Endocrine Pathology最新文献

{"title":"3rd Edition of Diagnostic Pathology: Endocrine by Vania Nosé.","authors":"Ozgur Mete","doi":"10.1007/s12022-023-09774-0","DOIUrl":"https://doi.org/10.1007/s12022-023-09774-0","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 2","pages":"271-272"},"PeriodicalIF":4.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9622120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FLCN-Driven Functional Adrenal Cortical Carcinoma with High Mitotic Tumor Grade: Extending the Endocrine Manifestations of Birt-Hogg-Dubé Syndrome.","authors":"Renee Hofstedter,&nbsp;María Carolina Sanabria-Salas,&nbsp;Maria Di Jiang,&nbsp;Shereen Ezzat,&nbsp;Ozgur Mete,&nbsp;Raymond H Kim","doi":"10.1007/s12022-023-09748-2","DOIUrl":"https://doi.org/10.1007/s12022-023-09748-2","url":null,"abstract":"<p><p>Adrenal cortical carcinoma is an aggressive and rare malignancy of steroidogenic cells of the adrenal gland. Most adult adrenal cortical carcinomas are sporadic, but a small fraction may be associated with inherited tumor syndromes, such as Li-Fraumeni, multiple endocrine neoplasia 1, Lynch syndrome, and Beckwith-Wiedemann syndrome, as well as isolated case reports of non-syndromic manifestations occurring in the context of other pathogenic germline variants. Birt-Hogg-Dubé (BHD) is a rare autosomal dominant syndrome caused by germline pathogenic variants in the FLCN gene. BHD syndrome causes a constellation of symptoms, including cutaneous manifestations, pulmonary cysts and pneumothorax, and risk of renal tumors. With the exception of a single case of adrenal cortical carcinoma, very few reports on the occurrence of adrenal cortical neoplasia in patients with BHD syndrome have been described. However, information on variant allele fraction in the tumor was not available in the index case, which precludes any mechanism supporting loss of heterozygosity. Here we present a case of an adult-onset adrenal cortical carcinoma in a 50-year-old female, found to harbor a germline likely pathogenic variant in the FLCN gene, denoted as c.694C > T (p.Gln232Ter). Genetic testing on the tumor revealed the same FLCN variant at an allele fraction of 83%, suggesting a contributory role to the pathogenesis of the adrenal cortical carcinoma. This case further supports the expansion of the clinical presentation and tumor spectrum of BHD syndrome and the need to consider germline FLCN testing in the clinical genetic workup of patients with adrenal cortical carcinomas.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 2","pages":"257-264"},"PeriodicalIF":4.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9626178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Nodules and Follicular Cell-Derived Thyroid Carcinomas in Children.","authors":"Jonathan C Slack,&nbsp;Monica Hollowell,&nbsp;Justine A Barletta","doi":"10.1007/s12022-023-09764-2","DOIUrl":"https://doi.org/10.1007/s12022-023-09764-2","url":null,"abstract":"<p><p>Although pediatric thyroid tumors have many similarities to those occurring in adults, significant differences are also recognized. For example, although thyroid nodules in children are much less common than in adults, a higher percentage is malignant. Moreover, while pediatric papillary thyroid carcinoma (PTC) is associated with more advanced disease, death due to disease in children and adolescents is very rare, even when distant metastases are present. Some subtypes of thyroid carcinoma, like diffuse sclerosing variant, are especially common in children and adolescents. Moreover, certain histologic findings, such as a tall cell morphology or increased mitotic activity, may not carry the same prognostic significance in children as in adults. Recent studies exploring the molecular underpinnings of pediatric thyroid carcinoma indicate that while driver alterations of thyroid tumorigenesis in children and adults are essentially the same, they occur at very different frequencies, with translocation-associated tumors (most commonly harboring RET and NTRK fusions) comprising a sizable and distinct group of pediatric PTC. DICER1 mutations, an infrequent mutation in adult thyroid tumors, are relatively frequent in pediatric encapsulated follicular-patterned thyroid tumors (with or without invasion or nuclear features of PTC). Additionally, tumor predisposition syndromes (most notably DICER1 syndrome and PTEN hamartoma tumor syndromes such as Cowden syndrome) should be considered in children with thyroid tumors, especially follicular-patterned thyroid tumors and poorly differentiated thyroid carcinoma. This review will explore the current state of knowledge of thyroid nodules and carcinomas in children and adolescents.