Adenomatoid tumor of the testis in a patient with history of cryptorchidism, male breast cancer, and thymic B2 thymoma: a case report and literature review

Abstract

Background

Adenomatoid tumor is a rare benign neoplasm of mesothelial origin, most commonly arising in the epididymis, vas deferens, and tunica vaginalis; primary occurrence in the testis is extremely rare. Cryptorchidism is recognized as a risk factor for testicular germ cell tumors, but its association with adenomatoid tumors remains hypothetical, as there is limited mechanistic evidence directly linking cryptorchidism to mesothelial tumorigenesis in the testis. Moreover, multiple primary malignancies may be related to impaired immune surveillance or genetic susceptibility, though these mechanisms require further validation. This case report aims to present a patient with a testicular adenomatoid tumor in the context of previous cryptorchidism, male breast cancer, and thymic B2 thymoma, and to discuss the possible mechanisms underlying multiple primary tumors and the role of intraoperative pathology in testis-sparing decisions.

Case summary

A 58-year-old man with a history of right-sided cryptorchidism treated by orchiopexy, with normal subsequent fertility, was found on magnetic resonance imaging (MRI) to have a solid nodule within the right testis suggestive of a probably benign testicular neoplasm. Serum markers of testicular malignancy were normal. Given his age, history of cryptorchidism, and multiple prior tumors, and after being informed of testis-sparing alternatives, the patient and his family requested a right radical orchiectomy. Pathology confirmed a right testicular adenomatoid tumor. The procedure was uneventful, recovery was good, and a two-year follow-up was unremarkable.

Conclusion

For testicular lesions in patients with a history of cryptorchidism, adenomatoid tumor should be included in the differential diagnosis, particularly when imaging findings and serum tumor markers suggest a benign lesion. In younger patients or patients desiring fertility preservation, intraoperative frozen section combined with rapid immunohistochemistry may improve the accuracy of differentiating benign from malignant lesions and reduce unnecessary radical orchiectomy, although diagnostic uncertainty and institutional availability should be considered. The coexistence of multiple primary tumors suggests possible immune or genetic susceptibility mechanisms. Thymoma-related immune dysregulation is better supported for malignant tumors, whereas genetic explanations remain speculative without molecular testing. Larger multicenter studies are needed to further evaluate these observations.

1. Introduction

Adenomatoid tumor (AT) is a benign neoplasm of mesothelial origin. Although rare in the genitourinary system overall, it classically arises in the epididymis, tunica, and vas deferens; primary involvement of the testicular parenchyma is exceedingly uncommon (1, 2). Cryptorchidism, as a developmental abnormality of the male reproductive system, has been established as a significant risk factor for testicular germ cell tumors (3). The germ-cell injury produced by the higher local temperature and altered endocrine milieu of an undescended testis is well documented; whether the same conditions can drive mesothelial proliferation is unknown. We raise this possibility only as an analogy, because no direct mechanistic or epidemiological evidence currently links cryptorchidism to the development of mesothelial tumors such as AT.

Furthermore, multiple primary malignancies have garnered increasing attention in recent years, with potential mechanisms involving genetic susceptibility, endocrine or gonadal dysfunction, and impaired immune surveillance (4, 5). Among these, immune dysregulation associated with thymic tumors is a better-supported mechanism, as thymomas are known to disrupt T-cell development and immune surveillance. In contrast, genetic explanations for multiple primary tumors remain speculative in the absence of molecular testing. Here we report this case of primary testicular AT arising after orchiopexy and coexisting with two other tumors and, together with a systematic review of the 2000 to 2025 literature, discuss the differential diagnosis of intratesticular lesions in men with a history of cryptorchidism, the possible basis for multiple primary tumors, and the role of intraoperative pathology in deciding whether to preserve the testis.

2. Case presentation and clinical course

Preoperative conditions

A 58-year-old male was admitted to our hospital due to a “right scrotal mass for 1 month”. The patient discovered the painless swelling during a routine physical examination, with no accompanying symptoms such as scrotal heaviness or dysuria. His medical history was notable for three major prior conditions: Right-sided cryptorchidism 24 years ago, treated with right orchiopexy, with normal postoperative fertility; Right breast invasive ductal carcinoma 10 years ago, confirmed by radical mastectomy pathology, with immunohistochemical results showing ER-positive, PR-positive, and HER2-negative status; Refractory myasthenia gravis 1 year ago, treated with thymectomy, with postoperative pathology indicating thymic B2 thymoma. The patient had no obvious family history of hereditary diseases or tumors.

