37‐YEAR‐OLD WOMAN WITH MULTIPLE INTRACRANIAL MASSES

CASE HISTORY

A 37‐year‐old woman presented with worsening visual problems for 8 months. On clinical examination, she had blurred vision but no focal neurological signs. Laboratory analysis showed the following: red blood cell (RBC) count, 2.59 × 1012/L; hemoglobin, 88.0 g/L; mean corpuscular volume, 106.3 fl; mean corpuscular hemoglobin (MCH), 35.0 pg; MCH concentration, 330.0 g/L; RBC distribution width, 29.0%; white blood cell count, 15.9 × 109/L; 55% orthochromatic erythroblasts; platelet count, 92.0 × 109/L

Cranial magnetic resonance imaging (MRI) showed multiple intracranial tumor‐like masses in bilateral frontotemporal area and the top of falx cerebri. The masses were of intermediate signal intensity on Tl‐weighted and low‐signal intensity on T2‐weighted images, and showed homogeneous enhancement after intravenous injection of gadolinium, but no perilesional edema. A meningeal tail sign could be found (Figure 3). In addition, the clivus showed uniformly low‐signal intensity on T1‐ and T2‐weighted images with inhomogeneous enhancement (Figure 1). Differential diagnosis was wide and included lymphoma, myeloma, leukemia, neuroblastoma, a metastatic disease, epidural hematoma, abscess, granulomatous diseases like tuberculosis and sarcoidosis, and pachymeningeal thickening related to rheumatoid disease. After a transfusion of blood and platelets, the patient underwent craniotomy for biopsy of the left lesion. The patient subsequently received whole‐brain irradiation (3 Gy) in eight fractions, which resulted in marked symptomatic improvement.

Figure 3.

Figure 1.

During operation, the tumor resection yielded dark red and tan tissue, measuring in aggregate approximately 3.0 × 2.5 × 1.0 cm. After removing the mass from the arachnoid and dura, no abnormalities of the brain were noted. Tissue submitted for frozen section showed diffuse foci of atypical cells and multinucleated megakaryocytes were found in inflammatory tissue. Microscopic examination showed a polymorphic cellular population (3, 2) with scattered multinucleated cells (4, 5). Immunohistochemical stains were positive for glycophorin A (Figure 6A), myeloperoxidase (Figure 6B,C) and CD61 (Figure 6D), respectively. A stain for leukocyte common antigen also revealed a few lymphocytes. These polymorphic cells were immunonegative for glial fibrillary acidic protein, pancytokeratin, vimentin and smooth muscle antibody. What is the diagnosis?

Figure 2.

Figure 4.

Figure 5.

Figure 6.

DIAGNOSIS

Multiple intracranial meningeal extramedullary hematopoiesis (EMH).

DISCUSSION

EMH occurs as a compensatory mechanism in a variety of disorders. Lymphoma and leukemia can also result in EMH. Intracranial EMH is rare. The pathway of EMH involvement of the dura is unknown, but it is postulated that the dura has hematopoietic capacity in the fetus, and EMH may originate from primitive rests. Various hypotheses exist to explain the development of hemopoietic tissue to supplement marrow production. Lyall (8) proposed the possibility of direct extension from marrow into epidural space. Knoblich (4) proposed that multipotential cells in the epidural space can be transformed into marrow under some circumstances.

EMH is typically asymptomatic but can cause neurological symptoms when the mass compresses adjacent tissue such as nerve roots in the spine or the optic nerve (5). Intracranial EMH patients can present with headaches, seizures, hemiplegia, altered consciousness and cranial nerve compression symptoms, although asymptomatic patients have been reported (10).

Diagnosis of EMH is based on the clinical circumstances, laboratory data and the use of different diagnostic imaging modalities. MRI is the examination of choice in patients suspected of having meningeal involvement, or cord or nerve compression. Multiplanar enhanced views are helpful in defining the extent. These masses are usually lobular, well‐circumscribed masses of intermediate signal intensity on T1‐weighted images and low‐signal intensity on T2‐weighted images. These masses may show significant enhancement after gadolinium administration. In this case, meningeal tail sign was displayed on T1‐weighted image after gadolinium administration. Meningeal tail sign is not the only indication of meningeoma, and can be shown in some diseases encroaching on meninges such as lymphoma, metastatic carcinoma and chronic inflammation. This is the reason why our case was misdiagnosed after MRI scan on admission.

Confirmation of EMH can be made by tissue biopsy. Grossly, EMH usually forms a soft, red mass resembling a hematoma on its cut surface (3). Histologically, all hematopoietic elements found consist of myeloid cells, erythroid cells at various stages of maturation, and megakaryocytes (7). In our case, hematoxylin and eosin stain showed collections of large immature cells resembling immature reticuloendothelial cells or hemocytoblasts just like immature granulocytes and mononuclear cells. And the clustered nucleated erythroblasts presented smaller rounded or oval cells with hyperchromatic nuclei, frequently admixed with mature RBCs. So the lesions consisted of hyperplasia of trilineage hemopoietic stem cells, including myeloid cells (granulocytes and mononuclear cells), mature and immature erythroid cells, and megakaryocytes. On immunohistological staining, intense expression of CD61 was observed in megakaryoblasts and megakaryocytes. The erythroid cells expressed the glycophorin A. The myeloid elements were positive for myeloperoxidase.

Management of EMH masses includes hypertransfusion, cytotoxic drugs, radiotherapy or combinations of these modalities. Hematopoietic tissue is highly sensitive to low‐dose radiation (6). Treatment of EMH is usually unnecessary except when complications occur (2). As hematopoietic tissue is highly sensitive to irradiation, radiotherapy is the treatment of choice for patients with nerve compression. Neurological improvement has been achieved in 3–7 days after initiation of treatment (9). Occasionally, the patient may need surgical intervention (1). Surgery confers the immediate relief of nerve compression and provides tissue for histological diagnosis. It has the disadvantages of incomplete excision, operating on anemic individuals who are poor surgical candidates, and it has the potential risk of profuse bleeding from the surgical site (9). Therefore, surgery is only indicated where immediate relief of spinal cord or nerve root compression is required to prevent permanent neurological damage. Blood transfusion and iron chelation with desferrioxamine is the ideal treatment for asymptomatic individuals. It relieves anemia and suppresses EMH, and is most effective when used as an adjunct to surgery or radiotherapy (9).

ABSTRACT

Extramedullary hematopoiesis (EMH), defined as the presence of hematopoiesis outside bone marrow and peripheral blood, occurs as a compensatory phenomenon in several hematologic disorders and bone marrow dysfunction. EMH predominantly affects reticuloendothelial system including the spleen, liver and lymph nodes. Here, we report a rare case of multiple intracranial meningeal EMH. A 37‐year‐old woman was anemic with gradually worsening vision for 8 months. Multiple extra‐axial masses were found on imaging and the patient underwent the biopsy for the left frontotemporal lesion. Final diagnosis was multiple intracranial meningeal EMH. Treatment of fractionated external beam radiotherapy resulted in marked symptomatic improvement. This case indicates that although the diagnosis of meningeal EMH is difficult, there is a need to consider EMH in the differential diagnosis of anemic patients with tumor‐like mass lesions in extramedullary sites.