Low-Grade Myofibroblastic Sarcoma on Back with Repeated Localized Recurrence and Regional Metastasis

Abstract

Low-grade myofibroblastic sarcoma (LGMS) is a rare spindle cell tumor with indolent course. Due to rarity and low-grade histologic features of LGMS, accurate diagnosis is challenging. We report a 63-year-old female patient with a three-month history of a 3.1 cm×2.5 cm sized, firm, skin-colored, painless, protruding left back mass. Initial excisional biopsy was performed and the mass was diagnosed as nodular fasciitis. After 18 months after excision, the mass recurred with pain and grew larger. Considering the clinical manifestations, diagnostic impression was changed as dermatofibrosarcoma protuberans not nodular fasciitis. Second wide excision was performed and the histopathology revealed proliferative atypical spindle cells with moderate nuclear atypia and a distinctive whorling pattern, which is suggestive of low-grade sarcoma. Additional computed tomography and positron emission tomography revealed no metastasis and suspicious residual viable malignant tissue. To remove suspicious residual tumor, third wide excision were performed and the diagnosis confirmed as LGMS. A microscopically clear resection was achieved with deep and lateral safety margin 0.6 cm each. Despite of postoperative radiotherapy with 35 times, recurrence of the tumor and lung metastasis was found after 7 months later. LGMS rarely metastasizes and occurs most commonly in the head and neck region. Thus, we report a rare case of LGMS on back which repeated localized recurrence and regional lung metastasis occurred despite wide excision and adjuvant radiotherapy.

INTRODUCTION

Low-grade myofibroblastic sarcoma (LGMS) is defined as an atypical myofibroblastic proliferation that develops in the bone or soft tissues and has many morphologic mimics. It is a rare soft tissue tumor and a relatively new entity that has been recognized only recently and described by Mentzel et al.¹ in 1988. LGMS is tend to have a relative indolent course with a low-grade but distinct myofibroblastic malignant potential, the tendency to recur locally, a low likelihood of distant metastasis and a predilection for occurring in the head and neck region and extremities². Herein, we report a rare case of LGMS on rare site – back with localized recurrence and regional lung metastasis.

CASE REPORT

A 63-year-old female visited our clinic with complaints of a 3.1 cm×2.5 cm sized, painless, firm, skin-colored, protruding left back mass (Fig. 1A). The mass was located near an area of previous acupuncture treatments and became larger by time. The patient didn’t complain of any other symptoms. The patient’s previous medical history was remarkable for diabetes mellitus.

Fig. 1. Clinical manifestation and gross specimen of the tumor. (A) A 3.1 cm×2.5 cm sized, painless, firm, skin-colored, protruding left back mass at the first visit and (B) a distorted, painful, fibrotic mass, 18 months after the initial excisional biopsy. (C) A microscopically clear resection was achieved with deep and lateral safety margin 0.6 cm each after the third wide excision. (D) A 11.5 cm×4.5 cm×1.8 cm sized gross specimen of the third wide excision. We received the patient’s consent form about publishing all photographic materials.

Initial excisional biopsy was performed under suspicion of an epidermal cyst. The pathology revealed ill-defined spindle cellular proliferation, central sclerotic change, and some foamy histiocytic collection, which diagnosed as nodular fasciitis. The patient later complained of a painful, distorted, protruding and fibrotic mass on previous site at a year and a half after the initial excisional biopsy (Fig. 1B). As the lesion was thought to be postoperative hypertrophic scar or postoperative change, intralesional triamcinolone mixed with hyaluronic acid was injected several times. However, the lesion became larger without improvement. Considering these new clinical manifestations, the diagnostic impression was changed as dermatofibrosarcoma protuberans (DFSP) not nodular fasciitis. To remove recurred mass, second wide-excision was performed. After the surgery, the histopathologic examination revealed proliferative and distinctive atypical spindle cells in the specimen, and mild to moderate nuclear atypia, a mitotic count of 7/10 per high-powered field (HPF), a distinctive whorling pattern, and some histiocytic infiltration (Fig. 2A, B). An infiltrative growth pattern to the skeletal muscles were also noted. Immunohistochemical analysis revealed positive only on smooth muscle actin (SMA) and negative on Desmin, Von-Kossa, and clusters of differentiation 34 and 68 (CD34, CD68) (Fig. 2C~G). All these histologic features suggested LGMS instead of benign or reactive myofibroblastic conditions or spindle cell tumor such as nodular fasciitis, inflammatory myofibroblastic tumor (IMT), fibrosarcoma and leiomyosarcoma. Since LGMS was suspected diagnosis, additional computed tomography (CT) and positron emission tomography (PET) were performed to exclude other metastasis or a recurring or hidden malignancy; the results indicated postoperative changes with possible small residual viable malignant tissue. To remove suspicious residual tumor which found on radiologic examination, third wide excision were performed and a microscopically clear resection was achieved with deep and lateral safety margin 0.6 cm each (Fig. 1C). The result of histopathologic and immunohistochemical analysis were similar to those of the previous result, with a proliferative and atypical spindle cell lesion with a whorling pattern arrangement, moderate mitotic counts (5~6/10 HPFs) and only SMA positive on spindle cells. Altogether, the diagnosis confirmed as LGMS. Despite of regular 35 times of postoperative radiotherapy, repeated localized recurrence and regional lung metastasis was found on regular follow up CT (Fig. 3) and PET after 7 months later. After referral to the oncology department, the patient was transferred to another hospital.

