Primary lung cancer presenting with gastrointestinal tract involvement: Clinicopathologic and immunohistochemical features in a series of 18 consecutive cases

Background: Lung cancer initially manifesting as gastrointestinal (GI)-tract metastasis is exceedingly rare, representing a diagnostic challenge and a late-stage disease sign. The clinicopathologic characteristics of the largest series of lung carcinomas initially presenting with GI involvement were described, focusing on differential diagnosis and therapeutic options. Methods: Eighteen consecutive cases of lung cancer (11 surgical specimens and 7 biopsies) initially diagnosed on GI histologic samples were identified during routine pathologist practice. All cases were immunostained with thyroid transcription factor-1 (TTF-1), caudal-related homeobox 2 (CDX2), and cytokeratins 7 (CK7) and 20 (CK20). Clinical and radiological data were obtained in all cases. Results: There were 10 women and 8 men with a mean age of 68.5 years. The small bowel was the most common GI involved site (12 cases), followed by the stomach (four) and large intestine (two). Only half of cases were correctly diagnosed on GI biopsies. Fourteen patients died shortly from disease (mean follow-up, 3 months); two are still alive with multiple metastases, and two patients with the GI tract as the unique site of metastasis underwent pulmonary lobectomy and chemotherapy and are alive without evidence of disease. At morphology, there were 10 large cell undifferentiated carcinomas and eight adenocarcinomas. All cases were immunostained for CK7 and 89% for TTF-1, whereas CK20 and CDX2 were completely negative. Conclusion: Lung cancer presenting as GI-tract metastasis is probably more frequent than expected, and pathologists should always keep in mind this possibility when dealing with undifferentiated GI carcinoma. Immunostaining with TTF-1, CDX2, CK7, and CK20 is helpful in highlighting lung primary. Although GI metastasis from lung cancer is associated with dismal outcomes, pulmonary resection coupled with chemotherapy might represent a therapeutic option in selected patients with a solitary GI-tract metastasis.