Nodal and extranodal plasmacytomas expressing immunoglobulin a: an indolent lymphoproliferative disorder with a low risk of clinical progression

Abstract

Plasmacytomas expressing immunoglobulin A are rare and not well characterized. In this study, 9 cases of IgA-positive plasmacytoma presenting in lymph node and 3 in extranodal sites were analyzed by morphology, immunohistochemistry, and polymerase chain reaction examination of immunoglobulin heavy and κ light chain genes. Laboratory features were correlated with clinical findings. There were 7 males and 5 females; age range was 10 to 66 years (median, 32 y). Six of the patients were younger than 30 years of age, 5 of whom had nodal disease. About 67% (6 of 9) of the patients with nodal disease had evidence of immune system dysfunction, including human immunodeficiency virus infection, T-cell deficiency, autoantibodies, arthritis, Sjögren syndrome, and decreased B cells. An IgA M-spike was detected in 6 of 11 cases, and the M-protein was nearly always less than 30 g/L. All patients had an indolent clinical course without progression to plasma cell myeloma. Histologically, nodal IgA plasmacytomas showed an interfollicular or diffuse pattern of plasma cell infiltration. The plasma cells were generally of mature Marschalko type with little or mild pleomorphism and exclusive expression of monotypic IgA. There was an equal expression of κ and λ light chains (ratio 6:6). Clonality was showed in 9 of 12 cases: by polymerase chain reaction in 7 cases, by cytogenetic analysis in 1 case, and by immunofixation in 1 case. Clonality did not correlate with pattern of lymph node infiltration. Our results suggest that IgA plasmacytomas may represent a distinct form of extramedullary plasmacytoma characterized by younger age at presentation, frequent lymph node involvement, and low risk of progression to plasma cell myeloma.

Figure 1

Histopathology of IgA plasmacytoma with an interfollicular plasma cell infiltrate, case 1. The lymph node showed marked follicular hyperplasia with hyperplastic germinal centers, distinct and polarized mantle zones (A), moderate increase in vascularity in the paracortex, and heavy infiltrate of mature plasma cells in the interfollicular areas admixed with few small lymphocytes, immunoblasts and eosinophils (B, 200x). The interfollicular plasma cells showed κ light-chain restriction (C, D) and exclusive expression of IgA (E, F, G, H). Small numbers of polyclonal plasma cells expressing IgG were present in the germinal centers (C, D, E, F, G, and H, upper left corners).

Figure 2

Histopathology of IgA plasmacytoma with interfollicular plasma cell infiltrate, cases 2, 3 and 8. Case 2 showed residual lymphoid aggregates with focal nodular expansion of plasma cells (A). Multinucleated plasma cells, Russell bodies and intranuclear cytoplasmic inclusions (inlet) were easily found (B, 400x). Case 3 showed follicular hyperplasia (C) and immature plasma cells with more open chromatin and higher N/C ratio (D, 400x). Case 8 showed markedly dilated sinuses with interfollicular and intrasinusoidal plasmacytosis (E). The plasma cells displayed significant pleomorphism with variation in size and shape, including some cells with markedly enlarged nuclei (F, 400x).

Figure 3

Histopathology of IgA nodal plasmacytoma with a diffuse plasma cell infiltrate, case 6. The lymph node showed effacement of nodal architecture and diffuse infiltrate of mature plasma cells (A, and B, 400x), with κ light-chain restriction (D) and exclusive expression of IgA (E, F). Pax5 and IgD immunohistochemical stains highlighted residual aggregates of mantle cells that were not apparent on Hematoxylin and eosin stained sections (C).