Bronchioloalveolar Carcinoma Research Articles

Abstract LB056: IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumors

Abstract Many solid tumors, such as colorectal cancer (CRC) and lung cancer, are dependent on epidermal growth factor receptor (EGFR) pathway for tumor growth. Antibodies that inhibit EGFR signaling, such as Cetuximab, show clinical efficacy but are associated with on-target toxicities that potentially limit the drug efficacy. To enhance the EGFR signaling inhibition and reduce on-target toxicities, we performed bioinformatics analysis for EGFR/TAA co-expression. We found that B7-H3, a member of the B7 family of immune checkpoint proteins, is broadly expressed in many solid tumors and their expression correlates with EGFR expression in multiple cancers, including lung cancer, head and neck cancer, pancreatic cancer and esophageal cancer. Using Innovent’s proprietary Innobody platform, we developed a bispecific antibody, IBI334, against B7-H3 and EGFR. IBI334 has an EGFR arm for signal blockage and is coupled with a fine-tuned B7-H3 arm with optimal affinity and binding domain. With the aid of B7-H3, IBI334 showed enhanced EGFR signal inhibition than Zalutumumab (EGFR mAb) and Amivantamab (c-met/EGFR bsAb). In addition, IBI334 is afucosylated to enhance its antibody-mediated cell cytotoxicity (ADCC) effects as compared to wild type antibody. IBI334 showed significantly better in vivo efficacy than Amivantamab in NCI-H358 (bronchioalveolar carcinoma with KRAS-G12C mutation), NCI-H292 (lymph node metastasis of a pulmonary mucoepidermoid carcinoma), SK-MES1 (lung cancer) and SK-MES1-LTC (lung cancer with EGFR L858R, T790M and C797S mutations) xenograft models and comparable efficacy in NCI-H322-EGFRexon20ins (lung cancer) model. Cetuximab, an EGFR monoclonal antibody, had high on-target toxicity with 50% early mortalities in cynomolgus monkeys at 120/75 mg/kg/week. With the careful design of B7-H3/EGFR bispecific antibody, IBI334 ameliorated the on-target toxicities and showed only slight hardening of the skin at the injection site at 120 mg/kg/week. As a result, IBI334 has a large therapeutic window of >200 folds. In conclusion, IBI334 is a potent B7-H3/EGFR bispecific antibody with broad application in many EGFR-driven solid tumors. The large therapeutic window enables safe and effective cancer treatment at high exposure levels. Citation Format: Jian Guan, Shuaixiang Zhou, Weiwei Wu, Tianyu Zhu, Lei Cao, Ming Wu, Ninghuan Li, Fenggen Fu, Zhengguan Liao, Shuming Lin, Zeyu Liu, Mengjia Zhu, Nana Luo, Ying Zhang, Tiong Sun Chia, Bingliang Chen, Kaijie He. IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB056.

Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas.

Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With < 70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6cm (range 1.6-8cm), with 24% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95%. Emperipolesis was identified in 88% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31%) harboring MET SNVs. In 1/5 (20%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to "type 1" PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.

Lung carcinogenicity by whole body inhalation exposure to Anatase-type Nano-titanium Dioxide in rats.

To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO2), F344/DuCrlCrlj rats were exposed to aNTiO2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m3. The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m3-exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m3-exposed females and were not statistically significant. However, the incidence in the 8 mg/m3-exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m3-exposed carcinogenicity groups. The aNTiO2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure.

Iodide-Induced Severe Encephalopathy: A Case Report and Literature Review.

A physically independent and mentally competent 61-year-old gentleman was diagnosed with left upper alveolar spindle cell carcinoma. He underwent left infrastructure maxillectomy with reconstruction and had bismuth iodoform paraffin paste packed in the post-operative cavities. The patient subsequently exhibited labile emotions and acute delirium. Further investigation showed that his urine iodine level was highly elevated. He eventually made a full recovery and returned home.

