An 89 year-old female with generalized adenopathy underwent left cervical neck lymph node biopsy.
Lymph node architecture was completely effaced by small well differentiated lymphocytes with irregular, variably interspersed and expanded “pale” zones containing small, medium and few larger cells with nucleoli. There was mild increase in background capillary sized blood vessels. No preserved germinal centers, subcapsular sinuses, or medullary spaces were seen. Focally, tumor cells extended beyond the capsule into surrounding adipose.
- A. Flow cytometry - 59% CD5+ monoclonal B-cell population, compatible with malignant B cell lymphoma with an immunophenotype suggestive of mildly atypical chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), requiring morphologic subclassification
a. CD45+ (moderate), CD19+, CD20+ (heterogeneous), CD5+, CD10-, CD23+, FMC7-, CD38+ , sIg kappa+ (bright)
- B. Immunohistochemistry - Paraffin immunohistochemical stains highlighted a mixture of PAX5+ B cells and nearly equal numbers of CD3+ T cells. Relative to PAX5+ B cell staining, there was a 40-50% Ki67 index. Tumor cells were p53 negative.
a. Deletion of 11q22.3(ATM) in 78% of cells.
b. Gain of CEP 12 in 32% of cells.
c. Gain of CEP 12 concurrent with deletion 13q14 in 16% of cells.
d. NEGATIVE for BCL1(CCND1)/IGH/ t(11;14)
- two non-rearranged copies of BCL1(CCND1) and IGH; two non-rearranged copies of 6q23, 11q13, 13q34, 14q32 and 17p13.1
Differential Diagnosis: Atypical CLL/SLL vs. CLL/SLL undergoing large cell (Richter’s) transformation vs. atypical mantle cell lymphoma vs. “paraimmunoblastic” lymphoma
Diagnosis: “Accelerated” small lymphocytic lymphoma/ chronic lymphocytic leukemia with increased proliferation centers and unfavorable cytogenetic features.
Educational comments: Typically, small lymphocytic lymphoma/chronic lymphocytic leukemia undergoes “transformation” in two forms, either large cell (Richter’s) transformation or prolymphocytic transformation. The concept of “accelerated” CLL/SLL is less clearly defined in pathologic terms. Historically, there have been scattered, murky reports describing atypical small lymphocytic lymphomas such as this case, that were confused by blurred distinctions between prolymphocytes, paraimmunoblasts, and large cells. Many or most of those earlier reports seem to better described as “accelerated” small lymphocytic lymphomas with "increased proliferation centers" (see reference). Although it is tempting to equate increased proliferation centers in tissue samples with increased prolymphocytes in circulating blood, it is not certain that these are equivalent features of disease progression in CLL/SLL.
In tissue sections, “accelerated” small lymphocytic lymphomas with "increased proliferation centers" lack features off large cell transformation and demonstrate increased numbers of expanded proliferation zones, intermediate levels of Ki67 staining (5-30%) and intermediate prevalence of positive p53 staining when compared to nonaccelerated CLL/SLL and diffuse large B cell lymphoma.
In support of an accelerated form of disease, which is associated with unfavorable overall survival, this tumor demonstrated adverse cytogenetic features deletion 11q22.3(ATM) and trisomy 12.
References: Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (“accelerated” chronic lymphocytic leukemia) with aggressive clinical behavior. Haematologica 2010;95(9):1526-1533
Fig. 1 - Conventional region of usual CLL/SLL (H&E)
Fig 2 - Proliferation zone (H&E)
Fig. 3 - Proliferation zone (Ki67)
Fig. 4 - del 11q22.3 (ATM) [MYBx2(Aqua),ATMx1(Green), p53x2(Orange)]
Fig. 5 - trisomy 12 [CEP12x3(Green), 13q14x2(Orange), 13q34x2(Aqua)]