Salivary gland lymphoid infiltrates associated with lymphoepithelial lesions: a clinicopathologic, immunophenotypic, and genotypic study.

The criteria for distinguishing benign lymphoepithelial lesions (BLEL) from low grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type in salivary glands and the significance of genotypically documented clonality in this setting are controversial. In addition, the clinical implications of a neoplastic diagnosis are unclear. The histopathologic features of 68 specimens from 49 patients with at least one salivary gland biopsy with LEL together with available clinical data were, therefore, reviewed. Paraffin section immunohistochemical (IHC) stains for kappa, lambda, CD3, CD20, and CD43; in situ hybridization (ISH) for kappa and lambda; and polymerase chain reaction (PCR) for immunoglobulin (Ig) HC rearrangement were performed. The 61 salivary gland specimens were classified as BLEL-13, BLEL with monocytoid B-cell (MBC) halos (BLEL-halo-8), low grade B-cell lymphoma of MALT type with confluent zones of MBC or other atypical lymphocytes (ML-MALT-24), low grade B-cell lymphoma of MALT type with monoclonal plasma cells (ML-MALT-PC-12), and high grade B-cell lymphoma of MALT type (MALT-high grade-4). Soft tissue and perineural invasion was not observed in BLEL and was most common in the MALT lymphomas. Lymph node involvement was identified in six patients at the time of their salivary gland MALT lymphomas but in none with BLEL. CD43+ B cells were seen most commonly in ML-MALT but were present in all other categories except MALT-high grade. Clonal B cells were identified by PCR in 5 of 12 BLEL, 5 of 8 BLEL-halo, 17 of 22 ML-MALT, 6 of 10 ML-MALT-PC, and 3 of 3 MALT-high grade biopsies. All ML-MALT-PC were clonal by ISH or IHC. Repeat biopsies in 14 patients most commonly showed a BLEL/ML-MALT lesion in an ipsilateral or contralateral salivary gland with one transformation to a MALT-high grade. Although only a few patients are known to have received chemoradiation or radiation therapy, most patients with low-grade lesions have pursued an indolent course. These data show the presence of two types of borderline lesions within the spectrum of lymphoid proliferations associated with salivary gland LEL. One has clonal B cells without histological features of neoplasia and the other nonconfluent MBC extending beyond the confines of LEL ("halos"). They share some features with the infrequent nonneoplastic BLEL and others with the more common low-grade B-cell lymphomas of MALT. A few high-grade B-cell lymphomas of MALT were also identified including a rare example of transformation from a low- to high-grade lesion. The optimal therapeutic approach for the borderline and low-grade lesions and the reason why so many of the lymphoproliferative lesions associated with LEL remain localized to the neck remain to be defined.