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. 2020 Apr 1;32:100564. doi: 10.1016/j.gore.2020.100564

Hepatoid carcinoma of the ovary – A case report and literature review

Ana Karla Uribe Rivera a,⁎, M Alvarez Larraondo b, L Taxa Rojas c, M Bravo Taxa d, A Zevallos Cardenas b
PMCID: PMC7171517  PMID: 32322647

Highlights

  • •

    We have compiled the reported cases of HCO since 1987, having 39 cases including our report.

  • •

    It is an extremely rare case report.

  • •

    To make a diagnosis it is necessary a pathologist specializing in gynecology oncology.

  • •

    All previous reports had radical open surgery, this is the first report of conservative and laparoscopic surgery.

Keywords: Case report, Hepatoid carcinoma of the ovary, Alpha-fetoprotein (AFP)

Abstract

We present the case of a 27-year old female with an ovarian tumor and alpha-fetoprotein (AFP) of 1210 ng/m, a right salpingo-oophorectomy was performed and had conservative complementary staging by gynecologic oncologists. The histopathological report was primary hepatoid carcinoma of the ovary (HCO), clinical stage IA, complementary treatment was adjuvant chemotherapy with BEP and remains clinical, imaging and biochemically disease free in three years follow up.

1. Introduction

Hepatoid carcinoma of the ovary (HCO) is a very rare group of extrahepatic aggressive tumors with similar hepatocarcinoma (HCC) clinical and pathological characteristics, unknown histogenesis, and most frequent in postmenopausal patients. This histopathologic variant is classified by some authors within the epithelial origin of ovarian tumors, however, there is still controversy about its origin. HCO was first reported in 1987 Ishikura and Scully (Ishikura and Scully, 1987), who carried out a review of rare undifferentiated ovarian tumors, and found 5 cases with hepatocellular morphology and histologic characteristics without liver injury, 38 cases have been reported to date.

2. Case presentation

A peruvian 27-year old female, childless, referring three months with pelvic pain, she had an abdominopelvic ultrasound reporting right adnexal mass. It was operated in her hometown on January 2016, performing right salpingo-oophorectomy. The pathology report was epithelioid malignant neoplasm suggestive of undifferentiated ovarian carcinoma, annex size was 10 cm and serum alpha fetoprotein (AFP) of 1210 ng/ml, for what it was referred to the National Institute of Neoplastic Diseases (INEN).

On admission, physical examination was normal, new reading plates was performed and reports: Primary hepatoid carcinoma of ovary (Fig. 1), fallopian tube without pathologic alterations or tumor involvement, ovarian capsule neoplasm free. No evidence of endodermal sinus component. Immunohistochemistry PANKERATIN (+), AFP (+), GLYPICAN (+), HER PAR 1 (+), SALL-4 (focal+) (Fig. 1).

Fig. 1.

Fig. 1

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Immunohistochemical findings.

ABDOMINAL MR was made in March 2016 and report right annex absent, rest unchanged. Tumor markers: AFP: 10 ng/ml, Ca125: 10.05 U/mL, Ca19.9: 7.77 U/mL, CEA: 0.69, hCG < 0,100 mIU/mL. For surgical indication, it was known that the staging need to be completed, however we took into account the age and desire to procreate of the patient, the possibility of disease recurrence was explained, and the final decision was a conservative surgical ovarian staging by laparoscopy on April 2016 (peritoneal cytology, bilateral pelvic lymphadenectomy, paraaortic lymphadenectomy, infracolic omentectomy and peritoneum biopsies). Pathology report: multiple biopsies and omentum negative, 0/19 pelvic lymphadenectomy and 0/6 retroperitoneal lymphatics. The clinical stage was IA, and tumor markers were negative after surgery. A multidisciplinary meeting was performed for determinate adjuvant treatment in an early stage case with complementary conservative surgery without active disease. At the time of the present case (2014), our country did not have the SALL-4 study and the decision of chemotherapy was like a germ cell tumor, based on age of presentation and tumor markers.

Began adjuvant chemotherapy at 12 weeks’ post-surgery, with three courses BEP (bleomycin, etoposide and platinum) culminating in November 2016, remaining under observation with negative imaging studies and tumor markers nowadays.

