Teratomatous Elements Research Articles

Mediastinal Teratoma with Angiosarcomatous Overgrowth in a Background of Vasculogenic Mesenchymal Tumor

Abstract Introduction/Objective Vasculogenic mesenchymal tumor refers to neoplastic reiteration of embryonic vasculogenesis. It is most commonly associated with nonseminomatous germ cell tumors of the mediastinum, in particular yolk sac tumor. In rare instances these lesions progress to angiosarcoma. Herein, we describe a case of angiosarcoma in a background of vasculogenic mesenchymal tumor in the setting of a mediastinal teratoma. Methods/Case Report A 33-year-old male, with a past medical history of anxiety, and right orchiectomy for testicular torsion, presented with shortness of breath, chest pain, and left arm swelling. Imaging studies demonstrated a mediastinal mass. Biopsy of the mass showed a germ cell tumor most compatible with a teratoma in the limited specimen. The patient received two rounds of chemotherapy and additional treatments were discontinued due to poor tolerance. Subsequent imaging showed continued increase in the size along with mass effect causing moderate to severe compression of the superior vena cava. Subsequently, the patient underwent resection of the mass. Grossly the mass was predominantly encapsulated with areas of capsular disruption. Sectioning revealed heterogeneous cut surfaces with fleshy, cystic, and necrotic areas. Morphologically the tumor was composed predominantly of teratomatous elements with areas of anastomosing atypical vascular channels within a hypocellular stroma suggestive of vascular genic mesenchymal as well as areas reminiscent of Masson lesion. Focally within these areas were malignant spindle cell proliferations compatible with angiosarcoma. The patient had an elevated AFP; however, no yolk sac tumor component was identified after thorough sampling. Final diagnosis of teratoma with angiosarcoma in a background of vasculogenic mesenchymal tumor was rendered after expert consultation. Results (if a Case Study enter NA) NA Conclusion Somatic-type malignancy and sarcomatous overgrowth are known to occur in mediastinal germ cell tumors; however, classification of the sarcomatous overgrowth can be challenging. Vasculogenic mesenchymal tumor is an exceedingly rare sarcomatous overgrowth that can rarely progress to angiosarcoma.

Discordance of retroperitoneal and thoracic histologic findings in patients with metastatic germ cell tumors at postchemotherapy residual tumor resection

Introduction and objectivesPostchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery.Patients and methodsFrom a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy.ResultsAll patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%.ConclusionThe data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen.

Molecular characterization of growing teratoma syndrome in patients with testicular germ cell tumor.

e17017 Background: Teratomas are unique neoplastic growths that encompass a diverse array of tissue types derived from multiple germ layers, often exhibiting varying degrees of differentiation. Among the phenomena associated with teratomas, the growing teratoma syndrome (GTS) stands out as a rare yet clinically significant occurrence. GTS, characterized by the persistence or regrowth of teratomatous elements despite initial treatment, poses challenges for both diagnosis and management. In this abstract, we present the results of our expression array analysis of teratomas, aiming to uncover novel insights into their molecular composition, heterogeneity, and potential implications for clinical management. Methods: This study included 53 patients with retroperitoneal teratoma (7 chemotherapy naïve and 46 with postchemotherapy teratoma) and 20 patients with viable postchemotherapy germ cell tumor from retroperitoneum that had surgery at National Cancer Institute in Slovakia and for whom formalin-fixed paraffin-embedded (FFPE) tumor tissue was available. Study also includes samples from 5 patients with normal testis as control group. Ten patients (18.9%) in this cohort had growing teratoma syndrome. Analysis was performed by HTG EdgeSeq Oncology Biomarker panel (HTG Molecular Diagnostics, Inc., Tucson, USA). Identified candidate genes associated with GTS were further validated by immunohistochemistry on FFPE. Results: Molecular profiling indicates no differences in expression profile in retroperitoneal teratomas regardless of previous chemotherapy. Expression analysis indicates 1586 genes being differently expressed with high significance ( p < 0.05) in teratomas compared to normal testis and 1571 genes differentially expressed compared postchemotherapy viable tumors. We identified 14 genes being differently expressed in growing teratoma syndrome compared to teratoma without growth (CYP4A22, IGFBP1, CXCL6, LTF, CYP2C8, CFTR, CCL20, PFKFB3, SLC2A3, LIPA, HMOX1, GPNMB, CCL18, DLK1. Pathway analysis revealed MAPK and PI3K−Akt signaling pathways are mostly dysregulated in GTS. Conclusions: This molecular profiling identify genes differentially expressed in teratomas that are potential biomarkers for prediction of teratoma element in postchemotherapy residues in testicular germ cell tumor patients. Moreover, inhibition of identified signaling pathways associated with GTS could represent potentially novel therapeutic targets in case of unresectable disease.

