hesi rn case study lung cancer

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Case Report: Combined Small Cell Lung Carcinoma With Pulmonary Adenocarcinoma

Associated data.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

Combined small cell lung carcinoma is defined as cancer tissues that mainly contain small cell lung cancer (SCLC) components with non-SCLC (NSCLC) histopathological types. The most common part of NSCLC is squamous cell carcinoma or large cell carcinoma. Combined SCLC (CSCLC) contains adenocarcinoma is extremely rare.

Case Presentation

We reported a case with surgically treated diagnosed as CSCLC with adenocarcinoma in an elderly and we summarized the clinical features of this disease. The patient has remained well for over 2 weeks after the treatment.

There are still few research reports on CSCLC. Since the survival time of patients with advanced CSCLC is shorter than that of simple SCLC, the recommended treatment for CSCLC is early detection and early surgery. In order to facilitate preoperative diagnosis and avoid misdiagnosis of such rare diseases, more cases need to be reported.

Introduction

The precise definition of combined small cell lung cancer is that the cancer foci are mainly small cell carcinoma with other types of non-small cell, including adenocarcinoma, squamous cell carcinoma, and large cell neuroendocrine carcinoma reported by the WHO ( 1 ). Only 13% of primary lung tumors are small cell lung cancer (SCLC). SCLC was first described by Barnard in 1926 as oat celled sarcoma which is the first statement of combined SCLC (CSCLC) in the world. CSCLC is rare in clinical patients, accounting for <1–3.2% of all SCLC ( 2 , 3 ). We report a case with surgically treated diagnosed as CSCLC with adenocarcinoma in an elderly and we summarized the clinical features of this disease.

Case Report

A 73-year-old man was admitted to our hospital for a routine health check and found a lung nodule by chest X-ray. He had a history of smoking. He had smoked a pack of cigarettes a day for the past 20 years and has now quit smoking for 9 months. When inquiring about the condition at the outpatient clinic, he denied any symptoms such as chest pain, hoarseness, hemoptysis, cough, and difficulty breathing. Physical examination revealed normal breath sounds in both lung fields. There was no obvious abnormality in the laboratory test results. The results of his lung function test and cardiovascular examination were within the normal range. A contrast-enhanced CT scan revealed a soft tissue mass measuring 2.4 cm × 3 cm in the lower lobe of the right lung ( Figures 1A,B ). Bronchoscopy did not show evidence of pathology. Then, the patient was subjected to lobectomy by utilizing a three-port video-assisted thoracic surgery (VATS). During the operation, we did not find the lesion invaded the adjacent tissue structure. After we cut off the lesion, we used biopsy forceps to remove the tissue from the mass in the specimen plate for rapid freezing pathology, and the pathological diagnosis was small cell lung cancer combined with adenocarcinoma. The postoperative course was uneventful. The patient was followed up for 2 weeks without evidence of recurrence to date.

Chest contrast-enhanced CT and histological features and of the case. (A,B) Contrast-enhanced CT scan showing a soft tissue, measuring 2.4 cm × 3 cm in size, in the lower lobe of the right lung. (C,D) H&E staining reveals the tumor consisted of dual disparate components, which were intermingled in a combined pattern with a definite boundary at low magnification ( C : ×100 and D : ×200).

According to 2004 WHO/International Association for the Study of Lung Cancer (IASLC) classification of lung and pleural tumors, CSCLC is defined as cancer tissues that mainly contain SCLC components with non-SCLC (NSCLC) histopathological types. The most common part of NSCLC is squamous cell carcinoma or large cell carcinoma ( 4 , 5 ). CSCLC contains adenocarcinoma is extremely rare ( 6 ). Only 15 cases including our patient of pulmonary SCLC combined with adenocarcinoma have been reported in 7 studies. As summarized in our Table, the ratio of male and female was 4:1 and the mean age was 68 years ( Table 1 ).

Clinicopathological features of the CSCLC.

M, male; F, female; LUL, left upper lobe; LLL, left lower lobe; RUL, right upper lobe; RLL, right lower lobe; VATS, video-assisted thoracic surgery; CT, chemotherapy; RT, radiation therapy;

In our analysis, CSCLC is usually asymptomatic and may be diagnosed as an incidental finding and the majority of male patients are smokers, and it illustrates the correlation between CSCLC and smoking. Analyzing the collection cases in our single-center, the patient had no symptoms such as pain or cough, and he was discovered during routine health check-ups. Because tumors are relatively rare, there is currently no definite radiological diagnostic standard for CSCLC. A chest radiograph is the most commonly used imaging method to evaluate lung mass, but it may not be able to distinguish CSCLC from pure SCLC.

