Mixed Nonseminomatous Germ Cell Tumor Research Articles

31. GENETIC CONTROL OF DECONVOLVED BRAIN CELL-TYPES

Choriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.We reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.Our cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).While PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

TU17. GENOME-WIDE ANALYSIS OF PSYCHOLOGICAL RESILIENCE

Choriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.We reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.Our cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).While PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

Duodenal teratoma: Rare case of extragonadal germ cell tumors and review of literature.

IntroductionDuodenal teratoma is a rare condition with only four cases reported in the English literature. Radiological imaging and tissue sample are necessary for diagnosis in addition to tumor markers. The most effective treatment is still complete excision with safety margins.Case presentationWe report a case of 26 years-old-man, in whom epigastric pain, decreased appetite, and postprandial bilious vomiting had been prevalent for 5–6 months and had exacerbated prior to the emergency room.Enhanced abdominal computed tomography revealed a 10 × 15cm heterogeneous solid mass with cystic component in the third duodenum segment. The inferior veina cava and aorta were both compressed, although there was no sign of lymphadenopathy or ascites. An ulcerating non-bleeding lesion at the D2-D3 junction of the duodenum was discovered during a gastroduodenoscopy. Biopsies and immunohistochemical investigations revealed findings that were consistent with a mixed non-seminomatous germ cell tumor. A PET-CT scan was performed, which revealed FDG uptake by the duodenal lesion but no evidence of metastatic lesions.A distal duodenal segmentectomy is performed, and then a duodeno-jejunal anastomosis is used to restore continuity. The final diagnosis was teratomatous tumor of the duodenum without malignant changes.ConclusionThis is the second adult case of main duodenal teratoma that has been reported. We publish it to encourage surgeons to think about this differential diagnosis and carefully plan surgery using a multidisciplinary approach.

Paraneoplastic Limbic Encephalitis Secondary To Mixed Non-Seminomatous Germ Cell Tumours

Abstract Casestudy: Testicular tumors account for 1–2% of all tumors in men, with 95% of these being germ cell tumors. The main risk factor for the development of testicular cancer is cryptorchidism. Paraneoplastic limbic encephalitis is a rare sequela of testicular tumor associated with anti-Ma2 and KLH11 antibodies. The most effective treatment for paraneoplastic limbic encephalitis is treatment of the primary malignancy. We present a 41-year-old male that presented to the emergency department with two weeks of episodic alteration of consciousness and memory disturbances. Negative neurologic evaluation and imaging led to concern for a paraneoplastic process from a distant malignancy. CT imaging revealed an enlarged, necrotic para-aortic lymph node and subsequent ultrasound demonstrated a right sided testicular mass. Right radical orchiectomy was performed. Microscopically, the mass consisted of mixed respiratory epithelium, gastrointestinal glands and squamous epithelium with keratinization consistent with a post-pubertal testicular teratoma with associated in-situ germ cell neoplasia. Resection of the para-aortic mass revealed large anaplastic cells with epithelioid features, nuclear pleomorphism and frequent mitoses. Immunostaining was positive for Pan-Keratin and OCT4, consistent with poorly differentiated embryonal carcinoma. Resection of the primary and metastatic disease, as well as treatment with corticosteroids resulted in resolution of the encephalitis. This presentation of severe neurological disturbances in the setting of a metastatic mixed nonseminomatous germ cell tumor represents a rare presentation of paraneoplastic limbic encephalitis.