3. Discussion

The first report was in 1987, by Ishikura and Scully (1987), they discovered five cases of ovarian tumors with cytological and morphology characteristics similar to hepatocarcinoma (HCC) without liver commitment. Age of presentation is 35–78 years, over 90% of cases present elevated AFP and Ca 125 can be raised in 60% of cases (Acosta and Pins, 2019).

The diagnosis is mostly in advanced clinical stages (III–IV), <20% of patients have confined disease, and of those cases more than a half progress (Acosta and Pins, 2019). Macroscopically are multinodular, solid tumors, occasionally with cystic component, size between 5 and 35 cm (mean: 12 cm), usually unilateral, but 22% of cases are bilateral (Acosta and Pins, 2019). The association with alpha-fetoprotein (AFP) is over 90%, however, 8% of cases are negative (Sung et al., 2013).

They have been described in various organs, most frequently at gastrointestinal tract (stomach) (Young et al., 1992), also in lungs, gallbladder, pancreas, bladder, kidney, ovaries and uterus. In the genital area, 75% of cases are present in ovary (Cascales Campos et al., 2013), the absence of lesions in the liver parenchyma supports their diagnosis, but the presence of liver and ovarian lesions simultaneously makes the diagnosis very difficult especially when hepatocellular carcinoma rarely metastasizes to the ovary (Young et al., 1992). The median survival is 12 months, between the first and second year is 83% and 53% respectively (Randolph et al., 2015).

Macroscopic general features are tumors with solid and cystic component with white to yellow cut surface; as well as it is common to find hemorrhage and necrosis. Histologic features are a diffuse, trabecular/sinusoidal pattern and nested growth, which often coexist. Also, it can show extracellular hyaline bodies. The cytological features are polygonal cells with moderate to abundant eosinophilic cytoplasm, with distinct cell borders and central round vesicular nuclei with moderate to marked cytologic atypia and some of them with ≥1 nucleoli. Intracytoplasmic hyaline bodies can be observed. Also, frequent mitoses, including atypical forms are observed (Nucci and Oliva, 2018). Inmunohistochemistry features are AFP, Hep-Par1, α-1-antitrypsin, glypican-3, albumin, ck7, ck19 and ck20 positive; while the Pan keratin and CK8 are focally positive; on the other hand, these tumors are negative for calretinin, inhibin, synaptophysin, estrogen receptor and progesterone receptor (Wang et al., 2009). Differential diagnoses are the yolk sac hepatoid tumors that are SALL4 positive, this marker is more sensitive than classical IHC markers, such as placental-like alkaline phosphatase (PLAP), AFP, or glypican3, and strongly stains more than 90% of tumor cells. Positive staining for glypican3, AFP, and PLAP is seen in 100%, 95%, and 66% of cases, which does not occur in hepatoid ovarian carcinoma (Rittiluechai et al., 2014). Another differential diagnosis are metastatic hepatocellular carcinomas that have a multinodular growth pattern; and Steroid cell tumors, which have androgenic manifestations and are smaller cells with vacuolated cytoplasm, positive for inhibin, calretinin, SF1, WT1 (Wang et al., 2009, Rittiluechai et al., 2014).

Thirty-eight cases have been reported, and is still insufficient data to determine optimal treatment of these patients, there is no standard, most patients are treated with surgery (maximum cytoreduction) and adjuvant chemotherapy.

The use of biological therapy extrapolated in relation to hepatocellular carcinoma, sustainable data having little use, since, despite having pathological similarity between HCC and HCO these are biologically different, HCO has clinical aspect in relation to epithelial tumor. In the study by Pandey and Truica (2011) reported the use of sorafenib, and showed no effects in these patients, other reviews mention progression-free survival of 7 months.

We have compiled the reported cases of HCO since 1987 to the present (Table 1), following the sequence performed by Randolph et al., 2015, Acosta and Pins, 2019, having 39 cases including our report. Of all these cases, our patient is the only one how comes out the usual scheme (age of presentation, laparoscopic conservation surgery and adjuvant treatment), she presented AFP 1210 ng/ml, following initial surgery was found in 10 ng/ml and after performing surgery and adjuvant chemotherapy AFP values have remained <7 ng/ml. This case demonstrates that it is possible considerate conservation surgery in an early stage with good outcomes in relation to disease free survival.

Table 1.

Clinical, laboratorial, pathological, immunohistochemical, treatment and outcomes of HCO.