Physical examination showed normal right scrotal skin without erythema or ulceration. A firm, smooth, well-circumscribed mass (1.7 cm × 1.3 cm) was palpable in the right scrotum, with no tenderness. MRI showed a round lesion within the right testis that was isointense on T1-weighted imaging and hypointense on T2-weighted imaging, consistent with a solid testicular nodule (Figure 1). Laboratory tests showed normal serum levels of alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), and lactate dehydrogenase (LDH), markers critical for excluding testicular germ cell tumors. Sex hormones (testosterone, estradiol, LH, and FSH) were also measured preoperatively and were within the reference ranges. Dedicated immunological studies (e.g., autoantibody or lymphocyte-subset testing) were not repeated at this admission, as the diagnostic priority was the differentiation between a benign and a malignant testicular lesion, for which serum germ-cell tumor markers were the relevant investigations.

Figure 1.

Magnetic resonance imaging (MRI) findings of testicular adenomatoid tumor. (A) T1-weighted Imaging (T1WI) shows an ovoid isointense signal in the right testicular region, with relatively clear boundaries; (B) T2-weighted Imaging (T2WI) shows a slightly hypointense signal of the lesion in the right testicular region, with uneven internal signal; (C) Diffusion-Weighted Imaging (DWI) shows a hyperintense signal of the lesion in the right testicular region, suggesting restricted diffusion; (D) Apparent Diffusion Coefficient (ADC) map shows a hypointense signal of the lesion in the right testicular region, which corresponds to the hyperintense signal on DWI and supports the presence of restricted diffusion.

Given the history of cryptorchidism and prior malignancies, preoperative evaluation focused on distinguishing a benign from a malignant lesion. The team discussed the options fully with the patient and his family. The imaging features, including relatively well-defined margins, sparse vascularity, small size, and normal markers, favored a benign process, and testis-sparing surgery was therefore offered to preserve endocrine and reproductive function; however, the background of cryptorchidism meant that malignancy could not be excluded preoperatively. The patient was elderly, had completed his family, and had experienced several prior tumors; his understandable anxiety led him to prefer the most definitive option. After being fully informed of the probably benign nature of the lesion, the alternatives, and the irreversibility of orchiectomy, the patient and his family chose radical resection; weighing the residual diagnostic uncertainty against the patient’s wishes, the team regarded this as a reasonable decision.

Surgical intervention

After completion of preoperative evaluation and exclusion of surgical contraindications, the patient underwent right radical orchiectomy under general anesthesia. Intraoperative frozen section was not performed because the patient and his family had already chosen radical resection, and rapid intraoperative immunohistochemistry was not available at our center at that time. Therefore, orchiectomy proceeded directly without frozen section assessment. Intraoperative exploration showed that the tumor was located within the testicular parenchyma, with clear boundaries and no obvious invasion of surrounding tissues.

Postoperative conditions

Gross pathological examination revealed a testicular tumor measuring 1.5 cm × 1.5 cm × 1.2 cm, with a gray-white, firm cut surface and well-defined margins. Histological examination (Figure 2) showed that tumor cells had minimal atypia, inconspicuous nucleoli, and rare mitotic figures; the remaining testicular tissue presented thickened basement membranes of seminiferous tubules with hyaline change, and epididymal tissue was unremarkable. Immunohistochemical (Figure 3) staining results were positive for cytokeratin (CK), vimentin (Vimentin), calretinin (Calretinin), and D2-40, which are characteristic markers for confirming the mesothelial origin of adenomatoid tumors. Pathological diagnosis was finally confirmed as testicular adenomatoid tumor.

Figure 2.

Histological staining (hematoxylin-eosin staining, HE staining) of testicular adenomatoid tumor. (A) Under low magnification (×10), the tumor tissue shows glandular, cord-like, or solid nest-like structures, with relatively clear boundaries from the surrounding tissues; (B) Under medium magnification (×20), the tumor cells have abundant cytoplasm, some cells show vacuoles, and lymphocyte infiltration is observed in the stroma; (C) Under high magnification (×40), the tumor cells have a bland morphology, mitotic figures are rare, and the vacuolar changes in the cytoplasm are more prominent.

