Search

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of nonsmall-cell lung cancer (NSCLC). It carries a poor prognosis, even among other subtypes of NSCLC. Currently, most treatment strategies for PSC are derived from regimens aimed at managing soft tissue sarcomas or NSCLC. The use of doxorubicin plus ifosfamide and pemetrexed has been well established in the management of soft tissue carcinoma and other nonsmall-cell lung cancers, respectively. We report the case of a 69-year-old male diagnosed with PSC who was managed with doxorubicin plus ifosfamide and pemetrexed therapy. Our patient initially responded to the therapy but had rapid progression and died 8 months after the initiation of treatment. Upon genetic analysis, it was revealed the patient had overexpression of the MDM2 protein, which has been associated with poor response to therapy. This case highlights the need for a personalized treatment approach, as well as the need for a standardized treatment regimen for managing PSC.

Sarcomatoid malignant mesothelioma (SMM) tends to occur in the pleura and is morphologically similar to lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP). Because SMM often does not express mesothelial markers, it is very difficult to distinguish from LSC and OP. GATA-binding protein 3 (GATA3) is a specific immunohistochemical (IHC) marker of breast and urothelial carcinoma. We routinely find that GATA is expressed in MM; however, GATA3 expression in SMM and its reference value for distinguishing SMM from LSC and OP remain unclear. Here, we used IHC methods to detect the expression of GATA3 and classic mesothelial markers in 17 SMM, 12 LSC, and 7 OP cases. We detected the following expression rates in SMM versus LSC cases: GATA3 (70.6% vs. 16.7%, p = 0.008), calretinin (52.9% vs. 8.3%, p = 0.019), Wilms tumor (WT)-1 (64.7% vs. 0%, p = 0.000), D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694), and pan-cytokeratin (CKpan) (88.2% vs. 100.0%, p = 0.498). The specificities of calretinin, WT-1, and GATA3 in distinguishing SMM from LSC were 91.7%, 100%, and 83.3%, respectively, and combinations of any two of these three markers exhibited 100% specificity for SMM. Notably, the sensitivity of calretinin+/WT1+ staining for SMM was only 23.5%, which increased to 64.7% after including GATA3. Furthermore, all OP cases showed partial or diffuse expression of CKpan, WT-1, and D2-40 but no GATA3 and calretinin expression. In conclusion, GATA3 is an IHC marker with excellent sensitivity and specificity for SMM, and the combined consideration of GATA3, calretinin, and WT-1 was best for distinguishing SMM from LSC. Moreover, CKpan, WT-1, and D2-40 had no value for distinguishing SMM from OP, and GATA3 and calretinin were the most specific markers for distinguishing these two lesions.

Objectives Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements. Methods We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers. Results Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response. Conclusion We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.

We previously reported a case of giant cell carcinoma in the lung, in which the use of antiprogrammed death 1 (PD-1) immunotherapy resulted in substantial tumor reduction. In the present study, we describe an additional clinical course. A 69-year-old woman was diagnosed with giant cell carcinoma of the lung in clinical stage IVB (T2bN0M1c, BRA). The tumor expressed programmed death ligand 1 (PD-L1) in a high proportion. The patient received stereotactic radiotherapy for two sites of small brain metastases, followed by immunotherapy using anti-PD-1 antibodies (pembrolizumab). The treatment exerted a substantial tumor reduction through four cycles. However, treatment was withdrawn due to renal dysfunction. The primary lung tumor continued to regress for an additional four months without any further therapy, resulting in a clinical stage of T1aN0M0. Salvage thoracic surgery was then performed to remove the tumor residue in the lung. Microscopic examination of the sample revealed no residual cancer. The patient was free from recurrence at 16 months post surgery. We then comprehensively reviewed lung sarcomatoid carcinoma cases in the literature, in which anti-PD-1 antibodies were implemented. The current literature and our own findings suggest sarcomatoid carcinomas express high levels of tumoral PD-L1 and can be effectively treated with anti-PD-1 antibodies.

