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Introduction: Although the use of 68Ga has increased substantially in nuclear medicine over the last decade, there is limited information available on occupational exposure due to 68Ga. The purpose of this study is to determine the occupational extremity exposure during the preparation, dispensing and administration of 68Ga-labelled radiopharmaceuticals. Method: Workers in eight centres wore a ring dosimeter for all tasks involving 68Ga-labelled radiopharmaceuticals for a minimum of one month. Additionally, the fingertip dose was monitored in two centres and the hand with the highest ring dose during 68Ga procedures was also identified in one centre. Results: The median normalised ring dose for 68Ga procedures was found to be 0.25 mSv GBq−1 (range 0.01–3.34). The normalised 68Ga ring doses recorded in this study are similar to that found in the literature for 18F. This study is consistent with previous findings that the highest extremity dose is found on the non-dominant hand. A limited sub study in two of the centres showed a median fingertip to base of the finger dose ratio of 4.3. Based on this median ratio, the extrapolated annual 68Ga fingertip dose for 94% of the workers monitored in this study would be below Category B dose limit (150 mSv) and no worker would exceed Category A dose limit (500 mSv). Conclusion: When appropriate shielding and radiation protection practices are employed, the extremity dose due to 68Ga is comparable to that of 18F and is expected to be well below the regulatory limits for the majority of workers.

Introduction Biclonal lymphoid disorders, when two distinct lymphoproliferative disorders (LPD) co-exist, are rare (incidence of 1.4%) and associated with a poor prognosis. NOTCH1 mutations occur in 10% of CLL at diagnosis, associated with a short disease-free interval and increased risk of Richter's transformation. We hypothesised that the incidence of NOTCH1 mutations in CLL with a second LPD may be increased, because the mutation occurs early in leukaemogenesis, permitting clonal divergence. Methods We identified 19 patients with biclonal LPD at diagnosis: 11 with CLL and a second LPD (group A) and 8 with a second distinct CLL (group B). NOTCH1 mutation analysis was performed and clinical outcome investigated. Results Ten of 19 (52%) were NOTCH1 mutated: 5 in group A (45%) and 5 in group B (62.5%) with a favourable clinical outcome observed among this cohort with 28.7 (range 1-99) months of follow-up. Conclusion In conclusion, we identified a significant (52%) incidence of NOTCH1 mutations in CLL in the context of biclonal LPD, associated with an indolent clinical course.

The exposure of the fingers is one of the major radiation protection concerns in nuclear medicine (NM). The purpose of this paper is to provide an overview of the exposure, dosimetry and protection of the extremities in NM. A wide range of reported finger doses were found in the literature. Historically, the highest finger doses are found at the fingertip in the preparation and dispensing of 18F for diagnostic procedures and 90Y for therapeutic procedures. Doses can be significantly reduced by following recommendations on source shielding, increasing distance and training. Additionally, important trends contributing to a lower dose to the fingers are the use of automated procedures (especially for positron emission tomography (PET)) and the use of prefilled syringes. On the other hand, the workload of PET procedures has substantially increased during the last ten years. In many cases, the accuracy of dose assessment is limited by the location of the dosimeter at the base of the finger and the maximum dose at the fingertip is underestimated (typical dose ratios between 1.4 and 7). It should also be noted that not all dosimeters are sensitive to low-energy beta particles and there is a risk for underestimation of the finger dose when the detector or its filter is too thick. While substantial information has been published on the most common procedures (using 99mTc, 18F and 90Y), less information is available for more recent applications, such as the use of 68Ga for PET imaging. Also, there is a need for continuous awareness with respect to contamination of the fingers, as this factor can contribute substantially to the finger dose.

A composite lymphoma is the rare simultaneous occurrence of two or more distinct lymphomas within a single tissue or organ. Herein, we describe a case of a 51-year-old man presenting with a history of lower limb rash, fatigue, and bulky abdominopelvic lymphadenopathy. An excisional left iliac lymph node biopsy was notable for the composite presence of two distinct lymphoid neoplasms, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), and follicular lymphoma (FL). Multiplex PCR and FISH analyses failed to demonstrate a t(14;18)(q32;q21) translocation in either composite lymphoma component. A clonal light-chain kappa (V/JC intron-kde) gene rearrangement was detected in the FL component only.

