Recurrent Intraosseous Spindle Myoepithelioma of the Distal Fibula: A Clinical and Radiological Challenge

Andrei Tuluca1*, Sai S. Kilaru1*, Gopi K. Nallani2

1 Central Michigan University College of Medicine; the United States;
2 Advanced Diagnostic Imaging, Department of Radiology- Covenant Healthcare; the United States.
*these co-first authors contributed equally to the work

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

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Correspondence to: Andrei Tuluca, Central Michigan University College of Medicine; the United States.
Email: tuluc1am@cmich.edu
Telephone: +1-(973)-294-0011

Received: March 10, 2021
Revised: March 20, 2021
Accepted: March 23 2021
Published online: April 28, 2021


A 42-year-old man with a past history of lipomas, presented with right ankle pain radiating to the hip and limited range of motion of the ankle. An initial x-ray was performed revealing an expansile lytic lesion in the right distal fibula. Next, an MRI was performed to confirm this expansile lytic lesion. Initial presumptive differential diagnoses included chondromyxoid fibroma, osteoblastoma, intraosseous ganglion cyst and Brodie’s abscess. However, upon bone biopsy the pathology report revealed that the lesion was smooth muscle actin (SMA) positive and an ultimate diagnosis of intraosseous spindle myoepithelioma (ISM) was made. Curettage was then performed on the initial lesion to excise the tumor. The patient since has had multiple recurrences of this lesion. The diagnosis of ISM is rare and can present with many challenges in diagnosis radiologically and clinically as this tumor can mimic many common diagnoses. Due to the paucity of literature on this topic, documentation of this case will help enhance the understanding of this rare lesion, its behavior, and possible genetic associations.

Key words: Intraosseous myoepithelioma; Fibula; Recurrent myoepithelioma; Spindle myoepithelioma; Smooth muscle actin; Orthopedic oncology

© 2021 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Tuluca A, Kilaru SS, Nallani GK. Recurrent Intraosseous Spindle Myoepithelioma of the Distal Fibula: A Clinical and Radiological Challenge. International Journal of Orthopaedics 2021; 8(2): 1463-1466 Available from: URL: http://www.ghrnet.org/index.php/ijo/article/view/3112


Intraosseous spindle myoepithelioma (ISM) are rare tumors that present with mixed pathology within the classification of myoepithelial tumors. Historically, myoepithelial tumors (MET) that occur in the soft tissue or the bone bear resemblance to those METs in the salivary glands[1]. The diagnosis of ISM has become more common within the recent years due to the increased use of diagnostic criteria such as immunohistochemical (IHC) markers to identify these tumors[2]. While IHC has increased the incidence of diagnosis, much remains unknown regarding these tumors including their associations, clinical course, and definitive treatment.

Review of previous literature has demonstrated a propensity of these tumors to occur in the mandible or typically an extra salivary gland location[2]. These locations are expected given the nature of myoepithelial cells which are commonly seen in glandular tissues. Myoepithelial tumors in non-traditional bony locations often are found to have gland formation that demonstrates a biphasic morphology[1]. Previous literature has also elucidated varying METs within these non-traditional bony locations like the ribs and the tibia[3,4].

In addition, myoepithelial carcinomas at a histological level are usually not correlated to their behavior. In fact, tumors with low histological grades can commonly behave in aggressive manners with distant metastasis to the liver, bone, lungs, kidneys and many more locations[3,4]. Interestingly, these locations are more common than regional lymph node metastasis[3,4]. This difficulty in diagnosing and predicting the clinical course of MET has made characterizing and understanding tumor behavior very elusive[2].

Recent advances in cytogenetics have brought to light another perspective in the diagnosis of METs, distinct molecular changes. Approximately 70% of the documented cases of intraosseous METs have been associated with Ewing sarcoma breakpoint region1 (EWSR1) gene rearrangements[5,6]. Cytogenetic analysis of various cases of intraosseous spindle myoepithelioma have revealed the wide variety of fusions possible between EWSR1 and other genes such as PBX1, PBX3, ZNF444, and POU5F1[7]. Despite the increased knowledge in the diagnostic criteria of intraosseous METs, which is rapidly evolving to become more specific and precise, much remains unknown on a case to case basis when involving intraosseous METs in rare locations.


A 42-year-old man with a past history of lipomas presented with right ankle pain radiating to the hip and limited range of dorsiflexion of the right ankle. Radiographs revealed an expansile lytic lesion with narrow zone of transition and sclerotic margin involving the distal one third shaft of the fibula at the level of inferior tibiofibular joint (Figure 1). Next, an MRI was performed and confirmed the lesion as seen on the radiograph. In addition, the T1 imaging revealed a sclerotic margin and mild marrow edema surrounding the bone marrow (Figure 2A). The post-contrast image showed intense peripheral enhancement in the right ankle (Figure 2C). Initial presumptive differential diagnoses after the MRI included chondromyxoid fibroma, osteoblastoma, intraosseous ganglion cyst, and Brodie’s abscess. However, upon bone biopsy the pathology report revealed multiple fragments of bone and soft tissue that were involved by a low grade spindle cell neoplasm in a myxoid background. No necrosis or mitosis were seen. The biopsy sample was smooth muscle actin (SMA) positive and negative for other immunohistochemical markers including S100, AE1/3, CD31, CD34, desmin, EMA, P63, and SOX10. An ultimate diagnosis of intraosseous spindle myoepithelioma (ISM) was made. The patient was then treated with curettage to excise the tumor and an argon beam was used to coagulate the bone defect. The bone was also filled with allograft croutons during surgery.

