Pathology

Tumor tissues were formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin. Immunohistochemistry was performed on a subset of the sections.(6) Gross findings showed that the right ovarian of 9×7×4 cm and the left one of 3.3×3×1.5 cm were both involved with malignancy. Under the microscope, the cords of hepatoid cells are arranged in thick trabecular structures, with abundant eosinophilic cytoplasm and clear boundaries. The structure was similar to that of hepatocellular carcinoma.(4) Mitotic images of tumor cells were occasionally observed. The immunohistochemistry staining of AFP was found positive inside the clear cell components and around the tumor cells (Fig.3A). SALL4, P53, AE1/AE3, EMA, CD10, and villin staining were also found to be extensively positive (Fig.3B, C, D), while Hepa-1, CD10, and HNF1-β were found to be focally positive. CK7, Arg-1, ER, PR, Vimentin, WT1, CK30, and Napsin A were all observed to be negative. No foci of yolk sac tumor, teratoma, or other malignant germ cell tumors were observed grossly or microscopically(7, 8). The ultimate histological diagnosis was hepatoid carcinoma of the ovary, a poorly differentiated adenocarcinoma with a hepatoid appearance.
Discussion
Primary hepatoid carcinoma of ovary is a poorly differentiated and aggressive ovarian malignant tumor that originates from an extrahepatic part but resembles hepatocellular tumor in histopathological type and immunophenotype. It is an uncommon tumor type that has now been reported in no more than fifty cases in literature since Ishikura and Scully first designated it in 1987(2). (listed in supplementary material Table 2.) Patients range in age from 27 to 79 years old, with a median age of 57.1, more common in postmenopausal women(6). Most patients have no obvious symptoms in early period and often present with abdominal distention, lower abdominal pain and a pelvic mass. The tumor mainly involves unilateral ovary and rarely bilateral. Elevated serum AFP is often detected, but there are still several cases exhibiting normal AFP level(6, 9). Due to the high degree of malignancy, most HCO cases are found in advanced stages, and pelvic and lung metastasis is common(10, 11). The average survival period after initial diagnosis is about 2 years(12).
Histopathological characteristics of hepatoid carcinoma of the ovary include microscopically tumor cells arranged in flakes, nests, or trabecular structures; rich in blood sinus, similar to the arrangement of liver cancer cells; containing abundant eosinophilic cytoplasm; uniformity of cell size; occasionally with giant bizzare cells and multinucleated tumor cells; and positive hyaline globules inside and outside the cytoplasm(13-15). The unique pathologic appearance of HCO must be distinguished from HCC and HYST. Currently, there is no reliable way of laboratory tests to completely rule out HCC unless combined with clinical and radiographical data. HYSTs are more common in a younger age group, mostly accompanied with gonadal dysgenesis, and pathologically characterized by uniform cells lacking giant bizzare cells with abundant cytoplasm(8), which is totally different from HCO. Immunohistochemical staining of AFP was broadly applied to diagnose HCO. However, negative AFP staining cannot exclude the diagnosis of HCO according to previous examples(6, 9, 16-18). More accurate diagnostic method should be established. In our case, immunohistochemical studies revealed SALL4 positivity. SALL4 is an important marker of germ-cell tumors(19), but it is not expressed in hepatocellular tumors, and there have also been reports of other hepatoid adenocarcinomas expressing SALL4(20-22). Therefore, SALL4 may be a potential indicator to differentiate HCO from metastatic HCC.
The histogenesis of this tumor is mostly recognized as surface epithelial ovarian tumors. There is abundant evidence to support this opinion. The onset age of HCO is similar to that of epithelial ovarian cancer(22). In some cases, the tumor tissue was mixed with serous or mucinous carcinoma, also suggesting epithelial origin on the ovarian surface(23). The fact that most patients have high levels of serum CA125 and CA125 antigen expression by immunohistochemistry is another crucial clue. Moreover, like high-grade serous carcinoma, most HCOs have an aggressive clinical history with rapid progression, extensive intraperitoneal dissemination, and poor treatment response(14). In spite of this, it is important to remember that the hepatoid phenotype is nonspecific, necessitating the integration of pathologic and clinical information to make a definite diagnosis.
There is still insufficient data to determine the optimal treatment of HCO patients. Although there is no standard regimen, most patients are treated with surgery (optimal or maximal cytoreduction) and adjuvant chemotherapy the same as epithelial ovarian cancer. According to the serological AFP level monitoring of our patient before and after chemotherapy, we can draw a conclusion that adjuvant chemotherapy can lower AFP in certain patients and lengthen their lives. Pandey et al. used Sorafenib, a hepatocellular carcinoma medication, as adjuvant treatment for postoperative HCO patients, however the outcomes were disappointing(13).