Skin often represents a target organ for adverse drug reactions and this also applies to the mRNA vaccines against Sars-CoV-2. Here we present a case of extensive livedoid reaction after 2nd dose of BNT162b-2 vaccine with massive blood skin extravasation and no systemic symptoms apart from anemization. The 30-year-old woman developed progressively enlarging livedoid lesions on limbs and abdomen. Histology showed a near-normal epidermis and a very mild interstitial mixed inflammatory infiltrate with extensive blood extravasation in mid- and deep dermis. Diagnosis was adverse reaction to vaccine with skin capillary hyperpermeability and anaemization with lower than diagnostic features of cutaneous small vessel vasculitis. To date, no cases of a livedoid skin reaction associated to Covid-19 vaccine have been reported, and this case illustrates that massive livedoid reaction can be another kind of skin reaction to mRNA Covid-19 vaccine.
{"title":"Livedoid skin reaction to 2nd dose of mRNA Covid-19 vaccine.","authors":"Ilaria Girolami, Klaus Eisendle, Reinhard Walther Kluge, Esther Hanspeter, Albino Eccher, Leonardo Vizziello, Pierfrancesco Zampieri, Guido Mazzoleni","doi":"10.32074/1591-951X-746","DOIUrl":"https://doi.org/10.32074/1591-951X-746","url":null,"abstract":"<p><p>Skin often represents a target organ for adverse drug reactions and this also applies to the mRNA vaccines against Sars-CoV-2. Here we present a case of extensive livedoid reaction after 2nd dose of BNT162b-2 vaccine with massive blood skin extravasation and no systemic symptoms apart from anemization. The 30-year-old woman developed progressively enlarging livedoid lesions on limbs and abdomen. Histology showed a near-normal epidermis and a very mild interstitial mixed inflammatory infiltrate with extensive blood extravasation in mid- and deep dermis. Diagnosis was adverse reaction to vaccine with skin capillary hyperpermeability and anaemization with lower than diagnostic features of cutaneous small vessel vasculitis. To date, no cases of a livedoid skin reaction associated to Covid-19 vaccine have been reported, and this case illustrates that massive livedoid reaction can be another kind of skin reaction to mRNA Covid-19 vaccine.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/e6/pathol-2022-04-322.PMC9624132.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caterina Fumagalli, Ilaria Betella, Alberto Ranghiero, Elena Guerini-Rocco, Giulio Bonaldo, Alessandra Rappa, Davide Vacirca, Nicoletta Colombo, Massimo Barberis
Background: Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy.
Methods: In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay.
Results: The overall percent agreement between AmoyDx and Myriad was 87.8% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100%).
Conclusions: The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.
{"title":"In-house testing for homologous recombination repair deficiency (HRD) testing in ovarian carcinoma: a feasibility study comparing AmoyDx HRD Focus panel with Myriad myChoiceCDx assay.","authors":"Caterina Fumagalli, Ilaria Betella, Alberto Ranghiero, Elena Guerini-Rocco, Giulio Bonaldo, Alessandra Rappa, Davide Vacirca, Nicoletta Colombo, Massimo Barberis","doi":"10.32074/1591-951X-791","DOIUrl":"https://doi.org/10.32074/1591-951X-791","url":null,"abstract":"<p><strong>Background: </strong>Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy.</p><p><strong>Methods: </strong>In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay.</p><p><strong>Results: </strong>The overall percent agreement between AmoyDx and Myriad was 87.8% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100%).</p><p><strong>Conclusions: </strong>The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/64/pathol-2022-04-288.PMC9624133.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claudio Guerrieri, Mark Lindner, Joanna Sesti, Abhishek Chakraborti, Rachel Hudacko
We report a rare case of a peripheral squamous cell carcinoma (SCC) of the lung in which most of the tumor displayed a "lepidic" growth pattern. The tumor cells also appeared to grow along the alveolar walls between the overlying pneumocytes and underlying basement membrane, a form reminiscent of the "pagetoid" mode of spread. The neoplastic cells were positive for the squamous markers p63 and p40. TTF-1 and CK7 highlighted residual non-neoplastic pneumocytes, which either covered the lepidic tumor cells or lined pseudoglandular formations created by the filling of alveolar spaces by the tumor. CK7 also stained the tumor cells, albeit focally and weakly, a not uncommon finding in peripheral lung SCC. The tumor cells were negative for TTF-1 (clone 8G7G3/1), but did show focal weak reactivity with the less specific clone SPT24. The invasive area measured 2.5 mm while the overall size of the tumor including the lepidic-pagetoid component was 9.0 mm. Even though the invasive component was < 0.5 cm, the only option according to existing staging criteria was to stage it as pT1a. Since the current staging system does not account for the non-invasive lepidic component of pulmonary SCC, the increasing awareness of this variant may require its inclusion within the classification and pathological staging of lung carcinoma.
