Keywords
intracranial choriocarcinoma - parieto-occipital lobes - woman - left homonymous hemianopsia
- delayed metastasis
Introduction
Primary intracranial germ cell tumors (PIGCTs) comprise 1% of all primary brain tumors
in adults.[1]
When an intracranial choriocarcinoma is documented, its location points to a primary
or metastatic origin. Primary intracranial germ cell tumors (PIGCTs), including choriocarcinoma,
comprise 1% of all primary brain tumors in adults,[1] and the most frequent sites are the pineal and sellar regions.[2] Locations outside these areas suggest metastatic disease. In cases of metastatic
lesions, there are two possibilities, gestational choriocarcinoma or choriocarcinoma
not associated with pregnancy.[3]
Gestational trophoblastic neoplasias (GTN) are a group of malignant tumors arising
from trophoblastic cells (choriocarcinoma, invasive mole, placental site trophoblastic
tumor, and epithelioid trophoblastic tumor). In this group, incidence of metastasis
is between 3 and 21.4%.[3] Usually, in 90% of cases, brain metastasis is part of a disseminated tumor. However,
in the 11.3% of the cases, brain metastasis is the only evidence of systemic disease.[4]
We present a case of a young woman with headache, ocular symptoms, and a right occipitoparietal
lobe lesion with dural attachment, with no evidence of a primary lesion elsewhere.
Choriocarcinoma was confirmed by histological analysis.
Case Report
A 25-year-old married woman with a history of three pregnancies and three children
(5-year-old girl, 2-year-old boy, and 6-month-old baby) was referred for evaluation.
No abnormal transvaginal bleeding was reported after the last pregnancy. The patient
started a month before admission, with pulsating right hemicranial headache (frontal
predominance), accompanied by nausea, vomiting, sonophobia, and photophobia. After
a week, scotomas appeared in the left eye and 3 days later, intense bilateral otalgia,
hyperthermia, and diaphoresis were added. She visited the emergency department of
her local hospital, and a diagnosis of urinary tract infection was issued. Analgesics
and antibiotics were prescribed, and the patient's condition was partially resolved.
However, visual disturbances persisted, the headache worsened, and diplopia was added.
Then, the patient was referred to our institute for further studies. Upon arrival,
general examination was normal. The patient was conscious, and well-oriented. Grade
I bilateral papilledema and left homonymous hemianopsia were documented. Also, she
had a bilateral sixth cranial nerve paresis with diplopia.
Complete blood count, blood chemistry, clotting times, and serum electrolytes were
normal. Cranial computed tomography (CT) scan showed an extra-axial heterogeneous
right parieto-occipital lobes lesion with intense perilesional edema; the lesion was
attached to the internal table of the diploe with secondary hyperostosis ([Fig. 1]). Magnetic resonance imaging revealed dural insertion; therefore, an atypical meningioma
was suspected. Dexamethasone 8 mg every 8 hours intravenously was initiated. The patient
underwent a right occipitoparietal craniotomy with excision of the lesion. Upon dural
opening, a darked-reddish parietal lesion with hard consistency was observed at the
level of the extra-axial right precuneus; the lesion was regularly vascularized with
a cleavage plane. An opaque-reddish ovoid tissue (72 × 45 × 40 mm), hemorrhagic when
cut, was sent for histopathological study.
Fig. 1 Noncontrast cranial computed tomography: (A) axial, (B) sagittal, and (C, D) coronal. The right occipitoparietal lobes show a supratentorial, intra-axial, corticosubcortical
lesion with partially defined and lobulated margins. It is heterogeneous, predominantly
hyperdense (64 UH), with a low-density center that could suggest necrosis (hollow
arrows). Vasogenic perilesional edema was associated (arrowheads) with narrowing of
adjacent sulcus, right displacement of the midline, and right subfalcine hernia (white
arrow).
