Testicular teratoma and primary retroperitoneal choriocarcinoma with lung metastasis: a case report

Introduction

Choriocarcinoma is usually incident in female reproductive system during the child-bearing ages. It is a very invasive malignant tumor formed from the dysplasia of the embryonic trophoblast cells. Primary retroperitoneal choriocarcinoma (PRC) is historically a rare extragonadal germ cell tumor which incidence rate is about 0.022 per 100,000 people (1). Male PRC is much rarer than female’s, which incidence in females is 12.5 times higher than that in males (2-4). Male PRC has a poor prognosis with a 5-year survival rate of 30% (1) because it easily gets hematogenously metastasized due to its highly vascular invasiveness (2-5). Once diagnosed, it is usually at a late stage with fast progression and poor prognosis with a low survival rate (1,5). Early diagnosis can help improve its prognosis. Surgery at an early stage combining with chemotherapy can help improve its prognosis.

PRC has atypical symptoms and often has pain in abdomen, which is easily misdiagnosed with appendicitis and mesenteric lymphadenitis. Male PRC can have some special signs of having breasts feminization, testicular atrophy, and hypaphrodisia (6,7). Male PRC is often diagnosed before puberty and very rare after puberty. No study reports co-occurrence of testicular teratoma and PRC diagnosed after puberty. Theoretically, this type of co-occurrence can be caused by the abnormal migration of primordial germ cells (PGCs) in the early stage of the pregnancy that can be interrupted by some adverse environmental factors. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-25-44/rc).

Case presentation

Patient information

A 23-year-old man presented with tolerable pain in the right lower abdomen for 10 days without any other symptoms and which pain was getting worse in day 11. He claimed he was not a smoker and did not have a history of any disease. He did not have a family history of choriocarcinoma or other cancers. He was a food delivery man working for a restaurant.

Clinical findings and timeline

The patient started having tolerable pain in the right low abdomen without any other symptoms from 9 to 18 October, 2023, which pain was getting worse on 19 October, 2023, and he presented to the Department of Surgery as an outpatient in The Zhejiang Chinese Medical University Affiliated Four-Province-Bordering Hospital of Traditional Chinese Medicine (Quzhou Hospital of Traditional Chinese Medicine) on 20 October, 2023. Physical examination found his pain got worse in supine position with a numerical rating scale pain score of 4 (the maximum score: 10) and the patient was asked for routine blood testing and ultrasound examination right away. When routine blood testing found the white blood cell count was 11.0×10⁹/L (reference range: 4.0 to 10.0 ×10⁹/L) and ultrasound indicated that there was a hypoechoic mass (about 0.8 cm × 0.5 cm) in the right testis, the patient was got hospitalized on the same day.

Diagnostic assessment after hospitalization

Physical examination found his pain got worse in supine position with the same pain score of 4. His body mass index (BMI) was 28.1 in kg/m². Testicular examination showed no differences in shape and hardness between the two testes.

Laboratory testing found that the white blood cell count was still high; the serum C-reactive protein was 40.0 mg/L (reference range: 0.068 to 8.2 mg/L in adults); the cytokeratin 19 fragment level was 4.64 ng/mL (reference range: 0 to 3.3 ng/mL); and the serum β human chorionic gonadotropin (β-hCG) was 5,350.27 IU/L (reference range: <5 IU/L in adult men). Serum α fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen (CA125) were all in normal range.

Computed tomography (CT) scanned the whole abdomen and found a retroperitoneal mass before orchiectomy. Due to its complicated location, a contrast-enhanced CT plus angiography and magnetic resonance imaging (MRI) were conducted for the surgical planning. The contrast-enhanced CT plus angiography showed the mass (42 mm × 42 mm) of non-uniform density [CT value was 26 Hounsfield unit (HU) in the middle and 55 HU around] seen under the left renal vein and on the left side of inferior vena cava (IVC) in Figure 1A, and significant enhancement around the arterial phase and insignificant enhancement in the middle observed in Figure 1B, which confirmed the retroperitoneal mass. MRI showed irregularly abnormal signals, obvious IVC under pressure, and high signals seen in T1W1 observed between retroperitoneal IVC and abdominal aorta (Figure 2A), and mixed high signals seen in fst2W1 (Figure 2B), which indicated the retroperitoneal mass bleeding with cystic degeneration that could also be hematoma from intra tumor bleeding which helped confirm this was malignant. Considering the high serum β-hCG level and the image results, the diagnosis of his tumor should be choriocarcinoma. Chest CT found multiple pulmonary nodules which indicated the metastasis of choriocarcinoma into the lung.

