Follicular center cell lymphoma. Morphologic data relating to observer reproducibility

Abstract

Subjectivity and observer variation in non-Hodgkin's lymphoma continues to plague current classification schemes. It was thought important to assess objectively derived morphometric data to see if three categories of follicular center cell (FCC) lymphomas, follicular small cleaved cell, follicular mixed small cleaved and large cell, and diffuse and nodular large cell, actually fall into distinctly separate classes based on nuclear parameters. Mean nuclear area, contour index and invagination depth of neoplastic lymphocytes, and the percentage of invaginated and clefted nuclear profiles in each example of FCC lymphoma were evaluated by three different approaches. Results obtained from distribution of the morphometric data in scatter diagrams, calculation of the overlap index, and linear regression values, all revealed considerable (but variable) degrees of overlap between the three FCC subtypes regardless of the nuclear parameter employed. Where separation between FCC lymphomas was maximal, although still incomplete, there was no consistent correlation between the nuclear parameter and the pair of FCC lymphomas being compared. At least in terms of nuclear morphological features, non-Hodgkin's lymphomas of FCC type seem to represent a continuum of one disease process. The information provides a basis for understanding some reasons underlying the problem of observer variation in non-Hodgkin's lymphoma.

Software-Automated Counting of Ki-67 Proliferation Index Correlates With Pathologic Grade and Disease Progression of Follicular Lymphomas

“…7,8 Current grading schemata rely on morphologic identification and quantitation of centroblasts; however, variations in fixation and staining can make this seemingly straightforward task relatively difficult. We investigated whether recent advances in the automated quantitation of IHC stains provide a reliable means to quantify the Ki-67 PI to improve the prognostication of FL.…”

“…5,6 In the 2008 WHO classification, grades 1 and 2 were combined into grade 1 to 2 (low-grade) FL due to poor interobserver reproducibility and lack of significant survival differences between grades 1 and 2. 2,7,8 …”

Immunohistochemical analysis of the antiapoptotic Mcl‐1 and Bcl‐2 proteins in follicular lymphoma

“…Grading of FL by the WHO recommended method of Mann and Berard (Nathwani et al , 2001) has no overall confirmed role in prognostication of FL patients, as in our series (Chau et al , 2003). This is partly caused by the difficult identification of centroblasts in specimens, relying upon morphology alone and the poor reproducibility of grading results (Dardick & Caldwell, 1986). Mcl‐1 staining has the potential to revive the prognostic value of grading.…”

Clinical and biological applications of image analysis in non-Hodgkin's lymphomas

“…28 Using a different approach, Dardick et al maintained that at least in terms of nuclear morphological features, non-Hodgkin's lymphomas of the follicular centre cell type seemed to be a continuum of one disease process. 29 They based this assumption on the considerable degrees of overlap that they observed between small, mixed and large cell follicular lymphomas, when pertinent morphometric data were analysed.…”