Spinal cord compression secondary to spinal extradural myeloid sarcoma in acute myeloid leukaemia: A case report and literature review

Objective To explore the clinicopathological features, imaging features and treatment of spinal cord myeloma in patients with spinal cord compression as the first symptom. Methods The retrospective cross-sectional study was conducted which the clinical data of five patients with spinal myeloid sarcoma confirmed by bone marrow aspiration and pathology from January 2014 to December 2017 in Changzheng Hospital. There were 3 males and 2 females, aged from 15 to 54 years old. the tumors were located in 3 cases of thoracic vertebrae and 2 cases of lumbar vertebrae. Four cases were treated with open surgery. After discharge, they were treated with chemotherapy and hematological tumors according to bone marrow puncture and pathological results. Another patient underwent conservative treatment (anti-inflammatory analgesia, nutritional support, chemotherapy, etc.). The observation items were analysed. Results All the 5 patients had a low back pain, three of them had a lower limbs weakness, and one of them was accompanied by paralysis of both lower limbs. X-ray examination showed no abnormal findings. CT and MRI showed bone destruction or soft tissue shadow. Bone marrow aspiration and postoperative pathological examination showed that five cases were leukemia including four acute myeloid leukemia(AML)and one chronic myeloid leukemia(CML). All patients' preoperative symptoms were relieved after treatment. All patients were followed up. One patient underwent IA regimen chemotherapy for five courses, and was treated with allogeneic hematopoietic stem cell transplantation. It had been followed up for 28 months after surgery and still in good condition without tumor recurrence. The other four patients relapsed after chemotherapy, all died of infection, and the survival period was from 5 to 26.5 months. Conclusions Spinal cord compression caused by myeloid sarcoma as an initial symptom is rare. The imaging manifestations of the myeloid sarcoma are lack of specificity and and it is easy to be misdiagnosed. Bone marrow aspiration and pathological examination can confirm the diagnosis. When the symptoms of spinal cord compression occur, it is recommended to perform early tumor decompression. The allogeneic hematopoietic stem cell transplantation and systemic chemotherapy should be performed after surgery. Key words: Sarcoma, myeloid; Leukemia; Spinal compression; Diagnosis; Treatment outcome

Multiple myeloma presenting with acute bony spinal cord compression and mechanical instability successfully managed nonoperatively

Spinal Cord Compression in Patients with Acute Myeloid and Lymphoid Leukemia

Acute myeloid leukemia (AML) is the most common malignancy in the acute leukemia category. AML is a very aggressive cancer with high mortality. The most common presentations include pancytopenia, bleeding, and recurrent infections. Unlike lymphoma, it rarely presents as a mass. Myeloid sarcoma is a peripheral collection of myeloid cells. Myeloid sarcoma most commonly involves the skin and gingival tissue and rarely it affects the central nervous system. Myeloid sarcoma involving the central nervous system is associated with high mortality. We present a patient with AML which evolved from myelofibrosis presented with acute spinal cord compression and found to have myeloid sarcoma involving the thoracic spinal cord. Despite acute radiation therapy, the patient could not recover her neurological function and passed away shortly after the diagnosis. We discuss the importance of early recognition of the complication due to myeloid sarcoma and treatment with neurosurgical intervention just like other mass causing acute cord compression.

