A8. Low-grade lymphomas (Chronic lymphocytic leukemia.

Follicular lymphoma)

• Chronic Lymphocytic Leukemia:

 both Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are
morphologically, phenotypically, and genotypically identical, differing only in the extent of
peripheral blood involvement.
 If peripheral blood lymphocytosis exceeds 4000 cells/mm^3 = CLL
 If not, patient has SLL
 CLL is the most common leukemia of adults

(From lecture…)

 Begins → Bone marrow and blood  leukemia

Lymph node  lymphoma

 Ends  Bone marrow, lymph node, liver, spleen, and blood

 Involves:
 Non-destructive growth, BM infiltration > 70%
 Prognosis depends on:
 Stage, tumor markers present (depends on mutation status, immunophenotype, cytogenetic
aberrations, proliferation index), general condition of the patient
 Cluster of Differentiation (CD)
 Cell surface molecules/pan-B cell markers present on white blood cells affected here include →
CD19+, CD20+, CD23+, CD5+
- CD5+ is only expressed with mantle cell lymphomas
 Pathophysiology
 Neoplastic B cells suppress normal B cell function, results in hypogammaglobinemia
 15% of patients have autoABs against autologous red cells; other autoABs can also be detected
 These autoABs are made by nontumor B cells = indicates breakdown in immune regulation
 As time passes, the tumor cells displace normal marrow elements, leading to  Anemia,
neutropenia, and thrombocytopenia
 Morphology
 Sheets of small, round lymphocytes and scattered ill-defined foci are larger
 Predominant cells are compact, small, resting lymphocytes with dark-staining round nuclei, scanty
cytoplasm, and little variation in size
 Foci of mitotically active cells are called proliferation centers
 In most patients there is an absolute lymphocytosis of small, mature-looking lymphocytes
 Neoplastic lymphocytes are often disrupted during preparation of smears creating characteristic
smudge cells
 Clinical Features
 Often asymptomatic at presentation
 Most common symptoms are nonspecific and include  Fatigue, weight loss, and anorexia
 Lymphadenopathy and hepatosplenomegaly are present in 50% to 60% of cases
 Hypogammaglobulinemia develops in more than 50% of patients, usually late in the course of the
disease (Causes increased susceptibility to bacterial infections)
 Less commonly, autoimmune hemolytic anemia and thrombocytopenia are seen
 Course and prognosis are extremely variable; some patients live for more than 10 years after
diagnosis, but the median survival is 4 to 6 years
 As time passes, CLL/SLL tends to transform to more aggressive tumors that resemble either pro-
lymphocytic leukemia or diffuse large B-cell lymphoma (Once transformation occurs, survival is less
than 1 year)
 Recapitulate follicular structures
 Indolent
 Bone marrow is often involved
 Methods of treatment involve Immuno and chemotherapy
 Morphology
 Lymph nodes are effaced by proliferations that have a distinctive nodular appearance
 Tumor cells resemble normal follicular center B cells
 The predominant neoplastic cells are, “centrocyte-like” cells slightly larger than resting lymphocytes
that have angular, “cleaved” nuclear contours with prominent indentations and linear infoldings
 Nuclear chromatin is coarse and condense, and nucleoli are indistinct
 Small cleaved cells are mixed with larger, “centroblast-like” cells that have vesicular chromatin,
several nucleoli, and modest amounts of cytoplasm
 Mitoses are infrequent, and single necrotic cells are not seen – help to distinguish neoplastic
follicles from reactive follicles, in which mitoses and apoptosis are prominent*** (They showed
pictures of reactive and neoplastic follicles in lecture)
 Clinical Features
 Occurs predominantly in older persons and affects males and females equally
 Presents a painless lymphadenopathy
 Bone marrow almost always contains lymphoma at time of diagnosis
 Median survival of 7 to 9 years, but follicular lymphoma is not easily curable (may be related to
elevated levels of bcl2, which may protect tumor cells from the effects of chemotherapy)
 In 40% of patients, follicular lymphoma progresses to a diffuse large B-cell lymphoma