ADRENOCORTICAL CARCINOMA PRESENTING AS A RETROPERITONEAL ABSCESS: AN UNUSUAL PRESENTATION OF A RARE TUMOR
Antonio Ramos-De la Medina, MD,* and Florencia G. Que, MD
INTRODUCTION
Adrenocortical carcinoma is a rare and aggressive neoplasm with an estimated incidence of 1 case per 1.7 million, accounting for 0.02% of cancers (1). The prog- nosis of adrenocortical carcinoma in adults is generally poor with most cases presenting in advanced stages. Most patients with nonfunctioning tumors present with pain, a palpable mass, or have an incidental radiographic find- ing. Only 30% of tumors are confined to the adrenal gland at the time of diagnosis (2), and the 5-year survival rate after resection is only 10% to 25% (3). We report a case of nonfunctioning adrenocortical carcinoma presenting as an intra-abdominal abscess. To our knowledge, this is the first such presentation reported in the literature.
CASE PRESENTATION
A 52-year-old man was referred to the Mayo Clinic in Rochester, Minnesota, for evaluation of monoclonal gammopathy and anemia. He presented 6 months earlier to an outside hospital with fever, sweating, anorexia, and left upper-quadrant pain. Laboratory testing at that time disclosed the following values: white blood cell count, 18 000/uL; aspartate aminotransferase, 1315 U/L; and cre- atine phosphokinase, 1900 U/L. Blood culture and viral serology test results were negative for hepatitis B virus, West Nile virus, Epstein-Barr virus, and cytomegalovirus. He was treated empirically with antibiotics, and his con- dition improved. He subsequently developed proteinuria,
anemia, and hypergammaglobulinemia. Results of serum protein electrophoresis were negative, but findings from immunofixation revealed IgG x and 2 monoclonal protein. A bone marrow biopsy specimen contained 7% plasma cells. His local physician started dexamethasone induction therapy for suspected multiple myeloma, and the patient was referred to our institution for further evaluation and treatment.
Laboratory values from further evaluation at our insti- tution were notable for: hemoglobin, 14.6 g/dL; white blood cell count, 15 800/uL; and platelets, 288x103/uL. Results from a fat aspirate were negative for amyloid, and findings from a bone survey did not reveal metastasis or multiple myeloma. The diagnosis of monoclonal gammop- athy of undetermined significance was made, dexametha- sone therapy was discontinued, and he was scheduled for follow-up.
Four weeks after his initial evaluation at Mayo Clinic, laboratory testing disclosed the following values: hemoglobin, 13 g/dL; white blood cell count, 16 100/uL; platelets, 450×103/uL; erythrocyte sedimentation rate, 75 mm/h; and C-reactive protein, 11.0 mg/dL. Computed tomography was performed (Fig. 1), which revealed a bilobed left upper-quadrant mass with internal necrosis and calcifications consistent with re-abscess. The more inferior component measured 8 cm in greatest diameter and displaced the upper pole of the left kidney. A second component extended cephalad along the undersurface of the left hemidiaphragm beyond the left hemidiaphragm medially to the pericardium. A computed tomography- guided percutaneous needle aspiration was performed, and the results showed purulent material. The specimens were sent for cytologic and microbiological studies. Pathologic findings included an epithelioid malignancy with positive immunohistochemical staining results for cytokeratin 5/6, cytokeratin 7, cytokeratin 20, keratin, and cell adhesion molecule 5.2 and negative results for prostate-specific antigen, x and 2 light chain, thyroid transcription factor 1, chromogranin, and synaptophysin. Gram stains of the aspirate showed streptococci and gram-negative bacilli,
From the Department of Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota.
@ 2007 AACE.
and culture results identified viridans streptococci. Results from analysis of 24-hour urine collection are shown in Table 1. An electrolyte panel revealed the following values: creatinine, 0.8 mg/dL (reference range, 0.9 to 1.4 mg/dL); bicarbonate, 24 mEq/L (reference range, 22 to 29 mEq/L); chloride, 98 mEq/L (reference range, 100 to 108 mEq/L); potassium, 4.3 mEq/L (reference range, 3.6 to 4.8 mEq/L); sodium, 138 mEq/L (reference range, 135 to 145 mEq/L);
and serum urea nitrogen, 10 mg/dL (reference range, 8 to 24 mg/dL). His calcium level was 9.5 mg/dL (reference range, 8.9 to 10.1 mg/dL).
