spindle-cell-carcinoma-of-the-lung-benefits-of-immunohistochemicalstud

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Sarcomatoid carcinomas are extremely rare tumors which are characterized by biphasic combination of malignant epithelial and mesenchymal cells. The lung is one of several primary sites of these tumors, which may affect the bladder, the colon, the uterus, ovaries and breasts. In 2004, the WHO histologic classification divided sarcomatoid carcinoma of the lung into five subtypes.

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Volume 8 • Issue 1 • 1000449 J Pulm Respir Med an open access journal ISSN: 2161-105X Journal of Pulmonary Respiratory Medicine ISSN: 2161-105X Journal of Pulmonary Respiratory Medicine Feki et al. J Pulm Respir Med 2018 8:1 DOI: 10.4172/2161-105X.1000449 Case Report Open Access Spindle Cell Carcinoma of the Lung: Benefits of Immunohistochemical Studies Feki W 1 Ketata W 1 Charf S 2 Bahloul N 1 Yangui I 1 and Kammoun S 1 1 Pneumology Department Hedi Chaker University Hospital Sfax Tunisia 2 Department of Pathology Habib Bourguiba Hospital Sfax Tunisia Abstract Sarcomatoid carcinoma is a rare histologic type of non-small cell lung cancers NSCLC which represents only 0.3 to 3 of primitive lung cancers. In 2004 the World Health Organization WHO defned in its classifcation a new entity sarcomatoid carcinoma as “any proliferation that can offer permanently epithelial-mesenchymal morphological transition.” The term sarcomatoid carcinoma is generic it includes various entities such as spindle cell carcinomas which are without well-known clinical and immunohistochemical features. We report the case of a 53-year-old smoker patient with a history of bullous emphysema discovered 8 years ago and who was hospitalized for exploration of a large pleuro parenchymal mass. The functional signs were dyspnea and alteration of the condition. Percutaneous Computed Tomography CT guided biopsy of the mass concluded to a pulmonary spindle cell carcinoma. Staging revealed adrenal nodule with mesenteric and peritoneal invasions. The patient died two months after diagnosis despite an attempt of chemotherapy based on carboplatin/docetaxel. Corresponding author: Walid Feki Pneumology Department Hedi Chaker University Hospital Sfax Tunisia T el: 00 216 97 051 789 E-mail: Fki_walidyahoo.fr Received February 22 2018 Accepted March 15 2018 Published March 19 2018 Citation: Feki W Ketata W Charf S Bahloul N Yangui I et al. 2018 Spindle Cell Carcinoma of the Lung: Benefts of Immunohistochemical Studies. J Pulm Respir Med 8: 449. doi: 10.4172/2161-105X.1000449 Copyright: © 2018 Feki W et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use distribution and reproduction in any medium provided the original author and source are credited. Keywords: Lung cancer Sarcomatoid carcinoma Spindle cell Immunohistochemistry Introduction Sarcomatoid carcinomas are extremely rare tumors which are characterized by biphasic combination of malignant epithelial and mesenchymal cells 1. Te lung is one of several primary sites of these tumors which may afect the bladder the colon the uterus ovaries and breasts. In 2004 the WHO histologic classifcation divided sarcomatoid carcinoma of the lung into fve subtypes 2. Teir radio-clinical presentations have some characteristics but do not enable doctors to make a positive or diferential diagnose. Te histopathological study plays an important role in the characterization and classifcation of these tumors requiring a specifc diagnosis and an adequate treatment. To the best of our knowledge very few cases of sarcomatoid spindle cell carcinomas has been published. Case Report A 53-year-old man a heavy ex-smoker smoking 60 packs/year quitting 3 months ago with a history of bullous emphysema discovered 8 years ago presented to the hospital because of a two months history of symptoms of worsening shortness of breath and alteration of the condition asthenia anorexia and unexplained weight loss. Physical examination revealed clubbing and thoracic decreased breath sounds at the lef pulmonary base and the two apexes. Abdominal examination showed abdominal distending with sloping side dullness. Te chest radiograph showed an heterogeneous lef hilar axillaire opacity measuring 11 cm associated with lucency at both lung apexes more marked on the lef and at the lef lung base. Biology showed leukocytosis to 33.770 elements/mm 3 and microcytic hypochromic anemia to 10.3 g/dl. Bronchoscopy disclosed an extrinsic compression at the lef lower lobe bronchus. A chest CT showed a large lingular and lef lower lobe mass with heterogeneous enhancement landscaping central areas of necrosis measuring 11 × 10 × 14 cm anteroposterior transverse and cranio caudal diameters Figure 1. Tis mass included a collapsed lingular bronchus and a still permeable lower lobe bronchus. It had invaded the mediastinal pleura parietal lef pericardium and the lef lower lobe artery Figure 2. Te analysis of the mediastinum showed right hilar lymph node invasion measuring 20 and 21 mm. All these abnormalities were associated with a signifcant paraseptal emphysema predominant in the upper lobes Figure 3. To determine the histological nature of this mass a percutaneous CT guided biopsy was performed. Pathological examination revealed Figure 1: Large lingular and left lower lobe mass with heterogeneous enhancement landscaping central areas of necrosis measuring 11 × 10 × 14 cm anteroposterior transverse and cranio caudal diameters.

