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Gestational Trophoblastic
Disease
Dr.CSBR.Prasad, M.D.
1. Chromosome # in ova and sperms
2. What do you understand by the terms
Haploid / Diploid
3. What do you mean by triploid...
• Gestational trophoblastic disease encompasses a heterogeneous
group of lesions characterized by an abnormal proliferatio...
• They are characterized by pregnancy associated
trophoblastic proliferations
• They range from tumor like conditions to
m...
WHOWHO
Histilogical classification ofHistilogical classification of
Gestational trophoblastic diseaseGestational trophobla...
Hydatidiform MoleHydatidiform Mole
Definition:
A hydatidiform mole represents a
noninvasive abnormal placenta
characterize...
Hydatidiform moleHydatidiform mole
• Several studies have shown that the risk of hydatidiform
mole is increased for women ...
• Cytogenetic studies have shown that chromosomal
abnormalities play a key role in the development of both
complete and pa...
CHROMOSOMAL ORIGIN OF A COMPLETE HYDATIDIFORM MOLE
Partial Mole
Partial moles have
a triploid karyotype and
evidence of an embryo or fetus
there is no consensus that all par...
Partial Mole
• When triploidy is present in a partial mole, the
chromosomal complement is XXY in 70 percent of
the cases, ...
CHROMOSOMAL ORIGIN OF A TRIPLOID PARTIAL
HYDATIDIFORM MOLE
Karyotypes of the partial mole most frequently show triploidy
(...
Why molar pregnancies occur?
• The formation of a mole is associated with
an excess of paternal compared with
maternal hap...
Complete mole
Definition:
The complete hydatidiform mole is
characterized by gross hydropic swelling
of most of the chorio...
Clinical features – Complete mole
• Complete moles typically present between the 11th
and 25th week of pregnancy at an ave...
Complete mole - Gross
• The complete mole is typically voluminous,
consisting of 300 to 500 cm3 or more of bloody
tissue.
...
This ultrasound views of the pelvis
demonstrates a large cystic mass
in the uterine cavity which is
consistent with a hyda...
This is a hydatidiform mole. Molar pregnancies are uncommon and occur when there is fertilization of an
ovum by a sperm bu...
Grape-like villi
Large avascular villi and areas of trophoblastic proliferation.
There are large avascular villi lined by cytotrophoblastic cells
along with atypical trophoblastic proliferation (inset—No...
Partial mole
Definition:
The partial hydatidiform mole has two
populations of chorionic villi, one of normal
size and the ...
• Occur between the ninth and thirty-fourth week of
pregnancy at an average gestational age of about 19
weeks.
• Usually t...
Partial mole - Gross
• Generally, the amount of tissue in a partial mole
is less than that found in a complete mole; the
t...
Partial mole
Partial mole
Partial mole - Microscopy
• The partial mole is characterized by a mixture of large edematous
villi and normal-sized villi...
Partial mole
Cystic villusCystic villus
IHC
The immunohistochemical localization of
hCG, hPL, and PlAP in complete and
partial moles is confined mostly to the
syn...
Marker to differentiate
hydatidiform mole and partial mole
p57
This is not expressed in
syncytiotrophoblasts and in stroma...
CLINICAL FEATURES OF COMPLETE AND
PARTIAL MOLES
Feature Complete Partial
Clinical
presentation
Spontaneous
abortion
Missed...
Invasive mole
Definition:
An invasive hydatidiform mole is one in which
hydropic chorionic villi are within the myometrium...
Invasive mole
• Invasive hydatidiform mole is a sequela to
hydatidiform mole, complete or partial.
• The pathologic diagno...
Invasive mole - Gross
On gross inspection, an invasive mole in the
uterus appears as an irregular
hemorrhagic lesion that ...
Invasive mole.
Invasion
Hemorrhage
Invasive mole
• The villi are enlarged but often not as enlarged as the villi of a
typical complete mole.
• Invasion of my...
Choriocarcinoma
Definition:
Choriocarcinoma is a malignant
neoplasm composed of trophoblast
arranged in a dimorphic patter...
