Case Report of International Journal of Case Reports
T Prolymphocytic Leukemia, a rare disease, case presentation with typical pathological findings and review of management
Mohammad AJ. Abdulla1, Firyal Ibrahim2, Mahmoud Aldapt1, Halima Elomri1, Ahmad Al-Sabbagh2, Dina Sameh Soliman2,3, Sonia Allouch4, Liam Fernyhough4, Mohamed A. Yassin1
1Department of Medical Oncology, Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
2Department of Laboratory Medicine, Hamad Medical Corporation, Doha, Qatar
3Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
4Weill Cornell Medicine in Qatar, Qatar Foundation, Doha, Qatar
Prolymphocytic leukemia (PLL) is a rare disease, accounting for < 2% of lymphoid leukemias .There are 2 quite different entities with distinct pathologic features and different therapeutic strategies, T-cell and B-cell . T-PLL is more common . 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 . 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.
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,-22/42,idem,-9,add(14)(p11.1),add(17)(p13)
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.
Keywords: T Prolymphocytic Leukemia, a rare disease, case report
How to cite this article:
Mohammad A. Abdulla, Firyal Ibrahim, Mahmoud Aldapt, Halima Elomri1, Ahmad Al-Sabbagh, Dina Sameh Soliman, Sonia Allouch, Liam Fernyhough, Mohamed A. Yassin.T Prolymphocytic Leukemia, a rare disease, case presentation with typical pathological findings and review of management. International Journal of Case Reports, 2018 3:49. DOI:10.28933/ijcr-2018-11-0907
1. Dearden C; Management of prolymphocytic leukemia; Hematology Am Soc Hematol Educ Pro-gram. 2015; 2015:361-7.
2. Catovsky D, Galetto J, Okos A, Galton DA, Wiltshaw E, Stathopoulos G; Prolymphocytic leu-kaemia of B and T cell type; Lancet. 1973 Aug 4;2(7823):232-4.
3. Matutes E, Brito-Babapulle V, Swansbury J et al; Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia; Blood. 1991 Dec 15;78(12):3269-74
4. Dearden C; How I treat prolymphocytic leukemia; Blood. 2012 Jul 19;120(3):538-51.
5. Vivekanandarajah A, Atallah JP, Gupta S; T-cell prolymphocytic leukaemia (T-PLL): a rare dis-ease with a grave prognosis; BMJ Case Rep. 2013 May 2;2013. pii: bcr2013009808.
6. Laribi K, Lemaire P, Sandrini J et al; Advances in the understanding and management of T-cell prolymphocytic leukemia, Oncotarget. 2017 Nov 1;8(61):104664-104686.
7. Herling M, Khoury JD, Washington LT et al; A systematic approach to diagnosis of mature T-cell leukemias reveals heterogeneity among WHO categories; Blood. 2004 Jul 15;104(2):328-35.
8. Hu Z, Medeiros LJ, Fang L et al; Prognostic significance of cytogenetic abnormalities in T-cell prolymphocytic leukemia; Am J Hematol. 2017 May;92(5):441-447.
9. Hopfinger G, Busch R, Pflug N et al; Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia; Cancer. 2013 Jun 15;119(12):2258-67.
10. Ravandi F, Aribi A, O’Brien S et al; Phase II study of alemtuzumab in combination with pento-statin in patients with T-cell neoplasms; J Clin Oncol. 2009 Nov 10;27(32):5425-30.
11. Dearden CE, Khot A, Else M et al; Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route; Blood. 2011 Nov 24;118(22):5799-802.
12. Mercieca J, Matutes E, Dearden C; The role of pentostatin in the treatment of T cell malignancies: analysis of response rate in 145 patients according to disease subtype; J Clin Oncol. 1994 Dec;12(12):2588-93.
13. Herbaux C, Genet P, Bouabdallah K et al; Bendamustine is effective in T-cell prolymphocytic leukaemia; Br J Haematol. 2015 Mar;168(6):916-9.
14. Krishnan B, Else M, Tjonnfjord GE et al; Stem cell transplantation after alemtuzumab in T-cell prolymphocytic leukaemia results in longer survival than after alemtuzumab alone: a multicentre retrospective study; Br J Haematol. 2010 Jun;149(6):907-10.
15. Dholaria BR, Ayala E, Sokol L et al, Allogeneic hematopoietic cell transplantation in T-cell pro-lymphocytic leukemia: A single-center experience; Leuk Res. 2018 Apr;67:1-5
16. Nusz KJ, Pang NK, Woog JJ; Periorbital edema as the initial presentation of T-cell prolymphocytic leukemia; Ophthal Plast Reconstr Surg. 2006 May-Jun;22(3):215-6.
17. Lee SS, Robinson MR, Morris JC, Mirtsching BC, Shen D, Chan CC et al, Conjunctival involvement with T-cell prolymphocytic leukemia: report of a case and review of the literature; Surv Ophthalmol. 2004 Sep-Oct;49(5):525-36.