Easily missed diagnosis of testicular choriocarcinoma with a large retroperitoneal mass as the primary symptom: a case report

doi:10.21203/rs.3.rs-2228713/v1

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Case Report

Easily missed diagnosis of testicular choriocarcinoma with a large retroperitoneal mass as the primary symptom: a case report

https://doi.org/10.21203/rs.3.rs-2228713/v1

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Testicular choriocarcinoma is a relatively rare malignancy with a highly aggressive nature. Timely diagnosis and treatment can help prolong the survival of patients and even cure them. This case reports a 29-year-old male who presented to the clinic for a month with epigastric pain without complaints of discomfort in the reproductive system. On examination, only a massive mass of approximately 9*10 cm could be palpated in the upper abdomen. When asked about his previous history, the patient only described a history of a right inguinal hernia that had been repaired 12 years earlier without knowing that a testicular descending fixation had been performed at the same time (we only found out afterward by asking his parents). The admission diagnosis was considered the retroperitoneal tumor, which was found to have metastasized to the liver and lungs after the completion of relevant tests. We then performed a CT-guided puncture biopsy of the lung tissue. The biopsy pathology suggested only a tiny heterotypic cell mass, and metastatic cancer was considered. As the symptoms of tumor compression gradually worsened, we nevertheless performed surgical treatment (retroperitoneal tumor resection + partial duodenal resection + enteroanastomosis). The postoperative pathology was choriocarcinoma. It was at this point that we pursued the patient's medical history in detail and, at the same time, performed a testicular ultrasound which revealed a substantial occupation of the right testicle. The diagnosis of testicular choriocarcinoma was finally considered (without pathological confirmation). We wanted to start salvage chemotherapy as soon as possible after surgery. However, the patient's postoperative condition was poor, with rapid progression of hepatopulmonary metastases and gradually increased thyrotoxicosis, and we started salvage chemotherapy (EP regimen: etoposide and cisplatin) on postoperative day 12. However, the patient was forced to stop due to a severe chemotherapy reaction and eventually died of respiratory and cardiac arrest in hospital. For men presenting with a large retroperitoneal mass without reproductive system-related complaints, a detailed history of the inguinal testicle should still be inquired with a detailed physical examination. Meanwhile, laboratory and image tests should be performed to rule out the possibility of a genital tumor to avoid a missed diagnosis that could lead to delayed treatment.

Missing diagnosis

Retroperitoneal mass

Testicular choriocarcinoma

Case report

Testicular choriocarcinoma is a rare malignancy that is highly malignant and extremely aggressive, with most patients presenting with extensive metastatic lesions and a poor prognosis [1]. In the United States, the 5-year survival rate for testicular choriocarcinoma is less than 80%, reflecting the invasiveness and pertinacity of the disease [2]. Currently, the treatment of testicular choriocarcinoma is mainly a comprehensive treatment based on surgery. Because of the disease's rarity, most of the literature is full of case reports, and there are still no clear guidelines for diagnosis and treatment. Testicular choriocarcinoma occurs mainly in young men (25y-30y). Typical clinical features include high hormone levels due to the tumor and/or the related symptoms of metastatic diseases, such as compression and bleeding. Signs may include gynecomastia, testicular swelling, etc [3]. However, in patients with atypical symptoms, especially in a subset of patients with extensive metastases, who do not detect a testicular mass on admission for physical examination, the rarity of the disease combined with the highly aggressive nature of choriocarcinoma makes it easy for clinicians to miss the diagnosis and delay treatment thereby increasing patient mortality and leading to tragic events. The purpose of this case report is to review a case of missed testicular choriocarcinoma at our center and to provide a cautionary tale for managing patients with atypical symptoms of testicular choriocarcinoma.

