Table of Contents
Definition / general | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative stainingCite this page: Stuart L.N. CD34. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd34.html. Accessed June 6th, 2023.
Definition / general
- Commonly used marker of hematopoietic progenitor cells and endothelial cells (OMIM: 142230 [Accessed 25 May 2021])
Terminology
- Also called hematopoietic progenitor cell antigen CD34
- CD34+ stromal cells are called dendritic interstitial cells
Pathophysiology
- Intercellular adhesion protein and cell surface glycoprotein; ligand is CD62L (L-selectin)
- May mediate attachment of hematopoietic stem cells to bone marrow extracellular matrix or directly to stromal cells, although specific function is unknown
- CD34 staining defines adult hematopoietic stem cells but CD34+ cells can also differentiate into neural cells (Exp Neurol 2006;197:399)
Clinical features
- In AML, detection of CD34+ cells by flow cytometry and immunohistochemistry are comparable (Arch Pathol Lab Med 2001;125:1063)
- CD34 staining of peritumoral stroma is positive in gastric adenocarcinoma diffuse type invading muscularis propria but negative in (J Clin Pathol 2001;54:846):
- Breast carcinoma (J Clin Pathol 2003;56:271)
- Colorectal adenocarcinoma (J Clin Pathol 2000;53:626)
- Gastric adenocarcinoma intestinal type and gastric adenocarcinoma diffuse type confined to submucosa (J Clin Pathol 2004;57:183)
Interpretation
- Membranous stain
- Endothelium acts as a positive internal control
- Staining represents presence of protein, not cross reactivity, despite wide range of tissues that are CD34+ (Am J Pathol 2000;156:21)
Uses by pathologists
- Dermatopathology and soft tissue:
- Distinguish CD34+ dermal neoplasms such as Kaposi’s sarcoma, dermatofibrosarcoma protuberans / DSFP (both CD34+) and epithelioid sarcoma (often CD34+) from dematofibroma (CD34-)
- Distinguish solitary fibrous tumor (CD34+) from desmoplastic mesothelioma (CD34-) (Hum Pathol 1995;26:428)
- Distinguish hemangiopericytoma (CD34+) from endometrial stromal sarcoma (CD34-) (Mod Pathol 2005;18:40)
- Classify other soft tissue tumors
- Hematopathology:
- Distinguish lymphocyte rich thymoma (CD34+ cells) from T-ALL (usually CD34-) (Am J Clin Pathol 2004;121:268)
- Quantify and purify lymphohematopoietic stem cell / progenitor cells for research and for clinical bone marrow transplantation (Folia Histochem Cytobiol 2006;44:53, Breast Cancer 2005;12:178)
- Identify blasts in general and in hypoplastic marrows (Am J Clin Pathol 2010;134:749)
- Distinguish acute leukemia and myelodysplastic syndrome (CD34+ blasts present) from aplastic anemia (no blasts / low marrow CD34+ cells) (Leukemia 2006;20:458)
- Identify hematogones and megakaryocytes (CD34+) but not all myeloblasts are CD34+ (Arch Pathol Lab Med 2002;126:823)
- May support diagnosis of essential thrombocythemia
- Poor prognostic factor in newly diagnosed AML (Neoplasma 2005;52:402)
- Other:
- Determine vascularization of tumors or disease processes (Saudi Med J 2006;27:154)
- Distinguish vascular invasion (CD34+) from displaced epithelium (CD34-) (J Clin Pathol 2002;55:780)
- Confirm diagnosis of GIST (Arch Pathol Lab Med 2002;126:1189)
- May confirm diagnosis of chronic intestinal pseudo-obstruction (Am J Surg Pathol 2003;27:228)
- Use with other stains to distinguish meningeal solitary fibrous tumor-hemangiopericytoma from meningioma (Am J Surg Pathol 2015;39:1377)