Case Age Site/size (cm) Stage Afp ng/ml Ca125 U/ml Ich Surgery Resection Post op. treatment Dissease control Outcome Reference
1 42 L 6.4; R 5.4 IIB NA NA AFP+/AAT+/ALB+/ACT+ TAH + BSO + AP R0 Ch-RT Relapse: 4 years - carcinomatosis Died (5 years) Ishikura and Scully (1987)
2 71 L 20 IIIC NA NA AFP+/AAT+/ALB+/ACT+ PC + TAH + BSO + AP + Om R1 RT Persistence: 3 months post op, parasigmoid tumor Alive (2 years) Ishikura and Scully (1987)
3 57 R 10.5 IIIC NA NA AFP+/AAT +/ALB+/ACT+ TAH + BSO + Om + PARASPLENIC RESECTION R1 NA Persistence: 3 months post op, lower abdomen tumor Died (4 months) Ishikura and Scully (1987)
4 78 NA IIIC 2420 (post op) NA AFP+/AAT +/ALB+/ACT+ BSO + COLECTOMY + POm R0 MFL Persistence: 4 months post op, tumor in left lobe of the liver Died (8 months) Ishikura and Scully (1987)
5 68 R 10 III NA NA AFP+/AAT +/ALB+/ACT+ BSO + COLECTOMY + POm R1 Ch-RT Relapse: months, lesions at pancreas, liver, stomach, small bowel, abdominal lymph nodes, and spleen. Died (10 months) Ishikura and Scully (1987)
6 64 R 18 IA 23,170 58 AFP+ R-SO R0 IP- CDDP No progression during follow up period Alive (2 years) Matsuta et al. (1991)
7 62 R 8.2 IA 2450 NA NA NA NA B/VLB/CDDP; CDDP/E; CTX/MMC/5-FU NA Died (13 months) Tamakoshi et al. (1993)
8 52 NA III 2500 Elevated NA NA NA CBDP/CTX/CDDP Relapse Recurred (7 months) Badreddine et al. (1993)
9 43 L 7; r 8 IIIC 74 158 CEA+/ALB+/EMA+/AFP + BSO + ATH + Om + RL NA CDDP/EPIDX/IFX No progression during follow up period Alive (2 years) Nishida et al. (1995)
10 72 L 9.5; r 5.5 III 500 (postop) 802 AFP + ATH + BSO + RIGHT HEMICOLECTOMY + IOm R0 CBDP Relapse: 5 months, clinical and biochemical Recurred (6 months) Scurry et al. (1996)
11 35 L 35 IIIA 358 NORMAL AFP+ L-SO + OMENTAL BIOPSY + ATH + R-SO + IOm R0 CTX/CDDP/CBDP/E, PCTXL Relapse: 18 months, tumor at pelvis, lower abdomen, liver metastases Recurred/died (18/22 months) Maymon et al. (1998)
12 53 L 9; R 8 III NA 250 NA DS NA CDDP/CTX Relapse Alive (12 months) Trivedi et al. (1998)
13 61 L 12 III 73,080 79.7 AFP+/CK7+/AAT+/ACT+ ATH + L-SO + POm R0 IP CDDP; CDDP/5-FU/E Relapse: 5 months laboratorial, 7 months paraesplenic mass and intraperitoneal tumor Died (20 months) Senzaki et al. (1999)
14 64 R 23 IIIC 900 52.7 AFP+ ATH + BSO + BPL + Om + SEGMENTAL RESECTION OF SMALL BOWL R0 CDDP/CTX; CDDP/PCTXL/RT; CDDP/PCTXL Relapse: 18 months, lesion in the mid‐line of the retroperitoneum. 2 years, paraaortic mass Recurred/died (18/5 years) Lee et al. (2002)
15 36 L 10 IIIC NA 888 AFP+/CEA+/AAT+ ATH + BSO + BPL + Pao NODE BIOPSY + Om R0 NA NA NA Watanabe et al. (2003)
16 69 L 12 IA 589.5 11 AFP+/CEA+/ALB+ L-SO R0 Patient declined NA NA Tochigi et al. (2003)
17 53 L 10 IIB 257,522 NORMAL AFP+/CEA+/ALB+ NA R0 CBDP/PCTXL No progression during follow up period Alive (13 months) Tochigi et al. (2003)
18 76 L 16 IIB 24,000 NA AFP+/CEA+/ALB+ ATH + BSO + PARTIAL COLECTOMY R0 None No progression during follow up period Alive (4 years) Tochigi et al. (2003)
19 57 R 13 NA 24,879 NA NA ATH + BSO + Om NA NA No progression during follow up period Alive (3 years) Tsung and yang (2004)
