An extramedullary hematopoietic lesion causing acute lumbar stenosis in the setting of sickle cell anemia: a case report and review of the literature

Introduction

Extramedullary hematopoiesis is the ectopic accumulation of hematologic progenitor cells as a compensatory response to impaired erythropoiesis, typically seen in patients with myeloproliferative deficiencies such as thalassemia, polycythemia, myelofibrosis, leukemia, lymphoma, and prior marrow radiation (1-4). Most commonly seen in the spleen and liver, extramedullary deposits may be found in the kidneys, lymph nodes, adrenal glands, lung pleura, and rarely, the spine (5). Spinal manifestations may be present in 11–15% of cases of extramedullary hematopoiesis (6). Though most cases are asymptomatic and are found incidentally on imaging, the possibility for cord compression and neurologic compromise depending on chronicity, size, and location of the lesion must be considered (7,8). Most documented cases of compressive extramedullary hematopoietic (EMH) lesions in the spine are secondary to thalassemia or hereditary spherocytosis, but reports of such lesions in the setting of sickle cell anemia are exceedingly uncommon. We present a rare case of a patient with sickle cell anemia who was found to have acute lumbar stenosis from extramedullary hematopoiesis and was successfully treated conservatively with radiotherapy, resulting in complete clinical and radiographic resolution within 3 months.

EMH lesions occurring in the lumbar spine producing significant neurologic compression are uncommon, as the thoracic spine is most commonly involved (5,7). This predilection is thought to arise from the comparatively narrow subarachnoid space and spinal canal in the thoracic region, where even a relatively small EMH mass can induce spinal stenosis and subsequent neurological symptoms due to the narrower canal diameter (7,9). It is, therefore, of significant clinical value to highlight this rare presentation as a contribution to the limited literature regarding spinal manifestations of EMH in the lumbar spine, so that this condition may be more readily considered in the diagnostic differential in future cases to expedite intervention and improve neurologic recovery.

The first documented case of spinal extramedullary lesions was described by Gatto et al. in 1954 and several case reports and case series have since been published with varying treatment options (6,10,11). The ideal management scheme for vertebral column manifestations of extramedullary hematopoiesis remains controversial. The low incidence of this rare condition has thus far precluded an adequately powered randomized prospective trial from being conducted, so a summary of the currently available literature is the highest level of evidence available to help clinicians determine the optimal strategy to individualize for their patients. Treatment options generally range from systemic therapy (i.e., transfusions, hydroxyurea), radiotherapy, steroids, or decompressive laminectomy with or without fusion. In this case, we demonstrate that full neurologic and radiographic recovery could be achieved with radiotherapy as a primary, standalone treatment modality. We present this case in accordance with the CARE reporting checklist (available at https://jss.amegroups.com/article/view/10.21037/jss-25-28/rc).

Case presentation

A 52-year-old female with known history of sickle cell anemia presented to our emergency department (ED) with complaints of new low back and right lower extremity pain radiating to her anterolateral thigh with associated thigh numbness after waking up from falling asleep on her couch 4 days prior. She described sharp radiating pain refractory to over-the-counter analgesics and denied history of antecedent fall, trauma, or heavy lifting. She denied changes in urinary or bowel continence, but became unable to ambulate due to the severity of the pain, prompting emergency room (ER) arrival. On exam, she had diminished sensation in the right L3/4 dermatome (lateral thigh to medial knee) and 4/5 strength in the right tibialis anterior. She has had two sickle cell crises in the past, most recently five years ago.

Initial laboratory values were unremarkable and were consistent with her baseline hematologic derangements. Hemoglobin was 9.9 g/dL with low mean corpuscular volume (MCV 64.3 fL), mean corpuscular hemoglobin (MCH 22.0 pg), and elevated red cell distribution width coefficient of variation (RDW-CV 17.1). Platelet count was 147,000 per µL.