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 2","pages":"165-175"},"PeriodicalIF":4.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9629603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Thyroid Mucoepidermoid Carcinoma (MEC) Is Clinically, Prognostically, and Molecularly Different from Sclerosing MEC with Eosinophilia: A Multicenter and Integrated Study.","authors":"Hieu Trong Le,&nbsp;Truong P X Nguyen,&nbsp;Mitsuyoshi Hirokawa,&nbsp;Ryohei Katoh,&nbsp;Norisato Mitsutake,&nbsp;Michiko Matsuse,&nbsp;Ayaka Sako,&nbsp;Tetsuo Kondo,&nbsp;Nilesh Vasan,&nbsp;Young Mi Kim,&nbsp;Ying Liu,&nbsp;Lewis Hassell,&nbsp;Kennichi Kakudo,&nbsp;Huy Gia Vuong","doi":"10.1007/s12022-022-09741-1","DOIUrl":"https://doi.org/10.1007/s12022-022-09741-1","url":null,"abstract":"<p><p>Mucoepidermoid carcinoma (MEC) and sclerosing MEC with eosinophilia (SMECE) are rare primary thyroid carcinomas. In this study, we aimed to present our multicenter series of MEC and SMECE and integrated our data with published literature to further investigate the clinicopathological characteristics and prognoses of these tumors. We found 2 MECs and 4 SMECEs in our multicenter archives. We performed fluorescence in situ hybridization (FISH) to determine the MAML2 gene rearrangement. We screened for mutations in BRAF, TERT promoter, and RAS mutations using Sanger sequencing and digital polymerase chain reaction. Histopathologically, MECs and SMECEs were composed of two main cell types including epidermoid and mucin-secreting cells, arranged in cords, nests, and tubules. SMECEs were characterized by a densely sclerotic stroma with abundant eosinophils. We did not detect any MAML2 fusion in any of our cases. Two MEC cases harbored concomitant BRAF p.V600E and TERT C228T mutations. RAS mutations were absent in all cases. Concurrent foci of another thyroid malignancy were more commonly seen in MECs (p < 0.001), whereas SMECEs were associated with chronic lymphocytic thyroiditis (p < 0.001). MECs and SMECEs had equivalent recurrence-free survival (RFS) but MECs conferred significantly dismal disease-specific survival (DSS) as compared to SMECEs (p = 0.007). In conclusion, MECs and SMECEs not only shared some similarities but also demonstrated differences in clinicopathological characteristics, prognoses, and molecular profiles. SMECEs had a superior DSS in comparison to MECs, suggesting that they are low-grade cancers. This could help clinicians better evaluate patient outcomes and decide appropriate treatment plans.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 1","pages":"100-111"},"PeriodicalIF":4.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9237138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?","authors":"Karolina Solhusløkk Höse,&nbsp;Adam Stenman,&nbsp;Fredrika Svahn,&nbsp;Catharina Larsson,&nbsp;C Christofer Juhlin","doi":"10.1007/s12022-022-09746-w","DOIUrl":"https://doi.org/10.1007/s12022-022-09746-w","url":null,"abstract":"<p><p>Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells. Even though only 10-15% of the tumors metastasize, all PPGLs are considered potentially malignant. Topoisomerase 2A (TOP2A) is a protein involved in cell proliferation and has been found to be over-expressed in metastatic PPGL. To provide support whether TOP2A could serve as a prognostic marker, 88 PPGLs (of which 8 metastatic/relapsing) and 10 normal adrenal gland samples were assessed for TOP2A mRNA expression using quantitative real-time PCR (qRT-PCR) and TOP2A immunohistochemistry. Comparisons to clinical parameters connected to metastatic behavior were made, and The Cancer Genome Atlas was used for validation of the results. A significant association between high TOP2A mRNA expression in primary PPGL and subsequent metastatic events (p = 0.008) was found, as well as to specific histological features and clinical parameters connected to metastatic behavior and mutations in SDHB. TOP2A immunoreactivity was calculated as an index of positive nuclei divided by the total amount of nuclei, and this index associated with TOP2A mRNA levels (p = 0.023) as well as the Ki-67 labeling index (p = 0.001). To conclude, TOP2A is a potential prognostic marker as it is frequently elevated in PPGL displaying subsequent metastatic disease, and future studies in larger cohorts are warranted to determine if a TOP2A index as assessed by immunohistochemistry could be a marker of poor outcome. Additionally, elevated levels of TOP2A could indicate a potential actionable event, and future studies with topoisomerase inhibitors would be of interest.