Case Conference August 8th 2018

08-Aug-2018, Divisi Ginekologi Onkologi RSCM

CASE CONFERENCE

Agustus 8th, 2018

Mrs. Christine Nathalia, P0A0, 35 yo, 426-09-89

Choriocarcinoma of ovarian stage 4

 

Objective :  What is the appropriate treatment for these patients (Choriocarcinoma ovary with resistent chemotheraphy EMA-CO and EMA-EP).

 

Case Description:

Patient referred from PIK Hospital with Choriocarcinoma of ovary stage 4 with specimens originated from right ovarian, omentum, appendix, ileum, sigmoid and plan for chemotherapy EMA-CO. She has been complained abnormal abdominal pain  and visited PIK Hospital. Performed laparatomy optimal debuliking, complete resection, no residual mass and made stoma. 

Pathologic Anatomy result of the specimens were: choriocarcinoma of ovary with metastastic on side wall of ileum and sigmoid.

Whole Abdominal and Pelvic MRI with Contrast Result from PIK Hospital on August 14th 2017 was a complex lesion (solid with cystic component in the central) with irregular peripheral thickness (dd/ papillary?) in the adnexa/right ovaria, sized 15 cm x 17 cm x 15 cm, dd/ the morphology of the lesion was very suspicious to malignant lesion. Liver: diameter nodule was +/- 3 cm in the IV segment. Para aorta lymph nodes enlargement.

Chest X ray after operation was Cardiomegaly. Infiltrat on both lung with improving condition compared than previous examination.

She has been given EMACO 6 series, MTX 1 seri, EMA-EP 2 series plus Carboplatin-Paclitaxel 1 seri and continiued EMA-EP 3th   , with the b-Hcg level result as the table below.

Date Chemotherapy Level b-Hcg

24/08/2017 (-) 70957,43

14/09/2017 (-) 6280,77

30/09/2017 (-) 196586,8

25/10/2017 EMA-CO I 472345,6

20/11/2017 EMA-CO II 70000 

04/12/2017 EMA-CO III 22886

27/12/2017 EMA-CO IV 1052

17/01/2018 EMA-CO V 744,20

07/02/2018 EMA-CO VI 218,50

28/02/2018 Plan EMA-EP I, dactinomycin and etoposide were not available  plan MTX 20 mg for 5 days 641

26/03/2018 EMA-EP I without dactinomycin because the drug not available and patient refused to buy it 5626

17/04/2018 EMA-EP II 5352

03/05/2018 EMA-EP III, postponed because etoposide was not available 117,4

06/06/2018 Carboplatin(599)-Paclitaxel(241), because etoposide was not available since  1 month 3682

28/06/2018 EMA-EP III 3728,73

 

Previous medical history: no history of metabolic disease, heart disease and malignancy.

 

Physical examination 

General state:

CM. BP: 97/56 mmHg, HR: 92 bpm, RR: 18 x/m, T:36oC, Height 158 cms, Weight 41 kgs

Head : Pale conjungtiva anemic (-/-)

Neck : supraclavicula lymph nodes (-/-)

Axilla : lymph nodes (-/-)

Thorax : symmetry shape

Lung : vesicular breath sound on both lungs, no wheezing or rhales

Cardia : no murmur, no gallop

Abd : flat, operation wound is fine, stoma (+)

Extremity: inguinal lymph nodes (-/-)

Gyn state:  

Inspection : external genitalia normal

RVT : vagina normal, portio smooth, uterus RF normal, no palpable mass at adnexa,  AST 

  normal, no rectal mass

 

 Laboratory finding :

-B-Hcg : 5732

-CBC : 12,9/ 37,6/ 2920/ 161000

-Electrolite : 129/ 3,8/ 91,3

A : Choriocarcinoma of ovary stage 4, post chemoterapy EMA-CO 6 series, EMA-EP 3 series ( resistant)

Advice DPJP : 

-Stop giving EMA-EP

-Perfomed CT Scan Abdomen with contrast

-Discuse this case in Tumor Board

 

Chest X-Ray, RSCM, July 19th, 2018

Comparison : thorax radiography on February 23th, 2018

Description: The heart was not enlarged, ratio cardiothoracic < 50 %. 

The aorta and the superior mediastinum were not enlarged. 

Trachea was in midline. Both hila were not thickened. 

The vascularization of lung in normal limit. There were no infiltrats/ noduls on both lung.

 The arch of the diaphragm and the costophrenicus angle were normal. The bones were still good.

