MASSIVE RETROPERITONEAL HEMORRHAGE FROM ADRENAL GLAND METASTASIS ALAN H. YAMADA, M.D. ANDY E. SHERROD, M.D. WILLIAM BOSWELL, M.D. DONALD G. SKINNER, M.D.
From the Departments of Urology, Pathology, and Radiology, University of Southern California, and Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles, California ABSTRACTWe report an unusual case of spontaneous massive retroperitoneal hemorrhage from an adrenal gland metastasis. After medical therapy failed to stabilize the patient’s condition, surgical exploration revealed a large retroperitoneal hematoma arising from a right adrenal gland metastasis. At the time of thoracoabdominal exploration in the lower lobe of right lung a small tumor nodule was palpated and resected. Pathologic examination of both lung and abdominal lesions revealed squamous cell carcinoma thought to have been primary in the lung. A review of the literature reveals that me&static lesions to the adrenal gland are infrequently encountered clinically and rarely hemorrhage; the first such case in which massive retroperitoneal hemorrhage was a complication is reported in the urologic literature.
The adrenal gland is a common site of metastatic involvement in certain malignancies such as carcinoma of the breast, lung, kidney, and malignant melanoma. 1,2 These lesions are rarely clinically significant and are usually discovered incidentally in autopsy studies3 However, improved imaging of the adrenal by computerized tomography (CT) and magnetic resonance imaging (MRI) has led to an increased awareness of the presence of metastases within the adrenal during life. To date, we are aware of only two reports in which significant hemorrhage from an adrenal metastasis required transfusion. 4 Herein, we report a case of massive adrenal hemorrhage caused by metastatic lung carcinoma. Case Report A sixty-three-year-old white man presented with a palpable left supraclavicular node. Biopsy specimen revealed a poorly differentiated squamous cell carcinoma. Extensive diagnostic workup including CT scans of the
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lung and abdomen failed to reveal a primary source of tumor. The adrenal glands were interpreted to be normal on initial abdominal CT scan. The patient had a normal blood cell count (CBC) and normal serum calcium level. He was treated for three months with cisplatin and 5fluorouracil combination chemotherapy followed by localized therapy to the supraclavicular area consisting of hyperthermia and radiation therapy. He had no evidence of recurrent disease including negative findings on CT scan of the abdomen three months prior to admission and a normal hemoglobin concentration level one month prior to admission. Eleven months after initial diagnosis, he presented to his local hospital complaining of malaise and pain in the right side of the abdomen. His hematocrit at that time was 28% but the patient was generally well with a blood pressure of 120/80 mm Hg. Positive physical findings included a palpable mass in the right side of abdomen, slight abdominal tenderness, and periumbilical ecchymoses. Three days later he
59
FIGURE 1. CT scan of massive retroperitoneal hemorrhage and mass effect. Fluid level in hematoma (amow) due to presence of recent and older blood within mass.
was seen at the Kenneth Norris Jr. Cancer Hospital where initial laboratory studies revealed a hemoglobin of 7.0 g/100 mL. Urinalysis, serum determinations of electrolytes, renal function, calcium, and a coagulation profile were normal. An enhanced abdominal CT scan demonstrated an extremely large hematoma of the right retroperitoneum displacing the kidney caudally and anteriorly (Fig. 1). The patient was admitted and treated medically with bed rest, and he was transfused with 3 units of blood. Serial CT scans revealed gradual enlargement of the hematoma. A CT scan done on the third hospital day suggested an adrenal etiology for the bleeding (Fig. 2). Aortography, including selective angiograms of the right renal and adrenal arteries were nondiagnostic other than confirming the presence of a large adrenal mass thought to be hematoma. After the patient received a total of 9 units of blood in the first five days of hospitalization, his condition became stable with a stable blood count for an additional five days. Then abruptly, on the tenth hospital day, his hemoglobin concentration again dropped and was associated with severe back pain, and he required an additional 3 units of blood. He was taken to the operating room and a right thoracoabdominal incision was made and a large hematoma was found adherent to the right kidney and extended down the iliopsoas muscle. A pale tumor was found that split the right adrenal gland and extended into the right renal hilum and underneath the inferior vena cava. En bloc resection of the hematoma, tumor mass, and
60
FIGURE 2. Contrast-enhanced CT suggests recent or active bleeding from right adrenal gland (arrow).