Fig. 2. Histopathological and immunohistochemical findings of the tumor. (A) Histopathologic examination revealed proliferative atypical spindle cells with distinctive whorling pattern (H&E, ×200) and (B) a mild to moderate nuclear atypia, bizarre mitotic features (black arrows) with storiform patterns (H&E, ×400). (C) The immunohistochemistry analysis revealed positive on only smooth muscle actin (SMA) and (D~G) negative on Desmin, Von-Kossa, and clusters of differentiation 34 and 68 (CD34, CD68) (original magnification, ×200).

Fig. 3. Computed tomographic images of the regional lung metastasis. Computed tomography (A) coronal and (B) transectional image revealed lung nodular metastasis (yellow arrows).

DISCUSSION

LGMS commonly arises from the myofibroblast and can be found in submucosal, intramuscular and intraosseous area. It infiltrates irregularly along connective tissue planes or into skeletal muscle and usually present with localized painless mass¹. Notably, LGMS is thought to occur commonly in the head and neck region, particularly in the oral cavity and extremities². Sex predilection of LGMS has conflicting results. Two previous case series have documented a slight male preponderance¹,³. However, a current population-based study showed a slight female preponderance². Development of LGMS in the upper back as seen in our patient, is rare and 19 truncal LGMS except breast LGMS cases documented before (Table 1)¹,³,⁴,⁵,⁶,⁷,⁸.

Table 1. Clinical features of previously reported cases of truncal LGMS except breast LGMS.

Year	Reference	Sex/age (yr)	Site	Tumor size (cm)	IHC	Treatment	Follow-up (mo)
1991	Eyden et al.4	F/77	Axilla	NA	SMA, S-100	E	D (42)
		M/64	Scapular area	NA	SMA	E	REC, M, D (28)
1998	Mentzel et al.1	F/29	Supraclavicular area	8	SMA	E	NED (20)
		M/52	Shoulder	4	None	E	NA
		F/42	Chest wall	7.5	SMA	E	Multiple M (108)
		M/56	Chest wall	4.5	CD99	WE	NA
2001	Montgomery et al.3	M/42	Axilla	5	SMA	E	NED (36)
2007	Meng et al.5	F/30	Shoulder	3.7	Vimentin, SMA, MSA, Desmin, Fibronectin	E	NED (22)
		F/40	Axilla	5	Vimentin, SMA, MSA, Fibronectin	E	REC, M
		M/9	Scapular area	3	Vimentin, SMA, MSA, Fibronectin	E	NED (41)
		M/40	Chest wall	4	Vimentin, SMA, MSA, Fibronectin	E	NED (27)
2018	Li et al.6	F/4	Back	4	NA	E+R	NED (36)
		F/30	Axilla	9.4		WE	NED (4)
		F/44	Shoulder	7		WE+R	NED (34)
2020	Kuo et al.7	M/77	Chest	811	SMA, Desmin	WE	NED (24)
2021	Kim et al.8	F/45	Chest wall	4.6×4.0×3.5	NA	E	REC (30)
		M/50	Shoulder	0.7×0.5×0.4		WE	NED (25)
		F/20	Shoulder	2.8×2.4×2.0		WE	NED (24)
		M/68	Shoulder	2.3×2.1×1.2		WE	NED (60)

LGMS: low-grade myofibroblastic sarcoma, F: female, M: male, IHC: immunohistochemistry, SMA: smooth muscle actin, MSA: muscle specific actin, E: excision, WE: wide excision, R: postoperative radiotherapy, D: died, M: metastasis, NED: no evidence of disease, REC: recurrence, NA: not available.

