Histological Entity Research Articles

New clinicopathological concept of endometrial carcinoma with integration of histological features and molecular profiles.

The dual-stratified pathway of endometrial carcinomas (ECs) has long been dominant. However, in 2013, The Cancer Genome Atlas (TCGA) defined four EC subgroups with distinctive prognoses. Inspired by TCGA, in 2018, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) provided four pragmatic molecular classifiers to apply surrogate immunohistochemical markers to TCGA subgroup categorization. These trends prompted the revision of 2020 WHO Classification of Female Genital Tumors, 5th edition (2020 WHO classification), in which four molecular subtypes are recognized: POLE-ultramutated; mismatch repair-deficient; p53-mutant; and no specific molecular profile. In the 2020 WHO classification, the diagnostic algorithm is characterized by prioritizing POLEmut over other molecular abnormalities. Following the 2020 WHO classification, Federation of International Gynecology and Obstetrics (FIGO) proposed a new staging system in 2023. The updated system focuses on diagnostic parameters, such as histological type and grade, lymphovascular space invasion, and molecular alterations. These new histomolecular diagnostic concepts of ECs are being accordingly introduced into the routine pathology practice. For the first time, the 2020 WHO classification includes mesonephric-like adenocarcinoma (MLA) as a novel histological entity, mimicking the conventional mesonephric adenocarcinoma, but is considered of Müllerian ductal origin.

Oral fibrolipoma in dogs: Retrospective case series study and comparative review.

Fibrolipoma is defined as a typical lipoma transected by variable amounts of paucicellular and collagenous fibrous components. Oral and lingual fibrolipomas are well-recognized histological entities in human medicine that are slightly more prevalent in females, occur most commonly after the fourth decade, and arise from the buccal mucosa. The documentation of this neoplasm in the oral cavity is lacking in veterinary medicine. Through a multi-institutional retrospective compilation of cases submitted to diagnostic pathology services, here we describe the clinical and pathologic features of oral fibrolipomas in dogs. A total of 112 cases of oral fibrolipomas in dogs were retrieved. The mean age was 10.1 years (range 2-16 years, ±2.63 years standard deviation), with an average tumor size of 1.7 cm (range 0.2-8 cm, ±1.1 cm standard deviation). The most common location was the tongue (57.1%, 64/112), followed by the buccal mucosa (15.2%, 16/112), sublingual area (8.0%, 9/112), gingiva and lip (4.5%, 5/112 each), and palate (1 case). The anatomical location of oral fibrolipomas only differed significantly among the dog breeds (P < .001) but not among sex, age, anamnesis, or reason for submission. The tumor was most commonly reported in males (69.7%, 78/112), and in 62.5% (70/112) of the cases, the tumor was an incidental finding. Fibrolipoma should be considered a differential diagnosis when considering benign lingual and other oral soft tissue masses in dogs.

Fertility-sparing strategy in a rare case of highly malignant Dicer-1-associated sarcoma of the cervix

IntroductionWe present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri.CaseThe patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free.DiscussionPrimary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors.ConclusionDecision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient.

Not every knee tumour is a ganglion - retrospective analysis of benign and malign tumour entities around the knee.

Due to a lack of routine, there is often uncertainty regarding diagnostics of tumours around the knee joint. This study aimed to provide knowledge about the frequency, distribution and diagnostic algorithm of different bone and soft tissue tumour entities of the knee at a large referral university hospital in Germany. Retrospective, longitudinal, single-centre study that reviewed adult patients from 2010 until 2020 with a suspected tumours diagnosis around the knee at a university cancer centre. Inclusion criteria were adults with true bone or soft-tissue tumours in the knee joint and in its adjacent compartments. Suspected diagnosis, histological tumour entity, localization and its surgical treatment by biopsy, resection, osteosynthesis or tumour endoprosthesis were investigated. A total number of 310 adult patients were included with a mean age of 54.2 ± 18.8 years. In total 160 (51.6%) soft-tissue tumours (69/43.1% benign; 74/46.2% malignant; 17/10.6% intermediate), 92 (29.6%) primary bone tumours (46/50% benign; 39/42.3% malignant; 7/7.6% intermediate), 36 (11.6%) metastases and 22 (7.1%) lymphomas were detected. 171 (55.1%) tumours were classified as malignant. Suspected diagnosis was matched with histology in 74.5% (231/310) of all cases. In 6 cases a primarily suspected benign diagnosis turned out to be malignant. The majority of primary bone tumours was cartilage derived (63.1%;58/92) and located in the distal 2/3 of the femur, whereas intracapsular tumours of the knee joint were rare (13.0%). Soft-tissue tumours were located primarily in the middle third of the thigh (36.8%). The MRI was the diagnostic tool of choice in 98.1% of soft tissue tumours and 82.6% bone tumours. Awareness is crucial for detecting rare and malignant tumours around the knee, with adipocytic tumours being the most common soft tissue tumour and chondrogenic tumours as the most prevalent malignant bone tumour. Accurate diagnosis of bone tumours necessitates radiographs and frequently an additional MRI scan, while soft tissue tumours require mandatory MRI scans. Incorrectly diagnosing a tumour can have severe consequences, emphasizing the need for histological confirmation in all cases. Additionally, malignant tumours within joint capsules in adults are infrequent.

