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Sarcomatoid carcinoma of lung - A case report and review of epidermal growth factor receptor mutation status.

Kakkar A, Jain D, Khanna P, Deo SS, Sarkar C - Lung India (2015 Sep-Oct)

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India E-mail: deepalijain76@gmail.com.

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Sir, Sarcomatoid carcinoma (SC) of the lung comprises conventional non-small cell lung carcinoma (NSCLC) along with a sarcoma-like (pleomorphic/spindle and/or giant cell) component... It is extremely rare, and has worse outcome than conventional NSCLCs... Fine-needle aspiration cytology from the mass showed abundant necrosis along with a malignant tumor composed of atypical polygonal and spindle-shaped cells [Figure 1]... Bronchoscopy did not reveal any endobronchial growth... Second-line chemotherapy and radiotherapy were planned... However, the patient did not return to hospital and expired at home 3 months later... EGFR is a proto-oncogene; abnormal activation of its tyrosine kinase activity by mutation, amplification or protein overexpression leads to increased cell survival, proliferation and invasion... It is well known that the therapeutic effect of TKIs correlates well with mutations of the EGFR gene... The conventional treatment protocol for SC is surgical resection followed by platinum-based double chemotherapy... However, recurrence is common, and survival of these patients remains poor as compared to other NSCLCs... Therefore, there is an urgent need to identify molecular alterations in these tumors that may serve as potential targets for personalized therapy, and the availability of TKIs necessitates the investigation of this group of NSCLCs for presence of EGFR mutations... Subsequently, Chang et al. assessed 42 SCs, while Jiang et al. examined 33 SCs for EGFR mutations... They found mutations in 23% and 21% of SCs, respectively, indicating that SCs are genetically heterogenous, and a subset may harbour EGFR mutations, rendering them susceptible to TKI therapy... Immunohistochemistry is decidedly useful when scant material is available to extract DNA for molecular testing, and it may serve as a valuable screening tool to evaluate SCs for EGFR mutations.

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Fluorescence in situ hybridization with EGFR locus specific (red) and CEP7 (green) probes did not show amplification (×1000)
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Figure 3: Fluorescence in situ hybridization with EGFR locus specific (red) and CEP7 (green) probes did not show amplification (×1000)

Mentions: This 68-year-old male, a chronic smoker, presented with history of intermittent fever since 1 month. There was no history of cough, chest pain, or hemoptysis. On examination, no peripheral lymphadenopathy was present. Computed tomography (CT) revealed a large, heterogenous, peripherally located mass in the posterior segment of upper lobe of right lung involving the parietal pleura, with a broad area of contact with the chest wall. Multiple enlarged right paratracheal and pretracheal lymph nodes were identified. Fine-needle aspiration cytology from the mass showed abundant necrosis along with a malignant tumor composed of atypical polygonal and spindle-shaped cells [Figure 1]. Bronchoscopy did not reveal any endobronchial growth. Trucut biopsy was performed which showed predominantly necrosis with few fragments from a NSCLC, immunopositive for TTF-1 and negative for p40, suggestive of adenocarcinoma. The patient underwent radical right upper lobectomy with mediastinal lymph node dissection. Intraoperatively, a friable mass was seen in the right upper lobe, abutting the horizontal fissure and invading the parietal pleura. Gross examination of the surgical specimen showed a 7-cm-sized solid greyish tumor with necrotic areas. Sections examined showed a biphasic tumor [Figure 2] composed of carcinomatous areas, along with areas composed of malignant spindle cells. The carcinomatous component was composed of sheets of polygonal cells with eosinophilic cytoplasm, large vesicular pleomorphic-appearing nuclei and prominent nucleoli. There was no evidence of gland formation or keratinization, making morphological distinction between squamous and adenocarcinoma difficult. The malignant spindle cell component consisted of epithelioid to slender tapered spindle cells arranged in sheets and fascicles. Nuclei were vesicular with prominent nucleoli, similar to the epithelial component. At places, the two components showed intimate admixture. Foci of necrosis, frequent mitotic figures and inflammatory cell infiltrate were evident throughout the tumor. While the epithelial component showed TTF-1 immunopositivity, the sarcomatous areas were positive for cytokeratin and vimentin. Immunohistochemistry was performed using antibodies specific for the E746-A750 del (6B6, dilution: 1:100; Cell Signaling Technology, Inc, MA, USA) and L858R EGFR mutations (43B2, dilution: 1:100; Cell Signaling Technology, Inc), and was negative for both. FISH using locus-specific probe for EGFR paired with a centromeric probe for chromosome 7, CEP7, (Vysis; Abbott Molecular, Des Plaines, IL, USA) did not show amplification [Figure 3]. A final diagnosis of sarcomatoid carcinoma immunopositive for TTF-1 and lacking EGFR mutation was rendered. The patient received four cycles of chemotherapy (paclitaxel and carboplatin). CT done 5 months postoperatively showed a large mass in the previously operated area of upper lobe, with erosion of the adjacent 3rd and 4th ribs, extending up to the tracheoesophageal groove and involving surrounding soft tissue. Due to the extensive nature of the tumor, the patient was deemed unsuitable for surgery. Second-line chemotherapy and radiotherapy were planned. However, the patient did not return to hospital and expired at home 3 months later.


