British Journal of Neurosurgery, 2015; Early Online: 1–3 © 2015 The Neurosurgical Foundation ISSN: 0268-8697 print / ISSN 1360-046X online DOI: 10.3109/02688697.2015.1023781
SHORT REPORT
Intracranial extramedullary haematopoiesis: A case report Samir Mehta1, Jonathan Shapey1, Ute Pohl2 & Raghu Vindlacheruvu1 1Department of Neurosurgery, Essex Neurosciences Centre, Queen’s Hospital, Romford, UK, and 2Department of Cellular
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 05/11/15 For personal use only.
Pathology, Queen’s Hospital, Romford, UK
Abstract Extramedullary haematopoiesis (EMH) is an ectopic production of blood cells to compensate for ineffective haematopoiesis. We report a rare symptomatic presentation of intracranial EMH and discuss its investigation and management. EMH should be considered a differential diagnosis in patients with haemoglobinopathies, haemolytic anaemias and myeloproliferative disorders, who present with symptoms of raised intracranial pressure.
Score (GCS) of 12 (E3 V3 M6). A CT brain scan demonstrated a left chronic subdural haematoma (SDH) with associated midline shift (Fig. 1a). The patient had a history of betathalassaemia minor and myelodysplastic syndrome with chronic thrombocytopaenia and anaemia. Three months prior to this admission, she had emergency burr-hole drainage of a chronic right SDH, and she developed a symptomatic recollection two weeks post-operatively, which was re-evacuated with good neurological outcome. Her new left-sided chronic SDH was managed with burr-hole evacuation performed with peri-operative platelet transfusion (Fig. 1b). Once again, despite initial good neurological recovery, nine days post-operatively her conscious level deteriorated. CT imaging revealed modest re-accumulation of the left SDH but not sufficient to explain her neurological state. The patient was therefore managed conservatively and other causes of obtundation were investigated. She also developed a worsening anaemia thought to be secondary to chronic intracranial blood loss. Her anaemia appeared to be exacerbated by her thalassaemia and myelodysplastic syndrome, with on-going thrombocytopaenia contributing to the recurrent bleeding state. She was therefore prescribed tranexamic acid and HLA-matched platelets, and a platelet count of 100 109/L was maintained during her acute neurosurgical care. Her subsequent hospital stay was characterised by recurrent fluctuations in neurological state and further subdural recollection (Fig. 1c). Thus, she underwent one further attempt at burr hole drainage and later a craniotomy and evacuation of her recurrent left SDH. Intra-operatively, a very thick and vascular skull was noted, associated with thickened dura. Beneath this, a 5 mm thick hardened gelatinous membrane was discovered encasing thick hemosiderin-stained material overlying the brain. Analysis of dura and membrane specimens showed EMH (Fig. 2a). Immunohistochemical staining demonstrated multiple haematopoietic foci positive for glycophorin C (erythropoietic islands), neutrophil elastase (myeloid cells) and CD42b (megakaryocytes) (Fig. 2b, c, d). No neoplastic cells
Keywords: extramedullary haematopoiesis; haemoglobinopathy; intracranial; myelodysplastic syndrome
Introduction Haematopoiesis, the formation of blood cells from pluripotent stem cells, is a process which normally occurs in the marrow of long bones and the vertebrae of an adult.1 Extramedullary haematopoiesis (EMH) is the ectopic production of blood cells in tissues outside the active bone marrow.2 In adults, this rare physiological process is caused by haematological or bone marrow pathology, and reflects the body’s attempt to compensate for the demands of ineffective haematopoiesis.2 EMH is associated with haemoglobinopathies such as thalassaemia, states of severe haemolytic anaemia such as severe hereditary spherocytosis, and malignant or proliferative disorders of the bone marrow such as myelofibrosis and myelodysplasia.3 The most common sites of EMH are those producing foetal haemoglobin, such as liver, spleen and lymph nodes. Rare cases of intracranial EMH have been reported in patients with severe haematological disorders although cases are usually asymptomatic and found incidentally1,3. Here we present a rare case of symptomatic intracranial EMH in a patient with multiple haematological pathologies.