- Determine microvessel density; high microvessel density (using CD34) is associated with:
- Poorer prognosis in esophageal squamous cell carcinoma (J Clin Pathol 2001;54:940)
- Poor survival in non-small cell lung cancer (J Clin Pathol 2004;57:591)
- PSA recurrence of prostate cancer (Am J Clin Pathol 2000;113:555)
Microscopic (histologic) images
Positive staining - normal
- Endothelium of blood vessels (including alveolar wall capillaries and glomeruli but not hepatic sinusoids or splenic sinusoids) (J Histochem Cytochem 2006;54:385), endothelium of some lymphatics
- Hematopoietic progenitor cells / hematogones (less mature) (Am J Clin Pathol 2009;132:573)
- Also dendritic interstitial cells, dermal dendrocytes, endometrial stroma, endoneurium (Mod Pathol 2003;16:293), fibroblasts, fibrocytes, follicle cells, interstitial cells of Cajal (20%) (Am J Pathol 2000;156:1157), mast cells, megakaryocytes, neural stem cells in CNS (Exp Neurol 2006;197:399), osteoblasts, perivascular stroma, umbilical cord blood (J Clin Pathol 2001;54:428), vascular adventitial fibroblastic cells in stomach
Positive staining - disease
- Acral pseudolymphomatous angiokeratoma of children (APACHE) (J Cutan Pathol 2015;42:50), acute lymphoblastic leukemia-preB (Am J Clin Pathol 2009;132:940, Am J Clin Pathol 2004;121:512), alveolar soft part sarcoma, AML (40 - 60%) (Arch Pathol Lab Med 2003;127:42), anal skin tags, angioblastoma / tufted angioma (J Clin Pathol 2005;58:214), angiofibroma-cellular (50%, Mod Pathol 2011;24:82), angiomyofibroblastoma (variable, Arch Pathol Lab Med 2000;124:1679), angiosarcoma (70%, Am J Surg Pathol 1998;22:683), atypical fibrous histiocytoma of skin (focal in 10%, Am J Surg Pathol 2002;26:35)
- Benign epithelioid peripheral nerve sheath tumor (fibroblasts are CD34+, Am J Surg Pathol 2005;29:39), benign stromal spindle cell tumors, blood vessels in tumors
- Calcifying fibrous pseudotumor (Int J Surg Pathol 2002;10:189), cellular angiofibroma (60%, Am J Surg Pathol 2004;28:1426), cellular blue nevus, cellular digital fibroma (J Cutan Pathol 2005;32:413), chordoid glioma (focal, Am J Surg Pathol 2002;26:1330), chronic myelomonocytic leukemia, congenital / infantile fibrosarcoma, cystic panfolliculoma-surrounding fibrotic stroma is CD34+ (Arch Pathol Lab Med 2006;130:389)
- Dendritic fibromyxolipoma, dendritic interstitial cells at margin of salivary gland tumors (Arch Pathol Lab Med 2001;125:232), dermal dendrocytoma (Am J Dermatopathol 2002;24:50), dermatofibrosarcoma protuberans (Br J Dermatol 1992;127:79, Am J Surg Pathol 2003;27:27)
- Elastofibroma (spindle cells), epithelioid hemangioendothelioma (Am J Clin Pathol 1991;96:25), epithelioid sarcoma (50%, Hum Pathol 1999;30:934, Am J Surg Pathol 1997;21:130)
- Fibroadenoma (breast), fibroblastic connective tissue nevus (Am J Surg Pathol 2012;36:1509), fibromas with solitary fibrous tumor-like features, fibrous hamartoma of infancy (Am J Surg Pathol 2014;38:394)
- Ganglioglioma, Gardner type fibroma of soft tissue, glioneural hamartoma, gastric carcinoma-diffuse type (vascular adventitial fibroblastic cells, J Clin Pathol 2004;57:970), gastrointestinal stromal tumor (50-80%, Am J Surg Pathol 2005;29:52), giant cell angiofibroma (Am J Surg Pathol 2000;24:971), giant cell fibroblastoma (Am J Surg Pathol 2003;27:27), glomus tumor / glomangioma (variable, J Cutan Pathol 1993;20:15, Tohoku J Exp Med 1997;182:241), granulocytic sarcoma (47%, Arch Pathol Lab Med 2001;125:1448)