Conclusion :

 Compared with previous thorax radiology on February 23th, 2018, for this condition :

 no radiological abnormality on lung and heart. 

 

CT Scan Whole Abdomen July 20th, 2018 

Technique: MSCT Scan abdomen with contrast lohexol 300mg / ml as much as 65 ml. DLP total 663,4  mGycm. Comparison: MRI abdomen March 20th, 2018 

 

Description: There was visualized  multiple solid oval lession with isodense, round bounded firmly, no warm up after contrast on left and center side abdominal with diameter 5,9 cm.

Liver : shape fine, size was enlargement with size craniocaudal +/- 17,9 cm. There was hipoden lession, bordered firmly, no warm up after contrast at 2,4,6,7 and 8 segments with larger size 3,7 cm at 6th segment. 

Portal vein was normal. Intra and post biliary system were not dilated. No ascites and pleural effusion.

Gallbladder : The shape, size, and edge of gallbladder was smooth, no stone.

Pancreas : normal size and shape, no focal lession. The pancreatic duct was not dilated. No calcification.

Spleen :  shape and good size, homogeneous density. No focal lession. Vena lienalis was not dilated.

Both kidney size and shape were normal. No stone and mass.. Pelvic renalis and calyx were normal. The supra renal glands was not dilated.

Gaster and intestines were fine.

Aorta is good caliber, no visible dilation. 

There were multiple noduls at Paraaortic and bilateral para iliaca lymph with larger diameter 0,8 cm.

The bladder shape and size were normal with no thickened wall. No mass or stone.

Uterus and adnexa was normal size.

  Bones were normal.

Conclusion: 

Compared with MRI abdomen March 20th, 2018 

Multiple solid mass at 2,4,6,7 and 8 Liver segments, and solid mass with size and number stqa relatively.

 

Work Up : 

Pathology Anatomy at PIK Hospital, Agustus 25th, 2018

Jaringan khusus : operasi ovarium kanan, omentum, appendiks, ileum, sigmoid

Makroskopik:

I.Kista terbelah 15x12x7 cm, tuba melekat 6 cm, hitam.

II.Omentum ukuran 20x7x0,7 cm

III.Appendiks 6x0,6 cm    ;  ileum 14x3x4 cm : tampak tumor 6x4 cm

IV.Sigmoid berukuran 14x5 cm, tampak massa tumor 1x2 cm

 

Mikroskopik: 

I.Ovarium : tampak perdarahan luas. Diantara bekuan darah terlihat sel-sel tumor berkelompok –kelompok. Sel tumor terdiri atas sel cytotrophoblast (sel dengan inti bulat dan anak inti sel jelas, sitoplasma jernih) dan sel syncytiotrophoblast (sel dengan inti spindel berkelompok, hiperkromatik).

II.Omentum : jaringan lemak normal.

III.Ileum : tampak bekuan darah dibagian luar dari serosa. Didalam daerah perdarahan itu terlihat sel tumor yang serupa dengan no I. Mukosa normal.    Appendik : fibrotik.

IV.Sigmoid : terlihat daerah perdarahan yang melekat pada lapisan serosa. Tampak sel-sel tumor yang serupa dengan no I. Mukosa normal. 

Kesimpulan:  ovarium : choriocarcinoma

          Metastasis pada dinding luar ileum dan sigmoid

 

Chest X-ray, PIK Hospital, September 16th 2017

(Compared with previous examination September 08th 2017 / different  condition)

There was still IV line attached with a  tip in the right paravertebra 7th  Th.

Heart : CTR > 50 %. Enlargement contour.

Lung : there was spots  on the right and left perihilar and paracardia, compared with previous examination was reduced intensely.

Right and left kostofrenicus angle was  taper. 

Conclusion :

Cardiomegaly.

Infiltrat on both lung with improving condition compared than previous examination.  

 

Laboratory finding 

(24/08/17) B-Hcg : 70957,43

(14/09/17) B-Hcg : 6280,77

(30/09/17) B-Hcg : 196586,8

 

(25/09/2017) Albumin : 2,9,    D-dimer : 3940

(13/10/2017) CBC : 8,4/ 26,7/ 15130/ 425000

Electrolit : 133/ 4/ 96,5

 

US FM, Desember 18th 2017

Description: anteflexed uterus was normal size, normal shape. The myometrium was homogenous. The uterine cavity was not contained abnormal mass. 

Stratum basalis endometrium was regular, thickecned 1 mm.

There was no mass at extracavum vascular.

Right ovary was not visualized.

