Rare Case of Inflammatory Myofibroblastic Tumour with Atypical Clinical and Pathological Features

INTRODUCTION

An inflammatory myofibroblastic tumour (IMT) is a rare tumour characterised by the proliferation of myofibroblastic and fibroblastic spindle cells, accompanied by a significant inflammatory component, including plasma cells, lymphocytes, and eosinophils. IMT most commonly affects children and young adults, but it can occur at any age.^[1,2] IMT can arise in various sites, with the abdominal soft tissues being the most common site. Other frequent locations include the lung, mediastinum, head and neck region, and the gastrointestinal and genitourinary tracts. IMTs rarely occur in unusual places such as the somatic soft tissues, pancreas, liver, and central nervous system.^[1-3] These tumours can present a diagnostic challenge due to their varied presentations and broad differential diagnosis, which includes other spindle cell neoplasms and reactive inflammatory conditions.^[2,3]

Our case was a 61-year-old male who presented with a two-year history of right thigh swelling. Upon histopathology and immunohistochemistry (IHC), the diagnosis was confirmed as an IMT. Additionally, the pathological findings included the presence of an organising hematoma and pseudogout.

This case is interesting due to the unusual location of the IMT in the thigh and the coexistence of an organising hematoma and pseudogout, which are not commonly associated with IMT. These additional pathologies may have contributed to the atypical clinical presentation and could have influenced the therapeutic approach and prognosis.

CASE REPORT

A 61-year-old male presented with a gradually increasing swelling on the posterolateral aspect of the right thigh for 2 years. The swelling measured 16 x 10 cm at initial presentation and was associated with pain and sinus discharge, suggesting possible infection or abscess formation. Magnetic resonance imaging revealed a large mass deep to the subcutaneous plane in the lateral aspect of the right thigh, specifically in the greater trochanteric and subtrochanteric regions. The lesion was closely adherent to the fascia lata, a finding that raised concerns for a potentially aggressive pathology. Based on the radiological findings, a differential diagnosis of soft tissue sarcoma or atypical lipoma was considered.

Routine blood investigations were within normal limits. Fine-needle aspiration cytology of the lesion revealed only blood. Multiple trucut biopsies were performed, which showed necrotic tissue, haemorrhage, and fibrocollagenous tissue fragments. Given the size of the lesion and the suspicion of a malignancy, a wide excision of the mass was done. The excised lesion on gross examination revealed a skin-covered, nodular, grey-white mass with sinus tracts. A dark brown, circumscribed, and friable lesion was identified on the cut section, measuring 13×9.5×6 cm within the subcutaneous and deep soft tissue [Figure 1a]. Histopathology revealed that the lesion was composed of extensive fibrinous material with proliferation of myofibroblastic cells in sheets, accompanied by oedema [Figures 1b-d]. Additionally, focal areas with dense acellular eosinophilic crystalloid material (pseudogout) were observed with a giant cell reaction. These features were consistent with the diagnosis of an IMT. IHC showed the tumour cells were negative for anaplastic lymphoma kinase (ALK), STAT6, and Desmin. However, the cells were positive for smooth muscle actin (SMA), indicating myofibroblastic differentiation. The Ki-67 proliferation index was 10%, indicating low to moderate proliferative activity [Figures 1e and f]. Based on these findings, the final pathological diagnosis was confirmed as an IMT with associated organising hematoma and pseudogout. The patient was closely followed up and has been doing well for 2 years after the excision.

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Figure 1: (a) Skin - covered nodular mass with grey-white cut surface (right thigh, 1x). (b) Histopathology showing granulation tissue with myofibroblastic proliferation (H&E, 40x). (c) Histopathology showing focal dense acellular eosinophilic material (H&E, 100x). (d) Histopathology showing dense neutrophilic infiltrate (H&E, 100x). (e) Immunohistochemistry showing SMA- positive (100x). (f) Immunohistochemistry showing Desmin negative (100x). H&E: Hematoxylin and eosin, SMA: Smooth muscle actin.

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DISCUSSION

IMTs are neoplasms of uncertain origin classified as having intermediate malignant potential. IMT affects children and young adults with a slight female predominance.^[2-5] IMTs are most commonly seen in the lung, mesentery, and omentum, but they can also occur in soft tissues and mucosal surfaces. The other rare sites include the liver, spleen, pancreas, genitourinary tract, central nervous system, head and neck regions, reflecting its wide but unpredictable distribution. The varied distribution of IMTs and their potential for local recurrence or metastasis underscores the importance of thorough diagnosis and management.^[3-6]

Abdominal IMTs may lead to gastrointestinal obstruction or bleeding, while pulmonary IMTs can present with chest pain and dyspnea. One-third of patients experience a clinical syndrome that may be cytokine-mediated. This is featured by fever, malaise, weight loss, and various laboratory abnormalities, including microcytic hypochromic anaemia, thrombocytosis, polyclonal hypergammaglobulinemia, elevated erythrocyte sedimentation rate (ESR), and elevated C-reactive protein (CRP) levels.^[2-7]

