PATHOLOGICA最新文献

{"title":"From dominance to decline: can we reverse the trend in small molecule and TKI cancer therapies?","authors":"Denis Horgan, Paul Hofman, Daniel Schneider, Umberto Malapelle, Vivek Subbiah","doi":"10.32074/1591-951X-N869","DOIUrl":"https://doi.org/10.32074/1591-951X-N869","url":null,"abstract":"<p><p>Over the past two decades, precision oncology has seen unprecedented advances, particularly with the rise of small molecule drugs. These drugs have significantly benefitted patients with cancer harboring somatic genomic alterations, contributing to precision cancer medicine. Despite their early promise, there is a growing concern that major pharmaceutical companies are recently moving away from developing small molecules and tyrosine kinase inhibitors (TKIs) due to market saturation, primary and secondary resistance, and economic factors. The Inflation Reduction Act (IRA) further threatens innovation by reducing incentives for small molecule drug development. Additionally, patient access to comprehensive genomic testing remains a significant barrier. To reverse this trend, a multifaceted approach is urgently needed. Embracing cutting-edge technologies, fostering collaborations, and regulatory innovation are essential. Addressing systemic deficiencies, improving patient access, and ensuring ongoing investment in personalized medicine are crucial for realizing the full potential of small molecule oncology drugs and improving patient outcomes. Collaboration among stakeholders is imperative for advancing effective cancer treatments.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-grade corded and hyalinized endometrioid carcinoma of \"no specific molecular profile\": report of two cases.","authors":"Antonio Travaglino, Damiano Arciuolo, Angela Santoro, Susanna Ronchi, Nicoletta D'Alessandris, Giulia Scaglione, Belen Padial Urtueta, Francesca Addante, Nadine Narducci, Michele Valente, Antonio Raffone, Jvan Casarin, Carla Facco, Stefano La Rosa, Gian Franco Zannoni","doi":"10.32074/1591-951X-1096","DOIUrl":"https://doi.org/10.32074/1591-951X-1096","url":null,"abstract":"<p><p>High-grade corded and hyalinized endometrioid carcinoma (CHEC) is an uncommon endometrial carcinoma variant which may mimic carcinosarcoma or dedifferentiated carcinoma and has shown association with mismatch repair deficiency (MMRd) and p53 abnormalities. Herein, we expand the spectrum of high-grade CHEC by presenting two cases showing a \"no specific molecular profile\" (NSMP). Case #1 was a 6-cm endometrial mass in a 25-year-old woman, infiltrating the deep myometrium and cervical stroma, with diffuse lymphovascular space invasion. Case #2 was an advanced, unresectable endometrial carcinoma involving the lower third of the vagina in an 81-year-old woman. On the endometrial biopsy specimen, both cases showed a markedly atypical and mitotically active corded component merging with a FIGO G3 endometrioid component and accompanied by squamous/morular differentiation. Both tumors showed nuclear β-catenin accumulation, retained MMR protein expression, wild-type p53 pattern, and no <i>POLE</i> mutations.</p><p><p>The corded component was absent in the hysterectomy specimen of case #1 and in the vaginal biopsy specimen of case #2. The present cases confirm the clinical and molecular heterogeneity of high-grade CHEC, including a wide age range at presentation, variable prognosis, and variable molecular background. Nonetheless, these cases retain unique features that support their distinction from carcinosarcoma and dedifferentiated carcinoma. We suggest to consider them as a variant of FIGO G3 endometrioid carcinoma. Further studies are necessary in this field.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"28-32"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033955","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}

{"title":"Morpho-molecular approach (NGS <i>plus</i> digital PCR) in diagnosis of malignant biliary strictures.","authors":"Francesco Vasuri, Elisa Albertini, Lucia Miranda, Thais Maloberti, Stefano Chillotti, Sara Coluccelli, Giovanni Tallini, Antonia D'Errico, Dario de Biase","doi":"10.32074/1591-951X-1117","DOIUrl":"https://doi.org/10.32074/1591-951X-1117","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the diagnostic accuracy and feasibility of <i>digital</i>-PCR (dPCR) combined with next-generation sequencing (NGS) in the ERCP-guided histological diagnosis of biliary strictures to overcome the issue represented by the scarcity of sampled material.</p><p><strong>Methods: </strong>Twenty-two prospective patients were included, and submitted to ERPC-guided biopsy or biliary resection. By histopathological analysis plus fluorescence in situ hybridization (FISH) for chromosomes 3, 7, and 17 aneuploidies, 8 cases (36.4%) were malignant, and 14 cases (63.6%) were negative. NGS was performed on paraffin-embedded tissue by a laboratory-developed panel allowing the analysis of hot-spot regions in 28 genes. Digital PCR (dPCR) was performed by QuantStudio™ AbsoluteQ™ solid dPCR and the copy-number variation (CNV) of the chromosomes 3, 7, and 17 analysed.</p><p><strong>Results: </strong>At dPCR, 1 case showed aneuploidy of chromosome 3, and 2 cases of both chromosomes 3 and 7. These 3 cases all belonged to the positive group (<i>p</i> = 0.014). At NGS, 6 cases showed at least one mutated gene, all in the positive group (<i>p <</i> 0.001). The 3 cases showing aneuploidy at dPCR also showed mutations at NGS. Basing on these observations, we can propose a diagnostic algorithm: dPCR can be applied first, allowing a diagnosis of malignancy in one working day if aneuploidies are observed. In the case of negative dPCR, a \"second-line\" NGS is performed on the same extracted material.</p><p><strong>Conclusions: </strong>The implementation of dPCR allowed the identification of nearly 40% of positive cases in just one working day. In cases of negative dPCR, the NGS procedure can start on the same extracted nucleic acid used for dPCR, requiring more time, but reaching a 75% sensitivity. More studies are required to identify other more sensitive and specific dPCR targets, but even if our algorithm does not increase diagnostic accuracy, the possibility of avoiding FISH and reaching a diagnosis in a more time- and money-saving fashion might be an important step.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"10-17"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057424","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}

