Pulmonary Spindle Cell Carcinoma Research Articles

Comprehensive genomic profiling of pulmonary spindle cell carcinoma using tissue and plasma samples: insights from a real-world cohort analysis.

Pulmonary spindle cell carcinoma (PSCC) is a rare and aggressive non-small cell lung cancer (NSCLC) subtype with a dismal prognosis. The molecular characteristics of PSCC are largely unknown due to its rarity, which limits the diagnosis and treatment of this historically poorly characterized malignancy. We present comprehensive genomic profiling results of baseline tumor samples from 22 patients histologically diagnosed with PSCC, representing the largest cohort to date. Somatic genetic variant detection was compared between paired plasma samples and primary tumors from 13 patients within our cohort. The associations among genomic features, treatment, and prognosis were also analyzed in representative patient cases. TP53 (54.5%), TERT (36.4%), CDKN2A (27.3%), and MET (22.7%) were most frequently mutated. Notably, 81.8% of patients had actionable targets in their baseline tumors, including MET (22.7%), ERBB2 (13.6%), EGFR (9.1%), KRAS (9.1%), ALK (9.1%), and ROS1 (4.5%). The median tumor mutation burden (TMB) for PSCC tumors was 5.5 mutations per megabase (muts/Mb). TMB-high tumors (>10 muts/Mb) exhibited a significantly higher mutation frequency in genes such as KRAS, ARID2, FOXL2, and LRP1B, as well as within the DNA mismatch repair pathway. The detection rates for single nucleotide variants and structural variants were comparable between matched tumor and plasma samples, with 48.6% of genetic variants being mutually identified in both sample types. Additionally, a patient with a high mutation load and positive PD-L1 expression demonstrated a 7-month survival benefit from chemoimmunotherapy. Furthermore, a patient with an ALK-rearranged tumor achieved a remarkable 3-year progression-free survival following crizotinib treatment. Overall, our findings deepen the understanding of the complex genomic landscape of PSCC, revealing actionable targets amenable to tailored treatment of this poorly characterized malignancy.

P1.22-09 Molecular Profiling Reveals Distinct Clinical and Genomic Features as Potential Therapeutic Targets in Pulmonary Spindle Cell Carcinoma

P1.22-09 Molecular Profiling Reveals Distinct Clinical and Genomic Features as Potential Therapeutic Targets in Pulmonary Spindle Cell Carcinoma

Development and validation of a prognostic predictive model of pulmonary spindle cell carcinoma from the surveillance, epidemiology and end results database.

BackgroundPulmonary spindle cell carcinoma (PSCC) is a rare type of non-small cell lung cancer (NSCLC). The prognostic influent factors and therapeutic methods of PSCC are unclear, for there are only some case reports or small samples’ analysis. This study aims to find prognosis related factors of PSCC, develop and validate a nomogram to predict their survival probability.MethodsThe Surveillance, Epidemiology, and End Results (SEER) 18 Registries database (2000–2018) was searched to study PSCC. According to diagnosed time, data was divided into primary cohort (2000–2015) and validation cohort (2016–2018), both followed until December 31 2018. Chosen by Least Absolute Shrinkage and Selection Operator (LASSO) regression, age, sex, stage, surgery, chemotherapy, N, size and history of malignancy were taken out as predictive variables. The primary cohort was used to develop a nomogram to predict 1-, 3- and 5-year overall survival (OS) probability, and be validated by the validation cohort using concordance index (C-index) and calibration curves. Both cohorts were used to conduct a Cox regression to find the influential factors on OS of PSCC.ResultsThe nomogram shows a good concordance and discrimination on the prediction of OS, both internal (n=457 and C-index is 0.79) and external validation (n=100 and C-index is 0.76). The median survival time of PSCC is 4 months, with 20.1% OS possibility in 5 years. Multivariate analysis identified patients of older age [hazard ratio (HR), 1.02; 95% confidence interval (CI): 1.01–1.04], larger size of neoplasm (HR, 1.01; 95% CI: 1.01–1.01), M1 (HR, 2.96; 95% CI: 2.17–4.04), N2 (HR, 2.55; 95% CI: 1.81–3.59) or N3 (HR, 2.99; 95% CI: 1.58–5.66), regional stages (HR, 2.11; 95% CI: 1.29–3.44) and distant stages (HR, 6.17; 95% CI: 3.83–9.94) had a lower OS possibility, while surgery (HR, 0.39; 95% CI: 0.28–0.53) and history of malignancy (HR, 0.68; 95% CI: 0.48–0.98) was protective factors for PSCC. PSCC survived longer with surgery performed instead of chemotherapy or radiotherapy.ConclusionsPatients of PSCC have a poor prognosis, and using the nomogram developed by this study can predict their 1-, 3- and 5-year OS probability. Surgery is a better choice for PSCC and more studies are necessary to find potential treatment like targeted therapy, programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1).

