Aggressive myxoinflammatory fibroblastic sarcoma with multiple site metastases

Abstract

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue sarcoma which was initially observed in acral sites and characterised by spindle cells, pleomorphic bizarre cells and distinctive large Reed-Sternberg–like cells admixed with an intense inflammatory cell infiltrates. MIFS manifests as a slow growing often superficial lesion which can be mistaken as infectious or chronic inflammatory process or benign tumours such as nodular fasciitis, giant cell tumour of tendon sheath or synovial pseudocyst. We report a rare presentation of a MIFS in a 38-year-old man with extensive local spread from subcutaneous tissue to the ankle joint and bones as well as multiple synchronous metastases to lung, sixth rib and vertebra. Our case is peculiar for its aggressive clinical behaviour with short duration, fast growth and extensive metastases, a feature infrequent in MIFS.

Background

We report an aggressive myxoinflammatory fibroblastic sarcoma (MIFS) with extensive local spread from subcutaneous tissue to the ankle joint and bones as well as multiple synchronous metastases to lung, sixth rib and vertebra. The awareness of this clinical entity is necessary as the tumour can present with high rate of local recurrence, however distant metastasis have been reported in few cases only. A close postoperative tumour surveillance is required and patient should be evaluated for the presence of local recurrence, regional nodal metastasis and distant metastasis including chest X-ray and other imaging studies to evaluate for potential pulmonary metastasis or metastasis to other distant sites including liver, skull and so on.

Case presentation

A 38-year-old man was referred to the oncology outpatient consult for an asymptomatic subcutaneous mass that had developed over the past 2 months in the ankle region of the right leg. He reported no history of trauma or prior surgery. The mass had grown progressively over the previous weeks and gave rise to mild discomfort. Physical examination revealed a well-defined, skin-coloured nodule that was firm on palpation. The nodule measured 4×3×2 cm. Clinical diagnosis of a cutaneous lipoma or soft-tissue tumour was considered.

Investigations

Blood tests including complete blood count, electrolytes and biochemistry were normal and imaging studies revealed an irregular ill-defined lobular heterogeneously hypoechoic mass lesion measuring 40×30 mm in relation to right ankle joint (figure 1A). The lesion was also involving the tibiotalar and tibiocalcaneal joints with erosion of the underlying bone in continuity with the soft tissue component. A 99 m Tc–MDP whole body bone scan revealed focal abnormal areas of increased uptake in the primary site in the right foot along with increased uptake in D6–D7, L1–L5 vertebrae and left fifth rib (figure 1B).

Figure 1.

Imaging findings: X-ray ankle joint revealing an irregular ill-defined lobular heterogeneously hypoechoic mass lesion involving the tibiotalar and tibiocalcaneal joints with erosion of the underlying bone (A). 99 m Tc–MDP whole body bone scan revealing focal abnormal areas of increased uptake in the primary site in the right foot along with increased uptake in D6–D7, L1–L5 vertebrae and left fifth rib (B). CECT of thorax showing multiple enhancing nodular densities in bilateral upper lobes and in left lingular lobe. Enhancing right basal pleural nodular thickening with minimal right pleural effusion (C,–D). CECT, contrast-enhanced CT.

A contrast-enhanced CT thorax showed multiple enhancing nodular densities in bilateral upper lobes and in left lingular lobe likely metastatic. Enhancing right basal pleural nodular thickening were seen with right basal atelectasis and minimal right pleural effusion. Sclerotic densities were evident in D6 and D7 body with complete collapse of D7. Expansile erosive changes were also present in the left sixth rib, mainly the posterolateral aspect. Findings were consistent with multiple site metastases (figure 1C,D). A deep incisional biopsy was performed and histological sections after staining with H&E showed a multilobular tumour having hypocellular and hypercellular lesions with an inflammatory infiltrate predominantly comprising lymphocytes, histiocyte and occasional neutrophils admixed with three morphological types of tumour cells in a myxoid and hyaline stroma (figure 2A–D). Various morphologies were evident with tumour cells including an epitheliod appearance, some of them with abundant basophilic cytoplasm with bizarre hyperchromatic nuclei and marked nuclear pleomorphism with some showing multiple vesicular nuclei and prominent eosinophilic nucleoli, similar to virocytes or Reed-Sternberg cells along with spindle-shaped neoplastic cells with basophilic cytoplasm and atypical nuclei. Another population of cells resembling lipoblasts (pseudolipoblast) with abundant cytoplasm containing numerous vacuoles was also seen (figure 2C–F).

