Orbital metastasis of myxofibrosarcoma

Abstract

Myxofibrosarcoma (MFS), a common sarcoma in adults, typically affects the extremities. Primary orbital involvement is uncommon, and orbital metastasis is exceedingly rare. We describe a case of orbital MFS due to metastasis and provide an updated literature review. A 56-year-old woman presented with 2 months of progressive right eye proptosis. Relevant history included left palmar MFS excised 2 years prior. Examination demonstrated proptosis and restriction in abduction of her right eye without optic nerve compromise. Imaging revealed a well-circumscribed right orbital mass. Initial biopsy showed glandular tissue with chronic inflammation without an evidence of malignancy. She subsequently developed worsening proptosis, complete ophthalmoplegia, and a new afferent pupillary defect. Repeat orbital excisional biopsy with deeper dissection demonstrated high-grade MFS consistent with metastasis. She underwent chemoradiation with resolution of her lesion. Literature review identified 12 previously reported cases of MFS, only two of which involved metastasis to the orbit and were associated with worse prognosis. This report highlights a rare case of orbital metastasis of MFS with high-grade features confirmed on histopathology and provides an updated literature review. Prompt diagnosis and complete removal of MFS located both systemically and in the orbit are essential due to the metastatic potential.

Introduction

Myxofibrosarcoma (MFS), a malignant soft-tissue tumor, is a common sarcoma in older adults. It typically arises in the extremities and presents as a painless, slow-growing nodule. While it can affect the head and neck, involvement of the orbit is very rare, with only 12 cases reported in the literature. The authors present a case of a patient with a history of left palmar MFS who presented with proptosis and was ultimately found to have orbital metastasis of MFS. All collection and evaluation of patient health information were HIPAA-compliant, written consent was obtained, and this report adheres to the Declaration of Helsinki.

Case Report

A 56-year-old woman presented with right eye pain, proptosis, and diplopia for 2 months. Her medical history was notable for excision of a left palmar high-grade MFS 2 years prior at an outside hospital with adjuvant local radiation of 50.4 Gy in 28 fractions. As this lesion had been removed piecemeal, the patient had undergone close observation with serial imaging of her left hand postoperatively without evidence of local lesion recurrence.

The patient’s initial examination revealed a visual acuity of 20/30 in her right eye and 20/25 in her left eye and normal intraocular pressures. External examination demonstrated hypoglobus and medial displacement of the right eye, with 5 mm of relative proptosis and complete restriction in abduction and elevation [Figure 1]. Anterior segment examination was notable for dilated temporal conjunctival vessels in the right eye, but the remainder of the anterior segment and dilated fundus exam was otherwise unremarkable. There was no evidence of optic nerve compromise. Magnetic resonance imaging of the orbits revealed a well-circumscribed mass of the right orbit measuring 3.8 cm × 1.6 cm × 2.0 cm centered around the right lateral rectus [Figure 2]. Given the rarity of orbital MFS, an incisional biopsy was performed through an anterior orbitotomy with biopsy of the lacrimal gland, which appeared white and rubbery, to obtain lesional tissue. Histopathology showed glandular tissue with chronic inflammation immunochemistry demonstrating CD20 and CD3 highlighting a few scattered B- and T-cells and plasma cells polytypic for kappa and lambda light chains as detected by in situ hybridization. There was no evidence of malignancy.

Figure 1.

External photographs of the patient demonstrating hypoglobus and medial displacement of the right eye with restriction in upgaze and abduction

Figure 2.

T1-weighted fat-suppressed magnetic resonance imaging. Coronal (a) and axial (b) images demonstrate an enhancing mass along the lateral aspect of the right orbit as indicated by white arrows