Global–local consistent semi-supervised segmentation of histopathological image with different perturbations

A histopathological image is a microscopic image applied to examine cellular and tissue structures and identify any abnormalities or disease processes. Histopathological image segmentation is a prerequisite step for analyzing histopathological images that can divide an image into meaningful regions or objects to accurately classify and analyze tissue structures, cellular regions, or particular histological entities. However, the existing deep learning based pathological image segmentation methods require huge annotation efforts from the pathologists, which is labor-intensive and time-consuming. In this scenario, it has become a hotspot to leverage abundantly available unlabeled data to help learn segmentation models given limited labeled data. In this paper, we propose a global–local consistent semi-supervised segmentation (GLCS) model that enforce the consistency of the segmentation results with weak and strong perturbations on unlabeled data. In GLCS, we firstly generate different weak perturbations for each unlabeled sample, and then add a regularization term to ensure the segmentation consistency among different weak perturbations. Next, different from the existing studies applying the regression methods to match the segmentation results among different perturbations, our methods are based on the generative adversarial learning that can keep the global structure consistency among unlabeled data with different strength of perturbations. Finally, we also add a patch-correlation based regularization term to preserve the local structure similarity among different perturbations images. We validate our GLCS on three datasets, i.e. Glas, Crag and MoNuSeg. The experimental results show that our method can achieve to the dice ratio of 90.35, 82.61 and 81.60 with 1:1 proportion of labeled data, which are significantly superior to the state-of-the-art semi-supervised histopathological image segmentation methods. Our code is public available at https://github.com/ISBELLAG/GLCS.

Sarcomatoid and Rhabdoid Renal Cell Carcinoma: Clinical, Pathologic, and Molecular Genetic Features.

Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid morphologies has an aggressive biological behavior and a typically poor prognosis. The current 2022 WHO classification of renal tumors does not include them as distinct histologic entities but rather as transformational changes that may arise in a background of various distinct histologic types of RCC. The sarcomatoid component shows malignant spindle cells that may grow as intersecting fascicles, which is reminiscent of pleomorphic undifferentiated sarcoma. The rhabdoid cells are epithelioid cells with eccentrically located vesicular nuclei with prominent nucleoli and large intracytoplasmic eosinophilic inclusions. Studies have shown that RCCs with sarcomatoid and rhabdoid differentiation have distinctive molecular features. Sarcomatoid RCC harbors shared genomic alterations in carcinomatous and rhabdoid components, but also enrichment of specific genomic alterations in the sarcomatoid element, suggesting molecular pathways for development of sarcomatoid growth from a common clonal ancestor. Rhabdoid differentiation also arises through clonal evolution although less is known of specific genomic alterations in rhabdoid cells. Historically, treatment has lacked efficacy, although recently immunotherapy with PD-1/PD-L1/CTLA-4 inhibitors has produced significant clinical responses. Reporting of sarcomatoid and rhabdoid features in renal cell carcinoma is required by the College of American Pathologists and the International Collaboration on Cancer Reporting. This manuscript reviews the clinical, pathologic, and molecular features of sarcomatoid RCC and rhabdoid RCC with emphasis on the morphologic features of these tumors, significance of diagnostic recognition, the molecular mechanisms of tumorigenesis and differentiation along sarcomatoid and rhabdoid lines, and advances in treatment, particularly immunotherapy.

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study

Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P=0.09) and overall survival (OS) (log-rank P=0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n=17) than in the IDC group (n=10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Umberto VeronesiFoundation.

Pleural mesothelioma in situ : a comprehensive review.

