D2-40 (Podoplanin)

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Stains & CD markers
D2-40 (Podoplanin)

Authors: Kemal Kösemehmetoğlu, M.D., Nat Pernick, M.D.

Editorial Board Member: Christian M. Schürch, M.D., Ph.D.

Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.

Last author update: 19 November 2021

Last staff update: 19 November 2021

Copyright: 2003-2022, PathologyOutlines.com, Inc.

PubMed Search: Podoplanin D2-40 [TIAB]

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Table of Contents

Cite this page: Kösemehmetoğlu K, Pernick N. D2-40 (Podoplanin). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsD240.html. Accessed May 18th, 2022.

Definition / general

Podoplanin is a 40 kDa, transmembrane, oncofetal, O linked sialoglycoprotein (mucin type) found on lymphatic endothelium, mesothelium and fetal testis (also other cells as indicated below)
D2-40 is a monoclonal antibody that reacts to podoplanin
Podoplanin expression is encoded by the PDPN gene (1p36.21) and regulated by the PROX1 gene

Essential features

D2-40 is a monoclonal antibody that reacts to podoplanin showing membranous staining
Mostly used to show lymphatics (e.g. lymphovascular invasion) and lymphatic differentiation in vascular tumors
Also useful as a part of IHC panel in mesothelioma versus adenocarcinoma and seminoma versus nonseminoma differentiation

Terminology

Podoplanin is also known as Aggrus, OTS8, gp36, M2A and T1A2

Pathophysiology

Increases endothelial cell adhesion, migration and tube formation
Platelet aggregation (Aggrus)
Barrier function in high endothelial venules
Maintenance of physical elasticity of lymph nodes
Reference: OMIM: Podoplanin; PDPN [Accessed 28 October 2021]

Interpretation

Membranous staining (Adv Anat Pathol 2006;13:83)
Dot-like (e.g. ependymoma) (Clin Neuropathol 2009;28:373)

Uses by pathologists

Limited use because of lack of specificity; most efficient in IHC when used in an IHC panel
To determine presence of lymphatics in various conditions (Am J Surg Pathol 2015;39:1511)
Confirmation of lymphovascular invasion (Ann Diagn Pathol 2009;13:168, Mod Pathol 2007;20:183, Mod Pathol 2009;22:216, Int J Colorectal Dis 2009;24:1069, J Cutan Pathol 2009;36:1157, Arch Dermatol 2008;144:462, Hum Pathol 2008;39:901, Am J Surg Pathol 1989;13:177)
Dermatopathology, bone and soft tissue pathology:
- Unlike other vascular markers (CD34, CD31, ERG, FLI1), D2-40 expression is limited to lymphatic differentiation
- To identify lymphatic differentiation in evaluation of vascular tumors
- Also expressed in a subset of angiosarcomas and Kaposi sarcomas, reflecting lymphatic differentiation in some of these tumors (Histopathology 2005;46:396, Mod Pathol 2002;15:434)
- Dermatofibroma (+) versus dermatofibrosarcoma protuberans (DFSP) (-) (Mod Pathol 2010;23:434)
- Primary skin adnexal tumors (+) versus metastatic adenocarcinoma (-) (Am J Dermatopathol 2018;40:389, J Cutan Pathol 2010;37:403)
- Chondrosarcoma (+) versus chordoma (-) (Acta Neuropathol 2007;113:87)
Uropathology:
- Seminoma (+) versus nonseminoma (-)
- Note that some embryonal carcinomas may also express D2-40 up to 30% (Virchows Arch 2006;449:200, Mod Pathol 2007;20:320)
- In situ germ cell neoplasm (+)
- Adrenocortical neoplasms (+) versus renal cell carcinoma (-) (J Clin Pathol 2008;61:293)
- Utility in distinguishing intraductal spread of urothelial carcinoma from prostatic stromal invasion (Anticancer Res 2008;28:2997)
Thoracic pathology:
- Mesothelioma (+), even in effusions, versus adenocarcinoma (-) (Diagn Cytopathol 2007;35:342, Cancer 2007;109:933)
- Note the presence of expression in significant proportion of ovarian, lung and breast carcinomas (30 - 50%) (Am J Surg Pathol 2006;30:878)
Hemangioblastoma (+) versus clear cell renal cell carcinoma metastasis

