Myeloid sarcoma transformed from myeloproliferative neoplasm: A case report and review of literature

Abstract

BACKGROUND

Myeloid sarcoma (MS) is a rare hematological malignancy that may be associated with myelodysplastic or myeloproliferative neoplasms. Herein, we report a case of transformation from myelofibrosis to MS.

CASE SUMMARY

A 56-year-old male patient was found to have multiple bone lesions by the pelvic magnetic resonance imaging. Pathological analysis of the lesions indicated a myeloid tumor, and immunohistochemistry revealed a TP53 mutation. Bone marrow aspiration was consistent with myelofibrosis. Based on the patient’s history of polycythemia and the immunohistochemical findings of the surgically resected lesions, a transformation from a myeloproliferative neoplasm to MS was suggested. The patient developed hematological toxicity after receiving chemotherapy with idarubicin plus cytarabine, and treatment was subsequently adjusted to ruxolitinib combined with venetoclax. However the patient exhibited suboptimal treatment response.

CONCLUSION

Cases of myelofibrosis transforming into MS are extremely rare. The TP53 mutation is a key molecular marker associated with poor tumor prognosis. Because it can be easily mistaken for other tumors, it is crucial to perform relevant examinations and establish a clear diagnosis as early as possible. This facilitates the timely formulation of an appropriate treatment plan and may help prolong the patient’s life.

Key Words: Myeloid sarcoma; Myelofibrosis; TP53; MYC amplification; Case report

Core Tip: This paper details the diagnosis and treatment process of an elderly male patient whose condition transformed from myelofibrosis to myeloid sarcoma. The diagnosis was confirmed through multiple examinations. This case highlights the significant impact of accurate diagnosis and flexible adjustment of treatment plans on patients' survival under complex disease conditions.

INTRODUCTION

Myeloid sarcoma (MS) is a rare and distinct hematological malignancy characterized by the formation of solid tumor masses composed of myeloid blasts or immature myeloid cells in extramedullary sites, that is, outside the bone marrow. This condition is often associated with acute myeloid leukemia (AML) but can also occur independently or as a precursor to AML[1,2].

The clinical presentation of MS is highly variable, as it can occur in virtually any organ or tissue, including the skin, lymph nodes, gastrointestinal tract, and central nervous system. This variability often leads to misdiagnosis, with MS being mistaken for lymphomas or other solid tumors. The diagnosis of MS is further complicated by its rarity and the overlapping features with other hematological disorders, such as myeloproliferative neoplasms (MPN) and myelodysplastic syndromes[3,4]. The main aim of this article is to present a case of myelofibrosis (MF) transforming into MS, furthering the clinical understanding of MS.

CASE PRESENTATION

Chief complaints

The patient was a 56-year-old male who had experienced left hip pain for over a month.

History of present illness

The patient developed left hip pain and discomfort more than one month ago and subsequently underwent surgical resection of the lesion.

History of past illness

The patient had a history of polycythemia and hypertension.

Personal and family history

No special notes.

Physical examination

The patient was underweight but in fair general condition. Tenderness was noted at the left hip joint.

Laboratory examinations

Laboratory test results were as follows: White blood cell count, 34.8 × 10⁹/L; absolute neutrophil count, 31.53 × 10⁹/L; hemoglobin, 156 g/L; platelet count, 871 × 10⁹/L; albumin, 41.8 g/L; lactate dehydrogenase, 567 U/L; and C-reactive protein, 68.9 mg/L.

Pathological examinations

Histological examination of the puncture biopsy from the left femoral head lesion revealed abnormal cells with areas of hemorrhage and extensive necrotic tissues. These cells expressed CD43 and showed partial positivity for myeloperoxidase (MPO), while testing negative for CD20, CD19, CD79a, CD138, CD3, and CD56. A TP53 mutation was also detected, indicating a myeloid tumor. Immunohistochemical examination of the lesion tissue obtained during surgery on the left femur showed positive expression of CD71(+), CD43(+), scattered CD34(+), and focal weak expression for CD117(+). Meanwhile, negative expression was observed for CD3, CD20, CD79a, CD138, MPO, and CK-PAN. The Ki-67 index was 70% (Figure 1). Combining the immunohistochemical findings with the clinical history, the results were consistent with transformation from a myeloproliferative disease to MS.

