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. 2025 Dec 9;13(12):e71658. doi: 10.1002/ccr3.71658

Esophageal Cancer With Neurologically Symptomatic Parapharyngeal Space Paraganglioma

Shintaro Nozu 1,✉, Takashi Fukuda 1, Shinichiro Shiomi 1, Daiji Oka 1, Satoshi Shirakura 2, Hiroki Ushijima 3
PMCID: PMC12689270  PMID: 41383529

ABSTRACT

Parapharyngeal space (PPS) tumors are rare neoplasms and can occasionally present with neuropathy. We report a case of advanced esophageal cancer (EC) complicated by a PPS paraganglioma. In this case, severe neurological symptoms were present, and treatment of the benign PPS paraganglioma was prioritized over treatment of the malignant EC. After radiotherapy for the paraganglioma, the paraganglioma markedly shrank and the neurological symptoms disappeared. Subsequent preoperative chemotherapy and thoracoscopic esophagectomy for the EC were performed without complication. To our knowledge, this is the first report describing EC with PPS paraganglioma. The surgical stress of thoracoscopic esophagectomy remains high, and the preoperative condition impacts both short‐term and long‐term outcomes. In cases with multiple lesions, it is essential to comprehensively decide on the treatment strategy, considering individual conditions and their influence on prognosis.

Keywords: esophageal cancer, paraganglioma, parapharyngeal space tumors, preoperative chemotherapy, thoracoscopic esophagectomy

Key Clinical Message

We report a rare case of advanced esophageal cancer (EC) complicated by a parapharyngeal space paraganglioma. The treatment of paraganglioma was prioritized over EC due to severe neurological symptoms. In cases with multiple lesions, considering individual conditions and influence on prognosis is essential to decide the treatment strategy.

A case of advanced esophageal cancers complicated by a parapharyngeal space paraganglioma. MRI showed a right PPS tumor with characteristic imaging features, and endoscopy revealed advanced tumors in both the upper and lower esophagus. Radiotherapy for the paraganglioma followed by neoadjuvant chemotherapy and esophagectomy for the esophageal cancer led to a favorable outcome.

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1. Introduction

Esophageal cancer (EC) is a malignancy carrying a poor prognosis. The standard treatment for clinical Stage II and III EC in Japan is preoperative chemotherapy followed by radical resection according to the current guidelines [1]. Although thoracoscopic surgery has become widespread due to being a minimally invasive surgical approach for EC, perioperative stress and complication rates, including those during the preoperative chemotherapy period, remain high, including the preoperative chemotherapy period [2, 3]. Good control of preoperative nutrition and comorbidities is essential. Parapharyngeal space (PPS) paraganglioma is rare in the head and neck region [4], and can occasionally compress cranial nerves or sympathetic nerves causing neuropathy [5, 6, 7]. Radical resection of PPS paraganglioma carries a high risk of injury to cranial nerves and cervical arteries [6, 7, 8, 9]. Recent reports have recommended radiotherapy as the first choice for PPS paraganglioma, and favorable long‐term outcomes with radiotherapy have been reported [10, 11]. To our knowledge, there are no previous reports of EC with PPS paraganglioma. We herein describe the therapeutic course of a patient with advanced EC complicated by a PPS paraganglioma producing neurological symptoms.

2. Case History

A 76‐year‐old man was referred to our hospital for further evaluation and treatment of a PPS mass. He had presented with nasal discharge and difficulty swallowing for 3 months, along with syncope, which had appeared 1 week before referral. Nasopharyngoscopy revealed right vocal cord paralysis. Contrast‐enhanced computed tomography (CT) imaging showed an irregularly shaped and heterogeneously enhanced right PPS mass measuring 40 × 28 × 68 mm. The mass encased the right internal carotid artery (ICA) (Figure 1). Gadolinium‐enhanced magnetic resonance imaging (MRI) revealed a rapidly enhancing PPS mass that extended into the right sigmoid sinus. The PPS mass exhibited inhomogeneous intermediate signal intensity on T1 and T2‐ weighted images (WI) and high signal intensity on diffusion‐weighted images. There were multiple punctate structures indicative of a signal void within the mass on T2WI. Dynamic contrast‐enhanced MRI T1‐weighted images showed rapid enhancement and a plateau pattern (Figure 2). Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET), performed to exclude a malignant paraganglioma, revealed increased fluorodeoxyglucose uptake within the PPS mass, with a maximum standardized uptake value (SUV) of 24.6, as well as showing the upper and lower thoracic esophagus with occasional maximum SUV of 15.7 and 12.5 (Figure 3). Upper gastrointestinal endoscopy showed a 50 mm Type 2 + IIc tumor between the 21 and 26 cm incisors and a 30 mm Type 2 + IIc tumor between the 34 and 37 cm incisors (Figure 4). Biopsies revealed squamous cell carcinoma (SCC) in samples from both esophageal lesions. The tumor marker SCC antigen was 1.3 ng/mL, that is, within the normal range. No swollen lymph nodes (LNs) were observed on CT.

