CD10 (CALLA, common acute lymphoblastic leukemia antigen, neutral endopeptidase-24.11, EC 3.4.24.11, NEP, encephalokinase, neprilysin)

CD10 is a 94 kDa zinc-dependent cell membrane metalloprotein which participates in the postsecretory processing of neuropeptides5, inactivating inflammatory and vasoactive peptides7. It is widely distributed in kidney, liver, small intestines, placenta, choroid plexus, brain, gonads, adrenal cortex and leucocytes5. CD10 is a marker for germinal centre cells and their derivative lymphomas4.

Previous antibodies were effective on fresh-frozen tissue only. The clone 56C6 works on paraffin-embedded tissue after antigen retrieval2,6.

Immunohistochemical expression

CD10 is not lineage-specific:

immature B cells
some immature T cells
mature granulocytes
Expressed by 75% of precursor B-cell ALL
some T-ALL/T-LBL
All subtypes of AML
>90% of CML in lymphoid blast crisis
Burkitt's lymphoma
Follicular lymphoma: CD10 may be lost in grade 3 follicular lymphoma in the the B-cells in the interfollicular zones of follicular lymphomas.
Some diffuse large B-cell lymphomas4
Myeloma
T-cell lymphomas are negative except angioimmunoblastic T-cell lymphoma

bcl-6

CD10

Follicular hyperplasia

19/1920

Nodal follicular lymphoma

28/2820

22/281, 36/3920

Splenic follicular lymphoma

6/720

4/1120

MALT lymphoma

0/1720

0/2420

Mantle cell lymphoma

0/18(reactive follicles were positive.)20

0/19(reactive follicles were positive.)20

Splenic marginal zone lymphoma

0/10(reactive follicles were positive.)20

0/13(reactive follicles were positive.)20

Diffuse large B cell lymphoma

39/4720

21/5420

10 cases had evidence of previous follicular lymphoma: all but one were positive for both bcl-6 and CD1020. Of 44 DLBCL, NOS20:
	CD10+	CD10-
bcl-6+	11	1
bcl-6-	21	11

Burkitt lymphoma

17/1720

20/2020

NLPHD

11/1320

0/1620

Classical HD

4/820

0/1320

Bile canaliculi and hepatocellular carcinomas in a canalicular pattern5.
Renal glomeruli and the brush border of proximal tubules19 It may act to cleave peptides such as bradykinin, angiotensin and substance P.
Carcinomas of kidney10, bladder, prostate and uterus5.
Solid-pseudopapillary tumour of the pancreas
Melanoma cell lines
vulval, vaginal and cervical tissues and some of their tumours:

	vulva	vagina	uterine cervix
squamous epithelium	4/117	2/37	18/437
squamous metaplasia			4/57
eccrine glands	1/37
apocrine glands	3/47
sebaceous glands	5/57
hair follicles	5/57
condyloma accuminata	0/27
ectopic breast tissue	0/27
endocervical stroma			1/4(weakly positive)13
endocervical glands			0/397
tunnel clusters			0/37
adenosis		0/27
microglandular hyperplasia			0/37
hidradenoma papilliferum	0/47
CIN			4/137
squamous cell carcinoma	0/4(keratinising)7	1/27	4/87
basaloid carcinoma	2/27
verrucous carcinoma	1/17
basal cell carcinoma	2/27
adenocarcinoma		0/17	0/14(2 cases in-situ, 12 cases invasive)7
clear cell adenocarcinoma, DES related		0/27
neuroendocrine carcinoma			0/27
mesonephric remnants			7/77
mesonephric hyperplasia			6/67
mesonephric adenocarcinoma			5/57, 1/1(uterine corpus)⁹
malignant melanoma	2/27

Endometrial stroma (but not glands), endometrial stromal nodules and low grade endometrial stromal sarcoma. Leiomyomatous tumours and undifferentiated carcinomas of the uterus are usually only focally and/or weakly staining3:

proliferative endometrium	5/5, 39/39(stroma positive, glands negative)7
secretory endometrium	5/5all diffuse strong, 10/10(stroma positive, glands negative)7
pregnancy (Arias-Stella)	10/10(stroma positive, glands negative)7
decidualised endometrial stroma	negative or weakly positive8
atrophic endometrium	3/3all focal strong, 9/9(stroma positive, glands negative)7
hyperplasia	7/7(stroma positive, glands negative)7
adenomyosis	8/8(stroma positive, glands negative)7
endometriosis	19/19(stroma positive, glands negative)7, 22/25(stroma positive, glands negative)13
endometrioid adenocarcinoma	1/167
adenocarcinoma with squamous metaplasia	4/67
mucinous adenocarcinoma	0/67
serous papillary adenocarcinoma	1/107
clear cell carcinoma	0/47
undifferentiated endometrial carcinoma	1/61: focal weak
atypical polypoid adenomyoma	2/27
endometrial stromal nodule	1/1diffuse moderate
low-grade endometrial stromal sarcoma	13/13
high-grade endometrial stromal sarcoma	4/6
mixed endometrial stromal-smooth muscle tumour	1/1focal weak
endometrial stromal neoplasm, NOS	4/47, 5/5 11
myometrium	negative8
leiomyoma	3/10, 0/67, 8/12(focal: less than 5% of cells)8
leiomyosarcoma	3/5, 0/37, 4/88
adult granulosa cell tumour	1/101: focal strong
carcinosarcoma	3/47
uterine carcinosarcoma with endometrial stromal component	1/1focal weak
uterine mesenchymal tumour with sex cord-like elements (type 2)	1/1focal moderate
adenomatoid tumour	0/37
placental chorionic stromal cells	positive8
cytotrophoblast	15/157, negative8
syncytiotrophoblast	15/157, positive on apical surface8
intermediate trophoblast	15/157
exaggerated placental site	3/37
placental site nodule	2/27
partial mole	3/37
complete mole	4/47
choriocarcinoma	2/27
placental site trophoblastic tumour	3/37

Fallopian tubes and ovaries:

Fallopian tube:	normal mucosa	1/227
	Walthard's rests	0/27
	Epoophoron	12/137
	FATWO	10/107
	Adenocarcinoma	10/107
Ovary:	surface epithelium/inclusion cysts	0/67
	oocytes	0/57
	granulosa cells	0/57
	thecal cells	0/57
	rete ovarii	15/157
	cyst of rete ovarii	1/27
	serous cystadeno(fibro)ma	1/67
	serous borderline tumour	0/47
	serous carcinoma	1/117
	mucinous cystadeno(fibro)ma	0/27
	mucinous borderline tumour	0/67
	mucinous carcinoma	1/37
	endometrial borderline tumour	2/37
	endometrioid carcinoma	0/57
	carcinosarcoma	0/27
	clear cell carcinoma	0/97
	Brenner tumour	1/27
	transitional cell carcinoma	0/27
	Sertoli-Leydig tumour	4/57
	adult type granulosa cell tumour	1/37
	juvenile type granulosa cell tumour	0/17
	sex cord tumour with annular tubules	0/17
	steroid cell tumour	0/17
	small cell carcinoma, hypercalcaemic	0/17
	struma ovarii	0/27
	carcinoid	1/27
	dysgerminoma	1/27
	embryonal carcinoma	0/27
	yolk sac tumour	2/27
	choriocarcinoma	1/17

Metastases to the genital tract:

breast carcinoma	0/27
gastric carcinoma (Krukenberg tumour)	0/27
colorectal carcinoma	3/37
renal carcinoma	3/37
carcinoid	1/27
malignant melanoma	2/27

Other tumours:

renal cell carcinoma	41/46 11, 2/2(metastatic to thyroid)12, see subtypes, 46/5426
transitional cell carcinoma	13/24 11
prostatic adenocarcinoma	11/18(apical surface)11
pancreatic adenocarcinoma	7/14(apical surface)11
rhabdomyosarcoma	3/511
Schwannoma	5/1111
malignant melanoma	12/30 11

CD10 expression by melanomas is associated with tumour progression17.

Atypical fibroxanthoma
Fibroblasts
Myoepithelial cells in normal breast. Stromal cells of prostate, breast, colorectum and lung carcinomas22. In gastric carcinoma, stromal positivity for CD10 has been correlated with vascular invasion and metastasis. In breast carcinoma, stromal CD10 expression is associated with negativity for ER, high tumour grade and decreased survival22.
Phyllodes tumours: stromal cells more often express CD10 in malignant than in benign or borderline phyllodes tumours24.

