Intracranial Extramedullary Hematopoiesis in a Recently Recovered Monkeypox Patient: A Case Report

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Case Report

Intracranial Extramedullary Hematopoiesis in a Recently Recovered Monkeypox Patient: A Case Report

https://doi.org/10.21203/rs.3.rs-4889260/v1

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Extramedullary hematopoiesis (EMH) is a compensatory response wherein blood cell production occurs outside the bone marrow, typically as a result of hematologic disorders that impair bone marrow function. Conditions such as myelofibrosis, thalassemia, and sickle cell disease often lead to EMH in organs like the liver and spleen, which serve as alternative sites for hematopoiesis. This case report highlights the importance of considering EMH in the differential diagnosis of intracranial lesions, exemplified by a 67-year-old woman who presented with headaches and generalized malaise. Her medical history included hypertension and mild anemia. Magnetic resonance imaging (MRI) revealed a cystic mass in the right inferomedial parietal lobe, which showed medial mural enhancement, edema, and mass effect, with an additional enhancing focus in the left parietal lobe. Initially suspected to be a hemangioblastoma, the resected mass was found to be a benign vascular lesion with endothelial hyperplasia, but without the characteristics of cavernous hemangioma or vascular malformation. The histopathological examination revealed foci of erythroid and myeloid precursors, and megakaryocytes, with immunohistochemical staining confirming the diagnosis of EMH. Subsequent investigations revealed no underlying hematological disorders, leading to a diagnosis of idiopathic intracranial EMH. The patient underwent intensity-modulated radiation therapy (IMRT) for the remaining lesion and showed significant improvement in symptoms at three months follow-up. This case underscores the diagnostic challenges associated with intracranial lesions and highlights the necessity of considering EMH, particularly when faced with atypical imaging and histopathological features. Future research is needed to optimize therapeutic strategies and assess long-term outcomes for intracranial EMH.

Neurobiology of Disease

Extramedullary hematopoiesis

CD31

Extramedullary hematopoiesis (EMH) represents an important physiological response to hematopoietic challenges, wherein blood cell production extends beyond the confines of the bone marrow [1]. While bone marrow is the primary site for hematopoiesis in adults, certain pathological conditions can trigger the emergence of blood cell production in extramedullary tissues [1]. This phenomenon plays a crucial compensatory role in sustaining hematopoiesis when the bone marrow's normal functioning is compromised [1]. Extramedullary hematopoiesis is often a consequence of hematologic disorders characterized by bone marrow dysfunction [2]. Conditions such as myelofibrosis, thalassemia, and sickle cell disease can lead to fibrosis or infiltration of the bone marrow, prompting the body to seek alternative sites for blood cell production [2]. The liver and spleen are primary sites where extramedullary hematopoiesis manifests, serving as reservoirs for erythropoiesis and myelopoiesis [2]. Understanding the predilection for specific organs in EMH provides valuable insights into the clinical presentation and potential complications associated with this phenomenon [3].

To highlight the importance of considering extramedullary hematopoiesis (EMH) as a potential differential diagnosis for brain lesions, we present the case of a 67-year-old woman with a history of headaches and generalized malaise. She had a medical history significant for hypertension and mild anemia. During the investigation of her headaches, magnetic resonance imaging (MRI) of the brain revealed a cystic mass measuring 3.7 cm in the right inferomedial parietal lobe. The mass exhibited medial mural enhancement, associated with edema and a noticeable mass effect. Additionally, a 3mm enhancing focus was observed in the left parietal lobe. Initially suspected as a hemangioblastoma, the resection of the larger mass disclosed a benign vascular lesion with endothelial hyperplasia, lacking the characteristic features of cavernous hemangioma or vascular malformation. Notably, the specimen exhibited foci of erythroid and myeloid precursors, along with megakaryocytes. Immunohistochemical stains were utilized to rule out alternative diagnoses, with negativity for GFAP, CK AE1/AE3, and inhibin, effectively excluding glial neoplasms, metastatic carcinoma, and hemangioblastoma, respectively. Importantly, hematopoietic cells tested positive for CD45, immature red cells for E-cadherin, and endothelial cells for CD31, consistent with a diagnosis of EMH (Figure).