Sarcomatoid carcinoma is a subtype of non-small cell lung cancer (NSCLC) characterized by mesenchymal – epithelial transition component and awful prognosis. In this report, based on a case of stage IV lung sarcomatoid carcinoma with an extraordinary evolution and survival over 4 years, we address unresolved questions about the treatment of this cancer. We also make a literature review about the key factors that characterize this histology and that should be considered when treating those patients. Sarcomatoid carcinoma presents with mutations as KRAS, EGFR, ALK or MET in up to 70% of cases, and an important expression of PD-L1 (also called B7-H1), which can influence treatment of those patients with new drugs as immune checkpoint inhibitors. Immunotherapy has changed the horizon of patients with stage IV lung cancers without driver mutations, as their survival has improved extraordinary. Moreover, radical treatments are being considered in long survivors with oligometastatic disease. In this report, we review targeted and radical therapy, treatment duration and the mechanisms responsible of disease evolution of sarcomatoid tumors., Highlights • Sarcomatoid lung cancer is a rare entity with awful prognosis. • It may express driver mutations for potential treatment of those patients. • There are arising data of efficacy of immunotherapy in sarcomatoid lung carcinoma.

Sarcomatoid mesothelioma, a histological subtype of malignant pleural mesothelioma, is a very aggressive tumor with a poor prognosis. Histological diagnosis of sarcomatoid mesothelioma largely depends on the histomorphological feature of spindled tumor cells with immunohistochemical reactivity to cytokeratins. Diagnosis also requires clinico-radiological and/or macroscopic evidence of an extrapulmonary location to differentiate it from lung sarcomatoid carcinoma. Although there are promising immunohistochemical antibody panels to differentiate mesothelioma from lung carcinoma, a consensus on the immunohistochemical markers that distinguish sarcomatoid mesothelioma from lung sarcomatoid carcinoma has not been reached and requires further study. We performed whole gene expression analysis of formalin-fixed paraffin-embedded tissue from sarcomatoid mesothelioma and lung sarcomatoid carcinoma and observed significant differences in the expression of MUC4 and other genes between sarcomatoid mesothelioma and lung sarcomatoid carcinoma. Immunohistochemistry demonstrated that MUC4 was expressed in the spindled tumor cells of lung sarcomatoid carcinoma (21/29, 72%) but was not expressed in any sarcomatoid mesothelioma (0/31, 0%). To differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma, negative MUC4 expression showed 100% sensitivity and 72% specificity and accuracy rate of 87%, which is higher than immunohistochemical markers such as calretinin, D2-40 and Claudin-4. Therefore, we recommend to include MUC4 as a novel and useful negative immunohistochemical marker for differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma.

Introduction Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC. Methods All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase. Results Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8–79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3–45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0–100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4–39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2). Conclusions Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung carcinoma with a poor prognosis and poor response to chemotherapy and radiotherapy. A previous study reported that psc expresses high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumours. We report 2 cases of patients with a lung sarcomatoid carcinoma. Both patients initially underwent curative lung resection, but developed early recurrent disease. Because PD-L1 was highly expressed in the tumour cells, we initiated therapy with nivolumab, which showed good efficacy, almost complete radiologic tumour remission, and a remarkable improvement in the condition of those patients. Immune checkpoint inhibitors targeting PD-1 might be a valuable therapy option for PSCS.

Paraneoplastic leukemoid reaction is a challenging differential diagnosis when it presents at the time of diagnosis of cancer. Severe hyperleukocytosis with elevation of blood neutrophils and monocytes counts can evoke myeloid hematologic malignancies. We report the case of a patient who presented with blood and bone marrow features highly suggestive of chronic myelomonocytic leukemia. The diagnosis of primary lung sarcomatoid carcinoma was performed. Surgical removal of this tumor which will always remain the priority led to full normalization of blood cell count.

Introduction MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. Methods Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. Results A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. Conclusion IHC is not a relevant screening tool for MET abnormalities in LSC.

Purpose To report a rare case of extreme leukocytosis and leukemoid reaction associated with lung sarcomatoid carcinoma (LSC) and increase people's awareness of the disease. Patients and methods A 58-year-old male patient was diagnosed with LSC; however, after the end of the second course of chemotherapy, his white blood cells increased gradually without fever or use of medications such as granulocyte colony-stimulating factor and steroids. A bone marrow biopsy then confirmed it to be a leukemoid reaction. Results The patient died of multiple organ failure 2 months after being diagnosed with leukocytosis. Conclusion LSC associated with leukemoid reaction is very rare and the prognosis is poor. When a patient's white blood cells are extremely elevated, we should think of the possible causes of the tumor itself and identify it with other diseases. However, more data and evidence are still needed to find an effective adjuvant therapy for these patients.

