Haematology

From the Image to the Diagnosis

Mike Leach, Barbara J. Bain

• Publisher: Wiley-Blackwell
• Year: 2021
• ISBN:
  9781119777526
• Edition: 1
• Topic: Medicine
• Subtopic: Hematology

Haematology

Diagnostic haematology requires the assessment of clinical and laboratory data together with a careful morphological assessment of cells in blood, bone marrow and tissue ­fluids. Subsequent investigations including flow cytometry, immunohistochemistry, cytogenetics and molecular studies are guided by the original morphological findings. These targeted investigations help generate a prompt unifying diagnosis. Haematology: From the Image to the Diagnosis presents a series of cases illustrating how skills in morphology can guide the investigative process. In this book, the authors capture a series of images to illustrate key features to recognize when undertaking a morphological review and show how they can be integrated with supplementary information to reach a final diagnosis.

Using a novel format of visual case studies, this text mimics 'real life' for the practising diagnostic haematologist – using brief clinical details and initial microscopic morphological triage to formulate a differential diagnosis and a plan for efficient and economical confirmatory investigation to deduce the correct final diagnosis. The carefully selected, high-quality photomicrographs and the clear, succinctdescriptions of key features, investigations and results will help haematologists, clinical scientists, haematology trainees and haematopathologists to make accurate diagnoses in their day-to-day work.

Covering a wide range of topics, and including paediatric as well as adult cases, Haematology: From the Image to the Diagnosis is a succinct visual guide which will be welcomed by consultants, trainees and scientists alike.

1
Anaplastic large cell lymphoma with haemophagocytic syndrome

A 50‐year‐old man from another health board was transferred to a local hospital for a surgical biopsy of a mediastinal lymph node. He had presented 6 weeks previously with fever, sweats and weight loss. No infective or neoplastic aetiology had been identified. He had progressive pancytopenia and hyperferritinaemia and a diagnosis of idiopathic haemophagocytic syndrome had been considered. He had already been treated at the base hospital with corticosteroids and etoposide. CT imaging, however, had shown abnormal mediastinal lymph nodes, which would not have been accessible by percutaneous needle biopsy.

On arrival at the local cardiothoracic unit he was clearly unwell. The full blood count showed Hb 90 g/l, WBC 2.5 × 10⁹/l, neutrophils 1.5 × 10⁹/l and platelets 25 × 10⁹/l. The coagulation screen showed PT 18 s, APTT 45 s, TT 18 s, fibrinogen 1.4 g/l and D dimer 5500 ng/ml (NR <230). Serum ferritin was >10 000 μg/l. The anaesthetic team phoned to ask for advice regarding management of the coagulopathy prior to surgery. The blood film showed rouleaux and was leucoerythroblastic with a few toxic granulated neutrophils but no neoplastic cell population was evident. We decided to cancel the surgery, review the imaging and perform a bone marrow aspirate and trephine biopsy. A CT scan showed definitely pathological mediastinal lymph nodes. The bone marrow aspirate showed a population of very large lymphoid cells with round or ovoid nuclei, indistinct nucleoli and partially condensed nuclear chromatin without cytoplasmic granules (top images). The cytoplasm of these cells showed prominent vacuolation, often concentrated in apparent pseudopodia (top images). In addition, there was a substantial population of macrophages showing haemophagocytosis, particularly of red cells and their precursors (all images above ×100 objective). The clinical, laboratory and morphological findings were in keeping with a haemophagocytic syndrome. Flow cytometry on the large cell population in the marrow aspirate showed these cells to express CD45, CD2, CD3, CD4 and CD30. No myeloid or B‐lineage antigens were expressed. The bone marrow trephine biopsy sections were also abnormal, showing prominent macrophages displaying haemophagocytosis on H&E staining (below, left image) and CD68R (below, centre image, immunoperoxidase), whilst the large neoplastic cells were highlighted using CD30 (below, right, immunoperoxidase) (all images below ×50). Immunohistochemistry showed the large cells to be ALK negative. The diagnosis was now confirmed as ALK‐negative anaplastic large cell lymphoma. The patient was transferred back to his local hospital with a view to commencing CHOP chemotherapy but after one cycle of treatment he deteriorated further and sadly died.