Pleural mesothelioma is a rare and aggressive cancer that affects the pleura. In recent years, there has been increasing interest and attention in detecting and diagnosing early-stage or precancerous forms of mesothelioma because of its severe prognosis and short life expectancy at the time of diagnosis. Mesothelioma in situ represents a clear opportunity to improve and innovate the diagnostic approach and the multimodality treatment of mesothelioma: the diagnosis of pleural mesothelioma at the 'in-situ phase' means early disease detection and thus paves the way to new possible curable strategies. Since 2021, when mesothelioma in situ was finally identified and described as a new histological entity, its diagnosis and management became a challenge and the subject of ongoing research; several aspects remain open and still outstanding as regards diagnostic techniques, time and probability of progression, need for and methods of follow up, aggressive and early surgery. This narrative review aims to provide a comprehensive overview of mesothelioma in situ covering its definition, risk factors, diagnostic criteria, and tricky aspects of early detection. It also highlights its clinical significance, new perspectives, and potential future indications in the context of pleural mesothelioma multidisciplinary management.

Biomarkers for Early Cancer Detection: A Landscape View of Recent Advancements, Spotlighting Pancreatic and Liver Cancers.

Cancer is one of the leading causes of death worldwide. Early cancer detection is critical because it can significantly improve treatment outcomes, thus saving lives, reducing suffering, and lessening psychological and economic burdens. Cancer biomarkers provide varied information about cancer, from early detection of malignancy to decisions on treatment and subsequent monitoring. A large variety of molecular, histologic, radiographic, or physiological entities or features are among the common types of cancer biomarkers. Sizeable recent methodological progress and insights have promoted significant developments in the field of early cancer detection biomarkers. Here we provide an overview of recent advances in the knowledge related to biomolecules and cellular entities used for early cancer detection. We examine data from the CAS Content Collection, the largest human-curated collection of published scientific information, as well as from the biomarker datasets at Excelra, and analyze the publication landscape of recent research. We also discuss the evolution of key concepts and cancer biomarkers development pipelines, with a particular focus on pancreatic and liver cancers, which are known to be remarkably difficult to detect early and to have particularly high morbidity and mortality. The objective of the paper is to provide a broad overview of the evolving landscape of current knowledge on cancer biomarkers and to outline challenges and evaluate growth opportunities, in order to further efforts in solving the problems that remain. The merit of this review stems from the extensive, wide-ranging coverage of the most up-to-date scientific information, allowing unique, unmatched breadth of landscape analysis and in-depth insights.

Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain.

Neuroinflammation is acknowledged as a pivotal pathological event after cerebral ischemia. However, there is limited knowledge of the molecular and spatial characteristics of nonneuronal cells, as well as of the interactions between cell types in the ischemic brain. Here, we used spatial transcriptomics to study the ischemic hemisphere in mice after stroke and sequenced the transcriptomes of 19,777 spots, allowing us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of ischemia-associated gene expression in the peri-infarct area of the ischemic hemisphere. Analysis of ligand-receptor interactions in cell communication revealed galectin-9 to cell-surface glycoprotein CD44 (LGALS9-CD44) as a critical signaling pathway after ischemic injury and identified microglia and macrophages as the main source of galectins after stroke. Extracellular vesicle-mediated Lgals9 delivery improved the long-term functional recovery in photothrombotic stroke mice. Knockdown of Cd44 partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation and remyelination. In summary, our study provides a detailed molecular and cellular characterization of the peri-infact area in a murine stroke model and revealed Lgals9 as potential treatment target that warrants further investigation.

INVASIVE MICROPAPILLARY BREAST CARCINOMA DISCOVERED DURING THE INVESTIGATION OF ACUTE RESPIRATORY DISTRESS IN A POSTPARTUM WOMAN: A CASE REPORT

Invasive micropapillary carcinoma of the breast is a rare histological entity among breast cancers, representing 2 to 3% of breast carcinomas. Its clinical and radiological presentation is similar to other carcinoma entities. Diagnosis is primarily histological but remains challenging and dependent on the operator. It is an aggressive tumor with both local and distant extension (lymphatic, cutaneous, etc.). In this study, we present a case of invasive micropapillary carcinoma of the breast discovered during acute respiratory distress due to serous extension (pleural effusion). Through this case, we will discuss the various clinical, radiological, therapeutic, and particularly histological aspects of this rare type of carcinoma.

Insights into the Distribution Patterns of Foot and Ankle Tumours: Update on the Perspective of a University Tumour Institute.

