Retroperitoneal Lymph Node Dissection Specimens Research Articles

Immunoreactivity of Histiocytes to OCT4; a diagnostic pitfall

Abstract Introduction/Objective Immunohistochemical stains are supposed to make a Pathologists’ life easier; however, interpretation of some stains in isolation can be a diagnostic pitfall. Immunoreactivity of paraganglia to OCT4 stain is a known pitfall for this stain when evaluating retroperitoneal lymph node dissection specimens for germ cell tumour metastasis. The purpose of this report is to highlight another pitfall of the OCT4 stain, albeit in a similar clinical scenario. Methods/Case Report A 49-year-old male with a history of left testicular seminoma metastatic to periaortic, retroperitoneal and left supraclavicular lymph nodes, status post orchiectomy and chemotherapy, presented with a rising B-HCG and PET scan evidence of recurrent/refractory disease. His imaging showed interval increase in FDG uptake of left periaortic lymph nodes despite a decrease in size. A biopsy was performed. Pathologic evaluation showed predominantly necrotic tissue with rare clusters of atypical cells with clear to pink cytoplasm, monotonous nuclei, and rare admixed lymphocytes. Immunohistochemical stains showed the atypical cells to be positive for OCT4 stain, raising the possibility of viable seminoma. However, additional satins showed the cells to be positive for CD68 and CD163, and negative for CD117, SALL-4, pancytokeratin, SF-1, GATA3 and synaptophysin. Therefore, the atypical cells were interpreted to represent histiocytes; no viable germ cell tumor was identified. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of using a panel of immunohistochemical stains, instead of relying on one stain, even if the stain is thought to be fairly specific. Pathologists need to be aware of immunoreactivity of histiocytes to OCT4 as a potential diagnostic pitfall in addition to the paraganglion cells staining for OCT4 being a pitfall.

Viable germ cell tumor and teratoma can be distinguished from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens by a combination of microRNA-371a-3p and 375-5p.

421 Background: Our objective was to identify a combination of microRNAs (miRNA) to differentiate between viable tumor (V) or teratoma (T) and necrosis/fibrosis (N) in pcRPLND specimens of metastatic nonseminomatous germ cell tumor (NSGCT) patients with residual masses ≥1cm after chemotherapy. Our hypothesis is that a biomarker guided therapy could reduce overtreatment with pcRPLND in patients with only N. Methods: Forty-eight patients were identified, n = 16 each with T/V/N. Representative regions of T/V/N were microdissected, subsequently total RNA was isolated and miRNA expression was analyzed for miR-371a-3p, 375-3p, and 375-5p using qPCR. ROC analysis was performed for each miRNA and for all combinations in order to determine the discriminatory capacity of V and T vs. N. Results: For the group comparisons of V vs. N miR-371a-3p achieved the highest fold change (FC) of 31.1 (p = 0.023) while for T vs. N miR-375-5p performed best (FC 64,2; p < 0.001). Likewise, the most accurate AUC for V was 0.75 using miR-371a-3p, for T 0.80 using miR-375-5p. Combining the best performing miRNAs for V and T resulted in an AUC of 0.94 with a sensitivity of 93.75, specificity of 93.75, PPV of 96.8 and NPV of 83.3. Conclusions: In pcRPLND tissue samples V and T could be distinguished from necrosis/fibrosis by combining miR-371a-3p and miR-375-5p with great accuracy. This combination of miRNAs might serve as new biomarker in the future, in order to spare miRNA-negative patients from pcRPLND. However, further studies analyzing patient’s serum are needed to confirm the clinical impact of these biomarkers.

Post-treatment Residual Clinicopathological Outcomes in Testicular Germ Cell Tumours.