Background This study aimmed to evaluate the expression of p53-inducible RR small subunit 2 homologue (p53R2) in Lung sarcomatoid carcinoma (LSC) and its association with clinicopathological parameters and prognosis. Methods In this study, clinicopathological factors and prognostic significance of the expression of p53R2 was investigated by immunohistochemistry (IHC) in 100 cases of LSC. Results The results showed that the expression of p53R2 was significantly correlated with clinical stage (P

Neocentromeres contribute to cancer progression by mitotically stabilizing acentric chromosomes containing amplified oncogenes. Macchia et al. show that... Genome amplification in the form of rings or giant rod-shaped marker chromosomes (RGMs) is a common genetic alteration in soft tissue tumors. The mitotic stability of these structures is often rescued by perfectly functioning analphoid neocentromeres, which therefore significantly contribute to cancer progression. Here, we disentangled the genomic architecture of many neocentromeres stabilizing marker chromosomes in well-differentiated liposarcoma and lung sarcomatoid carcinoma samples. In cells carrying heavily rearranged RGMs, these structures were assembled as patchworks of multiple short amplified sequences, disclosing an extremely high level of complexity and definitely ruling out the existence of regions prone to neocentromere seeding. Moreover, by studying two well-differentiated liposarcoma samples derived from the onset and the recurrence of the same tumor, we documented an expansion of the neocentromeric domain that occurred during tumor progression, which reflects a strong selective pressure acting toward the improvement of the neocentromeric functionality in cancer. In lung sarcomatoid carcinoma cells we documented, extensive “centromere sliding” phenomena giving rise to multiple, closely mapping neocentromeric epialleles on separate coexisting markers occur, likely due to the instability of neocentromeres arising in cancer cells. Finally, by investigating the transcriptional activity of neocentromeres, we came across a burst of chimeric transcripts, both by extremely complex genomic rearrangements, and cis/trans-splicing events. Post-transcriptional editing events have been reported to expand and variegate the genetic repertoire of higher eukaryotes, so they might have a determining role in cancer. The increased incidence of fusion transcripts, might act as a driving force for the genomic amplification process, together with the increased transcription of oncogenes.

Background Malignant mesothelioma is considered as a rare, aggressive malignant tumor that arises from mesothelial cells of the pleura. Pulmonary spindle cell carcinoma and pleomorphic carcinomas are considered as subtypes of sarcomatoid carcinoma, with an incidence of 2 and 3% of all lung malignancies. The differential diagnosis between sarcomatoid mesothelioma and lung sarcomatoid carcinoma by immunohistochemical markers has not been reached and requires further study. The aim of this study was to investigate the role of mucin 4 (MUC4) and D2-40 in differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma. Materials and methods The cases were divided into 20 cases of sarcomatoid mesothelioma and 14 cases of lung sarcomatoid carcinoma and were immunostained for MUC4 and D2-40 using streptavidin-biotin methods. Results MUC4 expression was seen in tumor cells of 11 (79%) lung sarcomatoid carcinoma cases. All cases of sarcomatoid mesothelioma showed negative immunostaining for MUC4 (0%). D2-40 immunostaining was positive in 16 (80%) cases of sarcomatoid mesothelioma. D2-40 expression was observed in two (14%) lung sarcomatoid carcinoma cases. The negative expression of MUC4 showed 78.57% sensitivity; however, specificity was 100%. The positive expression of D2-40 showed 80% sensitivity and 85.71% specificity. MUC4-negative expression and D2-40-positive expression were statistically significant. Conclusion We conclude that MUC4 and D2-40 immunohistochemical markers can differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma. The combination of the two markers increases sensitivity and specificity for both.

