Extensive pleural metastasis after surgery for pulmonary sarcomatoid carcinoma misdiagnosed as pyohemothorax: A Case Report and Literature Review

DOI: https://doi.org/10.21203/rs.3.rs-1616418/v1

Abstract

Pulmonary sarcomatoid carcinoma (PSC) is a rare group of poorly differentiated non-small cell lung cancer (NSCLC) with sarcomatoid differentiation, accounting for about 0.1-0.4% of all NSCLC [1,2]. Compared with other types of NSCLC, PSC is characterized by low incidence, poor differentiation, strong invasiveness and poor prognosis [3]. Early PSC is mainly treated with surgery, insensitive to radiotherapy and chemotherapy, and prone to recurrence and metastasis [4]. We report a 59-year-old male patient with PSC, no smoking history, 6.5cm*4.6cm left lower lobe mass, who underwent thoracoscopic left lower lobe resection and mediastinal lymph node dissection and recovered well. Postoperative patients with 50 days because of high fever, breathing can't lay down to hospital again, combined with the patient's symptoms, signs and auxiliary examination considered due to formation of purulent blood chest infection, postoperative puncture drainage in liquid viscous bloody difficult to elicit, give the left chest probe and pleural biopsy under thoracoscope, confirmed that the transfer of lung sarcomatoid carcinoma pleural widely, instead of pyohemothorax. After operation, the patient was given 12mg/d of anlotinib, but his condition did not improve, and he died due to the deterioration of his condition 12 days later. This is a special case of extensive pleural metastasis after PSC surgery misdiagnosed as pyohemothorax. Through the study of the patient's clinical manifestations, CT and prognosis, we hope to provide certain basis and support for the clinical diagnosis and treatment of PSC.

Introduce

PSC is a rare and highly aggressive subtype of NSCLC with epithelial carcinoma and stromal sarcomas or sarcomatoid components. According to the classification standard of lung malignant tumors by The World Health Organization (WHO) in 2015, PSC is a lung malignant epithelial tumor, which includes five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma [5]. PSC is commonly seen in elderly male patients with smoking history, and is characterized by low incidence, poor differentiation, strong invasiveness and poor prognosis. The 5-year survival rate is about 12.6% [3, 6]. This kind of disease has no typical clinical symptoms and has certain imaging characteristics, but the diagnosis requires pathological and immunohistochemical examination [7]. The treatment principle is similar to that of other NSCLC. Early PSC is mainly treated with surgery and is not sensitive to radiotherapy and chemotherapy, prone to recurrence and metastasis and poor prognosis [4]. With the development of molecular pathology, targeted therapy and immunotherapy may have a broad application prospect.

Case Report

The 59-year-old male patient had intermittent cough, expectoration and occasionally bloodshot sputum during the first month of admission to our hospital. The symptoms were improved after 1 week of self-anti-inflammatory treatment. On August 10, 2021, he was admitted to our hospital for chest CT (Fig. 1A1-2), which found space-occupying lesions in the lower lobe of left lung. After admission and on August 16, 2021, enhanced chest CT (Fig. 1B1-2) showed that a quasi-round soft tissue mass was observed in the lower lobe of the left lung, with uneven density, clear edge and lobulated shape, about 6.5cm*4.6cm in size, and "umbilical depression sign" was observed. After enhancement, the edge was evenly enhanced, and no enlarged lymph nodes were observed in the mediastinum. No malignant tumor was found in the tracheoscopic biopsy tissue. Erythrocyte sedimentation rate (ESR) was 69mm/H (reference interval: 0-15mm/H). Lung tumor markers were within the normal range, including neuron specific enolase (NSE) was 14.62ng/mL (reference interval: 0-18.3ng/mL), cytokeratin 19 fragments 21 − 1 (CYFRA21-1) was 1.89ng/ mL (reference interval: 0-3.3ng/ mL), carcinoembryonic antigen (CEA) was 0.75ng/ mL (reference interval: 0-5ng/ mL), Squamous cell carcinoma antigen (SCCA) was 1.060ng/ mL (reference interval: <2.7ng/mL). Brain CT, cervical lymph node color doppler ultrasound, abdominal color doppler ultrasound, whole body bone scan and other examinations showed no metastatic lesions. The patient had no smoking history and no family history of cancer. On August 20, 2021, thoracoscopic left lower lobe resection and mediastinal lymph node dissection were performed. Postoperative pathology (Fig. 2) was diagnosed as PSC, and no metastasis was found in mediastinal lymph nodes. On August 23, 2021, chest CT examination (Fig. 1C1-2) indicated good recovery, and discharged from hospital.

