A case report of esophageal squamous cell carcinoma with schwannoma-like features: from diagnosis to surgical management

Introduction

Approximately 2% of all esophageal tumors are benign, with esophageal schwannomas representing an exceedingly rare subset (1,2). Indications for surgical treatment of esophageal schwannomas include the presence of clinically significant dysphagia, rapid tumor growth, or the need for a definitive pathologic diagnosis. The surgical approach partially depends on tumor size: endoscopic per-oral approach is suitable for tumors <2 cm, surgical enucleation is recommended for tumors 2–8 cm, and esophagectomy may be required for tumors >8 cm (3,4). However, esophageal lesions <8 cm may require esophagectomy rather than enucleation if they have a wide, broad base or extensive mucosal erosion (4). In contrast, esophageal squamous cell carcinoma (SCC) is a more common and aggressive malignancy, necessitating a multimodal approach involving surgical resection, chemotherapy, and radiation. Standard treatment varies by stage: early-stage disease may be managed with endoscopic resection, locally advanced disease may be treated with definitive chemoradiation or multimodal therapy (neoadjuvant chemoradiotherapy followed by surgery), and metastatic disease necessitates chemoradiation plus immunotherapy (5,6). The prevalence, risk factors, and biology of schwannomas differ significantly from those of SCC. Esophageal SCC is primarily associated with tobacco use and heavy alcohol consumption (7,8). In contrast, conclusive risk factors for esophageal schwannomas have not been well described in the literature given its rarity and may present an unmet clinical need. There is no clinical evidence to suggest that benign esophageal schwannoma is a risk factor for SCC. A direct comparison of esophageal schwannoma and esophageal SCC is detailed in Table 1.

Herein, we report a patient with suspected esophageal schwannoma schwannoma who underwent a minimally invasive esophagectomy. Preoperative biopsy was consistent with schwannoma; however, the final pathology of the resected mass revealed invasive SCC with no evidence of schwannoma. To our knowledge, this is the first reported case of an esophageal mass with characteristics of both esophageal schwannoma and SCC. We present this article in accordance with the CARE reporting checklist (available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-5/rc).

Case presentation

A 62-year-old man presented with months of progressive dysphagia and associated weight loss. His past medical history was significant for non-Hodgkin’s lymphoma treated with chemotherapy, chronic (benign) gastric ulcer, long-standing gastroesophageal reflux, remote alcohol use disorder, and significant smoking history (50+ pack-years). His preoperative chest computed tomography (CT) was remarkable for asymmetric thickening of the distal esophagus (Figure 1).

Figure 1 Preoperative contrast-enhanced chest CT. (A) Axial view demonstrating asymmetric thickening of the distal esophagus (blue arrowheads). A feeding tube is present in the esophageal lumen (white arrow). (B) Coronal view showing air and fluid within the dilated upper esophagus and a filling defect (blue arrowhead) in the distal esophagus due to the known mass. The feeding tube is also shown (white arrow). CT, computed tomography.

Subsequently, he underwent diagnostic esophagogastroduodenoscopy (EGD), which showed a large esophageal mass extending 38 to 40 cm from the incisors (Figure 2). The mass was obstructive and partially circumferential, encompassing one-third of the lumen circumference. A cold forceps biopsy of the obstructing mass obtained during EGD was S-100 positive with negative smooth muscle markers (desmin) and gastrointestinal stromal tumor (GIST) markers (CD117, DOG1) on immunohistochemistry (IHC) staining, consistent with an esophageal schwannoma (Figure 3A,3B). Additional biopsies of the proximal and distal esophagus were remarkable for esophagitis without evidence of malignancy (Figure 3C,3D). The stomach and duodenum were inspected and showed no other pathology.

Figure 2 Endoscopic image of a large, obstructive esophageal mass (black arrow) extending 38 to 40 cm from the incisors. The stenosis was severe and measured 7 mm (inner diameter) × 3 cm (in length).