Postchemotherapy retroperitoneal lymph node dissection in patients presenting with very high HCG levels

PurposeChoriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels. MethodsWe reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen. ResultsOur cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]). ConclusionWhile PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

Primary Mediastinal Malignant Mixed (Non-seminomatous) Germ Cell Tumor Presenting as Superior Vena Cava Syndrome

Abstract Introduction Mediastinal germ cell tumors are commonly seen in children and young adults with male preponderance. They are clinically classified as teratomas, seminomas and nonseminomatous germ cell tumors. Primary mediastinal mixed germ cell tumor falls under the nonseminomatous classification and are very rare. These patients have poor prognoses despite multidimensional strategic approach (chemotherapy, radiotherapy, surgical intervention). Case Discussion A previously well 27-year old male initially presenting with non-productive cough and a right anterior neck mass unresponsive to antibiotic therapy is subsequently diagnosed to be an extra-gonadal germ cell tumor of the anterior mediastinum. Two months through the course of disease, patient’s symptoms have progressed presenting with facial edema, engorged neck veins and cardio-respiratory distress. He is later found to be admitted in the intensive care unit where further work-ups led to the diagnosis of primary mediastinal mixed (non-seminomatous) germ cell tumor. Chemotherapy (cisplatin, bleomycin, etoposide - 1 cycle) and chest radiotherapy (4 sessions) were initiated causing resolution of symptoms. One week after discharge, patient presented with seizures and sudden onset of dyspnea. Patient was brought to the emergency room where he subsequently expired. Discussion This case report presents an account of this rare disease entity from its initial presentation to post-mortem analysis. Primary mediastinal germ cell tumors are rare with a poor prognosis and should be strongly considered in the diagnosis of young men with a mediastinal mass and superior vena cava syndrome.

Treatment and Outcome of Patients with Stage IS Testicular Cancer: A Retrospective Study from the Spanish Germ Cell Cancer Group.

Stage IS testicular cancer is defined by the persistence of elevated serum tumor markers, including α-fetoprotein and/or β-human chorionic gonadotropin, after orchiectomy without radiological evidence of metastatic disease. Current treatment recommendations include cisplatin based chemotherapy up front but the recommendations are based on limited single center series. We retrospectively analyzed clinical and pathological characteristics, and long-term outcomes in 110 patients uniformly treated with primary chemotherapy between 1994 and 2016. The primary objective was to evaluate long-term disease-free survival. We also explored factors associated with the need for additional treatment. The elevated prechemotherapy tumor markers were α-fetoprotein in 48% of cases, β-human chorionic gonadotropin in 14%, and α-fetoprotein and β-human chorionic gonadotropin in 38%. Median α-fetoprotein and β-human chorionic gonadotropin values were 71 ng/ml and 80 mIU/ml, respectively. The IGCCCG (International Germ Cell Cancer Collaborative Group) prognostic classification was good in 94% of cases. Mixed nonseminomatous germ cell tumor was found in 78% of cases. Of the patients 103 achieved a complete response to chemotherapy. In 6 patients radiological signs of progressive disease developed during chemotherapy, while 8 experienced relapse after an initial complete response. At a median followup of 108 months 108 patients were alive and disease-free. Five and 10-year disease-free survival rates were 87% and 85%, respectively. The predominance of embryonal carcinoma in the primary tumor was the only factor associated with the probability of needing additional therapy. Stage IS testicular cancer is more commonly associated with elevated α-fetoprotein, an IGCCCG good prognosis and mixed nonseminomatous germ cell tumor. Treatment with cisplatin based chemotherapy leads to cure in most cases. However, a proportion of patients require the integration of additional therapies, including more frequently when embryonal carcinoma is not predominant.

Histopathological pattern of testicular diseases in western Saudi Arabia.