Biclonal lymphoid disorders, when two distinct lymphoproliferative disorders (LPD) co-exist, are rare (incidence of 1.4%) and associated with a poor prognosis. NOTCH1 mutations occur in 10% of CLL at diagnosis, associated with a short disease-free interval and increased risk of Richter's transformation. We hypothesised that the incidence of NOTCH1 mutations in CLL with a second LPD may be increased, because the mutation occurs early in leukaemogenesis, permitting clonal divergence.We identified 19 patients with biclonal LPD at diagnosis: 11 with CLL and a second LPD (group A) and 8 with a second distinct CLL (group B). NOTCH1 mutation analysis was performed and clinical outcome investigated.Ten of 19 (52%) were NOTCH1 mutated: 5 in group A (45%) and 5 in group B (62.5%) with a favourable clinical outcome observed among this cohort with 28.7 (range 1-99) months of follow-up.In conclusion, we identified a significant (52%) incidence of NOTCH1 mutations in CLL in the context of biclonal LPD, associated with an indolent clinical course.

Biclonal lymphoid disorders (BLD) are a rare (1.4%) but distinct entity in which Chronic lymphocytic leukaemia (CLL) co-exists with a second lymphoproliferative disorder (LPD) and are poorly understood in terms of pathogenesis and clinical impact. The NOTCH1 pathway is involved in cell proliferation, cell cycle progression and is anti-apoptotic, with mutations of the regulatory PEST domain causing constitutive up-regulation of the pathway. NOTCH1 mutations occur early in CLL leukaemogenesis and are found in 10% of poor prognosis CLL at diagnosis as well as being associated with 50% of Richter's transformation (both Hodgkin's and non-Hodgkin's subtype). We hypothesised that NOTCH1 mutations may be implicated in BLD pathogenesis both because they occur early in leukaemogenesis when clonal divergence is possible and because of its association with Hodgkin's Richter's, which is biologically distinct from CLL. We identified 19 patients with BLD at initial presentation, confirmed by flow cytometry and/or molecular analysis of the Immunoglobulin heavy (IgH) and light (IgL) chain genes between 2008 and 2015. This cohort consisted of 14 males and 5 females with a mean age of 72 (range 47-90) years. BLD was defined as follows: (1) co-existence of cells with different immunophenotypes such as a CD5+/CD19+ and CD5-/CD10- population confirming the co-existence of 2 diagnoses, (2) demonstration of both kappa (κ) and lambda (λ) light chain restriction on a CD5+/CD19+ population and (3) CD5+/CD19+ population without demonstrable surface light chains but with >2 clonal gene rearrangements of their IgH and IgL loci. All 19 cases were tested for a c.7544-7545delCT resulting in truncation of the regulatory C-terminal PEST domain of the NOTCH1 gene by PCR. Eleven of 19 patients had CLL co-existing with a different LPD as follows: Mantle Cell Lymphoma (MCL) (2), Hairy Cell Leukaemia (HCL) (2) and Marginal Zone Lymphoma (7). Of this subgroup 5 of 11 cases (45%) had a NOTCH1 mutation. Four samples in our cohort displayed dual κ and λ light chain expression detected by flow cytometry and confirmed molecularly by identifying 2 clonally distinct populations of LPD and 3 samples (75%) had a NOTCH1 mutation. Four samples were identified with >90% CD5+/CD19+ expression but no monoclonality by flow cytometry, but with 2 distinct populations identified by IgH and IgL rearrangements and of this subgroup 2 (50%) had NOTCH1 mutations. Clinical data was available on 13/19 patients, of whom 11 patients had Binet A and 2 Binet B disease. No patient has required CLL-directed treatment, 2 patients have died of other causes and 11 remain under surveillance. Three of 9 patients with a second LPD have required treatment: both patients with HCL received cladribine for pancytopaenia and a patient with MCL was treated with Rituximab and Bendamustine. Overall, 10 of the 19 (52%) patients with BLD had a NOTCH1 mutation at diagnosis, which is higher than the 10% reported in CLL literature. The absence of any germinal centre cell derived lymphoma in the cohort of patients with additional LPD is intriguing and needs confirmation in other series. The prognostic implications of BLD and NOTCH1 mutations are not possible to assess in this small cohort, but accurate characterization of BLD aids therapeutic decision-making as in the case of concurrent CLL and HCL. Light chain restriction by flow cytometry in a mature B-cell population confirms monoclonality and suggests malignancy, however dual κ and λ expressing CLL may give a polyclonal pattern resulting in failure to make a CLL diagnosis; therefore awareness of this rare subtype of CLL is important. In summary we have added a further association between NOTCH1 mutations and CLL associated disorders which currently includes: poor prognosis CLL at diagnosis, Hodgkin's and non Hodgkin's Richter's transformation and most recently BLD. Increased sensitivity of NOTCH1 detection by next generation sequencing techniques may provide a further insight into the evolutionary origin and pathogenesis of BLD and further elucidate the enigmatic role of NOTCH1. Disclosures Crotty: BMS, Takeda, Novartis, Janssen, Roche: Honoraria.