OBJECTIVE: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood.
UNASSIGNED: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed.
RESULTS: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients.
CONCLUSIONS: Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

BACKGROUND: The objective of this study was to investigate the clinical characteristics, diagnosis, and treatment of inflammatory myofibroblastoma tumor (IMT) in the thyroid gland.
METHODS: A total of 17 patients with IMT by pathology from 2010 to 2020 were included in this study. Clinical features, imaging features, treatment, and prognosis were analyzed in this retrospective study.
RESULTS: The case series comprised 5 males and 12 females, with an average age of 49.6 ± 15.36 years. The patients were divided into two cohorts: with IMT without further pathological changes and with further pathological changes of the thyroid gland (e.g., nodular goiter or autoimmune thyroid disease). No significant differences were detected in tumor size and extrathyroid extension between the two groups. Fine needle aspiration biopsy examination before the operation was performed in 2 cases, and rapid freezing pathology examination during the operation was performed in 7 cases. Ultrasound images of 5 cases with only one type of pathology, IMT, presented a high and intermediate risk of malignancy. In the other 11 cases with further pathological changes of the thyroid gland, the image could be very low risk of malignancy or benign feature. Only 2 cases showed a high risk of malignancy ultrasound features. 5/17 patients underwent preventive cervical lymph node dissection additional to thyroid surgery. None of the lymph nodes were confirmed positive by postoperative pathology. Thyroid ultrasound, computed tomography scan of the lungs, abdomen ultrasound, and thyroid function tests were routine follow-up tests. During the follow-up period of 26-141 months, 2 cases were lost, and remaining 15 cases had no recurrence or metastasis and were considered cured.
CONCLUSIONS: IMT in the thyroid gland is a rare disease with a good prognosis and surgical resection is the preferred treatment.

Inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm that frequently arises in the lung and accounts for ~1% of lung tumors. Distant metastatic IMT is extremely rare and has been poorly investigated. This analysis was specifically performed to explore the clinicopathological and genetic features of early distant metastatic IMT. Two typical patients with distant metastatic IMTs were selected, which accounted for 1.13% of all diagnosed IMTs in the last 5 years. One patient was a 55 year-old male, and the other patient was a 56 year-old female. Both primary tumors arose from the lung, and the initial clinical symptoms of the two patients involved coughing. Both of the imaging examinations showed low-density nodular shadows in the lungs with enhancement around the mass. Microscopically, dense arranged tumor cells, prominent cellular atypia, and high mitotic activity with atypical form were more prominent in the metastatic lesions than in the primary lesions. All of the primary and metastatic tumors in both cases showed positive anaplastic lymphoma kinase (ALK) immunostaining and ALK rearrangement via fluorescence in situ hybridization. The EML4 (exon 6)-ALK (exon 20) fusion variant (v3a/b) was identified by using next-generation sequencing (NGS) and was verified by using reverse transcription polymerase chain reaction (RT-PCR). Furthermore, intronic variants of NOTCH1 and synonymous variants of ARAF were also detected via NGS in one IMT for the first time and were verified in all of the primary and metastatic lesions via PCR. Distant metastasis occurred during a short period of time (1 and 2 months) after the first surgery. One patient presented with multiple metastases to the subcutaneous tissue and bone that responded to ALK inhibitor alectinib therapy, and the tumor was observed to regress 10 months after the initial ALK inhibitor therapy. In contrast, the other patient presented with subcutaneous neck metastasis without ALK inhibitor treatment and succumbed to the disease within 3 months after the surgery. This study demonstrated the possible role of EML4-ALKv3a/b in the malignant progression of IMT and proposed certain therapeutic effects of ALK inhibitors on multiple metastatic IMTs.

