Sarcomatoid carcinoma of the lung
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Trusha Tank, M.D.[2] Maria Fernanda Villarreal, M.D. [3]
Synonyms and keywords: Primary sarcoma of the lung; Lung sarcoma; Sarcomatoid tumor of the lung
Overview
Sarcomatoid carcinomas are a group of poorly differentiated non-small cell lung carcinomas. Sarcomatoid carcinoma is defined as a biphasic tumor with morphological characteristics of both, carcinomatous and sarcomatous. Sarcomatoid cancer of the lung is a rare type of malignancy and it comprises of only 0.3% to 1.3% of cases of all lung cancers. The pathogenesis of sarcomatoid carcinoma of the lung is characterized by a rare epithelial origin, and morphologic features suggestive of a malignant mesenchymal tumor. The EGFR gene and K-ras mutations have been associated with the development of sarcomatoid carcinoma of the lung. The prevalence of sarcomatoid carcinoma of the lung is approximately 0.4 cases per 100,000 individuals worldwide. Common risk factors in the development of sarcomatoid carcinoma of the lung are smoking, family history of lung cancer, exposure to high levels of air pollution, asbestos, radiation therapy to the chest, radon gas, occupational exposure to chemical carcinogens, and previous lung diseases. If left untreated, the majority of patients with sarcomatoid carcinoma of the lung may develop distant metastasis via the lymphogenic route. Common complications of sarcomatoid carcinoma of the lung include respiratory failure, pneumonia, and distant metastasis. Prognosis is generally poor, even worse than other non-small cell carcinoma of the lung. The 5-year survival rate for patients with sarcomatoid cancer of the lung is 28.7%.
Historical Perspective
- Sarcomatoid carcinoma was first described by Virchow in 1865 as a “biphasic” lesion of adenocarcinomatous or squamous cell components along with spindle or giant cell component.[1]
- In 1981, World Health Organization (WHO) classification on lung cancers, mentioned pleomorphic carcinomas showing a prevalence of spindle or giant cells as morphologic variants of squamous cell carcinomas and large-cell carcinomas, respectively, and defined carcinosarcomas as biphasic tumors consisting of an intimate admixture of carcinoma and sarcoma.[2]
Classification
Sarcomatoid carcinoma of the lung can be classified according to WHO classification into 5 subtypes:[2][3]
- Pleomorphic carcinoma
- Spindle cell carcinoma
- Giant cell carcinoma
- Carcinosarcoma
- Pulmonary blastoma
Sarcomatoid carcinoma of the lung can also be classified according to their location including:[3]
- Central
- Peripheral
Pathophysiology
- The pathogenesis of sarcomatoid carcinoma of the lung is characterized by a rare epithelial origin and morphologic features suggestive of a malignant mesenchymal tumor.[3][4]
- Four major hypotheses may explain sarcomatoid neoplasms:[5]
- The embryonic rest hypothesis: This theory suggests that sarcomatoid tumors were the result of misplaced “mini-organs” that is complete with epithelium and stroma.
- The collision hypothesis: This theory implies separate but concomitant proliferation of malignant epithelium and mesenchyme.
- The stromal induction/metaplasia hypothesis: This theory proposes that sarcomatous elements are an atypical response to the growth of a carcinoma rather than neoplastic; and the totipotential hypothesis, which is based on tumor origin from a single stem cell that differentiates into separate epithelial and mesenchymal components.
- Totipotential hypothesis: This hypothesis proposes an origin from a single totipotential stem cell that differentiates into epithelial and mesenchymal components.
- The EGFR and K-ras gene mutations have been associated with the development of sarcomatoid carcinoma of the lung.[6]
- On gross pathology, a large-sized mass lesion, with upper lobe and peripheral location are characteristic findings of sarcomatoid carcinoma of the lung.
Gross Pathology
- Sarcomatoid carcinomas can arise centrally or peripherally. Most commonly present as poorly circumscribed solitary peripheral masses.[7][8]
- Sarcomatoid carcinoma is commonly found in upper lobe of lungs.
- Tumors are large, ranging from 1 to 13 cm, with a median of 4.9 cm, and often invade the chest wall.
- Tumor consistency is described as soft and fleshy or firm, hard, or rubbery.
- Cut surfaces vary from white-grey to yellow, frequently show hemorrhagic and necrotic foci, and occasionally demonstrate cavitation.
Microscopic Pathology
- On microscopic histopathologically sarcomatoid carcinoma is classified into 5 subtypes:[9]
- Pleomorphic carcinoma
- Poorly differentiated, sarcomatoid carcinoma composed of malignant, spindle and giant cells.
- Spindle cell may vary from epithelioid to strikingly spindled and are arranged in haphazard fascicles or storiform pattern.
