Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare condition, which often responds poorly to treatment. We describe here a patient with IVLBCL affecting the pituitary and both adrenal glands who is currently in remission following successful treatment with immunochemotherapy. A 47-year-old woman of Indian ethnic origin presented with a 6-month history of secondary amenorrhoea and fatigue. Clinical examination was unremarkable, but investigations revealed hyponatraemia (Na 122 mmol/l; normal range, 133–146 mmol/l), anaemia (Hb 100 g/l; normal range, 130–170 g/l) and thrombocytopenia (platelet count 134 × 109/l; normal range, 150–410 × 109/l). Further investigations indicated partial anterior hypopituitarism and pituitary magnetic resonance imaging showed a mass consistent with a non-functioning macroadenoma (Fig 1A). Hydrocortisone and levothyroxine replacement was commenced and transsphenoidal hypophysectomy was planned. Four weeks later she reported deteriorating vision, increasing fatigue and night sweats. On examination, she was febrile and had easily palpable hepatomegaly. Her visual acuity had also declined. Investigations now showed a worsening bicytopenia (Hb 69 g/l, platelet count 122 × 109/l) and an elevated lactate dehydrogenase (1247 u/l). Fibrinogen was normal, but triglycerides and ferritin were raised (9·09 mmol/l and 1314 mg/l, respectively) and haemophagocytosis was seen in the bone marrow aspirate. A blood film was in keeping with iron deficiency and had evidence of red cell agglutination. Direct antigen testing, haemoglobinopathy screening and serum electrophoresis were all normal. Computed tomography of the chest, abdomen and pelvis revealed diffuse enlargement of both adrenal glands with hepatosplenomegaly (Fig 1B). Repeat pituitary imaging was unchanged. An adrenal biopsy was performed and reported as a poorly differentiated high-grade malignancy of uncertain primary, pending the results of a more comprehensive panel of immunohistochemistry. Empirical treatment with etoposide and cisplatin was commenced, with good initial clinical and radiological response. Subsequent immunohistochemistry of the adrenal biopsy showed the neoplastic cells to be CD20 and BCL2 positive, with a Ki67 of 98–100% and CD31 staining demonstrated intravascular localisation of the neoplastic cells (Fig 2). The final diagnosis was IVLBCL. The patient has completed therapy with cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) and intrathecal methotrexate, achieving complete resolution of the pituitary lesion (Fig 1C) and adrenal masses (Fig 1D). She remains well 1 year after her initial presentation. IVLBCL is an extremely heterogeneous condition. The Asian clinical variant of IVLBCL is typified by hepatosplenomegaly, cytopenias and haemophagocytic lymphohistiocytosis (Murase et al, 2000). Whilst IVLBCL of the endocrine glands has been reported (Matsue et al, 2007; Sawada et al, 2016), the presence of simultaneous pituitary and bilateral adrenal gland involvement is exceedingly rare and is associated with a poor prognosis (Matsue et al, 2007). Our patient's case is exceptional and instructive owing to the presentation with symptoms of a pituitary mass, the discovery of symmetrical involvement of both adrenal glands, and a favourable response to chemotherapy. All of the authors made a major contribution to the patient's clinical care and the intellectual content of this manuscript.
A 23-year-old Turkish woman with known coeliac disease presented to hospital with a fractured left femur (Figure 1 a) sustained when arising from bed. Two years prior, she sustained a fracture at the right humerus (Figure 1 b), caused by lifting the younger of her two children. Hypercalcemia was documented at the time of the first fracture, but she defaulted from follow-up.
Figure 1.
(a) Plain AP radiograph of the left femur demonstrates a pathological transverse fracture with full diaphyseal width medial displacement of the distal fragment. The underlying bone is abnormal with multiple lytic lesions in a background of …
A 49-year-old African man, with no known past medical history, presented to the emergency department with three day history of vomiting, lethargy, confusion and drowsiness on a background of two week history of thirst, polyuria with drinking up to 10 pints of water a day. More recently he had been drinking litres of non-diet lemonade in an effort to sustain energy levels.
