Down syndrome with cryptorchidism and retroperitoneal mixed germ cell tumour in an adult patient: a case report and literature review

Abstract

Background

An association between testicular cancer and Down syndrome has been reported by several studies. Down syndrome with cryptorchidism and retroperitoneal mixed germ cell tumours is rare, and yolk sac tumours are often considered secondary components of mixed germ cell tumours. Herein, we present a rare case of retroperitoneal mixed germ cell tumour with cryptorchidism accompanied by yolk sac tumour and seminoma in a patient with Down syndrome, along with its imaging features.

Case presentation

A 42-year-old man was admitted to the hospital for 6 months due to a worsening abdominal pain that was followed by syncope for 8 h. There was a significant increase in AFP and β-HCG levels. An enhanced computed tomography (CT) scan of the entire abdomen showed a mixed cystic solid mass in the retroperitoneal space. Fluorine-2-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography/CT examination showed an abnormal increase in the FDG uptake in the parenchymal part of the mass, with a maximum standardised uptake value of approximately 10.5. The pathological diagnosis was retroperitoneal mixed germ cell tumour (yolk sac tumour + seminoma). One and a half months postoperatively, the tumour recurred. Consequently, the patient underwent chemotherapy, and after one course of treatment, the patient developed bone marrow suppression. Finally, he died due to complications.

Conclusions

Yolk sac tumours, the main components of mixed germ cell tumours, are rare in adults and exhibit rapid growth, heightened malignancy, and poor prognoses. CT features play a crucial role in diagnosis. Down syndrome is a high-risk factor for malignant testicular germ cell tumours. Therefore, comprehensive examinations for gonadal and germ cell tumours in patients with Down syndrome are imperative and should be prioritised by clinicians.

Background

Down syndrome is the most common congenital defect caused by chromosomal mutations. An association between testicular cancer and Down syndrome has been reported. To our knowledge, no cases of Down syndrome with a retroperitoneal mixed germ cell tumour consisting of cryptorchidism with yolk sac tumour and seminoma have been reported to date. Herein, we present such a case along with its corresponding imaging features.

Case Presentation

A 42-year-old man unmarried and childless man was admitted to the hospital for 6 months due to a worsening abdominal pain that was followed by syncope for 8 h. The patient had Down syndrome and cryptorchidism with intellectual disability and was non-verbal since childhood. Physical examination revealed swelling in the lower abdomen and tenderness in the upper and middle abdomen; a hard mass with a diameter of 20 cm was palpated in the lower and middle abdomen. The left scrotum was empty, and the right scrotal testis was palpable. Tumour marker assay results were as follows: alpha-fetoprotein (AFP), 7604.0 µg/L; beta-human chorionic gonadotropin (β-HCG), 45 IU/L; and cancer antigen 125, 100.8 kU/L. An enhanced computed tomography (CT) scan of the entire abdomen showed a mixed cystic solid mass in the retroperitoneal space with a size of approximately 176 mm ×99 mm ×140 mm with clear boundaries. After enhancement, the solid components were significantly enhanced, but there was no enhancement in the cystic necrotic area. Multiple small vascular shadows supplied by the left testicular artery were observed inside the tumour. Surrounding the tumour was a fluid accumulation shadow, and the adjacent intestinal tract was pushed and displaced. Peritoneal thickening and exudation were found along with fluid accumulation shadows in the abdominal and pelvic cavities (Fig. 1). Fluorine-2-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography/CT (PET/CT) examination showed an abnormal increase in the FDG uptake in the parenchymal part of the mass, with a maximum standardised uptake value (SUV) of approximately 10.5, measured 1 h after the injection of the contrast agent. Large areas of sparse radioactive uptake were observed within the tumour. In addition, multiple flocculent thickening of the peritoneum and a mild increase in FDG uptake with a maximum SUV of approximately 3.3 were observed (Fig. 2-3).

A laparotomy was performed, which revealed a large tumour located behind the peritoneum. The tumour, measuring approximately 25 cm × 20 cm, was tough and partially cystic, containing a large amount of brown fluid. The blood supply to the tumour was provided by the left testicular artery. Additionally, the tumour capsule adhered to some parts of the small intestine and the transverse colon mesentery. The descending colon was pushed to the right side of the abdominal cavity by the tumour. The tumour invaded parts of the greater omentum, descending colon, and sigmoid colon. Thus, we decided to perform massive retromembranous tumour resection and left hemicolectomy. The postoperative pathological examination results showed a retroperitoneal mass measuring 21.2 cm × 17.5 cm × 12.8 cm. The cut surface was cystic and solid, with a solid area resembling fish flesh; it was greyish-red and soft in texture. Microscopically, the tumour consists of two components (Fig. 4). The cells in the spermatogonial region are sheet-like and nest-shaped, separated by fibrous septa containing lymphocytes. The tumour boundary is clear, and the cytoplasm is abundant (Fig. 5). The cells in the yolk sac area are reticular, and Schiller Duval’s bodies are proliferating (Fig. 6). Immunohistochemical examination showed that SALL4 was positive in both regions, CD117 and PLAP were positive in the seminomal region, and CK was positive in the yolk sac tumour region. The pathological diagnosis was retroperitoneal mixed germ cell tumour (yolk sac tumour + seminoma) with partial cystic transformation and haemorrhagic necrosis. The tumour invaded the mesentery and adhered to the serosal layer of the intestinal wall. After 3 weeks of postoperative follow-up, the AFP and β-HCG levels decreased significantly to 286 ug/L and 3.7 IU/L, respectively. One and a half months postoperatively, a CT scan showed multiple recurrent lesions in the abdominal cavity. EP chemotherapy (etoposide + cisplatin) was performed, and after one course of treatment, the patient developed bone marrow suppression. Finally, he died after 1 week due to complications.

