T-Cell Prolymphocytic Leukemia Involving Extramedullary Sites

Jose R. Valbuena, MD; Marco Herling, MD; Joan H. Admirand, MD; Anthony Padula, MD; Dan Jones, MD, PhD; L. Jeffrey Medeiros, MD


Am J Clin Pathol. 2005;123(3):456-464. 

In This Article


Although the clinical and morphologic features of T-PLL have been reported previously,[2,3,4,11,12] most of these studies have addressed the morphologic characteristics of this disease in the peripheral blood and bone marrow. The morphologic features of T-PLL involving extramedullary sites are poorly documented in the literature. The goal of this study was to focus on the pathologic findings of T-PLL involving extramedullary sites. To achieve this goal, we collected 19 biopsy specimens obtained from extramedullary sites in 14 patients, all whom had well-documented T-PLL at the time of initial diagnosis.

In the present study, none of the extramedullary biopsy specimens were obtained at the time of initial diagnosis; all were obtained later, at the time of disease progression. Presumably, extramedullary sites are not biopsied at the time of initial diagnosis at our institution because the diagnosis is established by examination of peripheral blood or bone marrow specimens. Nevertheless, most patients with T-PLL have extramedullary sites of involvement at the time of initial diagnosis, most often involving the spleen, liver, lymph nodes, and skin. In a review of 175 patients with T-PLL by Matutes and Catovsky,[4] splenomegaly was present in 74%, hepatomegaly in 55%, lymphadenopathy in 26%, and skin lesions in 25%. These sites also were involved in the 14 cases we report, although the frequency differed somewhat at the time of initial diagnosis; lymphadenopathy (69%) and skin lesions (46%) were more common, and hepatosplenomegaly was less common. At the time of disease progression when an extramedullary site was biopsied, skin lesions and hepatomegaly (both 57%) were relatively more common ( Table 2 ).

The skin was the anatomic site most commonly biopsied in this study group (10 specimens from 7 patients). Although other extramedullary sites were also commonly involved in these patients, presumably the skin was most often biopsied in our study group because it is readily accessible. In our review of the literature, we found surprisingly few reports describing the pathologic findings of T-PLL involving the skin. The largest study by Mallet et al[13] described 9 skin biopsy specimens obtained from 92 patients with T-PLL (including 26 patients who had clinical evidence of skin disease). Other pathologic studies of T-PLL involving skin have been case reports.[14,15,16]

Histologically, skin lesions involved by T-PLL have been described as atypical lymphoid infiltrates of variable density surrounding blood vessels and skin appendages with no epidermotropism.[13,14,16] Patients with skin nodules have had diffuse dermal involvement. Thus, the cases in the present study are in agreement with the literature. However, case 5 in this study is unusual. We are not aware of another patient with T-PLL described in the literature who had a large subcutaneous mass. Two other biopsy specimens (cases 12 and 13) also are of interest because the skin biopsy specimens had foci of epidermotropism. This has not been emphasized adequately in earlier reports of skin involvement by T-PLL.[13,14] In fact, 1 biopsy specimen had epidermotropism and epidermal changes, the latter including hyperkeratosis and parakeratosis. These changes raise the differential diagnosis with mycosis fungoides/Sézary syndrome. In addition, in 3 of the skin biopsy specimens we studied, the neoplastic cells had irregular or Sézary-like nuclear contours, as described by others.[2] However, the clinical setting of well-established T-PLL in the cases included in the present study prevented potential misdiagnosis.

The biopsy specimens in the present study show that the cytologic features of T-PLL in routinely stained tissue sections are heterogeneous. The typical description of T-PLL in peripheral blood or bone marrow smears, that being a monotonous population of medium-sized prolymphocytes with prominent central nucleoli, was not common in the cases we report. The T-PLL cells in 3 biopsy specimens, 2 skin and 1 lymph node, were monotonous with virtually all cells having a prominent nucleolus that could be observed readily at routine high-power magnification (×400). In 8 additional biopsy specimens, a subset of T-PLL cells had prominent nucleoli, although these cells initially were better detected at ×1,000 (oil immersion) magnification. In the remaining biopsy specimens, nucleoli were not prominent, even at ×1,000 magnification. The latter cases might correspond to the small cell variant of T-PLL described in blood and bone marrow.[1]

A number of chromosome abnormalities have been reported in T-PLL. The most distinctive cytogenetic abnormality known to occur is the inv(14)(q11q32), or the rare t(14;14)(q11;q32) and t(X;14)(28;q11). In the inv(14) and t(14;14), the tcl -1 oncogene is juxtaposed with the promoter/enhancer of the TCR ad locus at 14q11, resulting in TCL-1 overexpression.[16,17] Similarly, in the t(X;14) the mtcp -1 gene on chromosome Xq28 is juxtaposed with the TCR ad locus. Overexpression of TCL-1 is reported to be present in 80% to 90% of cases of T-PLL.[17] In TCL-1–negative cases, other genes in proximity at 14q32, such as tcl -1b, may also be involved.

In the present study, we demonstrated TCL-1 overexpression using immunohistochemical methods in biopsy specimens from 9 (64%) of 14 patients. In an earlier study, Herling and colleagues[18] demonstrated that TCL-1 expression is restricted to T-PLL among mature T-cell neoplasms, and, thus, TCL-1 expression can be useful in distinguishing this neoplasm from other T-cell neoplasms. However, TCL-1 immunostaining did not detect all cases of T-PLL in the present study. Furthermore, TCL-1 is not specific for T-PLL. By using immunohistochemical methods, Narducci et al[19] assessed TCL-1 expression in 194 cases, including neoplastic B- and T-cell lymphomas and reactive specimens. In reactive tissue, TCL-1 is expressed in most pre–germinal center B cells and some germinal center B cells but not in post–germinal center B cells, plasma cells, or mature T cells. TCL-1 also is expressed in many B-cell neoplasms, including cases of precursor B-cell lymphoblastic lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, and primary cutaneous B-cell lymphoma. Taken together, our results show that TCL-1 immunostaining in neoplasms known to be of T-cell lineage is a specific but not sensitive marker of T-PLL. These results, however, also suggest that T-PLL, as currently defined in the WHO classification, is not a completely homogeneous entity.

In summary, we describe the histologic findings of T-PLL involving 19 biopsy specimens obtained from extramedullary sites in 14 patients. Skin involvement was the most common extramedullary site biopsied, followed by liver and lymph nodes. At our institution, extramedullary sites of involvement, although present, were not biopsied at the time of initial diagnosis, presumably because peripheral blood and bone marrow are more appropriate and accessible for establishing the diagnosis. Instead, extramedullary sites of disease in patients with T-PLL at our institution were biopsied subsequently, to support the clinical impression of disease progression. Disease involving these extramedullary sites may have been less responsive to the therapy, because peripheral blood and bone marrow samples were negative or minimally involved in some of the patients.

In addition, we found the cytologic features of T-cell prolymphocytes difficult to recognize in routine H&E-stained tissue sections in many specimens. Thus, recognition of T-PLL involving extramedullary sites often requires morphologic evaluation at ×1,000 magnification and usually needs additional workup using ancillary methods. TCL-1 expression, assessed immunohistochemically, is a useful marker for documenting T-PLL involving extramedullary sites. However, absence of TCL-1 expression does not exclude involvement by T-PLL.


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