On September 28, 2021, chest CT (Fig. 1D1-2) showed a small amount of encapsulated fluid and air on the left side, but no discomfort. On October 5, 2021, the patient developed symptoms of chest tightness and shortness of breath, accompanied by intermittent low fever (< 37.5℃). The patient took anti-inflammatory drugs by herself, and the discomfort symptoms gradually became worse. On October 09, 2021, the patient was readmitted due to high fever (up to 39.5℃), wheezing and unable to lie flat. White blood cells (WBC) was 14.26*109/L (reference interval: 3.50–9.50*109/L), neutrophil percentage (NE) was 78% (reference interval: 40–75%), neutrophil absolute value (NAV) was 11.09*109/L (reference interval: 1.80–6.30*109/L), red blood cells (RBC) was 3.84*1012/L (reference interval: 4.30–5.80*1012/L), hemoglobin (HGB) 95g/L (reference interval: 130-175g/L), hematocrit (HCT) 0.291L/L (reference interval: 0.400-0.500L/L). Hypersensitive C-reactive protein (hs-CRP) was 252.92mg/L (reference interval: 0-3.5mg/L). Lung tumor marker NSE (51.12ng/mL) was significantly higher than that before surgery, while CYFRA21-1, CEA and SCCA were not significantly changed. Anti-infection and phlegm treatment were given, but the symptoms did not improve. On October 12, 2021, the re-examination of chest CT (Fig. 1E1-2) showed a significant aggravation of double pneumonia, with a large amount of effusion on the left pleural cavity and a little air accumulation, some of which were encapsulated. The amount of effusion was significantly increased compared with that on September 28, 2021. Combined with the patient's symptoms, signs and auxiliary examination, it was considered that the patient had pyohemothorax formed due to infection after surgery. Puncture drainage was performed on the thorax, and the drainage fluid was viscous and bloody and difficult to be extracted. On October 12, 2021, chest CTA (Fig. 3) showed no obvious signs of active bleeding in intrathoracic vessels. A thoracoscopic exploration of the left thoracic cavity and pleural biopsy was performed, which confirmed extensive pleural metastases of a sarcomatoid carcinoma of the lung rather than empyema (Fig. 4). The patient refused conventional chemoradiotherapy. Due to the short survival, the patient was given the oral molecular targeted drug anlotinib 12mg/d. After 2 days of administration, the patient developed hypertension (high pressure continued at 160mmHg), and the patient was treated with Levamlodipine besylate tablets (2.5mg/d). However, anlotinib failed to control the progression of the tumor, and after 12 days of taking it, his condition deteriorated and he died.

Discussion

PSC is a subtype of NSCLC containing sarcomatoid cells or sarcomatoid differentiation. Compared with other types of NSCLC, PSC is characterized by low incidence, poor differentiation, strong invasions and poor prognosis. PSC is more likely to occur in elderly men, and the onset age is mostly 65–75 years old [8]. However, studies have shown that smoking history has little correlation with survival [9, 10, 11]. The patient we provided had no smoking history and no bad habits. The specific etiology and inducement still need further study.

PSC mostly showed expansion growth, clear boundary, uniform density, lobulation and rare burr signs. PSC is most commonly presented as an isolated peripheral mass in the upper lobe of the lung [12], which usually metastases to the lung, bone, adrenal gland, pleura and brain, and a few metastases to the digestive tract, pancreas, kidney and skin [13]. Due to morphologic differences in tumors, initial or small biopsies may be inaccurate and easily missed. Preoperative diagnosis is difficult, and clinical manifestations lack specificity, early misdiagnosis of pneumonia, lung abscess or tuberculosis, etc. WHO recommends obtaining large enough surgical specimens combined with immunohistochemistry and microscopy to assist diagnosis [14]. Immunohistochemistry is helpful for the diagnosis and differential diagnosis of carcinosarcoma [7]. Chest CT scan suggested homogeneous mass density, irregular annular enhancement or patchy enhancement around the tumor after enhancement, and low enhancement area in the center. PET-CT can improve the diagnostic value of the disease, and it has been reported that PET-CT has a higher average SUVmax value in PSC patients [15, 16].

