30‐Year‐Old Man with Head Trauma Three Months Ago

Clinical History and Radiology

A 30‐year‐old man presented with progressive visual field defect, headache and nausea. He had a history of occipital area blunt head injury (hit by an iron pipe at work) three months before referral to our clinic. The initial diagnosis at the local clinic was brain contusion and concussion. On the initial X‐ray, no skull fracture was detected. However, owing to a progressive visual field defect and dizziness, epidural hemorrhage was suspected. A burr‐hole trephination for drainage was subsequently performed. Unexpectedly, the operating neurosurgeon found a tumor mass instead of hematoma. Although the biopsy sample was obtained, only H&E slides were made without ancillary immunohistochemical stains (IHC). He was then transferred to our hospital for furhter evaluation and more tissue was obtained. The patient had no past history of malignancy. All laboratory findings were within normal ranges, except AST 67 U/L (Normal range: 14–40), ALT 164 U/L (Normal range: 8–46) and serum lactated dehydrogenase (LDH) 532 U/L (Normal range: 218–472). Serologic tests for hepatitis, syphilis and HIV infection were negative. Magnetic resonance imaging (MRI) revealed an epidural mass, approximately 7.0 cm × 6.8 cm × 4.1 cm, with extracranial extension forming a coffee bean shaped mass crossing the parieto‐occipital lobe dura (Figure 1a–c). The epidural mass was hyperintense to isointense to gray matter on T2 weighted images (WI) (Fig. 1a), isointense on T1WI (Fig. 1b). Following contrast infusion, the epidural mass showed marked heterogeneous enhancement but the extracranial mass did not (Figure 1c). In view of the radiologic findings, a clinical diagnosis of meningioma was considered and the patient underwent a brain biopsy to confirm the nature of the brain lesion.

Figure 1.

 

Pathology

On microscopic examination, both masses showed highly cellular tumors with the same morphologic features and focal necrosis (Figure 1d). At high power, the tumor cells were monotonous with large oval or pleomorphic nuclei, minute but distinct nucleoli and scant eosinophilic cytoplasm (Figure 1e). The calvarium was diffusely infiltrated by tumor cells (Figure 1f). IHC revealed the majority of tumor cells were strong positive for CD117 (Figure 1g), lysozyme (Lys) (Figure 1h), CD99 (Figure 1i) and were negative for LCA, CD20, CD3, CD34, CD56 and myeloperoxidase (MPO). A few tumor cells were positive for CD68/KP1 (Figure 1j). Bone marrow biopsy revealed no abnormalities. Abdominal computed tomography (CT) and torso positron emission tomography (PET) showed no tumor involvement in other organs. What is your diagnosis?

Diagnosis

Isolated Extracranial–Intracranial myeloid sarcoma, monoblastic variant.

Discussion

Myeloid sarcoma (MS), previously known as granulocytic sarcoma or chloroma, may develop de novo (isolated) or concurrently with acute myeloid leukemia or other myeloid neoplastic conditions 2. Though any organ may be involved, intracranial MS is very rare and isolated intracranial MS is even rarer 4. Interestingly, only one case beside ours showed extracranial–intracranial mass formation crossing the dura and calvarium 4.

In this case, the patient's history of occipital area blunt trauma was misleading and led to the initial diagnosis of epidural hemorrhage secondary to head trauma.

From the pathologist's point of view, diagnosing MS solely based on morphology may be quite challenging. Many cases have been misdiagnosed as lymphoma or other non‐hematological malignancies. Therefore, ancillary tests including immunophenotyping, either IHC or flow cytometry (FC), are mandatory to establish the diagnosis of MS, in a suspected case. In practice, FC is often unavailable in an unexpected case, ie de novo form without previous history of hematologic malignancy. Our case was also de novo and the fresh tissue for FC was not obtained.

To establish the diagnosis of MS, immunohistochemical panels are used. CD68/KP1 is the most commonly expressed marker followed (in decreasing order) by MPO, CD117, CD99, CD68/PG‐M1, Lys, CD34, terminal deoxynucleotidyl transferase (TdT), CD56, von Willebrand factor, CD30, glycophorin, and CD4.

Pathologically, MS can be classified based on morphology and immunophenotyping as five variants (v.): 1) granulocytic v. [MPO+, CD68+/−, Lys+, CD34+/‐], 2) monoblastic v. [MPO−, CD68+, Lys+, CD34−], 3) myelomonoblastic v. [MPO+/−, CD68+, Lys+/−, CD34+/−], 4) megakaryoblastic v. [Factor VIII+, CD31+, CD61+] and 5) erythroid v. [glycophorin +, blood group antigens]. In 2001, The World Health Organization (WHO) classified MS into three categories based on the maturation of the tumor cells: blastic (myeloblasts), immature (myeloblasts and promyelocytes) and differentiated (promyelocytes and more mature myeloid cells). Among these variants, the blastic type is the most common, followed by monoblastic and myelomonocytic. However, these sub‐classification showed no practical relevance in a recently published study 1.

Our case showed an MPO−/CD68 focal +/lysozyme+/CD34− immunophenotype, consistent with the monoblastic variant. MPO expression is diagnostic of myeloid origin. However, it can be negative in the monoblastic variant, as in our case.

In a review article on MRI findings of MS, Shinagare et al pointed out that MS should be included in the differential diagnosis of new mildly T2‐hyperintense, homogeneously enhancing soft‐tissue masses 3. Radiologically, based on the MRI findings, the differential diagnosis of MS should include extranodal lymphoma or extraosseous myeloma, both of which typically have low to intermediate signal intensity on T1WI and mildly high signal intensity on T2WI. Other differential diagnoses should also be considered, including meningioma, carcinoma, sarcoma, infection, metastasis, hematoma and inflammatory process.

Following the pathologic diagnosis of the brain lesion, a bone marrow biopsy revealed no abnormality in our case. Abdominal CT and torso PET showed no tumor involvement in other organs. For treatment, induction chemotherapy with cytarabine and daunorubicin was started.

Central nervous system MS is a rare entity and de novo intracranial‐extracranial MS is even rarer. Diagnosis of this entity is quite challenging not only for primary physicians, radiologists, and even pathologists. Awareness of this entity and application of adequate ancillary tests including IHC panels (CD68/KP1, MPO, CD117, CD99, CD68/PG‐M1, lysozyme, CD34, etc) can help to establish the diagnosis.