Simultaneous Adrenal and Cervical Pheochromocytomas in Childhood MARVIN K. GIBBS, M.D., J. AIDAN CARNEY, M.B., PH.D., ALVIN B. HAYLES, M.D., ROBERT
PheochrDmocytoma is an uncommon tumor in childhood. The simultaneous occurrence of adrenal and cervical pheochromocytomas is a rare phenomenon; to our knowledge, this combination has been reported in the literature only once. Cervical pheochromocytomas are more accurately termed "aorticosympathetic paragangliomas." In children, 50% of pheochromocytomas are bilateral, multiple, or extra-adrenal. An increased familial incidence in the form of simple mendelian dominance is also noted in the pediatric age group. Bolus nephrotomography is extremely effective in identifying adrenal pheochromocytomas in children. To prepare the patient for surgery, an a-adrenergic blocking agent is administered from 7 to 10 days before operation and a f-blocking agent is administered 3 days before. A transabdominal approach is essential because of the frequent extra-adrenal sites and multicentricity of the tumor in children. A T THE MAYO CLINIC between 1926 and 1975,
A pheochromocytoma has been diagnosed in 178 patients, only 4 of whom have been children. Recently, we treated a 13-year-old girl who had functioning pheochromocytomas of the right adrenal gland and left cervical sympathetic chain. This combination of tumors has been reported only once before.' Case Report The patient was seen at the Mayo Clinic in July 1974, when she was referred for evaluation and treatment of pheochromocytoma diagnosed at another institution (Fig. 1). She had been well until 2 months before admission to her local hospital, when she began to experience easy fatigability, sweating, flushing, dyspnea, paresthesias, blurred vision, tremor, and fainting. One month before admission, she was found to have sustained hypertension (170/ 120 mm Hg). There were bilateral cervical masses, 4.5 by 4.0 cm on the left and 2.0 by 1.0 cm on the right. The electrocardiogram and chest roentgenogram were normal. The 24-hour urine value for catecholamines was 4,550 mg (normal 20 to 80 mg), for total metanephrines 17 mg (normal 0 to 1.3 mg), and for vanillylmandelic acid 15.6 mg (normal 0.5 to 8.6 mg). Results of thyroid function tests were normal. Intravenous pyelogram and nephrotomogram showed no abnormalities. Therapy was started with 20 mg of phenoxybenzamine every day and 10 mg of propranolol three times a day.
L. TELANDER,
M.D.
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
Study at our institution confirmed the previously mentioned studies, except that bolus nephrotomogram revealed a 4- to 5-cm partially necrotic tumor in the right suprarenal area (Fig. 2). The daily dose of phenoxybenzamine was increased to 30 mg, and the dose of propranolol was continued at 30 mg every day. Abdominal exploration and excision of the adrenal pheochromocytoma was planned, but, because the nature of the cervical masses was unknown, biopsy of one of these masses was performed prior to abdominal exploration. Frozen-section examination of the right cervical mass revealed a lymph node exhibiting benign reactive hyperplasia. On the presumption that the left cervical mass was similar, a primary right transverse abdominal incision extending across the midline was made. Thorough exploration of the abdomen revealed no abnormality except for the right adrenal excised, with minimal loss of blood and minimal fluctuations in blood pressure. The patient recovered satisfactorily after the operation, but she demonstrated persistent elevation of blood pressure. Repeat blood and urine catecholamine studies and investigation of the left cervical mass were undertaken. At cervical exploration, large, firm lymph nodes were found; frozen section showed benign hyperplasia. Further dissection revealed an additional mass beneath the lymph nodes; this was spongy and vascular and was found to arise from the left sympathetic chain. The blood pressure fluctuated widely during dissection (systolic ranged 100 to 210 mm Hg); the blocking agents had been discontinued after the first surgery. The mass was gently dissected free, and following its removal, the systolic pressure decreased to 90 mm Hg. The patient was dismissed from the hospital 2 days later, with blood pressures ranging from 130 to 150 mm Hg systolic and from 80 to 100 mm Hg diastolic. She has been followed with periodic blood pressure examinations and mailed-in urine specimens for catecholamine estimation studies (Table 1). She was asymptomatic and normotensive (130/60 mm Hg) when last seen 24 months after surgery. But there are persistent elevations of blood and urine catecholamines (Table 1). We must presume that the patient has an undiscovered functioning pheochromocytoma. Further studies have been performed, without demonstration of another tumor. tumor. This was
Pathologic Findings Right Adrenal Pheochromocytoma (Table 2). The
Submitted for publication July 30, 1976. Reprint requests: Dr. R. L. Telander, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55901.
tumor was encapsulated, weighed 43 gm, and measured
273
Ann. Surg.
GIBBS AND OTHERS
274
NEPHROTOMOGRAM-i
W.
