CASE REPORT
Adrenocortical Carcinoma and Sudden Death
Drew T. Marshall,1,2 John D. Gilbert,1 and Roger W. Byard1,2
1Forensic Science SA; and 2Department of Pathology, University of Adelaide, Adelaide, South Australia, Australia
Address for correspondence and reprints:
Roger W. Byard Forensic Science SA 21 Divett Place Adelaide 5000, Australia E-mail: byard.roger@saugov.sa.gov.au
Accepted for publication: April 8, 2006
Abstract
A 26-year-old man who presented with a 2-year history of intermittent gynecomastia with recent onset of fever, night sweats, and abdominal distension was found to have a left-sided adrenocortical carcinoma with metastases to the liver and spine. Sudden death occurred 1 month after his presentation. At autopsy a saddle pulmonary thromboembolus was found occluding the pulmonary outflow tract, with smaller more peripheral pulmonary thromboemboli. No tumor deposits were identified in the thromboemboli. The thromboemboli had arisen from a tongue of tumor that had grown through the left adrenal vein into the inferior vena cava. Despite a high rate of angio-invasion there are very few reports of sudden death resulting from this phenomenon in patients with adrenocortical carcinoma.
Key Words: Forensic pathology; adrenocortical carcinoma; sudden death; pulmonary thromboembolism.
(DOI: 10.1385/Forensic Sci. Med. Pathol .: 3:1:53)
INTRODUCTION
Adrenocortical carcinomas (ACCs) are rare tumors that have a generally poor prognosis (1). The clinical course is usually associated with complications arising from active hor- mone secretion or metastatic disease. The following case is presented to illustrate an exceptionally rare but devastating complication of ACC, that of massive pulmonary throm- boembolism arising from direct infiltration of tumor into the inferior vena cava (IVC) via the renal vein.
CASE REPORT
A 26-year-old male had been diagnosed with a left ACC approx 1 month prior to his death. He had presented with a 2-year history of intermittent gynecomastia with recent fever, night sweats, and abdominal distension, and imaging studies had shown a tumor of the left adrenal gland with extension into the IVC with metastases to the liver and to the thoracic and lumbar spine. Biopsy revealed an ACC, confirmed immunohistochemically, for which he had just completed his first cycle of chemotherapy. The deceased collapsed unex- pectedly at his home and could not be resuscitated.
At autopsy, the major finding involved his left adrenal gland, which was completely effaced by a large tumor mass measuring 190 × 130 × 80 mm and weighing 1264 g. There
was no connection between the tumor and the adjacent left kidney. The cut surface of the tumor was lobulated with a tan color and focal areas of hemorrhage and necrosis (Fig. 1). A tongue of reddish-colored gelatinous tumor and thombus had extended into the left adrenal vein and left renal vein, and then into the IVC (Figs. 2,3). The right adrenal gland was moderately atrophied. Histological examination of the tumor revealed aggregates of large, irregular eosinophilic cells with hyperchromatic nuclei and scattered mitotic figures in keep- ing with an ACC (Fig. 4). Deposits of metastatic tumor were identified in the liver and vertebrae and were also confirmed histologically.
The lungs were edematous with a combined weight of 1628 g. A large coiled saddle pulmonary thromboembolus (maximum diameter of 20 mm) was found occluding the pul- monary trunk and extending into the right pulmonary artery. Smaller thromboemboli were also noted in medium-sized pulmonary arteries. Histological examination of pulmonary emboli revealed thromboemboli with no evidence of tumor (Fig. 5). The left calf circumference was 32.5 cm and right 33 cm. Dissection of the right calf did not reveal any evidence of deep vein thrombosis. The remainder of the autopsy was unremarkable.
Death was attributed to pulmonary thromboembolism arising from an ACC that had infiltrated into the IVC.
DISCUSSION
ACC is a rare and aggressive tumor that is almost universally fatal, with a 5-year survival without treatment of only 3 to 12% (1,2). The clinical manifestations in patients with ACC may be the result of hormonal effects in actively secreting
tumors, with virilization, feminization, or manifestations of Cushing’s syndrome, or to mass effects on surrounding tissue and organs from tumor bulk (2-4). Tumors of the adrenal cor- tex can arise either sporadically or in association with certain diseases with genetic bases such as Li-Fraumeni syndrome, type 1 multiple endocrine neoplasia (MEN 1), Carney complex, or Beckwith-Wiedemann syndrome (5). Determination of the prognosis of ACCs from histopathological or DNA analyses has proven difficult (3,6).
One of the features of ACCs is their tendency to infiltrate the renal vein and IVC, with 15-20% of patients having some form of caval involvement (7,8). This involvement has been reported to extend as far as the right atrium (1,8). Despite this kind of vascular involvement, embolization of tumor or adherent blood clot has seldom been reported (9).
Tumor embolism may involve both large and small vessels with microvessel tumor embolism occurring commonly in many forms of neoplasia (10). Macrovessel embolism of frag- ments of tumor has been reported much less frequently and occurs in cases of chondrosarcoma, renal cell carcinoma, embryonal carcinoma, seminoma, right atrial myxoma, and Wilms’ tumors (10,11). In these cases, pulmonary embolism has presented with rapid onset, often with a fatal outcome. Paradoxical embolism may occur if there is communication between the right and left sides of the heart, as in the case of an 8-year-old boy who had a ventricular septal defect and died of cerebral infarction following paradoxical embolization from a Wilms’ tumor (12).
Despite the prominent infiltration of the adrenal tumor into the IVC in the reported case, emboli to the lungs were thromboemboli and did not contain tumor. The saddle embo- lus had, however, arisen from thrombus adherent to tumor that had infiltrated into the IVC. Additional predisposing factors to thromboembolism would have been the presence of underlying malignancy and possible reduced activity asso- ciated with metastatic disease. The case demonstrates, there- fore, a rare cause of sudden and unexpected death in patients with ACC that has not been emphasized in the literature previously, despite the angio-invasive nature of many cases of this neoplasm.
Educational Message
1. ACC may present with a prolonged history and nonspecific symptoms and signs.
2. The prognosis is poor with complications related to hor- mone production and/or metastatic disease.
3. Angio-invasion is common.
4. There is an association with certain rare inherited con- ditions that should be checked for at autopsy. These include Li-Fraumeni syndrome, MEN 1, Carney com- plex, and Beckwith-Wiedemann syndrome.
5. Sudden death resulting from pulmonary thrombo- or tumor embolism is a rare possibility.
ACKNOWLEDGMENTS
We would like to thank the South Australian State Coroner, Mr. M. Johns, for permission to publish details of this case.
The authors have stated that they do not have a significant financial interest or other relationship with any product man- ufacturer or provider of services discussed in this article.
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