Intestinal myeloid sarcoma mimicking gastrointestinal stromal tumor without leukemic manifestations: A case report and review of literature

Abstract

BACKGROUND

Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells, often associated with acute myeloid leukemia. Primary intestinal myeloid sarcoma without hematologic disease is uncommon and can mimic gastrointestinal stromal tumor (GIST).

CASE SUMMARY

A 52-year-old man presented with upper abdominal pain, distension, and nausea. Computed tomography revealed a small intestinal mass with obstruction, suggestive of GIST. Small bowel resection was performed. Intraoperative frozen section suggested lymphoma, but histopathology and immunohistochemistry confirmed myeloid sarcoma [positive for myeloperoxidase, cluster of differentiation (CD) 34, CD117, CD123, CD43]. No evidence of leukemia was identified in peripheral blood or bone marrow examinations. The patient recovered and remained disease-free at 6-month follow-up.

CONCLUSION

Intestinal myeloid sarcoma mimics GIST or lymphoma; definitive diagnosis requires histopathology and immunohistochemistry for appropriate therapy.

Key Words: Myeloid sarcoma; Gastrointestinal; Immunohistochemistry; Computed tomography; Rare diseases; Case report

Core Tip: This case highlights the diagnostic challenge of intestinal myeloid sarcoma mimicking gastrointestinal stromal tumor, emphasizing the necessity of immunohistochemistry to avoid misdiagnosis and delayed treatment.

INTRODUCTION

Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a rare malignant tumor composed of immature myeloid cells that arise outside the bone marrow[1]. MS may occur de novo, precede, or coincide with acute myeloid leukemia (AML)[2], and in rare cases, manifest as an isolated extramedullary lesion without concurrent hematologic abnormalities[3]. Isolated MS involving the gastrointestinal tract is especially rare and can present significant diagnostic challenges due to its resemblance to more common intestinal tumors such as gastrointestinal stromal tumors (GIST) or lymphomas[4,5].

Because of its nonspecific radiologic features and gastrointestinal symptoms, MS is often misdiagnosed. Immunohistochemical (IHC) staining is critical to distinguish MS from other neoplasms and to guide appropriate treatment[6]. Here, we present a rare case of primary small intestinal MS initially suspected to be a GIST, which was diagnosed postoperatively through histopathology and immunophenotyping.

CASE PRESENTATION

Chief complaints

A 52-year-old man of Asian ethnicity presented to our hospital with “abdominal pain for 7 days”.

History of present illness

Seven days before admission, the patient experienced left upper abdominal pain, which was described as tolerable. After receiving intravenous “omeprazole and phentolamine” in the emergency department, his abdominal pain improved. He was discharged and took “pantoprazole and aluminum carbonate chewable tablets” orally. Three days before admission, the abdominal pain recurred and was similar in nature. After another intravenous administration of “omeprazole and phentolamine”, the pain temporarily subsided. One day before admission, the abdominal pain worsened and was accompanied by abdominal distension, belching, and nausea.

History of past illness

The patient had a 2-year history of coronary heart disease and took “aspirin, rosuvastatin calcium tablets, metoprolol succinate extended-release tablets” daily. He also had a 20-year history of hemorrhoids.

Personal and family history

Personal and family histories were noncontributory.

Physical examination

On admission, physical examination revealed tenderness in the left upper quadrant but no other special discomfort.

Laboratory examinations

Laboratory analysis revealed a lymphocyte count of 0.85 × 10⁹/L (normal range, 1.1 × 10⁹/L to 3.2 × 10⁹/L), neutrophil percentage of 78.40% (normal range, 40%-75%), and lymphocyte percentage of 15.70% (normal range, 20%-50%). Routine blood tests, liver and kidney function tests, electrolytes, and tumor markers including carbohydrate antigen (CA)-50, CA-125, CA19-9, CA72-4, alpha-fetal protein, and carcinoembryonic antigen were not significantly abnormal.

Imaging examinations

An abdominal computed tomography (CT) scan revealed small intestinal obstruction. Contrast-enhanced CT of the abdomen suggested a mass in the right middle abdomen, highly suspicious for a tumor with proximal small intestinal obstruction, and the possibility of a GIST could not be excluded (Figure 1). Therefore, the patient was clinically diagnosed as a case of small intestinal tumor, most likely a GIST.

Figure 1 Contrast-enhanced abdominal computed tomography scan showing small intestinal mass. A: Arterial phase axial image showing a well-defined enhancing mass (arrow) in the right mid-abdomen, causing proximal small bowel dilation; B: Portal venous phase confirms the soft-tissue density mass (arrow) with associated small bowel obstruction, initially suspected to be a gastrointestinal stromal tumor.

