Mike Leach

Nodular lymphocyte predominant Hodgkin lymphoma behaves as a distinct clinical entity with good outcome: evidence from 14-year follow-up in the West of Scotland Cancer Network

Clinically and biologically, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has much more in common with germinal-center derived B-cell non-Hodgkin lymphoma (NHL) than with classical Hodgkin lymphoma (cHL). Management of NLPHL remains controversial. In a 14-year multicenter series, 69 cases were analyzed, and the median follow-up was 53 months (range 11–165.) B-symptoms were present in only 4.3% of patients, and 81.1% of patients had stage I/II disease. Treatment was with radiotherapy (53.6%), chemotherapy (21.7%), combined modality (17.4%), and observation (7.2%). In all, 10.1% of patients relapsed and 2.9% of patients developed high-grade transformation to DLBCL. All relapses and transformations were salvageable. No patient died of their disease. The 5-year relapse-free survival was 92%, transformation-free survival 98.4%, and overall survival 100%. We conclude that NLPHL behaves as a distinct clinical entity, often presenting at an early stage without risk factors. It has an excellent outcome. It may be possible, in early-stage disease, to reduce the intensity of therapy in NLPHL, to single-modality radiotherapy, without affecting OS.

Loss of utility of bone marrow biopsy as a staging evaluation for Hodgkin lymphoma in the positron emission tomography–computed tomography era: a West of Scotland study

Abstract Positron emission tomography–computed tomography (PET-CT) scanning has been shown to be more sensitive than bone marrow biopsy (BMB) in detecting bone marrow involvement (BMI) in classical Hodgkin lymphoma (cHL). In this 5-year retrospective series, 93 (54%) of all new cases of cHL were staged using PET-CT and BMB. PET-CT identified focal bone marrow uptake in 17/93 (18.3%), whilst only five of these (29.4%) were confirmed by BMB. Abnormal pelvic uptake was seen on PET-CT in these five cases. The other 12 cases were missed, giving BMB a sensitivity of 29.4% and a specificity of 100%. PET-CT upstaged 9.7% of patients compared to CT alone. BMB upstaged only one patient; however, this patient was already stage IV on PET-CT. BMB did not alter clinical management in any case. Bone positivity on PET-CT appeared to correlate with anemia, raised lactate dehydrogenase (LDH) and B symptoms. BMB has little or nothing to offer staging cHL in the PET-CT era.

Guidelines for the investigation and management of nodular lymphocyte predominant Hodgkin lymphoma.

Department of Haematology, Beatson West of Scotland Cancer Centre, Gartnavel Hospital, Glasgow, PETIC, Department of Radiology, University Hospital of Wales, Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, UK, Paediatric Haematology/Oncology Unit, Children’s Hospital, John Radcliffe Hospital, Headington, Oxford, Department of Haematology, University College London Hospitals, Department of Pathology, University College London Hospitals, and Department of Haematology, The Royal Free London NHS Trust, London, UK

Possible significance of cup-like blasts in acute myeloid leukaemia

A 73-year-old woman presented with a short history of spontaneous bruising, petechiae and rectal bleeding. Full blood count showed haemoglobin of 92 g/l, white cell count of 148 · 10/l and platelet count of 27 · 10/l. Coagulation studies showed prothrombin time 16 s, activated partial thromboplastin time 25 s, thrombin time 13AE1 s, fibrinogen 2AE81 g/l and D-dimer 61 608 ng/ml fibrinogen equivalent units. The blood film showed numerous granular myeloblasts with large nuclear indentations and invaginations – cup-like blasts (figures). Bone marrow examination showed similar blasts accounting for >90% of nucleated cells, with minimal maturation. Immunophenotyping confirmed acute myeloid leukaemia (CD117, CD13, CD33 and myeloperoxidase positive) but surprisingly the blasts were negative for CD34 and HLA-DR, a finding that is more characteristic of acute promyelocytic leukaemia [M3 acute myeloid leukaemia (AML)]. Cytogenetics studies showed a normal karyotype. Screening for FLT3 internal tandem duplication (ITD) and NPM1 mutations were both positive. Acute myeloid leukaemia with cup-like blasts is defined by characteristic cup-like indentations of the nuclei in myeloid blasts. This feature appears more prominent in peripheral blood than bone marrow smears. On electron microscopy, the nuclear invagination has been shown to be filled with cytoplasmic organelles. These blasts are typically negative for CD34 and HLA-DR on immunophenotyping, which in the presence of bleeding and laboratory evidence of disseminated intravascular coagulation may cause confusion with acute promyelocytic leukaemia. However, the karyotype associated with AML with cup-like blasts is usually normal but with molecular studies showing mutations in FLT3 and NPM1, either alone or in combination. AML with cup-like blasts may be a distinct biological entity. Its characteristic morphology and immunophenotype may be a clue to the associated FLT3 ITD and NPM1 mutation profile in normal karyotype AML.