ObjectivesTo determine the histopathological pattern of testicular diseases among Saudi patients in Madinah, Saudi Arabia.MethodsThis retrospective histopathology-based study was conducted in a tertiary care hospital in Madinah, Saudi Arabia, from January 2006 to December 2017. The data collected were entered into MS-Excel and analyzed using the Statistical Packages for Social Sciences Version 19.ResultsOf the 199 testicular specimens received, 108 (54.3%) of the biopsies were taken for diagnostic test, while 91 (45.7%) were for therapeutic test. The male infertility was the only indication in the diagnostic group, accounting for 108 (54.3%) with a mean age of 28±7.9 years. Benign conditions of the testes were the most common indication in the therapeutic group accounting for 76 cases (38.2%), followed by 15 cases (7.5%) of testicular tumors. Hemorrhagic infarction from testicular torsion was the most common histologic patterns in benign testicular conditions group, accounting for 46 (23.2%) of the cases with a mean age of patients 32.1±8.1 years. Mixed non-seminomatous germ cell tumor was the most common primary tumor in 7 (3.5%) cases, followed by seminoma occurring in 5 (2.5%) cases. Mean ages for these patients were 33.7±8.1 years for primary tumor and 35.6±9.1 years for seminoma.ConclusionsThe pattern of testicular diseases on the basis of histopathology experience in the Madinah region appears to conform to world literature and KSA.

Collaborating with our adult colleagues: A case series of robotic surgery for suspicious and cancerous lesions in children and young adults performed in a free-standing children's hospital

In adult urologic oncology the use of robotics has become commonplace; in pediatric urology it is rare. Herein, we describe a collaboration between an adult and a pediatric urologist performing robotic surgery for children and young adults with suspicious or cancerous genitourinary (GU) lesions. To evaluate clinical and oncologic outcomes in children and young adults undergoing robotic surgery for suspicious or cancerous lesions of the GU tract; to describe our collaborative model between an adult and pediatric surgeon at a free-standing children's hospital. We retrospectively reviewed all robotic cases performed at our institution from 2014 to 2016 for patients with a GU malignancy or a suspicious mass. The surgeries were performed by a pediatric urologist with robotic experience and a fellowship-trained MIS adult urologist specializing in oncology. Perioperative and oncologic outcomes were recorded. A total of eight robotic cases were performed: four partial nephrectomies (PN) with retroperitoneal lymph node dissection (LND) (OT 269-338min, EBL 5-300mL, LOS 3-6 days), one adrenalectomy with LND (6.4cm mass; OT 172 min, EBL 5mL, LOS 3 days), one nephrectomy with pericaval LND (9.8cm mass; 234min, EBL 25mL, LOS 3 days), and two retroperitoneal LNDs (OT 572 and 508min, EBL 250 and 100, LOS 3 and 4 days). Patient weights ranged from 14 to 79kg (mean 53.4kg). There were no major complications (Clavien 3-5). Pathology results for PN included papillary RCC (AJCC pT1aNx) and two cases of segmental cystic renal dysplasia with nephrogenic rests. Bilateral template RPLNDs yielded paratesticular rhabdomyosarcoma (43 nodes; COG low risk group II stage I) and mixed non-seminomatous germ cell tumor (74 nodes; COG stage III). The nephrectomy yielded an undifferentiated sarcoma, low grade; the adrenalectomy favorable-type ganglioneuroma. In pediatrics, urologic oncology cases are often managed with open surgery. Our series demonstrates the feasibility of using the robotic approach in carefully selected cases. In doing so, the patient benefits from a minimally invasive surgery, while the surgeon benefits from robotic surgical dexterity. We seamlessly advanced these new techniques through a step-wise collaboration between an adult urologist who routinely performs robotic oncology procedures and a pediatric urologist experienced in robotics for benign conditions. In this small series, we safely and effectively adapted adult robotic techniques for genitourinary oncology cases in children and young adults.

Clinical Outcome of Retroperitoneal Lymph Node Dissection after Chemotherapy in Patients with Pure Embryonal Carcinoma in the Orchiectomy Specimen

