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Neurological paraneoplastic syndrome is a relatively rare condition in patients with malignant tumors. Recently, it has been reported that anti-Aquaporin 4 (AQP4) antibody is highly specific for neuromyelitis optica. The patient was a 76-year-old man. He underwent right upper lobectomy for squamous cell carcinoma of the lung. Although the immediate postoperative course was uneventful, neurological symptoms became apparent from postoperative day (POD) 4. Magnetic resonance imaging showed longitudinally extended edematous lesions in the spinal cord, and a cerebrospinal fluid examination was positive for anti-AQP4 antibody, leading to the diagnosis of paraneoplastic neuromyelitis optica. Despite multiple rounds of steroid pulse therapy and plasma exchange, the neurological symptoms worsened and the patient died on POD 46. The development of neuromyelitis optica in the early postoperative period could be related to the influence of surgical stress or epidural anesthesia.

A 68-year-old woman with a past medical history of chronic obstructive pulmonary disease and squamous cell carcinoma of the lung with recent right upper and middle lobectomy was admitted for dyspnea and volume overload. She was diagnosed with right-sided heart failure (RHF) through clinical, laboratory, and echocardiographic means. In the setting of chronic respiratory failure, the recent right lung lobectomy was deemed to be the inciting factor of the RHF. The mechanism by which RHF occurs in this situation is multifactorial, and it is essential to undergo pre-operative risk stratification and post-operative monitoring to avoid emergent events.

Background Schizophyllum commune is a basidiomycete that lives in the environment and can cause infections, mainly those of the respiratory system. Although S. commune is increasingly reported as a cause of allergic bronchopulmonary mycosis and sinusitis, cases of fungal ball formation are extremely uncommon. Identification of S. commune is difficult using routine mycological diagnostic methods, and in clinically suspicious cases, internal transcribed spacer sequencing should be used for diagnosis. Here, we report a first case of lung cancer with a fungal ball formation of S. commune, confirmed by analyzing the internal transcribed spacer. Case presentation A 76-year-old man with diabetes and hypertension was admitted to the hospital with a chief complaint of hemosputum, which he had for about 19 months. A computed tomography image of the patient’s chest showed a cavity and internal nodule in the left upper lobe of his lung. A left upper lobectomy was performed, and histopathological examination revealed squamous cell carcinoma of the lung and a fungal ball. The isolate from the surgical specimen was identified as S. commune by analyzing the internal transcribed spacer. The patient had no recurrence of the infection during 5 months of follow-up. Conclusions Only three cases of lung fungal balls caused by S. commune have been previously reported, and this is the first case of lung cancer cavity with a fungal ball formation. In cases of fungal ball formation in the lung, S. commune should be considered a possible causative microorganism.

The pleural lobes are the origin of different pathologies, including malignant tumors, e.g., pleural mesothelioma. In some cases, clinical and macroscopic presentation point strongly to the diagnosis but often enough the patient has another underlying disease; malignant neoplasms of the lung as well as other organs (skin, pancreas, prostate or kidney) can mimic pleural mesothelioma and if so, are defined as ‘pseudo-mesothelioma’. We present eight cases that are clinically and macroscopically highly suspicious for pleural mesothelioma. All patients were autopsied due to medico-legal issues and work-related diseases. Six out of eight patients underwent autopsy to exclude possibility of asbestos-related malignancy and two out of eight due to exclusion of silicosis. From the eight cases, only three were real pleural mesotheliomas. Another three were adenocarcinomas of the lung mimicking pleural mesotheliomas. One had squamous cell carcinoma of the lung. Lastly, one patient had an extraordinary case of papillary renal cell carcinoma metastasizing universally in both pleura lobes. Due to striking morphological similarities, the exact final diagnosis was only possible after extended immunohistochemical analysis of the tissues. In summary, not only is it difficult to distinguish between real or pseudo pleural mesothelioma in patients having had contact with asbestos. Even patients with no evidence of asbestos contact can have clinical and pathological events strongly suggesting asbestosis and mesothelioma, without having it.

Background Multiple studies have suggested that patients with early-stage SCC of the lung treated with SBRT are more susceptible to local failure compared to other NSCLC histologies. It is unknown if higher BED leads to improved outcomes in this patient population. We evaluated the effect of “high” BED versus “low” BED SBRT on overall survival (OS) in SCC and non-SCC NSCLC patients. Methods The National Cancer Database was used to identify patients with cT1-2N0M0 NSCLC diagnosed between 2006–2016 treated with 3–5 fraction SBRT. Patients were grouped by BEDhigh (>150 Gy) and BEDlow (≤132 Gy). Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment (IPTW) weighting was used to account for selection bias. Results We identified 4,717 eligible SCC patients and 8,807 eligible non-SCC NSCLC patients. In SCC patients, BEDhigh was associated with improved OS in both univariate and multivariate analysis (MVA HR 0.84 95% CI 0.76–0.92, p Conclusions Our analysis suggests that in patients with early-stage NSCLC, SBRT regimens with BED > 150 Gy may confer a survival benefit in patients with SCC histology. Histology-based dose modification should be considered, and prospective validation may be warranted.

Tipifarnib is a novel targeted treatment for hematologic malignancies that is being recently studied for the treatment of advanced solid organ tumors with HRAS mutations. There have been scarce reports on kidney adverse events in initial phase I and II trials. We present a case of acute kidney injury in a patient that had started treatment with tipifarnib for advanced squamous cell carcinoma of the lung. Kidney biopsy revealed acute tubular necrosis together with acute interstitial nephritis. Tipifarnib was discontinued and the patient was started with high-dose corticosteroids with an early taper completing a five-week steroid course, with full recovery of kidney function.

Background: Chronic granulomatous disease (CGD), one of the phagocytic system defects, is the primary immunodeficiency caused by dysfunction of the NADPH oxidase complex which generates reactive oxygen species (ROS), which are essential for killing pathogenic microorganisms, especially catalase-positive bacteria and fungi. Objective: The objective of our study was to assess the clinical and laboratory characteristics, treatment modalities, and prognosis of patients with CGD. Methods: We retrospectively reviewed 63 patients with CGD who have been diagnosed, treated, and/or followed-up between 1984 and 2018 in Hacettepe University, Ankara, in Turkey, as a developing country. Results: The number of female and male patients was 26/37. The median age at diagnosis was 3.8 (IQR: 1.0–9.6) years. The rate of consanguinity was 63.5%. The most common physical examination finding was lymphadenopathy (44/63), growth retardation (33/63), and hepatomegaly (27/63). One adult patient had squamous cell carcinoma of the lung. The most common infections were lung infection (53/63), skin abscess (43/63), and lymphadenitis (19/63). Of the 63 patients with CGD, 6 patients had inflammatory bowel disease (IBD). Twelve of the 63 patients died during follow-up. CYBA, NCF1, CYBB, and NCF2 mutations were detected in 35%, 27.5%, 25%, and 12.5% of the patients, respectively. Conclusion: We identified 63 patients with CGD from a single center in Turkey. Unlike other cohort studies in Turkey, due to the high consanguineous marriage rate in our study group, AR form of CGD was more frequent, and gastrointestinal involvement were found at relatively lower rates. The rate of patients who treated with HSCT was lower in our research than in the literature. A majority of the patients in this study received conventional prophylactic therapies, which highlight on the outcome of individuals who have not undergone HSCT.