Histopathologically, as seen in our case, the tumor lesion is composed of two completely different parts, which can be clearly defined under the microscope. In the SCLC part, the central component is mostly composed of small, uniform, poorly differentiated necrotic cancers ( Figures 1C,D ), while the other half is considered to be adenocarcinoma with papillary and acinar features. Immunohistochemically, in the pulmonary tumor, TTF-1 vimentin and pancytokeratin were strongly expressed in 75% of the small cell carcinoma cells, and 20% of the small cell carcinoma cells strongly expressed CD56, synaptophysin, and S100 protein ( 10 , 11 ). As shown in Bai et al. ( 11 ) report, The components of SCLC are positive for synaptophysin (Syn), chromogranin A (CgA), and nerve cell adhesion molecule 1 (CD56), and have high proliferative activity by Ki-67 antigen immunostaining, while the adenocarcinoma area had low Ki-67 proliferation activity and was negative to others.

In addition to the analysis of gross specimen morphology and pathology under a microscope, clonality analysis of each component is also useful in CSCLC. In the research of Wagner et al. ( 7 ), using loss of heterozygosity (LOH) analysis included 3 and 17 p in the separate components of the lesion in each patient. In the study of Case 3, the alleles changing is inconsistent both in SCLC and NSCLC components. The alleles in SCLC are almost completely lost, while the number of the same alleles is greatly reduced in NSCLC. In case 2 in Table 1 , LOH is demonstrated only in the SCLC component. The point mutations in the p53 gene and LOH of chromosome 3p in each component were examined and the results showed that the small cell carcinoma and squamous cell carcinoma components in CSCLC are clone-related, but the adenocarcinoma component comes from a single clone and has no obvious correlation with small cell carcinoma ( 12 ).

Although small cell lung cancer is highly sensitive to chemotherapy and radiotherapy, most patients will eventually develop multiple organs metastasis of lung cancer cells. Surgical resection is only for patients with early-stage and no lymph node metastasis. The research suggests that the combination of etoposide and cisplatin is the traditional first-line treatment strategy for SCLC ( 9 ). In recent years, with the improvement of technology and detection methods, CSCLC has also been increasingly recognized by more surgeons. The role of surgery in the treatment of CSCLC is increasingly valued ( 6 ). For patients with no metastasis to the lymph node, lobectomy with systemic hilar and mediastinal lymphadenectomy are preferred ( 14 ). We can see from the Table 1 that the surgery was performed in all patients with video-assisted thoracic surgery (VATS) in six cases or lobectomy by standard thoracotomy in nine patients. Almost all patients with small cell lung cancer have a tendency to spread throughout the body. Therefore, combined chemotherapy and chest radiotherapy are the main treatments for this disease ( 15 , 16 ). In Table 1 , four patients underwent chemotherapy and three of them got radiation therapy. In case 7, reported by Iezumi et al. ( 10 ), CSCLC patients received a combined chemotherapy regimen of cisplatin and irinotecan hydrochloride and received radiotherapy for metastasis and recurrence in the forearm. For CSCLC patients with EGFR mutations, use currently mature epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and other drug-related molecular targeted therapies to exert anti-tumor activity ( 17 , 18 ).

Some researchers believe that pure SCLC and CSCLC have similar clinical manifestations and that the operation outcomes of both in a limited stage are similar. At present, the clinical characteristics and clinical data of these patients have been published ( 8 , 13 , 19 , 20 ). In one study, 5-year survival of patients with CSCLC was only 15.9% ( 20 ). They collected the clinical data of CSCLC patients and pure SCLC patients and made detailed comparisons. The final data showed that the prognosis of CSCLC patients and SCLC patients were similar, and there was no statistically significant difference. However, the rate of surgery for CSCLC was much higher compared with pure SCLC. For those advanced patients who did not undergo surgery but received equivalent chemotherapy, the overall survival rate (OS) of CSCLC patients is lower than that of pure SCLC patients ( 13 ). Hage et al. ( 19 ) also reported that surgical resection in selected patients with pretreatment clinical stage I combined and pure SCLC can be curative or offer long-term survival. However, The OS of patients with pure SCLC is significantly lower than that of patients with CSCLC in Babakoohi et al. ( 8 ) research. In their study, the 5-year survival rate of CSCLC patients with stage I or stage II was very good, almost reaching 100%, which is in contrast with the previous study by Hage et al. There are several limitations in this report. Firstly, the short-term follow-up is not enough to fully explain the prognosis in our patient. Secondly, the number of studies included and the simple scale were relatively small.