Diagnostic utility

Categorisation of acute leukaemias5.
Differential diagnosis of lymphomas2. Follicular lymphomas are positive for both bcl-6 and CD10, while other low grade lymphomas which may have a follicular growth pattern, particularly mantle cell lymphoma and marginal zone lymphoma (in which follicles may be colonised), are negative.
The diagnosis of endometrial stromal sarcoma:
- The identification of metastatic endometrial stromal sarcoma, which may occur many years after excision of the primary: at primary ovarian and metastatic sites the characteristic tongue-like growth pattern is not apparent.
- differentiation of endometrial stromal tumours from leiomyomatous tumours, in combination with h-caldesmon, desmin and SMA.
- In combination with a-inhibin, the differentiation of endometrial stromal tumours from adult granulosa cell tumour.
- In combination with CD45 and other lymphoid markers, the differentiation of endometrial stromal sarcoma from lymphoma: note that some lymphomas are positive (vide supra).
Identification of mesonephric tumours7 and differentiation for Mullerian tumours.
Differentiation of primary clear cell gynaecological tumours (negative)7 from clear cell tumours metastatic to the gynaecological tract, including kidney10 (positive).
Diagnosis of clear cell renal cell carcinoma. CD10 has a sensitivty of about 90% for clear cell renal cell carcinoma but also stains many hepatocellular, prostatic and urothelial carcinomas25. It is more often positive in clear cell renal cell carcinoma21 than in papillary renal cell carcinoma. For this differential, it needs to be used in combination with BerEP4 and renal cell carcinoma marker (both more often positive in papillary renal cell carcinoma)18.
Diagnosis of endometriosis. (This includes pure stromal endometriosis, devoid of glands, found especially within the cervix.)8,13
Identification of early myometrial invasion by endometrial adenocarcinomas. There is disagreement as to whether CD10 is helpful in this context. Afify et al14 found the stromal cells surrounding myoinvasive carcinoma to be negative or, at most, to show a thin layer, two or three cells thick, around the carcinoma to be positive. By contrast, Perunovic et al15 found immunoreactivity of the spindle cells around almost every invasive carcinoma, averaging five cells but in some cases more than ten cells wide: the conclusion was that CD10 was of no value in the identification of early invasion.
Differentiation of hepatocellular carcinoma from carcinoma metastatic to the liver: canalicular staining with CD 10 is specific for hepatocellular carcinoma.
Diagnosis of microvillous inclusion disease (familial microvillous atrophy) of the intestine: CD10, polyclonal CEA, alkaline phosphatase and PAS all show cytoplasmic, rather than brush border, reactivity in this condition16.

References

1 Kaufmann, O. Flath, B. Spath-Schwalbe, E. Possinger, K. Dietel, M. Immunohistochemical detection of CD10 with monoclonal antibody 56C6 on paraffin sections. Am J Clin Pathol 1999;111:117-22. Positivity seen in 22 of 28 cases.

2 Delsol G, New antibodies and new applications of old antibodies in the diagnosis of hematolymphoid neoplasms. In Immunohistochemistry Long Course, Nice, October 18-23, 1998.

3 McCluggage, W. G., Sumathi, V. P., Maxwell, P. CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histopathology 2001;39:273-278.

4 de Leval, L., Ferry, J. A., Falini, B., Shipp, M., Harris, N. L. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Path 2001;25:1277-1282.

5 Borscheri, N., Roessner, A., Rocken, C. Canalicular immunostaining of neprilysin (CD10) as a diagnostic marker for hepatocellular carcinomas. Am J Surg Pathol 2001;25:1297-1303.

6 Leong A S-Y, Cooper K and Leong FJ W-M. Manual of diagnostic antibodies for immunohistology. 2nd edition, 2003

7 Ordi, J., Romagosa, C., Tavassoli, F.A., Nogales, F., Palacin, A., Condom, E., Torne, A. and Cardesa, A. CD10 Expression in Epithelial Tissues and Tumors of the Gynecologic Tract: A Useful Marker in the Diagnosis of Mesonephric, Trophoblastic, and Clear Cell Tumors. Am J Surg Pathol 2003;27:178-86.

8 Toki, T., Shimizu, M., Takagi, Y., Ashida, T. and Konishi, I. CD10 is a marker for normal and neoplastic endometrial stromal cells. Int J Gynecol Pathol 2002;21:41-7.

9 Ordi, J., Nogales, F.F., Palacin, A., Marquez, M., Pahisa, J., Vanrell, J.A. and Cardesa, A. Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation. Am J Surg Pathol 2001;25:1540-5.

10 Avery, A.K., Beckstead, J., Renshaw, A.A. and Corless, C.L. Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms. Am J Surg Pathol 2000;24:203-10.

11 Chu, P. and Arber, D.A. Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma. Am J Clin Pathol 2000;113:374-82.

12 Ambrosiani, L., Declich, P., Bellone, S., Tavani, E., Pacilli, P., Guarneri, A., Rovellini, P. and Bianchi, A. Thyroid metastases from renal clear cell carcinoma: a cyto-histological study of two cases. Adv Clin Path 2001;5:11-6.

13 Sumathi, V.P. and McCluggage, W.G. CD10 is useful in demonstrating endometrial stroma at ectopic sites and in confirming a diagnosis of endometriosis. J Clin Pathol 2002;55:391-2.

14 Afi AM, Tan LC, Werness BA. The diagnostic utility of CD10 in evaluating endometrial lesions. Lab Invest 2002;82:189A-190A.