right radical nephrectomy was performed. In addition, a small nodule in right lower lobe of lung was palpable through the diaphragmatic incision and resected. Gross pathologic findings showed a right adrenal gland replaced by multiple lobulated white hemorrhagic tumor masses, the largest measuring 7 x 2.8 x 2 cm with a thin golden brown rim resembling stretched distorted adrenal cortex. Associated with the tumor and extending down toward the inferomedial aspect of the kidney was a hemorrhagic cavity 9.5 x 7 x 3 cm. Bleeding originated from the right central adrenal vein. Microscopic evaluation of the adrenal masses revealed moderately differentiated squamous cell carcinoma. The tumor was morphologically identical to the lung lesion which was interpreted as a primary pulmonary squamous cell carcinoma. The convalescence of the patient was uneventful, and he returned home on the seventh postoperative day. He died of complications of hypercalcemia one month later. Comment In autopsy studies as many as 27 percent of patients who died of cancer have been found to harbor adrenal me&stases.’ Carcinomas of the lung and breast, followed by malignant melanoma and renal cell carcinoma are the tumors most likely to metastasize to the adrenal gland.2 The adrenal metastasis rarely produces symptoms during life. For example, Siekavizza,
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Bernadino, and Samaan,5 in a review of 55 consecutive cases of adrenal metastases found on autopsy reported that all were clinically asymptomatic, and only a few were detected radiographically or ultrasonically before patient’s death.5 To date the reported primary complication of adrenal metastases has been adrenal insufficiency in patients with bilateral disease often associated with pain and adrenal hemorrhage. Bilateral adrenal hemorrhage has been reported in up to 1.1 percent of autopsy studies in adults, usually in patients who have sustained severe stress. It is classically seen in acute fulminating meningococcemia, the Waterhouse-Friedrickson syndrome, as well as other forms of severe sepsis. A number of other predisposing factors have been associated with adrenal hemorrhage including stresses like burns, surgery, pregnancy, cardiovascular disease, and trauma. It also has been associated with adrenocorticotropic hormone (ACTH) administration, anticoagulation therapy, adrenal venography, and hematologic disorders.3,6-13 In contrast, unilateral adrenal hemorrhage is a less common clinical presentation. It can be spontaneous or associated with trauma, a complicated pregnancy, or as a result of stress, but it should always raise the question of an underlying primary adrenal tumor. A primary adrenal tumor or cyst ranks fourth as the most common cause of spontaneous retroperitoneal hemorrhage after renal cell carcinoma, angiomyolipoma, and renal artery aneurysm.14 Of the adrenal tumors, rupture of a pheochromocytoma is the most common cause of massive bleeding, and rarely an adrenal carcinoma also has been reported to bleed. Cysts and myelolipomas have occasionally been reported to hemorrhage but adrenal adenomas, probably because of their avascular nature, have not been associated with spontaneous hemorrhage. 15-17 However, hemorrhage from adrenal metastasis is unusual. In the pre-CT scan era, Amador3 examined 4,325 autopsies of patients dying of malignancy and found only 3 cases of hemorrhagic adrenal metastasis. Since the development of CT scanning and MRI, a total of 7 cases of clinically significant hemorrhage resulting from metastases to the adrenal gland have been reported.18J0 Of these, 5 patients had primary adenocarcinoma of the lung, 1 patient had large-cell bronchogenic carcinoma of the lung, and 1 patient had a primary angiosarcoma of the liver. In each case the patient presented
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VOLUME 40, NUMBER