Case report A 67-year-old lady presented four days after a mechanical fall with confusion, drowsiness and an initial Glasgow Coma
Correspondence: Dr. Samir Kirti Mehta, Queen’s Hospital, Neurosurgery, Rom Valley Way, Romford, RM7 0AG United Kingdom. E-mail: dj_samir_mehta@ hotmail.com Received for publication 6 January 2015; accepted 22 February 2015
1
2 S. Mehta et al.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 05/11/15 For personal use only.
Fig. 1. Axial CT scans demonstrating left chronic SDH: before (a) and after burr hole drainage (b), and following recollection, prior to craniotomy and surgical evacuation (c).
or micro-organisms were identified. In the context of the patient’s previous positive bone marrow biopsy for RAEB-I myelodysplasia, these findings were consistent with immunohistochemical confirmation of intracranial EMH. After each operation her conscious state improved temporarily, but deteriorated again within days. Persistent intracranial bleeding continued to cause problems and the haematologists felt a course of palliative radiotherapy (20 Gy in 5 fractions) could be beneficial. Unfortunately, before this could be administered she deteriorated further and developed pneumonia, at which point treatment was no longer felt to be appropriate. She was therefore transferred to a hospice where she died two weeks later.
Discussion In EMH, ectopic tissues take on the role of adult blood production due to a failure of effective haematopoiesis in normal primary sites. EMH most frequently occurs in the liver, spleen, lymph nodes and paraspinal regions however cases have also been reported in the pleura, thymus, breast,
kidney, prostate, peritoneal surface, and intracranially in the dura and falx.3 Dural EMH is thought to relate to its mesenchymal origin and haematopoietic potential in the foetus.1 Recent studies have suggested the role of various cytokines (transforming and fibroblast growth factors [TGF and b-FGF]) in catalysing intracranial EMH in adults with bone marrow dysfunction. Previously reported cases have also highlighted a link between intracranial EMH and thalassaemia and myelofibrosis.2 The majority of patients with intracranial EMH are asymptomatic and are diagnosed incidentally on imaging or postmortem examination.3 Cases of symptomatic intracranial EMH are extremely rare. Patients may present with altered GCS that cannot be explained by other intracranial pathology, or as a result of raised intracranial pressure and/or compression of adjacent structures. Intracranial EMH may appear as multiple, extra-axial, heterogeneous masses on CT scanning, adjacent to and with a similar density to that of grey matter1. This may be associated with the hair-on-end appearance and diploic space thickening classically seen in patients with
Fig. 2. Histopathological slides demonstrating EMH: (a) Haematoxylin & Eosin (H&E) stain demonstrating all 3 cell lineages (erythropoietic, myeloid and megakaryocytes) (x 400 magnification). Immunohistochemistry stains demonstrating individual cell lineages: (b) Glycophorin C for erythropoietic islands (x 200 magnification); (c) Neutrophil elastase for myeloid cells (x 200 magnification); (d) CD42b for megakaryocytes (x 200 magnification).
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 05/11/15 For personal use only.
Case report of intracranial extramedullary haematopoiesis 3 haemoglobinopathies such as thalassaemia and sickle cell disease.1 If intracranial EMH is suspected, MRI is the investigation of choice. On MRI, EMH produces well circumscribed, lobulated masses with meningeal attachments of intermediate signal intensity on T1-weighted image, and markedly hypointense on T2-image.3 Tissue biopsy however provides definitive diagnosis.1,2 Haematopoietic foci are very radiosensitive. Intracranial EMH can therefore be treated with low dose radiotherapy which aims to shrink ectopic bone marrow production and reduce the symptoms of mass effect on adjacent brain.1 Recent publications have suggested an optimal radiation dose of 10–25 Gy delivered in multiple fractions.1 Reported side-effects include myelosuppresion due to radiodestruction of functional haematopoietic foci, and radiation-induced tissue oedema.1 Surgical excision remains an alternative to radiotherapy when EMH lies in close proximity to vital structures, but because of its high recurrence rate, radiotherapy is considered superior with over 70% of cases having full neurological recovery.1
Intracranial EMH is a rare condition, but should be considered a differential diagnosis in patients with a history of haemoglobinopathy or bone marrow dysfunction, that present with mass effect and symptoms of raised intracranial pressure. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Lee CM, Salzman KL, Blumenthal DT, Gaffney DK. Intracranial extramedullary haematopoiesis: brief review of response to radiation therapy. Am J Haematol 2005;78:151–52. 2. Musolino A, Guazzi A, Lazzaretti M, et al. Intracranial haematopoiesis in a patient with aids-related central nervous system lymphoma and severe pancytopenia. Haematologica 2007;92:e59–61. 3. Koch BL, Bisset GS, Bisset RR, Zimmer MB. Intracranial extramedullary haematopoiesis: MR findings with pathologic correlation. AJR 1994;162:1419–20.