Choriocarcinoma
• The reported prevalence of
choriocarcinoma varies widely throughout
the world, being
greatest in Asia, A...
Choriocarcinoma
• Women over the age of 40 years are at increased
risk for choriocarcinoma.
• Choriocarcinoma may be assoc...
Choriocarcinoma
• Epithelial malignant neoplasm of
trophoblastic cells derived from any form of
previously normal or abnor...
Incidence :
Uncommon. 1 in 20K to 30K pregnancies.
50% occur in hydatidiform moles
25% occur in previous abortions
22% occ...
Choriocarcinoma - Gross
• The typical gross appearance of
choriocarcinoma is that of a circumscribed
hemorrhagic mass, due...
This abdominal CT scan view of the pelvis demonstrates a solid and cystic mass (arrow) in the region
of the uterus extendi...
Choriocarcinoma – microscopy
• No chorionic villi
• The classic histologic pattern of choriocarcinoma
is dimorphic or biph...
Choriocarcinoma
Burnt out primary:
With secondaries in lungs and other sites
the primary can be completely absent.
This is due to their ab...
• US may show small masses in the uterus
• Irregular spotting (bloody, brown and
offensive)
• Mets may be found by chest x...
Treatment:
Depends on type & stage of tumor.
Options: evacuation, surgery, chemo
(MTX, actinomycin – 100% cure rate)
NOTE:...
Gestational Trophoblastic Disease
Type Histological features Clinical features
Complete
Hydatidiform Mole
Composed of larg...
E N D
Gestational trophoblastic disease
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Gestational trophoblastic disease

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Gestational trophoblastic disease

  1. 1. Gestational Trophoblastic Disease Dr.CSBR.Prasad, M.D.
  2. 2. 1. Chromosome # in ova and sperms 2. What do you understand by the terms Haploid / Diploid 3. What do you mean by triploidy 4. Name the substance secreted by trophoblastic tissue
  3. 3. • Gestational trophoblastic disease encompasses a heterogeneous group of lesions characterized by an abnormal proliferation of trophoblast. • Recent light-microscopic studies, complemented by immunocytochemical and cytogenetic techniques, have demonstrated profound differences in the pathogenesis, morphology, and clinical behavior of various forms of the disease. • Hydatidiform moles (complete, partial, and invasive) represent abnormally formed placentas with specific genetic abnormalities that are related to villous trophoblast, whereas choriocarcinoma and the placental site trophoblastic tumor are true neoplasms and are related to previllous and extravillous trophoblast, respectively. Trophoblastic DiseasesTrophoblastic Diseases
  4. 4. • They are characterized by pregnancy associated trophoblastic proliferations • They range from tumor like conditions to malignancy • Hydatidiform mole is a common complication of gestation (1 in 1000 to 2000) • They can be monitored by measuring HCG levels (to detect early recurrence and response to Tx) • Choriocarcinomas are highly responsive to chemotherapy Trophoblastic DiseasesTrophoblastic Diseases
  5. 5. WHOWHO Histilogical classification ofHistilogical classification of Gestational trophoblastic diseaseGestational trophoblastic disease • Hydatidiform mole Complete Partial • Invasive hydatidiform mole • Choriocarcinoma • Placental site trophoblastic tumor • Trophoblastic laesions, miscellaneous Excaggerated placental site Placental site nodule • Unclassified trophoblastic lesions
  6. 6. Hydatidiform MoleHydatidiform Mole Definition: A hydatidiform mole represents a noninvasive abnormal placenta characterized by grossly evident hydropic swelling of chorionic villi accompanied by trophoblastic proliferation.
  7. 7. Hydatidiform moleHydatidiform mole • Several studies have shown that the risk of hydatidiform mole is increased for women over the age of 45 years and for women under the age of 20 years. • Although other factors, including smoking, occupation, a history of infertility, consanguinity, blood groups of parents, age at menarche, patterns of menstruation, and use of different types of contraceptives have been analyzed to determine their association with the development of hydatidiform moles, none of these factors appear to be significant.