Two weeks later, the patient presented with worsening symptoms; her vision in her right eye decreased to E at 5 feet, with examination of her right eye demonstrating increasing proptosis, complete ophthalmoplegia, diffuse conjunctival injection with chemosis, and macular folds on dilated fundus examination concerning for mass effect on the globe. She also had a new afferent pupillary defect, which in combination with the decreased vision was concerning for optic nerve compromise. Repeat imaging demonstrated an interval increase in the intraconal orbital lesion, which was found to measure 4.9 cm × 2.0 cm × 3.2 cm, with increased mass effect on the right globe and right optic nerve sheath complex, worsening proptosis, and areas of cortical erosion of the right lateral orbital wall. She received 1 g of intravenous corticosteroids. Due to the concern for a potential metastatic lesion with inadequate sampling at the time of the first biopsy, she underwent repeat orbital biopsy 1 day after her second presentation and 2 weeks after her first biopsy with plan for a deeper dissection and tumor excision. A lateral orbitotomy was performed with a deeper dissection along the inside of the lateral orbital wall, which revealed a red, vascular lesion that was subsequently excised. Histopathology demonstrated a hypercellular neoplasm composed of cytologically malignant pleomorphic spindle cells and epithelioid cells enmeshed in a myxoid stroma containing arching and branching interconnecting blood vessels [Figure 3a and b]. Immunohistochemistry showed that the tumor cells were positive for CD34 and negative for keratin, CD20, CD30, and CD68. The constellation of morphological and immunohistochemical findings confirmed the diagnosis of high-grade MFS, with additional features including size <5 cm, 50% myxoid proportion, mitotic index of 5/10HPF, and 0% necrosis. This was found to be morphologically and immunohistochemically similar to that of the primary high-grade sarcoma that originated in the soft tissues of the left palm [Figure 3c and d]. Size was not specified for the original tumor, but was presumed to be <5 cm based on the initial imaging; other features of the original hand tumor included 20% myxoid proportion, mitotic index of 6/10HPF, and 0% necrosis. Given the histopathological findings, the patient was diagnosed with orbital metastasis of MFS.

Figure 3.

(a) Histopathology of the orbital mass demonstrates a hypercellular neoplasm composed of cytologically malignant pleomorphic spindle cells and epithelioid cells enmeshed in a myxoid stroma that contains arching, interconnecting blood vessels (H and E, original magnification ×100). (b) Mitotic figures are present (arrows), consistent with cytologic malignancy (H and E, original magnification ×400). The findings are morphologically similar to the primary high-grade lesion originating in the soft tissue of the left palm (c) H and E, original magnification ×40, (d) H and E, original magnification ×600, mitotic figures indicated by black arrows

The patient underwent a positron emission tomography scan to assess for systemic involvement, which demonstrated a right lower lobe pulmonary nodule, left axillary lymphadenopathy, and left hepatic lobe mass in addition to her right orbital mass, which was consistent with the American Joint Committee on Cancer T1N1M1G3 (Stage IV) disease. The patient received orbital radiation (30 Gy in 10 fractions) and received chemotherapy with six cycles of doxorubicin 75 mg/m and ifosfamide 10 g/m², with clinical improvement and radiographic resolution of her orbital disease [Figure 4]. She is undergoing close monitoring by a multidisciplinary team including oncology as her pulmonary nodule and hepatic lobe mass remain present at 15-month follow-up, although she has no clinical or radiographical evidence of recurrent orbital disease.

Figure 4.

Clinical and radiographic findings at follow-up. (a) External examination of the patient at 15-month follow-up after receiving treatment with orbital radiation and systemic chemotherapy demonstrate clinical resolution of her proptosis. T1-weighted fat-suppressed magnetic resonance imaging with coronal (b) and axial (c) images following treatment demonstrate postsurgical changes without evidence of orbital lesion recurrence

Discussion

MFS is a malignant soft tissue tumor first described in 1977.[1] It comprises approximately 20% of all soft tissue tumors and most commonly affects older adults. It tends to arise in the lower extremities, head and neck, and trunk,[2] and clinically presents as a slowly enlarging, usually painless mass. These tumors macroscopically appear as poorly defined gelatinous nodules spreading in a longitudinal pattern along the fascial planes. MFS is characterized by fascicles of cytologically malignant spindle, epithelioid, and stellate-shaped cells enmeshed in a myxoid stroma that contains arching and interconnecting blood vessels. The tumors usually exhibit pleomorphism and mitotic activity, as well as necrosis and hemorrhage.[2] Complete surgical excision of the lesion is often considered the standard of care, and there is an increased risk of local recurrence if the resection has positive margins, which may lead to low-grade lesions becoming higher grade and acquiring metastatic potential in subsequent recurrence.[3,4] Other predictors of metastasis include lesion size (>5 cm), myxoid proportion (<75% of stroma), mitotic index (>20/10 HPF), and tumor necrosis (>10%).[5] The 5-year overall survival rate has been reported as 77% with a 5-year local recurrence rate of 18%, and metastasis may occur in 9.5%–27.6% of patients, most often to the lungs.[6] Patients with metastatic disease have been reported to have poor outcomes; one study found 18 of 25 (72%) patients with metastatic disease were deceased at follow-up.[7] Local recurrence and grade 3 MFS are also associated with worse overall survival.[4,8] Chemotherapy and radiation have not yet been found to be significantly associated with overall survival outcomes.[4,6]

