Dr. M. B.

Swami

WHO classification of GTD

MODIFIED WHO CLASSIFICATION OF GESTATIONALTROPHOBLASTIC DISEASES Hydatidiform mole ---Complete ----Partial Invasive mole Choriocarcinoma Placental site trophoblastic tumor (PSTT) Epithelioid trophoblastic tumor Miscellaneous trophoblastic lesions -----Exaggerated placental site reaction -----Placental site nodule

 Choriocarcinoma is a malignant, trophoblastic

cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also classified as a germ cell tumor and may arise in the testis or ovary

Pulmonary metastasis
Multiple discrete lung lesions occur due to widely

disseminated hematogenous metastasis. The pattern can vary from

diffuse micro nodularshadows resembling

miliary disease to multiple large well defined masses cannon balls. Occasionally, cavitation or calcification can be

noted. Symptoms

Due to the interstitial location, these lesions are

often asymptomatic. Cough and hemoptysis are the usual symptoms.

Needle aspiration or trans-bronchial biopsy would

be the procedure of choice for confirmation of the nature of the lesion. Treatment
Chemotherapy is the choice when the tumor is

responsive. Occasional surgical resection of multiple lesions were attempted with some reported success. In refractory hemoptysis, selective occlusion of bronchial arteries by teflon is a consideration.

 Cannon balls Neoplasms with rich

vascular supply draining directly into the systemic venous system often present in this fashion. Miliary Pattern: This presentation is seen in patients with thyroid carcinoma renal cell carcinoma sarcoma of the bone trophoblastic disease.

 Cavitating lesions: Cavitation is identified in 4% of metastatic deposits and, as with

primary bronchial carcinoma, is more likely in squamous cell lesions. Colon, anus, cervix, breast and larynx account for 69% of such occurrences. Generally, small thin walled metastases usually indicate a primary site in the head or neck, where as most large, thick walled secondaries arise from the gastrointestinal tract. Avascular necrosis of the lesion secondary to vascular occlusion, is the presumed mechanism for cavitation. Calcification Calcification or ossification is rarely visible in metastasis to the thorax.
Calcification of metastasis from ovarian, thyroid, breast, and mucin

producing gastrointestinal neoplasms. Calcification in lymphomatous nodes has most often occurred following therapy. Lung metastasis may also calcify following therapy. Almost all calcified or ossified lung metastasis occurring prior to therapy are due to osteosarcoma or chondrosarcoma. Isolated cases of such metastasis have also been reported with synovial sarcoma and giant cell tumor of the bone.

 Solitary Pulmonary nodule Pulmonary metastases clinically present as a Solitary Pulmonary nodule. Similar to other Solitary Pulmonary nodular lesions, these are detected by routine chest x-rays. Of the Solitary Pulmonary nodular lesions, solitary metastases accounts for less than 3% of cases. Colon, chest, sarcoma, melanoma and genitourinary malignancies account for 79% of such instances. Solitary metastatic lesion can precede, follow or appear concomitantly with the malignancy. Diagnostic strategy When it appears concomitantly or following definitive therapy of the primary, thin needle aspiration of the lesion is probably the best procedure to establish the nature of the lesion. CT scans are superior to whole lung tomograms in evaluating the presence of other occult metastatic lesions. When the solitary pulmonary metastasis precedes clinical recognition of the primary, standard management of the Solitary Pulmonary nodular lesion should follow. This clinical presentation accounts for less than 1% and routine search for primary is not recommended.

 Treatment
Surgical resection of single metastasis should be

considered
when the primary tumor is resectable. No other organ metastasis is evident and no effective alternate therapy is available

Surgical resection of solitary lung lesions occurring a

few years following curative resection of primary have a better prognosis than the lesions that manifest concomitantly with the primary tumor.

Pathology
Characteristic feature is the identification of intimately

related syncytiotrophoblasts and cytotrophoblasts without formation of definite placental type villi. Syncytiotrophoblasts are large multi-nucleated cells with eosinophilic cytoplasm. They often surround the cytotrophoblasts, reminiscent of their normal anatomical relationship in chorionic villi. Cytotrophoblasts are polyhedral, mononuclear cells with hyperchromatic nuclei and a clear or pale cytoplasm. Extensive hemorrhage is a common finding

.
.

Choriocarcinoma is a highly malignant germ cell tumour which usually follows an abnormal pregnancy with a hydatidiform mole.
It may also occur after a spontaneous abortion, and rarely, may follow a normal pregnancy. The tumour metastasizes early, by means of vascular invasion and blood spread. Macroscopically it is characteristically haemorrhagic and necrotic, due to vascular invasion. Histologicallly it is composed of 2 types of malignant cells, which resemble the cytotrophoblast and syncytiotrophoblast of normal placental chorionic villi.