A 29-year-old Asian male was admitted to the hospital with progressively increasing epigastric distension for one month, accompanied by nausea after eating without vomiting and a weight loss of 5 kg over the past month. When asked about his past medical history, he said that he had undergone inguinal herniorrhaphy for a right inguinal hernia 12 years ago. There was no history of exposure to radiation or toxins. On admission, a 9*10 cm swelling in the upper abdomen was palpable. There was no significant gynecomastia or visual abnormality of the testes or penis. All vital signs were within normal limits. On the first laboratory examination, only the white blood cell count (11.5*10^9) and neutrophil percentage (84.6%) were high. There were no abnormalities in liver function, kidney function, electrolytes, and gastrointestinal tumor markers (CEA, AFP, and CA199). We then performed a preoperative imaging evaluation. Computed tomographic angiography (CTA) of the abdominal aorta suggested: 1. a right retroperitoneal occupying lesion (size approx. 11.3cm*10.7cm), considered malignant neoplastic (malignant stromal tumor? (suspected duodenal origin); the adjacent inferior vena cava was compressed and narrowed an unclear boundary with the tumor. 2. Multiple abnormal enhancing lesions in the liver, considering metastases (Fig. 1). High-resolution CT suggests multiple enhancing nodules in both lungs, considering multiple metastases in both lungs (Fig. 2). Magnetic Resonance Imaging (MRI) suggests 1. a malignant lesion in the right abdominal cavity with liver and multiple metastases in both lungs, 2. right ureter compression, right renal obstructive hydronephrosis, and multiple lymph nodes enlargement around the lesion (Fig. 3, three-dimensional reconstructions have been attached to the supplementary material.). After the examination, the diagnosis was considered retroperitoneal malignancy combined with hepatopulmonary metastases.

As the patient had distant metastases that were not eradicated by surgery, we wanted to obtain tumor pathology to guide the next treatment. In order to rule out a tumor of gastrointestinal origin, we had a gastroscopy, and the results suggest: 1. a submucosal bulge in the descending duodenum, which was considered a pressure change, but no biopsy was performed. 2. bile reflux gastritis. We then performed a CT-guided lung tissue puncture biopsy, in which pathology revealed a large area of hemorrhagic necrosis and normal lung tissue structure, with a few clusters of atypical cells, combined with immunohistochemical findings to diagnose metastatic carcinoma (Fig. 4a). During the refinement of the examination, the patient's epigastric distension and pain gradually increased, and he had severe insomnia at night with severe nausea and vomiting. At the same time, the heart rate gradually increased (the preoperative average heart rate reached 120 beats per minute). At that time, we considered that the onset of these symptoms could be related to a large occupying retroperitoneal lesion compressing the duodenum and the inferior vena cava. The decision to operate was made after the whole department discussion because the occupying effect can be reduced and pathology can be clarified so that comprehensive treatment can be started as soon as possible. The surgical treatment (retroperitoneal tumor resection + partial duodenal resection + enteroanastomosis) was performed on the 13th day of admission. The patient underwent an uneventful surgical procedure, which lasted six h. The intraoperative bleeding was approximately 1000 ml, and 1200 ml of suspended red blood cells were infused. Postoperative symptomatic and supportive treatment such as anti-infection, prevent vomiting, analgesia, fluid infusion, etc. The postoperative pathology showed that: microscopically, cancer tissue with a large area of bleeding and necrosis was seen, and combined with immunohistochemistry, it was considered choriocarcinoma. Immunohistochemistry: PCK, CK7, CK19 (+), CD10 (+/-), Hepa, TTF1, CD34, Syn, Gly-3, EMA, Villin, PLAP, CD30, AFP, OCT4, CD117 (-), GS focal weak (+), β-HCG (+), SALL4 local (+), KI-67: 80% (Fig. 4b).

