A 31-year-old woman with ankylosing spondylitis and a long history of recurrent gluteal masses was diagnosed with stage IV sacrococcygeal teratoma containing both adenocarcinoma and squamous cell carcinoma, according to a single-patient case report from physicians at Renmin Hospital of Wuhan University in China. The case involved prolonged treatment with tumor necrosis factor-alpha inhibitors, serial biopsies that documented a shift toward squamous histology, and tumor mutations in TP53 and KRAS G12D. Despite surgery, several chemotherapy regimens, radiotherapy and later systemic treatment, the cancer progressed to the lungs, liver, kidneys and bones. Because only one patient was studied, the findings cannot establish that TNF-alpha blockade caused the malignant transformation or that stopping the drugs improved survival.
The patient had undergone excisions of gluteal masses at approximately one and 20 years of age, although the pathology of those lesions was not established and regular follow-up was not documented. In June 2025, she presented with a painless 3-cm mass in the right buttock that she had noticed during the preceding week. Physical examination found no erythema, ulceration or discharge. Computed tomography showed a cystic-solid mass in the sacral and pelvic region, interpreted as suggestive of a dermoid cyst, along with a nodule in the basal segment of the right lower lung and multiple small pulmonary nodules. A laparoscopic retroperitoneal resection produced pathology consistent with mucinous adenocarcinoma, which was initially presumed to originate in the gastrointestinal tract. Immunohistochemistry showed positivity for Villin, CDX2, CK20, SATB2 and CK7, with a Ki-67 index of 80%.
Further evaluation led clinicians to reconsider the origin of the cancer. A pathology review of the pelvic specimen identified intestinal-type adenocarcinoma with an immunohistochemical profile suggestive of malignant transformation of a sacrococcygeal teratoma. Tumor testing found the cancer to be microsatellite stable and harboring TP53 and KRAS G12D mutations. Gastroscopy and colonoscopy disclosed chronic non-atrophic gastritis with erosions, proctitis and hemorrhoids, effectively excluding a primary gastrointestinal source in the investigators’ assessment. A 68Ga-FAPI PET-CT performed on June 26, 2025, also identified pelvic mesenteric and presacral soft-tissue lesions considered suggestive of metastases, a right gluteal mass consistent with local recurrence and multiple pulmonary nodules, some suspicious for metastasis. The first cycle of FOLFOX chemotherapy, comprising 5-fluorouracil and oxaliplatin, was administered on July 7.
The decisive biopsy came from the recurrent right gluteal lesion. Ultrasound-guided sampling on August 18 revealed a biphenotypic carcinoma composed of approximately 65% poorly differentiated squamous cell carcinoma and 35% low-to-moderately differentiated intestinal-type adenocarcinoma. The squamous component expressed P40 and CK5/6, while the adenocarcinoma expressed Villin, CDX2, CK20, SATB2 and CK7; the Ki-67 index was 85%. A multidisciplinary team from gynecology, gastrointestinal surgery, rheumatology and immunology, oncology and pathology considered the combined findings and diagnosed sacrococcygeal teratoma with malignant transformation into mixed adenocarcinoma and squamous cell carcinoma. Pelvic and right gluteal subcutaneous metastases placed the disease at stage IV, while the evaluation also excluded a tailgut cyst and sacral chordoma. The tumor was considered predominantly squamous, and four cycles of TP chemotherapy, consisting of paclitaxel polymeric micelle plus carboplatin, were administered between August and October 2025.
Imaging on October 2 and November 13 showed stable disease under the Response Evaluation Criteria in Solid Tumors. On November 20, the physicians removed the sacrococcygeal tumor and performed laparoscopic abdominal lymphadenectomy. Pathological examination again found a mixture of intestinal-type adenocarcinoma and squamous cell carcinoma, this time with intratumoral vascular invasion and perineural infiltration, and a Ki-67 index of 80%. A postoperative scan showed that the previously noted right-sided sacrococcygeal mass was no longer visible, although pulmonary nodules and a suspicious nodule near the liver capsule remained. The fifth and sixth cycles of TP chemotherapy were administered on December 11, 2025, and January 1, 2026. By January 23, however, CT had shown a slightly enlarged subpleural pulmonary nodule, a new left-liver lesion and enlarging right inguinal lymph nodes. A biopsy of a right inguinal node demonstrated metastatic squamous cell carcinoma with a Ki-67 index of 60%.
The inguinal tumor had lost the Villin, CDX2, CK20 and SATB2 expression seen in the earlier adenocarcinoma-containing samples, while P40 and CK5/6 remained positive. The team classified the disease as progressive and delivered radiotherapy to the hepatic lesion and inguinal nodes from January 30 to February 15, 2026, using 48 Gy in eight fractions for the hepatic internal gross tumor volume and 60 Gy in 15 fractions for the metastatic inguinal lymph nodes. Further CT on March 10 showed multiple bilateral pulmonary nodules, some cavitated, enlarged inguinal nodes, a new osteolytic lesion in the right sacrum with associated soft tissue and new presacral lesions. Because the patient had progressed after exposure to 5-fluorouracil, oxaliplatin, paclitaxel and carboplatin, the clinicians considered acquired resistance and administered four cycles of irinotecan monotherapy as third-line treatment. Irinotecan inhibits topoisomerase I and has activity against both adenocarcinomatous and squamous tumors, supporting its empirical selection for this biphenotypic malignancy.
