• braf mutations
• dabrafenib
• lung cancer
• non-small cell lung
• pleomorphic carcinoma
• trametinib

• driver oncogenes
• extensive chromosomal rearrangement
• high programmed cell death-ligand 1 expression
• immune checkpoint inhibitors
• massive bilateral adrenal metastases
• pleomorphic carcinoma of the lung

• Humans
• Male
• Middle Aged
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Lung Neoplasms/secondary
• Autopsy
• Fatal Outcome
• B7-H1 Antigen/genetics
• Chromosome Aberrations
• Carcinoma/genetics
• Carcinoma/secondary
• Carcinoma/pathology
• Antibodies, Monoclonal, Humanized/therapeutic use
• Adrenal Gland Neoplasms/genetics
• Adrenal Gland Neoplasms/secondary
• Adrenal Gland Neoplasms/pathology
• Adrenal Gland Neoplasms/diagnostic imaging

• PD-1 inhibitors
• Tuberculosis
• case report
• lung cancer
• pulmonary sarcomatoid carcinoma

• Driver mutation
• Pleomorphic carcinoma
• Survival
• Treatment

• chemotherapy
• diagnosis
• disease attributes
• lung neoplasms

• Humans
• Female
• Lung Neoplasms/diagnosis
• Lung Neoplasms/pathology
• Adult
• Diagnosis, Differential
• Sarcoma/diagnosis
• Sarcoma/pathology
• Carcinosarcoma/diagnosis
• Carcinosarcoma/pathology

• Lung cancer
• case report
• colon metastasis
• perforation
• pleomorphic carcinoma

• Aged
• Humans
• Male
• Biopsy
• Carcinoma/secondary
• Carcinoma/diagnostic imaging
• Colonic Neoplasms/pathology
• Colonic Neoplasms/secondary
• Fatal Outcome
• Intestinal Perforation/etiology
• Intestinal Perforation/surgery
• Intestinal Perforation/diagnostic imaging
• Lung Neoplasms/secondary
• Lung Neoplasms/pathology
• Lung Neoplasms/diagnostic imaging
• Tomography, X-Ray Computed
• Treatment Outcome

• Non-adenocarcionoma
• Non-small-cell lung cancer
• Squamous cell carcinoma
• Standardized uptake value
• Wedge resection

• Humans
• Male
• Female
• Retrospective Studies
• Lung Neoplasms/surgery
• Lung Neoplasms/pathology
• Lung Neoplasms/mortality
• Aged
• Middle Aged
• Prognosis
• Carcinoma, Squamous Cell/surgery
• Carcinoma, Squamous Cell/pathology
• Carcinoma, Squamous Cell/mortality
• Pneumonectomy/methods
• Disease-Free Survival
• Aged, 80 and over
• Adult
• Carcinoma, Non-Small-Cell Lung/surgery
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/mortality
• Neutrophils/pathology
• Neoplasm Staging
• Postoperative Complications

• case report
• gastrointestinal bleeding
• jejunal metastasis
• pleomorphic lung cancer

• Clinical features
• Genetic mutation
• Molecular characterization
• Next generation sequencing
• Pulmonary sarcomatoid carcinoma

• immune checkpoint inhibitor
• non-small-cell lung cancer with spindle cell and/or giant cell carcinoma
• overall survival
• programmed death ligand-1
• pulmonary sarcomatoid carcinoma

• camrelizumab
• case report
• obstructive atelectasis
• pulmonary sarcomatoid carcinoma
• tracheoscopic cryotherapy

• Beijing Science and Technology Planning Project

Pulmonary sarcomatoid carcinoma (PSC) is a rare form of poorly differentiated non-small-cell lung cancer that is prone to distant metastases. PSC is therapeutically challenging, with low sensitivity to conventional radiotherapy and a poor overall prognosis. The present study reported on the case of a 29-year-old male non-smoker diagnosed with both PSC and lung adenocarcinoma; the cancer had a complex etiology and rapidly metastasized after surgery. The patient presented with an EML4-ALK gene fusion in both tumors with high programmed death ligand-1 (PD-L1) expression. After initial treatment failure, Alectinib, Anlotinib and Tirelizumab were combined, which rapidly resolved the patient's symptoms and led to partial remission of disease at 6 weeks and effective control of the disease 7 months into the treatment. This case exemplifies the efficacy of combining targeted chemotherapy with immunotherapy for patients with PSC. Furthermore, this outcome suggests the usefulness of genetic testing and monitoring PD-L1 expression to identify patients with PSC who may be candidates likely to respond to this combined therapeutic regimen. The present study provides evidence of the success of a novel therapeutic strategy for patients with PSC.

