Adenomatoid tumor of the uterus: analysis of misdiagnosed cases and a literature review

Abstract

Adenomatoid tumors are rare, specific, benign tumors of the reproductive tract that originate from mesenchymal tissue. A patient was diagnosed with uterine fibroids 1 year previously when a mass of approximately 30 mm was found in the left adnexal region during a physical examination. At 1 year of follow-up, ultrasound showed that the mass in the left adnexal area had greatly increased to 61 × 45 × 50 mm. Contrast-enhanced pelvic magnetic resonance imaging (MRI) was performed before surgery and suggested a borderline tumor. Histopathology suggested signet ring cell carcinoma, and an immunohistochemical examination suggested a uterine adenomatoid tumor. Our suspicion of a borderline tumor was based mainly on the following features: the mass had increased in size within 1 year, the cancer antigen 125 concentration had increased, and several lymph nodes in the pelvic and groin regions showed positive signals on MRI enhancement. Uterine adenomatoid tumors are challenging to diagnose, especially adenomatosis with signet ring cells. However, the accuracy of diagnosing this disease can be greatly improved by combining ultrasound and MRI. This article describes the most comprehensive and reliable imaging features of ultrasound and MRI, which play an important role in diagnosing uterine adenomatoid tumors and provide useful information for clinicians.

Introduction

Adenomatoid tumors (ATs) are benign tumors that occur in the reproductive organs, especially in the uterus.^1,2 Most of the published cases of these tumors are single or a series, which causes difficulty in accurately assessing the epidemiological characteristics of this tumor. Sampling of small leiomyoma-like nodules during hysterectomy is uncommon. According to a survey, the frequency of adenoma lesions in hysterectomy ranges from <1% to 5%.^3–5 Clinically, ATs mainly occur in women of reproductive age. ATs are usually located in the myometrium of the uterus, near the subserosal cornu, are nodular in shape, and are characterized by a single nodule and small size.^6,7 The imaging findings of ATs can be classified into solid and cystic types, and the latter type is less common. ⁸ ATs are difficult to diagnose clinically because of their atypical clinical manifestations or lack of understanding of this disease and lack of accurate biochemical indicators. Therefore, an early diagnosis is important for the treatment and prognosis of ATs. Imaging findings are helpful in the accurate diagnosis and differential diagnosis of ATs.

We report a case of a uterine adenomatoid tumor (UAT) in an adult female patient. We also review the relevant literature to provide effective guidance for the diagnosis and treatment of UATs.

Case report

A female patient who was 38 years old was admitted to our hospital in November 2023 because of a pelvic mass. She had regular, 38-day cycles lasting for 7 days with a moderate menstrual flow, and had no history of dysmenorrhea or abnormal leucorrhea. She had no abdominal pain, bloating, or contact bleeding. She had been healthy in the past and had no family history of genetic, neurological, psychiatric, infectious, or similar diseases. During a physical examination in another hospital in November 2022, transvaginal ultrasound showed a mass of approximately 30 mm in diameter in the left adnexal area. The patient visited our hospital for further examination.

Pelvic magnetic resonance imaging (MRI) (Figure 1) showed a round, high-low mixed signal shadow in the left adnexal area. Diffusion-weighted imaging showed a localized area of a slightly high signal with clear borders, which measured approximately 27 mm in diameter, with a discrete low signal within. This finding suggested a cystadenoma in the left adnexal region. Contrast-enhanced pelvic-enhanced MRI was recommended to confirm the diagnosis because of the lack of obvious symptoms. On re-examination after admission, transvaginal ultrasound (Figure 2) showed a cystic solid mass measuring 61 × 45 ×50 mm in the left adnexal area. This mass had clear boundaries, good sound penetration in the cystic part of the mass, and a low echo area with a honeycomb pattern measuring 48 × 38 × 37 mm. Color Doppler flow imaging showed a blood flow signal in the solid part of the mass, and a resistance index of 0.65 was detected, which suggested a cystadenoma. Contrast-enhanced pelvic MRI (Figure 3) showed an abnormal oval signal in the left adnexal area. The tumor showed heterogeneous intensity on T1-weighted imaging, with mainly hypointensity and local isointensity, which appeared to be linear. Cystic signal intensity was observed on T2-weighted imaging, with mainly heterogeneous intensity in the middle, which was mainly cystic. Diffusion-weighted imaging showed limited diffusion of lesions in the middle region and uneven enhancement of solid components after enhancement. Multiple small lymph nodes adjacent to the iliac vessels on both sides and in the inguinal region suggested a borderline tumor in the left adnexal region. On a preoperative examination, the concentration of the tumor marker cancer antigen 125 (CA125) was 41.0 µ/mL (normal reference value, ≤35.0 µ/mL), and the tumor volume was increased.