Muscle metastases remain rare as a secondary localization for cancers in general and lung cancer in particular. They are discovered incidentally in most cases and in the advanced stages of cancer. We report the case of a 60-year-old man, followed for squamous cell carcinoma, who was found to have muscle metastases during the follow-up of associated muscle pain. This case highlights the existence of these metastases in lung squamous cell carcinoma, rare as it is, and requires particular attention from practitioners in the follow-up of patients to detect these cases as early as possible and improve patient survival. Computed Tomography (CT) remains an excellent exam for the detection of skeletal metastasis.

Multiple primary cancers (MPC) occurring in the same individual is considered rare but being increasingly recognized owing to the longer cancer survival nowadays. Despite of accumulating experience in diagnosis, effective treatment remains to be problematic in many scenarios. Genetic testing-based targeted therapy could be an invaluable option for both diagnosis and treatment of such patients. Here we present a 74-year-old male with triple primary cancers including kidney, prostate, and lung with metastatic tumor on the costal bones. The patient visited the hospital for persistent cough and hemoptysis, and a diagnosis of squamous cell carcinoma of the left lung was made by bioptic fiberoptic bronchoscopy. A previous history included renal cancer controlled by Sorafenib and prostate cancer controlled by Goserelin. Radiotherapy and platinum-based chemotherapy failed to help the patient and the tumor size increased over a period of 6 months. In order to seek better therapeutical options, we performed targeted sequencing using the cancerous tissues from his lung, kidney, and prostate cancers. Briefly, the results identified VHL, EGFR, PIK3CA, TP53, and AKT1 mutations in lung cancer, AKT1, FGFR2, and TP53 mutations in renal cancer, and FGFR2 mutations in prostate cancer. A combined medication targeting PIK3CA and AKT1 signaling was recommended and the patient was given BKM120 (PIK3CA, Phase III clinical trial) and MK2206 (AKT, phase III clinical trial). Revisit chest CTs after 4 months and 9 months showed a significant shrinkage of tumor size by 40% and 80%, respectively. Our experience demonstrated a good example that genetic analysis could be valuable to diagnose and precisely treat multiple primary cancers.

With the popularity of neoadjuvant therapy as first-line treatment, especially for advanced squamous cell carcinoma (SCC), the focus has become accurate individualized treatment. Specifically, toxic side effects of traditional platinum-doublet chemotherapy are high, so treatment with pembrolizumab plus platinum-doublet chemotherapy is safer and more effective. Pembrolizumab is a humanized monoclonal IgG4 kappa anti-PD1 antibody. It is devoid of any cytotoxic activity among the drug effect. Pembrolizumab has been tested clinically in a series of KEYNOTE studies and 12 categories of malignancies have been tested to determine their clinical effects. A 64-year-old man with IIIA SCC of the lung without any surgical contraindications in the preoperative period successfully underwent radical resection and had a great prognosis after neoadjuvant treatment. Chest computed tomography (CT) showed that the left upper lung lesion, hilar and mediastinal lymph nodes were obviously smaller than before, meanwhile, obstructive pneumonia was significantly absorbed. No sign of metastasis was detected by head-abdominopelvic CT and bone scan. Although radiation pneumonitis was an adverse event after postoperative adjuvant therapy, symptoms were relieved with low-dose glucocorticoids. In conclusion, traditional chemotherapy with single agents alone has been gradually replaced by pembrolizumab plus platinum-doublet chemotherapy as a first-line therapy now.

Rhabdomyosarcoma is an infrequent muscular cancer seen in adults. We present a case of ileal intussusception due to pleomorphic rhabdomyosarcoma in a patient diagnosed previously with squamous cell carcinoma of the lung (SCCL). The patient was a 68-year-old man with a history of SCCL. He was admitted to the emergency department for nausea, emesis and obstipation. Surgical investigation of the abdomen revealed an intussusception caused by a tumour located 160cm distal of the ligament of Treitz. Pathological examination showed that tumour was a primary rhabdomyosarcoma of the ileum. This case contributes to the literature by defining an infrequent presentation of rhabdomyosarcoma causing ileal intussusception in an adult patient.

Background ALK rearrangement is a very rare subset of squamous cell carcinoma (SCC) and one of the clinical features in patients is lack of data. Here, we report eight patients diagnosed with SCC of the lung harboring ALK rearrangement. Methods We collected primary NSCLC samples at the Beijing Chest Hospital between January 2012 and December 2018 for Ventana (D5F3) immunohistochemical detection. Among the 148 patients was diagnosed ALK‐rearranged non small cell lung cancer (NSCLC), only eight cases was SCC. We collected patients information from electronic patent records (EPRs). Results The eight cases of SCC were diagnosed by immunohistochemistry (IHC). Two were given crizotinib as second‐line therapy. One patient had stable disease (SD) and progression‐free survival (PFS) of six months. The other patient had progressive disease (PD) but PFS was only one month. The side effects were tolerable. This report identified 31 cases of ALK rearrangement in SCC patients from a literature search (including the eight patients in this study). These fusion genes are often seen in a younger age group (mean age: 55.6 years) and non‐smokers (18/31, 58.1%). A total of 20 cases received an ALK inhibitor as first‐ or second‐line treatment which included 11 with a partial response (PR), four with SD, and five with PD. The DCR and ORR was 75.0% (15/20) and 55.0% (11/20), respectively. The median duration time of therapy was 6.4 ± 4.4 months. Conclusions Patients with ALK‐rearranged SCC obtained clinical benefit from ALK‐inhibitor therapy, especially those who were non‐smokers and whose tumors had been identified by IHC+/FISH+., Clinical benefit was obtained from ALK‐inhibitor treatment in ALK‐rearranged SCC especially in non‐smokers and patients whose tumors had been identified by IHC+/FISH+.

