Gastroesophageal Junction Adenocarcinoma With Skeletal Muscle Metastases: A Case Report and Literature Review

Esophageal and gastroesophageal junction (GEJ) malignancies are aggressive, and survival is poor once metastasis occurs. The most common sites of metastatic involvement include the liver, lymph nodes, lung, peritoneum, adrenal glands, bone, and brain, while skeletal muscle (SM) involvement is rare. We report a case of a 68-year-old female who presented with intractable emesis for one month and was found to have a primary GEJ adenocarcinoma measuring up to 6.7 cm. Endoscopic biopsy revealed poorly differentiated GEJ adenocarcinoma with positive AE1/AE3 immunostains. Positron emission tomography/computed tomography and magnetic resonance imaging revealed metastases to the omentum and left lower extremity SMs, including the proximal adductor longus, adductor magnus, and gluteus minimus. This study reviews the literature on SM metastasis in esophageal and GEJ cancer, GEJ cancer classification, incidence, treatment, and prognosis.


Introduction
Survival becomes increasingly challenging once metastasis occurs in esophageal and gastroesophageal junction (GEJ) malignancies, which are known for their aggressive nature.In the United States, the five-year overall relative survival rate from 2013 to 2019 was 21.7%, but survival with distant metastases was notably lower at 5.6% [1].The most common sites for metastasis of both esophageal and GEJ tumors include the liver, distant lymph nodes, lung, peritoneum, adrenal glands, bone, and brain [2].Skeletal muscle (SM) involvement in esophageal cancer is very rare [3,4], comprising approximately 9% of metastatic sites in the literature up to 2017 [2].The researchers reviewed the literature to identify detailed case reports and case series of SM involvement in esophageal and GEJ cancers.There were only 16 detailed reports of esophageal cancer with SM metastasis in the English literature between 1986 and 2018, and only four such reports from these were of GEJ cancer between 2002 and 2016.We report the case of a 68-year-old female who presented with primary GEJ adenocarcinoma with this rare skeletal muscle metastasis (SMM).

Case Presentation
A 68-year-old female with a history of hypertension, diabetes mellitus, and hyperlipidemia presented with intractable emesis for a month.She felt that solid food was getting stuck in her chest and had to vomit after eating or drinking.She was frail-appearing and not acutely distressed; cardiopulmonary and abdominal examinations were unremarkable.Workup with computed tomography (CT) abdomen/pelvis with contrast revealed a GEJ mass measuring up to 6.7 cm, distal gastric fundus ulceration adjacent to the GEJ with concern of perforation, and thrombosis of the splenic vein and left adrenal vein (Figure 1).A follow-up esophagram was performed with Gastrografin, and there was no demonstration of perforation.During the esophagogastroduodenoscopy, a partially obstructing, likely malignant tumor was found at the GEJ and in the cardia, which was biopsied.The endoscopic ultrasound of the tumor was deferred due to concern about perforation.Histologic examination of the distal esophagus mass demonstrated moderately to poorly differentiated adenocarcinoma, with positive cytokeratin AE1/AE3 immunohistochemistry (IHC) and negative for p40; IHC for human epidermal growth factor receptor 2 was negative (Figure 2).The glands are negative for p40 IHC, which helps rule out squamous cell carcinoma.The positive background staining of the benign esophageal squamous mucosa is notable (Figure 2D).PET/CT: positron emission tomography/computed tomography; FDG: fludeoxyglucose F18; SUV max: maximum standardized uptake value A diagnostic laparoscopy was performed, and a small omental implant on the right side was biopsied.Later, it was confirmed to be metastatic adenocarcinoma morphologically similar to the esophageal tumor (Figure 4).There was no gross peritoneal carcinomatosis.The case was discussed in the multidisciplinary tumor board conference, and the consensus was to give palliative radiation therapy for local control of impending perforation at the tumor site.It was concluded that administering chemotherapy in cases of contained or potential tumor perforation carries a significant level of risk.However, following the patient's discharge from the hospital, outpatient palliative radiotherapy was unattainable due to the patient's illness.
A month after discharge, the patient presented with intractable emesis, inability to tolerate oral intake, and abdominal pain.The CT scan of the abdomen and pelvis showed the presence of free air under the diaphragm, suggestive of perforation, and an ulcerated gastric fundal mass with an enlarging left subphrenic irregular phlegmon measuring approximately 6 cm extending directly into the spleen.The patient was admitted for failure to thrive and sepsis due to possible aspiration pneumonia and phlegmon.The patient was deemed not a candidate for palliative surgery or radiation due to her frail condition.The case was discussed in a multidisciplinary tumor board conference with a consensus on the best supportive care.A palliative esophageal stent was placed due to complete obstruction caused by the esophageal mass.
The patient expired after four months after the initial diagnosis.

