CD Markers - CD10

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CD Markers

CD10

Reviewer: Charanjeet Singh, M.D., University of Minnesota (see Reviewers page)
Revised: 25 February 2011, last major update August 2010
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

Definition
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● Cell membrane metallopeptidase expressed by early B, pro-B and pre-B lymphocytes, and by lymph node germinal centers
● Also widely distributed in normal tissue, including brush border of small bowel mucosa
● Also expressed in neoplasms (epithelial cells and stroma)

Terminology
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● Also called Common Acute Lymphoblastic Leukemia Antigen (CALLA), neutral endopeptidase 24.11, neprilysin, enkephalinase

Pathophysiology
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● 90-110 kDa cell membrane metallopeptidase at 3q21-27 which inactivates bioactive peptides, including bombesin
● In epithelial cells, CD10 loss from methylation leads to increased cell migration, cell growth and cell survival, contributing to neoplastic development and progression (J Pediatr Hematol Oncol 2010;32:2)
● CD10 is found on non-T ALL cells which derive from pre-B lymphocytes, and in germinal center-related non-Hodgkin lymphoma such as Burkitt lymphoma and follicular lymphoma, but not on leukemia cells or lymphomas which originate in more mature B cells. (J Pediatr Hematol Oncol 2010;32:2)

Uses
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Acute lymphoblastic leukemia (ALL):
● One of the first markers to identify leukemic cells in children (hence its name)

Angioimmunoblastic T cell lymphoma:
● Tumor cells are CD10+ at nodal and extranodal sites other than bone marrow (Am J Surg Pathol 2004;28:54, Hum Pathol 2005;36:784) versus CD10- for other T cell lymphomas, but benign T cells may be CD10+ (Mod Pathol 2003;16:879)

Breast:
● Marker of myoepithelial cells (Mod Pathol 2002;15:397) and mammary myofibroblastoma (Virchows Arch 2007;450:727)
● Decreased CD10 expression may be associated with relapse in DCIS (Cancer Res 2009;69(24 Suppl):Abstract #2112, JCO 2009;27(May 20 Supp):e22053)
● Stromal CD10 expression in invasive carcinoma of the breast is associated with ER negativity, higher tumor grade and decreased survival (Mod Pathol 2007;20:84)

Burkitt's lymphoma:
● Used to confirm diagnosis

Diffuse large cell lymphoma:
● Marker for germinal center phenotype (also bcl6), which is associated with longer survival in some studies (Mod Pathol 2005;18:1113; Arch Pathol Lab Med 2002;126:956-primary intestinal tumors), but not others (Am J Clin Pathol 2001;116:183-only CD10+bcl2+ tumors have poorer survival; Virchows Arch 2004;445:545-no difference in survival)

Ectopic prostate:
● Used to confirm diagnosis in uterus and vagina (Am J Surg Pathol 2006;30:209)

Endometrial stromal tumors:
● Consistently CD10+ vs. CD10- smooth muscle tumors (Mod Pathol 2001;14:465), although leiomyoma and high grade leiomyosarcoma may be CD10+ (Mod Pathol 2002;15:923)

Follicular lymphoma:
● CD10+ may confirm diagnosis (Am J Clin Pathol 2002;117:291)
● CD10+ and bcl6+ patients may have more favorable prognosis (Am J Clin Pathol 2004;121:34)
● High grade follicular lymphomas and interfollicular infiltrates may be CD10- (Am J Clin Pathol 2001;115:862)
● Note: also described in mantle cell lymphoma (Am J Clin Pathol 2004;122:122), marginal zone lymphoma (J Clin Pathol 1999;52:849), other lymphomas with CD5 coexpression (Am J Clin Pathol 2003;119:218, Arch Pathol Lab Med 2001;125:951)

Gynecologic tumors:
● Mesonephric remnants and tumors are CD10+
● CD10 differentiates metastatic renal cell carcinoma (CD10+, Am J Surg Pathol 2003;27:178) from primary clear cell carcinoma (CD10-)
● CD10 is not useful in differentiating muscle invasive endometrial adenocarcinoma (CD10+ desmoplastic stroma) from endometrial adenocarcinoma invading adenomysosis (CD10+ stroma, (Mod Pathol 2003;16:22)
● Atypical polypoid adenomyoma has CD10- stroma with CD10+ squamous morules (internal control) versus myoinvasive endometrial adenocarcinoma with CD10+ desmoplastic stroma (Hum Pathol 2008;39:1446)