In short, there are still few research reports on CSCLC. Since the survival time of patients with advanced CSCLC is shorter than that of simple SCLC, the recommended treatment for CSCLC is early detection and early surgery. Surgical resection can only be performed in a small number of patients with conditions, whose can be cured or can obtain long-term survival from preoperative evaluation. In order to facilitate preoperative diagnosis and avoid misdiagnosis of such rare diseases, more cases need to be reported.

Data Availability Statement

Ethics statement.

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author Contributions

CS was involved in drafting the manuscript. GC designed and revised the manuscript. All authors have read and approved the final manuscript.

The Science and Technology Project of the Health Planning Committee of Sichuan (No. 19PJ242), Sichuan Province Science and Technology Support Program (No. 2020JDKP0023), and Chengdu science and technology Support Program (No. 2019-YFYF-00090-SN).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We greatly appreciate the assistance of the staff of the Department of Thoracic Surgery, West-China Hospital, Sichuan University, and thank them for their efforts.

• Biomarker-Driven Lung Cancer
• HER2-Positive Breast Cancer
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Case 1: 72-Year-Old Woman With Small Cell Lung Cancer

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Mark Socinski, MD: Thank you for joining us for this Targeted Oncology ™ Virtual Tumor Board ® focused on advanced lung cancer. In today’s presentations my colleagues and I will review three clinical cases. We will discuss an individualized approach to treatment for each patient, and we’ll review key clinical trial data that impact our decisions. I’m Dr. Mark Socinski from the AdventHealth cancer institute in Orlando, Florida. Today I’m joined by Dr Ed Kim, a medical oncologist from the Levine Cancer Institute in Charlotte, North Carolina; Dr Brendon Stiles, who is a thoracic surgeon from the Weill Cornell Medical Center in New York ; and Dr Tim Kruser, radiation oncologist from Northwestern Medicine Feinberg School of Medicine in Chicago. Thank you all for joining me today. We’re going to move to the first case, which is a case of small cell lung cancer. I’m going to ask Dr Kim to do the presentation.

Edward Kim, MD: Thanks, Mark. It’s my pleasure to walk us through the first case, which is small cell lung cancer. This is a case with a 72-year-old woman who presents with shortness of breath, a productive cough, chest pain, some fatigue, anorexia, a recent 18-pound weight loss, and a history of hypertension. She is a schoolteacher and has a 45-pack-a-year smoking history; she is currently a smoker. She is married, has 2 kids, and has a grandchild on the way. On physical exam she had some dullness to percussion with some decreased-breath sounds, and the chest x-ray shows a left hilar mass and a 5.4-cm left upper-lobe mass. CT scan reveals a hilar mass with a bilateral mediastinal extension. Negative for distant metastatic disease. PET scan shows activity in the left upper-lobe mass with supraclavicular nodal areas and liver lesions, and there are no metastases in the brain on MRI. The interventional radiographic test biopsy for liver reveals small cell, and her PS is 1. Right now we do have a patient who has extensive-stage small cell lung cancer. Unfortunately, it’s what we found. It’s very common to see this with liver metastases.

Transcript edited for clarity.

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Lung Cancer: A Case Study 

Submitted by Anna Stewart RN, BSN, MSN-C

Tags: cancer chemotherapy death end of life therapy treatment

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Lung cancer is the number one cause of cancer-related death in men and the second most common in women. Lung cancer is responsible for 1.3 million deaths worldwide annually. The main types of lung cancers consist primarily of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).  In 2008, the National Cancer Institute (NCI) estimated in the United States that there were 215,020 new cases and 161, 840 cancer related deaths of SCLC and NSCLC combined. The most common cause of lung cancer is smoking. Other risk factors include genetics, radon gas, asbestos and air pollution which includes secondhand smoke.

Diagnostics is an important part of cancer treatment. Distinction between lung cancers is important because of the difference in treatments. Chest radiograph and computed tomography (CT scan) are used to visualize the lung cancer. A biopsy is done to confirm the diagnosis and usually achieved via bronchoscopy or CT guided biopsy.  Categorization is done by viewing the cells under a microscope.  NSCLC arises from epithelial cells and SCLC begins in the nerve cells or hormone-producing cells of the lung. The term “small cell” refers to the size and shape of the cancer cells as seen under a microscope.  The histological classification of lung cancers is significant because it determines the type of treatment and prognosis, the stage (degree of metastasis), and patients performance status.

