Alveolar soft part sarcoma of the tongue: a case report and review of the literature

Abstract

Alveolar soft part sarcoma (ASPS) is a soft tissue malignant tumor of unknown origin in which tissues or cells are arranged like acini or organs. It usually presents in the deep muscles or fascia of the extremities, and rarely occurs in the head and neck, let alone the tongue. To our knowledge, only 49 cases of ASPS have been previously published in the tongue. Therefore, the course, age of onset, tumor size, and prognosis of ASPS in the tongue are not well understood. We present a case of ASPS in the dorsum of left tongue of a 24-year-old female. Histology of the resected tumor showed features of ASPS. She is currently disease-free at 12-month follow-up.

Introduction

Alveolar soft part sarcoma, named by Christopherson in 1952, is a rare soft tissue sarcoma with unique morphologic characteristics. ASPS is a slow-growing, painless tumor and often found by accident. The incidence of ASPS accounts for only 0.5% to 1.0% of soft tissue sarcomas. It is less common in head and neck, accounting for less than 0.1% of head and neck sarcomas. In adults, it mainly occurs in the lower extremities. In infants and children, tumors are often located in the head and neck. Fewer cases occur in the head and neck in adults, and when the lesion appears in the head and neck, it is mainly located in the deep muscles of the neck and the deep surface of the pharyngeal cavity [1]. The current case is a 24-year-old female with ASPS in the dorsum of left tongue.

Case report

Clinical history

A 24-year-old female presented with a 1-year history of an asymptomatic slowly growing lesion of the dorsum of left tongue, and at the time, she did not seek any treatment. She complained the tumor had slightly enlarged recently. The local skin temperature of the tumor was not high, the surface was not ulcerated, and there was no obvious fluctuance and edema.

Magnetic resonance imaging (MRI) revealed a 2.5×2.5×2.0 cm mass originating from the left tongue (Figure 1). The lesion had a high signal intensity on T1- and T2-weighted images and a uniform enhancement after intravenous contrast material administration. No obvious enlarged lymph nodes were noted in the neck. Imaging studies, including computed tomography of the chest, MRI of the brain and oral, positron emission tomography (PET) showed no metastatic lesions.

Figure 1.

Magnetic resonance imaging findings. Magnetic resonance imaging demonstrating a focal 2.5×2.5×2.0 cm lesion within the tongue (arrow).

The patient underwent an extended resection of the left tongue tumor under general anesthesia. During the operation, it was seen that the middle part of the left tongue protruded across the midline of the tongue to the opposite side. The mucosa around the tumor was deformed, and the blood supply around the tumor was abundant. The mass was solid, grayish white. The tumor envelope was intact, and the boundary with the surrounding tissue was clear.

Materials and methods

The resected specimen was fixed in 10% neutral phosphate-buffered formalin and embedded in paraffin. Sections were stained with hematoxylin-eosin (H&E), and periodic acid-Schiff (PAS), before and after diastase digestion.

Pathologic findings

The pathology of the resected specimen shows characteristic features of alveolar soft part sarcoma. The tumor cells have the same morphology, showing large round or polygonal shape, abundant cytoplasm, eosinophilic, fine granular, large nucleus, vacuole-like, obvious nucleoli, and obvious lack of adhesion between cells, forming acinar-like structures (Figure 2A). The tumor cell cytoplasm contains PAS-positive amylase-resistant substances (Figure 2B).

Figure 2.

Histologic features of the tumor. A. Tumor cells with abundant eosinophilic cytoplasm and prominent nucleoli. B. Tumor cells cytoplasm contains PAS-positive amylase-resistant substances.

Immunohistochemical results show strong nuclear immune response to TFE-3 (Figure 3A), MyoD1 (Figure 3B) is focally positive and the tumor cells are diffusely positive for SMA (Figure 3C), Vimentin (Figure 3D). There is no immunoreactivity for CK, Desmin, S-100, EMA, Syn, HMB-45, Melan A. Later, the patient went to two higher-level hospitals for pathologic section consultation and they performed FISH detection. The results were positive for t (Xp11.2) (TFE-3), that is, TFE-3 gene-related translocation. The patient has remained in good health and is disease-free 12-months after the initial diagnosis.

Figure 3.

Immunohistochemical findings. A. TFE-3 showing nuclear staining. B. Cytoplasmic staining with MyoD1. C. Tumor cells were diffusely positive for SMA. D. Tumor cells were diffusely positive for vimentin.