20 63 R 16 IA 454 84.59 AFP+/CK7+/CEA+/ACT+ ATH + BSO + POm R0 CDDP/CTX No progression during follow up period Alive (7 months) Yigit et al. (2006)
21 40 R 11 III 32,338 1297 AFP+/CK7/CK8/CK18 DS Nd ChT No progression during follow up period Alive (6 months) Kwon et al. (2006)
22 42 R 17 IA 600 (postop) ND AFP+/AAT+ ATH + BSO + BPL + AP + IOm R0 CBDP/PCTXL Relapse: 6 months, pulmonary metastatic tumor Died (16 months) Lazaro et al. (2007)
23 50 L 10; R 8 IIIC 1.7 538 AFP+/CK+/EMA+/CK-7+ ATH + BSO + Om + Tumor excision from the pelvis and ileostomy R2 CDDP/PCTXL; CDDP/GMZ; DXR Progress Died (2 years) Ozan et al. (2008)
24 65 R 12 III 329,732 401.9 NA ATH + BSO + Om R1 CDDP/PCTXL No progression during follow up period NA Gonzalez et al. (2008)
25 42 L 11 ND ND 70 NA ATH + BSO + Om R0 NA NA NA Zizi-Sermpetzoglou et al. (2009)
26 59 L 18 III 73,687 1599 AFP +/CK+/CEA+ ATH + BSO + POm + Low anterior resection of rectum R0 BEP NA NA Isonishi et al. (2009)
27 34 R 14 IIA NORMAL NORMAL NA DS NA ChT NA NA Sun et al. (2009)
28 42 L 6 I NA NA AFP+/CK7+/HEP PAR1+/AAT+/CEA-/INH-/CALRET-/ER-/PR - L-SO/ATH + R-SO + AP + Om R0 Ch-RT following recurrence Relapse: 2008, alive at follow up with local progression NA D’antonio et al. (2010)
29 46 L 4.5; R 6.5 III greater than30,000 414 CD99+/INH+/CALRET+/HepPar1-/AFP-/EMA- ATH + BSO + Om + BPL + DAF R1 CBP/PCTXL- SORAFENIB Relapse: 1 month, retroperitoneal and pelvic lymphadenopathy NA Pandey and Truica (2011)
30 55 L 11 IIIC 248.84 168 AFP+/HepPar1+/INH-/CALRET-/S100-/SYNAPTO- ATH + BSO + Om + DAF R1 IP nitrogen mustard; DCTXL/NEDAPLATIN Persistence abdominal disease Alive (10 months) Liu et al. (2012)
31 53 L 7; R9 IIIC 397 1247 AFP+ (FOCAL)/CK7+/INH+ (FOCAL)/P53+/CA125-/PLAP-/HepPar 1-/CEA-/EMA- ATH + BSO + COm + RDP + PP + AP R0 HYPER ChT/CBP/PCTXL- Relapse: RT Relapse: metastasis in the L2 vertebra Alive (28 months) Campos et al. (2013)
32 57 NA 12 IIIC 761 124 AFP+/INH-/ER-/PR-/PLAP- BILATERAL ADNEXA DISSECTION + Om + DISSECTION OF METASTATIC NODULES ON THE MESENTERY + DAF R0 CBP/PCTXL No progression during follow up period. Alive (15 months) Wang et al. (2013)
33 51 R 9; l 8 IVB 2.2 37 AFP-/HepPar1-/ER-/WT1-/P53+/P16+ ATH + BSO + AP + TUMORECTOMY OF SIGMOID COLON R2 1° line: CBP/PCTXL-2° line: DCTXL Progress: Left SC LP +, carcinomatosis, metastatic LN at retroperitoneum, bilateral iliac chain and retrocrural area. Abdominal mass, pleural effusion. Died (6 months) Sung et al. (2013)
34 73 L 24 IIIC 2396 (postop) NA AFP+/CK7+/HepPar1+(FOCAL)/SALL 4+/ARGINASE + CALRET– ATH + BSO + PARTIAL SMALL BOWEL RESECTION R0 CBP/PCTXL Progress: 7 weeks nodular mass in right upper quadrant, mass in the left side of the pelvis. Alive (26 months) Randolph et al. (2015)
35 78 R 9.9, L 4 IVB 150 100 AFP-/CK7-/HepPar1+/INH-/CALRET-/S100 -/SYNAPTO-/EMA- EXPLORATORY LAPAROSCOPY: PERITONEAL CARCINOMATOSIS None CBP/PCTXL Progress: 1 month. Eight dorsal vertebra and pulmonar metastasic disease Died (1 month) Mazouz et al. (2015)
36 47 NA 10/left lobe liver lesion 4 NA 6669 144 CK7+/HepPar1+/GLYPICAN + LEFT PARTIAL HEPATECTOMY + DS R0 HIPEC: P No progression during follow up period Alive(22 months) Naffouje et al. (2016)
