Lymphoproliferative disorders

Mature T-cell neoplasms


Patient:  46 year old female
History:  Skin rash, fatigue, weight loss, sweats, noticed new LNs in neck bilaterally
Lab Data:  Lymphocytosis (25 X109/L), Elevated Ca2+ - 3.4

The blood films were examined as shown:

Blood film Case1FJC01 as described below Blood film Case1FJC02 as described below Blood film Case1FJC03 as described below

The blood film confirms a lymphocytosis. The lymphocyte population is atypical and pleomorphic, variable in size with striking irregular nuclear convolutions and folding.

Blood immunophenotyping by FACS reveals the presence of the following antigens;-

immunophenotype as described below immunophenotype as described below immunophenotype as described below

Immunophenotyping demonstrates a clonal CD3+ T cell lymphocytosis in the peripheral blood at 92% of total cells. The T cell population is positive for CD2, CD5 (pan T cell antigens) but aberrantly negative for CD7. The T cells are also positive for CD4, CD25. 
The cells are negative for CD8, CD103, TCR gamma-delta, CD30 (small % only is positive at 4%), CD56, CD16 and CD57.

Conclusions

The immunophenotype taken together with the clinical findings is most consistent with Adult T-cell leukaemia/lymphoma (ATLL). The clinical history with systemic symptoms and hypercalcaemia point towards the acute variant of ATLL. 


ATLL: 

Endemic in SW Japan, Caribbean and Central Africa. A disease of adults. Associated with HTLV-1, which is causative in creating transcriptional activation of genes in infected lymphocytes. 

Blood involvement often not reflected in the degree of BM involvement. >50% of patients have skin involvement. 
Variants: acute, lymphomatous, smouldering, chronic.

Mature B-cell neoplasms

  Patient:  62 year old male
  History:  He is noted to have small volume generalised lymphadenopathy and a palpable spleen.
Lab Data:  Routine pre-operative full blood count: Haemoglobin 10.8, White Blood Cells 88.0 (Neuttophils 2.2, lymphocytes 82) and Platelets 86.

Further investigation using a blood film and peripheral blood immunophenotyping showed:

Blood film    peripheral blood immunophenotyping  Data chart as described below

The blood film confirms a lymphocytosis. The cells are small, mature lymphocytes, with scanty cytoplasm, their morphology is uniform. Smear (or smudge) cells are noted. There is no significant prolymphocyte population.

Lymphoid immunophenotyping demonstrates a CD19+ B cell population which is neoplastic. Clonality is demonstrated by lambda light chain restriction (the cells are lambda+, kappa-). 
The B cell phenotype shows aberrant and uniform CD5 expression on CD19+ B cells. The B cells are predominantly CD23+ and are negative for CD20, CD79b and CD10.

This immunophenotype is typical for B-CLL. 


Additional comments:

  • The cells are negative for CD103 (hairy cell leukaemia), CD34 (progenitors) and other T cell antigens (except CD5). 
  • The B cell population is negative for CD38, this may be associated with a favourable prognosis. 
  • CD38+ expression (on >30% of CLL cells) is associated with an adverse prognosis and correlates with unmutated Ig gene status.
  • The final diagnosis is chronic lymphocytic leukaemia (CLL). CLL is the most common leukaemia of adults in Western populations. It is predominantly seen in older adults aged >60. The incidence is 2-6 cases per 100,000 and increases with age. 
  • The disease predominantly involves peripheral blood and marrow, causing lymphocytosis and as the disease progresses, a reduction in other cell counts (Hb and platelets). 
  • Patients may also have lymphadenopathy, hepatosplenomegaly and occasionally extranodal disease. 
  • The majority of patients at presentation are asymptomatic. Some patients present symptomatic with fatigue, weight loss, sweats, recurrent infections, autoimmune haemolytic anaemia or bulky lymphadenopathy or splenomegaly.