Figure 1 Pathological results. A: Hematoxylin-eosin staining of the left femoral head section showing the pathological lesion; B-E: Histopathology of myeloid sarcoma with positive staining for CD42b (B), CD71 (C), Ki-67 (D), and myeloperoxidase (E); F: Reticular fiber staining in the bone marrow (magnification × 10).

Bone marrow analysis by cell morphology and flow cytometry showed no infiltration by myeloblasts. Bone marrow biopsy pathology indicated active marrow hyperplasia, an increased number of immature cells, and grade 2 bone marrow fibrosis. A positive JAK2 V617F mutation was subsequently detected.

Genomic analysis

The targeted next-generation sequencing panel (TruSight Myeloid Sequencing Panel, Illumina, San Diego, CA, United States) was used to establish the mutation profile. The panel targeted 54 genes and covered the full coding sequence of 15 genes and the exonic hotspots of 39 genes associated with myeloid malignancies. We identified sequence alterations with a variant allele frequency of ≥ 3%. The mutations were independently confirmed by Sanger sequencing. Using this technology, we identified clinically significant genetic variations, including TP53 p. (R248Q) (mutation frequency: 50.38%), TP53 p. (A76Cfs*73) (mutation frequency: 23.29%), and MYC amplification (amplification frequency: 8.68%).

Imaging examinations

Enhanced pelvic magnetic resonance imaging revealed extensive bone signal changes in the pelvic bones, lower lumbar vertebrae, and upper segments of both femurs, suggesting a malignant tumor, possibly of hematological origin. The 18F-fluorodeoxyglucose positron emission tomography (18F-FDG)/and computed tomography scan showed slightly increased diffuse bone density in the axial and appendicular skeleton, multiple focal bone destructions with increased FDG uptake, mainly in the left femoral head, and splenomegaly (Figure 2).

Figure 2 18F-fluorodeoxyglucose positron emission tomography/and computed tomography showing multiple focal bone destructions, mainly in the left femoral head. A: Non-enhanced computed tomography (CT) image; B: Positron emission tomography (PET) image; C: Fused PET and CT images; D: PET maximal intensity projection image in the coronal plane.

FINAL DIAGNOSIS

The final diagnosis in this case was MS, which had transformed from a MPN, characterized by a TP53 mutation and MYC amplification.

TREATMENT

The patient initially received induction treatment with idarubicin (6.5 mg/m², days 1-3) and cytarabine (Ara-C) (100 mg/m², days 1-7). However, severe hematological toxicity developed on the second day of chemotherapy, prompting a change in treatment to azacitidine (75 mg/m², days 1-7) combined with venetoclax (50 mg, days 1-28). Given the patient’s poor tolerance and subsequent complications, the treatment regimen was adjusted to ruxolitinib (5 mg, twice a day) combined with low-dose venetoclax (50 mg, days 1-28).

OUTCOME AND FOLLOW-UP

The patient exhibited suboptimal treatment response and was lost to regular follow-up.

DISCUSSION

MS is a rare extramedullary myeloid malignant proliferative disease often associated with MPN or AML[5,6]. As shown in Table 1[7-18], among the reported cases of MPN-associated MS (MPN-MS), the vast majority originate from chronic myeloid leukemia, whereas cases based on primary or secondary MF remain relatively uncommon. In the present case, an elderly male patient presented with left hip pain. Imaging revealed extensive bone destruction and increased FDG metabolism. Pathological immunohistochemistry combined with detection of the JAK2 V617F mutation suggested transformation from grade 2 MF to MS, accompanied by TP53 mutation and MYC amplification, revealing the molecular mechanisms underlying disease progression and their correlation with prognosis.

Table 1 Summary of previously published cases of myeloid sarcoma arising from myeloproliferative neoplasms.