{"title":"Pulmonary squamous cell carcinoma with a lepidic-pagetoid growth pattern.","authors":"Claudio Guerrieri, Mark Lindner, Joanna Sesti, Abhishek Chakraborti, Rachel Hudacko","doi":"10.32074/1591-951X-450","DOIUrl":"https://doi.org/10.32074/1591-951X-450","url":null,"abstract":"<p><p>We report a rare case of a peripheral squamous cell carcinoma (SCC) of the lung in which most of the tumor displayed a \"lepidic\" growth pattern. The tumor cells also appeared to grow along the alveolar walls between the overlying pneumocytes and underlying basement membrane, a form reminiscent of the \"pagetoid\" mode of spread. The neoplastic cells were positive for the squamous markers p63 and p40. TTF-1 and CK7 highlighted residual non-neoplastic pneumocytes, which either covered the lepidic tumor cells or lined pseudoglandular formations created by the filling of alveolar spaces by the tumor. CK7 also stained the tumor cells, albeit focally and weakly, a not uncommon finding in peripheral lung SCC. The tumor cells were negative for TTF-1 (clone 8G7G3/1), but did show focal weak reactivity with the less specific clone SPT24. The invasive area measured 2.5 mm while the overall size of the tumor including the lepidic-pagetoid component was 9.0 mm. Even though the invasive component was < 0.5 cm, the only option according to existing staging criteria was to stage it as pT1a. Since the current staging system does not account for the non-invasive lepidic component of pulmonary SCC, the increasing awareness of this variant may require its inclusion within the classification and pathological staging of lung carcinoma.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/3a/pathol-2022-04-304.PMC9624129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01Epub Date: 2022-09-08DOI: 10.32074/1591-951X-762
Andrea Ascione, Guido Martignoni, Giulia d'Amati, Carlo Della Rocca, Paolo Graziano, Angelina Pernazza
A 79-year-old woman underwent surgical resection of a peripheral, solitary, pulmonary lesion that was diagnosed as malignant PEComa. Her clinical history was positive for uterine leiomyosarcoma, excised 20 years before. Re-evaluation of the primary uterine lesion led to the final diagnosis of lung metastasis from uterine PEComa. While long latency between primary tumour and metastasis is a known and characteristic feature of PEComas, a 20-year interval is unprecedented in the literature.
{"title":"Extremely late-onset pulmonary metastasis from uterine PEComa.","authors":"Andrea Ascione, Guido Martignoni, Giulia d'Amati, Carlo Della Rocca, Paolo Graziano, Angelina Pernazza","doi":"10.32074/1591-951X-762","DOIUrl":"https://doi.org/10.32074/1591-951X-762","url":null,"abstract":"<p><p>A 79-year-old woman underwent surgical resection of a peripheral, solitary, pulmonary lesion that was diagnosed as malignant PEComa. Her clinical history was positive for uterine leiomyosarcoma, excised 20 years before. Re-evaluation of the primary uterine lesion led to the final diagnosis of lung metastasis from uterine PEComa. While long latency between primary tumour and metastasis is a known and characteristic feature of PEComas, a 20-year interval is unprecedented in the literature.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/43/96/pathol-2022-04-312.PMC9624134.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33455540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel S Liscia, Mariangela D'Andrea, Elena Biletta, Donata Bellis, Kejsi Demo, Franco Ferrero, Alberto Petti, Roberto Butinar, Enzo D'Andrea, Giuditta Davini
Objective: A common source of concern about digital pathology (DP) is that limited resolution could be a reason for an increased risk of malpractice. A frequent question being raised about this technology is whether it can be used to reliably detect Helicobacter pylori (HP) in gastric biopsies, which can be a significant burden in routine work. The main goal of this work is to show that a reliable diagnosis of HP infection can be made by DP even at low magnification. The secondary goal is to demonstrate that artificial intelligence (AI) algorithms can diagnose HP infections on virtual slides with sufficient accuracy.
