Undifferentiated Carcinoma of Esophagus with SMARCA4 Deletion Expressing Synaptophysin: A Potential Diagnostic Pitfall

Abstract

Undifferentiated carcinoma of the esophagus is an entity that is included in WHO classification of digestive systems fifth edition (2018). The definition of this entity is a malignant esophageal epithelial tumor that lacks definite microscopic features of squamous, glandular, or neuroendocrine differentiation. It is a challenging diagnosis to make due to lack of diagnostic criteria. We report a case from a 45 years old man with a mass in the lower third of esophagus. Biopsy showed an epitheloid neoplasm with sheet like growth pattern and no glandular formation. The tumor cells had prominent nucleoli and indistinct cell borders. There were occasional rhabdoid cells. By immunostains, tumor cells were focally positive for pankeratin, keratin 7, synaptophysin, negative for CDX2 and p40, INSM1, chromogranin, and CD56. Background intestinal metaplasia (Barrett esophagus) was present. Next generation sequencing of the tumor revealed SMARCA4 deep deletion. The tumor showed loss of SMARCA4 by immunostain. This case demonstrates that undifferentiated carcinoma of the esophagus with SMARCA4 deletion can express synaptophysin. Awareness of this entity is important for the correct classification of this tumor.

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

“…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.…”

“…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 ).…”

“…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 ).…”

“…Barrett’s esophagus was the most frequently associated risk factor ( 25 , 26 , 28 , 29 , 31 ). Horton et al indicated that Barrett’s esophagus was present in 67% (eight out of 12) of patients ( 31 ), whereas both patients (100%) reported by Ahmed et al had Barrett’s esophagus ( 29 ).…”

“…Horton et al indicated that Barrett’s esophagus was present in 67% (eight out of 12) of patients ( 31 ), whereas both patients (100%) reported by Ahmed et al had Barrett’s esophagus ( 29 ). Gastroesophageal reflux disease (GERD) is another commonly reported risk factor that has been reported in 20–50% of patients ( 25 , 26 , 28 , 29 ). Additionally, one study reported smoking in 60% (three out of five) of patients ( 28 ).…”