Demographics of the tumor formerly known as bronchiolo-alveolar carcinoma.

e20604 Background: Bronchiolo-alveolar carcinoma (BAC) is a rare subtype of non-small cell lung cancer of the lung periphery, often characterized by lepidic growth. Although BAC has undergone various reclassifications in recent years, International Classification of Disease codes still classifies these subtypes using the same codes that previously belonged to BAC. Changing diagnostic criteria and other factors cause BAC to be among the most overdiagnosed forms of lung cancer and thus a demographic study could provide insight into trends. Methods: A retrospective cohort analysis utilizing the National Cancer Database (NCDB) from 2004 – 2020 included patients with malignant forms of BAC (Invasive mucinous adenocarcinoma, mixed invasive mucinous, and nonmucinous adenocarcinoma) confirmed through histology. Demographic factors such as sex, age, race, Hispanic status, median household income, insurance status, facility type, county population, distance from facility, and Charlson Deyo score were analyzed by descriptive statistics and incidence trends. Results: In total, 12,607 patients were identified in the database with a confirmed diagnosis of BAC between 2004 – 2020. The number of cases per year remained steady (mean = 565.4) until 2018. From 2018 to 2020, the average number of diagnoses per year was 1575.0. The average age of diagnosis was 69.3 years (SD = 10.7, range = 10 to &gt; 90 years). 58.1% of the cases were female patients. The top primary sites were the lower and upper lobes (46.2% and 39.9% respectively). The majority (59.2%) had Charlson-Deyo comorbidity scores of 0. Most cases occurred in Non-Hispanic White persons (86.8%). More patients were in the top quartile of income earners (34.0%) compared to those in lower quartiles. Medicare was the insurance provider for most patients (65.0%). More patients were diagnosed in counties with a population over 1 million (52.4%). More patients were treated in comprehensive community cancer programs (38.1%) followed closely by academic cancer programs (35.2%). Patients lived an average of 31.6 miles (SD = 113.0, range = 0.1 – 2390.7) from the treatment facility. Conclusions: This is the first NCDB analysis on the demographics of BAC. The sudden rise in cases per year in 2018 aligns with the changing pathologic and histologic definitions for BAC. A 2006 review of BAC found that 50-70% of cases occur in female patients, similar to our results. The majority of BAC patients tend to be non-Hispanic and White with a primary site diagnosis in the lower lobe, followed by the upper lobe. BAC patients are more likely to be in the top income quartile, live in densely-populated metropolitan areas, and receive treatment in a non-academic program. Further research is needed to better understand the impact of demographic, socioeconomic, and environmental factors on the diagnosis and prognosis of BAC, especially because its diagnostic criteria have changed recently.

Upper Jaw Cancer: A Case Report of Surgical Intervention and Defect Repair in an Upper Alveolar Squamous Cell Carcinoma

Upper Jaw Cancer: A Case Report of Surgical Intervention and Defect Repair in an Upper Alveolar Squamous Cell Carcinoma

Bronchioloalveolar Carcinoma Mimicking Section as Pneumonia: A Case Report

Bronchioloalveolar Carcinoma (BAC) also known as alveolar cell carcinoma is a subtype of adenocarcinoma that is more common in women and non smokers. It accounts for almost 5% of all lung cancers. Bronchioloalveolar carcinoma may appear as a wide variety ranging from solitary nodule to patchy, lobar or multilobar opacities. The mucinous, non mucinous, ambiguous or mixed are the histological types of BAC. The mucinous variety of BAC sometimes may present as a consolidation which is indistinguishable from an infective pneumonia on a radiological picture. Hereby, authors present a case of 65-year-old male patient, who was evaluated for non resolving pneumonia for a time span of one year. He presented to the Respiratory Medicine Outpatient Department with a cough and expectoration for the past nine months. Antibiotic courses did not provide the patient any sort of relief and there was no change in the size of the lesion. Chest X-ray has shown right sided non homogenous opacity and later Contrast Enhanced Computerised Tomography (CECT) thorax and biopsy (computed tomography-guided) was done from the same site for further evaluation. Cytology done from CT-guided biopsy sample showed typical lepidic growth pattern. Histopathologically, it showed mucinous variety of BAC. Usually, the patients have no symptoms but an abnormal chest X-ray, while a few have features like coughing with expectoration and pain in the chest. Only cytology or biopsy can help with a proper diagnosis, which can be done via needle biopsy (CT or fluoroscopy guided) or transbronchial biopsy and Bronchoalveolar Lavage (BAL). It has rarely been documented in the literature that BAC masquerades as a consolidation with very little change.