Figure 3 Histology of the preoperative biopsies. (A) The approximately 3.0 mm esophageal nodule stained with H&E and (B) positive for S-100 immunostaining. Biopsies of the proximal (C) and distal (D) esophagus showed esophagitis with no evidence of malignancy (H&E). Images were acquired at 8× objective magnification. Original images were color balanced and cropped for presentation. No other digital alterations were performed. H&E, hematoxylin and eosin.

An endoscopic ultrasound (EUS) was performed shortly after and revealed a 3.5 cm × 2.3 cm hypoechoic mass with well-defined borders in the lower third of the esophagus (Figure 4). The mass was transmural and occupied all layers of the esophagus. There was sonographic evidence suggesting invasion into the adventitia and only a small plane of fat separation from the descending aorta. This invasion is uncharacteristic of benign schwannoma, which is usually confined to the submucosa layer (18,21). Although EUS suggested an invasive mass, no further imaging or preoperative biopsies were done since IHC staining of the biopsy was diagnostic of benign schwannoma. Additionally, the coexistence of schwannoma and invasive carcinoma is exceedingly rare. Finally, no malignant-appearing lymph nodes were identified on EUS which further lessened the suspicion for an invasive carcinoma.

Figure 4 Preoperative EUS. (A) Axial view showing the mass and its relationship to the aorta. The yellow arrow points to the fat plane separation between these two critical structures. (B) Axial view showing the mass measured in both the vertical and horizontal dimensions. EUS, endoscopic ultrasound.

Given the transmural nature of the mass, endoscopic resection and enucleation were not options, and the patient underwent a robotic-assisted transhiatal esophagectomy (Intuitive Inc., Sunnyvale, CA). During carbon dioxide insufflation, the patient developed acute hypotension and oliguria which subsided after laparotomy, thereby protecting the healthy conduit. In an effort to reduce operative time, the transhiatal approach was favored over the Ivor-Lewis approach. The resected specimen was remarkable for a 4 cm × 1.2 cm ulcerated, tan, papillary-looking mass with clear margins. The mass was centered 0.5 cm above the gastroesophageal (GE) junction and grossly involved the GE junction and proximal stomach. Twenty-one regional lymph nodes were resected, including one bulky celiac lymph node that required significant dissection. He had an unremarkable postoperative course and was discharged home in stable condition. He underwent an esophagram as an outpatient that showed no evidence of anastomotic leak.

Final pathology demonstrated moderately differentiated (grade 2) invasive SCC with negative margins and seven lymph nodes (including one celiac lymph node) showing positive metastases (Figure 5A-5C), consistent with stage IV (pT3N3) esophageal SCC. Final pathology also revealed reactive connective tissue surrounding the mass (Figure 5D,5E), chronic inactive gastritis, and intestinal metaplasia of the stomach. No evidence of a schwannoma was found in the resected specimen after thorough examination. The preoperative and postoperative pathology were reviewed and cross-examined multiple times by two different pathologists. Both studies of the preoperative biopsy were consistent with schwannoma without evidence of SCC (Figure 3). A positron emission tomography (PET)-CT identified additional potential lymph node metastases in the upper abdomen (Figure 6).

Figure 5 Histology of the resected specimen. (A,B) The resected specimens showed a moderately differentiated invasive squamous cell carcinoma with (C) lymph node metastases (H&E). (D,E) Reactive connective tissue was identified around the squamous cell carcinoma, but there was no discrete neural proliferation (H&E). Images were acquired at 4× (A,C) and 20× (B,D,E) objective magnification. Original images were color balanced and cropped for presentation. No other digital alterations were performed. H&E, hematoxylin and eosin.

Figure 6 PET-CT imaging three months after esophagectomy. (A) Axial cut showing increased ¹⁸F-FDG uptake at the anastomotic suture line consistent with post-surgical changes. (B) Coronal slice showing mildly increased FDG uptake in upper abdominal lymph nodes (foci of hyperintensity). CT, computed tomography; FDG, fluorodeoxyglucose; PET, positron emission tomography.