The rarity of foot and ankle tumours, together with the numerous histological entities, presents a challenge in accumulating sufficient patients to draw reliable conclusions. Therefore, we decided to present an update of a retrospective analysis of their distribution patterns, comprising 536 cases of foot and ankle tumours presented to our tumour board between June 1997 and June 2023. Our aim was to provide a comprehensive overview of the prevalence and distribution patterns of benign and malignant bone and soft tissue tumours of the foot and ankle. A total of 277 tumours involved bone (51.7%). Of these, 242 (87.4%) were benign and 35 (12.6%) were malignant. In addition, 259 soft tissue tumours (48.3%) were found, of which 191 (73.7%) were benign and 68 (26.3%) were malignant. The most common benign bone tumours were simple bone cysts, enchondromas, osteochondromas, aneurysmal bone cysts, and lipomas of bone. Common benign soft tissue tumours included a tenosynovial giant cell tumour, haemangioma, plantar fibromatosis, schwannoma, and lipoma. The most common malignant soft tissue tumours were synovial sarcoma, malignant melanoma, and myxofibrosarcoma. In terms of anatomical location, the hindfoot was the most common site (28.7%), followed by the midfoot (25.9%), ankle (25.4%), and forefoot (20.0%). The distribution of benign entities often follows typical patterns, which may facilitate an early diagnosis even without biopsy (e.g., simple bone cyst, plantar fibromatosis). On the other hand, the distribution patterns of many rare or malignant entities are inconsistent. Individual soft tissue malignancies occur very sporadically, even over long periods of time and in specialized tumour centres. It is therefore important to recognise that any suspicious mass in the foot and ankle must be considered a possible malignancy until proven otherwise.

Pleural malignant fibrosolitary tumor: A rare entity

Solitary fibrous tumors of the pleura represent a rare histological entity, belonging to the groups of pleural tumors of sub-mesothelial origin , therefore some authors evoke the hypothesis of its proliferation from submesothelial tissue of the pleura .The clinical manifestations are varied and the certain diagnostic can only be made by anatomopathological examination which evaluates precise malignancy criteria. Total surgical removal is the only way to ensure a definitive cure. We report the case of 65-year-old woman with a malignant solitary fibrous tumor operated by thoracotomy with complete resection. Through this presentation, we would like to underline the rarity of this entity

The influence of clinical experience on reliable evaluation of pharyngeal and laryngeal lesions: comparison of high-definition laryngoscopy using narrow band imaging with fibre-optic laryngoscopy.

Fibre-optic laryngoscopy is still widely used in daily clinical practice; however, high-definition laryngoscopy using narrow band imaging could be more reliable in characterising pharyngeal and laryngeal lesions. Endoscopic videos were assessed in a tertiary referral hospital by 12 observers with different levels of clinical experience. Thirty pairs of high-definition laryngoscopy with narrow band imaging and fibre-optic laryngoscopy videos were judged twice, with an interval of two to four weeks, in a random order. Inter- and intra-observer reliability, sensitivity and specificity were calculated in terms of detecting a malignant lesion and a specific histological entity, for beginners, trained observers and experts. Using high-definition laryngoscopy with narrow band imaging, inter-observer reliability for detecting malignant lesions increased from moderate to substantial in trained observers and experts (high-definition laryngoscopy with narrow band imaging κ = 0.66 and κ = 0.77 vs fibre-optic laryngoscopy κ = 0.51 and κ = 0.56, for trained observers and experts respectively) and sensitivity increased by 16 per cent. Inter-observer reliability increased with the level of clinical experience, especially when using high-definition laryngoscopy with narrow band imaging.

Contact Endoscopic Surface Vascular and Epithelial Morphology in Leukoplakia and Carcinoma of the Vocal Cords

Purpose Leukoplakia is a macroscopic morphological term for thick white or grey mucosal patches that can represent various histologic diagnostic entities ranging from hyperplasia to malignancy. Aim was the study morphology of the superficial mucosa and microvascular network of the vocal cords in patients with suspected glottic squamous cell carcinoma (SCC) using contact endoscopy (CE). Material and Methods Seventy-nine patients (21 female, 58 male), with a mean age of 57.5 years ± 7.12 (range, 32–73 years), were prospectively enrolled and evaluated. Of these patients, 58 had leukoplakia (Group A/41 males and 17 females, with a mean age of 53.7 years ± 6.65), and 21 (Group B/ 17males and 4 females/ with a mean age of 60.5 years ± 6.04) had malignant lesions (pT1, n = 6; p T2, n = 8; pT3, n = 8; Group B), as proven by the results of the histological examination. Further, 79 non-smokers (control group—group C) were studied. CE imaging findings were classified into five types (I to V) based on the features of the mucosal intra-epithelial capillary loops. CE findings were correlated to the histologic findings. A separate analysis involving smoking status was done. Results The CE-based intraepithelial papillary capillary loop classification score was strongly correlated with the histological findings. Age was strongly associated with both malignancy and bilateral involvement. Smoking habits didn’t significantly differ between patients with unilateral and bilateral SCC. Conclusions CE imaging of the vocal cord mucosal capillaries may be useful for the early detection of glottic SCC and pre-cancerous lesions.

