A rare case of isolated myeloid sarcoma of the small gut with inv(16)(p13;q22) without bone marrow involvement

Myeloid sarcoma represents the proliferation of myeloblasts of acute myeloid leukemia (AML) at extramedullary sites. While extramedullary involvement in AML is uncommon in itself, isolated myeloid sarcomas, that is, myeloid sarcomas without any bone marrow involvement, are extremely rare and pose a diagnostic and therapeutic challenge. Here, we present the case of a middle-aged woman with isolated myeloid sarcoma in the stomach—an organ seldom involved by this disease. Additionally, the literature on the epidemiology, diagnosis, pathology, prognosis, and therapeutic options in myeloid sarcomas has been reviewed.

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Clinical characteristics and treatment outcomes of isolated myeloid sarcoma without bone marrow involvement: a single-institution experience

Blood Research ◽

10.5045/br.2017.52.3.184 ◽

2017 ◽

Vol 52 (3) ◽

pp. 184 ◽

Cited By ~ 9

Author(s):

Jung Yeon Lee ◽

Haerim Chung ◽

Hyunsoo Cho ◽

Ji Eun Jang ◽

Yundeok Kim ◽

...

Keyword(s):

Bone Marrow ◽

Treatment Outcomes ◽

Clinical Characteristics ◽

Bone Marrow Involvement ◽

Myeloid Sarcoma ◽

Single Institution

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Differential diagnosis of isolated myeloid sarcoma: a case report and review of the literature

Hematology Reports ◽

10.4081/hr.2015.5709 ◽

2015 ◽

Vol 7 (2) ◽

Cited By ~ 12

Author(s):

Patrick A. Hagen ◽

Charanjeet Singh ◽

Melissa Hart ◽

Anne H. Blaes

Keyword(s):

Bone Marrow ◽

Marrow Transplantation ◽

Bone Marrow Involvement ◽

Lymph Node Biopsy ◽

Myeloid Sarcoma ◽

Unrelated Donor ◽

Peripheral Cell ◽

Bone Marrow Biopsies ◽

Cell Counts ◽

Extramedullary Tumor

Myeloid sarcoma (MS) is a rare disease entity identified as a variety of manifestations defined by the occurrence of extramedullary myeloid cell masses with or without bone marrow involvement. This case describes an unusual presentation of isolated MS in a 60-year-old otherwise healthy male, who initially presented to his primary care physician with vague abdominal pain. After extensive workup including three omental biopsies, umbilical core biopsy, and inguinal lymph node biopsy, he was ultimately diagnosed with isolated MS with extensive extramedullary tumor burden. Despite advanced extramedullary disease, peripheral cell counts were normal and bilateral bone marrow biopsies unremarkable with normal cellular lineages, morphology, and cytogenetics. The patient underwent induction chemotherapy and is now greater than 100 days post myeloablative unrelated donor marrow transplantation with no evidence of disease recurrence and 100% donor status with full chimerism. This case demonstrates that making a prompt diagnosis with rapid initiation of treatment in myeloid sarcoma can be challenging due to its varied clinical presentation, cytomorphology, cytochemistry, and cytogenetic overlap with other lymphoid malignancies. Once a diagnosis of MS has been made, moving quickly to induction therapy is important. Several studies have shown that improved overall survival is attained when MS is treated as acute myeloid leukemia and increased survival is noted for patients undergoing bone marrow transplantation. Further prospective studies are needed to elucidate the many remaining questions in regards to the natural history, prognosis, and optimal treatment strategies for this deadly disease.

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A rare case of a pericardial mass: Myelosarcoma from relapsed acute monoblastic leukaemia without bone marrow involvement

Australasian Journal of Ultrasound in Medicine ◽

10.1002/ajum.12073 ◽

2017 ◽

Vol 20 (4) ◽

pp. 178-180

Author(s):

Simon Binny ◽

Stephen Tomlinson ◽

Christopher Hammett ◽

Arun Dahiya ◽

Elango Pillai ◽

...

Keyword(s):

Bone Marrow ◽

Rare Case ◽

Bone Marrow Involvement ◽

Pericardial Mass

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Immunotherapy- (Blinatumomab-) Related Lineage Switch of KMT2A/AFF1 Rearranged B-Lymphoblastic Leukemia into Acute Myeloid Leukemia/Myeloid Sarcoma and Subsequently into B/Myeloid Mixed Phenotype Acute Leukemia

Case Reports in Hematology ◽

10.1155/2019/7394619 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Rui R. He ◽

Zacharia Nayer ◽

Matthew Hogan ◽

Raymund S. Cuevo ◽

Kimberly Woodward ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Bone Marrow Involvement ◽