SHORT REPORT
Intracranial extramedullary haematopoiesis: A case report Samir Mehta1, Jonathan Shapey1, Ute Pohl2 & Raghu Vindlacheruvu1 1Department of Neurosurgery, Essex Neurosciences Centre, Queen’s Hospital, Romford, UK, and 2Department of Cellular
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 05/11/15 For personal use only.
Pathology, Queen’s Hospital, Romford, UK
Abstract Extramedullary haematopoiesis (EMH) is an ectopic production of blood cells to compensate for ineffective haematopoiesis. We report a rare symptomatic presentation of intracranial EMH and discuss its investigation and management. EMH should be considered a differential diagnosis in patients with haemoglobinopathies, haemolytic anaemias and myeloproliferative disorders, who present with symptoms of raised intracranial pressure.
Score (GCS) of 12 (E3 V3 M6). A CT brain scan demonstrated a left chronic subdural haematoma (SDH) with associated midline shift (Fig. 1a). The patient had a history of betathalassaemia minor and myelodysplastic syndrome with chronic thrombocytopaenia and anaemia. Three months prior to this admission, she had emergency burr-hole drainage of a chronic right SDH, and she developed a symptomatic recollection two weeks post-operatively, which was re-evacuated with good neurological outcome. Her new left-sided chronic SDH was managed with burr-hole evacuation performed with peri-operative platelet transfusion (Fig. 1b). Once again, despite initial good neurological recovery, nine days post-operatively her conscious level deteriorated. CT imaging revealed modest re-accumulation of the left SDH but not sufficient to explain her neurological state. The patient was therefore managed conservatively and other causes of obtundation were investigated. She also developed a worsening anaemia thought to be secondary to chronic intracranial blood loss. Her anaemia appeared to be exacerbated by her thalassaemia and myelodysplastic syndrome, with on-going thrombocytopaenia contributing to the recurrent bleeding state. She was therefore prescribed tranexamic acid and HLA-matched platelets, and a platelet count of 100 109/L was maintained during her acute neurosurgical care. Her subsequent hospital stay was characterised by recurrent fluctuations in neurological state and further subdural recollection (Fig. 1c). Thus, she underwent one further attempt at burr hole drainage and later a craniotomy and evacuation of her recurrent left SDH. Intra-operatively, a very thick and vascular skull was noted, associated with thickened dura. Beneath this, a 5 mm thick hardened gelatinous membrane was discovered encasing thick hemosiderin-stained material overlying the brain. Analysis of dura and membrane specimens showed EMH (Fig. 2a). Immunohistochemical staining demonstrated multiple haematopoietic foci positive for glycophorin C (erythropoietic islands), neutrophil elastase (myeloid cells) and CD42b (megakaryocytes) (Fig. 2b, c, d). No neoplastic cells
Keywords: extramedullary haematopoiesis; haemoglobinopathy; intracranial; myelodysplastic syndrome
Introduction Haematopoiesis, the formation of blood cells from pluripotent stem cells, is a process which normally occurs in the marrow of long bones and the vertebrae of an adult.1 Extramedullary haematopoiesis (EMH) is the ectopic production of blood cells in tissues outside the active bone marrow.2 In adults, this rare physiological process is caused by haematological or bone marrow pathology, and reflects the body’s attempt to compensate for the demands of ineffective haematopoiesis.2 EMH is associated with haemoglobinopathies such as thalassaemia, states of severe haemolytic anaemia such as severe hereditary spherocytosis, and malignant or proliferative disorders of the bone marrow such as myelofibrosis and myelodysplasia.3 The most common sites of EMH are those producing foetal haemoglobin, such as liver, spleen and lymph nodes. Rare cases of intracranial EMH have been reported in patients with severe haematological disorders although cases are usually asymptomatic and found incidentally1,3. Here we present a rare case of symptomatic intracranial EMH in a patient with multiple haematological pathologies.
