Genital exam, a missed piece of the puzzle in medical diagnosis, can be lifesaving in men: A lesson from a case of a state of shock due to duodenal metastasis of testicular choriocarcinoma

Here we reported a case of a 17-year-old man with a history of weakness, vertigo, nausea, vomiting and dark stool within the last three months prior to admission. He was taken to the Emergency Room in a state of shock. After resuscitation, vital signs became stable, but due to low hemoglobin (HB = 5 g/dl), to find the source of bleeding, endoscopy was performed and a mass in the duodenum was detected. The pathology report was metastatic germ cell tumor. On genital physical exam (PE) there was a mass in the right testis; thus, the patient underwent radical orchiectomy and choriocarcinoma was diagnosed. The patient then received chemotherapy for six months, and he responded well to the treatment. This case report confirmed that genital PE should be part of a patients visit, even when we cannot find logical relation between clinical presentation and genital PE.


INTRODUCTION
Testicular cancer is one of the most frequently observed solid tumors amongst young males. 1 Metastasis of testicular cancer generally occurs through lymphatic drainage and hematogenous pathways. 1 The most common sites of metastases are the lung, liver, brain, gastrointestinal tract(GI), spleen, and adrenal glands. GI metastasis is seen in 5% of germ cell tumors (GCT)with occult blood or significant blood loss.However, hypovolemic shock as the first presentation of distant metastases has not yet been reported. [1] Here we report a duodenal mass that was founded to be metastatic from choriocarcinoma of the testis in a young man who was brought to the emergency room (ER) in a state of shock. Generally, GCT of the testis are considered quite curable; therefore, a complete physical examination (PE) including a genital examination (GE) is an easy and essential tool for male patients with longstanding complaints, to achieve the correct diagnosis as a timely and important issue.

CASE PRESENTATION
A 17-year-old man was brought in a state of shock to the ER of Namazi hospital affiliated with Shiraz University of Medical Sciences, Iran. Based on his medical history, he had been referred to several different physicianswith a chief complaint of weakness, vertigo, nausea, and vomiting. Three months prior to his admission, he had experienced pallor and frequent episodes of decreased blood pressure. He stated that he had experienced dark stools in recent days, which he thought was related to his diet. He had lost 9.8 kg of weight (14%) in the past three months. His laboratory results showed low hemoglobin (HB ¼ 5 g/dl), and a peripheral blood smear showed severe hypochromic microcytic anemia with anisocytosis, adequate platelets, and a white blood cell count in the normal range, and coagulation tests were normal. Following insertion of a naso-gastric tube (NGT), fresh blood was observed in the NGT, and then four bags of packed red blood cells were transfused. An upper and lower endoscopy was performed. This procedure revealed a large mass in the second part of the duodenum, which had extended to the third part. A biopsy was taken and sent to the pathology laboratory. His HB rose to 8 g/dl the day after the transfusion. A spiral CT scan of the abdomen and pelvis with contrast showed a 105 mm x 66mm x 60 mm,mildly enhanced mass lesion, located caudal to the pancreatic head,which was easily distinguishedand in close contact with the abdominal aorta in a way that angulated it more than 18 degrees and compressing the Inferior vena cava posteriorly. The findings favoreda neoplastic process of the pancreatic head ( Figure 1). The radiologist recommended further evaluation and biopsy. The surgical consultant recommended surgery.
Hematoxylin and eosin sections of endoscopic duodenal mass biopsy showed crowded tumor cells with indistinct cell borders and overlapping nuclei that were arranged in solid and glandular patterns. Most of the nuclei were hyperchromatic and sometimes had smudged chromatin mimicking syncytiotrophoblasts; mitotic figures were detected. Hemorrhagic and necrotic foci were easily detected. Immunohistochemistry (IHC) confirmed the diagnosis of a metastatic germ cell tumor. The IHC profile result revealed positivity forhuman chorionic gonadotropin (HCG),positivity forepithelial membrane antigen (EMA), weak positivity forplacental alkaline phosphatase(PLAP), negativity for C-Kit (cd117), and negativity forleukocyte common antigen ( Figure 2). The scrotal PE revealed a mass measuring4 cm £ 3 cm £ 3 cm in his right testis, which was confirmed by ultrasonography. Tumor markers were also requested. Results showed high HCG equal to 120,000 IU/ml and Alfa fetoprotein (AFP) equal to 7.7ng/ ml; both tumor markers were measured using the "Vidas" immunoassay system made in France. The patient underwent radical orchiectomy. Grossly, the tumor was mainly hemorrhagic and necrotic.Microscopically, there was an admixture of syncytiotrophoblast cells (large, multinucleated cells with large, irregular nuclei) and cytotrophoblast cells (pale cytoplasm with a single large nucleus and prominent nucleolus) and intermediate trophoblasts (larger than cytotrophoblasts) (Figure 3). This histologic picture was in favor of choriocarcinoma, which was confirmed by positivity for EMA and HCG in tumor cells on IHC staining. The patient received four cycle BEP chemotherapy (Bleomycin, Ectoposide, Cisplatin) every three weeks without any complications. He is still alive and well and has been followed-up monthly for the past six months by our team.