Figure 3.

Immunohistochemical staining results of testicular adenomatoid tumor. (A) Positive immunostaining for cytokeratin (CK) is observed in tumor cells (×10 magnification). (B) Positive immunostaining for vimentin is observed in tumor cells (×10 magnification). (C) Positive immunostaining for calretinin is observed in tumor cells (×10 magnification). (D) Positive immunostaining for D2–40 is observed in tumor cells (×10 magnification).

The patient recovered smoothly after surgery and did not receive adjuvant radiotherapy or chemotherapy. Regular follow-up at 3, 6, 12, and 24 months showed no signs of tumor recurrence or metastasis, consistent with the benign biological behavior of adenomatoid tumors (Table 1).

Table 1.

Timeline of major clinical and surgical events.

Date	Event type	Event
1999	Past Surgical History	Right orchiopexy for cryptorchidism
2013	Past Surgical History	Right radical mastectomy for breast cancer
2022	Past Medical History	Diagnosis of refractory myasthenia gravis (acute severe type, Stage IV B, IPI 4 – high risk, NCCN-IPI 6 – high risk)
2022	Past Surgical History	Thymectomy
2023-04-10	Scrotal Ultrasound	1. Postoperative changes of right cryptorchidism; 2. Solid lesion above right testis, nature indeterminate; 3. Cystic lesion of the right epididymis; 4. Left-sided varicocele
2023-04-11	Testicular MRI	1. Postoperative changes of right cryptorchidism; 2. Abnormal signal below right testis; 3. Abnormal signal adjacent to the right testis; 4. Left tunica vaginalis effusion
2023-04-18	Surgery	Right orchiectomy. Intraoperative findings: tumor located within testicular parenchyma, well-demarcated, no obvious invasion
2023-04-24	Pathology	Pathological diagnosis of the right testis and epididymis tissue
Postoperative	Follow-up	Uneventful recovery; follow-up at 3, 6, 12, and 24 months showed no recurrence or metastasis

Literature review process

To further clarify the clinical characteristics and management strategies of testicular adenomatoid tumors, we conducted a literature search using PubMed, PMC, and official journal websites, covering the period from 2000 to 2025. Inclusion criteria were case reports with complete imaging, pathological, or immunohistochemical data, and studies involving the molecular mechanism or clinical treatment of the disease. Exclusion criteria were conference abstracts, articles without available full text, and literature unrelated to the research topic. Finally, 20 representative publications were selected, including 33 cases of pathologically confirmed primary testicular adenomatoid tumors, for systematic summary and analysis (Supplementary Table 1).

3. Discussion

Tumor origin and histopathological features

Among the 33 cases reviewed in this study, 19 cases (19/33, 57.6%) involved the testicular parenchyma and 14 cases (14/33, 42.4%) originated from the tunica. Of the 14 cases originating from the tunica, 9 cases (9/14, 64.3%) showed extension into the adjacent testicular parenchyma. Although adenomatoid tumors are benign, this local infiltrative pattern may lead to intraoperative misinterpretation as malignancy.

Histologically, adenomatoid tumors are composed of cuboidal to flattened epithelioid cells arranged in tubular, cord-like, or gland-like structures. The cells usually show abundant cytoplasm, minimal nuclear atypia, and rare mitotic activity. Immunohistochemistry is important for diagnosis. These tumors are typically positive for CK, vimentin, calretinin, WT1, and D2-40, and negative for PLAP, AFP, HCG, and SALL4. This immunophenotype helps distinguish adenomatoid tumor from germ cell tumors and sex cord stromal tumors.

Clinical presentation and epidemiology

The reported age range was 14 months to 63 years. Adults accounted for 93.9% (31/33) of cases, and most patients were between 30 and 58 years of age. Only two pediatric cases have been reported, involving patients aged 14 months and 12 years, and both lesions arose in the testicular parenchyma. Most patients were asymptomatic, and the lesion was detected incidentally during physical examination or imaging. Symptomatic patients usually presented with a scrotal mass, swelling, or pain. A few cases were associated with azoospermia or unrelated comorbidities, such as kidney stones. These findings suggest that testicular adenomatoid tumor usually presents as a small and clinically indolent lesion, but its intratesticular location may still raise concern for malignancy.

