Problems in the Diagnosis of Adrenal Tumors 1
Diagnostic Radiology
Philip Costello, M.D., Melvin E. Clouse, M.D., Robert A. Kane, M.D., and Alan Paris, M.D. The angiographic findings of cortical nodular hyperplasia, adenolipoma, and intracaval extension of recurrent pheochromocytoma were correlated with the pathological findings. Adenolipoma was angiographically similar to other adrenal neoplasms, adding difficulties to its differential diagnosis. Two cases of cortical nodular hyperplasia showed possibly pathognomonic patterns of discrete vascular cortical accumulations of contrast media which represent capillary malformations within the hyperplastic nodules. Intracaval extension of recurrent pheochromocytoma was found to be similar to other tumors which invade veins. INDEX TERMS: (Adrenal disorder, 8[6] .540) • Adrenals, angiography, 8[6] .1245 • Adrenals, hyperplasia • Adrenals, neoplasms, 8[6] .300 • Pheochromocytoma
Radiology 125:335-341, November 1977
· S
INCE THE ADVENT of the Seldinger technique, the
venous phase (Fig. 1, B and C). The aortogram revealed a questionable abnormality in the left adrenal area, and because a good selective study of this gland could not be obtained, both adrenals were explored at laparotomy. The right adrenal was removed. It was enlarged, with multiple discrete cortical nodules from 3 to 12 mm in diameter (Fig. 2, A and B). Microscopic examination showed these nodules to be delineated from the surrounding normal tissue. They were composed of small clusters of cortical cells arranged in irregular cords separated by small blood vessels and capillaries. The cords of cells and blood vessels radiated out from large central vascular complexes consisting of many dilated and/or sclerosed blood vessels. The diagnosis was cortical nodular hyperplasia.
angiographic findings of adrenal tumors such as carcinoma and pheochromocytoma have been well documented (1-4,9-11). The angiographic findings in cases of cortical nodular hyperplasia, adenolipoma and intravenous extension of pheochromocytoma have not been reported. During the past two years we have encountered these findings in 4 of 12 patients originally considered to have a pheochromocytoma. CASE REPORTS CASE I: Cortical Nodular Hyperplasia. A 46-year-old woman was examined for hypertension 6 years prior to her current admission. At that time, her catecholamine levels were normal. She was found to be hyperthyroid, and treated with 1311. One year later, a cerebrovascular accident resulted in a residual left hemiparesis. Her current admission was caused by hypertensive encephalopathy and a grand mal seizure. The admission blood pressure was 200/120. Urinary vanilylmandelic acid levels (VMA) were at the upper limits of normal: 9.1, 9.6, and 9.4 }1g/24 hours (normal = 2-10). Urinary catecholamine levels were normal [33,50, 17, and 20 mg per 24 hours (normal = 100 mg per 24 hours)]. The excretory urogram was within normal limits. Angiography was performed because of persistently high normal VMAs. Abdominal aortography with selective renal angiograms, with and without epinephrine, revealed good filling of the right inferior adrenal artery. The gland was enlarged, measuring 2.8 X 1.8 cm in diameter (Fig. 1, A). A distinct capillary blush was evident throughout the gland, but there were no definite tumor vessels. In the periphery of the gland were multiple small collections of contrast varying from 2 to 5 mm in diameter which persisted through the arterial phase and into the late
CASE II: Cortical Nodular Hyperplasia. A 54-year-old man presented with a right renal mass. Angiography revealed a large vascular mass in the lower pole of the kidney. The renal vein was uninvolved. A prominent right inferior adrenal artery filled during the injection of the renal artery, demonstrating enlargement of the adrenal gland, with multiple hypervascular zones in the periphery of the gland from 2 to 4 mm in diameter. These zones were identical in appearance to the vascular zones of our first case, and they persisted from the late arterial to the late venous phase (Fig. 3, A and B). Although the alternative diagnosis of metastatic deposits from the renal carcinoma was considered, pathology revealed that the lesions were cortical nodular hyperplasia.
