Adrenocortical Carcinoma Presenting With a Peritoneal Effusion
Leonidas D. Arvanitis, M.D.,* Lisa A. Pitelka, M.D., and Paolo Gattuso, M.D.
In this report, we describe the fine-needle aspiration findings of a case of adrenocortical carcinoma (ACC) that spread to the peritoneal cavity in an 80-year-old female. Cytologically, the peritoneal fluid exhibited clusters and single, small uniform cells with round nuclei and a fine chromatin pattern, which in con- junction with the immunohistochemical stains was diagnostic of ACC. Although ACC is the most common malignant neoplasm of the adrenal gland, its metastatic spread to the peritoneal cavity is exceptionally unusual. Diagn. Cytopathol. 2010;38:514- 516. @ 2009 Wiley-Liss, Inc.
Key Words: adrenocortical carcinoma; adrenal gland; metasta- ses; ascites; fine-needle aspiration
Adrenocortical carcinoma (ACC) is a rare neoplasm with a relatively poor prognosis. Patients may present with an endocrine syndrome or symptoms related to a retroperito- neal occupying mass. Despite aggressive surgical cura- tive resection, the majority of patients have local recur- rence and distant metastases. The most common sites of metastases are liver, lung, and bone.2 Here, we describe an unusual case of ACC presenting as a carcinomatous peritoneal effusion.
Case Report
The patient was an 80-year-old female who presented to Rush University Medical Center with weakness and altered mental status changes of 1-month duration. Labo- ratory data showed hyponatremia and hypokalemia along with metabolic alkalosis. Her morning cortisol level was 70 mcg/dL (6 AM), and the repeat value was 79 mcg/dL (5 AM) [normal range 6-23 mcg/dL]. Plasma ACTH was 7 pg/mL [normal range 9-52 pg/mL].
Department of Pathology, Rush University Medical Center, Chicago, Illinois
*Correspondence to: Leonidas D. Arvanitis, M.D., 1653 West Harrison St, Room 570 Jelke, Chicago, IL 60611.
E-mail: Leonidas_Arvanitis@rush.edu
Received 12 August 2009; Accepted 6 October 2009 DOI 10.1002/dc.21261
Published online 25 November 2009 in Wiley InterScience (www. interscience.wiley.com).
Clinical suspicion for an adrenal cortical tumor was enter- tained. The patient underwent a CT scan of the abdomen, which demonstrated a 5-cm lobulated left adrenal mass abut- ting the pancreas with a large peritoneal effusion. Fine-nee- dle aspiration of the left adrenal gland mass was performed.
Cytologic Features
Diff-Quik stain showed a uniform population of round cells with focal acinar differentiation and minimal aniso- cytosis (Fig. 1). The background of the smear showed focal adrenal cortical naked nuclei and fine vacuolization.
Peritoneal fluid was also sampled and sent to the cyto- pathology laboratory for evaluation. ThinPrep of the peri- toneal fluid showed clusters and single, small uniform cells with round nuclei and a fine chromatin pattern (Fig. 2). The cell block preparation showed mostly single uni- form cells with rare tumor clusters (Fig. 3).
Immunohistochemical staining performed on the cell block material of the peritoneal fluid showed the tumor cells to be strongly positive for synaptophysin (Fig. 4), whereas both chromogranin and calretinin were negative. Cytokeratins 8/18 and AE1/AE3 stained the mesothelial cells; however, the tumor cells were negative (Fig. 5).
The tumor cells of the cell block material of the adre- nal gland fine-needle aspirate showed a similar immuno- histochemical pattern to those of the peritoneal fluid.
Based on the cytological features of the adrenal gland aspirate, peritoneal fluid, immunohistochemical pattern, and clinical presentation of the patient, the diagnosis of an adrenal cortical carcinoma was rendered.
Discussion
ACC is a rare tumor with an estimated worldwide annual incidence of two per million.3,4 It is responsible for only ~0.2% of all cancer deaths in the United States annually, and it is the second most aggressive endocrine malig- nancy behind anaplastic thyroid cancer. Women are more frequently affected than men (1.5:1), and patients present with evidence of adrenocortical hormonal excess in 40- 60% of cases.2,5 The prognosis of ACCs is generally poor
because most patients present with large tumors and advanced disease. Approximately 50-70% of patients have extra-adrenal disease at the time of presentation.6
The cytologic features of ACC are well established on fine-needle aspiration material and consist of very cellular smears with predominantly single cells. Loose-cellular clusters are also usually present. Capillary vasculature tra- versing the tumor clusters has been described. Tumor cells may have uniform to markedly pleomorphic nuclei with coarse chromatin, depending upon the differentiation of the tumor. Nucleoli are usually prominent. Multinu- cleation and bizarre nuclear forms are common in poorly- differentiated ACCs. Cytoplasm is usually densely granu- lar, and intranuclear pseudoinclusions may be present. Finely vacuolated (lipid-rich) cytoplasm may be present
in some tumors but is rarely observed in fine-needle aspi- ration specimens. Frequent mitotic figures, including atyp- ical ones and necrosis, are commonly seen in poorly-dif- ferentiated tumors, but they are less frequently observed in fine-needle aspirates.7-10 7-10
It is important to distinguish ACC from adenomas on fine-needle aspirate material. Adrenocortical adenomas yield moderately cellular smears that have a characteristic pattern. The smears show numerous isolated naked nuclei dispersed in a bubbly and granular background. Some overlapping nuclei show slight molding. There may be variation in size with occasional large nuclei, but mitoses are usually absent. Occasional cells with intact, bubbly (microvesicular) cytoplasm can be identified. Some adenomas contain abundant intracellular lipofuscin pig-
ment.11,12 However, well-differentiated adrenal cortical carcinomas at times are very difficult to differentiate from adrenal cortical adenomas, as our present case illustrates.