- Hamartomatous tumors of chronic drug resistant epilepsy, hemangioblastoma, hemangioendothelioma, hemangioma (variable, Am J Surg Pathol 1999;23:97), hemosiderotic fibrohistiocytic lipomatous lesion, hepatic sinusoids in conditions associated with altered vascular flow and neoplasms, hepatocellular carcinoma (staining of almost all sinusoidal spaces, Am J Surg Pathol 2008;32:433)
- Inflammatory fibrous polyps of stomach / GI tract (Hum Pathol 2002;33:307, Am J Surg Pathol 2004;28:107)
- Juxtaglomerular cell tumor (may be focal, Am J Clin Pathol 2001;116:854, Am J Surg Pathol 2004;28:1098)
- Kaposiform hemangioendothelioma (Am J Surg Pathol 2004;28:559), Kaposi sarcoma (90%, strong and diffuse in spindle cells), Kaposi sarcoma-like pyogenic granuloma (J Clin Pathol 2002;55:619)
- Lipomatous hemangiopericytoma, lipomatous tumors (benign and malignant, Am J Surg Pathol 1997;21:195), liposarcoma (myxoid, pleomorphic, well-differentiated, Am J Surg Pathol 2002;26:601), lymphangioma (50%, Hum Pathol 2005;36:426), lymphangioendothelioma, lymphatic endothelial cells in tumors (Am J Pathol 2006;168:1045)
- Malignant fibrous histiocytoma, malignant peripheral nerve sheath tumors (low grade stronger / more frequent than high grade, Am J Surg Pathol 2003;27:1337), meningioma (some, Am J Surg Pathol 2002;26:125), metanephric adenofibroma (often), metanephric adenosarcoma of kidney(stroma only, Am J Surg Pathol 2001;25:1451), metanephric stromal tumorof kidney (patchy, Am J Surg Pathol 2000;24:917), microcystic adnexal carcinoma (Am J Surg Pathol 2001;25:464), mucosal epithelioid nerve sheath tumors (Am J Surg Pathol 2005;29:1310), myelodysplastic syndrome (myeloid blasts), myofibroblastoma (breast, cervicovaginal, soft tissue, Am J Surg Pathol 2001;25:1022), myxofibrosarcoma (38%, J Clin Pathol 2003;56:666), myxoma of heart, myxoma of soft tissue (50%)
- Neurofibroma (may be focal, Am J Clin Pathol 2000;114:123), nuchal fibrocartilaginous pseudotumor of soft tissue, nuchal type fibroma
- Onychomatricoma (Am J Dermatopathol 2010;32:1), papillary thyroid carcinoma, paratesticular leiomyosarcoma (30%), paratesticular fibrous pseudotumor (Am J Surg Pathol 2010;34:569), periductal stromal sarcoma of breast (Am J Surg Pathol 2003;27:343), perineurioma (variable, Am J Surg Pathol 2005;29:859), phyllodes tumor of breast (more common if benign, J Surg Res 2000;94:84), pleomorphic fibroma of skin, pleomorphic hyalinizing angiectatic tumor (Arch Pathol Lab Med 2000;124:423), primary renal myxofibrosarcoma (Pathol Res Pract 2015;211:619), pseudoangiomatous stromal hyperplasia of breast (J Clin Pathol 1998;51:204, Am J Surg Pathol 1995;19:270), pseudocyst of adrenal gland
- Reactive angioendotheliomatosis of skin
- Schwannoma (Antoni B areas, Am J Clin Pathol 2000;114:123), sclerosing angiomatoid nodular transformation of spleen (capillaries, Am J Surg Pathol 2004;28:1268), sclerosing hemangioma of lung, sclerosing liposarcoma (spindle and atypical cells), solitary fibrous tumor (Am J Surg Pathol 1994;18:992, Hum Pathol 1995;26:440, expression may be lost in high grade areas, Am J Surg Pathol 2009;33:1314), solitary sclerotic fibroma of skin (J Cutan Pathol 2003;30:631), spindle cell epithelioma of vagina, spindle cell lipoma / pleomorphic lipoma, storiform collagenoma, stromal sarcoma of prostate, subconjunctival herniated orbital fat (Am J Surg Pathol 2007;31:193), superficial acral fibromyxoma (Hum Pathol 2001;32:704), superficial cervicovaginal myofibroblastoma, superficial CD34-positive fibroblastic tumor (Pathology 2015;47:479)
