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).