Upper Jaw Cancer: A Case Report of Surgical Intervention and Defect Repair in an Upper Alveolar Squamous Cell Carcinoma

Upper Jaw Cancer: A Case Report of Surgical Intervention and Defect Repair in an Upper Alveolar Squamous Cell Carcinoma

Biphasic squamoid alveolar papillary renal cell carcinoma: A unique papillary renal cell carcinoma with distinctive morphology, immunophenotype and molecular genetic features.

Biphasic squamoid alveolar papillary renal cell carcinoma (BSARCC) is a recently described renal tumor, considered as a unique rare morphological pattern of PRCC in the 2022 WHO classification. We aimed to further explore the clinicopathological, immunophenotypic, and molecular genetic characteristics of BSARCC in a Chinese cohort. The clinicopathological data of 8 patients with BSARCC were collected for morphology observation and immunohistochemical staining. QRT-PCR was performed to detect BRAF gene mutation. The abnormalities of chromosomes 7, 17 and Y, and CCND1 gene were investigated by fluorescence in situ hybridization (FISH). Among the 8 cases, 5 were males and 3 were females. 6 cases were revealed by physical examination incidentally, and 2 cases were presented with low back pain and hematuria. Microscopically, the tumors were mainly composed of small cells with different proportions of large cells. The small cells were arranged in acinar, compact and long narrow tubular, solid sheet or papillary structures. Single or clustered large cells were arranged in glomerular structures in the acinar cavity formed by small cells. Among the 8 cases, 2 cases had a small amount of typical type I papillary renal cell carcinoma without large cells at the edge of the tumor. And 5 cases presented the swallowing phenomenon of lymphocytes or neutrophils in the cytoplasm of a few large cells. Immunohistochemical staining showed both large and small cells were diffusely and strongly positive for CK7, P504s, EMA, and vimentin. MET was expressed in most tumors (6/8), and large cells (70-90%) exhibited a prominent higher positive rate than small cells (20-90%). CD57 was positive in both large and small cells in 5 cases. Notably, CyclinD1 was exclusively expressed in large cells, while RCC marker was mainly expressed in small cells. Large cells showed a higher ki67 index than small cells. BRAF V600E mutation was negative in all cases. FISH showed 4 cases had chromosome 7 trisomy, 2 cases had chromosome 17 trisomy, and 4 of 5 male patients had Y chromosome deletion. CCND1 gene amplification or rearrangement was not revealed in any case. Follow-up data were available in 8 cases ranging from 3 to 66 months, and there was no recurrence or metastasis of the tumor. BSARCC is a rare unique morphological pattern of papillary renal cell carcinoma, featured by the presence of two cell populations of different morphology and immunophenotype. Distinctive CyclinD1 and RCC immunostainings are essential in diagnosing this type of renal tumor. Large and small cells may be tumor cells in different stages of proliferation and differentiation, and large cells immunoreactive to CyclinD1 and presenting higher ki67 index might be more aggressive than small cells. The anomalous expression of CyclinD1 in large cells is not due to the aberrance of CCND1 gene itself. Most BSARCC is low-stage and inert with a favorable prognosis. Our study not only validates previously described clinicopathological features, but also supplements the clinicopathological features and expands the potential genetic alterations and available clinical outcome data of BSARCC.

