Pseudomyogenic hemangioendothelioma

A 12-year-old female with a history of four months non-traumatic right knee pain along patella was presented to the orthopedic surgeon. The pain was progressing and gradually worsening. A clear atrophy of the right vastus medialis as well as painful movement of the patella were observed clinically.

Radiograph of the right knee depicted expansile, lobulated osteolytic lesions with sclerotic borders in femur, tibia and fibula. A pathologic fracture with periosteal reaction was depicted on distal metadiaphysis of the femur medially. (Figure 1).

MRI showed septate, hyperintense lesions on T2W and hypointense on T1W images. A hyperintense periosteal reaction around femoral fracture was present (Figure 2). On PET/CT lesions were metabolically active (SUV max. 10.8) (Figure 3). Additional lesions were visible at patella, large trochanter, and individual foot bones. A biopsy of distal femur and immunohistochemical examination were required. A histopathological examination showed a diffusely infiltrative tumor composed of plump spindle and epithelioid cells with abundant eosinophilic cytoplasm (Figure 4). Immunohistochemically, the tumour cells were positive for cytokeratin AE1AE3, ERG and FOSB, focally positive for CD31, negative for cytokeratin MNF116, and CAMTA1. A targeted RNA sequencing showed an ACTB-FOSB fusion, confirming the diagnosis of PMHE. MRI after therapy with sirolimus showed no changes in dynamics.

PMHE is a very rare soft tissue tumour, with only 164 known cases, that mostly affects young men [1,-3,5,10-12].  PHME usually arises in soft tissues of the lower limbs (54%), less frequently in the upper limbs (24%), trunk (18%) or head and neck (4%) [4,5]. It most commonly presents as multiple discontinuous nodules (painful in 50 % of cases), typically involving multiple tissue planes, most often the dermis and subcutaneous layers [6,7]. Lesions of the deeper soft tissue and bone can cause symptoms related to the mass effect of the tumour [1]. It rarely metastasizes but a local recurrence or additional nodules in the same anatomic region appear in about 60% of patients [3,4]. The mortality rate is low and is to the best of our knowledge ranging from around 3-20%. These percentages are based on available follow-up data of previous studies [2,4].

On imaging PMHE usually appears as lobulated and well-defined lesions [2]. Cross-sectional imaging has an important role in the diagnosis and localisation of the PHME due to the occurrence in different anatomic tissue planes [3]. On plain radiographs PMHE in bone appears as osteolytic expansile lobulated lesions without periosteal reaction, associated with well-defined borders and sclerotic rim. Osteolytic lesions may cause cortical destruction and pathological fracture of the affected bone. Oedema is easily observed when the tumour occurs in the epidermis or subcutaneous tissue. On CT scans osseous lesions are expansile osteolytic and well-demarcated without signs of bone destruction or periosteal reaction. Soft tissue lesions might appear as non-specific lobulated well-delineated masses. On MRI the lesions have low-intermediate signal intensity on T1-weighted images and hyperintense on T2-weighted images [3]. Intramuscular nodules can be identified on T1 fat-saturated post-gadolinium MR images as well-defined, hyperintense, enhancing foci. Whole body PET-CT is recommended due to frequent multicentric presentation of the disease. There could be a potential role of whole body MRI due to its great sensitivity, however the metabolic activity in lesions is easier to detect on PET-CT which displays an intensive FDG uptake [8]. To the best of our knowledge, all physicians used PET-CT for localisation of lesions rather than whole-body MRI.

Microscopic features of PHME include sheets of spindled to epithelioid cells, many tumour cells resemble rhabdomyoblasts [4,7]. By immunohistochemistry, PHME is positive for cytokeratin AE1AE3 and vascular markers ERG, CD31 (in about 50% of cases). Nuclear staining for FOSB in PHME shows either a SERPINE1-FOSB or an ACTB-FOSB fusion [6,7,9].

Treatment includes wide excision of the lesion with adjuvant therapy (radiotherapy or chemotherapy). It usually has favourable prognosis but amputation of the limb may rarely be required due to local recurrence [6].

In conclusion PMHE is a very rare soft tissue tumour with intermediate malignant potential [3]. The diagnosis is made by advanced immunohistochemical analysis and molecular confirmation in correlation with imaging findings. Recognition of PMHE is very important in order not to misdiagnose it as a more aggressive tumour (e.g., epithelioid sarcoma) [1,3].

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