Immunohistochemistry is generally not used in routine diagnosis to distinguish benign from malignant adrenocorti- cal tumors. However, the differential diagnosis of adrenal cortical carcinoma must include other adrenal and extra-ad- renal tumors with similar morphological features, including pheochromocytomas, direct extension from renal cell and hepatocellular carcinomas, as well as metastatic tumors.13
Alpha-inhibin and melan A antibodies are the most sen- sitive markers for determination of the adrenocortical ori- gin of adrenal cortical carcinoma, although they are not highly specific. Compared with other types of carcinoma, adrenal cortical carcinoma is usually negative or only focally positive for different types of cytokeratins and EMA. Negative staining for CD10 and antihepatocyte antigen militates against a renal and liver neoplasm, respectively. Positivity for neuroendocrine markers is re- stricted to synaptophysin, whereas chromogranin A is invariably negative, a feature that helps to distinguish ACC from pheochromocytoma. 13,14
ACC typically spreads through the adrenal veins, inferior vena cava, and regional lymphatics to the lungs, liver, bones, and paraaortic lymph nodes. Metastasis to the serosal cav- ities is rare. Nakata et al. in 1993 reported a 53-year-old
woman with a history of ACC that presented with a massive pericardial effusion and a giant pericardial mass.15 Bilimoria et al. in 2008 cites the incidence of pertitoneal metastasis in patients with advanced ACC as less than 1%.2
In conclusion, we present an unusual case of ACC that spread to the peritoneal cavity, revealed by the cytological and immunohistochemical examination of the peritoneal fluid cells, causing carcinomatous ascites.
References
1. van Ditzhuijsen CI, van de Weijer R, Haak HR. Adrenocortical car- cinoma. Neth J Med 2007;65:55-60.
2. Bilimoria KY, Shen WT, Elaraj D, et al. Adrenocortical carcinoma in the United States: Treatment utilization and prognostic factors. Cancer 2008;113:3130-3136.
3. Icard P, Goudet P, Charpenay C, et al. Adrenocortical carcinomas: Surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons study group. World J Surg 2001;25:891-897.
4. Paton BL, Novitsky YW, Zerey M, et al. Outcomes of adrenal corti- cal carcinoma in the United States. Surgery 2006;140:914-920; dis- cussion 919-920.
5. Wajchenberg BL, Albergaria Pereira MA, Medonca BB, et al. Adre- nocortical carcinoma: Clinical and laboratory observations. Cancer 2000;88:711-736.
6. Phan AT. Adrenal cortical carcinoma-Review of current knowl- edge and treatment practices. Hematol Oncol Clin North Am 2007;21:489-507; viii-ix.
7. Sidawy MKASZ. Fine needle aspiration cytology. Philadelphia: Churchill Livingstone Elsevier; 2007. 352 p. vi.
8. Serrano R, Rodriguez-Peralto JL, Santos-Briz A, de Agustin P. Fine needle aspiration cytology of metastatic hepatic adrenocortical car- cinoma mimicking hepatocellular carcinoma: A case report. Acta Cytol 2001;45:768-770.
9. Sharma S, Singh R, Verma K. Cytomorphology of adrenocortical carcinoma and comparison with renal cell carcinoma. Acta Cytol 1997;41:385-392.
10. de Agustin P, Lopez-Rios F, Alberti N, Perez-Barrios A. Fine-nee- dle aspiration biopsy of the adrenal glands: A ten-year experience. Diagn Cytopathol 1999;21:92-97.
11. Cibas ESDBS. Cytology: Diagnostic principles and clinical correlates. 2nd ed. Edinburgh: Saunders Ltd .; New York; 2003. 493 p. vi.
12. Wu HH, Cramer HM, Kho J, Elsheikh TM. Fine needle aspiration cytology of benign adrenal cortical nodules. A comparison of cyto- logic findings with those of primary and metastatic adrenal malig- nancies. Acta Cytol 1998;42:1352-1358.
13. Volante M, Buttigliero C, Greco E, Berruti A, Papotti M. Pathologi- cal and molecular features of adrenocortical carcinoma: An update. J Clin Pathol 2008;61:787-793.
14. Jorda M, De MB, Nadji M. Calretinin and inhibin are useful in sep- arating adrenocortical neoplasms from pheochromocytomas. Appl Immunohistochem Mol Morphol 2002; 10:67-70.
15. Nakata A, Yagi S, Oyama K, Kida H, Sugioka G. Adrenocortical carcinoma with a giant pericardial mass. Intern Med 1993;32:438- 440.