On examination, Glasgow Coma Score was 6 (eyes 4, verbal 1, motor 1). He was severely dehydrated with dry mucous membranes, blood pressure 75/40 mmHg, pulse rate 120 bpm and cool peripheries. He was pyrexial 38.5°C, and hypoxic (oxygen saturations 84% on room air). Cardiovascular and respiratory examination was otherwise unremarkable. On arrival to the emergency department, he was intubated and ventilated due to hypoxaemia and poor conscious level. Baseline investigations are shown in Box 1. Chest radiograph showed patchy consolidation in the right base, suggestive of an aspiration pneumonia. A diagnosis of HHS, acute renal failure and severe mixed metabolic and respiratory acidosis was made. The patient was managed on the intensive care unit (ICU) with careful fluid resuscitation with 0.9% saline, according to central venous pressure. Slow reduction of plasma glucose was an explicit aim, using a maximum of 1 unit per hour of intravenous insulin, aiming to reduce plasma glucose by no faster than 1 mmol/L every 4 hours.1 He was fully anticoagulated in view of his high risk of stroke, and was given broad spectrum antibiotics. On ICU, he required inotropic support to maintain blood pressure, and haemofiltration in view of his acute renal failure and severe acidosis.
Box 1
Investigations on admission
Sodium 157 mmol/L (136–146 mmol/L)
Corrected Sodium 181 mmol/L (136–146 mmol/L)
Potassium 3.9 mmol/L (3.5–5.1 mmol/L)
Urea 23.7 mmol/L (2.5–6.4 mmol/L)
Creatinine 253 µmol/L (62–106 µmol/L)
Creatine Kinase 1097 mmol/L (9–168 IU/L)
Calcium 2.45 mmol/L (2.15–2.58 mmol/L)
Phosphate 1.52 mmol/L (0.74–1.52 mmol/L)
Serum osmolality 480 mOsm/kg (280–295 mOsm/kg)
Haemoglobin 14.8 g/dl (11.5–16.6)
White cell count 17.6 × 109/l (4–11)
Platelets 211 × 109/l (150–400)
Plasma Glucose 90.3 mmol/L (4–7 mmol/L)
pH 6.998 (7.35–7.45)
pCO2 5.54 kPa (4.67–6.40 kPa)
pO2 (on 100% oxygen) 12.9 kPa (11.1–14.4 kPa)
Bicarbonate 14.3 mmol/L (22–26 mmol/L)
Lactate 5.6 mmol/L (0.5–1.6 mmol/L)
Base Excess −12.3 mmol/L (−3–+3 mmol/L)
Chest radiograph Right sided volume loss and patchy consolidation
ECG Sinus tachycardia
Urinalysis Protein +
Ketones trace
Blood + + +
Leucocytes negative
Nitrites negative
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His condition did not improve despite full intensive care. Serum creatine kinase continued to increase to a peak of 417,907 IU/L, and a presumptive diagnosis of compartment syndrome leading to muscle infarction and acute rhabdomyolysis was made, which was supported by raised compartment pressures in the thigh and calf muscles. He underwent multiple fasciotomies, which confirmed necrotic muscle. His acidosis did not resolve despite haemofiltration, and oxygenation deteriorated, probably as a result of acute lung injury. He developed uncontrollable bleeding from disseminated intravascular coagulopathy, and after careful discussion with his family, further support was withdrawn, and he died 72 hours after arrival in hospital.
Post mortem examination showed a fatty liver, evidence of muscle infarction in the legs, but no evidence of cardiovascular or cerebrovascular events.
Elevated high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease, and variation in HDL-C levels has been shown to be approximately 50% heritable. Overexpression of endothelial lipase (EL), a member of the lipoprotein lipase gene family, markedly reduces HDL-C levels in mouse models. We hypothesized that genetic variation in EL might be associated with elevated HDL-C.All exons and 1.2 kilobase of promoter of the EL gene were sequenced in 20 unrelated human subjects with high HDL-C levels. A total of 17 variants were identified. Six of these were potentially functional and were confirmed by restriction enzyme analysis. Four variants result in amino acid changes (Gly26Ser, Thr111Ile, Thr298Ser, and Asn396Ser,) and 2 variants were in the promoter (-303A/C and -410C/G). The genotype frequencies of each variant were determined in 176 black controls, 165 white controls, and 123 whites with high HDL-C. The Thr111Ile variant was the most common, with an allele frequency of 10.3% in blacks, 31.2% in white controls, and 32.6% in the high HDL-C group. The remaining variants all had allele frequencies <5.0% but differed in frequency among the 3 groups. Interestingly, Gly26Ser, Thr298Ser, and -303A/C were found in the black and high HDL-C white cohorts but were absent in the control white group.Six new potentially functional variants in EL were discovered through sequencing of the EL gene in subjects with high HDL-C levels. Differences in allele frequencies exist between blacks and whites and between control subjects and those with high HDL-C levels.
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