The tumor was composed of blood lakes delimited by two types of cells; some were cubic
with a round, central nucleus (cytotrophoblast); and others were large, multinucleated
(syncytiotrophoblast). Extensive areas of necrosis and hemorrhage were present. Although
no mitotic activity was observed, Ki67 staining was positive in 90% of the neoplastic
cells. The cells stained intensely with antibodies against chorionic gonadotropin
and β-catenin, confirming the diagnosis of choriocarcinoma ([Fig. 2]).
Fig. 2 (A) The tumor was composed of blood lakes (L), surrounded by at least two types of cells
(arrows; hematoxylin and eosin [H&E]), 50X. (B) Cubic cells with a single nucleus (arrow), cytotrophoblast type, and large multinucleated
cells (S) syncytiotrophoblast type, were observed. H&E 100X. (C) Detail of syncytiotrophoblast. H&E, 400X. Immunohistochemistry: (D) Chorionic gonadotropin, with cytoplasmic staining in syncytiotrophoblast. (E) Beta-catenin with membranous staining in the cytotrophoblast. (F) Ki67, nuclear staining in 80% of neoplastic cells (arrows).
After the surgery, the patient referred loss of vision and complex visual hallucinations
that consisted of seeing people and animals, which caused her a lot of anxiety. Neuro-ophthalmological
examination showed simple bilateral conjunctival hyperemia, a bilateral visual acuity
of 20/50, and abnormal eye mobility with endotropia at 30 prismatic diopters, and
severe (++ + ) limitation of bilateral abduction, at the primary gaze position. A
left homonymous hemianopia with macular damage was documented. Fundus examination
showed papillae effacement, and hemorrhagic exudates. The macula showed waxy exudates.
A final diagnosis of bilateral grade II acute papilledema with macular edema and bilateral
VI cranial nerve paresis and a left homonymous hemianopsia in relation to right occipital
lesion was issued.
The postsurgical imaging study showed residual tumor ([Fig. 3]). Based on the diagnosis of choriocarcinoma and its location, a metastasis was suspected,
and the patient was extensively searched for a primary lesion. Full-body CT did not
reveal any abnormalities ([Fig. 4]). The patient was referred immediately to an oncology institute for an integral
treatment. There, a positron emission tomography-computed tomography (images not available)
showed sclerosis in the right iliac artery; however, no areas of hypermetabolism were
observed in relation to a primary site or other metastatic sites. Patient did not
return for her oncological treatment to that institution.
Fig. 3 Postsurgical noncontrast cranial computed tomography. Bone window (A) with postoperative changes due to right occipitoparietal craniotomy. Axial (B), sagittal (C), and coronal (D) with right occipitoparietal surgical cavity, pneumocephalus, and hyperdense margins
that could correspond to postsurgical hemorrhage or residual tumor. Contrast-enhanced
magnetic resonance imaging 2 months after surgery. Axial T1-weighted imaging (T1WI)
(E), contrast-enhanced T1WI (F), T2WI (G), and susceptibility-weighted imaging (SWI; H) with heterogeneous residual tumor, which has hyperintense areas on T1, hypointensity
on T2 and SWI corresponding to hemorrhage; heterogeneous enhancement was observed.
Adjacent vasogenic edema persists, causing displacement of the right lateral ventricle.
Fig. 4 Contrast-enhanced abdominal computed tomography. The uterus (white arrow) and both
ovaries (arrowheads) are normal. No pelvic masses were observed.
Discussion
Choriocarcinoma is a highly vascular trophoblastic tumor. Trophoblast cells undergo
differentiation into cytotrophoblast (mononuclear) and syncytiotrophoblast (multinuclear).