Fig. 1

Computed tomography (CT) image shows that the tumour cells are cystic and solid, with abundant internal blood vessels supplied by the left testicular artery

Fig. 2

Abdominal fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18 F-FDG PET/CT) fusion image, showing a large mass in the abdominal cavity with uneven radiation uptake and SUVmax of 10.5

Fig. 3

Image reveals the highest density projection, showing the high metabolic zone of the abdominal mass

Fig. 4

20X, H&E, Tumour is composed of two components: the seminoma area on the upper right and the yolk sac tumour area on the lower left

Fig. 5

400X, H&E, Clear cell boundaries with abundant cytoplasm in seminoma, separated by fibrous septa containing lymphocytes are observed

Fig. 6

100X, H&E, Schiller Duval bodies are seen in the yolk sac area

Discussion and conclusions

Patients with Down syndrome have a significantly higher risk of developing leukaemia and testicular cancer than the general population [1, 2]. These patients are also more susceptible to respiratory infections, and many children have a shorter survival period. However, with improvements in medical standards, the life expectancy of these patients has increased; moreover, reports of testicular cancer have increased. According to Satge et al. [3], the risk of testicular cancer in patients with Down syndrome is approximately 50 times higher than expected. Furthermore, men with Down syndrome have a higher risk of cryptorchidism than the general population [4], and patients with cryptorchidism have a risk of testicular germ cell malignancy that is several times higher than that of the general population. If the testicles are located in the abdominal cavity, the risk of developing germ cell tumours is greater than if they are located in the groin [5]. The malignant transformation of cryptorchidism may be related to factors such as abnormal testicular germ cells, blood supply disorders, high temperature, endocrine disorders, and underdeveloped gonads. Testicular tumours can be divided into seminomas and nonseminomas based on their tissue origin. Nonseminomas include teratomas, embryonal carcinomas, choriocarcinomas, yolk sac tumours, and polyembryoma [6].

Nonseminomas can appear in simple or mixed forms, with mixed forms accounting for 40–45% [7]. The most common mixed forms are embryonic carcinomas and teratomas [8]. Yolk sac tumours are usually secondary components interspersed between the main components. Case reports of Down syndrome combined with cryptorchidism and germ cell tumours have been very rare. Kurada et al. [9] reported a case of adult Down syndrome complicated by left inguinal cryptorchidism and a mixed germ cell tumour, predominantly composed of embryonic carcinoma. They also identified eight previous cases, of which six had pathological results of seminomas, one had embryonal carcinoma, and one had malignant germ cell tumours. In contrast, our case was a rare mixed form, with yolk sac tumours comprising the majority and seminoma as a minor component; the tumour is located retroperitoneally. To our knowledge, no such cases have been reported to date.

Our patient exhibited a significantly elevated AFP level of 7604.0 µg/L, indicating that it was mainly a yolk sac tumour; however, the β-HCG level was also elevated, indicating a mixed germ cell tumour. Postoperatively, there was a significant decrease in AFP and β-HCG levels.

The early detection of malignant tumours in the retroperitoneum is difficult. Often, when seeking medical treatment, the tumour is already large, making a qualitative diagnosis challenging. CT is the primary method of qualitative diagnosis. The histology of primary retroperitoneal mixed germ cell tumours is similar to that of primary gonadal germ cell tumours, and their CT manifestations are also partially similar depending on the type of mixed germ cells. The CT manifestations of yolk sac tumours and seminomas are similar, both presenting as well-defined, oval-shaped masses with a capsule. The masses are cystic and solid, with common liquefaction and necrosis within the masses. In the present case, after enhancement, the solid components showed gradual enhancement, whereas the necrotic parts showed no enhancement. Our patient also presented with a mixed cystic solid mass shadow, with cystic necrotic areas visible within the mass. In addition, enhanced yolk sac tumours often show abundant blood vessels, which is consistent with the CT findings in the present case. Moreover, abundant small vascular shadows were observed inside the tumour, indicating that the main component of the tumour was a yolk sac tumour. The tumour was supplied by the left testicular artery, indicating a malignant transformation of the left cryptorchidism.

¹⁸F-FDG PET/CT imaging is of great significance for diagnosis, treatment, and prognosis, as it can simultaneously display primary and metastatic lesions. The ¹⁸F-FDG PET/CT imaging of our patient in this case, showed a huge abdominal mass with uneven metabolic uptake (SUVmax of 10.5) and no distant metastasis of the tumour.

Mixed germ cell tumours originating from the retroperitoneum must be differentiated from other retroperitoneal tumours. (a) Liposarcoma: Liposarcoma is the most common primary retroperitoneal sarcoma and is more common in middle-aged and older adult populations, with no sex differences [10]. They are usually larger in volume, contain fatty components, and have thick, irregular partitions after enhancement. (b) Smooth muscle sarcoma: Widespread necrosis or cystic changes are often seen in the body of the tumour, characterised by easy invasion of abdominal blood vessels. (c) Paraganglioma: The shape is relatively regular with clear boundaries and is prone to necrosis, bleeding, and cystic changes. It may have calcification and obvious enhancement.

In summary, yolk sac tumours, the main components of mixed germ cell tumours, are rare in adults and exhibit rapid growth, heightened malignancy, and poor prognoses. CT features play a crucial role in diagnosis. Down syndrome is a high-risk factor for malignant testicular germ cell tumours. Therefore, comprehensive examinations for gonadal and germ cell tumours in patients with Down syndrome are imperative and should be prioritised by clinicians.