CASE III: Adenolipoma. A 59-year-old woman experienced increasing back pain for one year. The physical examination was normal, and she was not hypertensive. Excretory urography revealed mottled calcification in an
1 From the Departments of Radiology (P.C., M.E.C., R.A.K.) and Pathology (A.P.), New England Deaconess Hospital, Boston, Mass. Accepted for publication in June, 1977. ss
335
336
PHILIP COSTELLO AND OTHERS
s-cm mass in the right adrenal area; the mass displaced the right kidney inferiorly (Fig. 4, A). Selective right renal angiography revealed a normal kidney and an enlarged inferior adrenal artery supplying the adrenal mass. Selective catheterization and injection into the inferior adrenal artery demonstrated the blood supply to be peripherally distributed around the mass, with penetrating vessels entering in a spoke-wheel configuration (Fig. 4, B). Puddling of contrast in several areas appeared in the late capillary phase and persisted well beyond the venous phase (Fig. 4, C). Several of these areas measured up to 5 mm in diameter. The venous drainage was prominent, with enlarged veins draped around the mass emptying by the single large adrenal vein into the inferior vena cava. The blood pressure rose by 20 mm Hg during the examination, but it returned to normal within 5 min. At surgery, a well-encapsulated 8 X 6 X 4-cm mass weighing 106 g was removed . The surface was yellowish white with occasional red areas. The
November 1977
cut surface had cystic and yellowish necrotic areas (Fig. 4,0). Microscopic examination revealed the tumor to be composed predominantly of adipose tissue which, in areas, had undergone various stages of degeneration, hemorrhage, fibrosis and calcification (Fig. 4, E). There was a small rim of hyperplastic and fibrotic adrenal cortical tissue on one side. The interface between these two tissues was irregular and contained multiple dilated blood vessels . Adrenal medullary tissue or myeloid tissue was not present. The diagnosis was adenolipoma. CASE IV: Recurrent Phenochromocytoma. A 52year-old man had had a left adrenal pheochromocytoma removed one year previously. He presented with recurrent symptoms of sweating, headaches and blurring of vision. His blood pressure was 180/110. The urinary catecholamine, metanephrine, and VMA levels were elevated,
c
Fig. 1. A. Late arterial phase of selective renal angiogram. Positioned above the kidney is the enlarged adrenal gland, which filled from an inferior adrenal artery . B. Midarterial phase. Note the filling of the inferior adrenal artery and a renal capsular branch passing inferior to the adrenal gland. Multiple pools of contrast medium (arrow) appear in the periphery of the adrenal gland. C. Venous phase of the same study. Note the persistence of the 2-5 mm collections of contrast medium (arrows) in the cortex of the adrenal gland.
337
ADRENAL TUMORS
Vol. 125
confirming the presence of a recurring pheochromocytoma. Angiography was performed to localize the tumor. The angiographic examinations on three occasions included abdominal, pelvic and arch aortography. Selective injections were made into the renal, celiac, superior and inferior mesenteric, both phrenic, first three lumbar, and common carotid arteries. All studies were negative except for a questionable blush in the region of the previously resected left adrenal gland, and small linear arterial branches extending superiorly from the right phrenic artery into the lower zone of the right hilus parallel to the spine (Fig. 5, A). These findings were considered to be hypervascularity resulting from chronic lung disease, possibly bronchiectasis of the lower lobe . A laparotomy was perfomed with retroperitoneal exploration . The left adrenal bed was found to be normal, as was the right adrenal gland. Inferior vena cava manipulation resulted in a rise in the blood pressure to 300 mm Hg systolic. Tumor tissue was found in the left adrenal vein at the site of the previous ligation. A tumor cast could be palpated filling the left renal vein and extending into the right atrium from the inferior vena cava. The multiple fine parallel arteries coursing into the right lower lung base in the paraspinal area represented tumor vessels in the inferior vena cava. An inferior venacavogram delineated a large mass in the inferior vena cava which extended upward into the right atrium (Fig. 5, B). At subsequent surgery, the superior portion of the tumor was floating free in the cava, but it was attached to the caval wall near the orifice of the left renal vein. Complete removal of the tumor involved cardiac and abdominal surgery with extracorporeal circulation . Postoperatively, the cava was seen to be free of tumor. The specimen from the inferior vena cava consisted of multiple fragments of tan fibrous tissue and a portion of the caval wall. Microscopic study showed that the segment of the caval wall was basically unaltered. The tumor was attached to (or had replaced) the intima in several locations (Fig. 5, C). The vasa vasorum was substantially dilated. The tumor was composed of multiple small nests of large cells with indistinct marg ins, large round nuclei, and a granular dichromate-positive cytoplasm. The tumor was richly vascular, with each cellular nest surrounded by a capillary network .