CYSTIC ADENOMATOID MALFORMATION OF THE LUNG IN AN ADULT: A CASE REPORT

CYSTIC ADENOMATOID MALFORMATION OF THE LUNG IN AN ADULT: A CASE REPORT

Biphasic squamoid alveolar renal cell carcinoma: description of a rare case and a literature analysis.

Biphasic squamoid alveolar renal cell carcinoma: description of a rare case and a literature analysis.

Microwave Reduced Graphene Oxide as Efficient NIR Photothermal Agent

Current study reports the enhanced cancer cells photothermal ablation efficiency of Microwave Reduced Graphene Oxide (MRGO). Reduction of chemically exfoliated graphene oxide has been carried out using a microwave (700W for 5 minutes). The produced MRGO have been characterized with TEM, SEM, XRD, FTIR, RAMAN, AFM and UV-Vis spectroscopy. MRGO nano size sheets with average lateral dimension ~200nm, exhibited higher NIR absorption efficiency, in comparison to Graphene Oxide (GO). Photothermal efficacy (at optimized NIR laser 808 nm, power of 5.0W/cm2 for 5 min) of MRGO have been tested against human alveolar epithelial carcinoma cell (A549) and human colorectal carcinoma cells (HCT116). As a result, a significant decrease in cell viability by 84% and 80% for A549 and HCT116 cell lines respectively has been estimated. No significant toxicity has been observed with MRGO (in absence of NIR treatment) at the concentrations well above the doses needed for photothermal heating against the same cancer cells. Our study introduces MRGO as a biocompatible and efficient photothermal agent.

Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study

BackgroundConsidering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure.MethodsRats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice.ResultsDWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans.ConclusionsOur results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored.

PEComa-like Neoplasms Characterized by ASPSCR1-TFE3 Fusion: Another Face of TFE3-related Mesenchymal Neoplasia.

Identical TFE3-related gene fusions may be found in renal cell carcinoma and mesenchymal neoplasms such as alveolar soft part sarcoma and TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Among mesenchymal neoplasms, the ASPSCR1-TFE3 gene fusion has previously been described only in alveolar soft part sarcoma. We report 3 unusual mesenchymal neoplasms harboring the ASPSCR1-TFE3 gene fusion, the morphologic phenotype of which more closely matches PEComa rather than alveolar soft part sarcoma. All 3 neoplasms occurred in females ranging in age from 18 to 34 years and were located in the viscera (kidney, bladder, and uterus). All 3 contained nests of epithelioid cells bounded by fibrovascular septa. However, all were associated with hyalinized stroma, tight nested architecture, mixed spindle cell and epithelioid pattern, clear cytoplasm, and lacked significant discohesion. Overall, morphologic features closely resembled PEComa, being distinct from the typical alveolar soft part sarcoma phenotype. While none of the neoplasms labeled for HMB45, cytokeratin, or PAX8 all showed positivity for TFE3 and cathepsin K, and all except 1 were positive for smooth muscle actin. One patient developed a liver metastasis 7 years after nephrectomy. These cases bridge the gap between 2 TFE3-rearranged neoplasms, specifically alveolar soft part sarcoma and Xp11 translocation PEComa, highlighting the relatedness and overlap among Xp11 translocation neoplasms. While most TFE3-rearranged neoplasms can be confidently placed into a specific diagnostic category such as alveolar soft part sarcoma, PEComa, or Xp11 translocation renal cell carcinoma, occasional cases have overlapping features, highlighting the potential role that the cell of origin and the specific gene fusion play in the phenotype of these neoplasms.

