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| CASE REPORT |
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| Year : 2020 | Volume
: 57
| Issue : 4 | Page : 463-466 |
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Double trouble: Extrauterine epithelioid trophoblastic tumor with uterine choriocarcinoma - An autopsy report
Kusum Jashnani1, Alshifa Yagana1, Niraj Mahajan2
1 Department of Pathology, Topiwala National Medical College and BYL Nair Charitable Hospital, Mumbai, Maharashtra, India
2 Department of Obstetrics and Gynaecology, Topiwala National Medical College and BYL Nair Charitable Hospital, Mumbai, Maharashtra, India
| Date of Submission | 13-Mar-2019 |
| Date of Decision | 30-Jun-2019 |
| Date of Acceptance | 12-Jul-2019 |
| Date of Web Publication | 05-Aug-2020 |
Correspondence Address:
Alshifa Yagana
Department of Pathology, Topiwala National Medical College and BYL Nair Charitable Hospital, Mumbai, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijc.IJC_220_19
Gestational trophoblastic tumors (GTTs) include choriocarcinoma, epithelioid trophoblastic tumor, and placental site trophoblastic tumor. The occurrence of mixed GTT is rare. We report such a case in a 24-year-old woman who presented with menorrhagia since 2 months and obstetric history of two abortions, one of which was a molar pregnancy. She was undergoing evaluation for carcinoma cervix and treatment for pulmonary tuberculosis from another hospital when she was admitted at our institute for further workup and treatment. However, she succumbed and an autopsy was performed. Histologic evaluation after the autopsy revealed uterine choriocarcinoma with metastatic epithelioid trophoblastic tumor (ETT) in the lung and spleen.
Keywords: Dual malignancy, dual pathology, Gestational trophoblastic tumor, post-mortem
How to cite this article:
Jashnani K, Yagana A, Mahajan N. Double trouble: Extrauterine epithelioid trophoblastic tumor with uterine choriocarcinoma - An autopsy report. Indian J Cancer 2020;57:463-6 |
How to cite this URL:
Jashnani K, Yagana A, Mahajan N. Double trouble: Extrauterine epithelioid trophoblastic tumor with uterine choriocarcinoma - An autopsy report. Indian J Cancer [serial online] 2020 [cited 2021 Jan 19];57:463-6. Available from: https://www.indianjcancer.com/text.asp?2020/57/4/463/291409 |
| » Introduction | |  |
Gestational trophoblastic tumors (GTTs) are a group of fetal trophoblastic neoplasms including choriocarcinomas, epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs).[1] Choriocarcinoma consists of a dimorphic admixture of syncytiotrophoblasts and cytotrophoblasts in addition to a minor component of intermediate trophoblasts (ITs), whereas ETT and PSTT show neoplastic proliferation of chorionic and implantation-type ITs, respectively. Mixed GTTs, consisting of a combination of any of the aforementioned tumors, have also been described.[2],[3],[4],[5]
In this report, we present one such case of mixed choriocarcinoma and ETT.
| » Case History | | |
A 24-year-old woman (para 0, abortion 2) presented with menorrhagia following her second abortion and dyspnea on exertion (The New York Heart Association [NYHA] class III) since 2 months.
Her first abortus was diagnosed to be a molar pregnancy on dilatation and evacuation (D and E) done at a local hospital at 4 months of amenorrhea. Her second pregnancy also resulted in an abortion at 5 months of amenorrhea. Antitubercular therapy was started 2 months back in view of breathlessness and areas of consolidation noted on chest X-ray.
She was admitted to another hospital where a cervical biopsy was planned for suspected carcinoma of the cervix. However, she left the hospital against medical advice and presented at our institute with the aforementioned history.
On examination, she was poorly built and nourished with severe pallor and bilateral pedal edema. Per-abdominal examination revealed a 14-week-sized mass arising from the pelvis. No side-to-side motility was noted. On per-vaginal examination, multiple blue nodules were noted on the right vaginal wall, the largest measuring 2 × 2 cm. Decreased breath sounds and bilateral coarse crepitations were present on auscultation of the chest.
The urine pregnancy test was positive. Serum β-hCG (beta-human chorionic gonadotropin) value was >300,000 mIU/mL. Ultrasonography of the pelvis showed a mass involving the uterus, ovaries, and bilateral ureters. After 2 days of admission, she became breathless and had a bradycardic arrest. Resuscitation was attempted but the patient succumbed.
At autopsy, the serosa of uterus revealed tumor nodules. The cut surface showed a hemorrhagic, shaggy necrotic mass completely obliterating the endometrial cavity infiltrating the myometrium and the cervix and extending to the cervical wall. The vaginal wall had multiple tumor nodules measuring 1 × 1.5 cm to 1.5 × 2 cm. The right ovary was enlarged and replaced by a hemorrhagic and necrotic tumor mass.
The lungs showed multiple well-circumscribed yellow-white hemorrhagic tumor nodules, the largest measuring 3 cm in diameter.
The spleen revealed multiple whitish tumor nodules, approximately 1.5 cm in diameter.