Typically, choriocarcinoma develops within a gestational event, but nongestational-choriocarcinoma
arises from germ cells in gonadal or extragonadal locations, such as the mediastinum,
retroperitoneum, or pineal gland.[5]
In the case presented, owing to the location, the dural insertion, and the intra-tumoral
necrosis, an atypical meningioma was considered at admission.[6] However, with the histopathological diagnosis and the location of the tumor, a search
for a primary tumor outside the central nervous system began. It is known that choriocarcinoma
spreads through lymphatic route (retroperitoneal lymph node system) and by hematogenous
via. The most affected organs include the lungs, liver, and brain (especially frontal
lobes).[7] After ruling out a primary lesion, delayed metastasis was suspected due to the location
and the relatively recent pregnancy and birth. The patient did not report any gynecological
problems during pregnancy or postpartum. There are studies of choriocarcinoma following
term pregnancy, but patients present generally, persistent vaginal bleeding,[8] with a maximum of 19 weeks delay from onset of symptoms to treatment.[9] The presentation of choriocarcinoma after a molar pregnancy is something that most
physicians are familiar with, however, after a full-term pregnancy and apparently
a normal postpartum period is an exceptional event.[10] In fact, gestational choriocarcinoma occurs after molar pregnancies (50%), term
pregnancies (25%), and other gestational events (35%).[11] However, there are few reported cases in the same situation of our case. A 22-year-old
woman presented with left parietal metastasis, seizure syndrome, and intracranial
hypertension. The histopathological diagnosis was choriocarcinoma and after resection,
the β-human chorionic gonadotrophin (β-HGC) hormone levels were 20,000 IU. The patient
had had a normal pregnancy and delivery 2 years previously and at the time of surgery
she had no gynecological abnormalities, nor was a primary lesion found.[12]
In our case, the diagnosis of choriocarcinoma was confirmed at the oncology hospital,
but after her initial visit and the completion of extension studies, the patient no
longer returned to that institution and we do not know her subsequent evolution. However,
although brain metastases imply stage IV disease, in the case of gestational choriocarcinoma,
the chances of survival, with appropriate treatment, are good.[13] In a French series of 21 patients with GTN and brain metastasis, three (14%) patients
died within 1 month due to cerebral hemorrhage, three (14%) patients died 1 month
after starting treatment, and the total 5-year survival was 70%.[13]
The term GTN includes pathologies such as invasive mole, choriocarcinoma, placental
site trophoblastic tumor, epithelioid trophoblastic tumor, and atypical placental
site nodule. One case in 40,000 pregnancies will present with choriocarcinoma, while
this tumor is expected in 1 in 40 hydatidiform moles. The diagnosis of GTN is based
on serum levels of (β-HGC) and this marker is basic to evaluate response to treatment.[14]
Treatment of GTN depends on its classification. Using the International Federation
of Gynecology and Obstetrics (FIGO) classification, the patient corresponded to stage
IV (GTN extending to all other metastatic sites). According to the modified World
Health Organization (WHO) prognostic index score, she had a high score (>6). For those
low-risk GTN (FIGO/WHO score <6) a medical treatment with one of two single-agent
drugs, methotrexate (MTX, methotrexate with folinic acid, 8-day and MTX 5-day regimen)
or actinomycin-D, is recommended, obtaining complete remission between 81.8 and 83.5%
in the low-risk group. Multiagent therapy is used for high-risk patients. EMA-CO regimen
(etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) is recommended,
with a complete response in 71 to 78% of cases and long-term survival rates of 85
to 94%.[14] In high- and low-risk groups, chemotherapy should be continued for at least two
to three consolidation courses after the first hCG normalization. In the other hand,
immunotherapy is indicated in drug-resistant disease.[14]
Choriocarcinoma is a very chemosensitive tumor; however, hysterectomy in low-risk
patients is indicated if the patient is satisfied with the number of children, in
chemoresistant disease, or in cases with severe vaginal hemorrhage.[15]
In the case of brain metastases and diagnosis of choriocarcinoma, systemic therapy
is the frontline treatment; radiotherapy is considered for resistant/recurrent disease
or in clinical trials. Surgery is indicated to relieve intracranial pressure and bleeding.[16]
Finally, knowledge of the genetics of gestational choriocarcinoma may provide new
diagnostic and treatment strategies in the future. This tumor is characterized by
overexpression of epidermal growth factor receptor, TP53 and MDM2 proto-oncogene[17] and aberrations of methylation pattern (hypermethylation is strongly associated
with gene downregulation).[18]
Conclusion
Although rare, gestational choriocarcinoma can manifest as a late or delayed metastasis,
after a normal delivery, without gynecological alterations during or after pregnancy.