Figure 2.

Histopathology findings: photomicrographs of MIFS showing hypocellular and hypercellular areas comprising basophilic myxoid material alternating with fibrohyaline stroma (A,B). Tumour comprising large, atypical mononuclear and binucleated epitheliod cells along with pseudolipoblasts (C,D). Areas of spindle cells haphazardly arranged in myxoid background admixed with inflammatory cells predominantly comprising lymphocytes and plasma cells (E,F) (H&E, original magnifications ×40(A,B); ×400(C,D); ×100(E,F)). MIFS, myxoinflammatory fibroblastic sarcoma.

Immunohistochemistry (IHC) revealed that all three tumor cell populations were strongly positive for vimentin and negative for S-100, EMA(epithelial membrane antigen), TLE 1 (Transducin-like enhancer protein 1), smooth muscle actin, cluster of differentiation 34 and desmin. Although there was marked cellular atypia, however, the number of mitoses were low (Ki-67 proliferation index <5%) (figure 3A–D). A diagnosis of MIFS was made on the basis of the clinicoradiological, histopathological and IHC findings.

Figure 3.

Immunohistochemistry findings: photomicrograph showing vimentin positive in tumour cells (A). Tumour cells negative for CD34, SMA and desmin (C,D) (original magnification ×100 (A–D)). CD34, cluster of differentiation 34; SMA, smooth muscle actin.

Differential diagnosis

The clinicians had difficulty in distinguishing the lesion from chronic inflammatory process and benign tumours. Histopathologically, the lesion is frequently confused with various benign entities including inflammatory pseudotumour (bizarre giant cells being sometimes difficult to identify in the inflammatory infiltrate), in case of marked emperipolesis, Rosai-Dorfman disease may mimic MIFS and giant cell tumour; the malignant neoplasm mimicking MIFS usually have myxoid background including myxofibrosarcoma, myxoid malignant fibrous histiocytoma and myxoid liposarcoma. However, inflammatory myofibroblastic tumour, epitheliod sarcoma and pleomorphic liposarcoma may also mimic MIFS and can be considered in the differential diagnosis^1–5

Treatment

The patient was given a preoperative radiotherapy followed by wide local excision along with postoperative radiotherapy and chemotherapy.

Outcome and follow-up

The patient responded well to the treatment and after 9 months of follow-up, there were no clinical and radiological evidence of local recurrence or distant metastases.

Discussion

MIFS was first described as a new entity in 1998 by three pathologists Meis-Kindblom and Kindblom, Montgomery et al and Michal in there independent reports.^{1 3 6} MIFS is a rare but about 400 cases have been reported in the literature including a large cohort of 104 cases.⁷ The entity was initially named as acral MIFS as it mostly involved the proximal regions of the limb, however, these lesions were also reported in the non-acral regions which include neck, scalp and trunk including the back, chest wall and shoulder, which has led to the bowdlerisation of the word acral from the WHO nomenclature.^{2 3} Clinically, MIFS is a superficial tumour limited to the subcutaneous tissues and tendinofascial planes of predominantly acral sites. The upper extremities are affected more commonly followed by lower extremities and the soft tissues of the fingers and hand. The peak incidence occurs in fourth and fifth decades but the age distribution is wide, with cases reported in the paediatric population and up to the 10th decade.^{1 3 8} MIFS is a low-grade malignancy but usually presenting with high rate of local recurrence accounting about 22%–67%, with first recurrence usually occurring between 3 months and 5 years after initial diagnosis.^{2 9 10} Distant metastasis was also found in few cases but is rare with <2% reported cases in the literature.² MIFS may metastasize to inguinal lymph node, lung, liver along with rare sites including the neck and base of the skull are also reported.^{9 11 12} The recommended management includes wide local excision with follow-up observation up to 5 years, cases presenting with local recurrence are given radiotherapy and metastatic disease are treated by chemotherapy.¹³ Laskin et al studied 104 cases and compared the clinical and histopathological parameters and found no significant association between high-grade histopathology of tumour and morbidity of the patients, however for disease-free survival, a complete surgical excision is required.⁷