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Citation: Feki W Ketata W Charf S Bahloul N Yangui I et al. 2018 Spindle Cell Carcinoma of the Lung: Benefts of Immunohistochemical Studies. J Pulm Respir Med 8: 449. doi: 10.4172/2161-105X.1000449 Page 2 of 3 Volume 8 • Issue 1 • 1000449 J Pulm Respir Med an open access journal ISSN: 2161-105X a malignant proliferation made of spindle or epithelioid cells Figure 4. Te cytoplasm was scant and the nucleus was hyper chromatic. Mitoses were numerous and atypical. Tese cells were arranged in short fascicles. Te immunohistochemical study showed positive immunostaining for keratin 7 Figure 5 and vimentin. Immunostaining for TTF1 calretinen HBME1 and Keratin 20 were negative. Te diagnosis of pulmonary sarcomatoid carcinoma was considered. To stage the disease a brain scan and an abdominal CT scan were performed and confrmed a right adrenal nodule measuring 25 × 14 mm with mesenteric and peritoneal invasion. Chemotherapy based on carboplatin/docetaxel was started. However the subsequent evolution was marked by the rapid deterioration of the general condition and our patient died two months afer the diagnosis. Discussion Lung sarcomatoid carcinomas are rare tumors representing 0.3 to 3 of all primitive lung cancers 3. Tey represent an heterogeneous group including NSCLC containing a sarcoma or sarcoma-like component 4. According to the WHO classifcation in 2004 fve diferent subtypes have been recognized: pleomorphic carcinoma spindle cell carcinoma giant cell carcinoma carcinosarcoma and pulmonary blastoma 2. Clinically these tumors have a similar presentation to other NSCLC. Although difcult to use for positive or diferential diagnosis several common features of sarcomatoid carcinomas may be mentioned 5. Patients are predominantly male sex ratio of 4/1. Te mean age at diagnosis is higher 65-70 years with an age bracket of 30 years to 85 years. All patients are heavy smokers or ex-heavy smokers. A signifcant proportion of patients is symptomatic at diagnosis and depend on the location of the tumor. In cases of proximal tumors symptoms are especially cough hemoptysis 50 of cases progressive dyspnea or recurrent pneumonia due to bronchial obstruction 3. Whereas in peripheral tumors chest pain was ofen described especially in pleomorphic carcinomas 25 of cases 6. Radiologically sarcomatoid carcinomas are ofen presented as a single large lesion measuring 2 cm to 18 cm in diameter mean of 7 cm with peripheral location and ofen in the upper lobes. A pleural parietal and / or vascular invasion is frequent 40-70 of cases 6 as our case. At gross exam sarcomatoid carcinomas are morphologically very variable refecting the heterogeneity of the diferent subtypes. Tus peripheral tumors are ofen greater than 5 cm well demarcated and unencapsulated. Te cut sections show that these tumors are grey- yellow with mucoid or hemorrhagic necrosis. Whereas proximal tumors are ofen endobronchial sessile or pedunculated and smaller with infltration of the adjacent lung parenchyma. Te histopathological diagnosis of sarcomatoid carcinoma is difcult. Te preoperative diagnosis of sarcomatoid carcinoma is unknown in nearly 60 of cases 6. Diferent morphological components must be mentioned in the fnal histopathological report. Te immunohistochemical expression of epithelial markers in spindle and giant cells is not required for the diagnosis of sarcomatoid carcinoma if there is an epithelial and diferentiated component type 7. In other cases the expression of cytokeratin and epithelial membrane antigen EMA are needed to highlight the epithelial cells in the sarcomatous component. Te expression of cytokeratin-20 and surfactant protein-A is consistently negative 8 in contrast to the expression of TTF-1 and keratin-7 which can be found in the spindle and giant cells in respectively 55 and 70 of patients. In our case Figure 2: Invasion of the mediastinal pleura and parietal left pericardium and the left lower lobe artery. Figure 3: Signifcant paraseptal emphysema in the upper lobes. Figure 4: Proliferation of atypical spindle cells arranged in fascicles. Figure 5: Tumor cells were positive for Keratin 7.