Figure 1.

(a) Pelvic magnetic resonance imaging shows a round high-low mixed signal shadow in the left adnexal area (arrow) and (b) diffusion-weighted imaging shows a localized area of slight hyperintensity with clear borders and a discrete low signal within (arrow).

Figure 2.

(a) Transvaginal ultrasound shows a cystic solid mass in the left adnexal area, with clear boundaries, good sound penetration in the cystic part, and a low echo area with a honeycomb pattern (arrow) and (b) Color Doppler flow imaging shows blood flow signals in the solid part of the mass (arrow).

Figure 3.

(a) Contrast-enhanced pelvic magnetic resonance imaging of the tumor shows heterogeneous intensity on T1-weighted imaging, with mainly hypointensity and local isointensity (arrow) and (b) cystic signal intensity can be seen on T2-weighted imaging, with mainly heterogeneous intensity in the middle, which is mainly cystic (arrow).

After the exclusion of contraindications, laparoscopic myomectomy, resection of the left ovarian lesion, and pelvic adhesion lysis were performed under general anesthesia. The surgical procedure showed a cystic mass measuring approximately 60 × 50 mm with a smooth surface and clear border with the surrounding tissue in the proximal broad ligament of the left anterior uterine wall (Figure 4). Intraoperative frozen sections suggested leiomyoma with cystic and mucinous degeneration (containing more mucinous components), but could not exclude mucoid malignancy or other types of malignancy. Routine histopathology showed that there were many signet ring-like tumor cells distributed between the smooth muscle tissue under a microscope (Figure 5). The morphology of the tumor cells was bland and round, and the nuclei were eccentric. Additionally, the cytoplasm was abundant and lightly stained, and it was “signet ring-like.” Variably sized lumens lined with flat cells were observed locally, and the possibility of signet ring cell carcinoma was not ruled out.

Figure 4.

(a, b) Gross appearance of the tumor during surgery (arrows).

Figure 5.

(a, b) Histological examination of tumor tissue using hematoxylin and eosin staining. (a) 10× and (b) 20×.

We then decided to perform an immunohistochemical analysis, and the results were as follows: cytokeratin (+), paired box protein-8 (−), Wilms’ tumor gene 1 (+), cytokeratin 20 (−), cytokeratin 7 (+), carcinoembryonic antigen (−), Ki-67 (5%+), villin (−), calretinin (+), podoplanin (+), cluster of differentiation 10 (−), and thyroid transcription factor 1 (−). Signet ring cell carcinoma was able to be ruled out because the Ki-67 proliferation index was only 5%. In addition, the positive Wilms’ tumor gene 1 and calretinin results suggested the diagnosis of UAT with signet ring cell features. Therefore, UAT was finally diagnosed.

Three months postoperatively, the patient underwent an ultrasound examination, and no obvious signs of disease recurrence were observed. Additionally, the CA125 concentration had returned to normal (30.1 µ/mL). One year of continuous follow-up was planned for this patient, and we have currently completed a 6-month follow-up without any disease recurrence.

The reporting of this study conforms to the CARE guidelines. ⁹ The patient provided verbal informed consent for publication of her anonymized data. Ethical committee approval was not required for this case report.