Neutrophil‐specific granule deficiency

A 25-year-old male was referred for further investigation of chronic neutropenia, monocytosis and recurrent bacterial infections, mainly streptococcal and staphylococcal, from an early age. A variety of anatomical sites had been affected, including skin and soft tissues (with abscess formation), middle ear, sinuses and lung. He had suffered an episode of bacterial meningitis and a subdural empyema complicating a pan-sinusitis. His mother and sister gave a similar history of infection. An automated full blood count showed normal Hb, white blood cell and platelet count but there was an apparent neutropenia (1 2 9 10/l) and monocytosis (3 5 9 10/l). He had a non-healing, previously infected skin ulcer over the left lateral malleolus resulting from pressure incurred by a plaster cast following a tibial fracture. A blood film showed neutrophils with reduced granulation and incomplete nuclear segmentation with some bilobed forms, such that they could be difficult to differentiate from monocytes (top). His mother and sister have identical cytological features. Manual neutrophil and monocyte counts were normal and examination of the automated analyser forward/side scatter plot (Sysmex XE-2100) showed many of the neutrophils to have much reduced side scatter such that they were superimposed on the monocyte zone (centre patient left, control right, neutrophils red, monocytes blue, lymphocytes green). A diagnosis of neutrophil-specific granule deficiency (NSGD), previously known as lactoferrin deficiency, was made. Low numbers of neutrophil type 1 and type 2 granules were demonstrated by electron microscopy (bottom left, control right) with resultant reduced myeloperoxidase and lactoferrin. Neutrophil membrane expression of CD15, CD16 and CD66 was reduced. NSGD is a rare inherited defect with only a few families reported. A CEBPE mutation is sometimes identified. The neutrophils show impaired chemotaxis, phagocytosis and bactericidal activity resulting in recurrent pyogenic infections from infancy.

A British Society for Haematology Good Practice Paper on the Diagnosis and Investigation of Patients with Mantle Cell Lymphoma

Pamela McKay, Mike Leach, Bob Jackson, Stephen Robinson and Simon Rule Department of Haematology, Beatson West of Scotland Cancer Centre, Gartnavel Hospital, Department of Pathology, Queen Elizabeth University Hospital, Glasgow, Department of Haematology, University Hospitals Bristol, Bristol, and Department of Haematology, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK

Guideline for the Management of Mantle Cell Lymphoma

This guideline was compiled according to the British Society for Haematology (BSH) process at www.b-s-h.org.uk. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http:// www.gradeworkinggroup.org. MEDLINE, EMBASE, DYNAMED, TRIP and NHS EVIDENCE were searched systematically for publications in English from 1980 to 2017 using the