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Citation: Feki W Ketata W Charf S Bahloul N Yangui I et al. 2018 Spindle Cell Carcinoma of the Lung: Benefts of Immunohistochemical Studies. J Pulm Respir Med 8: 449. doi: 10.4172/2161-105X.1000449 Page 3 of 3 Volume 8 • Issue 1 • 1000449 J Pulm Respir Med an open access journal ISSN: 2161-105X immunohistochemical study showed positivity for vimentin and keratin 7 whereas immunostaining for TTF1 was negative. Besides its importance for positive diagnosis the immunohistochemical study may play an essential role in the diferential diagnosis especially in cases of mesotheliomas or sarcomas 9. Sarcomatoid carcinomas are known to be aggressive tumors 10. In fact systemic metastases occur early not only in the usual NSCLC metastatic sites brain bone liver but also in unusual sites such as the esophagus the small intestine the peritoneum the subcutaneous tissue and the kidney 11. Terapeutic alternatives are similar to those of other NSCLC. In the early stages most series reported in the literature are surgical. Surgery may provide sufcient local control 12. Te role of adjuvant therapy is difcult to assess due to the lack of controlled prospective series. However the frequency of parietal mediastinal and vascular involvement and early local relapse make eligible the indication of chemotherapy and radiotherapy as recommended for other NSCLC 13. Accurate modalities of adjuvant radiotherapy or chemotherapy are’nt detailed in the available publications and their efectiveness is difcult to assess especially in terms of local or systemic control. Overall survival remains worse than other NSCLC even afer adjuvant therapy. In metastatic stages cytotoxic agents reported to have been used are identical to those used for NSCLC. No response even partial has been reported. In some published cases the association Adriamycin/ cyclophosphamide/vincristine is indicated with a rationale based on obtaining cytotoxicity in both epithelial and pseudosarcomatoid components. Tumor control rates remain low 14. A recent Japanese observation reported a response to carboplatin paclitaxel and bevacizumab 15. Te indication of inhibitors of the tyrosine kinase of the EGFR in sarcomatoid carcinoma is limited. No activating mutation of EGFR has been demonstrated in limited series. Te prognosis of these tumors remains a subject of controversy. In fact some reports suggest a poor prognosis 16 and others show no diference with other NSCLC. Tis controversy is due on the one hand to the small number of studies focusing on the prognostic aspect and on the other hand to the small-sized studies with limited information about evolution. Among these studies Fishback et al. 16 identifed some prognostic factors such as tumor size5 cm mediastinal lymph node involvement and advanced tumor remains as in the majority of NSCLC main prognostic factor. Other factors such as pleural invasion and sarcomatoid portion 50 tumor volume were discussed in the study of Nakajima et al. 7. However the histologic subtype epithelial- predominant adenocarcinoma squamous cell carcinoma or large cell carcinoma has not been retained as signifcant prognostic factor. As in all NSCLC early detection accurate diagnosis and complete surgical resection are predictors of better survival. Te median disease-free survival is shorter compared to other types of NSCLC. It is between 6 and 8 months with rare local recurrences 15 of all recurrences 17 and ofen systemic occurring in more than 60 