Bone Marrow Examination ◽

Myeloid Sarcoma ◽

Poor Prognostic Factor ◽

Lineage Switch ◽

Acute Myeloid

The presence of KMT2A/AFF1 rearrangement in B-lymphoblastic leukemia (B-ALL) is an independent poor prognostic factor and has been associated with higher rate of treatment failure and higher risk of linage switch under therapy. Blinatumomab has shown promising therapeutic results in refractory or relapsed B-ALL; however, it has potential risk of inducing lineage switch, especially in KMT2A/AFF1 rearranged B-ALL into acute myeloid leukemia and/or myeloid sarcoma. We report a 40-year-old female with KMT2A/AFF1-rearranged B-ALL that was refractory to conventional chemotherapy. Following administration of blinatumomab, she developed a breast mass proven to be myeloid sarcoma, in addition to bone marrow involvement by AML. Approximately six weeks after cessation of blinatumomab, a repeat bone marrow examination revealed B/myeloid MPAL.

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Genomic Analysis of Congenital Myeloid Sarcoma Identifies Significant Bone Marrow Involvement in the Absence of Morphologic Blasts

Blood ◽

10.1182/blood-2020-142168 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 41-41

Author(s):

Jennifer Kamens ◽

Jinjun Dang ◽

Sarah Aldridge ◽

Jing Ma ◽

Yuanyuan Wang ◽

...

Keyword(s):

Bone Marrow ◽

Fusion Gene ◽

Bone Marrow Involvement ◽

Pi3k Pathway ◽

Myeloid Sarcoma ◽

Whole Genome ◽

Murine Bone Marrow ◽

Congenital Leukemia ◽

Leukemia Cutis ◽

Targeted Deep Sequencing

Myeloid sarcoma is a tumor mass consisting of blasts at extramedullary sites, most frequently the skin and soft tissues. Skin involvement, also termed leukemia cutis, is a well-described entity in congenital leukemia and is present in approximately 50% of patients diagnosed within the first 4 weeks of life. Most cases of congenital leukemia cutis harbor KMT2A rearrangements, as do up to 80% of cases of infantile leukemia, and are typically accompanied by bone marrow involvement. Here we describe a rare CIC-rearrangement as the driver mutation for a case of congenital cutaneous myeloid sarcoma in a newborn female who was noted at birth to have a violaceous, nodular rash. Skin biopsy of the nodular rash shortly after birth with immunohistochemical staining was consistent with myeloid sarcoma. Bilateral bone marrow aspirates and biopsies were also performed, but failed to reveal an aberrant blast population by morphology and flow cytometry. Cytogenetics of the cutaneous myeloid sarcoma was significant for t(10;19)(q23;q13.2) and fluorescence in situ hybridization performed on the tumor confirmed a CIC-rearrangement. CIC-rearranged sarcomas are a new entity of undifferentiated small round cell sarcoma characterized by fusion events involving the CIC gene but are not a known to be driver mutations in myeloid neoplasms. Despite the absence of a blast population in the bone marrow, 75% of analyzed metaphases carried the t(10;19)(q23;q13.2). To further explore the underlying genomic events, whole genome, exome, and transcriptome sequencing was performed on both sarcoma and bone marrow specimens. Sequencing revealed an in-frame CIC-NUTM2A fusion gene present in both the skin and the bone marrow which has been previously described in a single case of undifferentiated soft tissue sarcoma. There were no large-scale chromosomal losses or gains and no copy neutral loss of heterozygosity events. Two exonic single nucleotide variations (SNVs) were detected, both of which were limited to the skin sarcoma and not predicted to be pathogenic. In vitro and in vivo modeling demonstrated that the CIC-NUTM2A fusion protein was highly leukemogenic. Colony forming assays performed using transduced murine bone marrow revealed that the CIC-NUTM2A fusion conferred self-renewal in contrast to CIC, NUTM2A, and the reciprocal NUTM2A-CIC product which failed to serially replate (p<0.001). Transplantation of CIC-NUTM2A modified murine bone marrow cells resulted in a fully penetrant myeloid leukemia with a median survival of 21 days in primary transplants and 16 days in secondary transplants. Transcriptome analysis of these tumors revealed a distinct gene expression profile when compared to several classic myeloid associated fusion genes including AML1-ETO and MLL-AF6. To further understand the acquisition of a malignant phenotype by morphology between the bone marrow and the sarcoma, targeted deep sequencing was performed for all tier 1, 2 and 3 mutations identified by whole genome and exome sequencing. A shared ancestral clone was identified in both specimens along with three subclones specific to the sarcoma. Four SNVs acquired in the sarcoma were found to be present in regulatory regions of genes that were also differentially expressed between the sarcoma and the bone marrow including C6orf120, SMURF1, TJAP1, and PID1. PID1 was found to be downregulated in the malignant sarcoma specimen and has been previously shown to be a regulator of the AKT/PI3K pathway. Low PID1 expression has been associated with poor outcomes in other malignancies, including pediatric glioblastoma. A genome wide CRISPR screen of our CIC-NUTM2A positive murine leukemia cells revealed an enrichment for PID1 deficient cells as well as PTEN confirming the cooperativity between CIC-NUTM2A and the AKT/PI3K pathway (p=0.009 and p=0.005 respectively). In conclusion, we describe a rare fusion gene, CIC-NUTM2A, which leads to an aggressive myeloid malignancy in both humans and mice. Targeted deep sequencing demonstrated the clonal evolution from the bone marrow and acquisition of a cooperating mutation targeting the AKT/PI3K pathway in a subset of extramedullary cells that led to morphologic transformation. A thorough interrogation of the bone marrow in patients with myeloid sarcoma is warranted even in the absence of morphologic and immunophenotypic blasts by flow cytometry to optimally track residual disease during treatment. Disclosures No relevant conflicts of interest to declare.