Acute kidney injury from tumour lysis syndrome and urate crystalluria

A 74-year-old man with B-cell chronic lymphocytic leukaemia and anaemia due to stage C disease, commenced treatment with intravenous bendamustine 100 mg/m on days 1 and 2. A full blood count (FBC) at the time of treatment showed Hb 90 g/l, white blood cells (WBC) 71 4 9 10/l and platelets 158 9 10/l with impaired renal function [urea 3 2 mmol/l, creatinine 118 lmol/l, estimated glomerular filtration rate (eGFR) 52 ml/min]. A recent computerized tomography (CT) scan had shown no significant lymphadenopathy, organomegaly or renal abnormality. He had a long history of gout treated intermittently with analgesics. He was not given allopurinol because of the perceived high incidence of rashes when this drug is used together with bendamustine. The patient was admitted 1 week later with profound fatigue, vomiting and oliguria. The FBC now showed pancytopenia (WBC 1 3 9 10/l, Hb 67 g/l, platelets 115 9 10/l) with serum creatinine 846 lmol/l, potassium 5 9 mmol/l, calcium 2 14 mmol/l, phosphate 2 91 mmol/l, urate 1 24 mmol/l and eGFR 5 ml/min. The acute kidney injury was deemed secondary to tumour lysis syndrome. Non-contrast CT imaging showed dilatation of the collecting systems of both kidneys (long arrows) and significant perinephric stranding bilaterally. There were foci of high density in the bladder (short arrows) and distal ureters suggestive of uric acid crystallization. He was treated with intravenous fluids, insulin, dextrose and rasburicase. Within hours his urine output recovered, following which there was a polyuric phase with progressive recovery of renal function (creatinine 93 lmol/l, potassium 3 6 mmol/l, urate < 0 06 mmol/l and eGFR > 60 ml/min by day 5 of admission). This patient illustrates the potential danger of administering chemotherapy in the absence of allopurinol or rasburicase prophylaxis. The case is unusual in that, in addition to direct renal damage from hyperuricaemia, there was also an element of post-renal obstructive uropathy from urate crystalluria, which was visible on imaging. The patient was very close to requiring renal dialysis, but with the recovery of urine output following rasburicase treatment, this was not ultimately required.

The value of small bowel magnetic resonance imaging in the management of enteropathy associated T-cell lymphoma.

A 50-year-old female with a 9-year history of coeliac disease, presented with an acute jejunal perforation. Resection of the distal jejunem and primary anastomosis was carried out. Histology showed a high grade T-cell lymphoma on a background of coeliac disease [Enteropathy associated T-cell lymphoma (EATCL)]. A computed tomography (CT) scan carried out postoperatively showed no lymphadenopathy or evidence of residual lymphoma mass in the abdomen or pelvis. The patient then received three cycles of CHOP (cyclophosphamide, adriamycin, oncovin and prednisolone), but remained symptomatic with abdominal pain, anorexia and diarrhoea. A CT scan of the abdomen was normal. A magnetic resonance imaging (MRI) small bowel study was then carried out, which clearly demonstrated a residual mass in the small bowel consistent with lymphoma (Fig 1A). Her treatment was escalated and she received three cycles of ESHAP (cisplatin, cytarabine, etoposide, methylprednisolone) with stem cell harvesting on recovery from the first cycle. A repeat MRI after two cycles showed resolution of the mass. Treatment was completed with a BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] conditioned autologous stem cell transplant, as has been advocated in responding patients who are able to tolerate the procedure (Lennard et al, 2002; Bishton & Haynes, 2006). A further MRI small bowel study, carried out 2 months post-transplant, was normal (Fig 1B) and she remains well after 9 months of follow up. The EATCL is an aggressive lymphoma with a poor prognosis. Traditional radiological imaging techniques, such as CT, can be insensitive at detecting this lymphoma, particularly when disease may be confined to the epithelial layer of the bowel wall and be multi-focal. Positron emission tomography techniques can be of value in imaging EATCL, but false positives do occur (Hoffmann et al, 2003; Bernstein et al, 2005). MRI offers several advantages over these techniques without exposure to radiation. It can provide cross-sectional images in multiple planes with high soft tissue contrast resolution, thus giving functional as well as anatomic information. We believe this case demonstrates an important role for MRI small bowel studies in assessing response to treatment in EATCL.

Hypomegakaryocytic thrombocytopenia and increased number of PNH-phenotype cells - an emerging subgroup of myelodysplastic syndrome showing frequent response to immunosuppression

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