Spectrum of Pathologic Findings in “In Situ” Mantle Cell Lymphoma
B Shrestha, A Dogan, AL Feldman. Mayo Clinic, Rochester, MN
Background: Mantle cell lymphoma (MCL) is a B-cell lymphoma believed to derive from cells of the inner mantle zone. MCL typically demonstrates a diffuse growth pattern and has a more aggressive clinical course than other small B-cell lymphomas. An “in situ” pattern of involvement (I-MCL), sometimes with more indolent behavior, has been described in several reports of 1-2 cases each, but the pathologic findings have not been studied in larger series.
Design: Morphologic features were reviewed in 11 cases of I-MCL (M: 6, F: 5; mean age, 69 y). Cases with no morphologic abnormality of the mantle zone were considered true “in situ” (IS) lesions, while those with a mildly expanded mantle zone were considered variants of the mantle zone pattern (MZ). Immunohistochemistry was performed in all cases and compared to a cohort of 78 MCLs with typical (non-in situ) patterns of involvement. Fluorescence in situ hybridization (FISH) was performed using a dual-fusion CCND1/IGH probe.
Results: I-MCLs had an IS pattern in 7 and MZ pattern in 4. In 8 cases, the MCL was an incidental finding. Six of these were composite lymphomas and phenotyping studies led to the identification of the MCL (5 in lymph nodes, 1 in appendix). Two were discovered incidentally after bowel resection and excision of a lipoma. In only 3 cases, all MZ pattern, did the MCL lead to the biopsy (lymphadenopathy in 2, tonsillar enlargement in 1); two of these patients had bone marrow involvement. All tumors were positive for cyclin D1. CD5 was negative in 6/11 cases (55%), compared to 1/78 (1%) of typical MCLs (p=8 x 10-10, χ2 test). 4/11 were additionally negative for CD43. CCND1/IGH translocation exceeded the normal cut-off of 2.5% in 7 of 8 tested cases (mean, 14% of nuclei; range, 6% to 35%).
Conclusions: I-MCLs represent a diagnostic challenge. Most cases (and all with the IS pattern) in this series were discovered incidentally, particularly after studies performed to phenotype another lymphoma. Since composite lymphomas are rare, but were seen in 6/11 cases in this series, it is likely that I-MCLs occurring in isolation often go undetected. Compounding the diagnostic difficulty of I-MCL is the frequent lack of aberrant CD5 (and often CD43) co-expression by these lesions. This finding also may indicate that I-MCL is a precursor lesion to, or possibly an entirely separate entity from, typical MCL. Thus, a larger, ideally multi-center, study to determine the clinical behavior of I-MCL is warranted to determine the best approach to manage these patients.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 192, Monday Morning