Suspected Richter transformation: positron emission tomography/computed tomography tells us who should have a biopsy and where

Abstract

Most patients with newly diagnosed chronic lymphocytic leukemia (CLL) do not require immediate therapy, which is only considered when there is obvious progression of the disease. Th e indications for treatment are given according to a clinical assessment based upon an internationally accepted consensus. In general the extent of the disease and staging are based on a simple clinical examination of the patient and the consideration of routine blood count values and parameters, clearly defi ned by the Rai and Binet staging systems. Th ese staging systems were introduced more than three decades ago, long before the era of modern imaging technology including positron emission tomography (PET), alone or in combination with computed tomography (PET/CT). Even today, according to current clinical guidelines (international workshop on CLL [IWCLL] 2008), PET and PET/CT have no place in the diagnostic work-up or follow-up for patients with CLL, not even in the setting of clinical trials. For clinical trials, inclusion of CT scans is recommended, in order to evaluate the usefulness in assessment of prognosis and minimal residual disease [1]. Th e only indication for PET in current clinical guidelines is in the case of suspected Richter transformation (RT), which is essentially the development of aggressive lymphoma in a patient with CLL. RT occurs in about 3 – 10% of patients with CLL, and its incidence has probably been underestimated over the years. Th e study by Papaj i k et al . in this issue of Leukemia and Lymphoma challenges the role of PET/CT for patients with CLL in a prospective design, and confi rms that PET/CT is useful in the case of RT for patients with CLL but not at diagnosis, progression or follow-up [2]. Based on the results from this study, the use of PET/CT is indicated for patients with CLL when RT or secondary malignancies are suspected. Th e authors examine the value of measuring the standardized uptake value (SUV), a semiquantitative measure of PET tracer uptake and thus a surrogate for tumor metabolism. If PET negativity or SUV max 5 – 6 is demonstrated, the suspicion of RT may be rebutted in most cases. A previous retrospective study of 37 consecutive patients diagnosed with CLL who underwent PET/CT showed that SUV max values up to 7.9 may be seen in the case of non-transformed CLL, with bone marrow values up to 9.3, whereas cases with RT showed SUV max values in the range of 7.4 – 39.4 [3]. Another retrospective study with 40 consecutive patients who had transformed from indolent lymphomas (only six cases of CLL) and underwent PET/CT showed a single case of RT with an SUV max of 3.2, whereas the remaining patients with RT had SUV max values of 7.6 – 40.0 [4]. However, the prospective study of 44 patients with CLL who underwent PET/CT that is reported in this issue of Leukemia and Lymphoma revealed no cases of RT with SUV max values less than 7.2, and none without RT above SUV max of 5.9. Th e only exceptions were patients with a positive PET due to infectious foci outside of lymph node regions. In the case of PET positivity for suspected RT of CLL, the lesion with the highest SUV should be used to guide the site of choice for biopsy. Th ereby, the probability of correctly demonstrating cytological or histological evidence of RT or secondary malignancy will be increased, and the risk of false negative fi ndings decreased. One important caveat addressed by Papaj i k et al . is the risk of iatrogenic invasive procedures due to false positive PET results. A PET positive infl ammatory focus was identifi ed for seven of the patients (16%) [2]. Even though these cases may resolve upon conservative approaches, the demonstration of PET positivity increases the risk of invasive and potentially harmful procedures that may or may not be relevant to the treatment of the patient. In this study, seven of eight patients with RT had B symptoms (night sweats, weight loss, fewer), and no cases of RT were identifi ed without initial clinical suspicion, even though only patients with lymph nodes 5 cm, liver or spleen enlargement, or Binet stage B or C were included. Th us, there appears to be no benefi t from routine PET/