Immunoarchitectural patterns in follicular lymphoma: efficacy of HGAL and LMO2 in the detection of the interfollicular and diffuse components

Abstract

Follicular lymphoma (FL) can exhibit variant histologic patterns that can lead to confusion with other B-cell lymphomas and reactive conditions. Diagnostic markers such as CD10 and BCL2 may be difficult to interpret in variant FL patterns, and are often diminished or absent in the interfollicular and diffuse components. We evaluated 2 recently characterized germinal center B-cell markers, human germinal center associated lymphoma (HGAL), and LIM-only transcription factor 2 (LMO2), in 127 FL patient biopsies (94 nodal, 33 extranodal), and correlated the findings with histologic pattern, cellular composition, grade, and additional immunostains (CD20, CD3, CD21, CD10, BCL2, and BCL6). Architectural patterns included predominantly follicular (75%) and follicular and diffuse components (25%); 10 cases showed marginal zone differentiation and 3 were floral variants. Eighty-nine cases were low grade (38 grade 1; 51 grade 2) and 38 were grade 3 (29 grade 3A and 9 grade 3B). HGAL had the highest overall sensitivity of detecting FL and was superior in detecting the interfollicular and diffuse components compared with BCL2, LMO2, CD10, and BCL6. All 28 cases that lacked CD10, expressed HGAL, and the majority also expressed LMO2. Our results show that HGAL and LMO2 are sensitive markers for FL diagnosis. The addition of HGAL and LMO2 to the immunohistologic panel is beneficial in the work-up of nodal and extranodal B-cell lymphomas and the efficacy of HGAL in detecting the follicular, interfollicular and diffuse components of FL is of particular value in the setting of variant immunoarchitectural patterns.

Figure 1. Architectural Patterns in Follicular Lymphoma

Architectural pattern of follicular lymphoma and representative cartoons showing the distribution of neoplastic B-cells. These patterns include: (A) Follicular pattern, characterized by complete effacement of normal architecture by variably sized neoplastic follicles containing a variable mixture of centrocytes and centroblasts; (B) Follicular and diffuse architecture, characterized by at least a partial follicular pattern associated with between 10–90% diffuse areas with sheets of neoplastic cells; (C) Marginal zone differentiation, characterized by monocytoid cells with moderate to abundant pale cytoplasm and rounded centrally placed nuclei were seen in clusters, or more commonly, surrounding neoplastic follicles; (D) Floral variant with invaginations of mantle zone lymphocytes into neoplastic follicles distorting the follicular architecture.

Figure 2. Spectrum of Follicle Morphology

Neoplastic follicles in follicular lymphoma showed either crowded (A) or spaced-apart (B) follicles, and many also showed involvement of the capsule (C). In addition, the follicles also showed wide variation in the shape and size: typical examples of irregular (D), coalesced (E), serpiginous (F), mantle zone differentiation (G), confluent (H), and serrated (I) follicles are illustrated.

Figure 3. Spectrum of Cytologic Features

The cellular composition and cytologic features of the neoplastic follicles showed variation and include: (A) follicles with tingible body macrophages, (B) monocytoid differentiation, (C) signet-ring like features with eccentric nuclei and abundant cytoplasm or cytoplasmic inclusions, and (D) a rare example of FL with Hodgkin/Reed-Sternberg-like cells within follicles.

Figure 4. Immunoarchitectural Patterns of Follicualr lymphoma

Typical examples of the immunostaining patterns of CD10 (A and B), BCL6 (C and D), BCL2 (E and F), HGAL (G and H), and LMO2 (I and J) are shown. The staining in neoplastic follicles as well as the staining in interfollicular neoplastic B-cells are illustrated. The third column includes panels at higher magnification showing details of staining in the interfollicular component.

Figure 5. Case Example of Follicular Lymphoma

A representative example of a FL case that lacked CD10 (A) and BCL2 (B) is illustrated. In this case example, both HGAL (C) and LMO2 (D) are positive in the follicular and interfollicular components, and confirm the diagnosis of follicular lymphoma. Higher magnification insets showing the interfollicular component are included in all panels.