Esophageal carcinoma with SMARCA4 mutation: Unique diagnostic challenges

Cui, Min; Lemmon, Kayla K.; Jin, Zhicheng; Uboha, Nataliya Volodymyrivna

doi:10.1016/j.prp.2023.154692

Cited by 3 publications

(31 citation statements)

References 14 publications

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“…Table 2 lists the nine publications and summarizes the patient characteristics, clinical presentation, associated risk factors, treatment, and follow-up information. Notably, one case reported in the study by Cui et al ( 25 ) was previously documented in a separate case report ( 26 ); therefore, these two publications were summarized together. Similarly, one case reported in the study by Gupta et al ( 28 ) was previously documented in a standalone case report ( 23 ); consequently, the results of these two publications were consolidated into a singular summary.…”

Section: Search Resultsmentioning

confidence: 99%

“…Similarly, Gupta et al reported that three out of five tumors were from the distal esophagus, one from the GEJ, and one from the mid to distal esophagus ( 28 ). All four patients from the series reported by Cui et al had a tumor from the distal esophagus ( 25 , 26 ), whereas all four patients reported by Chang et al had a tumor from the GEJ ( 30 ). The tumors detected on EGD varied in size, ranging from 2.5 to 10.0 cm ( 25 , 26 , 28 - 30 ).…”

Section: Clinical Features and Associated Risk Factors ( ...mentioning

confidence: 89%

“…Dysphagia is the most common presentation in studies reporting symptoms of esophageal carcinoma with a SMARCA4 mutation, including dysphagia, odynophagia, abdominal pain, dark stool, nausea, vomiting, and non-specific signs, including fever, fatigue, poor appetite, and weight loss ( 23 , 25 - 27 , 29 ). Rarely, patients initially present with symptoms of metastasis in distant organs including the lungs and liver ( 28 ).…”

Section: Clinical Features and Associated Risk Factors ( ...mentioning

confidence: 99%

“…Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Most esophageal carcinomas with SMARCA4 mutations occur in the distal esophagus and GEJ, and present as mass lesions on EGD ( 23 , 25 - 32 ). Horton et al reported that of the 12 tumors, five were from the distal esophagus, two from the GEJ, two from the mid-esophagus, and three from the non-specific regions of the esophagus ( 31 ).…”

Section: Clinical Features and Associated Risk Factors ( ...mentioning

confidence: 99%

“…This disease can be considered a variant of undifferentiated esophageal carcinoma according to the World Health Organization classification, which typically lacks the overly common features of squamous, glandular, or neuroendocrine differentiation ( 24 ). However, only a few case series and case reports of esophageal carcinoma with SMARCA4 mutations have been published in the English literature ( 23 , 25 - 32 ). To the best of our knowledge, there are no previously published comprehensive review articles for esophageal carcinoma with SMARCA4 mutations covering its epidemiological, clinical, pathological, and molecular features.…”

Section: Introductionmentioning

confidence: 99%

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Esophageal carcinoma with SMARCA4 mutation: a narrative review for this rare entity

Xu,

Chi

2024

Transl Gastroenterol Hepatol

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Background and Objective Esophageal carcinoma with switch/sucrose nonfermenting (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 ( SMARCA4 ) mutation is a rare variant of malignant esophageal epithelial neoplasm, which is characterized by the loss of SMARCA4/BRG1 protein on immunohistochemistry or alterations in the SMARCA4 gene on sequencing. Only a few case series and case reports of esophageal carcinoma with SMARCA4 mutations have been published in the English literature; the rarity of the disease poses significant diagnostic challenges for surgical pathologists and could potentially lead to delayed or suboptimal patient care. Herein, we reviewed the available literature on esophageal carcinoma with SMARCA4 mutations to discuss its epidemiology, clinical presentation, pathological and molecular features, diagnostic challenges, treatment, and prognosis. Methods The PubMed, Scopus, Ovid, and Google Scholar databases were extensively reviewed. The references included in the articles were cross-examined to identify any missing articles. We searched for all published literature on esophageal carcinoma with SMARCA4 mutations from inception of the databases to date. Key Content and Findings Esophageal carcinoma with SMARCA4 mutations is most common in middle-aged and older men. Barrett esophagus and gastroesophageal reflux disease (GERD) are the most associated risk factors. Dysphagia was the most common initial clinical presentation. Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Microscopically, the tumor cells exhibited epithelioid features mixed with variable components of rhabdoid and glandular differentiation. The tumor cells showed variable immunoreactivity for cytokeratin and sometimes weakly expressed neuroendocrine or B-lymphocyte markers (Pax5), which are potential diagnostic pitfalls. Melanoma marker tests showed negative results. The SMARCB1/INI1 protein remains intact, and a definitive diagnosis necessitates the presence of either SMARCA4/BRG1 protein loss or SMARCA4 gene mutations. Esophageal carcinoma with SMARCA4 mutations shows overly aggressive behavior and presents with advanced stages of disease; most patients succumb to the disease within 1 year of initial diagnosis. Conclusions Esophageal carcinoma with SMARCA4 mutation is an overly aggressive disease, and further research on the affected molecular pathway may help improve its prognosis.

