Pulmonary basaloid squamous cell carcinoma in a dog

A 9-year-old neutered male crossbred dog with a 4-week history of progressive vestibulocerebellar signs was presented for necropsy examination. Gross examination revealed neoplastic growth in the lungs, thoracic lymph nodes, the left kidney and the cerebellum. Microscopically, the tumour consisted of an infiltrative, densely cellular, basaloid epithelial neoplastic growth with extensive areas of abrupt keratinization. Immunohistochemically, neoplastic cells expressed p63 and partially expressed cytokeratins 5/6. Based on these findings, the tumour was diagnosed as a primary pulmonary basaloid squamous cell carcinoma (BSSC) with metastasis to regional lymph nodes, kidney and brain. As far as the authors are aware, this is the first description of BSCC in an animal species

heterogeneity of large cell carcinoma of the lung an immunophenotypic and mirna based analysis

Large cell carcinomas (LCCs) of the lung are heterogeneous and may be of different cell lineages. We analyzed 56 surgically resected lung tumors classified as LCC on the basis of pure morphologic grounds, using a panel of immunophenotypic markers (adenocarcinoma [ADC]-specific, thyroid transcription factor-1, cytokeratin 7, and napsin A; squamous cell carcinoma [SQCC]–specific, p63, cytokeratin 5, desmocollin 3, and Δnp63) and the quantitative analysis of microRNA-205 (microRNA sample score [mRSS]). Based on immunoprofiles 19 (34%) of the cases were reclassified as ADC and 14 (25%) as SQCC; 23 (41%) of the cases were unclassifiable. Of these 23 cases, 18 were classified as ADC and 5 as SQCC according to the mRSS. Our data show that an extended panel of immunohistochemical markers can reclassify around 60% of LCCs as ADC or SQCC. However, a relevant percentage of LCCs may escape convincing immunohistochemical classification, and mRSS could be used for further typing, but its clinical relevance needs further confirmation. Large cell carcinoma (LCC) of the lung is 1 of 4 major histopathologic tumor subtypes recognized by current classifications of lung tumors. However, although squamous cell carcinoma (SQCC), adenocarcinoma (ADC), and small cell carcinoma are well-defined entities with typical morphologic, immunophenotypic, and molecular features, LCCs, with the exception of the rare neuroendocrine, rhabdoid, basaloid, and lymphoepithelioma-like subtypes, are defined as poorly differentiated non–small cell tumors lacking features of ADC and SQCC. Therefore, the term LCC has frequently and improperly been used as a synonym of undifferentiated non–small cell lung carcinoma (NSCLC) and has been used as a "wastebasket" for tumors lacking a definite morphologic pattern. Studies show that, by using ancillary techniques, a relevant percentage of LCCs could be reclassified as SQCC or ADC. Gene profiling shows that most LCCs have profiles quite similar to ADC or SQCC. 1-3 Similarly, by using appropriate immunohistochemical stains, almost two thirds of LCCs can be reclassified as poorly differentiated ADC or SQCC. 4,5 These studies have profound clinical relevance because rendering a diagnosis of LCC may represent a challenge for oncologists who need accurate subtyping of lung cancers to provide patients with optimal targeted chemotherapeutic agents, showing different efficacy with specific NSCLC categories (usually effective for ADC and not for others). 6,

