This document presents a case study of a 42-year-old male who presented with abdominal pain and was found to have a markedly elevated lymphocyte count on blood tests. Further testing revealed the lymphocytes to be abnormal in morphology. Bone marrow biopsies and additional testing led to a diagnosis of T-cell prolymphocytic leukemia (T-PLL), a rare and aggressive form of T-cell lymphoma. The document discusses the clinical features, distinguishing characteristics from other lymphomas, molecular genetics, disease progression, and poor prognosis of T-PLL.

1. A rare cause of lymphocytosis
Dr. Soma Pradhan
Senior Resident
Department of Hematology
Sir Ganga Ram Hospital, New Delhi.

2. HISTORY
 On 13th July 2019, a 42 yrs old male presented to
Clinical Hematology OPD with a complaints of pain
abdomen since last 15 days.
 There was no history of fever and weight loss.
 On examination, there is no pallor, lymphadenopathy
and spleen was not palpable.

3.  The patient was evaluated outside:
 CBC:
 Hb- 13.5 gm/dl
 TLC : 31,200/µl
 Platelet count :1,16,000/µl
 Peripheral smear examination:
 Marked lymphocytosis with 85% lymphocytes and
atypical lymphoid morphology.

4. INVESTIGATIONS
 CBC:
 Hb- 13.3 gm/dL
 RBC: 4.13 millions/µl
 PCV :38.9%
 MCV:94.2 fl
 MCH:32.2 pg
 RDW:12.5 %
 Platelets : 80,000/µl
 TLC : 31,660/µl
 DLC :
 Neutrophils- 11%, Lymphocytes-08%, Monocytes- 03%,
Eosinophils-01%, Abnormal lymphoid cells-77%

5. PERIPHERAL BLOOD
Peripheral Blood smear -4x

6. Peripheral Blood smear -40x

7. Peripheral Blood smear -100x

8. BONE MARROW
ASPIRATION
Bone marrow aspiration smear -4x

9. Bone marrow aspiration smear - 10x

10. Bone marrow aspiration
smear - 100x
Bone marrow aspiration smear - 40x

11. BONE MARROW IMPRINTS

12. BONE MARROW BIOPSY
Bone marrow biopsy - 10x

13. Bone marrow biopsy - 40x

14. Bone marrow biopsy - 40x

15. Bone marrow biopsy - 100x

17. DIAGNOSIS
T- CELL PROLYMPHOCYTIC LEUKEMIA.

18. T-cell lymphomas

20. T-cell Prolymphocytic Leukemia:(T-PLL)
 T-PLL accounts for 2% of mature lymphocytic leukemia
in adults.
 Median Age : 61 yrs (30 -94 yrs)
 Male >>> Female
 Rare, aggressive T-cell neoplasm.
 Patients with ataxia telangiectasia are at increased risk of
developing T-PLL

21. CLINICAL FEATURES
 Lymphocytosis with lymphocyte count >100 x 109/L
 Generalised lymphadenopathy
 Splenomegaly
 Skin infiltration – 20% of the cases
 Anemia
 Thrombocytopenia

22. DIFFERENTIATING FEATURES
Features T-PLL LGL leukemia Sezary
Syndrome
ATLL
Morphology prolymphocyte Large granular
lymphocyte
cerebriform Flower cell
Phenotype CD4+ CD8- CD8+ CD4- CD4+CD8- CD4+ CD8-
CD4+ CD8+ CD57+ CD3+ CD 25 +
CD7+ CD52+ CD16+/CD94+ CD7- CD26- CD7-
Histology
Spleen Red pulp Red pulp - -
Skin dermal - Dermal and
epidermal
Dermal and
epidermal
HTLV-1 Negative Negative Negative Positive
Clinical
course
Aggressive Indolent Chronic Aggressive-
Acute,
lymphatous
types

23. A B
C D
 A- T-PLL
 B- LGL Leukemia
 C- Sezary Syndrome
 D- ATLL

24. MOLECULAR GENETICS
 T-cell receptor genes are rearranged and are identical, confirming a
clonal expansion of T-cells.
 The most frequently observed group of cytogenetic abnormalities
involve chromosome 14.
 inv(14) (q11;q32), t(14;14)(q11;q32)
 The above translocations juxtaposes between TRA LOCUS with
TCL1A & TCL1B oncogenes at14q32.1
 t(X;14)(q28;q11) :MTCP1 (mature T cell proliferation 1 gene),
which is located on the X chromosome.
 Cytogenetic abnormalities involving chromosome 8 are the next
most frequently observed (idic(8p11), t(8;8) and trisomy 8q).

26.  Other recurrent abnormalities seen with conventional
techniques include :
 loss of 11q23 (ATM inactivation) together with additional
losses (22q, 13q, 6q, 9p, 12p,17p) and gains (22q and 6p).
 12p13 deletion occurs in 50% of the cases.
 highly recurrent, largely exclusive, gain-of-function
mutations involving IL2RG, JAK1/3, and STAT5B,
which lead to constitutive STAT5 signaling.

28. DISEASE PROGRESSION &
PROGNOSIS
 T-PLL is aggressive and often resistant to therapy.
 Median survival is 1-2 years.
 The best responses have been reported with the monoclonal
antibody alemtuzumab (anti―CD52).
 Autologous or allogeneic stem cell transplantation.
 High levels of expression of both TCL1 and AKT1 have been
identified as poor prognostic markers.
 STAT5B mutations have been documented to have a negative
prognostic impact.