Prognostic factors

Controversial results of prognostic significance in detecting lymphovascular invasion with D2-40 compared to H&E in breast and other cancers (Mod Pathol 2009;22:216, Mod Pathol 2007;20:183, Hum Pathol 2018;77:98, Cancer Med 2016;5:3121, Anticancer Res 2008;28:2997, Cancer Lett 2007;246:167)
D2-40 expression in cutaneous squamous cell carcinoma (SCC) is associated with metastasis and poor prognosis (J Histotechnol 2020;43:147, J Cutan Pathol 2017;44:144, J Am Acad Dermatol 2012;67:1310)

Microscopic (histologic) images

Contributed by Kemal Kemal Kösemehmetoğlu, M.D. and Debra Zynger, M.D.

Dysgerminoma

D2-40 in dysgerminoma

Tumor emboli or not?

D2-40 against lymphatic emboli

Dermal breast cancer lymhatic emboli or not?

D2-40 proves lymphatic emboli

Schwannoma

D2-40 expression in schwannoma

Ependymoma

D2-40 expression in ependymoma

Kaposi sarcoma

D2-40 expression in Kaposi sarcoma

Lymphatic malformation

D2-40 expression
proves lymphatic
malformation

Differential endoothelial D2-40 expression

Differential endothelial
D2-40 expression

D2-40 expression in MIFS

Cecal lymphangioma

D2-40 in cecal lymphangioma

Kaposiform hemangio-endothelioma

D2-40 in kaposiform hemangio-endothelioma

Malignant mesothelioma

D2-40 in malignant mesothelioma

Sarcomatoid areas of malignant mesothelioma

D2-40 in sarcomatoid malignant mesothelioma

Seminoma with IHC

D2-40

Testis

D2-40 in prostate basal cells

Virtual slides

Images hosted on other servers:

Blood vessels, tufted hemangioma

Brain, angiomatous meningioma

Breast, Paget disease of the nipple

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, in normal and neoplastic breast (Hum Pathol 2008;39:175)
Follicular dendritic cells (Appl Immunohistochem Mol Morphol 2009;17:102)
Granulosa cells (Am J Pathol 2005;166:913)
Mesothelium, normal and reactive (Mod Pathol 2005;18:105)
Prostatic basal cells (Anticancer Res 2008;28:2997)
Odontogenic epithelial cells (J Oral Pathol Med 2017;46:618)
Skin, basal cells of hair follicle outer root sheath (J Cutan Pathol 2008;35:926)
Developing testis (Virchows Arch 2006;449:200)
Developing brain (Mod Pathol 2006;19:974)
Basal cells of squamous mucosal epithelium (tonsil, esophagus)