Imaging and laboratory features

Ultrasonography is usually the initial imaging modality for testicular adenomatoid tumors. In the reviewed cases, parenchymal lesions commonly appeared as hypoechoic or isoechoic nodules, whereas lesions originating from the tunica were located on or near the testicular surface and showed clear or slightly indistinct margins. MRI may provide additional information about tumor location and local extension. Most reported lesions showed low signal intensity on T2-weighted imaging, sometimes with capsular enhancement.

In the present case, MRI showed a round intratesticular lesion that was isointense on T1-weighted imaging and hypointense on T2-weighted imaging. Because of their cellularity and fibrous stroma, adenomatoid tumors may show restricted diffusion on diffusion-weighted imaging and may therefore be misinterpreted as malignant. This feature partly explains the difficulty of preoperative characterization.

Serum AFP, β-HCG, and LDH were normal in all reviewed cases, including the present patient. Normal tumor markers support, but do not prove, a benign diagnosis. Because neither ultrasonography nor MRI is sufficiently specific for a definitive preoperative diagnosis, intraoperative pathology and immunohistochemistry remain important when testis-sparing surgery is being considered.

Treatment strategies and clinical limitations of intraoperative pathology

Management options for testicular adenomatoid tumor include testis-sparing surgery, such as local tumor excision or partial orchiectomy, and radical orchiectomy. Among the 33 reviewed cases, 14 patients (14/33, 42.4%) underwent radical orchiectomy and 19 patients (19/33, 57.6%) underwent testis-sparing surgery. In our literature review, among the 14 tunica-origin cases, 11 underwent radical orchiectomy (11/14, 78.6%; Supplementary Table 1). Because all lesions were ultimately pathologically confirmed as benign adenomatoid tumors, we considered these radical resections to represent potential overtreatment. This may be partly attributable to the locally infiltrative growth pattern of these lesions, which can mimic malignancy during surgery.

Frozen section was used in approximately 84.8% (28/33; Supplementary Table 1) of reported cases. However, frozen section alone may be insufficient in this entity because adenomatoid tumor can overlap morphologically with seminoma and sex cord stromal tumors. This diagnostic overlap may contribute to overtreatment. Features suggestive of a benign lesion include small tumor size, normal serum tumor markers, well-defined imaging margins, and sparse vascularity. When frozen section is combined with immunohistochemistry, including calretinin, WT1, D2-40, and PLAP, diagnostic confidence may improve. Published testis-sparing series of small or marker-negative testicular masses have reported that approximately 60% to 80% of these lesions are benign and suitable for testis-sparing surgery (14, 15). These figures should be interpreted cautiously because the availability and turnaround time of rapid immunohistochemistry vary among institutions. Therefore, a stepwise approach based on preoperative imaging, intraoperative frozen section, and immunohistochemistry when available may help reduce unnecessary orchiectomy while maintaining oncological safety.

Cryptorchidism and testicular adenomatoid tumor

Cryptorchidism is a recognized risk factor for testicular germ cell tumors. Proposed mechanisms include abnormal testicular development, increased local temperature, and endocrine disturbance (3, 6). In the present patient, adenomatoid tumor developed after orchiopexy, which raises the possibility that previous cryptorchidism may have contributed to local changes in the testicular environment. However, this interpretation remains speculative. There is currently no direct evidence that cryptorchidism induces mesothelial transformation, and no large cohort or systematic study has confirmed a causal relationship between cryptorchidism and testicular adenomatoid tumor. Therefore, the coexistence of cryptorchidism and adenomatoid tumor in this patient should be interpreted cautiously.

Thymic B2 thymoma and immune dysregulation

Thymic B2 thymoma is a thymic epithelial tumor associated with myasthenia gravis and immune dysregulation (7). The thymus plays a central role in T-cell development and immune tolerance. Thymoma may disturb T-cell selection and contribute to systemic immune abnormalities (8, 9). Previous studies have suggested that patients with thymoma may have an increased risk of additional malignancies, possibly related to impaired immune surveillance.

In the present patient, breast cancer was diagnosed approximately nine years before thymoma. Because thymoma can remain clinically silent for a long period, it is possible that immune dysregulation preceded the diagnosis of thymoma, although this temporal relationship cannot be confirmed. More importantly, this explanation applies mainly to malignant tumors. Adenomatoid tumor is benign, and no available evidence links thymoma-related immune dysregulation to benign mesothelial tumorigenesis. Therefore, the coexistence of adenomatoid tumor and thymoma in this patient should be regarded as a possible coincidence rather than an established mechanistic association.

