Gastric Adenocarcinoma With Enteroblastic Differentiation Presenting as Lung Nodules: A Diagnostic Dilemma

Gastric Adenocarcinoma with enteroblastic differentiation (GAED) is a rare subtype of alpha fetoprotein-producing gastric cancers characterized by a tubulo-papillary pattern resembling fetal gastrointestinal epithelium. It expresses at least one of the following enteroblastic markers (EMs): glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), and α-fetoprotein (AFP).

A 78-year-old man with a history of chronic dry cough was found to have multiple lung nodules on Chest X-ray and CT, suspicious for a malignancy. Therefore, percutaneous biopsy of the lung nodule was performed which showed CDX-2 positivity on immunohistochemistry (IHC). Next Generation Sequencing (NGS) and Caris GPSai were inconclusive. Therefore, a search for the primary site was initiated. Endoscopy revealed a fungating mass at the gastroesophageal junction while colonoscopy was unrevealing. Histology revealed well-differentiated adenocarcinoma with mucinous features. IHC was positive for SALL-4 and GPC3. HER2 expression returned a 3+ score. Alpha-fetoprotein (AFP) level was elevated. The patient was started on capecitabine and oxaliplatin in addition to trastuzumab with subsequent clinical and radiological improvement.

Lung malignancy, primary or metastatic, can present as chronic cough. It is imperative for patients to undergo a thorough workup for a timely diagnosis. IHC plays a vital role in delineating the origin of the malignant cells. GPC3 expression is the most sensitive marker for GAED. High serum AFP levels directly correlate with the strength of immunostaining and are associated with a poor prognosis. High HER2 expression and PDL-1 immunostaining is commonly seen in GAED cases with the most common mutation being p53. Currently, there are no set guidelines for management of GAED. Unresectable, metastatic HER2 positive conventional adenocarcinoma is being managed using platinum-fluoropyrimidine doublet therapy with anti-HER2 monoclonal antibody trastuzumab. This case report calls for aggressive IHC staining for prompt diagnosis where necessary as well as proper guidelines for management.