P30-8 Sarcomatoid changes of pulmonary squamous cell carcinoma to pulmonary spindle cell carcinoma

Pulmonary spindle cell carcinoma (PSCC) is a very rare subtype of pulmonary sarcomatoid carcinoma (PSC), which consists of spindle cells only. We report a PSCC case in an 80-year-old man with systemic multiple metastases; however, the pathological image showed a sarcoma.

Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse.

BackgroundThe relationship between infection and tumors has attracted increasing attention. Trichoderma spp. are often isolated from tumors. However, their potential role remains unclear. We recently reported the isolation of Trichoderma longibrachiatum from a patient with pulmonary spindle cell carcinoma that was confirmed as primary infection by application of laser capture microdissection and polymerase chain reaction. To explore whether the strain is pathogenic and whether it can cause atypical cell proliferation and infiltration of NK cells and T cells, we designed a mouse infection experiment.MethodsTwelve ICR mice were randomly separated into three groups. Cyclophosphamide was used to inhibit the immunity of mice. A mouse model of Trichoderma infection was successfully established by intracutaneous injection on the back skin with a suspension of strain PKUT180420015. The pathological manifestations of Trichoderma infection and the interaction between immune cells and fungi were observed by histopathology, immunohistochemistry and intensive fungal staining. Reisolation of the fungus was observed by infected tissue culture. The inoculated sites exhibited swelling 3 days after inoculation, and ulcers developed at approximately 14 days. Skin specimens were obtained and then cultured at 3, 7, and 14 days after inoculation. We selected mice 14 days after inoculation in Group 3, whose ulcers were the most typical, for histological analysis.ResultsInflammation, angioinvasion and necrosis were observed. Immunohistochemistry showed positive markers of Ki67, CD3, CD56, GZMB, and PRF. Periodic acid-Schiff staining, periodic acid-silver methenamine staining, and Calcofluor staining showed fungal spores in the vascular lumen, vascular walls and around the blood vessels.ConclusionsOur studies showed that a T. longibrachiatum strain (PKUT180420015) isolated from a biopsy specimen in a patient with pulmonary spindle cell carcinoma could induce atypical hyperplasia, with the expression of Ki67, CD3, CD56, GZMB, and PRF in mice. These data indicate that the fungus may be involved in inducing atypical hyperplasia or tumorigenesis.

Pulmonary spindle cell carcinoma with hemothorax: A rare case report.

BackgroundPulmonary spindle cell carcinoma is a type of variant sarcomatoid carcinoma, which is a very rare case.Case presentationA 53-year-old male presented with weakness, 95% oxygen saturation with nasal cannula 3 L/min, asymmetric chest movement, and problem in the right lung (dull to percussion, and low vesicular auscultation). X-ray and CT-Scan supported hemothorax and lung malignancies in the right lung. The patient had a chest drain inserted which confirmed the hemothorax and was transferred to the operating room for emergency thoracotomy to stop the bleeding. Bleeding was still massive so re-thoracotomy and lobectomy were performed. The lung tissue was examined for anatomical pathology, and the results showed spindle cell carcinoma. The patient was given pemetrexed and carboplatin chemotherapy. The patient refused to continue therapy and died 3 months after the first chemotherapy.DiscussionImmunohistochemistry markers are the parameter for diagnosis of pulmonary spindle cell carcinoma that is highly positive for pan-cytokeratin, vimentin, and Ki67. The treatment is similar to other NSCLC, depending on the staging, and may include surgical resection, chemotherapy, and radiotherapy.ConclusionPulmonary spindle cell carcinoma is very rare and has a poor prognosis, especially in the presence of hemothorax.

A case of pulmonary spindle cell carcinoma incidentally identified in surgical specimen for pneumothorax

A case of pulmonary spindle cell carcinoma incidentally identified in surgical specimen for pneumothorax

Surgical resection of a rapidly growing pulmonary spindle cell carcinoma by robot-assisted thoracoscopic surgery: a case report

BackgroundPulmonary spindle cell carcinoma (PSCC) is an extremely rare tumor that is highly malignant and fast-growing. As chemotherapy and radiation therapy are ineffective, early surgical resection is effective for PSCC.Case presentationA 70-year-old woman with rheumatoid arthritis was referred to our hospital with an abnormal shadow. Chest computed tomography revealed a 33-mm-wide lobular mass in the right upper lobe. She was diagnosed with non-small cell lung cancer by bronchoscopic smear cytology. Although staging evaluation indicated stage IIIB (T3N2M0) disease, she required continued administration of immunosuppressants and prednisolone for rheumatoid arthritis. Therefore, robot-assisted thoracoscopic surgery (RATS) right upper lobectomy followed by lymph node dissection was performed without preoperative chemotherapy and radiotherapy. Pathological findings revealed PSCC.ConclusionsWe report a very rare case of pulmonary spindle cell carcinoma, successfully resected with RATS.