Relapse-free and overall survival in patients with non-seminomatous testicular germ cell tumours with teratoma-free primaries.

421 Background: Characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate. Methods: We performed a retrospective analysis including 557 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". Results: Of the eligible 557 patients with NSGCT, 237 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 320 (58%) were teratoma-free. Teratoma-containing primaries had a significantly higher clinical stage (p=0.002) and worse prognosis (p=0.051) compared to teratoma-free specimens. Lymph node metastasis were significantly larger before (4.5 vs 2.5cm; p<0.001) and after chemotherapy (3.5 vs 2.5 cm; p<0.001) in teratoma-containing primaries. Post-chemotherapy retroperitoneal lymph node dissection was performed in 57% of all patients. As teratoma-containing specimens revealed a significantly lower number of complete responses after chemotherapy, PC-PRLND was more often performed, with teratomatous elements being more often present in the PC-RPLND specimens compared to non-teratoma containing primaries. Kaplan-Meier estimates revealed that 19% of all patients relapsed during a median follow-up of 56 months [29-112] with a median time to relapse of 10 months. Teratoma-containing had a significantly lower relapse-free survival (RFS) compared to teratoma-free NSGCT (relapse rate 24% vs 16%, p=0.020). 8% (45/533) of all patients died due to their disease. There was no difference regarding the tumour-specific survival between teratoma-containing NSGCT and teratoma-free NSGCT when looking at the entire cohort of patients (8% vs. 9%, p=0.563), however median overall survival was not reached. Conclusions: In our study, NSGCT patients with teratoma-containing primaries showed a significantly higher clinical stage and worse prognosis at time of presentation compared to teratoma-free primaries. Furthermore, patients with teratoma-containing primaries showed a significantly worse relapse-free survival. Consequently, treating physicians should be aware of these patients portending a dismal prognosis and the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

Management of Residual Nonretroperitoneal Disease in Postchemotherapy Nonseminomatous Germ-Cell Tumors.

The majority of patients with advanced nonseminomatous germ-cell tumor are cured with combination chemotherapy and surgical resection of residual disease when appropriate. In patients with both retroperitoneal (RP) and non-RP postchemotherapy residual disease, management of the non-RP disease is typically guided by pathologic findings at the time of RP resection. There are limited data to help guide management decisions in patients with non-RP postchemotherapy residual disease alone. The prospectively maintained Indiana University testicular cancer database was queried for patients with metastatic nonseminomatous germ-cell tumor treated between 1990 and 2021 who had residual non-RP disease in the absence of residual RP disease after completing either first-line or salvage chemotherapy. One hundred twenty-nine patients met eligibility and were included in this analysis. Seventy-five patients had teratoma in the primary tumor site, while 54 did not. Of those with teratoma in the primary, 55% had at least one postchemotherapy non-RP surgical specimen with teratomatous elements compared with 17% of those without teratoma in the primary (P < .001). Of those without teratoma in the primary site, 56% had at least one postchemotherapy non-RP surgical specimen with active germ-cell tumor compared with 31% of those with teratoma in the primary (P = .0046). The presence of teratoma in the primary tumor site is associated with a higher rate of teratoma in postchemotherapy residual non-RP disease. Patients without teratoma in the primary tumor should still be considered for resection of residual postchemotherapy disease that could harbor teratoma or active germ-cell tumor.

