Primary non gestational extra gonadal choriocarcinoma of the lung
Primary Non Gestational Extra- gonadal Choriocarcinoma of the Lung
By: Muhamad Na’im B. Ab Razak, Universiti Sains Malaysia
Choriocarcinoma is a germ cell tumor containing syncytiotrophoblastic giant cells and often
secreting a biological tumor marker (β-HCG). [Jong-Rung Tsai et al, 2002]. It is basically
classified as gestational and non gestational.
Simply put, gestational choriocarcinoma arises from or in association with a gestational event. In
this form, the placenta is the site of origin of the tumor. The incidence increases after
spontaneous abortions or a molar pregnancy or ectopic pregnancy. [Vadivel Ganapathy et al,
1999] A rare form of gonadal choriocarcinoma, called neonatal or infantile choriocarcinoma may
develop in the baby during the neonatal period. This lesion is originally thought to arise from
placenta which metastasizes to other part of fetal organ in vitro.
Meanwhile, non gestational choriocarcinoma or primary carcinoma is the similar pathology
which develops without any relation to pregnancy. It occurs in extra placental tissue of non
gravid uterus and may be classify as either gonadal or extra gonadal type. Compared to
gestational choriocarcinoma, non gestational choriocarcinoma is extremely rare but it can occur
in both male and female.
In female, it should be listed as one of the differential diagnosis when patient presented with
amenorrhea or sign and symptoms of pregnancy but without clinical and sonographic finding of
intrauterine or ectopic pregnancy. Apart from that, pregnancy of unknown location may be
suspected as well. However, if β-HCG persistently high even after treatment for pregnancy of
unknown location, therefore non gestational choriocarcinoma is most likely.
Gonadal Choriocarcinoma arise from testis in male and ovary in females. Tumor arises from
testis is more common world widely as compared to the ovary and may occur together with
seminoma, teratoma, and embryonal carcinoma. Primary (non-gestational) choriocarcinoma of
the ovary is an uncommon condition and accounts for less than 0.6% of all ovarian tumors. It
occurs most frequently as a component of a mixed germ cell tumour, and the presence of other
germ cell elements establishes the non-gestational origin of the tumour. [P.C. Lorigan et al,
Extragonadal germ cell tumors are rare, and most of them occur in the midline structures such as
sacrum, mediastinal, and the central nervous system. [Huaiyin Shi et al, 2009] One of the least
common sites is the lung [M.A. Corpa Rodriguez et al, 2009] with the reported case are less than
30. Other rare sites include liver, peritoneum, small intestine, prostate and urinary bladder.
Before diagnosing the Extragonadal germ cell tumor as a primary pathology, one needs to
exclude the possibility of the metastasis from the gonadal choriocarcinoma.
Because the lung is a frequent site of metastatic choriocarcinoma, the diagnosis of the primary
tumor should be made carefully. [Jong-Rung T et al, 2002]. Magrath, Golding and Bagshawe
found that 36 of 179 patients had pulmonary presenting symptoms. [Robert P et al, 1979]
Common presentations are respiratory symptoms like cough, recurrent haemoptysis, pleuritic
chest pain and shortness of breath together with persistently high serum β-HCG level. Female
patients may present with hormonal problems such as amenorrhoea, vaginal spotting or genital
bleeding. [Usha Kini& M.K Babu, 2006] Apart from that, patient may also presented with
endocrine symptoms [Usha Kini& M.K Babu, 2006] and male may have signs of feminization
like gynecomastia, loss of libido, and testicular atrophy. [Anna Arslanian et al, 2003]. Bleeding
tendency of the primary and metastatic sites and the constant elevation of serum β-HCG levels
are two entities defining choriocarcinoma syndrome.
The origin of this type of tumor is not clear, although a range of theories have been put forward.