The patient was admitted to the hospital for adminis- tration of intravenous antibiotics and computed tomogra- phy-guided percutaneous drainage. Results from staging studies were negative for metastasis, and levels of pros- tate-specific antigen, ß-human chorionic gonadotropin, and a-fetoprotein were all within the reference range. The urinary free cortisol level was within the reference range at 45 µg/24 h. No magnetic resonance imaging was per- formed. The patient’s condition improved, and after 3 weeks of drainage and antibiotics, surgery was performed. On surgical exploration, a 13-cm abscessed adrenal mass was identified. A left adrenalectomy, left nephrectomy, total gastrectomy, distal pancreatectomy, splenectomy, wedge pneumonectomy, resection and reconstruction of the left hemidiaphragm, and Roux-en-Y esophagojejunos- tomy were performed to completely excise the tumor and the associated abscess. Pathologic findings included an adrenocortical carcinoma forming a 13 × 8 × 7-cm adre- nal mass with marked areas of inflammation and abscess formation. The tumor was encasing the renal vasculature and invaded into the attached portion of the diaphragm and stomach wall with negative surgical margins.
Metastatic disease was not found in the 9 resected lymph nodes. The patient had an uneventful postopera- tive recovery and was discharged home from the hospital 2 weeks after the operation. He refused further therapy with mitotane, and the monoclonal gammopathy of unknown
| Analyte | Result | Reference Range |
|---|---|---|
| Androsterone, mg/24 h | 1 | 0.9 to 6.1 |
| Etiocholanolone, mg/24 h | 2.8 | 0.9 to 5.2 |
| Dehydroepiandrosterone, mg/24 h | 0.1 | 0 to 3.1 |
| 11-Ketoandrosterone, mg/24 h | 0.9 | 0 to 0.5 |
| 11-Ketoetiocholanolone mg/24 h | 0.6 | 0 to 1.6 |
| 11-hydroxyandrosterone, mg/24 h | 1.4 | 0.2 to 1.6 |
| 11-hydroxyetiocholanolone, mg/24 h | 1.1 | 0.1 to 0.9 |
| Pregnanetriol, mg/24 h | 1.2 | 0.2 to 2 |
| Norepinephrine, ug/24 h | 127 | 15 to 80 |
| Epinephrine, ug/24 h | 2 | 0 to 20 |
| Dopamine, ug/24 h | 361 | 65 to 400 |
| 17-Ketosteroids, mg/24 h | 11 | 6 to 21 |
| Metanephrine, ug/24 h | 185 | 44 to 261 |
| Normetanephrine, ug/24 h | 1146 | 128 to 484 |
| Total metanephrine, ug/24 h | 1331 | 222 to 680 |
| Cortisone, ug/24 h | 168 | 17 to 129 |
| Free cortisol, ug/24 h | 45 | 3.5 to 45 |
significance was not re-evaluated. The patient was fol- lowed up every 3 to 6 months postoperatively. He devel- oped a biopsy-proven small cell lung cancer 22 months after resection and died of lung cancer 26 months postre- section of his adrenocortical cancer.
DISCUSSION
Adrenocortical carcinoma is a rare neoplasm, with equal incidence in both sexes. Although adrenocorti- cal carcinoma can develop at any age, it has a bimodal age distribution, with disease peaks before age 5 years and in the fourth to fifth decades of life (1). Between 33% and 62% of tumors are functional, and symptoms of unregu- lated hormonal production lead to investigation and diag- nosis in these patients. Cortisol is the hormone most fre- quently overexpressed by adrenocortical tumors, including adrenocortical carcinoma. Androgens and estrogens are the next most common class of hormones produced by adre- nocortical carcinoma. Androgen secretion is associated with long-term survival while glucocorticoid secretion is associated with poor survival in univariate and multivari- ate analyses (4).
Nonfunctioning tumors usually present at a more advanced stage with symptoms of tumor growth. Less common symptoms can include weight loss, fever, mal- aise, hypertension, hematuria, and varicocele. Many cases are detected as distant metastasis or as incidental masses found on radiographic studies. Other less frequent forms of presentation reported include invasion and thrombosis of the inferior vena cava, retroperitoneal hemorrhage, and acute abdomen (5-7). Adrenal abscess is very rare in adults (7). It has been mainly reported among neonates secondary to adrenal hemorrhage or as a complication of fine-needle aspiration.