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 1","pages":"129-141"},"PeriodicalIF":4.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on C-Cell Neuroendocrine Neoplasm: Prognostic and Predictive Histopathologic and Molecular Features of Medullary Thyroid Carcinoma.","authors":"Chan Kwon Jung,&nbsp;Shipra Agarwal,&nbsp;Jen-Fan Hang,&nbsp;Dong-Jun Lim,&nbsp;Andrey Bychkov,&nbsp;Ozgur Mete","doi":"10.1007/s12022-023-09753-5","DOIUrl":"https://doi.org/10.1007/s12022-023-09753-5","url":null,"abstract":"<p><p>Medullary thyroid carcinoma (MTC) is a C-cell-derived epithelial neuroendocrine neoplasm. With the exception of rare examples, most are well-differentiated epithelial neuroendocrine neoplasms (also known as neuroendocrine tumors in the taxonomy of the International Agency for Research on Cancer [IARC] of the World Health Organization [WHO]). This review provides an overview and recent evidence-based data on the molecular genetics, disease risk stratification based on clinicopathologic variables including molecular profiling and histopathologic variables, and targeted molecular therapies in patients with advanced MTC. While MTC is not the only neuroendocrine neoplasm in the thyroid gland, other neuroendocrine neoplasms in the thyroid include intrathyroidal thymic neuroendocrine neoplasms, intrathyroidal parathyroid neoplasms, and primary thyroid paragangliomas as well as metastatic neuroendocrine neoplasms. Therefore, the first responsibility of a pathologist is to distinguish MTC from other mimics using appropriate biomarkers. The second responsibility includes meticulous assessment of the status of angioinvasion (defined as tumor cells invading through a vessel wall and forming tumor-fibrin complexes, or intravascular tumor cells admixed with fibrin/thrombus), tumor necrosis, proliferative rate (mitotic count and Ki67 labeling index), and tumor grade (low- or high-grade) along with the tumor stage and the resection margins. Given the morphologic and proliferative heterogeneity in these neoplasms, an exhaustive sampling is strongly recommended. Routine molecular testing for pathogenic germline RET variants is typically performed in all patients with a diagnosis of MTC; however, multifocal C-cell hyperplasia in association with at least a single focus of MTC and/or multifocal C-cell neoplasia are morphological harbingers of germline RET alterations. It is of interest to assess the status of pathogenic molecular alterations involving genes other than RET like the MET variants in MTC families with no pathogenic germline RET variants. Furthermore, the status of somatic RET alterations should be determined in all advanced/progressive or metastatic diseases, especially when selective RET inhibitor therapy (e.g., selpercatinib or pralsetinib) is considered. While the role of routine SSTR2/5 immunohistochemistry remains to be further clarified, evidence suggests that patients with somatostatin receptor (SSTR)-avid metastatic disease may also benefit from the option of ¹⁷⁷Lu-DOTATATE peptide radionuclide receptor therapy. Finally, the authors of this review make a call to support the nomenclature change of MTC to C-cell neuroendocrine neoplasm to align this entity with the IARC/WHO taxonomy since MTCs represent epithelial neuroendocrine neoplasms of endoderm-derived C-cells.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 1","pages":"1-22"},"PeriodicalIF":4.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9110432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Thyroid Pathologist Meets Therapeutic Pharmacology.","authors":"Christopher M Sande,&nbsp;Isabella Tondi Resta,&nbsp;Virginia A Livolsi","doi":"10.1007/s12022-023-09749-1","DOIUrl":"https://doi.org/10.1007/s12022-023-09749-1","url":null,"abstract":"<p><p>The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia-changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 1","pages":"48-56"},"PeriodicalIF":4.