A Long-term Survival in Two Cases of Pulmonary Spindle Cell Carcinoma Treated with Pembrolizumab

背景．肺紡錘細胞癌は原発性肺癌の0.2%ほどと稀で，予後不良である．肺紡錘細胞癌にペムブロリズマブを投与し，長期に奏効した症例を経験したので報告する．症例1．70歳，男性．左胸痛を契機に左S3に腫瘤を指摘された．胸壁浸潤を伴う左上葉肺癌（cT3N0M0）疑いで左上葉切除を施行し，肺紡錘細胞癌と診断された．術後4カ月目のCTで左腋窩リンパ節，左副腎，膵臓に再発を認め，ペムブロリズマブ投与を開始した．現在ペムブロリズマブ23コース目で膵病巣のみ残存し，SDを維持している．症例2．75歳，女性．腹痛を契機に上行結腸癌が疑われ，精査で結腸，左下葉を含む悪性腫瘍の多発遠隔転移が疑われた．肺生検では診断に至らず，症状改善目的に上行結腸切除を先行し，紡錘形悪性腫瘍と診断された．肺原発を疑い，診断的治療目的に左下葉部分切除を施行し，肺紡錘細胞癌（pT2N0M1c）と診断された．ペムブロリズマブ投与を開始し，現在29コース目で画像的に同定可能な病巣を認めず，near CRを維持している．結論．肺紡錘細胞癌は予後不良であるが，ペムブロリズマブが奏効し，長期生存が得られる症例も存在する．

Clinicopathological characteristics and prognosis of pulmonary spindle cell carcinoma (PSCC): a population-based retrospective study.

In consideration of the scarceness and importance of histological analysis, the clinic pathological features of pulmonary spindle cell carcinoma (PSCC) were comprehensively analyzed in the present work to improve the treatment and deepen our understanding of the disease. Data of the PSCC patients from 2008 to 2013 in the Surveillance, Epidemiology, and End Results (SEER) database were acquired, analyzed and contrasted to that of the subjects with non-small cell lung cancer (NSCLC). Overall survival (OS) was evaluated based on the Kaplan-Meier method, univariate analysis (UVA) and multivariate analysis (MVA) were applied for the Cox proportional hazards regression. The risk factors related to 1-, 3-, and 5-year OS in PSCC subjects were identified. The data of 171 subjects considered to suffer from PSCC were collected and compared with that of 41,438 NSCLC patients. There was a poor differentiation in 72.9% of PSCC, and 44.4% were at the stage IV of American Joint Committee on Cancer (AJCC). The median OS time of PSCC was 8 months [95% confidence interval (CI): 6.23-10.72] with 5-year OS as 23.9% (95% CI: 21.5-25.7%). Tumors of PSCC were significantly undifferentiated, which exhibited the higher rate to be resected by surgery, with more lymph node metastases and distant metastases than that of NSCLC (P<0.001). It was demonstrated in UVA and MVA that the N stage, M stage, and surgery served independently as the risk factors of OS. The calibration variable for the nomogram was 0.735 (lower than 0.8). There were specific clinicopathologic features in PSCC. The results revealed that there was an independent correlation between N stage, M stage, or surgery with OS. However, 1-, 3- and 5-year OS could not be precisely predicted by the nomogram.

Minimally Invasive Surgery for Pulmonary Spindle Cell Carcinoma – Uncommon Aggressive Variant

Minimally Invasive Surgery for Pulmonary Spindle Cell Carcinoma – Uncommon Aggressive Variant

Infarct-Like Spindle Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 4 Cases.