Age	Sex	MPN subtype	Mutations (TP53/MYC/other)	Treatment regimen	Outcome	Ref.
63	M	MDS/MPN overlap syndrome	TP53 (+); MYC (-); Complex cytogenetics (monosomies 18/19/21, 5q/7q abnormalities)	Decitabine + venetoclax → SCT	CR with complete cytogenetic response	[7]
18	M	CML	TP53 (-); MYC (-); t(9;22) (BCR-ABL1+)	Nilotinib	Alive, 2 years post-treatment	[8]
39	M	CML	TP53 (-); MYC (-); t(9;22)	Imatinib + Ara-C + high-dose dexamethasone + local radiotherapy	Dead, 2 months post-treatment	[9]
49	M	CML	TP53 (-); MYC (-); t(9;22)	Busulfan + local radiotherapy + surgery	Outcome not available	[10]
50	F	CML	TP53 (-); MYC (-); t(9;22)	Surgery + radiotherapy	Outcome not available	[11]
50	M	MPN (unspecified)	TP53 (-); MYC (-); BCR-ABL1 (+)	Dasatinib + Ara-C + SCT	Dead, 76 days post-SCT	[12]
59	F	ET	TP53 (-); MYC (-); +1, der (1;13) (q10;q10), del(7) (q22q32)	Imatinib + Ara-C + ETP	Dead, 1 month post-treatment	[13]
62	M	CML	TP53 (-); MYC (-); complex karyotype [including t(9;22)]	Imatinib	Dead	[14]
63	M	MF	TP53 (-); MYC (-); JAK2 (+)	Ruxolitinib	Dead, 10 months post-treatment	[15]
60	M	PMF, (CALR-positive)	TP53: Negative; MYC: Negative; other: CALR L367fs*46, ASXL1 E635R, KRAS A146T, SH2B3 R265Q	Death intraoperatively due to irreversible hemorrhagic shock	Death intraoperatively due to irreversible hemorrhagic shock	[16]
53-	M	PMF, (pre-fibrotic)	TP53: Negative; MYC: Negative; Other: CALR type-2 (ins5-bp), NPM1 (nuclear dislocation)	Palliative splenectomy	Complete morphologic/immunophenotypic remission; subcutaneous nodules resolved; residual FDG-PET uptake	[17]
51-	F	PMF, (JAK2-mutated)	TP53: Negative; MYC: Negative; other: JAK2 V617F	“3 + 7” induction chemotherapy (daunorubicin + Ara-C); consolidation with intermediate-dose Ara-C; radiotherapy (contralateral arm)	Orbital MS regression; leukemic transformation to AML; death 6 months post-diagnosis due to aspergillus pneumonia, sepsis, and multiple organ failure	[18]

MDS: Myelodysplastic syndromes/neoplasms; MPN: Myeloproliferative neoplasms; CML: Chronic myeloid leukemia; ET: Essential thrombocythemia; MF: Myelofibrosis; Ara-C: Cytarabin; ETP: Etoposide; PMF: Primary myelofibrosis; CR: Complete remission; TP53: Tumor protein 53; F: Female; M: Male.

The patient had a prior history of polycythemia, and bone marrow biopsy with reticulin staining indicated grade 2 MF, reflecting the underlying lesion. The occurrence of MS is often linked to clonal evolution in the late stages of MPN. Approximately 5% to 10% of patients with MF may progress to MS[19], a process possibly driven by abnormal proliferation of hematopoietic stem cells due to JAK2 mutation and microenvironmental disturbances[20]. Herein, immunohistochemistry of the lesion showed strong CD43 expression, partial positivity for MPO, and negativity for lymphoid markers (CD20, CD3, CD79a). Combined with the absence of blast infiltration in the bone marrow, extramedullary leukemia infiltration was excluded, supporting the diagnosis of transformation from MPN to MS.

It is essential to note that the pathological morphology of MS can be easily misinterpreted as that of lymphoma, plasmacytoma, or other malignancies, and incomplete examinations may result in a misdiagnosis. Therefore, histopathological analysis of the lesion is essential for a definitive diagnosis. In this case, the positive expression of CD43 and co-expression of Kappa and Lambda light chains in the left femoral head lesion necessitated differentiation from plasma cell tumors. The absence of CD20, CD19, and CD79a ruled out B-cell lymphoma, while negativity for CD3 excluded T-cell lymphoma. Moreover, the lack of CD138 expression, partial positivity for MPO, and evidence of erythroid, myeloid, and megakaryocytic differentiation in the bone marrow excluded a plasma cell origin. Furthermore, the low expression of CD34 and CD117 indicated that the tumor cells were relatively mature, consistent with the pathological features of MF progressing to MS[21].

