Mediastinal cystic teratoma misdiagnosed as pleural tuberculosis: A case report and review of 53 cases revealed by pleural effusion

Abstract Mediastinal teratoma (MT) can be misdiagnosed for a long period and revealed by fatal pleural effusion at any age. In high burden tuberculosis settings, it is important to consider MT for extra‐pulmonary tuberculosis not responding to medical treatment.


| INTRODUCTION
Mediastinal cystic teratoma is a rare diagnosis in adolescence from a low-income setting. Pleural effusion can often mislead infections and delay the resection. We report a case from a high burden tuberculosis country and analyze data from the literature. Clinical record of an adolescent patient from the Democratic Republic of Congo reported here and 53 records from other institutions identified via Medline from its inception to November 2017 were analyzed. We described demographic, clinic-pathologic characteristics, and surgery outcomes and follow-up of patients. Of 54 cases, 59% were females (mean (SD) age: 26 (12) years) and mostly from high-income countries. Cough, shortness of breath, fever, and chest pain were mostly reported. Misdiagnosis was common, with periods between the onset of clinical manifestations to accurate diagnosis ranging from 1 week to 2 years. Our case was treated twice as tuberculosis. Duration of hospitalization varied from 4 days to 6 months and septic as well neurologic complications were frequently reported. With a follow-up period ranged from 1 week to 2 years, five percent of patients died after surgery and 26 percent relapsed. The present report expands the spectrum of our knowledge showing the scarcity of reported mediastinal cystic teratoma in low-income countries and that uncontrolled pleural effusion should help evoking the diagnosis.
A teratoma is defined as a type of germ cell tumor that may contain several different types of tissue such as hair, muscle, and bone. 1 It may be immature or mature, based on how normal cells looked under a microscope; sometimes it is a mixture of both. They may occur in different parts depending on the sex (testicles, ovaries) or either in the chest, nervous system, or abdomen. They may be benign or malignant. 1,2 Mediastinal teratomas are the most common extra-gonadal germ cell tumors. They account for approximately 15% of anterior mediastinal masses in adults and 25% in children and 50%-70% of mediastinal tumors. 3,4 They may be symptomatic through different ways either by mass effect, endocrine function impaired or by rupture creating pleural effusion. [3][4][5][6][7][8] The pleural effusion can often lead to a misdiagnosis of respiratory infections especially in low-income settings. We report on case of a cystic teratoma in a 15-year-old girl from a low-income setting treated twice as tuberculosis. We also performed a review on cystic mediastinal teratoma with pleural effusion in the literature. In addition to our patient, we reviewed. Fifty-three records from other institutions identified via Medline from inception to November 2017 that were well documented. Our review focused on analysis of clinical presentations, pathology findings, surgery procedures, and immediate and follow-up outcomes.  Figure 1). Mediastinal teratoma was diagnosed by anatomo-pathologic findings after surgery resection or during medico-legal expertise. The records of 54 patients were used for clinical analysis. We excluded 10 patients from whom clinical details and surgery outcomes were not obtained through our search. From full-text articles, we extracted age of the patient at diagnosis, sex, country, first symptoms developed, type of surgery, anatomo-pathologic findings (mature/immature, benign/malignant, type of tissue found) as reported and patients' outcomes after surgery (death/relapse). The time to diagnosis was calculated from the first onset of respiratory symptoms and the confirmation of diagnosis through histological analysis after surgery resection or autopsy. Chest X-ray and CT examination were the major tools for establishing preoperative diagnosis. Descriptive analysis was essentially conducted for the report of the literature review. Categorical variables were expressed as proportions and continuous variables were expressed by means and standard deviations (±SD

| Patient presentation
A 15-year-old girl was transferred to our hospital with pleural effusion symptomatology along with respiratory distress (RD) which had occurred on multiple occasions. Her respiratory distress could have been relieved only by repetitive pleural tapping as much as 36 times for the last 3 years at the sequence of every 4 weeks before the actual transfer. She came from a rural setting in the East of DR Congo and resided in an informal settlement. Her medical history acknowledged that she was born healthy to nonconsanguineous parents, the sixth of eight healthy children. She apparently started developing the symptoms 3 years prior to the transfer with an increasing shortness of breath (SB) requiring medical assistance and incapacitated her to pursue studies and to accomplish ordinary activities. She had then been twice on 6 months of antituberculosis drugs first line regimen and had completed the treatment 6 months before the transfer. According to the medical report that accompanied the patient, she was treated for extra-pulmonary tuberculosis with negative microscopy in accordance with national recommendations after both smear and pleural fluid were negative for Zielh-Neelsen test and respiratory symptoms did not resolve after nonspecific antibiotic therapy. Of note, culture and GeneXpert testing could not have been conducted in the patient's geographical area nor samples been sent elsewhere due to political instability. On examination, weight was 53.2 kg, blood pressure: 100/70 mm Hg, heart rate: 82/min, and respiratory rate: 22/ min and 36.5°C. Our clinical assessment confirmed a woody note and a silent auscultation on the left thorax. The right thorax presented a normal vesicular breath sound. Hemoglobin was slightly low: 11 g/dL (range: 12-15) and both hepatitis C antibodies and hepatitis B surfaces antigen were nonreactive.
The chest X-ray ( Figure 2A) and the CT-Scan ( Figure 2B) revealed a giant mediastinal mass with a collapsed left lung and consolidation. In brief, there was evidence of a large well defined complex cystic mass lesion involving antero-superior mediastinum and extending to left to occupy the entire left hemithorax. The lesion consists of solid component with fatty elements, calcic foci, and multiple loculated cystic areas F I G U R E 2 Chest X-ray and CT Scan: a 15-y-old girl presenting with a large teratoma expressed by pleural effusion in South Kivu, Democratic Republic of Congo There was partial atelectasis of the entire left lung, more so the lower lobe and seen compressed posteriorly. Mediastinum was shifted to the right side and lying lateral to the midline. However, mediastinal vessels were appeared normal as well as the right lung. No obvious focal lung lesion, septal thickening, or brochectatic changes were seen on the right side. A minimal left pleural reaction was noted.