- Giant cells are discohesive, uni/multinucleated, have moderate to abundant, dense, eosinophilic cytoplasm which may show emperipolesis by polymorphonuclear leukocytes or lymphocytes.
- Giant cells are anaplastic, with many bizarre forms.
- Tumor cells are embedded in a fibrous or myxoid stroma.
- Spindle cell carcinoma
- Sarcomatoid carcinoma composed only of spindle-shaped tumor cells.
- Giant cell carcinoma:
- Sarcomatoid carcinoma composed only of anaplastic, giant tumor cells.
- Carcinosarcoma:
- A mixture of carcinoma and true sarcomas such as malignant bone sarcoma, cartilage, or skeletal muscle sarcoma.
- The carcinoma component may be squamous cell carcinoma, adenocarcinoma, adenocarcinoma mixed with squamous cell carcinoma, and large cell carcinoma, whereas the sarcoma component may be rhabdomyosarcoma, osteosarcoma mixed with chondrosarcoma, and osteosarcoma.
- pulmonary blastoma:
- A biphasic tumor composed of a primitive epithelial component with well-differentiated, fetal adenocarcinoma and a primitive mesenchymal stroma that may contain rhabdomyosarcoma, osteosarcoma, or chondrosarcoma.
- Pleomorphic carcinoma
Causes
There are no direct causes of sarcomatoid carcinoma of lung. However, there are a few risk factors that can lead to genetic mutation and cause sarcomatoid carcinoma of lung.
Differentiating sarcomatoid carcinoma of the lung from other Diseases
Sarcomatoid carcinoma of the lung must be differentiated from other diseases that cause cough, weight loss, hemoptysis, and dyspnea among adults, such as:
- Tuberculosis
- Adenocarcinoma of the lung
- Small cell carcinoma of the lung
- Pulmonary fungal disease
- Lung abscess
Epidemiology and Demographics
Prevalence
- The prevalence of sarcomatoid carcinoma of the lung is approximately 0.4 cases per 100,000 individuals worldwide.[4]
- Sarcomatoid carcinoma comprises of 0.3% to 1.3% of total lung malignancies.[10]
- The overall prevalence of sarcomatoid carcinoma of the lung is 0.1% to 0.4% of all non-small cell lung malignancies.[3]
Age
- Sarcomatoid carcinoma of the lung is more commonly diagnosed among patients aged 65 to 75 years old.[11]
- Sarcomatoid carcinoma of the lung is more commonly observed among elderly patients and adults.
- Biphasic blastoma subtype is an exception and an average age of 35 years old patients being more commonly diagnosed
Gender
- Males are more commonly affected with sarcomatoid carcinoma of the lung than females.[12][13]
- the male to female ratio is 4:1.[11]
- Biphasic blastoma subtype is an exception, that affects men and women equally.
Race
- There is no racial predilection for sarcomatoid carcinoma of the lung.
Region
Geographical location has no effect on epidemiology of sarcomatoid carcinoma of the lung.
Risk Factors
Common risk factors in the development of sarcomatoid carcinoma of the lung are the following:[14][15][16][17][18]
- History of cigarettes, cigars, or pipe smoking
- Secondhand or passive smoking
- Family history of lung cancer
- Genetic predesposition
- High levels of air pollution
- Radiation therapy to the chest
- Heavy alcohol consumption
- Radon gas
- Occupational exposure to silica, asbetos, Uranium or nuclear radiation
- Previous history of lung diseases
Natural History, Complications and Prognosis
- The majority of patients with sarcomatoid carcinoma of the lung remain are initially asymptomatic.
- Early clinical features include chronic cough, hemoptysis, dyspnea, weight loss and fatigue.[19]
- The majority of patients with central sarcomatoid carcinoma of the lung may develop distant metastasis to esophagus, jejunum, rectum and kidney.
- Sarcomatoid carcinoma of lung located in the periphery of lungs tends be diagnosed later in the advanced stages with the large size and metastasis to the pleura and chest wall.
- Common complications of sarcomatoid carcinoma of the lung include respiratory failure, pneumonia, and distant metastasis.
- If left untreated Sarcomatoid carcinoma progresses to death.
- Prognosis is generally poor.[20][9]
- According to a study, the 3-year and 5-year survival rates for patients with sarcomatoid cancer of lung are 35.8 and 28.7%.[13]
Diagnosis
Diagnostic Criteria
- The diagnosis of sarcomatoid carcinoma of the lung is made by lung biopsy.