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with abdominal and flank pain and had localized hematomas. Although blood counts in several patients showed an initial drop in hemoglobin concentration, most of the patients were stabilized hemodynamically and required no further transfusions or surgical intervention. Massive bleeding from an adrenal metastasis requiring surgical intervention has been reported in 2 patients, Both patients were found to have metastatic lung carcinoma and had persistent hemorrhage that required adrenalectomy to control the bleeding.4 Diagnostically, the CT scan and MRI are specific and sensitive aids in the diagnosis of adrenal hemorrhage. Typically, CT findings show an inhomogeneous, mixed-density adrenal mass with extensive perirenal changes. lo Findings may vary from symmetric enlargement of both adrenal glandszOto massive hemorrhage with obliteration of the gland, as in our case.4x21CT scanning cannot only detect, quantitate, and localize adrenal hemorrhage, it also may provide an etiologic explanation for the bleeding by demonstrating ongoing adrenal hemorrhage. Acute bleeding is often identified on contrast-enhanced CT scanning by areas of higher density within the mass.22 Characteristics of adrenal hemorrhage on MRI also have been described. 18,22,23 The clinical course of our case and the other patients with massive adrenal hemorrhage from an adrenal metastasis illustrate the need for close medical observation and occasionally decisive surgical intervention. 2025 Zonal Avenue Suite GH5900 Los Angeles, California 90033 References 1. Abrams HL, Spiro R, and Goldstein N: Metastases in carcinoma, Cancer 3: 74 (1959). 2. Page DL, DeLellis RA, and Hough AJ: Tumors of the adrenal, AFIP 23: 159 (1986). 3. Amador E: Adrenal hemorrhage during anticoagulant therapy: a clinical and pathologic study of ten cases, Ann Intern Med 63: 559 (1965). 4. Rowinsky EK, Jones RJ, and Abeloff MD: Massive adrenal hemorrhage secondary to me&static lung carcinoma, Med Pediatr Oncol 14: 234 (1986). 5. Siekavizza JL, Bernardino ME, and Samaan NA: Suprarenal mass and its differential diagnosis, Urology 18: 625 (1981). 6. Zornoza J, Bracken R, and Wallace S: Radiologic features of adrenal metastases, Urology 8: 295 (1976). 7. Xarli VP, et al: Adrenal hemorrhage in the adult, Medicine 57: 211 (1978). 8. Lawson DW, Patton AS, and Austen WC: Massive retroperitoneal adrenal hemorrhage, Surg Gynecol Obstet 129: 989 (1969).
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9. Botteri A, and Ore1 SD: Adrenal hemorrhage and necrosis in the adult, a clinicopathological study of 23 cases, Acta Med Stand 175: 409 (1964). 10. Clark OH: Postoperative adrenal hemorrhage, Ann Surg 182: 124 (1975). 11. Greendyke RM: Adrenal hemorrhage, Am J Clin Path01 43: 210 (1965). 12. Miller EH, Woldenberg DH, Gittler RD, and Zumoff B: Bilateral adrenal hemorrhage following surgery, NY State J Med 86: 651 (1986). 13. Marcus HI, Connon JJ, and Stern HS: Bilateral adrenal hemorrhage during ACTH treatments of ulcerative colitis, Dis Colon Rectum 29: 130 (1986). 14. Swift DL, Lingeman JE, and Baum WC: Spontaneous retroperitoneal hemorrhage: a diagnostic challenge, J Urol 123: 577 (1980). 15. Rubin HB, Hirose F, and Benfield JR: Myelolipoma of the adrenal gland. Angiographic findings and review of the literature, Am J Surg 130: 354 (1975). 16. Cerise EJ, and Hammon JW Jr: Adrenal cyst, Surgery 63:
62
903 (1968). 17. de Resind-Alves JB, de Alvarenga RJ, Kingma J, and Meyer TN: Adenoma and hemorrhage of the adrenal gland, Int Surg 61: 429 (1976). 18. Outwater E, and Bankoff MS: Clinically significant adrenal hemorrhage secondary to metastaxs, computed tomography observations, Clin Imaging 13: 195 (1989). 19. Shah HR, et al: Hemorrhagic adrenal metastases: CT findings, J Comput Assist Tomogr 13: 77 (1989). 20. Wolverson MK, and Kannegiesser H: CT of bilateral adrenal hemorrhage with acute adrenal insufficiency in the adult, AJR 142: 311 (1984). 21. Ferris EJ, et al: RSNA image interpretation session, Radiographics 9: 109 (1989). 22. Liu L, Haskin ME, Rove LI, and Bemis CE: Diagnosis of bilateral adrenocortical hemorrhage by computerized tomography, Ann Intern Med 97: 720 (1982). 23. Itoh K, Yamashita K, Satoh Y, and Sawada H: MR imaging of bilateral adrenal hemorrhage, J Comput Assist Tomogr 12: 1054 (1988).
