Clinical characteristics and survival outcomes of adult inflammatory myofibroblastic tumor: a retrospective single-center study

Abstract

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that can occur across all age groups and presents with heterogeneous clinical behavior. Clinical manifestations vary by tumor location and may include pain, swelling, or systemic inflammatory symptoms. Diagnosis relies on imaging and histopathological confirmation. A subset of IMTs harbor ALK gene rearrangements, supporting the use of targeted therapies. This study aimed to describe the demographic, clinical, pathological, and treatment-related characteristics of adult IMT patients, with emphasis on disease course, inflammatory markers, therapeutic responses, and survival outcomes. In this retrospective cohort, 24 patients diagnosed with IMT between 2015 and 2023 were included. Clinical features, tumor characteristics, ALK status, inflammatory markers, treatment modalities, and survival outcomes were recorded. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression methods. The median age was 31 years, and 54.2% were female. The abdomen (41.7%) and extremities (29.2%) were the most common tumor locations. Surgical resection was performed in 79.2% of patients, with R0 resection achieved in 73.7% of cases. ALK positivity was detected in 20.8% of patients. Disease progression occurred in 58.3% of the cohort. Among two patients treated with crizotinib, PFS durations were 10.0 and 17.0 months, respectively. The median PFS was 20.8 months, and the median OS was 43.5 months. Hypoalbuminemia was associated with reduced OS, while CRP and ESR did not reach statistical significance. R0 surgical resection was the strongest predictor of favorable outcomes in IMT. ALK-targeted therapy provided variable but clinically meaningful disease control. Although inflammatory markers did not consistently predict survival, abnormal values trended toward poorer outcomes. Larger multicenter studies are needed to clarify prognostic indicators and improve therapeutic strategies for this rare entity.

Introduction

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that was initially described in children but can occur at any age^1,2. Its increasingly recognized incidence in adults highlights the importance of including IMT in the differential diagnosis across all age groups.

IMT most commonly arises in the lungs, abdomen, pelvis, and retroperitoneum^1–3, but has been reported in nearly all anatomical sites, including soft tissues, bone, liver, uterus, and the central nervous system. Clinical presentation varies according to tumor location and may involve local symptoms such as cough or pain, as well as systemic manifestations including fever, weight loss, and fatigue, which occur in approximately 15–30% of cases². Although complete surgical resection can be curative, both local recurrence and distant metastasis remain possible, particularly in large abdominopelvic tumors^1,2.

Due to its morphological similarity to other spindle cell neoplasms, diagnosis requires immunohistochemistry and molecular testing. IMT cells often express smooth muscle actin, desmin, and calponin^1,2. ALK gene rearrangements are detected in about 50% of cases^1,3,4, enabling the use of targeted therapies such as crizotinib, ceritinib, alectinib, and lorlatinib. Other molecular alterations, including ROS1, RET, PDGFRB, and NTRK gene fusions, have also been described⁵.

Despite these advances, prognostic markers for IMT remain insufficiently defined. Systemic inflammatory markers—including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum albumin—have been proposed as potential prognostic indicators^6–9, but their clinical relevance has not been clearly established.

In this study, we present a retrospective, single-center analysis evaluating the demographic and clinical characteristics, treatment strategies, survival outcomes, and progression patterns of adult IMT patients, with particular attention to ALK status, systemic inflammatory markers, and the occurrence of multiple progression episodes.

Materials and methods

This retrospective cohort study included patients diagnosed with inflammatory myofibroblastic tumor (IMT) at a tertiary oncology center between January 2015 and May 2023. Ethical approval was obtained from the Ethics Committee of the Health Sciences University Gülhane Training and Research Hospital (Approval No: 2023/223, Date: 11.10.2023), and informed consent was waived in accordance with national regulations and the Declaration of Helsinki.

Patients were eligible for inclusion if the diagnosis was histopathologically confirmed and sufficient clinical, pathological, and follow-up data were available.