After obtaining the pathological results, we took a detailed history from the patient's parents and learned that the patient had undergone a testicular descent surgery while performing the right inguinal hernia 12 years earlier. On palpation of the testis, the right testis was found to have no apparent substantial mass but was poorly mobile and surface not smooth. Testicular ultrasound was performed, and the findings suggested a solid right testicular mass with multiple calcified spots. The diagnosis of testicular choriocarcinoma with liver, lung, and retroperitoneal metastases was basically confirmed. The patient's heart rate dropped to an average of 80 beats/min within three days after surgery but gradually increased to 130 beats/min by the seventh postoperative day, and his general condition was deteriorating. After the operation, the patient showed no obvious signs of bleeding, but the hemoglobin was still dropping slowly, and he was given an intermittent infusion of suspended red blood cells. On the third postoperative day, liquid food was possible, but the amount of food consumed was low, and a small amount of parenteral nutrition still needed to be given. Insomnia was increasing at night, and the basal metabolic rate was above 40%, and a review of the literature revealed that excessive human chorionic gonadotropin might lead to thyrotoxicosis [4–6].

On the same day, thyroid function was urgently checked: T3, FT3, T4, and FT4 were all significantly elevated. Propranolol (20 mg orally 4/day) was given to control the heart rate, but the mean heart rate was still high (mean 120 beats/min). The sixth postoperative CT of the chest and abdomen showed rapid progression of liver and lung metastases. (Fig. 5). To improve the patient's survival, we wanted to start salvaging chemotherapy as a matter of urgency. Considering the patient's lung tumor load, we used the EP regimen (etoposide and cisplatin) without bleomycin to avoid the development of potentially fatal respiratory failure. We started the first chemotherapy on postoperative day 12 but were forced to stop as the patient developed a severe coughing up of blood. The patient did not undergo an orchiectomy. He eventually died of respiratory and cardiac arrest on postoperative day 14.

Testicular choriocarcinoma is a specific type of testicular cancer representing a subtype of non-seminomatous germ cell tumors (NSGCT). It often presents with high levels of hCG, is found with extensive metastases, has rapidly progressive disease, is highly resistant to chemotherapy, and has an inferior prognosis [7]. Diagnosing early and treating can prolong the patient's survival. The typical clinical manifestations of the disease include testicular masses, gynecomastia, elevated serum hCG, multiple metastatic lesions throughout the body, anemia, and hyperthyroidism. In this report, we detail the patient's history from admission to death and the relevant imaging data in the hope that clinicians can learn from this experience and each other. Initially, we also considered the possibility of a genital source (limited to visualization) but did not perform a careful exclusion, which is where we missed the mark. If the patient had been screened with testicular ultrasound or even PET-CT on admission, this might not have led to such an error. Of course, a lack of knowledge of rare diseases is a common reason for clinicians to miss a diagnosis, especially if it is outside their expertise. When the diagnosis is unclear, a multidisciplinary consultation can be considered to reduce the rate of underdiagnosis. We recommend that patients presenting with a retroperitoneal mass as the primary symptom should routinely undergo a genital ultrasound to screen for the source. For patients with hepatic and pulmonary metastases, PET-CT can be performed, if available, to detect the presence of cancer throughout the body and, firstly, to determine the primary and metastatic foci. Secondly, it can help to prevent complications associated with metastases in different locations. For example, the risk of intracranial hemorrhage can be assessed if the patient has metastases in the skull.

Choriocarcinoma is one of the malignancies that can be cured by chemotherapy. Serum hCG levels are often indicative of tumor activity as well as tumor burden [8]. This patient's serum hCG was above the upper line even after surgery, indicating a severe tumor load and a poor prognosis. Meanwhile, in the present case, the patient had a normal-sized testis but presented with a large abdominal mass as the primary symptom, with hepatopulmonary metastases. The literature has reported that the rare simple choriocarcinoma that exhibits features of hepatopulmonary metastasis with normal testicular morphology is the most aggressive and has an abysmal prognosis [9].

