T- cell prolymphocytic leukemia - a rare case.

T- cell Prolymhocytic leukemia (T-PLL) is a rare mature post-thymic T-cell malignancy that is usually reported in the elderly and follows an aggressive course. A 68 year old male presented with a history of weakness and weight loss of two months duration. Clinical examination revealed pallor, enlarged cervical and axillary lymph nodes and splenomegaly. He also had a maculo- papular skin rash. There was marked leucocytosis, anemia and thrombocytopenia (WBC 445 x 103 sub/ml, Hb 8.5 gm/dl, Platelet 25 x 103 sub/microl) with 60% prolymphocytes in the peripheral blood. Bone marrow was hypercellular with an excess of prolymphocytes. Flow cytometric analysis of the bone marrow showed positivity for CD2, CD3, CD4, CD5 and CD 7. T- PLL is a rare T cell disorder with characteristic clinical and laboratory features. Currently, no optimal treatment exists although there has been some success with 2'- deoxycoformycin or Campath-1H.

An indolent case of T-prolymphocytic leukemia with t(3;22)(q21;q11.2) and elevated serum beta2-microglobulin.

We report a novel case of T-prolymphocytic leukemia, small cell variant, associated with complex cytogenetic findings including t(3;22)(q21;11.2) and elevated serum beta2-microglobulin. The diagnosis is based on morphologic, immunophenotypic, cytogenetic, and molecular analysis of peripheral blood and bone marrow. In contrast to most reported cases of T-prolymphocytic leukemia, this patient did not present with lymphadenopathy or organomegaly. Moreover, only a moderate leukocytosis (25.3 x 10(3)/microL) was evident at presentation. In the absence of any specific treatment, the patient is doing well, with a stable white blood cell count 12 months following presentation. Further investigation may be warranted to determine whether the unusual cytogenetic findings and elevated serum beta2-microglobulin are associated with the indolent clinical course in this patient.

Nonmyeloablative peripheral blood stem cell transplant for T-cell prolymphocytic leukaemia complicated by fulminant haemolysis and acute renal failure at engraftment secondary to minor ABO incompatibility.

We present a 54-year-old man who underwent human leucocyte antigen-identical sibling nonmyeloablative peripheral blood stem cell transplant for primary refractory T-cell prolymphocytic leukaemia (T-PLL). His clinical course was complicated by fulminant haemolysis and acute renal failure at the time of engraftment because of minor ABO incompatibility between the donor and the recipient. This case highlights the curative potential of nonmyeloablative transplantation for T-PLL as well as the potential severity of immune haemolysis secondary to minor ABO incompatibility.

Discrimination of chronic lymphocytic leukemia (CLL) and CLL/PL by cytomorphology can clearly be correlated to specific genetic markers as investigated by interphase fluorescence in situ hybridization (FISH).

Although interphase fluorescence in situ hybridization (FISH) is routinely used in chronic lymphocytic leukemia (CLL), differences in the chromosomal pattern with respect to morphological subtypes of CLL (typical CLL, CLL/PL, PLL) are still under debate. We studied 153 patients with CLL and correlated cytomorphology on peripheral blood stains with FISH analysis and other prognostic markers. The percentage of prolymphocytes was calculated as a continuous variable and followed published thresholds in parallel while being correlated to FISH analysis. Higher percentages of prolymphocytes were associated significantly with deletion of 17p13. Deletion of 17p13 was most frequently observed in patients with more than 30% prolymphocytes. Trisomy 12 was found mainly in cases with 6-30% prolymphocytes. The percentage of prolymphocytes did not correlate with deletions of 11q23 or with 13q14 abnormalities. In conclusion, we suggest that further research focus on the percentage of prolymphocytes in CLL. Doing so, biologically relevant thresholds for the percentages of prolymphocytes in the peripheral blood and their association to underlying genetic markers could be investigated together with other biologically and especially prognostic markers.

Prolymphocytic leukaemia--report of three cases.

Prolymphocytic leukaemia is a rare subtype of chronic lymphocytic leukaemia. Three such cases were reported here along with clinical details. All these cases were seen in males above 5th decade. These patients showed moderate to massive splenomegaly, inconspicuous lymphadenoapthy in two cases and one with minimal lymphadenopathy. Peripheral smear showed high leukocyte count with more than 55% of prolymphocytes. Bone marrow aspiration showed diffuse involvement and in one with minimal lymphadenopathy, lymphnode aspiration showed prolymphocytes. All the three patients died within a year after diagnosis.

CD3-negative, CD20-positive T-cell prolymphocytic leukemia: case report and review of the literature.