Pulmonary pleomorphic carcinoma (PPC) is well-known for its aggressive nature that is usually resistant to platinum-based chemotherapy. On the other hand, the efficacy of an immune checkpoint inhibitor-based regimen in PPC has been elucidated. PPCs harboring epidermal growth factor receptor (EGFR) mutations are extremely rare, and the efficacy of EGFR-tyrosine kinase inhibitors in PPC is limited compared to their efficacy in EGFR-mutated adenocarcinoma. A 43-year-old female patient presenting with a lung mass with multiple brain metastases, carcinomatous pericarditis, and multiple bone metastases was referred to our department. Transbronchial biopsy confirmed the diagnosis of PPC harboring an EGFR mutation with exon 19 deletion. Subsequently, she was treated with osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, which resulted in partial response with shrinkage of the primary lesion and brain metastases. This partial response remained durable for 11 months with an ongoing regimen. The current case suggests that osimertinib would show promising effects as a first-line treatment for PPCs harboring EGFR mutations, as well as a reasonable sequence of therapy followed by immune checkpoint inhibitor-based regimens.

Pulmonary pleomorphic carcinoma (PPC) is a rare tumor, and it usually has an aggressive clinical course and poor prognosis. We aim to analyze the clinicopathological features, management and prognostic factors of pulmonary pleomorphic carcinoma.

Using the surveillance, epidemiology, and end results (SEER) database, we identified 461 patients of pulmonary pleomorphic carcinoma from 2004 to 2014 including clinicopathological characteristics, treatment modalities and outcome data.

The mean age of all PPC patients was 66 years and 58% of the patients were male. Most patients (80%) were white people, 53% were found in the right lung, and lesions were mostly observed in upper lobe (56%). The median overall survival was 9 months and overall 1-, 3- and 5-year survival rate was 45%, 29%, 23%. In Kaplan–Meier analysis, age, marital status, tumor primary site, gender, laterality, SEER summary stage, chemotherapy and surgery were associated with overall survival. Patients received surgery or chemotherapy had a better OS for patients with PPC. Multivariate Cox analysis revealed that SEER summary stage, age, surgery and chemotherapy were found to be independently associated with the OS. Surgery could significantly prolong survival in patients with localized stage and regional stage (HR = 0.120, 95% CI 0.038–0.383, p < 0.001; HR = 0.351, 95% CI 0.212–0.582, p < 0.001) while it did not have great impact on survival in patients with distant stage (p = 0.192). Chemotherapy decreased risk of death by 46% (HR = 0.544, 95% CI 0.393–0.752, p < 0.001) for patients with distant stage, whereas chemotherapy did not confer survival benefits to patients with localized stage and regional stage. But radiation did not have great impact on survival of patients with different stages in this study.

PPC mostly occurred in white people, with a median age of 66 years, and men were more susceptible to this disease. The SEER summary stage, age, surgery and chemotherapy were independently associated with prognosis. Surgery should be considered for the PPC patients with localized stage or regional stage, and chemotherapy should be recommended for the treatment of patients with distant stage.

• Clinicopathological characteristics
• Pleomorphic carcinoma
• SEER database
• Treatment and outcome

Sarcomatoid carcinoma (SC) is a rare lung cancer subtype with poor prognosis and lack of effective treatment regimens. Studies concerning SC indicated common programmed death ligand-1 (PD-L1) overexpression and higher tumor mutational burden, leading to potential benefits from immunotherapy. The present case is the first report employing PD-L1 inhibitor durvalumab following definitive concurrent chemoradiotherapy (cCRT) in a patient with mediastinal lymph node metastatic SC, which was considered as a high probability of pulmonary origin but unclear primary lesion. After the 19-month follow-up, there was neither local recurrence nor distant metastasis. The patient was in a good condition, with the thoracic lesion controlled at Partial response-Response Evaluation Criteria in Solid Tumors (PR-RECIST). Except for grade 2 esophagitis, none of the other adverse events was observed. Our first attempt to adopt the consolidation immunotherapy after cCRT in unresectable locally advanced mediastinal SC exhibited improved local control, manageable safety, and potential survival benefits, representing a novel and promising therapeutic option for SC and encouraging further research exploration of this regimen in the future.