Diagnostic Radiology
normal gland (glomerulosa, fasiculatis , reticularis), but did retain the general parenchymal pattern common to many endocrine tissues, i.e., cords of cortical cells separated by capillaries. When the nodules were as thick as the gland, there was a unique vascular pattern of capsular arterioles entering from the periphery, with venous drainage from the opposite pole. Scattered throughout these nodules were capillaries that would occasionally coalesce to form localized collections of vascular channels. The gross pathology explains the angiographic findings of multiple localized discrete collections of contrast material in the angiomatous malformations (2 to 5 mm in diameter) scattered throughout the gland. These collect ions of contrast material persisted from the early arterial through the late venous phases (Fig. 1, B and C). Although we have not found prior reports of the angiographic abnormalities in cortical nodular hyperplas ia, it is a common condition pathologically. It should be suspected
f·
A
DISCUSSION
Cortical nodular hyperplasia and adrenal adenolipoma are well recognized pathological entities. Dobbie (5) described the histology of adrenal cortical nodular hyperplasia in 113 consecutive autopsies; 57 % had mild nodularity of the gland, and 14 % had distinct nodules. In another series (5), cortical nodules were present in 69 of 71 adrenals examined; 12 adrenals contained nodules larger than 20 mm in diameter-7 of which contained large hemangiomatous malformations in the center of the nodules. These nodules did not have the recognizable zones of a
Fig. 2. A. Whole-mount photograph of a cross section of the removed adrenal. The inferior aspect of the adrenal gland is expanded by a large conglomerate of hyperplastic nodules. Several of the larger nodules contain dilated vessels (dark areas). B. Diagrammatic representation of the evolution of nodular hyperplasia. In the cortex, nodular collections of cells appear separated by blood vessels and capillaries. With progressive enlargement, the center of the nodule may acquire a vascular complex. Angiography presumably demonstrates these larger vascular malformations (rnmedulla; vc-vascular complex in center of nodule; bv-blood vessel in gland).
338
PHILIP COSTELLO AND OTHERS
when an enlarged gland is seen with multiple (possibly bilateral) focal accumulations of contrast and with some variance in the size of the foci. The etiology of this condition is not clear; the incidence in older age groups and the fact that many of these patients had coexistent vascular disease led to attempts to establish a correlation between these findings. Dobbie (5) speculates that since many of these glands show areas of segmental atrophy, the areas of focal hyperplasia may be a response to loss of cortical substance secondary to ischemia, with subsequent areas of regeneration. Adenolipoma of the adrenal is an uncommon adrenal tumor. A similar condition termed myelolipoma (14) has been noted in the radiological literature (12), but the latter lesion contains red marrow in addition to fatty tissue. Myelolipoma is felt to be a metaplastic process. Bone marrow interspersed with fatty tissue and fibrous tissue is often present and, not surprisingly, calcification is seen. The adrenal tumor in our CASE III did not contain any myeloid elements; consequently, it represents the rarer adenolipoma or hibernoma (15) of the adrenal gland. The areas of degeneration and calcification were presumably secondary to areas of hemorrhage and necrosis within the tumor.
November 1977
The angiographic differential diagnosis of adrenal tumors has been described by many authors. Pheochromocytomas (1-4) are usually vascular, with an homogeneous accumulation of contrast medium in the capillary phase. Cortical adenomas and carcinomas have a more variable vascularity, from a finely reticular to a coarse pattern, with venous lakes and wide irregular veins (4, 11). These venous lakes have been said to be a characteristic feature of adenomas and carcinomas (2, 10). In adrenal hyperplasia, an enlarged gland with an increase in the size and number of vessels is evident bilaterally. No detectable correlation between the extent of vascularity and the presence or absence of malignancy has been found in either pheochromocytomas or adrenal cortical tumors (4, 11) Importance has been attached to the peripheral draping of tumor vessels around the capsule of the mass (4), a pattern more specific for benign tumors. Calcification in the adenolipoma is not surprising, since it may occur in almost any adrenal tumor (4, 12, 13), particularly when there is degeneration, hemorrhage, and necrosis. In our CASE III there was peripheral draping of the arterial supply around the tumor and large veins were arranged in a similar fashion. This finding is suggestive of
Fig. 3. A. Filling of the inferior adrenal artery during the injection of the renal artery. The arrow points to one of the small collections of contrast in the cortex of the adrenal. B. Late capillary phase reveals (arrows) that small contrast collections persist.
ADRENAL TUMORS
Vol. 125
339
Diagnostic Radiology
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Fig. 4. A. Adrenal mass containing diffuse amorphous calcifications with inferior displacement of the right kidney. B. and C. Selective inferior adrenal angiogram . Late arterial phase (B)-irregular pools of contrast (up to 5 mm in diameter) appear throughout the gland;oand venous phase (C)-persistence of irregular contrast pools with appearance of blood in dilated peripherally situated veins draining into the inferior vena cava . D. Gross photograph of sectioned mass reveals the nonhomogenous nature. with lighter fatty zones and darker zones of hemorrhage and necrosis . E. Microscopic section with fatty tissue on right. some adrenal cells centrally. and fibrous tissue to the left.