Discussion

ASPS is a rare soft tissue tumor that accounts for about 0.5% to 1% of soft tissue sarcomas. In the population, the age of onset is mostly 15 to 35 years [2], which is more common in females than males [3]. The tumor grows slowly and is painless in the early stages. It often occurs in the deep muscles or fascia of the extremities, and a few can be found in the abdominal wall, para-anal area, tongue, retroperitoneum, and back of neck. Fanburg-Smith et al. [4] reported 266 cases of ASPS from 1970 to 2004, of which only 14 were located in the tongue, accounting for only 5% of all ASPS. ASPS usually metastasizes early, and distant metastasis will occur even if there is no tumor recurrence at the primary site. The ASPS that occurs in the tongue involves important organs and is superficial. It is usually found earlier than other parts and does not spread far away. The patient was a 24-year-old woman whose tumor occurred in the dorsum of left tongue. She had a medical history of nearly one year, no obvious pain, no significant increase in mass, and a relatively limited lesion. Imaging studies showed no metastatic lesions.

Table 1 summarizes all reported cases of tongue ASPS, totaling fifty cases, including the present series. Affected were 26 females and 24 males. Presenting symptoms and signs occurred between 0.5 month and 108 months prior to diagnosis (median 5 months) and the median age at diagnosis was 8.5 years, ranging from 0.9 to 64 years. In all patients, the dorsal surface and the base of the tongue were affected in 28% (14/50) and 24% (12/50) of the cases, respectively. 1/50 cases involved both the dorsal surface and the base of the tongue, and 23/50 cases did not provide the specific location of the tumor in the tongue. The tumor size was reported in 38 cases, ranging from 8 to 80 mm (mean, 2.8 cm). The median follow-up time was 3 years (0.3-32 years). During follow-up, the majority of patients (33/50, 66%) still showed no signs of disease. Recurrence or metastasis occurred in 3 cases after diagnosis, and 2 cases died of ASPS. In 12/50 patients, no specific clinical course information was available.

Table 1.

