Double Trouble? An Uncommon Case of Combined Small-Cell Lung Carcinoma

Document Type

Article

Abstract

INTRODUCTION: Combined Small Cell Lung Carcinoma is a pulmonary tumor that contains components of small cell lung carcinoma and non-small cell lung carcinoma. While it has been defined by the WHO since 1999, it has an overall low incidence of 2% within the SEER database (1) and is felt to be underdiagnosed due to conventional biopsy techniques. Its overall pathogenesis is unclear, but theories include single progenitor cell differentiation into two separate components or oncologic transformation between cell types. Here we present a case of a patient diagnosed with Combined Small Cell Lung Carcinoma.

CASE PRESENTATION: A 76-year-old Caucasian Male presents with the complaints of urinary frequency and lower extremity swelling. He carries a medical history of R arm melanoma with excision and negative sentinel lymph nodes as well as a L shoulder squamous cell carcinoma with excision and clear margins. He is a former 40 pack year smoker. No known history of lung disease. Denies pulmonary symptoms. Denies type B symptoms. He was found to have a left lower lobe mass on CXR. CT chest confirmed the mass and mediastinal lymphadenopathy. Transbronchial biopsy via EBUS of 4R was positive for atypical squamous cells positive for CK5/6, AE1/AE2, p40 and positive for small cells with high N:C ratio positive for synaptophysin, chromogranin, TTF-1 and a very high Ki67. SOX10 was negative. He was subsequently diagnosed with Combined Small Cell Lung Carcinoma. He declined therapy and proceeded to hospice level of care.

DISCUSSION: Combined Small Cell Lung Carcinoma is theorized to potentially stem from a pluripotent pulmonary progenitor stem cell with both epithelial and neuroendocrine components which mature into two cell types. A secondary hypothesis involves cellular transformation due to NOTCH-1 histone H3 methylation which in-vitro has been shown to cause differentiation of SCLC into NSCLC (2). This theory includes the basis of accumulated mutations which lead to activation/repression of genes leading to transformation of cells between cell lines. C-SCLC is most commonly diagnosed via surgical resection of lung nodules and infrequently based on fine needle aspiration due to the amount of tissue retrieved on sampling for pathology. While categorized under the SCLC family, it is less responsive to chemo and radiotherapy, but more responsive to gene directed therapies akin to NSCLC making it an interesting clinical entity (3). Prognosis more closely matches that of SCLC and if diagnosed at an early stage amenable to surgical resection, it provides the best outcomes as compared to higher stage disease treated with medical therapies (1).

CONCLUSIONS: While uncommon, it is important to be aware of the diagnosis of combined small cell lung carcinoma. Due to its distinct histology and proposed differentiation pathway, it appears to respond well to surgical approaches at lower stages and immunotherapy akin to non-small cell lung carcinomas as compared to small cell lung carcinoma which is traditionally treated with chemotherapy.

First Page

A4240

Last Page

A4241

DOI

10.1016/j.chest.2023.07.2762

Publication Date

10-2023

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