In a study of 44 cases, Meis-Kindblom and Kindblom reported histologically proven lymph node metastasis in 1 patient, whereas another had lung metastasis. After follow-up, 23 patients were alive and well, 11 were alive with disease and 2 were dead of other causes without evidence of tumour.¹ Sakaki et al observed metastasis to a regional lymph node 3 months after resection in one patient and Hassanein et al reported two cases with distant metastases, one to the lung and the other to the skull at 3 months and 5 years, respectively.^{9 11} Lombardi et al in 2013 reviewed 133 cases from the literature and found four cases presenting with lung metastasis.¹⁴ Our case was characterised by an unusual fast progression of tumour presenting as local extension with a soft tissue mass involving the right foot extending to ankle joint viz the tibiotalar and tibiocalcaneal joints as well as metastases to distant bony sites including the vertebrae, rib and lung. The lung lesions presented as multiple enhancing nodular densities in bilateral upper lobes and in left lingular lobe in imaging studies. Vertebral lesions were sclerotic densities seen in D6 and D7 body with complete collapse of D7. Expansile erosive changes were also seen in left sixth rib. Hassanein et al reported the presence of skull lesion in MIFS case,¹¹ however, up till now MIFS presenting with multiple site metastases has not been reported yet in the literature.

MIFS is difficult to diagnose only on the basis of clinicoradiological findings, however, histopathological findings are also not conclusive due to overlaps in morphology and variable expression of IHCmarkers. Few emerging genetic findings have been found to be associated with MIFS. Lambert et al¹⁵ first described a reciprocal translocation t(1;10)(p22;q24) associated with increased FGF8, however reciprocal t(1;10) has been similarly reported in a haemosiderotic fibrolipomatous tumour (HFLT) also. Two distinct pathways were studied by Hallor et al in eight cases of MIFS, first is the breakpoints in t(1;10) to TGFBR3 in 1p22 and MGEA5 in 10q24 as a result NPM3 and FGF8 upregulation occurs. The second pathway identified a ring chromosome with a commonly amplified region in chromosome 3 associated with an overexpression of VGLL3 and CHMP2B.¹⁶ Molecular genetic studies have not been used for the diagnosis of MIFS and show inconsistent results. Zreik et al reported that most pure MIFS lack specific genetic findings and that TGFBR3 and MGEA5 rearrangements are more common in hybrid HFTL–MIFS tumours than in classic MIFS.¹⁷ The variability in clinicoradiological, histopathological and molecular findings, the diagnosis of MIFS is still a diagnostic challenge for clinicians and pathologists.

Learning points.

• Myxoinflammatory fibroblastic sarcoma (MIFS) needs to be adequately characterised, not just for its risk of local recurrence but also because a small proportion of lesions can metastasize to distant sites.

• A lesion with low-grade morphology can have an aggressive behaviour and present as multiple site metastases as well as invade the underlying bone.

• Long-term follow-up is required since there is high rate of local recurrence, but infrequent reports of distant metastasis exist. Our case highlights that the tumour may present as locally aggressive disease with multiple site metastases, hence whole body screening for metastases is required in a case with a diagnosis of MIFS.