Pulmonary Sarcomatoid Carcinoma Presenting as Massive Pleural Effusion

ABBREVIATIONS USED IN THIS ARTICLE

AFB = Acid-fast bacilli; ADA = Adenosine deaminase; ATT = Anti-tubercular therapy; CECT = Contrast-enhanced computed tomography; IHC = Immune histochemical; NSCLC = Non-small cell lung carcinoma; PSC = Pulmonary sarcomatoid carcinoma.

INTRODUCTION

Pulmonary sarcomatoid carcinoma (PSC) is a unique, invasive, and rare subtype of non-small cell lung carcinoma (NSCLC). It accounts for nearly 0.1–0.4% of the lung cancer. It is commonly seen in elderly males, smoker and has an upper lobe predominant with non-specific clinical features. The diagnosis is made if tumor contains both the sarcomatoid and epithelial components with at least 10% of the tumor and usually requires IHC staining for confirmation. Pleural involvement with effusion uncommon presenting feature of PSC. Massive pleural effusion is very rarely seen with this type of tumor. We are reporting a case of PSC in a middle-aged, non-smoker lady with massive pleural effusion.

CASE DESCRIPTION

A 54-year-old woman, a non-smoker from Ladakh with biomass fuel exposure for the last 30–35 years presented with complaints of dry cough, breathlessness, and left-sided chest pain of 3 weeks duration. There was no history of hemoptysis, sputum, fever, loss of weight, or decreased appetite. No history of anti-tubercular therapy (ATT). There was a history of pleural aspiration 3 times in the last 2 weeks. She was a housewife by occupation and had no history of exposure to fumes/dust. On examination, her vital signs were normal. On respiratory system examination there were reduced movements on the left side with a dull note on percussion and absent breath sounds of all areas of the left side except supraclavicular, and suprascapular areas. Other systemic examinations were within normal limits. The routine blood investigations were normal. The chest X-ray showed left-sided opaque hemithorax. The pleural fluid was lymphocytic, exudative with an adenosine deaminase (ADA) level of 12.8 U/L. The fluid was also negative for malignant cells thrice. The pleural fluid was negative for acid-fast bacilli (AFB)/GeneXpert. The pyogenic and fungal cultures were sterile. The contrast-enhanced computed tomography (CECT) of the chest showed gross left pleural effusion with contrast-enhancing multiple pleural nodules and thickening (Fig. 1). The bronchoscopy revealed a normal bronchial tree with no endo-bronchial lesion. Bronchial washing was negative for malignant cells and AFB. On thoracoscopy, multiple whitish glistening nodules were seen all over the costal pleural both anteriorly and posteriorly. Multiple pleural biopsies were taken from the nodules (Fig. 2). Lung expanded after thoraxcoscopy, however, a pulmonary opacity persists on the left upper zone. The computed tomography (CT) guided biopsy of lung mass was also performed from that lesion.

The pleural biopsy showed a tumor made up of spindle cells and polygonal cells with marked pleomorphism and nuclear atypia. Another section showed inflammatory cells with isolated atypical cells. The finding was suggestive of sarcomatoid carcinoma. The immune histochemical (IHC) staining of the biopsy specimen showed diffuse positivity with TTF-1 and Vimentin and focal positivity with Cytokeratin and negative for BCL-2 and calretinin (Fig. 3). The biopsy of lung mass was also positive for malignancy however the histopathological typing was not possible in that sample. The ultrasound abdomen and pelvis was normal. She was finally diagnosed with sarcomatoid carcinoma of the lung with pleural metastasis on the basis of hisptopathological finding. The lung cancer was stage IV_A as per new lung cancer classification.¹ After confirmation of diagnosis, thoracic surgery consultation was taken and she was not a candidate for surgical management. The patient was then referred to a pulmonary oncologist. She received chemotherapy with carboplatin and pemetrexed. Till the last follow she completed 6 cycles of chemotherapy. The treatment was well tolerated and the clinical response was without recurrent pleural effusion. Repeat CECT chest after 6 cycles of chemotherapy showing stable disease with complete resolution of pleural effusion (Fig. 4).