[M.A. Corpa Rodriguez et al, 2009] In a literature by Holt et al, 1965, they listed 5 theories that
contribute to the origin of extra gonadal choriocarcinoma which includes 1) originate from
teratoma, 2) Origin from a "germinal rest" either of toti-potential cells left during the blastula or
morula stage of embryonic development or from primordial germ-cell rests, which, on separating
from the urogenital ridge in embryo, did not complete the migration to the site of the normal
testis, 3) Originate from primitive mesenchymal cells, 4) Originate from a dormant trophoblastic
embolus acquired in fetal life, and 5) Metaplasia and dedifferentiation of a carcinoma or that
embryonal carcinoma is a stage in the development of choriocarcinoma and that embryonal
carcinomata themselves arise from multipotential cells.
Autopsies performed on women who died during birth or after miscarriage have found
trophoblastic cells in pulmonary arteries, suggesting that choriocarcinoma of the lung in women
could be due to pulmonary embolization caused—during birth or miscarriage—by these cells,
which might subsequently become malignant. The tumor may even appear years later. [M.A.
Corpa Rodriguez et al, 2009]
The diagnostic criteria of the primary non gestational choriocarcinoma of the lung would include
lack of a previous gynecologic malignancy, solitary or predominant lung lesion with the
exclusion of a gonadal primary site, raised serum β-HCG level titers that become normal after
surgery or chemotherapy, and pathologic confirmation of the disease. [Anna Arslanian et al,
Hematologic analysis shows also leukocytosis with neutrophilia and elevated sedimentation rate.
Although urinary β-HCG has considerable diagnostic and prognostic value, a negative test result
does not exclude presence of these neoplasms. [Anna Arslanian et al, 2003] Urine pregnancy test
is a simple and convenient method that would be very useful in the rapid diagnosis of primary
pulmonary choriocarcinoma. [Jong-Rung Tsai et al, 2002]
Imaging features may include well defined solitary lobulated opacity located at the central part in
relation to bronchus, mediastinal shift to the opposite side, collapse of any adjacent tissue,
peripheral ground glass opacity due to pulmonary hemorrhage and co exist pleural effusion.
Multiple nodule and mediastinal or hilar lymphadenopathy is uncommon. In the asymptomatic
patient, pulmonary mass could be an incidental finding at routine chest x ray. [Usha Kini& M.K
CT can identify the lung lesion better and assess whether enlarged lymph nodes are present.
Fiberoptic bronchoscopy can also be done, although the result may be negative. Fine-needle
percutaneous biopsy will often reveal cells considered as squamous. Definitive diagnosis is
histological, after lung biopsy, although it is not uncommon to reach a diagnosis after analyzing
the resected specimen when another type of tumor with a more common histology had been
suspected. Sometimes, diagnosis is made at autopsy. [M.A. Corpa Rodriguez et al, 2009]
Histopathology examination may shows the present of malignant cells resembling either
cytothrophoblast or multinucleate syncytiotrophoblast cells with large and bizarre nuclei which
arrange themselves in alternating layers to mimic the structure of chorionic villi. However, true
chorionic villi are not present. Area of necrosis and hemorrhage usually present due to the
tendency of the trophoblastic cells to invade the blood vessel walls. This may explain why this
malignancy is highly metastasizing to other part of the body.
As for the treatment, there is no standardized regime for chemotherapy due to the rarity of this
problem. EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and
vincristine) regime may be used as well as regime for treating non small cell lung cancer which
is bleomycin, etoposide, and cisplatin. In a low risk patient, treatment with methotrexate, folinic
acid and actinomycin D may be justified.
A return to normal β-hCG levels after therapy is indicative of good response, and increasing
levels may point to recurrence. For monitoring and detection of recurrences, regular β-hCG
measurements and radiological examinations should be performed.
The prognosis of primary tumor of the lung is worst as compared to gestational choriocarcinoma
because of its rapid progression and spread, mainly to the brain and kidney. The outcome is
usually fatal and the prognosis poor despite treatment, with survival of less than 1 year in most
cases. According to Umemori et al, mean survival is 5 months and the survival at 1 year 34.6%
(9 patients). The 2 cases described previously also had a fatal outcome. [M.A. Corpa Rodriguez
et al, 2009]
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