Figure 1 Enhanced CT images of the patient with lung metastasis from male primary retroperitoneal choriocarcinoma. (A) A mass (42 mm × 42 mm) of non-uniform density (CT value was 26 HU) in the middle and 55 HU around) seen under the left renal vein and on the left side of inferior vena cava. (B) Significant enhancement around the arterial phase and insignificant enhancement in the middle. CT, computed tomography; HU, Hounsfield unit.

Figure 2 Magnetic resonance imaging images of the patient. (A) Irregularly abnormal signals, obvious inferior vena cava under pressure, and high signals seen in T1W1 observed between retroperitoneal inferior vena cava and abdominal aorta and (B) mixed high signals seen in fst2W1.

Therapeutic intervention

Orchiectomy was done to remove the testicular mass (about 0.8 cm × 0.5 cm) in the right testis under the general anesthesia on 27 October, 2023. The cryopathologic results showed there were small tissues of cartilage and squamous epithelium with mature differentiation which suggested the diagnosis of mature teratoma (Figure 3A). Its immunochemical marker testing showed Ki-67+ (positive), CK20– (negative), CK–, CEA–, EMA–, inhibin A+, vimentin+, and WT-1+ (Figure 3B).

Figure 3 Pathohistological results of the right testicular mass (A,B) and the retroperitoneal mass (C-F). (A) Cryopathological results of the right testicular mass which showed some small tissues of cartilage and squamous epithelium with mature differentiation indicated by an arrow seen under a microscope with 5×. (B) Results of immunochemical markers of the right testicular mass: Ki-67+ (positive), CK20– (negative), CK–, CEA–, EMA–, inhibin A+, vimentin+, and WT-1+ seen under a microscope with 10×. (C) Pathohistological results of the retroperitoneal mass that showed the malignant tumor of choriocarcinoma with massive necroses and neural invasion seen under a microscope with 20×. (D-F) Results of immunochemical markers of the retroperitoneal mass: inhibin A+, Melan-A–, HCG+, CK7+, CK+, Ki-67(80%+), P40(partial+), TTF-1–, CD34(vascular+), and vimentin–, and having obvious bleeding with partial necrosis in the tumor, the bilateral plexiform structure formed by the cytotrophoblast cells and syncytiotrophoblast cells closely mixed with proliferation, and the huge syncytiotrophoblast cells with big and atypical nucleus in the hematoxylin-eosin staining slides seen under a microscope with 10× (D), 20× (E) and 40× (F; with the left arrow pointing to a trophoblast cell and the two right arrows pointing to the two syncytiotrophoblast cells). CEA, carcinoembryonic antigen.

After careful planning for the surgery, the excision of the retroperitoneal mass was done under the general anesthesia on 3 November, 2023. The mass was seen under the left renal vein and on the left side of IVC, and during the operation, it was observed significantly adhering to IVC with many hyperplastic blood vessels and the tumor capsule wrapping IVC which made very difficult to remove the whole tumor capsule. In order not to hurt IVC, ligation of free blood vessels around was done and then completed excising the whole mass after flipping it over but leaving some tumor capsule which was wrapping IVC. Surgery helped relieve his pain and obtain the tissues for histopathology. Its histopathological results indicated the malignant tumor of choriocarcinoma with massive necroses and neural invasion (Figure 3C), and having obvious bleeding with partial necrosis in the tumor, the bilateral plexiform structure formed by the cytotrophoblast cells and syncytiotrophoblast cells closely mixed with proliferation, and the huge syncytiotrophoblast cells with big and atypical nucleus in the hematoxylin-eosin staining slides seen under a microscope with 10× (Figure 3D), 20× (Figure 3E) and 40× (Figure 3F), the left arrow pointing to a trophoblast cell and the two right arrows pointing to the two syncytiotrophoblast cells). Its immunochemical markers testing showed inhibin A+, Melan-A–, HCG+, CK7+, CK+, Ki-67(80%+), P40(partial+), TTF-1–, CD34(vascular +), and vimentin–.

After being discharged from the surgery department, the patient went for routine chemotherapy because choriocarcinoma is believed to be sensitive to chemo. According to the last phone call follow-up, he was taking chemotherapy for choriocarcinoma and suffering some side effects from chemo. He died on 27 September, 2024 based on the record in the Death Registration System.

