Esophageal squamous cell carcinoma metastasizing to the oral cavity: a case report and literature review

Abstract

Introduction and Importance:

Metastatic esophageal carcinoma to the oral cavity has been rarely reported, and most cases were adenocarcinoma metastasizing to the mandible. This first report of a case of metastatic esophageal squamous cell carcinoma to the floor of the mouth is crucial due to its rarity and difficulties in diagnosing and managing this condition.

Case Presentation:

A 53-year-old male had a painful submucosal mass on the left side of the floor of the mouth for 2 months. A biopsy indicated a moderately differentiated squamous cell carcinoma. Six months before the intraoral mass appeared, the patient had a moderately differentiated squamous cell carcinoma of the thoracic esophagus and was treated with concurrent chemoradiotherapy. With the previous history and pathological review, the diagnosis of metastatic esophageal squamous cell carcinoma to the floor of the mouth was made. Panendoscopy and an 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan revealed no other abnormality or other distant metastasis. The patient underwent surgical resection with postoperative chemoradiotherapy. He was able to take a regular diet and had good speech function. Ten months after treatment completion, he has had recurrent disease at the floor of the mouth with lung metastasis.

Conclusions:

Oral metastasis from esophageal squamous cell carcinoma is very rare and should be differentiated from primary oral cancer using clinical and pathological features. 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning is the preferred imaging method to exclude primary tumor persistence and other metastases. Treatment is usually palliative; however, function-preserving surgery may be an option for a patient with limited disease in the oral cavity.

Introduction

Highlights

• Metastatic esophageal squamous cell carcinoma to the floor of the mouth is very rare.

• Patients usually had dysphagia or a history of esophageal carcinoma.

• 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan is the preferred imaging to exclude other metastases.

• This disease carries a poor prognosis; treatment is usually palliative.

• Function-preserving surgery may be an option for patients with limited disease.

Metastatic carcinomas to the oral cavity account for 1–3% of all oral cavity malignancies¹. In a recent systematic review, the most common primary malignancies metastasizing to the oral cavity were the lung (30.6%), followed by the breast (22.2%), liver (15.5%), prostate (9%), thyroid gland (8.1%), and kidney (7.3%)¹. Oral metastases may occur in the jawbones or the soft tissues. In the case of the bone, the mandible was affected more commonly than the maxilla. The predilected soft tissue metastases were the alveolar mucosa and the tongue¹. In another systematic review regarding metastatic esophageal cancers to unexpected sites, the most common distal metastatic site was the head and neck (42%), followed by the abdomen and pelvis (25%), thorax (17%), and extremities (9%)². In addition, the eye, jaw, skull, and thyroid were the common metastatic organs in the head and neck area².

From the previous systematic reviews, metastatic esophageal carcinoma to the oral cavity has been rarely reported, and most reports involved adenocarcinomas metastasizing to the mandibles. This study aims to report the first case of metastatic esophageal squamous cell carcinoma to the floor of the mouth and review similar articles regarding clinical features, investigation, and management. The case has been reported in line with the Surgical CAse REport (SCARE) 2020 criteria³.

Presentation of case

A 53-year-old male presented to the outpatient clinic of our hospital, a tertiary-level care center, with complaints of progressively increasing pain and swelling at the floor of the mouth for 2 months. Intraoral examination revealed a painful submucosal mass, size 2×2 cm, at the left side of the floor of the mouth (Fig. 1A), and a 1×1 cm mass at level II of the left cervical lymph node was noted. A biopsy of the intraoral mass reported a moderately differentiated squamous cell carcinoma. His medical history revealed that 6 months before the intraoral mass developed, he had presented with a moderately differentiated squamous cell carcinoma at the upper part of the thoracic esophagus, stage T3N1M0. He was treated with definitive concurrent chemoradiotherapy, a combination of three cycles of carboplatin/paclitaxel therapy (carboplatin AUC 2 and paclitaxel 50 mg/m²), and irradiation (60 Gy in 30 fractions). Clinical examination with a computerized tomographic (CT) scan follow-up at 3 months showed no evidence of tumor persistence. The patient was a former smoker and an alcohol drinker but stopped just before the treatment. He had no allergies, drug history, family history of cancer or genetic disorders and was never operated on before. With the previous history and pathological features, the histological examination of the esophagus and the floor of the mouth was reviewed. A final diagnosis of metastatic esophageal squamous cell carcinoma to the floor of the mouth was made (Fig. 2). Panendoscopy and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDGPET/CT) scanning revealed no other abnormality in the upper aerodigestive tract and no other distant metastasis (Fig. 3A–C). Following a multidisciplinary discussion that considered the patient’s preference, he underwent wide excision of the floor of the mouth, marginal mandibulectomy, left comprehensive neck dissection, right selective neck dissection, and submental island flap reconstruction by the senior surgeon (P.S.) (Fig. 1B). The final pathological report confirmed metastatic squamous cell carcinoma to the floor of the mouth with a pathological positive right lateral margin and no evidence of metastatic cervical lymph node. Postoperative concurrent chemoradiotherapy of weekly cisplatin 40 mg/m² and irradiation (66 Gy in 33 fractions) was administered. His postoperative recovery was uneventful. The patient could take a regular diet and had good speech function (Fig. 1C). Ten months after treatment completion, he had a recurrent disease at the floor of the mouth with lung metastasis and underwent palliative chemotherapy.

