1 Background

Gonadoblastoma is a rare tumor often associated with gonadal hypoplasia. Although it is a benign tumor, it has the potential to develop into seminoma and other malignant reproductive tumors. Bilateral incidence of gonadoblastoma is as high as 40%, so the recommended standard treatment is bilateral gonadectomy. A male hermaphrodite malformation complicated with rare adenoblastoma complicated with asexual cell tumor was admitted to our hospital recently.

A male patient, 27 years old, was admitted to the urology department of Ya ‘an People’s Hospital due to infertility after one year of marriage. Physical examination showed that the penis and pubic hair developed normally, the scrotum and the testicles on both sides of the groin were not palpated, and ultrasound was not detected. With bilateral cryptorchidism The diagnosis was sent to the hospital. The results showed that no sperm was found by semen centrifugation, and the chromosome karyotype was 46,XY (GTG), and the gene test was normal. MRI showed normal penis and prostate size, empty scrotum and no testicles. The uterus is visible in the pelvic cavity, and the endometrium is small in shape and about 0.6 cm thick. The upper vaginal segment, about 0.8 cm in length and diameter, is located between the bladder and two seminal vesicles, and the middle and lower segments are not shown; Bilateral appendages shown (testis/ovaries not recognized). Preoperative sex hormone examination showed that follicle-stimulating hormone FSH and luteinizing hormone LH were slightly elevated, and serum prolactin PRL, estradiol E2, progesterone Prog and testosterone Testo were normal.

2 Method

This study was reviewed by the Ethics Committee of Ya ‘an People’s Hospital (YA2023137). The study was conducted in accordance with the 2021 standard guidelines of the Campbell Urology [1] and Endoscopic Surgery Sections of the Pediatric Surgery Society of the Chinese Medical Association [2].

We plan to perform laparoscopic exploratory surgery, during which the uterus can be clearly seen, which is small and located behind the bladder. The gonadal organs are visible on both sides, but cannot be identified as testis or ovaries, nor can the spermatic vessels or fallopian tubes at the junction (Fig. 1). Subsequently, bilateral gonad specimens were taken and intraoperative frozen biopsy was performed. Freezing reports suggest (right gonad) gonadoblastoma with asexual tumor (Fig. 2); (left gonadal gland) testicular tissue under microscope, deep tissue after freezing, focal suspicious microgonadoblastoma (Fig. 3). Considering the presence of endometrium and partial residual vaginal tissue in the uterus, consult a gynecologist during the operation, considering the presence of endometrium and partial residual vaginal tissue, there may be menstruation in the future, resulting in deposition in the residual vaginal cavity. We performed total hysterectomy plus bilateral gonadal tumor organ resection, closed the stump of the vagina, sent for pathological examination, and local radiotherapy after surgery.

Fig. 1
figure 1

Observations under laparoscopy. Bilateral visible gonadal organs, testicles or ovaries cannot be confirmed, and the connection between spermatic cord blood vessels or fallopian tubes cannot be confirmed

Full size image
Fig. 2
figure 2

Right gonadal freezing and postoperative pathological examination. Bilateral gonads were sampled and intraoperative frozen biopsy was performed. Frozen report prompt: Gonadoblastoma combined with asexual cell tumor

Full size image
Fig. 3
figure 3

Left gonadal cryopreservation and postoperative pathological examination. This is testicular tissue, which has been frozen and deeply incised. It is suspected to have a focal small adenoblastoma

Full size image

The surgery was successfully completed, and the postoperative pathological report showed that the endometrium in the uterus was in a proliferative state, consistent with the preoperative imaging examination; The right gonad was diagnosed as a combination of gonadoblastoma and malignant germ cell tumor (asexual cell tumor/seminoma), with hardened and atrophic testicular tissue visible. No proliferation of germ cells or supporting cells was found in the Qujing tubules. The left gonad is a gonadoblastoma. Postoperative changes in sex hormones: Testosterone decreased from 3.61 ng/ml before surgery to 1.16 ng/ml, with no significant changes in other sex hormones. We administered testosterone undecanoate to supplement androgens, with an initial dose of 120-160 mg/day. After taking it for 3 weeks, it gradually decreased to a maintenance dose of 40 mg/day based on the follow-up results, and was taken with meals.

3 Discussion

Gonadoblastoma is a relatively rare type of gonadal tumor that often occurs before and after puberty, mostly between the ages of 16 and 25. The youngest reported in literature is only 4 weeks old. Gonadoblastoma can be clinically classified into three types [3]: ① Female phenotype, accompanied by masculinization symptoms, without Turner syndrome, with primary amenorrhea, deep voice, excessive hair, clitoral hypertrophy, breast atrophy, etc. The main manifestations during surgery are mostly female reproductive organs, but with poor development. ② Female manifestation, without masculine symptoms. The highest incidence rate of this type of incidence rate is in the three types, with Turner syndrome. The patients mostly show the secondary sexual syndrome, genital dysplasia, primary amenorrhea, poor or underdeveloped breast. ③ Male phenotype, this type of disease is extremely rare and often accompanied by male pseudohermaphroditism [4]. The nature of the gonads is often unknown, and about 80% of them are accompanied by cryptorchidism or hypospadias. It has the potential to develop into seminoma and other malignant reproductive tumors. The reported case belongs to the third category, and gonadoblastoma has progressed with the presence of asexual cell carcinoma. Changchien et al. studied a patient with excessive growth of asexual cell carcinoma [5]. They analyzed DNA ploidy, the presence of Y chromosome DNA sequence, and the chromosomal 12p arm in tumor cells using cell photometry, confirming a strong correlation between gonadoblastoma and asexual cell carcinoma and Y chromosome. The excessive growth of asexual cell carcinoma is further caused by chromosomal aberrations [6].

Gonadoblastoma can be divided into mixed type and simple type based on pathological characteristics. Mixed type refers to the mixture of other tumor components derived from germ cells in the tumor, and the common type is asexual cell tumor, which is sensitive to radiotherapy and chemotherapy [7]; Simple adenoblastoma is often arranged into three types of structures: small and long sex cord like cells radiating around large and round reproductive cells, forming a floral ring like structure; Sex cord like cells surround a single germ cell, forming a structure similar to a primordial follicle; Deep stained spindle shaped sex cord cells are arranged around amorphous, eosinophilic, and glassy substances, forming a structure similar to Call Exner bodies [8]. Gonadoblastoma is relatively rare, and due to its unique morphology, it is generally less likely to be misdiagnosed as another tumor. However, pathological diagnosis needs to be differentiated from circular tubular adenoma, other sex cord/gonadal stromal tumors, granulosa cell tumors, non gonadoblastoma mixed germ cell sex cord stromal tumors, etc [9]. Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) has revolutionized the field of cancer treatment [10]. Responsiveness to immune checkpoint inhibitors was considerably enhanced and a robust anti-cancer effect was demonstrated with the combination treatment of M[Formula: see text]-SDNPs and anti-PD-1 antibody [11]. Through single-cell RNA sequencing, we found the differences in tumor cells’ expression programs and differentiation tracks [12].

About 80% of these tumors are women, most of them are primary amenorrhea, and the other 20% are men. Most of them are cryptorchidism, azoospermia, hypospadias, and other diseases, and the bilateral incidence rate is about 40% [13]. Once the pathological section report is confirmed, surgical resection and corresponding radiotherapy and chemotherapy should be performed, and close follow-up should be conducted. In this case, the patient discovered that the tumor had undergone changes in its biological behavior and progressed to malignancy. The prognosis still needs further follow-up observation.