Methods: The method we propose is based on the Warthin-Starry (W-S) silver stain which allows faster detection of HP in virtual slides. A software tool, based on regular expressions, performed a specific search to select 679 biopsies on which a W-S stain was done. From this dataset 185 virtual slides were selected to be assessed by WSI and compared with microscopy slide readings. To determine whether HP infections could be accurately diagnosed with machine learning. AI was used as a service (AIaaS) on a neural network-based web platform trained with 468 images. A test dataset of 210 images was used to assess the classifier performance.
Results: In 185 gastric biopsies read with DP we recorded only 4 false positives and 4 false negatives with an overall agreement of 95.6%. Compared with microscopy, defined as the "gold standard" for the diagnosis of HP infections, WSI had a sensitivity and specificity of 0.95 and 0.96, respectively. The ROC curve of our AI classifier generated on a testing dataset of 210 images had an AUC of 0.938.
Conclusions: This study demonstrates that DP and AI can be used to reliably identify HP at 20X resolution.
{"title":"Use of digital pathology and artificial intelligence for the diagnosis of Helicobacter pylori in gastric biopsies.","authors":"Daniel S Liscia, Mariangela D'Andrea, Elena Biletta, Donata Bellis, Kejsi Demo, Franco Ferrero, Alberto Petti, Roberto Butinar, Enzo D'Andrea, Giuditta Davini","doi":"10.32074/1591-951X-751","DOIUrl":"https://doi.org/10.32074/1591-951X-751","url":null,"abstract":"<p><strong>Objective: </strong>A common source of concern about digital pathology (DP) is that limited resolution could be a reason for an increased risk of malpractice. A frequent question being raised about this technology is whether it can be used to reliably detect <i>Helicobacter pylori</i> (HP) in gastric biopsies, which can be a significant burden in routine work. The main goal of this work is to show that a reliable diagnosis of HP infection can be made by DP even at low magnification. The secondary goal is to demonstrate that artificial intelligence (AI) algorithms can diagnose HP infections on virtual slides with sufficient accuracy.</p><p><strong>Methods: </strong>The method we propose is based on the Warthin-Starry (W-S) silver stain which allows faster detection of HP in virtual slides. A software tool, based on regular expressions, performed a specific search to select 679 biopsies on which a W-S stain was done. From this dataset 185 virtual slides were selected to be assessed by WSI and compared with microscopy slide readings. To determine whether HP infections could be accurately diagnosed with machine learning. AI was used as a service (AIaaS) on a neural network-based web platform trained with 468 images. A test dataset of 210 images was used to assess the classifier performance.</p><p><strong>Results: </strong>In 185 gastric biopsies read with DP we recorded only 4 false positives and 4 false negatives with an overall agreement of 95.6%. Compared with microscopy, defined as the \"gold standard\" for the diagnosis of HP infections, WSI had a sensitivity and specificity of 0.95 and 0.96, respectively. The ROC curve of our AI classifier generated on a testing dataset of 210 images had an AUC of 0.938.</p><p><strong>Conclusions: </strong>This study demonstrates that DP and AI can be used to reliably identify HP at 20X resolution.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/08/pathol-2022-04-295.PMC9624136.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luca Ventura, Lorenzo Arrizza, Raimondo Quaresima, Mattia Capulli
The renal stone found in the natural mummy of an anonymous nobleman dating to 19th century was investigated using advanced imaging modalities and analytic investigations. By this multidisciplinary approach we were able to identify the chemical components and their distribution throughout the sample. These results allowed to understand the lifestyle habits of the subject, as well as the exact pathogenesis of his disease.
