A case report of angiosarcoma originating from the tongue

Abstract

Key Clinical Message

Angiosarcoma is a rare malignant disease with an extremely poor prognosis, showing rapid progression of the local tumor and/or distant metastases. Although multidisciplinary approach including systemic chemotherapy and radiation therapy is ideal for this disease, surgical resection have a role in disease control and should be performed as soon as possible.

Abstract

Angiosarcomas originating from the tongue are rare and have extremely malignant features, leading to a poor prognosis. Herein, we report the case of a patient with angiosarcoma arising from the tongue who was successfully treated surgically. A 71‐year‐old man was diagnosed with a mass on the right side of his tongue and visited the Department of Oral and Maxillofacial Surgery at our hospital. The patient was referred to our department for further examination and treatment after a biopsy of the right edge of the tongue. An irregularly raised tumor 50 mm in length was noted on the right lingual border. The preoperative diagnosis was a primary angiosarcoma of the tongue (clinical stage, T3N2bM0, Stage IV). As his tumor had been growing rapidly, he emergently underwent partial right‐sided tongue resection and right neck dissection without reconstructive surgery. The histopathological diagnosis was pT3N0. Postoperatively, the patient showed no signs of recurrence or metastasis during the 1‐year follow‐up. As for angiosarcomas, surgical resection is the only curative treatment, and surgery should be performed as soon as possible after the final diagnosis.

Surgical treatment of angiosarcoma of the tongue.

1. INTRODUCTION

Angiosarcoma is a malignant disease, accounting for approximately 2%–3% of all sarcomas, approximately half of which occur on the skin of the head and neck region (approximately 50%) and approximately 1% in the oral cavity. ¹ Other sites have been reported, including the breast parenchyma, soft tissue, heart, and bone. ² Angiosarcoma develops and spreads rapidly, and its prognosis is extremely poor, with a 5‐year survival rate of 12%–35%. ³ , ⁴ , ⁵ Eight cases of angiosarcoma arising from the tongue have been reported to date ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ (Table 1); however, no standard treatment has yet been established. Only one advanced case has been reported so far. ⁷ We present an extremely rare advanced case of angiosarcoma arising from the tongue and discuss the literature review.

TABLE 1.

Case reports of angiosarcoma of the tongue.

	Report	Age	Sex	Tongue sub site	Size (mm)	Neck disease	Distant metastasis	Clinical TNM	Clinical stage	Surgery (partial resection)	Surgery (neck dissection)	Radiation	Chemotherapy	Clinical outcome	Follow‐up period (months)
1	Harter 6	53	M	Dorsum	7 × 7	−	−	T1N0M0	I	+	−	Unknown	Unknown	Alive without disease	Unknown
2	Rao et al. 7	52	M	Dorsum	Unknown	+	+(skin)	TxN1M1	IVC	−	−	+	−	Died of disease	Unknown
3	Frick and McDaniel 8	63	M	Dorsum	10 × 10	−	−	T1N0M0	I	+	−	−	−	Died of other disease	7
4	Tabata et al. 9	81	M	Dorsum	30 × 30	−	−	T2N0M0	II	+	−	−	+	Died of other disease	4
5	Yasumatsu et al. 10	38	F	Lateral	40 × 30	−	−	T2N0M0	II	−	−	−	+	Died of disease	24
6	Chadha et al. 11	50	F	Lateral	40	−	−	T2N0M0	II	+	−	−	−	Alive without disease	Unknown
7	Nagata et al. 12	78	F	Lateral	60 × 50	+	−	T2bN1M0	IV	+	+	−	−	Died of disease	6
								(AJCC)	(AJCC)
8	Patel et al. 13	57	M	Lateral	50 × 30	+	−	T2bN1M0	IV	+	+	+	−	Died of disease	21
								(AJCC)	(AJCC)
9	Present case	71	M	Lateral	50	+	−	T3N2bM0	IVA	+	+	−	−	Alive without disease	12

Note: The TNM classification and stage of cases in 7 and 8 are according to AJCC (American Joint Committee on Center). ¹⁷

2. CASE HISTORY AND EXAMINATION

A 71‐year‐old man was aware of a mass on the right side of his tongue and visited the Department of Oral and Maxillofacial Surgery at our hospital. The patient was referred to our department for further examination and treatment after a biopsy of the right edge of the tongue. His medical history included dementia and gout. The ECOG performance status was one. The oral cavity was edentulous, tongue mobility was good, and an irregularly raised tumor 50 mm in length was found on the right lingual border (Figure 1A). No apparent lymphadenopathy was observed in the neck. Magnetic resonance imaging revealed a mass with a contrast effect at the right lingual border on Gd enhanced T1 weighted imaging (Figure 1B). Fluorodeoxyglucose positron emission tomography revealed a 51 × 43 × 28 mm tumor extending from the right side of the tongue showing an abnormal accumulation with a maximum standardized uptake value (SUV) of 37.41. Lymphadenopathies were found in the right level IB, IIA, IIB, and III regions with abnormal accumulation, and lymph node metastasis was suspected. No distant metastases were observed (Figure 1C–E). Histopathological examination of the biopsy specimen with hematoxylin–eosin (H&E) staining showed a thickened keratinized epithelium under which large, round‐ to spindle‐shaped cells were proliferating, forming relatively small, irregular lumen‐like structures. Individual cells had a high nucleocytoplasmic ratio, with well‐defined nucleoli, and scattered mitotic figures. The immunohistochemical staining was positive for D2‐40 and partially positive for CD31 (Figure 3B,C). The preoperative diagnosis was a primary angiosarcoma of the tongue (clinical stage, T3N2bM0, and Stage IV).