Two years after the initial surgical encounter the patient returned again with right ankle pain. Again, a lesion was seen on MRI with a biopsy that was positive for smooth muscle actin and polytypic cytokeratin. The patient was then treated similarly to the first time in respect to the right fibular lesion, however, during this procedure one angiolipoma and two lipomas from the right arm as well as one angiolipoma and one lipoma from the left arm we removed. One year later the patient for the third time presented with ankle pain and another recurrence of myoepithelioma confirmed by X-ray and MRI and was treated with curettage. The final known recurrence happened another year after the second recurrence and was confirmed by biopsy. This time the patient presented with an enlarging lump on the ankle with pain and sought a more definitive treatment. Therefore, the right distal fibula was removed in its entirety and a 3D reconstructed distal fibula was placed.

Figure 1 (a) Anteroposterior view, (b) sagittal view, (c) oblique view of the right fibula lesion showing intense peripheral enhancement.

Figure 2 (a) shows a T1 image with sclerotic margin and mild marrow edema in the surrounding bone marrow, (b) shows a T2 image again showing a sclerotic margin, (c) is a post contrast image showing intense peripheral enhancement.


Myoepithelial tumors vary in terms of immunohistological markers making the tumors hard to characterize clinically[8]. While it has become widely accepted that the presence of S100 and smooth muscle actin (SMA) are generally consistent with the presence of METs, not all METs display this pattern including our patient who was S100 negative. In fact, there are other cases reported in which myoepithelial tumors are not S100 positive[9,10,11]. This is especially true in rare locations like the fibula[1]. A previously reported myoepithelioma in the distal femur was S100 negative just like our patient[11]. This adds an additional diagnostic challenge to correctly identify S100 or SMA negative tumors. In addition to S100 and SMA, myoepitheliomas can be positive for many other markers including cytokeratins, GFAP, EMA, and AE3[8].

Over the last decade there have been numerous studies suggesting that there is a connection between myoepithelial tumors and the EWSR1 gene rearrangement[1,4,5]. EWSR1 gene rearrangement and fusion has been implicated in almost 70% of intraosseous myoepitheliomas[5]. Literature has elucidated a subset of METs with known cytogenetic rearrangements between EWSR1 and multiple other genes. The importance behind delineating these rearrangements lies within the ability to accurately diagnose such tumors at novel locations cytogenetically. Such novel locations for reported intraosseous myoepitheliomas have been in the posterior mediastinum, metatarsal bone, ankle, and soft tissue of the index finger[1,6,12]. Of these cases, all reported some fusion between EWSR1 and a complementary gene. Furthermore, previous literature has reported that EWSR1 negative myoepithelioma tumors are more likely to be located superficially in the skin or subcutaneous tissue, thus making diagnosis of intraosseous myoepithelioma less likely for EWSR1 negative tumors[1]. Recently, however, EWSR1-PBX3 has gained traction in recent reports given its newly formed association between superficial myoepithelioma and EWSR1 positive tumors[13].

Presently, our case demonstrated a patient who possessed both multiple lipomas, angiolipomas, and recurrent intraosseous spindle myoepithelioma. Prior research has loosely associated EWSR1 positivity with strictly deep tissue or bone myoepithelioma with no superficial tumors. With the unique finding of a cutaneous syncytial myoepithelioma (CSM) in research literature bearing the EWSR1-PBX3 fusion, there is a possibility to draw an association between the recurrence of ISM and lipomas present in our patient presenting with both deep bony tumors and superficial soft tissue tumors[13].

In addition to the findings present above, EWSR1-PBX3 has been reported as a “Single Case” fusion for myoepithelioma/mixed tumors indicating that recurrence events are extremely unlikely[14]. Presently, our patient presents with multiple recurrences over the course of a five year clinical period possibly indicating, although unconfirmed, the first report of a EWSR1-PBX3 fusion presenting with multiple recurrences of both superficial soft tissue and deep bony tumors. In addition, consistent with our histology report, two previous cases of EWSR1-PBX3 gene fusion described the histology of biopsy specimens as partially myoxid to collagenous matrix with nests or sheets of epithelioid to spindled cells[1,4,5].

Current treatment includes curettage or resection of the tumor despite the possibility of local recurrence[2]. Although recurrence of this rare tumor has not been extensively studied due to both rarity of these tumors and short-term follow ups of other cases, our patient is an example of a case with multiple recurrences over a five-year period with an ultimate treatment of a reconstructed fibula. In conclusion, there is still much to be understood regarding the diagnosis and prognosis of primary intraosseous myoepitheliomas as well as their associations with other benign tumors like lipomas. Our future work with the approval of the patient and IRB will hope to explore the potential connection between intraosseous myoepitheliomas and lipomas through the use of genetic sequencing to check for potential fusion genes.


The authors would like to thank Brenda Johnroe for helping us acquire all necessary approvals and Dr. Rajiv M. Patel for his guidance.


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