{"title":"Multidisciplinary investigation of an ancient renal stone in a mummy from Popoli, central Italy.","authors":"Luca Ventura, Lorenzo Arrizza, Raimondo Quaresima, Mattia Capulli","doi":"10.32074/1591-951X-260","DOIUrl":"https://doi.org/10.32074/1591-951X-260","url":null,"abstract":"<p><p>The renal stone found in the natural mummy of an anonymous nobleman dating to 19<sup>th</sup> century was investigated using advanced imaging modalities and analytic investigations. By this multidisciplinary approach we were able to identify the chemical components and their distribution throughout the sample. These results allowed to understand the lifestyle habits of the subject, as well as the exact pathogenesis of his disease.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/ac/pathol-2022-04-339.PMC9624137.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alveolar adenoma is a rare tumour of the lung. It is typically found in asymptomatic adults as a peripheral or subplerual nodule on imaging examination. Microscopically, the tumour is composed of admixture of epithelial and mesenchymal component in variable sized cystic or alveolar structures. The tumour shows a benign nature. There have been no reported recurrences or metastases. Malignant transformation of alveolar adenoma and coexisting with lung carcinoma have been rarely described. In this article, we report a case of an alveolar adenoma and coexisting atypical adenomatous hyperplasia. This case, contributing to the limited numbers of cases described to date, illustrates the importance of awareness on the possibility of alveolar adenoma being associated with lung carcinoma and its precursor lesions especially when diagnosed by small biopsy specimens.
{"title":"Alveolar adenoma and coexisting atypical adenomatous hyperplasia: a case report and literature review.","authors":"Yen-Wen Lu, Shih-Lung Chang, Yi-Chen Yeh, Yei-San Hsieh","doi":"10.32074/1591-951X-755","DOIUrl":"https://doi.org/10.32074/1591-951X-755","url":null,"abstract":"<p><p>Alveolar adenoma is a rare tumour of the lung. It is typically found in asymptomatic adults as a peripheral or subplerual nodule on imaging examination. Microscopically, the tumour is composed of admixture of epithelial and mesenchymal component in variable sized cystic or alveolar structures. The tumour shows a benign nature. There have been no reported recurrences or metastases. Malignant transformation of alveolar adenoma and coexisting with lung carcinoma have been rarely described. In this article, we report a case of an alveolar adenoma and coexisting atypical adenomatous hyperplasia. This case, contributing to the limited numbers of cases described to date, illustrates the importance of awareness on the possibility of alveolar adenoma being associated with lung carcinoma and its precursor lesions especially when diagnosed by small biopsy specimens.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/ba/pathol-2022-04-326.PMC9624131.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This is an open access journal distributed in accordance with the CC-BY-NC-ND (Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International) license: the work can be used by mentioning the author and the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons. org/licenses/by-nc-nd/4.0/deed.en PATHOLOGICA 2022;114:4-6 DOI: 10.32074/1591-951X-782
{"title":"Fixation in histopathology: the mandate to renew.","authors":"Gianni Bussolati","doi":"10.32074/1591-951X-782","DOIUrl":"https://doi.org/10.32074/1591-951X-782","url":null,"abstract":"This is an open access journal distributed in accordance with the CC-BY-NC-ND (Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International) license: the work can be used by mentioning the author and the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons. org/licenses/by-nc-nd/4.0/deed.en PATHOLOGICA 2022;114:4-6 DOI: 10.32074/1591-951X-782","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/e9/pathol-2022-04-275.PMC9624139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01Epub Date: 2022-09-08DOI: 10.32074/1591-951X-756
Paolo Bironzo, Laura Melocchi, Valentina Monica, Dario Trebeschi, Fausto Barbieri, Evaristo Maiello, Maria Rita Migliorino, Alessandra Lombardi, Marcello Tiseo, Luisella Righi, Paolo Graziano, Giulio Rossi, Silvia Novello
Introduction: ALK rearrangement is the only druggable oncogenic driver detectable by immunohistochemistry (IHC) not requiring further confirmation of positivity in accessing first-line specific inhibitors. ALK-positive patients experience clinical benefit from pemetrexed-based chemotherapy possibly due to lower thymidylate synthase (TS) levels. This study assesses agreement with three different ALK IHC clones in 37 FISH-positive NSCLC. TS expression by real time (RT)-PCR was compared with ALK FISH-negative cases.