Definition and classification of GEJ cancer
Gastric and esophageal cancers include esophageal squamous cell carcinoma, proximal GEJ adenocarcinomas (in the esophagus and gastric cardia), and distal gastric adenocarcinoma.The vast majority of these tumors are histologically adenocarcinomas.
GEJ tumors are classified into three different subtypes by the Siewert classification, developed by the German surgeon Jörg Rüdiger Siewert.Siewert type I GEJ tumors are between 1 and 5 cm proximal to the GEJ.Siewert type II tumors cross the anatomic GEJ with their epicenter up to 2 cm below GEJ, and Siewert type III tumors span between 2 and 5 cm into the stomach [5].The Siewert classification has been broadly used to determine surgical approaches for GEJ tumors.Siewert type I GEJ tumors are treated as esophageal cancer requiring partial gastrectomy, while type III GEJ tumors are treated as gastric cancer requiring total gastrectomy according to the consensus from randomized controlled trials [6].Siewert type II GEJ tumors are treated as esophageal cancer, similar to type I, but with differing regions of mediastinal lymph nodes to be resected based on tumor invasion [6].All three Siewert types require abdominal lymph node resection, with increasing amounts to be resected with increasing Siewert grade [6].Our patient presented with a type III GEJ tumor due to its distension into the gastric cardia.However, due to the presence of metastases, systemic chemotherapy would have been required rather than the proposed surgical resection and/or radiotherapy.

Metastasis of GEJ cancers in the SM
SM involvement in GEJ cancers is rare [3,4].We reviewed the literature on SMM from esophageal and GEJ tumors reported in PubMed between 1986 and 2024 (Tables 1, 2).Even though SM comprises 50% of the body mass and is highly vascularized, SMM is uncommon in patients with GEJ metastatic disease, with less than 10% of patients having metastatic involvement limited to SM [2].The rarity of these metastases can be attributed to various factors.These include the variability of blood flow in muscles during rest and exercise, which reduces the adherence of tumor cells to the surrounding tissues.SMs also produce substances like leukemia inhibitory factor and interleukin-6 that have anticancer properties [21].Additionally, the microvasculature of actively contracting SMs may have the ability to biomechanically destroy cancer cells, which is in contrast to denervated and noncontracting muscle in which cancer cell survival is relatively greater [22].
Muscle metastasis poses a diagnostic challenge because it is usually asymptomatic.To detect SM involvement, PET/CT imaging is widely used to stage esophageal carcinoma and can detect distant metastases that may be missed by other imaging studies [7][8][9].SMM cases have been identified in patients staged with PET/CT, suggesting that the increased incidence of SMM in esophageal carcinoma may be due to improved diagnostic capabilities and better control of the primary tumor through combined treatment approaches.A diagnostic biopsy is required for confirmation.
There is limited knowledge about the outcomes and optimal management strategies for patients with SMM in GEJ metastasis, and most of the information available comes from anecdotal reports.General recommendations for managing SMM, including SMM of esophageal carcinoma, focus on symptom control and tailoring the therapeutic approach based on the affected muscle.Surgery may be the preferred option for isolated SMM, as it can provide the best control and also help establish the diagnosis.External beam radiation may be used for inoperable or recurrent SMM, especially when combined with platinum-based chemotherapy [4].The role of systemic chemotherapy in managing SMM appears to follow the general GEJ metastasis treatment guideline, but it may be considered in patients with widespread metastases and good general condition [23].

Conclusions
In this article, a case of SMM of primary GEJ cancer is reported, and the literature on SMM in GEJ cancer is reviewed.A confirmatory biopsy is required for diagnosis.Given the limited number of reported cases of SMM, it is challenging to generalize prognostic effects and outcomes.With the increased incidence of GEJ adenocarcinomas in Western countries from improved imaging, it would be crucial to diagnose and treat GEJ adenocarcinomas effectively.Further studies of SMM from upper GI origin will elucidate the prognosis and treatment of GEJ cancers.

FIGURE 1 :
FIGURE 1: CT abdomen/pelvis with contrast showing a GEJ mass.GEJ mass measuring up to 6.7 cm (red arrow).Distal gastric fundus ulceration is adjacent to the GEJ, with concern for perforation (blue arrow) CT: computed tomography; GEJ: gastroesophageal junction

FIGURE 3 :
FIGURE 3: PET/CT.FDG avid necrotic distal esophagus and gastric fundus lesion (red arrow), SUV max 14, consistent with biopsy-proven adenocarcinoma of the esophagus.Focal FDG avidity along the proximal left adductor muscle (blue arrow), SUV max 6.49, representing intramuscular metastasis.FDG avid left adrenal nodule measuring up to 2 x 1.5 cm, SUV max 7.02, likely metastatic in etiology.FDG avid right lower quadrant peritoneal soft-tissue attenuation lesion measuring 2.4 x 1.8 cm, SUV max 8.7, likely reflective of peritoneal metastasis (green arrow)

FIGURE 5 :
FIGURE 5: MRI of the left femur with contrast demonstrating a 1.2 x 1.2 x 2.5 cm enhancing lesion within the proximal left adductor longus muscle, which corresponded to the hypermetabolic focus seen on PET/CT scan (blue arrow) MRI: magnetic resonance imaging; PET/CT: positron emission tomography/computed tomography