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9111900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of the 2022 WHO Classification of Thyroid Neoplasms on Everyday Practice of Cytopathology.","authors":"Esther Diana Rossi, Zubair Baloch","doi":"10.1007/s12022-023-09756-2","DOIUrl":"10.1007/s12022-023-09756-2","url":null,"abstract":"<p><p>This review outlines how the alterations in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors of the thyroid gland are likely to impact thyroid cytopathology. It is important to note that WHO subclassifies thyroid tumors into several new categories based on increased comprehension of the cell of origin, pathologic features (including cytopathology), molecular classification, and biological behavior. The 3rd edition of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) will debut in the near future and will include changes in diagnostic category designations. The changes in the 5th edition of the WHO will in some instances subtly, and in other instances significantly, impact the cytological diagnoses. Moreover, these changes will also affect other thyroid FNA classification schemes used internationally for classifying thyroid FNA specimens.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 1","pages":"23-33"},"PeriodicalIF":11.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9479488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Presence of Typical \"BRAFV600E-Like\" Atypia in Papillary Thyroid Carcinoma is Highly Specific for the Presence of the BRAFV600E Mutation.","authors":"John Turchini,&nbsp;Loretta Sioson,&nbsp;Adele Clarkson,&nbsp;Amy Sheen,&nbsp;Leigh Delbridge,&nbsp;Anthony Glover,&nbsp;Mark Sywak,&nbsp;Stan Sidhu,&nbsp;Anthony J Gill","doi":"10.1007/s12022-022-09747-9","DOIUrl":"https://doi.org/10.1007/s12022-022-09747-9","url":null,"abstract":"<p><p>Papillary thyroid carcinomas (PTCs) are driven by a variety of molecular abnormalities including BRAF, RAS, ALK, RET, and NTRK alterations. PTCs driven by the BRAFV600E mutation, or tumours which demonstrate a similar gene expression profile to PTCs driven by this mutation, have been reported to demonstrate specific morphological features sometimes termed \"BRAFV600E-like\" atypia. BRAFV600E-like atypia is characterised by a well-developed papillary architecture, infiltrative growth, marked nuclear clearing, prominent intranuclear pseudoinclusions, abundant eosinophilic cytoplasm, and scattered psammoma bodies. We sought to investigate the sensitivity and specificity of these morphological features for the presence of BRAFV600E mutation in PTCs as determined by mutation specific immunohistochemistry. An unselected cohort of 495 PTCs was reviewed by a single pathologist and categorised into three groups: typical BRAFV600E-like atypia (145 cases, 29%), possible BRAFV600E-like atypia (166 cases, 33%) and little/no BRAFV600E-like atypia (184 cases, 37%). The specificity and sensitivity of typical BRAFV600E-like atypia for the BRAFV600E mutation was 97.2% and 44.3%, respectively. When typical and possible BRAFV600E-like atypia were analysed together, the specificity was 70.6% and the sensitivity was 81.7%. In the morphologically little/no BRAFV600E-like atypia group, 58 cases (31.5%) had a BRAFV600E mutation. We conclude that typical BRAFV600E-like atypia is highly specific for the presence of the BRAFV600E mutation; however, the absence of BRAFV600E-like atypia does not exclude this mutation.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 1","pages":"112-118"},"PeriodicalIF":4.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcomatous Transformation of a Medically Treated Lactotroph Pituitary Neuroendocrine Tumor?","authors":"Merryl Terry,&nbsp;Gerald Reis,&nbsp;Andrew Horvai,&nbsp;Melike Pekmezci,&nbsp;Arie Perry","doi":"10.1007/s12022-023-09757-1","DOIUrl":"https://doi.org/10.1007/s12022-023-09757-1","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"34 1","pages":"161-163"},"PeriodicalIF":4.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9226309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}