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Haematology. Barbara J. Bain
Читать онлайн.Название Haematology
Год выпуска 0
isbn 9781119777526
Автор произведения Barbara J. Bain
Жанр Медицина
Издательство John Wiley & Sons Limited
MCQ
1 Molecular mechanisms underlying primary myelofibrosis include:BCR‐ABL1CALR mutationJAK2 V617FJAK2 exon 12 mutationMPL mutationFor answers and discussion, see page 206.
6 Sarcoidosis
A 50‐year‐old man was referred for investigation of low‐volume lymphadenopathy and mild splenomegaly noted on a CT scan performed as part of the investigation of loin pain. Renal stones had been suspected. He had no specific respiratory symptoms but did describe occasional night sweats. Widespread small‐volume lymphadenopathy involving cervical, axillary, mediastinal and mesenteric nodes had been identified. The spleen measured 15 cm in long axis. Notably the lung imaging showed some non‐specific lower zone inflammatory/infective changes. His full blood count showed Hb 127 g/l, WBC 4.3 × 109/l, neutrophils 2.5 × 109/l, lymphocytes 0.6 × 109/l and platelets 206 × 109/l. Serum angiotensin‐converting enzyme (ACE) and LDH were both normal. He underwent a bone marrow aspirate and trephine biopsy. The aspirate was initially reported as showing reactive changes but no specific pathology. The trephine biopsy sections were abnormal, showing very well demarcated non‐caseating granulomas (top images, H&E ×10 objective). There were very prominent multinucleated giant cells present within the granulomas (bottom images, H&E ×50 objective). There was no evidence of a low‐grade or high‐grade lymphoma. The working diagnosis, despite the normal serum ACE level, was sarcoidosis. A lymph node core biopsy also showed non‐caseating granulomas. The patient was referred to the Respiratory team who performed a transbronchial lung biopsy which showed features of intra‐alveolar inflammation and a small granuloma. A Ziehl–Neelsen stain and mycobacterial cultures were negative.
Sarcoidosis is an intriguing condition where there are many pathological features of a cell‐mediated reaction to an unknown stimulus. It is typically a pulmonary disease (suggesting a primary pulmonary pathogen) but can evolve into a systemic disorder with potentially serious consequences (neurosarcoidosis and myocardial sarcoidosis). The diagnosis is one of exclusion as no single investigation carries high specificity and the serum ACE level, classically described as being elevated, can be normal. Hodgkin lymphoma enters into the differential diagnosis since sarcoidosis can cause weight loss, night sweats and fatigue with hilar and mediastinal lymphadenopathy.
On reviewing the bone marrow aspirate a number of disrupted granulomas were evident (images below ×50). This presents a good example as to how co‐reporting of the aspirate and trephine biopsy specimen can yield a unified diagnosis. Many haematologists reporting and identifying these aspirate abnormalities in isolation would likely fail to appreciate their significance.
MCQ
1 Caseating granulomas can be a feature of:Fungal infectionGranulomatous response to follicular lymphomaGranulomatous response to multiple myelomaSarcoidosisTuberculosisFor answers and discussion, see page 206.
7 Visceral leishmaniasis
A 5‐year‐old boy was referred for investigation of anorexia, abdominal bloating and intermittent fever. On examination he appeared pale and underweight and had palpable splenomegaly. His full blood count showed Hb 100 g/l, WBC 4 × 109/l, neutrophils 2 × 109/l and platelets 247 × 109/l. The blood film showed no specific features. He had a polyclonal increase in immunoglobulins, low serum albumin at 26 g/l and a direct Coombs test that was positive for IgG. CT imaging confirmed splenomegaly but no lymphadenopathy was apparent. A lymphoma was suspected, but in the absence of a suitable biopsy target, bone marrow aspiration and trephine biopsy were performed.
The aspirate was particulate with cellular trails. There was no lymphomatous infiltrate. There were, however, increased numbers of macrophages containing Leishmania promastigotes (left and centre images ×100 objective). Note that the macrophage cytoplasm was disrupted in some cells with the parasites appearing free in the film (centre images). Note that each parasite has a nucleus and a smaller rod‐shaped kinetoplast. Microscopy alone is sufficient to make a diagnosis but serology and molecular studies can be used for confirmation and determining species, respectively. The bone marrow trephine biopsy sections showed maximal cellularity with large numbers of macrophages harbouring parasites being visible (right images ×50). On further questioning regarding the travel history, it was learned that the family had visited Malta on a 2‐week holiday some months previously. The patient was treated with intravenous liposomal amphotericin and made a full recovery.
The term leishmaniasis encompasses multiple clinical syndromes resulting from Phlebotomus sand fly transmission of a variety of Leishmania species; cutaneous, mucocutaneous and visceral forms (the case described above) of the disease result, sometimes many months or years after primary infection. It is present in the tropics, subtropics and southern Europe including the Mediterranean area. It is endemic in dogs in Malta with the implicated organism being Leishmania infantum. Visceral leishmaniasis is a serious infection which should never be overlooked and bone marrow biopsy material should be carefully scrutinised whenever this diagnosis is possible. In this case, the marrow biopsy was taken looking for involvement by lymphoma and the condition was encountered almost by accident. This was also the case for another patient who presented with a perianal ulcer. The biopsy showed granulomatous inflammation and a diagnosis of Crohn’s disease was assumed. He was commenced on azathioprine therapy but developed progressive pancytopenia. A bone marrow aspirate and trephine biopsy were taken, assuming the cause to be drug toxicity but Leishmania parasites were seen and accurately identified in the aspirate films. Review of the skin biopsy showed the granulomatous skin ulcer to be due to cutaneous Leishmania infection.
In tropical and subtropical countries where the infection is endemic, a rapid field hospital method of making a diagnosis is microscopy of a splenic aspirate, taken under local anaesthetic. The images below (×100) are of an MGG‐stained splenic aspirate showing visceral leishmaniasis.
MCQ
1 Leishmaniasis involving the bone marrow:Can be complicated by a haemophagocytic syndromeCan cause granuloma formationCan lead to significant dyserythropoiesisIs easily detected with Grocott’s methenamine silver stainIs often associated with increased plasma cellsFor answers and discussion, see page 206.
8 Gelatinous transformation of the bone marrow
A 60‐year‐old man with chronic debility due to neurosarcoidosis was referred for investigation of a normocytic anaemia with Hb 100 g/l and normal leucocyte and platelet counts. The blood film was not informative. He underwent bone marrow aspiration. The aspirate was hypocellular but did not show any