A 76-year-old female was diagnosed 3 years ago as suffering from chronic lymphocytic leukemia (CLL). 

She does not need any treatment until she is healthy 4 weeks ago. 

Now, she complains of tiredness, polyuria, and lethargy, and also notices a swollen abdomen. 

On examination, she is pale, not jaundiced, but she does have lymphadenopathy in both axillae. 

Notice the obvious swelling of the left elbow. 

The spleen is easily palpable and there is ascites. 

A neurological examination is normal. 

Q1. Comment on the peripheral blood film findings. 

Q2. Comment on the abdominal computed tomography (CT) scan. 

 

Q3. What is the likeliest diagnosis? 

A1. The film shows abnormal lymphoid cells that do not look like the mature B lymphocytes of CLL. 

These are larger cells with plentiful basophilic cytoplasm. 

These appearances are in keeping with an immunoblastic transformation of CLL. 

The bone marrow biopsy is shown below; it 

is hypercellular and hugely infiltrated by pleomorphic lymphocytes. 

Flow cytometry will show that the cells in classic CLL are positive for the T-cell marker cluster of differentiation 5 (CD5) and the mature B-cell markers CD19, 20, and 23. 

FMC7 is negative on classic CLL but is usually positive after transformed conditions; CD5 may also become negative. 

In classic CLL, the expression of protein kinases ZAP-70 and CD38 is more common when the immunoglobulin heavy chain (IgH) site is germline (not mutated), all of these features are associated with a poor prognosis. 

Chromosome and fluorescence in situ hybridization (FISH) analysis will provide useful prognostic information, for example, p53 deletion is often seen in advanced CLL, and 13q deletion is associated with a good prognosis. 

A2. The CT scan shows enlarged retroperitoneal lymph nodes. 

These affect the ureter, may cause ureteral obstruction, and may also affect the intestines. 

History suggests that she may be developing kidney failure. 

A3. Richter’s syndrome denotes a transformation of CLL into a more aggressive tumor, often with enlargement of lymph node tissue in unusual sites (e.g. retroperitoneally). 

This patient also had massive axillary and epitrochlear nodes. 

This condition responds poorly to treatment and usually progresses rapidly. 

Treatment approaches in CLL have evolved rapidly. 

Advanced disease may respond to treatment with the anti-CD20 monoclonal antibody rituximab combined with intensive chemotherapy – for example, R plus fludarabine and cyclophosphamide. 

Other monoclonal, such as ofatumumab, may also work. 

Ibrutinib is an oral, highly effective, selective, and irreversible small-molecule tyrosine kinase inhibitor. 

It is an important part of the B cell receptor signaling pathway. 

It has recently been approved for use in relapsed CLL patients. 

It can be used as a single drug or in combination with monoclonal antibodies and chemotherapy. 

Venetoclax is a new drug targeting BCL2 protein and has activity in refractory CLL. 

Venetoclax targets BCL2 protein and shows activity in relapsed and refractory CLL.