UROLOGY
I JULY 1992 I VOLUME 40, NUMBER 1
From the Departments of Urology, Pathology, and Radiology, University of Southern California, and Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles, California ABSTRACTWe report an unusual case of spontaneous massive retroperitoneal hemorrhage from an adrenal gland metastasis. After medical therapy failed to stabilize the patient’s condition, surgical exploration revealed a large retroperitoneal hematoma arising from a right adrenal gland metastasis. At the time of thoracoabdominal exploration in the lower lobe of right lung a small tumor nodule was palpated and resected. Pathologic examination of both lung and abdominal lesions revealed squamous cell carcinoma thought to have been primary in the lung. A review of the literature reveals that me&static lesions to the adrenal gland are infrequently encountered clinically and rarely hemorrhage; the first such case in which massive retroperitoneal hemorrhage was a complication is reported in the urologic literature.
The adrenal gland is a common site of metastatic involvement in certain malignancies such as carcinoma of the breast, lung, kidney, and malignant melanoma. 1,2 These lesions are rarely clinically significant and are usually discovered incidentally in autopsy studies3 However, improved imaging of the adrenal by computerized tomography (CT) and magnetic resonance imaging (MRI) has led to an increased awareness of the presence of metastases within the adrenal during life. To date, we are aware of only two reports in which significant hemorrhage from an adrenal metastasis required transfusion. 4 Herein, we report a case of massive adrenal hemorrhage caused by metastatic lung carcinoma. Case Report A sixty-three-year-old white man presented with a palpable left supraclavicular node. Biopsy specimen revealed a poorly differentiated squamous cell carcinoma. Extensive diagnostic workup including CT scans of the
UROLOGY
/
JULY 1992
/
VOLUME
40, NUMBER
1
lung and abdomen failed to reveal a primary source of tumor. The adrenal glands were interpreted to be normal on initial abdominal CT scan. The patient had a normal blood cell count (CBC) and normal serum calcium level. He was treated for three months with cisplatin and 5fluorouracil combination chemotherapy followed by localized therapy to the supraclavicular area consisting of hyperthermia and radiation therapy. He had no evidence of recurrent disease including negative findings on CT scan of the abdomen three months prior to admission and a normal hemoglobin concentration level one month prior to admission. Eleven months after initial diagnosis, he presented to his local hospital complaining of malaise and pain in the right side of the abdomen. His hematocrit at that time was 28% but the patient was generally well with a blood pressure of 120/80 mm Hg. Positive physical findings included a palpable mass in the right side of abdomen, slight abdominal tenderness, and periumbilical ecchymoses. Three days later he
59
FIGURE 1. CT scan of massive retroperitoneal hemorrhage and mass effect. Fluid level in hematoma (amow) due to presence of recent and older blood within mass.
was seen at the Kenneth Norris Jr. Cancer Hospital where initial laboratory studies revealed a hemoglobin of 7.0 g/100 mL. Urinalysis, serum determinations of electrolytes, renal function, calcium, and a coagulation profile were normal. An enhanced abdominal CT scan demonstrated an extremely large hematoma of the right retroperitoneum displacing the kidney caudally and anteriorly (Fig. 1). The patient was admitted and treated medically with bed rest, and he was transfused with 3 units of blood. Serial CT scans revealed gradual enlargement of the hematoma. A CT scan done on the third hospital day suggested an adrenal etiology for the bleeding (Fig. 2). Aortography, including selective angiograms of the right renal and adrenal arteries were nondiagnostic other than confirming the presence of a large adrenal mass thought to be hematoma. After the patient received a total of 9 units of blood in the first five days of hospitalization, his condition became stable with a stable blood count for an additional five days. Then abruptly, on the tenth hospital day, his hemoglobin concentration again dropped and was associated with severe back pain, and he required an additional 3 units of blood. He was taken to the operating room and a right thoracoabdominal incision was made and a large hematoma was found adherent to the right kidney and extended down the iliopsoas muscle. A pale tumor was found that split the right adrenal gland and extended into the right renal hilum and underneath the inferior vena cava. En bloc resection of the hematoma, tumor mass, and
60
FIGURE 2. Contrast-enhanced CT suggests recent or active bleeding from right adrenal gland (arrow).