• PD-L1 inhibitors
• case report
• chemoradiotherapy
• immunotherapy
• sarcomatoid carcinoma

Pulmonary pleomorphic carcinoma is often refractory to chemotherapy and follows an aggressive clinical course. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced lung cancer, and a few cases with pleomorphic carcinoma have been reported to show tumor shrinkage after therapy with ICIs. When treating patients with ICIs, patient selection is essential, and monitoring and management of immune‐related adverse events, including pneumonitis, are needed. We herein report a case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia treated with pembrolizumab, antiprogrammed cell death 1 antibody. Our report highlights important considerations necessary when treating advanced pleomorphic carcinoma patients complicated with interstitial pneumonia. We also review the literature regarding the use of ICIs in such patients.

• interstitial pneumonia
• pembrolizumab
• pulmonary pleomorphic carcinoma

• PD‐L1
• pembrolizumab
• pulmonary pleomorphic carcinoma

Pleomorphic carcinoma of the lung is a rare malignant epithelial tumor. Due to its rarity, its clinicopathological characteristics are not clear, and there is no defined therapeutic path for this type of tumor.

We retrospectively analyzed the medical and pathological reports of 8 patients who underwent surgical resection for pleomorphic carcinoma between 2007 and 2010.

Eight patients were analyzed (7 males and 1 female, mean age 60). All patients underwent CT scans, and the average diameter of the nodules was 56 mm. Four patients were also investigated with FDG-PET with hypermetabolic activity in all four cases. In four patients, the carcinomatous component was adenocarcinoma (all with sarcomatoid component of spindle cell and giant cell carcinoma), although in two patients, it was squamous cell carcinoma (one with spindle cell and one with giant cell). In the two remaining patients, one showed a non-small cell carcinoma with giant cell carcinoma, and the other was a non-small cell carcinoma and squamous cell carcinoma with spindle and giant cell carcinoma. All cases were treated with surgical resection. Only two patients underwent neoadjuvant chemotherapy. At the time of data analysis, only one patient treated with neoadjuvant chemotherapy was alive.

The prognosis for these patients with a diagnosis of pleomorphic carcinoma undergoing surgery is generally better than those not treated with surgical resection, however the survival remains poor. Although with low number of patients, our research would suggest to consider neoadjuvant chemotherapy an appropriate approach for improving the outcomes before surgery.

•

Pleomorphic carcinoma of the lung

• Carcinoma
• Lung cancer
• NSCLC
• Pleomorphic
• Rare tumor

Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.

• Chemoradiotherapy
• durvalumab
• post‐operative recurrence
• programmed cell death‐ligand 1
• pulmonary pleomorphic carcinoma

This study aimed to investigate the incidence of the pulmonary sarcomatoid carcinoma (PSC), to compare the clinical characteristics and overall survival (OS) of patients with PSC and those with other non-small-cell lung cancer (oNSCLC), so as to analyze the factors affecting the OS of patients with PSC and construct a nomogram prediction model.

Data of patients with PSC and those with oNSCLC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results database were collected. The age-adjusted incidence of PSC was calculated. The characteristics of patients with PSC and those with oNSCLC were compared, then the patients were matched 1:2 for further survival analysis. Patients with PSC were randomly divided into training set and testing set with a ratio of 7:3. The Cox proportional hazards model was used to identify the covariates associated with the OS. Significant covariates were used to construct the nomogram, and the C-index was calculated to measure the discrimination ability. The accuracy of the nomogram was compared with the tumor–node–metastasis (TNM) clinical stage, and the corresponding area under the curve was achieved.

A total of 1049 patients with PSC were enrolled, the incidence of PSC was slowly decreased from 0.120/100,000 in 2004 to 0.092/100,000 in 2015. Before PSM, 793 PSC patients and 191356 oNSCLC patients were identified, the proportion of male, younger patients (<65 years), grade IV, TNM clinical stage IV was higher in the PSC. The patients with PSC had significantly poorer OS compared with those with oNSCLC. After PSM, PSC still had an extremely inferior prognosis. Age, sex, TNM clinical stage, chemotherapy, radiotherapy, and surgery were independent factors for OS. Next, a nomogram was established based on these factors, and the C-indexs were 0.775 and 0.790 for the training and testing set, respectively. Moreover, the nomogram model indicated a more comprehensive and accurate prediction than the TNM clinical stage.

