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Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors
Rita Dorantes-Heredia1, José Manuel Ruiz-Morales2, Fernando Cano-García1
1Anatomical Pathology Department, Hospital Médica Sur, México City, México ;
Abstract:
Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3-15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuron-specific enolase.
Insights
Lung cancer patients on targeted therapy can develop resistance, sometimes transforming into small-cell lung cancer (SCLC). Early detection via biopsy is crucial for timely diagnosis and treatment adjustments.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- Lung cancer remains a leading cause of cancer mortality globally.
- Targeted therapies like tyrosine kinase inhibitors (TKIs) have improved outcomes for specific non-small-cell lung carcinoma (NSCLC) patient groups.
- Acquired resistance to targeted therapies, including the EGFR Thr790Met mutation, and histopathological transformation to small-cell lung cancer (SCLC) are significant clinical challenges.
Purpose of the Study:
- To review the phenomenon of histopathological transformation from NSCLC to SCLC during targeted therapy.
- To highlight diagnostic methods for SCLC, including hematoxylin and eosin staining and immunohistochemistry.
- To discuss the genetic underpinnings of SCLC transformation, such as RB1 loss and potential roles of NOTCH and ASCL1 pathways.
Main Methods:
- Review of current literature on NSCLC to SCLC transformation.
- Discussion of diagnostic criteria for SCLC, including H&E staining and IHC.
- Exploration of genetic alterations associated with SCLC development.
Main Results:
- Histopathological transformation to SCLC occurs in 3-15% of NSCLC patients undergoing targeted therapy.
- Loss of retinoblastoma 1 (RB1) protein is a hallmark of SCLC, present in 100% of cases.
- Clinical deterioration during treatment may indicate SCLC transformation, necessitating biopsy.
Conclusions:
- Histopathological transformation to SCLC is a critical event in NSCLC treatment, requiring vigilant monitoring.
- Accurate diagnosis relies on histological and immunohistochemical evaluation, with RB1 loss being a key indicator.
- Further research is exploring noninvasive methods, like serum neuron-specific enolase, for detecting SCLC transformation.
