Isolated Extracranial-Intracranial myeloid sarcoma, monoblastic variant
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 (6). Though any organ may be involved, intracranial MS is very rare and isolated intracranial MS is even rarer (1, 3-5, 8, 9). Interestingly, only one case beside ours showed extracranial-intracranial mass formation crossing the dura and calvarium (8).
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, i.e. 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, IHC 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-classifications showed no practical relevance in a recently published study (2).
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 (7). Radiologically, based on MRI findings, the differential diagnosis of MS should include extranodal lymphoma and 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 processes.
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 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.
Contributed by Kyung Jin Seo, MD, PhD, Tae-Gyu Lee, MD, PhD, Young Joo Kim, MD, PhD, Hyunjong Kim, MD, PhD, Hye Sung Won, MD, Ok Ran Shin, MD. PhD