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Case Report Open Access

Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report

  • Authors:
    • Nobuhito Hara
    • Rika Sasaki
    • Yoshiki Kojitani
    • Yumi Yoshii
    • Masahide Ota
    • Shunsuke Okazaki
    • Yuji Nitta
    • Tomoko Uchiyama
    • Akihiko Yoshizawa
    • Ryo Miyata
    • Masatsugu Hamaji
    • Hirotaka Kajihara
    • Masayuki Takeda

  • View Affiliations / Copyright

    Affiliations: Department of Cancer Genomics and Medical Oncology, Nara Medical University, Kashihara, Nara 634‑8521, Japan, Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara 634‑8521, Japan, Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Kashihara, Nara 634‑8521, Japan, Department of Obstetrics and Gynecology, Osaka Gyomeikan Hospital, Osaka, Osaka 554‑0012, Japan
    Copyright: © Hara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 148
    |
    Published online on: February 25, 2026
       https://doi.org/10.3892/ol.2026.15501
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Abstract

The present report describes a rare case of cervical adenocarcinoma with a coexisting neuroendocrine tumor (NET) G2 component that developed pulmonary metastases with proliferative escalation and possible transformation to neuroendocrine carcinoma (NEC). A 43‑year‑old woman with cervical adenocarcinoma (International Federation of Gynaecology and Obstetrics 2018 stage IB1) underwent radical hysterectomy, bilateral salpingectomy and pelvic lymph node dissection. The primary tumor had morphologic features of mixed adenocarcinoma and NET G2 [Ki‑67, 3‑30%; 5‑8 mitoses/10 high‑power fields (HPFs)], classified as postoperative pathological stage IB1 (pT1b1 N0 M0; American Joint Committee on Cancer 9th edition). After 2 years, chest computed tomography revealed multiple pulmonary nodules. Resection of a right middle lobe lesion revealed metastatic NET with increased proliferative activity (G3 based on gastrointestinal NET criteria; Ki‑67 hotspot, 35%; >50 mitoses/10 HPFs). A left upper lobe lesion exhibited predominantly NET morphology, but focal areas exhibited high proliferative activity (Ki‑67 hotspot, 93%; 50 mitoses per 10 HPFs) with features compatible with small cell carcinoma. The current case suggests a stepwise progression from NET toward NEC, highlighting the importance of monitoring proliferative indices in cervical NETs, re‑evaluating metastatic lesions histologically and considering multimodal treatment strategies.
View Figures

Figure 1

(A) Non-contrast chest CT scan obtained in March 2024 showing a small nodule in the left upper lobe. (B) Non-contrast chest CT scan obtained in March 2024 showing a small nodule in the left lower lobe. (C) Non-contrast chest CT scan obtained in March 2024 showing a small nodule in the right middle lobe. (D) Non-contrast chest CT scan obtained in June 2024 showing enlargement of the left upper lobe nodule. (E) Non-contrast chest CT scan obtained in June 2024 showing enlargement of the nodules in the right middle and left lower lobes. (F) Non-contrast chest CT scan obtained in December 2024 showing further enlargement of the left upper lobe nodule. (G) Non-contrast chest CT scan obtained in December 2024 showing further enlargement of the left lower lobe nodule. (H) Non-contrast chest CT scan obtained in April 2025 showing further enlargement of the left upper lobe nodule. (I) Non-contrast chest CT scan obtained in Apri 2025 showing further enlargement of the left lower lobe nodule. Overall, the nodules gradually increased in size over time. Red arrows indicate the tumor lesions.

Figure 2

Histopathological and immunohistochemical findings of the cervical tumor. (A) H&E staining (ocular, ×10; objective, ×4; final magnification, ×40) showing mixed histology. (B) H&E staining (ocular, ×10; objective, ×10; final magnification, ×100) revealing coexistence of adenocarcinoma and neuroendocrine components. (C) H&E staining of the neuroendocrine component (ocular, ×10; objective, ×40; final magnification, ×400). (D-L) Immunohistochemical analysis of the neuroendocrine component (ocular, ×10; objective, ×40; final magnification, ×400) revealing the following: (D) Synaptophysin, positive; (E) chromogranin A, positive; (F) p16, positive; (G) yes-associated protein 1, negative; (H) thyroid transcription factor-1, negative; (I) retinoblastoma protein, wild-type expression; (J) paired box 8, negative; (K) Ki-67, low proliferative activity; and (L) Ki-67, hotspot with high proliferative activity.