Background: Myeloid sarcoma (MS) is a distinct form of acute myeloid leukemia (AML) found in ~10% of patients, in which mass-forming myeloid blasts proliferate in extramedullary sites. MS may present as an isolated lesion as the primary manifestation of disease, co-occur with AML, or, more commonly, arise in the setting of AML relapse. It is associated with poor outcomes, and treatment options are sparse. While increased knowledge of AML and its biology have improved the care and survival of AML patients, those with MS continue to have limited successful treatment options, as MS has typically not been included in AML genetic and genomic profiling efforts, and patients are excluded from clinical trials. Leukemia cutis (LC) is a form of extramedullary AML characterized by cutaneous involvement, often with an infiltrative and non-mass forming pattern of growth. Still, historically the literature has not made a clear distinction between MS and LC. Although recent small pilot studies have suggested differences in AML-associated mutations between medullary AML and MS, knowledge of the complete molecular and cellular composition of MS and comprehensive comparison with AML is lacking. While molecular characterization of the extramedullary disease site is encouraged in the updated clinical recommendations, no definitive guidance exists for changes in the management and care of AML patients with MS, given the substantial gap in our current knowledge and understanding of extramedullary AML. Methods: Here, we performed RNA-Seq (n=96), single-cell (sc) RNA-Seq (n=33), and mutation profiling using either whole exome sequencing (WES, n=6) or a 409-gene targeted sequencing panel (n=48) of MS or LC patient samples and bone marrow (BM) aspirates from AML patients with and without extramedullary disease to present the first comprehensive characterization of MS and LC. Results: Our WES data showed thatMS and LC evolve independently in the extramedullary site from concurrent medullary disease with distinct dominant clones, characterized by higher median tumor mutation burden (1.66 vs. 064 mutations per megabase, respectively; p=0.0059) and increased copy number aberrations, which both validated in an MS Tet2 HR mouse model. Notably, we observed location-specific molecular evolution in patients with multiple concurrent MS sites (Figure 1A) and patients with recurring MS in WES and targeted panel data. While targetable mutations (i.e., IDH1/2 mutations and FLT3-ITD/TKD) occur, the inter-site variability of molecular aberrations may explain the short-lived responses of AML patients with MS to IDH/FLT3 inhibitors. Transcriptional profile differences between MS and associated medullary disease included up-regulation of extracellular matrix organization and cell-substrate adhesion and down-regulation of inflammatory response pathways in both bulk and scRNA-seq data (Figure 1B). Further, involved BM malignant cells of MS patients compared to patients without MS up-regulated specific pathways, including interferon-gamma response observed in both bulk and scRNA-seq, as well as chromatin organization and splicing. We further revealed that MS patients without overt BM involvement show remodeling of the BM immune microenvironment, with increased fractions of hematopoietic stem and progenitor cells that down-regulate HLA class II genes. Comparing LC and MS in the skin revealed distinct differences in their expression profiles, including high expression of genes involved in cell migration and immune response in LC, suggesting LC and MS represent distinct disease entities. Lastly, we demonstrated high expression of BCL2 in extramedullary disease (p=0.0074) and presented initial evidence that treatment with BH3-mimetics may be beneficial for the treatment of isolated MS. Conclusions: Myeloid sarcoma shows distinct molecular evolution and microenvironmental composition compared to medullary disease, including location-specific evolution necessitating personalized management consideration. Leukemia cutis is distinct from MS tumorous lesions and should be considered a separate entity. High BCL2 expression in extramedullary disease might represent a promising targetable vulnerability in patients with isolated MS.

Exploiting RAS pathway addiction as a therapeutic vulnerability in myeloid sarcoma

Myeloid sarcomas (MS) preceding acute myeloid leukemia (AML) are rare, which presenting as acute spinal cord compression is even rare. Here we report two new cases of myeloid sarcoma patients, whose outcomes were different. Twenty-seven patients with spinal MS preceding AML have been reported to date, including the two cases presented in this article. Surgical decompression was performed in 25 of the 27 patients, and 23 of these received additional anti-AML therapy. Considering our patients and the published cases in the literature we suggest that immunohistochemical study plays an essential role in arriving at a correct diagnosis of MS, and that emergency surgery to resect spinal MS is an available treatment to make neural function recovery, and that the disease must be treated with intensive chemotherapy similar to that used to treat AML as soon as possible after resection or irradiation of the tumor.

Introduction/BackgroundBreast extramedullary myeloid or granulocytic sarcoma (GS) is a rare tumor. It is considered as a form of acute myeloid leukemia (AML). The clinical and radiographic features of the breast...

A 75-Year-Old Woman With Thoracic Spinal Cord Compression and Chloroma (granulocytic sarcoma)

Receptor tyrosine kinase mutations in myeloid neoplasms.