Haemophagocytic syndrome is a rare constellation of clinicopathological features including fever, weight loss, sweats and organomegaly, together with laboratory abnormalities including cytopenias, hyperferritinaemia, hypertriglyceridaemia, coagulopathy and bone marrow haemophagocytosis. Interestingly, according to strict diagnostic criteria, and despite the name, demonstration of the latter is not absolutely essential. In adults the typical triggers for a confirmed haemophagocytic syndrome are infective or neoplastic. In adult patients a neoplastic cause is very likely and high‐grade T‐cell and NK‐cell neoplasms are the usual culprits. In paediatric practice there are a number of inherited immunodeficiency syndromes that strongly predispose to a haemophagocytic syndrome, but neoplastic and infective triggers similar to the above have also to be considered. It is absolutely essential to consider a neoplastic cause in adult patients; this focuses attention on looking for an underlying neoplasm with subsequent targeted treatment, in which case the haemophagocytic syndrome will gradually resolve.

MCQ

1. ALK‐negative anaplastic large cell lymphoma:
   1. Generally occurs at an older age than ALK‐positive cases
   2. Has a better prognosis than ALK‐positive anaplastic large cell lymphoma
   3. Has similar histological and immunophenotypic features to breast implant‐associated anaplastic large cell lymphoma
   4. Is usually associated with t(2;5)(p23.2‐23.1;q35.1)
   5. Usually presents with localised disease
   For answers and discussion, see page 206.

2
Bone marrow AL amyloidosis

A 47‐year‐old man presented with peripheral oedema due to nephrotic syndrome and a kidney biopsy was planned. Full blood count showed Hb 154 g/l, WBC 7.8 × 10⁹/l and platelets 355 × 10⁹/l. Serum creatinine was 136 μmol/l, estimated glomerular filtration rate (eGFR) 49 ml/min/1.73 m², albumin 17 g/l and urine protein 5.4 g/l. A serum IgA lambda paraprotein (9 g/l) and excess serum free lambda light chains at 103.5 mg/l (NR 5.7–26.3) were identified.

A bone marrow aspirate identified deposits of amorphous, purple‐staining material suggestive of amyloid protein (top left image) (all images ×50 objective). The trephine biopsy sections showed diffuse eosinophilic amorphous material (top right, H&E) in keeping with amyloid deposited around fat cells, around erythroid islands, in the walls of small vessels and throughout the interstitium. Immunohistochemistry for CD138 revealed 7% plasma cells with non‐specific binding to the amyloid deposits (bottom left, immunoperoxidase) the latter deposits staining also with Sirius red (bottom right). These findings are indicative of extensive bone marrow amyloid deposition due to primary AL amyloidosis. In view of these findings the renal biopsy was now not deemed necessary.

This case illustrates the striking morphological abnormalities encountered in amyloidosis; accurate recognition of these features is important in bringing together a unified clinical diagnosis.

A second patient presented with back pain and vertebral collapse. MRI suggested a marrow infiltrative disease such as myeloma. Indeed, he was shown to have raised serum free lambda light chains (367 mg/l) but no paraprotein was detected. The bone marrow aspirate, however, was hypocellular and showed low level (<1%) involvement by plasma cells so the diagnosis was questioned. The trephine biopsy sections showed heavy involvement by AL amyloidosis (all images below, H&E, left ×10, centre and right ×50) occupying well over 80% of the marrow space, with notable involvement of vessel walls. In the cellular areas well over 90% of cells were neoplastic plasma cells. Elsewhere small pockets of malignant plasma cells were ident...