Case 3 -
Metastatic Placental Site Trophoblastic Tumor Presenting as Vaginal Polyps
Kenneth R. Lee
Brigham and Women's Hospital
Click on each slide thumbnail image for an enlarged view
A 33 year-old woman described a sensation of "falling out." She was found to have 4 or 5 discrete
vaginal polyps, each 1 to 2 cm, in the area of the hymenal ring. One of these was biopsied.
Case 3 - Figure 1 - Vaginal polyp at low power showing normal surface squamous epithelium and cellular and edematous stroma.
Case 3 - Figure 2 - Higher power demonstrating a zone of connective tissue separating the surface from the more cellular deep stroma.
Case 3 - Figure 3 - Vaginal polyp with atypical epithelioid cells in a "cuffing" pattern around a blood vessel.
Case 3 - Figure 4 - Mononuclear and multinucleated cells in an edematous stroma with rare mitotic figures (shown).
Case 3 - Figure 5 - Mononuclear and multinucleated cells with small and large cytoplasmic vacuoles.
Metastatic placental site trophoblastic tumor presenting as vaginal polyps
The polyp contained a benign squamous surface overlying a
proliferation of mostly single epithelioid cells with abundant eosinophilic, foamy or vacuolated
cytoplasm and round to oval nuclei with rare mitotic figures in an edematous stroma.
Differential diagnosis of vaginal polyps
with atypical stromal cells
cellular pseudosarcomatous 
Post operative spindle cell nodule
Prolapsed fallopian tube
Yolk sac tumor
Carcinoma (Uterus, Ovaries, Colon)
Sarcoma, Melanoma 
Based on the microscopic appearance he remaining considerations were:
|Fibroepithelial polyp with stromal typia|
|Metastatic carcinoma or melanoma|
|Epithelioid smooth muscle tumor (primary or metastatic)|
|Metastatic trophoblastic neoplasm|
Special stain results were as follows:
Positive: AE1/AE3, CK7, CK20, EMA, HCG(few), HPL(rare)
Negative: S-100, SMA, Desmin, Inhibin, Calretinin, Mucin
These results narrowed the considerations to metastatic carcinoma or a trophoblastic
neoplasm, with the fairly convincing HCG staining strongly supporting the latter. Additional history
revealed that the patient had delivered a term infant 13 months previously, had no pregnancies prior to
this, and was not currently pregnant or experiencing vaginal bleeding. A serum B-hCG was ordered and was
"slightly elevated" at 16 mIU/ml. A D&C was recommended and it revealed blood clot containing cells
similar to those in the vaginal polyp. A hysterectomy and vaginal polypectomies were performed. The
uterus contained a placental site trophoblastic tumor (PSTT) involving the fundus and invading to the
serosa. Residual PSTT was present in the vaginal polyps. The patient was subsequently treated with
several cycles of a six-drug combination chemotherapy regimen until the B-hCG normalized. She has been
without signs of a recurrence six months after presentation.
Placental site trophoblastic tumor
1976 – Designated "trophoblastic pseudotumor"  based on 12 cases and felt to be an exaggerated form
of "syncytial endometritis." Characterized as composed of large aggregates of cells resembling
intermediate trophoblasts  but with nuclear pleopmorphism and variable mitotic activity. These cells
extend between the myometrial fibers without extensive hemorrhage or necrosis. Replacement of vascular
endothelium and extensive fibrin around vessels and elsewhere are characteristic .
1981 – Potential for malignant behavior recognized, term "PSTT" coined for this neoplasm derived from
implantation site trophoblasts
1999 – Review of reported experience totaling 88 cases : Average age – 29y, most common symptom –
vaginal bleeding, mean B-hCG – 800 (1 to 8300), usual antecedent - normal pregnancy, followed by abortion
(either spontaneous or induced) and then complete mole.
83 cases with follow-up:
Stage I & II - 62 cases, 3 deaths
Stage III & IV – 21 cases, 15 deaths
Metastases correlate with prior term delivery (82% vs 57%) and longer interval to symptoms (24 mo vs
No ability to predict behavior with age, mitotic count (although some small series indicated increased
mitoses as a predictor), hCG level, ploidy
Immunohistochemistry of PSTT
Ki-67 (14% + 7%)
|Negative (or rare positive cells)|
Differential diagnosis of PSTT 
|Exaggerated placental site|
|Placental site nodule|
|Epithelioid trophoblastic tumor|
|Smooth muscle tumors|
The exaggerated placental site (EPS) is a variant of a normal implantation wherein the trophoblastic
proliferation is exuberant. It differs from a PSTT by the absence of large confluent accumulations of
trophoblasts and with somewhat less nuclear atypia. Decidua and villi are often present, and there are
more multinucleated cells than in PSTT. Importantly, there are no mitoses in contrast to their presence
in PSTT. Mitoses may be difficult to evaluate in curettings, and the use of the Ki-67 index as a
surrogate marker has been recommended. It is virtually zero in EST and averages around 14% in PSTT. It
may however, be difficult to determine which cells are marking with Ki-67. Thus, some have advocated a
double labeling technique using the Mel-CAM antibody to mark the cytoplasm of the trophoblast cells .
The placental site nodule
may be confused with PSTT in a curetting. The cells, however, surround
a central fibrin deposit and are amitotic. It is usually an incidental finding in the lower uterine
A choriocarcinoma (CCA) should not be confused with PSTT since it is biphasic with a prominent
syncytiotrophoblast component not present in PSTT. There is usually abundant mitotic activity,
hemorrhage and necrosis in CCA. Immunostains may help as CCA should be strongly positive for hCG and
only minimally positive or negative for HPL, the reverse of that seen in PSTT.
The epithelioid trophoblastic tumor (ETT)  is a recently described trophoblastic neoplasm felt to be
the malignant counterpart of the intermediate trophoblasts of the chorion leave, which have an epitheliod
appearance. It is considered by some to be part of the spectrum of PSTT and has a similar behavior. It
is distinguished from PSTT by its sharply demarcated, "geographic" pattern of nests and cords of cells
and by extensive hyaline material and necrosis. The epithelioid cells are smaller than those of PSTT.
It is negative or only focally positive for HPL, HCG, PLAP, and Mel-CAM. The more common mimic of ETT is
carcinoma, especially squamous carcinoma since the hyaline material resembles keratin, and unless one is
aware of ETT this might be readily diagnosed as such.
PSTT may also be diagnosed as carcinoma to those unwary. A non-keratinizing squamous carcinoma might
readily be considered in curettings. Melanoma and epithelioid smooth muscle tumors might also appear
similar to PSTT. Immunostains are diagnostic, but obviously require an awareness of the various
The current case is the only one recorded, as far as I can determine, in which the patient presented with
a vaginal polyp as the only sign. Although 8 of 88 PSTT cases had vaginal metastases, in all of these
the uterine tumor was found simultaneously with or preceded the vaginal tumor. The current case is also
unusual in that the morphology and immunohistochemistry are not typical of PSTT. The cells have a
sometimes vacuolated or spongy cytoplasm; they do not replace the myometrial vascular endothelium, and
are not associated with abundant fibrin; the HPL is positive in only rare cells, whereas HCG is more
diffusely positive and the inhibin is negative. Perhaps this variant morphology is related to the
unusual presentation without uterine symptoms in this unique case.
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