It is increasingly apparent that cancer development depends not only on genetic alterations, but also on epigenetic changes involving histone modifications. GASC1, member of the histone demethylases affecting heterochromatin formation and transcriptional repression, has been found to be dysregulation in many types of cancers including breast cancer, prostate cancer, metastatic lung sarcomatoid carcinoma, and leukemia. In this study, we examined the expression of GASC1 and certain GASC1-targeted genes (KLF4, MYC, SOX2, PPARG, MDM2, and NANOG) and identified a three-gene prognostic signature (PPARG, MDM2, and NANOG), using risk scores based on immunohistochemical analyses of 149 tumor specimens from patients with esophageal squamous cell carcinoma (ESCC). The presence of a high-risk three-gene signature in the ESCC tumors was significantly associated with decreased overall survival (OS) of the patients. We validated the predictive value of the three-gene signature in a second independent cohort of 101 patients with ESCC in order to determine whether it had predictive value. The results were similar to those in 149 patients. According to multivariate Cox proportional hazards analyses, the predictive model of a three-gene signature was an independent predictor for OS (p = 0.005 in cohort 1, p = 0.025 in cohort 2). In addition, ROC analysis indicated that the predictive ability of the three-gene model was more robust than that of a single biomarker. Therefore, our three-gene signature is closely associated with OS among patients with ESCC and may serve as a predictor for the poor prognosis of ESCC patients. What's new? Epigenetic alterations that involve modifications to histones are thought to play critical roles in cancer, with effects on processes ranging from tumor development to metastasis. The present investigation focused on the expression of the histone demethylase GASC1 and its gene targets in tumors from patients with esophageal squamous cell carcinoma (ESCC). Using risk scores from immunohistochemical analyses, the authors developed a three-gene prognostic signature involving the genes PPARG, MDM2, and NANOG. The signature was associated with a reduction in overall survival of ESCC patients, suggesting that it is predictive for poor prognosis in ESCC.

Immunohistochemistry is often used to distinguish pulmonary sarcomatoid carcinoma from morphologic mimics. Napsin-A is a pulmonary adenocarcinoma marker, but literature on expression in sarcomatoid carcinoma is limited. Thirty-six cases of sarcomatoid carcinoma were stained for napsin, TTF-1, Oscar, CAM5.2, AE1/AE3, desmin, SMA, S-100, CK5/6, calretinin, D2-40, and WT1. Patients were 24 men and 12 women (mean, 70 years; range, 46-93). There were 27 pleomorphic carcinomas, 5 spindle cell carcinomas, 3 carcinosarcomas, and 1 giant cell carcinoma. Cases were positive for at least 1 keratin: AE1/3 was positive in all 36 cases; Oscar, in 34 cases (94%); and CAM5.2, in 32 cases (89%, weaker/more focal). Napsin was positive in 14 cases (39%): 8 diffuse, 3 focal, and 3 rare cells. TTF-1 was positive in 22 cases (61%): 15 diffuse, 3 focal, and 4 rare cells. No cases were napsin positive and negative for TTF-1. Variable staining for mesothelial markers was observed, including positivity for calretinin (12 cases, 33%), WT1 (6 cases, 17%), D2-40 (5 cases, 14%), and CK5/6 (9 cases, 25%). Mesenchymal markers were also sometimes positive (usually focal), including S-100 (4 cases, 11%), desmin (4 cases, 11%), and SMA (7 cases, 19%, 1 diffuse). In conclusion, TTF-1 is more sensitive than napsin for detection of sarcomatoid carcinoma, and no cases were positive for napsin but negative for TTF-1. CAM5.2 is less sensitive than AE1/AE3 and Oscar. Use of a thoughtful immunohistochemical panel is important in the evaluation of sarcomatoid carcinoma because mesothelial and mesenchymal markers can be expressed.

Background: Sarcomatoid carcinomas (SCs) are rare tumors that may arise in the lung, accounting for 0.4% of non–small-cell lung cancers; the prognosis is poor. Only few retrospective small-size series have studied the efficacy of chemotherapy (CT) for metastatic SC. Methods: Multicenter study of patients with advanced or metastatic SC who received first-line CT. Clinical characteristics at baseline, response to first-line CT (Response Evaluation Criteria in Solid Tumors version 1.1), progression-free survival (PFS), and overall survival (OS) were retrospectively collected. Results: Ninety-seven patients were included. Median age was 62 (54–72) years. The majority of patients were men (70%), white (84%), and smokers (84%). Overall, 73% of patients received first-line platinum-based CT. At first tumor evaluation, 69% of patients experienced progression, 31% had disease control, and 16.5% had partial response. Partial response was observed in 20% of patients receiving platinum-based CT, and in none of those receiving non–platinum-based CT ( p = 0.018). Median PFS was 2.0 months (confidence interval [CI] 95%: 1.8–2.3). PFS was not statistically different between patients receiving or not receiving a platinum-based CT. Median OS was 6.3 months (CI 95%: 4.7–7.8). There was a trend toward better OS for patients treated with platinum-based CT (7.0 months [CI 95%: 4.9–9.0] versus 5.3 months [CI 95%: 2.8–7.6]; p = 0.096). In multivariate analysis, disease control at first evaluation (hazard ratio=0.38 [CI 95%: 0.21–0.59]) and at platinum-based CT (hazard ratio=0.92 [CI 95%: 0.85–0.99]) was associated with better OS. Conclusion: SC is associated with poor prognosis and high rate of resistance to conventional first-line CT. New therapeutic strategies are needed, based on better knowledge of the carcinogenesis of SC.

Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis. Thirty-six patients who underwent surgical resection of a PSGSCC were included. PD-L1 (E1L3N) expression on tumor cells and PD1 (NAT105) expression by tumor infiltrating lymphocytes (TILs) were performed by immunohistochemistry. Results were compared to immunohistochemistry tests of TTF1, Napsin A, p40 and to molecular study of EGFR, KRAS, BRAF and HER2. Seventy-five % of PSCGCC were considered as positive for PD-L1.PD-L1 expression in PSGSCC is associated with TTF-1 and/or Napsin A expression (47.2%, p = 0.039). Few p40 positive PSCGCC expressed PD-L1 (8.3%, p = 0.013). PD1 expression was not related to TTF-1 and/or Napsin A expression (p = 0.47), p40 expression (p = 0.68) or survival (p = 0.14). PD-L1 or PD1 expression were not related to the age, gender, pT, pN, stage, visceral pleura invasion, histopathological subtype, the presence of giant cell component, the predominance of sarcomatoid component, and the presence of EGFR or BRAF or HER2 or PIK3CA mutation (p>0.05). PD-L1 expression was correlated with a worse overall survival in PSCGCC (p = 0.045). PD-L1 expression is frequent in PSCGCC and might be associated with the expression of adenocarcinoma markers (TTF-1, Napsin A) or the lack of expression of squamous cell carcinoma marker (p40).

Sarcomatoid carcinoma of the lung is a rare, poorly differentiated, low-grade carcinoma in the non-small cell lung cancer (NSCLC) group. It is a very aggressive tumor; the 5-year survival rate in patients with sarcomatoid carcinoma does not exceed 20%. There are a limited number of retrospective screenings of sarcomatoid carcinoma cases and case reports in the literature. The diagnosis, treatment, and prognostic features of sarcomatoid carcinoma are not well known compared with other NSCLCs. However, studies of sarcomatoid carcinoma have demonstrated that the prognosis is poor and response to standard chemotherapy treatment is not as good as seen with other NSCLCs. Presently described is a rare case diagnosed by thoracic ultrasonography-guided transthoracic biopsy.

Sarcomatoid carcinoma is a biphasic neoplasm composed of highly complex, intimately admixed malignant epithelial and mesenchymal elements. We herein report a rare case of cutaneous metastasis of pulmonary sarcomatoid carcinoma that contains liposarcomatous, rhabdosarcomatous and chondrosarcomatous heterologous differentiation, and review relevant literatures to lead to a better understanding of this rare but highly aggressive tumor.

