| Popis: |
Background: Prolymphocytic leukemia (PLL) is a rare disease, accounting for < 2% of lymphoid leukemias [1].There are 2 quite different entities with distinct pathologic features and different therapeutic strategies, T-cell and B-cell [2]. T-PLL is more common [3]. Although termed ‘prolymphocytic,’ T-PLL is characterized by the proliferation of post-thymic T-lymphocytes. It is estimated that physicians will see a case of T-PLL every five to ten years [4]. Over the last 15 years, 3 cases of T-PLL were diagnosed in our center. We present here the latest case, with typical pathological findings. Case Report: A 63-year-old British gentleman, previously healthy with good performance, presented with fatigue for 6 – 8 weeks with puffiness of face and eyelids and weight loss of 5 kilograms. Physical exam showed periorbital edema and conjunctival injection (Figure 1), cervical lymphadenopathy, and hepatosplenomegaly. Initial complete blood count (CBC): white blood cells (WBCs) 331.9 x109/L (4.0 – 10.0), with 94% lymphocytes, hemoglobin (Hb) 119 gm/L (130 – 170), platelets (Plts) 128 x109/L (150 – 400). Lactate dehydrogenase 10.4 µkat/L (2.1 – 3.7), uric acid 537 µmol/L (210 – 420). Abdomen ultrasound showed markedly enlarged spleen (20.3 cm). The peripheral blood smear showed profound leukocytosis with 94% abnormal lymphoid cells. The cells were small to medium in size with high nucleo-cytoplasmic ratio, moderately condensed chromatin and almost all with prominent nucleolus. Substantial number of the cells show irregular nuclear contour with short indentation. The cytoplasm was basophilic agranular and many cells show irregular cytoplasmic protrusions (Figure 2). Flow cytometry on peripheral blood revealed one homogenous abnormal population positive for cluster of differentiation 45 (CD45) and express the pan T-cell markers (CD3, CD2, CD5 and CD7). All were positive for CD4, T-cell receptor (TCR) alpha/beta, CD43 and BCl2 with partial expression of CD38. These cells were negative for CD56, CD57, CD16, CD25, CD103, CD10, CD117, Terminal deoxynucleotidyl transferase (TdT), CD1a and CD34. (Figure3A) TCRVb region analysis by flow cytometry using IO Test Beta Mark TCR Repertoire kit (Beckman Coulter, Brea, CA, USA) using the panel of 24 monoclonal antibodies to TCR Vb families showed restricted expansion of region 13.1 in 99%. (Figure 3B) Bone marrow aspirate was remarkably hypercellular and extensively infiltrated with abnormal lymphoid cells comprising approximately 75% of total nucleated cells, morphologically similar to those seen in peripheral blood. The biopsy showed extensive diffuse infiltration with small to moderately sized lymphoid cells with prominent nuclear irregularity (Figure 4A&B). The immunophenotype was confirmed by immunohistochemistry and the cells were positive for CD3, CD5, CD7, CD2, CD4, BCL2 as well as for Zap70. BCL6 was uniformly negative. Based on the morphology and the immunophenotypic profile, a diagnosis of CD4+/CD8− T-prolymphocytic leukemia was made. FISH analysis revealed ATM deletion at 11q22 and TRA/D rearrangement in 93% of the cells analyzed and karyotype was complex with multiple numeric and structural abnormalities including inv(14)(q11.2q32); Karyotype: 43,XY,del(11)(q14),add(11)(p15),-13,inv(14)(q11.2q32),der(19)t(13;19)(q11;q13.4),-20,-22[7]/42,idem,-9,add(14)(p11.1),add(17)(p13)[23] After confirming the diagnosis of T-PLL the patient travelled back to his home country. He was started on treatment with alemtuzumab, then pentostatin was added in week 4, after 10 weeks of treatment he achieved complete remission. After that he received reduced intensity conditioned allogeneic stem cell transplant from a matched brother, complicated by mild acute graft versus host disease. Until the time of writing this report he was doing fine. |