Figure 1.

Intraoral picture showing a submucosal mass, size 2×2 cm., at the left side of the floor of the mouth (black arrow) (A). In addition, intraoral pictures demonstrating a submental island flap reconstruction following surgical resection (B) and 2 months after treatment completion (C).

Figure 2.

18F-fluorodeoxyglucose positron emission tomography-computed tomography scan revealing evidence of hypermetabolic-active cancer at the left side of the floor of the mouth (white arrows) without other abnormality in the aerodigestive tract or distant organs (A and B), and coronal view of the computed tomography scan showing the submucosal mass at the left side of the floor of the mouth (C).

Figure 3.

Photomicrographs of the esophageal (A) and the floor of the mouth (B) squamous cell carcinoma. Note that the morphologic features are similar, and the tumor at the floor of the mouth was found solely under normal mucosa without intraepithelial dysplasia or a definite transformative zone. (hematoxylin–eosin stain, × 100 magnification).

Discussion

Esophageal cancer is globally the seventh most common malignancy. It occurs more frequently in males than in females, with a ratio of 2.5 to 1⁴. Squamous cell carcinoma accounts for 87% of worldwide; however, in North America, Australia, and Europe, adenocarcinoma is the predominant cell type, accounting for 70%⁴. Approximately 50% of patients have metastases to distant lymph nodes, lungs, liver, bone, adrenal glands, and the brain². The rare oral cavity metastases from esophageal cancers, both in the bones or soft tissues, were classified as unexpected metastatic sites². Hematogenous dissemination is believed to cause distant metastasis with four venous circuits, specifically the pulmonary, vena cava, portal, and vertebral veins. However, the vertebral veins communicate with the pterygoid plexus, cavernous sinus, and pharyngeal plexus, providing a pathway for metastasis to the oral cavity^1,2. In addition, the arterial route could also be the way for tumor emboli to be transferred to the distal terminal organs².

A literature search using the terms ‘metastatic esophageal carcinoma’ and ‘oral metastasis’ in PubMed identified 14 articles in English describing a total of 14 cases of esophageal carcinoma metastatic to the oral cavity, as summarized in Table 1 ^5–18. Out of the 15 cases, which include the single case in the present study, the mean age was 52 years old (range, 30–69 years old), and almost all were of male sex (13 males and 1 female). Adenocarcinoma was the predominated cell type, detected in 11 cases, while squamous cell carcinoma was found in four cases. Oral metastases were commonly in bone (nine cases in the mandible and three in the maxilla). In contrast, only three cases were found in soft tissue, one in the tongue and two in the floor of the mouth, including our case. Based on the 13 cases with available data, 6 cases had a history of previously treated esophageal carcinoma with an interval between detection of the primary and the metastasis of 4 months to 7 years. The other seven cases had esophageal cancer detected within 1 month of the diagnosis of oral metastasis, six had symptoms of dysphagia, and the remainder was detected from routine endoscopic examination and barium swallowing work-up for a second primary cancer. In addition, all 12 cases with available data were reported as having other metastatic organs, including cervical lymph nodes in 5 cases, bone in 5 cases, lung in 3 cases, liver in 2 cases, and brain in 2 cases.

Table 1.

Reports in the literature pertinent to esophageal carcinoma metastasizing to the oral cavity.

References	Age (years)	Sex	Histological diagnosis	Time between primary diagnosis and metastasis	Symptom of primary cancer	Oral metastatic sites	Other metastatic locations	Treatment of oral metastases	Outcome after treatment
Tideman et al.5	59	M	Adeno ca	Concurrent	Dysphagia	Maxilla	Cervical LN, liver	Maxillectomy	Died after 5 months
Sokolosky et al. 6	30	M	SCCA	Concurrent	Dysphagia	Mandible	Supraclavicular LN	Palliative chemotherapy	Died after 3 months
Jones et al.7	54	M	Adeno ca	Concurrent	Dysphagia	Mandible	Cervical LN	Best supportive care	Died after 6 weeks
Anderson et al.8	61	M	Adeno ca	Concurrent	Dysphagia	Mandible	Rib, ischium, and femur	Palliative radiotherapy	NA
Koyama et al.9	54	M	SCCA	Concurrent	No (abnormal Ba swallow)	Mandible	Liver	Mandibulectomy	Died after 3 months
Willard et al.10	41	M	Adeno ca	9 months	—	Maxilla	Lung, brain, liver, and spine	Palliative surgical debulking	Died after 10 months
Sánchez-Jiménez et al.11	63	M	Adeno ca	4 months	—	Maxilla	Pelvis, rib, and vertebra	Best supportive care	Died after 2 weeks
Tamiolakis et al.12	NA	NA	Adeno ca	NA	NA	Mandible	NA	NA	NA
Jham et al.13	67	F	Adeno ca	NA	NA	Mandible	NA	NA	NA
Lawes et al.14	69	M	Adeno ca	7 years	—	Mandible	Humerus, pelvis, and femur	Palliative radiotherapy	NA
Murillo et al.15	50	M	Adeno ca	Concurrent	NA	The floor of the mouth	NA	NA	NA
Tunio et al.16	55	M	Adeno ca	1 year	—	Oral tongue	Supraclavicular, mediastinal, and retroperitoneal LN	Palliative chemotherapy	Died after 2 months
O’Brien et al.17	69	M	Adeno ca	Concurrent	Dysphagia	Mandible	Lung and spine	Palliative chemoradiotherapy	Died after 1 month
Rocha et al.18	61	M	SCCA	4 months	—	Mandible	Brain	Best supportive care	Died after 1 month
Present study	53	M	SCCA	6 months	—	The floor of the mouth	Lung	Definitive surgical resection and postoperative chemoradiotherapy	Recurrence and lung metastasis after 10 months