Reported cases of tongue ASPS

Case	Author	Year	Age (years)/Sex	Tumour size (cm)/Tumour duration (months)	Location on the tongue	Treatment	Follow-up (years)	Clinical course
1	Spector RA [17]	1979	17/F	4.8/3	Right base	WSE	3	Metastases to lung, buttock
2	King VV [18]	1983	5/F	1/5	Right anterior	WSE	2	NED
3	Komori A [19]	1984	11/F	2.5/ND	Left side of the base	WSE	5	NED
4	Donald PJ [20]	1987	19/F	ND/36	Left side	WSE	1.5	NED
5	Simmons WB [21]	1989	1.6/F	2.5/2.3	Midline dorsal	WSE	3.6	NED
6	Cetik F [22]	1989	13/F	1.5/3	Left middle part	WSE	ND	ND
7	Takita MA [23]	1990	19/M	ND/ND	Dorsum	WSE	3	NED
8	Ooi LP [24]	1993	21/M	4/12	Dorsum	WSE	0.3	NED
9	Carson HJ [25]	1993	64/M	8/ND	Base	External beam radiation therapy and Adriamytin	3	DOD
10	Castle JT [26]	1999	3/M	ND/0.7	Mid-dorsum	WSE	0.7	NED
11	Bentley RP [27]	1999	5/F	ND/ND	Left of the midline	WSE	1	recurrence and metastatic
12	Yoshida K [28]	2000	2/F	2/ND	Left dorsum	WSE	7.2	NED
13	Aiken AH [29]	2003	34/F	ND/3	Right base	Surgery	ND	ND
14	Fanburg-Smith JC [4]	2004	3/F	2.5/6	Right side	Surgery	11	NED
15	Fanburg-Smith JC [4]	2004	3/M	0.8/1	Right side	Surgery	4	NED
16	Fanburg-Smith JC [4]	2004	3/F	ND/ND	Left lateral side	Surgery	10	NED
17	Fanburg-Smith JC [4]	2004	5/M	ND/ND	Base	Surgery	11	Alive
18	Fanburg-Smith JC [4]	2004	5/F	5/2	Right lateral side	Surgery	32	NED
19	Fanburg-Smith JC [4]	2004	5/F	1/0.5	Midportion	Surgery	22	NED
20	Fanburg-Smith JC [4]	2004	5/F	ND/24	Left side	Surgery	ND	ND
21	Fanburg-Smith JC [4]	2004	6/M	ND/12	Tongue	Surgery	ND	ND
22	Fanburg-Smith JC [4]	2004	6/M	2.5/5	Dorsum	Surgery	28	Alive
23	Fanburg-Smith JC [4]	2004	7/M	1.3/ND	Undersurface	Surgery	27	Alive
24	Fanburg-Smith JC [4]	2004	7/M	2.5/ND	Left side	Surgery	16	NED
25	Fanburg-Smith JC [4]	2004	17/M	2.5/ND	Posterior	Surgery	25	NED
26	Fanburg-Smith JC [4]	2004	20/M	1/3	Right posterior	Surgery	ND	ND
27	Fanburg-Smith JC [4]	2004	21/F	3/ND	Left side	Surgery	ND	ND
28	Kim HS [30]	2005	16/M	ND/6	Tongue	WSE	6	NED
29	Kim HS [30]	2005	4/F	ND/8	Tongue	WSE	8	NED
30	Nascimento Souza KC [31]	2005	13/F	3/108	Left side of the dorsum	Surgery	5	NED
31	Raghunandhan S [32]	2007	13/F	2.5/4	Base	WSE	0.5	NED
32	Tapisiz OL [33]	2008	18/F	4.5/5	Right dorsum	ND	ND	Unknown
33	Rodríguez-Velasco A [34]	2009	2/F	1.5/3	Lateral right	Chemotherapy	2.8	NED
34	Baglam T [35]	2009	18/F	6/6	Base	WSE	0.8	DOD
35	Noussios G [16]	2010	3/M	3.3/6	Mid-dorsum area of the tongue extending to its base	WSE	3.5	NED
36	Eley KA [36]	2010	24/M	1/1.4	Left lateral	WSE	1	NED
37	Kumar M [37]	2010	7/M	2.5/30	Right dorsolateral aspect	Surgery	0.9	NED
38	Anbarasi K [38]	2011	25/M	4/36	Right dorsum	WSE	3	NED
39	Argyris PP [39]	2013	4/M	2/ND	Left dorsal side	WSE	0.6	NED
40	Wang HW [1]	2015	20/F	2.5/ND	Base	ND	2.8	NED
41	Wang HW [1]	2015	3/F	3.5/ND	Base	ND	0.8	NED
42	Wang HW [1]	2015	11/M	3/ND	Dorsal	ND	1.2	NED
43	Wang HW [1]	2015	7/M	4/ND	Base	ND	2.4	NED
44	Wang HW [1]	2015	16/F	3.3/ND	Base	ND	2.9	NED
45	Wang HW [1]	2015	10/M	3.5/ND	Base	ND	6.4	NED
46	Yoshihiro T [40]	2017	23/M	ND/24	Tongue	Surgery	0.3	Recurrence and Metastatic
47	Alegría-Landa V [41]	2019	53/M	2/8	Right side of the tip	WSE	ND	ND
48	Ruffle A [42]	2019	0.9/F	3.7/ND	Right aspect	Surgery	1.2	NED
49	Hsu CW [43]	2019	3/M	1.2/3	Right posterior dorsal	Surgery	ND	ND
50	Present case	2019	24/F	2.5/12	Midline dorsal	Surgery	1	NED

F, female; M, male; ND, no data; NED, no evidence of disease; DOD, dead of disease; WSE, indicates wide surgical excision.

Most of the ASPS tumors are round, oval, or nodular, and a few may have an envelope. Tumors that occur in the tongue are usually smaller and most of the tumors on the extremities are larger. Tumors are separated into cell nests of different sizes by fibrous spaces of varying widths. Cell nests tend to be uniform and have pseudoglandular structures. The interstitial fibrous connective tissue compartment contains a flat endothelial-lined sinus-shaped blood channel. Histologically, tumor cells are round or polygonal, the size and shape are more consistent, and the nucleoli are obvious. Cell boundaries are clear, cytoplasm is rich, eosinophilic, and finely granular. The specimen of this case was gray-white, the capsule was intact, and the tumor cells were arranged in organoid pattern. The tumor cells were large round, with obvious nucleoli; a vascular network was seen around the tumor cell cluster, and needle-like or rod-like crystals were seen by PAS staining.