The frequency of NSCLC is 80.4% compared to 16.8% of cases of SCLC. Other types of lung cancers (carcinoid, sarcoma and unspecified lung cancers) are less than 3%.  Surgery, chemotherapy, and radiotherapy are possible treatments.  The NCI states that the five year survival rate is 15% with treatment.

SCLC has the poorest prognosis of lung cancer because it is the fastest growing and has usually metastasized by the time a diagnosis is made. Although lung cancer can metastasize anywhere in the body, the most common sites are the lymph nodes, lungs, bones, brain, liver, and the adrenal glands. Metastases from lung cancer can cause additional difficulties such as breathing problems, bone pain, abdominal or back pain, headache, weakness, seizures, and/or speech difficulties. Lung tumors can release hormones that result in chemical imbalances, such as low blood sodium levels or high blood calcium levels, but this is uncommon (NCI, 2008).

Staging of small cell lung cancer

Because almost all small cell lung cancer has spread outside the lung when discovered, very few patients with small cell lung cancer are treated with surgery, and all receive chemotherapy. Some patients with small cell lung cancer can benefit from radiation therapy. The staging for small cell lung cancer helps identify which patients can be treated with radiation therapy in addition to chemotherapy. Small cell lung cancer is classified as either limited stage or extensive stage:

• Limited stage means the cancer is located on one side of the chest and involves a single region of the lung and adjacent lymph nodes. This region can be treated in its entirety with radiation therapy. About 30% of patients have limited stage.
• Extensive stage means the cancer has spread to other regions of the chest, or outside of the chest, and cannot be treated completely with radiation therapy. Most patients (70%) have extensive stage disease and are treated with chemotherapy only (McCance, 2006).

Treatment of small cell lung cancer

The treatment of small cell lung cancer depends on the stage. Small cell lung cancer spreads quickly, so systemic chemotherapy is the primary treatment for all patients. The most commonly used chemotherapy regimen is etoposide (VePesid, Lastet, Etopoph plus cisplatin (Platinol) or carboplatin (Paraplatin). Patients with limited stage small cell lung cancer are best treated with simultaneous chemotherapy plus radiation therapy to the chest given twice a day. Radiation therapy is best when given during the first or second month of chemotherapy. Patients with extensive stage cancer are treated with chemotherapy only. Chemotherapy is given for three to six months. Surgery is rarely appropriate for patients with small cell lung cancer and is only considered for patients with very early-stage disease, such as a small lung nodule. In those cases, chemotherapy, with or without radiation therapy is given afterwards.

In patients whose tumors have diminished after chemotherapy, radiation therapy to the head cuts the risk that the cancer will spread to the brain. This preventative radiation to the head is called prophylactic cranial irradiation (PCI) and has been shown to extend the lives of these patients.

Like patients with advanced NSCLC, patients with small cell lung cancer of any stage face the risk that the cancer can return, even when it is initially controlled. All patients with small cell lung cancer must be followed closely by their doctors with x-rays, scans, and check-ups.

Most patients with lung cancer are treated by more than one specialist with more than one type of treatment. For example, chemotherapy can be prescribed before or after surgery, or before, during, or after radiation therapy. Patients should have a sense that their doctors have a coordinated plan of care and are communicating effectively with one another. If patients do not feel that the surgeon, radiation oncologist, or medical oncologist is communicating effectively with them or each other about the goals of treatment and the plan of care, patients should discuss their concerns with their doctors or seek additional opinions before treatment (Roman & Brigham, 2007).

Radiation therapy

Radiation therapy is the use of high energy x-rays or other particles to kill cancer cells. Radiation therapy is performed by a specialist called a radiation oncologist. Like surgery, radiation therapy cannot be used to treat widespread cancer. Radiation only kills cancer cells directly in the path of the radiation beam. It also damages the normal cells caught in its path, and for this reason, it cannot be used to treat large areas of the body. Patients with lung cancer treated with radiation therapy often experience fatigue and loss of appetite. If radiation therapy is given to the neck, or center of the chest, patients may also develop a sore throat and have difficulty swallowing. Skin irritation, like sunburn, may occur at the treatment site. Most side effects go away soon after treatment is finished.

