Müllerian adenosarcoma likely arising from adenomyosis: A case report of a rare diagnostic challenge

MAS arising from adenomyosis is an extremely rare phenomenon, with fewer than 10 cases reported in the literature [ 1 , 7 ]. This rarity contributes to frequent clinical misdiagnosis, as the intramural origin of this tumor, lacking endometrial surface involvement, often results in inaccurate or misleading initial assessments [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] ]. A major diagnostic challenge lies in the potential for inadequate or nonrepresentative sampling. Superficial biopsies/curettages frequently fail to identify the malignant stromal component, which is typically located within the myometrium in adenomyosis-associated cases. This was evident in our patient, whose two prior curettages yielded a benign-appearing endometrial tissue without any malignant features, delaying accurate diagnosis. Similar diagnostic challenges have been encountered in prior reports of intramural MAS [ 3 , 4 , 9 ]. The intramural growth pattern further complicates clinical recognition; while MAS arises within adenomyosis, it expands in the myometrium rather than projecting into the endometrial cavity, resulting in a deep-seated mass that may lack the classic polyploid or pedunculated intracavitary appearance seen in typical uterine adenosarcomas [ 1 , 5 , 7 ]. This pattern was clearly demonstrated in our MRI findings ( Fig. 2 ), where the mass appeared bulky, infiltrative, and centered within the myometrium with clear disruption of the junctional zone and extension into both superficial and deep myometrium. Imaging is therefore often limited in terms of specificity. On US, the lesion may appear as a nonspecific hyper-echoic heterogeneous mass that cannot be distinguished from what could be a fibroid, endometrial polyp, or focal adenomyosis, as was the case in our patient ( Fig. 1 ). MRI, although supposedly superior in identifying myometrial invasion, typically shows heterogeneous T2 hyperintensity with variable enhancement and junctional zone irregularity, findings that overlap with those of high-grade endometrial carcinoma, uterine sarcomas, and adenomyosis lesions. Our patient’s MRI showed a complete cavity occupation, irregular enhancement, and a deep myometrial infiltration, leading to a presumptive diagnosis of FIGO stage IB endometrial carcinoma. Further CT imaging ( Fig. 3 ) contributed to the ambiguity by demonstrating a heterogeneous mass with internal air locules, which could represent necrosis, infection, or recent instrumentation. These overlapping features can complicate the radiological differentiation of MAS from a more common benign or malignant uterine lesion. Ultimately, accurate diagnosis depends on thorough histopathological examination. Key diagnostic features include periglandular stromal cuffing, malignant and variably differentiated stroma, and increased mitosis activity. We can only appreciate the lesions associated with adenomyosis foci in large excision specimens, therefore requiring deep tissue sampling, as small curettings frequently only capture benign glandular components or stromal areas lacking malignant cytologic criteria [ 3 , 4 , 6 ]. In our case, the decisive shift in diagnosis occurred only after review by multiple pathologists, underscoring the value of additional pathology consultation and multidisciplinary collaboration when MAS is being considered. Staging remains problematic to this day due to the limitations of the current FIGO system. This system presumes that the origin of the mass is endometrial and does not account for intramural or adenomyosis-derived tumors [ 1 , 5 ]. As a result, the depth of myometrial invasion can be misinterpreted, which can consequently impact risk stratification and therapeutic planning. Clark et al. further highlight how tumors with unusual growth patterns often fall outside the traditional staging algorithms, complicating prognostic assessment [ 6 ]. These issues underscore the need for modified staging approaches that include unusual presentations such as intramural MAS. The prognosis in MAS from adenomyosis is primarily determined by the presence of sarcomatous overgrowth and the depth of myometrial invasion, as these factors are associated with higher recurrence rates and poorer outcomes [ 3 , 4 ]. Although our case did not show any sarcomatous overgrowth, the substantial infiltration and mitosis activity warranted classification as a lesion with intermediate risk. The scarcity of reports and guidelines in the literature for MAS arising from adenomyosis precludes accurate prognostic modeling, thereby reinforcing the need for individualized management [ 2 , 7 ]. Surgery remains the mainstay of treatment, while fertility-preserving excision may be attempted in specific patients. The decision for definitive hysterectomy and adjuvant therapy in this case aligns with current recommendations for tumors exhibiting deep invasion or persistent radiologic concern [ 2 , 6 , 9 ]. Given the high complexity and rarity of such cases, a multidisciplinary approach is essential for managing patients, as well as second-opinion pathology review to identify the cause. In our case, collaboration from the radiology, gynecology, and pathology departments was essential in revising an appropriate treatment plan. Overall, this case provides valuable insights into the limited existing literature on MAS arising from adenomyosis. It raises multiple critical points that can be considered in a clinical setting, including repeated false negative biopsies; nonspecific imaging characteristics that can mimic both benign and malignant presentations; the necessity for deep histologic sampling; as well as prognostic challenges due to inaccurate staging. Reporting such cases can enhance clinical awareness and help generate diagnostic algorithms and targeted management plans for these uncommon phenomena.