Discussion

ATs occur mainly in the reproductive system of both sexes, with a higher incidence in men than in women.^1,10 This tumor is benign and its pathogenesis may be related to immunosuppression and TRAF7 gene mutation. ¹¹ In women, ATs can occur in the uterus, fallopian tubes, ovaries, and broad ligaments, and in men, they can occur in the epididymis and spermatic cord.^7,12 In addition, these tumors can occur in organs other than the reproductive system, such as the adrenal glands, pancreas, heart, omentum, mesentery, and mediastinum.^1,13 Although there are many hypotheses about their tissue origin (e.g., mesonephric, Müllerian, endothelial, and mesothelial) according to the World Health Organization (2003) definition, UATs in the female reproductive system are clearly derived from the serosal mesothelial cells of the uterus. ¹⁴ This disease usually occurs in the subserous membrane of the uterus and close to the serous membrane. No migration relationship has been observed between tumor components and serous mesothelial cells. ⁶ The mesothelium is hypothesized to remain during embryonic development or is caused by migration of sediment from the surface cavity into the uterine wall. ⁶ According to a previous study, ¹⁵ the incidence of UATs before 1990 was only 0.12% to 1.2%, but in 2013, Nakayama ⁵ et al. reported a detection rate of 5%. This finding suggests that the true incidence of UATs may be higher because these tumors are small, often coexist with other conditions, such as uterine adenomyoma and leiomyoma, and frequently have clear boundaries on imaging. If the mass is solid, it can easily be confused with a uterine leiomyoma, leading to a missed diagnosis or misdiagnosis. This disease occurs mainly in women of reproductive age, most commonly between the ages of 40 and 49 years. ¹⁶ The clinical manifestations of UATs are non-specific and usually present with symptoms associated with concomitant disease, such as irregular menstruation, progressive dysmenorrhea, menorrhagia, and abdominal bloating. However, in most cases, the findings are incidental to a physical examination. ¹⁷ Histologically, ATs can be divided into four types: adenoid, hemangiomatoid, solid, and cystic. Of these, adenoid and angiomatoid are the most common types, while the cystic type is relatively rare.^18,19

Currently, ultrasound and MRI are the primary methods of initial screening for ATs because they are non-invasive and direct. With the rapid development of imaging technology and the deepening of physicians’ understanding of ATs, the detection rate of this disease has greatly increased. On ultrasound, ATs usually appear as single solid nodules. In rare cases, there are multiple nodules, ranging in diameter from 2 to 10 cm, but they are usually <5 cm.^6,16 Sixty percent of these tumors occur in the subserous membrane of the uterus, followed by the intermuscular wall, and are rarely found in the endometrium or ovary. ²⁰ In most cases, ATs appear hypoechoic or hyperechoic on ultrasound and are rarely cystic. In most cases, the border is clear and there is little blood supply around it. If an AT is a solid lump, it can easily be confused with a fibroid or adenomyoma. The following features can be used to distinguish ATs. ATs are present if an ultrasound scan shows irregular echo nodules, scattered areas of fluid inside, peripheral blood flow signals, internal blood flow appears as a star or short line, and the blood flow resistance index is slightly high.^21,22 Ultrasound in our patient showed a single lesion that was located in the serosal layer of the uterus, and the lesion showed a solid component with visible blood supply. In addition, we also measured a slightly high flow resistance index (0.65), which is consistent with previous reports.^6,16,20,22 The tumor in our patient was a rare cystic solid type with a large size. On ultrasound images, the cystic part showed poor sound transmission and the solid part showed a honeycomb-like pattern, which initially suggested cystadenoma. However, on further review of the literature on ATs, we found some important differences in the identification of cystadenomas. When ATs appear cystic, they are often subserous and large.^7,8 According to ATs’ characteristics, they can be divided into simple cystic and cystic solid types.^8,21–23 The simple cystic type is visualized as a floating spot echo and many thin separated echoes, forming a multilocular cystic structure, and a blood flow signal can be observed on separation.^21–23 The parenchymal part of the cystic solid type shows a high echo, and the interior is similar to a honeycomb. Additionally, there are many thin compartments in the echoless area, forming a multilocular cystic structure, and blood flow signals are visible in the parenchymal part of the tumor and in the compartments.