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340
PHILIP COSTELLO AND OTHERS
a benign tumor, but is otherwise nonspecific. The venous lakes are related to the enlarged blood sinuses within the tumor. It is evident that this latter sign is in no way specific for adrenal cortical tumors. In fact, there is an overlap between the signs demonstrated in this tumor and those described for cortical tumors, both benign and malignant. We have not found previous reports of intravenous neoplastic extension of a pheochromocytoma. Kahn and Ferris (7, 8) first described the intravenous neoplastic pattern of growth in renal cell carcinoma . Gregg and Wallace (6) reported the same phenomenon with primary hepatocellular carc inoma and retroperitoneal osteosarcoma growing into the inferior vena cava. The linear vascular pattern seen with selective angiography of the inferior phrenic artery is identical to the parallel arterial channels demonstrated by Gregg, who suggested that the vessels sometimes represented enlargement of the vasa vasorum (6). In this case, the vascular pattern was produced by arteries within the tumor, as well as vascular channels in the vasa vasorum of the
November 1977
inferior vena cava near the origin of the left renal vein. The tumor had therefore parasitised its blood supply from the inferior phrenic artery via the vasa vasorum of the caval wall. The striated pattern of vessels within other tumors (such as a hypernephroma growing in this manner) has been found to be composed of arterial channels derived directly from the blood supply of the primary tumor .
REFERENCES 1. Agee OF, Kaude J, Lepasdon J: Preoperative localization of pheochromocytoma . Acta Radiol (Diagn) 14:545-559, 1973 2. Alfidi RJ, Gill W Jr. Klein HJ: Arteriography of adrenal neoplasms. Am J RoentgenoI106:635-641 , Jul 1969 3. Boijsen E, Williams CM, Judkins MP: Angiography of pheochromocytoma. Am J Roentgenol 98:225-232. Sep 1966 4. Colapinto RF, Steed BL: Arter iography of adrenal tumors. Radiology 100:343-350, Aug 1971 5. Dobbie JW: Adrenocortical nodular hyperplasia. J Pathol 99:1-18,1969 6. Gregg FP, Goldstein HM. Wallace S, et al: Arteriograph ic demonstration of intravenous tumor extension. Am J Roentgenol 123: 100-105, Jan 1975
c Fig. 5. A. Selective right inferior phrenic angiogram. Note (between arrows) multiple fine linear vessels parallel to the spine, passing from the level of the first lumbar vertebra to the right atrium. These lines represent the blood supply to the intracaval portion of the recurrent pheochromocytoma. B. Inferior vena cavogram. A large intraluminal filling defect extends from the first lumbar vertebral body (at the site of the entry of the left renal vein) into the right atrium. The recurrent pheochromocytoma originated at the site of ligation of the left adrenal vein within the renal vein. C. Microscopic section of the removed tumor shows the caval wall on the right with a dilated vasa vasorum. The tumor to the left is adherent to the intima but has not become invasive. Note the vessel penetrating the wall of the cava and extending into the tumor. Many small arteries are scattered throughout the intraluminal pheochromocytoma .
Vol. 125
ADRENAL TUMORS
7. Ferris EJ, Bosniak MA, O'Connor JF: Angiographic sign demonstratingextension of renal carcinoma into renal vein and inferior vena cava. Am J RoentgenoI102:384-391, Feb 1968 8. Kahn PC: Epinephrine effect in selective renal arteriography. Radiology 85:301-305, Aug 1965 9. Lagergren C: Angiographic changes in the adrenal glands. Am J RoentgenoI101:732-7388, Nov 1967 10. Lanner LO, Rosencrantz M: Arteriographic appearances of pheochromocytomas. Acta Radiol (Diagn) 10:35-48, 1970 11. Lee KR, Lin F, Sibala J: Adrenal adenoma and hyperplasia: the importanceof arteriographicdifferential diagnosis. Am J Roentgenol 119:796-804, Dec 1973 12. Martin JF: Suprarenal clacification. Radiol Clin North Am 3:129-138, Apr 1965
341
Diagnostic Radiology
13. Twerksy J, Levin DC: Metastatic melanoma of the adrenal. Radiology 116:627-628, Sep 1975 14. Tulcinsky D, Deutsch V, Bubis JJ: Myelolipoma of the adrenal gland. Br J Surg 57:465-467, Jun 1970 15. McGregor AL: Hibernoma of the adrenal. Acta Med Scand 306:107-110,1955
