The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique.

BACKGROUND: Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN). METHODS: We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case. RESULTS: In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases, > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case. CONCLUSIONS: Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.

Recent advancement on PD-L1 expression quantification: the radiologist perspective on CT-guided FNAC.

PURPOSE: We aimed to evaluate the feasibility, accuracy, and safety of Programmed Death-1/ Programmed Death-Ligand 1 (PD-1/ PD-L1) expression quantification in cytology cell-block samples obtained through transthoracic CT-guided fine-needle aspiration cytology (FNAC) from the interventional radiologist's perspective. METHODS: We performed a consecutive unselected series of 361 CT-guided biopsies of pulmonary nodules and masses which came to our observation from June 2017 to October 2018. For each case, exhaustive clinical, morphologic, molecular and tomographic data were available. All the material obtained was fixed in formalin to obtain a cell-block for the pathologist, who performed immunohistochemical analysis to detect PD-L1 expression levels on each sample. RESULTS: Of all the analyzed samples, 93.6% (338/361) were defined to be diagnostic, including neoplastic (72%, 260/361) and non-neoplastic lesions (21.6%, 78/361); only 6.4% (23/361) of them resulted in nondiagnostic specimens. Non-small cell lung cancer (NSCLC) accounted for 73.8% of neoplastic lesions (192/260): most of them were adenocarcinoma (83%, 160/192), followed by squamous carcinoma (14%, 27/192) and poorly differentiated carcinoma (3%, 5/192). In 96% of NSCLC (184/192), the diagnosis was reached either in the absence of complications or with early minor complications. PD-L1 expression was evaluated in all 192 NSCLC cytology specimens: 180 immunostainings were found to be adequate for PD-L1 testing. In 76% of cases, PD-L1 expression level was lower than 50%. CONCLUSION: The findings of our study indicate that PD-L1 quantification using a cell-block approach on CT-guided FNAC is a feasible and safe technique and should be taken into account alongside with core biopsy approach, especially in case of advanced disease and/or fragile and older patients.

Low-Grade Papillary Schneiderian Carcinoma: Report of a Case with Molecular Characterization.

In 2015, Lewis et al. first described low-grade papillary Scheneiderian carcinoma (LGPSC) of the sinonasal tract. Their case resembled a sinonasal papilloma clinically and histopathologically; however, invasion and metastasis resulted in the death of the patient despite absence of malignant cytologic features. Additional reports established LGPSC as a distinct entity and characterized its immunohistochemical profile. Diffuse expression of low molecular weight cytokeratins, positivity for p16 and p53 in at least 50% of cells, a high Ki-67 index, and absence of human papillomavirus (HPV)-DNA was observed across all reported cases. We report an additional case of LGPSC and describe the clinical, histologic, and immunohistochemical features. In contrast to sinonasal papillomas, the case was negative for HPV-DNA and showed no mutations in the EGFR and KRAS hotspot regions.

An underrated copmlication of the organs' transplantations

INTRODUCTION: Tacrolimus is routinely used to prevent rejection after organs' transplantation. Neurotoxicity is underrated side effect, where no typical clinical, radiological, or histopathological patterns have yet been found. The present study is targeted to a review of the literature on tacrolimus-induced neurotoxicity secondary to organs' transplantation, aimed to its prompt diagnosis. MATERIALS AND METHODS: Multiple PubMed searches were performed to review relevant articles regarding tacrolimusinduced neurotoxicity. An illustrative case is also presented. RESULTS: Twenty articles published between 1997 and 2019 were identified and reviewed. Clinical manifestations of tacrolimus-induced neurotoxicity varied. MRI showed subcortical white matter involvement in most cases. Symptoms and radiological signs occurred at various drug dosages and blood tacrolimus levels. Tacrolimus discontinuation resulted in disappearance or marked reduction of neurological symptoms and imaging lesions in every case. CONCLUSION: Neurotoxicity is an underrated reversible side effect of chronic tacrolimus administration after organs' transplantation. Its prompt diagnosis, based on T2 and FLAIR MRI sequences neuroimaging combined with stereotactic biopsy, allows the discontinuation of the drug and a recovery of the patient in most of the cases. KEY WORDS: Stereotactic Biopsy, Neurotoxicity, Tacrolimus, Transplant Complications, Transplantation, Tumorlike Lesion.

Imaging Accuracy in Preoperative Staging of T3-T4 Laryngeal Cancers.

