Clinical Case Summary

Neuroendocrine carcinomas (NEC) of the esophagus are extremely rare, as they represent 0.4 to 2% of all esophagus tumors, and 0.04% of all neuroendocrine tumors.
While the most commonly reported symptoms are dysphagia or abdominal discomfort, some tumors might be discovered incidentally during endoscopy.
With very few studies found in the literature, the knowledge surrounding NEC is reduced with the lack of standardized guidelines for its treatment and conflicting data regarding its prognosis.
Due to improved diagnostic techniques, NEC have become an important diagnostic differential to consider, with incidence rates gradually increasing since 1970s.
A 62-year-old man, with history of chronic smoking for over 40 years, was admitted in our ward for chronic dysphagia.
He had a prolonged history of swallowing difficulties with multiple episodes of vomiting accompanied with a weight loss of 20 kgs in the last 6 months.
The physical examination showed a cachectic body habitus with a non-distended abdomen. No hepatomegaly or large palpable gallbladder was palpable.
Other than a 3.3 mmol/l hypokalemia and a 132 mmol/l hyponatremia, routine blood and urine tests were normal.
The patient proceeded to an upper endoscopy, which revealed a hemi-circumferential ulcer-budding process in the lower part of the esophagus.
The biopsy revealed synaptophysin and CD56 immunostaining positive tumor (with a negative CK7 and P40) indicating poorly differentiated large cell neuroendocrine carcinoma (Figure 1).
A CT, for extension purposes was performed, revealing a 35mm stenosing and circumferential process of the lower part of the esophagus, spanning at least 110mm in craniocaudal dimensions, without any secondary location (Figure 2).
After a multidisciplinary concertation meeting, the resection of the mass was recommended.
Unfortunately, right before programming his surgery, the patient died at home with his family.

Clinical Case Summary

We report the case of a 50-year-old woman with a history of arterial hypertension who consulted for progressive dysphagia to solids since seven months, tolerating only liquids in the last week. In addition, retrosternal knotting sensation, regurgitations, weight loss and a painful whitish plaque on the oral mucosa. Hospital admission was decided to complete study and to ensure the nutritional status.
Gastroscopy was performed, observing a punctiform stenosis of the esophageal lumen at 18 cm of the dental arch, which did not allow the passage of the endoscope. We observed erythematous mucosa and fibrinous exudate covering almost all of it (Figure 1), biopsies were taken.
Barium esophagogram showed two strictures, a short one at the proximal esophagus level and a second one of approximately 7 cm in distal third (Figure 2). Biopsies were negative for microbiology, histological study showed Civatte bodies, compatible with erosive lichen planus.
Endoscopic dilatation of stenoses was considered but this entailed a high risk of complications. Finally, it was decided jointly with Dermatology and Systemic Diseases Department to start systemic corticosteroids and oral acitretin. In the following days, patient showed clinical improvement with adecuate tolerance to a liquid-shredded diet. Nowadays, the patient takes methotrexate and oral acitretin, improving findings in gastroscopy and tolerance to diet.
Lichen planus is a common cutaneous-mucosal disease, where symptomatic esophageal involvement is exceptional. The diagnosis is established by histological study, highlighting the degeneration of the keratinocytes of the basal layer of the epithelium "Civatte bodies". Therapeutic options are varied, the first line being the use of systemic corticosteroids, with patients presenting a rapid response but high percentage of relapses. In addition, immunosuppressants can be used, although all of them have low long-term response rate. JAK-kinase inhibitors are being studied.

References

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) guideline-Uptodate 2021.
Malagelada JR, Bazzoli F, Boeckxstaens G, et al. Directrices globales de la organización mundial de gastroenterología: disfagia: actualización de las pautas globales y cascadas de septiembre de 2014. J Clin Gastroenterol 2015; 49:370.
Le Cleach L, Chosidow O. Práctica clínica. Liquen plano. N Engl J Med 2012; 366:723.

