Rare Brain Tumor Puzzle: Fetal-Type Cancer in the Cerebellopontine Angle With No Lung Primary Found

What the microscope revealed instead was an adenocarcinoma with high-grade fetal morphology, a malignant gland-forming cancer whose cells eerily resemble embryonic lung tissue.

The case, published as a case report in Frontiers in Oncology by radiologists Xiaowen Liu and Chengxin Yan of the Second Affiliated Hospital of Shandong First Medical University, is less a story about a single rare cancer than a masterclass in diagnostic humility. The authors deliberately stopped short of calling the tumor pulmonary high-grade fetal adenocarcinoma, the diagnosis that morphology alone seemed to invite. Because no lung lesion appeared on the initial thoracic CT, no primary was confirmed pathologically, and systemic staging was never completed, they settled on a more cautious label: metastatic adenocarcinoma with high-grade fetal morphology, favoring pulmonary origin. That distinction, they argue, matters enormously for how such cases are reported, studied, and compared.

The cerebellopontine angle is a crowded crossroads of the nervous system. It hosts the facial and vestibulocochlear nerve complex, the lower cranial nerves, and critical brainstem structures, and it is the classic home of vestibular schwannomas, meningiomas, and epidermoid cysts. Metastatic cancers do appear there, occasionally in patients with no known malignancy, and they can imitate the benign trio with unsettling fidelity. In this patient, the clinical picture initially pointed toward a schwannoma: hearing loss and dizziness are its signature complaints. But several imaging features broke the pattern. The internal auditory canal was not enlarged, and no definite intracanalicular component was seen, both atypical for a vestibular schwannoma.

Magnetic resonance imaging mapped a lobulated mass measuring 37.6 by 24.7 by 35.9 millimeters, with the transverse and anteroposterior dimensions taken on axial contrast-enhanced T1-weighted images and the craniocaudal dimension on a sagittal image. The lesion compressed the brainstem, cerebellum, and fourth ventricle, and the interface with the brainstem raised suspicion of invasion, although definite parenchymal invasion was never established. Enhancement was heterogeneous and avid, with small nonenhancing foci, and diffusion imaging showed no definite restriction. There was no broad dural attachment, no dural tail, no calcification, and no hyperostosis, findings that weakened the case for meningioma. The combination of a short symptom history, heterogeneous enhancement, surrounding edema, and suspected brainstem involvement pushed metastasis up the differential list.

The search for a source came up empty. Initial thoracic CT revealed no suspicious pulmonary lesion, no hilar or mediastinal lymphadenopathy, no pleural abnormality, and no thoracic mass. Whole-body FDG PET/CT and serial thoracic CT were never performed, so systemic staging remained incomplete. Blood tests offered only a whisper of a clue: carcinoembryonic antigen was elevated at 13.30 nanograms per milliliter against a reference interval of 0 to 5, while alpha-fetoprotein and a broad panel of other tumor markers, including CA125, CA19-9, prostate-specific antigen, and neuron-specific enolase, all fell within normal limits.

Surgery proceeded through a retrosigmoid approach. Intraoperatively, the tumor proved firm and hypervascular, densely adherent to the facial-vestibulocochlear complex, the lower cranial nerves, and the brainstem. After opening the capsule and mapping nerve courses with electrophysiology, the surgical team removed the tumor piecemeal but intentionally left a small residual component to avoid catastrophic injury, resulting in a subtotal resection. The authors note that dense adhesion alone did not establish histological brainstem invasion, another example of the careful language that runs through the entire report.

