Navigating Diagnostic Challenges in Pseudoachalasia: A Case Study of Esophagogastric Junction Adenocarcinoma

Introduction

Pseudoachalasia is an esophageal motility disorder characterized by clinical and diagnostic findings that mimic idiopathic achalasia. It accounts for approximately 2.4% to 4% of patients exhibiting manometric findings consistent with achalasia [1]. Achalasia is a primary esophageal motility disorder characterized by the progressive degeneration of ganglion cells within the myenteric plexus of the esophageal wall, which results in impaired relaxation of the lower esophageal sphincter (LES) and a subsequent loss of coordinated peristaltic activity in the distal esophagus, leading to functional obstruction and dysphagia [2]. Ogilvie first identified pseudoachalasia in 1947 as a variant of achalasia resulting from gastric adenocarcinoma involving the cardia region [3]. The most common etiologies of pseudoachalasia are primary malignancy of the esophagus, followed by secondary metastasis and other benign causes such as amyloidosis, sarcoidosis, paraneoplastic diseases, and Chagas disease [4]. In contrast, the underlying etiology of achalasia with ganglion cell depletion remains incompletely understood, although autoimmune mechanisms and neurodegenerative processes have been implicated [2].

Achalasia and pseudoachalasia exhibit overlapping clinical manifestations, most notably dysphagia and regurgitation. Pseudoachalasia is more frequently observed in older individuals and is characterized by a relatively shorter duration of dysphagia, typically lasting 1 year or less, and exhibits more pronounced weight loss compared to those with primary achalasia [5]. Early diagnosis of the causes of pseudoachalasia is often difficult because its achalasia-like symptoms overlap with a wide range of differential diagnoses, and the diagnostic accuracy of imaging methods varies. There are several case reports showing delayed and missed diagnosis [6,7]. The prognosis of these patients was quite poor. However, it is unusual to misdiagnose this disease using combined multiple imaging and biopsy methods [8]. Furthermore, the consensus on early diagnosis and management of this disease is not fully established. Here, we presented a case of delayed diagnosis of pseudoachalasia caused by cardia adenocarcinoma with negative imaging results, endoscopy with multiple biopsies, and endoscopic ultrasound (EUS).

Case Report

A 62-year-old man with a long history of tobacco use and gastroesophageal reflux disease (GERD) presented with progressively worsening severe dysphagia. Two years before this presentation, he experienced mild dysphagia limited to solids. He reported no weight loss, chest pain, or cough. During this period, he experienced gradually worsening mild dysphagia at intervals of approximately 3 to 4 months. However, since the symptoms did not substantially affect daily activities, he felt that no medical intervention was necessary at that time. Two months before admission, the dysphagia extended to both solids and liquids, prompting him to seek care at a local hospital. The physical examination revealed no significant findings. The first esophagogastroduodenoscopy (EGD) demonstrated dilation of the proximal one-third of the esophagus and difficulty passing through the esophagogastric junction (EGJ), with no other abnormalities noted in the esophagus or stomach (Figure 1A, 1B). A chest X-ray demonstrated an 8- to 10-mm nodule with no clear margin on the upper left lung (Figure 1C). High-resolution manometry (HMR) was performed to evaluate for esophageal motility disorder and demonstrated the average integrated relaxation pressure (IRP) 4s of 17.5 mmHg (upper limit <19 mmHg), with 4 instances exceeding 19 mmHg, and 20% premature contractions, consistent with esophagogastric junction (EGJ) outflow obstruction (Chicago version 3) (Figure 1D). Chest MRI was conducted to evaluate the EGJ and lung nodule instead of a CT scan based on the doctor’s judgment. MRI showed a small nodule of the upper lobe of the left lung, suspected to be a tuberculosis (TB) lesion, no dilated esophagus, mild thickening of the muscle layer of the distal esophagus, and EGJ. Blood QuantiFERON was positive. The patient was empirically treated with a TB regimen and followed up after 1 month.

One month later, his swallowing difficulties had worsened, making it impossible for him to drink water, which led him to discontinue TB treatment. He did not have any adverse effects of TB treatment, and his doctor assumed that the local EGJ disease was progressively worsening. During this evaluation, the physical examination and basic lab test results were normal. An EGD revealed a dilated esophagus, retained saliva, and increased difficulty passing the scope through the EGJ compared to the initial EGD. An EUS was performed due to concerns about malignancy, showing concentric thickening of the muscle layer at the distal esophagus (1.65–3.56 mm) and at the EGJ (1.8 mm), but no signs of tumors were detected (Figure 2). The scope of EUS was unable to enter the stomach. A peroral endoscopic myotomy (POEM) was attempted to alleviate his symptoms, but the procedure was unsuccessful. A nasogastric (NG) tube was placed under endoscopic guidance for nutrition support.