DISCUSSION

The massive effusion can be caused by various pathologies including infective, inflammatory, and malignancy. The most common causes of pleural effusion in developing countries are tuberculosis and malignancy.^2,3 Malignant pleural effusion is an exudative pleural effusion with the presence of malignant cells or tumor tissue. Metastatic pleural involvement is the second most common cause of exudative pleural effusion. Carcinoma of the lung, breast, and lymphoma are the most common causes with account for nearly 75% of malignant effusions.^3,4 The pleural effusion with lung cancer is classified as a metastatic disease with M1a and staging as stage IV disease.¹ The lung cancer with effusion has less survival than those without effusion and such patients are not curable with surgical treatment.⁵ So the confirmative diagnosis is important in every malignant pleural effusion before treatment. The common, simple, and confirmative diagnostic test for malignant effusion is a cytological examination of pleural fluid. However, the diagnostic yield is highly variable with ranges from 40 to 87%.⁴

The other method for confirmative diagnosis of pleural effusion is pleural biopsy. The types of pleural biopsy methods are close pleural biopsy and thoracoscopic biopsy. The close biopsy had been the investigation of choice for undiagnosed pleural effusion (can be done where thoracoscopy is not available). With advances in thoracoscopy this investigation is not regularly performed.^2,3 The diagnostic yield of the procedure is also highly variable with 39–75% in malignant effusion. Recent studies from India have shown that the diagnostic yield of 40–57% in malignant effusion.^6–7 The procedure is simple, easily available, cost-effective, and has low complications. Thoracoscopy is a safe, simple, and accurate technique with a high diagnostic yield of >90%. Therefore, it is considered as an investigation of choice when other investigations turned negative.^3,9 The direct inspection of pleura along with pleural biopsy, and the potential for pleurodesis with thoracoscopy is helpful for staging and can also establish operative eligibility. However, a few limitations like the need for expertise, cost, invasiveness, and limited ability restrict its widespread use.^3,7,8

Another common differential diagnosis is malignant mesothelioma. It should be considered as a diagnosis whenever fluid cytology or pleural histopathology suggests adenocarcinoma. The histopathology/cytology examination of malignant mesothelioma is difficult to differentiate from adenocarcinoma without IHC staining.^4,9 In the present case malignant mesothelioma is highly suspected as massive effusion with pleural thickening and nodules in a middle-aged non-smoker female. Pleural thickening with irregular and nodular lesions is characteristic of mesothelioma and pleural effusion is seen in 75–90%. The mediastinal pleural involvement, rind-like pleural involvement, and pleural thickness >1 cm with malignant effusion is more favor of mesothelioma than other metastatic diseases.¹⁰

Tubercular effusion is common, especially in the developing world and accounts for near 30% of effusion. The confirmative diagnosis is difficult as there is no specific clinical presentation and the yield of microbiological diagnosis nearly 30–35%.¹¹ The effusion is usually unilateral and mild to moderate on the X-ray chest. The diffuse thickening of both pleura with a ‘split pleural sign’ on the CT chest is characteristic. Sub pleural and peribronchovascular micro-nodules and interlobular septal thickening in the form of parenchymal abnormalities were common findings of tubercular effusion.^11,12 The diagnostic yield of pleural biopsy is high with >70% with close and >90% with thoracoscopy.^7,11 Being a non-smoker middle-aged woman without a history of exposure and unilateral effusion with pleural thickening from India should be considered for tuberculosis diagnosis until proven other ways.

Pulmonary sarcomatoid carcinoma is a unique, highly invasive, and very rare type of lung tumor, that accounts for nearly 0.1–0.4% of all lung cancer. It is commonly seen in elderly males, heavy smokers and predominantly in the upper lobe with non-specific clinical findings. The tumor is highly aggressive with poor prognosis and usually treatment resistant.^13,14 The preoperative diagnosis is usually difficult and challenging due to heterogeneity. In preoperative small bronchoscopic biopsies, some of the components of tumor may be missing, overrepresented, and under-presented. This leads to delayed and missed diagnosis. So larger sampling is required for pathologists for histopathological diagnosis of such rare tumor, which frequently needs IHC staining for confirmation of diagnosis.^14,15 Our case is a rare presentation of sarcomatoid carcinoma in a middle-aged, non-smoker female with massive effusion, with a diagnosis on thoracoscopic pleural biopsy.

Pathologically it is a rare type of poorly differentiated NSCLC that contains both mesenchymal and epithelial components. The diagnosis confirmed if the sarcomatoid component consists of the spindle or pleomorphic giant cells, or both contain at least 10% of the tumor.^13,14,16 According to WHO criteria, PSC is further sub-classified as pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma.^17,18 The commonest reported subtype was pleomorphic carcinoma. It is formed by malignant spindle and/or giant cells with epithelial components. The gaint and/or spindle cells appear as cohesive aggregates of the tumor cell, with no squamous or glandular differentiation. The spindle cells are in loose clusters or isolated, commonly elongated and polymorphic with prominent nucleoli and the nuclei are spindled, solitary and large.^13,16,18 As per genomic analysis, the origin of both the mesenchymal and epithelial elements is common. The mechanism that gives rise to this is thought the epithelial-mesenchymal transition. The IHC staining of both epithelial and sarcomatoid-like cytokeratin, TTF-1, Napsin A, P40, Vimentin, Desmin, carcinoembryonic antigen, CD34, S100, and WT1 are helpful in diagnoses.^13,15,16,18 The confirmatory diagnosis of the present case was done by the pathological finding of spindle and polygonal cells with marked pleomorphism and nuclear atypia and also confirmed by positive IHC marker of both epithelial and sarcomatoid. The final confirmative pathological diagnosis of all rare types of lung/pleural cancer is very important, as the prognosis and treatment of such rare tumors are different than common type NSCLC.