  8. 8. • Cytogenetic studies have shown that chromosomal abnormalities play a key role in the development of both complete and partial moles. • Most complete hydatidiform moles are diploid with a 46,XX karyotype, but rare examples are triploid or tetraploid; all the chromosome complements are paternally derived. • In the diploid complete mole, both X chromosomes result from duplication of a haploid sperm pronucleus in an empty ovum that has lost its maternal chromosomal haploid set. • Duplication of a 23,Y sperm results in a nonviable 46,YY cell. Approximately 3 to 13 percent of complete moles have a 46,XY chromosome complement, presumably as a result of dispermy, in which an empty ovum is fertilized by two sperm pronuclei, one with an X and the other with a Y chromosome. • The embryo or fetus is absent in the complete mole; cases in which a fetus is present represent twin gestations, one of which is molar. Hydatidiform mole
  9. 9. CHROMOSOMAL ORIGIN OF A COMPLETE HYDATIDIFORM MOLE
  10. 10. Partial Mole Partial moles have a triploid karyotype and evidence of an embryo or fetus there is no consensus that all partial moles have these features. 69
  11. 11. Partial Mole • When triploidy is present in a partial mole, the chromosomal complement is XXY in 70 percent of the cases, XXX in 27 percent, and XYY in 3 percent. • These abnormal conceptuses result from the fertilization of an egg with a haploid set of chromosomes by either two sperms, each with a set of haploid chromosomes, or by a single sperm with a diploid 46,XY complement. • Partial moles have a triploid karyotype and evidence of an embryo or fetus, there is no consensus that all partial moles have these features.
  12. 12. CHROMOSOMAL ORIGIN OF A TRIPLOID PARTIAL HYDATIDIFORM MOLE Karyotypes of the partial mole most frequently show triploidy (69 chromosomes), with two paternal sets and a maternal chromosome complement.
  13. 13. Why molar pregnancies occur? • The formation of a mole is associated with an excess of paternal compared with maternal haploid contributions. • The higher the ratio of paternal to maternal chromosomes, the greater the molar change. • Complete moles show a 2:0 ratio of paternal to maternal chromosomes, whereas partial moles show a 2:1 ratio. • This hypothesis is supported by experimental evidence in mice.
  14. 14. Complete mole Definition: The complete hydatidiform mole is characterized by gross hydropic swelling of most of the chorionic villi. It typically has a diploid karyotype.
  15. 15. Clinical features – Complete mole • Complete moles typically present between the 11th and 25th week of pregnancy at an average gestational age of 16 weeks. • Marked uterine enlargement is common and is often accompanied by severe vomiting (hyperemesis gravidarum) and pregnancy-induced hypertension and occasionally by hyperthyroidism. • Vaginal bleeding or passage of molar vesicles. • Ovarian enlargement due to multiple theca-lutein cysts (hyperreactio luteinalis) • Pelvic ultrasonography often discloses a classic "snowstorm" appearance.
  16. 16. Complete mole - Gross • The complete mole is typically voluminous, consisting of 300 to 500 cm3 or more of bloody tissue. • The most characteristic feature of the complete mole is the presence of grape-like transparent vesicles 1 to 2 cm in diameter. • When the complete mole is encountered in a hysterectomy specimen, the uterus is enlarged, and molar vesicles protrude when it is opened.
  17. 17. This ultrasound views of the pelvis demonstrates a large cystic mass in the uterine cavity which is consistent with a hydatidiform mole.
  18. 18. This is a hydatidiform mole. Molar pregnancies are uncommon and occur when there is fertilization of an ovum by a sperm but loss of maternal chromosomes, leaving a 46XX karyotype composed only of paternal chromosomes, enough to form a placenta, but not a fetus. The result is a mass of tissue with grape-like swollen villi
  19. 19. Grape-like villi
  20. 20. Large avascular villi and areas of trophoblastic proliferation.
  21. 21. There are large avascular villi lined by cytotrophoblastic cells along with atypical trophoblastic proliferation (inset—Normal villi)
  22. 22. Partial mole Definition: The partial hydatidiform mole has two populations of chorionic villi, one of normal size and the other grossly hydropic. It usually has a triploid karyotype.