BACKGROUND: Tumor mutational burden (TMB) has been identified as one of the predictors for the response to anti-programmed cell death-1 (anti-PD-1) antibody therapy and reported to correlate with smoking history in lung adenocarcinoma. However, in squamous cell carcinoma of the lung, the association between TMB and clinicopathological background factors, such as smoking history, has not been reported, including in our previous study. The mutational signature is a tool to identify the mutagens that are contributing to the mutational spectrum of a tumor by investigating the pattern of DNA changes. Here, we analyzed the mutational signature in lung squamous cell carcinoma to identify mutagens affecting the TMB. METHODS: Seven representative mutational signatures including signature 7 (SI7) [ultraviolet (UV)-related], SI4 (smoking), SI6/15 [mismatch repair (MMR)], SI2/13 [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)], and SI5 (clock-like) were analyzed in Japanese patients with lung squamous cell carcinoma (n=67) using data generated by next-generation sequencing consisting of a 415-gene panel. The relationships between signatures and clinico-pathological data including TMB and programmed death-ligand 1 (PD-L1) expression were analyzed. RESULTS: Although the reconstructed mutational counts were small with targeted sequencing (median: 30.1, range: 13.3–98.7), the distributions of signatures were comparable among samples, with 56 cases containing more than four signatures. The smoking-related SI4 was found in 45 cases and was significantly related with pack-year index (PYI) (P=0.026). The reconstructed mutation counts were highly correlated with SI4 (r=0.51, P

Cutaneous squamous cell carcinoma has presented an increasing burden globally, with the occurrence of metastatic cutaneous squamous cell carcinoma being a relatively rare event but presenting with significant challenges in management, and a paucity of treatment options. Waldenström’s macroglobulinemia is similarly an infrequent diagnosis. We present a rare case of a synchronous diagnosis of cutaneous squamous cell carcinoma and Waldenström’s macroglobulinemia with an associated lung mass with squamous differentiation. The considered origin of the lung mass was either metastatic cutaneous squamous cell carcinoma or a primary squamous cell carcinoma of the lung, representing a third primary malignancy. The report highlights complexities in diagnosis and management, particularly in a patient with multiple synchronous malignancies. It further emphasizes the need for expanded global availability of specific therapies, including PD-1 inhibitors.

The immune checkpoint inhibitors (ICIs) have transformed the standards of care in cancer treatment and has dramatically improved patient prognoses. As a result of the introduction of these novel treatments several types of adverse events related to ICIs (immune related adverse events ((irAEs)) have been observed and reported. In this case series we describe the clinical course of four patients, with unusual ICI induced toxicities. The first patient was a 59 year-old female who received chemo-immunotherapy (pembrolizumab) for stage 4- lung adenocarcinoma, and developed autonomic neuropathy (AN). The second and third patients were both 63 year-old males who also received chemo-immunotherapy (pembrolizumab) for stage 4-A lung adenocarcinoma. One of those patients developed palmoplantar keratoderma and one developed conjunctivitis, urethritis and arthritis (Reiter syndrome). The fourth patient was an 80 year-old male who received chemo-immunotherapy (pembrolizumab) for stage 3-A squamous cell carcinoma of the lung and developed myasthenia gravis.

Tumour-to-tumour metastasis is very unusual and has been defined as a tumour metastasis into another histologically different tumour. It is extremely rare in bone. We report a case of lung squamous cell carcinoma metastasized to an enchondroma in the femur of a patient with Ollier disease. A 60-year-old female had a history of a poorly differentiated squamous cell carcinoma of the lung. She underwent a video-assisted thoracoscopic lobectomy, and a follow-up MRI scan showed three lesions in the left distal femur and proximal tibia, which were initially interpreted as metastasis on radiology. Resection of the left proximal tibial lesion was performed, and the pathological findings were consistent with enchondroma with no evidence of metastasis. Subsequent curettage of lesions in the distal left femur revealed metastatic poorly differentiated carcinoma with foci of hyaline cartilage, which was most consistent with metastatic carcinoma in a pre-existing enchondroma. The MRI films were re-reviewed. Characteristic MRI features of enchondroma were found in the lesion in the left proximal tibia and one of the lesions in the left distal femur, while the features of the other lesion in the left distal femur included cortical destruction and extensive oedema in surrounding soft tissue, which were consistent with a malignant tumour. In addition, the enchondroma in the lateral condyle showed blurring and irregular inner margin and adjacent bone oedema, which likely represents a co-existing metastatic tumour and enchondroma. The difference in lineage was confirmed by immunohistochemistry. The final diagnosis was metastatic poorly differentiated carcinoma of the lung into a co-existent enchondroma. The diagnosis can be challenging and could be easily overlooked both radiologically and histologically. Thorough clinical and radiological information is critical for the diagnosis, and despite a very unusual event, awareness of the tumour-to-tumour metastasis phenomenon can avoid an inaccurate diagnosis by the pathologist, therefore preventing inappropriate clinical intervention.

Introduction. There is evidence that disseminated tumor cells (DOCs) in the bone marrow (BM) are precursors of subsequent distant metastases. The detection of DOCs in non-small cell lung cancer (NSCLC) will provide important information about the features of metastasis, as well as the possibilities of identifying new targets for the treatment of NSCLC. Purpose of the study is to evaluate the possibility of detection DOCs in BM and to identify the frequency of BM involvement in patients with NSCLC. Materials and methods . Morphological and immunological methods studied 62 BM samples from patients with NSCLC. DOCs analysis was performed using flow cytometry (FACSCanto II, USA, Kaluza Analysis v 2.1 software), monoclonal antibodies to CD45, cytokeratins directly labeled with various fluorochromes were used. Results . DOCs (EPCAM+CD45–) in the BM were found in 43.5 % of patients (threshold level: 1 cell per 10 million myelocaricytes). The presence of DOCs did not correlate with tumor size, lymph node status, stage of the tumor process. The highest detection rates of DOCs were observed at stages IA and IIA: 60.7 % (3/5) and 58.3 % (7/12) respectively. BM involvement in adenocarcinoma was observed in 45 % (15/33) cases, in squamous cell carcinoma – in 37 % (10/27) samples (p = 0.501). It was found that DOCs are more often detected in more differentiated tumors (p = 0.023). Significant correlations between the presence of DOCs in the BM and myelogram parameters have not been established. A decrease in the number of granulocyte germ cells was observed in 4 % of BM involvement (p = 0.036). Conclusion. The possibility of detecting DOCs in the BM of NSCLC patients has been established. BM involvement was 43.5 %. DOCs are detected even in the early stages of NSCLC. Relationship between BM involvement and the degree of tumor differentiation was found. More frequent BM involvement was observed in adenocarcinoma compared with squamous cell carcinoma of the lung. Compliance with patient rights and principles of bioethics The study protocol was approved by the biomedical ethics committee of N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. All patients gave written informed consent to participate in the study.

