A 42-year-old woman was admitted to Weifang Second People’s Hospital on 20 June 2024 following an incidental finding of a pulmonary nodule (21 × 27 mm²) during a routine physical examination 1 year previously. Although serial imaging over the following year showed stable size and morphology, suggesting a benign nature, malignancy remained possible. The patient had no significant medical, family, or psychosocial history, and denied tobacco and alcohol use. Preoperative evaluation included fine-needle aspiration cytology, which revealed spindle cells with lymphoplasmacytic infiltration. Contrast-enhanced chest computed tomography demonstrated a lobulated left upper lobe nodule with heterogeneous enhancement and partial bronchial obstruction (Fig 1). Magnetic resonance imaging of the brain and abdominal ultrasound showed no metastasis. Based on the above investigations and considering the patient’s financial circumstances, a positron emission tomography scan was not performed. Tumour marker levels were within the normal range—neuron-specific enolase: 13.06 ng/mL, carbohydrate antigen 19-9: 9.76 U/mL, carcinoembryonic antigen: 1.54 ng/mL, cytokeratin 19 fragment: 1.23 ng/mL, and squamous cell carcinoma antigen: 0.51 ng/mL. Thoracoscopic left upper lobectomy was performed on 22 June 2024. Histopathology revealed proliferating spindle myofibroblasts/fibroblasts with lymphoplasmacytic infiltration and focal mucin deposition (Fig 2). Immunohistochemistry confirmed inflammatory myofibroblastic tumour (IMT): positive for cytokeratin, vimentin, smooth muscle actin (SMA), and epithelial membrane antigen; STAT6 (signal transducer and activator of transcription 6) negative with a Ki-67 index of 30%. The patient recovered well, with no recurrence at 3-month follow-up, although long-term surveillance was recommended.

Inflammatory myofibroblastic tumour, originally termed inflammatory pseudotumour (IPT) in 1939, has been reclassified through molecular insights from a reactive proliferation to a true neoplasm.1 Although IPT remains a non-neoplastic inflammatory lesion with regression potential, IMT is now defined as a clonal neoplasm composed of myofibroblastic spindle cells within a plasma cell/lymphocyte/eosinophil-rich stroma. This distinction is crucial clinically since IMT exhibits local invasiveness and recurrence risk, unlike IPT’s benign course.2

Inflammatory myofibroblastic tumour is a rare mesenchymal neoplasm that primarily affects children and young adults, with lower incidence in adults.3 Its broad anatomical distribution most commonly involves the lungs (0.7% of pulmonary tumours)4 and the abdomen/mesentery/retroperitoneum; rare sites include the oesophagus, cardiac chambers, and adrenal glands. As a borderline malignancy, recurrence rates differ by site (pulmonary 2% vs extrapulmonary 25%), with less than 5% risk of distant metastasis.5 Symptoms vary anatomically: pulmonary cases may present with cough or haemoptysis (including incidental detection), abdominal lesions may cause pain or obstruction, while systemic symptoms include fever and weight loss. Pulmonary IMTs, as observed in our patient, may present with cough, atypical chest pain, haemoptysis, or dyspnoea, although incidental detection during routine health screening, as in our case, is not uncommon.

The non-specific radiological features of IMT pose significant diagnostic challenges, necessitating histopathological confirmation. In our patient, the nodule was identified during a routine physical examination 1 year prior to admission, and serial imaging demonstrated stable lesion size. This supported a benign nature but did not entirely exclude malignancy. Although minimally invasive techniques such as fine-needle aspiration biopsy and bronchoscopic sampling are often attempted, these methods frequently yield insufficient tissue for definitive diagnosis. Complete surgical resection therefore remains the gold standard for both diagnostic confirmation and therapeutic intervention.

Histopathological examination typically reveals spindle-shaped myofibroblastic proliferation within variable stromal matrices (myxoid, collagenous, or calcified patterns), accompanied by a polymorphic inflammatory infiltrate. In our patient, the histopathological features were consistent with IMT, showing proliferating spindle-shaped myofibroblasts/fibroblasts with abundant lymphoplasmacytic infiltration and focal mucin deposition. The diagnosis was further supported by immunohistochemical findings, including positivity for cytokeratin, vimentin, SMA, and epithelial membrane antigen, although anaplastic lymphoma kinase (ALK) and STAT6 were negative.

Molecular studies have identified chromosomal 2p23 translocations in approximately 50% of IMT cases, leading to constitutive activation of ALK pathways.6 This genetic aberration correlates with tumour aggressiveness and local recurrence, supporting IMT’s classification as a true neoplasm rather than a reactive pseudotumour. Immunophenotypically, most IMTs express mesenchymal markers such as ALK (cytoplasmic/membranous), caldesmon, desmin, and SMA, with ALK reactivity aiding differentiation from histological mimics. Notably, our case showed an atypical immunoprofile with SMA positivity and ALK negativity, reflecting the phenotypic heterogeneity and the need for comprehensive molecular profiling in challenging cases.