{"title":"Digital and computational transition in the pathology lab: when did it start?","authors":"Rodolfo Montironi, Antonio Lopez-Beltran, Alessia Cimadamore, Liang Cheng","doi":"10.32074/1591-951X-N824","DOIUrl":"https://doi.org/10.32074/1591-951X-N824","url":null,"abstract":"","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"60-62"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038992","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}

{"title":"The pathogenesis of idiopathic pulmonary fibrosis: from \"folies à deux\" to \"Culprit cell Trio\".","authors":"Marco Chilosi, Claudia Ravaglia, Claudio Doglioni, Sara Piciucchi, Lavinia Stefanizzi, Venerino Poletti","doi":"10.32074/1591-951X-1123","DOIUrl":"https://doi.org/10.32074/1591-951X-1123","url":null,"abstract":"","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"3-9"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005823","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}

{"title":"The Morgagni Anatomical Theatre: 100 Years of Pathological Anatomy Education at the University of Padua (1924-2024).","authors":"Alberto Zanatta, Giovanni Magno, Cristina Basso","doi":"10.32074/1591-951X-1075","DOIUrl":"https://doi.org/10.32074/1591-951X-1075","url":null,"abstract":"<p><p>Between the 15^th and 16^th centuries, the medical school in Padua revolutionised the field of anatomy through a series of scientific discoveries and educational innovations, culminating in the construction of the world's first stable anatomical theatre. This theatre was inaugurated in 1595 within Bo Palace by Hieronymus Fabricius (1533-1619).</p><p><p>The anatomical theatre was used for lectures until March 7, 1874, and the structure was preserved as a museum at the request of Giampaolo Vlacovich (1825-1899), the last anatomy professor to use it. Soon after, new theatres were built under the direction of Lodovico Brunetti (1813-1899) at the former convent of San Mattia, where many disciplines relocated to stay close to the new Giustinianeo Hospital. Subsequently, in the early 20^th century, under the leadership of Augusto Bonome (1857-1922) and Vittorio Rossi (1865-1938), the Rector of the University of Padua, it was decided to construct a new building for anatomical studies to replace the inadequate facilities at San Mattia. Construction of this ambitious project began in July 1920, starting with the autopsy room, called the Morgagni Theatre, which was completed in December 1922. Today, the theatre commissioned by Bonome just re-opened after a respectful restoration, with the aim of continuing the important educational activities in anatomical pathology as in the past.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"45-51"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064904","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}

{"title":"Inflammatory cloacogenic polyp with low grade mucinous dysplasia in orthotopic neobladder: expect the unexpected.","authors":"Carlo Pescia, Marianna D'Ercole, Edoardo Olmeda, Antonio Brescia, Gennaro Musi, Stefano Luzzago, Francesco Alessandro Mistretta, Ottavio De Cobelli, Giuseppe Renne, Nicola Fusco","doi":"10.32074/1591-951X-1005","DOIUrl":"https://doi.org/10.32074/1591-951X-1005","url":null,"abstract":"","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"63-66"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990336","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}

