Fine Needle Aspiration Cytology of Metastatic Hepatic Adrenocortical Carcinoma Mimicking Hepatocellular Carcinoma
A Case Report
Rosario Serrano, M.D., José Luis Rodríguez-Peralto, M.D., Angel Santos-Briz, M.D., and Pedro de Agustín, Ph.D., F.I.A.C.
BACKGROUND: Adrenocortical carcinoma (AC) is a rare neoplasm, usually considered one of the most morbid and lethal human tumors. It occurs primarily in children and young adults and often presents with advanced and/or metastatic disease. CASE: A 9-year-old boy with a previous diagnosis of adrenocortical carcinoma underwent computed tomog- raphy (CT)-guided fine nee- dle aspiration (FNA) for preoperative investigation of a hepatic mass. All smears revealed abundant groups of cells surrounding an interconnective, thin-walled, cen- tral vascular core. These cells showed finely vacuolated, large cytoplasm with eccentrically placed nuclei. Occa- sionally, cells underwent a sudden, marked increase in size, with prominent atypia. Multinucleated, atypical giant cells and high mitotic rate were also evident. The cytologic findings resembled the previous histologic
adrenocortical carcinoma features.
This case demonstrates the accuracy of CT-localized FNA in diagnosing a tumor metastatic to the liver in a child …
CONCLUSION: The cytologic features of metastatic he- patic adrenocortical carcino- ma may mimic those of hepa- tocellular carcinoma. How- ever, the presence of atypical multinucleated and pleomor- phic cells with microvacuo- lated cytoplasm and eccen- tric nuclei as well as the absence of naked nuclei and endothelial linings yield the diagnosis of adrenocortical carcinoma. Nevertheless, other space-occupying liver lesions in children must also be considered. This case demonstrates the usefulness of CT-localized FNA biopsy in hepatic masses in children and discusses the possible cytologic differential diagno- sis. (Acta Cytol 2001;45:768-770)
Keywords: adrenocortical cancer, hepatocellular carcinoma, liver neoplasms, aspiration biopsy.
From the Department of Pathology, Hospital “Doce de Octubre,” Madrid, Spain.
Drs. Serrano and Santos-Briz are Pathologists.
Dr. Rodríguez-Peralto is Staff Member, Division of Cytopathology, Department of Pathology.
Dr. de Agustín is Chief, Division of Cytopathology, Department of Pathology.
Address reprint requests to: José Luis Rodríguez-Peralto, M.D., Department of Pathology, Hospital “Doce de Octubre,” Ctra Andalucía Km 5.400, 28041 Madrid, Spain (jrodriguezp@hdoc.insalud.es).
Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.
Received for publication June 13, 2000.
Accepted for publication October 19, 2000.
Acta Cytologica
Adrenocortical carcinoma (AC), though rare, re- mains one of the most morbid and lethal human tu- mors. AC comprises 0.05-0.2% of all cancers and usually occurs in children and young adults, al- though the peak incidence is in the fourth and fifth decades.4
Patients with AC often present with advanced and/or metastatic disease.2 Following initial com- plete resection, the patients have local recurrences as well as lymph node metastases in 68% of cases and may develop synchronous or metachronous pulmonary (71%), hepatic (42%) and bony (26%) metastatic disease.
This paper presents a case of adrenocortical carci- noma with liver metastases diagnosed by fine nee- dle aspiration (FNA) cytology in a 9-year-old boy.
Case Report
A 7-year-old boy complained of severe abdominal pain. On physical examination, there was tender- ness in the right hypochondrium, without a palpa- ble mass. Abdominal ultrasound revealed a 5.5-cm, right adrenal mass. Routine laboratory data were within normal limits. Hormonal investigations showed abnormally high secretions of 44 an- drostenedione (195 ng/dL versus normal, 155 ±13) and 35 mg/24 h urinary dehydroepiandrosterone (normal, 0.5-4.3). Plasma cortisol and other steroid hormones were within normal levels. The surgical- ly removed 61 ×53 ×35-mm tumor was microscopi- cally diagnosed as adrenocortical carcinoma.