FIGURE 1.

FIGURE 1

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Initial enhanced computed tomography. An irregularly shaped and heterogeneously enhanced mass (40 × 28 × 68 mm) at the right parapharyngeal space (circle). The mass encased the right internal carotid artery (arrow). Coronal image (a), and axial image (b).

FIGURE 2.

FIGURE 2

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Initial gadolinium‐enhanced magnetic resonance imaging. An irregularly‐shaped mass at the right parapharyngeal space, extending into the right sigmoid sinus. T1‐weighted image (a) and T2‐weighted image (b) showed heterogeneous intermediate intensity. Enlarged T2‐weighted image (c) showed multiple punctate structures indicative of a signal void; “salt and pepper appearance” within the mass (arrows). Diffusion‐weighted image (d) showed high signal intensity. Dynamic contrast‐enhanced MRI T1‐weighted images showed rapid enhancement in the early phase (e), and a plateau pattern in the delayed phase (f).

FIGURE 3.

FIGURE 3

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Fluorodeoxyglucose‐positron emission tomography and enhanced computed tomography. Increased fluorodeoxyglucose uptake within a parapharyngeal space mass (SUV max 24.6) (black arrow), as well as in the upper thoracic esophagus (SUV max 15.7) (white arrow) and in the lower thoracic esophagus (SUV max 12.5) (white arrowhead) (a). Examination of the initial enhanced computed tomography retrospectively revealed irregular thickening of the upper and lower esophageal walls (b, c).

FIGURE 4.

FIGURE 4

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Upper gastrointestinal endoscopy. (a–c) A circumferential type 2 + IIc tumor centered on the right wall between the 21 and 26 cm incisors (upper thoracic esophagus). White light imaging (a), Narrow band imaging (b), post‐radiotherapy follow‐up (c). (d–f) A semi‐circumferential Type 2 + IIc tumor centered on the right anterior wall between the 34 and 37 cm incisors (lower thoracic esophagus). White light imaging (d), Narrow band imaging (e), post‐radiotherapy follow‐up (f). After radiotherapy for the parapharyngeal space tumor, no apparent changes were observed in the upper thoracic esophagus lesion (c), while progression was noted in the lower thoracic esophagus lesion (f).

3. Methods (Differential Diagnosis, Investigations and Treatment)

The PPS tumor was most likely diagnosed as a paraganglioma due to its hypervascularity and location, and was classified as benign because no distant metastases were identified. The esophageal double cancers were classified as clinical Stage II (Ut, T2 / Lt, T2, N0M0) according to the Japanese Classification of Esophageal Cancer, 12th Edition. We originally planned to prioritize treating the ECs as these tumors had the greatest prognostic significance. However, he developed neurological symptoms including orthostatic hypotension, vertigo, and syncopal attacks while waiting for preoperative chemotherapy, which was planned as the standard treatment for EC. His activities of daily living worsened abruptly, and his performance status (PS) declined markedly from 0 to 3. The treatment protocol was thus reconsidered, and the PPS paraganglioma was prioritized. Given the invasion of the sigmoid sinus, surgical resection was predicted to be risky. Two months after referral, he underwent three‐dimensional conformal radiotherapy. A total dose of 52 gray in 22 fractions was delivered.