MyoD1 was positive in the cytoplasm in ASPS, and it was occasionally positive for desmin, S-100 protein and NSE staining, but these were not diagnostic. Epithelial markers and endocrine markers such as CK, EMA, CgA, and Syn were negative. Manystudies have shown that TFE-3 polyclonal antibodies have a certain specificity for the diagnosis of ASPS, and the sensitivity and specificity can even exceed 95% [5]. In 1995, the non-equilibrium t (x; 17) (p11.2; q25) chromosomal translocation was first discovered in ASPS, and the ASPL-TFE3 fusion gene produced by this translocation was detected. This expression, is highly specific in ASPS [6,7]. Many studies have confirmed the existence of ASPL-TFE-3 fusion transcripts in ASPS patients [8]. Immunohistochemical results of the patient showed a strong nuclear immune response to TFE-3. The tumor cells were diffusely positive for vimentin, SMA. MyoD1, Ki-67 were focally positive, and the FISH detection showed t (Xp11.2) (TFE-3): (+), that is, TFE-3 gene-related translocation.

The location of ASPS has a great impact on the diagnosis of ASPS. When tumors occur in the tongue, they should be distinguished from the following diseases. Granular cell tumors mostly occur in middle-aged and elderly people. There is no capillary network and no cytoplasmic glycogen in fibrous connective tissue. PAS staining was negative, while S-100, SOX10, inhibitor, nestin were positive [9]. PEComa is similar to ASPS, with eosinophilic cytoplasm, granular cytoplasm that is PAS positive, and nuclear TFE-3 is positive. However, PEComa expresses MART-1 and HMB-45, while ASPS does not [10]. Rhabdomyosarcoma occurs in skeletal muscle. The cells are large and polygonal, with vacuoles in the cytoplasm and no nuclear atypia. Granular or rod-shaped inclusions in the cytoplasm are similar to the PAS-stained crystals of ASPS cytoplasm. Desmin and myogenin positive expression is seen in rhabdomyoblast cells. Paragangliomas occur in middle-aged and elderly people. The predominant site is the peritoneum, followed by the head and neck. Primary paragangliomas express neuroendocrine markers such as Syn, CgA, and S-100. However, PAS staining is negative. Alveolar rhabdomyosarcoma shows small, round or oval tumor cells separated by connective tissue into nests, lacking sinusoidal vascular network, strong eosinophilic cytoplasm, and occasionally multinucleated tumor giant cells. Tumor cells can express myogenin, or MyoD1, of which MyoD1 is nuclear-positive, but MyoD1 is expressed in the cytoplasm in ASPS.

20% to 25% of patients have tumor that has metastasized at the beginning of consultation, so the prognosis is poor. Wang et al. [11] reported that surgery and radiotherapy for patients with non-metastatic disease can achieve better results. Especially with postoperative treatment, Blackmon et al. [12] reported that surgery for patients with stage IV ASPS is still effective. The status of the surgical margin plays a vital role in the prognosis. Once the surgical margin is positive, the risk of postoperative recurrence increases, and the prognosis is poor [13]. However, ASPS of the tongue has its own characteristics: the course of ASPS in the tongue is shorter and the rate of metastasis is lower. Due to the limited size of tissue in the area, the complete expansion and resection of the mass often seriously affects the patient’s body function. Therefore, for ASPS of the tongue that cannot be resected, postoperative adjuvant radiotherapy effective. A study by Ogose et al. [14] found that postoperative adjuvant radiotherapy can help delay local tumor recurrence. For patients with distant metastases and patients with advanced disease, in recent years, there has been more and more research on antiangiogenic drugs. In particular, sildenib has been demonstrated in large-scale clinical studies for its significant activity and safety [15]. The current patient underwent an extended resection of the tumor of the left tongue. An intact capsule was seen during the operation. Because of the preoperative tendency to benign lesions, no cryopathology was done. Imaging studies showed no metastatic lesions. No radiotherapy or radiotherapy was performed after the operation, and the patient is currently in stable condition. After 12-month of follow-up, no recurrence or metastasis was found.

Conclusion

In summary, ASPS rarely occurs in the head and neck and it occurs more rarely in the tongue. It can be found from this report that the ASPS in the tongue typically occurs in children and adolescents. Literature review indicates that tongue ASPS tends to be small, and it is found mainly in the base of the tongue and dorsal surface. The prognostic factors of ASPS are related to the age of onset, the size of the primary lesion, whether the surgical resection is complete, and whether metastasis has occurred [16]. Due to the short course of ASPS that occurs in the tongue and the smaller size, the prognosis is better after complete resection.

Disclosure of conflict of interest

None.