Radiologically, IMTs often appear as lobulated, heterogeneous solid masses that may or may not exhibit calcification. Grossly, these tumours typically present as nodular, circumscribed, or multinodular masses. The cut surface of the mass can appear tan, whorled, fleshy, or myxoid, with areas of variable haemorrhage, necrosis, and calcification. Microscopically, IMTs exhibit a range of histological features, with three basic patterns being recognised: Myxoid Pattern consists of loosely arranged, plump or spindled myofibroblasts set in an edematous myxoid background. The stroma is often rich in blood vessels and accompanied by an inflammatory infiltrate that includes plasma cells, lymphocytes, and eosinophils. Hypercellular pattern: Characterised by a compact proliferation of spindle cells arranged in fascicles, this pattern shows a variable myxoid and collagenous stroma. The inflammatory infiltrate is also variable, contributing to the overall cellularity of the lesion. Hypocellular fibrous pattern: This pattern is marked by a hyalinized collagenous stroma with lower cellularity. The sparse spindle cells and the inflammatory infiltrate are seen compared to the other patterns. These varied histopathological features underscore the diagnostic complexity of IMTs and resemble other spindle cell neoplasms and inflammatory conditions. Therefore, a combination of histopathology, IHC, and clinical correlation is essential for an accurate diagnosis.^[4-9]

In our case, the patient underwent multiple biopsies and did not provide a definitive diagnosis, highlighting the challenges of diagnosing IMTs through limited tissue sampling. However, the excision specimen revealed atypical histology of IMTs. The necrotic tissue and haemorrhage in the initial biopsies could reflect the tumour’s vascularity and organising hematoma, which was later confirmed in the excision specimen. The giant cell reaction to the eosinophilic material could be related to the pseudogout or other metabolic processes within the tumour. The exact mechanism remains unclear. The combination of chronic inflammation, tissue damage, and repair observed in IMTs may contribute to the rare features of pseudogout.^[8-10] This case underscores the importance of obtaining an adequate tissue sample for histopathological evaluation. In our case, the excision specimen provided the necessary tissue architecture and cellular details to confirm the diagnosis of IMT with associated organising hematoma and pseudogout.

The literature review emphasises that the histopathological differential diagnoses of IMT include both benign and malignant spindle cell lesions, requiring careful distinction based on morphology, IHC, and molecular features. IMT is to be differentiated from spindle cell sarcomas such as leiomyosarcoma, fibrosarcoma, and low-grade myofibroblastic sarcoma, as well as reactive/inflammatory conditions like nodular fasciitis and inflammatory pseudotumour. Other important mimics include gastrointestinal stromal tumour (GIST), desmoid-type fibromatosis, solitary fibrous tumour, and malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, which may show overlapping spindle cell proliferation. The presence of lymphoplasmacytic and lymphocyte infiltrates, ALK positivity, and characteristic myofibroblastic morphology are key distinguishing features that help separate IMT from other histological mimickers. In such cases, immunohistochemical staining is a crucial tool for distinguishing IMT from these other neoplasms.^[5-10] Leiomyosarcomas, for example, typically exhibit a fascicular growth pattern and contain myofibrillar elements. Leiomyosarcoma is characterised by marked cytologic atypia, nuclear hyperchromasia, and atypical mitotic figures, which reflect its malignant behaviour. Leiomyosarcomas generally lack the delicate vascular network and the interspersed inflammatory cells commonly seen in IMTs.^[6-10] IHC further assists in differentiating these entities:

IMTs typically express SMA and may or may not be favourable for ALK, depending on the presence of ALK gene rearrangements. They are usually negative for markers such as Desmin, MyoD1, and Myogenin, which are more specific to muscle differentiation. Focal keratin immunoreactivity can be observed in up to 30% of cases, reflecting the tumour’s complex differentiation. Notably, ALK immunoreactivity, present in 50-60% of IMT cases, is associated with ALK gene rearrangements. ALK staining can help confirm the diagnosis in cases where the histological features are ambiguous.^[6-10]

Leiomyosarcomas are usually positive for SMA, Desmin, and h-caldesmon, markers associated with smooth muscle differentiation. The presence of these markers, along with the distinct histopathological features, helps differentiate leiomyosarcoma from IMT.^[7-10]

In our case, the lack of ALK and STAT6 immunoreactivity may suggest a different molecular pathogenesis or subtype of IMT, as ALK-positive IMTs are more common. The positivity for SMA confirms the myofibroblastic nature of the tumour.^[6-8] The presence of pseudogout adds a unique aspect to the case, as it is not commonly reported in association with IMT, and this could have implications for both the clinical presentation and the overall understanding of the tumour’s pathology. Close follow-up is essential for monitoring such rare tumours, especially when they present in unusual locations with atypical manifestations.

CONCLUSION

An IMT can be challenging, given its overlapping morphological features with various spindle cell tumours. The case we describe is especially notable because it involves IMT with pseudogout formation, a scarce combination. This unusual presentation highlights the importance of thorough histopathological examination and IHC in accurately diagnosing IMT and distinguishing it from histological mimickers.