right radical nephrectomy was performed. In addition, a small nodule in right lower lobe of lung was palpable through the diaphragmatic incision and resected. Gross pathologic findings showed a right adrenal gland replaced by multiple lobulated white hemorrhagic tumor masses, the largest measuring 7 x 2.8 x 2 cm with a thin golden brown rim resembling stretched distorted adrenal cortex. Associated with the tumor and extending down toward the inferomedial aspect of the kidney was a hemorrhagic cavity 9.5 x 7 x 3 cm. Bleeding originated from the right central adrenal vein. Microscopic evaluation of the adrenal masses revealed moderately differentiated squamous cell carcinoma. The tumor was morphologically identical to the lung lesion which was interpreted as a primary pulmonary squamous cell carcinoma. The convalescence of the patient was uneventful, and he returned home on the seventh postoperative day. He died of complications of hypercalcemia one month later. Comment In autopsy studies as many as 27 percent of patients who died of cancer have been found to harbor adrenal me&stases.’ Carcinomas of the lung and breast, followed by malignant melanoma and renal cell carcinoma are the tumors most likely to metastasize to the adrenal gland.2 The adrenal metastasis rarely produces symptoms during life. For example, Siekavizza,
UROLOGY
I JULY1992 / VOLUME40,NUMBERl
Bernadino, and Samaan,5 in a review of 55 consecutive cases of adrenal metastases found on autopsy reported that all were clinically asymptomatic, and only a few were detected radiographically or ultrasonically before patient’s death.5 To date the reported primary complication of adrenal metastases has been adrenal insufficiency in patients with bilateral disease often associated with pain and adrenal hemorrhage. Bilateral adrenal hemorrhage has been reported in up to 1.1 percent of autopsy studies in adults, usually in patients who have sustained severe stress. It is classically seen in acute fulminating meningococcemia, the Waterhouse-Friedrickson syndrome, as well as other forms of severe sepsis. A number of other predisposing factors have been associated with adrenal hemorrhage including stresses like burns, surgery, pregnancy, cardiovascular disease, and trauma. It also has been associated with adrenocorticotropic hormone (ACTH) administration, anticoagulation therapy, adrenal venography, and hematologic disorders.3,6-13 In contrast, unilateral adrenal hemorrhage is a less common clinical presentation. It can be spontaneous or associated with trauma, a complicated pregnancy, or as a result of stress, but it should always raise the question of an underlying primary adrenal tumor. A primary adrenal tumor or cyst ranks fourth as the most common cause of spontaneous retroperitoneal hemorrhage after renal cell carcinoma, angiomyolipoma, and renal artery aneurysm.14 Of the adrenal tumors, rupture of a pheochromocytoma is the most common cause of massive bleeding, and rarely an adrenal carcinoma also has been reported to bleed. Cysts and myelolipomas have occasionally been reported to hemorrhage but adrenal adenomas, probably because of their avascular nature, have not been associated with spontaneous hemorrhage. 15-17 However, hemorrhage from adrenal metastasis is unusual. In the pre-CT scan era, Amador3 examined 4,325 autopsies of patients dying of malignancy and found only 3 cases of hemorrhagic adrenal metastasis. Since the development of CT scanning and MRI, a total of 7 cases of clinically significant hemorrhage resulting from metastases to the adrenal gland have been reported.18J0 Of these, 5 patients had primary adenocarcinoma of the lung, 1 patient had large-cell bronchogenic carcinoma of the lung, and 1 patient had a primary angiosarcoma of the liver. In each case the patient presented
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I JULY 1992
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VOLUME 40, NUMBER
1