The incidence of PSC was slowly decreased. PSC had a significantly poor prognosis compared with oNSCLC. The nomogram constructed in this study accurately predicted the prognosis of PSC, performed better than the TNM clinical stage.

• SEER database
• clinical characteristics
• nomogram
• prediction model
• pulmonary sarcomatoid carcinoma

A 66-year old man with non-smoking history was diagnosed with pulmonary pleomorphic carcinoma of the right lower lobe. The carcinoma metastasized to the brain, lungs, pleura, and mediastinal lymph nodes. It was positive for epidermal growth factor receptor (EGFR) L858R mutation, and tumor cells highly expressed programmed death-ligand 1(PD-L1). Atezolizumab was initiated as the fourth treatment. After three days, he developed cardiac tamponade and immediately underwent pericardial drainage. Computed tomography showed bilateral ground-glass opacity (GGO), significant worsening of multiple lung metastases, and increased size of metastatic lesions. Newly developed metastasis was noted in the lung, and the patient's respiratory condition rapidly deteriorated. He died of respiratory failure on day 13 after atezolizumab administration. The autopsy showed widespread metastasis in all lobes of the bilateral lungs, cardiac tamponade due to carcinomatous pericarditis, carcinomatous lymphangiopathy, and multiple lung metastases, which were thought to be comprehensively the cause of death. These symptoms suggested hyperprogressive disease (HPD). Hence, we report the first case of HPD following atezolizumab therapy for pulmonary pleomorphic carcinoma with EGFR mutation.

• Epidermal growth factor receptor (EGFR) mutation
• Hyperprogressive disease (HPD)
• Immune-checkpoint inhibitor (ICI)
• Immune-related adverse events (irAE)
• Pulmonary pleomorphic carcinoma

A 66-year-old male patient who had received chemoradiotherapy (CRT) for laryngeal cancer 2 years ago visited a local doctor complaining of dyspnoea and wheezing. CT scan showed narrowing of the trachea caused by a tumour. We intubated the trachea over the tumour using a bronchoscope. A week later, the truncated tracheal tumour obstructed the tracheal tube, compromising the patient’s breathing. We removed the obstructed tube and inserted a new one. We submitted the tissue from the tube to a pathologist. Histopathological diagnosis was pleomorphic carcinoma, a subtype of sarcomatoid carcinoma. The mechanism of epithelial–mesenchymal transition (EMT) occurring after CRT was detected in the tumour. Because he had undergone CRT for laryngeal cancer, surgery was not indicated, and we started radiation therapy. Sarcomatoid carcinomas including pleomorphic carcinoma of the trachea are extremely rare, with few reported cases, and EMT is associated with this histological type and CRT.

• palliative care
• pathology
• respiratory cancer
• smoking and tobacco

• biological characteristics
• clinicopathological characteristics
• molecular typing
• pulmonary sarcomatoid carcinoma (PSC)
• therapies

• Case report
• Giant cells
• PD-L1
• Pleomorphic carcinoma
• Undifferentiated

• Comutation
• TP53 mutation
• next-generation sequencing
• pleomorphic carcinoma

• Adult
• Aged
• Female
• High-Throughput Nucleotide Sequencing/methods
• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Male
• Middle Aged
• Mutation

• Health Foundation
• Health Foundation

Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer (NSCLC), is poorly differentiated and highly aggressive. Treatment is limited, and the prognosis is poor. Pembrolizumab is an anti-programmed death (PD)-1 antibody with good efficacy in NSCLC. Recent studies have demonstrated that PD-ligand 1 (PD-L1) overexpression is common in PSCs, which suggests that anti-PD-L1 treatment is an ideal option. However, the response to pembrolizumab in PSC has not been studied.

We present a PSC case with PD-L1 overexpression that significantly benefited from pembrolizumab. A 73-year-old Chinese male was detected with a right lung lesion. Pathological analysis of the right upper lobectomy confirmed PSC. The PD-L1 test revealed overexpression (TPS: 90%). Multiple metastases occurred 1 mo after surgery, representing stage IV PSC. Neither first-line chemotherapy nor second-line antiangiogenic agents showed any benefit. Radiotherapy (1200 cGy) was administered to relieve chest wall pain. The patient received the PD-1 inhibitor pembrolizumab (100 mg) as third-line therapy; however, because of fever and severe infection, he refused to receive immunotherapy any longer. Thus, only one dose of pembrolizumab was administered. Deep sustained remission of most of the metastases was achieved except for lesions in the right adrenal gland, which first shrank and then progressed. The patient died because of disease progression in the right adrenal gland. He achieved a progression-free survival time of 8 mo and an overall survival time of 9 mo with third-line pembrolizumab.

