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	-1	++++1	++++1	+++1	-1
	b-hCG	-1	-1	- (multinucleate cells +)1	-1	++++1
	hPL	-1	-/++++ (towards the distal end)1	++++1	-/+1	++++1
	Cytokeratin 18	++++2	++++2	++++2	++++2	++++2
	Mel-CAM	-1	-/++++ (towards the distal end)1	++++1	-/+1	-1
	PLAP	-1	-1	-1	+++1	-1
	Ki-67 index	25-50%1	>90%1	0%1	3-10%1	0%1
	p63	++++2	-2	-2	+++ (mainly cells with eosinophilic cytoplasm)2	-2

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

Classification

• Molar lesion

  • partial hydatidiform mole

  • complete hydatidiform mole

  • invasive hydatidiform mole

• Non-molar lesions

  • non-neoplastic

    • placental site nodule

    • exaggerated placental site

  • neoplastic

    • placental site trophoblastic tumour

    • epithelioid trophoblastic tumour

    • choriocarcinoma

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	18/18 (mainly in cells with eosinophilic cytoplasm)2	5/8 (<5% of cells positive)2
	HLA-G	9/91	14/141	16/161	13/131	14/14 (positive in intermediate trophoblast)1
	b-hCG	-/+ (mainly multinucleate cells)2	-/+ (mainly multinucleate cells)1	-1, -/+2	-1, -/+2	positive in syncytiotrophoblast1
	hPL	++++ (cited as +++2)1	++++ (cited as +++2)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
	Ki-67 index	0%1	>10%1	3-10%1	>10%1	>50% of mononuclear cells (there is a discrepancy between references 1 and 2, but >50% was recommended by the author on inquiry)2

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

This page last revised 23.9.2006.

©SMUHT/PW Bishop