If the radiation therapy irritates or inflames the lung, patients may develop a cough, fever, or shortness of breath which may begin months or years after the radiation therapy. This condition occurs in about 15% of patients and is called radiation pneumonitis. If it is mild, radiation pneumonitis does not require treatment and resolves on its own. If it is severe, radiation pneumonitis may require treatment with steroid medications, such as prednisone. Radiation therapy may also cause permanent scarring of the lung tissue near the site of the original tumor. Typically, the scarring does not lead to symptoms. Widespread scarring can lead to permanent cough and shortness of breath. For this reason, radiation oncologists carefully plan the treatments using CT scans of the chest to minimize the amount of normal lung tissue exposed to the radiation beam (Wikipedia, 2009).

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. Chemotherapy is given by a medical oncologist. Most chemotherapy used for lung cancer is given intravenously. The side effects of chemotherapy depend on the individual and the dose used, but can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. Nausea and vomiting are often avoidable; for more information, read the What to Know: ASCO's Guideline on Preventing Nausea and Vomiting Caused by Cancer Treatment. These side effects usually go away once treatment is finished.

Chemotherapy may also damage normal cells in the body, including blood cells, skin cells, and nerve cells. This may result in low blood counts, an increased risk of infection, hair loss, mouth sores, and/or numbness or tingling in the hands and feet. Your medical oncologist can often prescribe drugs to help provide relief from many side effects. Hormone injections are also used to prevent white and red blood cell counts from becoming too low.

Newer chemotherapies cause fewer side effects and are as effective as older treatments. Chemotherapy has been shown to improve both the length and quality of life in people with lung cancer of all stages.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases (Swierzewski, 2007).

DH is a 70 year old female with a diagnosis of small cell carcinoma of the lung limited stage disease.  The patient was diagnosed August, 2007 and treated from 10/2007 through 11/2007 with Carboplatin and VP16.  The patient had no response to the initial treatment.  She was subsequently treated Carboplatin and Taxol from 12/2007 through 3/2008.

After completion of chemotherapy plans were made for her to receive radiation therapy. The plans for radiation were delayed due to the discovery of a parotid tumor. This tumor was identified as a Warthin’s tumor (benign neoplasm of the salivary glands).  The patient did receive radiation therapy from 7/2008 to 10/2008.  Dosing of 5,580 cGy (cGy= centigray, the gray measures the deposited energy of radiation) and 31 fractions (the smaller, divided doses of radiation that are given each day) was administered over 70 days. 

DH has been off chemotherapy since 3/2008 and radiation therapy since 10/2008 with no further treatment. DH returns today in follow up. She has had a relatively stable weight and good appetite.  The patient had a mammogram, CT/Abd-Pelvis and chest x-ray on February 3, 2009.  All were normal with the exception of a slight prominence of the left hilum thought to be related to original tumor.  Patient also had colonoscopy and endoscopy done on 3/30/2009.  The endoscopy was negative but the colonoscopy was positive for diverticuli.  PET CT done on 3/25/2009 at local hospital showed areas of enlarged nodes located around the bronchial tree, abdomen and left axillary. DH is to return to her primary care physician (PCP) to have an area in the abdomen removed and biopsied.  She has an appointment with the PCP on Friday, April 10, 2009. She does complain of non-exertional chest pain and has a history of hypertension.  DH does have some general medical arthritis as well as paresthesias and numbness from Taxol therapy.

Patient’s labs values are stable with Hgb of 12.6, and Hct 39.1.  Platelets have improved from previous visit from 312 to 371.  White blood cell count continues to improve as well up from 7.52 to 8.0.  Lymphocytes and monocytes are stable at 14 and 9 prospectively.

Explanations are given to DH and her husband regarding the possibility of further chemo and radiation therapies pending biopsy results. Patient and husband verbalize understanding and agree to plan of care.  Biopsy is scheduled with PCP in two days.  Patient scheduled for follow up visit with oncologist in two weeks.

• Brashers, V. (2006). Alterations of Pulmonary Function (pp.1237-1243). In McCance, Pathophysiology The Biologic Basis for Disease in Adults and Children (5th ed.)St. Louis, Mosby Elsevier.
• National Cancer Institute (2009).  Small Cell Lung Cancer Treatment (PDQ),
• Retrieved April 13, 2009 from: meb.uni-bonn.de/cancer.gov.
• Roman, J., & Brigham, K., (2007) Neoplastic Disorders of the Lung (pp259-263),
• Andreoli and Carpenter’s: Cecil Essentials of Medicine (7th ed.), Philadelphia, W.B. Sanders Company.
• Swierzewski, S. (2007). Chemotherapy. Retrieved April 13, 2009 from: oncologychannel.com. 
• Wikipedia (2009).  Lung Cancer, Retrieved April 22, 2009 from: wikipedia.org. 

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