Department of Radiology New England Deaconess Hospital 185 Pilgrim Rd. Boston, Mass. 02215
Diagnostic Radiology
Philip Costello, M.D., Melvin E. Clouse, M.D., Robert A. Kane, M.D., and Alan Paris, M.D. The angiographic findings of cortical nodular hyperplasia, adenolipoma, and intracaval extension of recurrent pheochromocytoma were correlated with the pathological findings. Adenolipoma was angiographically similar to other adrenal neoplasms, adding difficulties to its differential diagnosis. Two cases of cortical nodular hyperplasia showed possibly pathognomonic patterns of discrete vascular cortical accumulations of contrast media which represent capillary malformations within the hyperplastic nodules. Intracaval extension of recurrent pheochromocytoma was found to be similar to other tumors which invade veins. INDEX TERMS: (Adrenal disorder, 8[6] .540) • Adrenals, angiography, 8[6] .1245 • Adrenals, hyperplasia • Adrenals, neoplasms, 8[6] .300 • Pheochromocytoma
Radiology 125:335-341, November 1977
· S
INCE THE ADVENT of the Seldinger technique, the
venous phase (Fig. 1, B and C). The aortogram revealed a questionable abnormality in the left adrenal area, and because a good selective study of this gland could not be obtained, both adrenals were explored at laparotomy. The right adrenal was removed. It was enlarged, with multiple discrete cortical nodules from 3 to 12 mm in diameter (Fig. 2, A and B). Microscopic examination showed these nodules to be delineated from the surrounding normal tissue. They were composed of small clusters of cortical cells arranged in irregular cords separated by small blood vessels and capillaries. The cords of cells and blood vessels radiated out from large central vascular complexes consisting of many dilated and/or sclerosed blood vessels. The diagnosis was cortical nodular hyperplasia.
angiographic findings of adrenal tumors such as carcinoma and pheochromocytoma have been well documented (1-4,9-11). The angiographic findings in cases of cortical nodular hyperplasia, adenolipoma and intravenous extension of pheochromocytoma have not been reported. During the past two years we have encountered these findings in 4 of 12 patients originally considered to have a pheochromocytoma. CASE REPORTS CASE I: Cortical Nodular Hyperplasia. A 46-year-old woman was examined for hypertension 6 years prior to her current admission. At that time, her catecholamine levels were normal. She was found to be hyperthyroid, and treated with 1311. One year later, a cerebrovascular accident resulted in a residual left hemiparesis. Her current admission was caused by hypertensive encephalopathy and a grand mal seizure. The admission blood pressure was 200/120. Urinary vanilylmandelic acid levels (VMA) were at the upper limits of normal: 9.1, 9.6, and 9.4 }1g/24 hours (normal = 2-10). Urinary catecholamine levels were normal [33,50, 17, and 20 mg per 24 hours (normal = 100 mg per 24 hours)]. The excretory urogram was within normal limits. Angiography was performed because of persistently high normal VMAs. Abdominal aortography with selective renal angiograms, with and without epinephrine, revealed good filling of the right inferior adrenal artery. The gland was enlarged, measuring 2.8 X 1.8 cm in diameter (Fig. 1, A). A distinct capillary blush was evident throughout the gland, but there were no definite tumor vessels. In the periphery of the gland were multiple small collections of contrast varying from 2 to 5 mm in diameter which persisted through the arterial phase and into the late
CASE II: Cortical Nodular Hyperplasia. A 54-year-old man presented with a right renal mass. Angiography revealed a large vascular mass in the lower pole of the kidney. The renal vein was uninvolved. A prominent right inferior adrenal artery filled during the injection of the renal artery, demonstrating enlargement of the adrenal gland, with multiple hypervascular zones in the periphery of the gland from 2 to 4 mm in diameter. These zones were identical in appearance to the vascular zones of our first case, and they persisted from the late arterial to the late venous phase (Fig. 3, A and B). Although the alternative diagnosis of metastatic deposits from the renal carcinoma was considered, pathology revealed that the lesions were cortical nodular hyperplasia.
