The Japanese Society of Pathology
Ovarian Mucinous Cystadenoca rcino ma Producing a Ipha- Fetoprotein A Case Report
Kouichi Nomura', Yuri Miyasaka', Masamoto Murae2, Yoshiteru Terashima2, and Shigeo Aizawa'
A 62-year old woman with a complaint of abdominal distention underwent surgery to remove a tumor in her left ovary. The serum alpha-fetoprotein (AFP) level was 4,130 ng/ml. Histologically, the tumor was diagnosed as a mucinous cystadenocarcinoma with a small area of solid proliferation of tumor cells. The cells of the latter part were shown immu nohistochemically to possess AFP. We suppose that a part of the mucinous cystadenocarcinoma dedifferentiates and produces AFP. Acta Pathol Jpn 42: 372-375. 1992.
static masses were found in the omentum. Before surgery, serum AFP level was 4,130 ng/ml, dropping after surgery to 10 ng/ml. The concanavalin A (Con A) reactive fraction rate of AFP was 90%. Serum CEA level was 408ng/ml. HCG was not measured. She died of post-transfusion graft-versus-host disease and the autopsy was carried out on the 31st day after surgery.
Key words : Alpha-fetoprotein, Mucinous cystadenocar-
cinoma, Ovary Gross findings of the t u m o r AFP is produced by the fetal liver, yolk sac, and fetal gastrointestinal tract (1). In tumors, hepatocellular carcinoma (HCC) and yolk sac tumor (YST) often produce AFP. However, surface epithelial-stromal tumors of the ovary producing AFP are rarely reported (2, 3). We present a case of ovarian mucinous cystadenocarcinoma with a high level of serum AFP.
CLINICAL SUMMARY A 62-year old, gravida 5, para 3, Japanese female, whose uterus, right ovary and fallopian tube had been resected because of leiomyoma of the uterus at the age of 46, admitted with a complaint of abdominal fullness and loss of weight. She underwent left salpingo-oophorectomy, omentectomy and resection of lymph nodes due to the tumor in the left ovary. A t surgery, meta-
Received November 7, 1991. Accepted for publication December 24, 1991. Departments of 'Pathology and 20bstetrics and Gynecology, The Jikei University School of Medicine, Tokyo. Mailing address : Kouichi Nomura, M.D., Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105, Japan.
The tumor of the left ovary measured 14x 1 2 cm, had a smooth surface and a multicystic cut surface with papillary projections (Fig. 1). Microscopic findings of t h e t u m o r The formalin-fixed, paraffin-embedded specimens obtained at surgery were stained with HE, PAS with and without diastase digestion and alcian blue. Most areas of the tumor (about 90%) consisted of mucinous cystadenocarcinoma of both intestinal and endocervical types (Fig. 2), while the remainder was composed of a solid proliferation of tumor cells arranged in sheets (Fig. 3). In the latter component, the tumor cells had round nuclei, lacked prominent nucleoli and had clear or slightly eosinophilic cytoplasm (Fig. 4), containing glycogen. Gland - like structures were observed. Mitoses were prominent. Only a few tumor cells contained mucin. A few hyaline bodies were found. No trophoblast-like giant cells were observed. Areas of transition between the two patterns were observed (Fig. 5). In the metastatic lesions to the lymph nodes and omentum, the tumor cells proliferated with glandular, cribriform and cord-like patterns resembling clear cell adenoca rcino ma.
Acta Pathologica Japonica 42 (5) : 1992
Figure 1. Gross appearance of the ovarian tumor. a : Surface. b : Cut surface showing cystic lesion with papillary projections. Bar=5 cm.
Immunohistochemical findings lmmunohistochemical staining was carried out by the peroxidase-antiperoxidase (PAP) method (4) or avidinbiotin-peroxidase complex (ABC) method (5). The antibodies used were those against: AFP (Dakopatts, Copenhagen, Denmark, 1 : 200, PAP), hCG (Dakopatts, 1 : 200, PAP), cytokeratin-PKK1 (Labsystems, Helsinki, Finland, 1 : 200, ABC), vimentin (Amersham, Buckinghamshire, England, 1 : 100, ABC), CEA (Dakopatts, 1 : 20, ABC), and epithelial membrane antigen (EMA) (Dakopatts, 1 : 100, ABC). In the solid proliferation area, moderate numbers of
Figure 2. Area of mucinous adenocarcinoma (HE).
cells showed AFP positivity (Fig. 6a) and a small number showed hCG positivity (Fig. 6b) but only a few cells showed cytokeratin, EMA and CEA. The areas of mucinous adenocarcinoma had both AFP and hCG negativity and cytokeratin, EMA and CEA positivity. Vimentin was negative in both areas. Autopsy findings Small nodules of the tumor remained on the peritoneum and diaphragm, resembling clear cell adenocarcinoma. However, none of the organs, including the liver and gastrointestinal tract, had tumorous lesions.
