Cytologic differential diagnosis of follicular lymphoma grades 1 and 2 from reactive follicular hyperplasia: Cytologic features of fine‐needle aspiration smears with Pap stain and fluorescence in situ hybridization analysis to detect t(14;18)(q32;q21) chromosomal translocation
Fine-needle aspiration cytology (FNAC) is a well-established technique for diagnosis of malignant lymphoma (ML). Generally, Giemsa but not Pap stain is used in FNAC. However, cytologic features obtained from Pap stain are also valuable. Very few studies on the cytologic characteristics of ML, as determined by Pap stain, are available. It is easier to observe nuclear irregularity and to identify nucleoli in ML cells by Pap stain than by Giemsa stain. Here, we applied Pap stain for cytomorphologic differential diagnosis of follicular lymphoma (FL) from reactive follicular hyperplasia (RFH).
Eighteen biopsy-confirmed cases of FL grades 1 and 2, with available FNAC smears, and six cases of RFH were selected for this study. Low-power magnification showed well-known features, and tingible body macrophages and lymphoid cell aggregates were observed frequently in RFH and FL, respectively. In addition, the so-called two-nuclei-like cleaved cells were observed frequently in FL. These cells showed notably cleaved nuclei, and therefore, appeared to possess two nuclei. Under high-power magnification, the occurrence of cells with nucleoli >1 μm and of cleaved cells was high in FL compared to RFH.
It is believed that FL derives from centrocytes and that FL cells are slightly larger than non-neoplastic small lymphocytes. However, analysis of cell diameter in this study indicated that small lymphoma cells were predominant in half the cases of FL grades 1 and 2, and the percentage of these cells was similar to that in RFH, showing why false-negative diagnosis of FL grades 1 and 2 occasionally occurs. There are limitations of FNAC in the diagnosis of FL. However, we believe that the appearance of two-nuclei-like cleaved cells and the high percentage of nucleoli-possessing cells, which we describe here, provide significant and valuable clues for the differential diagnosis of FL from RFH.
Of 18 cases of FL grades 1 and 2, t(14;18)(q32;q21) was found in 13 cases with the use of destained FNAC smears. Our study suggests that, together with the cytomorphologic findings described earlier, FISH analysis for the chromosomal translocation, t(14;18)(q32;q21), is crucial for final cytologic diagnosis of FL grades 1 and 2. Diagn. Cytopathol. 2006;34:11–17.
"The t(14;18) translocation rate in FL1-2 in this study was 73.5%, which was close to Japanese data [23,24], and slightly lower than most of the western reports (80-90%) . This difference may be caused by regional and ethnical differences. "
[Show abstract][Hide abstract] ABSTRACT: The revised 2008 World Health Organization classification maintains a histological grading system (grades 1-3) for follicular lymphoma (FL). The value of grading FL has been debated. This study will yield deeper insights into the morphologic, immunophenotypic characterization and t(14;18) translocation in FL and explore their significance of diagnosisof Chinese FL subgroups.Methods; We retrospectively reviewed the FL diagnoses according to the 2008 WHO classification in all diagnostic specimens from a multicentric cohort of 122 Chinese patients. Upon review, 115 cases proved to be truly FL. CD10, BCL6, MUM1, BCL2 and t(14;18) (q32;q21) translocation were detected by Envision immunostaining technique and fluorescence in situ hybridization.
FL1 has larger proportion of follicular pattern (93.0%) than that of FL2 (73.7%, P = 0.036), FL3B (63.6%, P = 0.003) and FL3A (77.4%, P = 0.053), although the last P value was more than 0.05 (Pearson's chi-squared test). Areas of DLBCL were present in 25.8% (8/31) of FL3A and more frequent in FL3B (59.1%, 13/22; P = 0.015). The positivity of CD10 andBCL2 in FL1-2 were significantly higher than those in FL3 (P < 0.001, P = 0.043, respectively). The positivity of MUM1 in FL1-2 was significantly lower than that in FL3 (10.2% vs. 51.0%; P < 0.001). Furthermore the positivity of MUM1 in FL3A was significantly lower than that in FL3B (37.9% vs. 68.2%; P = 0.032). The positivity of t(14;18) was higher in FL1-2 than in FL3 (73.5% vs. 35.6%, P < 0.001), and was higher in FL3A than in FL3B (51.9% vs. 11.1%, P = 0.005). t(14;18) was significantly correlated with CD10+ (R = 0.453, P < 0.001) and MUM1+ (R = 0.482, P < 0.001).