International audience; ObjectivesPulmonary sarcomatoid carcinomas (SC) are rare tumors, associated with worse prognosis and resistant to platinum-based regimens. Therapies targeting the PD-1/PD-L1 pathway are an emerging treatment for lung cancer. By characterizing intra-tumoral immune infiltration and evaluating PD-L1 expression, it could be possible to predict the efficacy of these new treatments.Materials and MethodsFrom 1997 to 2013, data from all patients with SC who underwent lung resection was collected. Tumor-immune infiltration and PD-L1 expression were studied by immunochemistry tests, analyzing CD3 (clone SP7), CD4 (clone 1F6), CD8 (clone C8/144b), CD20 (clone L26), CD163 (clone 10D6), MPO (clone 59A5), and PD-L1 (clone 5H1). Results were compared to those of 54 NSCLC.ResultsIn total, 75 SC were included. Forty (53%) SC expressed PD-L1 vs 11 NSCLC (20%) (p < 0.0001). CD3+ tumor-infiltrating lymphocytes and CD163+ tumor-associated macrophages were more important in SC than in NSCLC (median 23%[17–30] of tumoral surface vs 17% [7–27], p = 0.011 and 23% [17–30] vs 20% [13–23], p = 0.002, respectively). In SC, the presence of Kirsten Ras (KRAS) mutations, blood vessel invasion, and TTF1+ positivity were associated with PDL1 expression. On multivariate analysis, only CD163+ macrophages and blood-vessel invasion were associated with tumoral PD-L1 expression. High levels of tumor-infiltrating lymphocytes (CD3+ or CD4+ and not CD8 + ) constituted a factor of good prognosis on survival. Interestingly, PD-L1 expression distinguishes subpopulations within tumor-infiltrating lymphocytes (CD3+ or CD4 + ) with different prognosisConclusionsPD-L1 expression was higher in SC than in NSCLC as well as immune-cell infiltration by TCD3 cells and macrophages. This suggests that targeting the PD-1/PD-L1 pathway could represent a new potential therapy.

Background Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology. Patients and methods We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes. Results In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold. Conclusion Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.

The EML4-ALK gene translocation was described in a non small cell lung cancer (NSCLC) subset, with a potent oncogenic activity. It represents one of the newest molecular targets in NSCLC. We report on the case of a metachronous second primary lung sarcomatoid carcinoma after resection of lung adenocarcinoma both with ALK translocation, in a non-smoking patient. EML4-ALK rearrangement was detected with immunohistochemistry and confirmed with fluorescent in situ hybridization (FISH). To assess the clonal relationship between the two tumors, both adenocarcinoma and sarcomatoid carcinoma were analyzed by array comparative genomic hybridization (aCGH). We observed different genomic profiles suggesting that the tumors arose independently and were thus multiple primaries. To the best of our knowledge, this is the first report concerning the presence of the EML4-ALK fusion gene in a sarcomatoid carcinoma of the lung. Crizotinib, the ALK tyrosine kinase inhibitor, is highly effective in ALK-rearranged NSCLC; therefore, it may be imperative to identify all NSCLC that harbor ALK translocations in the near future. Starting from our evidence, tumors with sarcomatoid histology may need to be screened for the presence of EML4-ALK rearrangement.

Sarcomatoid carcinoma is an extremely rare biphasic tumor characterized by a combination of malignant epithelial and mesenchymal cells. Limited data on sarcomatoid carcinoma showed that most cases occurred with advanced local disease and metastasis, and paraneoplastic syndromes were rare. We present the case of a 63-year-old man with lung sarcomatoid carcinoma associated with jejunum metastasis and leukocytosis, and its clinical, macroscopic, and histopathological features. This case emphasizes the importance of recognizing paraneoplastic syndromes and metastasis of sarcomatoid carcinoma at diagnosis.

1 Anatomic Pathology Unit, San Camillo-Forlanini Hospital, Rome, Italy 2 Department of Cardiovascular and Respiratory Sciences, San Camillo-Forlanini Hospital, Rome, Italy 3 Thoracic Surgery Unit, San Camillo-Forlanini Hospital, Rome, Italy Medical Oncology Unit, San Camillo-Forlanini Hospital, Rome, Italy 5 1st Oncological Pulmonary Unit, San Camillo-Forlanini Hospital, Rome, Italy 6 2nd Oncological Pulmonary Unit, San Camillo-Forlanini Hospital, Rome, Italy

International audience; Sarcomatoid carcinomas (SC) of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous cell components and characterized by a more aggressive outcome than other histological subtypes of nonsmall cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR)-targeted therapies have emerged as a promising therapeutic approach in patients with advanced typical NSCLC such as adenocarcinoma, the potential clinical activity of these drugs in lung SC is still unknown. To investigate this point, we have analyzed the status of 4 EGFR pathways biomarkers in a series of lung SC. EGFR protein expression, EGFR gene copy number, EGFR mutational status and KRAS mutational status were assessed in a series of 22 consecutive cases of primary lung SC. EGFR protein overexpression was observed in all the cases. High level of polysomy (>or=4 copies of the gene in >40% of cells) was detected in 5 cases (23%). No EGFR mutation was detected. KRAS mutations were found in 8 patients (38%; Gly12Cys in 6 cases and Gly12Val in 2 cases). The consistent EGFR protein overexpression and the high rate of KRAS mutation may contribute to the poorer outcome of lung SC in comparison with typical NSCLC. The rare incidence of increased EGFR gene copy number, the lack of EGFR mutation and the high rate of KRAS mutation observed in our series also suggest that most patients with lung SC are not likely to benefit from anti-EGFR therapies.