Orbital MFS is rare, with only 12 cases previously reported upon review of the literature through PubMed with the search terms of “myxofibrosarcoma”, “MFS”, and “orbit”; including our patient, there are 13 cases total [Table 1].[9,10,11,12,13,14,15,16,17,18,19,20] Patients tended to present with proptosis, painless mass, eyelid swelling, and decreased vision, with duration of symptoms ranging from 6 weeks to 33 years. The majority of patients underwent excision of the orbital lesion (n = 10), and most patients received radiation (n = 7), while fewer patients received chemotherapy (n = 2) or a combination of chemotherapy and radiation (n = 2). Histopathology of the lesion demonstrated low-grade MFS in five patients, high-grade MFS in six patients, and was not specified in two patients. Two patients had recurrence of their orbital lesion despite excision.

Table 1.

Literature review of orbital myxofibrosarcoma

Reference	Age/sex	Location	Presentation	Previous history of MFS?	Duration prior to presentation	Lesion Size (cm)	Surgery	Chemotherapy	Radiation	Histopathology	Follow-up	Local Recurrence	Metastasis	Survival
Primary orbital lesions
Strickland (1966)[9]	34/male	Right orbit and temporal fossa	Progressive enlargement of Right orbit mass	No	33 years	10×7 × 7	None	No	No	High-grade MFS	12 days	No	No	Deceased
Zhang et al., (2010)[10]	27/female	Left superolateral orbit with erosion of frontal bone	Painless mass in left upper eyelid and eyebrow area	No	6 weeks	3×3	Fronto-orbital craniotomy with mass excision	Yes	No	High-grade MFS	6 months	No	No	Alive
Gire et al., (2012)[11]	17/male	Left inferomedial orbit	Painless left inferior eyelid edema	No	6 months	2	Mass excision	No	Yes	Low-grade MFS	2 years	No	No	Alive
Cante et al. (2013)[12]	66/male	Left maxillary sinus mass with extension to the orbital floor	Left facial, swollen cheek, and ipsilateral facial palsy	No	NS	NS	None due to patient refusal	Yes	Yes	MFS, grade NS	18 months	No	No	Alive
Pujari et al. (2014)[13]	27/male	Left inferomedial orbit	Painless progressive proptosis and diplopia	No	1 year	2.3×1.9×1.6	Mass excision	No	Yes	Low-grade MFS	18 months	No	No	Alive
Meel et al. (2016)[14]	25/male	Left superior orbit	Progressive vision loss, decreased extraocular movement, and lagophthalmos	No	25 years	7×5	Exenteration	No	No	High-grade MFS	6 months	No*	No	Alive
Wong et al. (2017)[15]	61/female	Left sinus mass with intraorbital extension and destruction of the left medial and inferior orbital walls	Progressive facial pain and pressure	No	6 weeks	NS	Combined open and endoscopic resection of the left-sided lesion with orbital exenteration	No	Yes	Intermediate to high-grade MFS	NS	NS	NS	NS
Clair et al. (2018)[16]	87/female	Right superolateral orbit	Intermittent binocular vertical diplopia, mild right hypoglobus and proptosis with painless progression of symptoms	No	1 year	4.2×3.1×1.9	Mass excision	No	Yes	Low-grade MFS	4 years	Yes	No	Alive
Primary orbital lesions
Du et al. (2020)[17]	70/female	Right superolateral orbit	Right upper eyelid swelling	No	1 year	NS	Mass excision	No	No	High-grade MFS	5 years	Yes (twice)	No	Alive
Andrew et al. (2020)[18]	71/male	Left retrobulbar	Left proptosis and decreased vision	No	2 months	NS	Mass excision through craniotomy with the left eye enucleation	No	No	Low-grade MFS	NS	NS	NS	NS
Orbital metastasis
Wang et al. (2008)[19]	63/male	Left inferomedial orbit	Proptosis and decreased vision	No	10 days	NS	Mass excision	No	No	Low-grade MFS	2 months	No	Yes’	Deceased
Shin et al. (2015)[20]	62/male	Left medial orbit with involvement of the medial rectus	Proptosis and ophthalmoplegia	Yes	NS	NS	Mass excision through an endoscopic transnasal approach	Yes	No	MFS, grade NS	3 months	No	Yes"	Deceased
This case (2023)	56/female	Right lateral orbit centered within lateral rectus	Right eye pain, proptosis, and diplopia	Yes	2 months	3.8×1.6×2.0	Mass excision with orbitotomy	Yes	Yes	High-grade MFS	15 months	No	Yes	Alive