Materials and methods: 37 ALK FISH-positive NSCLC cases diagnosed between 2010 and 2015 in 7 Italian centres were investigated with ICH using three different anti-ALK antibodies (ALK1, 5A4 and D5F3). Staining for ALK1 and 5A4 was graded as 0+,1+,2+, and 3+, while the scoring for D5F3 was recorded as negative or positive. Proportion agreement analysis was done using Cohen's unweighted kappa (k). TS and β-actin expression levels were analysed by quantitative RT-PCR. Comparison between TS expression in ALK FISH-positive specimens and a control cohort of ALK FISH-negative ones was performed with the Mann-Whitney and Kruskal-Wallis tests.
Results: Considering 2+ and 3+ as positive, the proportion of IHC agreement was 0.1691 (95% CI 0-0.4595) for ALK1/5A4, 0.1691 (95% CI 0-0.4595) for ALK1/D5F3, and 1 for D5F3/5A4. Considering 3+ as positive, it was 0.1543 (95% CI 0-0.4665) for ALK1/ 5A4, 0.0212 (95% CI 0-0.1736) for ALK1/D5F3, and 0.2269 (95% CI 0-0.5462) for 5A4/D5F3. Median TS expression was 6.07 (1.28-14.94) and ALK-positive cases had a significant lower TS expression than ALK-negative tumours (p = 0.002).
Conclusions: IHC proved to be a reliable tool for the diagnosis of ALK-rearranged NSCLC. D5F3 and 5A4 clones have the highest percentage of agreement. TS levels are significantly lower in FISH-positive patients.
ALK重排是免疫组化(IHC)检测到的唯一可用药的致癌驱动因素,在获得一线特异性抑制剂时无需进一步确认阳性。alk阳性患者从培美曲塞为基础的化疗中获益,可能是由于胸腺苷酸合成酶(TS)水平较低。本研究在37例fish阳性NSCLC中评估了三种不同的ALK IHC克隆的一致性。实时(RT)-PCR法比较ALK - fish阴性患者的TS表达情况。材料和方法:2010年至2015年间,意大利7个中心诊断的37例ALK fish阳性非小细胞肺癌患者使用三种不同的抗ALK抗体(ALK1, 5A4和D5F3)进行ICH调查。ALK1和5A4染色分为0+、1+、2+和3+,D5F3评分为阴性或阳性。采用Cohen's未加权kappa (k)进行比例一致性分析。采用定量RT-PCR分析TS和β-actin表达水平。采用Mann-Whitney和Kruskal-Wallis试验比较ALK fish阳性标本和ALK fish阴性对照标本中TS的表达。结果:考虑2+和3+为阳性,ALK1/ 5a4的IHC一致性比例为0.1691 (95% CI 0-0.4595), ALK1/D5F3为0.1691 (95% CI 0-0.4595), D5F3/ 5a4为1。考虑到3+为阳性,ALK1/ 5A4为0.1543 (95% CI 0-0.4665), ALK1/D5F3为0.0212 (95% CI 0-0.1736), 5A4/D5F3为0.2269 (95% CI 0-0.5462)。TS的中位表达量为6.07 (1.28-14.94),alk阳性患者的TS表达量显著低于alk阴性患者(p = 0.002)。结论:免疫组化是诊断alk重排非小细胞肺癌的可靠工具。D5F3和5A4克隆的一致性百分比最高。fish阳性患者的TS水平显著降低。
{"title":"Immunohistochemistry with 3 different clones in anaplastic lymphoma kinase fluorescence in situ hybridization positive non-small-cell lung cancer with thymidylate synthase expression analysis: a multicentre, retrospective, Italian study.","authors":"Paolo Bironzo, Laura Melocchi, Valentina Monica, Dario Trebeschi, Fausto Barbieri, Evaristo Maiello, Maria Rita Migliorino, Alessandra Lombardi, Marcello Tiseo, Luisella Righi, Paolo Graziano, Giulio Rossi, Silvia Novello","doi":"10.32074/1591-951X-756","DOIUrl":"https://doi.org/10.32074/1591-951X-756","url":null,"abstract":"<p><strong>Introduction: </strong><i>ALK</i> rearrangement is the only druggable oncogenic driver detectable by immunohistochemistry (IHC) not requiring further confirmation of positivity in accessing first-line specific inhibitors. ALK-positive patients experience clinical benefit from pemetrexed-based chemotherapy possibly due to lower thymidylate synthase (TS) levels. This study assesses agreement with three different ALK IHC clones in 37 FISH-positive NSCLC. TS expression by real time (RT)-PCR was compared with <i>ALK</i> FISH-negative cases.</p><p><strong>Materials and methods: </strong>37 ALK FISH-positive NSCLC cases diagnosed between 2010 and 2015 in 7 Italian centres were investigated with ICH using three different anti-ALK antibodies (ALK1, 5A4 and D5F3). Staining for ALK1 and 5A4 was graded as 0+,1+,2+, and 3+, while the scoring for D5F3 was recorded as negative or positive. Proportion agreement analysis was done using Cohen's unweighted kappa (k). TS and β-actin expression levels were analysed by quantitative RT-PCR. Comparison between TS expression in ALK FISH-positive specimens and a control cohort of ALK FISH-negative ones was performed with the Mann-Whitney and Kruskal-Wallis tests.