Background: Inflammatory myofibroblastic tumor (IMFT) is a rare neoplasm mainly affecting children and young adults. We conducted a retrospective study to evaluate the clinical features and treatment alternatives of childhood inflammatory myofibroblastic tumors. Methods: A total of 19 patients who were pathologically diagnosed with IMT between December 2008 and October 2018 were included. Collected data were demographic information, main complaints, tumor characteristics, treatment, pathological results, immunohistochemical analysis, and prognosis. Results: The male/female ratio was 13:6. The mean age at disease onset was 44.9 ± 33.9 months (range 4 to 111 months). The mean tumor size was 6.5 ± 4.0 cm (range 1.2 to 17.0 cm). The most common site was the abdomen (13/19). The most commonly used detection tool was CT. Eleven patients (57.9%) had aggressive tumor growth, including eight receiving extensive resection and three receiving palliative resection due to high local invasiveness and postoperative chemotherapy. Eight cases whose tumors were completely enveloped received complete resection. Immunohistochemistry was performed for 17 patients and ALK positivity was found in 11 patients. Despite three children lost to follow-up, sixteen patients were followed up for 6 to 132 months (average 63.9 months, median 66 months). Of which, twelve children survived with no evidence of IMT, and four cases (21%) showed local recurrences (two of them died). No distant metastasis was detected. Conclusions: IMT is rare in children with various locations, mostly appearing in the abdomen. Whether the tumor could be completely removed, the location and the invasiveness of surrounding tissues might be highly prognosis-related.

Uterine inflammatory myofibroblastic tumors (IMTs) have been reported in association with pregnancy and, in some instances, secondarily involve the placenta. The clinicopathological spectrum of these tumors in the setting of pregnancy is not well defined. We investigated the clinical, morphologic, immunohistochemical, molecular cytogenetic, and genetic features of 6 uterine IMTs occurring in pregnant women. Each tumor was discovered at parturition, and none was identified by prenatal ultrasound. Patient age ranged from 25 to 41 years (mean 31.5). Tumor size ranged from 1.5 to 9 cm (mean 4.7). Four of 6 had usual IMT features, with at least focal deciduoid change in 3. Necrosis was identified in 3 tumors; and multinucleated cells, in 3 tumors. Sex hormone receptor expression was consistent with estrogen receptor negative or focally weakly positive and progesterone receptor diffusely moderately or moderately to strongly positive in all 6 tumors. ALK immunohistochemistry was strongly positive in 5 tumors, and all of these had an ALK rearrangement detected by break-apart fluorescence in situ hybridization. Subsequent RNA sequencing of these 5 tumors identified a TIMP3-ALK fusion in 4 and a THBS1-ALK in 1. In the ALK-negative tumor, RNA sequencing detected a novel TIMP3-RET fusion that was confirmed by RET break-apart fluorescence in situ hybridization. Follow-up was available for 2 of 6 patients 5 and 19 months after diagnosis. Neither patient developed recurrence. ALK immunohistochemistry will distinguish most uterine IMTs, but if ALK expression and gene studies are negative, in the appropriate morphologic context, evaluation of other tyrosine kinase genes known to be more commonly altered in extrauterine IMTs such as ROS1, NTRK3, PDGFRβ, and RET may be necessary for diagnostic confirmation.

Based on histological findings, calcifying fibrous tumor (CFT) may be a late (burned out) stage of inflammatory myofibroblastic tumor (IMT). This concept, however, has not been proven by molecular means. Five CFTs were analyzed for IMT-related rearrangements in ALK, ROS1 and RET using fluorescence in situ hybridization (FISH). Additionally, genome-wide methylation patterns were investigated and compared with IMT (n = 7), leiomyoma (n = 7), angioleiomyoma (n = 9), myopericytoma (n = 7) and reactive soft tissue lesions (n = 10) using unsupervised hierarchical cluster analysis and t distributed stochastic neighbor embedding. CFT patients, 4 females and 1 male, had a median age of 20 years ranging from 7 to 43 years. Two patients were younger than 18 years old. The tumors originated in the abdomen (n = 4) and axilla (n = 1). Histologically, all lesions were (multi) nodular and hypocellular consisting of bland looking (myo)fibroblasts embedded in a collagenous matrix with calcifications. FISH analysis brought up negative results for ALK, RET and ROS1 rearrangements. However, genome-wide methylation analysis revealed overlapping methylation patterns of CFT and IMT forming a distinct homogeneous methylation cluster with exception of one case clustering with myopericytoma/angioleiomyoma. In conclusion, DNA methylation profiling supports the concept that CFT and IMT represent both ends of a spectrum of one entity with CFT being the burn out stage of IMT.