Pulmonary spindle cell carcinoma is a rare and aggressive malignancy that often mimics benign conditions. We report 4 cases that simulate a pulmonary infarction, 2 of which were misdiagnosed. Patients were 3 men and 1 woman, smokers, presenting chest pain. All cases appeared as pleural-based, solitary, and rounded nodules. Patients underwent wedge resections followed by adjuvant chemotherapy (3/4) but died of disease. At histology, lesions consisted of widely necrotic nodules surrounded by organizing fibrosis and pleuritis. Examination and immunostains with pan-cytokeratins and epithelial membrane antigen (EMA) revealed atypical spindle cells encircling necrotic tissue and involving the vascular wall. Positive staining with PD-L1 was noted. Molecular analysis showed KRAS (2/4) and TP53 (1/4) mutations, whereas EGFR, ALK, and ROS1 alterations were not detected. Although in a limited series, these cases further evidence the treacherous appearance of spindle cell carcinomas and the need for careful attention when examining pulmonary infarcted tissue, thus requiring extensive sampling, meticulous examination of vascular structures, and immunostaining with cytokeratins.

The promising role of mucin 4 in association with D2-40 immunohistochemistry in differentiating pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

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.

Pulmonary spindle cell carcinoma: case report and literature review

Pulmonary spindle cell carcinoma: case report and literature review

Primary pulmonary spindle cell carcinoma in a young nonsmoker patient

Spindle cell carcinoma (SCC) is a very rare type of tumor. Very few case reports of primary pulmonary SCC have been reported in the literature. It is a type of sarcomatoid carcinoma with very poor prognosis. It is usually seen in patients in the age group of 50–80 years. Exact etiology is unknown till now. We report a rare case of primary pulmonary SCC in a young nonsmoker patient who presented in a very advanced stage.

Spindle Cell Carcinoma of the Lung: Benefits of Immunohistochemical Studies

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) defined in its classification 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.

肺静脈内に急速に進展し完全切除後早期に再発した肺紡錘細胞癌の1例

肺静脈内に急速に進展し完全切除後早期に再発した肺紡錘細胞癌の1例

Spindle cell carcinoma of the lung

We report a rare case of spindle cell carcinoma in the lung. A 73-year-old woman was admitted because of a lung tumor, which was indicated during a group examination. Chest computed tomography revealed a tumor located in the right lung accompanied by spiculation. Right upper lobectomy with lymph nodal dissection was performed. Histological findings revealed only spindle-shaped tumor cells, and immunohistochemical stain showed that they were cytokeratin-positive. We diagnosed it as a pulmonary spindle cell carcinoma.

An Autopsy Case of Pulmonary Spindle-cell Carcinoma with Metastases to the Stomach

背景．肺紡錘細胞癌は紡錘形腫瘍細胞のみからなる低分化の非小細胞癌で稀である．また原発性肺癌の胃転移も稀とされる．症例．症例は65歳男性．咳・血痰が出現し当院入院．胸部CT上，右肺下葉の腫瘤影と縦隔浸潤像を認めた．気管支鏡下擦過細胞診により原発性肺癌（非小細胞癌，T4N2M0：stage IIIB）の診断で，化学療法cisplatin+vinorelbineを3クール施行したが腫瘍は増大．下部食道を狭窄し嚥下困難が出現したため食道ステントを留置．この時胃体部に粘膜下腫瘍様の隆起性病変及び潰瘍性病変を認めた．その後肺化膿症を発症し，入院より5カ月で永眠された．病理解剖にてcytokeratin 7，vimentinが陽性を示す紡錘形腫瘍細胞が肺及び胃に認められ，肺紡錘細胞癌及び胃転移と診断した．結論．胃転移を来した肺紡錘細胞癌の1例を報告した．肺紡錘細胞癌及び肺癌の胃転移は稀で予後不良である．今後さらなる症例の蓄積により本疾患の理解や，より有効な治療法確立が必要である．

A Patient with Pulmonary Spindle Cell Carcinoma

Background. Pulmonary spindle cell carcinoma is a rare lung cancer which was first classified in 1999 by the World Health Organization (WHO). Case. A 70-year-old man was admitted to our hospital because of bloody sputum, right-side chest and back pain, and an abnormal lung shadow. He was originally given a diagnosis of poorly differentiated non-small cell lung carcinoma based on cytology. The tumor had invaded the bones, and the patient received radiotherapy and chemotherapy, both of which were ineffective. The cancer progressed and he died 5 months later. An autopsy revealed that the cancer was sarcomatoid carcinoma (subgroup, spindle cell carcinoma) according to the 2004 WHO classification of tumors. It was difficult to distinguish the carcinoma from sarcomatoid mesothelioma by pathological examination alone. Initial chest computed tomography had showed a lung mass that led to the diagnosis of sarcomatoid carcinoma. The cause directly leading to his death was respiratory failure caused by diffuse alveolar damage. Conclusion. Pulmonary spindle cell carcinoma is believed to have a poor prognosis and is sometimes difficult to distinguish from sarcomatoid mesothelioma. Additional study of cases is needed to confirm this disease entity and to develop better treatments.