The patient’s journey began more than four months before her admission, when the low back pain first appeared without any identifiable trigger. By February 2026, dizziness and fatigue prompted her admission to the Department of Neurology at The First People’s Hospital of Yancheng. Cranial computed tomography revealed nothing abnormal, but the story changed dramatically when she underwent whole-body positron emission tomography combined with computed tomography, a technique that maps glucose metabolism throughout the body and lights up tissues consuming energy at malignant rates. The scan showed a hypermetabolic mass in the right lower uterine body near the cervix, with a maximum standardized uptake value of approximately 12.4, a figure firmly in the range of aggressive malignancy. Surrounding that finding were multiple diffuse nodules in both lungs, a nodule in liver segment five, enlarged iliac and para-aortic lymph nodes, and numerous osteoblastic bone lesions scattered across the skeleton, all showing elevated glucose metabolism.

Given the dominant uterine lesion and the pattern of spread, the imaging team’s initial interpretation was entirely reasonable: a primary uterine malignancy that had already metastasized widely. A diagnostic curettage performed in February 2026, however, returned only mucinous tissue from the endocervical canal and chronic inflammation of the cervix, with no malignant cells identified. That false negative, the authors explain, likely reflected the limited sampling area of curettage and the patchy, heterogeneous distribution of metastatic deposits within the uterus. Gastroscopy and colonoscopy were then used to exclude a gastrointestinal primary, yielding only a benign fundic gland polyp. Pelvic magnetic resonance imaging subsequently showed an abnormal signal at the uterine-cervical junction and metastatic signals in the right ilium and left acetabulum, prompting an ultrasound-guided percutaneous core-needle biopsy that would finally supply the tissue needed to solve the puzzle.

Under the microscope, the biopsy revealed poorly differentiated adenocarcinoma: tumor cells arranged in solid nests and sheets, lacking obvious glandular differentiation, with large irregular nuclei, coarse chromatin, prominent nuclear atypia, increased mitotic figures, and focal invasion of the supporting stroma. The problem was that this morphology overlapped almost completely with a poorly differentiated primary uterine adenocarcinoma. Morphology alone, the case demonstrates, simply cannot distinguish a metastasis from a primary tumor when the cancer has lost the architectural features that betray its origin. This diagnostic ambiguity is precisely why the case carries such educational weight, and why the authors argue that tissue-based diagnosis must extend far beyond routine staining when a patient presents with multiorgan disease of uncertain origin.

The decisive evidence came from immunohistochemistry, a technique that uses antibodies to detect specific proteins in tissue sections and thereby fingerprints a tumor’s cellular ancestry. The uterine lesion stained positive for TTF-1 and Napsin A, two markers highly characteristic of lung adenocarcinoma, and positive for CK7, a keratin consistent with pulmonary and other epithelial origins. Critically, the tumor was negative for PAX8, estrogen receptor, and progesterone receptor, the markers that typically define primary uterine adenocarcinomas. The authors are careful to note the nuance: TTF-1 positivity has occasionally been reported in a small number of endometrial adenocarcinomas, so no single marker is absolutely diagnostic. It is the combined signature, TTF-1, Napsin A, and CK7 positivity alongside PAX8, ER, and PR negativity, integrated with the clinical and imaging context, that pointed decisively to the lung.

Genomic testing then delivered both confirmation and a therapeutic roadmap. Using next-generation sequencing across a full exon panel on the biopsy tissue, the team detected an EGFR exon 21 p.L858R mutation, one of the commonest sensitizing alterations in lung adenocarcinoma and a well-established predictor of response to tyrosine kinase inhibitors. No other actionable gene alterations were found. A multidisciplinary team spanning gynecology, medical oncology, radiation oncology, pathology, radiology, and nuclear medicine therefore established the final diagnosis: stage IV lung adenocarcinoma with synchronous metastases to the uterus, lungs, liver, and bone, harboring a druggable EGFR mutation. The uterine mass, in other words, was never a uterine cancer at all; it was lung cancer wearing a disguise that only molecular analysis could strip away.

