Expanding the Immunophenotype Spectrum of SMARCA4-Deficient Non-Small Cell Lung Carcinomas: A Case Series with Neuroendocrine Markers Expression

2021 ◽  
pp. 106689692110479
Author(s):  
Ruiqi Mao ◽  
Min Liu ◽  
Xiangfang Shu ◽  
Wenli Li ◽  
Wei Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Hot Spot ◽  
Case Series ◽  
Clinical History ◽  
Nonsmall Cell Lung Cancer ◽  
Large Cell ◽  
Variable Expression ◽  
Neuroendocrine Markers ◽  
Undifferentiated Histology ◽  
Poorly Differentiated

Aims. In recent years, SMARCA4-deficient nonsmall cell lung cancer (NSCLC) has been recognized as a distinct new subtype of lung cancer, which is characterized by loss of SMARCA4 (Brahma-related gene-1 [BRG1]) protein expression. Only a limited number of SMARCA4-deficient NSCLC case series have been reported, and their clinicopathological features have not yet been fully elucidated. Our main aim was to analyze the clinical history, histology, immunohistochemistry, and molecular pathology of 5 SMARCA4-deficient NSCLC patients with poorly differentiated or undifferentiated histology and neuroendocrine markers expression. Methods and results. Five patients with complete loss of nuclear BRG1 immunostaining were identified among 53 patients of poorly differentiated/undifferentiated NSCLC. We then performed immunohistochemical staining and gene mutation analysis using a real-time polymerase chain reaction. All patients were male aged between 58 and 82 years (average 67.6 years), with smoking exposure. Histologically, the tumors had a relatively monotonous morphology and showed solid nest-like, sheet-like growth, and geographic necrosis. Thyroid transcription factor 1, cytokeratin 7, and Napsin A were all negative (5 of 5). Moreover, all tumors showed a variable expression of neuroendocrine markers, including synaptophysin, chromogranin A and CD56. Hot spot epidermal growth factor receptor/anaplastic large-cell lymphoma kinase/c-ros oncogene 1 mutations were not detected in any of the 5 tumors. Conclusions. To the best of our knowledge, this is the first study that has reported the poorly differentiated morphology with a frequent expression of neuroendocrine markers. Our results have expanded the immunophenotype spectrum of SMARCA4-deficient NSCLC. However, the clinicopathological significance of this subset of SMARCA4-deficient NSCLC should be further clarified in larger series studies.

scholarly journals SMARCA4/BRG1–Deficient Non–Small Cell Lung Carcinomas: A Case Series and Review of the Literature

2020 ◽  
Vol 145 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Aruna Nambirajan ◽  
Varsha Singh ◽  
Nishu Bhardwaj ◽  
Saurabh Mittal ◽  
Sunil Kumar ◽  
...  
Keyword(s):  
Case Series ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Lung Carcinomas ◽  
Anaplastic Lymphoma ◽  
Thyroid Transcription Factor 1 ◽  
Poorly Differentiated

Context.— Somatic mutations in SMARCA4 (SWI/SNF–related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and/or BRG1 (Brahma-related gene 1) loss identifies a subset of non–small cell lung carcinomas (NSCLCs) lacking alterations in EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase), and ROS1 (ROS proto-oncogene 1) genes. Preliminary observations suggest responsiveness to immunotherapy and targeted therapies. Objective.— To study BRG1 loss in NSCLCs and elucidate the clinicopathologic profile of such SMARCA4-deficient NSCLCs. Design.— Non–small cell lung carcinomas diagnosed during 6 years were subject to immunohistochemistry for BRG1 and BRM (Brahma). Tumors with BRG1 loss were stained with antibodies against thyroid transcription factor 1 (TTF-1), p40, cytokeratins, hepatocyte paraffin 1 (Hep Par 1), Sal-like protein 4 (SALL4), CD34, SRY-box 2 (SOX2), chromogranin, synaptophysin, p53, integrase interactor 1, ALK, and ROS1. EGFR mutation testing was performed by polymerase chain reaction–based method. Results.— Among 100 NSCLCs tested, 4 cases (4%) showed BRG1 loss. The histology ranged from solid adenocarcinomas (n = 1) to large cell/poorly differentiated carcinomas (n = 3) with clear cell cytology in 2 cases. All showed loss/reduction of BRM with variable cytokeratin and SALL4 expression, and were negative for TTF-1, p40, Hep Par 1, ALK, ROS1, and EGFR mutations. CD34 and SOX2 were negative in all 4 cases. Isolated BRM loss was common (21%), distributed across all NSCLC subtypes including squamous cell carcinomas and a hepatoid adenocarcinoma. Conclusions.— BRG1 loss occurs in a subset of TTF-1/p40–negative poorly differentiated NSCLCs. Identification and follow-up will clarify the prognosis, diagnostic criteria, and potential for therapeutic personalization.

