Lymphangiosis carcinomatosa in squamous cell carcinomas of larynx and hypopharynx – value of conventional evaluation and additional immunohistochemical staining of D2-40

Abstract

Background: Recent studies revealed a predictive value of lymphatic vessel invasion (L1) for the nodal metastasizing and poor prognosis in malignant tumors at different sites. The monoclonal antibody D2-40 (podoplanin) stains specifically endothelial cells of lymphatic vessels and improves the search for L1. However, the importance of this immunohistochemical staining was not investigated in squamous cell carcinomas (SCC) of larynx and hypopharynx.

Impact of podoplanin expression in oral squamous cell carcinoma: clinical and histopathologic correlations

“…Recent studies identified podoplanin as a potential predictor of lymphatic dissemination in OSCC [1,23,25,26]. Podoplanin is a mucin-type transmembrane glycoprotein that is specifically expressed in lymphatic endothelial cells but not in blood endothelial cells [27,28].…”

Head and neck squamous cell carcinoma lymphatic spread and survival: Relevance of vascular endothelial growth factor family for tumor evaluation

“…Podoplanin is a glycoprotein that is recognized by the monoclonal antibody D2–40, which is considered the most reliable marker of lymphangiogenesis . Zhao et al examined podoplanin expression in OSCC and reported the proliferation of intratumoral and peritumoral lymphatics, suggesting that the spread of metastatic cells also occurs via intratumoral vessels.…”

“…44 Podoplanin is a glycoprotein that is recognized by the monoclonal antibody D2-40, which is considered the most reliable marker of lymphangiogenesis. 14,17,18,22,23,26,45 Zhao et al 26 examined podoplanin expression in OSCC and reported the proliferation of intratumoral and peritumoral lymphatics, suggesting that the spread of metastatic cells also occurs via intratumoral vessels. Jin et al 46 have argued that the intratumoral region contains no functional lymphatic vessels and that lymphatic vessels in the tumor margin facilitate dissemination of tumor cells in non-small cell lung cancer.…”

“…Podoplanin is a 38-kDa membrane glycoprotein that is recognized by the monoclonal antibody D2-40, which has been used in research and clinical practice to distinguish lymphatic endothelium from endothelial cells of blood vessels (the latter does not express podoplanin). 14,18,22,23 Patients with a high lymphatic vessel density (LVD) are at increased risk for lymph node metastasis, supporting the hypothesis that LVD mediates lymphatic spread in oral carcinoma. 17,21,22,24 Based on findings that metastatic spread of head and neck tumors usually occurs via the lymphatic system and because lymphangiogenesis studies in various cancers have generated contradictory results, we measured the expression of lymphangiogenesis markers in HNSCC by immunohistochemistry.…”

“…One of the most reliable markers that is used to determine the presence of lymphatic vessels is podoplanin. Podoplanin is a 38‐kDa membrane glycoprotein that is recognized by the monoclonal antibody D2‐40, which has been used in research and clinical practice to distinguish lymphatic endothelium from endothelial cells of blood vessels (the latter does not express podoplanin) . Patients with a high lymphatic vessel density (LVD) are at increased risk for lymph node metastasis, supporting the hypothesis that LVD mediates lymphatic spread in oral carcinoma …”