Biphasic squamoid alveolar renal cell carcinoma: Cytologic features of a rare entity

Biphasic squamoid alveolar renal cell carcinoma is a newly described rare morphologic variant of papillary renal cell carcinoma. Its characteristic histomorphology and immunophenotype have been well described in the literature. Namely, BSARCC is composed of a dual-cell population with nests of larger squamoid cells surrounded by a single layer of cuboidal cells in alveolar arrangements. Invariably, the squamoid component expresses cyclin D1. More recently, MET alterations have been identified within a subset of BSARCC, raising the possibility for targeted MET inhibitor therapy. To the best of our knowledge the cytomorphologic features of BSARCC have yet to be described. Herein we correlate the cytologic features (percutaneous image-guided fine needle aspiration) of BSARCC to its corresponding histomorphology and immunophenotype (core needle biopsy).

Role of Computed Tomography Chest and Bronchoscopy in the Diagnosis of Endobronchial Masses

Endobronchial Masses (EBM) can present with Central Airway Obstruction (CAO). Causes of EBM can be benign or malignant in origin. Malignant endobronchial masses are more common than expected. However, they are underdiagnosed because of their non specific clinical and radiological presentations. The authors present a case series of seven cases of endobronchial growth. Three cases were of squamous cell carcinoma, one was bronchioloalveolar carcinoma, one was a typical carcinoid, and another one was Endobronchial Tuberculosis (EBTB). All were males, and five were above 50 years of age. Breathlessness, cough, wheeze, and haemoptysis were the common symptoms. In three patient diagnoses were delayed as Computed Tomography (CT) chest and bronchoscopy were not done during the initial evaluation. In one of the cases, empiric treatments for pulmonary tuberculosis delayed definite diagnoses of endobronchial growths. In another patient, empiric treatments for pleural tuberculosis delayed the diagnosis of carcinoma of the lung. In one patient empiric treatment with corticosteroids for asthma delayed the diagnosis of EBTB. However, in three patients early CT chest and bronchoscopy revealed the diagnoses of different types of carcinomas of the lung despite acute symptoms. One patient had carcinoma of the lung and EBTB. Early and optimal use of chest CT and bronchoscopy can clinch the diagnoses. Investigation should be done for both EBTB and malignancy in a case of endobronchial growth.

Pathological and epidemiological aspects of ovine pulmonary adenocarcinoma: An overview

Ovine pulmonary adenocarcinoma (OPA) has been identified in several sheep rearing countries around the world with the exception of a few countries like Australia, New Zealand and Iceland. The outbreak reports from various countries reveal that OPA has emerged as an important economic and animal welfare problem. In addition to its importance as a veterinary problem, OPA has wider relevance for fundamental studies on cancer as it has pathological and epidemiological features similar to bronchioloalveolar carcinoma in humans. Therefore, OPA has been considered as a useful animal model to study various aspects of pulmonary carcinogenesis. There are no reliable diagnostic tests to detect the disease in the pre-clinical stage. The molecular tests developed to detect the infection in clinical samples are less sensitive and have their own limitations. In the absence of serological tests for diagnosis in the flock, eradication of this disease becomes difficult. It was found that once animals get infected, it becomes carrier for life. Due to unavailability of reliable diagnostic tests and an effective vaccine, the control on spread of the OPA virus is difficult. In India, the disease is rarely studied for the detection of OPA and limited to the outbreaks and histopathological diagnosis only. The present overview discusses the major issues of OPA research related to etiology, epizootiology, pathology and prevention with recent advancement.

Pulmonary arterial thromboses and gall bladder wall oedema in a cat with bronchioloalveolar carcinoma

AbstractAn 11‐year‐old male neutered British Shorthair cat presented with acute collapse, dyspnoea and paraparesis. Left atrial enlargement and left‐sided congestive heart failure were excluded by point‐of‐care ultrasonography, and gall bladder wall oedema was detected. Comparative venous blood gas analyses confirmed ischaemia of the hindlimbs, and echocardiography was consistent with pulmonary hypertension. The patient was euthanased and a postmortem examination revealed pulmonary artery thromboses associated with bronchioloalveolar carcinoma.