To determine the pathologic findings and clinical outcome of patients with pure embryonal carcinoma (EC) of the testis who were diagnosed with testis cancer from January 1989 to January 2013 who underwent an orchiectomy, cisplatin-based chemotherapy and a postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We compared those patients with 100% EC with those with mixed nonseminomatous germ cell tumor pathology who underwent a PC-RPLND. Of 1105 patients who underwent a PC-RPLND, 145 had pure EC. Twenty-six percent of patients presented with metastatic disease outside the retroperitoneum. Patients with mixed histologies tended to have worse International Germ Cell Cancer Collaborative Group risk compared to those with EC at orchiectomy (P = .037). Histology at PC-RPLND revealed fibrosis or necrosis in 76%, mature teratoma in 19% and viable cancer in 4%. Over one-third of the patients had a residual mass of <1 cm prior to RPLND; of whom 15% harbored mature teratoma in PC-RPLND histology. The Kaplan-Meier estimated probability of recurrence at 5 years of follow-up was 3.1% (95% CI 1.2%, 8.0%) for EC histology, 7.3% lower than mixed histology. For cancer-specific mortality, the Kaplan-Meier estimated probability at 5 years was 4.6% (95% CI 3.3%, 6.3%) and 1.7% (95% CI 0.4%, 6.8%) for mixed and pure EC histologies, respectively. Approximately 20% of patients with pure EC had teratoma at PC-RPLND. We have shown that those with a maximum node size of <1 cm should not be precluded from RPLND.

Adolescent and Young Adult Testicular Germ Cell Tumors: Special Considerations.

While testicular germ cell tumors (T-GCTs) make up only 0.5% of pediatric malignancies and less than 2% of adult malignancies, they comprise 14% of adolescent malignancies, making it the most common solid tumor in this age group. The transition in incidence at this age is also accompanied by a transition in tumor histology with adolescents having mostly pure embryonal carcinoma and mixed nonseminomatous germ cell tumors. Similar to T-GCTs of all ages, surgical excision with orchiectomy is the standard initial step in treatment. Chemotherapy, retroperitoneal lymph node dissection, and targeted treatment of distant metastases make even widely disseminated disease treatable and curable. For this reason, in many ways, the future focus has expanded beyond survival alone to emphasize quality of life issues such as fertility and hypogonadism. However, adolescents remain the age group least studied or understood as they fall in between the ages included in most study designs. Also, they require the most psychosocial support because of the challenges unique to the adolescent period. In this review, we aim to highlight the known outcome data for T-GCTs in this population and also to discuss the unique aspects of treatment and support for this age group.

Histologic determinants of long-term overall survival in patients (pts) with germ cell tumors (GCT).

4555 Background: GCT display totipotential differentiation ranging from pluripotent embryonal carcinoma to extraembryonic (choriocarcinoma, yolk sac) to somatic cell types (teratoma [T]). We hypothesized that long-term survival after platinum-based chemotherapy (PC) is dependent upon histology. Methods: Advanced GCT pts who received PC from 4/1975 to 5/1996 and had a pre-PC primary tumor specimen available were included. Each pre-PC cell type was reviewed and confirmed. Residual tumor size post-PC was recorded when available. Differences in cumulative incidence (CUI) of death due to disease (DOD) between histologic cell types and other baseline characteristics were evaluated using a competing risks approach and the Fine &amp; Gray test. Results: Pre-PC primary tumor specimens (96% testis, 3% mediastinum) were available from 231 pts. Median age was 29 years (y) and median followup 17 y (range 0.3-35 y). 41 pts had pure seminoma; of the remaining 190 with nonseminomatous GCT (NSGCT), 81 had an element of T (n=29 mature T, n=42 immature T, n=10 both). At PC start, 60% of pts were IGCCCG good risk, 26% intermediate, and 13% poor with no difference for NSGCT based on presence vs. absence of T (p=0.53). Of 72 deaths, 50 were DOD, 20 from other causes, and 2 from unknown causes. The 5, 10, and 15 y CUI of death from any cause was 20%, 23%, and 26%, respectively. CUI of DOD at 5, 10 and 15 y was 18%, 20%, 22%, respectively. CUI of DOD at 2, 5, 10 and 15 y by histologic group is provided in the Table. Presence of T was associated with greater CUI of DOD vs. NSGCT without T (p=0.04) and mature T with a greater CUI of DOD vs. immature T (p=0.03). NSGCT pts with T were also more likely to have residual retroperitoneal disease &gt;1cm after PC vs. those without T (50 vs. 4.2%; p=0.01). Conclusions: With long-term followup, the presence of an element of T, particularly mature T, in mixed NSGCT was associated with a higher risk of DOD than tumors without T, which have the same risk of DOD as pure seminoma. These data suggest that the presence of T in the primary tumor may be an important clinical predictor of long-term outcome in men with GCT. [Table: see text]

