Multiple myeloma - Histology

What is Multiple Myeloma?

Multiple myeloma is a type of plasma cell cancer that originates in the bone marrow. Plasma cells are a type of white blood cell that produce antibodies to help fight infections. In multiple myeloma, these cells become malignant and proliferate uncontrollably, leading to a variety of complications.

Histological Features

In a histological examination, multiple myeloma is characterized by the presence of abnormal plasma cells. These cells can be identified by their large, eccentric nuclei and abundant cytoplasm. The nuclear chromatin is often coarse and clumped, and nucleoli may be prominent. In advanced stages, plasma cells may show pleomorphism and an increased mitotic rate.

Bone Marrow Examination

A bone marrow biopsy is critical for the diagnosis of multiple myeloma. The biopsy typically reveals an increased number of plasma cells, which can range from 10% to more than 90% of the cellularity. These plasma cells often form clusters and sheets, disrupting the normal architecture of the bone marrow. Immunohistochemistry can be used to confirm the plasma cell nature of the infiltrate by staining for CD138 and CD38.

Role of Immunohistochemistry

Immunohistochemistry is essential in the histological diagnosis of multiple myeloma. Specific markers such as CD138, CD38, and monoclonal immunoglobulin light chains (kappa and lambda) are used to identify and confirm the plasma cell lineage. Aberrant expression of markers like CD56, CD117, and cyclin D1 can also provide additional diagnostic and prognostic information.

Histopathological Variants

Multiple myeloma can present in several histopathological variants, including plasmacytoma, plasmablastic myeloma, and small cell myeloma. Each variant has unique morphological features that can influence the prognosis and treatment approach. For example, plasmablastic myeloma is characterized by cells with a high nuclear-to-cytoplasmic ratio and prominent nucleoli, and it is often associated with a more aggressive clinical course.

Cytogenetic and Molecular Studies

Cytogenetic and molecular studies complement histological findings and provide important prognostic information. Common abnormalities include translocations involving the immunoglobulin heavy chain (IgH) locus on chromosome 14, deletions of chromosome 13, and mutations in genes such as TP53 and RAS. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) are commonly used techniques to detect these abnormalities.

Bone Lesions

Multiple myeloma is often associated with osteolytic bone lesions due to increased activity of osteoclasts and suppression of osteoblast function. Histologically, these lesions show a loss of normal bone architecture, replacement by plasma cells, and increased numbers of osteoclasts. The presence of bone lesions can be confirmed by imaging techniques such as X-rays, MRI, or CT scans.

Clinical Correlation

The histological findings in multiple myeloma correlate with various clinical features such as bone pain, anemia, hypercalcemia, and renal dysfunction. The extent of plasma cell infiltration and the presence of specific histopathological features can influence the prognosis and guide the choice of therapeutic strategies.

Conclusion

Histological examination plays a crucial role in the diagnosis and management of multiple myeloma. The identification of abnormal plasma cells, supported by immunohistochemical and molecular studies, provides essential information for accurate diagnosis and prognosis. Understanding the histological features and their clinical implications is vital for optimizing patient care in multiple myeloma.



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