The research team, led by Şenay Yıldırım and colleagues, screened 500 presumed ovarian mature teratomas evaluated at their single center between January 2006 and December 2021. After applying strict exclusion criteria, which removed immature teratomas, cases whose diagnosis did not hold up on review, and records with incomplete clinical, radiological, or pathological data, 385 women with histologically confirmed mature teratomas entered the final analysis. Every histopathological slide was systematically re-evaluated by expert pathologists according to current diagnostic criteria, a rigorous archival review that the authors credit with improving detection sensitivity, particularly for rare histological variants and focal lesions that routine sampling might otherwise overlook.

The headline finding is a frequency of 3.1 percent for somatic neoplasms of any kind, benign or malignant, arising within these teratomas, corresponding to 12 cases. Of these, eight were malignant, yielding a malignant transformation rate of 2.07 percent, which sits within the widely reported literature range of 0.17 to 5.5 percent. The histological spectrum proved strikingly heterogeneous. On the benign side, the team documented paraganglioma, choroid plexus papilloma, and a benign skin adnexal tumor. On the malignant side, the diagnoses included squamous cell carcinoma, which was by far the most frequent subtype at roughly one-third of all somatic neoplasms, glioblastoma, anaplastic astrocytoma, adult-type granulosa cell tumor, and a mixed carcinoma containing squamous, high-grade adenocarcinoma, and mucinous adenocarcinoma components.

From a technical standpoint, the diagnostic workup relied on a comprehensive immunohistochemistry panel performed on representative paraffin-embedded blocks using the Roche Ventana Benchmark Ultra system. Squamous cell carcinomas showed sheets and nests of atypical squamous cells infiltrating the stroma, prominent keratin pearl formation, extensive intercellular bridges, and diffuse nuclear p63 and p40 positivity. The adult-type granulosa cell tumor displayed trabecular, insular, and microfollicular growth patterns containing pathognomonic Call-Exner bodies, with the characteristic pale, angulated, grooved coffee-bean nuclei and diffuse cytoplasmic positivity for inhibin and calretinin. Paragangliomas exhibited the classic Zellballen nesting pattern with moderate synaptophysin expression, while the choroid plexus papilloma showed complex papillary architecture lined by uniform epithelial cells strongly positive for S100 protein.

Perhaps the most remarkable cases were the central nervous system-type malignancies. The glioblastoma arising within a mature teratoma in a 20-year-old patient demonstrated markedly increased cellularity, prominent nuclear atypia, frequent atypical mitoses, and necrosis with pseudopalisading, supported by diffuse GFAP positivity, retained ATRX expression, strong p53 overexpression, a remarkably high Ki-67 proliferation index, and an IDH-wildtype phenotype. In contrast, the anaplastic astrocytoma in a 22-year-old presented as a glial proliferation adjacent to mature teratoma epithelia with moderate pleomorphism, no necrosis, loss of nuclear ATRX, strong mutant IDH1-R132H immunoreactivity, and a low Ki-67 index of just 5 percent. The authors note that glial neoplasms within mature cystic teratomas are exceptionally rare, and that precisely measuring or isolating the boundaries of the astrocytic component within an ovarian germ cell tumor framework carries inherent diagnostic difficulty, underscoring the critical importance of extensive sampling and a broad immunohistochemical panel to prevent diagnostic pitfalls.

When the researchers compared the 12 SN-MT cases against the 373 uncomplicated mature teratomas, two features emerged as powerful discriminators. First, tumors with somatic neoplasia were significantly larger, with a mean diameter of 9.45 centimeters compared with 6.67 centimeters in the benign group, a difference that reached statistical significance. When tumor size was analyzed by laterality, left-sided tumors differed significantly between the groups, with larger tumors in the SN-MT group, although right-sided tumors did not differ significantly. Second, and even more striking, the gross cut-surface architecture proved to be a powerful predictor: 83.3 percent of SN-MT cases showed mixed solid-cystic components on macroscopic examination, whereas only 22.3 percent of uncomplicated teratomas did, a difference with a p-value below 0.0001 and an odds ratio of 17.169. The statistical analysis employed Pearson’s chi-square and Fisher’s exact tests for categorical comparisons and the Mann-Whitney U test for continuous variables, given that the data did not follow a normal distribution on Shapiro-Wilk testing.