CASE III: Adenolipoma. A 59-year-old woman experienced increasing back pain for one year. The physical examination was normal, and she was not hypertensive. Excretory urography revealed mottled calcification in an
1 From the Departments of Radiology (P.C., M.E.C., R.A.K.) and Pathology (A.P.), New England Deaconess Hospital, Boston, Mass. Accepted for publication in June, 1977. ss
335
336
PHILIP COSTELLO AND OTHERS
s-cm mass in the right adrenal area; the mass displaced the right kidney inferiorly (Fig. 4, A). Selective right renal angiography revealed a normal kidney and an enlarged inferior adrenal artery supplying the adrenal mass. Selective catheterization and injection into the inferior adrenal artery demonstrated the blood supply to be peripherally distributed around the mass, with penetrating vessels entering in a spoke-wheel configuration (Fig. 4, B). Puddling of contrast in several areas appeared in the late capillary phase and persisted well beyond the venous phase (Fig. 4, C). Several of these areas measured up to 5 mm in diameter. The venous drainage was prominent, with enlarged veins draped around the mass emptying by the single large adrenal vein into the inferior vena cava. The blood pressure rose by 20 mm Hg during the examination, but it returned to normal within 5 min. At surgery, a well-encapsulated 8 X 6 X 4-cm mass weighing 106 g was removed . The surface was yellowish white with occasional red areas. The
November 1977
cut surface had cystic and yellowish necrotic areas (Fig. 4,0). Microscopic examination revealed the tumor to be composed predominantly of adipose tissue which, in areas, had undergone various stages of degeneration, hemorrhage, fibrosis and calcification (Fig. 4, E). There was a small rim of hyperplastic and fibrotic adrenal cortical tissue on one side. The interface between these two tissues was irregular and contained multiple dilated blood vessels . Adrenal medullary tissue or myeloid tissue was not present. The diagnosis was adenolipoma. CASE IV: Recurrent Phenochromocytoma. A 52year-old man had had a left adrenal pheochromocytoma removed one year previously. He presented with recurrent symptoms of sweating, headaches and blurring of vision. His blood pressure was 180/110. The urinary catecholamine, metanephrine, and VMA levels were elevated,
c
Fig. 1. A. Late arterial phase of selective renal angiogram. Positioned above the kidney is the enlarged adrenal gland, which filled from an inferior adrenal artery . B. Midarterial phase. Note the filling of the inferior adrenal artery and a renal capsular branch passing inferior to the adrenal gland. Multiple pools of contrast medium (arrow) appear in the periphery of the adrenal gland. C. Venous phase of the same study. Note the persistence of the 2-5 mm collections of contrast medium (arrows) in the cortex of the adrenal gland.
337
ADRENAL TUMORS
Vol. 125
confirming the presence of a recurring pheochromocytoma. Angiography was performed to localize the tumor. The angiographic examinations on three occasions included abdominal, pelvic and arch aortography. Selective injections were made into the renal, celiac, superior and inferior mesenteric, both phrenic, first three lumbar, and common carotid arteries. All studies were negative except for a questionable blush in the region of the previously resected left adrenal gland, and small linear arterial branches extending superiorly from the right phrenic artery into the lower zone of the right hilus parallel to the spine (Fig. 5, A). These findings were considered to be hypervascularity resulting from chronic lung disease, possibly bronchiectasis of the lower lobe . A laparotomy was perfomed with retroperitoneal exploration . The left adrenal bed was found to be normal, as was the right adrenal gland. Inferior vena cava manipulation resulted in a rise in the blood pressure to 300 mm Hg systolic. Tumor tissue was found in the left adrenal vein at the site of the previous ligation. A tumor cast could be palpated filling the left renal vein and extending into the right atrium from the inferior vena cava. The multiple fine parallel arteries coursing into the right lower lung base in the paraspinal area represented tumor vessels in the inferior vena cava. An inferior venacavogram delineated a large mass in the inferior vena cava which extended upward into the right atrium (Fig. 5, B). At subsequent surgery, the superior portion of the tumor was floating free in the cava, but it was attached to the caval wall near the orifice of the left renal vein. Complete removal of the tumor involved cardiac and abdominal surgery with extracorporeal circulation . Postoperatively, the cava was seen to be free of tumor. The specimen from the inferior vena cava consisted of multiple fragments of tan fibrous tissue and a portion of the caval wall. Microscopic study showed that the segment of the caval wall was basically unaltered. The tumor was attached to (or had replaced) the intima in several locations (Fig. 5, C). The vasa vasorum was substantially dilated. The tumor was composed of multiple small nests of large cells with indistinct marg ins, large round nuclei, and a granular dichromate-positive cytoplasm. The tumor was richly vascular, with each cellular nest surrounded by a capillary network .
