Title: Undifferentiated Carcinoma of the Lung: A Rare Diagnosis with High Mortality

Author(s): Arman Hemmat, MD; Gregory Polcha, DO; Chitsimraan Mann, MD; Muneer Al Zoby, MD; Aaron Taylor

Email: Ahemmat@mercy.com

Introduction:  Lung cancer is the leading cause of death by cancer in the United States [1]. Non-small cell lung carcinoma (NSCLC) accounts for 85% of lung cancers. Undifferentiated carcinoma of the lung (UCL) is a rare subtype of NSCLC characterized by lack of specialization of tumor cells. Due to the unknown origin, it is difficult to identify a treatment paradigm.

Case Presentation:  A 56-year-old male with medical history of COPD, asbestos exposure, and tobacco abuse presented dyspnea, shortness of breath, fever, and arthralgias. On presentation, labs were significant for elevated ESR, leukocytosis, and hyponatremia. Infectious etiologies were eliminated via cultures, PCR, urine antigens, and AFB stain. Chest CT showed bilateral ground-glass opacities, pleural effusion, and septal thickening. Patient was empirically treated with antibiotics but continued to deteriorate. A diagnostic wedge resection of right upper, middle and lower lobes was performed due to continued worsening clinical status. Biopsies revealed mesothelial hyperplasia and undifferentiated carcinoma with “spread through airspaces (STAS)” and lymphangitic patterns, involving the inked staple line. Immunohistochemical analysis was positive for Calretinin, Pankeratin, Moc31, CDX2 and CK7. The patient was diagnosed with UCL but died prior to additional workup of her lung carcinoma.

Discussion:  UCL is challenging to diagnose and treat due to its presence indicating advanced metastatic disease. UCL tends to present as a large mass in the lung, with symptoms such as cough, chest pain, and shortness of breath. It is an aggressive cancer with median survival of <1 year and five-year survival rate of less than 5% [2]. Due to the lack of specific features, a combination of imaging studies including CT and PET scan leading to surgical resection of tumor is needed to guide treatment [2]. However, pathology results may not definitively state the type of cancer, and markers may be non-diagnostic, as was the case with this patient. When ambiguity occurs, molecular testing for Pankeratin, Moc31, CK7, Calretinin, and CDX2 and genetic testing is required to guide treatment [3]. Unfortunately, there is currently no standard treatment for UCL while responses to current treatments are generally poor. Surgery, radiation therapy, and chemotherapy may be used, but there is limited data on the efficacy of these treatments [2].

Conclusions:   In this case, the patient died before genetic testing could be completed. The aggressive nature and late diagnosis in this case highlights the need for more effective diagnostic and treatment approaches for UCL. Changes in diagnostic testing or consideration for changes in molecular and genetic testing strategies may allow diagnosis prior to the advanced stage which occurred in our patient.