Surgical resection is a generally accepted treatment for residual masses after chemotherapy for metastatic testicular germ cell tumour (GCT). About half the patients have necrosis in post-chemotherapy residual masses, whereas rest have viable tumour and teratoma. The likelihood of leaving behind teratoma with its subsequent complications such as growing teratoma syndrome necessitates resection outweighing its surgical complications. Ours is a retrospective observational study and aims at assessing post-chemotherapy residual masses in testicular GCTs and to predict importance of teratomatous and non-seminomatous components. A total of 62 cases of testicular GCTs resected after chemotherapy between January 2012 and June 2019 were included. Demographic, clinical, biochemical and imageological findings were noted and categorised according to WHO classification (2016). They were divided into two groups - those who underwent retroperitoneal lymph node dissection (RPLND) post-high inguinal orchidectomy (HIO) and chemotherapy (CT) as group 1 (n = 40) and those who underwent HIO and/or RPLND post-chemotherapy as group 2 (n = 22). The gross and microscopic examination was carried out to assess response to chemotherapy in terms of residual viable tumour, necrosis and teratoma. Viable tumour, necrosis and teratoma were 10%, 62.5% and 35% respectively in group 1 and in group 2, the same were 15%, 70% and 25% respectively in HIO specimen and 7%, 50% and 21% respectively in RPLND specimen. All the cases with viable tumour were proven to be yolk sac tumours (YST) based on morphology and immunohistochemistry (IHC).Twenty cases had teratoma in the post-CT residual masses out of which 11 cases had teratoma despite reduction in size. At a median follow-up of 47.85months, 5 cases in group 1 and 2 cases in group 2 showed relapse and it was observed that group 1 had a prolonged relapse-free survival over group 2. Our study re-emphasises the importance of performing resection of residual mass post-CT irrespective of the size, imageological or biochemical evidence of tumour regression. There does not appear to be reliable predictors of post-chemotherapy histology of residual masses indicating the continued need for surgical resection in specialised centres.

Advanced germ cell tumor patients undergoing post-chemotherapy retroperitoneal lymph node dissection: Impact of residual teratoma on prognosis.

To evaluate the histologic findings and clinical outcomes of post-chemotherapy retroperitoneal lymph node dissection for advanced germ cell tumor. We analyzed the medical records of 66 patients who underwent post-chemotherapy retroperitoneal lymph node dissection between 2005 and 2019 at Tsukuba University Hospital. The proportions of necrosis, teratoma, and viable germ cell tumor in the specimens were 62.1%, 36.4%, and 1.5%, respectively. The 5-year progression-free and overall survival rates were 82.3% and 91.3%, respectively. The 5-year overall survival rate of patients with residual teratoma was significantly worse than that of patients with necrosis only (74.1% vs 100%). Overall, three patients died: one from cancer and two from teratoma with somatic-type malignancy. Of these, two patients relapsed after incomplete resection of residual teratoma. When limited to patients with completely resected teratoma, the 5-year overall survival rate was 91.7%, which did not differ from that for patients with necrosis only. Multivariate analysis showed that presence of teratoma in the primary site and decrease in retroperitoneal lymph node mass to less than 50% of the initial tumor size were independent factors for residual teratoma. However, the absence of these factors could not reliably predict necrosis only in retroperitoneal lymph node dissection specimens. In our series, 98% of post-chemotherapy retroperitoneal lymph node dissection pathology was either necrosis or teratoma, with viable germ cell tumor only found in 2% of patients. Residual teratoma was associated with poorer prognosis, especially in cases of incomplete resection.

P0658 - The combination of microRNA-371a-3p and 375-5p can distinguish viable germ cell tumor and teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens

P0658 - The combination of microRNA-371a-3p and 375-5p can distinguish viable germ cell tumor and teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens

The combination of microRNA-371a-3p and 375-5p can distinguish viable germ cell tumor and teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens.