Soluvapaa DNA ei-pienisoluisessa keuhkosyövässä

Keuhkosyöpä aiheutti vuonna 2018 eniten syöpäkuolemia. Laaja-alaisesta tutkimuksesta huolimatta keuhkosyöpäpotilaiden ennuste on edelleen keskimäärin huono. Keuhkosyöpä jaetaan erilaisiin histologisiin alatyyppeihin. Kaksi pääalatyyppiä ovat ei-pienisoluinen keuhkosyöpä ja pienisoluinen keuhkosyöpä. Nykyään keuhkosyöpädiagnostiikan kulmakivinä ovat kuvantamistutkimukset ja kudosnäytteen ottaminen. Parantavaan eli kuratiiviseen hoitotulokseen päästään useimmiten vain kirurgisella hoitolinjalla paikallisessa varhaisen vaiheen ei-pienisoluisessa keuhkosyövässä. Vain 20–25% ei-pienisoluisista keuhkosyövistä soveltuvat kuratiiviseen kirurgiseen hoitoon. Lisäksi 30–55%:lla kuratiivisen kirurgisen hoidon saaneista potilaista syöpä uusiutuu. Soluvapaa DNA (cfDNA) on solun ulkopuolista DNA:ta, jota vapautuu kaikista kehon soluista ruumiin nesteisiin, kuten verenkiertoon. Kun cfDNA on peräisin syöpäsoluista, kutsutaan sitä kiertäväksi kasvain-DNA:ksi (ctDNA). Viime vuosina ctDNA:n käyttö syöpämarkkerina on herättänyt kiinnostusta, koska sitä voisi käyttää keuhkosyöpäpotilaan hoitoketjun eri vaiheissa, kuten tuumorin aikaisemmassa havaitsemisessa, diagnostiikassa, yksilöllisen hoitovalinnan tukena, hoitovasteen seurannassa ja syövän uusiutumisen toteamisessa. Soluvapaa DNA -näytteitä voidaan ottaa nestebiopsioiden muodossa esimerkiksi verestä tai pleuranesteestä. Yksi nestebiopsian eduista on se, että se on nykyään usein käytettyyn radiologisesti ohjattuun kudosbiopsiaan verrattuna vähemmän kajoavampi ja mahdollistaa taudin seurannan. Nestebiopsia voisi tulevaisuudessa ainakin osittain korvata kudosnäytteen ottamisen. Vaikka cfDNA:n käyttö kliinisessä työssä vaatii vielä lisää tutkimuksia, on hyvin mahdollista, että cfDNA:sta tulee tulevaisuudessa keskeinen osa onkologisia hoitoja.Lung cancer caused the most cancer related deaths world-wide in 2018 and despite extensive research the prognosis of a lung cancer patient remains generally poor. Lung cancer is divided into different histological subtypes the two main types being non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Currently lung cancer is diagnosed with radiological imaging and tissue biopsies. Generally, curative treatment can be achieved only by surgical treatment of early-stage NSCLC. Only 20–25% of NSCLC are eligible for curative intent surgery. Furthermore, 30–55% of these patients have a fatal recurrence of lung cancer. Cell-free DNA (cfDNA) has gained interest in the field of oncology. Generally, cfDNA refers to all the DNA in the body that is free from cellular confinement. Circulating tumor DNA (ctDNA) is cfDNA that originates from cancer cells. It has potential to be a minimally invasive method used in various parts of cancer management including early detection, diagnosis, treatment, monitoring the response for treatment and identification of drug resistance. While the use of cfDNA still lacks clinical trials to be widely used in a clinical setting, it is highly possible that cfDNA analysis establishes a central role in the future in the oncological field

NUT Carcinoma of the Salivary Glands: Clinicopathologic and Molecular Analysis of 3 Cases and a Survey of NUT Expression in Salivary Gland Carcinomas.

NUT carcinoma (NC) represents a rare subset of highly aggressive poorly differentiated carcinomas characterized by rearrangement of the NUT (aka NUTM1, nuclear protein in testis) gene, most commonly fused to BRD4. Originally described as a mediastinal/thymic malignancy, NC has been reported at a variety of anatomic regions including the upper and lower aerodigestive tract. To date, only 7 NC cases of probable salivary gland origin have been reported. We herein describe 3 new cases (all affecting the parotid gland) in 2 women (39- and 55-y old) and 1 man (35-y old). Histologic examination showed poorly differentiated neoplasms composed of poorly cohesive small-sized to medium-sized cells with variable squamoid cell component that was focal and abrupt. Immunohistochemistry showed uniform expression of p63 and distinctive punctate expression of the NUT antigen in the tumor cell nuclei. Review of the reported salivary gland NC cases (total, 10) showed a male:female ratio of 1.5:1 and an age range of 12 to 55 years (median, 29 y). Site of the primary tumor was the parotid (7), sublingual (2), and submandibular (1) glands. All presented as rapidly growing masses treated by surgery followed by adjuvant radiotherapy/chemotherapy. Initial nodal status was positive in 8/10. At last follow-up (1 to 24 mo; median, 5 mo), 7/10 patients died of disease at a median of 5.5 months (1 to 24 mo) and only 2 were disease free at 7 and 14 months. Of 9 cases with genetic data, the fusion partner was BRD4 (n=7), non-BRD4/3 (n=1), or undetermined (n=1). None of 306 carcinomas spanning the spectrum of salivary carcinoma types screened by NUT immunohistochemistry was positive. This is the first small series on salivary NC highlighting the importance to include this rare disease in the differential diagnosis of poorly differentiated salivary gland carcinomas and in cases of presumable poorly differentiated carcinoma of unknown origin

Evaluation of Epidermal Growth Factor Receptor by Mutation Specific Immunohistochemistry in Non Small Cell Lung Carcinomas