March 1977
BLOOD CATS
URINEVMA
*URINE HVA
*URINE METS. URINE CATS.
FIG. 2. Bolus nephrotomogram showing right adrenal tumor.
characteristically situated in an eccentric location within the vesicle. Cervical Paraganglioma (Table 2). The solid, encapsulated tumor measured 4.0 by 2.5 by 2.0 cm (Fig. 4 a), and its pale-tan, cut surface was slightly mottled by hemorrhage. Microscopically, the tumor cells were similar in size, shape, and quality of cytoplasm to those seen in the adrenal tumor. However, the nuclei were regular, and mitotic figures were not found. The tumor cells were arranged in a well-delineated organoid pattern (Fig. 4 b). The vasculature was predominantly capillary, but areas with large dilated sinusoidal channels gave the tumor a focally angiomatous appearance. Electron microscopy of tumor cells showed dense-cored vesicles (Fig. 4 c) similar to those present in the adrenal tumor.
FIG. 1. Thirteen-year-old girl with functioning pheochromocytomas of the right adrenal gland and left cervical sympathetic chain. cm. Extensive cystic and hemorrhagic degeneration was evident on the cut surface (Fig. 3 a). Microscopically, it was composed of large, polygonal epithelial-like cells that were arranged in a poorly delineated alveolar pattern and supported by a delicate stroma containing numerous capillaries. The cytoplasm of the tumor cells was acidophilic and finely granular. Considerable variation in nuclear size was evident; in several areas, bizarre giant nuclear forms were present (Fig. 3 b). Mitotic figures were not observed among tumor cells. Electron microscopy revealed numerous dense-cored membrane-limited granules in the tumor cells. The dense core was
5 by 5 by 3
Genetic Aspects
The family history on the patient's maternal side positive for pheochromocytoma inherited in auto-
was
TABLE 1. Laboratory Studies
Normal
Blood catecholamines (Mg/dl) Urine VMA (mg/mg
creatinine) Urine HVA (mg/mg creatinine) Urine metanephrines (mg/24h) Urine catecholamines (mg/24h)
7/9/74 (preop.)
7/17/74 (between op. I & 2)
8/19/74 (1 mo postop.)
10/28/74 (3 mo postop.)
6/24/75 (10 mo postop.)
140.6
513
2.0 to 32.0
707.3
0.25 to 3.25
20.7
19.1
5.0
4.5
3.4
0.25 to 12.0
4.7
3.4
4.5
3.9
3.4
< 1.3
6.2
1.1
1.2
1.0
PheochrDmocytoma is an uncommon tumor in childhood. The simultaneous occurrence of adrenal and cervical pheochromocytomas is a rare phenomenon; to our knowledge, this combination has been reported in the literature only once. Cervical pheochromocytomas are more accurately termed "aorticosympathetic paragangliomas." In children, 50% of pheochromocytomas are bilateral, multiple, or extra-adrenal. An increased familial incidence in the form of simple mendelian dominance is also noted in the pediatric age group. Bolus nephrotomography is extremely effective in identifying adrenal pheochromocytomas in children. To prepare the patient for surgery, an a-adrenergic blocking agent is administered from 7 to 10 days before operation and a f-blocking agent is administered 3 days before. A transabdominal approach is essential because of the frequent extra-adrenal sites and multicentricity of the tumor in children. A T THE MAYO CLINIC between 1926 and 1975,
A pheochromocytoma has been diagnosed in 178 patients, only 4 of whom have been children. Recently, we treated a 13-year-old girl who had functioning pheochromocytomas of the right adrenal gland and left cervical sympathetic chain. This combination of tumors has been reported only once before.' Case Report The patient was seen at the Mayo Clinic in July 1974, when she was referred for evaluation and treatment of pheochromocytoma diagnosed at another institution (Fig. 1). She had been well until 2 months before admission to her local hospital, when she began to experience easy fatigability, sweating, flushing, dyspnea, paresthesias, blurred vision, tremor, and fainting. One month before admission, she was found to have sustained hypertension (170/ 120 mm Hg). There were bilateral cervical masses, 4.5 by 4.0 cm on the left and 2.0 by 1.0 cm on the right. The electrocardiogram and chest roentgenogram were normal. The 24-hour urine value for catecholamines was 4,550 mg (normal 20 to 80 mg), for total metanephrines 17 mg (normal 0 to 1.3 mg), and for vanillylmandelic acid 15.6 mg (normal 0.5 to 8.6 mg). Results of thyroid function tests were normal. Intravenous pyelogram and nephrotomogram showed no abnormalities. Therapy was started with 20 mg of phenoxybenzamine every day and 10 mg of propranolol three times a day.
L. TELANDER,
M.D.
