Inferior vena cava (IVC) thrombus is a rare presentation of adrenal carcinoma. Hyperladosteronism is rarely associated with it. We report a case of an aldosterone-producing left adrenal carcinoma with IVC thrombus and invasion of multiple organs, treated with neoadjuvant chemotherapy and salvage surgery. The patient is alive and asymptomatic after 46 months. Surgical aspects and therapeutic options are discussed and compared with the current medical literature. This is believed to be the first report of multiple organ resection combined with IVC thrombus removal for a functioning adrenal carcinoma.
adrenocortical cancer;hyperaldosteronism;inferior vena cava thrombus
Adrenal carcinomas are rare, with an incidence of 0.7 to 2 cases per 1 million population per year.1 They are more common in women, with a female to male ratio of 1.5 to 1.2 Female patients seem to have a higher probability of presenting with functioning malignant tumors, which apparently hold a better prognosis than nonfunctioning adrenal neoplasms.2 Also, adrenal cancers have been associated with familial syndromes and gene mutations, and rarely with hyperaldosteronism.3 ; 4
There is limited experience in the treatment of advanced adrenal carcinoma. Current strategies are based on retrospective analysis and case reports. Recently, large multicenter trials have elucidated some aspects of multiagent chemotherapy usage for advanced disease.5 ; 6 However, salvage surgery is not routine, and is performed in a minority of patients.5 ; 6
Adrenal carcinomas in general do not invade adjacent organs.2 Left-sided adrenal carcinoma with inferior vena cava (IVC) thrombus is a rare presentation for this uncommon malignancy.7; 8; 9 ; 10 Salvage surgery for adrenal carcinoma with IVC thrombus and multiple organ invasion has never been previously reported.
We describe an unusual case of a 42-year-old female patient diagnosed with a left-sided adrenal carcinoma with invasion of multiple organs and an IVC thrombus subjected to neoadjuvant chemotherapy and salvage surgery.
A 42-year-old woman was referred to our Surgical Oncology Department after an unsuccessful attempt to remove a voluminous left adrenal carcinoma with an IVC thrombus extending to the retrohepatic cava (Fig. 1). The patient also complained of bilateral inferior limb edema and refractory hypertension due to hyperaldosteronism (supine aldosterone blood levels = 36.4 ng/dL). Potassium blood levels were normal (3.5 mEq/L). Family history was negligible.
Computed tomography scan showing a voluminous mass, with inferior vena cava thrombus, extending to the suprahepatic vein level. VCI = inferior vena cava; LESAO = adrenal cancer and the vena cava thrombus; RIM ESQ = left kidney (Note that abbreviations were in Portuguese).
Salvage chemotherapy with etoposide, doxorubicin, cisplatin, and mitotane was administered for 6 months. During chemotherapy, two hypertensive crisis episodes were diagnosed. After chemotherapy, a 30% mass reduction was observed and salvage surgery was indicated. No metastasis had been found before surgery.
At laparotomy, a large mass with mesocolon, left colic artery, spleen, pancreas, and left kidney invasion was seen. Left radical adrenalectomy with left nephrectomy, splenectomy, caudal pancreatectomy, and resection of the left mesocolon with ligation of the left colic artery were performed. The IVC was clamped at the retrohepatic diaphragmatic level. A right cavotomy with total removal of the thrombus was performed and the IVC was sutured. An associated left-sided retroperitoneal lymphadenectomy was executed. No postoperative complications were diagnosed, and resection was considered to leave no residual disease (R0). Blood pressure and aldosterone levels normalized soon after surgery and mitotane was maintained for 6 months.
After 18 months, bilateral pulmonary metastases were detected. Aldosterone blood levels were normal and hypertension was not present. Gemcitabine was administered for six months and continuous daily mitotane was initiated. Metastases stability was achieved.
Currently, the patient has survived for 46 months and is asymptomatic with stable disease. No hypertensive episodes have been documented since the radical surgical procedure.
Left adrenal carcinoma with IVC thrombus and multiple organ invasion has rarely, if ever, been reported.
Our case demonstrates an initially inoperable female patient with a voluminous adrenal tumor and refractory hypertension. A combination chemotherapy regimen with etoposide, cisplatin, doxorubicin, and mitotane was started and seems to be the most active combination for advanced disease.5 ; 6 It was used as a salvage chemotherapy regimen and allowed surgery to be performed after a 6-month period.
Surgery remains the most important pillar in adrenal carcinoma treatment. In our opinion, salvage surgical procedures should always be attempted, because they probably represent the best option for the patient.6; 7 ; 11 Furthermore, they have been associated with extended overall survival.2; 4 ; 11 In this case, the patient remained asymptomatic for 24 months. It is important to note that recurrence occurred as nonfunctioning disease, demonstrating that its behavior cannot be predicted.
Mitotane has been widely used in adrenal carcinoma. It seems capable of prolonging survival, especially in patients previously subjected to radical surgical resection.13
High aldosterone blood levels are found in 1.5–5% of hypertensive patients. However, aldosterone-producing adrenal cancer is rarely the cause.14; 15 ; 16 Removal of functioning adrenal tumors usually corrects hypertension. Nevertheless, some patients can remain hypertensive in spite of R0 resection.17 It is important to mention that primary functioning adrenal carcinomas seem not to correlate with the metastasis pattern. Our patient had nonfunctioning metastases, whereas the opposite has been described elsewhere.4 ; 17
Finally, it seems that aldosterone-producing tumors have a better prognosis than cortisol-producing neoplasms.18 ; 19 Our patient had aldosterone-producing adrenal cancer associated with refractory hypertension. Surgical resection gave the only possibility of palliative control. The prolonged survival seems to ratify the current belief that aldosterone-producing neoplasms, either benign or malignant, do have a better outcome than cortisol-producing tumors.