Treatment proceeded along two complementary tracks. The patient received palliative radiotherapy, 30 gray delivered in 10 fractions using 6 MV-X helical tomotherapy, targeting the osteoblastic bone lesions and the local uterine mass to relieve pain and reduce tumor burden. Simultaneously, she began oral osimertinib, a third-generation tyrosine kinase inhibitor that selectively inhibits mutant EGFR and has become first-line standard therapy for advanced EGFR-mutant lung adenocarcinoma. The combination demands vigilance, because radiotherapy and targeted therapy share potential overlapping toxicities, most notably radiation pneumonitis and myelosuppression. Throughout treatment, the team monitored blood counts and pulmonary function closely. Adverse events were limited to radiation-induced fatigue and mild myelosuppression, both of which improved with supportive care, demonstrating that the combined regimen is clinically feasible and well tolerated in this setting.

By the follow-up examination on July 30, 2026, contrast-enhanced CT of the chest and abdomen showed a marked reduction in the uterine tumor and pelvic lymph nodes, with pulmonary nodules essentially unchanged, a partial response by the RECIST 1.1 criteria. The authors emphasize that long-term follow-up will be needed to verify durability, but the early result underscores a broader principle of modern oncology: when genomic profiling identifies an actionable mutation, even a patient with widely metastatic, atypically presenting disease can achieve meaningful disease control and quality-of-life gains with targeted therapy rather than conventional chemotherapy.

The rarity of this presentation is what makes the case scientifically valuable. Among secondary tumors of the female genital tract, the ovaries account for roughly 76 percent of metastases and the vagina for about 13 percent, while the uterus represents only about 8 percent. A recent retrospective series of five patients, the largest to date, found that most presented with abnormal vaginal bleeding or abdominal pain and bloating. This patient differed on nearly every count: she was older, her symptoms were entirely non-gynecologic, imaging pointed toward a uterine primary, an initial curettage was negative, and her management combined palliative radiotherapy with osimertinib, a sequence rarely reported for uterine metastasis. Primary uterine malignancies typically announce themselves with abnormal bleeding or pelvic pain, whereas metastatic uterine tumors often lack these classic features, a contrast that directly contributed to the initial misdirection.

The clinical lesson the authors draw is unambiguous. Imaging, however sophisticated, can suggest but never confirm a tumor’s origin in patients with multiorgan lesions, and clinicians should resist anchoring on the most visually dominant lesion. The path to the correct diagnosis ran through targeted biopsy, a multi-index immunohistochemical panel, and molecular genetic testing, each layer correcting the assumptions of the last. For patients with cancer of unknown primary origin, this integrated approach is not optional but mandatory, because identifying the true primary site determines whether a patient receives chemotherapy, hormone therapy, or, as in this case, a mutation-targeted drug that can shrink disease across the body. As lung adenocarcinoma, which accounts for roughly 40 percent of all lung cancers, continues to lead global cancer mortality, awareness of its rarest metastatic patterns may be the difference between a delayed, misdirected workup and an early, precise, life-extending intervention.

Subject of Research: Uterine metastasis of lung adenocarcinoma mimicking a primary uterine malignancy

Article Title: Metastatic Lung Adenocarcinoma to the Uterus Mimicking a Primary Uterine Malignancy: A Case Report

Article References: Sun, P., & Wang, Y. (2026). Metastatic Lung Adenocarcinoma to the Uterus Mimicking a Primary Uterine Malignancy: A Case Report. Cancer Reports, 9(10), Article e70706. https://doi.org/10.1002/cnr2.70706

Image Credits: AI Generated

DOI: 10.1002/cnr2.70706

Keywords: lung adenocarcinoma, uterine metastasis, EGFR L858R, osimertinib, immunohistochemistry, TTF-1, Napsin A, PET-CT, misdiagnosis, targeted therapy, case report, palliative radiotherapy