Under the microscope, two pathologists found complex glandular and papillary architecture, clear to eosinophilic cytoplasm with prominent supranuclear and subnuclear vacuoles, high-grade atypia, and patchy necrosis, the histological fingerprint of fetal-type differentiation. Immunohistochemistry showed diffuse strong pan-cytokeratin, focal CK7, focal nuclear TTF-1 and SALL4, partial synaptophysin, and focal weak CD56, with a Ki-67 proliferation index of approximately 80 percent in a hotspot. A long list of stains came back negative: CK20, SATB2, PAX8, PAX2, NKX3.1, GFAP, Napsin A, S100, SOX10, OCT3/4, and CD117. Focal TTF-1 lent limited support to pulmonary differentiation, but the authors stress it did not establish pulmonary origin, and negative Napsin A neither excluded lung adenocarcinoma nor provided positive evidence for it.

The differential diagnosis read like an atlas of rare intracranial neoplasms. Adult medulloblastoma was considered but rejected because the tumor lacked primitive small-cell morphology and instead showed complex epithelial glands with diffuse keratin expression. Atypical teratoid/rhabdoid tumor was less likely without characteristic rhabdoid morphology, though INI1/SMARCB1 and BRG1/SMARCA4 testing was unavailable. Embryonal tumor with multilayered rosettes was improbable given the patient’s age and the absence of multilayered rosettes or neuropil-rich architecture. Choroid plexus carcinoma remained incompletely resolved because Kir7.1, stanniocalcin-1, and transthyretin were never assessed. Yolk sac and hepatoid tumors were weighed against SALL4 positivity, but normal serum AFP could not replace tissue assessment, and remaining paraffin-embedded tissue was simply insufficient for additional immunohistochemistry.

The aftermath was grim and instructive. Postoperatively, the patient developed dysphagia with coughing and choking on liquids, along with facial nerve dysfunction including impaired cheek puffing and lagophthalmos, deficits anatomically compatible with the operative findings. After tertiary-center consultation, no systemic anticancer therapy or radiotherapy was initiated, and he received best supportive care at a local hospital. Molecular testing for EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, and NTRK, as well as PD-L1 assessment, were never performed, and detailed records of the treatment decision were unavailable. He died three months after surgery, with the immediate cause undocumented. The authors explicitly warn that this short survival interval cannot be used as evidence of prognosis for pulmonary high-grade fetal adenocarcinoma, given the confounding effects of residual tumor, impaired swallowing, incomplete staging, and the absence of tumor-directed therapy.

The broader lesson the authors draw is twofold. First, metastasis belongs on the differential for any atypical cerebellopontine angle mass, even when the initial chest CT is negative, because a single negative scan cannot exclude an occult primary and incomplete staging leaves the question open. Second, diagnostic terminology must reflect uncertainty: they consistently used the phrase metastatic adenocarcinoma with high-grade fetal morphology, favoring pulmonary origin, rather than claiming a confirmed pulmonary high-grade fetal adenocarcinoma. They also note that a reported pulmonary case with MET amplification and brain metastasis responded to savolitinib, illustrating how molecular findings might have informed treatment discussions here, though such testing would neither have identified the primary site nor guaranteed benefit. In an era when genomic profiling increasingly guides cancer care, this case stands as a reminder that the most advanced diagnostic tools are only as good as the tissue available to test, and that honest reporting of what remains unknown is itself a scientific contribution.

Subject of Research: A case report of cerebellopontine angle metastatic adenocarcinoma with high-grade fetal morphology and no identifiable pulmonary primary on initial CT

Article Title: Case Report: Cerebellopontine angle metastatic adenocarcinoma with high-grade fetal morphology and no identifiable pulmonary primary on initial CT

Article References: Liu, X., & Yan, C. (2026). Case Report: Cerebellopontine angle metastatic adenocarcinoma with high-grade fetal morphology and no identifiable pulmonary primary on initial CT. Frontiers in Oncology, 16, Article 1942218. https://doi.org/10.3389/fonc.2026.1942218

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1942218

Keywords: cerebellopontine angle, metastatic adenocarcinoma, high-grade fetal adenocarcinoma, fetal morphology, brain metastasis, TTF-1, SALL4, immunohistochemistry, differential diagnosis, case report, lung cancer, neuroimaging