All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study has been approved by the Ethics Committee at The Zhejiang Chinese Medical University Affiliated Four-Province-Bordering Hospital of Traditional Chinese Medicine (Quzhou Hospital of Traditional Chinese Medicine) (approval No. 2022-02-030). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

This is the first study that has reported such a rare co-occurrence of male PRC with lung metastasis and testicular mature teratoma with feminization body shape diagnosed after puberty. These two rare tumors diagnosed after puberty indicate they tend to be two different tumors formed from the PGCs stayed in the testis and retroperitoneum, respectively, through the migration of PGCs in the early stage during his mother’s pregnancy with him. Theoretically, PGCs can stay in any migration location if the pregnancy is interrupted by any adverse environmental factors. This patient had survived only for about 11 months.

Surgery is the first choice for testicular teratoma and male PRC though the location of the retroperitoneal mass makes the surgery very difficult to complete because of the mass adhering to IVC with many hyperplastic blood vessels and the tumor capsule wrapping IVC which made very difficult to remove the whole tumor capsule. The thorough evaluation of the retroperitoneal tumor before surgery critically helps the surgeon to pick an appropriate operation program. Surgery helped relieve the pain caused by the tumor masses and obtain the tissues for histopathology which results provide some evidence for the subsequent treatment and prognosis prediction.

This patient survived for less than one year which means his 5-year survival rate is 0%, significantly lower than that in male patients with diagnosis of PRC alone (30%) (1). His poorer prognosis is predicted by both tumors having high percentage of Ki-67+, the retroperitoneal tumor having lung metastasis, and high malignancy of male PRC at the late stage. Both male PRC and teratoma have 80% and 100% of Ki-67+, respectively, which indicate his two kinds of tumors grow fast with low differentiation but they should be sensitive to chemotherapy. In addition, his PRC tumor has vascular and neural invasiveness with lung metastasis and necrosis which also predicts poor prognosis though he has atypical symptoms only with pain in abdomen for 11 days, which is easily misdiagnosed with appendicitis or mesenteric lymphadenitis. Lastly male PRC at the late stage has high malignancy and recurrence which is consistently reported in the literature (1-4,8,9).

This case had a high serum β-hCG level of 5,350.27 IU/L that reaches a 7-week-gestation pregnant woman’ serum level, much higher than the normal level in adult men, which β-hCG level supports his obvious feminization body shape that made him overweight (BMI =28.1 kg/m²) though he had enough daily physical activity from food delivery. Our findings of his feminization signs in this case are consistent with the reported literature (5-7,9).

There are several challenges/limitations in this study. Biopsy was not able to be done before surgery which is not a good option due to its location of retroperitoneum which also challenged the surgeons to remove the whole tumor capsule that was wrapping IVC though they completed excising the whole mass. The reliance on imaging modalities including CT and MRI for retroperitoneal tumor evaluation may limit surgical planning. This is a very rare disease, so diagnosis mainly relies on the role of immunohistochemistry due to lack of standardized diagnostic criteria. The patient refused to have genetic test; thus our study lacks genetic profiling to elucidate potential etiological factors or therapeutic targets for co-occurrence of the aggressive nature of male PRC and high-grade teratoma.

Conclusions

This is the first study that has reported such a rare co-occurrence of male PRC with lung metastasis and testicular mature teratoma with feminization body shape diagnosed after puberty. Surgery was the first choice for this case which helped relieve the pain caused by the tumor masses and obtain the tissues for histopathology. The location of this retroperitoneal tumor made the surgery very difficult to complete due to the tumor involving the blood vessels, but a thorough evaluation of the retroperitoneal tumor, including CT, contrast-enhanced CT plus angiography, MRI and other examinations, was done before the surgery which helped the surgeons to pick a better operation program. Immunochemical markers testing provided some evidence for the subsequent treatment and prognosis prediction. The prognosis of this case is very poor which is evident that his 5-year survival rate is significantly lower than that in male patients with PRC alone. His poorer prognosis is also supported by both tumors having high percentage of Ki-67+, the retroperitoneal tumor having vascular and neural invasiveness with lung metastasis, and high malignancy of male PRC at the late stage.

Acknowledgments

We sincerely thank all medical doctors, nurses and staff who participated in this study.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-25-44/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-25-44/prf

Funding: This research was funded by the Key Project of the Quzhou City Bureau of Science and Technology Grant (No. 2023K154) and the Key Project of the Zhejiang Chinese Medical University Affiliated Hospital Special Science Research Fund (No. 2021FSYYZZ11).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-25-44/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study has been approved by the Ethics Committee at The Zhejiang Chinese Medical University Affiliated Four-Province-Bordering Hospital of Traditional Chinese Medicine (Quzhou Hospital of Traditional Chinese Medicine) (approval No. 2022-02-030). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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