PMC6420994_01
Composite chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and T-prolymphocytic leukemia (T-PLL). This lymph node shows partial effacement of the architecture by a vaguely nodular/follicular proliferation of small-to-medium-sized lymphocytes surrounded by a dense infiltrate of small-to-intermediate-size lymphocytes. Hematoxylin and eosin stain (a-c). Immunohistochemistry shows that the nodular/follicular areas react with the B-cell marker CD20 (d), whereas the interfollicular areas are highlighted with the T-cell marker CD3 (e, f). Note that the follicular areas are also faintly positive with CD5 (g) and dimly positive with CD23 (h), supporting CLL/SLL (h). This distribution of CLL/SLL centered on follicular dendritic cell meshworks highlighted with CD23 is extremely unusual and supports the so-called follicular pattern of CLL/SLL.
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Interestingly, the pattern of CLL/SLL in the lymph node was unusual, as it seemed that the neoplastic cells were restricted to lymphoid follicles, a pattern known as the follicular pattern of CLL/SLL (Figures 1(a)-1(h)).
Annular erythematous maculopapular lesions on the upper and lower back (a, b). Dermal infiltration of small-to-medium-sized mature lymphocytes with periadnexal and perivascular distribution (c, d, e). These lymphocytes reacted predominantly with CD3 (f) and CD5 (not shown); only rare lymphocytes were positive for CD20 (g).
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At the time of initial diagnosis of CLL/SLL in early 2016, the patient noted a skin rash, mainly in the back with a waxing and waning clinical course (Figures 2(a) and 2(b)). Multiple skin biopsies were performed on these lesions diagnosed as superficial and deep dermis small T-cells and rare small lymphocytes with a periadnexal and perivascular distribution; a diagnosis of B-cell lymphoma was excluded (Figures 2(c)-2(g)). PCR for IGH in the same specimens was consistently negative (Figures 2(a)-2(g)).
(a) Trending of WBC count from the time of diagnosis in January 2016 to the latest follow-up in March 2018. The arrow points to the WBC count at the time of bone marrow biopsy. It is noted that subsequent therapy led to leukopenia. (b) and (c) Computed tomography (CT) of mid-upper thorax shows multiple enlarged lymph nodes (arrows) in the mediastinum and axilla (b), while CT of the upper abdomen demonstrates a markedly enlarged spleen (arrow) (c).
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The peripheral blood WBC count rose to 117 x 109/L, compared with 12.5 x 109/L at diagnosis (Figure 3(a)). A new staging computed tomography (CT) scan showed multicompartmental lymphadenopathy and splenomegaly (Figures 3(b) and 3(c)). A substantial reduction in previous splenomegaly was observed (Figure 3).
T-PLL in bone marrow biopsy specimen. A bone marrow clot section shows multiple lymphoid aggregates (white circle) composed predominantly of small-to-intermediate-size lymphocytes ((a), low power, (b), high power). The B-cell marker CD20 highlights scattered small lymphocytes (c). The T-cell marker CD3 highlights most lymphocytes in the lymphoid aggregates (d, e). Bone marrow aspirate smear shows numerous small-to-intermediate-size lymphocytes with scant cytoplasm displaying small projections and central nuclei with distinct nucleoli (f). The spectrum of T-PLL lymphocytes in the peripheral blood is shown (g); lymphocytes are predominantly small to intermediate in size with oval to slightly irregular nuclei and distinct nucleoli. The cell contours show blebs, while the cytoplasm is bluish and eccentric. Similar peripheral blood features were noted at initial presentation 3 years before.
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T-PLL, representing ~70% of bone marrow cells, (b) minor population of CLL, representing 1.2% of bone marrow cells, and (c) CD5-negative small monotypic B-cells, representing 2.8% of bone marrow cells. The concurrent peripheral blood smear showed predominance of small-to-medium-sized lymphocytes with irregular nuclear contours, clumped chromatin, and conspicuous nucleoli (Figures 4(a)-4(g)).
T-PLL involvement of lymph node (a, b) and skin (c, d). T-cells in the interfollicular areas are positive for TCL1 immunostain ((a), 200X and (b), 500X). T-cell aggregates in the dermis are positive for TCL1 ((c), 100X, (d), 400X). The insets in figure (c) show expression of CD3 (top) and lack of expression of CD20 (bottom) in neoplastic cells.
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In light of the new diagnosis of T-PLL, the diagnostic tissues from original pelvic lymph node, obtained at the time of prostatectomy and from one of the skin biopsy specimens, were reanalyzed with TCL1 immunostain to evaluate if T-PLL was present at the time of diagnosis of CLL (Figures 5(a)-5(d)).
Composite CLL/SLL and T-PLL. Flow cytometry immunophenotype ((a) and (b)) of a bone marrow aspirate specimen. Panel (a) shows a prominent T-cell population (CD5+, CD19-) as well as a minor CD19+/CD5+ B-cell population that corresponds to CLL/SLL. Panel (b) shows that 46% of the analyzed bone marrow cells were CD4+/CD8+ corresponding to T-PLL, as detected in 25% of T-PLL cases. This lymphocyte population also expressed CD7 (bright and homogenous) and CD26, further supporting the diagnosis of T-PLL. FISH analysis ((c) and (d)): (c) FISH analysis with ATM (green) and TP53 (red) exhibits 2 red, 1 green signal pattern, indicating ATM gene deletion; (d) FISH analysis with a TCL1 break-apart probe exhibits 1 red, 1 green (split), and 1 yellow signal, indicating TCL1 rearrangement.
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Also identified were two monotypic B-cell populations with 1.2% of total cells being CD5-positive and 2.8% of total cells being CD5-negative (Figures 6(a) and 6(b)).
Timeline of most important pathologic findings from the diagnosis of prostate adenocarcinoma to T-PLL (abbreviations: BM: bone marrow, CLL: chronic lymphocytic leukemia, LAP: lymphadenopathy, LN: lymph node, PB: peripheral blood, Rx: treatment, SLL: small lymphocytic lymphoma, T-PLL: T-cell prolymphocytic leukemia, WBC: white blood cell count).
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