Trophoblastic Disease Flashcards
Complete Hydatidiform Mole
- Anuclear ovum + sperm
- Either 2 sperm or 1 that replicates
- Diploid
- Diandric –> two sets of paternal chromosomes
- 46XX or 46XY
- Risk of choriocarcinoma (<5%)
- Treat with medication and removal
- Follow serum hCG for disease monitoring
Clinical:
* Very high serum hCG (>100k)
* Large uterus
* Bleeding
* Snowstorm on USS
Macro:
* Hydropic, grape-like villi
Micro:
* Diffusely hydropic villi
* Irregular in size and shape, clublike extensions
* Cistern formation –> fluid filled cavities
* Avascular –> no foetal RBC
* Circumferential trophoblastic proliferation –> cytotrophoblasts may have marked nuclear pleomorphism
* Syncytiotrophoblasts can form lacy medusa head festoons on villous surface
IHC:
* Absent/sparce (<10%) p57 nuclear staining of cytotrophoblast and villous stromal cells
Partial Hydatidiform Mole
- Diandric triploidy
- One maternal and two paternal sets of chromosomes
- Usually small/normal uterus
- Normal/mildly elevated hCG
- Usually good outcome
- <1% risk of persistant disease or subsequent tumour
Macro:
* Unremarkable
* Gestational sac / Foetal parts may be present
Micro:
* Two populations of villi:
Enlarged, hydropic villi
Small/normal sized fibrous villi
* Irregular villi with scalloped borders
* Occasional cistern formation
* Trophoblastic proliferation
* Stromal blood vessels and foetal RBCs may be present
Molecular:
* Diandric triploidy 69XXY
IHC:
* Retained staining with p57
Trophoblastic Lesions
HPL +, b-HCG ++
* Ki67 >90%
* Choriocarcinoma
HPL +/-, p63++
* Ki67 < 8%, Cyclin E - –> Placental site nodule
* Ki67 >10%, Cyclin E + –> Epithelioid trophoblastic tumour
HPL ++, p63 -
* Ki67 < 1% –> Exaggerated placental site
* Ki67 >10% –> Placental site trophoblastic tumour
Placental Site Nodule
- Placental site nodule (PSN) is a rare benign lesion of chorionic type intermediate trophoblast
Clinical:
* Single to multiple, small (usually < 5 mm), well circumscribed nodular aggregates
* Intermediate trophoblastic cells embedded in a hyalinized stroma
* Mitotic inactivity
* Benign counterpart of epithelioid trophoblastic tumor (ETT)
* Atypical placental site nodule (APSN) –> significant nuclear atypia or borderline proliferation index
* APSN is considered a precursor to ETT
Sites
* Uterus: endometrium (56%), cervix (40%)
* Rarely, fallopian tubes and ovary, presumably following an ectopic
Macro:
* Usually small, ranging from 1 to 14 mm (average 2.1 mm)
* Occasionally, multiple and sizable (> 5 mm)
* Yellow-white and necrotic appearing nodule in the endometrium or superficial myometrium
Micro:
* Well circumscribed
* Thin rim of chronic inflammatory cells
* Occasionally decidualized stroma
* Trophoblastic cells are arranged in a haphazard pattern, dispersed singly, in small clusters and cords or occasionally diffusely throughout the nodule
* Central hyalinized extracellular matrix
* Multinucleated cells are occasionally present
* Mitotic figures are absent or rare
Positive stains
PLAP
Inhibin
HLA-G
p63
EMA
Cytokeratins (CAM5.2, AE1 / AE3, CK18)
Vimentin
CD10
Epithelioid trophoblastic tumor
- Epithelioid trophoblastic tumor (ETT) is a very rare gestational trophoblastic tumor derived from neoplastic chorionic type intermediate trophoblasts
Sites
* Uterus: 50% of cases arise from uterine cervix or lower uterine segment
* Rarely extrauterine locations: vagina, fallopian tube, ovary and pelvic peritoneum
* Distant metastasis in 25% of patients: lungs (most common) liver, gallbladder, kidney, pancreas and spine
Prognostic factors
* Metastasis is seen in 25% of patients
* Survival rate of 87 - 90%
Poor prognosis is associated with:
* FIGO stage IV disease
* Interval between antecedent pregnancy and diagnosis of > 4 years or > 120 months
* Mitotic count more than 5 per 10 high power fields
Macro:
* Expansile mass
* White yellowish fleshy, solid appearance on cut surface
* Invades the underlying stroma
* Necrosis and hemorrhage may also be present
* Ulceration and fistula formation is common
Micro:
* Relatively uniform, medium sized tumor cells arranged in nests, cords or large sheets
* Tumor cells have a moderate amount of finely granular, eosinophilic to clear cytoplasm
* Moderate nuclear atypia is seen in most of the tumors
* Well circumscribed tumor border is characteristic; however focal infiltrative peripheral areas are not uncommon
Molecular:
* LPCAT1::TERT fusion and TERT upregulation
* Short tandem repeat multiplex PCR assay shows paternal alleles, confirming trophoblastic origin
IHC:
p63
HLA-G
HSD3B1
Inhibin-alpha
Cyclin E
GATA3
CD10
EMA
CK (CK7, CK18, CAM 5.2, AE1 / AE3)
Ki67 labeling index > 10%
Exaggerated Placental Site
- Exaggeration of normal physiologic process
- Intermediate trophoblasts (IT) invade through endometrium into the superficial third of myometrium
- Normal structure of endometrial glands, myometrium and vessels is usually maintained
- Ki67 indices of near zero indicate increased number of intermediate trophoblasts in EPS is not a result of de novo proliferation of IT in the implantation site
Micro:
* Extensive infiltration of endometrium and myometrium by implantation site intermediate trophoblasts
* Often multinucleate
* Endometrial glands and spiral arterioles can show invasion by trophoblasts
* Smooth muscle cells of myometrium are separated by cords, nests and individual trophoblastic cells
* No necrosis or mitoses
IHC:
HPL (diffuse)
MUC4
CK18
HLA-G
Placental site trophoblastic tumor
- Placental site trophoblastic tumor (PSTT), a rare gestational trophoblastic disease
- Neoplastic proliferation of intermediate trophoblasts at placental implantation site
- Serum levels of beta hCG are generally low
Micro:
* Infiltrative growth pattern consisting of aggregates or sheets of large, polyhedral to round, predominantly mononucleated cells composed of implantation site intermediate trophoblastic cells
* Scattered multinucleated implantation site trophoblastic cells are common
* Vascular invasion is often present, in which the tumor cells replace the wall of myometrial vessels –> diagnostic for PSTT
* Most tumors have a low mitotic count
* Decidua or an Arias-Stella reaction may be present in the adjacent, uninvolved endometrium
* Villi are almost never identified
* Necrosis may be present
Molecular:
* Presence of paternally derived X chromosome and absence of Y chromosome
IHC:
HPL
Cytokeratin
MUC4
HSD3B1
HLA-G
MEL-CAM (CD146)
CD10
GATA3
PDL1
Ki67 is expressed in 8 - 20% of cells
