Footing the diagnosis – Inflammatory myofibroblastic tumor of the ankle

INTRODUCTION

Inflammatory myofibroblastic tumor (IMT) is a rare, borderline neoplasm characterized by the proliferation of myofibroblastic spindle cells within an inflammatory microenvironment.^[1] Initially considered a reactive lesion, IMT is now recognized as a true neoplasm due to its potential for local recurrence, rare metastasis, and association with specific genetic alterations, particularly involving the ALK gene. IMT predominantly affects children and young adults. IMTs can occur in various soft tissues and organs; however, occurrence in the ankle is exceptionally rare. Other common sites affected are the lungs, orbit, abdomen, and soft tissues.^[1,2] Clinically, patients may present with non-specific symptoms such as fever, weight loss, or pain, depending on the tumor’s location. Despite its generally indolent behavior, IMT’s unpredictable clinical course underscores the need for accurate diagnosis and tailored management.

CASE REPORT

A 37-year-old female presented with complaints of pain and swelling in the right ankle and leg region for the last 1 month. All the laboratory parameters were normal. On examination, there was a 7 × 5 cm soft, non-tender swelling in the posteromedial aspect of the distal leg and ankle [Figure 1]. On ultrasound (USG), there was a well-defined lobulated soft-tissue lesion in the posteromedial aspect of the distal leg underneath the Achilles tendon without its involvement [Figure 2]. On color Doppler, the posterior tibial artery was adjacent to the lesion, and mild vascularity was seen within the lesion [Figure 3]. On magnetic resonance imaging, the lesion was heterogeneously hyperintense on T2 and isointense on proton density, with heterogeneous post-contrast enhancement [Figure 4]. There was no fat content within the lesion, and it showed no blooming on gradient echo (GRE) sequences. The lesion was seen separate from the tendons and the nerves, with maintained fat planes. There were maintained fat planes with the adjacent bone. There were no adjacent inflammatory changes. A USG-guided percutaneous biopsy was performed via the lateral approach by avoiding the neurovascular bundle. Histopathology showed benign myofibroblastic proliferation.

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Figure 1:

A 37-year-old female presented with pain and swelling in the right ankle and leg region. Clinical examination shows a 7 × 5 cm soft, non-tender swelling in the posteromedial aspect of the right distal leg and ankle (white arrow).

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Figure 2:

A 37-year-old female presented with pain and swelling in the right ankle and leg region. Ultrasound of the right ankle in the (a) longitudinal and (b) short axis views shows a multilobulated hypoechoic lesion (* in a and b) in the posterior compartment of the distal leg, measuring 2.2 × 3.9 × 5.8 cm. It was deep to the Achilles tendon (white arrow in a and b) and superficial to the flexor hallucis longus (FHL) with loss of fat planes with adjacent FHL.

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Figure 3:

A 37-year-old female presented with pain and swelling in the right ankle and leg region. (a) On color Doppler, there is mild vascularity within the lesion (*). (b) The posterior tibial artery (white arrow) is adjacent to the lesion (*).

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Figure 4:

A 37-year-old female presented with pain and swelling in the right ankle and leg region. (a) Axial T2-weighted sequence of the magnetic resonance imaging of the ankle shows a well-defined lobulated lesion (*) of intermediate signal intensity in the posterior aspect, superficial to the flexor hallucis longus and deep to the Achilles tendon (white arrow). (b) Sagittal non-fat saturated proton density sequence shows the lesion (*) with isointense signal intensity as compared to the muscles. (c) Axial gradient echo sequence shows no areas of susceptibility within the lesion (*).

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DISCUSSION

“Inflammatory” suggests that there is inflammation, and “myofibroblastic” refers to the myofibroblasts, which are the cells involved in wound healing and fibrosis. “Tumor” indicates growth. Hence, IMT is a tumor composed of myofibroblasts with inflammation.

IMT is a rare neoplasm of the mesodermal cells that form the connective tissues, which support virtually all of the organs and tissues of the body. IMT was formerly termed an inflammatory pseudotumor. At present, however, inflammatory pseudotumor designates a large and heterogeneous group of soft tissue tumors that include IMT, plasma cell granuloma, xanthomata’s pseudotumor, solitary mast cell granuloma, inflammatory fibrosarcoma, pseudosarcomatous myofibroblastic proliferation, myofibroblastoma, inflammatory myofibrohistiocytic proliferation, and other tumors that develop from connective tissue cells.