Figure 3. Area of solid proliferation of the tumor cells (HE).
Mucinous Adenocarcinoma Producing AFP (Nomura ef a\.)
Figure4. High-power view of tumor cells in the solid area with round nuclei, lacking prominent nucleoli and with clear or slightly eosinophilic cytoplasm (HE).
Figure 5. Areas of transition between adenocarcinoma and the solid area (HE).
Figure 6. Positive immunostaining for AFP (arrows) (a) and hCG (b) in the tumor cells in the solid area (PAP).
DISCUSSION HCC and YST are well-known t o produce AFP. Gastric carcinoma (6),pancreatic carcinoma (7), lung carcinoma (8) and renal cell carcinoma (9) have also been reported as AFP-producing tumors. In the present case, the primary tumor of the ovary is thought to have
produced AFP, because the autopsy findings revealed that no organs had a tumorous lesion except for small metastatic nodules of the peritoneum and diaphragm. AFP derived from the liver differs from that from the yolk sac in the structure of sugar chains. The Con A reactive fraction rate of AFP is about 97% in HCC and about 55% in YST(10, 11). In our case, the rate was
Acta Pathologica Japonica 42 (5) : 1992
90% resembling that of HCC. Germ cell tumors of the ovary sometimes produce AFP, especially YST and embryonal carcinoma. The tumor in the present case was mucinous cystadenocarcinoma with a small area of solid proliferation of the tumor cells producing AFP. No component of germ cell tumor was found in spite of the extensive histological search. Neither the age nor the Con A reactive fraction rate of AFP corresponded with those commonly associated with germ cell tumor. The present case was thought not to be of germ cell origin. Two cases of surface epithelial-stromal tumors producing AFP have been reported in the international literature (2, 3). One case was a serous papillary cystadenocarcinoma in a 74-year-old woman (2). The serum AFP level was 2,050 ng/ml and the tumor cells showing papillary o r tubular structures showed positivity for AFP immunohistochemically. The other was a mucinous cystadenocarcinoma in a 53-year-old woman (3). The serum AFP level was 1,12Ong/ml and AFP was mostly localized in the tumor cells arranged in solid nests, although some cells lining lumina also showed positivity for AFP. In our case, AFP positivity was localized only in the tumor cells of the solid area. lshikura and Scully (12) reported 5 cases of ovarian tumor composed of cells resembling those of HCC on routine staining and staining for AFP, and designated them hepatoid carcinoma of the ovary. The tumor cells were arranged predominantly in sheets and contained moderate to abundant amounts of eosinophilic cytoplasm. In our case, the solid area did not resemble HCC microscopically. This case does not seem to resemble their description of hepatoid carcinoma. lmmunohistochemically, a small number of tumor cells of the solid area were positive for hCG. Concerning the mechanism of ectopic hormone production by malignant nonendocrine tumors, Hollander and Aponte (13) stated that all cells contain the same genetic information, but much of it is repressed as differentiation advances, and in the neoplastic process, some of these repressed genes may be activated, leading to production of normal pep tides. In our case, hCG production may show dedifferentiation of the tumor cells. Konishi et a/. (3) stated that it is not surprising that some mucinous ovarian carcinomas of intestinal type, which may be the result of endodermal metaplasia of the ovarian surface epithelium, do produce AFP. However, reports of tumors of mesodermal origin such as ovarian serous papillary cystadenocarcinoma (2), renal cell carcinoma (9),adenocarcinoma of the uterine body (14) showed that AFP-producing tumors are not restricted to those of endodermal origin. In the present case, AFP production was localized in the tumor cells of the solid
area and areas of transition were observed between the mucinous carcinoma and the solid area. Therefore, we speculate that AFP production may be due to dedifferentiation of mucinous cystadenocarcinoma. Acknowledgements : The authors thank Miss Michiko Takagi and Miss Teruko Takarabe for technical assistance.
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