Sarcomatoid (Spindle Cell) Carcinoma Arising in Mature Cystic Teratoma as a Mural Nodule: A Case Report

Mature cystic teratomas are the most common ovarian germ cell tumours.Malignant transformation is rare in mature cystic teratoma. Spindle cell/sarcomatoid carcinoma is an uncommon type of squamous cell carcinoma. A 45-year- old female presented with abdominal distention and discomfort. Magnetic Resonance Imaging (MRI) showed multiloculated cystic mass measuring 21×20×14 cm with heterogeneously enhancing solid component measuring 5x3.5 cm in right adnexal region. Excision of the mass done. Macroscopic examination showed irregular cystic mass containing pultaceous material and hair, and a mural nodule measuring 5x5 cm. On histopathological examination, the cyst wall showed mature teratomatous elements. Sections from mural nodule showed sheets of atypical spindle cells with increased mitosis and foci of necrosis. On immunohistochemical examination, the spindle cells showed patchy weak to moderate positivity for cytokeratin, 34 beta E12, CK5/6 and P40. Diagnosis of spindle cell/sarcomatoid carcinoma arising in mature cystic teratoma was given. Malignant transformation in mature cystic teratoma is rare and should be suspected in large sized tumours in older patients. Sarcomatoid carcinoma is an extremely rare form of secondary malignant neoplasm arising from mature cystic teratoma.

Cytologic features of gynecologic germ cell tumors and carcinomas exhibiting germ cell tumor differentiation.

In this study, the authors sought to describe the cytologic features of primary gynecologic germ cell tumors and carcinomas exhibiting germ cell differentiation because little information currently exists. An institutional database search was performed to identify histologically confirmed gynecologic germ cell tumors and carcinomas with germ cell tumor differentiation. Available cytologic material was reviewed by three observers, and morphologic features were recorded in addition to patient age at original diagnosis, primary tumor site, site(s) from which the examined cytologic material was obtained, and the type of examined cytologic preparations. In total, 15 cytologic specimens from 12 women (aged 19-82years) were identified and included touch preparations of core biopsies from various sites (n=6), fine-needle biopsies (n=2), pelvic washings (n=1), ascitic fluids (n=4), pelvic cyst fluid (n=1), and endometrial aspirate (n=1). Of the 12 patients, seven had primary gynecologic germ cell tumors, four had gynecologic (ovarian and endometrial) tumors exhibiting somatic yolk sac tumor-like differentiation, and the remaining patient had an intestinal-type adenocarcinoma arising within an ovarian teratoma. There was morphologic overlap among many of the cases, although cytoplasmic vacuolation/granular cytoplasm was seen in 75% of primary yolk sac tumors or carcinomas with yolk sac tumor differentiation, and dense/squamoid cytoplasm was seen in 100% of teratomatous elements that were sampled. Germ cell tumors and somatic neoplasms exhibiting germ cell tumor differentiation occurring in adult women share some cytologic features and may be difficult to distinguish from one another, although some tumor types showed characteristic cytomorphologic findings.

Morphologic Changes in the Thymus Following Chemotherapy for Anterior Mediastinal Germ Cell Tumors: A Study of 91 Cases Emphasizing Pseudoneoplastic Features.

The interpretation of postchemotherapy resections of anterior mediastinal germ cell tumors plays a critical role in determining future patient management and prognosis. Treatment-related changes in the thymus may mimic residual teratoma or microcystic-pattern yolk sac tumor. There is limited extant information concerning therapy-related pseudoneoplastic thymic alterations. To provide diagnostic assistance to distinguish nonneoplastic thymic abnormalities secondary to chemotherapy from residual germ cell tumor. We retrospectively reviewed 91 resections of primary anterior mediastinal germ cell tumors with recognizable thymic gland following cisplatin-based chemotherapy. The cohort included 90 men and 1 woman (median age, 29 years). A spectrum of thymic epithelial alterations occurred, including cystic change (macrocysts [n = 21] or microcysts [n = 20]); hyperplasia with reactive atypia (n = 8); ciliated, mucinous, or columnar cell metaplasia (n = 3); and mature squamous metaplasia (n = 2). These changes were similar to so-called acquired multilocular thymic cysts, were often contiguous with and adjacent to normal thymic epithelium, and lacked the neoplastic-type atypia seen in teratomatous elements in this setting. In 1 case, confluent microcysts closely mimicked the appearance of yolk sac tumor but lacked other distinctive features of that neoplasm and its characteristic immunoreactivity. Recognition of therapy-induced thymic changes is important to avoid misinterpretation as residual teratoma or yolk sac tumor. Continuity with and proximity to benign thymic epithelium, absence of neoplastic-type atypia, and awareness of this phenomenon are important in avoiding this pitfall.

Management of residual nonretroperitoneal disease in nonseminomatous germ-cell tumors (NSGCT).

