The WHO recently recommended the new Xpert MTB/RIF Ultra assay (Ultra) instead of the Xpert MTB/RIF assay because Ultra has improved sensitivity. We report the diagnostic accuracy of Ultra for ...tuberculous adenitis in a tuberculosis and HIV endemic setting.
We obtained fine-needle aspirates (FNA) and lymph node tissue by core-needle biopsy in adult patients with peripheral lymphadenopathy of >20 mm. Ultra and mycobacterial culture were performed on FNA and tissue specimens, with histological examination of tissue specimens. We assessed the diagnostic accuracy of Ultra against a composite reference standard of 'definite tuberculosis' (microbiological criteria) or 'probable tuberculosis' (histological and clinical criteria).
We prospectively evaluated 99 participants of whom 50 were HIV positive: 21 had 'definite tuberculosis', 15 'probable tuberculosis' and 63 did not have tuberculosis (of whom 38% had lymphoma and 19% disseminated malignancy). Using the composite reference standard the Ultra sensitivity on FNA was 70% (95% CI 51-85; 21 of 30), and on tissue was 67% (45-84; 16/24) these were far superior to the detection of acid-fast bacilli on an FNA (26%; 7/27); AFB on tissue (33%; 8/24); or tissue culture (39%; 9/23). The detection of granulomas on histology had high senstivity (83%) but the lowest specficity. When compared with culture the Ultra on FNA had a sensitvity of 78% (40-97; 7/9) and tissue 90% (55-100; 9/10).
Ultra performed on FNA or tissue of a lymph node had good sensitivity and high specificity. Ultra had a higher yield than culture and has the advantage of being a rapid test. Ultra on FNA would be an appropriate initial investigation for lymphadenopathy in tuberculosis endemic areas followed by a core biopsy for histopathology with a repeat Ultra on tissue if granulomas are present.
Little is known about the pathway to diagnosis of lymphoma in Sub-Saharan Africa, despite the increased risk of lymphoma in people living with HIV (PLHIV). The challenges of diagnosis in this setting ...include diagnostic confusion with extrapulmonary tuberculosis (EPTB), which commonly causes lymphadenopathy in PLHIV.
We analysed the time to diagnosis and treatment in patients using predetermined time intervals. Univariate and multivariable analyses were performed to determine the relationship between patient and disease-specific variables with delays to diagnosis. We were particularly interested in the impact of HIV, empiric tuberculosis therapy and fine-needle aspirate for cytology (FNAC) in contributing to delay.
Patients (n = 163), 29% HIV-infected, waited a median of 4 weeks before seeking medical attention. It took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention, termed the healthcare practitioner interval. In multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease (OR 2.3, 95% CI 1.1-5.2) and Hodgkin lymphoma (HL) (OR 3.0, 95% CI 1.1-8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3-2.2). The median time to diagnosis was a median of 4 weeks longer for patients on tuberculous (TB) therapy (n = 16, p = 0.28) and patients who underwent an FNAC (n = 63, p = 0.04). Where FNAC was performed, it was diagnostic for lymphoma in only 11%. Diagnostic delay was not associated with overall survival.
Time-to-diagnosis of lymphoma in South Africa was similar to that reported from high-income countries and shows significant periods of delay between the onset of symptoms to diagnosis and treatment. The longest period of delay was in the health practitioner interval. Education regarding the significance of lymphadenopathy for both patients and health care practitioners and appropriate investigative steps preferably by best-practice algorithms specific to TB-endemic areas are needed to shorten the time-to-diagnosis of lymphoma.
Infectious disease epidemics may overshadow and exacerbate existing challenges in diagnosing lymphoma. We describe pragmatic strategies we have implemented to overcome diagnostic obstacles caused by ...the local tuberculosis (TB) and HIV epidemics in South Africa, which may serve as a guide to minimize diagnostic delay during the COVID-19 pandemic. We report on the diagnostic utility of a rapid-access lymph node core-biopsy clinic, where lymph node biopsies are taken from outpatients at their first visit. Analysis of tissue biopsies (n = 110) revealed the three most common conditions diagnosed were TB adenitis (34%), lymphoma (29%), and disseminated malignancy (20%). A first-attempt core-biopsy was able to diagnose lymphoma in 27/32 (84%) of cases. Compared with a historical cohort, the diagnostic interval (time from first health visit to diagnostic biopsy) for patients with lymphoma was significantly shorter, 13.5 vs 48 days (p = 0.002).
Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is subdivided according to the cell-of-origin (COO) classification into germinal centre B-cell (GCB) and activated B-cell (ABC) ...subtypes, each with different molecular profiles and clinical behaviour. This study aims to describe the pattern of the COO subtypes, the proportion of Epstein–Barr virus (EBV) co-infection, and their influence on survival outcomes in a setting of high HIV prevalence.
This retrospective cohort study included patients diagnosed with de novo DLBCL NOS at our tertiary academic centre in Cape Town, South Africa over a 14-year period. Immunohistochemical stains were performed for COO classification, according to the Hans algorithm. Tumour EBV co-infection was established by EBV-encoded ribonucleic acid in situ hybridisation (EBER-ISH) staining. The effect of the COO subtypes and EBV co-infection on overall survival were described by means of univariate, bivariate and multivariate analyses.
A total of 181 patients with DLBCL NOS were included, which comprised 131 HIV-uninfected and 50 HIV-infected patients. There was an equal distribution of GCB and ABC subtypes in the HIV-infected and HIV-uninfected groups. EBV co-infection was detected in 16% of the HIV-infected cases and in 7% of the HIV-uninfected cases (p=0.09). There was no significant difference in the incidence of EBV co-infection between the GCB and ABC subtypes (p=0.67). HIV-infected patients with CD4 ≥150 cells/mm3 had similar survival to HIV-uninfected patients (p=0.005). Multivariate regression analysis showed that in the HIV-infected group with marked immunosuppression (CD4 <150 cells/mm3), there was significantly poorer overall survival compared to the HIV-uninfected group (HR 2.4, 95% CI 1.3–4.1). There were no statistically significant differences in overall survival by DLBCL COO subtype.
There was no difference in the proportion of DLBCL COO subtypes, regardless of HIV status. EBV co-infection was more common in the HIV-infected group, but less than described in the literature. Unexpectedly, there were no significant differences in survival outcomes between the GCB and ABC subtypes. Higher CD4 counts in the HIV-infected group had good survival outcomes, while lower CD4 counts predicted adverse survival outcomes. Further research is needed to explore the genetic mutational landscape of HIV-associated DLBCL.
In tuberculosis (TB)-endemic areas, lymphadenopathy is frequently due to TB adenitis, but lymphoma and cancers are important differential diagnoses and critical to diagnose at the earliest ...opportunity. Key obstacles to lymphoma diagnosis include empiric TB treatment and difficulty accessing a biopsy. We report on a specialized clinic utilizing high-yield investigations for patients with lymphadenopathy.
This prospective interventional study investigated the utility of a core biopsy and the Xpert MTB/RIF Ultra (Ultra) on fine-needle aspirate (FNA) and tissue in a newly established lymph node biopsy clinic over 4 years. Electronic referral facilitated patient assessment within a week. Hematology fellows without specialist surgical or radiological expertise performed the biopsy on the first visit.
In 277 patients, including 43% people with HIV, TB was the most frequent diagnosis (34%), followed by lymphoma (27%) and other cancers (17%). Patients were seen a median of 5 days interquartile range (IQR) 2-8.5 days from referral. Core biopsy provided sufficient tissue for diagnosis in 96% of patients with lymphoma (72/75) and 94% of patients with cancer (44/47). FNA Ultra had a sensitivity of 73.9% 34/46; 95% confidence interval (CI) 58.9-85.7, and tissue Ultra 73% (46/63; 95% CI 60.3-83.4). There were six false-positive Ultra tests, highlighting the value of histology to either support TB or make an alternative diagnosis.
Core biopsies collected under the conditions described are safe and sensitive and can yield a rapid diagnosis. Combining Ultra and a core biopsy can accurately diagnose TB and cancer. This clinic provides an implementation model for resource-constrained and TB-endemic areas.