</p><p><strong>Results: </strong>Considering 2+ and 3+ as positive, the proportion of IHC agreement was 0.1691 (95% CI 0-0.4595) for ALK1/5A4, 0.1691 (95% CI 0-0.4595) for ALK1/D5F3, and 1 for D5F3/5A4. Considering 3+ as positive, it was 0.1543 (95% CI 0-0.4665) for ALK1/ 5A4, 0.0212 (95% CI 0-0.1736) for ALK1/D5F3, and 0.2269 (95% CI 0-0.5462) for 5A4/D5F3. Median TS expression was 6.07 (1.28-14.94) and ALK-positive cases had a significant lower TS expression than ALK-negative tumours <i>(p = 0.002).</i></p><p><strong>Conclusions: </strong>IHC proved to be a reliable tool for the diagnosis of ALK-rearranged NSCLC. D5F3 and 5A4 clones have the highest percentage of agreement. TS levels are significantly lower in FISH-positive patients.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/8c/pathol-2022-04-278.PMC9624140.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33455087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The thoracic district is the most frequent visceral location of synovial sarcoma, generally involving lung and pleura as a large solid mass. We present herein a 57-year-old man with recurrent pneumothorax and a localized bulla at the lingula. The lesion was excised by a Video-Assisted-Thoracoscopic-Surgery (VATS) wedge resection and surprisingly consisted of a unilocular cyst with fibrous wall intermingled by a longitudinal proliferation of bland-looking, dense, monomorphic spindle cells diffusely expressing EMA, CD99, CD56 and focally staining with cytokeratins. Fluorescent in situ hybridization demonstrated the presence of SYT rearrangement and a diagnosis of pulmonary cystic monophasic synovial sarcoma was made. Only few similar cases have been reported in literature, mainly occurring in young male adults. A meticulous examination of all resected tissue from pneumothorax is the prerequisite to suspect this extremely challenging condition, while immuno-molecular studies are mandatory to achieve the correct diagnosis.
{"title":"An unexpected cause of recurrent pneumothorax.","authors":"Giulio Rossi, Anna Farnedi, Fabio Davoli, Adolfo D'Agostino, Tommaso Bizzarro, Paride D'Angelo, Rita Sargiacomo","doi":"10.32074/1591-951X-377","DOIUrl":"https://doi.org/10.32074/1591-951X-377","url":null,"abstract":"<p><p>The thoracic district is the most frequent visceral location of synovial sarcoma, generally involving lung and pleura as a large solid mass. We present herein a 57-year-old man with recurrent pneumothorax and a localized bulla at the lingula. The lesion was excised by a Video-Assisted-Thoracoscopic-Surgery (VATS) wedge resection and surprisingly consisted of a unilocular cyst with fibrous wall intermingled by a longitudinal proliferation of bland-looking, dense, monomorphic spindle cells diffusely expressing EMA, CD99, CD56 and focally staining with cytokeratins. Fluorescent in situ hybridization demonstrated the presence of SYT rearrangement and a diagnosis of pulmonary cystic monophasic synovial sarcoma was made. Only few similar cases have been reported in literature, mainly occurring in young male adults. A meticulous examination of all resected tissue from pneumothorax is the prerequisite to suspect this extremely challenging condition, while immuno-molecular studies are mandatory to achieve the correct diagnosis.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/dc/pathol-2022-04-316.PMC9624130.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}