Ovarian tumours - immunohistochemistry

cytokeratins

CK7

CK20

CEA

EMA

Ca19.9

CA125

vimentin

S-100

SMA

desmin

inhibin

CD99

oestrogen and progesterone receptors

low MW

high MW

serous tumours

17/172

10/172

+

-

4/172

+

17/172

4/172

-

endocervical-type mucinous tumours

+

-

(+)

+

-

+

intestinal type mucinous tumours

+

+

+

+

-

-

endometrioid tumours

+

-

Brenner tumours

+

-

+

+

+

-

granulosa cell tumours

30-60%

neg

100%4

50%4

90%4

-

+

90%

PR +ve3, ER -ve3

juvenile granulosa cell tumours

~50%

-

+

+

Sertoli(-Leydig) cell tumour

50%4

-

100%4

100%4

+

var

Leydig cell tumour

neg4

pos4

SCTAT

-

+

+

steroid cell tumours

30-50%

+

30%

+

small cell carcinoma

+

30-75%

+

-

See also: Melan-A (A103) immunostaining in ovarian sex cord stromal tumours.

One case of thyroglobulin-positivity in a series of 17 papillary serous carcinomas has been reported².

Differential diagnoses

• Sex cord stromal tumour versus sertoliform endometrioid carcinoma: inhibin and EMA (or CK 7) appear most useful. Beware of inhibin positivity in reactive stromal cells associated with carcinomas; this occurs most frequently in association with mucinous carcinomas⁸.

	SCST	endometrioid carcinoma
broad spectrum anti-cytokeratins	positive, except pure Leydig cell tumours	positive
Cytokeratin 7	negative, except for Retiform areas of Sertoli-Leydig cell tumours5	positive, including 5/6 sex cord-like endometrioid carcinomas5
CD99	90% of granulosa cell tumours, variably in Sertoli-Leydig cell tumours6	positive in some sex cord-like endometrioid carcinoma (but not membranous staining)6
inhibin	positive (vide supra [that's Latin for "see above"])	negative
EMA	negative	usually positive, but may only be focal7

• Sex cord stromal tumour versus sarcoma: the possible sarcomas include haemangiopericytoma, leiomyosarcoma and endometrial stromal sarcoma. This may particularly be a problem with late recurrences of granulosa cell tumour. The sarcomas are negative for inhibin. Endometrial stromal sarcoma is positive for CD10. When endometrial stroma sarcoma has sex cord-like elements, these structures are usually positive for a-inhibin. Calretinin may be helpful in inhibin-negative sarcomatous sex cord stromal tumours. Luteinised granulosa cell tumour may resemble an epithelioid smooth muscle tumour and may be positive for smooth muscle actin. Luteinised granulosa cell tumours are reliably positive for a-inhibin. whereas inhibin positivity has not been reported in smooth muscle tumours.

• Granulosa cell tumour versus yolk sac tumour. Hepatoid yolk sac tumour may resemble juvenile granulosa cell tumour, which may also show minor foci of hepatoid differentiation. Foci of syncytiotrophoblast in mixed germ cells tumours are likely to be intensely positive for a-inhibin.

• Hypercalcaemic type small cell carcinoma may particularly resemble juvenile granulosa cell tumour but cells have less cytoplasm in the former. Both may have a high mitotic rate.

	granulosa cell tumour	hypercalcaemic small cell carcinoma	yolk sac tumour
a-inhibin	positive	negative	negative; may be focally positive in hepatoid yolk sac tumour
CD99	positive	positive	negative
a-fetoprotein	negative	negative	positive
a-antitypsin	negative	negative	positive
CEA	negative	negative	positive

• Metastatic adenocarcinomas of colon or breast may mimic primitive sex cord stromal tumours. a-inhibin may be focally and weakly positivity. The rare benign signet ring stromal tumour resembles signet ring cell carcinoma (Krukenberg tumour).

	signet-ring stromal tumour	Krukenberg tumour
a-inhibin	positive	negative (stromal cells may be positive)
EMA	negative	positive
SMA	positive	negative
CEA	negative	positive
pancytokeratin	negative	positive

• Oxyphilic tumours. The following tumours may all appear oxyphilic:

  • oxyphilic variant of Sertoli cell tumour
    
  • steroid cell (lipid, lipoid) tumour
    
  • ovarian clear cell carcinoma
    
  • endometrioid carcinoma
    
  • carcinoid
    
  • struma ovarii

  • metastatic renal cell carcinoma
    

  • metastatic hepatocellular carcinoma

References

Diagnostic histopathology of tumors. Edited by CDM Fletcher. 2nd edition. Churchill Livingstone. Pages 567-625.

²Keen, C. E., Szakacs, S., Okon, E., Rubin, J. S., Bryant, B. M. CA125 and thyroglobulin staining in papillary carcinomas of thyroid and ovarian origin is not completely specific for site of origin Histopathology 1999;34:113-117

³Kato, N., Fukase, M., Ono, I., Matsumoto, K., Okazaki, E., Motoyama, T. Sertoli-stromal cell tumor of the ovary: immunohistochemical, ultrastructural, and genetic studies. Hum Pathol 2001;32:796-802

⁴Zheng, W., Senturk, B.Z. and Parkash, V. Inhibin immunohistochemical staining: a practical approach for the surgical pathologist in the diagnoses of ovarian sex cord-stromal tumors. Adv Anat Pathol 2003;10:27-38.

⁵Guerrieri, C., Franlund, B., Malmstrom, H. and Boeryd, B. Ovarian endometrioid carcinomas simulating sex cord-stromal tumors: a study using inhibin and cytokeratin 7. Int J Gynecol Pathol 1998;17:266-71.

⁶Matias-Guiu, X., Pons, C. and Prat, J. Mullerian inhibiting substance, alpha-inhibin, and CD99 expression in sex cord-stromal tumors and endometrioid ovarian carcinomas resembling sex cord-stromal tumors. Hum Pathol 1998;29:840-5.

⁷Ordi, J., Schammel, D.P., Rasekh, L. and Tavassoli, F.A. Sertoliform endometrioid carcinomas of the ovary: a clinicopathologic and immunohistochemical study of 13 cases. Mod Pathol 1999;12:933-40.

⁸Rishi, M., Howard, L.N., Bratthauer, G.L. and Tavassoli, F.A. Use of monoclonal antibody against human inhibin as a marker for sex cord-stromal tumors of the ovary. Am J Surg Pathol 1997;21:583-9.

This page last revised 3.9.2001.