What is the diagnosis and management of a myofibroblastic tumour (soft tissue neoplasm)?

Myofibroblastic Tumour: Diagnosis and Management

Overview and Classification

Myofibroblastic tumours represent a heterogeneous group of neoplasms ranging from benign to locally aggressive, with inflammatory myofibroblastic tumour (IMT) being the most clinically significant subtype requiring specialized management. 1

These tumours are classified in the 2020 WHO classification system based on biologic behavior: benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant categories. 2 Myofibroblastic tumours demonstrate spindle cells with ultrastructural features of both smooth muscle cells and fibroblasts. 3

Immediate Referral Criteria

• All patients with suspected myofibroblastic tumours must be referred immediately to a specialist sarcoma multidisciplinary team (MDT) for comprehensive evaluation and management. 1, 4
• Referral should occur for any unexplained deep soft tissue mass or superficial lesion ≥5 cm in diameter. 1
• The MDT should include pathologists, radiologists, surgical oncologists, radiation oncologists, and medical oncologists. 1

Diagnostic Workup

Imaging Protocol

• MRI is the primary imaging modality for extremity and soft tissue lesions, providing optimal detail for diagnosis and surgical planning. 1, 4, 5
• CT chest is mandatory to exclude pulmonary metastases, as metastases occur in <5% of IMT cases but represent a critical prognostic factor. 1
• Standard radiographs may be useful initially to rule out bone involvement and detect calcifications. 1
• Consider FDG-PET/CT before radical surgery, though not yet proven as routine investigation. 4

Tissue Diagnosis

• Multiple core needle biopsies using 14-16G needles represent the standard diagnostic approach. 1, 5
• The biopsy must be planned by the sarcoma MDT so the biopsy tract can be safely excised during definitive surgery. 1, 4, 5
• Excisional biopsy may be appropriate for superficial lesions <3 cm. 1
• Fine-needle aspiration is not recommended outside specialized centers with specific expertise. 1
• Collect fresh snap-frozen tissue when possible to allow subsequent molecular assessments. 1

Pathological Assessment

• Histological diagnosis must follow the 2020 WHO Classification for soft tissue and bone tumours. 1, 4
• Expert pathology review is mandatory for all diagnoses made outside reference centers, as discrepancy rates range from 8-11% for major discordance and 16-35% for minor discordance. 1, 4
• Immunohistochemistry should include vimentin, muscle actin (HHF35), alpha-smooth muscle actin, calponin, and desmin. 6
• Molecular testing for ALK gene fusions is critical, as these occur in 50-60% of IMTs and determine targeted therapy eligibility. 1
• Testing for NTRK fusions should be performed in ALK fusion-negative cases, as these rarely occur but have therapeutic implications. 1
• DNA flow cytometry may help predict biological behavior, as aneuploid tumours demonstrate higher risk of recurrence or metastasis. 3

Treatment Strategy

Localized Disease

• Complete surgical resection with negative margins (R0 resection) is the primary curative treatment for localized myofibroblastic tumours. 1, 5, 7
• Surgery should be performed at a sarcoma reference center treating high volumes of patients annually. 1, 5
• Local recurrence occurs in 25% of children with extrapulmonary IMT, necessitating wide excision. 1
• Complete resection can be associated with significant morbidity depending on anatomic location. 1

Advanced or Unresectable Disease

• For ALK fusion-positive IMT that is unresectable or metastatic, crizotinib represents first-line targeted therapy with response rates exceeding 80%. 1
• This recommendation is based on anecdotal evidence of crizotinib activity in inflammatory myofibroblastic tumours with ALK translocations. 1
• Patients should be treated at reference centers, preferably within clinical trials or prospective registries. 1

NTRK Fusion-Positive Tumours

• For the rare NTRK fusion-positive myofibroblastic tumours, TRK inhibitors should be considered as targeted therapy. 1
• These patients require molecular confirmation and should be managed in specialized centers. 1

Prognostic Factors

• ALK fusion-negative IMT may have worse prognosis, accounting for all metastatic cases in some series. 1
• Aneuploid DNA content by flow cytometry correlates with local recurrence or distant metastases. 3
• Tumour size, location, and completeness of resection significantly impact outcomes. 1, 7

Follow-Up Protocol

• High-risk patients require follow-up every 3-4 months for the first 2-3 years, every 6 months up to year 5, and annually thereafter. 1, 8
• Surveillance should focus on chest imaging (CT preferred for earlier detection of pulmonary metastases) and local recurrence assessment with MRI. 1, 8
• Low-risk patients may be followed every 4-6 months with less frequent chest imaging in the first 3-5 years, then annually. 1, 8

Critical Pitfalls to Avoid

• Never perform biopsy before MDT discussion, as improper biopsy tract placement can compromise definitive surgical resection. 1, 4, 5
• Do not rely on frozen section technique for immediate diagnosis, as it does not allow complete diagnosis and may underestimate malignancy grade. 1
• Avoid managing these patients outside specialized sarcoma centers, as outcomes are significantly better with centralized care. 1
• Do not assume benign behavior based solely on histologic appearance, as some IMTs with benign morphology demonstrate malignant clinical course. 3
• Always test for ALK fusions, as missing this diagnosis denies patients highly effective targeted therapy. 1