In an asymptomatic 77-yearold woman, former 55 packyears smoker, a routine X-ray showed a 45-mm superior left lobe lesion. A chest CT scan confirmed a 36-mm superior left lobe lesion and an aortic-pulmonary lymph node enlargement measuring 42 mm, suspicious for neoplasia. A PET-CT scan showed an elevated uptake in the primary lesion, in the aortic-pulmonary lymph node, and in the left hilar lymph node with a standardized uptake value - 40 and 4.3, respectively. CT-guided lung biopsy showed a lung squamous cell carcinoma. An endobronchial ultrasound-guided transbronchial needle aspiration for lymph-node staging was negative for lymph node spread. Brain MRI was negative. Final staging was determined to be a IIIA (T2bN2) squamous cell carcinoma of the lung.

Background Immune checkpoint inhibitors, such as pembrolizumab, a humanized monoclonal antibody against programmed death-1, elicit antitumor activity in various types of cancers, including lung cancer. However, pembrolizumab has been reported to cause diverse immune-related adverse events associated with T-cell activation. Case presentation We present the case of a 61-year-old man with advanced non-small cell lung cancer who was administered pembrolizumab as first-line treatment. After the first dose, radiotherapy was also administered because of rapid progression of dyspnea due to bronchial obstruction by the tumor. After the fourth cycle of pembrolizumab treatment, the patient presented with severe oral pain and multiple oral ulcers on the lips and throughout the oral cavity. Diagnostic tests including viral serology, fungal cultures, and esophagogastroscopy did not provide conclusive results. A biopsy of the damaged oral mucosa showed infiltration of inflammatory cells with no other specific findings. In addition, multiple skin rashes were observed on various areas of the patient’s body, most notably in the area that had previously been irradiated. Given that there was no other apparent cause, the patient’s symptoms were considered to be an immune-related adverse event due to pembrolizumab treatment. The oral mucositis and skin rash gradually improved over a month with corticosteroid treatment. Conclusion Immune checkpoint inhibitors have recently been introduced into the clinical practice. Their use is gradually increasing as monotherapy or in combination with other cytotoxic chemotherapeutic agents. Since immune check point inhibitors such as pembrolizumab have not been used in the clinical setting for very long, we wish to share this case report in order to build a better understating of the rare and unknown side effects of treatment with immune check point inhibitors. The potential side effects of combined therapy must be monitored carefully.

There are no universally accepted grading systems in pulmonary squamous cell carcinoma (pSQCC). Recently, tumor budding, cell nest size, and spread through airspaces (STAS) have been proposed as grading scheme candidates. Tumor budding is a well-established independent prognostic factor in colorectal cancer. The International Tumor Budding Consensus Conference (ITBCC) provided consensus on scoring in 2016, albeit for colorectal cancers. Here, we aimed to validate the ITBCC method in pSQCC and evaluate additional proposed grading parameters. We analyzed a fully clinico-pathologically annotated Western single-center cohort of 354 consecutive primary resected pSQCC (resected 2000-2013). Patients with SQCC of other organs were excluded to reliably exclude lung metastases. We assessed conventional grading, keratinization, STAS, and tumor budding according to ITBCC recommendations, and correlated them with clinico-pathological parameters and survival. Tumor budding was low (0-4 buds/0.785 mm2) in 41%, intermediate (5-9 buds/0.785 mm2) in 30%, and high (≥10 buds/0.785 mm2) in 29% of cases (mean bud count = 7.45 (HE 95% CI 1.186-2.108; P = 0.002), disease-specific survival (HR = 1.710; 95% CI 1.111-2.632; P = 0.015), and PFS (HR = 1.457; 95% CI 1.123-1.890; P = 0.005). STAS or conventional tumor grade had no prognostic value. In conclusion, we confirm tumor budding as an independent prognostic marker in pSQCC and validate the ITBCC 2016 scoring recommendations in pSQCC.

Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment. High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs). A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities. This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and MUC1 in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.

In the era of coronavirus disease 2019 (COVID-19) pandemic, many cases may be misdiagnosed based on their semiology, laboratory tests or chest computed tomography (CT) images and further evaluation might be helpful in appropriately selected cases Methods:We are discussing usefulness of fluorodeoxyglucose (FDG) positron emission tomography PET/CT scan in appropriately selected suspicious cases of COVID-19 infection We are discussing two interesting cases on how18F-FDG PET/CT scan might be helpful to avoid COVID-19 infection diagnostic error Both cases had clinical symptoms suggestive for COVID-19 infection with nonspecific chest CT scan findings including lung nodules, ground glass opacities (GGOs), consolidations, and mosaic perfusion patterns This case series was approved by our institutional review board and informed consent obtained from both patients Results: In one case,18F-FDG PET/CT images demonstrated hypermetabolic mostly peripheral GGOs and nodules in both lungs with subsequent evaluation confirming COVID-19 infection The second case demonstrated right perihilar consolidation, not well appreciated on noncontrast chest CT images in addition to GGOs and further evaluation confirmed diagnosis of poorly differentiated squamous cell carcinoma of the lung Conclusion: During COVID-19 pandemic, many cases might be misdiagnosed by either clinicians or radiologists In appropriately selected cases, FDG PET/CT scan may be helpful during COVID-19 outbreak to avoid diagnostic errors © 2020 Biomedical and Biotechnology Research Journal (BBRJ) ;Published by Wolters Kluwer - Medknow

Highlights • Extremely rare case of appendiceal metastasis of squamous cell carcinoma of the lung. • Metastatic appendiceal tumor tend to perforate. • Surgery is recommended. • CT and PET-CT are useful for diagnosis., Introduction Lung cancer is one of the most common cancers. On the other hand, lung cancer metastasis to the appendix is extremely rare, and in many cases it has been diagnosed with the onset of acute perforating appendicitis. Presentation of case An 85-year-old man with fever and abdominal pain visited our hospital. He had a history of squamous cell carcinoma of the left upper and lower lobes, metastasis to the ipsilateral lung and femur. CT showed that a finding of acute perforating appendicitis, emergency cecal resection was performed. Examination of the resected specimen showed that the appendix was thickened overall, with a white nodular structure at the root and a perforation in the middle. The final diagnosis was acute perforating appendicitis caused by metastatic squamous cell carcinoma from the lung. The patient had no particular problems during the postoperative course. Discussion A PubMed search was performed, this appears to be the first reported case of appendiceal metastasis of squamous cell carcinoma of the lung. Since squamous cell carcinoma of the lung has a stronger tendency for local extension than other histological types, perforating appendicitis due to distant metastasis to the abdominal organs and metastasis to the appendix was reported as a very valuable case. Conclusion Because the progression of concomitant or secondary appendicitis is rapid, we recommend frequent imaging modalities, prophylactic appendectomy be considered for patients who also have lung cancer and imaging findings show suspected metastasis to the appendix.

