On 26 November 2019, a 48-year-old, HIV-negative man presented to the Primary Health Care Facility in Johannesburg, South Africa, with symptoms suspicious of TB. His sputum was collected and sent for GeneXpert testing. This confirmed a diagnosis of rifampicin-sensitive TB. On 28 November 2019 he was referred to the Clinical HIV Research Unit for screening for an observational study called TB Sequel. The TB Sequel project's aim is:
[T]o advance the understanding of the clinical, microbiologic, environmental and host immune factors affecting the long-term sequelae of pulmonary TB; to determine occurrence of reversible and irreversible costs and socioeconomic consequences for TB patients and health care systems; and to facilitate novel interventions to restore and preserve overall health, well-being and financial protection in patients with TB.
At the screening visit, the patient complained of a 3 month history of cough, fatigue, night sweats, body weakness, loss of appetite, loss of weight, chest pain, shortness of breath, nausea and vomiting. He also complained of an intermittent fever since February 2019. He had no significant family history of malignancy.
On examination, he was generally wasted but apyrexial and the rest of his vital signs were normal. He had cervical and axillary lymphadenopathy and a hepatomegaly (without splenomegaly). His chest examination revealed scattered lung crackles. He was managed by his Primary Health Care Facility according to the National Tuberculosis Management Guidelines and was thus started on treatment for rifampicin-sensitive TB, rifafour (rifampicin, isoniazid, pyrazinamide and ethambutol), pyridoxine and vitamin BCO on the same day.
He was enrolled onto the TB Sequel study on 02 December 2019 and routine baseline investigations were performed. His chest X-ray showed bilateral infiltrates, left hilar lymphadenopathy and a right pleural effusion, with approximately 80% of his lungs affected. His baseline bloods, along with repeated blood results (see Table 1), showed abnormalities in the full blood count, specifically of the white blood cells. His blood results were suggestive of a lymphoproliferative disorder which required further workup.
The patient was admitted to a tertiary public hospital in Johannesburg on 11 December 2019 for further investigation. His full blood count, differential count and peripheral smear upon admission showed a profound absolute lymphocytosis, comprising predominantly small mature forms, with occasional smudge cells and large granular lymphocytes. Approximately 3% of these were larger more primitive cells with features in keeping with prolymphocytes. No increase in blasts was noted. No other secondary causes for eosinophilia and thrombocytosis were discovered and both were regarded as reactive in nature. His lactate dehydrogenase (LDH) from 12 December 2019 was 262 U/L (reference range: 100-190 U/L). His renal function and liver function tests were normal.
A bone marrow aspirate and trephine biopsy was performed on 12 December 2019 and referred to the National Health Laboratory Service for routine analysis. The report described a hypercellular bone marrow with extensive diffuse infiltration by small mature lymphocytes. Fluorescence in situ hybridisation (FISH) performed on the bone marrow aspirate sample confirmed that all screened cells were negative for (1) deletion of the tumour protein p53 (TP53) and ATM serine/threonine kinase (ATM) genes, (2) deletion of the long arm of chromosome 13 (13q14.3) and (3) trisomy of chromosome 12. Flow cytometry immunophenotyping performed on the bone marrow aspirate showed a population ('81%) of clonal (kappa light chain restricted) B-cells, which expressed the following markers: CD19+, CD5+/++, CD20++, CD23 dim/+, CD45+/++, CD22+, CD38 and possible dim FMC7. CD10 was not expressed.
These morphological and immunophenotypical findings were in line with a diagnosis of CLL.
A staging computed tomography (CT) scan was performed on 18 December 2019, which showed an extensive bilateral tree-in-bud pattern, and a right-sided pleural effusion, both are suggestive of active pulmonary TB. Signs of pulmonary artery hypertension as well as supraclavicular, mediastinal and intra-abdominal lymphadenopathy were also noted. Furthermore, a thrombus in the inferior vena cava (IVC) was seen, starting from the level of the renal veins and extending distally. Although a hepatomegaly was found on clinical examination, the CT scan confirmed a normal liver and spleen, with no focal lesions. An echocardiogram was performed on 19 December 2019, which was normal.
Based on all of the above results, the patient was classified as stage I under the Rai classification and stage B using the Binet classification of CLL. He had both good (Rai I) and bad (male sex, Binet B, diffuse bone marrow appearance, CD38 expression and raised LDH) prognostic indicators, which would affect his management.
The patient was initially anticoagulated and monitored by the tertiary public hospital's coagulation clinic for the IVC thrombus and subsequently referred to the oncology unit at Charlotte Maxeke Johannesburg Academic Hospital for further management of his CLL. As cure is rare in CLL, treatment is mainly symptomatic and the risk-benefit analysis of available treatments should be considered on a case-by-case basis.
Ethical approval to conduct the study was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand (Reference number: R14/49, Protocol No: M1911204) on 29 January 2020. Informed consent for publication of this case report was obtained from the patient.