The patient’s symptoms failed to improve, leading to a referral to our hospital 2 months after the first EGD. The failure of the POEM procedure, coupled with significant difficulty in traversing the EGJ, as well as HMR results, raised the suspicion of etiologies other than achalasia, with a high likelihood of an underlying tumor, infiltration, autoimmune diseases, or TB. High suspicion of malignancy prompted the performance of a chest CT scan (Figure 3A) and EGD, which revealed no new findings compared to the previous evaluation. Multiple adequately sampled consecutive biopsies from different regions of the EGJ to take deeper tissue demonstrated normal histological findings. The patient underwent 3 sessions of pneumatic dilation of the EGJ to relieve his symptoms, with normal repeated EGJ biopsy results; however, dysphagia recurred rapidly within 1 to 2 weeks after dilation. Additional testing for secondary causes of EGJ outflow obstruction revealed positive speckled antinuclear antibodies (ANA), but negative results for other autoimmune panels, low immunoglobulin G4 (IgG4) levels, and negative tuberculosis culture from bronchial lavage, alongside normal biopsy results from the distal esophagus and EGJ.

Esophagogastric junction stent replacement was performed to alleviate the symptoms; however, the stent was removed 2 weeks later due to severe pain and pneumonia. Surgical intervention was postponed until the patient’s condition stabilized. He was managed with antibiotics for pneumonia, pain control, and nutrition support via NG tube and partially by intravenous nutrition. One month from the stent removal (6 months after the first EGD), a preoperative chest CT scan revealed a similar thickening of the EGJ; however, there were no clear borders of the esophagus and the left liver (Figure 3B). The patient subsequently underwent distal esophageal and partial gastric resection, along with the placement of a gastrostomy tube for nutritional support and palliative care management. The EGJ specimen demonstrated a 2×1.5 cm adenocarcinoma mass invading the left liver. Adenocarcinoma was observed to predominantly invade the surrounding tissues, including areas adjacent to neurons and lymphatic vessels. Histological examination of biopsy specimens revealed no evidence of tumor infiltration into the gastric mucosa of the cardia. These findings suggest that the adenocarcinoma may have originated in the deeper layers of the cardia rather than the mucosal surface, and subsequently invaded the surrounding structures. Immunohistochemical analysis indicated the adenocarcinoma likely originated from the pancreas and biliary system (Figure 4), although imaging studies did not support this finding. The patient was treated with chemotherapy consisting of 8 cycles of m-FOLFOX-6, experiencing 2 episodes of neutropenia during treatment. The patient has continued to follow up with oncology specialists for 6 months.

Discussion

This case underscores the diagnostic challenges associated with pseudoachalasia, particularly in a patient with a delayed presentation due to esophagogastric junction (EGJ) adenocarcinoma, who did not exhibit weight loss and had negative imaging and biopsy results. Clinicians, particularly primary care physicians, should maintain a high index of suspicion for pseudoachalasia in patients over 50 years of age who present with rapidly progressive dysphagia that fails to improve with standard achalasia treatments, irrespective of the symptom duration or negative imaging findings. In such cases, surgical exploration may be considered early for patients with an inconclusive diagnosis of pseudoachalasia, despite a comprehensive diagnostic workup.

Pseudoachalasia is a rare condition mimicking achalasia, occurring in 2.4% to 4% of cases presenting with achalasia-like symptoms [1]. The median age of this disease is 61 years, with a male predominance (male-to-female ratio 1.8: 1) [5]. Unlike idiopathic achalasia, pseudoachalasia is usually secondary to malignancy, where tumors infiltrate the esophageal myenteric plexus or compress the esophagogastric junction, leading to functional obstruction as the main pathogenetic mechanism [8]. Many case series and case reports have tried to differentiate between pseudoachalasia and idiopathic achalasia [7,9], but this issue remains a challenging problem for physicians. Compared to achalasia, pseudoachalasia usually presents in patients over 50 years of age with a short period of progressive dysphagia (<6 months to 1 year), significant weight loss, and other characteristics of the underlying diseases. Furthermore, positive occult blood tests, lesions on endoscopy and CT scan, and no improvement with pneumatic dilation also support pseudoachalasia [4]. Our case remained suspicious for secondary causes despite the absence of weight loss and the prolonged onset of symptoms.