Computed tomography (CT) imaging of her spine showed an asymmetric hyperattenuating soft tissue density within the right lateral aspect of the spinal canal at the L2–3 level (Figure 1). Magnetic resonance imaging (MRI) with and without gadolinium showed a non-enhancing soft tissue signal intensity within the right lateral epidural space at L2–3 containing minimal fat signal on the pre-contrast T1-weighted images, causing mild central stenosis with mild to moderate right foraminal stenosis (Figure 2). The lack of contrast enhancement and the relatively well-defined borders made malignancy a less likely diagnosis. Epidural hematoma could not be excluded, but the heterogenous soft tissue signal in conjunction with her history of sickle cell anemia without prior trauma were less consistent. The radiographic findings were therefore suggestive of an epidural EMH lesion.

Figure 1 Asymmetric hyperattenuating soft tissue density within the right lateral aspect of the spinal canal at the level of L2–L3, spanning approximately 24 mm in a craniocaudal dimension.

Figure 2 Pretreatment T2 MRI (top), T1 MRI without gadolinium (middle), T1 MRI with gadolinium (bottom). Sequences show a non-enhancing soft tissue signal intensity within the right lateral epidural space at L2–3 containing minimal fat signal on the pre-contrast T1-weighted images, causing mild central stenosis with mild to moderate proximal right foraminal stenosis. MRI, magnetic resonance imaging.

An initial course of dexamethasone 4 mg IV q8h was administered, and pain was well-controlled on IV morphine 4 mg PRN and gabapentin 300 mg PO bid. After 48 hours, the patient reported subjective improvement in symptoms with intermittent exacerbation with ambulation. A transition from IV dexamethasone to a Medrol dose pack was planned, but steroids were discontinued at the patient’s request.

Due to the initial encouraging response to corticosteroids in conjunction with mild to moderate presenting symptoms, we decided to pursue conservative management. A consultation with Radiation Oncology was obtained to evaluate the potential efficacy of radiation therapy. Though their experience with radiating such lesions was primarily in the setting of acute leukemic circumstances and rarely from hematologic conditions, it was determined that a good response could be expected from radiation therapy in the form of 24 Gy/12 fractions. Radiotherapy began on hospital day 6 with a plan for a total of 12 total doses to be delivered outpatient. While adjunctive systemic therapies such as transfusion or hydroxyurea were also considered, our patient’s labwork did not demonstrate any hematologic aberrancies from her baseline status. As systemic therapies are typically slow acting and less effective for acute neurologic relief, isolated radiotherapy was pursued as the primary standalone treatment to avoid potential unnecessary transfusion related complications such as iron overload, alloimmunization, and infection transmission.

The patient had continued subjective improvement of symptoms over the following two days and was subsequently discharged on hospital day 8 with plans to follow up with her primary hematologist and radiation oncologist. She completed her scheduled course of radiation treatment over an elapsed time of 15 days. At final follow up visit 3 months after initial ER presentation, she had complete resolution of her symptoms with normal sensation and full strength throughout. A post-treatment MRI revealed full radiographic eradication of the compressive hematopoietic lesion (Figure 3).

Figure 3 Post treatment MRI in the sagittal (A) and axial (B) planes reveals full radiographic eradication of the compressive hematopoietic lesion. MRI, magnetic resonance imaging.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Discussion

In the spine, extramedullary hematopoiesis can lead to a range of neurological symptoms due to nerve compression. Its exact origin remains unclear, with theories suggesting direct extrusion of hyperplastic marrow through trabecular bone or reactivation of embryonic hematopoietic cell remnants in response to chronic anemia. Regardless of the mechanism, the hematopoietic tissue in the spinal canal forms a sinusoidal network consisting of erythroid and myeloid precursors, eventually infiltrating fibroadipose tissue and potentially causing mass effect on the spinal cord or nerve roots (12).

Early diagnosis and treatment of EMH lesions causing neurologic compression is crucial, though the consensus on the optimal treatment approach remains uncertain. Haidar et al. conducted a comprehensive literature review of spinal extramedullary hematopoiesis and proposed a treatment algorithm based on the severity of neurologic compromise. Management strategies include isolated or combined use of radiation therapy, systemic treatments (hypertransfusion, fetal hemoglobin-inducing agents such as hydroxyurea), steroids, and/or decompressive laminectomy (12).