5034 Background: The management of NSGCT patients (pts) with post-chemotherapy residual non-retroperitoneal disease (RP) remains unsettled. Decisions for surveillance vs surgical resection are commonly steered by pathology from retroperitoneal lymph node dissection (RPLND). Data is limited in pts who do not require RPLND (normal or normalized RP post-chemo). Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT who completed first-line chemotherapy and had residual extra-RP disease without residual RP disease. Pts with post-chemo non-RP surgical resection were included. Results: 134 pts met eligibility. Median age at diagnosis was 28.6 (range, 16.2-51.5). Primary tumor predominant histology was embryonal (35.1%), mixed (25.4%), seminoma (2.2%), yolk sac (9.7%), choriocarcinoma (15.7%), teratoma (11.2%). 76 pts (56.7%) had teratoma in the primary tumor. Metastatic sites at diagnosis were RP (15.7%), mediastinal LN (8.2%), lung (28.4%), liver (11.2%), bone (6.7%), brain (21.6%). Those with RP mets at diagnosis had normalization of RP nodes after chemo. IGCCCG risk was good in 57, intermediate in 21, and poor in 56 pts. Median pre-chemo AFP was 66 (0.9-467,000). hCG was 960.5 (0.5-1,300,000). First-line chemo was BEPX4 in 68, BEPx3 in 29, EPX4 in 10, VIPX4 in 9, and other in 18 pts. All pts had surgical resection of non-RP disease. None had RPLND. 84 pts had lung nodule resection, 16 had mediastinal LN, 8 had cervical LN, 5 had liver, 6 had bone, and 20 had brain met resection. Of the 76 pts with teratomatous elements in the orchiectomy, 41 (53.9%) had teratoma and 24 (31.6%) had non-teratoma GCT in post-chemo non-RP surgical specimens. Of the 58 pts without teratoma in the orchiectomy, 9 (15.5%) had teratoma and 34 (58.6%) had non-teratoma GCT in the non-RP surgical resection specimens. Teratoma in the orchiectomy was a predictor of non-RP teratoma (Fisher’s exact test P&lt;0.0001). Conclusions: The presence of teratoma in orchiectomy predicts teratoma in residual post-chemo non-RP disease in pts who do not undergo RPLND. The absence of teratoma in orchiectomy should not preclude resection of residual non-RP disease given a subset of patients had persistent GCT. [Table: see text]

Structure of residual metastases in patients with advanced testicular non-seminomatous germ cell tumors and incomplete serological and radiological response to chemotherapy

Objective: to analyze histological structure and identify predictors of detecting malignant non-seminoma in residual tumor masses obtained from patients with testicular non-seminomatous germ cell tumors (TNSGCTs) who had not achieved complete serological and radiological response to chemotherapy (CT).Materials and methods. This study included 96 out of 703 patients with TNSGCTs (13.7 %) operated on in N.N. Blokhin National Medical Research Center of Oncology. The inclusion criteria were as follows: verified advanced TNSGCT, elevated levels of alpha-fetoprotein and/or chorionic gonadotropin at the moment of CT initiation, at least 3 completed courses of first-line or second-line platinum-based CT, residual tumor foci after CT visualized with radiological methods, alpha-fetoprotein &gt;7.29 IU/mL or chorionic gonadotropin &gt;5 mIU/mL 3 weeks after the initiation of the last CT course, and surgery after CT. Histological examination of the primary tumors demonstrated that they contained elements of seminoma (n = 14; 14.6 %), teratoma (n = 29; 30.2 %), choriocarcinoma in (n = 23; 23.9 %), embryonal carcinoma (n = 45; 46.9 %), and yolk sac (n = 18; 18.8 %). All study participants received first-line CT; 58 of them (60.4 %) also received second-line CT. All patients underwent surgery after CT, including retroperitoneal lymph node dissection (RPLND) (n = 96; 100 %) and excision of extra-retroperitoneal lesions (n = 8; 8.3 %).Results. Histological examination of excised retroperitoneal masses showed that they contained areas of necrosis and fibrosis (n = 25; 26.0 %), teratoma (n = 29; 30.2 %), and viable malignant non-seminoma (n = 42; 43.8 %). There was a strong positive correlation between the existence of residual malignant non-seminomatous components in retroperitoneal masses and presence of choriocarcinoma (r = 0.300; р = 0.004), as well as the absence of embryonal carcinoma in the primary tumor (r = –0.300; р = 0.004), invasion of retroperitoneal metastases into major vessels and/or adjacent organs (r = 0.243; р = 0.017), and second-line CT prior to RPLND (r = 0.413; р &lt;0.0001). Patients having ≥3 risk factors were significantly more likely to have residual malignant non-seminoma in retroperitoneal masses than patients who had 0–2 risk factors (73.5 % vs 27.3 %; р &lt;0.0001). Excised residual extra-retroperitoneal masses contained areas of necrosis and fibrosis (n = 3; 37.5 %), teratoma (n = 1; 12.5 %), and malignant non-seminoma (n = 4; 62.5 %). Concordant structure of retroperitoneal and extra-retroperitoneal lesions was observed in 4 patients (50.0 %).Conclusion. Malignant non-seminomas were detected in 43.8 % of retroperitoneal and 62.5 % of extra-retroperitoneal residual tumorsremoved after CT in patients with advanced TNSGCTs and incomplete serological and radiological response. Discordant structure of metastases at different locations was observed in 50 % of patients. Our finding can be used to select candidates for surgical excision of residual tumors among these patients.