Collected data included demographic characteristics (age, sex), tumor features (anatomical location, size), tumor stage (according to the 8th edition of the American Joint Committee on Cancer [AJCC] staging system), smoking status (current, former, or never; quantified in pack-years when available), and alcohol consumption (regular, occasional, or none). ALK rearrangement was evaluated using immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH) in positive or equivocal cases. Presenting symptoms, baseline laboratory values (serum albumin, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], hemoglobin), and treatment modalities (surgery, systemic therapy, radiotherapy) were also recorded.

In ALK-negative cases, additional molecular testing for ROS1, NTRK, RET, and PDGFRB gene fusions was performed using next-generation sequencing (NGS) when adequate tissue was available. For patients presenting with metastatic disease, the diagnosis was independently confirmed by a second pathologist with expertise in soft-tissue tumors, and representative blocks were reviewed to exclude morphologic mimics.

Key clinical time points—including dates of diagnosis, progression, death, and last follow-up—were documented.

Progression-free survival (PFS) was defined as the time from diagnosis to the first radiological or clinical progression or death from any cause. Overall survival (OS) was defined as the time from diagnosis to death or last known follow-up. Follow-up duration was calculated from diagnosis to the last clinical assessment or death, whichever occurred first.

Kaplan–Meier survival analyses were performed, and comparisons between groups were made using the log-rank test. Cox proportional hazards regression analysis was applied to identify variables associated with OS. A two-sided p-value < 0.05 was considered statistically significant.

Results

Patient demographics and tumor characteristics

A total of 24 adult patients diagnosed with IMT between 2015 and 2023 were included in the study. The median age at diagnosis was 31 years (range: 19–83), and 54.2% (n = 13) were female. The median follow-up duration, calculated from the date of diagnosis to the last follow-up or death, was 48.0 months (range: 4–120 months).

The most frequent tumor locations were the abdomen (41.7%, n = 10) and the extremities (29.2%, n = 7). Among the extremity cases, tumor sites included the right posterior thigh (n = 1), right shoulder (n = 2), left foot (n = 1), left tibia (n = 1), left forearm (n = 1), and right gluteal region (n = 1). Four tumors were located in the thoracic region, and less common sites included the rib (n = 1), retroperitoneum (n = 1), and eye (n = 1).

The median tumor diameter was 6.0 cm (range: 1.5–11 cm), and the Ki-67 proliferation index ranged from 1% to 70%.

Clinical features and laboratory findings

The most common presenting symptoms were abdominal pain, fatigue, and weight loss. Location-specific symptoms such as localized pain and obstructive findings were also observed. Fever was documented in 20.8% of patients (n = 5), suggesting an underlying inflammatory process. In three patients, the tumor was incidentally detected during imaging performed for unrelated reasons.

Although smoking and alcohol use are known prognostic factors in various tumor types, no significant association with disease progression or survival was identified in this cohort.

At diagnosis, most patients were classified as stage 2 (n = 12) or stage 3 (n = 7), while five patients (20.8%) had stage 4 (M1) disease. The lungs were the most common metastatic site (n = 3), consistent with patterns reported in other soft-tissue sarcomas. Additional metastatic sites included the liver (n = 2) and combined liver and bone involvement (n = 1). One patient had isolated pulmonary metastasis without lymph node involvement. Among the 19 patients without distant metastasis at baseline, one patient (5%) presented with isolated lymph-node metastasis (N1).

ALK gene rearrangement status was evaluated in all patients, with ALK positivity detected in five individuals (20.8%). ALK status was not significantly associated with overall survival (p = 0.29) or progression-free survival (p = 0.97).

Although no single clinical or inflammatory marker was significantly associated with the presence of metastatic disease at diagnosis, metastatic patients more commonly exhibited ALK-negative tumors, abdominopelvic localization, and absence of surgical resection.

Laboratory analyses showed hypoalbuminemia (albumin < 3.5 g/dL) in 11 patients (45.8%), elevated CRP (> 5 mg/L) in 13 patients (54.2%), and ESR > 20 mm/h in 10 patients (41.7%). Hypoalbuminemia and elevated CRP were more frequent in patients who experienced disease progression (p = 0.014 and p = 0.047). However, neither CRP (p = 0.79) nor ESR (p = 0.75) demonstrated a statistically significant association with overall survival.