Equally important were the features that failed to discriminate. Age did not differ significantly between the groups, whether assessed as a continuous variable or stratified by a 45-year threshold, suggesting that advanced age alone should not drive clinical suspicion. Tumor laterality also did not differ significantly overall, and the authors caution that the higher frequency of right-sided tumors in the SN-MT group reflects random variation in a small sample rather than a clear biological mechanism. Preoperative serum tumor markers, including CA 125, CA 19-9, and CEA, showed no significant discriminatory value between the two groups, with all comparisons yielding p-values of 0.99. This finding is consistent with previous reports indicating limited diagnostic utility of these markers in predicting somatic transformation, meaning clinicians cannot rely on blood tests to flag the problem preoperatively.

Intraoperative frozen section analysis, often the surgeon’s only real-time diagnostic tool, also revealed significant limitations. Frozen sections were performed in seven of the 12 SN-MT cases, and while three were correctly reported as malignant, four were falsely reported as benign, with final pathology revealing glioblastoma, anaplastic astrocytoma, and squamous cell carcinoma. The authors attribute these false-negative results to the focal distribution of the malignant lesions, which may be missed when only limited sampling is performed intraoperatively. Their experience suggests that careful procurement of samples specifically targeting the solid components of the mass during frozen section may help minimize diagnostic pitfalls. In the five SN-MT cases where frozen sections were not performed, microscopic evaluation of permanent sections revealed the development of choroid plexus papilloma, paraganglioma, skin adnexal tumor, and adult-type granulosa cell tumor, diagnoses that would have been impossible to anticipate intraoperatively.

Surgical management reflected the impact of suspicion on decision-making. Among the uncomplicated mature teratomas, cystectomy was performed in 60.5 percent of patients, unilateral salpingo-oophorectomy in 20 percent, and total abdominal hysterectomy with bilateral salpingo-oophorectomy in 19.5 percent. In the SN-MT group, the more radical procedures were more common, with hysterectomy and bilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy each performed in 41.7 percent of cases and cystectomy in only 16.6 percent. According to the American Joint Committee on Cancer staging system, five malignant cases were stage I and three were stage III. Follow-up ranged from 50 to 132 months with a mean of 80.3 months. Four of the eight patients with malignant transformation died, including one with squamous cell carcinoma who developed para-aortic lymph node metastasis at diagnosis and right adrenal metastasis at 31 months, confirmed to be of ovarian origin by whole-body PET-CT imaging that excluded any other primary tumor focus. The mixed carcinoma patient received VAC-IE chemotherapy, while the glial malignancy patients received BEP regimens, reflecting the individualized adjuvant strategies that somatic components demand rather than conventional germ cell protocols.

The authors acknowledge several methodological limitations, including the retrospective design, incomplete serum marker assessment, the small number of SN-MT cases constraining subtype-specific analyses, and the absence of molecular and genetic investigations, which limited mechanistic and prognostic interpretation. Notably, in their adult-type granulosa cell tumor case, FOXL2 mutation analysis could not be performed due to institutional constraints, although the distinct histological demarcation between the tumor and the teratoma, the absence of a transitional differentiation zone, and their entirely different embryological lineages supported the collision tumor interpretation. Nevertheless, the systematic re-evaluation of all cases by expert pathologists, the long study period, and the large overall cohort strengthen the significance of the findings. The practical takeaway for clinicians and pathologists is clear: large tumor size and the presence of solid components on macroscopic examination should raise suspicion of somatic transformation, and given the limitations of frozen section analysis and serum markers, rigorous macroscopic sampling with at least one tissue section per centimeter of maximum tumor diameter, combined with expert pathological examination, remains the gold standard for diagnosis. While early-stage disease carries a favorable prognosis, the heterogeneity of subtypes necessitates individualized management, and the authors call for future multicenter prospective studies incorporating molecular profiling to elucidate the biology of these rare neoplasms.

Subject of Research: Somatic neoplasms arising in ovarian mature teratomas

Article Title: Frequency and clinicopathological features of somatic neoplasms arising in ovarian mature teratomas: a single-center experience

Article References: Yıldırım, Ş., Bülbül, G. A., Nergiz, D., Yıldırım, H. T., Önder, A. H., & Üreyen, I. (2026). Frequency and clinicopathological features of somatic neoplasms arising in ovarian mature teratomas: a single-center experience. Pathology & Oncology Research, 32, Article 1612455. https://doi.org/10.3389/pore.2026.1612455

Image Credits: AI Generated

DOI: 10.3389/pore.2026.1612455

Keywords: mature teratoma, somatic malignant transformation, squamous cell carcinoma, glioblastoma, granulosa cell tumor, ovarian pathology, tumor markers, frozen section, Frequency, clinicopathological, features, somatic