Low Molecular Weight Cytokeratin Immunohistochemistry Reveals That Most Salivary Gland Warthin Tumors and Lymphadenomas Arise in Intraparotid Lymph Nodes

The nature of the lymphoid stromal component in Warthin tumor and lymphadenoma of the parotid gland has been a controversial topic in salivary gland pathology for decades. Two theories exist: first, that these tumors arise from salivary gland inclusions within intraparotid lymph nodes; and second, that they arise within salivary gland parenchyma and induce tumor-associated lymphoid proliferation (TALP). A recent study demonstrated that low molecular weight cytokeratin is effective in distinguishing salivary gland tumors within lymph nodes from those inducing TALP via identification of extrafollicular reticulum cells, which are only found in true lymph nodes. Twenty-one Warthin tumors and 4 lymphadenomas were retrieved from the archives of the Department of Pathology at University of Texas Southwestern Medical Center. Cam5.2 immunohistochemistry was performed on each case and independently evaluated by two pathologists. Extrafollicular reticulum cells were identified by Cam5.2 immunostaining in 21 of 21 Warthin tumors (100%), and 3 of 4 lymphadenomas (75%). Extrafollicular reticulum cells were consistently localized to the perisinusoidal and paracortical areas of the lesions studied. Extrafollicular reticulum cells were identified via low molecular weight cytokeratin Cam5.2 immunohistochemistry in all of the Warthin tumors and most of the lymphadenomas evaluated. This finding strongly supports the notion that these most if not all of these tumors arise within intraparotid lymph nodes, presumably from salivary gland inclusions entrapped during embryonic development.