Sarcomatoid carcinoma of lung - A case report and review of epidermal growth factor receptor mutation status.

Kakkar A, Jain D, Khanna P, Deo SS, Sarkar C - Lung India (2015 Sep-Oct)

Fluorescence in situ hybridization with EGFR locus specific (red) and CEP7 (green) probes did not show amplification (×1000)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4587021&req=5

Figure 3: Fluorescence in situ hybridization with EGFR locus specific (red) and CEP7 (green) probes did not show amplification (×1000)
Mentions: This 68-year-old male, a chronic smoker, presented with history of intermittent fever since 1 month. There was no history of cough, chest pain, or hemoptysis. On examination, no peripheral lymphadenopathy was present. Computed tomography (CT) revealed a large, heterogenous, peripherally located mass in the posterior segment of upper lobe of right lung involving the parietal pleura, with a broad area of contact with the chest wall. Multiple enlarged right paratracheal and pretracheal lymph nodes were identified. Fine-needle aspiration cytology from the mass showed abundant necrosis along with a malignant tumor composed of atypical polygonal and spindle-shaped cells [Figure 1]. Bronchoscopy did not reveal any endobronchial growth. Trucut biopsy was performed which showed predominantly necrosis with few fragments from a NSCLC, immunopositive for TTF-1 and negative for p40, suggestive of adenocarcinoma. The patient underwent radical right upper lobectomy with mediastinal lymph node dissection. Intraoperatively, a friable mass was seen in the right upper lobe, abutting the horizontal fissure and invading the parietal pleura. Gross examination of the surgical specimen showed a 7-cm-sized solid greyish tumor with necrotic areas. Sections examined showed a biphasic tumor [Figure 2] composed of carcinomatous areas, along with areas composed of malignant spindle cells. The carcinomatous component was composed of sheets of polygonal cells with eosinophilic cytoplasm, large vesicular pleomorphic-appearing nuclei and prominent nucleoli. There was no evidence of gland formation or keratinization, making morphological distinction between squamous and adenocarcinoma difficult. The malignant spindle cell component consisted of epithelioid to slender tapered spindle cells arranged in sheets and fascicles. Nuclei were vesicular with prominent nucleoli, similar to the epithelial component. At places, the two components showed intimate admixture. Foci of necrosis, frequent mitotic figures and inflammatory cell infiltrate were evident throughout the tumor. While the epithelial component showed TTF-1 immunopositivity, the sarcomatous areas were positive for cytokeratin and vimentin. Immunohistochemistry was performed using antibodies specific for the E746-A750 del (6B6, dilution: 1:100; Cell Signaling Technology, Inc, MA, USA) and L858R EGFR mutations (43B2, dilution: 1:100; Cell Signaling Technology, Inc), and was negative for both. FISH using locus-specific probe for EGFR paired with a centromeric probe for chromosome 7, CEP7, (Vysis; Abbott Molecular, Des Plaines, IL, USA) did not show amplification [Figure 3]. A final diagnosis of sarcomatoid carcinoma immunopositive for TTF-1 and lacking EGFR mutation was rendered. The patient received four cycles of chemotherapy (paclitaxel and carboplatin). CT done 5 months postoperatively showed a large mass in the previously operated area of upper lobe, with erosion of the adjacent 3rd and 4th ribs, extending up to the tracheoesophageal groove and involving surrounding soft tissue. Due to the extensive nature of the tumor, the patient was deemed unsuitable for surgery. Second-line chemotherapy and radiotherapy were planned. However, the patient did not return to hospital and expired at home 3 months later.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India E-mail: deepalijain76@gmail.com.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Sir, Sarcomatoid carcinoma (SC) of the lung comprises conventional non-small cell lung carcinoma (NSCLC) along with a sarcoma-like (pleomorphic/spindle and/or giant cell) component... It is extremely rare, and has worse outcome than conventional NSCLCs... Fine-needle aspiration cytology from the mass showed abundant necrosis along with a malignant tumor composed of atypical polygonal and spindle-shaped cells [Figure 1]... Bronchoscopy did not reveal any endobronchial growth... Second-line chemotherapy and radiotherapy were planned... However, the patient did not return to hospital and expired at home 3 months later... EGFR is a proto-oncogene; abnormal activation of its tyrosine kinase activity by mutation, amplification or protein overexpression leads to increased cell survival, proliferation and invasion... It is well known that the therapeutic effect of TKIs correlates well with mutations of the EGFR gene... The conventional treatment protocol for SC is surgical resection followed by platinum-based double chemotherapy... However, recurrence is common, and survival of these patients remains poor as compared to other NSCLCs... Therefore, there is an urgent need to identify molecular alterations in these tumors that may serve as potential targets for personalized therapy, and the availability of TKIs necessitates the investigation of this group of NSCLCs for presence of EGFR mutations... Subsequently, Chang et al. assessed 42 SCs, while Jiang et al. examined 33 SCs for EGFR mutations... They found mutations in 23% and 21% of SCs, respectively, indicating that SCs are genetically heterogenous, and a subset may harbour EGFR mutations, rendering them susceptible to TKI therapy... Immunohistochemistry is decidedly useful when scant material is available to extract DNA for molecular testing, and it may serve as a valuable screening tool to evaluate SCs for EGFR mutations.

No MeSH data available.