 April 26, 2001 www.nejm.org


19. Bird DJB, Seiler MW. Aorticopulmonary paraganglioma (aortic bodytumor): report of a case. Ultrastruct Pathol 1991;15:475-9.20. Glenner GG, Grimley PM. Tumors of the extra-adrenal paraganglionsystem (including chemoreceptors). Atlas of tumor pathology. 2nd series.Fascicle 9. Washington, D.C.: Armed Forces Institute of Pathology, 1974.21. Capella C, R iva C, Cornaggia M, Chiaravalli AM, Frigerio B, Solcia E.

Histopathology, cytology and cytochemistry of pheochromocytomas andparagangliomas including chemodectomas. Pathol Res Pract 1988;183:176-87.

Copyright 2001 Massachusetts Medical Society.

35-MILLIMETER SLIDES FOR THE CASE RECORDS

Any reader of theJournalwho uses the Case Records of the Massachusetts General Hospital as amedical teaching exercise or reference material is eligible to receive 35-mm slides, with identifyinglegends, of the pertinent x-ray films, electrocardiograms, gross specimens, and photomicrographs ofeach case. The slides are 2 in. by 2 in., for use with a standard 35-mm projector. These slides, whichillustrate the current cases in theJournal, are mailed from the Department of Pathology to correspondto 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. Applicationforms for the current subscr iption year, which began in January, may be obtained from Lantern SlidesService, 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.


Feocromocitoma Extra Adrenal

Documents

Transcript of Feocromocitoma Extra Adrenal