Therapeutic strategies for IMT depend on disease stage and resectability. For localised lesions, complete surgical resection (R0 margins) achieves a 2% recurrence rate, whereas incomplete resection (R1/R2) increases recurrence risk to 60% (P<0.01).7 In our patient, thoracoscopic left upper lobectomy was performed with negative surgical margins, and no tumour recurrence was observed during the initial 3-month postoperative follow-up. Nonetheless, longer-term surveillance is recommended to confirm the absence of tumour recurrence. Non-resectable or recurrent cases require multimodal approaches, including radiotherapy (45-50 Gy), platinum-based chemotherapy, and ALK inhibitors for ALK-positive subtypes.

Emerging molecular insights have identified ALK rearrangements as key oncogenic drivers, positioning ALK-targeted therapies as both diagnostic and therapeutic tools.8 Clinical trials have demonstrated the efficacy of crizotinib: an initial phase 1 study (NCT01121588)9 achieved a 42.9% partial response rate in refractory paediatric/young adult IMTs (n=7), while cohort expansion (n=14) improved the overall response rate (ORR) to 86% (36% complete responses). Japanese studies corroborate these findings, with 100% ORR (1 complete response, 2 partial responses) in ALK-rearranged IMTs treated with crizotinib or alectinib.10 Nonetheless, therapeutic heterogeneity (ORR: 36%-100%), small sample sizes, and geographical bias necessitate standardised multicentre trials to validate efficacy and durability.

In summary, IMT represents a rare borderline neoplasm with intermediate malignant potential, distinct from the historically described IPT. The present case highlights the importance of accurate histopathological and immunohistochemical diagnosis, particularly in immunophenotypically atypical lesions, and underscores the need for long-term follow-up to monitor for potential recurrence.

Concept or design: X Mo.
Acquisition of data: Y Zhuang.
Analysis or interpretation of data: L Zhang.
Drafting of the manuscript: X Mo.
Critical revision of the manuscript for important intellectual content: C Chen.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This study was supported by the Science and Technology Development Project of Weifang (Ref No.: 2024YX077) and Weifang Youth Medical Talent Cultivation Support Program, China. The funders had no role in the study design, data collection/analysis/interpretation, or manuscript preparation.

This study was approved by the Ethics Committee of Weifang Second People’s Hospital, China (Ref No.: KY2024-077-01) and was conducted in accordance with the Declaration of Helsinki. The patient provided written informed consent for participation and publication of this case report, including the accompanying clinical images.

1. Höhne S, Milzsch M, Adams J, Kunze C, Finke R. Inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT): a representative literature review occasioned by a rare IMT of the transverse colon in a 9-year-old child. Tumori 2015;101:249-56. Crossref

2. Sagar AE, Jimenez CA, Shannon VR. Clinical and histopathologic correlates and management strategies for inflammatory myofibroblastic tumor of the lung. A case series and review of the literature. Med Oncol 2018;35:102. Crossref

3. Kiratli H, Uzun S, Varan A, Akyüz C, Orhan D. Management of anaplastic lymphoma kinase positive orbito-conjunctival inflammatory myofibroblastic tumor with crizotinib. J AAPOS 2016;20:260-3. Crossref

4. Surabhi VR, Chua S, Patel RP, Takahashi N, Lalwani N, Prasad SR. Inflammatory myofibroblastic tumors: current update. Radiol Clin North Am 2016;54:553-63. Crossref

5. Bedi D, Clark BZ, Carter GJ, et al. Prognostic significance of three-tiered World Health Organization classification of phyllodes tumor and correlation to Singapore General Hospital nomogram. Am J Clin Pathol 2022;158:362-71. Crossref

6. Pacheco E, Llorente JL, López-Hernández A, et al. Absence of chromosomal translocations and protein expression of ALK in sinonasal adenocarcinomas [in English, Spanish]. Acta Otorrinolaringol Esp 2017;68:9-14. Crossref

7. Baldi GG, Brahmi M, Lo Vullo S, et al. The activity of chemotherapy in inflammatory myofibroblastic tumors: a multicenter, European retrospective case series analysis. Oncologist 2020;25:e1777-84. Crossref

8. Mossé YP, Lim MS, Voss SD, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study. Lancet Oncol 2013;14:472-80. Crossref

9. Antoniu SA. Crizotinib for EML4-ALK positive lung adenocarcinoma: a hope for the advanced disease? Evaluation of Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. N Engl J Med 2010;363(18):1693-703. Expert Opin Ther Targets 2011;15:351-3. Crossref

10. Takeyasu Y, Okuma HS, Kojima Y, et al. Impact of ALK inhibitors in patients with ALK-rearranged nonlung solid tumors. JCO Precis Oncol 2021;5:PO.20.00383. Crossref