The prognostic impact of tumoral programmed death-ligand 1 (PD-L1) expression in correlation with neutrophil-to-lymphocyte ratio (NLR) was retrospectively assessed in 83 patients with completely resected stage I squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Forty-three patients (51.8%) had tumor with positive PD-L1 expression. There was no significant correlation between PD-L1 expression and NLR. PD-L1-positivity failed to provide a significant prognostic impact (overall survival [OS] rate at 5 years, 53.0% in PD-L1-positive patients versus 70.1% in PD-L1-negative patients; P = 0.117). Among NLR-low (P = 0.020). In contrast, among NLR-high (≥2.2) patients, PD-L1-positivity provided no prognostic impact (P = 0.680). When NLR status and tumoral PD-L1 status were combined, “NLR-low and PD-L1-negative” was a significant and independent factor to predict a favorable recurrence-free survival (hazard ratio, 0.237 [95% confidence interval, 0.083 to 0.674]; P = 0.007) and OS (hazard ratio, 0.260 [0.091 to 0.745]; P = 0.012). These results suggest the prognostic impact of tumoral PD-L1 expression might be influenced by the status of NLR.

This case report describes a patient with squamous cell carcinoma of the lung (cT4 (Infiltration of left pulmonary artery) cN2 cM0, TNM eighth edition) and subsequent tumor-induced atelectasis of the left upper lobe. Despite initially presenting himself with a poor performance status (ECOG-PS III) and diminished lung function, the patient was treated with image-guided thoracic irradiation to a total dose of 45.0 Gy (to the whole planning target volume) / 52.5 Gy (as simultaneous integrated boost to the Primary Tumor) applied in 15 daily fractions. Through the radiation treatment, the upper lobe could be reaerated, and the patient’s lung function and performance were improved.

OBJECTIVES: To compare patterns of care and overall survival (OS) between stereotactic body radiotherapy (SBRT) and percutaneous local tumor ablation (LTA) for non-surgically managed early-stage non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2014 for adults with non-metastatic, node-negative invasive adenocarcinoma or squamous cell carcinoma of the lung with primary tumor size ≤5.0 cm who did not undergo surgery or chemotherapy and received SBRT or LTA. Patterns of care were assessed with multivariate logistic regression. After propensity-score weighting with generalized boosted regression, OS was assessed with univariate and doubly-robust multivariate Cox regression. RESULTS: Of 15,792 patients, 14,651 (93%) received SBRT and 1141 (7%) received LTA. Increasing age (OR 1.01, p = .035), treatment at an academic institution (OR 2.94, p < .001), increasing tumor size (OR 1.05, p < .001), and more recent year of diagnosis (OR 1.43, p < .001) were predictive of treatment with SBRT, whereas comorbidities (OR 0.74, p = .003) and treatment at a high-volume facility (OR 0.05, p < .001) were predictive for LTA. At a median follow-up of 26.2 months, SBRT was associated with improved OS relative to LTA within a propensity-score weighted doubly-robust multivariate analysis (HR 0.71, p < .001). On weighted subgroup analyses, improved OS was observed with SBRT for tumor sizes > 2.0 cm (HR 0.72, p < .001) and for those treated at high-volume facilities (HR 0.71, p < .001). No OS difference was found with SBRT or LTA in tumor sizes ≤2.0 cm (HR 0.90, p = .227). CONCLUSION: Within the NCDB, SBRT was more commonly utilized and was associated with improved OS when compared to percutaneous LTA for patients with non-surgically managed early-stage NSCLC. Patients with small tumor volumes likely represent an appropriate population for future prospective randomized comparisons between SBRT and LTA.

Background Systemic response to local anticancer treatment is a phenomenon called ‘abscopal effect’. The immune system is thought to play a pivotal role in its occurrence. To date, several cases have been reported, particularly in patients receiving combined local treatment and immune checkpoint inhibitors. In such cases, it is impossible to discriminate between the effects of local and systemic treatment. Only a few cases of abscopal effect have been described with radiotherapy alone. Case presentation Here, we report on the case of an 81-year-old woman with recurrent metastatic squamous cell carcinoma of the lung with mediastinal tumor bulk, lymph node and bone metastases. The patient refused to undergo systemic treatment, and palliative stereotactic radiotherapy of the mediastinal tumor was performed. At restaging with FDG-PET/CT, the patient presented with a decrease in size and FDG-avidity both of the irradiated site and of the lymph node and bone metastases (which did not receive radiotherapy). At 25 months after radiotherapy, the patient is still in remission at all sites. Conclusions This is a rare case of an abscopal effect after radiotherapy as monotherapy. It is one of the few hitherto reported for lung cancer. Several ongoing studies with a combination of radiotherapy and immunotherapy are seeking to exploit a potential synergy to induce abscopal effects.

Obstructive endobronchial tumours often cause decreased quality of life. Bronchial ethanol injection (BEI) therapy is considered an effective modality for airway dilatation or haemoptysis without specialist equipment. Here, we report experiences of two cases in which BEI therapy was effective for obstructive endobronchial tumours. In Case 1 with adenoid cystic carcinoma of the lung, BEI therapy and balloon dilatation were performed as treatment for the left main bronchus restenosis after metallic stent insertion. In Case 2 with squamous cell carcinoma of the lung, BEI therapy was performed after radiation therapy to the lesion that recurred in the entrance of the superior segment of the right lower lobe. Tumour progression was controlled with multiple BEI therapy. We consider BEI therapy useful because this procedure is easy to conduct, has low cost and can be done under particular conditions including post‐tracheobronchial stent placement and post‐radiation., Obstructive endobronchial tumours often cause decreased quality of life. Bronchial ethanol injection (BEI) therapy is considered an effective modality for airway dilatation or haemoptysis without specialist equipment. Here, we report experiences of two cases in which BEI therapy was effective for obstructive endobronchial tumours.