The genetics of portal hypertension: Recent developments and the road ahead.

Portal hypertension (PH), defined as a pathological increase in the portal vein pressure, has different aetiologies and causes. Intrahepatic PH is mostly secondary to the presence of underlying liver disease leading to cirrhosis, characterized by parenchymal changes with deregulated accumulation of extracellular matrix and vascular abnormalities; liver sinusoidal endothelial cells and hepatic stellate cells are key players in PH progression, able to influence each other. However, PH may also develop independently of parenchymal damage, as occur in portosinusoidal vascular disorder (PSVD), a group of clinical and histological entities characterized by portal vasculature dysfunctions. In this particular group of disorders, the pathophysiology of PH is still poorly understood. In the last years, several genetic studies, based on genome-wide association studies or whole-exome sequencing analysis, have highlighted the importance of genetic heritability in PH pathogenesis, both in cirrhotic and non-cirrhotic cases. The common PNPLA3 p.I148M variant, one of the main determinants of the susceptibility to steatotic liver disease, has also been associated with decompensation in patients with PH. Genetic variations at loci influencing coagulation, mainly the ABO locus, may directly contribute to the pathogenesis of PH. Rare genetic variants have been associated with familiar cases of progressive PSVD. In this review, we summarize the recent knowledges on genetic variants predisposing to PH development, contributing to better understand the role of genetic factors in PH pathogenesis.

ALK Gene Rearrangement Screened by Immunohistochemistry and FISH in Non-Small Cell Bronchopulmonary Cancer (NSCLC) in Senegalese Subjects

Introduction: Bronchopulmonary cancer is a worldwide scourge. In Senegal, the prevalence is 3.8%. The main objective of this work is to study ALK gene rearrangement, by immunohistochemistry and FISH, to propose a more targeted therapy to our patients. Patients and Methods: A multicenter, cross-sectional, descriptive, prospective study between 2018 and 2020 of bronchopulmonary cancer cases. Histology, immunohistochemistry, and FISH were performed. Results/Discussion: The mean age of patients was 60.29 ± 6.7 years. Non-small-cell lung cancer (NSCLC) predominated (92% of patients). In NSCLC, adenocarcinoma was the most frequent histological entity (34.2%). The ALK-antibody was searched in all NSCLC. Immunohistochemistry, confirmed by FISH, yielded positive results for ALK expression in 4.5% of cases. The majority of ALK-positive patients were male (66.6%) and non-smokers (66%). Significant associations between ALK gene rearrangement and histological type, notably adenocarcinoma (p=0.001) and squamous cell carcinoma (p=0.002), were found. Age (p=0.5), gender (p=0.4), and smoking (p=0.4) were not significantly associated with ALK rearrangement. Despite the relatively low incidence, ALK rearrangement should be routinely investigated in NSCLC, particularly in patients with adenocarcinoma. The discovery of the molecular anomaly should lead to the prescription of targeted therapies with tyrosine kinase inhibitors, which will considerably improve our patients' survival. Conclusion: IHC analysis confirmed by FISH yielded positive results for ALK expression in 4.5% of patients. Progress in understanding oncogenesis has led to the development of targeted therapies. Therefore, the prescription of these drugs is conditioned by the presence of the target molecular anomaly, which must be routinely sought in our patients.

False-Positive Atypical Endocervical Cells in Conventional Pap Smears: Cyto-Histological Correlation and Analysis

