Adrenal cortical carcinoma associated with venous tumour thrombus extension
A.J. FIGUEROA, J.P. STEIN, G. LIESKOVSKY and D.G. SKINNER
Department of Urology, University of Southern California School of Medicine, Norris Cancer Center, Los Angeles, California, USA
Objective To report the diagnosis and treatment of six patients with adrenocortical adenocarcinoma and venous tumour thrombus extension.
Patients and methods All six patients (four female and two male, age range 14-83 years) were approached surgically through a thoracoabdominal incision and all underwent radical ablative surgery with removal of the primary tumour, regional retroperitoneal lym- phadenectomy and en bloc extraction of the venous tumour thrombus.
Results Five patients with right-sided tumours had vena caval tumour thrombus involvement and one patient
with a left-sided tumour had extension of tumour thrombus into the splenic vein. All patients had appro- priate radiographic evaluation pre-operatively and all underwent successful radical surgery with en bloc resection of the venous tumour thrombus.
Conclusion For optimal management of this rare neo- plasm, it is paramount that accurate diagnostic imag- ing be performed pre-operatively to help dictate the ideal surgical approach and to optimize successful treatment of this disease.
Keywords Adrenocortical adenocarcinoma, tumour thrombus, imaging
Introduction
Adrenocortical carcinoma (ACC) is a rare tumour, with an incidence of about 2 per million of the population [1]. Although rare, this tumour resembles renal cell adenocarcinoma in its ability to develop venous tumour thrombus extension [2,3]. Aggressive radical surgery is the recommended form of therapy, as no effective adju- vant treatment (chemotherapy or radiation therapy) is currently available. Accurate pre-operative radiographic evaluation of the primary tumour and determination of any venous tumour thrombus involvement is therefore absolutely critical to the surgical approach and successful management. We present six cases of ACC with venous tumour thrombus extension treated at our institution between April 1988 and November 1996.
Patients and methods
Case 1
An 83-year-old woman was found to have an incidental left adrenal mass on ultrasonography during an investi- gation of an abdominal bruit; the adrenal mass was confirmed with CT. Clinically, the tumour was func- tionally ‘silent’ and surgery was not performed. Two years later, she re-presented with weight loss, nausea
and left upper quadrant pain. Repeat abdominal CT detected a 7.4 ×6.2 cm left suprarenal mass invading the ipsilateral kidney, the tail of the pancreas and spleen. In addition, a splenic vein tumour thrombus was clearly identified (Fig. 1). She was then referred to our institution for definitive treatment. The patient subsequently under- went a left thoracoabdominal radical nephrectomy, adrenalectomy, with en bloc distal pancreatectomy, splen- ectomy and extraction of a splenic vein tumour throm- bus, without complications. Pathology confirmed a poorly differentiated ACC invading the kidney, pancreas and spleen, associated with tumour thrombus extension into the splenic vein. Her post-operative course was uneventful and she was discharged to home 9 days after
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surgery. She subsequently died from unrelated causes 2 months later.
Case 2
A 54-year-old woman noted worsening hirsutism and baldness over 6 years; on presentation, her serum testos- terone and urinary 17-ketosteroid levels were elevated. The initial radiographic evaluation included IVU which showed caudal displacement of the right kidney by a suprarenal mass. Abdominal CT detected a large right adrenal mass and MRI confirmed this, with a level III (intra-atrial) tumour thrombus extending into the vena cava and up into the right atrium. There was no evidence of metastatic disease. She subsequently underwent a right thoracoabdominal radical nephrectomy, adrenalec- tomy and en bloc removal of a level III intracaval tumour thrombus extending into the right atrium, without com- plications. Pathology confirmed an ACC with no meta- static disease to the lymph nodes. The patient fared well post-operatively and was discharged to home 6 days after surgery. She is currently alive with no evidence of disease 1 year after surgery, with complete resolution of her hirsutism and baldness.
