Trophoblastic tumours

Cytotrophoblast is the proliferative component, while syncytiotrophoblast is terminally differentiated. Intermediate trophoblast differentiates from the trophoblastic columns that anchor the chorionic villi to the endometrium and are of an intermediate degree of differentiation. The implantation site intermediate trophoblast is that which infiltrates the decidua, myometrium and spiral arteries: it gives rise to exaggerated placental site (benign) and placental site trophoblastic tumour (malignant). Chorionic type intermediate trophoblast is that found on the chorion laeve of the fetal membranes: it gives rise to placental site nodule (benign) and epithelioid trophoblastic tumour (malignant). The exact origin of choriocarcinomas is uncertain, although they may arise from the trophoblastic column of villi2.

Immunohistochemistry

Immunoreactivity in normal early placenta2:

 

 

Cytotrophoblast

Intermediate trophoblast

syncytiotrophoblast

  

villous

implantation site

chorionic

HLA-G

negative1

++++1

++++1

+++1

negative1

b-hCG

negative1

negative1

negative (multinucleate cells +)1

negative1

++++1

hPL

negative1

negative/ ++++1

++++1

negative/+1

++++1

Cytokeratin 18

++++2

++++2

++++2

++++2

++++2

Mel-CAM

negative1

negative/ ++++1

++++1

negative/+1

negative1

PLAP

negative1

negative1

negative1

+++1

negative1

Ki-67 index

25-50%1

>90%1

0%1

3-10%1

0%1

p63

++++2

negative2

negative2

+++2

negative2

HSD3B1

negative4

positive4

positive4

positive4

positive4
           

key: +; <25%, ++;25-50%, +++;50-75%, ++++;>75% of cells reactive

 

Classification

 

Immunoreactivity with a panel of markers may be helpful in differentiating between gestational trophoblastic tumours1:

 

 

Intermediate trophoblast

 

 

choriocarcinoma

  

implantation site lesions

chorionic-type lesions

exaggerated placental site

placental site trophoblastic tumour

placental site nodule

epithelioid trophoblastic tumour

p63

0/152

0/222

20/202

18/182

5/82

HLA-G

9/91

14/141

16/161

13/131

14/141

b-hCG

-/+2

-/+1

-1, -/+2

-1, -/+2

positive in syncytiotrophoblast1

hPL

++++1

++++1

-/+2

-/+2

positive in intermediate trophoblast and syncytiotrophoblast1

 

Cytokeratin 18

++++2

++++2

++++2

++++2

positive2

Mel-CAM

++++1

++++1

-/+1

-/+1

positive in intermediate trophoblast1

 

PLAP

-/+1

-/+1

+/++1

+/++1

-1

Cyclin E

most cases diffuse intense positivity3

most cases diffuse intense positivity3

staining usually limited, with a H-score of <40

15/21 cases diffuse intense positivity, with a H-score of >2003

most cases diffuse intense positivity3

HSD3B1

positive4

positive4

positive4

positive4

positive4

Ki-67 index

0%1

>10%1

3-10%1

>10%1

> 50% of mononuclear cells2
           

key: +; <25%, ++;25-50%, +++;50-75%, ++++;>75% of cells reactive

 

Diagnostic utility

A diagnostic algorithm has been proposed2:

negative for CK18 and HLA-G

positive for CK18 and HLA-G

 

not a trophoblastic lesion

trophoblastic lesion

hCG highlights syncytiotrophoblast

p63 - & hPL +++

p63 +++ & hPL -/+

implantation site

chorionic type intermediate trophoblast

Ki-67 < 1%

Ki-67 > 1%

Ki-67 < 10%

Ki-67 > 10%

exaggerated placental site

placental site trophoblastic tumour

placental site nodule

epithelioid trophoblastic tumour

 All types of trophoblastic lesions are consistently negative for p16, in contrast to the positivity seen in most cervical carcinomas3.

References

1Singer, G., R. J. Kurman, et al. (2002). "HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis." Am J Surg Pathol 26(7): 914-20.

2Shih Ie, M. and R. J. Kurman (2004). "p63 expression is useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations." Am J Surg Pathol 28(9): 1177-83.

3 Mao TL, Seidman JD, Kurman RJ, et al. Cyclin E and p16 Immunoreactivity in Epithelioid Trophoblastic Tumor-An Aid in Differential Diagnosis. Am J Surg Pathol 2006; 30:1105-1110

4 Mao TL, Kurman RJ, Jeng YM, et al. HSD3B1 as a novel trophoblast-associated marker that assists in the differential diagnosis of trophoblastic tumors and tumorlike lesions. Am J Surg Pathol 2008; 32:236-42

 

This page last revised 1.4.2008.

©SMUHT/PW Bishop