Rapid killer: Lung squamous cell cancer

Background: Lung cancer is one of the leading causes of death despite improvement in treatment modalities such as immunotherapy with chemotherapy and precise radiotherapy. NSCLC is a heterogeneous group of diseases that differs in cytology and includes adenocarcinoma, squamous cell carcinoma, bronchioloalveolar carcinoma, and poorly differentiated carcinoma. Usually, NSCLC, in contrast to SCLC, spreads locally, and the doubling time of squamous cell carcinoma is 133 days which classifies it as a relatively slow-growing tumor.Case presentation: We present the case of a 72-year-old male, recently diagnosed with squamous cell carcinoma in the right upper lobe along with secondary deposits. Few days after diagnosis, the patient had severe respiratory distress. This endobronchial tumor has increased significantly in size upon bronchoscopic visualization causing a complete obstruction of his right main bronchus and hypoxemic respiratory failure requiring intubation.Conclusion: To our knowledge, there are few reported cases where lung adenocarcinoma progressed rapidly over days. Squamous cell carcinoma usually takes 3 to 6 months to double in size, but in our case, the progression was very fast. In the last decade, it was confirmed that the doubling time of a tumor is an independent factor in the prognosis of lung cancer patients. On the other hand, further studies are needed to identify genes associated with rapid progression and a worse prognosis for lung squamous cell carcinoma. Hence, this aggressive tumor is a “rapid killer.”

Diagnosis-to-surgery interval and survival for different histologies of stage I-IIA lung cancer.

BackgroundGuidelines on timeliness of lung cancer surgery are inconsistent. Lung cancer histologic subtypes have different prognosis and treatment. It is important to understand the consequences of delayed surgery for each lung cancer histologic subtype. This study aimed to examine the association between diagnosis-to-surgery time interval and survival for early stage lung cancer and selected histologic subtypes.MethodsPatients diagnosed with stage I–IIA lung cancer between 2004 and 2015 receiving definitive surgery and being followed up until Dec. 31, 2018, were identified from Surveillance, Epidemiology, and End Results database. Histologic subtypes included adenocarcinoma, squamous or epidermoid carcinoma, bronchioloalveolar carcinoma, large cell carcinoma, adenosquamous carcinoma, carcinoid carcinoma, and small cell carcinoma. Diagnosis-to-surgery interval was treated as multi-categorical variables (<1, 1–2, 2–3, and ≥3 months) and binary variables (≥1 vs. <1 month, ≥2 vs. <2 months, and ≥3 vs. <3 months). Outcomes included cancer-specific and overall survival. Covariates included age at diagnosis, sex, race, marital status, tumor size, grade, surgery type, chemotherapy, radiotherapy, and study period. Kaplan-Meier survival curves and Cox proportional hazards regression models were applied to examine the survival differences.ResultsWith a median follow-up time of 51 months, a total of 40,612 patients were analyzed, including 40.1% adenocarcinoma and 24.5% squamous or epidermoid carcinoma. The proportion of patients receiving surgery <1, 1–2, 2–3, and ≥3 months from diagnosis were 34.2%, 33.9%, 19.8%, and 12.1%, respectively. Delayed surgery was associated with worse cancer-specific and overall survival for all lung cancers, adenocarcinoma, squamous or epidermoid, bronchioloalveolar, and large cell carcinoma (20–40% increased risk). Dose-dependent effects (longer delay, worse survival) were observed in all lung cancers, adenocarcinoma, and squamous and epidermoid carcinoma. No significant association between surgery delay and survival was observed in adenosquamous, carcinoid, and small cell carcinoma.ConclusionsOur findings support the guidelines of undertaking surgery within 1 month from diagnosis in patients with stage I–IIA lung cancer. The observed dose-dependent effects emphasize the clinical importance of early surgery. Future studies with larger sample size of less frequent histologic subtypes are warranted to provide more evidence for histology-specific lung cancer treatment guidelines.