Robot-assisted retroperitoneal lymph node dissection (RA-RPLND) in the adolescent population

Robot-assisted retroperitoneal lymph node dissection (RA-RPLND) has built on success and techniques of laparoscopic RPLND, with the added benefits of robotic technology. This paper demonstrates use of the da Vinci Xi® system for RA-RPLND in two adolescent patients. Case #1: A 17-year-old male presented with a left testicular mass and elevated alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). Pathology revealed a mixed non-seminomatous germ cell tumor (60% embryonal, 35% yolk sac, 5% choriocarcinoma, + lymphovascular invasion). Tumor marker normalized post-orchiectomy, and staging imaging was without evidence of metastatic disease. After discussion of options he opted to undergo RA-RPLND. Case #2: A 15-year-old male presented with a right para-testicular mass and negative tumor markers. He underwent inguinal exploration and excision of the paratesticular mass. Final pathology revealed an ectomesenchymoma with a spindle cell rhabdomyosarcoma component. Staging imaging was negative, and after discussion of options he underwent completion orchiectomy and RA-RPLND. The patient in Case #1 underwent a left modified-template nerve-sparing RA-RPLND. Sixteen lymph nodes were negative for tumor. The patient in Case #2 underwent complete bilateral nerve-sparing RA-RPLND. Forty-two lymph nodes were negative for tumor. Estimated blood loss was <50cc for both cases, and console time averaged 262min. This was a report of two cases of RA-RPLND in the adolescent population. RA-RPLND is technically feasible in this population, and further study of RA-RPLND is needed to determine long-term outcomes, as this technique is becoming more widely adopted.

Nonseminomatous germ cell tumor of the testis: Prognostic factors for a lethal phenotype.

390 Background: Cancer is a heterogeneous disease. Studying cancer heterogeneity may enable us to elucidate the various subtypes of a particular cancer, and improve the diagnosis, prognostication, and therapy of cancer. Nonseminomatous germ cell tumor (NSGCT) is a prime example of a heterogeneous disease. We determined potential lethality of NSGCT by characterizing the histological makeup of primary testicular tumors, the tumor burden, psychosocial issues, and surgical factors. Methods: From November 1997 to October 2012, 142 consecutive patients diagnosed with a NSGCT of the testis were evaluated for this study. The log-rank test was used to identify prognostic factors in univariate Kaplan-Meier analysis. A multivariate Cox regression model was used to evaluate predictive factors for overall survival. Results: Patient and tumor characteristics: median (range) age 25 (12 to 53); pathology – embryonal carcinoma 15%, teratoma 6%, and mixed NSGCT 79%; stage – I 46%, II 32%, and III 21%. Ten (7%) patients died from their NSGCT. Seven (5%) patients had incurable NSGCT. Multivariate analysis showed that presence of seminoma (p=0.007), presence of yolk sac tumor (p=0.019), clinical stage (p=0.027), and psychosocial issues (p=0.04), have unfavorable prognostic significance. Conclusions: Certain subtypes of NSGCT containing yolk sac tumor and seminoma are inherently chemotherapy resistant and potentially lethal. Psychosocial factors can delay the diagnosis and treatment of patients with such tumors and adversely affect their clinical outcome. Results of this study need to be validated in another data base or a prospective clinical trial.