Our findings highlight and offer direct evidence of the efficacy of pembrolizumab in PD-L1-overexpressing PSCs. Combined radiotherapy and immunotherapy may enhance treatment efficacy.

• Pulmonary sarcomatoid carcinoma
• Immunotherapy
• Programmed death-ligand 1
• Pembrolizumab
• Radiotherapy
• Case report

• Chemoradiotherapy
• durvalumab
• immune checkpoint inhibitor
• pleomorphic carcinoma
• programmed death-ligand 1

• PD-L1
• WHO
• c-MET
• carcinoma
• cytokeratins
• immunohistochemistry
• sarcomatoid

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin β3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.

• GRP78/BiP
• TS
• TUBB3
• Topo-II
• VEGFR2
• drug sensitivity
• immunohistochemistry
• lung
• pleomorphic carcinoma
• stathmin 1

• Immunohistochemistry
• Pulmonary
• Sarcomatoid
• ZEB1
• Zinc E-box 1

Pulmonary sarcomatoid carcinoma (PSC) is a rare and poorly differentiated type of non-small cell lung cancer (NSCLC) with specific characteristics, which usually presents a challenge in clinical practice. Mesenchymal–epithelial transition (MET) gene has been identified as a promising target for treatments in the past few years. Here, we report a case of a patient with PSC harboring MET exon 14 mutation, who responded to a novel MET inhibitor – savolitinib.

A 75-year-old male patient with symptoms of cough, dyspnea and intermittent chest pain was diagnosed with sarcomatoid carcinoma. The tumor involved the right lung, the right hilum and multiple lesions in the right pleura, indicating a clinical disease stage IV. Next-generation sequencing of lung biopsy specimen indicated a MET exon 14 skipping mutation (NM_000245:c.3028+3A>G), with a variant allele frequency of 73.9%. The patient achieved a rapid and durable partial response with the initiation of savolitinib administration (600 mg, orally, once daily). The progression-free survival in this patient was 36 weeks. There were no ≥grade 3 adverse events reported and there was no dose reduction during treatment. Following savolitinib treatment, the allele frequency of MET exon 14 mutation in plasma circulating tumor DNA decreased with the reduction in tumor size. At the time of disease progression, fibroblast growth factor receptor 1 (FGFR1), EGFR and KRAS gene amplification were newly identified in tumor biopsy sample.

This patient with PSC harboring MET exon 14 skipping mutation achieved significant clinical benefit with savolitinib treatment. Emergence of FGFR1, EGFR and KRAS gene amplification at the time of disease progression was likely responsible for the resistance to savolitinib in this case.

• acquired resistance
• lung cancer
• targeted therapy
• tumor response

• Pleomorphic carcinoma
• pulmonary
• thin-walled lung cavity

• Genomic mutation
• Pulmonary sarcomatoid carcinoma
• Targeted next-generation sequencing
• Tumor mutation burden

• 4F2hc
• Immunohistochemistry
• LAT1
• Lung
• Pleomorhic carcinoma
• Prognosis

Pulmonary pleomorphic carcinoma (PPC) has a poor prognosis due to the poor results of treatment with systemic chemotherapy. We report the case of a 73-year-old woman with PPC who showed a favorable response to nivolumab. As first-line treatment for postoperative recurrence, she received carboplatin and nanoparticle albumin-bound paclitaxel. However, 12 months later, a new metastatic lymph node appeared. Nivolumab was administered as second-line treatment, and the patient showed a favorable prolonged response. The effects of treatment of PPC with nivolumab seem promising. The results of a future prospective study are expected to identify indicators for the treatment of PPC.

• Nivolumab
• Programmed cell death ligand-1
• Pulmonary pleomorphic carcinoma

Carcinosarcoma is a rare histological type of non-small cell carcinoma (NSCLC), and its prognosis has been reported to be worse compared with other NSCLCs. Nanoparticle albumin-bound paclitaxel (nab-PTX) + carboplatin (CBDCA) achieves a favorable response rate in patients with non-small cell lung cancer (NSCLC). We administered nab-PTX + CBDCA to a 68-year-old man with postoperative recurrent carcinosarcoma with interstitial lung disease (ILD). A partial response was evident after four cycles of chemotherapy. To the best of our knowledge, the present study is the first to report the safety and efficacy of nab-PTX + CBDCA for treating carcinosarcoma with ILD.