Introduction LGI1 encephalitis is a rare form of limbic encephalitis, that was first recognised as a primary autoimmune phenomenon, and subsequently described in association with a limited number of malignancies.1 We report a novel case of LGI-1 encephalitis occurring concurrent to a high-grade papillary urothelial carcinoma. Case Presentation A previously well 72-year-old male presented to a rural hospital with a first episode generalised tonic-clonic seizure, confusion and progressive behavioural change. He was diagnosed with LGI-1 encephalitis, with positive CSF antibodies, and mesial temporal T2 hyperintensity on MRI brain. There was no response to first line treatment with steroids, intravenous immunoglobulin, and mycophenolate. Malignancy screening revealed a lesion within the upper pole of the left kidney, favoured to represent a transitional cell carcinoma. Biopsy demonstrated a low grade papillary urothelial carcinoma. The patient’s encephalopathy continued to worsen over a period of months, despite ongoing immunosuppression. He underwent a left nephrouretectomy, and histology demonstrated a high-grade papillary urothelial carcinoma. Subsequent to this, there was improvement in cognition and behaviour. Psychotropic and immunosuppressive medications were slowly weaned. At 9-month follow-up, the patient has returned close to baseline function, and has been clinically stable off all immunosuppressive treatment. Conclusions LGI-1 encephalitis has previously been described in association with thymoma, lymphoma, teratoma, and more recently with lung and prostate cancer.2 3 We believe our case is the first report of association between LGI-1 encephalitis and high grade papillary urothelial carcinoma. References van Sonderen A, et al. Anti- LGI1 encephalitis. NeurologyOct 2016;87(14):1449–1456. Navalli D, Mutalik NR, Jayalakshmi G. Leucine-rich glioma-inactivated protein 1 antibody-positive limbic encephalitis in a patient with adenocarcinoma of prostate: a case report. Ann Indian Acad Neurol Jan-Mar 2019:22(1):121–122. Virupakshaiah A, Dalakas M, Desai N, Mintzer S, Ratliff J. A report on LGI1 encephalitis in association with squamous cell carcinoma of the lung. Neurology Apr 2019;92(15 Supp):2.2–028.

Disseminated tumor cells (DTCs) in the bone marrow (BM) have been shown to be progenitors to distant metastases. The discovery of DTCs in non-small cell lung cancer (NSCLC) will provide crucial information on the characteristics of metastasis, as well as the potential for discovering new targets for NSCLC treatment. The goal of the study is to see if DTC can be detected in BM and to determine the incidence of BM involvement in NSCLC patients, as well as their impact on the BM lymphocyte population. Morphological and immunological approaches were used to examine 62 bone marrow samples from NSCLC patients. DTCs analysis was performed using flow cytometry (FACS Canto II, the USA, Kaluza Analysis v2.1 software), monoclonal antibodies to CD45, EPCAM, CD133, lymphocyte populations CD3, CD4, CD8, CD19, CD20, CD16, CD27, directly labeled with various fluorochromes were used. The EPCAM+CD45- (DTCs) in the BM were found in 43.5% of patients (threshold level: 1 cell per 10 million myelocaricytes). The CD133+EPCAM+CD45-cells were found in 33,3% (9/27) cases. The presence of DTCs had no relationship to tumour size, lymph node status, or tumour stage. DTCs were detected at the highest rates in stages IA and IIA: 60.7 percent and 58.3 percent, respectively. In adenocarcinoma, BM involvement was found in 45 percent of cases, while in squamous cell carcinoma, it was found in 37 percent of samples (p = 0.501). DTCs were observed to be more common in highly differentiated tumours (p = 0.023). There are no significant connections between the presence of DTCs in the BM and myelogram parameters. A decrease in the number of granulocytic lineage cells was observed in 4% of BM involvement (p = 0.036). A significant increase in the level of subpopulations of CD16 + CD4-NK-cells (p = 0.002), CD27 + CD3 + T-cells (p = 0.015) with BM damage was revealed. Conclusion: It has been proven that DTCs can be detected in the BM of NSCLC patients.43.5 percent of the participants were from the BM. Even in the early stages of NSCLC, DTCs are found. There was a link discovered between BM involvement and the degree of tumour differentiation. Adenocarcinoma of the lung had a higher rate of BM involvement than squamous cell carcinoma of the lung. A relationship between DTCs and BM lymphocyte populations was revealed: subpopulations of CD16 + CD4-, CD27 + CD3+.

BackgroundSLC15A family members are known as electrogenic transporters that take up peptides into cells through the proton-motive force. Accumulating evidence indicates that aberrant expression of SLC15A family members may play crucial roles in tumorigenesis and tumor progression in various cancers, as they participate in tumor metabolism. However, the exact prognostic role of each member of the SLC15A family in human lung cancer has not yet been elucidated.Materials and MethodsWe investigated the SLC15A family members in lung cancer through accumulated data from TCGA and other available online databases by integrated bioinformatics analysis to reveal the prognostic value, potential clinical application and underlying molecular mechanisms of SLC15A family members in lung cancer.ResultsAlthough all family members exhibited an association with the clinical outcomes of patients with NSCLC, we found that none of them could be used for squamous cell carcinoma of the lung and that SLC15A2 and SLC15A4 could serve as biomarkers for lung adenocarcinoma. In addition, we further investigated SLC15A4-related genes and regulatory networks, revealing its core molecular pathways in lung adenocarcinoma. Moreover, the IHC staining pattern of SLC15A4 in lung adenocarcinoma may help clinicians predict clinical outcomes.ConclusionSLC15A4 could be used as a survival prediction biomarker for lung adenocarcinoma due to its potential role in cell division regulation. However, more studies including large patient cohorts are required to validate the clinical utility of SLC15A4 in lung adenocarcinoma.

Background The treatment strategy for aortic valve and lung cancer patients includes concomitant or two-stage procedures. Conventional simultaneous operations are usually performed under the median sternotomy. Case presentation A 72-year-old man was admitted to our hospital after experiencing chest tightness after activity for two months. Aortic valve regurgitation had been confirmed when squamous cell carcinoma of the lung was discovered. The therapeutic strategy for these patients is controversial. Considering the potential risk of tumour metastasis and the risk of cardiopulmonary bypass (CPB), we recommended concomitant transcatheter aortic valve implantation (TAVI) and a lobectomy. A trans-apical TAVI with left-sided intercostal thoracotomy was successfully performed, followed by an immediate video-assisted thoracoscopic surgery (VATS) lobectomy and selective lymph node dissection. Conclusions We suggest that a one-stage surgery of pulmonary resection following TAVI is an acceptable and safe choice after careful evaluation and should be performed as soon as possible in response to lung cancer in elderly patients with aortic valve disease.

Squamous cell carcinoma (SCC), one of the most common forms of lung cancer, shows accelerated progression and aggressive growth and usually is observed at advanced stages. SCC originates from morphological changes in the bronchial epithelium that occur during chronic inflammation: basal cell hyperplasia, squamous metaplasia, and dysplasia I-III. However, the process is not inevitable; it can be stopped at any stage, remain in the stable state indefinitely and either progress or regress. The reasons and mechanisms of different scenarios of the evolution of premalignant lesions in the respiratory epithelium are not fully understood. In this review, we summarized the literature data (including our own data) regarding genetic, epigenetic, transcriptomic and proteomic profiles of the premalignant lesions and highlighted factors (environmental causes, inflammation, and gene polymorphism) that may govern their progression or regression. In conclusion, we reviewed strategies for lung cancer prevention and proposed new models and research directions for studying premalignant lesions and developing new tools to predict the risk of their malignant transformation.

