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

The cat arrived at the Colorado State University Veterinary Teaching Hospital after its owner noticed a growing mass in the neck. Two weeks earlier, the family veterinarian had measured it at 3.7 by 2.1 centimeters, but by the time of the referral examination it had expanded to roughly 5 centimeters long and 4 centimeters wide, filling the ventral part of the neck. The owner also described six months of gradually worsening snoring noises, lethargy, and a mildly reduced appetite. On physical examination, the cat was bright and alert but showed intermittent stertor and stridor, the harsh breathing sounds produced when the upper airway is partially obstructed. A large, fixed, painless mass dominated the left side of the throat.

Advanced imaging revealed the true scale of the problem. A triple-phase computed tomography scan showed a lobular, strongly and heterogeneously enhancing soft tissue mass measuring 5.2 by 4.1 by 3.9 centimeters that completely enveloped the common carotid artery, the main vessel supplying the head. The mass compressed and displaced the thyroid glands, pushed the pharynx, larynx, and hyoid apparatus markedly to the right, and extended toward the skull base near the tympanic bulla. Multiple branching vessels penetrated deep into the tumor interior, a hallmark of the rich blood supply characteristic of chemoreceptor tissue. A board-certified radiologist judged the growth pattern inconsistent with thyroid carcinoma, and the differential diagnosis narrowed to a carotid body tumor, a metastatic lymph node mass, or a primary soft tissue sarcoma.

Fine-needle aspiration cytology of the mass showed an epithelial neoplasm with endocrine and neuroendocrine morphology: densely cohesive clusters of round to polygonal cells with scant basophilic cytoplasm, ropey chromatin, and absent nucleoli. Critically, immunocytochemical staining for Thyroid Transcription Factor-1, a marker of thyroid origin, came back negative, making a thyroid tumor far less likely. The absence of any secretory phenotype, no hyperthyroidism and no hypercalcemia on bloodwork, further separated this tumor from the functional thyroid and parathyroid carcinomas that typically arise in the feline neck. Taken together with the tumor’s location hugging the carotid bifurcation, the team concluded the mass was most consistent with a paraganglioma of the carotid body, a tumor type never before documented in a cat.

That diagnosis matters because carotid body paragangliomas, also called chemodectomas, arise from the chemoreceptor organs that sense oxygen and carbon dioxide in blood. They are well described in dogs and humans, in whom they are notoriously invasive, enveloping major vessels at the base of the skull and causing retropharyngeal masses, difficulty swallowing, respiratory distress, stridor, gagging, and laryngeal paralysis. This cat’s presentation, including left-sided laryngeal paralysis and bilateral tonsillar protrusion noted on a sedated oral exam, matched that pattern almost exactly. Yet in cats, paragangliomas had only ever been reported in the abdomen, around the kidneys and retroperitoneum, at the aortic body, in the heart, and in the orbit, never at the carotid body, despite the fact that cats possess these normal anatomic structures.

Surgery was off the table. After reviewing the imaging, a board-certified surgical oncologist judged the mass unresectable because of its extensive involvement of the carotid artery, larynx, and hyoid apparatus, and warned that any biopsy attempt risked catastrophic hemorrhage and airway-compromising swelling. The oncology team instead offered definitive-intent stereotactic body radiotherapy, a technique that delivers ablative radiation doses in a handful of fractions with submillimeter targeting. The rationale was technical as much as biological: compared with a conventional 16 to 20 fraction course, a three-fraction protocol meant only three anesthesia episodes for a cat that was already difficult to intubate, with far less cumulative acute toxicity to the pharynx and trachea.

The treatment plan was built on the treatment planning system using pre- and post-contrast CT sequences. The gross target volume encompassed all abnormal contrast-enhancing tissue and abnormal vasculature, including the left tonsil. A 2-millimeter planning target volume expansion accounted for setup uncertainty, but was cropped away from organs at risk, the skin, pharynx, trachea, esophagus, brain, spinal cord, and eyes, to prioritize normal tissue sparing. Two coplanar arcs of 6-megavolt photons delivered 10 Gy per day for three consecutive days, for a total of 30 Gy, using volumetric modulated arc therapy. Dosimetry was calculated with the Acuros algorithm, and quality assurance with an electronic portal imaging device achieved a gamma passing rate above 95 percent at 3 millimeters and 3 percent, confirming the planned dose distribution matched delivery.