scholarly journals Undifferentiated large cell/rhabdoid carcinoma presenting in the intestines of patients with concurrent or recent non-small cell lung cancer (NSCLC): clinicopathologic and molecular analysis of 14 cases indicates an unusual pattern of dedifferentiated metastases

2021 ◽  
Author(s):  
Abbas Agaimy ◽  
Ondrej Daum ◽  
Michal Michal ◽  
Mona W. Schmidt ◽  
Robert Stoehr ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Large Cell ◽  
Undifferentiated Carcinoma ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Gastrointestinal Carcinoma ◽  
Undifferentiated Histology

AbstractUndifferentiated carcinoma metastatic to the bowel is uncommon in surgical pathology practice and might be confused with primary gastrointestinal carcinoma, melanoma, lymphoma, and others. We present 14 cases of uni- (n = 9) or multifocal (n = 5) undifferentiated large cell/rhabdoid carcinoma presenting in the bowel of patients with concurrent (n = 9) or recent (diagnosed 1 to 25 months earlier; median, 4) non-small cell lung cancer (NSCLC). Patients were 6 females and 8 males, aged 52 to 85 years. Primary NSCLC was verified histologically in 10 cases and by imaging in 4. The undifferentiated histology was present in the lung biopsy in 4/10 patients (as sole pattern in 3 and combined with adenocarcinoma in 1) and was limited to the intestinal metastases in the remainder. PDL1 was strongly expressed in 7/9 cases (CPS: 41 to 100). Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case. PBRM1 loss was observed in one tumor. Successful molecular testing of 11 cases revealed BRAF mutations in 4 (3 were non-V600E variants), KRAS mutations in 3, and wildtype in 4. None had EGFR mutations. Analysis of 4 paired samples revealed concordant KRAS (2) and BRAF (1) mutations or wildtype (1). Our study indicates that undifferentiated carcinoma within the intestines of patients with concurrent/recent NSCLC represents dedifferentiated metastasis from the NSCLC. Recognition of this unusual presentation is cardinal to avoid misdiagnosis with inappropriate therapeutic and prognostic implications.

scholarly journals Expression of TTF-1 And CK-7 in the Diagnosis of Pleural Effusion Cytology Suspected Lung Adencarcinoma

2015 ◽  
Vol 1 (1) ◽  
pp. 22
Author(s):  
Patricia Diana Prasetiyo ◽  
Ika Pawitra ◽  
Indra Wijaya
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Pearson Correlation ◽  
Large Cell Carcinoma ◽  
Nonsmall Cell Lung Cancer ◽  
Large Cell ◽  
P Value ◽  
Lung Malignancy ◽  
Pearson Correlation Test ◽  
Observational Study Design

Background : Lung cancer is the mayor disease that cause death worldwide including Indonesia especially Nonsmall cell lung cancer (NSCLC) consisting of adenocarcinoma, squamus carcinoma (SqCCA) and large cell carcinoma. Incidency of lung adenocarcinoma continues to rise recently about 40% of all NSCLC.Methods : Descriptive observational study design. The study population included the patients who were hospitalized at Kariadi central hospital in Semarang and had thorax X-ray or CT scan of thorax with a diagnosis of suspected lung malignancy, at the period of January 2012 – 2013. The variables assessed are expression of TTF-1 and CK-7.Result : A total of 20 samples subjected to Pearson correlation test with result of p value = < 0,001 and r = 0,867. Presentation of the highest expression TTF-1 in the all study sample is Adenocarcinoma 73,3% and highest expression CK-7 is also Adenocarcinoma 68,6%.Conclusion : Immunocytochemistry of TTF-1 and CK-7 can be used to determine Adenocarcinoma malignancy on cytological sample of suspected malignant pleural effusion

scholarly journals Are neuroendocrine negative small cell lung cancer and large cell neuroendocrine carcinoma with WT RB1 two faces of the same entity?

