GATA3-Positive Metastatic Esophageal Adenocarcinoma: A Rare Diagnostic Challenge

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Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

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Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

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Federal Practitioner - 42(9)s
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Federal Practitioner - 42(9)s
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S14
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