Case 3
A 35-year-old man presented with a 3-month history of a right varicocele; abdominal ultrasonography suggested the presence of a right suprarenal mass. Abdominal CT confirmed a large right-sided calcified adrenal mass with obvious involvement of the vena cava and inferior venacavography detected a level II (intra-hepatic) intra- caval tumour thrombus (Fig. 2). The bone scan was normal but a chest radiograph and chest CT revealed a solitary right pulmonary nodule. All laboratory values were within normal limits. The patient subsequently underwent a right thoracoabdominal radical nephrec- tomy, adrenalectomy and en bloc removal of a level II intracaval tumour thrombus, with resection of a solitary pulmonary metastasis, without complications. Pathology confirmed an ACC with metastatic disease to one retrop- eritoneal lymph node and to the ipsilateral pulmonary nodule. He was discharged home 8 days after surgery, subsequently received mitotane adjuvant chemotherapy and is currently alive with no evidence of disease 5 years post-operatively.
Case 4
A 14-year-old girl presented with complaints of hirsutism and arrest of secondary sexual development. Abdominal CT detected a large right adrenal mass with vena caval tumour thrombus extension; inferior venacavography
and MRI confirmed the presence of a level II intracaval tumour thrombus. Her serum cortisol was normal but she had a markedly elevated serum testosterone level. She underwent a right thoracoabdominal radical neph- rectomy, adrenalectomy and en bloc extraction of a level II vena caval tumour thrombus, without complications. Pathology confirmed an ACC with no evidence of meta- static disease to the lymph nodes. Her post-operative course was uneventful and she was discharged home 8 days after surgery; currently, the patient is free of disease 6 years post-operatively.
Case 5
A 41-year-old woman presented with a 7-month history of palpitation, hypertension and headache, and a 3-month history of bilateral leg oedema. IVU detected caudal displacement of the right kidney and abdominal CT showed a large right suprarenal mass with a vena caval tumour thrombus extending into the right atrium. MRI confirmed the right suprarenal mass with a level
III tumour thrombus extending into the vena cava and up into the right atrium. There was no evidence of metastatic disease and all laboratory values were within normal limits. She subsequently underwent a right thor- acoabdominal radical nephrectomy, adrenalectomy and en bloc extraction of a level III intracaval tumour throm- bus that extended into the right atrium. In addition, a wedge resection of a right solitary lower lung nodule was performed. The patient tolerated the procedure well and was discharged home 9 days after surgery, without complications. Post-operatively, she received carboplati- num adjuvant chemotherapy but developed a solitary right pulmonary recurrence one year later that was successfully resected surgically. Metastatic disease to the lung and brain developed 5 years post-operatively and she subsequently died from the disease.
Case 6
A 57-year-old man presented with complaints of vague abdominal pain and fatigue upon exertion, symptoms prompting a radiographic evaluation of the abdomen with CT, which revealed a large right adrenal mass associated with a vena caval tumour thrombus and local extension of the tumour into the liver (Fig. 3). MRI confirmed the presence of a level II caval tumour throm- bus (Fig. 4). Further metastatic evaluation and all labora- tory values were within normal limits. He subsequently underwent a right thoracoabdominal radical nephrec- tomy, adrenalectomy, en bloc removal of a level II intracaval tumour thrombus and partial right hepatic resection, without complications. Pathology confirmed a poorly differentiated ACC with tumour extension into the adrenal vein and vena cava, with invasion of the hepatic parenchyma by tumour; all lymph nodes were negative. The patient was discharged home 11 days
after surgery, without complications. He subsequently died from the disease 8 months after surgery.
