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Extragonadal Germ Cell Tumors Pdf Download
Germ cell tumors (GCTs) in children are rare neoplasms with diverse pathological findings according to the site and age of presentation. The most common symptoms in children with mediastinal GCTs, which are nonspecific, are dyspnea, chest pain, cough, hemoptysis, vena cava occlusion syndrome, and fatigue/weakness. Because of these nonspecific symptoms, it is difficult to suspect a mediastinal mass. A posterior mediastinal tumor causing spinal cord compression is an important example of an oncologic emergency arising from a neurogenic tumor.
Extragonadal Germ Cell Tumors Pdf Download
Germ cell tumors (GCTs) in children are rare neoplasms with diverse pathological findings according to the site and age of presentation. Pediatric GCTs predominantly occur in the midline of the trunk: in the intracranium, mediastinum, gonads, and sacrococcygeum. Histologic subtypes of mediastinal GCTs in children include mature teratoma, 60%; mixed GCTs, 20%; and embryonal carcinoma, 20% (including seminoma/germinoma, immature teratoma, yolk sac tumor, and choriocarcinoma). About 5% of all extragonadal germ cell tumors originate from the mediastinum in children younger than 15 years [1, 2].
Steroid administration after direct decompression surgery aims to prevent secondary injury caused by posttraumatic spinal ischemia, and to improve neurologic function and spinal cord blood flow [8]. The key mechanism in the theory of secondary injury is posttraumatic ischemia in the spinal cord with resultant infarction followed by alterations in microvascular perfusion, inflammation, lipid peroxidation, free radical generation, apoptotic/necrotic cell death, and dysregulation of ionic homeostasis [9]. Based on this theory of secondary injury after direct decompression surgery, the patient received steroid pulse therapy and maintenance therapy at a physiologic dose. In a previous report, preoperative spinal angiography in pediatric inferior posterior mediastinal tumors was used to prevent secondary spinal cord ischemia due to guiding surgical resection [10].
The most common presentation of Klinefelter syndrome (KS) is infertility and features of hypogonadism. Currently no consensus exists on the risk of malignancy in this syndrome. Several case reports show an incidence of extragonadal germ cells tumors (eGCT) of 1.5 per 1000 KS patients (OR 50 against healthy population). Malignant germ cell tumors are rare in children. They account for 3% of all children cancers. Young patients with a germ cell tumor are not routinely tested for Klinefelter syndrome. This can therefore result in underdiagnosing. Literature data suggest a correlation between eGCT and KS. To the best of our knowledge there is no precise description of the primary locations of germ cell tumors in KS patients. The purpose of this study is to evaluate age groups and primary locations of extragonadal germ cell tumors in Klinefelter patients. With this data we investigate whether it is necessary to perform a cytogenetic analysis for KS in every eGCT patient.
These data suggest a correlation between primary extragonadal germ cell tumors and Klinefelter syndrome. There appears to be an indication for screening on KS in young patients with an eGCT in the mediastinum. A low threshold for radiologic examinations should be considered to discover eGCT. We emphasize the need for genetic analysis in all cases of a male with a mediastinal germ cell tumor for the underdiagnosed Klinefelter syndrome.
Our data suggest there is a strong correlation between primary germ cell tumors and Klinefelter syndrome. A higher prevalence of germ cell tumors in KS patients is seen in the mediastinum of young adults. We recommend that there is an indication to perform genetic analysis to confirm Klinefelter syndrome in young patients with an extragonadal germ cell tumor in the mediastinum.
Screening every patient with Klinefelter syndrome for early detection of germ cell tumors can be deliberated. Patients with Klinefelter syndrome should be closely monitored and provided with adequate information on the risk of malignancy.
Hematologic malignancies arising in the setting of established germ cell tumors have been previously described and have a dismal prognosis. Identification of targetable mutations and pathway dysregulation through massively parallel sequencing and functional assays provides new approaches to disease management.
Written informed consent was obtained from the patient to participate in a trial which would allow collection and sequencing of his leukemic blasts for sequencing and testing against a panel of small molecule inhibitors. In addition, he consented to sequencing of his normal tissue and his germ cell tumor. The patient is deceased and had no next of kin or legal guardian, so consent for publication of this case report and any accompanying images was not obtained. This lack of support contributed to his inability to proceed to allogeneic stem cell transplant.
Yolk sac tumor (YST) is a germ cell tumor. It is primarily located in the gonads but can also occur extragonadally (extragonadal yolk sac tumor - EGYST), most commonly in the pelvis, retroperitoneum or mediastinum. Only a few YSTs of the urachus have been described.