- Thymoma (ectopic hamartomatous variant; otherwise weak (Am J Surg Pathol 2005;29:1208), transient myeloproliferative disorder (staining of blasts, Am J Clin Pathol 2001;116:204)
- Vaginal mixed tumor / spindle cell epithelioma (Mod Pathol 2004;17:1243), vulvar fibroma-prepubertal (Am J Surg Pathol 2004;28:1601)
Negative staining
- Normal hepatic sinusoids, bone marrow mast cells
- Adenomatoid tumor (Am J Surg Pathol 2003;27:969), angiomyxofibromatous tumor (Am J Surg Pathol 2006;30:545), anaplastic sarcoma of kidney, angiomyolipoma
- Benign fibrous histiocytoma (but deep tumors are often CD34+), benign vascular proliferations in irradiated skin (Am J Surg Pathol 2002;26:328)
- Calcifying aponeurotic fibroma of soft tissue, carcinoma, chondromyxoid fibroma, clear cell sarcoma of kidney
- Desmoplastic fibroblastoma
- Epithelioid sarcoma-like hemangioendothelioma (Am J Surg Pathol 2003;27:48, Ewing sarcoma / PNET
- Fibroblastic polyp of colon (may be weak / focal, Am J Surg Pathol 2004;28:374), fibroepithelial polyp of renal pelvis, fibromatosis (J Clin Pathol 2004;57:1119, Am J Surg Pathol 2002;26:1296), follicular dendritic cell sarcoma
- Giant cell tumor of tendon sheath, gliosarcoma (Arch Pathol Lab Med 1997;121:129)
- Hemangioblastoma, hibernoma (but spindle cell subtype is CD34+), histiocytic sarcoma (Am J Surg Pathol 2004;28:1133)
- Inflammatory myofibroblastic tumor, interdigitating dendritic cell sarcoma (Am J Surg Pathol 2002;26:530)
- Leiomyoma (usually, Am J Surg Pathol 2001;25:1355) and vascular leiomyoma (J Clin Pathol 2002;55:395), leiomyosarcoma (usually), leukemia cutis (Am J Clin Pathol 2009;132:101), littoral cell angioma of spleen (Am J Surg Pathol 1997;21:827), low grade fibromyxoid sarcoma
- Mammary NOS-type sarcoma (Am J Surg Pathol 2006;30:450), melanoma (rarely CD34+, J Cutan Pathol 2005;32:685), mesothelial cyst (Am J Surg Pathol 1997;21:334), mesoplastic nephroma, metaplastic carcinoma of breast-spindle cell type, multicentric reticulohistiocytosis, myelolipoma (Am J Surg Pathol 2006;30:838), myoepithelioma of breast, myofibrosarcoma of breast, , myoid gonadal stromal tumor (Am J Clin Pathol 2014;142:675), myointimoma
- Nodular fasciitis
- Ossifying fibromyxoid tumor (Diagn Cytopathol 2015;43:646), PEComa (Am J Surg Pathol 2005;29:1558), pigmented villonodular synovitis, plexiform fibrohistiocytic tumor, plexiform fibromyxoma (Am J Surg Pathol 2009;33:1624), plexiform xanthomatous tumor (Am J Surg Pathol 2002;26:1302), pseudomycogenic hemangioendothelioma (Am J Surg Pathol 2011;35:190)
- Reactive fibroblastic and myofibroblastic proliferation of vulva (Am J Surg Pathol 2011;35:110)
- Schwannoma, sclerosing epithelioid fibrosarcoma of the kidney (Diagn Pathol 2015;10:186), sclerosing epithelioid fibrosarcoma of soft tissue, sclerosing hemangioma of lung (Hum Pathol 2004;35:503), sclerosing paraganglioma (Head Neck Pathol 2015;9:300), sclerosing perineurioma, sinonasal hemangiopericytoma (Arch Pathol Lab Med 2001;125:686), synovial sarcoma (focal in 6% of monophasic tumors, Am J Surg Pathol 2002;26:1434)
- Thymoma