FINAL DIAGNOSIS

The patient was clinically diagnosed as a case of small intestinal tumor, most likely a GIST.

TREATMENT

On December 18, 2024, the patient underwent partial resection of the small intestine. Intraoperative exploration of the abdominal cavity identified an intraluminal tumor located approximately 70 cm from the terminal ileum. The tumor measured 4 cm × 5 cm and exhibited a 0.5 cm ulcer penetrating deeply into its core. Additionally, enlarged lymph nodes were observed at the mesenteric root. A rapid frozen section analysis of the lymph nodes indicated a potential diagnosis of lymphoma. However, a definitive classification is pending further evaluation using conventional methods and IHC. Subsequent examination of paraffin-embedded sections from the resected small intestine and mesenteric lymph nodes confirmed the presence of MS. IHC staining revealed positive results for myeloperoxidase (MPO), cluster of differentiation (CD) 34, CD117, CD123 and CD43, c-Myc protein expression was positive in 70% of tumor cells and a Ki67 proliferation index of approximately 70% (Figures 2 and 3). Consequently, a diagnosis of MS was established. Notably, no tumor tissue was detected in the mesenteric lymph nodes. The patient was asymptomatic postoperatively, with no signs of leukemia in peripheral blood or bone marrow. The patient underwent uneventful surgery and was discharged on postoperative day 8. Details of adjuvant treatment received at another hospital were unavailable. See “outcome and follow-up” section for follow-up results.

Figure 2 Histopathology of (hematoxylin and eosin staining) the resected small intestinal mass. A and B: Histopathology of the resected small intestinal mass (× 200; scale bar, 100 μm). Tumor cells of medium size with a fairly uniform morphology infiltrate and grow diffusely in the intestinal wall (arrows). They have large, round or ovoid nuclei and scant cytoplasm. Nuclear chromatin is finely and evenly distributed, and in some cases, nucleoli of varying sizes are evident.

Figure 3 Immunohistochemical staining of tumor cells. A: Myeloperoxidase strong cytoplasmic positivity confirming myeloid lineage; B-E: The tumor shows positive immune responses to myeloid markers cluster of differentiation (CD) 34 (B), CD117 (C), CD123 (D), and CD43 (E) (× 200; scale bar, 100 μm).

OUTCOME AND FOLLOW-UP

The patient underwent uneventful surgery and was discharged on postoperative day 8. The patient received adjuvant treatment at another hospital after discharge. Follow-up six month later showed no recurrence, and there were no signs of leukemia in peripheral blood or bone marrow.

DISCUSSION

Primary intestinal MS is rare and is more likely to be overlooked in the absence of leukaemia[7]. The current World Health Organization classification categorizes MS as a major subtype of AML[8,9]. MS can disseminate to multiple anatomical sites. According to the presence of bone marrow involvement, MS is classified as synchronous MS or isolated MS[10]. Population-based studies have reported an incidence of 0.7 per 100000 children and a slight male predominance across age groups[11,12]. Isolated MS arising in the small intestine is exceptionally rare.

Radiological evaluation is important for early recognition of MS. CT and magnetic resonance imaging (MRI) can determine tumor size and location and can support differentiation from lesions such as haematomas or abscesses[13]. Nevertheless, intestinal MS can mimic GIST on imaging[14]. In the present case, imaging showed a localized small-bowel mass with obstruction, which led to an initial impression of GIST, the most common mesenchymal neoplasm of the gastrointestinal tract. Such tumors commonly present with pain, nausea, or obstruction. A prospective study comparing positron emission tomography (PET) imaging with clinical examination and histological analysis reported an incidence of 22% and showed a sensitivity of 77% and a specificity of 97% for fluorodeoxyglucose-PET[15]. Detection of extramedullary disease using (18)F-fluorodeoxyglucose PET/CT may support individualized treatment algorithms for high-risk patients[16]. In the present case, PET was not performed preoperatively, highlighting the need for increased diagnostic vigilance when imaging findings are atypical.

MS, particularly isolated MS without bone marrow involvement, remains a diagnostic challenge in patients presenting with extramedullary masses[17]. To reduce misdiagnosis and enable timely management, a multidisciplinary strategy is required. This strategy should integrate radiological suspicion, intraoperative pathological consultation, comprehensive IHC screening, and molecular testing.