with abdominal and flank pain and had localized hematomas. Although blood counts in several patients showed an initial drop in hemoglobin concentration, most of the patients were stabilized hemodynamically and required no further transfusions or surgical intervention. Massive bleeding from an adrenal metastasis requiring surgical intervention has been reported in 2 patients, Both patients were found to have metastatic lung carcinoma and had persistent hemorrhage that required adrenalectomy to control the bleeding.4 Diagnostically, the CT scan and MRI are specific and sensitive aids in the diagnosis of adrenal hemorrhage. Typically, CT findings show an inhomogeneous, mixed-density adrenal mass with extensive perirenal changes. lo Findings may vary from symmetric enlargement of both adrenal glandszOto massive hemorrhage with obliteration of the gland, as in our case.4x21CT scanning cannot only detect, quantitate, and localize adrenal hemorrhage, it also may provide an etiologic explanation for the bleeding by demonstrating ongoing adrenal hemorrhage. Acute bleeding is often identified on contrast-enhanced CT scanning by areas of higher density within the mass.22 Characteristics of adrenal hemorrhage on MRI also have been described. 18,22,23 The clinical course of our case and the other patients with massive adrenal hemorrhage from an adrenal metastasis illustrate the need for close medical observation and occasionally decisive surgical intervention. 2025 Zonal Avenue Suite GH5900 Los Angeles, California 90033 References 1. Abrams HL, Spiro R, and Goldstein N: Metastases in carcinoma, Cancer 3: 74 (1959). 2. Page DL, DeLellis RA, and Hough AJ: Tumors of the adrenal, AFIP 23: 159 (1986). 3. Amador E: Adrenal hemorrhage during anticoagulant therapy: a clinical and pathologic study of ten cases, Ann Intern Med 63: 559 (1965). 4. Rowinsky EK, Jones RJ, and Abeloff MD: Massive adrenal hemorrhage secondary to me&static lung carcinoma, Med Pediatr Oncol 14: 234 (1986). 5. Siekavizza JL, Bernardino ME, and Samaan NA: Suprarenal mass and its differential diagnosis, Urology 18: 625 (1981). 6. Zornoza J, Bracken R, and Wallace S: Radiologic features of adrenal metastases, Urology 8: 295 (1976). 7. Xarli VP, et al: Adrenal hemorrhage in the adult, Medicine 57: 211 (1978). 8. Lawson DW, Patton AS, and Austen WC: Massive retroperitoneal adrenal hemorrhage, Surg Gynecol Obstet 129: 989 (1969).
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9. Botteri A, and Ore1 SD: Adrenal hemorrhage and necrosis in the adult, a clinicopathological study of 23 cases, Acta Med Stand 175: 409 (1964). 10. Clark OH: Postoperative adrenal hemorrhage, Ann Surg 182: 124 (1975). 11. Greendyke RM: Adrenal hemorrhage, Am J Clin Path01 43: 210 (1965). 12. Miller EH, Woldenberg DH, Gittler RD, and Zumoff B: Bilateral adrenal hemorrhage following surgery, NY State J Med 86: 651 (1986). 13. Marcus HI, Connon JJ, and Stern HS: Bilateral adrenal hemorrhage during ACTH treatments of ulcerative colitis, Dis Colon Rectum 29: 130 (1986). 14. Swift DL, Lingeman JE, and Baum WC: Spontaneous retroperitoneal hemorrhage: a diagnostic challenge, J Urol 123: 577 (1980). 15. Rubin HB, Hirose F, and Benfield JR: Myelolipoma of the adrenal gland. Angiographic findings and review of the literature, Am J Surg 130: 354 (1975). 16. Cerise EJ, and Hammon JW Jr: Adrenal cyst, Surgery 63:
62
903 (1968). 17. de Resind-Alves JB, de Alvarenga RJ, Kingma J, and Meyer TN: Adenoma and hemorrhage of the adrenal gland, Int Surg 61: 429 (1976). 18. Outwater E, and Bankoff MS: Clinically significant adrenal hemorrhage secondary to metastaxs, computed tomography observations, Clin Imaging 13: 195 (1989). 19. Shah HR, et al: Hemorrhagic adrenal metastases: CT findings, J Comput Assist Tomogr 13: 77 (1989). 20. Wolverson MK, and Kannegiesser H: CT of bilateral adrenal hemorrhage with acute adrenal insufficiency in the adult, AJR 142: 311 (1984). 21. Ferris EJ, et al: RSNA image interpretation session, Radiographics 9: 109 (1989). 22. Liu L, Haskin ME, Rove LI, and Bemis CE: Diagnosis of bilateral adrenocortical hemorrhage by computerized tomography, Ann Intern Med 97: 720 (1982). 23. Itoh K, Yamashita K, Satoh Y, and Sawada H: MR imaging of bilateral adrenal hemorrhage, J Comput Assist Tomogr 12: 1054 (1988).
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I JULY 1992 I VOLUME 40, NUMBER 1