  23. 23. • Occur between the ninth and thirty-fourth week of pregnancy at an average gestational age of about 19 weeks. • Usually the patient presents with abnormal uterine bleeding and is clinically thought to have a spontaneous or missed abortion. This presentation differs from that of complete moles, which are usually diagnosed before curettage. • The uterus is typically normal in size or small for the gestational age, and serum hCG levels generally do not show the marked elevation seen in association with the complete mole. Clinical features – Partial mole
  24. 24. Partial mole - Gross • Generally, the amount of tissue in a partial mole is less than that found in a complete mole; the total volume is often no greater than 200 cm3. • The gross specimen contains large hydropic villi similar to those seen in the complete mole mixed with nonmolar placental tissue. • A fetus is nearly always present with a partial mole.
  25. 25. Partial mole
  26. 26. Partial mole
  27. 27. Partial mole - Microscopy • The partial mole is characterized by a mixture of large edematous villi and normal-sized villi. • In comparison with the complete mole, the degree of hydropic swelling in the partial mole tends to be less pronounced. At least some of the hydropic villi contain a central acellular cistern. • The chorionic villi often have a scalloped outline, compared to the typically round, distended appearance of the villi in the complete mole. • Trophoblastic inclusions. • The villous capillaries of the partial mole frequently contain fetal (nucleated) erythrocytes. • The trophoblast covering the villi is typically only focally and mildly hyperplastic.
  28. 28. Partial mole
  29. 29. Cystic villusCystic villus
  30. 30. IHC The immunohistochemical localization of hCG, hPL, and PlAP in complete and partial moles is confined mostly to the syncytiotrophoblast.
  31. 31. Marker to differentiate hydatidiform mole and partial mole p57 This is not expressed in syncytiotrophoblasts and in stromal cells in complete moles. p57 is maternally derived cell cycle inhibitor gene.
  32. 32. CLINICAL FEATURES OF COMPLETE AND PARTIAL MOLES Feature Complete Partial Clinical presentation Spontaneous abortion Missed or spontaneous abortion Gestational age 16-18 weeks 18-20 weeks Uterine size Often large for dates Often small for dates Serum hCG ++++ + Behavior 10-30% develop persistent GTD 4-11% develop persistent GTD
  33. 33. Invasive mole Definition: An invasive hydatidiform mole is one in which hydropic chorionic villi are within the myometrium or its vascular spaces or at distant sites, notably the vagina or lung. “Mole that penetrates and even perforates the uterine wall”.
  34. 34. Invasive mole • Invasive hydatidiform mole is a sequela to hydatidiform mole, complete or partial. • The pathologic diagnosis of invasive mole is made by establishing the presence of molar villi growing into the myometrium and broad ligament. • The diagnosis of an invasive mole cannot be made on examination of curettage specimens except when curetted fragments of myometrium contain invasive molar villi.
  35. 35. Invasive mole - Gross On gross inspection, an invasive mole in the uterus appears as an irregular hemorrhagic lesion that invades the myometrium. It may grow through the myometrium, perforating the serosa and extending into the broad ligament with involvement of the adnexa.
  36. 36. Invasive mole. Invasion Hemorrhage
  37. 37. Invasive mole • The villi are enlarged but often not as enlarged as the villi of a typical complete mole. • Invasion of myometrium by hydropic villi. • Invasion may be seen involving the parametrium and BVs. • Proliferation of both cytotrophoblast and syncytiotrophoblasts. • Immunohistochemistry. Invasive moles display a pattern of staining similar to that of complete moles because most invasive moles are derived from complete moles. • Hydropic villi may metastasize to distant site, but fail to grow as true mets (they usually regress). • Persistent elevation of ß-HCG and lutenization of ovaries.
  38. 38. Choriocarcinoma Definition: Choriocarcinoma is a malignant neoplasm composed of trophoblast arranged in a dimorphic pattern and lacking chorionic villi.