We report a case of CD3-negative, CD20-positive T-cell prolymphocytic leukemia (T-PLL). The leukemic cells were of medium-to-large size, mature-looking, and did not have cytoplasmic granules. The leukemic cells were negative for surface CD3, CD2, and CD7 and strongly positive for CD20. T-cell lineage markers such as CD4, CD5, and cytoplasmic CD3 were also positive. A monoclonal rearrangement of the T-cell receptor (TCR) beta chain gene was detected. CD3-negative T-PLL has been reported often, but CD20-positive T-PLL has not. We reviewed seven cases of CD20-positive immature and mature T-cell leukemias, including the present case. Three were immature T-cell leukemias (acute lymphoblastic leukemia), and four were mature T-cell leukemias (granular lymphocytic leukemia, small lymphocytic lymphoma/chronic lymphocytic leukemia, adult T-cell leukemia, and the present case). Splenomegaly was a common feature. However, our case alone had "bright" CD20 expression on the leukemic cells. This is the first report of CD20(+) T-PLL.

T-cell prolymphocytic leukemia with hemorrhagic gastrointestinal involvement and a new chromosomal abnormality.

We report a case of T-cell prolymphocytic leukemia in a 56-year-old woman who exhibited hemorrhaging with gastric involvement as the first manifestation. This patient's condition was diagnosed as T-cell prolymphocytic leukemia based on the findings of lymphocytosis, abnormal immunophenotype, hepatosplenomegaly, lymphadenopathy, and cutaneous involvement. Endoscopic examination of the upper gastrointestinal tract revealed hemorrhage from a gastric lesion with histological involvement. Cytogenetic analysis revealed chromosomal abnormalities, 46,XX,der(1), add(1)(p36), that have not previously been described in T-cell prolymphocytic leukemia. In spite of a transient response to chemotherapy, the patient died 15 months after onset of the disease.

Flow cytometry and the study of central nervous disease in patients with acute leukaemia.

Central nervous system (CNS) leukaemia is still a matter of debate and new technologies are required to improve the classic morphological definition. One hundred and sixty-eight cerebrospinal fluid (CSF) samples from 31 patients with acute leukaemia were analysed by flow cytometry and conventional cytology. Concordant positive and negative findings were found in 158 samples but 10 produced discrepant results. Cytology seemed to offer more precise information in one CSF sample and flow cytometric accuracy could be demonstrated in five samples. We conclude that flow cytometry is of great help in confirming CNS leukaemia and eliminating other conditions. Therefore, leukaemic patients can benefit from double cytological and flow cytometric CSF studies.

Seropositive polyarthritis and skin manifestations in T-prolymphocytic leukemia/Sezary cell leukemia variant.

Sezary cell leukemia (SCL) is a rare T cell neoplasia that has been suggested to be a variant of T-prolymphocytic leukemia (T-PLL). Both disorders have an aggressive clinical course, lymphocytosis with characteristic morphology, lymphadenopathy, hepatomegaly, characteristic cytogenetic abnormalities and mature T cell phenotypes. Skin lesions, however, are mainly found in T-PLL. We describe a patient with T-PLL/SCL, who atypically presented with severe seropositive polyarthritis and skin lesions, responding to treatment with human CD52 antibody, CAMPATH-1H and pentostatin. Meningeal leukemia and an assumed myocardial infiltration subsequently developed. Polyarthritis is common in T large granular lymphocyte leukemia and adult T cell lymphoma-leukemia, but both entities could be ruled out in the present case. In rheumatoid arthritis, an expansion of CD4+ and/or CD8+ T lymphocytes is well documented and this phenomenon is believed to be of pathogenetic importance. We speculate that the T cell clone in the present case had special homing properties or cytokine effects resulting in synovitis.

Serum levels of parathyroid hormone-related protein are not elevated in patients with T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm which shares most clinical features with adult T-cell leukemia (ATL). We measured serum level of C-terminal parathyroid hormone-related protein (C-PTHrP) in patients with T-PLL and ATL. Serum C-PTHrP levels of eight patients with T-PLL (median 36.8 pmol/l; range 27.0-50.2 pmol/l) did not differ from those of 30 human T-lymphotropic virus type I (HTLV-I)-seronegative blood donors (median 37.0 pmol/l; range 22.6-54.0 pmol/l). The C-PTHrP levels in ten ATL patients (median 69.6 pmol/l; range 42.5-899.4 pmol/l) were significantly higher than those in healthy controls (p<0.0001) or T-PLL patients (p=0.001). We suggest that the serum level of PTHrP can provide useful information for differentiating between T-PLL and ATL.

T-cell prolymphocytic leukemia with a novel translocation (6;11)(q21;q23).

T-cell prolymphocytic leukemia (T-PLL) is an uncommon chronic lymphoproliferative disorder characterized by lymphadenopathy, splenomegaly, and lymphocytosis. The leukemic cells have the appearance of prolymphocytes and usually an immunophenotype of T-helper cells (CD3+ CD4+ CD8-). Inv(14q), del(11q), i(8q), and rearranged Xq28 are the commonest nonrandom chromosomal abnormalities in T-PLL. Recently, it has been shown that the ataxia-telangiectasia mutated (ATM) gene located at 11q23 is often deleted in T-PLL, suggesting a tumor suppressor role of the ATM gene on tumorigenesis of T-PLL. We report a case of T-PLL with t(6;11)(q21;q23) as the sole chromosomal abnormality and suggest that the cytogenetically identified translocation also implicates the ATM gene.

Cutaneous involvement as the first manifestation in a case of T-cell prolymphocytic leukaemia.