Results
Six patients with ACC had venous tumour thrombus extension, five with right-sided adrenal tumours and one with a left-sided adrenal tumour. Overall, five of the six patients had inferior vena cava (IVC) tumour thrombus extension, three with level II (intrahepatic) and two with level III (intra-atrial) venous tumour extension. Abdominal CT correctly identified IVC tumour thrombus extension in all five cases, including the left-sided adreno- cortical carcinoma with splenic vein tumour thrombus involvement. Furthermore, the extent of IVC tumour thrombus was accurately predicted by MRI and con- firmed intra-operatively at the time of surgery in all five patients.
All patients were approached surgically through a thoracoabdominal incision and all patients underwent radical ablative surgery with removal of the primary tumour, regional retroperitoneal lymphadenectomy and en bloc extraction of the venous tumour thrombus. There were no peri-operative deaths. Two patients had involve- ment of retroperitoneal nodal disease; one patient with a solitary lung metastasis who is currently alive 5 years post-operatively after mitotane adjuvant chemotherapy, and the patient with splenic and renal tumour involve- ment who died of unrelated causes 2 months post- operatively. Two patients are currently alive with >5 years of follow-up.
Discussion
Adrenocortical carcinoma is a rare tumour with a unique ability for venous tumour thrombus extension [1].
Although the first reported case of vena caval tumour thrombus involvement was found at autopsy in 1963 [4], it was not until 1972 that it was described intra- operatively by Castleman et al. [5]. Vena caval tumour thrombus involvement can occur by either direct invasion or more commonly by intraluminal extension of the tumour thrombus via the adrenal or renal vein. We and others [2,6,7] have seen a propensity for right- sided tumours to be associated with IVC tumour throm- bus extension, which may be attributed to the shorter right adrenal vein.
Appropriate radiographic imaging is most critical in successfully managing patients with ACC. Proper surgi- cal planning and resection requires an accurate pre- operative evaluation, including the determination of any local tumour extension or venous tumour thrombus involvement. In the latter situation it is essential that diagnostic imaging be performed pre-operatively to deter- mine accurately the cephalad extent of the tumour thrombus. Various levels of caval involvement may occur, each of which influences the surgical approach. Abdominal CT is the standard radiographic method for evaluating the primary tumour, adjacent organ involve- ment [8] and for evaluating metastatic disease. MRI currently offers the most accurate pre-operative tech- nique to evaluate the extent of a venous tumour throm- bus, being closely correlated with the anatomical findings [8,9]. Sagittal and coronal views allow imaging perpen- dicular to tissue planes, which provides the most accu- rate assessment of adjacent organ involvement and tumour thrombus extension. In addition, because MRI is non-invasive and does not require the administration of intravenous contrast media, it has replaced the need to perform inferior venacavography.
ACC is generally an aggressive tumour; because there is no effective adjuvant chemotherapy or radiation ther- apy, the prognosis clearly depends on the size of the primary lesion, the degree of local and distant extension of the tumour at diagnosis and early radical surgery [10]. Overall, survival rates in patients with ACC have been generally poor [10,11]. In the present limited series of ACC with venous tumour thrombus extension, three of six patients are currently alive and free of disease, two of whom have been followed for >5 years. In addition, one patient with a level III caval tumour thrombus with a solitary pulmonary metastasis survived for 5 years before developing metastatic recurrence and dying from disease.
In conclusion, appropriate radiographic evaluation is critical in assessing the primary tumour and any venous
tumour thrombus involvement and should include CT to define the primary tumour mass and any local tumour extension or distant metastasis. If venous tumour throm- bus is suspected, then MRI is recommended to define the exact extent of the thrombus. We recommend aggressive radical surgery for this neoplasm, as no effective adjuvant treatment is currently available.
References
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Authors
A.J. Figueroa, MD, Chief Resident.
J.P. Stein, MD, Assistant Professor.
G. Lieskovsky, MD, Professor.
D.G. Skinner, MD, Professor and Chairman.
Correspondence: Dr A.J. Figueroa, University of Southern California, Department of Urology, Norris Cancer Center, Mail Stop 74, 1441 Eastlake Avenue, Suite 7414, Los Angeles, California 90033, USA.