FL1 and FL2 were immunophenotypically and genomically similar, while FL3A and FL3B were partly immunophenotypically similar but morphologically, genomically distinct. FL3A was genomically closer to FL1-2, whereas FL3A was genomically closer DLBCL. Thus wehypothesize that FL may in fact be a heterogeneous indolent lymphoma encompassing entities with distinct molecular pathogenesis and genetic characteristics. Immunohistochemical and genetic characterization helps to distinguish subgroups of FLs.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1334018129864616.
"At higher power, the nodules correspond to numerous FCFs populated by small to intermediate-sized centrocytic cells with cleaved nuclei and clumped chromatin (Figure 4(c)). Cells with deeply cleaved, apparently bilobed nuclei can be conspicuous . Larger centroblasts characterized by noncleaved nuclei, less dense chromatin, and a narrow rim of dense cytoplasm are rare in grade 1 FL, but occur with increasing frequency in grade 2 where both cell populations may be present in equal numbers. "
[Show abstract][Hide abstract] ABSTRACT: Fine needle sampling is a fast, safe, and potentially cost-effective method of obtaining tissue for cytomorphologic assessment aimed at both initial triage and, in some cases, complete diagnosis of patients that present clinically with lymphadenopathy. The cytologic diagnosis of B-cell non-Hodgkin lymphomas composed of small-/intermediate-sized cells, however, has been seen as an area of great difficulty even for experienced observers due to the morphologic overlap between lymphoma and reactive lymphadenopathies as well as between the lymphoma entities themselves. Although ancillary testing has improved diagnostic accuracy, the results from these tests must be interpreted within the morphological and clinical context to avoid misinterpretation. Importantly, the recognition of specific cytologic features is crucial in guiding the appropriate selection of ancillary tests which will either confirm or refute a tentative diagnosis. For these reasons, we here review the cytologic characteristics particular to five common B-cell non-Hodgkin lymphomas which typically cause the most diagnostic confusion based on cytological assessment alone: marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and lymphoplasmacytic lymphoma. We summarize the most pertinent cytomorphologic features for each entity as well as for reactive lymphoid hyperplasia, contrast them with each other to facilitate their recognition, and highlight common diagnostic pitfalls.
Pathology Research International 05/2012; 2012:164934. DOI:10.1155/2012/164934
[Show abstract][Hide abstract] ABSTRACT: Fine-needle aspiration (FNA) has proven to be a rapid, cost-effective, and accurate means for evaluating a wide variety of conditions in most organ systems, although the FNA diagnosis of lymphoma (especially the primary diagnosis) remains controversial. However, recent changes to the World Health Organization classification of lymphomas place more emphasis on cytology and less emphasis on architecture, thus opening the door to a more expanded use of FNA, particularly in non-Hodgkin lymphomas. A review of the literature over the past 10 years reveals sensitivity in the range of 66%–100% and specificity in the range of 58%–100%. The complementary use of cytomorphology, immunohistochemistry, and flow cytometry has proven more accurate that any single modality alone. Sophisticated techniques once reserved for the research laboratory (ie, FISH and PCR) are now often used in the clinical setting and provide important diagnostic and prognostic information. The evaluation of Hodgkin lymphomas and some large-cell non-Hodgkin lymphomas remains problematic and may require tissue core biopsy. We also briefly consider the use of FNA in workup of metastatic tumors in lymph nodes. Rapid and accurate assessment of metastatic disease, particularly carcinomas and melanomas, is readily accomplished by FNA biopsy, with an overall sensitivity, specificity, and accuracy of over 90%. In these cases, cell block material can be obtained to perform various ancillary studies for additional useful prognostic information.
Pathology Case Reviews 01/2007; 12(1):10-26. DOI:10.1097/01.pcr.0000252857.12872.52
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