We presented this case at a multidisciplinary tumor board meeting and reviewed the imaging and pathology. Given the bulky celiac lymph node that was heavily dissected during surgery and the PET-CT findings showing metabolically active upper abdominal lymph nodes, we were concerned for remaining metastatic disease. The upper abdominal lymph nodes were not easily accessible by biopsy, and the board recommended proceeding with systemic therapy. He completed six months of adjuvant immunochemotherapy followed by maintenance immunotherapy. Repeat PET-CT demonstrated resolution of metabolically active lymph nodes with no evidence of new metastases. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

We present a case in which a patient presented with dysphagia and weight loss secondary to a suspected schwannoma that was later diagnosed as invasive SCC in the absence of schwannoma. The latency period between the schwannoma diagnosis on biopsy and surgical resection was less than three months. A secondary review of pathology on both the preoperative biopsy and surgically resected tissue confirmed the findings. The reason behind the discrepancy between the preoperative biopsy and resected specimen pathologic findings is not clear. We considered several possibilities, including malignant tumor transformation and pathology misdiagnosis.

Transformation of the mass from schwannoma to invasive SCC is a consideration. Schwannoma transformation in general is exceedingly rare and results in the formation of peripheral nerve sheath tumors, not SCCs (22). Additionally, schwannomas and SCCs arise from fundamentally different cell types, with schwannomas arising from Schwann cells of peripheral nerves and SCC originating from epithelial cells, making a direct or even clonal transformation from schwannoma to SCC exceedingly unlikely.

A false positive schwannoma diagnosis on pathology from the preoperative biopsy was considered, given the pathologic diagnosis of an esophageal schwannoma can be difficult. Esophageal tumors are biopsied endoscopically, which are often superficial and may not obtain adequate biopsy samples, resulting in false negatives (23,24). However, while the diagnosis of esophageal schwannoma through pathology has reported challenges with sensitivity, it generally has good specificity (24,25). The most reliable diagnostic method for esophageal schwannoma is IHC staining, and S-100 is a specific molecular marker of neural cells characteristic of schwannomas (16,26,27). The combination of positive S-100 and negative smooth muscle (desmin) and GIST markers (CD117, DOG1) in the preoperative biopsy helps rule out other common esophageal subepithelial lesions such as leiomyomas and GISTs and strongly suggests a schwannoma diagnosis (28). Moreover, since most esophageal tissue does not express S-100 positivity, this is highly specific for cells that originate from the neural crest (23,25,28).

In the context of known SCC from the resected specimen, reactive neural proliferation—a well-documented phenomenon in peritumoral stromal responses to malignancy—is the most likely explanation for the observed S-100 immunoreactivity on the preoperative biopsy (29). This suggests a sampling error: the biopsy inadvertently captured benign, reactive neural tissue adjacent to the SCC rather than the carcinoma itself. Consequently, the S-100 positivity (a hallmark of neural differentiation) was misinterpreted as evidence of schwannoma, while the underlying SCC remained undetected. However, no benign neural proliferations were found adjacent to the SCC seen in the resected specimen, suggesting that the original neural proliferation was completely removed during preoperative biopsy or it was entirely displaced by the SCC expansion. Regardless, there was no evidence of concurrent SCC and neural proliferation in the preoperative biopsy or resected specimen, making this case a difficult diagnostic challenge. Additionally, no case of esophageal SCC mimicking a schwannoma has ever been reported. In summary, although IHC staining is considered the gold standard for schwannoma diagnosis, there is the possibility of a false positive diagnosis. This case also demonstrated a falsely negative biopsy for invasive malignancy, a more common phenomenon that should also be considered even when a benign diagnosis like schwanomma is found on biopsy.

Conclusions

Reactive neural proliferation associated with an esophageal SCC may mimic an esophageal schwannoma on biopsy. A diagnosis of esophageal schwannoma on biopsy may be less specific than previously described and should be interpreted with caution. Surgeons may also support utilizing a more comprehensive preoperative workup for esophageal schwannoma, including additional biopsies and advanced imaging techniques like PET-CT, to better characterize esophageal lesions and guide appropriate treatment decisions.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-5/rc

Peer Review File: Available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-5/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-5/coif). C.N.E. serves as an unpaid editorial board member of Annals of Esophagus from September 2024 to December 2026. C.N.E. received speaker honoraria from AtriCure and consultation fees from Johnson & Johnson MedTech and Cook Medical (expired). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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