Left ovary enlargement, contained solid mass with shape and edge irreguler, size  65x60x50 mm( volume 100 cc), suspect from invasion mass. 

Liver and both kidney were normal. There was no ascites.

Conclusion: Left solid ovarian neoplasm suspect invasion mass.

Non visualized right ovary.

 

 

 

 

 

 

 

 

 

 

 

MRI Pelvic with contrast, RSCM, March 20th 2018

Technique: MRI Pelvic with intravenous gadobutrol 5ml.

Description: There was visualized  multiple solid with heterogenous-hyperintens T1W1-T2W1, round bounded firmly, with diffusion restriction, on left side of lower abdominal with diameter 5,6 cm and on center side with diameter 6,3 cm. There was no infiltration mass to intestines.

There are colostomy stoma on left lower hemiabdominal.

Uterus was normal size, homogen intencity, no SOL.

Inlet pelvic was normal, ilium wing and bilateral iliopsoas muscle were simetrically fine.

The bladder seemed distended and normal with no thickened wall.

There was free fluid at retrouterine.

Vascular structure of minor pelvic was good.

There was no lymphadenopathy at obturator, iliaca, parailiaca and bilateral inguinal.

The shape and articulation of the femoral caput and acetabulum were normal. The bone marrow was normal.

Conclusion: 

Multiple solid mass, with diffusion restriction, on left side center side of lower abdominal. DD/ mecenterila metastatic.

Minimal ascites  at retrouterine.

There was no lymphadenopathy at pelvic region.

 

MRI Upper Abdominal with contrast, RSCM, March 20th 2018

Technique: MRI Upper Abdominal with intravenous gadobutrol 5ml.

Description: Liver: size was enlargement, smooth surface. There was hyperintens mulitple nodul T1W1 – T2W1 with diffusion restriction, round bounded firmly, with varian size at 2,4,6,7 and 8 segments with larger size 3,9 cm at 6th segment. Intra and post biliary system were not dilated. Portal vein was normal. Gallbladder: The shape, size, and edge of gallbladder was smooth, and shows homogeneous signal intensity. Pancreas: normal size and shape, homogeneous caput, corpus and caudal intensity. The pancreatic duct was not dilated. Both kidney size and shape were normal. Internal structure of kidney parenchymal were normal. Pelvic renalis and calyx were normal. The supra renal glands position and shape were normal.

Aorta was normal.

There was multiple noduls at Paraaorta lymph with diffusion restriction, short axis diameter < 1 cm.

Conclusion: 

Hepatomegaly with Multiple solid mass that spreading on both hepar lobus suggestif metastatic.

Multiple noduls at Paraaorta lymph with diffusion restriction, short axis diameter < 1 cm.

There was no abnormality with another upper abdominal organs.   

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Introduction

Choriocarcinoma of the ovary is a rare and aggressive tumor arising from germ cells, constituting less than 5% of all ovarian malignancies in Western countries. Ovarian choriocarcinoma can be divided into three groups: as a metastatic gestational choriocarcinoma due to a regressed or occult primary gestational choriocarcinoma in other parts of the genital tract (mostly uterine corpus); as a primary gestational choriocarcinoma arising from an ectopic ovarian pregnancy, and as a non-gestational germ cell tumor differentiating to trophoblastic components. All types secret β-hCG. However, β-hCG levels are usually lower in nongestational variants in comparison to gestational types. Monitoring of serum β-hCG can be useful method in evaluating response to therapy. Serum β-hCG elevation leads to isosexsual pseudopuberty in premenarchal patients, while patients in reproductive age usually present with menstrual abnormalities (mainly amenorrhea).

Pure nongestational ovarian choriocarcinomas are extremely rare and highly malignant tumors frequently metastasizing through the lymphatics with intra-abdominal spread. Non-gestational type choriocarcinoma involves the patients with average age of 13 and is largely confined to females under 20. The presence of a well developed corpus luteum of pregnancy adjacent to the tumor may be indicative of a gestational origin. However, a search for paternal DNA in tumor allows a definite distinction between gestational and nongestational types. Tumors with gestational origin have paternal genomic structure while nongestational tumors have genomes of only maternal origin without any alleles from paternal origin.

It is generally believed that non-gestational choriocarcinoma has a worse outcome than a gestational one.

 

 

Problem to be discussed 

What is the appropriate treatment for these patients (Choriocarcinoma ovary with resistent chemotheraphy EMA-CO and EMA-EP). 