Myeloid sarcoma (MS) is an extramedullary tumor of immature myeloid cells. We analyzed 131 patients with MS, including: (1) de novo MS; (2) MS with concomitant acute myeloid leukemia (AML); (3) MS following myelodysplastic syndrome, myeloproliferative neoplasm, or chronic myelogenous leukemia; and (4) MS as a recurrence of AML. The most common development site was the lymph node. Testicular lesions were statistically more frequent in MS as a recurrence of AML than in other types of MS (P=0.0183). MS tended to lack myeloid markers (myeloperoxidase was present in 63.2%, CD68 in 51.3%, CD13 in 48.7%, and CD33 in 48.7% of patients) and express T-cell markers such as CD3 (20.7%) and CD5 (34.2%). All T-cell marker-positive MS cases were negative for the αβ and γδ T-cell receptors on immunohistochemistry. Underlying myelodysplastic syndrome or myeloproliferative neoplasm was a poor prognostic factor (vs. de novo MS: P=0.0383; vs. MS with concomitant AML: P=0.0143). However, there was no statistical difference in prognosis between de novo MS and MS with concomitant AML (P=0.288). There were no significant differences in prognosis between the prognoses of T-cell marker-positive and T-cell marker-negative MS cases. In addition, CXCR4 expression was a poor prognostic factor in MS (P=0.0229). This study involves the largest MS cohort to date and expands the clinical and pathologic knowledge of the disease.

Investigation of Epidemiological Factors and Site of Primary Tumor on the Development of AML As Second Primary Cancer after Diagnosis of Myeloid Sarcoma and the Impact of Chemotherapy on Overall Survival

A Comparison of Clinical Characteristics and Treatment Outcome in Myeloid Sarcoma Versus Acute Myeloid Leukemia Patients without Extramedullary Involvement — Case Control Study of the Polish Adult Leukemia Group (PALG)

Granulocytic sarcoma (GS) is a rare solid tumor of myeloid origin, which usually precedes or occurs concurrently with myeloid leukemia, or with other types of myeloproliferative and myelodysplastic disorders. Spinal affections of GS have been described but are uncommon, particularly in association with essential thrombocythemia. We present a case of a 75-year-old woman with a long history of essential thrombocythemia who developed 2 tumors: 1 in the bodies of T3 - 6 vertebras extending epidurally, and the other in the right frontal lobe, adherent to dura, thus, mimicking meningioma. The patient died because of massive pulmonary thrombembolia. Microscopical and immunohistochemical features of spinal and intracranial tumor samples obtained at autopsy were consistent with the diagnosis of GS with focal megakaryocytic differentiation. Clinicians and pathologists should be aware of this rare tumor being so diverse in its clinical presentation, as well as in microscopical and immunohistochemical features. Careful evaluation of morphology, in conjunction with immunohistochemistry for evidence of myeloid differentiation are required to avoid frequent errors in diagnostics of GS. The suggested panel includes chloroacetate esterase, myeloperoxidase, lysozyme, CD117, CD43, CD79a and CD3. Only early correct diagnosis will enable proper treatment which may be successful despite the highly malignant potential of GS.

Granulocytic sarcoma (GS) is a rare extramedullary solid tumor defined as an accumulation of myeloblasts or immature myeloid cells. It can cooccur with or precede the acute myeloid leukemia (AML) as well as following treated AML. The incidence of GS in AML patients is 3–8% but it significantly rises in M2 FAB subtype AML. This variety of AML harbors t(8;21) in up to 20–25% of cases (especially in children and black ones of African origin) and, at a molecular level, it is characterized by the generation of a fusion gene known as RUNX1-RUNX1T1. Approximately 10% of M2 AML patients will develop GS, as a consequence, the t(8;21) and the relative transcript represent the most common cytogenetic and molecular abnormalities in GS. FLT3-ITD mutation was rarely described in AML patients presenting with GS. FLT3 ITD is generally strongly associated with poor prognosis in AML, and is rarely reported in patients with t(8;21). GS presentation is extremely variable depending on organs involved; in general, cranial bones and sinus are very rarely affected sites. We report a rare case of GS occurring as a recurrence of a previously treated t(8;21), FLT3-ITD positive AML, involving mastoid bones and paravertebral tissues.