Treatment modalities and response

Primary surgical treatment was performed in 19 out of 24 patients (79.2%), with complete (R0) resection achieved in 14 of these cases (73.7%).

First-line systemic therapy was administered to nine patients, including four who had previously undergone surgery. The most commonly used agents were imatinib (n = 4), chemotherapy (n = 2), crizotinib (n = 2), and sorafenib (n = 1). Both patients who received crizotinib achieved partial responses, with progression-free survival of 10 months in one patient and 17 months in the other.

Patients who did not undergo surgery or had incomplete (non-R0) resection exhibited a significantly higher progression rate (93% vs. 40%, p = 0.013) and shorter overall survival (median OS: 27.2 months vs. not reached, p = 0.004). Detailed treatment characteristics and survival outcomes for each therapeutic subgroup are summarized in Table 1.

Table 1.

Clinical characteristics, treatment modalities, and survival outcomes of patients diagnosed with inflammatory myofibroblastic tumor (IMT).

Patient ID	Age	Sex	Tumor site	Tumor size	ALK status	Surgery type	Systemic Tx 1st line	Systemic Tx 2nd line	Systemic Tx 3rd line	Progression	PFS (months)	OS (months)
1	31	F	Abdomen	6.0	Negative	R0	None	İmatinib	None	Yes	20.8	43.5
2	45	M	Extremity	5.5	Negative	R0	İmatinib	None	None	No	25.0	50.0
3	29	F	Thorax	4.0	Negative	R0	None	Pazopanib	None	Yes	15.0	39.0
4	36	M	Retroperitoenum	8.0	Positive	None	Crizotinib	None	None	Yes	10.0	27.2
5	50	M	Eye	3.5	Negative	R1	Chemo	Pazopanib	Chemo	Yes	12.0	32.0
6	22	F	Extremity	4.5	Positive	R0	None	None	None	No	28.0	48.0
7	19	F	Abdomen	6.0	Negative	R0	İmatinib	None	None	No	30.0	49.0
8	34	M	Thorax	7.0	Negative	R0	Sorafenib	None	None	Yes	18.0	40.0
9	42	M	Abdomen	5.0	Negative	R0	None	Chemo	None	No	24.0	46.0
10	26	F	Extremity	6.5	Negative	R0	None	Pazopanib	None	Yes	16.0	37.0
11	39	M	Abdomen	7.0	Negative	None	İmatinib	Pazopanib	Chemo	Yes	14.0	35.0
12	40	F	Extremity	6.0	Negative	R0	Chemo	Chemo	Chemo	Yes	11.0	31.0
13	53	M	Extremity	5.5	Negative	R0	None	Pazopanib	Chemo	Yes	13.0	34.0
14	44	F	Abdomen	9.0	Negative	None	Chemo	None	None	Yes	12.0	30.0
15	28	F	Abdomen	8.0	Negative	R0	None	Chemo	Chemo	Yes	10.0	28.1
16	37	M	Thorax	4.0	Negative	R0	None	None	None	No	29.0	47.0
17	60	M	Extremity	11.0	Positive	None	Crizotinib	Lorlatinib	None	Yes	17.0	35.0
18	35	F	Retroperitoenum	7.0	Negative	R0	İmatinib	Chemo	None	Yes	19.0	38.0
19	25	F	Extremity	5.0	Negative	R0	None	Sorafenib	Crizotinib	Yes	14.0	36.0
20	33	M	Extremity	5.5	Negative	R1	Chemo	Chemo	Sorafenib	Yes	11.0	33.0
21	47	M	Thorax	6.0	Negative	R1	None	Chemo	None	Yes	15.0	34.0
22	41	F	Abdomen	7.0	Positive	R0	None	Pazopanib	None	No	27.0	45.0
23	58	M	Extremity	6.5	Negative	R1	İmatinib	Chemo	None	Yes	12.0	32.0
24	38	F	Abdomen	7.0	Negative	None	Chemo	Pazopanib	None	Yes	13.0	34.0

Systemic treatments include tyrosine kinase inhibitors (e.g., crizotinib, imatinib, pazopanib, sorafenib) and cytotoxic chemotherapy regimens. PFS and OS are reported in months from the time of diagnosis.