The authors certify that they have obtained written informed consent from the patient for the publication of this case report and any accompanying images.

Our case highlights a rare presentation of MAS likely arising from adenomyosis. Although extremely uncommon, this diagnosis should be considered when clinical features, imaging, and repeated biopsies are discordant. While definitive diagnosis ultimately depends on thorough histopathologic evaluation, careful imaging assessment can support early suspicion and guide appropriate management. Continued reporting of such cases is essential for improving recognition and informing future diagnostic and therapeutic strategies.

1. US examination did not include Doppler assessment. 2. Histopathology images could not be retrieved. 3. The patient continued care at another facility, and follow-up is unavailable. US examination did not include Doppler assessment. Histopathology images could not be retrieved. The patient continued care at another facility, and follow-up is unavailable.

Müllerian adenosarcoma (MAS) is an uncommon biphasic neoplasm characterized by either a benign or mildly atypical Müllerian epithelial component along with a malignant, typically low-grade, stromal component. The uterine corpus is the most common site of origin, with most tumors arising from the native endometrial surface. MAS arising from adenomyosis is, however, extremely rare with only five total cases reported in the literature so far [ [1] , [2] , [3] ]. Talia et al. identified eight published cases of uterine corpus adenosarcoma without surface endometrial involvement, with three of these arising in adenomyomas and only five arising from adenomyosis [ 1 ]. Epidemiologically, MAS accounts for less than 0.5% of all uterine malignancies, with a mean age at diagnosis of 50 years, though some cases have been reported as early as 13 years of age. The true incidence of an adenosarcoma arising from adenomyosis remains unknown due to the rarity of the presentation, but it is considered an exceptional phenomenon within the spectrum of uterine sarcomas [ 4 , 5 ]. Clinically, these tumors may present with nonspecific symptoms such as abnormal uterine bleeding or pelvic pain; for this reason, most of them are diagnosed postoperatively. Imaging, particularly MRI, may aid in preoperative assessment, but distinguishing adenosarcoma from other uterine masses remains challenging, especially for intramural lesions without endometrial involvement. Histopathological assessment is therefore essential. These tumors usually present with phyllodes-like architectures, periglandular stromal cuffing, and a malignant stromal component, with or without sarcomatous overgrowth [ 4 , 6 ]. Prognostic factors of these tumors include the presence of sarcomatous overgrowth and depth of endometrial invasion, both of which are associated with poorer outcomes and increased risk of recurrence. The current FIGO staging system for uterine adenosarcomas assumes that the endometrial surface is the origin and does not account for intramural tumors arising from adenomyosis. For such reasons, there is still no consensus on optimal management of these rare presentations, and treatment is typically more individualized [ 1 ]. Overall, MAS arising from adenomyosis represents a diagnostic, staging, and therapeutic challenge underscoring the need for further clinicopathological and molecular studies to inform evidence-based management [ [1] , [2] , [3] ].