Histopathological examination of the diffusely infiltrative uterine mass revealed a choriocarcinoma showing proliferation of syncytiotrophoblasts and cytotrophoblasts with areas of necrosis and hemorrhage [Figure 1]. Chorionic villi were absent. This tumor also involved the cervix, vagina, and right ovary. Immunohistochemistry (IHC) was positive for β-hCG (Biogenics, dilution- 1:50). The hemorrhagic lung nodules showed a plexiform dimorphic arrangement of cytotrophoblasts and syncytiotrophoblasts, suggestive of choriocarcinoma metastasis. | Figure 1: (a) Cut section of uterus showing necrotic mass reaching up to the cervix; (b) Cut section of ovary showing parenchyma replaced by a hemorrhagic, necrotic tumor mass; (c and d) Cut section of spleen (c) and lung (d) showing solid, metastatic nodules; (e and f) Histopathological section from uterus showing admixture of cyto, syncytio, and intermediate trophoblasts in choriocarcinoma (H and E, e: 100×; f: 400×)
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Sections from the white nodules in the lung and spleen showed monomorphic tumor cells arranged in cohesive nests. These cells had distinct borders, clear cytoplasm, and relatively uniform nuclei with fine chromatin. There were areas of eosinophilic hyaline-like material deposited at places in between the tumor islands. Necrotic or hemorrhagic areas were not seen. IHC staining was positive for AE1/AE3 (Biogenics; dilution, 1:50), cyclin E (Dako; dilution, 1:40) and negative for p63 (Dako; dilution, 1:40), hPL (Dako; dilution, 1:50). These findings were suggestive of an epithelioid trophoblastic tumor [Figure 2]. | Figure 2: (a-c) Histopathological section showing tumor composed of cohesive nests of chorionic-type intermediate trophoblast in lung and splenic metastatic nodules (a and c), and central eosinophilic hyaline-like material (b) (H and E, a, b: 100x; c: 400x); (d) Positive AE1/AE3 (IHC, 100×); (e) Positive cyclin E (IHC, 100×); (f) Negative p63 (IHC, 100×)
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A gestational choriocarcinoma of uterus and cervix with widespread metastasis of epithelioid trophoblastic tumor was the final cause of death.
| » Discussion | | |
GTTs (choriocarcinoma, ETT, and PSTT) are a group of rare epithelial tumors representing semi-allografts (the trophoblastic cells being of fetal origin). Differences in definition and diagnosis lead to variable data on incidence and prevalence.[6] The incidence of choriocarcinoma is higher in Southeast Asia (9.2 in 40,000 pregnancies) than in the Western world (1 in 40,000).[7] ETT, which originates from extravillous trophoblasts of chorionic leave, has only 110 reported cases.[8] Mixed GTT includes tumors with a combination of any one of the three tumors. Besides our case report, only 16 such cases have been noted in the literature.[2],[3],[4],[9],[10],[11],[12],[13],[14],[15]
The term epithelioid trophoblastic tumor (ETT) was first proposed by Mazur and Kurman[16] in 1994. This tumor was initially found as lung metastasis in patients after chemotherapy for uterine choriocarcinoma. In these tumors, the typical dimorphic pattern of choriocarcinoma disappeared, with residual tumor appearing in an unusual monomorphic pattern. Hamazaki et al.[17] considered ETT a dedifferentiated variant of choriocarcinoma. The detailed clinicopathologic and immunohistochemical features of ETT were described by Shih and Kurman[2] in 1998. ETTs have been reported to coexist with choriocarcinoma in the lung[11] and with placental site trophoblastic tumor in the uterus.[2]
Our case is similar to the first case described by Mazur and Kurman in 1994, though there is no history of chemotherapy in our patient. The literature states that some chemotherapeutic agents might induce phenotypic alterations of trophoblast, including structure, function, and differentiation, since most patients with ETT had a history of chemotherapy. It is possible that chorion-type IT may be more selected in this process.
To elucidate the pathogenesis of GTT, studies use molecular analysis through gene-expression profiling and compare their patterns with those of healthy placentas.[18] As per the proposed model, transformed trophoblastic cells (most likely cytotrophoblast stem cells) retain differentiation plasticity. They are able to differentiate into cytotrophoblast, syncytiotrophoblast, or chorionic or implantation type ITs through various pathways similar to the early stages of placental development.[2],[18],[19],[20] The existence of mixed tumors and response to chemotherapy can both be explained by this model. Choriocarcinoma, which resembles the previllous blastocyst, is the most primitive of all three GTTs and also the most chemoresponsive. On the other hand, ETT and PSTT are more differentiated and, therefore, more chemoresistant.
Any pregnancy event can give rise to GTT but the most common association is seen with molar pregnancies. Thus, serial hCG monitoring in these cases is recommended for early diagnosis.[21] Patients may present early or as late as 15 years after the index pregnancy; sometimes coming to attention only after menopause.[22],[23]
Symptoms range from typical (abnormal uterine bleeding) to uncommon (cardiopulmonary, gastrointestinal, neurological, or endocrine manifestations depending upon the site of metastasis).[24] Local examination may show vulvovaginal masses simulating infected Bartholin's cysts or hemorrhagic cervical masses.[25],[26],[27]
The varied period of presentation, atypical symptoms, and failure to elicit a history of molar pregnancy make the early diagnosis of GTT more challenging. While the confirmatory diagnosis is still by histological morphology, a trophogram using IHC panel including pancytokeratin, cytokeratin-18, HLA-G, HSD3B1, β-hCG, β-catenin, hPL, cyclin E, p63, and Ki-67 can help in establishing a correct diagnosis in difficult cases.
To differentiate between ETT and PSTT, Shih[28] suggests p63 and hPL. In our case, the ETT was p63 negative. This has been noted in 20% of cases reported in the literature.[29] In the cases of intrauterine IT tumors, IHC staining by p16 is used to rule out cervical squamous carcinoma.[29] This was not done in our case as the intrauterine tumor was choriocarcinoma.
| » Conclusion | | |
Mixed GTTs are rare neoplasms. A high index of suspicion based on obstetric history, serum β-hCG values, and histopathological examination is needed to make a timely diagnosis and start treatment. The presence of ETT in a case of choriocarcinoma may be the reason for the nonresponsiveness of the patient to chemotherapy.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| » References | | |
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[Figure 1], [Figure 2]
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