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Outcomes In Acute Myeloid Leukemia (AML) Patients Diagnosed with Myeloid Sarcoma with and without Bone Marrow Involvement

Blood ◽

10.1182/blood.v116.21.2165.2165 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2165-2165 ◽

Cited By ~ 1

Author(s):

Marc Earl ◽

Alex Fu ◽

Matt Kalaycio ◽

Anjali Advani ◽

Yogen Saunthararajah ◽

...

Keyword(s):

Bone Marrow ◽

De Novo ◽

Bone Marrow Involvement ◽

Tumor Lysis Syndrome ◽

Myeloid Sarcoma ◽

Regression Analyses ◽

Tumor Lysis ◽

Entire Cohort ◽

Induction Regimen ◽

De Novo Aml

Abstract Abstract 2165 Background: Few AML studies report data on AML patients (pts) with extramedullary hematopoiesis. While AML pts diagnosed with an isolated myeloid sarcoma (MS) purportedly have a better outcome than those with AML without MS, it is unknown whether these outcomes differed for pts diagnosed with MS with or without bone marrow involvement compared to AML without MS. We compared these groups, and also evaluated whether or not the diagnosis of MS increased the rate of tumor lysis syndrome (TLS), due to greater tumor volume. Methods: We reviewed all AML pts newly diagnosed between 1994 and 2009 and treated with a cytarabine-based induction regimen. Pts with a diagnosis of MS with BM involvement (≥5% blasts) or without BM involvement (<5% blasts) were then identified and validated using the pathology database. A 1:2 case-control matching analysis was conducted, in which AML pts with MS with or without BM involvement were defined as cases, while AML pts without MS functioned as controls. Matching was based on age (± 5 years), induction regimen, WBC (± 1 log), AML etiology, diagnosis year (± 5 years), and cytogenetics (risk defined by CALGB 8461). Regression analyses further controlled for age, gender, presenting white blood cell count (WBC), and year of diagnosis. The rate of TLS was compared in univariate analyses. Results: Of the 477 AML pts treated with a cytarabine-based induction regimen, 19 (4%) had MS, either with (n=12, 2.5%) or without (n=7, 1.5%) BM involvement. The mean age (+/−SD) of the entire cohort was 57.5 (14.5) years, and 58 years (24-80) for MS pts; within the entire cohort, 47% were female, 64% had de novo AML, mean WBC was 31k/ml, and 52% had good/intermediate risk cytogenetics, while for MS pts, 32% were female, 74% had de novo AML, mean WBC was 31k/ml, and 74% had good/intermediate cytogenetics. Comparing all MS cases to matched controls, baseline characteristics were similar, as expected. Outcomes were similar for the pooled case and control groups for CR rates (63.2% vs. 65.7%, p=.85) and median OS (0.7 vs. 0.8 years, p=.95). Incidence of tumor lysis syndrome was low in both groups (case 5%, control 3%, p=1.0). Focusing on comparing MS with BM involvement to matched controls, outcomes remained similar for CR rates (58% vs. 71%, p=.44), OS (.53 vs. 1.12 years, p=.4), and TLS (8% vs. 5%, p=1.0), both in univariate and regression analyses. Comparing MS pts without BM involvement to controls, however, CR rates were higher for MS patients (71% vs. 57%, OR 15.5, p=.15), as was median OS (1.14 vs. .64 years, HR .15, p=.027) in univariate and regression analyses. There were no cases of tumor lysis syndrome in either group. Conclusions: AML pts diagnosed with MS without BM involvement and treated with cytarabine-based induction regimen have a superior overall survival to patients with usual presentation of AML treated with a similar regimen. There was no difference in outcome for AML pts with MS with BM involvement, compared to AML pts without MS. Patients with MS were not at significantly higher risk of TLS. Cox model survival curve MS without BM involvement=dotted line AML=continuous line HR=.15, p=.027 Disclosures: No relevant conflicts of interest to declare.

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