Adeno ca, adenocarcinoma; Ba swallow, barium swallow study; LN, lymph node; NA, data not available; SCCA, squamous cell carcinoma.

Squamous cell carcinoma is the most common malignant tumor accounting for 80–90% of the oral cavity, including the floor of the mouth. The characteristic clinical manifestation is the presence of an ulcer, exophytic mass, or submucosal mass, and these features are also the presentation in oral soft tissue metastases¹⁹. Notably, of the three cases with soft tissue metastases, all presented with a mass or submucosal mass without mucosal ulceration. In addition, cervical lymph nodes can be observed in patients with oral metastases, as presented in four cases^5–7,16. Therefore, differentiation between primary oral squamous cell carcinoma and metastatic squamous cell carcinoma to the oral cavity is challenging. There are criteria for considering a malignant neoplasm to be metastatic, including there must be a histologically verified primary, the secondary lesion must be histologically similar to the primary, and the possibility of direct extension from the primary must be excluded²⁰. Although ~25% of oral metastases are the first sign of a metastatic spread¹⁹, based on our review, 12 cases out of 13 cases had either a history of esophageal cancer or a concurrent symptom of dysphagia, and in the other case, esophageal cancer was discovered from routine work-up.

Esophageal cancer had a reported prevalence of 7.7% of unusual soft tissue metastasis, higher than those of lymphoma and lung². Therefore, screening for this condition should be considered in oral cancer patients with a suspected history, physical findings, or histological results. In addition, an 18F-FDGPET/CT scan was more suitable than conventional imaging, which may have underestimated the true soft tissue metastasis².

Patients with esophageal cancer have a 5-year survival rate of under 5% in those with distant metastases^1,4. Therefore, treatment of oral metastases is usually palliative^1,2. Surgery with or without adjuvant radiotherapy or chemoradiotherapy is undertaken when the primary is controlled, and there is no evidence of other metastases¹¹. The treatment summary from the review was palliative therapy in 10 cases (radiotherapy, chemotherapy, debulking, and best supportive care) and surgical resection in three cases (mandibulectomy, maxillectomy, and wide excision). Based on the review, oral metastases from esophageal cancer had an abysmal prognosis with a mean survival of 3 months (range, 2 weeks to 10 months). Even in the curative surgical resection patients, death occurred within 5 months. In addition, in our case, with a curative-intent treatment, the patient still suffered from tumor recurrence and distant metastasis.

Conclusions

Oral metastases should be considered in patients with either adenocarcinoma or squamous cell carcinoma of the oral cavity presenting with a submucosal mass and a history of esophageal carcinoma or a symptom of dysphagia. The management guidelines include a pathological review to confirm the diagnosis, an endoscopic examination to identify the presence of primary and secondary cancer, and an 18F-FDGPET/CT scan to exclude other metastatic lesions. These patients have poor prognoses, and palliative treatment is usually required. However, without other metastases and primary esophageal cancer being controlled, function-preserving surgery, with or without postoperative adjuvant treatment to provide a good quality of life, may be an option.

Ethical approval

This case report was approved by the Research Ethics Committee of the Faculty of Medicine, Chiang Mai University, approved on 3 April 2023 (approval number: 9483/2023).

Informed consent statement

Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Patient consent

Written informed consent was signed by the patient.

Sources of funding

Not applicable.

Author contribution

P.S.: conceptualization, design of the study, acquisition of data, writing the original draft; D.R.: conceptualization, design of the study, writing-reviewing, and editing. S.L.: acquisition of data, writing-reviewing, and editing. All authors read and approved the final manuscript.

Conflicts of interest disclosure

The authors declare that they have no financial conflict of interest with regard to the content of this report.

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1. Registry used: Research Registry.

2. Unique Identifying number or registration ID: researchregistry9057.

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Guarantor

Pichit Sittitrai, MD.

Data availability statement

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

Provenance and peer review

Not commissioned, externally peer-reviewed.