Michael Cibull, MD, Professor of Pathology and Laboratory Medicine and Director of Surgical Pathology, University of Kentucky Medical Center, Lexington
Subodh Lele, MD Assistant Professor of Pathology and Laboratory Medicine, University of Kentucky Medical Center
Melissa Kesler, MD, Hematopathology Fellow, University of Texas Southwestern Medical Center at Dallas
Variation in the diagnosis of follicular variant of papillary thyroid carcinoma
Prevalence of KIT expression in human tumors
Atypical marginal zone hyperplasia of mucosa-associated lymphoid
Variation in the diagnosis of follicular variant of
papillary thyroid carcinoma
The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma can be difficult. Recent reports have suggested that this neoplasm frequently may be overdiagnosed by pathologists. The authors examined the observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) in 87 tumors diagnosed by 10 experienced thyroid pathologists. They also assessed the criteria that the reviewers considered most helpful for making a diagnosis of FVPCA. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39. In this series, 24.1 percent of the patients had metastatic disease (n=21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7 percent, and seven of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100 percent. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable, even among experienced thyroid pathologists, most reviewers agree on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve consistency in diagnosing FVPCA. Since most cases with metastatic disease have obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.
Lloyd RV, Erickson LA, Casey MB, et al. Observer variation in the diagnosis
of follicular variant of papillary thyroid carcinoma. Am
J Surg Pathol. 2004;28:1336-1340.
Reprints: Dr. Ricardo V. Lloyd, Dept. of Laboratory Medicine and Pathology,
Mayo Clinic, 200 First St. SW, Rochester, MN 55905; firstname.lastname@example.org
Prevalence of KIT expression in human tumors
KIT is a target for imatinib mesylate (Gleevec, Novartis Pharma, Basel, Switzerland). Gastrointestinal stromal tumors (GISTs) express KIT and respond favorably to imatinib therapy. To determine in which other tumors such a molecular-targeted therapy might be indicated, the authors investigated KIT expression in different human tumor types. Because recent studies of GISTs suggest that KIT-activating mutations predict response to imatinib therapy, the authors also sequenced a subset of positive tumors. More than 3,000 tumors from more than 120 tumor categories were analyzed by immunohistochemistry in a tissue microarray format. Seven commercially available anti-KIT antibodies were evaluated initially. The antibody A4502 (Dako) was selected for analysis because of a high frequency of positivity in GIST and low staining background in other tissues. To determine the frequency of KIT mutations in various tumor types, the exons 2, 8, 9, 11, 13, and 17 (where mutations previously were reported) were sequenced in 36 tumors with strong KIT expression. KIT positivity was detected in all of the 28 GISTs (100 percent), 42 of 50 seminomas (84 percent), 34 of 52 adenoid-cystic carcinomas (65 percent), 14 of 39 malignant melanomas (35 percent), and eight of 47 large-cell carcinomas of the lung (17 percent), as well as in 47 additional tumor types. KIT mutations were found in six of 12 (50 percent) analyzed GISTs, but in only one of 24 (four percent) other tumors. The results suggest that KIT expression occurs infrequently in most tumor types and that, with the exception of GISTs, KIT gene mutations are rare in immunohistochemically KIT-positive tumors.
Went PT, Dirnhofer S, Bundi M, et al. Prevalence of KIT expression in human
tumors. J Clin Oncol. 2004;22(22):4514-4522.
Reprints: Dr. Guido Sauter, Institute of Pathology, University of Basel, Schönbeinstrasse
40, 4031 Basel, Switzerland; email@example.com
Atypical marginal zone hyperplasia of mucosa-associated lymphoid tissue
Mucosa-associated lymphoid tissue lymphomas typically arise at sites of acquired MALT and are uncommon in native MALT—for example, Peyer patches and tonsil. Malignancy in these low-grade lymphomas is often inferred by CD43 expression and immunoglobulin light chain restriction; molecular genetic evidence is sought only if these are in doubt. The authors reported on six cases of marginal zone (MZ) hyperplasia in four tonsils and two appendices of children aged three to 11 years that showed histologic and immunophenotypic features of lymphoma yet were polyclonal by molecular analysis. All patients were alive and well (median followup, 35.3 months) despite lack of lymphoma-directed therapy. The tonsils and appendices showed florid MZ hyperplasia with prominent intraepithelial B cells (IEBCs). Both MZ B cells and IEBCs showed a high proliferation index and a CD20+, CD21+, CD27-, CD43+, MUM-1-, IgM+, IgD+, lambda-restricted phenotype. Polymerase chain reaction for IgH and lambda light chain gene rearrangements showed that the B cells were polyclonal and the IgH genes nonmutated. The MZ intraepithelial B cells of six control tonsils had a similar immunophenotype, except that they were CD27+ and expressed polytypic light chain. They too were polyclonal by molecular analysis, but Ig genes were mutated. The authors concluded that caution is warranted when evaluating for MALT lymphoma, even in the presence of CD43 expression and light chain restriction.
Attygalle A, Liu H, Shirali S, et al. Atypical marginal zone hyperplasia of
mucosa-associated lymphoid tissue: a reactive condition of childhood showing
immunoglobulin lambda light-chain restriction. Blood.
Reprints: Peter G. Isaacson, Dept. of Histopathology, Royal Free and University
College Medical School, Rockefeller Bldg., University St., London WC1E 6JJ,