Cutaneous metastasis from testicular germ cell tumour

The skin is an unusual site of metastases from solid organ malignancies. We report the case of a patient with a malignant mixed non-seminomatous germ cell tumor of the testis, presenting with cutaneous metastasis, which was treated with salvage chemotherapy.

Prediction of a potential lethal phenotype in testicular nonseminomatous germ cell tumor.

e15575 Background: Cancer is a heterogeneous disease. The nature of heterogeneity provides clues about the biologic origin of cancer. Studying cancer heterogeneity may enable us to elucidate the various subtypes of a particular cancer, and improve the diagnosis, prognostication, and therapy of cancer. Nonseminomatous germ cell tumor (NSGCT) is a prime example of a heterogeneous disease. We determined the lethality of NSGCT by characterizing the histological makeup of primary testicular tumors (proportion of embryonal carcinoma [EC], choriocarcinoma, seminoma, yolk sac tumor [YST], and teratoma) and their tumor burden. Methods: From November 1997 to October 2012, 142 consecutive patients diagnosed with a NSGCT were included for this study. Predictors significant in univariate analysis: tumor stage, tumor size, percentage of YST component, and percentage of EC component were used as predictors of cancer specific death or incurability in a multivariate binary logistic regression model. The outcome of the model is probability of death or incurability. Results: Patient characteristics: age, median (range) – 25 (12-53); race – Caucasians 65%, Hispanics 28%; pathology – embryonal carcinoma 15%, teratoma 6%, mixed NSGCT 79%; stage – I 43%, II 33%, III 24%; size of primary tumor, median (range) – 3.8 cm (0.9-27); HCG&lt;5,000 95%, &gt;5,000 4%; AFP&lt;1,000 85%, &gt;1,000 13%; therapy – salvage chemotherapy 15%, RPLND 34%, HD chemotherapy w/ SCT 1%, WBRT 1%. Univariate analysis showed that clinical stage (p=.0001), presence of YST (p&lt;.005), size of primary tumor (p=.005), and absence of EC (&lt;.01) have prognostic significance. We developed a nomogram to identify patients who are most likely to succumb to their NSGCT based on the histologic makeup of their primary tumor, size of the primary tumor, initial tumor markers, and appropriate surgeries after chemotherapy. Conclusions: Presence of YST in advanced NSGCT predicts chemotherapy resistance in a potentially lethal phenotype. Early diagnosis and timely treatment with chemotherapy and surgery may improve the clinical outcome of these patients. Results of this study need to be validated in another data base or a prospective clinical trial.

971 A COMPREHENSIVE REVIEW OF THE CLINICAL PRESENTATION, PATHOLOGIC FINDINGS, AND OUTCOMES IN REGRESSED TESTICULAR GERM CELL TUMORS

INTRODUCTION AND OBJECTIVES: Regressed testicular tumors (RTTs) account for a significant proportion of what were once considered to be extragonadal germ cell tumors (GCTs). The clinical presentation and outcomes of patients with “burned-out” primary tumors are poorly understood as are their pathologic characteristics. We describe our experience with this unique subset of testicular GCTs. METHODS: We reviewed our prospectively-maintained testicular cancer database for radical orchiectomies performed from 1977– 2009. Specimens without viable tumor were reviewed by dedicated genitourinary pathologists blinded as to whether or not the patient had received prior chemotherapy. Kaplan-Meier curves were generated to describe recurrence-free and overall survival. RESULTS: We identified 80 patients with testicular or extragonadal GCTs but with no viable tumor in the radical orchiectomy specimen. A total of 28 patients had not received prior chemotherapy. Pathologic findings at the time of retroperitoneal lymph node dissection or biopsy of a metastatic site included non-seminomatous GCT (NSGCT) in 11 (39%), seminoma in 6 (21%), unspecified GCT in 3 (11%), and sarcoma in 1 (4%). Benign disease was identified in the remaining 7 patients (25%). The 11 patients with NSGCT included 4 with embryonal carcinoma (14%), 2 with choriocarcinoma (7%), 2 with teratoma (7%), 2 with mixed NSGCT (7%), and 1 with yolk sac (4%). At presentation, the clinical stage was I in 3 patients (14%), II in 10 patients (45%), and III in 9 patients (41%). Based on the IGCCCG classification system, 10 were good risk (56%), 3 were intermediate risk (17%), and 5 were poor risk (28%). Intratubular germ cell neoplasia was identified in 8 patients (29%). Additional findings included hyalinization in 24 (86%), nodular scar in 22 (79%), Sertoli cell-only pattern in 21 (75%), interstitial fibrosis in 22 (79%), inflammation in 13 (46%), tubular calcification in 11 (39%), coarse calcification in 10 (36%), psammomatous calcification in 7 (25%), and necrosis in 1 (4%). Fiveyear recurrence-free, cancer-specific, and overall survival rates were 83% (95% CI: 61%, 93%), 96% (95% CI: 75%, 99%), and 96% (95% CI: 75%, 99%), respectively. CONCLUSIONS: To our knowledge, this is the largest published review of patients with RTT. We describe in detail the pathologic findings in this unique subset of testicular GCTs as well as their clinical presentation and outcomes.