In the phase 3 LUX-Lung 8 study, the ERBB family blocker, afatinib, significantly prolonged progression-free survival and overall survival relative to erlotinib in patients with relapsed/refractory squamous cell carcinoma of the lung. We describe the case of a 53-year-old Asian male enrolled in LUX-Lung 8 who experienced long-term benefit from afatinib following failure of platinum-based chemotherapy. The patient received afatinib, and remained progression-free for 14.7 months according to investigator review. Overall survival was 17.7 months. Tolerability-guided dose adjustments helped facilitate long-term afatinib use by mitigating drug-related adverse effects. Next-generation sequencing revealed that multiple genetic aberrations were present, including epidermal growth factor receptor copy number amplification, and mutations in ERBB4, ALK, RET, and BRCA2. These findings may help to explain the enhanced response to afatinib and highlight the importance of biomarker analysis in guiding treatment decisions in patients with squamous cell carcinoma of the lung.

Background The potentially curative and/or palliative therapy for non-resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub-typing of non-small cell lung carcinoma (NCSLC) has become paramount. Objectives As there are few data from South Africa, we aimed to determine utility of TTF-1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin-fixed paraffin-embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas. Methods All cases of NSCLC diagnosed during a 3-year period were retrospectively identified. All FNA biopsy and formalin-fixed paraffin-embedded cases that were stained with TTF-1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data. Results We included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF-1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF-1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma. Conclusion All four immunostaining methods had high sensitivities. TTF-1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF-1. The specificity of CK5 for squamous cell carcinoma was higher than p63.

BACKGROUND Squamous cell carcinoma (SCC) is one the most common subtypes of non-small cell lung cancer, yet the treatment options for it remain limited. Here, we report a case of advanced SCC and review the related literature focusing on the multiline therapy method. CASE SUMMARY We report the case of a 45-year-old man with advanced SCC who was deemed inoperable at the time of advanced SCC diagnosis. The patient had been referred to our hospital in April 2013 with complaints of a stuffy feeling in the chest, dyspnea, and pain in the right shoulder lasting for 1 mo. Physical examination found no obvious abnormalities, except for lower breath sound in the right lower lung. Laboratory data were within normal limits. Immunohistochemistry analysis of the tumor tissue showed CK5/6 (+), p63 (+), CD56 (+), and Ki-67 (+, approximately 30%), and genetic testing detected no EGFR mutation. He received a multiline treatment that included chemotherapy, radiotherapy, targeted therapy, and antiangiogenic therapy. After more than 5-year comprehensive treatment, the patient remains alive. CONCLUSION This typical case highlights the importance of appropriate multiline therapy for those patients with advanced SCC.

The growth pattern of peripheral squamous cell carcinoma (SCC) of the lung is divided into two types: alveolar space-filling (ASF) growth and alveolar space-destructive (ASD) growth. The aim of this study was to investigate the clinicopathological differences between cancer cells displaying ASF and ASD growth. We analyzed 155 patients with peripheral SCC measuring 30 mm or less in diameter. The proportion of ASF in the total tumor area (%ASF) was determined using digital image analysis. We examined the clinicopathological characteristics of the cancer cells and compared the immunophenotypes of high %ASF tumors (> 30%) and low %ASF tumors (0%). Finally, we analyzed the prognostic impact of ASD area with small SCC cases (≤ 2.0 cm, n = 72). Cases of high %ASF tumors showed significantly lower frequencies of lymphovascular invasion (p = 0.008). Immunohistochemical staining revealed that the expression score of laminin-5, invasive-related molecule, in cancer cells was significantly lower in high %ASF cases than in low %ASF cases (p = 0.001). Within the same tumor, laminin-5 expression in the ASF area was significantly lower than that in the ASD area (p = 0.001). The overall 5-year survival rate of patients with a larger ASD area (> 1.0 cm2) was significantly lower than that of patients with a smaller ASD area (≤ 1.0 cm2) (p = 0.017). In this study, we clearly showed that cancer cells presenting with ASF represents a “less invasive phenotype” in peripheral SCC.

Background Afatinib is a selective, irreversible ErbB family blocker that has shown survival benefit in lung squamous-cell carcinoma (SCC) patients. Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody to the programmed cell death 1 (PD-1) receptor, has also shown survival benefit in lung SCC. Concurrent inhibition of the PD-1 and epidermal growth factor receptor (EGFR) pathways represents a rational approach to improve responses and delay the onset of treatment resistance in lung SCC. Trial Design This phase II, open-label, single-arm study ( NCT03157089 ) is designed to assess the efficacy and safety of afatinib in combination with pembrolizumab in patients with stage IIIB/IV lung SCC that has progressed during/after first-line platinum-based chemotherapy. Eligible patients must have ≥1 target lesion (as per Response Evaluation Criteria in Solid Tumors version 1.1) and must have not received previous immune checkpoint inhibitor/EGFR-targeted therapy. The recommended phase II dose (RP2D) and safety profile will be determined during a safety run-in with oral afatinib (starting dose, 40 mg/d) with intravenous pembrolizumab (200 mg every 3 weeks). In the main study, all patients will receive afatinib at the RP2D with pembrolizumab until disease progression, unacceptable toxicity, or for up to 35 cycles. The primary end point is objective response (complete + partial response). Other end points include disease control, duration of objective response, progression-free survival, overall survival, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will be performed. This study is being conducted in the United States, Spain, France, South Korea, and Turkey. Enrollment commenced in September 2017, with a target of 50 to 62 patients.

Background Patients with liver metastasis from non-small lung cancer (NSCLC) usually have multiple metastases at other sites and thus rarely undergo liver surgery. We present a case involving successful resection of rapidly growing liver metastasis from squamous cell carcinoma of the lung. Case presentation A 74-year-old man had undergone left lower lobectomy for squamous cell carcinoma of the lung, which was diagnosed pathologically as stage IA. A computed tomography (CT) scan that was taken 12 months after lung resection showed an irregularly shaped mass lesion (size, 8.3 cm) in segment five of the liver. Retrospectively, the mass was identifiable on CT 6 months before this initial recognition. Although the lesion showed rapid growth, positron emission tomography and brain magnetic resonance imaging ruled out the possibility of other metastatic lesions. Therefore, we performed right hepatectomy 14 months after the initial lung surgery. The patient was pathologically diagnosed with liver metastasis from lung cancer and has remained free from recurrence 41 months after the liver surgery, without receiving any adjuvant chemotherapy. Conclusions Although there is no reliable clinical indicator for selecting oligo-recurrence, hepatectomy could be an option for solitary liver metastasis from NSCLC for patients who are in good health.

