Endocrine Pathology Case Studies


CASE 4: Pheochromocytoma


Clinical History:

A 30-year-old woman presented to an acupuncturist with complaints of periodic headaches, palpitations, nervousness, and perspiration for the past 2 months. She also reported having lost 4 kg during that time without dieting or a change in appetite. She is referred to a physician. Physical examination reveals vital signs with temperature 37.1 C, pulse 100/minute, respirations 17/minute, and blood pressure 160/110 mm Hg. Laboratory studies show her serum T4 is 7.0 micrograms/dl with normal T3 uptake and T3 of 94 ng/dl (normal range 74-166). What additional tests might prove helpful?
What additional tests might prove helpful? A 24-hour urine for VMA (vanillylmandelic acid) and urine metanephrines and free urinary catecholamines were obtained and all were elevated. You wouldn't order these tests on every hypertensive patient or everyone with an anxiety attack, but the history here is suggestive of catecholamine excess.
The major catecholamines are epinephrine, norepinephrine, and dopamine. The metabolic end products of the first two are metanephrins and VMA, while metabolism of the latter yields HVA. HVA is measured along with VMA in children with neuroblastomas.
A CT scan of the abdomen revealed a 4 to 5 cm mass involving the right adrenal. The mass was surgically excised.
  1. What is the diagnosis?

    2. This is a pheochromocytoma of adrenal gland arising in the medulla, identified in the CT scan (image 4.1). The gross appearance is that of a circumscribed mass (image 4.2) that turns brown in dichromate fixative (image 4.3). At low power in image 4.4 can be seen normal adrenal cortex to the right, whilt the tumor appears darker. This distinction is also seen in image 4.5, with adrenal cortical cells having pale cytoplasm at the lower right. In image 4.6 can be seen the characteristic nesting pattern of cells (Zellballen) with surrounding vessels. At high magnification (image 4.7) the neoplastic cells have dark purple cytoplasm.

  2. Why did the neoplasm turn brown in dichromate fixative?

    3. The tumor cells contain chromaffin granules with catecholamines that are oxidized by a fixative containing potassium dichromate. This reaction gives the characteristic brown color.

  3. How would you tell if this were malignant?

    4. The only reliable way is metastasis.

  4. What would be seen in this tumor by electron microscopy?

    5. The characteristic EM feature is presence of rounded, electron dense neurosecretory granules in the tumor cell cytoplasm.

  5. Where else in the body might such tumors arise?

    6. About 10% of pheochromocytomas arise in extra-adrenal paraganglia.

  6. What other tumors could be associated with this lesion when inherited as an autosomal dominant syndrome?

    7. Multiple endocrine neoplasia type IIa (Sipple's syndrome) could have associated medullary carcinoma of thyroid and parathyroid hyperplasia or adenoma.