- Biopsy findings associated with sarcomatoid carcinoma of the lung will depend on the subtype of tumor histology, common findings include:[9]
- Pleomorphic carcinoma subtype
- Spindle cell carcinoma subtype
- Giant cell carcinoma subtype
- Carcinosarcoma subtype
- Pulmonary blastoma subtype
Symptoms
Common symptoms of sarcomatoid carcinoma of the lung include:[21][9]
- Shortness of breath
- Cough
- Hemoptysis
- Chest pain
- Weight loss
- Fatigue
Physical Examination
- Patients with sarcomatoid carcinoma of the lung usually appear older in age in relation to their chronological age.[9]
- Physical examination may be remarkable for:
Inspection
- Hoarseness
- Rapid rate of breathing
- Cachexia
Auscultation
- pleural friction rub
- Eegophony
- Crackling or bubbling noises
- Present whispered pectoriloquy
- Decreased/absent breath sounds
Percussion
- Hyporesonance
- Dull percussion
- Tactile fremitus
- Reduced chest expansion
Laboratory Findings
- There are no specific laboratory findings associated with sarcomatoid carcinoma of the lung.
Imaging Findings
- CT scan of chest is the imaging investigation of choice for sarcomatoid carcinoma of the lung.
- On CT, sarcomatoid carcinoma of the lung is characterized by the following findings:[9]
- Sarcomatoid carcinoma of the lung are typically peripherally located
- Usually measure approximately 4 cm in diameter
- Perihilar and mediastinal involvement
- Ground glass opacity
- Rapid growth
- PET-CT[22]
Other Diagnostic Studies
- Sarcomatoid carcinoma of the lung may also be diagnosed using bronchoscopy, mediastinoscopy, and transthoracic percutaneous fine needle aspiration.
Treatment
Medical Therapy
- The mainstay of therapy of sarcomatoid carcinoma of the lung is supportive care.
- Common medical treatment for sarcomatoid carcinoma of the lung is the platinum-based chemotherapy.[9]
Surgery
- Surgery is the mainstay of therapy for sarcomatoid carcinoma of the lung.
- Lobectomy along with regional lymph nodes (peribronchial and perihilar lymph node dissection) in conjunction with pathological evaluation is the most common approach to the treatment of sarcomatoid carcinoma of the lung.
Prevention
- Effective measures for the primary prevention of sarcomatoid carcinoma of the lung include CT screening.[9]
- According to the U.S. Preventive Services Task Force (USPSTF), screening for lung cancer by low-dose computed tomography is recommended every year among smokers who are between 55 to 80 years old and who have history of smoke 30 pack-years or more and either continue to smoke or have quit within the past 15 years (grade B recommendation)
- Once diagnosed and successfully treated, patients with sarcomatoid carcinoma of the lung are followed-up every year. Follow-up testing includes CT screening.
References
- ↑ Virchow, Rudolf (1863). Die KRANKHAFTEN GESCHWÜLSTE. 2. Retrieved 1864. Check date values in:
|access-date=(help) - ↑ 2.0 2.1 Sobin LH (1981). "The international histological classification of tumours". Bull. World Health Organ. 59 (6): 813–9. PMC 2396133. PMID 6978190.
- ↑ 3.0 3.1 3.2 3.3 Brambilla, E.; Travis, W.D.; Colby, T.V.; Corrin, B.; Shimosato, Y. (2001). "The new World Health Organization classification of lung tumours". European Respiratory Journal. 18 (6): 1059–1068. doi:10.1183/09031936.01.00275301. ISSN 0903-1936.
- ↑ 4.0 4.1 Franks TJ, Galvin JR (2010). "Sarcomatoid carcinoma of the lung: histologic criteria and common lesions in the differential diagnosis". Arch. Pathol. Lab. Med. 134 (1): 49–54. doi:10.1043/2008-0547-RAR.1. PMID 20073605.
- ↑ Thompson L, Chang B, Barsky SH (March 1996). "Monoclonal origins of malignant mixed tumors (carcinosarcomas). Evidence for a divergent histogenesis". Am. J. Surg. Pathol. 20 (3): 277–85. PMID 8772780.
- ↑ Billah, Shahreen; Stewart, John; Staerkel, Gregg; Chen, Su; Gong, Yun; Guo, Ming (2011). "EGFR and KRAS mutations in lung carcinoma". Cancer Cytopathology. 119 (2): 111–117. doi:10.1002/cncy.20151. ISSN 1934-662X.
- ↑ Rossi G, Cavazza A, Sturm N, Migaldi M, Facciolongo N, Longo L, Maiorana A, Brambilla E (March 2003). "Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases". Am. J. Surg. Pathol. 27 (3): 311–24. PMID 12604887.
- ↑ Koss MN, Hochholzer L, Frommelt RA (December 1999). "Carcinosarcomas of the lung: a clinicopathologic study of 66 patients". Am. J. Surg. Pathol. 23 (12): 1514–26. PMID 10584705.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 Hountis P, Moraitis S, Dedeilias P, Ikonomidis P, Douzinas M (June 2009). "Sarcomatoid lung carcinomas: a case series". Cases J. 2: 7900. doi:10.4076/1757-1626-2-7900. PMC 2740247. PMID 19830024.