*The authors report the lesion recurred after resections 22 and 13 years prior to presentation, but no histopathology was available for these resections. There was no recurrence following exenteration by the authors. ’Involvement of the lung hilum, abdomen, pelvis, and ribs reported at presentation.[19] "Patient reported to have systemic disease at presentation without specified primary lesions.[20]. MFS=Myxofibrosarcoma, NS=Not specified

Two cases presented in the sinus with local invasion to the orbit, and two previously reported cases involved metastatic disease from distant primary sites. Of the patients with metastatic disease, one patient had evidence of lesions in the lung hilum, abdomen, pelvis, and ribs at the time of diagnosis of an orbital MFS with low-grade features on histopathology; of note, the temporal association between the orbital and systemic lesions to determine which was the primary lesion was not described.[19] In a case series describing an endoscopic transnasal approach to resect locally aggressive orbital tumors, one patient was reported to have orbital MFS due to metastasis of systemic disease; however, details including the primary source of the MFS or the histopathologic grade of orbital lesion were not included.[20] The remainder of patients presented with primary orbital MFS. Overall, the prognosis was worse for the metastatic group, with two of three patients reported as deceased on follow-up compared to two of 10 patients with primary orbital MFS, including one who did not receive any treatment including surgical excision, radiation, or chemotherapy.

Our case highlights a rare orbital metastasis of MFS with high-grade features demonstrated on histopathology in a patient with primary disease of the extremities that had been previously resected. Interestingly, our patient’s hand lesion only had one of the characteristics associated with metastasis: a myxoid proportion <75%. As this patient’s palmar tumor had been removed piecemeal, it is possible that there was an incomplete surgical excision or microscopic spread of residual tumor that may have subsequently resulted in orbital metastasis despite local radiation. This emphasizes the importance of complete surgical excision and suggests a role for possible adjuvant chemotherapy in addition to local radiation to reduce the risk of microscopic spread. In addition, our patient demonstrated an excellent clinical response of her orbital disease without local recurrence after radiation and chemotherapy with doxorubicin and ifosfamide, which may indicate a role for these treatment modalities in addition to surgical excision for lesions located in the orbit. Neither chemotherapy nor radiation has currently been shown to be significantly associated with the overall survival in patients with MFS; however, the results of our patient, especially in contrast to the other patients reported with metastatic orbital disease who underwent either excision alone or excision and chemotherapy and were deceased at 2–3-month follow-up, suggest that future studies are needed to assess the efficacy of multimodal therapy for orbital metastasis of MFS.

Orbital MFS is rare, while orbital metastasis of MFS is even less common. This case represents a very rare report of orbital metastasis of MFS with high-grade features demonstrated on histopathology in a patient with a known primary disease of the extremities that had been previously resected and treated with local radiation. Our patient demonstrated an excellent clinical response of her orbital lesion without local disease recurrence after a combination of surgical excision, radiation, and chemotherapy. This case emphasizes the importance of obtaining a thorough history, maintaining a broad differential for orbital lesions including metastasis, and considering an additional deeper biopsy of tissue if initial biopsy is unrevealing and clinical suspicion remains high for neoplasm. Moreover, it highlights the importance of complete removal of MFS located both systemically and in the orbit due to metastatic potential and suggests a possible role for adjuvant radiation or chemotherapy to limit microscopic spread of disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors declare that there are no conflicts of interests of this paper.