of the patients. Te median overall survival is between 6 and 20 months with a 5-year survival less than 10-20 6. Conclusion Sarcomatoid carcinomas are aggressive tumors occurring mainly in male smokers. Given the lack of specifc tests for the early detection diagnosis of these tumors is ofen made when therapy resources are no longer efective. Tese advanced stages are due to systemic extension with frequent unusual metastases. Te prognosis of these tumors is more reserved than in other NSCLC because of their greater aggressiveness high metastatic potential and chemoresistance. References 1. Brambilla E Travis WD Colby TV Corrin B Shimosato Y 2001 The new World Health Organization classifcation of lung tumours. Eur Respir J 18: 1059-1068. 2. 2.Travis WDBE Müller HHK Harris CC. WHO Classifcation of Tumours. Pathology and Genetics of Tumours of the Lung Pleura Thymus and Heart 10. 3rd edn. 2004. 3. Pelosi G Sonzogni A De Pas T Galetta D Veronesi G et al. 2010 pulmonary sarcomatoid carcinomas: A practical overview. Intern j surg path 18: 103-120. 4. Terada T 2010 Spindle cell carcinoma of the lung: Frequency clinical features and immunohistochemical studies of three cases. Respi Med 3: 241-245. 5. Franks TJ Galvin JR 2010 Sarcomatoid carcinoma of the lung. Histologic criteria and common lesions in the differential diagnosis. Arch Pathol Lab Med 134: 49-54. 6. Raveglia F Mezzetti M Panigalli T Furia S Giuliani L et al. 2004 Personal experience in surgical management of pulmonary pleomorphic carcinoma. The Anna thora surg 78: 1742-1747. 7. Masayoshi N Takahiko K Hiroshi H Yasushi I Hideo M 1999 Sarcomatoid Carcinoma of the Lung. A Clinicopathologic Study of 37 Cases. Cancer 86: 608-616. 8. Ro JY Oxen JL Lee JS Sahin AA Ordóñez NG et al. 1992 Sarcomatoid carcinoma of the lung. Immunohistochemieal and ultrastructural studies of 14 cases. Cancer 69: 376-386. 9. Takeshima Y 2009 Value of immunohistochemistry in the differential diagnosis of pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma. Histopathology 54: 667-676. 10. Shin MSJL Shelton RW Greene RE 1986 Giant cell carcinoma of the lung. Clinical and roentgenographic manifestations. Chest. 89: 366-369. 11. Chang YL Lee YC Shih JY Wu CT 2001. Pulmonary pleomorphic spindle cell carcinoma: Peculiar clinicopathologic manifestations different from ordinary non-small cell carcinoma. Lung cancer 34: 91-97. 12. Lee HJ Goo JM Kim KW Im JG JH K 2004 Pulmonary blastoma: Radiologic fndings in fve patients. Clin Imaging 28: 113-118. 13. Ito K Oizumi S Fukumoto S Harada M Ishida T et al. 2010 Clinical characteristics of pleomorphic carcinoma of the lung. Lung cancer 68: 204-210. 14. Koss MN Hochholzer L RA F 1999. Carcinosarcomas of the lung: A clinicopathologic study of 66 patients. Am J Surg Pathol 23: 1514-1526. 15. Sugano T Mori M Namba Y Uenami T Kagami S et al. 2011 Case of sarcomatoid carcinoma of the lung successfully treated with carboplatin paclitaxel and bevacizumab. Nihon Kokyuki Gakkai Zasshi 49: 304-308. 16. Nancy FWDT Cesar AM Guinee DG William FM Michael NK 1994 Pleomorphic spindle/giant cell carcinoma of the lung. A clinicopathologic correlation of 78 cases. Cancer 73: 2936-2945 17. Pelosi G Fraggetta F Nappi O Pastorino U Maisonneuve P et al. 2003 Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation cell cycle control tumor growth and tumor cell motility: A clinicopathologic and immunohistochemical study of 31 cases. Am J Surg Pathol 27: 1203-1215.

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