4. Conclusions and Results (Outcome and Follow‐Up)—1

MRI 3 weeks after completion of radiation therapy showed significant shrinkage of the PPS tumor (Figure 5). The neurological symptoms, including vocal cord paralysis, gradually disappeared. His activities of daily living improved, and his PS was restored to 0. On the other hand, post‐radiotherapy upper gastrointestinal endoscopy (Figure 4c,f) and CT (Figure 6) revealed no obvious changes in the upper EC; however, there was progression of the lower EC with infiltration into the adventitia, along with swelling of a left cervical paraesophageal LN. The tumor marker SCC antigen level had risen to 4.8 ng/mL. The ECs were classified as clinical Stage IIIA (Ut, T2/Lt, T3, N1M0) at this point. We again planned esophagectomy following preoperative chemotherapy. One month after radiotherapy, we administered intravenous docetaxel (70 mg/m2, day 1), cisplatin (70 mg/m2, day 1), and 5‐fluorouracil (750 mg/m2, 96 h), DCF, at three‐week intervals. The PPS tumor did not regrow, and the neurological symptoms did not recur during the preoperative chemotherapy period. After three courses of DCF chemotherapy, the ECs were partially reduced, and the left cervical paraesophageal LN had stabilized in size on CT examinations. The overall response was assessed as Stable Disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 classification. The tumor marker SCC antigen decreased to 2.6 ng/mL. Seven months after referral, radical thoracoscopic subtotal esophagectomy and gastric tube reconstruction were performed.

FIGURE 5.

FIGURE 5

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Magnetic resonance imaging after radiotherapy. Marked shrinkage of the parapharyngeal space tumor to be indistinct. T1‐weighted image (a), T2‐weighted image (b), Diffusion‐weighted image (c).

FIGURE 6.

FIGURE 6

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Enhanced computed tomography after radiotherapy. No obvious changes in the lesion of the upper thoracic esophagus (a). The lesion of the lower thoracic esophagus had progressed to infiltrate the adventitia (b), and a swollen left cervical paraesophageal lymph node had become evident (15 × 12 mm: Arrow) (c).

5. Conclusions and Results (Outcome and Follow‐Up)—2

The postoperative course was uneventful, and he was discharged on postoperative day 14 with no complications. The histopathological diagnoses were double ECs, Lt, Type 3, SCC, CT‐pT3, therapeutic effect; Grade 1a, and Ut, Type 0‐IIc, SCC, CT‐pT1b, therapeutic effect; Grade 2. Metastatic lesions were detected in two LNs (pN1; No. 101L: left cervical paraesophageal LN and No. 106recR: right recurrent laryngeal nerve LN). At 10 months after surgery, the patient remains free of recurrence of either the EC or the paraganglioma.

6. Discussion

In 2020, EC was the sixth most common cause of cancer‐related death [12], and its prognosis is comparatively poor. The 5‐year overall survival of patients with clinical Stage II EC is 64.3%, and those with clinical Stage III is 45.9% according to the latest report based on the nationwide database in Japan [13]. The Esophageal Cancer Practice Guidelines in Japan [1] recommend preoperative chemotherapy followed by radical resection for patients with clinical Stage II or III EC as the first‐line therapy, assuming that they can tolerate surgical intervention. However, DCF chemotherapy, which is recommended as the standard regimen of preoperative chemotherapy for EC, is particularly potent and requires cautious application due to the high frequency of adverse effects [14]. Patients with poor PS or older patients may not be able to receive a sufficient dose of the drug, and their tolerability may be impaired by adverse effects. Some reports have described preoperative DCF therapy as not improving the outcomes of older patients with poor PS [3, 15]. Regarding surgery, minimally invasive esophagectomy (MIE) has been widely applied as the standard approach for EC in Japan. Although surgical techniques and perioperative management have also improved, MIE remains a highly invasive procedure leading to high rates of mortality and morbidity [2, 16]. A 2024 report using the 2018–2019 Japanese national database stated that the incidence of overall complications exceeding Grade IIIa was 20.3% [17]. Yet other reports have described perioperative complications as affecting long‐term outcomes [18, 19]. Considering these factors together, individual assessment of surgical risk is essential for accurately determining surgical indications [20, 21].

PPS paraganglioma is one of the PPS tumor subtypes, which represent only 0.5% of all head and neck tumors. There are up to 70 different PPS tumor subtypes, and they are classified broadly into salivary gland neoplasms (40%–50%) and neurogenic neoplasms (22%–41%) [4, 22]. Regarding the latter, depending on the series, the first and second most common tumors are paragangliomas or schwannomas, followed by neurofibromas [22, 23]. Paraganglioma is a hypervascular tumor, and it has characteristic findings of low signal intensity on T1WI, high signal intensity on T2WI, intense contrast enhancement, “salt and pepper appearance” representing flow voids, and encasement of the ICA [5, 7]. Hence, paraganglioma can easily be differentiated from other PPS tumors such as pleomorphic adenomas and schwannomas [5, 7]. The diagnosis of paragangliomas is generally based on radiological appearance because biopsy is challenging due to their anatomical locations and vascularity [22]. The majority of paragangliomas in head and neck lesions are benign tumors, with only 6% to 19% developing metastases and showing malignant behavior [24]. The most common places for metastases are the bones, cervical lymph nodes, lungs, liver, and thyroid [25]. FDG PET is very useful in localizing primary paragangliomas and metastatic lesions [24].

