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While metastasis develops in only 10\u201315% of adrenal-origin, this rate can rise up to 50% in those with extra-adrenal localization. This study aims to investigate the potential predictive effect of known histopathological features in PCC\/PGL, alongside SDHB, S100, Ki-67 proliferation index, and the expression of MAML3 and MCM6 in predicting metastatic disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The specimens of 71 patients who were diagnosed with PCC\/PGL and underwent total excision between 2010 and 2021 were re-examined. Demographic, clinical, and histopathological data, as well as immunohistochemical results for Ki-67, S100, SDHB, MCM6, and MAML3, were recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      While distant organ metastasis was observed in 3.4% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091\/29) of PCC and 21.2% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097\/33) of head and neck PGL, this rate was found to be significantly higher at 66.7% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096\/9) in abdominal PGL (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). No MAML3 overexpression was observed in any of the cases. Distant organ metastasis was more frequently detected in cases with MCM6 overexpression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although there is still no definitive feature that predicts metastasis, in line with the literature, extra-adrenal localization, vascular invasion, capsular invasion, nuclear pleomorphism, hyperchromasia, and confluent necrosis were found to be associated with distant organ metastasis in our study. Additionally, in the multivariate analysis, larger tumor size (&gt;\u20095.1\u00a0cm), the presence of &gt;\u20093\/10 HPF mitosis, and SDHB loss were associated with lower metastasis-free survival. While no conclusions could be drawn regarding MAML3, the prognostic value of MCM6 appears promising.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40618-025-02610-8","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T06:27:45Z","timestamp":1748586465000},"page":"2077-2086","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prognostic markers in pheochromocytomas\/paragangliomas: the role of histopathology, SDHB, MAML3 and MCM6 expression"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7297-9869","authenticated-orcid":false,"given":"Emel","family":"Yald\u0131r","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e7a Beg\u00fcm","family":"Cengiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman Furkan","family":"M\u00fclkem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzaffer","family":"Bilgin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Fuat","family":"A\u00e7\u0131kal\u0131n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"issue":"6","key":"2610_CR1","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1210\/jc.2014-1498","volume":"99","author":"JW Lenders","year":"2014","unstructured":"Lenders JW, Duh Q-Y, Eisenhofer G, Gimenez-Roqueplo A-P, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr (2014) Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. 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