Introduction
Lymphoma and extrapulmonary tuberculosis (EPTB) are common in HIV and may cause peripheral lymphadenopathy. EPTB can be difficult to diagnose and consequently, patients with ...lymphadenopathy in TB-endemic regions are frequently placed on empiric TB treatment. This may result in a missed or delayed diagnosis of lymphoma.
In the local setting, in Cape Town (South Africa), primary level doctors have difficulty accessing lymph node excision biopsies which rely on an over-burdened surgical service. Core-needle biopsy is not currently routinely performed for peripheral lymphadenopathy in the investigation of lymphadenopathy.
Methods
A prospective study of patients with peripheral lymphadenopathy >2cm was performed. A rapid access lymph node biopsy clinic examined the performance of three methods of investigation on a lymph node: the fine-needle aspirate for cytology (FNAC), the Xpert MTB/Rif Ultra (on both aspirate and tissue specimens), and the ultrasound-guided core-needle biopsy. In all patients a final histological diagnosis was sought, including referral for excision biopsy if core-needle histology was inconclusive. If >0.5ml of pus was aspirated this was tested with the Xpert MTB/Rif and a biopsy was not performed.
Results
Sixty-two patients including 48% HIV+ have undergone investigation. The final diagnosis is known for 56 patients: lymphoma in 34%, TB in 30%, cancer in 12%. Ultra had a 64% sensitivity on the aspirate (95% CI 31-89%), and 73% on tissue (95% CI 39-94). In both cases specificity was 100%. FNAC was diagnostic in 0% of lymphoma cases (reported atypical in 24%); it was diagnostic for TB (+AFBs) in 27% with TB; and diagnostic in 36% of disseminated cancer cases. The core biopsy was able to make a diagnosis in 83% of cases (including sub-typing in 89% of lymphoma cases).
Conclusion
The Ultra shows promising sensitivity and should routinely be performed for both HIV+ and -patients at the first visit in the investigation of unexplained lymphadenopathy in a TB-endemic region. If the Ultra is negative, a core-needle biopsy is the most appropriate next investigation. In a TB-endemic region, FNAC should be reserved for patients >50 years who are HIV negative. There is no role for empiric TB treatment for patients with peripheral lymphadenopathy in the era of new TB diagnostic tests, and the application of these investigations with early biopsy for patients with negative TB tests will result in earlier detection of lymphoma.
No relevant conflicts of interest to declare.
Autologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and ...high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting.
We retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019.
146 patients – majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 – 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 – 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 – 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 – 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 – 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14–15 days) and 16 days (95% CI 15–16 days) respectively.
PM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.
The characteristics and outcomes of patients with acute promyelocytic leukemia (APL) from sub-Saharan Africa have not been published.
We report retrospectively on consecutively diagnosed APL patients ...treated in Cape Town, South Africa, during 1998-2019. A total of 69 patients were treated, of whom 27 (39%) were classified as having high risk APL.
Early death rates at 7 and 30 days were 7% and 13%, respectively, including 4 patients who died before any treatment could be administered. Overall survival at 3 years was 76.5% (95% confidence interval, 63.9-85.2) for the entire cohort, and 82.5% (95% confidence interval, 69.7-90.2) if patients who died within 7 days of diagnosis were excluded. For 13 patients (18.8%), there was a delay of 5 or more days from time of initial presentation at a peripheral hospital until arrival at the leukemia center and administration of all-trans retinoic acid; only 1 of these patients died within 30 days.
Despite the challenges faced in the public healthcare system of a developing country, outcomes of APL patients treated at our center are similar to outcomes from developed countries.
To assess the characteristics and outcomes of patients with acute promyelocytic leukemia (APL) from sub-Saharan Africa, we retrospectively analyzed data from consecutively diagnosed APL patients treated in Cape Town, South Africa, during 1998-2019. Early death rates at 7 and 30 days were 7% and 13%, respectively; overall survival at 3 years was 76.5%. Outcomes of APL patients treated at our center are similar to outcomes from developed countries.
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