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 below. 

Blood film
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;-

FACS plot
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 hypercalaemia 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:-

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.