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D2-40 (Podoplanin)

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 22 September 2012, last major update September 2012 - IN PROGRESS
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.


● 38 kDa membrane mucoprotein originally detected on surface of rat podocytes
● Antibody D2-40 reacts to an O-linked, 40 kDa sialoglycoprotein found on lymphatic endothelium, fetal testis and on the surface of testicular germ cell tumors (also other cells as indicated below)

Additional references to review:
Am J Surg Pathol 2011;35:1441
Arch Pathol Lab Med 2012;136:301
Hum Pathol 2011;42:1596
Mod Pathol 2011;24:502
Mod Pathol 2010;23:434
Med Oncol 2012;Apr 18 [Epub ahead of print]
J Am Acad Dermatol 2012;Apr 19 [Epub ahead of print]
Cell Tissue Res 2012;348:515
J Surg Oncol 2012;105:277
Pediatr Dev Pathol 2011;Dec 9 [Epub ahead of print]
Urol Oncol 2011;Oct 3 [Epub ahead of print]
Am J Dermatopathol 2011;33:669
Pathol Oncol Res 2012;18:365
J Breast Cancer 2011;14:104
Diagn Pathol 2011;6:59
J Am Acad Dermatol 2011;64:1123.e1
Pathol Oncol Res 2011;17:843
Int J Clin Exp Pathol 2011;4:175
J Am Acad Dermatol 2011;64:336
Lung 2011;189:57
Placenta 2011;32:27

Uses by pathologists

● Identify lymphatic endothelium to determine presence of lymphatics in various conditions, as well as origin of vascular tumors (J Histochem Cytochem 2009;57:643)
● Identify lymphatic endothelium to determine lymphatic invasion (Ann Diagn Pathol 2009;13:168)
● Differentiate mesothelioma (positive, even in effusions, Diagn Cytopatho; 2007;35:342) from adenocarcinoma (negative, Cancer 2007;109:933)

Note: prognostic significance of lymphatic invasion using D2-40 versus H&E only is unclear:
● Not clearly significant - breast carcinoma (Mod Pathol 2009;22:216)
● Appears significant - colon carcinoma (Int J Colorectal Dis 2009;24:1069), melanoma (J Cutan Pathol 2009;36:1157, Arch Dermatol 2008;144:462)

Micro images

Lymphatics in normal lymph node (fig A) and normal breast          Mesothelium (pleura)

Skin vessels (normal)               Lymphatics versus endothelium
                                                    (site unspecified)

Angiomyolipoma - lymphatics are prominent          Angiosarcoma and

Colon-ulcerative colitis        Colon-various polyps           Colon-invasive carcinoma

Invasive breast carcinoma - lymphatics are D2-40 positive

Invasive breast carcinoma - lymphatics are D2-40 positive

Kaposiís sarcoma                 Epithelioid                               Kaposiform
                                                angiosarcoma                         hemangioendothelioma

Melanoma lymphatics              Melanoma tumor emboli

Mesothelioma (fig b)                 Follicular dendritic cell tumors

Seminoma of testis                   Embryonal carcinoma of testis

Lymphatic invasion in clear cell renal cell carcinoma

Lymphatic invasion in gastric carcinoma

Lymphatic invasion:             In papillary thyroid carcinoma          In laryngeal squamous
within venous media             angiosarcoma                                    cell carcinoma

Positive staining - normal

● Lymphatic endothelium (Am J Pathol 1999;154:385)
● Adrenal cortical cells (normal and neoplastic, J Clin Pathol 2008;61:293)
● Breast myoepithelium (patchy, Hum Pathol 2008;39:175) in normal and neoplastic breast
● Follicular dendritic cells (Appl Immunohistochem Mol Morphol 2009;17:102)
● Mesothelium - normal and reactive (Mod Pathol 2005;18:105)
● Skin - basal cells of hair follicle outer root sheath (J Cutan Pathol 2008;35:926)
● Developing testis (Virchows Arch 2006;449:200) and developing brain (Mod Pathol 2006;19:974)

Positive staining - disease

● Angiomyolipoma - lymphatics are prominent (Mod Pathol 2006;19:669, Hum Pathol 2009;40:374)
● Angiosarcoma (most, Am J Pathol 1999;1545:385)
● Atypical vascular proliferations of breast post-radiation (Cancer 2007;109:1584)
● Chondroid and chordoid tumors: skeletal myxoid chondrosarcoma (100%), enchondroma (96%), low grade chondrosarcoma (95%), chordoid meningioma (80%) and chordoid glioma (75%), but not chordoma or extraskeletal myxoid chondrosarcoma (Am J Surg Pathol 2009;33:669)
● Crohnís disease (due to increased lymphatics, Virchows Arch 2008;452:57)
● Dysgerminoma (Int J Gynecol Pathol 2009;28:347)
● Epithelioid hemangioendothelioma of liver (Mod Pathol 2008;21:125)
● Follicular dendritic cell tumor (Int J Clin Exp Pathol 2008;1:276)
● Hemangioblastoma (Acta Neuropathol 2005;109:497)
● Kaposiís sarcoma (Am J Pathol 1999;154:385), kaposiform hemangioendothelioma (J Cutan Pathol 2006;33:492)
● Lung - pleomorphic carcinomas (some, Pathol Int 2008;58:771)
● Lymphangioma (Histopathology 2005;46:396)
● Lymphatic invasion in tumors - examples include melanoma (Hum Pathol 2008;39:901), renal cell carcinoma-clear cell type (Mod Pathol 2006;19:746)
● Mesothelioma (Mod Pathol 2006;19:34, Mod Pathol 2005;18:105), including sarcomatoid subtype (Am J Surg Pathol 2008;32:123)
● Schwannoma, occasional neurofibromas or MPNST (Am J Clin Pathol 2008;129:886)
● Seminoma (Am J Clin Pathol 2007;128:767), some embryonal carcinomas of testis (Mod Pathol 2007;20:320)
● Serous cystadenocarcinoma / carcinoma of gynecologic tract (23%, Mod Pathol 2008;21:1147)
● Sinonasal hemangiopericytoma (Virchows Arch 2006;448:459)
● Skin adnexal carcinoma (Am J Surg Pathol 2007;31:304)
● Solitary fibrous tumor (some, Pathol Int 2007;57:618, but see Virchows Arch 2006;448:459)

Negative staining

● Capillary endothelium
● Retiform hemagioendothelioma (usually, Am J Dermatopathol 2008;30:31)

Electron microscopy images

Dermal lymphatics

Additional references

● Comparison of D2-40 and LYVE-1 antibodies (Lymphology 2008;41:103)

End of Stains > D2-40 (Podoplanin)

Ref Updated: 7/3/12

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