Our case is unique due to several specific findings. First, our patient was diagnosed more than 2 years after onset of the disease. In the report of Schizas et al, the median time from symptom onset to diagnosis of pseudoachalasia was 5 months, with a duration of almost 12 months in some cases [8]. Pseudoachalasia typically progresses over a relatively short duration of symptoms (less than 1 year). Consequently, our case underscores the necessity of considering pseudoachalasia as a potential diagnosis, irrespective of the duration of symptom onset. Second, clinical manifestations, imaging findings, and progression of esophageal adenocarcinoma were inconsistent. The patient experienced symptoms for 2 years, during which combined imaging, EUS, and multiple biopsies yielded negative results. This may be because the early-stage adenocarcinoma at EGJ was quite small and was located in deeper layers of the esophagus, which could not be detected by several imaging methods, and may have affected the neuronal plexus at the EGJ, resulting in achalasia-like symptoms. Therefore, both motility dysfunction and malignant mechanical obstruction may have contributed to the presentation. Compared to other cases of pseudoachalasia, almost all cases were detected on endoscopy or EUS [6,10,11]. Third, the diagnosis was delayed, with significant challenges due to a broad differential diagnosis. Our patient was initiated on a TB regimen while concurrently ruling out autoimmune etiologies, tuberculosis, and other potential causes of esophageal infiltration. Similarly, in another case of delayed diagnosis attributed to nonspecific symptoms and lack of response to gastritis treatment, the patient was diagnosed with EGJ adenocarcinoma only after experiencing progressive dysphagia over a 4-month period [7]. Fourth, the origin of malignancy in our case was most likely from the primary esophageal adenocarcinoma despite immunohistochemistry suggesting it arose from the biliary tract and pancreas. Furthermore, adenocarcinoma often develops at the mucosa and then invades the other layers of the esophagus. In our case, the tumor may have exhibited a growth pattern in the opposite direction.

It can be challenging to diagnose in the early stages of the disease, especially in our case with negative imaging and biopsy results. Some studies showed that diagnostic results from barium and endoscopy with biopsies can have low diagnostic yield, showing a false-negative rate of up to 25% for cancer detection [9,12]. In terms of CT scan, pseudoachalasia can be suspected when there is significant asymmetric thickening of the esophageal wall, the presence of a mass near the gastroesophageal junction, or mediastinal lymphadenopathy. However, normal CT findings cannot ensure the exclusion of malignancy etiologies [8]. Positron emission tomography (PET)/computed tomography (CT) scans are useful for identifying tumors or metastatic lesions that may account for pseudoachalasia. However, PET/CT may have limitations in detecting small tumors/T-staging or dissemination to locoregional lymph nodes [13]. EUS is a valuable tool for detecting hidden tumors that may be causing pseudoachalasia. The accuracy of EUS in staging esophageal cancer varies by T-staging, with reported rates ranging from 81% to 85% [14]. However, another study showed it had low accuracy in distinguishing between mucosal and submucosal lesions at the lower esophagus or EGJ [15]. Table 1 summarizes 5 reported cases of pseudoachalasia caused by adenocarcinoma, published in PubMed between 2010 and 2025. In 2 cases, EGD with EGJ biopsies yielded negative results. A mass was detected by CT in 2 of 5 cases, in 2 of 5 cases by EUS, and in 1 case using a small scope that visualized the lesion at the gastric cardia. In our case, abnormal findings were identified on CT 6 months after the initial EGD. It has been suggested that the combination of investigative modalities in atypical and selected patients can identify most cases of pseudoachalasia [5]. Furthermore, repeated EUS or surgical exploration may be conducted to enhance the possibility of an early diagnosis of pseudoachalasia [5,16]. There is no consensus on the optimal time to perform surgery. However, after reviewing our case, we think surgical exploration should be promptly done after the first failed interventions for achalasia treatment – particularly after peroral endoscopic myotomy (POEM) – to prevent poor prognosis and associated complications.

Conclusions

This case highlights the diagnostic challenge of a patient with delayed presentation of pseudoachalasia caused by EGJ adenocarcinoma without weight loss and with negative results from imaging and biopsy. Primary physicians should maintain a high index of suspicion for pseudoachalasia in patients over 50 years of age presenting with rapidly progressive dysphagia that does not improve with interventions for achalasia, regardless of the duration of symptoms or imaging findings. Surgical exploration may also be considered in selected patients without a definite diagnosis of pseudoachalasia despite using multiple investigation methods. The early diagnosis and prompt treatment of underlying causes improve prognosis and survival.