With surgery above the prognosis was poor, as illustrated by the above Clinical History.
With the addition of modern cytotoxic chemotherapy, the prognosis has improved greatly (>80 over 5 years survived).

Micrograph of choriocarcinoma showing both of the components necessary for the diagnosis - cytotrophoblasts and syncytiotrophoblasts. The syncytiotrophoblasts are multinucleated and have a dark staining cytoplasm. The cytotrophoblasts are mononuclear and have a pale staining cytoplasm. H&E stain.

choriocarcinoma a

Etiology/Epidemiology
Choriocarcinoma of the

placenta during pregnancy is preceded by: hydatidiform mole (50% of cases) spontaneous abortion(20% of cases) ectopic pregnancy (2% of cases) normal term pregnancy (2030% of cases)

 Rarely, choriocarcinoma occurs in primary locations

other than the placenta; very rarely, it occurs in testicles. Although trophoblastic components are common components of mixed germ cell tumors, pure choriocarcinoma of the adult testis is rare. Pure choriocarcinoma of the testis represents the most aggressive pathologic variant of germ cell tumors in adults, characteristically with early hematogenous and lymphatic metastatic spread. Because of early spread and inherent resistance to anticancer drugs, patients have poor prognosis. Elements of choriocarcinoma in a mixed testicular tumor have no prognostic importance. Choriocarcinomas can also occur in the ovaries.

Symptoms/Signs/Labs

increased quantitative -hCG levels vaginal bleeding shortness of breath hemoptysis (coughing up blood) chest pain chest X-ray shows multiple infiltrates of various shapes in both lungs presents in males as a testicular neoplasm, sometimes with skin hyperpigmentation (from excess beta hCG cross reacting with the alpha MSH receptor), gynecomastia, and weight loss (from excess beta hCG cross reacting with the TSH receptor) in males can present with increased TSH

 Symptoms
A possible symptom is continued vaginal bleeding in a

woman with a recent history of hydatidiform mole, abortion, or pregnancy. Additional symptoms may include: Irregular vaginal bleeding Ovarian cysts Uneven swelling of the uterus Pain

Signs
A pregnancy test will be positive even when you are not

pregnant. Pregnancy hormone (HCG) levels will be persistently high. A pelvic examination may reveal continued uterine swelling or a tumor.

Laboratory Tests

Blood tests that may be done include: Quantitative serum HCG Complete blood count Kidney function tests Liver function tests Imaging tests that may be done include: CT scan MRI

Treatment

After an initial diagnosis, a careful history and

examination are done to make sure the cancer has not spread to other organs. Chemotherapy is the main type of treatment. A hysterectomy and radiation therapy are rarely needed.
Since gestational choriocarcinoma (which arises from

a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy The cure rate, even for metastatic gestational choriocarcinoma, is around 90-95%.

 At present, treatment with single-agent methotrexate is

recommended for low-risk disease, --------while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and vincristine (Oncovin) -----are recommended for intermediate or high-risk disease. Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding. Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary.

 Expectations (prognosis) Most women whose cancer has not spread can be cured

and will maintain reproductive function. The condition is harder to cure if the cancer has spread and one of more of the following events occur: Disease has spread to the liver or brain Pregnancy hormone (HCG) level is greater than 40,000 mIU/mL at the time treatment begins Cancer returns after having chemotherapy in the past Symptoms or pregnancy occurred for more than 4 months before treatment began Choriocarcinoma occurred after a pregnancy that resulted in the birth of a child Many women (about 70%) who initially have a poor outlook go into remission (a disease-free state).

 Complications A choriocarcinoma may come back after treatment,

usually within several months but possibly as late as 3 years. Complications associated with chemotherapy can also occur.

 Prevention
Careful monitoring after the removal of hydatidiform

mole or termination of pregnancy can lead to early diagnosis of a choriocarcinoma, which improves outcome.

Summary
CHORIOCARCINOMA IS---------------------- Malignant tumor derived from the trophoblast Actually a tumor allograft in the host mother 1 in 30,000 pregnancies in the U.S. (greater in theOrient) Incidence seems to be related to the degree ofabnormality of the pregnancy (1 in 160,000 normalgestations, 1 in 15,000 spontaneous abortions, 1 in5,000 ectopic pregnancies, 1 in 40 molar pregnancies) Well-circumscribed hemorrhagic mass with central necrosis and hemorrhage

 Dimorphic: cytotrophoblasts + syncytiotrophoblasts (novilli) with

extensive necrosis and hemorrhage Invades primarily through venous sinuses inmyometrium Metastasizes widely via hematogenous route, especiallyto the lungs (90%), brain, GIT, liver, vagina (may be thefirst sign) Most frequent initial indication is abnormal uterinebleeding In some cases, evident after 10 years or more after thelast pregnancy Today, survival rates (with chemotherapy) above 70%with metastatic disease 100% remission if localized Serial serum hCG levels used to monitor effectiveness of treatment.