Subsequent investigations revealed no underlying hematological disorders, leading to the diagnosis of idiopathic intracranial EMH. The patient underwent intensity-modulated radiation therapy (IMRT) for the remaining left parietal lesion. Three months into regular follow-up, a significant improvement in her headache and malaise was noted. This case highlights the diagnostic challenges associated with intracranial lesions and underscores the necessity of considering EMH in the differential diagnosis, particularly when atypical features are present.

Intracranial EMH is a rare condition in which hematopoietic tissue proliferates outside of the bone marrow, often within the central nervous system. This can occur in response to conditions such as myelofibrosis, thalassemia, or other chronic anemias, leading to the development of masses or nodules within the brain or spinal cord. These masses can manifest as symptomatic space-occupying lesions, causing symptoms such as headaches, visual disturbances, or neurological deficits. The diagnosis of intracranial extramedullary hematopoiesis is typically made through imaging studies such as MRI or CT scans, followed by tissue biopsy to confirm the presence of hematopoietic tissue [5].

The rarity of idiopathic intracranial EMH necessitated a comprehensive workup to exclude underlying hematological disorders. While our case did not reveal any such associations, it is crucial to recognize the potential systemic implications of EMH and consider appropriate investigations, as reported by Tefferi et al. [2]. Additionally, the utilization of intensity-modulated radiation therapy (IMRT) for the residual lesion in our patient aligns with the approach reported by Stein et al. in managing intracranial EMH lesions [1]. A study by Nicholas N. et al. [6] described a case of intracranial EMH in a patient with thalassemia major who presented with symptoms of increased intracranial pressure and visual disturbances. Similarly, a case report by Manara R. et al [7] reported a rare case of an asymptomatic thalassemic patient who was incidentally found to have intracranial EMH on imaging studies. These reports highlight the importance of considering intracranial EMH in the differential diagnosis of neurological symptoms in patients with underlying hemolytic disorders. In considering the broader context of hematopoietic disorders and intracranial manifestations, the work of Cervantes et al. emphasizes the need for a thorough hematological evaluation, especially in cases of extramedullary hematopoiesis where systemic implications may exist [3]. Furthermore, the study by Barbui et al. discusses the evolving landscape of therapeutic strategies for myeloproliferative neoplasms, shedding light on potential considerations for cases associated with intracranial manifestations [4]. However, in our case. The patient did not have any underlying hematologic disorders or malignancy.

Intracranial EMH is a challenging condition to manage, as these masses can be difficult to access and may pose a risk of bleeding during surgical intervention. Treatment options may include radiation therapy or chemotherapy to reduce the size of the masses and alleviate symptoms, though these approaches may not always be effective. In some cases, surgical resection may be necessary to relieve pressure on the surrounding brain tissue and improve neurological function. Long-term monitoring is also important, as these masses can recur or progress over time. Overall, the management of intracranial extramedullary hematopoiesis requires a multidisciplinary approach involving neurosurgeons, hematologists, and radiation oncologists to optimize patient outcomes [5].

The favorable clinical outcome observed in our patient, with a significant improvement in headaches and malaise after three months of follow-up, suggests that timely identification and targeted intervention for intracranial EMH can lead to positive outcomes. However, the long-term implications and recurrence risks warrant continued surveillance and follow-up, as suggested by Tefferi et al. [2].

In conclusion, this case emphasizes the importance of considering extramedullary hematopoiesis in the differential diagnosis of intracranial lesions, especially when confronted with unusual radiological and histopathological features. Comprehensive evaluation, including immunohistochemical analysis and appropriate imaging, is crucial for accurate diagnosis and subsequent management. Future studies and continued clinical vigilance are warranted to further elucidate the optimal therapeutic approaches and long-term outcomes associated with intracranial EMH.

All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report.

Consent was given by the patient for publication and research purposes

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The authors declare no competing interests.

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Intracranial Extramedullary Hematopoiesis in a Recently Recovered Monkeypox Patient: A Case Report

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