Hepatocellular carcinoma vs. nonhepatocellular carcinomas:
● 52-68% sensitive and >95% specific with canalicular pattern (Am J Surg Pathol 2001;25:1297, Am J Surg Pathol 2002;26:978), although another study recommends use of Hepatocyte, MOC31 and pCEA but not CD10 (Mod Pathol 2002;15:1279)

Mesothelioma (malignant):
● Diffuse malignant mesothelioma has patchy, moderately intense cytoplasmic CD10 staining versus intense cytoplasmic and membranous CD10 staining in metastatic renal cell carcinoma (Arch Pathol Lab Med 2006;130:823)

Microvillous inclusion disease:
● Strong CD10+ cytoplasmic staining vs. linear brush border staining in normals (Am J Surg Pathol 2002;26:902)

Multiple myeloma:
● CD10+ and lack of light chain isotype suppression (suppression of normal immunoglobulins containing the light chain of the same isotype as the abnormal paraprotein) in blood lymphocytes are early markers of progressive disease (Br J Haematol 1987;67:39)

Pancreas:
● Solid and pseudopapillary tumor is CD10+ (Am J Surg Pathol 2000;24:1361)
● Differentiates mucinous cystic neoplasms (CD10+/CK20+) from intraductal papillary mucinous neoplasm of branch duct type (CD10-/CK20-) (Pancreas 2009;38:558)
● In pancreatic neuroendocrine tumors, CD10 expression is associated with poor survival, large tumor size, high Ki-67 index, metastases (Hum Pathol 2006;37:802)

Skin Tumors:
● Differentiates trichoblastomas with peritumoral stromal staining and basal cell carcinomas with epithelial staining; if stroma and epithelial areas are CD10+, suggests basal cell carcinoma with follicular differentiation (Int J Dermatol 2009;48:713)
● Differentiates atypical fibroxanthoma (diffuse membranocytoplasmic staining) from spindle cell melanoma and sarcomatoid squamous cell carcinoma (CD10-, J Cutan Pathol 2010;37:744)

Vascular tumors:
● Differentiates hemangioblastoma (CD10-) from metastatic renal cell carcinoma (CD10+, Mod Pathol 2005;18:788)
● Epithelioid hemangioendothelioma can be strong/diffuse CD10+ and mimic metastatic renal cell carcinoma (Arch Pathol Lab Med 2009;133:1965)

Interpretation
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● Apical surface only: malignant glandular cells of well-differentiated colonic, pancreatic and prostatic adenocarcinoma
● Diffuse cytoplasmic or membranous/Golgi patterns: poorly differentiated adenocarcinoma, melanoma, urothelial carcinoma, renal cell carcinoma, endometrial stromal sarcoma (Am J Clin Pathol 2000;113:374)

Positive stains - normal
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Hematopoietic cells:
● Pre-B cells
● Pre-T cells; some T cells
● Follicular center (germinal center) cells
● Granulocytes

Other cells:
● Adrenal cortex
● Brain
● Choroid plexus
● Endometrial stroma
● Endothelial cells
● Fibroblasts
● Genitourinary (male) epithelium
● Hepatocytes
● Kidney microvilli
● Liver
● Mesonephric remnants
● Myoepithelial cells (breast, Mod Pathol 2002;15:397, J Clin Pathol 2004;57:625)
● Ovary
● Placenta (cytotrophoblast, intermediate trophoblast, syncytiotrophoblast)
● Prostate basal and secretory cells
● Small intestine (linear brush border staining)
● Wolffian (but not mullerian) type epithelium

Positive stains - disease
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Leukemia/lymphoma:
● PreB ALL (75%), preT ALL (63%, Arch Pathol Lab Med 2000;124:704)
● Angioimmunoblastic T cell
● Burkitt’s
● CML in blast crisis (90%)
● Diffuse large B cell (variable)
● Follicular center cell (70%)
● Hairy cell leukemia (10%, Am J Clin Pathol 2003;120:228)
● Myeloma (some)
● Plasmablastic (variable)
● Primary cutaneous diffuse large B cell (variable)
● Primary mediastinal B cell (32%, Am J Surg Pathol 2001;25:1277)