According to this treatment algorithm, patients with mild neurological symptoms should receive a short course of blood transfusion +/− hydroxyurea. Since extramedullary hematopoiesis arises as a compensatory response to chronic anemia, transfusions reduce the body’s reliance on such responses, resulting in regression. However, neurological improvement is reported to be slow, and whether transfusions fully reverse compression remains debated (7,13,14). Thus, its role in treating patients with acute onset of neurological symptoms is limited. Additionally, blood transfusion therapy is associated with risks, including iron overload, alloimmunization, and infection transmission (12).

For patients with acute onset and moderate neurological symptoms, low-dose radiation (900–3,500 cGy) has been shown as an effective treatment due to the high radiosensitivity of hematopoietic tissue. Previous studies have reported significant clinical efficacy with neurological improvements as soon as 3–7 days in 50% of patients treated with low-dose radiation alone (15-19). While recurrence is a risk, recurrent masses respond well to additional treatment doses. In a study by Jackson et al., 3 of 16 patients (19%) experienced recurrence within 16 months of initial radiotherapy (15–35 Gy); however, all three patients were successfully treated with subsequent doses (16). In severe cases, adjuvant radiotherapy helps prevent recurrence post-laminectomy (20). Given its noninvasive nature and proven efficacy, radiotherapy is a highly effective modality for managing neurological symptoms associated with extramedullary hematopoiesis.

For patients presenting with severe neurological deterioration, paraparesis, or acute neurological symptoms unresponsive to radiotherapy, laminectomy is indicated. Surgery provides the advantage of immediate decompression and enables definitive histopathological diagnosis (7,21,22). Coşkun et al. describe a case involving a 37-year-old male with thalassemia who presented with progressive low back pain and lower extremity weakness for four months. Thoracic MRI revealed a T4–T7 lobulated soft tissue mass. As his neurological condition deteriorated rapidly to paraplegia with sphincter dysfunction, a laminectomy was performed. The mass was successfully removed; histological analysis confirmed extramedullary hematopoiesis. Postoperatively, the patient demonstrated significant neurological improvement, with full restoration of urinary and bowel function. A six-month follow-up revealed no neurological abnormalities with no residual mass on MRI (23).

However, surgical intervention carries several drawbacks, including risks associated with general anesthesia and potential cardiovascular instability, particularly in patients with chronic anemia. Recurrence is another concern, as illustrated by Bukhari et al. in the case involving an 18-year-old patient with beta-thalassemia major. This patient developed paraplegia four months after a laminectomy for a spinal cord compressing mass (T6–L3). To remove the recurrent mass, a subsequent laminectomy (T4–T10) was performed, followed by two cycles of low-dose radiotherapy to minimize the risk of future recurrence. This combination treatment was successful. At the two-year follow-up, the patient had regained full strength in both lower limbs, walked independently, and showed no residual mass or spinal cord compression on MRI (20). Considering these risks and potential long-term complications, surgery should be reserved for patients with severe neurological symptoms or those unresponsive to less invasive treatments, particularly in this population with impaired hemodynamic stability.

Direct neurologic compression from extramedullary hematopoiesis in sickle cell anemia, as seen in our patient, is exceptionally rare. Our comprehensive review of the existing literature revealed only three cases, each treated with different approaches, demonstrating varying degrees of effectiveness.

In the first case, a 28-year-old man with sickle cell anemia developed progressive weakness over a period of 2 months that advanced to complete paraplegia. By the time of admission, he had been wheelchair-bound for 18 months with diminished sensation below the T7 dermatome. Myelography identified an extradural mass compressing the spinal cord from T3 to T5. Due to the severity of his neurological symptoms, a laminectomy was performed, successfully excising a mass of erythroid elements and megakaryocytes, as confirmed by pathology. Postoperative management of physical therapy and rehabilitation over an eight-month period, led to significant neurological recovery, with the patient ultimately regaining the ability to ambulate independently (24).