CONCLUSION

In conclusion, PSC is a very rare type of NSCLC with no specific clinical characteristics. The preoperative pathological diagnosis is difficult due to rarity, heterogeneity, and under/over presentation of one component over another. Immunohistochemical (IHC) marker of both components should be in the suspect case for further confirmation. The tumor is usually locally advanced with poor response to treatment and poor survival.

REFERENCES

1. Detterbeck FC, Boffa DJ, Kim AW, et al. Eighth edition lung cancer stage classification. Chest 2017;151(1):193–203. DOI: 10.1016/j.chest.2016.10.010.

2. Balamugesh T. Are the day of closedpleural biopsy over? No. Lung India 2015;32(6):641–643. DOI: 10.4103/0970-2113.168140.

3. Dixit R, Agarwal KC, Gokhroo A, et al. Diagnosis and management options in malignant pleural effusions. Lung India 2017;34(2):160–166. DOI: 10.4103/0970-2113.201305.

4. Light RW. Pleural Diseases, 6th edition. Philadelphia: Lippincott Williamsand Wilkins; 2013. p. 1437.

5. Sugiura S, Ando Y, Minami H, et al. Prognostic value of pleural effusion in patients with non-small cell lung cancer. Clin Cancer Res 1997;3(1):47–50. PMID: 9815536.

6. Saha K, Maikap MK, Maji A, et al. Demographic, clinical, biochemical, radiological andetiological characteristics of malignant pleural effusions from Eastern India. Indian J Cancer 2017;54(1):257–261. DOI: 10.4103/0019-509X.219575.

7. Spalgais S, Pal RS, Gothi D et al. The role of closed pleural biopsy in the era of thoracoscopy International Journal of current Medical and Applied sciences 2016;10(3):129–132. Available from: www.ijcmaas.com.

8. Lee P, Colt HG. Pleuroscopy in 2013. Clin Chest Med 2013;34(1):81–91. DOI: 10.1016/j.ccm.2012.11.003.

9. Branscheid D, Krysa S, Bauer E, et al. Diagnostic and therapeutic strategy in malignant pleural mesothelioma. Br J Cardiothorac Surg 1991;5(9):466–472. DOI: 10.1016/1010-7940(91)90142-7.

10. Metintas M, Ucgun I, Elbek O, et al. Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases. Eur J Radio 2002;41(1):1–9. DOI: 10.1016/s0720-048x(01)00426-0.

11. Shaw JA, Diacon AH, Koegelenberg CFN. Tuberculous pleural effusion. Respirology 2019;24(10):962–971. DOI: 10.1111/resp.13673.

12. Skoura E, Zumla A, Bomanji J. Imaging in tuberculosis. Int J Infect Dis 2015;32:87–93. DOI: 10.1016/j.ijid.2014.12.007.

13. Roesel C, Terjung S, Weinreich G, et al. Sarcomatoid carcinoma of the lung: A rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages. Interact Cardio Vasc Thorac Surg 2017;24(3):407–413. DOI: 10.1093/icvts/ivw392.

14. Huang SY, Shen SJ, Li XY. Pulmonary sarcomatoid carcinoma: A clinicopathologic study and prognostic analysis of 51 cases. World J Surg Oncol 2013;11:252. DOI: 10.1186/1477-7819-11-252.

15. Franks TJ, Galvin JR. Sarcomatoid carcinoma of the lung: Histologic criteria and common lesions in the differential diagnosis. Arch Pathol Lab Med 2010;134(1):49–54. DOI: 10.5858/2008-0547-RAR.1.

16. Karim NA, Schuster J, Eldessouki I, et al. Pulmonary sarcomatoid carcinoma: University of Cincinnati experience. Oncotarget 2018;9(3):4102–4108. DOI: 10.18632/oncotarget.23468.

17. Beasley MB, Brambilla E, Travis WD. The 2004 World Health Organization classification of lung tumors. Semin Roentgenol 2005;40(2):90–97. DOI: 10.1053/j.ro.2005.01.001.

18. Travis WD, Brambilla E, Burke AP, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, 4th edition. IARC. 2015. pp. 88–94.