Histologically, LGMS shows a distinctive whorling pattern with some histiocytic infiltration, a diffuse fascicular growth pattern, and mild to moderate nuclear atypia that infiltrate the surrounding tissues³. According to soft tissue sarcoma grading system of Federation Nationale des Centres de Lutte le Cancer (FNCLCC), the grading system is based on 3 parameters – tumor differentiation, mitotic index, and tumor necrosis. These parameters are scored 1 to 3 for differentiation and mitotic index and 0 to 2 for necrosis. A 3-grade system is obtained by summing the scores obtained for each of these 3 parameters. Grade 1 is defined as a total of 2 or 3; grade 2 as a total of 4 or 5; and grade 3 as a total of 6 to 8⁹. Our case obtained score 1 on differentiation parameter, score 0 on mitotic index parameter, score 0 on necrosis parameter and classified as grade 1, LGMS. The cytological characteristics of neoplastic cells are consistent with myofibroblasts, and tumor cells in LGMS demonstrate variable immunohistochemical results¹⁰. Immunohistochemical staining may be positive, to some degree, for SMA, muscle specific antigen (MSA), fibronectin, desmin, calponin, and vimentin¹¹. Montgomery et al.³ reported that 80%, 80% and 44% LGMS patients showed positive on SMA, MSA, and desmin respectively. All cases tested were negative for all cytokeratins, S-100 protein, and CD34.

As LGMS has low-grade histologic features, differential diagnosis of LGMS can be challenging. A combination of clinical studies, careful morphologic analysis, and a full panel of immunomarkers especially genetic studies is helpful in confirming the diagnosis. The differential diagnosis of LGMS includes a variety of benign or malignant lesions, including nodular fasciitis, IMT, fibrosarcoma and leiomyosarcoma¹². Fibrosarcomas are composed of malignant spindle cells showing fibroblastic differentiation, which are distinguished from myofibroblasts by the absence of immunohistochemical evidence of fibronectin and SMA¹³. Leiomyosarcomas show more eosinophilic and longitudinally fibrillary cytoplasm and cigar-shaped vesicular nuclei with paranuclear vacuolation. In contrast, the spindle-shaped cells of LGMS exhibit indistinct and paler cytoplasm, which is less fibrillary than that in leiomyosarcoma, and have a tapering rather than blunt-ended nucleus with common infiltration of inflammatory cells in the stroma. Immunohistochemically, previous studies demonstrated the stable expression of h-caldesmon in most smooth muscle tumors; in contrast, h-caldesmon was consistently negative staining in myofibroblastic tumors¹⁴. Nodular fasciitis is less cellular and uniform than LGMS, and has a heterogeneous appearance with cellular, myxoid, and fibrous areas¹⁵. LGMS is more cellular, fascicular, and infiltrative, especially into muscle, than nodular fasciitis, and careful examination will reveal hyperchromatic, enlarged nuclei, which are not observed nodular fasciitis¹⁶. Finally, IMT is mainly composed of myofibroblastic spindle cells mixed with prominently lymphocytic and plasmacytic infiltration, and is positive for anaplastic lymphoma kinase (ALK) or cytokeratin while LGMS has a more uniform histological pattern, with a greater degree of nuclear atypia and more mitotic figures, and it is negative for ALK and cytokeratin at immunohistochemistry¹⁷.

Due to rarity of truncal LGMS, exact recurrence and metastatic rate of truncal LGMS are not reported yet. In maxillofacial region, metastases occur rarely and 43.9% (18/41) of cases develop local recurrence, although LGMS is a low-grade malignancy¹⁶,¹⁸. Summarizing the published reports, in cases treated with local excision alone, 75% (8/12) relapsed, while only one of 14 cases with wide excision, with or without postoperative radiotherapy, relapsed. LGMS is thought to be poorly responsive to radiation therapy in the literature¹⁹,²⁰. LGMS patients who treated with surgery and radiation showed no significant difference with patients who treated with surgery alone in overall survival or disease-specific survival on univariate or multivariate analysis². Either role for chemotherapy in the management of LGMS is limited¹⁸,¹⁹. Chan et al.² reported that multivariate analysis showed that only older age (≥60 year) was significantly associated with worse survival. Considering our case of repeated localized recurrence after local excision and even wide excision with adjuvant radiation therapy, the treatment of LGMS with excision with wide surgical margins and/or adjuvant radiotherapy or chemotherapy should be considered in patient with older age or with aggressive clinical feature such as rapid growing or recurrence.

LGMS are relatively benign and low grade malignancies. Also, LGMS may exhibit diverse histological appearance and can easily be diagnosed as benign tumor like our case initially diagnosed as nodular fasciitis. Our case demonstrated aggressive feature with repeated local recurrence, an infiltrative growth pattern to the skeletal muscles and lung metastasis unlike other LGMS. Although we performed wide excision two times with tumor-free margin and adjuvant radiotherapy, the tumor metastasized to regional organ – lung. Therefore, careful and prompt morphologic and histopathologic analyses will be needed for exact diagnosis when mild spindle cell neoplasm. Furthermore, in patient with older than 60 years or with aggressive clinical feature, excision with wide surgical margins and/or adjuvant radiotherapy, chemotherapy and regular short term follow up should be considered.