In recent years, with the widespread use of MRI, the detection rate of UATs has increased yearly. MRI findings of UATs are divided into solid nodules and cystic nodules.^16,19,24 Solid nodules show isointensity on T1-weighted imaging, hypointensity on T2-weighted imaging, and isointensity on diffusion-weighted imaging. An enhanced scan shows moderate uniform enhancement of the nodules, but it is less than that of the myometrium. This finding may be due to the presence of more smooth muscle in this tumor and the slit-like arrangement of the cells, leading to fewer interstitial blood vessels. If ATs are angiomatous, cystic changes and bleeding within the tumor can be seen on MRI, and the liquid–liquid plane sign forms owing to differences in the amount of blood produced at different times. ²⁴ In an enhanced scan, enhancement of the solid part of the tumor is higher than that of the myometrium. Cystic nodules do not usually show considerable enhancement, but moderate enhancement can be seen in the solid part of these nodules. ²⁴ More than 90% of UATs are solid, and 75% of the nodules have moderate enhancement similar to that of the myometrium. ²⁵ When these nodules are cystic, they tend to show hypointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging, with a slight rim and septations. Contrast-enhanced pelvic MRI findings in our patient are consistent with contrast-enhanced pelvic MRI findings of the cystic type of UAT mentioned in the above-mentioned two studies.^24,25 Takeuchi ¹² et al. analyzed the MRI findings of 10 cases of UATs and found that these nodules could be indicated as ATs if they showed clear areas of hyperintensity and blurred areas of hypointensity on T2-weighted imaging. This was especially the case if peripheral annular hyperintensity enhancement was shown on T2-weighted imaging and diffusion-weighted imaging. In addition, dynamic MRI is helpful in differentiating uterine leiomyomas. Although AT is characteristic on MRI, it must be carefully differentiated from other related diseases, such as uterine fibroids, uterine adenomyoma, leiomyomatous cystic degeneration, and cystic adenomyosis.

While the cystic type of UAT is a rare, benign tumor, signet ring cell characteristics of UATs are even more rare. To the best of our knowledge, there have been only two reports^26,27 that referred to UATs with signet ring cells, but these tumors were substantial nodules rather than cystic nodules. One of the reports ²⁶ stated that the reason why UATs are easily misdiagnosed as metastatic signet ring cell carcinoma in an intraoperative frozen pathological diagnosis is that adenomatoid cells of the uterus are distributed in an infiltrating manner among the smooth muscle tissue, some cells are signet ring-like, and the nuclei have certain atypia. Further immunohistochemical tests can help to diagnose this type of UAT. In this type of UAT, cytokeratin 20 and carcinoembryonic antigen are negative, and Wilms’ tumor gene 1, calretinin, and vimentin are positive. The immunohistochemical findings in our patient are consistent with this indication. A detailed histological analysis of 75 cases of AUTs was performed in another study, ²⁷ and only 2 cases were found to have signet ring cell features. The histological morphology of UATs overlaps with a variety of tumors, and it should be differentiated from uterine fibroids, adenomyosis or adenomyoma, adenocarcinoma (signet ring cell carcinoma), and malignant mesothelioma. High cytokeratin 5/6 and Ki-67 expression suggests malignant mesothelioma and physicians should be vigilant. In our case, the Ki-67 index was 5%, which is a low expression level. This finding allowed us to eliminate the possibility of signet ring cell carcinoma, combined with positivity of Wilms’ tumor gene 1 and calretinin, and UAT was finally diagnosed.

Regarding treatment, if hysterectomy is not possible for other reasons, simple tumor resection can be used to treat UATs. No cases of malignant transformation or recurrence have been reported.

Conclusion

This patient had no obvious clinical symptoms, even though the mass had doubled in size on a repeated examination. The decision was made to proceed with surgical treatment because of the rapid growth rate of the mass and the concomitant increase in concentrations of the tumor marker CA125. Ultrasonic and CA125 measurement at 3 months after surgery showed normal results.

In conclusion, UATs lack specific clinical manifestations and have diverse imaging characteristics, which increases the diagnostic difficulty and the risk of misdiagnosis to a certain extent. With the continuous improvement in the detection rate of this disease and the gradual improvement of clinicians’ knowledge, we have summarized the imaging characteristics and corresponding classification of this disease. On the basis of these findings, clinicians can improve the accuracy of diagnosis of UATs and develop individualized, comprehensive, and effective treatment plans, ultimately improving patients’ outcomes.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605241282389 - Supplemental material for Adenomatoid tumor of the uterus: analysis of misdiagnosed cases and a literature review

Supplemental material, sj-pdf-1-imr-10.1177_03000605241282389 for Adenomatoid tumor of the uterus: analysis of misdiagnosed cases and a literature review by Yan-Yu Li, Guang-Juan Kan, Qian Wang, Song Guo, Chen-Xi Wu and Jiang Zhu in Journal of International Medical Research