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<p>Pituitary neuroendocrine tumors (PitNETs) are generally benign, but a small subset may demonstrate aggressive behavior or undergo malignant transformation. Neuroendocrine carcinoma (NEC), defined as a high-grade, poorly differentiated neuroendocrine neoplasm, is extremely rare in the pituitary, and its existence as a primary entity remains controversial. We report two cases of corticotroph PitNETs in female patients with Cushing disease, in which NEC components emerged several years after radiotherapy. Case 1 presented as an invasive macroadenoma with cavernous sinus invasion, and Case 2 as a 5 mm microadenoma. In both cases, recurrent tumors developed following subsequent radiotherapy. NEC components exhibited marked nuclear pleomorphism, necrosis, elevated Ki-67 indices, diffuse p53 expression, and loss or reduction of ACTH and TPIT expression. In Case 2, faint TPIT expression and discontinuous tumor growth within the sella raised the possibility of a metastatic NEC to the pituitary could not be excluded. These cases highlight the emergence of NEC features in corticotroph PitNETs, most likely as a result of post-radiotherapy transformation. However, due to faint TPIT expression and an unusual tumor distribution in Case 2, the possibility of a primary NEC or metastatic neuroendocrine neoplasm from another organ cannot be definitively excluded.</p>

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Emergence of NEC features in corticotroph PitNETs: primary tumor, radiation-induced transformation, or metastasis?

  • 期刊论文

  • 发表日期：

    2025年9月3日

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  • Naoko Inoshita,
  • Hiroshi Nishioka,
  • Noriaki Fukuhara,
  • Keita Tatsushima,
  • Akira Takeshita,
  • Yasuhiro Takeuchi,
  • Yutaka Takazawa,
  • Naotetsu Kanamoto,
  • Shozo Yamada

摘要

Pituitary neuroendocrine tumors (PitNETs) are generally benign, but a small subset may demonstrate aggressive behavior or undergo malignant transformation. Neuroendocrine carcinoma (NEC), defined as a high-grade, poorly differentiated neuroendocrine neoplasm, is extremely rare in the pituitary, and its existence as a primary entity remains controversial. We report two cases of corticotroph PitNETs in female patients with Cushing disease, in which NEC components emerged several years after radiotherapy. Case 1 presented as an invasive macroadenoma with cavernous sinus invasion, and Case 2 as a 5 mm microadenoma. In both cases, recurrent tumors developed following subsequent radiotherapy. NEC components exhibited marked nuclear pleomorphism, necrosis, elevated Ki-67 indices, diffuse p53 expression, and loss or reduction of ACTH and TPIT expression. In Case 2, faint TPIT expression and discontinuous tumor growth within the sella raised the possibility of a metastatic NEC to the pituitary could not be excluded. These cases highlight the emergence of NEC features in corticotroph PitNETs, most likely as a result of post-radiotherapy transformation. However, due to faint TPIT expression and an unusual tumor distribution in Case 2, the possibility of a primary NEC or metastatic neuroendocrine neoplasm from another organ cannot be definitively excluded.