BACKGROUND: Preoperative imaging impacts treatment planning and prognosis in laryngeal cancers. We investigated the accuracy of standard computed tomography (CT) in evaluating tumor invasions at critical glottic areas. METHODS: CT scans of glottic cancers treated by partial or total laryngectomy between Jan 2015 and Aug 2019 were reviewed to assess levels of tumor invasion at critical glottic subsites. CT accuracy in the identification of tumor extensions was determined against the gold standard of histopathological analysis of surgical samples. RESULTS: This study included 64 patients. In the anterior commissure, CT showed high rates of false positives at all levels (sensitivity 56.2-70%, specificity 87.8-92.3%); in the anterior vocal fold, it overestimated the deep invasion (19.5% specificity, 90.3% sensitivity), while it underestimated the extralaryngeal spread (63.6% sensitivity, 98.1% specificity). In the posterior paraglottic space (pPGS), false negative results were more frequent for superficial extensions (25% sensitivity, 95.8% specificity) and deep invasions (58.8% sensitivity, 82.3% specificity). Shorter disease-specific and disease-free survivals were associated with pStage IV (p: 0.045 and 0.008) and with the pathological involvement of pPGS (p: 0.045 and 0.015). CONCLUSIONS: Negative prognostic correlation of pPGS involvement was confirmed on histopathological data. CT staging did not provide a satisfactory prognostic stratification and should be complemented with magnetic resonance imaging.

Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review.

BACKGROUND: Surgical approaches to orbital apex lesions involve the medial and lateral corridors. The transorbital neuroendoscopic (TONE) approach has been recently proposed as an elegant, bone-sparing, and minimally invasive alternative for tumors of the lateral orbital compartment. However, its effectiveness compared with the standard lateral orbitotomy approach still requires confirmation. The aim of the present report was to describe the key technical aspects of the lateral trans-eyebrow TONE approach and to review the relevant reported data on the surgical management of ectopic orbital intraconal meningiomas. CASE DESCRIPTION: The TONE approach was used in a 63-year-old man with a diagnosis of a left ectopic intraconal meningioma of the orbital apex involving the lateral compartment. The TONE approach involves performing a lateral 3-cm eyebrow skin incision. A subperiosteal dissection of the periorbita permits intermittent medialization of the eyeball and extracapsular access to the orbital apex region. A lateral periorbital incision under full endoscopic view allows for early access to 2 different intermuscular corridors that do not require mechanical retraction of the oculomotor muscles. The reported data included studies of 23 cases of intraconal meningioma, which were usually benign, although the meningothelial variant has been associated with a greater recurrence rate. CONCLUSIONS: In our limited experience, the lateral TONE approach proved to be an effective, feasible, versatile, and minimally invasive promising alternative to resect orbital apex meningiomas involving the lateral compartment. Its technical strengths include increased illumination and magnification of the surgical field and an unparalleled lateral view of the orbital apex.

Dysembryoplastic Neuroepithelial Tumors: What You Need to Know.

OBJECTIVE: An updated and comprehensive review on dysembryoplastic neuroepithelial tumor (DNET) focusing on differential diagnosis, atypical presentation, seizure outcome, and risk of malignant transformation. METHODS: A PubMed/MEDLINE-based literature search has been performed using "dysembryoplastic neuroepithelial tumor" as a keyword. Two treated cases characterized by an atypical presentation have been reviewed. RESULTS: Of 1162 articles, 200 relevant studies have been selected. DNET is a benign mixed neuronal-glial tumor causing drug-resistant epilepsy primarily in children and young adults. The typical radiological pattern is a magnetic resonance imaging (MRI) T1-hypointense, T2-, and fluid-attenuated inversion-recovery hyperintense multicystic lesion involving the cerebral cortex with no edema. Contrast enhancement may be present and a focal cortical dysplasia is commonly associated with it. MRI diffusion, perfusion, and spectroscopy have a paramount role in the differential diagnosis. The "specific glioneuronal elements" are pathognomonic. They are positive for S100 protein, synaptofisin, neuronal nuclei, oligodendrocyte transcription factor, neurite outgrowth inhibitor, and microtubule-associated protein 2, but negative for glial fibrillary acidic protein. As opposed to v-myb avian myeloblastosis viral oncogene homolog, isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutation and codeletion 1p-19q, fibroblast growth factor receptor 1 and BRAF V600E mutations are present. The effectiveness of surgery on seizure outcome has been established. Rare malignant transformations have been reported, especially in extra-temporal and complex forms. CONCLUSIONS: Advanced MRI techniques are fundamental in the differential diagnosis for DNET versus other low-grade gliomas. Immuno-phenotype assessment and search for fibroblast growth factor receptor 1 and BRAF V600E mutations limit the risk of misdiagnoses. A gross total tumor removal is generally associated with a seizure-free outcome. Recurrences and malignant transformations may rarely follow, legitimizing MRI surveillance in cases of subtotal tumor resection.