Cold Agglutinin Disease

Lessons From the Friday Unknowns

The patient is a 67-year-old man with autoimmune hemolytic anemia associated with cold agglutinins.

Peripheral blood:

WBC: 4.2 K/uL, Hgb 8.5 g/dL, MCV 96.8 fL, Platelet 248 K/uL

Mild normocytic, normochromic anemia with red cell agglutinates, normal leukocyte count with rare atypical lymphocytes and no circulating blasts, normal platelet count with unremarkable morphology

Flow cytometry immunophenotyping performed on bone marrow aspirate showed kappa monoclonal B-cell population (1.4% of total events) with the following immunophenotype:
Positive: CD11c partial, CD19, CD20, CD23 partial and monoclonal for immunoglobulin kappa light chain
Negative: CD5 and CD10

The bone marrow core biopsy is adequate with cellularity of 90%. Erythroids are relatively increased. Megakaryocytes are adequate with unremarkable morphology. An atypical lymphoid infiltrate nodular interstitial and paratrabecular pattern composed of small mature lymphocytes is noted, positive for CD20, Pax5, BCL2, and negative for CD3, CD5, BCL6, CD10, CD21, CD23 and cyclin D1 expression. The infiltrate represents 5–10% % of marrow cellularity. CD138 highlights plasma cells which represent 1–2% of marrow cellularity. Proliferation index as assessed by Ki67 is low (< 5%) in the lymphoid nodules. CD34 highlights no increase in blasts.

Cytogenetic study showed abnormal male karyotype: 47,XY,+3[4]/46,XY[16]

In summary, the above morphologic and immunophenotypic findings are consistent with bone marrow involvement by low-grade B-cell lymphoma which involves 5–10% of marrow cellularity, most consistent with the diagnosis of cold agglutinin disease.

Link to digital slides: bit.ly/3oFkQqh | Case 4