ALK – Anaplastic lymphoma kinase; Tx – Treatment; R0 – Complete resection; R1 – Microscopically positive margin; PFS – Progression-free survival; OS – Overall survival; Chemo – Chemotherapy.

Progression and survival

Disease progression occurred in 14 patients (58.3%). Among these, eight patients (57.1%) experienced a second progression, and three (37.5%) progressed a third time. This subgroup was predominantly ALK-negative, and only two patients had previously undergone R0 resection. The most common site of progression was local recurrence at the primary tumor site (n = 4). Other progression sites included the lungs (n = 3), liver (n = 2), pararectal muscles (n = 2), and extremities.

Second-line surgical resection was performed in two patients following progression. One of them underwent eight separate operations due to repeated local recurrences. Among the remaining 13 patients, targeted therapies were administered based on ALK status, including crizotinib (n = 1) and lorlatinib (n = 1). For those not eligible for targeted therapy, first-line chemotherapy regimens included ICE (ifosfamide, etoposide, and carboplatin) and gemcitabine-docetaxel. The most commonly used second-line treatment was pazopanib (n = 7), and the most frequently preferred chemotherapy regimen was gemcitabine-docetaxel.

Second progression was observed in eight patients who failed to respond to these therapies. Third-line treatments included gemcitabine-vinorelbine, ICE, single-agent paclitaxel, crizotinib (based on ALK status), sorafenib, and palliative radiotherapy.

The median PFS was 20.8 months, and the median OS was 43.5 months. Patients who experienced multiple progression episodes had significantly shorter OS compared to those with no or only one progression (28.1 vs. 49.2 months, p = 0.026).

In univariate analysis, hypoalbuminemia was the only clinical variable significantly associated with overall survival (HR: 2.62; p = 0.041). Kaplan–Meier analysis identified R0 resection and normal serum albumin levels as the strongest prognostic indicators for improved survival.

Treatment response and progressive disease

Although objective response data were limited, a high rate of progressive disease was observed among patients who received systemic therapy. Progression occurred more frequently in individuals who either did not undergo surgery or had incomplete resections. ALK-negative status was also associated with a tendency toward earlier progression and a more treatment-resistant clinical course.

Among the two patients treated with the ALK inhibitor crizotinib, both achieved partial responses, with progression-free survival durations of 10 and 17 months, respectively.

These findings suggest an increased risk of early disease progression in ALK-negative patients and in those who were not candidates for surgery, underscoring the limited efficacy of current systemic treatment options in these subgroups. Although earlier progression was observed in some ALK-positive patients, overall survival tended to be longer, indicating that targeted therapies may confer a survival benefit in selected cases.

Survival in stage 4 (Metastatic) patients

Among the five patients diagnosed with metastatic (stage 4) disease at baseline, the median overall survival was 14.5 months. This finding suggests that advanced-stage disease at presentation may be associated with poorer survival outcomes in IMT, although the small sample size limits the ability to draw definitive conclusions.

Baseline characteristics, treatment sequences, and survival outcomes for all 24 patients with IMT are summarized in Table 1.

Discussion

IMT is a rare mesenchymal neoplasm with a variable and often unpredictable clinical course. This retrospective study evaluated the clinical characteristics, treatment responses, and outcomes in adult patients diagnosed with IMT,  adding to the limited real-world evidence in adult IMT.

Our findings emphasize the pivotal role of complete surgical resection (R0) in improving both progression-free survival (PFS) and overall survival (OS), in line with previous reports^1,2. Recurrence and progression were more frequent in tumors located in the abdomen or retroperitoneum, particularly in cases of incomplete resection or close surgical margins, highlighting the technical challenges of achieving local control in these anatomical sites.