INTRODUCTION: Lung Carcinoma is the leading cause of cancer related deaths worldwide. They are classified broadly into small cell and non small cell carcinomas by updated WHO 2015 classification. Non small cell lung carcinomas are caused by many genetic alterations,of which EGFR mutation plays a key role. EGFR mutation is significant since it can be targeted by pharmacological inhibitors. This study was conducted at Coimbatore medical college Hospital to evaluate the EGFR mutation expression by Immunohistochemistry in non small cell lung carcinomas. MATERIALS AND METHODS: This was a prospective study done for a period of one year. 30 samples diagnosed as non small cell carcinomas favouring adenocarcinoma or squamous cell carcinoma, were studied for EGFR mutations by immunohistochemistry using monoclonal antibody. The staining intensity was graded based on a scoring system.They were then compared with those in the literature. RESULTS: Out of 30 cases studied, Squamous cell carcinoma was the most common histological subtype(17 cases). There appears to be a significant correlation between males, higher age and squamous cell carcinoma histology. EGFR mutation expression do not have any association with age, sex and personal history of smoking. EGFR expression and histological subtype do not reveal any significant association in this study. But EGFR expression was found to be more common in adenocarcinomas. CONCLUSION: This prospective study concludes that though there is no statistically significant association between EGFR expression and tumor histology,EGFR expression was found to be more common in adenocarcinomas.The staining intensity was 3+ in 17 cases, 2+ in 5 cases. 1+ in 6 cases, negative in 2 cases. Thus EGFR mutation analysis by Immunohistochemistry can be used as a guidance for targeted therapy in low resource settings where molecular studies are limited

A study of Expression of Epidermal growth factor receptor (EGFR) in Lung Cancers.

INTRODUCTION: Lung cancer is a highly aggressive malignancy causing high morbidity and mortality. An increasing incidence of lung cancer has been observed in India. For those with non-small cell lung cancer and patients with more advanced disease, targeted therapy has been a cornerstone of treatment. Several molecular markers in lung cancer has been introduced in the recent past. They are recent topics of interest which has emerged not only as a prognostic marker but also as markers to predict therapy response especially the EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR). The expression of this marker forms important criteria for prognosis and therapy of lung carcinomas. The aim of this study is to assess the patterns of expression of EGFR and to assess the clinical and morphological characteristics of lung carcinomas. AIMS AND OBJECTIVES: The aim of this study is to assess the expression of Epidermal Growth Factors Receptor (EGFR) in lung cancers. To compare the expression of EGFR with clinicopathological parameters in lung carcinoma. To assess the prognostic and predictive values of EGFR MATERIALS AND METHODS: Out of 412 lung specimens received during the two year study period, 178 cases were non-small cell lung carcinoma. 60 cases are randomly selected for assessing EGFR expression which includes 20 cases each of adenocarcinoma, squamous cell carcinoma and non-small cell lung carcinoma-not otherwise specified(NSCLC-NOS). RESULTS: 68.33% of the cases are positive for EGFR expression. 90.48% of the females are positive for EGFR expression96.67% of the EGFR positive cases are smokers and 40% are non smokers. Among the EGFR positive histological subtype, adenocarcinoma is the most common type with 43.90% followed by squamous cell carcinoma with 36.59% & NSCLCNOS with 19.51%. CONCLUSION: The identification of EGFR expression gives a fascinating opportunity for the development of tyrosine kinase inhibitors against non-small cell lung cancers. It is very clear from the comparison of various studies from our studies that EGFR expression is more common in females, never smokers and adenocarcinoma histological type. EGFR, being a poor prognostic factor, its expression is very important to identify the tyrosine kinase inhibitors sensitivity. Hence it is very important to find the association between EGFR expression and its clinocopathological parameters in order to select the patients for targeted therapy like erlotinib, gefitinib for advanced lung cancers. In conclusion, it is recommended that EGFR expression should be a routine test after lung resection for all non-small lung carcinoma especially adenocarcinoma and squamous cell carcinoma for better treatment for the patients

An overview on molecular characterization of thymic tumors: Old and new targets for clinical advances

Thymic tumors are a group of rare mediastinal malignancies that include three different histological subtypes with completely different clinical behavior: the thymic carcinomas, the thymomas, and the rarest thymic neuroendocrine tumors. Nowadays, few therapeutic options are available for relapsed and refractory thymic tumors after a first-line platinum-based chemotherapy. In the last years, the deepening of knowledge on thymus’ biological characterization has opened possibilities for new treatment options. Several clinical trials have been conducted, the majority with disappointing results mainly due to inaccurate patient selection, but recently some encouraging results have been presented. In this review, we summarize the molecular alterations observed in thymic tumors, underlying the great biological differences among the different histology, and the promising targeted therapies for the future