2019 ◽  
Vol 8 (2) ◽  
pp. LMT13 ◽  
Author(s):  
Dmitriy Sonkin ◽  
Anish Thomas ◽  
Beverly A Teicher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Neuroendocrine Carcinoma ◽  
Cell Lung Cancer ◽  
Genomic Data ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Therapeutic Implications ◽  
Neuroendocrine Markers

Until recently, small cell lung cancer (SCLC) was described as SCLC and SCLC variant, based upon cellular morphology and loss of neuroendocrine markers in the SCLC variant. However, based on recent research advances, driven in part by the increase in comprehensive genomic data, it has become clear that there are multiple SCLC subtypes including an ASCL1 and NEUROD1 low, YAP1 high (SCLC-Y) subtype enriched for WT RB1. Comparing morphological and other features of this SCLC subtype to neuroendocrine negative RB1, KEAP1, STK11 WT LCNEC raises a number of important questions with diagnostic and therapeutic implications.

scholarly journals Lung Cancer Presenting as Skin Metastasis of the Back and Hand: A Case Series and Literature Review

2019 ◽  
Vol 12 (2) ◽  
pp. 480-487 ◽  
Author(s):  
Misbahuddin Khaja ◽  
Daniel Mundt ◽  
Rizwan Ahmed Dudekula ◽  
Umair Ashraf ◽  
Shehriyar Mehershahi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ct Scan ◽  
Left Lung ◽  
Case Series ◽  
The United States ◽  
Middle Lobe ◽  
Skin Metastasis ◽  
Smoking History ◽  
Poorly Differentiated ◽  
The Right

Lung cancer has the highest mortality of all cancers in the United States. The incidence of lung cancer with metastases to the skin varies between 1–12%, with the highest incidence seen in men. Here, we present two cases of lung cancer presenting as skin metastasis. The first patient was an 80-year-old African American male who presented to the hospital for evaluation of a right upper back mass. A few months prior to admission, he was found to have a left lung mass on CT scan of the chest, he underwent biopsy which showed poorly differentiated SCC of the lung. He also had a skin biopsy which showed poorly differentiated carcinoma in the dermis consistent with metastatic SCC. He was started on chemotherapy, but could not tolerate it. He was accepted to hospice. The second patient was a 78-year-old Hispanic female who presented to the hospital with dyspnea, and a dry cough. Upon physical examination, a 2 × 2 cm ulcerated, wart-like nodule on the right palm was noted. Subsequent CT scan of the chest showed a partial collapse of the right middle lobe. A biopsy of the hand mass revealed well-to-moderately differentiated metastatic SCC favoring lung origin. A bronchoscopy biopsy showed invasive SCC. Subsequently her condition worsened and she passed away. Metastasis to the skin is an unusual presenting symptom of lung cancer. It is therefore essential to consider metastasis as a diagnosis in a patient with both a skin lesion and a smoking history.

scholarly journals Concomitant Acute Motor Sensory Axonal Neuropathy and Squamous Lung Cancer-induced Intramedullary Spinal Cord Metastasis

2019 ◽  
Author(s):  
Hamid Reza Fateh ◽  
Alireza Khoshnevisan ◽  
Mina Meshkini ◽  
Aidin Heidari
Keyword(s):  
Lung Cancer ◽  
Spinal Cord ◽  
Cell Lung Cancer ◽  
Axonal Neuropathy ◽  
Nonsmall Cell Lung Cancer ◽  
Intramedullary Spinal Cord ◽  
Intramedullary Lesion ◽  
Squamous Lung Cancer ◽  
Poorly Differentiated ◽  
Spine Mri