BackgroundTo identify a combination of microRNAs (miRNA) to differentiate between viable tumor (V) or teratoma (T) and necrosis/fibrosis (N) in pcRPLND specimens of metastatic germ cell tumor (GCT) patients with residual masses ≥1 cm after chemotherapy. Biomarker guided therapy could reduce overtreatment with pcRPLND in patients with only N.MethodsWe selected 48 metastatic GCT patients who had undergone pcRPLND. V, pure T and N was shown in the resected tissue of 16 patients, respectively. Of these areas total RNA was isolated and miRNA expression was analyzed for miR-371a-3p, 375-3p, and 375-5p using qPCR. ROC analysis was performed for each miRNA and for all combinations in order to determine the discriminatory capacity of V and T vs. N.ResultsOn comparing V vs. N miR-371a-3p achieved the highest fold change (FC) of 31.1 (P=0.023) while for T vs. N miR-375-5p performed best (FC 64.2; P<0.001). Likewise, the most accurate AUC for V was 0.75 using miR-371a-3p, for T 0.80 using miR-375-5p. Combining the best performing miRNAs for V and T resulted in an AUC of 0.94 with a sensitivity of 93.75, specificity of 93.75, PPV of 96.8 and NPV of 83.3.ConclusionsBy combining miR-371a-3p and miR-375-5p in pcRPLND tissue samples V and T could be distinguished from necrosis/fibrosis with great accuracy. This combination of miRNAs might serve as new biomarker in the future, in order to spare miRNA-negative patients from pcRPLND. However, further studies analyzing patient’s serum are needed to confirm the clinical impact of these biomarkers.

Four Cycles of Etoposide plus Cisplatin for Patients with Good-Risk Advanced Germ Cell Tumors

BackgroundThe National Comprehensive Cancer Network recommends either three cycles of bleomycin, etoposide, and cisplatin or four cycles of etoposide and cisplatin (EPx4) as initial chemotherapy for the treatment of good‐risk germ cell tumors (GCTs). To assess the response, toxicity, and survival outcomes of EPx4, we analyzed our experience.Material and MethodsResponse and survival outcomes, selected toxicities, and adherence to chemotherapy dose and schedule were assessed in patients with good‐risk GCT who received EPx4 at Memorial Sloan Kettering Cancer Center between 1982 and 2016. The results were compared with our past results and published data.ResultsBetween 1982 and 2016, 944 patients with GCT were treated with EPx4, 289 who were previously reported plus 655 treated between January 2000 and August 2016. A favorable response was achieved in 928 of 944 patients (98.3%). Five‐year progression‐free, disease‐specific, and overall survival rates were 93.9%, 98.6%, and 97.9%, respectively. Median follow‐up was 7.3 years (range, 2.8 months to 35.5 years). Viable, nonteratomatous malignant GCT was present in 3.5% of 432 postchemotherapy retroperitoneal lymph node dissection specimens from patients with nonseminomatous GCT. Febrile neutropenia and thromboembolic events occurred in 16.0% and 8.9%, respectively, with one treatment‐related death. In the more recent 655‐patient cohort, full‐dose EPx4 was administered to 631 (96.3%), with deviations from planned treatment driven mainly by vascular (n = 13), hematologic (n = 11), renal (n = 7), or infectious (n = 5) events.ConclusionEPx4 is highly effective and well tolerated in patients with good‐risk GCTs and remains a standard of care.Implications for PracticeFour cycles of etoposide and cisplatin (EPx4) is a standard‐of‐care regimen for all patients with good‐risk germ cell tumors with a favorable response rate and disease‐specific survival of 98%. Full‐dose administration of etoposide and cisplatin and complete resection of residual disease lead to optimal outcomes. EPx4 should be the recommended regimen in active smokers, patients with reduced or borderline kidney function, and patients aged 50 years or older, which are patient groups at increased risk for bleomycin pulmonary toxicity. Because of a risk of acquired severe pulmonary illness, EPx4 may also be favored for patients who vape or use e‐cigarettes and during ongoing transmission of severe acute respiratory syndrome coronavirus 2.

Prognostic Value of Teratoma in Primary Tumor and Postchemotherapy Retroperitoneal Lymph Node Dissection Specimens in Patients With Metastatic Germ Cell Tumor.