Clinical Case Summary

This case presents a 64-year old man with verrucous carcinoma of the esophagus (VCE), a rare variant of squamous cell carcinoma. The patient has a history of type 2 diabetes and tobacco abuse, and presented in September 2019 with complaints of dysphagia. Upper endoscopy revealed reflux-, and candida esophagitis, and a proximal stenosis. Treatment was initiated with proton pump inhibitors, antifungal therapy, and dilatations. Over three years, multiple endoscopies were conducted, almost all revealing extensive white hyperkeratotic and exophytic lesions. Histopathology reports described fungal threads and no dysplasia, leading to a diagnosis of therapy-resistant candida esophagitis due to poorly regulated diabetes. After two times failure of intravenous antifungal therapy, in February 2023, the patient was referred to our center, a tertiary hospital. Targeted bite on bite biopsies revealed candida aggregates, parakeratosis, and squamous cell proliferation, highly suggestive of well-differentiated VCE. A PET-CT showed no signs of metastatic disease; therefore, considering the early stage and endoscopic extent of the lesion, a laparoscopic esophagostomy was performed.

The prolonged interval from clinical presentation to VCE diagnosis is thought to result from the hyperkeratotic growth pattern, which causes inadequate material for histologic confirmation of underlying neoplastic tissue. Additionally, the presence of fungal threads and white lesions results in diagnosis of candida esophagitis, misleading physicians and causing diagnostic delay. In patients with therapy-resistant candida esophagitis and atypical hyperkeratotic esophageal lesions VCE should be considered, enabling early diagnosis and treatment.

References

Figures that will be presented when accepted:
Figure 1: upper GI endoscopy during initial presentation showing white/yellow keratotic plaques and a proximal stenosis.
Figure 2: upper GI endoscopy at time of VCE diagnosis at our center 4-years after the initial presentation, showing a circumferentially narrowed esophagus, with white, granular and keratotic plaques and lesions at white light endoscopy
Figure 3: upper GI endoscopy at time of VCE diagnosis at our center 4-years after the initial presentation, with NBI showing a circumferentially narrowed esophagus, and diffusely irregular mucosa with white plaques and keratotic lesions.

References:
1. Sweetser S, Jacobs NL, Wong Kee Song LM. Endoscopic diagnosis and treatment of esophageal verrucous squamous cell cancer. Dis Esophagus. 2014;27(5):452-6.
2. Egeland C, Achiam MP, Federspiel B, Svendsen LB. Verrucous Squamous Cell Cancer in the Esophagus: An Obscure Diagnosis. Case Rep Gastroenterol. 2016;10(2):466-71.
3. Tabuchi S, Koyanagi K, Nagata K, Ozawa S, Kawachi S. Verrucous carcinoma of the esophagus: a case report and literature review. Surg Case Rep. 2020;6(1):35.

Clinical Case Summary

A middle-aged woman with chronic, severe iron deficiency anemia and mixed dysphagia was referred to our Gastroenterology Unit for endoscopic examination. The patient displayed koilonichia and angular cheilitis as well as cachexia. Barium swallow described a 5mm long stenosis in the upper esophagus. Initial endoscopy revealed a short, circumferential, fibrous stricture located in the proximal esophagus, covered by normal epithelium, which was not passable even with the slim gastroscope, with marked friability and areas of mucosal detachement involving the entire esophageal length. We performed endoscopic dilation using Savary bougies (5-7-9-11mm) and took biopsies from the stenosis, which were compatible with Plummer-Vinson syndrome. Following iron replacement therapy with little response, the patient was scheduled for a second dilation. Due to important mucosal frailty and upper gastrointestinal bleeding, the procedure was postponed and the patient was prescribed oral Budesonide with symptom resolution and improvement in the appearance of the esophageal mucosa, as showed by the follow-up endoscopy performed at 1 month. The patient underwent a second dilation and is currently symptom free.
Plummer-Vinson syndrome, or Patterson-Kelly syndrome, is extremely rare and given its association with an increased risk of squamous cell carcinoma of the pharynx or the esophagus, the patients should be diagnosed early and followed up properly.