Introduction: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant glandular lesions overlap with histologically proven reactive lesions. Methods: A total of 45 conventional Pap smears diagnosed as atypical endocervical cells, not otherwise specified (AEC, NOS) with human papillomavirus (HPV) status available were blindly evaluated in a search for 38 cytomorphological features representing background, architectural, cellular, and nuclear features. Of the cases, 30 represented histologically proven benign changes, and 15 represented histologically proven adenocarcinoma in situ (AIS) or endocervical adenocarcinoma (EAC) cases. The benign biopsies were re-evaluated, and the associations of the cytomorphological features or combinations of them with specific histological features and entities were statistically examined. Results: The most frequent histological findings in the benign group were squamous metaplasia, inflammation, tubal metaplasia, and microglandular hyperplasia. The statistical analysis revealed cytological features associated with squamous metaplastic changes, inflammation, and microglandular hyperplasia. Unfortunately, no cytomorphological feature was sufficiently specific to confidently leave the lesion without follow-up and histological correlation. Degeneration and nuclear crowding were the most salient features that distinguished the instances of glandular atypia with benign follow-up histology from those with histologically proven AIS or EAC (26.7 vs. 60.0%, p = 0.030, and 50.0 vs. 86.7%, p = 0.017). Conclusion: Additional methods besides cytomorphology are required to reliably distinguish smears with AEC, NOS harbouring only benign histological changes from those exhibiting endocervical glandular malignancy.

Evaluation of ALK, EGFR and PD-L1 Mutations in Pulmonary Carcinomas through Immunohistochemistry

Introduction: Lung cancer, with about 2.2 million new cases and 1.8 million deaths, is the second most commonly diagnosed cancer and the leading cause of cancer death in 2020. Immunohistochemistry (IHC) now is used not only to diagnose and classify lung tumors into subtypes, but also to determine the eligibility of patients for different molecular-targeted therapies. &#x0D; Objectives : Study of ALK, EGFR and PD-L1 mutations in Pulmonary Carcinomas through immunohistochemistry examinations to help determine the prognosis and cases that may benefit from target therapy. Detection of possible links between ALK, EGFR, PD-L1 and other variables such as age, sex, histological entity and degree of tumor differentiation. &#x0D; Materials and Methodology: The study is retrospective and includes 266 patients diagnosed with lung cancer who underwent biopsy at the American Hospital in the period 2016-2020. Tissues obtained were subjected to IHC examination using antibodies against factors EGFR, ALK, PD-L1, etc. &#x0D; Results: The study showed that out of 266 patients, 24% of lung cancer cases are females and 76% are males. The average age was 61.8 years. No statistically significant relationship was found between ALK, PD-L1 and EGFR with variables such as age, gender and degree of differentiation of adenocarcinomas. No significant link was found between ALK and PD-L1 and the histological entity, but a significant link was found between EGFR and histological type of pulmonary carcinomas. &#x0D; Conclusions : Lung cancer is one of the most common cancers, found mainly in men, but also in women. Nowadays, IHC helps not only to diagnose lung cancer, but also to determine patients who can respond to target therapy and their prognosis. Therefore, the use of IHC to detect ALK, EGFR, PDL-1 mutations and their links to patient characteristics is becoming increasingly necessary.

Two Head and Neck Carcinomas With Squamous and Mucinous Components and Human Papillomavirus Associations: Maxillary Mucoepidermoid Carcinoma ex Sinonasal Schneiderian Papilloma and Tonsillar Invasive Stratified Mucin Producing Carcinoma (ISMC).

Carcinomas of the head-and-neck region with squamous and glandular/mucinous features constitute a heterogeneous group, with a significant minority of tumors showing an human papillomavirus (HPV) association. The differential diagnosis is usually between mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma. We present here two tumors that exemplify both the challenges of diagnostic classification, as well as the complex relationship to HPV: (a) a low risk HPV positive/p16 negative carcinoma that is most consistent with a relatively typical intermediate grade mucoepidermoid type carcinoma with complete MEC phenotype (three cell types), originating from intranasal sinonasal papillomas with exophytic and inverted patterns, and invading surrounding maxillary compartments, and (b) a p16 and keratin 7 (KRT7) positive carcinoma of the right tonsil, characterized by stratified squamous and mucinous cell (mucocyte) features. Whereas the first tumor represents a typical MEC ex-Schneiderian papilloma, the second is morphologically most consistent with the, novel for this anatomic location, diagnosis of "invasive stratified mucin producing carcinoma" (ISMC), pointing to an analogy to similar, high-risk HPV-driven malignancies recently described in the gynecologic (GYN) and genitourinary (GU) areas. Both tumors, despite their mucoepidermoid-like features had no connection to salivary glands and lacked the MAML2 translocation typical of salivary gland MEC, pointing to a mucosal/non-salivary gland origin. Using these two carcinomas as examples, we attempt to address questions related to: (a) the histological distinction between MEC, adenosquamous carcinoma, and ISMC, (b) similarities and differences between these histological entities in mucosal sites versus morphologically similar salivary gland tumors, and (c) the role of HPV in these tumors.