A Superficial areas of the resected tumor showed urothelial carcinoma with papillary morphology. B Different parts of similar tumors are shown, including solid and adenoid areas with clear cells and hyaline globules (stars). C Carcinoma nests were found among smooth muscle fascicles of the bladder wall. D There were glandular formations within the tumor. E There were clear cells and hyaline globules. Immunostaining: (F) Glypican-3 was present in tumor cells. G Keratins AE1/AE3 were present in tumor cells. H SALL4 was present in tumor cell nuclei. I AFP was present in tumor cells. J CDX2 was present in tumor cell nuclei
YST differentiation of somatic tumors is relatively rare, and reported cases of YST differentiation of urothelial tumors are even less common [6, 16, 17]. Histologically, tumors can contain both YST and somatic tumor structures. The YST component corresponds to the germ cell tumor, and it is not uncommon for the YST component to grow larger than the somatic tumor component due to its higher proliferative activity [18]. Somatic malignancies with YST differentiation are characterized by the presence of different patterns, the most typical being the glandular pattern [1]. In our case, solid and papillary patterns were the main patterns found in the biopsy. The glandular pattern that is usually described as typical for YST differentiation was observed only focally (Fig. 2). There are available data on AFP-producing urothelial tumors [19,20,21]. Most of these tumors present hepatoid tissue areas in the context of adenocarcinoma or urothelial carcinoma and show AFP positivity. In our case, no area with a hepatoid pattern similar to that in the YST were observed. Samaratunga et al. published a case report of urothelial carcinoma of the renal pelvis with focal hepatoid adenocarcinoma differentiation, and the tumor showed strong AFP immunoreactivity and serum AFP positivity [16]. There are also documented cases of bladder adenocarcinomas that have shown both immunoreactivity for AFP and elevated serum AFP levels [16]. Recently, a case of urothelial tumor with YST differentiation was presented by Espejo-Herrera et al. The patient was a 76-year-old male with a history of recurrent urothelial carcinoma of the bladder [17].
In addition to the abovementioned microscopic features, immunohistochemical methods are essential for accurate diagnosis. Extragonadal tumors usually show the same immunoreactivity as their gonadal counterparts [11]. AFP and GPC3 are characteristic immunohistochemical markers of YST, which may correlate with their serum levels [1, 22]. Some stem and pluripotent cell antigens (SALL4, Lin28 or IMP3) may also be helpful in diagnosis.
AFP remains the standard marker for YST, even though it can also be produced by several non-germ cell tumors, especially those of the female genital tract, and tumors of endodermal origin with a frequent hepatoid component [1]. AFP staining shows strong granular cytoplasmic positivity, and AFP may also be expressed in hyaline globules, although this is not always present [1]. Determination of serum AFP is useful in the diagnosis and follow-up of patients with YST or EGYST.
Genetic alterations are common in germ cell tumors, including isochromosome 12p, p53 alteration, and other changes [27, 28]. We did not find a gain of 12p when we tested for numerical changes in the 12p region by FISH. Extragonadal germ cell tumors do not appear to share a common genetic basis with their gonadal counterparts.
Prognostically, extragonadal forms of germ cell tumors are significantly worse than those in the gonads [29]. Tumors with a YST component are diagnosed at a younger age and may be more likely to be pure EGYSTs [6]. The determination of whether a tumor is EGYST or a somatic tumor with YST differentiation also has a major impact on therapy. While most gonadal YSTs respond relatively well to chemotherapy, a benefit of chemotherapy for EGYST is more likely to be seen in younger patients. The benefit of chemotherapy for somatic tumors with YST differentiation is unclear [6]. In the case of advanced or metastatic germ cell cancer, cisplatin-based chemotherapy is the mainstay. Five-year survival rates range from 40 to 90%, with a more favorable prognosis for seminomas or retroperitoneal tumors than for nonseminomas or mediastinal tumors [29].
Thymic carcinomas are rare but highly aggressive, early-metastasizing cancers derived from thymic epithelial cells. They are also the most common cancers of the anterior mediastinum, comprising (collectively with thymomas) about 20% of all mediastinal cancers and 10% of all thymic tumors.[5] They can be further differentiated into squamous cell carcinoma, basaloid carcinoma, mucoepidermoid carcinoma, lymphoepithelial-like carcinoma, sarcomatoid carcinoma, clear-cell carcinoma, adenocarcinoma, NUT (nuclear protein of testis) carcinoma, and undifferentiated carcinoma.[5] Like thymomas, thymic carcinomas occur in the 40 to 60 age range.[6] Thymic carcinomas have a fibrous stroma comixed with areas of necrosis, cystic changes, and calcifications. An initial diagnostic approach involves an evaluation by an MRI or CT though the former is sometimes favored. These scans will delineate the extent of the disease, its invasiveness, and hence its potential for complete resection. PET scanning has a less clear role as false-positive results occur in non-cancerous entities such as fibrosing mediastinitis, thymic hyperplasia, and infections.[7] Thymomas, being well-differentiated, tend to be PET negative, while thymic carcinomas are positive. Mediastinal thymic carcinoma is notably PET-positive; its presence portends a poorer prognosis.