IMT typically consists of myofibroblastic spindle cells, i.e., specialized cells that are longer than wide, have a microscopic appearance that merges the appearances of fibroblasts and smooth muscle cells, occur in normal as well as tumor tissues, and in normal tissues are commonly designated as fibroblasts. However, some cases are dominated by sheets of epithelioid cells (which may have rounded shapes) with only a minor component of spindle cells. Tumors with these characteristics are regarded as a subtype of IMT termed epithelioid inflammatory myofibroblastic sarcoma.

IMT may have an association with infections or inflammatory processes. An underlying genetic alteration, such as the ALK gene rearrangement, may predispose to IMT (which may serve as a potential therapeutic target).^[3]

Imaging plays a pivotal role in the diagnosis, staging, treatment planning, and follow-up of IMT. While histopathology and molecular testing confirm the diagnosis, imaging provides critical insights into tumor location, extent, and behavior. USG is useful in cases of superficial lesions (e.g., abdominal wall and pediatric cases). The lesions are well defined with a heterogeneous hypoechoic echotexture. Color Doppler shows internal vascularity. Apart from diagnosis, USG plays an important role in image-guided percutaneous biopsies. On computed tomography, these tumors are usually hypodense to the skeletal muscle. Fat stranding is common adjacent to the tumors, implying the inflammatory nature. There is variable enhancement. Calcifications and necrosis are rare.^[4] On magnetic resonance imaging, they have intermediate to low signal intensity on both T1 and T2 sequences. The edematous components are hyperintense on T2, whereas the fibrotic areas are hypointense. The enhancement pattern is variable. Restriction on diffusion weighted imaging sequence depends on the cellularity of the tumor, ranging from strong to no restriction. IMT of the urinary bladder shows no diffusion restriction due to the abundant edematous mucus background.^[5] Maxillofacial lesions exhibit marked enhancement.^[6] Radiology plays an important role in delineating the exact extent of the lesion for planning of surgical resection.

Radiological pointers that predict the likelihood of post-surgical recurrence include large tumor size, ill-defined/spiculated margins, infiltration into adjacent structures, heterogeneous appearance and enhancement, diffusion restriction, etc. Calcification and fibrosis are inversely related to the risk of recurrence.

Histopathologic examination of the tumors in IMT generally reveals myofibroblastic spindle cell sheets in a myxoid background. The matrix also contains inflammatory cells, particularly plasma cells and lymphocytes, occasionally mixed with eosinophils and neutrophils. On immunohistochemical analysis, IMTs are positive for ALK (50–60%), smooth muscle actin, and desmin.

The differentials for IMT are extensive and include pathologies under broad categories such as inflammatory lesions (immunoglobulin G4-related disease, granulomatous diseases, nodular fasciitis), benign soft-tissue tumors (fibromatosis, solitary fibrous tumor, and giant cell tumor [GCT] of tendon sheath), as well as malignancies (leiomyosarcoma, spindle cell sarcoma, and lymphoma). The most common differential in our case would have been a GCT of the tendon sheath; however, there was no susceptibility on GRE sequences, and the lesion was separate from the tendons and the tendon sheath.

Table 1 enlists the points for the differential diagnoses:

The route for USG-guided percutaneous biopsy should avoid the uninvolved anatomical compartments, elude the potential site for surgical incision, while protecting the neurovascular bundles. For lesions in the posterior ankle, such as in our case, a posterolateral approach is recommended (lateral to the Achilles tendon and medial to the peroneal tendons), directed anteriorly into the Kager’s fat pad. This route avoids the standard posterior midline Achilles splitting or posteromedial incision used typically for tumor resection.^[7] The biopsy tract is kept within the tissue, which can be excised along with the primary tumor, minimizing the risk for tumor seeding outside the resection field. Furthermore, the posterior tibial and the sural nerve are spared when done correctly. The sample should be collected from the non-necrotic areas, which show enhancement or diffusion restriction. These sites ensure maximum yield for histopathological examination.

The treatment includes surgical excision of the lesion, especially in symptomatic patients. There are chances of recurrence. These tumors also respond to steroid therapy, thus implying the inflammatory nature of the lesion. Molecular therapy (Crizotinib) may have a role in the management by targeting the ALK gene.^[3]

CONCLUSION

Inflammatory myofibroblastic tumors (IMFT) are borderline neoplasms with varied imaging characteristics. They are heterogenously hypoechoic on ultrasound with vascularity on colour Doppler. They are hypodense to the muscle on CT and hypointense on both T1 and T2 sequences. The common differential diagnoses are tendon sheath GCT and neurogenic tumors.