References

1. https://pubmed.ncbi.nlm.nih.gov/16978405/
2. https://pubmed.ncbi.nlm.nih.gov/29089792/

Clinical Case Summary

Actinomycosis is a rare granulomatous disease caused by Actinomyces spp that rarely affects the esophagus. It was reported in both immunocompromised and immunocompetent patients. The infection is often misdiagnosed because it can mimic other pathological conditions (like oesophageal cancer in our case).
We report a case of esophageal actinomycosis in an immunocompetent 92-year-old man. The patient was admitted with symptoms of dysphagia. Upper endoscopy revealed a stricture at 15 cm from the incisors. Biopsies were taken from the inflamed esophageal mucosa and the proximal lumen of the stricture. Contrast-enhanced computed tomography (CT) of the chest with oral barium contrast showed 2 cm irregular narrowing in the cervical esophagus, but no abnormalities in the rest of the esophagus ,mediastinal or pulmonary pathology. The esophageal biopsy indicated acute and chronic inflammation with filamentous sulfur granules consistent with Actinomyces;. The cytology was negative for malignant cells.Bacteriological culture of oesophageal biopsies was negative
The patient was started on intravenous penicillin for 2 weeks followed by 8 weeks of amoxicillin with clinical amelioration.
Given that actinomycosis can mimic other diseases and a diagnosis can be delayed, clinicians should be vigilant about this rare but serious infection, especially in patients with impaired immunity, brakes in the mucosal lining of the GI or GU tract, and refractory symptoms despite initial therapy and even among immunocompetent individuals where the location of a disease may be atypical such as a cervical esophagal peptic stricture occurring in our case. Histology confirms the diagnosis and prologed antibiotherapy with penicillim is the tretment of choice.

Clinical Case Summary

A 58-year-old woman with no relevant medical history, presenting with progressive dysphagia and odynophagia over a 2-month period. Upper gastrointestinal endoscopy (UGE) revealed a circumferential lesion with a verrucous appearance and exophytic papillomatous component spanning from 20 to 30 cm from the dental arch. These lesions raised suspicion of malignancy; however, biopsies showed only hyperplastic mucosa with chronic inflammation. In an attempt to obtain histological documentation, additional UGE were performed, with repeat biopsies and macrobiopsy of one of the more exophytic components, all without confirmation of neoplasia by multiple pathologists. Immunohistochemistry showed positivity for p16. Additional imaging studies confirmed extensive and locally invasive neoplastic formation with nodal involvement, leading to an empirical diagnosis of verrucous carcinoma of the esophagus (VCE), prompting initiation of neoadjuvant chemoradiotherapy. Subsequently, exploratory thoracoscopy revealed unresectable disease. Palliative chemotherapy was initiated, and a repeat endoscopy shows regression of the lesion.
Discussion: VCE, an extremely rare variant of squamous cell carcinoma, presents with slow growth, local invasiveness, and rare nodal metastases. Although its exact etiology is uncertain, associations with chronic inflammation caused by factors such as smoking, reflux esophagitis, or alcoholism are reported. Human papillomavirus (HPV) infection has also been suggested as a potential contributor. Due to the proliferative nature of VCE, superficial biopsies often show nonspecific inflammatory changes, making diagnosis challenging. Despite the lack of confirmatory histopathology, the unique endoscopic findings, presence of p16 (associated with HPV-related carcinomas), and clinical deterioration led to the empirical diagnosis of VCE. This case highlights the diagnostic complexity and therapeutic challenge associated with this rare variant of esophageal carcinoma.

References

• Minielly, J. A., Harrison, E. G., Fontana, R. S. & Payne, W. S. Verrucous squamous cell carcinoma of the esophagus. Cancer 20, 2078–2087 (1967).
  
• Cappellesso, R. et al. Human papillomavirus infection is not involved in esophageal verrucous carcinoma. Hum Pathol 85, 50–57 (2019).
• Tonna, J. et al. Esophageal verrucous carcinoma arising from hyperkeratotic plaques associated with human papilloma virus type 51. Diseases of the Esophagus 23, (2010).
• Ramani, C., Shah, N. & Nathan, R. S. Verrucous carcinoma of the esophagus: A case report and literature review. World Journal of Clinical Cases : WJCC 2, 284 (2014).
• Osborn, N. K., Keate, R. F., Trastek, V. F. & Nguyen, C. C. Verrucous carcinoma of the esophagus: Clinicopathophysiologic features and treatment of a rare entity. Dig Dis Sci 48, 465–474 (2003).
• Devlin, S., Falck, V., Urbanski, S. J., Mitchell, P. & Romagnuolo, J. Verrucous carcinoma of the esophagus eluding multiple sets of endoscopic biopsies and endoscopic ultrasund: A case report and review of the literature. Canadian Journal of Gastroenterology 18, 459–462 (2004).