Objective: To present 15 cases of inflammatory myofibroblastic tumor (IMT) in genitor-urinary system, and analyze the characteristics, diagnosis and treatment of the disease. Methods: The diagnostic and therapeutic process of 15 confirmed cases admitted to Sun Yat-sen University Cancer Center between March 2009 and September 2017 were retrospectively analyzed. Of the total cases, 11 cases were diagnosed with cystic IMT with a maximum diameter of 1.0-4.5 cm, 8 cases underwent transurethral resection of bladder tumor(TURBT)and 4 of them underwent partial cystectomy after TURBT and 3 underwent partial cystectomy directly. Two cases were renal IMT with a maximum diameter of 4.0-9.0 cm, one underwent partial nephrectomy and the other accepted radical nephrectomy. One case who was diagnosed with prostatic IMT with a maximum diameter of 3.4 cm underwent transurethral resection of the prostate (TURP) and postoperative radiotherapy. One case who was diagnosed with perineal IMT with a maximum diameter of 2.1 cm underwent tumor resection. Results: The patients were followed up for 10-32 months with a median time of 27 months. No cases relapsed during the follow-up. Conclusion: Surgery is the preferred method for treating IMT in genitor-urinary system. Retrospective study shows a good prognosis in IMT patients, but a long-term follow-up is still required.
目的： 探讨发生于泌尿生殖系统炎性肌纤维母细胞瘤（IMT）的临床特点与诊治方法。 方法： 回顾性分析中山大学附属肿瘤医院2009年3月至2017年9月收治15例发生于泌尿生殖系统IMT、并且接受外科治疗的临床资料。其中男5例，女10例；年龄20~76岁，平均47岁；其中膀胱IMT 11例，肿瘤最大直径1.0~4.5 cm；经尿道膀胱肿瘤电切术8例，其中4例经尿道膀胱肿瘤电切术后行膀胱部分切除；直接行膀胱部分切除术3例；肾脏IMT 2例，肿瘤最大直径4.0~9.0 cm；肾部分切除术1例，肾切除术1例；前列腺IMT 1例，行经尿道前列腺电切术，肿瘤较大，术后复查提示肿瘤残留，行术后放疗；外阴IMT 1例，行手术切除。 结果： 随访10~32个月，平均27个月，膀胱肿瘤术后无复发；肾脏IMT手术治疗2例均无复发；前列腺IMT术后行辅助放疗、外阴IMT术后随访均无复发。 结论： 泌尿生殖系统炎性肌纤维母细胞瘤临床少见，治疗以手术切除为主，手术尽量将肿瘤连续完整切除以及尽可能保留器官功能。虽然预后良好，仍需要长期随访。.

Inflammatory myofibroblastic tumors (IMT) are a rare clinicopathological entity of yet unknown etiology and those located retroperitoneally are even rarer. Clinical outcome is unpredictable and complete surgical resection of the tumor remains the principal treatment. We report the case of a 41-year old man presented with abdominal pain. An abdominal magnetic resonance imaging scan revealed a retroperitoneal tumor located between the pancreas, stomach small curvature and big vessels. A laparotomy with biopsy was performed because the tumor was not amenable to surgical resection. Histopathological examination concluded to an IMT with overexpression of protein p53. Epstein-Barr virus and Human Herpesvirus-8 investigation was negative. Postoperative outcome was unfavorable.

Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal tumors initially described in the lung. About half of them exhibit expression of the ALK1 protein, generally resulting from a gene rearrangement. Paranasal sinus IMTs are extremely uncommon, and gene rearrangement of ALK1 is very rare in this localization. A 47-year-old woman presented with rapidly progressive vision loss in her left eye. Clinical and imaging work-up revealed a tumor invading the left ethmoidal and sphenoidal sinuses and extending into the nasal cavity, the orbit and the skull base. Complete tumor resection was performed using an endonasal approach. Pathological examination revealed a paranasal localization of IMT, positive for ALK1 immunostaining. FISH analysis showed an ALK1 gene rearrangement. This case illustrates the local aggressive potential for IMTs. Treatment is primarily surgical, but targeted therapies (crizotinib) might be a solution for ALK1 rearranged cases with a poor prognosis.