Other:
● Breast cancer associated stroma
● Breast metaplastic carcinoma
● Choriocarcinoma
● Colonic carcinoma and high grade dysplasia associated stroma (Hum Pathol 2002;33:806)
● Dermatofibroma
● Dermatofibrosarcoma
● Endometrial adenocarcinoma (may also be present in desmoplastic stroma, Am J Surg Pathol 2003;27:786)
● Endometrial adenomyosis
● Endometrial stromal tumors
● Epithelioid hemangioendothelioma (Arch Pathol Lab Med 2009;133:1965)
● Ewing’s sarcoma
● Gastric carcinoma associated stroma (Jpn J Clin Oncol 2005;35:245)
● Glioma
● Hepatocellular carcinoma (canalicular pattern similar to polyclonal CEA, Am J Pathol 2001;159:1415)
● Malignant fibrous histiocytoma
● Malignant mixed mullerian tumors
● Mammary myofibroblastoma (Virchows Arch 2007;450:727)
● Mediastinal germ cell tumors
● Melanoma (40%, associated with tumor progression, Mod Pathol 2004;17:1251)
● Mesonephric tumors (Am J Surg Pathol 2001;25:1540)
● Mesothelioma (malignant, Arch Pathol Lab Med 2006;130:823)
● Microvillous inclusion disease (strong cytoplasmic staining)
● Mullerian adenosarcoma
● Pancreatic adenocarcinoma (50%)
● Pancreatic solid-pseudopapillary tumor
● Placental site trophoblastic tumor
● Prostate carcinoma (some Gleason pattern 4 and 5 cases)
● Renal cell carcinoma (most clear cell, variable papillary, “aggressive” chromophobe subtypes, Am J Surg Pathol 2000;24:203, Mod Pathol 2005;18:535, Mod Pathol 2004;17:1455)
● Renal cell sarcoma
● Rhabdomyosarcoma (60%) and other sarcomas
● Schwannoma (45%)
● Spindle cell lipoma (Virchows Arch 2007;450:727)
● Tumor of wolffian origin of broad ligament and ovary
● Urothelial carcinoma (54%)
● Uterine cellular leiomyoma (50%)
● Uterine leiomyosarcoma and other uterine sarcomas
● Yolk sac tumor

Negative stains
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Leukemia/lymphomas:
● AML
● Burkitt’s-like
● CLL
● EBV+ lymphoproliferative disorders
● Lymphoplasmacytic
● Mantle cell
● Marginal zone
● Pyothorax associated

Other
● Myeloid and erythroid precursors
● Clear cell carcinomas of female genital tract
● Prostate adenocarcinoma (all Gleason patterns 2 and 3, some 4 and 5)
● High grade PIN and prostatic basal cell hyperplasia (Hum Pathol 2003;34:450)
● CNS hemangioblastoma
● Atypical polypoid adenomyoma (stromal cells)

Micro images
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Leukemia / lymphomas

Diffuse large B cell lymphoma

Pre-T ALL

Reactive T cells may be CD10+

Breast

Myoepithelium Adenosis DCIS

Invasive ductal carcinoma of breast

Endometrial stromal sarcoma

#1: Extrauterine #2: Myxoid-fibrous
Fig 4, inset ER Fig 4

Other uterine lesions

Leiomyoma (focal CD10+)

CD10+ stroma cells in endometriosis

CD10- stromal cells in endometriosis-like tissue

Endometrial adenocarcinoma and adenomyosis

Malignant mixed mullerian tumor

Hepatocellular carcinoma

Canalicular pattern in hepatocellular carcinoma (figure B)

Other

Hemangioblastoma (CD10-) versus metastatic renal cell carcinoma (CD10+)

Melanoma

Metastatic prostate carcinoma

Epithelioid hemangioendothelioma is CD10+

Malignant mesothelioma versus renal cell carcinoma

Flow cytometry images
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CD10+ versus CD10- diffuse large B cell lymphoma

Additional references
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● OMIM 120520, Am J Clin Pathol 2000;113:374, Adv Anat Pathol 2004;11:310 (female genital tract tumors), Am J Clin Pathol 2005;124:371 (urothelial neoplasoms)

End of CD Markers > CD10

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