In our present case, the mass was highly enhanced and irregularly shaped, encasing the ICA on MRI. It had the characteristic “salt and pepper” appearance, and the patient was diagnosed with PPS paraganglioma based on radiological findings. FDG PET showed no distant lesions except for the esophageal lesions.

Regarding clinical presentation, PPS tumor, including paraganglioma, lacks specific symptoms. The most frequent presenting symptoms involve a cervical mass, which has been noted to be present in half of the patients with PPS tumors. Expanding into the post‐styloid compartment may compress cranial nerves IX through XII, with cranial nerve neuropathy [23, 24]. In the present case, the tumor had expanded beyond the jugular foramen, and the patient presented with right vocal cord paralysis. LNs along the recurrent laryngeal nerve have the highest frequency of metastases among thoracic ECs. Metastatic LN can impair recurrent laryngeal nerve function, leading to vocal cord paralysis, and identifying the cause was thus important in our present case. His right vocal cord paralysis disappeared after the PPS paraganglioma was reduced in size by radiotherapy.

Conventionally, the mainstay of the treatment for most PPS tumors is surgical resection, with the approach depending on the histology, location, and extent of the lesion, and the patient's medical condition [7]. Surgical resection carries risks for cranial nerve palsies and stroke. Radiotherapy is usually the primary modality for patients with unresectable lesions or who have surgical contraindications. Among PPS paragangliomas, especially when the lesion extends into the jugular foramen, total resection is associated with high morbidity because of their vascularity as well as the involvement of critical vascular and neural structures [6, 7, 8, 9]. Consequently, some authors recommend therapeutic radiation as a first line approach [10, 11]. Furthermore, a systematic review conducted by Suarez et al. [11] focused on the management of jugular and vagal paragangliomas and found that the likelihood of local control was better after radiotherapy and that the probability of a major complication was lower than with surgery. In the present case, we chose radiotherapy considering the high risk of surgical injury due to the patient's severe neurological symptoms, the extent of the tumor, and the involvement of the cervical vasculature. The PPS paraganglioma shrank markedly in response to radiotherapy. The neurological symptoms disappeared and his PS recovered.

The present case had advanced EC accompanied by PPS paraganglioma with vagal neuropathy. A literature search through June 2025 using the terms “esophageal cancer” and “parapharyngeal space tumor” or “paraganglioma” on PubMed and Google Scholar yielded no similar prognosis. Initially, we considered prioritizing treatment for EC, given that this malignancy has a very poor prognosis. However, the neurological symptoms worsened and his PS also deteriorated. We anticipated that it would be impracticable to administer adequate doses of chemotherapy, let alone safe perioperative management of EC. The EC was clinical Stage II at the time of diagnosis, and progression of the lesion during the prioritized treatment for PPS paraganglioma was deemed to present an acceptable risk. After delivery of radiotherapy for the PPS paraganglioma, the EC progressed from clinical Stage II to III. However, subsequent preoperative DCF therapy and MIE were performed as standard treatments, allowing resection with no residual tumor to be achieved, and there were no complications during the postoperative course.

In conclusion, we experienced a case of EC with PPS paraganglioma, which has not been reported previously. We prioritized radiotherapy for the PPS paraganglioma due to worsening neurological symptoms, and the subsequent treatment for EC was performed uneventfully. When a patient has multiple lesions of different types, it is essential to determine the treatment strategy comprehensively, considering the individual conditions and their influences on clinical outcomes.

Author Contributions

Shintaro Nozu: conceptualization, data curation, writing – original draft. Takashi Fukuda: supervision, writing – review and editing. Shinichiro Shiomi: writing – review and editing. Daiji Oka: writing – review and editing. Satoshi Shirakura: writing – review and editing. Hiroki Ushijima: writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

The authors have nothing to report.

Nozu S., Fukuda T., Shiomi S., Oka D., Shirakura S., and Ushijima H., “Esophageal Cancer With Neurologically Symptomatic Parapharyngeal Space Paraganglioma,” Clinical Case Reports 13, no. 12 (2025): e71658, 10.1002/ccr3.71658.

Data Availability Statement

The data supporting the findings of this study are available within the article. Additional information (e.g., blood test results) is available from the corresponding author upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data supporting the findings of this study are available within the article. Additional information (e.g., blood test results) is available from the corresponding author upon reasonable request.

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