 

Discussion

Treatment of primary ovary choriocarcinoma should be carefully chosen according to the situation of the patients. In a woman who desires further child-bearing, conservative surgery may be employed if the tumor does not involve the uterus or the other ovary. If the tumor is extensive, especially if the etiology is non-gestational, intensive cytoreductive surgery should be performed. Most of the patients under 30 years old received conservative surgery, seven underwent radical surgery of total abdominal hysterectomy and salpingo-oophorectomy with or without pelvic lymph node dissection. It was showed as the table below :

 

 

 

 

 

 

 

Advances in chemotherapy significantly promote the survival rate of ovarian choriocarcinoma, and make determinations of the etiology of an ovarian choriocarcinoma important. It is generally accepted that GCO can be treated with methotrexate, actinomycin D or etoposide as a single agent, or with combined agents such as EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) when high risk factors are present. However, NGCO are generally treated with BEP (bleomycin, etoposide, cisplatin) regimen. 

Nan Jia et all assigned an EP-EMA regimen to their patient before the DNA analysis results came out hoping to cover both trophoblastic and germ cell tumor, and received satisfactory results. This case report shows the successful management of a patient with primary choriocarcinoma of ovary. The therapy done for this patient was laparoscopic dissection of cystic mass of the right ovary  and post operative chemotherapy EP-EMA. There was no recurrence of the disease after 32 months and gave birth to a healthy baby 25 months after chemotherapy. 

Narges Izadi et all reported two case, first : A 31-year-old woman, with a gestational history of G9, P1, Ab8 and L1 was admitted to Mirza Koochak Khan Hospital, Tehran, Iran in June 2001 with the symptoms and signs of acute abdomen. She had 5 years secondary infertility of unknown reason following her last abortion and gave the history of a missed menstrual period as well as 50 days of spotting. The serum β-hCG level was more than 1000 mIU/ml. Pelvic sonography revealed enlarged right ovary and a 2.7 cm left ovarian cyst. No abnormal finding was detected in uterus. In view of an adnexal mass along with positive pregnancy test, a possibility of ectopic pregnancy was considered. A right salpingo-oophorectomy was carried out. Gross examination of right ovary revealed a 7×7×4.5 cm3 mass with a hemorrhagic cut surface. Following thorough sampling of the ovarian mass (1 section per cm of the greatest dimension of the tumor), microscopic examination revealed characteristic histological features of choriocarcinoma, composed of bilami-nar structures of cytotrophoblasts and syncyti-otrophoblasts with severe nuclear atypia and mitotic figures admixed with necrotic tissue. The patient received Etoposide/ Metotrexate / Actinomycin D/ Cisplatin/ Etoposide (EMA-CE) regimen for treatment and serum β-hCG level decreased to 70 mIU/mL. She underwent second laparotomy for careful examination of tumoral involvement. Specimens from left ovary and omentum revealed no histologic features of malignancy. A corpus luteum cyst was detected in the left ovary. Computed tomographic scan revealed no brain or lung metastases. Serum alpha- fetoprotein (AFP) was in normal range. After the surgery, she took 4 courses of chemotherapy with EMA-CE regimen. The level of β-hCG decreased to below the cut-off value. There has been no evidence of tumor recurrence during seven years follow-up.

Second case : A 32-year-old woman with a gestational history of G3, P2, Ab1 and L2 was admitted to Mirza Koochak Khan Hospital, Tehran, Iran in September 2003 with nausea, vomiting and vaginal spotting. Sonography revealed a large necrotic mass in the left adnexa. Serum β-hCG level was 5500 mIU/mL and AFP level was within the normal range. A large necrotic mass in left ovary with extension to the posterior aspect of uterus was identified in laparotomy. Total abdominal hysterectomy and bilateral salpingo-oophorectomy, tumor debulkation and infracolic omentectomy were performed. On gross examination, there was a left ovarian mass measuring 13×11×10 cm3 with lobulated and hemorrhagic-necrotic cut surface. The tumor was attached to the posterior surface of uterus. However, only serosal lining showed tumor extension. No tumoral involvement was identified in endomyometrium. Computed tomography of chest, abdomen and brain showed no abnormal findings. Since the initial impression of the clinician was more in favor of nongestational choriocarcinoma, the patient at first received 3 courses of Bleomycin/ Etoposide/ Platinum (BEP) regimen for 3 months. Due to incomplete response, the chemotherapy regimen was switched to EMA-CE. After 4 courses of new treatment, the serum β-hCG level reached to less than 5 mIU/mL. No recurrence has been identified during five years follow-up.

 

Conclucion

1.We recommended to perfom palliative treatment for this patient due to multiple nodul on liver

,