Male breast cancer and multiple primary tumor susceptibility

Male breast cancer accounts for less than 1% of all breast cancer cases (10). The coexistence of male breast cancer, thymic B2 thymoma, and testicular adenomatoid tumor in one patient is rare. Genetic factors, including BRCA1 and BRCA2 mutations, have been associated with male breast cancer (11, 12). However, germline or molecular testing was not performed in this patient, so genetic susceptibility cannot be confirmed. Thymoma-related immune dysfunction may be a possible contributor to the malignant tumors in this patient, but it cannot explain the benign adenomatoid tumor. In addition, the patient’s breast cancer was ER-positive and PR-positive, suggesting a possible endocrine background. However, preoperative sex hormone levels were within the reference ranges, and no direct evidence of endocrine disturbance was identified in this case. Therefore, both genetic and endocrine explanations remain unproven (13).

Prognosis and follow-up

Follow-up data were available for 3 to 60 months in the reviewed cases, and no recurrence or metastasis was reported. Patients who underwent testis-sparing surgery generally maintained fertility and endocrine function, supporting the benign behavior of adenomatoid tumor. Complete surgical excision is usually curative, and adjuvant radiotherapy or chemotherapy is not required. Periodic postoperative ultrasonography may be sufficient in most cases, especially after complete resection and pathological confirmation of benign disease.

Study strengths, limitations and future prospects

This report provides detailed clinical, imaging, pathological, immunohistochemical, and follow-up information for a rare case of testicular adenomatoid tumor after orchiopexy. The literature-based review of 33 cases also summarizes the reported clinical presentation, tumor origin, imaging features, pathological findings, treatment choices, and outcomes of this rare entity.

This study has several limitations. First, the number of reported cases remains small, which limits the reliability of statistical interpretation. Second, the literature review was mainly based on case reports, and publication bias cannot be excluded. Third, molecular or germline genetic testing was not performed, so the genetic basis of the patient’s multiple tumors could not be evaluated. Fourth, rapid intraoperative immunohistochemistry is not available in all hospitals, which limits the generalizability of a testis-sparing strategy based on frozen section and immunohistochemistry. Future multicenter studies with standardized pathological evaluation and molecular testing are needed to clarify the relationship between cryptorchidism, mesothelial tumorigenesis, and multiple primary tumors.

4. Conclusion

We report a rare case of testicular adenomatoid tumor after orchiopexy in a patient with previous male breast cancer and thymic B2 thymoma. In patients with a history of cryptorchidism and a testicular lesion, adenomatoid tumor should be considered in the differential diagnosis, particularly when imaging findings and serum tumor markers suggest a benign lesion. The association between cryptorchidism and adenomatoid tumor remains hypothetical and should be interpreted cautiously. Frozen section combined with rapid immunohistochemistry may help guide testis-sparing surgery when feasible, although its use is limited by diagnostic uncertainty and institutional availability. Thymoma-related immune dysfunction may contribute to malignant tumors, but there is no evidence that it promotes benign mesothelial tumorigenesis. Larger case series with molecular testing are needed to clarify these associations.

5. Patient perspective

The patient expressed satisfaction with the definitive diagnosis and preservation of testicular function. Postoperative recovery was uneventful, with no psychological burden, and the patient actively adhered to regular follow-up. The patient emphasized the importance of early detection and evidence-based management.

Funding Statement

The author(s) declared that financial support was received for this work and/or its publication. This work is supported by Hebei Provincial Department of Human Resources and Social Security Project (A202101130), Shijiazhuang Science and Technology Bureau Project (231460203), and the Hebei Provincial Health Commission Project (20260927).

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

Ethics statement

The studies involving humans were approved by the Ethics Committee of The People’s Hospital of Shijiazhuang. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.

Author contributions

YC: Conceptualization, Data curation, Investigation, Writing – original draft. XZ: Data curation, Investigation, Validation, Writing – original draft. FS: Validation, Visualization, Writing – review & editing. LL: Project administration, Supervision, Writing – review & editing. XC: Project administration, Supervision, Visualization, Writing – review & editing. SL: Project administration, Supervision, Writing – review & editing. CL: Project administration, Supervision, Writing – review & editing. SS: Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review & editing.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2026.1865829/full#supplementary-material