Diagnostic Radiology
normal gland (glomerulosa, fasiculatis , reticularis), but did retain the general parenchymal pattern common to many endocrine tissues, i.e., cords of cortical cells separated by capillaries. When the nodules were as thick as the gland, there was a unique vascular pattern of capsular arterioles entering from the periphery, with venous drainage from the opposite pole. Scattered throughout these nodules were capillaries that would occasionally coalesce to form localized collections of vascular channels. The gross pathology explains the angiographic findings of multiple localized discrete collections of contrast material in the angiomatous malformations (2 to 5 mm in diameter) scattered throughout the gland. These collect ions of contrast material persisted from the early arterial through the late venous phases (Fig. 1, B and C). Although we have not found prior reports of the angiographic abnormalities in cortical nodular hyperplas ia, it is a common condition pathologically. It should be suspected
f·
A
DISCUSSION
Cortical nodular hyperplasia and adrenal adenolipoma are well recognized pathological entities. Dobbie (5) described the histology of adrenal cortical nodular hyperplasia in 113 consecutive autopsies; 57 % had mild nodularity of the gland, and 14 % had distinct nodules. In another series (5), cortical nodules were present in 69 of 71 adrenals examined; 12 adrenals contained nodules larger than 20 mm in diameter-7 of which contained large hemangiomatous malformations in the center of the nodules. These nodules did not have the recognizable zones of a
Fig. 2. A. Whole-mount photograph of a cross section of the removed adrenal. The inferior aspect of the adrenal gland is expanded by a large conglomerate of hyperplastic nodules. Several of the larger nodules contain dilated vessels (dark areas). B. Diagrammatic representation of the evolution of nodular hyperplasia. In the cortex, nodular collections of cells appear separated by blood vessels and capillaries. With progressive enlargement, the center of the nodule may acquire a vascular complex. Angiography presumably demonstrates these larger vascular malformations (rnmedulla; vc-vascular complex in center of nodule; bv-blood vessel in gland).
338
PHILIP COSTELLO AND OTHERS
when an enlarged gland is seen with multiple (possibly bilateral) focal accumulations of contrast and with some variance in the size of the foci. The etiology of this condition is not clear; the incidence in older age groups and the fact that many of these patients had coexistent vascular disease led to attempts to establish a correlation between these findings. Dobbie (5) speculates that since many of these glands show areas of segmental atrophy, the areas of focal hyperplasia may be a response to loss of cortical substance secondary to ischemia, with subsequent areas of regeneration. Adenolipoma of the adrenal is an uncommon adrenal tumor. A similar condition termed myelolipoma (14) has been noted in the radiological literature (12), but the latter lesion contains red marrow in addition to fatty tissue. Myelolipoma is felt to be a metaplastic process. Bone marrow interspersed with fatty tissue and fibrous tissue is often present and, not surprisingly, calcification is seen. The adrenal tumor in our CASE III did not contain any myeloid elements; consequently, it represents the rarer adenolipoma or hibernoma (15) of the adrenal gland. The areas of degeneration and calcification were presumably secondary to areas of hemorrhage and necrosis within the tumor.
November 1977
The angiographic differential diagnosis of adrenal tumors has been described by many authors. Pheochromocytomas (1-4) are usually vascular, with an homogeneous accumulation of contrast medium in the capillary phase. Cortical adenomas and carcinomas have a more variable vascularity, from a finely reticular to a coarse pattern, with venous lakes and wide irregular veins (4, 11). These venous lakes have been said to be a characteristic feature of adenomas and carcinomas (2, 10). In adrenal hyperplasia, an enlarged gland with an increase in the size and number of vessels is evident bilaterally. No detectable correlation between the extent of vascularity and the presence or absence of malignancy has been found in either pheochromocytomas or adrenal cortical tumors (4, 11) Importance has been attached to the peripheral draping of tumor vessels around the capsule of the mass (4), a pattern more specific for benign tumors. Calcification in the adenolipoma is not surprising, since it may occur in almost any adrenal tumor (4, 12, 13), particularly when there is degeneration, hemorrhage, and necrosis. In our CASE III there was peripheral draping of the arterial supply around the tumor and large veins were arranged in a similar fashion. This finding is suggestive of
Fig. 3. A. Filling of the inferior adrenal artery during the injection of the renal artery. The arrow points to one of the small collections of contrast in the cortex of the adrenal. B. Late capillary phase reveals (arrows) that small contrast collections persist.
ADRENAL TUMORS
Vol. 125
339
Diagnostic Radiology
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Fig. 4. A. Adrenal mass containing diffuse amorphous calcifications with inferior displacement of the right kidney. B. and C. Selective inferior adrenal angiogram . Late arterial phase (B)-irregular pools of contrast (up to 5 mm in diameter) appear throughout the gland;oand venous phase (C)-persistence of irregular contrast pools with appearance of blood in dilated peripherally situated veins draining into the inferior vena cava . D. Gross photograph of sectioned mass reveals the nonhomogenous nature. with lighter fatty zones and darker zones of hemorrhage and necrosis . E. Microscopic section with fatty tissue on right. some adrenal cells centrally. and fibrous tissue to the left.
