Podoplanin

Synonyms: D2-40, PDPN

by Jan Klos

Background

It is a 40 kDa O-linked sialoglycoprotein known as oncofoetal M2A. It is integral membrane glycoprotein with diverse distribution in human tissues. The physiological function is largely unknown and may be related to its mucin-type character.

Staining pattern is predominantly membranous with some cytoplasmic positivity.

Staining in normal tissues

This antigen is expressed by a variety of tissues, including endothelial cells in lymphatic vessels but not  endothelium in blood vessels, mesothelial cells, adrenal cortical cells, myoepithelial cells in breast, follicular dendritic cells and foetal testes, lung alveolar cells, kidney podocytes, and neural tissue.

Staining in tumors

More than 90% of Kaposi`s sarcomas are positive but only 40% angiosarcomas show positive staining. Positivity is reported in more than 80% of hemangioblastomas (clear cells). Antibody reacts mainly with epithelioid component of mesotheliomas (85-100%) showing diffuse predominantly membranous reactivity often along apical surface of the cells. Sarcomatoid component of mesothelioma shows usually weaker staining and sometimes may be negative. Primary skin adnexal carcinomas and benign skin adnexal tumors show variable positivity but metastatic carcinomas are negative. Squamous cell carcinoma of the skin is positive.

Germ cell tumors

Uniform strong predominantly membrane staining was reported in 100% of seminomas and germ cell neoplasia in situ. Focal staining in 69% of embryonal carcinomas, 29% of teratomas and 25% of yolk sac tumors is also reported. Immature Sertoli cells are also positive.

Mesenchymal tumors

Strong reactivity is reported in meningiomas, schwannomas, GIST, leiomyosarcomas, epithelioid component of synovial sarcomas and chondroid tumors. Some reactivity is seen also in solitary fibrous tumors, dermatofibromas, desmoids and malignant peripheral nerve sheath tumors (MPNST). Pseudoangiomatous stromal hyperplasia (PASH) of the breast is as a rule negative however rare positive cases are reported.
Some spindle cell melanomas are also reported positive.

Only certain usually low percentage of lung and breast carcinomas is positive while majority of adenocarcinomas in other organs are negative. Serous carcinomas of the ovary may show weak focal membranous staining (15-65%). No reactivity with other carcinomas has been reported.

Application

  • Differential diagnosis of mesothelioma as one of the first line mesothelial markers (in addition to Calretinin, WT-1 andCK5/6) vs. metastatic adenocarcinoma (first line carcinoma markers: EP-CAM, m-CEA, ER/PgR, organ/tissue specific markers like TTF-1, CDX-2, PSA etc)
  • Primary skin adnexal tumors vs. metastatic carcinomas
  • Supporting diagnosis of Kaposi`s sarcoma
  • Confirming diagnosis of seminoma and ITGCN
  • Identification of lymphatic vessels (in neoplastic tissue, immunostaining of lymphatic endothelium has been shown to be useful in identifying lymphatic invasion of primary tumors).

Selected references

  1. Bandarchi B1, Ma L, Marginean C, et al. D2-40, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans. Mod Pathol. 2010 Mar;23(3):434-8. doi: 10.1038/modpathol.2009.176. Epub 2010 Jan 8.
  2. Bowman E, Oprea G, Okoli J, et al. Pseudoangiomatous stromal hyperplasia (PASH) of the breast: a series of 24 patients. Breast J. 2012 May-Jun;18(3):242-7. doi: 10.1111/j.1524-4741.2012.01230.x. PMID: 22583194
  3. Browning L1, Bailey D, Parker A. D2-40 is a sensitive and specific marker in differentiating primary adrenal cortical tumours from both metastatic clear cell renal cell carcinoma and phaeochromocytoma. J Clin Pathol. 2008 Mar;61(3):293-6. Epub 2007 Jul 27.
  4. Chu AY1, Litzky LA, Pasha TL, et al. Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma. Mod Pathol. 2005 Jan;18(1):105-10.
  5. Debelenko LV1, Perez-Atayde AR, Mulliken JB, et al. D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma. Mod Pathol. 2005 Nov;18(11):1454-60.
  6. Huse JT1, Pasha TL, Zhang PJ. D2-40 functions as an effective chondroid marker distinguishing true chondroid tumors from chordoma. Acta Neuropathol. 2007 Jan;113(1):87-94. Epub 2006 Sep 26.
  7. Liang H1, Wu H, Giorgadze TA, et al. Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Am J Surg Pathol. 2007 Feb;31(2):304-10.
  8. Marks A1, Sutherland DR, Bailey D, et al. Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours. Br J Cancer. 1999 May;80(3-4):569-78.
  9. Ordóñez NG1. Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Arch Pathol Lab Med. 2005 Nov;129(11):1407-14.
  10. Rabban JT1, Chen YY. D2-40 expression by breast myoepithelium: potential pitfalls in distinguishing intralymphatic carcinoma from in situ carcinoma. Hum Pathol. 2008 Feb;39(2):175-83. doi: 10.1016/j.humpath.2007.06.018.
  11. Roy S1, Chu A, Trojanowski JQ, et al. D2-40, a novel monoclonal antibody against the M2A antigen as a marker to distinguish hemangioblastomas from renal cell carcinomas. Acta Neuropathol. 2005 May;109(5):497-502. Epub 2005 Apr 27.