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Section: Search Resultsmentioning

confidence: 99%

Section: Clinical Features and Associated Risk Factors ( ...mentioning

confidence: 89%

Section: Clinical Features and Associated Risk Factors ( ...mentioning

confidence: 99%

Section: Clinical Features and Associated Risk Factors ( ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Esophageal carcinoma with SMARCA4 mutation: a narrative review for this rare entity

Xu,

Chi

2024

Transl Gastroenterol Hepatol

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SMARCA4-Deficient Undifferentiated Esophageal Carcinoma: A Clinical Case Series and Literature Review

Shweikeh,

Hong,

Walter

et al. 2024

J Gastrointest Canc

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Purpose Undifferentiated carcinoma of the esophagus (UEC) is a rare malignancy. Deficiency in SMARCA genes, critical for chromatin regulation, has been observed in cases of UEC. Research in UEC is sparse, however, and we present a case series along with a comprehensive review of the literature. Case Series Case 1 is a 49-year-old female with abdominal pain and dysphagia and esophagogastroduodenoscopy (EGD) showing a friable mass at the gastroesophageal (GE) junction. Biopsies showed a poorly differentiated neoplasm and immunohistochemistry showed loss for SMARCA4. With metastatic disease, she agreed to undergo palliative chemotherapy and radiation, passing away at 4 months. Case 2 is an 88-year-old male with dysphagia, nausea, vomiting, and distal esophageal mass with biopsy showing a malignancy with loss of SMARCA4 expression. Due to extensive metastases, he was counseled on hospice care. Case 3 is a 53-year-old male with extensive alcohol and smoking history presenting with hematemesis, passing away shortly. Posthumous histopathology consistent with undifferentiated SMARCA4-deficient carcinoma of the esophagus. Results of the literature review indicate a predilection towards males (75.0%) and a variable age range (39–88 years). Majority (76.2%) reported with a distal esophagus location. Metastatic disease was common at initial presentation. Median survival was 2.60 months. Some were managed with chemotherapy and radiation. Conclusions Research in SMARCA-deficient UEC is very limited. It is more common in men, age is variable, and associated with Barret’s esophagus. Further research is necessary to better understand it and to establish treatment guidelines; however, it is clear that SMARCA4-deficient UEC carries a significantly poor prognosis.

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SMARCA4-Deficient Undifferentiated Esophageal Carcinoma: A Clinical Case Series and Literature Review

Shweikeh,

Hong,

Walter

et al. 2024

Preprint

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Purpose Undifferentiated carcinoma of the esophagus (UEC) is a rare malignancy. Deficiency in SMARCA genes, critical for chromatin regulation, has been observed in cases of UEC. Research in UEC is sparse, however, and we present a case series along with a comprehensive review of the literature. Case Series Case 1 is a 47-year-old female with abdominal pain and dysphagia and esophagogastroduodenoscopy (EGD) showing a friable mass at GE junction. Biopsies showed a poorly differentiated neoplasm and immunohistochemistry showed loss for SMARCA4. With metastatic disease, she agreed to undergo palliative chemotherapy and radiation, passing away at 4 months. Case 2 is an 85-year-old male with dysphagia, nausea, vomiting, and distal esophageal mass with biopsy showing a malignancy with loss of SMARCA4 expression. Due to extensive metastases, he was counseled on hospice care. Case 3 is a 50-year-old male with extensive alcohol and smoking history presenting with hematemesis, passing away shortly. Posthumous histopathology consistent with undifferentiated SMARCA4-deficient carcinoma. Results of literature review indicates higher in males (73.9%) and variable age range (39-86 years). Majority (80.0%) reported in the distal esophagus. Metastatic disease common at presentation. Average survival was 2.35 months. Some managed with chemotherapy and radiation. Conclusions Research in SMARCA-deficient UEC is very limited. It is more common in men, age is variable, and associated with Barret’s esophagus. Further research is necessary to better understand it and to establish treatment guidelines; however, it is clear that SMARCA4-deficient UEC carries a significantly poor prognosis.

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Esophageal carcinoma with SMARCA4 mutation: Unique diagnostic challenges

Cited by 3 publications

References 14 publications

Esophageal carcinoma with SMARCA4 mutation: a narrative review for this rare entity

Esophageal carcinoma with SMARCA4 mutation: a narrative review for this rare entity

SMARCA4-Deficient Undifferentiated Esophageal Carcinoma: A Clinical Case Series and Literature Review

SMARCA4-Deficient Undifferentiated Esophageal Carcinoma: A Clinical Case Series and Literature Review

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