| Surgical procedure
The surgery by left posterolateral thoracotomy noted a dense adhesion between the mass and the chest walls, pericardium and left lung. The left lower lung lobe was completely deflated and incarcerated by the mass with islands of epithelial tissue, hair, and calcified tissue. A total resection of the mass and decortication of the left lung were then conducted. Anatomopathological findings led to the diagnosis of a mediastinal mature cystic teratoma. The patient was then transferred to the intensive care unit for 3 days and required a prolonged stay in the wards due to the collapsed left lung. The latter required flexible bronchoscopy twice along with prolonged chest tube drained in situ. The chest tube was finally removed 15 days later after few trials of chest tube clamping followed by chest X-ray.

| Patient evolution
No other complication occurred during the intervention. With adequate antibiotics prescribed for 14 days along with planed physiotherapy exercises and diet restrictions, the patient did not present any late complications (infection, respiratory distress) or story of collapsed lung. The patient was then discharged with antalgic that she took for almost 3 weeks. She stays in the city within a benevolent family to avoid exposition to biomass fuel smoking and to reduce risk of pulmonary infections inherent to the rural area. After 5 years of follow-up, our patient did not complain about respiratory symptoms and she is now starting her first year at university.

| Review of 63 cases of mature teratoma with pleural effusion
Fifty-three cases were reported and analyzed from our search findings. 59% were females and mean (±SD) age was 26 (±12) years. Most of them come from high-income countries. Cough, shortness of breath, fever, and chest pain were mostly reported. Most cases were misdiagnosed with time to first clinical symptoms ranged from 1 week to 2 years. Further, our case was first treated twice as tuberculosis (different regimens). About 91% showed an immature aspect while 16% were malignant. Ovarian and pancreatic tissues were mostly retrieved as content. Duration of hospitalization varied from 4 days to 6 months and septic as well neurologic complications were mostly reported. With a follow-up period (of half

| DISCUSSION
To our knowledge, there has no previous review of literature reporting on mediastinal cystic teratoma with pleural effusion. We found that mature teratoma with pleural effusion presented a high proportion in female patients during their young adult life. However, the literature search demonstrates the occurrence of mature teratoma with pleural effusion in patients as young as at 25 weeks of gestation and as old as 51 years. 2, Respiratory symptoms are predominant and not specific which has led often to a delay in the diagnosis for as long as 2 years. 2,[9][10][11]19,20,22,28,30, The majority of studies were reported in high-income countries. The requirement for the diagnosis to be made by CT scan and histopathology might explain the fact that such diagnosis is mostly reported in high-income countries. Tissues found in the tumor appeared mostly immature and of ovarian and pancreatic origin. Except for cases that presented complications, the duration of hospitalization was short with variable lengths of follow-up periods. Complications related to infections and metastases were reported in less than 10 cases. Relapses occurred for some cases and death was a rare outcome and was reported in 10 cases due to respiratory complications essentially. 17,22,24,32 The major strength of our study is the systematic search of literature and the number of cases reported. This will allow a more systematic assessment of the prevalence of the disease and could raise awareness among clinicians from low and middle-income countries. Our results have highlighted a substantial proportion of cases from low-income settings. Ascertainment misclassification following difficulties to diagnose mediastinal cystic teratoma might preside over the wrong impression of its rarity in poor settings. Regarding the high burden of respiratory infection diseases in such a region, clinicians might consider mediastinal tumors after an attempt to treat an infection disease not specified otherwise.
Although a systematic search of literature through Medline, among limitations of our study are the nonsystematic search of ≥3 databases and the exclusion of studies without full texts. Another limitation was related to the nature of the study that reported only on cases thus not representative of the populations from which the cases came from. However, the review has highlighted the need to consider such a differential diagnosis when assessing a patient with signs of pleural effusion especially in early childhood or young adult life.

| CONCLUSION
Not all is about tuberculosis in sub-Saharan Africa. We describe an original report of a giant mature cyst teratoma that required excision with left lung decortication in a young female Congolese after she has been treated twice as having pulmonary tuberculosis. This is the first documented case in the region. Diagnosis is difficult via noninvasive procedure, but clinicians should bear it in mind as a differential diagnosis to avoid delaying surgery.