FIGURE 1.

(A) Intraoral view of the patient. An irregularly raised tumor, 50 mm in length, is found on the right lingual border. Tongue mobility is good. (B) T1‐weighted magnetic resonance imaging showing high intensity on the right lingual border (arrow). (C) Axial image (oral level). (D) Axial image (neck level). (E) Coronal fluorodeoxyglucose positron emission tomography (FDG‐PET). FDG‐PET reveals a 51 × 43 × 28 mm tumor extending from the right side of the tongue to the midline with an abnormal accumulation with a maximum standardized uptake value (SUV) of 37.41 (C, arrow). Lymphadenopathy is found in the right level IB, IIA, IIB, and III regions, with abnormal accumulation up to an SUV of 3.35 (D, arrow), and lymph node metastasis is suspected. No distant metastases are observed.

FIGURE 3.

Histopathological findings. Since similar results were obtained both in biopsy specimens and surgically removed specimens, we used materials from surgically removed specimens in this figure. (A) Hematoxylin–eosin staining of the tongue tumor (×200). (B), (C) Positive immunohistochemical staining for CD31 (B) and D2‐40 (C). Diffuse immunoreactivity is found on the specimens.

3. TREATMENT

As his tumor had been growing rapidly, emergent surgical resection was planned. Because of the deterioration of his general condition and dementia, surgical reconstruction was avoided, and he underwent partial right‐sided tongue resection with a efficient safety margin and right neck dissection (I–IV) 22 days after his first visit to our hospital. Right modified radical neck dissection was performed with preservation of the cervical structures except for the mandibular marginal branch of the facial nerve. Level II showed two lymph nodes 10 mm in length bordering the internal jugular vein, which were slightly firm and suspected of metastasis. The tongue tumor was fragile and soft, showing exophilic growing and the intralingual invasion was approximately 10 mm at the deepest point on palpation. A 10 mm safety margin was established, the tumor was resected, and the tongue wound was sutured in a single stage (Figure 2).

FIGURE 2.

(A) The intraoperative view of the tumor. A partial right‐sided tongue resection is performed. (B) The tongue tumor is removed. The tumor measures 70 × 50 × 20 mm and is dark red, soft, and fragile. (C) Cut surface of the specimen. The tumor is whitish and substantial.

4. DIFFERENTIAL DIAGNOSIS

Histopathological examination showed atypical cells with a large nucleolytic cell and round‐ to spindle‐shaped proliferating nuclei, showing a full or vascular‐like structure. The tumor invaded the muscle layer, with a thickness of 18 mm. All cervical lymph nodes tested negative for metastases. The final histopathological diagnosis was pT3N0. Immunohistochemical analysis revealed positivity for vimentin, CD31, D2‐40, and factor VIII (Figure 3).

5. OUTCOME AND FOLLOW‐UP

Postoperatively, the patient showed no signs of recurrence or metastasis during the 1‐year follow‐up. His swallowing and speech disturbance were not so severe that his daily life was maintained independently.

6. DISCUSSION

Herein, we present a unique case of advanced angiosarcoma of the tongue. External stimuli, such as trauma, ultraviolet light, and radiation, have been identified as factors in the development of angiosarcoma. ³ In the present case, no obvious factor was observed except for the possibility of stimulation by the denture.

Angiosarcomas arising in the oral cavity appear as rapidly enlarging, dark red, soft, and fragile tumors. Histopathological findings include an increase in irregularly dilated, anastomosing vascular spaces and atypical or pleomorphic endothelial cell proliferation, which may make the diagnosis difficult to confirm. However, H&E staining alone makes it difficult to confirm the diagnosis of angiosarcoma. Immunohistochemical staining revealed no specific markers for angiosarcoma; however, the expression of the vascular endothelial cell markers CD31, CD34, and Factor VIII as well as the lymphatic endothelial cell marker D2‐40 helped in the diagnosis of angiosarcoma. CD31 is highly sensitive and specific and is considered useful. ¹⁴ In our case, H&E staining revealed atypical cells with a high nucleocytoplasmic ratio, round‐ to spindle‐shaped nuclei, and proliferation in a vascular‐like pattern. These cells were also positive for CD31, Factor VIII, and D2‐40 (Figure 3), which led to the diagnosis of angiosarcoma. Although the histopathological diagnosis is difficult to confirm, angiosarcoma can be suspected if the gross findings show a soft, brittle, rapidly growing, dark‐red tumor, characteristic of angiosarcoma. Because clinical information is a major clue for histopathological diagnosis, it is extremely important to provide clinical information to pathologists. Mutations in PTPRB and PLCG1 have been identified as molecular abnormalities in some angiosarcomas, and the involvement of the MAPK pathway has been postulated. ¹⁵ It has also been reported that c‐Myc is amplified in all cases of angiosarcoma secondary to irradiation of breast cancer or chronic lymphedema. ¹⁶ However, gene expression was not examined in the present study.