Figure 3

Histopathological and immunohistochemical findings of the right middle lobe lung tumor. (A-C) H&E staining of the resected specimen showing exclusively neuroendocrine tumor components. (A) Ocular, ×10; objective, ×4; final magnification, ×40. (B) Ocular, ×10; objective, ×10; final magnification, ×100. (C) Ocular, ×10; objective, ×40; final magnification, ×400. (D) Chromogranin A immunostaining (ocular, ×10; objective, ×40; final magnification, ×400) demonstrating positive expression in tumor cells.

Figure 4

Histopathological and immunohistochemical findings of the left upper lobe lung tumor. (A) Low-power view of H&E staining (scale bar, 2.5 mm). (B) H&E staining (ocular, ×10; objective, ×10; final magnification, ×100). (C) H&E staining (ocular, ×10; objective, ×20; final magnification, ×200). (A-C) The tumor consisted predominantly of NET components but with areas of increased chromatin and a higher nuclear-to-cytoplasmic ratio, suggesting the presence of NEC components. (D-K) Immunohistochemical analysis (ocular, ×10; objective, ×10; final magnification, ×100) revealed the following: (D) Synaptophysin, positive in NET areas but weaker in suspected NEC areas; (E) chromogranin A, positive; (F) p16, positive; (G) yes-associated protein 1, negative; (H) thyroid transcription factor-1, negative in NET areas but focally positive in suspected NEC areas; (I) retinoblastoma protein, wild-type expression; (J) paired box 8, negative; and (K) Ki-67, high proliferative index in suspected NEC areas. NEC, neuroendocrine carcinoma; NET, neuroendocrine tumor.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Hara N, Sasaki R, Kojitani Y, Yoshii Y, Ota M, Okazaki S, Nitta Y, Uchiyama T, Yoshizawa A, Miyata R, Miyata R, et al: Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report. Oncol Lett 31: 148, 2026.
APA
Hara, N., Sasaki, R., Kojitani, Y., Yoshii, Y., Ota, M., Okazaki, S. ... Takeda, M. (2026). Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report. Oncology Letters, 31, 148. https://doi.org/10.3892/ol.2026.15501
MLA
Hara, N., Sasaki, R., Kojitani, Y., Yoshii, Y., Ota, M., Okazaki, S., Nitta, Y., Uchiyama, T., Yoshizawa, A., Miyata, R., Hamaji, M., Kajihara, H., Takeda, M."Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report". Oncology Letters 31.4 (2026): 148.
Chicago
Hara, N., Sasaki, R., Kojitani, Y., Yoshii, Y., Ota, M., Okazaki, S., Nitta, Y., Uchiyama, T., Yoshizawa, A., Miyata, R., Hamaji, M., Kajihara, H., Takeda, M."Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report". Oncology Letters 31, no. 4 (2026): 148. https://doi.org/10.3892/ol.2026.15501
Copy and paste a formatted citation
x
Spandidos Publications style
Hara N, Sasaki R, Kojitani Y, Yoshii Y, Ota M, Okazaki S, Nitta Y, Uchiyama T, Yoshizawa A, Miyata R, Miyata R, et al: Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report. Oncol Lett 31: 148, 2026.
APA
Hara, N., Sasaki, R., Kojitani, Y., Yoshii, Y., Ota, M., Okazaki, S. ... Takeda, M. (2026). Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report. Oncology Letters, 31, 148. https://doi.org/10.3892/ol.2026.15501
MLA
Hara, N., Sasaki, R., Kojitani, Y., Yoshii, Y., Ota, M., Okazaki, S., Nitta, Y., Uchiyama, T., Yoshizawa, A., Miyata, R., Hamaji, M., Kajihara, H., Takeda, M."Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report". Oncology Letters 31.4 (2026): 148.
Chicago
Hara, N., Sasaki, R., Kojitani, Y., Yoshii, Y., Ota, M., Okazaki, S., Nitta, Y., Uchiyama, T., Yoshizawa, A., Miyata, R., Hamaji, M., Kajihara, H., Takeda, M."Proliferative escalation and possible neuroendocrine carcinoma transformation in pulmonary metastases of a cervical neuroendocrine tumor: A case report". Oncology Letters 31, no. 4 (2026): 148. https://doi.org/10.3892/ol.2026.15501
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