The stage at presentation and complete surgical resec- tion are recognized as the strongest predictors of long-term survival (8). Complete surgical resection is the only poten- tially curative treatment for adrenocortical carcinoma. The high frequency of local and metastatic recurrences has prompted the use of adjuvant therapies. The efficacy of mitotane remains disputed. Reported response rates from some older series are as high as 35%, although findings from more recent series have shown lower response rates. Two phase II trials of combination chemotherapy and sur- gery showed a 22% to 50% response rate with doxorubi- cin, cisplatin, and mitotane, suggesting a superior response to mitotane therapy alone (4,9).
Findings from multiple series have demonstrated that the 5-year actuarial survival ranges from 36% to 46% for patients who undergo complete resection. In our institu- tional series reported in 2001 (10), 47% of the patients presented with functional tumors, and a curative resec- tion was accomplished in 71% of the cases. We identi- fied nonfunctioning tumors, early tumor stage, and use of
chemotherapy for stage III and IV disease as predictors of longer survival. We confirmed that re-resection improved survival. Perioperative mortality was 5%, and recurrence was documented in 73% of patients with a median time to recurrence of 17 months. Five-year survival was 37%.
Of 16 pathologic features examined in a study of 46 patients with adrenocortical carcinoma undergoing surgi- cal resection at Memorial Sloan-Kettering Cancer Center (11), only tumor size, abnormal mitotic figures, and the presence of intratumoral hemorrhage were independent prognostic factors. Extended resection and presence of tumor thrombus in the renal vein or inferior vena cava do not predict poor prognosis if complete, margin-negative tumor resection is achieved. Tumor diameter larger than 12 cm, 6 or more mitotic figures per 10 high-power fields, and the presence of histologic evidence of intratumoral hemorrhage are all associated with poor survival (12).
CONCLUSION
Adrenocortical carcinoma is a rare tumor that can present in different forms. To our knowledge, this is the first reported case of an adrenocortical carcinoma present- ing as a retroperitoneal abscess. Aggressive surgical man- agement is justified when a complete margin-free resection can be achieved.
DISCLOSURE
The authors have no conflicts of interest to disclose.
REFERENCES
1. Vaughan ED. Diseases of the adrenal gland. Med Clin North Am. 2004;88:443-466.
2. Norton JA. Adrenal tumors. In: De Vita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 1997: 1659-1677.
3. Wooten MD, King DK. Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer. 1993;72:3145-3155.
4. Berruti A, Terzolo M, Sperone P, et al. Etoposide, doxo- rubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005;12;657-666.
5. Stamoulis JS, Antonopoulou Z, Safioleas M. Haemorrhagic shock from the spontaneous rupture of an adrenal cortical carcinoma: a case report. Acta ChirBelg. 2004;104:226-228.
6. Leung LY, Leung WY, Chan KF, Fan TW, Chung KW, Chan CH. Ruptured adrenocortical carcinoma as a cause of paediatric acute abdomen. Pediatr Surg Int. 2002;18: 730-732.
7. Echaniz A, de Miguel Prieto J, Arnal F, Pedreira JD. Escherichia coli abscess as an adrenal mass. Ann Intern Med. 1985;103:481.
570 Abscessed Adrenocortical Carcinoma, Endocr Pract. 2007;13(No. 5)
8. Allolio B, Hahner S, Weismann D, Fassnacht M. Management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2004;60:273-287.
9. Abraham J, Bakke S, Rutt A, et al. A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continu- ous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist. Cancer. 2002;94:2333-2343.
10. Kendrick ML, Lloyd R, Erickson L, et al. Adrenocortical carcinoma: surgical progress or status quo? Arch Surg. 2001;136:543-549.
11. Harrison LE, Gaudin P, Brennan MF. Pathologic features of prognostic significance for adrenocortical carcinoma after curative resection. Arch Surg. 1999;134:181-185.
12. Schulick RD, Brennan MF. Long-term survival after com- plete resection and repeat resection in patients with adreno- cortical carcinoma. Ann Surg Oncol. 1999;6:719-726.