Dutcher body
Summary
Dutcher bodies are intranuclear, PAS-positive pseudoinclusions seen in plasma cells, made of invaginations of cytoplasm containing immunoglobulin. They are classically associated with Waldenström macroglobulinemia (lymphoplasmacytic lymphoma) and other plasma cell/lymphoplasmacytic neoplasms such as multiple myeloma.
Detail
**Definition:** A Dutcher body is a round, eosinophilic, PAS-positive intranuclear "inclusion" in a plasma cell or plasmacytoid lymphocyte. It is a pseudoinclusion: electron microscopy shows an invagination of cytoplasm into the nucleus, surrounded by a nuclear membrane. The material is immunoglobulin, usually IgM. A Russell body is the cytoplasmic counterpart.
**Pathophysiology:** Neoplastic lymphoplasmacytic cells make large amounts of monoclonal immunoglobulin. The excess accumulates in the rough ER. Cytoplasm containing this protein then invaginates into the nucleus, and the result looks like an intranuclear inclusion.
**Clinical associations:** - **Waldenström macroglobulinemia (lymphoplasmacytic lymphoma):** the classic association. It involves monoclonal IgM, the MYD88 L265P mutation (>90%), and sometimes CXCR4 mutations. - Features come from IgM paraprotein: hyperviscosity (headache, visual changes, epistaxis, confusion), cryoglobulinemia, cold agglutinin disease, and peripheral neuropathy (anti-MAG). - Marrow involvement causes cytopenias. - Lymphadenopathy and hepatosplenomegaly may occur. - There are **no lytic bone lesions**, unlike multiple myeloma. - **Multiple myeloma:** Dutcher bodies can appear, along with Russell bodies (cytoplasmic), Mott cells (grape-like cells filled with Russell bodies), and flame cells (IgA myeloma). - They are also seen in other B-cell neoplasms with plasmacytic differentiation, such as marginal zone lymphoma and CLL.
**Board pearls:** - Dutcher body = intranuclear immunoglobulin pseudoinclusion. Russell body = cytoplasmic immunoglobulin inclusion. - Waldenström: IgM spike, hyperviscosity, rouleaux on smear, and a "plasmacytoid lymphocyte" morphology. - Treatment of symptomatic hyperviscosity is plasmapheresis. Definitive therapy is rituximab-based chemoimmunotherapy or BTK inhibitors (e.g., ibrutinib, zanubrutinib). - Dutcher bodies are not specific and are not diagnostic alone. Diagnosis needs marrow biopsy, serum protein electrophoresis/immunofixation showing IgM, and often MYD88 testing.
Sources
- Robbins & Cotran Pathologic Basis of Disease (Neoplasms of white cells: lymphoplasmacytic lymphoma and plasma cell neoplasms)
- First Aid for the USMLE Step 1 (Hematology and Oncology: Waldenström macroglobulinemia, plasma cell dyscrasias)
- Harrison's Principles of Internal Medicine (Plasma cell disorders)
- Swerdlow SH et al., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
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