Such patients should be treated with urgent chemotherapy to improve survival, but the best time to start chemotherapy in postoperative patients is uncertain, so clinical judgment is necessary. The time point for starting chemotherapy in this patient was day 12 postoperatively, which should have been more delayed in terms of outcome. Perhaps chemotherapy should have been started when the patient could eat liquid food and before the heart rate had risen again. At that time, it was considered that the patient's surgery was long and traumatic and that the postoperative recovery might be adversely affected after chemotherapy. The optimal timing of chemotherapy for such cases needs to be further explored.

It is worth noting that the rapid progression of hepatopulmonary metastases in patients after resectioning a sizeable retroperitoneal mass is associated with the metastases becoming more aggressive after reducing the tumor load. Because guidelines suggest that testicular cancer may transform into a more aggressive malignancy at the time of metastasis, a biopsy of metastases is not recommended [10]. Whether reducing the tumor load also leads to a similar transformation needs to be further explored. Another topic for discussion is the choice of the chemotherapy regimen. Because each patient's general condition and tumor load are different, individualized treatment regimens should be given to achieve optimal results while reducing the side effects of chemotherapy. The typical treatment regimen for testicular choriocarcinoma is the BEP regimen (bleomycin, etoposide, and cisplatin), for which most patients have been reported to tolerate well and achieve high-quality remission with a controlled total hCG level of 600 IU/L at six-month follow-up [11]. Papiani et al. [12] used high-dose carboplatin in combination with etoposide in conjunction with autologous peripheral blood stem cell transplantation to treat simple male choriocarcinoma and achieved good results. In this patient, we used the EP regimen, as the patient was considered to have a severe postoperative lung tumor load to avoid potential respiratory failure resulting from bleomycin. However, due to the aggressive nature of choriocarcinoma, we propose to add bleomycin to the subsequent chemotherapy cycles. Unfortunately, the patient experienced a severe gastrointestinal reaction on the first day of chemotherapy and was forced to stop. The small number of patients with this type of disease makes clinical research tricky. As mentioned above, control of advanced choriocarcinoma has been reported with non-standard therapies. Hopefully, a better understanding and evaluation of novel therapies for male testicular choriocarcinoma patients will require continued basic and translational research.

With the development of science, technology, and the economy, standard screening equipment is available in some basic hospitals. The rate of underdiagnosis of common diseases by clinicians has gradually decreased, but the rate of underdiagnosis and misdiagnosis of rare diseases is still high. One reason may be that clinicians rely too heavily on equipment and neglect to improve their diagnostic skills. Secondly, with the increasing specialist experience, doctors are losing sight of knowledge that is not part of their specialty. Machines cannot replace the role of human beings, and it is an essential requirement for doctors in the new era to improve their abilities and constantly enrich their knowledge base. This is to be responsible for each patient and to safeguard one's medical career.

In practice, clinicians can easily miss the diagnosis of rare diseases, especially when the disease has no typical symptoms. This situation often leads to delayed treatment and potentially severe consequences. We aim to review this case as a reminder that patients with retroperitoneal masses should constantly be screened for possible reproductive system tumors (either from physical examination, tests, or examinations). If multiple distant metastases accompany the retroperitoneal tumor, such as liver and lung metastases, conditions allow PET-CT examination to help to judge metastases and primary lesions to avoid missed diagnosis.

MRI

Magnetic Resonance Imaging

Computed Tomography

NSGCT

Non-Seminomatous Germ Cell Tumors

hCG

human Chorionic Gonadotropin

PET

Positron Emission Tomography

CTA

Computed tomographic angiograph

year

CEA

Carcinoma Embryonic Antigen

AFP

Alpha Fetal Protein

BEP

Bleomycin, Etoposide, and Platinum

Free Triiodothyronine

Conflict of Interest

No conflict of interest was declared by the authors.

Financial Disclosure

The authors declared that this study has received no financial support.

Ethical Approval

Ethical approval is not required by our institution. This was a case report, and permission and consent have been taken from the patient.