The response was fast and durable. Two weeks after the final fraction, the tumor had shrunk roughly 30 percent in length and 37.5 percent in width on caliper measurement, the cat’s breathing signs had resolved, and its appetite had normalized. By three months, the mass was no longer palpable at all. Ultrasound at 15 months showed a residual soft tissue structure surrounding the left carotid artery, and a 24-month scan by a second radiologist documented a highly vascular mass measuring 3.2 by 2.2 centimeters, a persistent partial response under RECIST 1.0 criteria with no local or systemic progression for 755 days. Thyroid hormone values, which had been suppressed by euthyroid sick syndrome at presentation, returned to and remained within normal ranges through repeated monitoring.

Tolerability was equally striking. The only radiation-related adverse event was leukotrichia, whitening of the fur in the treatment field, graded as a mild VRTOG grade 1 late skin toxicity. A transient episode of hiding, drooling, and poor appetite after the first fraction resolved when gabapentin was stopped and an anti-nausea drug given. Later weight loss at 20 to 24 months was traced to newly diagnosed chronic kidney disease and a progressively enlarging hepatic cystadenoma, both judged unrelated to the cervical tumor or its radiation. At the time of manuscript submission, the cat was alive with no evidence of disease progression, more than two years after treatment.

The authors caution that without surgical histopathology, which was deliberately avoided given the hemorrhage risk, the diagnosis remains presumptive; cytology alone cannot fully exclude ectopic thyroid or parathyroid tumors, and the definitive classification would have required immunohistochemistry on tissue. Even so, the convergence of imaging, cytomorphology, TTF-1 negativity, and the non-secretory clinical picture makes carotid body origin the leading explanation. The team recommends that carotid body paraganglioma be added to the differential list for feline cervical neuroendocrine masses, and that endocrine function screening be built into both initial work-up and long-term follow-up, since radiation can induce endocrine changes, as seen in dogs. For veterinary oncologists facing cats with otherwise untreatable advanced neck tumors, the report suggests external beam radiotherapy, and stereotactic body radiotherapy in particular, can now be offered as a definitive local option rather than a palliative afterthought.

Beyond this single patient, the case fills a genuine gap in comparative oncology. In human medicine, carotid body paragangliomas are the most common head and neck paragangliomas, and while surgery remains the mainstay, definitive radiotherapy and stereotactic techniques are established alternatives for tumors encasing the carotid artery, where resection carries stroke risk. In dogs, these tumors are typically encountered as incidental, slowly growing masses at the heart base, and complete surgical excision is rarely achieved. The feline report suggests that the radiotherapy experience accumulated in those species may translate across species lines.

The diagnostic work-up also illustrates a subtlety of feline endocrinology. The cat’s low total thyroxine with inappropriately low thyroid-stimulating hormone was interpreted as euthyroid sick syndrome, a reversible suppression of thyroid hormone values caused by non-thyroidal illness, rather than true hypothyroidism. Recognizing this pattern prevented a misdiagnosis that could have steered the work-up toward thyroid disease, and the later normalization of thyroid values on follow-up confirmed the interpretation.

Finally, the durability of response matters for fractionation debates in veterinary radiation oncology. Ablative hypofractionated schedules trade convenience and reduced anesthesia exposure against uncertainty about late toxicity, and this report, with more than two years of follow-up and only grade 1 leukotrichia, provides early evidence that such schedules can be both effective and well tolerated in cats with deeply seated cervical disease.

Subject of Research: First reported use of stereotactic body radiotherapy to treat a suspected feline carotid body paraganglioma

Article Title: Locally advanced cervical neuroendocrine tumor of presumptive carotid body origin in a cat treated with stereotactic body radiotherapy (SBRT): a case report

Article References: Gualtieri, P., Benedict, W. M., Tremolada, G., & Boss, M.-K. (2026). Locally advanced cervical neuroendocrine tumor of presumptive carotid body origin in a cat treated with stereotactic body radiotherapy (SBRT): a case report. Veterinary Oncology, 3(1), Article 18. https://doi.org/10.1186/s44356-026-00071-6

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00071-6

Keywords: cat, carotid body, paraganglioma, chemodectoma, neuroendocrine tumor, SBRT, stereotactic body radiotherapy, veterinary oncology, VMAT, cervical mass, TTF-1, radiation therapy