Aims: The differential diagnosis of pleural sarcomatoid mesothelioma (SM) from lung sarcomatoid carcinoma (LSC) invading parietal pleura and chest wall is a challenging issue. The aim of this study was to identify useful antibodies that can be used for the differential diagnosis of pleural SM from LSC. Methods and results: Forty-five cases of pleural SM and 27 cases of LSC were immunohistochemically analysed by using 15 commercially available antibodies, including D2-40 and antibodies to calretinin, thrombomodulin, Wilms’ Tumour 1, carcinoembryonic antigen (CEA), Napsin A, thyroid transcription factor (TTF)-1, pan-cytokeratin, CAM5.2, epithelial membrane antigen, Ber-EP4, MOC-31, α-smooth muscle actin, h-caldesmon and desmin. The results revealed that D2-40 positivity was significantly higher in pleural SM (86.7%) than in LSC (25.9%). The positivity of the adenocarcinoma markers, including CEA, Napsin A, and TTF-1, was low even in LSC. Conclusions: Evaluating the positivity and degree of staining of the well-known mesothelial marker D2-40 could be applied to differentiate pleural SM from the sarcomatoid component of LSC, in addition to assessing clinical and radiological information.

Background: Sarcomatoid carcinoma of the lung is a very rare type of tumor characterized by distant metastasis. However, metastasis to the gingiva is an uncommon event. Occasionally, an oral metastatic lesion may be the preliminary clinical feature observed before the diagnosis of the primary tumor. Methods: The clinical features of gingival metastasis as an initial presentation of lung sarcomatoid carcinoma are discussed. A 55-year-old male patient presented with a rapidly growing pedunculated exophytic mass on the gingiva at the left side of the lower jaw. Incisional biopsy was performed. Results: The histologic and immunohistochemical diagnosis was metastatic carcinoma. To locate the primary tumor, we analyzed the lung lesion by chest computerized tomography (CT) scans and biopsy. The patient was ultimately diagnosed with sarcomatoid carcinoma of the lung with gingival metastasis. Palliative chemotherapy for lung cancer was administered. The gingival lesion disappeared after chemotherapy. Conclusion: Although this case is unusual, periodontists should recognize that gingival masses similar to benign or inflammatory lesions may represent an initial sign of underlying malignant tumors.

Sarcomatoid carcinoma of the lung (LSC) is a rare lung cancer characterized by an admixture of carcinoma and sarcoma components. Data concerning the genomic alterations of LSC are almost nonexistent. Here, we report on the first molecular cytogenetic characterization of a metastatic LSC. Cytogenetic and multicolor fluorescence in situ hybridization (M-FISH) analyses showed a near-triploid karyotype with numerous structural aberrations and four to six small supernumerary marker chromosomes containing chromosome 9 sequences. Comparative genomic hybridization on arrays (array CGH) detected an amplification of 9p23 approximately p24.3 and gains of 1q11 approximately q23.3, 3q26.2 approximately q29, and 17q23.2 approximately q24.1. The 9p amplification was also detected in the primary tumor and another metastasis of the same patient, indicating it was a significant element in the pathogenesis of this LSC case. Complementary FISH analysis showed that the small supernumerary chromosomes were isochromosomes for 9p23 approximately p24.3. These isochromosomes were lacking alpha-satellite sequences although they were still stable after 55 passages in culture. As demonstrated by immunostaining with anti-centromere antibodies, they contained a functional centromere. So-called analphoid "neocentromeres" are rare and have been mainly described in constitutional abnormal karyotypes. This case is the third description of the identification of neocentromeres in cancer, (i.e. well-differentiated liposarcoma and acute myeloid leukemia), and is the first one in a carcinoma. Our results suggest that the 9p23 neocentromere of this case of LSC might be similar to a 9p23 neocentromere previously identified in two constitutional cases. The frequency of neocentromere formation in solid tumors may indeed be underestimated and may have a significant implication in chromosomal instability in tumor cells.