• Carboplatin
• Carcinosarcoma
• Chemotherapy
• Interstitial lung disease
• Nab-paclitaxel

Pulmonary pleomorphic carcinoma (PPC) is a very rare type of primary lung cancer with an aggressive clinical course. Few reports have documented therapeutic options for PPC with EGFR mutations. Herein, we report a case of PPC with EGFR mutation treated with EGFR‐tyrosine kinase inhibitors (TKIs). A 65‐year‐old Japanese woman was diagnosed with stage IV lung adenocarcinoma with L858R point mutation in exon 21. Despite treatment with erlotinib, the patient died after two weeks as a result of rapid disease progression. Postmortem examination indicated that the thoracic tumors consisted primarily of spindle/sarcomatous components, while expression of the mutated EGFR protein was only observed in adenocarcinoma components. We speculate that the tumor was not driven by EGFR mutation. Clinicians should bear in mind the possibility of pleomorphic carcinoma if EGFR‐TKI treatment fails to achieve a clinical response for adenocarcinoma harboring an activating EGFR mutation diagnosed on the basis of small biopsy specimens.

• Epidermal growth factor receptor
• heterogeneity
• oncogene addiction
• pleomorphic carcinoma

We report a case of pleomorphic carcinoma with exon 18 mutation (G719X) of the epidermal growth factor receptor (EGFR), which showed good response to afatinib and resulted in successful resection. To our knowledge, this is the first report on the use of afatinib for pleomorphic carcinoma followed by the surgical resection. The patient was a 59-year-old woman, who visited our hospital because chest computed tomography showed a 28 × 28-mm nodule in the left upper lobe. Bronchoscopy was performed and the histological findings of transbronchial biopsy revealed adenosquamous carcinoma positive for G719X mutation in exon 18 of the EGFR. Since fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography revealed a positive accumulation in the bilateral hilar and mediastinal lymph nodes, the disease was diagnosed as cT1bN3M0, stage IIIB. After 3 months of afatinib therapy, FDG accumulation in primary tumor was almost gone. However, FDG accumulation in lymph nodes remained unchanged. Video-assisted thoracic surgery was planned for further diagnostic information and left upper lobectomy with mediastinal lymph node dissection was performed. The resected tumor included adenocarcinoma, squamous cell carcinoma, and spindle cell components, without lymph node metastasis. Thus, the disease was diagnosed as pleomorphic carcinoma (pT2aN0M0, stage IB). All components in the resected specimen had the same G719X mutation in exon 18 of the EGFR. The patient has shown no signs of recurrence at 1 year after the operation. The present case indicates the possibility of minor EGFR mutations in pleomorphic carcinoma and successful outcome by the use of afatinib and surgical resection.

• Afatinib
• Epidermal growth factor receptor mutation
• Exon 18
• Pleomorphic carcinoma

• ALK
• EGFR
• Histology
• KRAS
• Lung adenocarcinoma
• Lung carcinoma
• MET

Pulmonary Sarcomatoid Carcinoma (PSC) constitutes a heterogeneous group of non-small-cell lung carcinomas (NSCLCs) with a poor prognosis. In this study, a group of 7 patients with PSC was studied. Microscope analysis of all 7 cases revealed a pleomorphic carcinoma subtype. Moreover, 5 cases (71.4%) were composed entirely of malignant sarcomatoid-like elements, and 2 cases (28.6%) were composed of malignant sarcomatoid-like elements and at least 10% adenocarcinoma-like elements. Immunohistochemically, the PSC components of all 7 cases were positive for vimentin and cytokeratins, including cytokeratin (CK) and cytokeratin 7 (CK7). Next-Generation Sequencing (NGS) was performed, and a total of 136 putative somatic variants and one gene fusion were identified, of which 16 variants were considered hot spot mutations, including the genes EGFR, EML4-ALK, MET, BRAF, PIK3CA, and TP53. Of these hot spot mutations, one sample expressing an EML4-ALK fusion was further confirmed by Ventana IHC, and one sample containing an EGFR exon 19 deletion was also confirmed. The NGS results imply that TP53 mutations occur often in PSCs and that EML4-ALK fusion events and EGFR exon deletions also occur in these rare tumors. Molecular targeted therapy may be a useful treatment strategy for these rare lung tumors.