The onset of PSC is insidic, and the clinical symptoms and signs are mainly related to the lesion site and the size of the mass. The first symptoms are common with dry cough, expectoration, blood in expectoration and chest pain, accompanied by varying degrees of chest tightness, dyspnea, fever, etc., which can also be accidentally discovered during physical examination. PSC grows rapidly and is often found to have formed a large mass, which is more common in patients larger than 5cm. The case we provided had no specific clinical manifestations, and the symptoms were significantly relieved after anti-inflammatory, which delayed the diagnosis of the disease. In addition, the tumor was highly invasive and grew fast, reaching 6.5cm*4.6cm at the time of discovery.

At present, the treatment of PSC is basically the same as that of other types of NSCLC, which mainly adopts surgical treatment, supplemented by radiotherapy and chemotherapy. The overall treatment effect is not as good as that of other types of NSCLC, and it is prone to relapse, with metastasis occurring in 50% within half a year, and the median survival period is significantly shortened after relapse, about 2.6 months [17]. PSC is more aggressive and has a worse prognosis than other types of NSCLC, which may be related to early vascular invasion and metastasis, higher tumor activity of sarcomatoid components, and inactivation of tumor suppressor genes. In a multicenter study of 148 patients with PSC, Lococo et al. found that the overall median survival was 19 months and the 5-year survival was 12.6% [6]. For resectable PSC, lobectomy and mediastinal lymph node dissection were performed, and the 5-year survival rate was 12.6%-54.3% [18]. Platinum-based combined chemotherapy is mainly used in PSC, but PSC is not sensitive to radiotherapy and chemotherapy, and whether it benefits from radiotherapy and chemotherapy in perioperative period needs to be further confirmed [19, 20, 21].

Traditional radiotherapy and chemotherapy have poor efficacy for NSCLC. In recent years, new target drugs keep emerging, bringing survival benefits that cannot be achieved by conventional radiotherapy and chemotherapy for patients with driver gene positive NSCLC, and changing the treatment mode of advanced NSCLC. Due to the rare clinical PSC, there are few studies on the efficacy of targeted therapy. How is the efficacy of new targeted drugs for lung cancer in patients with PSC? Is there a survival benefit? Some scholars have carried out active exploration in order to improve the prognosis of such tumors. Studies have shown that targeted drugs such as androtinib can achieve certain therapeutic effects for PSC patients [22]. The patient refused further anti-tumor therapy after the initial operation, and was readmitted to hospital on the 50th day after the operation due to deterioration of his condition. Subsequently, the patient was diagnosed with tumor recurrence and extensive pleural metastasis. Due to various reasons, the patient was given targeted treatment of antiandrotinib, but no therapeutic effect was achieved, which may be related to missing the best treatment opportunity.

PSC is a rare NSCLC with high invasiveness and poor prognosis. Its clinical and imaging manifestations are non-specific and easy to be misdiagnosed. Pathological and immunohistochemical examinations are the main methods to diagnose PSC, while surgical resection is the main treatment method. Clinicians should improve the understanding of this disease, early detection, early diagnosis, early treatment, to reduce its mortality.

Conclusions

PSC is a rare type of NSCLC with poor prognosis and short-term recurrence (about one month) is easy to be ignored, especially after the first manifestation of fever, which is easy to be confused with postoperative chest bleeding and infection. It is hoped that the study of this case can improve the understanding of PSC.

Abbreviations

PSC

Pulmonary sarcomatoid carcinoma

NSCLC

non-small cell lung cancer

WHO

World Health Organization

ESR

Erythrocyte sedimentation rate

NSE

Neuron specific enolase

CYFRA21-1

Cytokeratin 19 fragments 21 − 1

CEA

Carcinoembryonic antigen

SCCA

Squamous cell carcinoma antigen

WBC

White blood cells

NE

Neutrophil percentage

NAV

Neutrophil absolute value

RBC

Red blood cells

HGB

Hemoglobin

HCT

Hematocrit

hs-CRP

C-reactive protein

Declarations

Acknowledgements: None 

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Contributions: Yao Zhang and ShiYun Feng wrote the main manuscript text and ShiYun Feng prepared figures 1-4. Two authors reviewed the manuscript.

Ethical Approval: No approval required.

Consent for publication: All patients provided informed consent.

Competing interests: The authors declare that they have no competing interests.

Availability of data and material: All data generated or analysed during this study are included in this published article.

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