Intramedullary Spinal Cord Metastases (ISCMs) are rare, especially in squamous non-small cell lung cancer simultaneous with Acute Motor and Sensory Axonal Neuropathy (AMSAN); diagnosing these phenomena may be challenging. We report a 56-year-old man presenting with rapidly symmetrical progressive ascending weakness and paresthesia, especially in lower extremities, urinary and fecal incontinence, without any pain or respiratory symptoms. Thoracic spine MRI with and without gadolinium revealed an enhancing intramedullary lesion at the T3-T5 level. Chest CT discovered subpleural pulmonary lesion. The result lung biopsy was consistent with poorly differentiated squamous cell carcinoma, and electrodiagnosis noted severe axonal loss in motor and sensory studies with significant membrane instability and neurogenic findings in electromyography. After 8 months, the patient received just one cycle of chemotherapy and died 6 months later. AMSAN was associated with ISCM of nonsmall cell lung cancer in this case, who has not been previously reported in the literature.

Primary gastroenteropancreatic poorly differentiated neuroendocrine carcinoma: Clinico-pathologic analysis of 68 cases

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15616-e15616
Author(s):  
M. H. Bukhari ◽  
E. Byron ◽  
J. R. Strosberg ◽  
N. A. Nasir ◽  
E. Henderson-Jackson ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Patient Survival ◽  
Large Cell Carcinoma ◽  
Distant Metastases ◽  
Large Cell ◽  
Histologic Subtype ◽  
Neuroendocrine Markers ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Metastatic Setting ◽  
Poorly Differentiated

e15616 Background: Primary gastro-entero-pancreatic poorly differentiated neuroendocrine carcinomas (GEP-PDNECAs) are highly aggressive neoplasms with a very poor prognosis. This study was conducted to evaluate the immuno-morphological spectrum of GEP-PDNECA, and patient survival with systemic platinum and etoposide therapy. Methods: Under an IRB-approved protocol, clinico-pathologic data were collected on 68 adult patients with GEP-PDNECA who had undergone biopsy / resection at MCC or outside institution. Data sources: Pathology archives, consultation files, tumor registry and social security index. All available slides were reviewed and tumors were histologically sub-typed. Subsequently, clinico-pathologic data and patient survival were analyzed. Results: Patients: 41 M/27 F. Age: 25–76 yrs (mean 42 yrs). Sites: Colo-rectum 39, pancreas 19, small intestine (SI) 4, stomach 3, colon/SI/pancreas 3. 63 of 68 (93%) patients presented with lymph node/distant metastases. Of 68 tumors 37 (54%) were classified as small cell carcinoma (SCCA), 16 (24%) large cell carcinoma (LCCA), 5 (7%) mixed small and large cell (MSLCCA) and 10 (15%) poorly differentiated carcinoma with neuroendocrine features (PDCA-NEF). Tumors were positive for chromogranin in 38/65 (55%), synaptophysin in 62/67 (92%), and CD56 in 17/21 (81%) cases. One marker was positive in 22/68 (32%), 2 in 40/68 (59%) and all 3 were positive in 9/68 (13%) cases. Fifty eight of 68 (85%) patients were treated with platinum and etoposide. Overall survival at 1, 3 and 5 years was 85%, 40% and 24% respectively. Patient survival was independent of age (r= -0.1022), sex (r= -0.909) and histologic subtype (r= - 0.1028) (p= 0.128) but was related to distant metastases (r=0.306; p=0.0383). Conclusions: Diagnosis of GEP-PDNECA can be based on histo-morphologic features and expression of neuroendocrine markers. Synaptophysin was the most sensitive marker; however, a panel of 2 or 3 neuroendocrine markers (Syn, Cg and CD56) may be more useful to avoid under-diagnosis of GEP-PDNECA, especially in the metastatic setting. Although survival of GEP-PDNECA patients following platinum and etoposide in our series was relatively favorable, there is need for novel therapies to improve patient survival. No significant financial relationships to disclose.

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