Postchemotherapy Laparoscopic Retroperitoneal Lymph Node Dissection in Nonseminomatous Germ-Cell Tumor

Postchemotherapy retroperitoneal lymph node dissection (RPLND) remains essential in the management of metastatic testicular carcinoma and represents a surgical challenge. We determined to assess the feasibility and complications of laparoscopic RPLND in patients who were treated with induction chemotherapy for testis cancer. We performed a retrospective analysis of data that was prospectively recorded from 26 patients who underwent laparoscopic RPLND postplatinum-based chemotherapy between 2000 and 2006. The surgical technique consisted of excision of the residual mass plus unilateral template dissection. A transperitoneal technique was used in 24 patients, and an extraperitoneal approach was used in 2 patients. Operative details, perioperative morbidity data, and histologic findings were assessed for the study. Primary pathologic evaluation of the testis tumor revealed pure embryonal carcinoma in 4 patients, teratocarcinoma in 1 patient, and mixed nonseminomatous germ-cell tumors in 21 patients. All patients had residual disease in the retroperitoneum on a preoperative CT scan, with a median size of 3.4 cm (range 2-6 cm). Procedures in three (11.5%) patients were converted to open surgery. Median operative time was 183 minutes (range 120-260 min). Median estimated blood loss was 400 mL (range 100-600 mL), and blood transfusion was necessary in one patient. Median hospital stay was 5 days (range 2-6 d). Median number of lymph nodes obtained on final histologic examination was 7 (range 4-13). Perioperative complications included eight lymphovascular and one intestinal. At a mean follow-up of 27 months (range 14-36 mos), no recurrences have been observed and no patient was lost to follow-up. Postchemotherapy laparoscopic RPLND is technically feasible. The most frequent complications and causes of conversion are lymphovascular.

Spontaneous regression of testicular germ cell tumors: an analysis of 42 cases: Balzer BL, Ulbright TM, Department of Pathology, Stanford University Hospital and Clinics, Stanford, CA