The second case involved a 34-year-old man with sickle cell anemia, who presented with severe back pain. Advanced imaging revealed two extradural lesions within the lower thoracic spinal canal, displacing the cord posteriorly. Due to the absence of severe symptoms that would necessitate immediate decompression and the ventral location of the mass, radiation therapy was selected as the treatment modality. The patient received a total dose of 24 Gy administered in eight sessions. This approach led to immediate alleviation of back pain and notable improvement in symptoms (25). Radiation therapy proved effective for symptomatic management in this case.

The third case describes a 43-year-old man with sickle cell anemia who developed acute flaccid paralysis due to epidural extramedullary hematopoiesis. He was admitted overnight with lower thoracic and abdominal pain, initially ambulatory, with no neurological deficits. By morning, he experienced rapid-onset of right leg paralysis, which progressed to complete lower extremity flaccid paralysis. Myelography revealed a complete blockage of contrast at the lower T9 border. Emergency decompressive laminectomy revealed a thickened epidural membrane with recent hemorrhage and infiltrating hematopoietic tissue. Postoperatively, the patient received local radiotherapy and underwent exchange transfusion to reduce hemoglobin S levels. Despite these interventions, the patient’s condition remained unchanged, with persistent flaccid paralysis and atonic bladder (26). This case highlights the necessity of early diagnosis and prompt treatment to prevent severe and irreversible spinal cord injury.

In our case, a 52-year-old female with sickle cell anemia presented with acute lumbar stenosis from extramedullary hematopoiesis, and conservative management via low-dose radiation therapy was initiated. Given her moderate neurological symptoms, radiotherapy offered a non-invasive treatment option while minimizing the risks associated with surgery, such as complications from anesthesia and hematological stress. Radiotherapy at a total dose of 2,400 cGy administered in 200 cGy increments over a period of 15 days proved highly effective for our patient, with complete resolution of symptoms at the final follow-up 3 months later. An MRI conducted 17 days after the final radiation session revealed complete resolution of the soft tissue signal in the right lateral epidural space at the L2–L3 level, confirming successful eradication of the EMH mass.

When weighing the various treatment options for symptomatic spinal extramedullary hematopoiesis, perhaps the most important factor to consider is the clinical severity of presenting symptoms. A case with mild neurologic symptoms and a slow, indolent onset may best be treated with corticosteroids and transfusion therapy alone, particularly if their hematologic lab values indicate an acute or acute-on-chronic state of anemia. Radiotherapy may be indicated if symptoms persist despite systemic therapy or in cases with an acute onset with mild to moderate focal symptoms (27). Radiotherapy does carry potential risks including fibrosis, wound healing complications, local tissue damage, secondary malignancy, and recurrence, so its implementation should be judicious, but it does provide an effective noninvasive and fast-acting option as was demonstrated in our patient. Location of pathology should also be carefully considered, as ventral lesions in cervical or thoracic levels may be more amenable to radiotherapy than direct surgical decompression. In those patients refractory to radiotherapy or with severe neurologic deficits at presentation, decompressive laminectomy may be indicated with or without adjuvant radiotherapy. An added benefit of surgical decompression is the ability to obtain histological diagnosis, but the risk of hemodynamic compromise may be higher in this population of patients.

Conclusions

Extramedullary hematopoiesis in the setting of Sickle Cell Anemia causing symptomatic stenosis is an exceedingly rare occurrence, especially in the lumbar spine, but rapid diagnosis and appropriate intervention can result in excellent outcomes. We present the case of a 52-year-old female with sickle cell disease who presented with an L2–3 epidural lesion caused by EMH and experienced complete clinical and radiographic resolution within 3 months of beginning radiation therapy alone. Further literature regarding this rare pathology is needed, but radiotherapy is a safe and effective treatment modality in cases of mild to moderate stenosis.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-25-28/rc

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-28/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-25-28/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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