Low Molecular Weight Cytokeratin Immunostaining for Extrafollicular Reticulum Cells is an Effective Means of Separating Salivary Gland Tumor-Associated Lymphoid Proliferation from True Lymph Node Involvement

Tumor-associated lymphoid proliferation (TALP) is a well-recognized lymphocytic reaction that is commonly associated with certain salivary gland tumors. A salivary carcinoma with TALP may be confused for true lymph node involvement by that tumor, constituting a potential pitfall in tumor staging that may result in unnecessary therapeutic intervention or erroneous prognostication for patients. True lymph nodes harbor populations of extrafollicular reticulum cells (ERCs), which can be highlighted by low molecular weight cytokeratin immunohistochemistry. We sought to determine whether low molecular weight cytokeratin Cam5.2 immunostaining may be utilized to differentiate true lymph node involvement by salivary gland tumors from TALP. The surgical pathology archives of the University of Texas Southwestern Medical Center was searched for cases of salivary gland neoplasms exhibiting either TALP or true lymph node involvement. Hematoxylin and eosin-stained sections were examined. Cases were classified on the basis of a definitive lymph node capsule and subcapsular sinus, as seen on routine histologic evaluation. Low molecular weight cytokeratin Cam5.2 immunostaining was performed and evaluated on all cases. Twenty-three salivary gland carcinomas with TALP and 16 carcinomas involving a lymph node (14 carcinomas metastatic to regional lymph nodes and 2 carcinomas arising from benign lymph node inclusions) were identified. Numerous Cam5.2-positive ERCs were identified within the nodal tissue of all true lymph nodes involved by carcinoma (16 of 16 cases), while Cam5.2-positive ERCs were completely absent in all cases of salivary gland lesions with TALP (0 of 23 cases) (100% vs. 0%, p < .0001, Fisher’s Exact). Utilization of low molecular weight cytokeratin Cam 5.2 immunostaining for ERCs is a highly useful tool for distinguishing true lymph node involvement by salivary gland carcinomas from TALP. This strategy may be useful in identifying genuine nodal metastasis in histologically ambiguous cases, and to avoid erroneously upstaging tumor with TALP as nodal metastasis with the resulting prognostic and therapeutic implications. Moreover, low molecular weight cytokeratin immunostaining may be useful in confirming the rare examples of salivary gland tumors arising from intranodal salivary gland inclusions.