• Human placental lactogen (hPL) is produced by the syncytiotrophoblast from

Hu
about the time when production of hCG begins to diminish. Production of hPL is

proportional to placental growth, and its level reflects placental well-being. hPL

exerts GH-like effects in both fetal and maternal compartments. In the fetus, it

promotes the formation of insulin-like growth factor and growth factors believed

to promote growth of most, if not all, fetal tissues. In the mother, hPL promotes

nitrogen retention and utilization of free fatty acids, and it creates a state of mild

insulin resistance that benefits the fetus because it increases the availability of

maternal glucose for fetal consumption. In the mother, hPL also exerts a

prolactin-like effect and, with estrogen and progesterone, promotes ductal and

alveolar growth in the mammary gland during the third trimester of pregnancy.

However, prolactin is believed to be more important than hPL in this effect.

Placental site trophoblastic tumors — PSTT
Initially described in 1981, is a rare, potentially malignant neoplasm originating
from extravillous (intermediate) trophoblast cells. Approximately 300 cases
of PSTT had been reported. They can occur months to years after a
pregnancy. PSTTs most commonly develop after a term gestation, but also
occur after a molar pregnancy in approximately 8 % of cases; a PSTT can
develop after any type of pregnancy. The majority of PSTTs, approximately
70 %, act in a benign manner, while the remaining 30 % can develop
metastasis and even result in death. Interestingly, PSTTs are usually diploid
and molecular genotyping has shown them to have a female predominance
or 46XX
On histologic examination, PSTT generally presents as a proliferation of
extravillous or intermediate trophoblast in the myometrium or
endomyometrium. Chorionic villi are rarely found and the typical dimorphic
pattern of choriocarcinoma is absent. Instead, there is a characteristic
pattern consisting of a relatively monomorphic population of predominantly
mononuclear trophoblastic cells infiltrating the myometrium and splitting
apart the muscle fibers. Scattered multinucleated trophoblasts are also
present as are multinucleated syncytiotrophoblastic-like cells. Nuclear atypia
is quite variable as is the cytoplasm, which is most often amphophilic but can
also be eosinophilic or clear. Spindling of tumor cells may be present. In
addition, there is usually abundant fibrinoid material and prominent vascular
invasion. A variable amount of inflammation and necrosis is identified but the
marked hemorrhage and necrosis typical of choriocarcinoma is not present.
• Immunohistochemical staining for human placental lactogen (hPL), CD146 (MEL-CAM), and
placental alkaline phosphatase (PLAP) are additional diagnostic tests for PSTT that have a
specificity of approximately 60 percent. Mel-CAM and hPL are usually strongly positive, while
PLAP is focally positive consistent with origin from implantation site trophoblast. In addition,
high proliferative activity (as assessed by Ki-67 staining) and positive staining for alpha-
inhibin and cytokeratin 8/18 and negative smooth muscle markers confirm the diagnosis of
PSTT. Most PSTTs are diploid, although a report of a tumor with triploid cells has been
published.

• Although the majority of PSTTs are considered benign, there is no specific clinical or
pathologic feature on which one may rely to determine malignant behavior. However, there
are a number of adverse prognostic factors which, when present, confer a greater likelihood
of malignant behavior. These include advanced stage, older age, longer interval from
previous pregnancy, previous term pregnancy, higher serum hCG level, higher mitotic rate,
coagulative tumor necrosis, and clear cytoplasm. When a PSTT is malignant, it is fairly
resistant to chemotherapy.
Placental site trophoblastic tumor (PSTT) consists of a neoplastic proliferation of intermediate or
extravillous trophoblast (also known as X cells). Pregnancy-associated major basic protein
(pMBP) is a marker for placental intermediate trophoblast. We compared the distribution of
pMBP and human placental lactogen (hPL) in 24 PSTT and 3 exaggerated placental site (EPS)
specimens using two distinct immunohistologic methods. Statistical analyses were used to
compare staining intensities in metastatic and nonmetastatic lesions. By immunofluorescence,
77% of the PSTT specimens and 100% of the EPS specimens stained with antibodies to pMBP,
and the pMBP was localized in intermediate trophoblast and surrounding extracellular areas. By
immunohistochemistry, 78% of the PSTT specimens and 100% of the EPS specimens stained
for pMBP with a pattern comparable with that of immunofluorescence. Likewise, by immuno-
histochemistry, hPL stained 96% of the PSTT specimens and 100% of the EPS specimens.
Immunohistochemical staining intensities for pMBP and hPL correlated (r 2 = +.24; P = .013),
but hPL staining was mainly confined to intermediate trophoblast and was more intense. Anti-
pMBP tended to stain metastatic PSTT weakly. Thus, pMBP is a useful marker for intermediate
trophoblast tumors and could help distinguish these from other forms of trophoblastic disease.