To clarify the prognostic impact of tumor-infiltrating effector regulatory T cells (eTregs) in non-small cell lung cancer (NSCLC), eTregs were evaluated by immunohistochemical detection of CCR4 and Foxp3 in 108 consecutive surgical NSCLC tumors. Multivariate analysis showed that a high ratio of CCR4

We aimed to clarify the incidence of lymph node (LN) metastasis and its predictive factors in clinical stage IA squamous cell carcinoma (SqCC) based on radiological classification to provide surgical indications for segmentectomy. We retrospectively reviewed 192 patients with clinical stage IA SqCC who underwent complete resection with lobectomy and LN dissection at our institution between 2003 and 2019. To evaluate the incidence of LN metastasis from the perspective of indications for segmentectomy, we classified them into outer and inner groups based on the location of the tumor in the radiological findings. Regarding tumor location, 123 patients had tumors in the outer location and 69 patients had tumors in the inner location. The incidence of LN metastasis was 6% in clinical stage IA SqCC, which included 6% in the outer location and 7% in the inner location (p = 0.669). In the outer location, all LN metastases were in N1 (6%); whereas in the inner location, the incidence of N1 and N2 metastasis were 6% and 1%, respectively. Only tumors sized > 2.0 cm were found to be significantly associated with LN metastasis in clinical stage IA SqCC. We demonstrated that the incidence of LN metastasis in clinical stage IA SqCC was comparable to that of the previously reported clinical stage IA NSCLC. The incidence of LN metastasis in the outer location was similar to that in the inner location. Tumor size was only a significant factor affecting LN metastasis in clinical stage IA SqCC.

Introduction Glycoprotein NMB is a transmembrane protein linked with poor prognosis and is expressed in most squamous lung cancer. Glembatumumab vedotin is an antibody-drug conjugate targeting glycoprotein NMB, administered intravenously every 3 weeks in this phase 1 study to determine the safety, tolerability, and maximum tolerated dose in patients who had progressed on any number of previous therapies. Results A total of 13 patients were enrolled; adverse events (of any grade) including dyspnea, neutropenia, respiratory failure, anemia, increased aspartate transaminase/alanine transaminase, diarrhea, and hypophosphatemia were seen in 15% of patients. Grade 5 events included two cases of respiratory failure, either completely or partially attributed to cancer progression. The only other grade 5 event was "disease progression." The most common adverse events (23%) were decreased appetite, fatigue, rash, and weight loss. The median overall and progression-free survivals were 5.7 months (90% confidence interval: 2.5–16.8) and 2.5 months (90% confidence interval: 1.6–5.8) respectively. Conclusions Glembatumumab vedotin exhibited no serious or unexpected toxicity in this heavily pretreated population, except those caused by disease progression. Modest anticancer activity was observed with a recommendation for a phase 2 dose of 1.9 mg/kg. This portion of the study was not undertaken owing to the company's decision to discontinue drug development.

BackgroundHistological transformation of lung cancer to small cell lung cancer (SCLC) is uncommon. It is a small subset of the possible resistance mechanisms, even in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors. Reports on programmed cell death-1 (PD-1) inhibitors are rare. We report two cases of lung squamous carcinomas that transformed to SCLC during anti-PD-1 therapy, and present a detailed description of histological examination of the pre-and post-transformation tissues, hitherto absent from reports on the topic.Case PresentationCase 1: A 69-year-old man was diagnosed with stage IVa squamous cell carcinoma of the lung. He had a programmed cell death-ligand 1 tumor proportion score ≥50%. He achieved partial response after four cycles of sintilimab as first-line treatment. However, sintilimab was discontinued because of severe decrease in hemoglobin levels and platelet counts. Moreover, the occurrence of pleural effusion favored disease progression. Interestingly, bone marrow puncture and biopsy showed transformation to SCLC. Case 2: A 71-year-old man diagnosed with stage IIIa lung squamous cell carcinoma received neoadjuvant chemotherapy, underwent radical surgery, and finally received adjuvant chemotherapy. Five months later, he presented with tumor recurrence. He was treated with nivolumab, though disease progression was observed after four cycles. Notably, a subsequent computed tomography-guided biopsy showed SCLC.ConclusionPhenotypic transformation to SCLC is a potential mechanism of resistance to immunotherapy in squamous cell carcinomas of the lung. Disease progression should prompt re-biopsy to diagnose potential histological changes to assess the requirement for change in treatment.

This chapter discusses the problematic issue of occult breast carcinoma. In considering the predicament of occult breast carcinoma, five clinical situations are similarly reviewed and discussed: management of breast carcinoma presenting as axillary nodal metastases in the absence of a clinically evident primary; carcinoma in the patient who presents with an incidental, serous nipple discharge in the absence of a palpable breast mass; carcinoma occurring in a benign fibroadenoma; hemorrhage into the breast resulting from trauma obscuring underlying carcinoma; and finally, Paget’s disease of the breast. In addition to melanoma and squamous cell carcinoma of the lung, other primary sites of origin to be considered when axillary nodal metastases are shown to contain metastatic adenocarcinoma are thyroid, renal cell, stomach, pancreas, colon, and ovary. After a careful history and physical examination, bilateral mammography should be the first screening test performed. Adenofibromas represent one of the two major classes of fibroepithelial tumors of the breast.

A 70-year-old woman with metastatic squamous cell carcinoma of the lung was admitted to hospital in September 2020 with a 3-week history of generalised abdominal pain and postprandial vomiting. She had been diagnosed with squamous cell carcinoma of the lung with a programmed death ligand-1 expression of 90% and only small-volume lung metastases in February 2019. She was soon after commenced on first-line pembrolizumab, a monoclonal antibody targeting programmed cell death protein 1 (PD- 1), which led to a reduction in the size of both primary tumour and metastatic lung nodules. Medical history was significant for dyspepsia diagnosed several years prior and treated with long-term omeprazole 40 mg once a day, chronic obstructive pulmonary disease, ischaemic heart disease and type 2 diabetes. She had no history of non-steroidal …

The purpose of this study is to investigate the significance of alpha-enolase (ENO1) expression in squamous cell carcinoma of the lung (LUSC), its prognostic value, and prospective molecular mechanism. Using multiplatforms data, including in-house immunohistochemistry, in-house real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), in-house microarray, and public high-throughput data, the expression significance and prognostic role of ENO1 in LUSC tissues were analyzed comprehensively. With the combination of all eligible cases, compared with 941 non-LUSC lung tissues, ENO1 was significantly overexpressed in 1163 cases of LUSC (standardized mean difference (SMD) = 1.23, 95% confidence interval (CI) = 0.76–1.70, P P = 0.043). ENO1 and its related genes mainly participated in the pathways of cell division and proliferation. In conclusion, the upregulation of ENO1 could affect the carcinogenesis and unfavorable outcome of LUSC.