Rare pathological types——complex small cell lung cancer

Chen-Chen Zhao ,Tong Wu

1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China;2Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China.3Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China.

With the accelerated pace of modern life,lung cancer has become a common and multiple malignant tumor.According to the latest global cancer statistics report in 2019,lung cancer is the malignant tumor with the highest incidence in the world [1] and one of the main causes of death of cancer patients.In our country,the situation of lung cancer is also not optimistic,and the overall incidence rate ranks first [2].

The pathological types of lung cancer mainly include small cell lung cancer and non-small cell lung cancer.Among them,15%–20% of the pathological types are small cell lung cancer [3–4],and small cell carcinoma (SCLC) is a type of lung cancer with high morbidity and mortality.Its biological behavior is significantly different from other pathological types of lung cancer [5].SCLC is a malignant tumor composed of small cells lacking cytoplasm,unclear borders,small granular nuclei,and no or very small nucleoli.Past data show that [6–7],2%–23% of the pathological types of SCLC are a mixture of small cell lung cancer and non-small cell lung cancer,which is called compound small cell lung cancer.The non-small cell lung cancer (NSCLC) components can be squamous cell carcinoma,adenocarcinoma,large cell neuroendocrine tumors,even spindle cell carcinoma,giant cell carcinoma,etc.The mixed components can be one or more,and currently mixed squamous cell carcinoma is the most common [8].SCLC that is not mixed with non-small cell components is called pure small cell lung cancer.At present,most researches focus on pure small cell lung cancer [9–10],or study the 2 subtypes as a whole,but the research on complex small cell lung cancer (CSCLC) is very limited,and further research is needed.

There is still no clear conclusion on the pathogenesis of C-SCLC.There are several possibilities:(1) tumor stem cell theory [11];(2) collision cancer theory [12];(3) pathological subtype conversion theory [13] and so on.In a study to explore the expression level of histone acetylation in C-SCLC and NSCLC in the promoter Notch1 region [14],the chromatin immunoprecipitation method was used to measure the expression level of acetylated histone H3 in the promoter Notch1 region.,It was found that the expression level of acetylated histone H3 was lower in lung cancer cells that did not express the Notch1 region of the promoter.In small cell lung cancer,the appearance of epithelioid cell glands will cause the expression of promoter Notch1,and the expression of neuroendocrine markers will decrease.In addition,acetylated histone in the Notch1 region of the promoter of small cell lung cancer cells can inhibit the expression of Notch1 protein,and the restoration of Notch1 protein expression may also lead to the appearance of epithelioid regions in SCLC tissues,suggesting the potential formation mechanism of CSCLC.For the first time,some scholars [15] applied next-generation sequencing technology to 3 C-SCLC patients and found 81 mutations.All mutations can be found in the human gene mutation pathogenic annotation database,of which 62 (76.5%).For nonsynonymous mutations,11 mutations (13.5%) were found in the somatic mutation catalog database in tumors,and 8 mutations (10%) were predicted by the FATHMM method to cause protein missense mutations.Disease effect [16].

With the rapid development of modern inspection technology,the detection rate of small cell carcinoma combined with squamous cell carcinoma is also increasing while the level of early tumor diagnosis has improved.Literature studies found that related reports focused on small cell carcinoma and squamous cell carcinoma combined with lung cancer [17–18],esophageal small cell carcinoma with squamous cell carcinoma [19–20],bladder small cell carcinoma with poorly differentiated squamous cell carcinoma [21],throat Several aspects such as small cell carcinoma with squamous cell carcinoma [22–23] and small cell carcinoma of the colon with squamous cell carcinoma [24] are involved in imaging diagnosis and clinical treatment.In the era of precision medicine today,the niche population cannot be ignored either.Due to the low incidence and diagnosis rate of C-SCLC,its discovery and recognition time is not long.At present,the basic research on C-SCLC is only in the preliminary stage,and its origin,differentiation process and biological characteristics are still unclear.And the difference and connection with SCLC.In particular,whether the NSCLC components in C-SCLC are expressed and how they are expressed,whether and how they affect the biological characteristics of C-SCLC,whether further targeted therapy research can be carried out,whether there are expansion of treatment methods,and immunosuppressive therapy that is currently popular Whether it can be applied to C-SCLC requires further exploration in the field of molecular biology to in-depth study of the source,mechanism,onset and treatment of C-SCLC.In the clinic,the data of previous clinical case studies are mostly based on retrospective analysis,and the case data is very limited,and there is still a lack of multi-center prospective studies and large sample data reports,as well as sufficient evidence-based medical evidence.C-SCLC has not yet reached a comprehensive and extensive clinical expert consensus and guidelines.It is necessary to further explore how to improve its clinical detection rate,disease diagnosis rate,and explore appropriate pathological staging,treatment modes,and methods for accurately predicting disease prognosis.In addition,how to use current and future basic research,through translational medicine platforms,to reveal and translate into scientific research results that can clearly benefit patients,and how to use clinically observed disease phenomena and characteristics,and summarized treatment experience to guide basic scientific research is the focus and difficulty of close collaboration between scientific researchers and clinicians.