- ↑ Travis WD; Brambilla E; Müller-Hermelink K; Harris C; Kleihues C; Sobin P. https://www.iarc.fr/wp-content/uploads/2018/07/BB10.pdf
|chapterurl=missing title (help) (PDF). World Health Organization Classification of Tumours; Pathology and genetics of tumors of the lung, pleura, thymus, and heart. IARC Press. pp. 53–58. ISBN ISBN 92 832 2418 3 Check|isbn=value: invalid character (help). - ↑ 11.0 11.1 Ouziane, Imane; Boutayeb, Saber; Mrabti, Hind; Lalya, Issam; Rimani, Mouna; Errihani, Hassan (2014). "Sarcomatoid carcinoma of the lung: A model of resistance of chemotherapy". North American Journal of Medical Sciences. 6 (7): 342. doi:10.4103/1947-2714.136920. ISSN 1947-2714.
- ↑ Petrov, D.B; Vlassov, V.I; Kalaydjiev, G.T; Plochev, M.A; Obretenov, E.D; Stanoev, V.I; Danon, S.E (2003). "Primary pulmonary sarcomas and carcinosarcomas – postoperative results and comparative survival analysis". European Journal of Cardio-Thoracic Surgery. 23 (4): 461–466. doi:10.1016/S1010-7940(03)00024-1. ISSN 1010-7940.
- ↑ 13.0 13.1 Roesel, Christian; Terjung, Sarah; Weinreich, Gerhard; Hager, Thomas; Chalvatzoulis, Eleftherios; Metzenmacher, Martin; Welter, Stefan (2016). "Sarcomatoid carcinoma of the lung: a rare histological subtype of non-small cell lung cancer with a poor prognosis even at earlier tumour stages". Interactive CardioVascular and Thoracic Surgery: ivw392. doi:10.1093/icvts/ivw392. ISSN 1569-9293.
- ↑ Davis MP, Eagan RT, Weiland LH, Pairolero PC (September 1984). "Carcinosarcoma of the lung: Mayo Clinic experience and response to chemotherapy". Mayo Clin. Proc. 59 (9): 598–603. PMID 6381913.
- ↑ Henley SJ, Thun MJ, Chao A, Calle EE (June 2004). "Association between exclusive pipe smoking and mortality from cancer and other diseases". J. Natl. Cancer Inst. 96 (11): 853–61. PMID 15173269.
- ↑ Hackshaw AK, Law MR, Wald NJ (October 1997). "The accumulated evidence on lung cancer and environmental tobacco smoke". BMJ. 315 (7114): 980–8. PMC 2127653. PMID 9365295.
- ↑ Freudenheim JL, Ritz J, Smith-Warner SA, Albanes D, Bandera EV, van den Brandt PA, Colditz G, Feskanich D, Goldbohm RA, Harnack L, Miller AB, Rimm E, Rohan TE, Sellers TA, Virtamo J, Willett WC, Hunter DJ (September 2005). "Alcohol consumption and risk of lung cancer: a pooled analysis of cohort studies". Am. J. Clin. Nutr. 82 (3): 657–67. doi:10.1093/ajcn.82.3.657. PMID 16155281.
- ↑ Boffetta P (August 2004). "Epidemiology of environmental and occupational cancer". Oncogene. 23 (38): 6392–403. doi:10.1038/sj.onc.1207715. PMID 15322513.
- ↑ Travis WD; Brambilla E; Müller-Hermelink K; Harris C; Kleihues C; Sobin P. https://www.iarc.fr/wp-content/uploads/2018/07/BB10.pdf
|chapterurl=missing title (help) (PDF). World Health Organization Classification of Tumours; Pathology and genetics of tumors of the lung, pleura, thymus, and heart. IARC Press. pp. 53–58. ISBN ISBN 92 832 2418 3 Check|isbn=value: invalid character (help). - ↑ Yendamuri S, Caty L, Pine M, Adem S, Bogner P, Miller A, Demmy TL, Groman A, Reid M (2012). "Outcomes of sarcomatoid carcinoma of the lung: a Surveillance, Epidemiology, and End Results Database analysis". Surgery. 152 (3): 397–402. doi:10.1016/j.surg.2012.05.007. PMID 22739072.
- ↑ Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (May 2008). "Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship". Mayo Clin. Proc. 83 (5): 584–94. doi:10.4065/83.5.584. PMC 2718421. PMID 18452692.
- ↑ Silvestri, Gerard A.; Gould, Michael K.; Margolis, Mitchell L.; Tanoue, Lynn T.; McCrory, Douglas; Toloza, Eric; Detterbeck, Frank (2007). "Noninvasive Staging of Non-small Cell Lung Cancer". Chest. 132 (3): 178S–201S. doi:10.1378/chest.07-1360. ISSN 0012-3692.