MATURE B-CELL NEOPLASMS
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are very similar; they both represent an abnormal proliferation of B cells. Patients who pres-ent with lymph node findings are classified as having SLL. Patients who present with blood findings are classified as having CLL; 50% of CLL patients also have lymph node involvement.
• CLL is the most indolent of all of the leukemias.
• Mean age at time of diagnosis is age 60.
• The malignant cells are nonfunctional, so patients develop hypogammaglobu-linemia, leading to an increased risk of infections.
• CLL is associated with warm autoimmune hemolytic anemia (AIHA) (10% of cases), which will cause spherocytes to be observed in peripheral blood.
• CLL rarely transforms into a worse disease such as prolymphocytic leukemia or large cell lymphoma (Richter syndrome).
CLL and SLL can be categorized by the markers present on the B cells:
• B-chronic lymphocytic leukemia cells (95% of cases) have B-cell markers, such as CD19 and CD20. One T-cell marker, CD5, is also present. Also important is that the cells are CD23 positive and CD10 negative.
• SLL occurs only as this type.
• T-chronic lymphocytic leukemia cells (5% of cases) have T-cell markers. The histology of affected lymph nodes reveals only a diffuse pattern (not nodular), but proliferation centers may also be present.
• Peripheral blood findings show increased numbers of normal-appearing lym-phocytes. Numerous smudge cells (“parachute cells”) are also present; the smudge cells result from the fact that the neoplastic lymphocytes are unusu-ally fragile.
• Bone marrow shows numerous normal-appearing neoplastic lymphocytes.
Hairy cell leukemia is a rare B-cell neoplasm that causes indolent disease in middle-aged Caucasian men. There can be a “dry tap” with bone marrow aspiration. Lym-phocytes have “hairlike” cytoplasmic projections; the diagnostic stain is positive tartrate-resistant acid phosphatase (TRAP).
Physical examination shows a markedly enlarged spleen (splenomegaly) due to infil-tration of red pulp by malignant cells.
Treatment is 2-chloro-deoxyadenosine (2-CdA), which inhibits adenosine deami-nase (ADA) and increases levels of toxic deoxyadenosine.
Follicular lymphoma is a well-differentiated B -cell lymphoma with follicular archi-tecture. All follicular lymphomas are derived from B lymphocytes.
• Most common form of non-Hodgkin lymphoma in the United States
• Characteristic translocation is t(14;18), involving the immunoglobulin heavy chain gene and BCL2 gene (activation of bcl-2 inhibits apoptosis by blocking the bax channel)
• Frequently presents with disseminated disease (more advanced stage)
• Prognosis is better than diffuse lymphoma, but it doesn’t respond to therapy (unlike the more aggressive diffuse non-Hodgkin lymphomas)
Diffuse large B-cell lymphoma is a high grade large B-cell lymphoma with a diffuse growth pattern. It is an aggressive, rapidly proliferating tumor which may respond to therapy. Special subtypes include immunodeficiency-associated B-cell lymphomas (often infected with Epstein-Barr virus) and body-cavity large B-cell lymphomas (sometimes associated with human herpes virus [HHV]-8).
Small noncleaved lymphoma (Burkitt lymphoma) is a high grade B-cell lymphoma. It is composed of intermediate-sized lymphoid cells with a “starry sky” appearance due to numerous reactive tingible-body macrophages (phagocytosis of apoptotic tumor cells). There is a characteristic t(8;14) translocation juxtaposing MYC to the immunoglobulin heavy chain locus in most cases.
• African type: endemic form
°° Involvement of mandible or maxilla is characteristic; is associated with Epstein-Barr virus
• American type: nonendemic, sporadic form
°° Involvement of the abdomen (such as bowel, retroperitoneum, or ova-ries); has a high incidence in AIDS patients
Both endemic and sporadic forms of Burkitt lymphoma are seen most often in children and young adults.
Mantle cell lymphoma (MCL) is a rare B-cell lymphoma in which the tumor cells arise from mantle zone B lymphocytes (positive for CD19, CD20, and CD5; nega-tive for CD23). The characteristic translocation is t(11;14), involving CCD1 and the heavy chain locus.
Marginal zone lymphoma (MALToma) is a diverse group of B-cell neoplasms that arise within lymph nodes, spleen, or extranodal tissue. It is associated with mucosa-associated lymphoid tissue (MALTomas). The lesion begins as a reactive polyclonal reaction and may be associated with previous autoimmune disorders or infectious disease (e.g., Sjögren disease, Hashimoto thyroiditis, Helicobacter gastritis). The lymphoma remains localized for long periods of time.
Multiple myeloma is a malignant neoplasm of plasma cells.
• Most common primary tumor arising in the bone marrow of adults
• Lab studies show increased serum protein with normal serum albumin; an M spike in serum electrophoresis is a monoclonal immunoglobulin spike—most commonly IgG (60%) and next most commonly IgA (20%)
• Bence Jones proteins are light chains that are small and can be filtered into urine.
Histologically, bone marrow shows increased plasma cells (>20% is characteristic). Peripheral blood may show rouleaux formation (“stack of coins”). Multiple lytic bone lesions are due to the osteoclastic activating factor. Lytic bone lesions cause hypercalcemia, bone pain, and increased risk of fracture.
Increased risk of infection is the most common cause of death. Other complications include renal disease (such as myeloma nephrosis) and primary amyloidosis (10% of patients) due to amyloid light (AL) chains. Increased amounts of IL-6 are associated with a poorer prognosis because survival of myeloma cells is dependent on IL-6.
Plasmacytoma is a solitary myeloma within bone or soft tissue.
• Within bone: precursor lesion that can later develop into myeloma
• Outside bone (extramedullary): usually found within upper respiratory tract
Monoclonal gammopathy of undetermined significance (MGUS) (an old name was benign monoclonal gammopathy). Serum M protein is found in 1–3% of asymp-tomatic individuals age >50; the incidence increases with increasing age. The annual risk of developing a plasma cell dyscrasia, usually multiple myeloma, is 1–2% per year. MGUS may also evolve into Waldenström macroglobulinemia, primary amy-loidosis, B-cell lymphoma, or CLL.
Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia) is a small lym-phocytic lymphoma with plasmacytic differentiation. It is a cross between multiple myeloma and SLL.
Like myeloma, it has an M spike (IgM). Like SLL (and unlike myeloma), the neo-plastic cells infiltrate many organs (e.g., lymph nodes, spleen, bone marrow). Also unlike multiple myeloma, there are no lytic bone lesions and there is no increase in serum calcium. Russell bodies (cytoplasmic immunoglobulin) and Dutcher bodies (intranuclear immunoglobulin) may be present.
• May have hyperviscosity syndrome, because IgM is a large pentamer
• Visual abnormalities may be due to vascular dilatations and hemorrhages in the retina
• Neurologic symptoms include headaches and confusion
• Bleeding and cryoglobulinemia can be due to abnormal globulins, which pre-cipitate at low temperature and may cause Raynaud phenomenon