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340
PHILIP COSTELLO AND OTHERS
a benign tumor, but is otherwise nonspecific. The venous lakes are related to the enlarged blood sinuses within the tumor. It is evident that this latter sign is in no way specific for adrenal cortical tumors. In fact, there is an overlap between the signs demonstrated in this tumor and those described for cortical tumors, both benign and malignant. We have not found previous reports of intravenous neoplastic extension of a pheochromocytoma. Kahn and Ferris (7, 8) first described the intravenous neoplastic pattern of growth in renal cell carcinoma . Gregg and Wallace (6) reported the same phenomenon with primary hepatocellular carc inoma and retroperitoneal osteosarcoma growing into the inferior vena cava. The linear vascular pattern seen with selective angiography of the inferior phrenic artery is identical to the parallel arterial channels demonstrated by Gregg, who suggested that the vessels sometimes represented enlargement of the vasa vasorum (6). In this case, the vascular pattern was produced by arteries within the tumor, as well as vascular channels in the vasa vasorum of the
November 1977
inferior vena cava near the origin of the left renal vein. The tumor had therefore parasitised its blood supply from the inferior phrenic artery via the vasa vasorum of the caval wall. The striated pattern of vessels within other tumors (such as a hypernephroma growing in this manner) has been found to be composed of arterial channels derived directly from the blood supply of the primary tumor .
REFERENCES 1. Agee OF, Kaude J, Lepasdon J: Preoperative localization of pheochromocytoma . Acta Radiol (Diagn) 14:545-559, 1973 2. Alfidi RJ, Gill W Jr. Klein HJ: Arteriography of adrenal neoplasms. Am J RoentgenoI106:635-641 , Jul 1969 3. Boijsen E, Williams CM, Judkins MP: Angiography of pheochromocytoma. Am J Roentgenol 98:225-232. Sep 1966 4. Colapinto RF, Steed BL: Arter iography of adrenal tumors. Radiology 100:343-350, Aug 1971 5. Dobbie JW: Adrenocortical nodular hyperplasia. J Pathol 99:1-18,1969 6. Gregg FP, Goldstein HM. Wallace S, et al: Arteriograph ic demonstration of intravenous tumor extension. Am J Roentgenol 123: 100-105, Jan 1975
c Fig. 5. A. Selective right inferior phrenic angiogram. Note (between arrows) multiple fine linear vessels parallel to the spine, passing from the level of the first lumbar vertebra to the right atrium. These lines represent the blood supply to the intracaval portion of the recurrent pheochromocytoma. B. Inferior vena cavogram. A large intraluminal filling defect extends from the first lumbar vertebral body (at the site of the entry of the left renal vein) into the right atrium. The recurrent pheochromocytoma originated at the site of ligation of the left adrenal vein within the renal vein. C. Microscopic section of the removed tumor shows the caval wall on the right with a dilated vasa vasorum. The tumor to the left is adherent to the intima but has not become invasive. Note the vessel penetrating the wall of the cava and extending into the tumor. Many small arteries are scattered throughout the intraluminal pheochromocytoma .
Vol. 125
ADRENAL TUMORS
7. Ferris EJ, Bosniak MA, O'Connor JF: Angiographic sign demonstratingextension of renal carcinoma into renal vein and inferior vena cava. Am J RoentgenoI102:384-391, Feb 1968 8. Kahn PC: Epinephrine effect in selective renal arteriography. Radiology 85:301-305, Aug 1965 9. Lagergren C: Angiographic changes in the adrenal glands. Am J RoentgenoI101:732-7388, Nov 1967 10. Lanner LO, Rosencrantz M: Arteriographic appearances of pheochromocytomas. Acta Radiol (Diagn) 10:35-48, 1970 11. Lee KR, Lin F, Sibala J: Adrenal adenoma and hyperplasia: the importanceof arteriographicdifferential diagnosis. Am J Roentgenol 119:796-804, Dec 1973 12. Martin JF: Suprarenal clacification. Radiol Clin North Am 3:129-138, Apr 1965
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Diagnostic Radiology
13. Twerksy J, Levin DC: Metastatic melanoma of the adrenal. Radiology 116:627-628, Sep 1975 14. Tulcinsky D, Deutsch V, Bubis JJ: Myelolipoma of the adrenal gland. Br J Surg 57:465-467, Jun 1970 15. McGregor AL: Hibernoma of the adrenal. Acta Med Scand 306:107-110,1955
Department of Radiology New England Deaconess Hospital 185 Pilgrim Rd. Boston, Mass. 02215