{"title":"The invisible killer: fetal vascular malperfusion in stillbirths without macroscopic cord abnormalities.","authors":"Laura Avagliano, Francesca Monari, Beatrice Melis, Fabio Facchinetti, Gaetano Bulfamante","doi":"10.32074/1591-951X-1070","DOIUrl":"https://doi.org/10.32074/1591-951X-1070","url":null,"abstract":"<p><strong>Objective: </strong>The aim was to evaluate the association between fetal vascular malperfusion (FVM) and the umbilical cord characteristics in stillbirth. FVM is a category of placental lesions consistent with restriction/interruption of fetal blood flow, frequently associated with a \"cord accident\". In some stillbirths, gross umbilical cord abnormalities unravel at birth, helping to elucidate the cause of death; however, other cases do not show any structural alterations and therefore these cases do not have an obvious cause of death.</p><p><strong>Methods: </strong>Retrospective histopathological evaluation of singleton antepartum stillbirths affected by of FVM. Clinical and histopathological findings were compared among cases with or without gross umbilical cord abnormalities.</p><p><strong>Results: </strong>One hundred and three cases were evaluated. Forty-eight cases (48/103; 46.6%) of stillbirth with FVM showed gross umbilical cord abnormalities, whereas 55/103 cases (53.4%) did not show any gross anomalies. Clinical risk factors for stillbirth were equally distributed between cases. Notably, the main histological lesion observed in cases without gross umbilical cord abnormalities was fatal thrombosis of the fetal vessels along the cord-placental vascular tree. This finding implies that the absence of macroscopic cord anomalies is not a sufficient criterion to exclude reduction/interruption of fetal blood flow and cord accidents as a potential cause of stillbirth.</p><p><strong>Conclusion: </strong>Knowing the cause of fetal death is paramount both for bereaved parents and clinicians, helping in stillbirth acceptance and future prevention strategies. Our findings show the occurrence of FVM in cases without macroscopic umbilical cord anomalies. Therefore, an in-depth placental histopathological examination is mandatory to unravel signs of fetal blood flow obstruction in cases in which umbilical cord looks grossly normal. This knowledge helps parents, and health care providers in the real identification of the pathogenesis of fetal death, as the first step for personalized future actions of stillbirth prevention.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"18-27"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040339","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}

{"title":"Foetal cardiac rhabdomyoma due to paternal <i>TSC1</i> Mutation: a case report and literature review.","authors":"Eleonora Nardi, Angela Silvano, Oumaima Ammar, Francesca Gensini, Annabella Marozza, Lucia Pasquini, Francesca Castiglione, Viola Seravalli","doi":"10.32074/1591-951X-1099","DOIUrl":"https://doi.org/10.32074/1591-951X-1099","url":null,"abstract":"<p><p>Rhabdomyomas are the most common prenatal cardiac tumours, and are often associated with tuberous sclerosis complex (TSC). They have been shown to grow during foetal development, but may often regress or shrink in early childhood.</p><p><p>In the present case, ultrasonography at 20+2 gestational weeks identified two echogenic masses suspicious of rhabdomyomas in the foetal heart. Neither of these tumours caused significant haemodynamic instability. Genetic testing of DNA extracted from amniocytes revealed a pathogenic variant of the <i>TSC1</i> gene, supporting the diagnosis of tuberous sclerosis. The pregnancy was terminated at 21+1 weeks. Pathological examination confirmed the presence of two cardiac rhabdomyomas, histologically characterised by distinctive large vacuolated cells with central nuclei and radial cytoplasmic extensions.</p><p><p>Further research and a multidisciplinary approach are highly recommended to improve management and outcomes of prenatal tumours.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"33-38"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053467","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}

{"title":"Lipoblastoma-like tumor of the inguinal region: a close mimicker of myxoid liposarcoma.","authors":"Manuel Mazzucchelli, Giuseppe Angelico, Lucia Salvatorelli, Giada Maria Vecchio, Chiara Romano, Paolo Vigneri, Maria Paola Mariani, Gerardo Ferrara, Gaetano Giuseppe Magro","doi":"10.32074/1591-951X-964","DOIUrl":"https://doi.org/10.32074/1591-951X-964","url":null,"abstract":"<p><p>Lipoblastoma-like tumor is a rare mesenchymal neoplasm, typically arising in the vulvar region of young women. Although it is considered a benign tumor, rare local recurrences and exceptionally distant metastases have been reported. Histological examination reveals a well-circumscribed tumor with lobulated pattern, composed of a mixture of mature adipocytes, spindle cells and lipoblasts set in abundant myxoid stroma with numerous thin-walled capillary-like vessels. Due to the rarity of this neoplasm and its morphological resemblance with other benign and malignant lipomatous tumors, the diagnosis of <i>lipoblastoma-like tumor</i> is often challenging. Herein, we present a case occurring in the inguinal region of a 28-year-old woman. Histological examination showed a mixture of mature adipocytes, bland-looking spindle cells with fibrillary cytoplasm, and numerous univacuolated lipoblasts set in a prominent myxoid matrix containing numerous thin-walled branching vessels. Immunohistochemically, neoplastic cells showed diffuse immunostaining for CD34 and negativity for α-smooth muscle actin, desmin, Rb1, MDM2 and STAT6. The main differential diagnoses included myxoid liposarcoma, spindle cell lipoma and cellular angiofibroma. FISH was negative for <i>DDIT3</i>; moreover, no evidence of regional gain or loss of <i>RB1</i> was identified by FISH. Based on morphological, immunohistochemical and cytogenetic/molecular findings, a final diagnosis of \"<i>lipoblastoma-like tumor\"</i> of the inguinal region was rendered.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 1","pages":"39-44"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053470","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}