Positive staining - disease

Soft tissue tumors
- Vascular tumors / lesions
  - Angiosarcoma (40 - 80%) (Am J Pathol 1999;154:385, Histopathology 2005;46:396, Mod Pathol 2002;15:434)
  - Kaposi sarcoma (100%) (Am J Pathol 1999;154:385, Histopathology 2005;46:396, Mod Pathol 2002;15:434)
  - Kaposiform hemangioendothelioma (95 - 100%) (J Cutan Pathol 2006;33:492, Mod Pathol 2005;18:1454)
  - Atypical vascular proliferations of breast postradiation (Cancer 2007;109:1584)
  - Epithelioid hemangioendothelioma of liver (80%) (Mod Pathol 2008;21:125)
  - Lymphatic malformations (Histopathology 2005;46:396)
- Dermatofibroma, including cellular variant (Mod Pathol 2010;23:434)
- Sinonasal hemangiopericytoma (Virchows Arch 2006;448:459)
- Solitary fibrous tumor (some, Pathol Int 2007;57:618 but see Virchows Arch 2006;448:459)
- Myxoinflammatory fibroblastic sarcoma (80 - 90%) (Am J Surg Pathol 2014;38:1)
CNS tumors
- Myoxid / chondromyxoid lesions of CNS:
  - 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 (Mod Pathol 2006;19:746, Acta Neuropathol 2007;113:87)
- Hemangioblastoma (Acta Neuropathol 2005;109:497)
- Schwannoma, most of epithelioid malignant peripheral nerve sheath tumors (MPNSTs), occasional neurofibromas or MPNSTs (Am J Clin Pathol 2008;129:886)
- Ependymoma but also widely expressed in other CNS tumors, such as meningioma, glioblastoma, choroid plexus tumors, pilocytic astrocytoma (Clin Neuropathol 2009;28:373, Virchows Arch 2006;448:493)
Follicular dendritic cell tumor (Int J Clin Exp Pathol 2008;1:276)
Malignant mesothelioma, including sarcomatoid subtype (Mod Pathol 2006;19:34, Mod Pathol 2005;18:105, Am J Surg Pathol 2008;32:123)
Germ cell tumors
- Gonadal / extragonadal seminoma (dysgerminoma) (Am J Clin Pathol 2007;128:767, Int J Gynecol Pathol 2009;28:347)
- Some (30%) embryonal carcinomas of testis (Mod Pathol 2007;20:320)
Epithelial neoplasia / carcinomas
- Serous carcinoma of gynecologic tract (ovarian 23%, endometrial 43%) (Mod Pathol 2008;21:1147)
- In effusion cytology, ovarian (58%), lung (33%), breast (30%), adenocarcinomas of unknown origin (42%), usually focal staining in contrast to mesothelioma (Mod Pathol 2005;18:105)
- Squamous cell carcinoma (80%) (Am J Pathol 2005;166:913)
- Lung, pleomorphic carcinomas (33%) (Pathol Int 2008;58:771)
- Skin, adnexal carcinoma (Am J Surg Pathol 2007;31:304)
- Adrenocortical carcinomas (J Clin Pathol 2008;61:293)
- Ameloblastic tumors (most) (J Oral Pathol Med 2017;46:618)
Renal angiomyolipoma, lymphatics are prominent; not in liver angiomyolipoma (Mod Pathol 2006;19:669, Hum Pathol 2009;40:374, Mod Pathol 2008;21:125)
Crohn's disease due to increased lymphatics (Virchows Arch 2008;452:57)

Negative staining

Capillary endothelium
Glomus tumor (Histopathology 2005;46:396)
Retiform hemangioendothelioma, usually (Am J Dermatopathol 2008;30:31)
Dermatofibrosarcoma protuberans (DFSP) (Mod Pathol 2010;23:434)
Chordoma (Acta Neuropathol 2007;113:87)
Clear cell renal cell carcinoma (Acta Neuropathol 2005;109:497)

Electron microscopy images

Images hosted on other servers:

Dermal lymphatics

Sample pathology report

Right breast, core biopsy:
- Infiltrative ductal carcinoma, grade II (see comment)
- Comment: The presence of lymphovascular invasion was supported by D2-40, which highlighted lymphatic endothelium of vessels with tumor emboli.

Additional references

Adv Anat Pathol 2009;16:23

Board review style question #1

Which of the markers is expressed in the tumor shown above?

AFP
CD20
CD30
D2-40
Inhibin

Board review style answer #1

D. D2-40

Comment Here

Reference: D2-40 (Podoplanin)

Board review style question #2

In which of the following differential diagnoses is D2-40 useful?

Adrenocortical carcinoma versus adrenocortical adenoma
Kaposi sarcoma versus angiosarcoma
Mesothelioma versus squamous cell carcinoma
Prostatic stromal invasion versus intraductal spread of urothelial carcinoma
Seminoma versus in situ germ cell neoplasm

Board review style answer #2

D. Prostatic stromal invasion versus intraductal spread of urothelial carcinoma

Comment Here

Reference: D2-40 (Podoplanin)

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