Table 1 shows the previous reports of angiosarcoma originating from the tongue. The TNM classification and stage of Cases 10 and 11 are according to AJCC (American Joint Committee on Center). ¹⁷ Angiosarcomas are usually treated with surgery, radiation therapy, chemotherapy, and immunotherapy, either alone or in combination. There is no established treatment for angiosarcomas of the head and neck region. The treatment plan was reviewed according to the Cutaneous Angiosarcoma Clinical Practice Guidelines (2021). The best way to predict the outcome of angiosarcoma is by obtaining a clear diagnosis. Subsequently, each case should be examined independently. Currently, there is no effective treatment for inoperable cases, and even with multidisciplinary treatments combining radiation therapy, chemotherapy, and immunotherapy, the prognosis of patients is poor. However, further studies are needed to confirm this hypothesis. Only paclitaxel, with a reported response rate of 89%, is covered by insurance when combined with chemotherapy. ¹⁸ Recently, clinical trials for treatment with molecular‐targeted agents have been conducted. Pazopanib, a multi‐kinase inhibitor and molecularly targeted treatment for malignant soft tissue sarcoma, is covered by health insurance in Japan. The disease control rate in 10 patients with angiosarcoma treated with pazopanib was 70% (1 CR, 5 PR, and 1 SD). ¹⁹

In the present case, the tumor was resected with sufficient margins because it was operable. Radiation therapy and chemotherapy were considered as postoperative treatments; however, because the patient had dementia and his cognitive status deteriorated, surgical resection alone was performed. Early diagnosis was possible from the initial diagnosis based on the gross and pathological findings in this case. Surgical treatment can be performed in a relatively short period, which is thought to have enabled the control of difficult‐to‐treat angiosarcomas. There is a possibility of survival without recurrence or metastasis, even in advanced cases, such as the present case. However, local recurrence has been reported to occur in many patients after surgery alone. ²⁰ Although no recurrence or metastasis was observed 1 year after surgery, there is a high possibility of recurrence or metastasis in the future, and strict and regular follow‐ups are necessary.

7. CONCLUSION

We present a rare case of advanced angiosarcoma of the tongue. Angiosarcoma is a rare malignant disease with an extremely poor prognosis, showing rapid progression of the local tumor, and/or distant metastases. However, it is difficult to confirm the diagnosis of angiosarcoma using H&E staining alone, which may delay the diagnosis. Positivity of immunohistological staining for CD31, factor VIII, and D2‐40 lead to the accurate diagnosis of angiosarcoma. Clinicians who see suspected patients with angiosarcoma should transfer to the pathologist to facilitate rapid and accurate histopathologic diagnosis. Even advanced cases that only undergo surgery, such as in the present case, may survive without recurrence or metastasis. Local recurrence is reported to occur at a high rate after surgery alone. There is a high possibility of future recurrence or metastasis, and strict and regular follow‐up is necessary.

AUTHOR CONTRIBUTIONS

Iori Kusaka: Conceptualization; writing – original draft. Katsunori Katagiri: Funding acquisition; investigation. Daisuke Saito: Funding acquisition; investigation. Yu Ohashi: Investigation. Shin‐ichi Oikawa: Investigation. Kodai Tsuchida: Investigation. Jun Miyaguchi: Investigation. Takahiro Kusaka: Investigation. Ryoukichi ikeda: Writing – original draft; writing – review and editing. Kiyoto Shiga: Conceptualization; funding acquisition; investigation; writing – review and editing.

FUNDING INFORMATION

None.

CONFLICT OF INTEREST STATEMENT

The authors declare that they have no conflicts of interests.

ETHICS

This manuscript was written in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). The anonymity of the patient was confirmed. Informed consent was obtained from the participant presented in the study. This study was approved by the Institutional Review Board (MH2020‐209). This material has not been published in completely or in part elsewhere.

CONSENT STATEMENT

Written informed consent was obtained from the patient to publish this report.

Kusaka I, Katagiri K, Saito D, et al. A case report of angiosarcoma originating from the tongue. Clin Case Rep. 2023;11:e8330. doi: 10.1002/ccr3.8330

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.