Spontaneous regression of testicular germ cell tumors (GCTs) is a well-recognized phenomenon but has been incompletely characterized. Many pathologists are not familiar with the findings that support a diagnosis of a “burnt-out” primary in a patient with metastatic GCT. We therefore report the clinical, gross, and histologic findings in 42 cases of testicular GCT that showed either complete (26) or greater than 50% scarring (16) Thirty-seven patients (88%) had either known GCT metastasis or some residual testicular GCT, and none had treatment before orchiectomy. The patients were 17 to 67 years old, with a median of 32. Thirty presented with symptoms of metastasis, 7 with a testicular mass, 2 with elevated human chronic gonadotropin, and 1 with testicular pain. In 2 patients the presentation was unknown. Two patients had prior orchiopexy; another had an intraabdominal testis, and 2 others had prior contralateral seminoma (20 and 42 years previously). Gross descriptions in 37 cases identified white to tan scars, 0.6 to 2.4 cm, in 33. These were circumscribed in 16, with 15 of these having nodular or multinodular configurations and 1 a band-like appearance. In 9 cases the scar was ill defined or stellate, and in 8 cases no further details concerning the scar configuration were available. In 4 cases no scar was apparent; 2 of these had received intraoperative biopsy. Microscopically, all cases showed circumscribed to irregular foci of scarring, distinct from the adjacent parenchyma, in association with widespread testicular atrophy. Other common features were lymphoplasmacytic infiltrates in the scars (37/42) and “ghost” tubules in scars (31/42). Less common features in the scars included angiomatous foci (22/42), siderophages (15/42), and coarse intratubular calcifications (6/42); in the surrounding testis they included intratubular germ cell neoplasia, unclassified (IGCNU) (22/42), Leydig cell prominence (18/42), and necrosis (5/42). Tubular microliths occurred in 13 cases, 12 peripheral to the scar and 1 within it. Metastases in 31 cases were: pure seminoma (17, 3 with residual testicular seminoma), mixed GCT with seminoma (4, 3 with residual testicular seminoma), mixed nonseminomatous GCT (4, 3 with residual testicular GCT), pure embryonal carcinoma (2), pure teratoma (2, 1 with residual testicular teratoma), and pure yolk sac tumor (2). In 5 cases with clinically diagnosed metastases, there was no histologic documentation of the nature of the metastatic tumor. Testicular tumors in the remaining 6 cases having residual primaries without concomitant metastases were pure seminoma (3), mixed GCT with seminoma (2), and pure embryonal carcinoma (1). The most specific histologic findings of a regressed GCT are a distinct scar in association with either IGCNU or coarse intratubular calcifications; however, many cases lack the latter 2 features. In such cases additional features supportive of regressed GCT include testicular atrophy, microlithiasis and, in the scar, lymphoplasmacytic infiltrates and prominent vascularity. Ghost tubules in many scars are not evidence of a non-neoplastic process but likely reflect regression of tumors with intertubular growth. Intertubular growth is a common finding in seminoma, which is the single most frequent type of regressed GCT, occurring either in pure or mixed form in the metastases of 68% (21/31) of the cases and identifiable in 62% (10/16) of persistent testicular tumors. We conclude that regression of testicular GCTs shows a distinctive constellation of findings that usually permits its recognition. In contrast, nonspecific atrophy lacks distinct scars, and scars from non-neoplastic causes lack most of the associated findings seen in our cases.

Mixed Nonseminomatous Germ Cell Tumor Presenting as a Subcutaneous Tissue Mass

Extragonadal germ cell tumors most commonly arise in the midline of the retroperitoneum or the mediastinum. Primary tumors involving the skin are very rare. Only one case of malignant primary germ cell tumor located in the skin has been reported. We present the case of a 44-year-old white man with a primary subcutaneous mixed nonseminomatous germ cell tumor. This man had a long-lasting subcutaneous lump of the breast, which became painful. Surgery revealed 3 juxtaposed nodules. Microscopic examination showed a mixed germ cell tumor with a 90% immature teratoma component and a 10% embryonal carcinoma component. Testicular ultrasound and computed tomography of the chest, abdomen, pelvis, and brain were normal. Serum human chorionic gonadotrophin, beta-human chorionic gonadotrophin, alpha-fetoprotein, and lactate dehydrogenase were within normal ranges. A further surgical excision was performed. The patient is presently alive with no evidence of disease after a follow-up of 7 years. Review of the literature indicates that primary cutaneous extragonadal germ cell tumors usually occur as cutaneous or subcutaneous solitary nodules or as ulcerated lesions. They mainly consist of mature teratomas in children. Only 2 cases have been reported in adults.