Sinonasal teratocarcinosarcoma: a case report

&lt;p class="abstract"&gt;Sinonasal teratocarcinosarcoma (TCS) is a very rare malignant neoplasm of sinonasal tract with intermixed teratomatous, carcinomatous and sarcomatous elements. While the diagnosis is largely based on tissue analysis and immunohistochemistry, the mode of management demands further study. Surgical resection with or without chemotherapy and radiation therapy is currently the most accepted treatment regimen. Locally aggressive, while also associated with metastatic lesions, SNTCS is not easily resectable owing to its location and possible intracranial extension. Due to its aggressive nature over one-third of TCS tend to recur leading to treatment failure with a mean survival time of 1.9 years. Possible differentials include squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma, malignant mixed tumor of salivary gland type, undifferentiated carcinoma, malignant craniopharyngioma, mucoepidermoid carcinoma, transitional carcinoma of Schneiderian type and adenosquamous carcinoma. In this report, we present a case of TCS in a 55 years old male patient who presented to us with complaints of hyposmia, blurring of vision, diplopia and epiphora.&lt;/p&gt;

A SHEEP IN WOLF'S CLOTHING: BENIGN TERATOMA MASQUERADING AS MALIGNANT THYMOMA

TOPIC: Disorders of the Mediastinum TYPE: Medical Student/Resident Case Reports INTRODUCTION: Metastatic parietal pleural implants can be seen in patients with thymoma. Benign teratomas are not associated with parietal pleural implants. We describe resection of a benign teratoma, appearing as a locally advanced thymoma with parietal pleural implants. CASE PRESENTATION: A 37-year-old healthy female was found to have an incidental large pericardial mass on screening breast MRI. A CT Chest showed a 9.4 cm well-defined hypoattenuating calcified cystic lesion with mass effect on the right atrium (Figure 1). Her preliminary diagnosis was thymoma. In the operating room, thoracoscopy demonstrated a large mass with involvement of the pulmonary parenchyma, pericardium, parietal pleural implants, and visceral pleural implants. (Figure 2A, B, C). Robotic en bloc resection was performed. The mass was mobilized with the resection of portions of the upper and middle lobes, pericardium and away from the remaining thoracic structures including the phrenic nerves (Figure 2C, D). Intra-operative frozen section of the mass revealed benign teratoma. Frozen section of the parietal pleural implants revealed fibrosis with teratomatous elements on final pathology (Figure 3). A single chest drain was placed. The patient did well postoperatively and was discharged on postoperative day four. DISCUSSION: To our knowledge, this is the first report of a benign mature teratoma masquerading as a metastatic thymoma. Approximately half of all mediastinal masses in adults are in the anterior mediastinum. The most common mediastinal tumor in adults is thymoma. Thymoma, although considered a low-grade neoplasm, has a propensity for locally invasiveness and recurrence. For these reasons, all thymomas should be approached as aggressive(1). In contrast, benign mature teratomas are well-circumscribed and indolent. Although there is potential for malignant transformation, complete resection results in cure(2). The current recommendation for diagnosis of anterior mediastinal mass is up front resection unless neoadjuvant or medical therapy is being pursued as treatment(1). Preoperative imaging, while helpful, cannot reliably delineate between thymoma and teratoma(3). The higher incidence of thymoma in adults makes the preoperative diagnosis of thymoma more likely. CONCLUSIONS: This case highlights the importance of performing an R0 resection given the known aggressiveness of thymomas as well as highlighting that things are not always as they seem. REFERENCE #1: Detterbeck FC ed. Pathology of the Mediastinum. New York: Cambridge University Press, 2014 REFERENCE #2: Lewis BD, Hurt RD, Payne WS et al Benign Teratomas of the Mediastinum J Thorac Cardiovasc Surg 1983; 86 (5): 727-731. REFERENCE #3: Tomiyana N, Honda O, Tsubamoto M et al Anterior Mediastinal Tumors: Diagnostic Accuracy of CT and MRI. Eur J Radiol. 2009; 69 (2): 280-288. DISCLOSURES: No relevant relationships by Mia DeBarros, source=Web Response No relevant relationships by Grant Fischer, source=Web Response No relevant relationships by M. Blair Marshall, source=Web Response No relevant relationships by Sue Wang, source=Web Response

Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

Introduction: The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. Methods: We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. Results: Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, p = 0.031), visceral metastases (58 vs. 32%, p = 0.015), and poor prognosis (p = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, p = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, p = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (p = 0.049) during a median follow-up of 36 months (10–115.5). Conclusions: The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

GCT-70. INTRACRANIAL GROWING TERATOMA SYNDROME IN CHILDREN

Germ cell tumors account for less than 5% of all intracranial malignancies in children. Intracranial growing teratoma syndrome (GTS) is a rare pathophysiologic process characterized by growth of mature teratoma elements of a non-germinomatous germ cell tumor (NGGCT) during or following treatment with chemotherapy, in addition to normalization of or declining AFP/βHCG of the cerebral spinal fluid (CSF)/serum. A 13-year-old male presented with headache, emesis, and diplopia. MRI of the brain/spine revealed a localized 3.1 x 3.1 x 3.2 cm pineal tumor. Biopsy confirmed NGGCT (germinoma, immature and mature teratoma). Serum AFP (227ng/ul) and βHCG (12 IU/L) and CSF AFP (21ng/ul) and βHCG (31 IU/L) were elevated. Prior to cycle two of chemotherapy, he developed unstable gait and moderate hearing loss. Repeat MRI brain demonstrated tumor enlargement (4.4 x 5.2 x 5.1 cm) and obstructive hydrocephalus, although serum AFP/βHCG had normalized. Gross total resection of tumor confirmed GTS, without residual immature/malignant elements. Following six cycles of multiagent chemotherapy (carboplatin, etoposide, ifosfamide) and proton beam craniospinal irradiation (36 Gy with 18 Gy boost), he remains free of disease at eleven months since diagnosis. The pathogenesis of GTS remains unclear. Care must be taken to avoid misdiagnosing GTS as progressive NGGCT, as treatment and prognosis differ significantly. Second-look surgery, with a goal of complete resection, should be considered in cases of NGGCT when residual tumor grows during or following therapy, as this may represent GTS. Although histologically benign, GTS can be fatal. In patients with GTS, complete resection is usually curative.

Pineal teratoma with nephroblastic component in a newborn male: Case report and review of the literature

Neonatal germ cell tumors are rare and comprise both benign and malignant neoplasms. Teratoma with nephroblastoma is a malignant subset defined pathologically by the presence of nephroblastoma and teratoma elements. Although teratoma with nephroblastoma is most often found in the kidney, 24 of 59 reported cases are associated with extrarenal locations, such as the mediastinum or retroperitoneum. To our knowledge, this is the first patient in the literature with intracranial/pineal teratoma with nephroblastoma, which was managed with staged transcranial approaches resulting in gross total resection and no adjuvant therapy (surveillance observation imaging). We further augmented the patient’s management by comprehensive genomic profiling of the tumor to better understand the molecular biology and explore options for targeted therapy.

PT374 - Teratomatous elements in orchiectomy specimens are associated with a reduced relapse-free survival in metastasized testicular germ cell tumors

PT374 - Teratomatous elements in orchiectomy specimens are associated with a reduced relapse-free survival in metastasized testicular germ cell tumors

Recurrent Loss of SMARCA4 in Sinonasal Teratocarcinosarcoma.