The TP53 mutation is a key molecular feature in this case. Its incidence in patients with MPN transforming to myeloid malignancies is approximately 10% to 20% and is often associated with disease progression and poor prognosis[22]. Studies have shown that TP53 mutation promotes abnormal proliferation of myeloid cells and treatment resistance by disrupting genomic stability[23]. As a key tumor suppressor gene, TP53 maintains genomic stability by regulating cell cycle checkpoints and apoptotic pathways; its mutation leads to loss of function, gain of oncogenic function, or dominant negative effects, thereby promoting abnormal myeloid cell proliferation and treatment resistance[24]. The coexistence of TP53 mutation and MYC amplification in this case represents a core driver of MF-to-MS transformation and therapeutic refractoriness. TP53 inactivation abrogates cell cycle control and apoptotic surveillance, enabling MYC-mediated oncogenic programs including uncontrolled proliferation and metabolic reprogramming. Synergistically, these aberrations accelerate malignant progression through epigenetic dysregulation and immune evasion[25]. At the level of therapeutic resistance, TP53 inactivation compromises drug sensitivity, whereas MYC amplification augments drug efflux and upregulates anti-apoptotic proteins—together mediating a synergistic drug-resistant phenotype[26]. Clinically, co-occurrence of TP53 and MYC abnormalities correlates with lower remission rates and shorter overall survival in myeloid neoplasms, with preclinical models validating their synergistic tumorigenic and drug-resistant effects[24]. The patient’s poor response to the regimen of idarubicin combined with Ara-C (IA) and rapid development of severe hematologic toxicity further support TP53 mutation as a potential predictor of chemotherapy resistance. The Ki-67 index, a robust marker of cellular proliferation, was 70% in this case—consistent with high-grade malignancy, indicating active tumor cell division, enhanced invasive potential, and elevated recurrence risk. This finding explains the underlying pathological basis for poor disease control and underscores the value of Ki-67 in prognostic stratification and therapeutic decision-making for MS.

For MS transformed from MPN, traditional chemotherapy regimens such as IA have low remission rates and significant toxicity[27]. For our patient, bone marrow suppression on the second day of chemotherapy. Azacitidine in combination with venetoclax is an established therapeutic regimen for TP53-mutated AML and high-risk myelodysplastic syndromes[28]. As a hypomethylating agent, azacitidine improves outcomes by restoring tumor suppressor gene expression—an effect particularly critical for TP53-mutated cells, which often exhibit exacerbated malignant phenotypes due to secondary epigenetic silencing[29]. Venetoclax targets the BCL-2 protein to induce tumor cell apoptosis and confers potential efficacy in TP53-mutated myeloid neoplasms. Thus, the patient’s treatment was adjusted to azacitidine combined with venetoclax. Despite this rationale, the present patient failed to benefit from azacitidine + venetoclax due to poor tolerance, developing recurrent fever, pulmonary infection, and metabolic encephalopathy. Given the patient’s MF background and JAK2 V617F mutation, therapy was switched to ruxolitinib (a JAK1/2 inhibitor) combined with low-dose venetoclax, based on evidence that JAK2 inhibitors enhance venetoclax sensitivity by downregulating MCL-1 expression[30]. Hematopoietic stem cell transplantation was not considered due to the patient’s poor performance status and biallelic TP53 mutation, which confer high transplant-related mortality and low relapse-free survival. This clinical course highlights the urgent need for more precise, individualized therapeutic strategies for TP53/MYC co-mutated MPN-MS.

Given the high aggressiveness of MS and the patient’s high-risk molecular profile (TP53 mutation, MYC amplification), minimal residual disease (MRD) monitoring holds significant clinical value. As a solid manifestation of myeloid malignancy, MS is prone to residual disease persistence in the bone marrow or occult extramedullary sites even after primary lesion regression—detection of which is beyond the sensitivity of conventional imaging and morphological assessment[31]. MRD monitoring, via techniques such as multi-parameter flow cytometry, enables sensitive detection of trace malignant cells, providing objective evidence for treatment response assessment, relapse risk stratification, and therapeutic adjustment[31]. In this case, initial bone marrow evaluation by flow cytometry showed no involvement, and subsequent serial MRD monitoring remained negative. These findings support the integration of MRD monitoring into routine management strategies for high-risk MS patients to guide clinical decision-making and relapse surveillance.

CONCLUSION

This present case highlights the importance of a multimodal approach in diagnosing MS. Combining imaging findings (bone destruction and high FDG uptake), pathological immunohistochemistry (positive myeloid markers and exclusion of lymphoid markers), and molecular testing (JAK2, TP53, MYC) can help prevent missed or incorrect diagnoses. In patients with MPN, the appearance of extramedullary masses or bone destruction should raise strong suspicion of transformation to MS, especially in those harboring TP53 mutations. For these patients, intensive treatment should be initiated promptly, and hematopoietic stem cell transplantation considered. Future research should focus on elucidating the role of TP53 mutations and MYC amplification in MS progression and on developing targeted therapies to improve outcomes in this refractory disease.