Case report A 67-year-old lady presented four days after a mechanical fall with confusion, drowsiness and an initial Glasgow Coma
Correspondence: Dr. Samir Kirti Mehta, Queen’s Hospital, Neurosurgery, Rom Valley Way, Romford, RM7 0AG United Kingdom. E-mail: dj_samir_mehta@ hotmail.com Received for publication 6 January 2015; accepted 22 February 2015
1
2 S. Mehta et al.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 05/11/15 For personal use only.
Fig. 1. Axial CT scans demonstrating left chronic SDH: before (a) and after burr hole drainage (b), and following recollection, prior to craniotomy and surgical evacuation (c).
or micro-organisms were identified. In the context of the patient’s previous positive bone marrow biopsy for RAEB-I myelodysplasia, these findings were consistent with immunohistochemical confirmation of intracranial EMH. After each operation her conscious state improved temporarily, but deteriorated again within days. Persistent intracranial bleeding continued to cause problems and the haematologists felt a course of palliative radiotherapy (20 Gy in 5 fractions) could be beneficial. Unfortunately, before this could be administered she deteriorated further and developed pneumonia, at which point treatment was no longer felt to be appropriate. She was therefore transferred to a hospice where she died two weeks later.
Discussion In EMH, ectopic tissues take on the role of adult blood production due to a failure of effective haematopoiesis in normal primary sites. EMH most frequently occurs in the liver, spleen, lymph nodes and paraspinal regions however cases have also been reported in the pleura, thymus, breast,
kidney, prostate, peritoneal surface, and intracranially in the dura and falx.3 Dural EMH is thought to relate to its mesenchymal origin and haematopoietic potential in the foetus.1 Recent studies have suggested the role of various cytokines (transforming and fibroblast growth factors [TGF and b-FGF]) in catalysing intracranial EMH in adults with bone marrow dysfunction. Previously reported cases have also highlighted a link between intracranial EMH and thalassaemia and myelofibrosis.2 The majority of patients with intracranial EMH are asymptomatic and are diagnosed incidentally on imaging or postmortem examination.3 Cases of symptomatic intracranial EMH are extremely rare. Patients may present with altered GCS that cannot be explained by other intracranial pathology, or as a result of raised intracranial pressure and/or compression of adjacent structures. Intracranial EMH may appear as multiple, extra-axial, heterogeneous masses on CT scanning, adjacent to and with a similar density to that of grey matter1. This may be associated with the hair-on-end appearance and diploic space thickening classically seen in patients with
Fig. 2. Histopathological slides demonstrating EMH: (a) Haematoxylin & Eosin (H&E) stain demonstrating all 3 cell lineages (erythropoietic, myeloid and megakaryocytes) (x 400 magnification). Immunohistochemistry stains demonstrating individual cell lineages: (b) Glycophorin C for erythropoietic islands (x 200 magnification); (c) Neutrophil elastase for myeloid cells (x 200 magnification); (d) CD42b for megakaryocytes (x 200 magnification).
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 05/11/15 For personal use only.
Case report of intracranial extramedullary haematopoiesis 3 haemoglobinopathies such as thalassaemia and sickle cell disease.1 If intracranial EMH is suspected, MRI is the investigation of choice. On MRI, EMH produces well circumscribed, lobulated masses with meningeal attachments of intermediate signal intensity on T1-weighted image, and markedly hypointense on T2-image.3 Tissue biopsy however provides definitive diagnosis.1,2 Haematopoietic foci are very radiosensitive. Intracranial EMH can therefore be treated with low dose radiotherapy which aims to shrink ectopic bone marrow production and reduce the symptoms of mass effect on adjacent brain.1 Recent publications have suggested an optimal radiation dose of 10–25 Gy delivered in multiple fractions.1 Reported side-effects include myelosuppresion due to radiodestruction of functional haematopoietic foci, and radiation-induced tissue oedema.1 Surgical excision remains an alternative to radiotherapy when EMH lies in close proximity to vital structures, but because of its high recurrence rate, radiotherapy is considered superior with over 70% of cases having full neurological recovery.1
Intracranial EMH is a rare condition, but should be considered a differential diagnosis in patients with a history of haemoglobinopathy or bone marrow dysfunction, that present with mass effect and symptoms of raised intracranial pressure. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Lee CM, Salzman KL, Blumenthal DT, Gaffney DK. Intracranial extramedullary haematopoiesis: brief review of response to radiation therapy. Am J Haematol 2005;78:151–52. 2. Musolino A, Guazzi A, Lazzaretti M, et al. Intracranial haematopoiesis in a patient with aids-related central nervous system lymphoma and severe pancytopenia. Haematologica 2007;92:e59–61. 3. Koch BL, Bisset GS, Bisset RR, Zimmer MB. Intracranial extramedullary haematopoiesis: MR findings with pathologic correlation. AJR 1994;162:1419–20.