Consent

The authors have obtained a written informed consent from the patient for publication of this case report and also accompanying images. A copy of the written consent is available on request.

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available due to the closed management of patient information in military hospitals and at the same time, the data are not publically available as they are pseudonymised medical records. But are available from the corresponding author on reasonable request

Author contributions

Bin Zhong and Tao Zhang helped in writing the abstract, figure collections, writing, and format. Yi Dong helped in writing and format. Wei Yin helped in writing and editing. Jian-Xin Zhang and Wei-Dong Jin helped in review and final editing

Reilley MJ, Pagliaro LC. Testicular choriocarcinoma: a rare variant that requires a unique treatment approach. Current oncology reports. 2015;17(2):2. https://doi.org/10.1007/s11912-014-0430-0
Stang A, Jansen L, Trabert B, Rusner C, Eberle A, Katalinic A, et al. Survival after a diagnosis of testicular germ cell cancers in Germany and the United States, 2002–2006: a high resolution study by histology and age. Cancer epidemiology. 2013;37(4):492–7. https://doi.org/10.1016/j.canep.2013.03.017
Lin YN, Liang SJ. Unilateral gynecomastia in a young adult. Internal medicine (Tokyo, Japan). 2011;50(12):1355. https://doi.org/10.2169/internalmedicine.50.5442
Morley JE, Jacobson RJ, Melamed J, Hershman JM. Choriocarcinoma as a cause of thyrotoxicosis. The American journal of medicine. 1976;60(7):1036–40. https://doi.org/10.1016/0002-9343(76)90577-5
Gleason PE, Elliott DS, Zimmerman D, Smithson WA, Kramer SA. Metastatic testicular choriocarcinoma and secondary hyperthyroidism: case report and review of the literature. The Journal of urology. 1994;151(4):1063–4. https://doi.org/10.1016/s0022-5347(17)35183-2
Goodarzi MO, Van Herle AJ. Thyrotoxicosis in a male patient associated with excess human chorionic gonadotropin production by germ cell tumor. Thyroid: official journal of the American Thyroid Association. 2000;10(7):611–9. https://doi.org/10.1089/thy.2000.10.611
Hanna NH, Einhorn LH. Testicular cancer–discoveries and updates. N Engl J Med. 2014;371(21):2005–16. https://doi.org/10.1056/NEJMra1407550
Li MC, Hertz R, Bergenstal DM. Therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists. N Engl J Med. 1958;259(2):66–74. https://doi.org/10.1056/nejm195807102590204
Choyke PL, Hayes WS, Sesterhenn IA. Primary extragonadal germ cell tumors of the retroperitoneum: differentiation of primary and secondary tumors. Radiographics: a review publication of the Radiological Society of North America, Inc. 1993;13(6):1365–75; quiz 77 – 8. https://doi.org/10.1148/radiographics.13.6.8290730
Gilligan T, Lin DW, Aggarwal R, Chism D, Cost N, Derweesh IH, et al. Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network: JNCCN. 2019;17(12):1529–54. https://doi.org/10.6004/jnccn.2019.0058
Ouarssani A, Asseban M, Ftouhi M, Rguibi MI. [Hemoptysis revealing an endobronchial metastasis of testicular choriocarcinoma]. Revue des maladies respiratoires. 2013;30(1):81–3. https://doi.org/10.1016/j.rmr.2012.06.013
Papiani G, Einhorn LH. Salvage chemotherapy with high-dose carboplatin plus etoposide and autologous peripheral blood stem cell transplant in male pure choriocarcinoma: a retrospective analysis of 13 cases. Bone marrow transplantation. 2007;40(3):235–7. https://doi.org/10.1038/sj.bmt.1705697

No competing interests reported.

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Easily missed diagnosis of testicular choriocarcinoma with a large retroperitoneal mass as the primary symptom: a case report

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Abstract

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1. Introduction

2. Case Report

3. Discussion

4. Conclusion

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