Mature T-cell malignancies of extracutaneous origin are rare disorders. T-cell prolymphocytic leukaemia (T-PLL) is the most common form of all mature T-cell leukaemias in adults. Secondary skill involvement by T-PLL has been reported in 25% of patients. A case of T-PLL which presented with cutaneous infiltration mimicking a cellulitis-like lesion resistant to antibiotic therapy is described. The diagnosis of T-PLL was subsequently fully supported by the clinical, laboratory and cytological findings, as well as by the immunophenotypic study of the skin biopsy. The present case stresses the importance of accurate evaluation of skin lesions in the diagnosis of some haematological conditions and gives additional information about T-PLL such as a previously non-reported cytogenetic abnormality [t(6;6)] and lack of cutaneous lymphocytic-associated antigen expression.

Deleted HTLV provirus in peripheral blood cells of a patient with T-cell prolymphocytic leukaemia.

We describe the first case of T-cell prolymphocytic leukaemia (T-PLL) in which the peripheral blood cells contained a human T-lymphotropic virus (HTLV) related tax sequence. Serum screening tests for anti-HTLV-I/II antibodies were negative. Polymerase chain reaction disclosed the presence of an HTLV-I tax sequence in the peripheral blood. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and the long terminal repeat regions and for the HTLV-II pol region were negative in the DNA of the cells. Although patients with T-PLL have been reported to be seronegative for HTLV-I, our findings point to the possibility that HTLV-I infection might be involved in the aetiology of at least some cases of T-PLL and that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis.

Granulocyte-macrophage colony-stimulating factor receptor: stage-specific expression and function on late B cells.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors (GMR) are expressed on myeloid cells throughout their maturational sequence. During myelopoiesis, GM-CSF induces the proliferation of precursors and has multiple effects on more mature cells; such effects include induction of maturation and priming for subsequent stimulation. GMR is expressed on a range of other cell types including acute leukemic blasts of myeloid and lymphoid lineage, but has been little studied on more mature lymphoid cells. Using sensitive triple-layer immunophenotypic techniques, we show here that both the alpha and beta c chains of the GMR are expressed on hairy cells (HCs) and myelomatous plasma cells (PCs), but not on chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) lymphocytes. The receptor was demonstrable on normal PCs in tonsil, but not on either activated or resting tonsillar B cells or on circulating normal B lymphocytes. The expression of the receptor is therefore stage specific, rather than a feature of activation. Perhaps, surprisingly, in view of its effects on myeloid cells, GM-CSF did not stimulate the proliferation or differentiation of HCs and did not protect them from apoptosis. However, the cytokine had a profound effect on the interaction of the HC with its environment. Thus, the cytokine caused a major cytoskeletal reorganization resulting in the inhibition of motility and loss of adhesion to cellular and matrix ligands. These studies indicate the importance of GM-CSF outside myelopoiesis and demonstrate a previously unrecognized stage specific role for the cytokine in B-cell biology. Taken together with our previous report that M-CSF enhances B-cell motility, the present findings indicate that myeloid growth factors act in concert to facilitate the controlled migration of certain B cells into and within tissues.

B-cell prolymphocytic leukemia expressing discordant myeloid-associated antigens in simultaneous specimens from bone marrow and peripheral blood.

The case of a 73-year-old man with B-cell prolymphocytic leukemia (PLL) and rapid clinical demise is reported. Flow cytometric immunophenotyping results of specimens obtained from the patient demonstrated a monoclonal CD5 positive B-cell population with myeloid-associated marker expression, which was discordant: CD15 and CD11b were expressed in bone marrow leukemic cells, whereas peripheral blood leukemic cells showed virtually no expression of these markers. Discordant immunophenotyping results between bone marrow and peripheral blood cells have been reported recently. Additionally, investigators have associated expression of CD13 and CD11b by chronic B-cell lymphoid leukemias with a more aggressive clinical course and shorter survival. Expression of these myeloid-associated antigens by B-cell prolymphocytes in PLL has not been widely reported. Cytogenetic analysis revealed a karyotype of 46,XY/?44,XYdel(1q),del (3p), whereas molecular genetic studies demonstrated immunoglobulin gene rearrangements in both heavy and light chain regions. Cytochemical staining for PAS (periodic acid-Schiff), nonspecific esterase and methyl-green-pyronin was positive in leukemic cells.

Potential diagnostic pitfalls caused by blood film artifacts in prolymphocytic leukaemia. Observations in two cases.

The diagnosis of lymphoproliferative disorders is based on a combined evaluation of the clinical, immunological and morphological findings. Cytological details may vary with the quality of the smear. We report two cases of prolymphocytic leukaemia in which cytoplasmic hairs or protrusions were observed when the films were not dried quickly. In one case the artifacts led to an initial erroneous interpretation of hairy cell leukaemia 'variant'. The cytoplasmic outline was smooth in both cases when the smears were immediately fan-dried. The findings underscore the necessity of high standards of excellence, even for the simple technique of blood film preparation, in order to avoid undesirable artifacts which may result in diagnostic misinterpretation.