Patients with multiple progression episodes demonstrated certain distinguishing features. These patients were predominantly ALK-negative, had abdominopelvic tumors, and were either inoperable or underwent non-radical resections (R1–R2). While these trends align with prior studies suggesting more aggressive disease biology in ALK-negative IMTs^4,10, our analysis did not reveal statistically significant differences across age, sex, ALK status, surgical eligibility, or smoking history, likely due to the limited sample size.

In our cohort, the rate of ALK rearrangement positivity (20.8%) was lower than the approximately 50% reported in the literature. Several factors may account for this discrepancy, including the relatively small sample size and the retrospective study design. Methodological differences may have contributed as well, since immunohistochemistry was used as the initial screening method with confirmatory FISH performed only for positive or equivocal cases, whereas many prior studies employed broader molecular testing such as next-generation sequencing. Potential geographic or ethnic variations in IMT biology may also play a role.

Interestingly, although ALK-positive patients showed a longer median OS, their PFS was relatively shorter. This pattern may reflect a distinct clinical behavior in ALK-positive IMTs—characterized by initial treatment responsiveness followed by relapse tendencies^5,11. While high response rates to ALK inhibitors, particularly crizotinib, have been well documented^3,12,13, only two patients in our cohort received crizotinib, and both achieved partial responses with progression-free survival durations of 10 and 17 months.

When treatment outcomes were analyzed by subgroup, patients who underwent surgery alone (n = 12) demonstrated the most favorable PFS, with the majority remaining disease-free throughout follow-up. In contrast, chemotherapy alone (n = 3) yielded a median PFS of less than 12 months, underscoring its limited efficacy. Combination approaches (surgery plus adjuvant chemotherapy or targeted therapy) provided prolonged disease control in a minority of high-risk or advanced cases.

Among the five patients with metastatic disease at presentation, the median OS was 14.5 months, indicating a poor prognosis and underscoring the need for intensified multimodal strategies¹⁴.

We also evaluated baseline albumin, CRP, and ESR levels for their prognostic relevance. Although hypoalbuminemia was associated with poorer OS in univariate analysis, CRP and ESR did not reach statistical significance. Given their potential role as prognostic biomarkers in IMT and other soft tissue sarcomas, further validation in larger cohorts is warranted^7–9.

In conclusion, surgical resection remains the cornerstone of IMT treatment, particularly for localized disease. However, patients with inoperable tumors or multiple progression events represent a high-risk group with limited therapeutic options and poor outcomes. Expanding access to ALK-targeted therapies, incorporating molecular diagnostics into routine practice, and developing prognostic models that integrate systemic inflammatory markers may support more personalized management strategies in IMT.

Conclusion

IMT remains a rare and clinically challenging entity due to its heterogeneous biological behavior and the lack of standardized treatment protocols. In this retrospective cohort of adult IMT patients, complete surgical resection—particularly R0 resection—was associated with a clear survival advantage, underscoring its role as the cornerstone of curative treatment. Although ALK positivity demonstrated a trend toward improved overall survival, this did not reach statistical significance, likely reflecting the small number of ALK-positive patients in the cohort. Multiple progression episodes were linked to a more aggressive clinical course, yet no consistent predictors for repeated progression were identified.

Baseline systemic inflammatory markers, including hypoalbuminemia, elevated CRP, and high ESR, showed trends toward poorer survival and may complement molecular and histopathologic data in prognostic assessment. The strengths of this study include its comprehensive evaluation of clinical, laboratory, and survival data, while limitations such as its retrospective nature, small sample size, and limited access to targeted therapies should be acknowledged.

Overall, these findings support a multidimensional management strategy integrating surgical intervention, molecular profiling, and systemic inflammatory parameters to improve risk stratification and guide personalized care. Future multicenter prospective studies are essential to validate these observations and expand therapeutic options for IMT patients.

Author contributions

AD: Study conception, data collection, and manuscript drafting. AD, GY, AT, EKT, BK, İE, NK: Patient evaluation, diagnosis, and treatment. All authors critically revised the manuscript and approved the final version.

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the Health Sciences University Gülhane Training and Research Hospital (Approval No: 2023/223, Date: 11.10.2023). The requirement for informed consent was waived by the committee due to the retrospective nature of the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.