37 47 R 10 NA 451 NA AFP+ ATH + BSO R0.Infiltration of marrow, pancytopenia. ChT: NA NA Died (3 months) Lakhotia et al. (2016)
38 41 L 5 IIIC 335 114 HepPar1+/ARGINASE+/GLYPICAN 3+/INH-/PAX8-/SALL 4- CORE BIOPSY OF OMENTAL NODULE R2. C. Sorafenib. Progress: ChT CBP/PCTXL Progress: 2 months Died (2 months) Mahmood et al. (2017)
39 27 R 10 IA 1210 (post op) 10.05 PANKERATIN+/AFP +/GLYPICAN+/HepPar 1+/SALL-4 focal + R-SO + PC + BPL + PAoL + IOm + PB R0 ChT: BEP No progression during follow up period Alive (3 years) Present case
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Abbreviations: IHC, immunohistochemistry; AAT, a1 antitrypsin; ACT, a1 antichymotrypsin; AFP, a-fetoprotein; ALB, albumin; CALRET, calretinin; Chromo, chromogranin; CK7, cytokeratin 7; EMA, epithelial membrane antigen; ER, estrogen receptor; HepPar1, hepatocyte-paraffin antigen 1; INH, inhibin; PAX 8, paired box gene 8; PR, progesterone receptor; SALL 4, Spalt-like transcription factor 4; WT1, Wilms tumor 1; RT, radiotherapy. C, carcinomatosisDS, Debulking surgery; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; R-SO, right salpingo-oophorectomy; L-SO: lenft salpingo-oophorectomy; Om, omentectomy; POm, partial omentectomy; COm, complete omentectomy; IOm, infracolic omentectomy; PC, peritoneal cytology; AP, appendectomy; RL, retroperitoneal lymphadenectomy; BPL, bilateral pelvic lymphadenectomy; PAoL, paraaortic lymphadenectomy; PB, peritoneum biopsies; RDP, right diaphragmatic peritonectomy; PP, pelvic peritonectomy; DAF, drainage of ascitic fluid; SC, supraclavicular; LN, lymph node; ChT: chemotherapy; CBP, carboplatin; PCTXL, paclitaxel; MFL, melphalan; EPIDX, epirrubicin, VLB, vinblastine; DCTXL, docetaxel; CDDP, cisplatin; BEP: bleomycin-etoposide-cisplatin; CDDP, cisplatin; CBDP, carboplatin; 5-FU, 5- fluorouracil; CTX, cyclophosphamide; GMZ, gemcitabine; DXR, doxorrubicine; MMc, mitomicine; IFX, ifosfamide; MMC, mitomicine; HIPER, hyperthermic intraoperative intraperitoneal chemotherapy; IP, intraperitoneal.NA, not available, R: right, L: left.

4. Conclusions

Hepatoid carcinoma of the ovary is a rare neoplasm, highly aggressive, the most frequent presentation is in perimenopausal and postmenopausal age and usually the diagnosis it’s in advanced disease. The treatment must be optimal cytoreductive surgery followed by chemotherapy. This is the first case reported in our institution and had conservative management. The clinical, imaging and laboratory evolution has been favorable with no evidence of disease relapse at 3 years follow-up.

Author contribution

This case report it’s the first one presented in our country. Being an unusual pathology makes the treatment a challenge, and the presentation of this case is in age range it’s uncommon.

However, radical surgery has been the standard treatment in the cases reported internationally, this is the first case report with different management with conservative surgery under laparoscopic guidance and the disease free survival until now it’s 3 years.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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