DISCUSSION
GI bleeding presents with various manifestations, including hematemesis, melena, and hematochezia, that can cause a positive occult blood test and hemodynamic disorders. The severity of these clinical symptoms, thepresence or absence of underlying diseases, age, gender, drug or alcohol abuse, and complete blood count parameters can assist physicians in the determination of bleeding etiology. 1,2 Gastric and duodenal peptic ulcer, gastritis, erosive diseases, Mallory-Weiss syndromes, GI tract malignancies, esophageal varices, hematological disorders, and other factors should be considered as the proximate causes of GI bleeding. [3] Therefore, primary evaluations should includea complete patient history, PE, and laboratory findings, all of which are crucial in determining the source of bleeding. In 90% of melena cases, the source of the bleeding is the proximal segment. 3,4,5 Routine coagulation tests and a peripheral blood smear are recommended, since they can provide beneficial information in the case of hematological malignancies. 3,6 In this report, the patient was 17 years old with a negative past medical history, negative history of drug or alcohol abuse, and a non-smoker. Furthermore, the patient had noticed a tarry stool once in the last week prior to arriving in a state of shock, but he had ignored it. Weight loss of 9.8 kg in our patient during the past few months was an indication of a serious problem, most likely a malignancy. Considering the patient's age, non-GI malignancies should be ruled out first. In a patient like our case, a study of tumor markers such as serum AFP, HCG, and LDH (lactate dehydrogenase) levelsis recommended, but when the patient was brought to the ER in a state of shock, this study was missed. Duodenal metastasis is seen in 1.4% of GCT 7,8 with the initial presentation of abdominal pain (46%), melena (44%), hematemesis and melena (24%), and, to a lesser extent, low hemoglobin. 9 GI bleeding also is seen after chemotherapy because of chemotherapyinduced tumor cell necrosis. 10 Abdominal pain may be the first clue to GCT recurrence within two years after orchiectomy and chemotherapy. 11,12 The combination of the unusual GI presentation of GCTand the rarity of this tumor make the diagnosis of GCT easy to miss, as in our case. Hence, we recommended GE as an essential part of complete PE, because GCT of the testis are quite curable nowadays. 13 In a survey in 2016, only 21% of 8720 new testis cancer was anticipated. Hence the importance of history taking and a complete PE  including a GE to assist us in obtaining useful differential diagnoses leading to the correct diagnosis. 7 From an ethical and legal point of view, the lack of an accurate physical and laboratory examination can lead to a loss of valuable time,resulting in increased mortality and morbidity as well as increased treatment costs for the patient and insurance companies. Therefore, a thorough genital system examination in the primary stages seems to be crucial in any young male patient. In our patient,the abovementioned examinationwas not only omitted on several clinic visits, but it was also not performedat the time of admission. A tumor marker study was also missed. The pathological diagnosis led us to perform GE, while the reverse route is correct; because we might have missed a golden opportunity. Only one week after admission, a pathological diagnosis of metastatic germ cell tumorof the duodenum was made, and we were remindedof the genital exam. Hence, wehave termed the GE "the missed piece of thepuzzle" in medical diagnosis. We do not know how many patients have diedbecause their physicians missed this piece. Testicular choriocarcinoma is an invasive and rapidly growing rare tumor amongst young men with a dominant metastatic pattern to the lung, liver, and brain 4,5,6 ; however, metastasis to the GI tract has been rarely reported.

CONCLUSION
A GE should be performed in any young man with important or longstanding complaints that cause several clinic referrals or at the time of hospital admission. The sooner we diagnose important genital diseases, the better our chances of initiating treatment during the golden time, and, consequently, the rate of mortality and morbidity as well as the cost of treatment will be reduced significantly.