  39. 39. Choriocarcinoma • The reported prevalence of choriocarcinoma varies widely throughout the world, being greatest in Asia, Africa, and Latin America & substantially lower in North America, Europe, and Australia.
  40. 40. Choriocarcinoma • Women over the age of 40 years are at increased risk for choriocarcinoma. • Choriocarcinoma may be associated with any form of gestation. More abnormal types of pregnancy are more likely to be associated with choriocarcinoma. • Blood group A is more frequent and group O less common in patients with choriocarcinoma. • Generally, choriocarcinoma follows an identifiable gestational event such as a hydatidiform mole, an abortion, or a term gestation by a few months.
  41. 41. Choriocarcinoma • Epithelial malignant neoplasm of trophoblastic cells derived from any form of previously normal or abnormal pregnancy. • They are rapidly invasive, widely metastsizing malignant neoplasm. • BUT, reponds to chemotherapy well.
  42. 42. Incidence : Uncommon. 1 in 20K to 30K pregnancies. 50% occur in hydatidiform moles 25% occur in previous abortions 22% occur in normal pregnancies Rest occur in ectopic pregancies & teratomas Choriocarcinoma
  43. 43. Choriocarcinoma - Gross • The typical gross appearance of choriocarcinoma is that of a circumscribed hemorrhagic mass, due to its rapid proliferation combined with blood vessel invasion. • The tumors vary from pinpoint-sized lesions to large destructive masses. The central portion of the lesion is typically hemorrhagic and necrotic, with only a thin rim of viable tumor at the periphery.
  44. 44. This abdominal CT scan view of the pelvis demonstrates a solid and cystic mass (arrow) in the region of the uterus extending into the pelvis which is consistent with a choriocarcinoma.
  45. 45. Choriocarcinoma – microscopy • No chorionic villi • The classic histologic pattern of choriocarcinoma is dimorphic or biphasic, indicating an alternating arrangement of cytotrophoblast and syncytiotrophoblast or intermediate trophoblast and syncytiotrophoblast. • Atypical mitotic activity • Spread: Blood, permeation thru lymphatics • Mets: Lung, brain, bones and Liver.
  46. 46. Choriocarcinoma
  47. 47. Burnt out primary: With secondaries in lungs and other sites the primary can be completely absent. This is due to their ability to invade larger vessels there by causing ischemia and necrosis of the primary tumor. Choriocarcinoma – microscopy
  48. 48. • US may show small masses in the uterus • Irregular spotting (bloody, brown and offensive) • Mets may be found by chest x-ray • ß-HCG level are levated enormously • Wide spread mets are common (Lungs 50%, vagina 30%) Choriocarcinoma – clinical features
  49. 49. Treatment: Depends on type & stage of tumor. Options: evacuation, surgery, chemo (MTX, actinomycin – 100% cure rate) NOTE: Non-gestational choriocarcinomas are much more resistant to Tx. Choriocarcinoma
  50. 50. Gestational Trophoblastic Disease Type Histological features Clinical features Complete Hydatidiform Mole Composed of large, avascular villi with trophoblastic proliferation Occurs when a fertilized ovum contains only paternal chromosomes (usually 46, XX karyotype); produces marked uterine enlargement; "snowstorm" effect with no fetus on ultrasonography; some give rise to choriocarcinoma Partial Hydatidiform Mole Some villi are enlarged with minimal trophoblastic proliferation. Fetus may be present. Typically are triploid (69, XXX or 69, XXY or 69, XYY); a malformed fetus is present that rarely goes to term; rarely gives rise to choriocarcinoma Choriocarcinoma A malignant proliferation of syncytiotrophoblast with no villi; often hemorrhagic; no fetus is present HCG levels are often extremely high; can metastasize; many are sensitive to chemotherapy Placental Site Trophoblastic Tumor A rare localized proliferation of intermediate trophoblast that can produce a grossly visible nodule Most are bening; rare malignant cases Placental Site Nodule or Plaque A rare proliferation of intermediate trophoblast that is microscopic Of no major consequence
  51. 51. E N D

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