Within this strategy, IHC is essential because intraoperative frozen section assessment is often unreliable for this entity. Frozen section analysis has recognized limitations in differentiating MS from high-grade lymphoma or undifferentiated carcinoma. Misinterpretation is also common in rare small-bowel mesenchymal lesions[18]. Reported misdiagnosis rates for isolated MS range from 25% to 47%. Inadequate or incomplete IHC panels have been identified as the most frequent contributing factor[19].

A comprehensive IHC panel is mandatory for accurate lineage assignment. To address the differential diagnosis systematically, a lineage-oriented strategy should be applied. For confirmation of MS, markers of myeloid differentiation include MPO, which is the most specific, together with CD117, CD13, CD33, and lysozyme. Monocytic markers such as CD68, CD163, CD14, and CD11c support identification of MS with monocytic differentiation[20,21]. To exclude lymphomas, which represent the main morphological mimickers, B-cell markers including CD20 and CD79a and T-cell markers including CD3 and CD45RO should be assessed. Positivity for these lymphoid markers in the absence of myeloid marker expression supports lymphoma[22]. To exclude carcinomas and sarcomas, cytokeratin and epithelial membrane antigen are essential for ruling out carcinoma. Desmin and S-100 can assist in excluding selected sarcomas and melanomas. MS is consistently negative for these markers.

This approach is supported by the findings in the present case. Intraoperatively, enlarged mesenteric lymph nodes shifted the clinical impression toward lymphoma. However, histopathological evaluation combined with an immunophenotype showing co-expression of MPO, CD34, and CD117 established the diagnosis of MS. In addition, CD68-KP1, lysozyme, and Bcl-2 were included. This combination has been reported to increase diagnostic sensitivity for MS to > 95%[23]. In the present case, strong positivity for Bcl-2 and vimentin further supported the diagnosis[23].

Subsequent bone marrow biopsy and peripheral blood examination showed no evidence of haematological disease. These findings confirmed isolated MS and emphasized the need for complete staging to exclude systemic leukaemia. Cytogenetic and molecular testing contributes to ancillary diagnosis, risk stratification, and prognostic assessment in MS[24]. Isolated MS has a substantial risk of leukemic transformation. A nationwide French cohort published in 2023 (n = 142) reported progression to AML in 28% of cases within 24 months, with a median time to transformation of 11.4 months[25]. Molecular profiling indicates that approximately 40% of isolated MS harbour FLT3 internal tandem duplication (ITD) or NPM1 mutations. These alterations are associated with increased risk of transformation[26]. Next-generation sequencing was not available at the study center. Molecular analysis is planned using archived paraffin blocks to refine risk stratification.

Based on previous reports, MS is treated with systemic chemotherapy, surgery, radiotherapy, haematopoietic stem-cell transplantation, or combinations of these approaches. The European LeukemiaNet 2024 recommendations support risk-adapted therapy. Patients with FLT3-ITD or adverse-risk mutations should receive FLAG-IDA (fludarabine, cytarabine, idarubicin and granulocyte colony-stimulating factor) induction followed by allogeneic haematopoietic stem-cell transplantation in first complete remission[27,28]. For patients unfit for intensive chemotherapy, venetoclax combined with a hypomethylating agent achieved a composite complete remission rate of 71% in a single-arm phase II trial including 24 adults with extramedullary MS[29]. Imaging surveillance should also be standardized. A retrospective multicenter study proposed alternating whole-body MRI and PET-CT every 6 months during the first 2 years. This strategy enabled detection of extramedullary relapse before bone marrow involvement[30].

In the present case, adjuvant chemotherapy was administered at another hospital. The patient remained leukaemia-free at 6 months. This outcome reflects disease heterogeneity and highlights the need for vigilant, multidisciplinary follow-up to detect systemic progression early and to avoid misclassification as more common intestinal tumors.

This case has several implications for clinical practice. First, intestinal MS should be included in the differential diagnosis of small-bowel masses with atypical imaging features, particularly when preoperative biopsy is inconclusive. Second, intraoperative frozen section assessment is unreliable for rare mesenchymal lesions. Third, comprehensive immunohistochemistry is required to establish the diagnosis and to differentiate MS from GIST or lymphoma. Early recognition and risk-adapted therapy remain essential to improve outcomes in this rare entity.

CONCLUSION

In summary, this case highlights diagnostic pitfalls in primary intestinal MS, which can mimic GIST or lymphoma. Accurate classification requires integration of imaging findings, comprehensive immunohistochemistry, molecular characterization, and risk-adapted therapy. This approach may improve outcomes and reduce misclassification of this rare entity.

ACKNOWLEDGEMENTS

Authors acknowledge the Department of Pathology for their diagnostic support, the patient for their cooperation, and all healthcare staff involved for their dedication.