After two cycles of irinotecan, CT showed stable disease. Additional radiotherapy to the pelvic mass was delivered from March 12 to March 20, 2026, with a gross tumor volume of 33.6 Gy in seven fractions. By June, the pulmonary nodules had enlarged or developed more solid components, liver lesions had increased in number and size, new sacral and renal lesions had appeared, and an abscess had formed at the surgical incision. A liver biopsy confirmed metastatic squamous cell carcinoma with a Ki-67 index of 70% and negative Villin, CDX2 and CK20 staining. With widespread metastases to the lungs, liver, kidneys and bones, the multidisciplinary team judged the patient unsuitable for further surgery and recommended conservative medical management. TNF-alpha inhibitors were temporarily stopped on June 15, 2026, as a guideline-informed precautionary decision amid concern that continued blockade could theoretically weaken tumor immune surveillance.
The authors emphasized that this was an individualized clinical judgment rather than a universal protocol. A review of 45 interventional and 10 observational studies involving more than 57,000 patients had found no statistically significant association between TNF-alpha inhibitor exposure and overall malignancy risk. A separate analysis focused on psoriasis patients indicated an association between TNF-alpha inhibitors and non-melanoma skin cancer, with a particularly pronounced risk for squamous cell carcinoma. French recommendations endorsed by the French National Authority for Health advise stopping TNF-alpha antagonists when a solid malignancy is diagnosed. In this case, the team combined that precautionary guidance with the aggressive, treatment-refractory course of the cancer and the feasibility of temporarily managing ankylosing spondylitis with other agents. The report does not establish that withdrawal altered the tumor’s course or support routine discontinuation in all patients with cancer.
The patient subsequently received paclitaxel liposome combined with anlotinib, a multitarget tyrosine kinase inhibitor that acts on VEGFR, PDGFR and FGFR and has been approved in China for later-line treatment of advanced soft-tissue sarcoma that has progressed or recurred after anthracycline-based chemotherapy. This constituted salvage treatment for refractory malignant sacrococcygeal teratoma; the report did not identify anlotinib as a treatment selected because of the KRAS G12D mutation. The authors noted that anlotinib’s anti-VEGFR, anti-FGFR and anti-PDGFR effects could interfere with angiogenesis and fibroblast function, requiring close monitoring and integrated wound management because of potential wound complications. Separately, they described the KRAS G12D alteration as a possible rationale for investigating targeted agents in future clinical trials, but no KRAS G12D inhibitor was reported as part of this patient’s treatment.
Two unresolved questions remain. Molecular clonality analysis was not performed, so the changing biopsies cannot distinguish independent malignant clones, treatment-driven selection of a pre-existing squamous clone, or lineage plasticity in which an adenocarcinoma clone changed toward squamous differentiation. Multi-region sequencing or single-cell genomic approaches would be needed to separate those mechanisms. In addition, the tumor TP53 finding was not accompanied by germline testing or formal genetic counseling, leaving unresolved whether a pathogenic germline variant and Li-Fraumeni syndrome should be investigated. The authors regard recurrent masses of uncertain identity as warranting definitive biopsy and regular follow-up, while emphasizing that a single-case design is hypothesis-generating and cannot be generalized. Serial examinations of anatomically separate lesions captured changing histology and influenced pathology-adapted treatment, but the strongest conclusions remain descriptive: this patient’s adult sacrococcygeal teratoma contained mixed malignant components, its histological profile shifted toward squamous cell carcinoma, and the disease progressed despite multimodal treatment. Whether prolonged TNF-alpha inhibition contributed remains unknown.
Subject of Research: Single-patient report of biphenotypic malignant transformation of an adult sacrococcygeal teratoma during TNF-alpha inhibitor therapy.
Article Title: Case Report: Sacrococcygeal teratoma with malignant transformation into mixed adenocarcinoma and squamous cell carcinoma following TNF-α inhibitor therapy for ankylosing spondylitis
Article References: Luo, P., Zhang, M., Zhang, R., Deng, J., & Zheng, Y. (2026). Case Report: Sacrococcygeal teratoma with malignant transformation into mixed adenocarcinoma and squamous cell carcinoma following TNF-α inhibitor therapy for ankylosing spondylitis. Frontiers in Oncology, 16, Article 1969865. https://doi.org/10.3389/fonc.2026.1969865
Image Credits: AI Generated
DOI: 10.3389/fonc.2026.1969865
Keywords: sacrococcygeal teratoma, malignant transformation, adenocarcinoma, squamous cell carcinoma, TNF-alpha inhibitors, ankylosing spondylitis, TP53 mutation, KRAS G12D, case report, multidisciplinary oncology, Case, Report
News Source: Nathaniel Bowman. (October 22, 2026). Sacrococcygeal teratoma with mixed malignant transformation during TNF-α inhibitor therapy. Scienmag.