Presence of teratoma in patients with metastatic testicular germ cell tumor (GCT) is of unknown prognostic significance. We report survival outcomes of patients with or without teratoma in primary tumor and postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen and assess impact on prognosis. Patients with metastatic nonseminomatous GCT (NSGCT) who were evaluated at Indiana University between 1990 and 2016 and had primary testicular tumor specimen from orchiectomy (ORCH) were included. All patients were treated with cisplatin-based combination chemotherapy. The cohort was divided into 2 groups according to presence or absence of teratoma in ORCH specimen. Survival data were correlated with histopathologic findings. Differences in progression-free (PFS) and overall survival (OS) were evaluated using log-rank tests and Cox proportional hazards models to adjust for known adverse prognostic factors. We identified 1,224 consecutive patients evaluated at Indiana University between 1990 and 2016 who met inclusion criteria. Median age was 27 years (range, 13-71 years); 689 patients had teratoma in ORCH specimen, and 535 did not. With median follow-up of 2.3 years, 5-year PFS was 61.9% (95% CI, 57.1% to 66.2%) for those with teratoma versus 63.1% (95% CI, 58.0% to 67.8%) for those without (P = .66); 5-year OS was 82.2% (95% CI, 77.9% to 85.8%) versus 81.4% (95% CI, 76.5% to 85.3%; P = .91), respectively. A total of 473 patients underwent PC-RPLND; 5-year PFS for patients with pure teratoma in PC-RPLND specimen versus necrosis only was 65.9% versus 79.1% (P = .06), and 5-year OS was 90.3% versus 93.4% (P = .21), respectively. Presence of teratoma in ORCH and PC-RPLND specimens was not a prognostic factor in this large retrospective study of patients with NSGCT.

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor

Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy. Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity. miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02). Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

Detailed pathologic analysis on the co-occurrence of non-seminomatous germ cell tumor subtypes in matched orchiectomy and retroperitoneal lymph node dissections.

The frequency of co-occurrence between germ cell tumor (GCT) components in non-seminomatous germ cell tumor (NSGCT) orchiectomy specimens and their correlation with histologic findings in subsequent retroperitoneal lymph node dissection (RPLND) specimens have not been well characterized. The objective of the study was to report the first detailed clinicopathologic analysis of NSGCT orchiectomy and RPLND samples to determine the likelihood and agreement of the co-occurrence of GCT components. A total of 118 consecutive patients with NSGCT treated between 1988 and 2012 who underwent both orchiectomy and RPLND at a single academic tertiary care center were analyzed. Statistical analysis of co-occurrence likelihood and agreement of GCT components was performed, both within and between orchiectomy and RPLND specimens. Embryonal carcinoma was the most frequent component present in orchiectomy specimens, and there were multiple significant associations between orchiectomy GCT components; seminoma occurred less frequently with embryonal carcinoma (OR 0.29 [95% confidence interval (CI) 0.11-0.75]; p<0.01), and teratoma more frequently occurred with choriocarcinoma (OR 9.64 [95% CI 1.22-76.12]; p=0.01). Presence of teratoma in the orchiectomy specimen predicted for a fourfold increase in distant metastasis on multivariate analysis (HR 4.92 [1.14-18.9]; p=0.02). The only significant association of co-occurrence in the RPLND specimen was between embryonal carcinoma and teratoma (OR 0.01 [95% CI 0-0.07]; p<0.001), where it was significantly less likely for them to occur together. Our findings are limited by their retrospective nature. The co-occurrence of GCT components within orchiectomy specimens does not appear to be a completely random process. However, there is less agreement and more randomness between the occurrence of the GCT components in matched orchiectomy and RPLND samples. In this report, we look at the co-occurrence of different GCT components within matched orchiectomy and RPLND pathology specimens and show that co-occurrence is not a completely random process.

Post-chemotherapy retroperitoneal teratoma in nonseminomatous germ cell tumors: Do predictive factors exist? Results from a national multicenter study.