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
Study at our institution confirmed the previously mentioned studies, except that bolus nephrotomogram revealed a 4- to 5-cm partially necrotic tumor in the right suprarenal area (Fig. 2). The daily dose of phenoxybenzamine was increased to 30 mg, and the dose of propranolol was continued at 30 mg every day. Abdominal exploration and excision of the adrenal pheochromocytoma was planned, but, because the nature of the cervical masses was unknown, biopsy of one of these masses was performed prior to abdominal exploration. Frozen-section examination of the right cervical mass revealed a lymph node exhibiting benign reactive hyperplasia. On the presumption that the left cervical mass was similar, a primary right transverse abdominal incision extending across the midline was made. Thorough exploration of the abdomen revealed no abnormality except for the right adrenal excised, with minimal loss of blood and minimal fluctuations in blood pressure. The patient recovered satisfactorily after the operation, but she demonstrated persistent elevation of blood pressure. Repeat blood and urine catecholamine studies and investigation of the left cervical mass were undertaken. At cervical exploration, large, firm lymph nodes were found; frozen section showed benign hyperplasia. Further dissection revealed an additional mass beneath the lymph nodes; this was spongy and vascular and was found to arise from the left sympathetic chain. The blood pressure fluctuated widely during dissection (systolic ranged 100 to 210 mm Hg); the blocking agents had been discontinued after the first surgery. The mass was gently dissected free, and following its removal, the systolic pressure decreased to 90 mm Hg. The patient was dismissed from the hospital 2 days later, with blood pressures ranging from 130 to 150 mm Hg systolic and from 80 to 100 mm Hg diastolic. She has been followed with periodic blood pressure examinations and mailed-in urine specimens for catecholamine estimation studies (Table 1). She was asymptomatic and normotensive (130/60 mm Hg) when last seen 24 months after surgery. But there are persistent elevations of blood and urine catecholamines (Table 1). We must presume that the patient has an undiscovered functioning pheochromocytoma. Further studies have been performed, without demonstration of another tumor. tumor. This was
Pathologic Findings Right Adrenal Pheochromocytoma (Table 2). The
Submitted for publication July 30, 1976. Reprint requests: Dr. R. L. Telander, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55901.
tumor was encapsulated, weighed 43 gm, and measured
273
Ann. Surg.
GIBBS AND OTHERS
274
NEPHROTOMOGRAM-i
W.
March 1977
BLOOD CATS
URINEVMA
*URINE HVA
*URINE METS. URINE CATS.
FIG. 2. Bolus nephrotomogram showing right adrenal tumor.
characteristically situated in an eccentric location within the vesicle. Cervical Paraganglioma (Table 2). The solid, encapsulated tumor measured 4.0 by 2.5 by 2.0 cm (Fig. 4 a), and its pale-tan, cut surface was slightly mottled by hemorrhage. Microscopically, the tumor cells were similar in size, shape, and quality of cytoplasm to those seen in the adrenal tumor. However, the nuclei were regular, and mitotic figures were not found. The tumor cells were arranged in a well-delineated organoid pattern (Fig. 4 b). The vasculature was predominantly capillary, but areas with large dilated sinusoidal channels gave the tumor a focally angiomatous appearance. Electron microscopy of tumor cells showed dense-cored vesicles (Fig. 4 c) similar to those present in the adrenal tumor.
FIG. 1. Thirteen-year-old girl with functioning pheochromocytomas of the right adrenal gland and left cervical sympathetic chain. cm. Extensive cystic and hemorrhagic degeneration was evident on the cut surface (Fig. 3 a). Microscopically, it was composed of large, polygonal epithelial-like cells that were arranged in a poorly delineated alveolar pattern and supported by a delicate stroma containing numerous capillaries. The cytoplasm of the tumor cells was acidophilic and finely granular. Considerable variation in nuclear size was evident; in several areas, bizarre giant nuclear forms were present (Fig. 3 b). Mitotic figures were not observed among tumor cells. Electron microscopy revealed numerous dense-cored membrane-limited granules in the tumor cells. The dense core was
5 by 5 by 3
Genetic Aspects
The family history on the patient's maternal side positive for pheochromocytoma inherited in auto-
was
TABLE 1. Laboratory Studies
Normal
Blood catecholamines (Mg/dl) Urine VMA (mg/mg
creatinine) Urine HVA (mg/mg creatinine) Urine metanephrines (mg/24h) Urine catecholamines (mg/24h)
7/9/74 (preop.)
7/17/74 (between op. I & 2)
8/19/74 (1 mo postop.)
10/28/74 (3 mo postop.)
6/24/75 (10 mo postop.)
140.6
513
2.0 to 32.0
707.3
0.25 to 3.25
20.7
19.1
5.0
4.5
3.4
0.25 to 12.0
4.7
3.4
4.5
3.9
3.4
< 1.3
6.2
1.1
1.2
1.0