Molecular analysis has reshaped the landscape of high grade sinonasal tumors by defining novel entities and identifying recurrent mutations in established tumor types. However, sinonasal teratocarcinosarcoma (TCS), a rare and aggressive tumor with intermixed teratomatous, carcinomatous, and sarcomatous elements, remains poorly understood. The multiphenotypic differentiation of TCS has engendered persistent controversy about its histogenesis and leads to diagnostic overlap with several other malignancies. In this study, we evaluated the molecular underpinnings of TCS to clarify its pathogenesis and diagnosis. We performed SMARCA4 immunohistochemistry (IHC) on 22 TCS and 153 other sinonasal tumors. We identified loss of SMARCA4 expression in 18 TCS (82%), including 15 (68%) with complete loss and 3 (14%) with partial loss. Although we also identified partial SMARCA4 loss in 1 of 8 SMARCB1-deficient sinonasal carcinomas (13%), SMARCA4 was intact in all other sinonasal carcinomas and neuroendocrine tumors. We then selected 3 TCS with complete SMARCA4 loss by IHC for a targeted next-generation sequencing panel that included 1425 cancer-related genes. We confirmed biallelic somatic inactivation of SMARCA4 without other known oncogenic mutations in these 3 cases. Overall, these findings suggest that SMARCA4 inactivation may be the dominant genetic event in TCS, expanding understanding of this gene's role in sinonasal tumorigenesis. They also raise the possibility that TCS is on a diagnostic spectrum with the newly described SMARCA4-deficient sinonasal carcinoma, blurring the lines between established and emerging sinonasal entities. In addition, SMARCA4 IHC may provide a useful adjunct for confirming a diagnosis of TCS in limited material.

Impact of Teratoma on the Cumulative Incidence of Disease-Related Death in Patients With Advanced Germ Cell Tumors.

In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT. Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed. Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status (P < .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status (P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01). The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.

An Unusual Transformation of a Nonseminomatous Germ Cell Tumor to Adenocarcinoma

Transformation of germ cell tumor to an alternate malignancy is rare; and it is believed to be secondary to teratomatous elements of the initial tumor surviving chemotherapy and subsequently proliferating. Here, we describe a patient with transformation of a nonseminomatous germ cell tumor to adenocarcinoma. A 55-year-old male with history of nonseminomatous germ cell tumor of the left testicle, previously resected, followed by four cycles of BEP chemotherapy, on active surveillance, presented nearly 20 years later with nausea and rising alpha-fetoprotein levels. Computed tomography (CT) abdomen revealed bulky retrocrural lymphadenopathy with increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan. Biopsy revealed metastatic adenocarcinoma, staining strongly positive for SALL4 and CDX2, with focal rare positivity for CK20 in the tumor cells, consistent with germ cell origin. FOLFOX therapy was therefore initiated. This is one of few documented cases showing transformation of nonseminomatous germ cell tumor to adenocarcinoma, for which surgical resection is favored as primary therapy. However, aggressive adjuvant chemotherapy may be considered and should be directed towards the most aggressive found histology. J Med Cases. 2019;10(5):123-125 doi: https://doi.org/10.14740/jmc3301

A case of adult thymic neuroblastoma associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Neuroblastoma is a tumour of childhood that is rarely seen in adults. We present a case of a thymic neuroblastoma in a 62-year-old man with associated SIADH. The patient presented with nonspecific constitutional symptoms. Bloodwork revealed a sodium level of 115 mmol/L and chest CT showed a mediastinal mass (subsequently resected). Macroscopically tumour was well defined and firm, with a variegated grey and tan cut surface. Histopathology revealed features of a poorly differentiated thymic neuroblastoma, schwannian stroma poor, characterised by minimal neuronal differentiation, significant necrosis and frequent mitoses (with Ki67 showing a proliferative index of 20%). Residual thymus was seen, suggesting a thymic origin. No elements of teratoma were identified (a proposed histogenic origin for thymic neuroblastoma).1 Stains for CD56, synaptophysin, chromogranin and NSE were positive, supporting the diagnosis.2 Fewer than 10 cases of thymic neuroblastoma were identified in the literature. SIADH appears to be a common but not universal feature of these tumours. The presence of poor differentiation, necrosis, mitoses and focal invasion are poor prognostic features consistent with the generally poor prognosis of adult neuroblastoma.3