Morphological subclassification of follicular lymphoma: variability of diagnoses among hematopathologists, a collaborative study between the Repository Center and Pathology Panel for Lymphoma Clinical Studies.

Abstract

A collaborative study between the Repository Center for Lymphoma Clinical Studies and the members of the lymphoma pathology subcommittee of the major cooperative oncology groups was undertaken in an effort to ascertain the reproducibility and the interobserver agreement for the cytologic diagnosis of follicular lymphomas. A group of 105 patients with follicular lymphomas were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes, and Collins, and Working Formulation systems. In these systems, follicular lymphomas are subclassified by estimation of the different cell populations without the actual counting of cells. With this method, great variability in diagnosis was noted. For example: (1) The consensus diagnosis was that of poorly differentiated lymphocytic lymphoma (PDL) in 39 cases, but among the individual pathologists the number of cases thus diagnosed ranged from 24 to 65; (2) In 40 cases, the consensus diagnosis was follicular lymphoma, mixed-cell type; however, all seven pathologists independently agreed on this subtype in only one case; (3) A major disagreement was noted in 39 cases (37%), in which both diagnostic extremes (small cleaved and large noncleaved) were expressed. In the second method, only precise counts of different cells were made, according to a modification of the method recommended by Berard. With this counting method, diagnoses were independently derived based on the counts provided by the seven pathologists for large cleaved, small noncleaved, and large noncleaved cells. The variability in the results was wide also with this second method. For example, the average number of large cells found by each pathologist was ascertained, and the ranges were determined. The average range was 28 cells, which was considered high. The same determinations were performed only for large noncleaved cells, and the range was found to be 15 cells, which was also considered high. When the diagnoses derived from counts of only large noncleaved cells were compared with the traditional, more subjective diagnoses, fairly close agreement was obtained. In summary, the great variability in diagnoses of follicular lymphomas among pathologists may be attributed to the difficulties inherent in accurate determination of cell size and of the precise percentages of different cells. Until solutions to these problems are developed, one can subclassify follicular lymphomas according to the Berard method or the estimation method.

Insights into the molecular pathogenesis of follicular lymphoma arising from analysis of geographic variation

“…27 With the recent introduction of the World Health Organization classification system, 28 the criteria for the cytologic subclassification of FL will be changed to that initially proposed by Mann and Berard, 29 which yields a higher proportion of FL subtypes than previously used cytologic classification systems. 30,31 Applying population-based overall incidence figures for NHL to the estimated proportion of follicular NHL from the available studies (if more than one study from a given country was available, the mean figure was used), yields estimated annual incidence rates for FL in Asian countries in the range of 0.15 to 0.38 per 100 000 population per year (Table 2). 18,22,25,[32][33][34] This is clearly much lower than the rate of 1.3 to 3.0 per 100 000 population per year seen in …”

The prognostic significance of the intra-follicular tumor cell proliferative rate in follicular lymphoma

“…4,5 Given identical treatment, patients with grade 3 follicular lymphoma have a worse prognosis than those with grade 1 or 2 follicular lymphoma, but when treatment is intensified by anthracycline-containing regimens, this difference disappears. [6][7][8] A major problem in histological grading is the considerable intra-and inter-observer variability, 9,10 due to the subjective nature of the technique. Although the fraction of proliferating cells is prognostic in aggressive lymphomas, 11,12 its predictive value in follicular lymphoma is less clear.…”

Características clínicas de los pacientes con LNH del Hospital Arnau de Vilanova de Valencia

“…Incluso entre patólogos expertos existe una sorprendente discordancia de diagnósticos, como prueban los estudios de los mayores grupos de trabajo sobre LNH (11): El Southwest Oncology Group -SWOG- (16)(17), el Southeastern Cancer Study Group (18) y el Eastern Oncology Group -ECOG- (19). En estos grupos la concordancia de diagnósti-cos varió ampliamente, entre el 86 y el 53% (20).…”

“…De los diferentes subtipos en los que se divide esta clasificación, hemos encontrado una mayor frecuencia de casos pertenecientes a los tipos: linfoma difuso de células grandes, linfoma linfocítico de células pequeñas (LLC), linfoma plasmocitoide y linfoma centrofolicular (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”