Two years later, a routine abdominopelvic com-
puted tomography (CT) scan demonstrated a well- defined, 4-cm, solid mass in the right lobe of the liver. FNA biopsy using a 22-gauge needle under CT guidance showed abundant, well-preserved sheets of cells intermingled with isolated cells in a dispersed pattern. Individual cells showed large, finely vacuolated cytoplasm with indistinct borders and voluminous, irregular and eccentrically placed nuclei (Figure 1). These nuclei were hyperchromat- ic, with coarse chromatin clumping and usually in- conspicuous nucleoli. Although most cells were generally monomorphic, occasional prominent atypical cells with a markedly increased size, three to five times larger than neighboring cells, were ev- ident. Multinucleated, atypical giant cells were also present (Figure 1). The sheets of cells were inter- connected by a thin-walled, central, vascular core also surrounded by large, atypical cells (Figure 2). Mitotic figures were conspicuous.
A hepatic right lobectomy performed after FNA biopsy confirmed the cytologic diagnosis of meta- static adrenocortical carcinoma (Figure 3). Seven months after excision the patient was well, without recurrence or metastases.
Discussion
Tumors and pseudotumors of the liver account for fewer than 2% of childhood neoplasms and vary considerably in incidence throughout the pediatric age range.8 Hemangioma is the most common be- nign hepatic tumor.6 Hepatoblastoma, infantile he- mangioendothelioma and mesenchymal hamar-
A
B
toma are more frequently observed in the first two years of life, while hepatocellular carcinoma, focal nodular hyperplasia and undifferentiated embry- onal sarcoma are noted in older children.
With any liver tumor, even in the pediatric range, primary hepatocellular carcinoma should always be considered. Cytologic criteria for diagnosing he- patocellular carcinoma by FNA1,7 include groups of malignant cells with peripheral endothelial lining cells and atypical naked nuclei. The cells of hepato- cellular carcinoma are more reminiscent of hepato- cytes and will vary in their cytologic appearance with the grade of the tumor; they are monotonous, bizarre or pleomorphic. They are generally also polyhedral, with a central, ovoid nucleus; thick nuclear membrane; and prominent nucleolus. The cytologic findings of the present case, although ex- hibiting the appearance of hepatocellular differenti- ation, did not show endothelial linings or atypical naked nuclei. Moreover, our case presented distinc- tive cytologic features, such as abundant cytoplas- mic microvacuolation, an eccentric nuclear location with cytoplasmic protrusions and focal, dramatic anisonucleosis without conspicuous nucleoli. The absence of biliary intracytoplasmic pigment may also support the diagnosis of metastatic adrenocor- tical carcinoma.
Focal nodular hyperplasia, seen more frequently in midlife, occurs at any age, including childhood.
FNA specimens5 contain numerous hepatocytes with a normal appearance traversed by parallel rows of fibroblasts and bile duct epithelium. The hepatocytes are polygonal, without evidence of vacuolated cytoplasm, pleomorphism or mitotic ac- tivity, as occurs in adrenocortical carcinoma.
Undifferentiated (embryonal) sarcoma of the liver is a rare tumor of childhood. FNA cytologic specimens3 reveal a pleomorphic cell population within a myxoid background. The cells are either small and round or spindle and large, with fusiform or pleomorphic nuclei and nucleoli. The cytoplasm is moderately abundant and pale staining and often contains poorly defined vacuoles. There are many multinucleated giant cells with abundant cyto- plasm packed with hyaline globules. Mitotic figures are visible. In spite of the presence of poorly defined cytoplasmic vacuoles, undifferentiated sarcoma differs from the present case because of the pres- ence of myxoid stroma and the absence of features of epithelial differentiation.
In summary, we present, for the first time, the FNA cytologic features of a metastatic hepatic adrenocortical carcinoma in a 9-year-old boy. This case demonstrates the accuracy of CT-localized FNA in diagnosing a tumor metastatic to the liver in a child, avoiding unnecessary invasive techniques.
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