To identify predictive preoperative factors of the presence of teratoma in retroperitoneal lymph node dissection specimens. We performed a 20 years multicenter retrospective analysis of all patients who underwent retroperitoneal lymph node dissection for residual masses after chemotherapy (PC-RPLND). Patients had undergone PC-RPLND after chemotherapy for advanced testicular cancer. The histologic components of the primary tumor were compared with those of the residual masses using logistic regression. A total of 469 NSGCT patients underwent PC-RPLND (complete data available for 211). By PC-RPLND, necrosis was found in 84 cases, teratoma in 102 cases, and viable tumor in 25 cases. The univariate and multivariate analyses showed that teratoma (P = 0.001 and P = 0.002, respectively) and yolk sac tumor (P = 0.009 and P = 0.035, respectively) in orchiectomy specimens were statistically significant predictors of the presence of teratoma in retroperitoneal lymph nodes. PC-RPLND is the standard treatment for any supracentimetric residual lesion. This procedure is associated with a high morbidity, and almost half patients are overtreated. The presence of teratoma and yolk sac tumor in the orchiectomy specimen were independent significant predictors of teratoma in retroperitoneal masses. J. Surg. Oncol. 2016;114:992-996. © 2016 Wiley Periodicals, Inc.

Retroperitoneal lymph node dissection (RPLND) for malignant phenotype Leydig cell tumours of the testis: a 10-year experience

Retroperitoneal lymph node dissection (RPLND) is a prognostic, palliative, and potentially therapeutic procedure for patients with malignant phenotype Leydig cell tumours of the testis. We reviewed the records of patients diagnosed with malignant phenotype Leydig cell tumours of the testis treated by RPLND. Modified template dissection was performed in all cases with extra-template excision of tumour mass in Stage II disease. Routine clinico-radiological follow-up was performed. Six open RPLNDs (1 re-do procedure) were performed on 5 patients diagnosed with Stage I (n = 3) and Stage II (n = 2) malignant phenotype Leydig cell tumour of the testis. Median age = 63 years (range = 55-72). Median peri-operative blood loss = 1500 ml (range = 500-1500 ml). Median operating time = 6 h (range = 4.5-6.5). Two patients with Stage II disease developed post-operative complications of acute kidney injury (n = 1) and pneumonia (n = 1). Median length of stay was 8 days (range = 6-11). RPLND specimens from patients with Stage I were tumour-free, whilst patients with Stage II disease had evidence of metastatic tumour. At latest follow-up (median = 13 months, range = 7-22), no patient with Stage I disease had radiological evidence of recurrence, however the two patients with Stage II disease had died due to tumour recurrence at 13 months and 36 months. RPLND for malignant phenotype Leydig cell testicular tumours appears to be well tolerated. Despite surgery, overall outcomes for Stage II appear to be poor due to the disease phenotype. Larger prospective multi-centre studies are required to determine the definitive criteria for surgery in Stage I disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-014-0781-x) contains supplementary material, which is available to authorized users.

The role of OCT4 immunohistochemistry in evaluation of retroperitoneal lymph node dissections: a pilot study

We investigated the role of OCT4 immunohistochemical staining in detecting germ cell tumor lymph node metastases. Retroperitoneal lymph node dissection is important for staging and treatment of testicular germ cell tumors, and OCT4 is sensitive and specific for pluripotent testicular germ cell tumors; however, micrometastases, particularly from seminoma, can be difficult to detect. We examined 262 lymph nodes in 45 retroperitoneal lymph node dissection specimens from germ cell tumor patients. Specimens were categorized as postchemotherapy and untreated retroperitoneal lymph node dissection with or without clinical suspicion, based on lymphadenopathy or elevated serum germ cell tumor markers. Sections were stained with anti-OCT4 antibody. Twenty-one additional positive lymph nodes in 12 cases were detected to harbor scattered seminoma cells, singly and in small clusters, from 256 previously considered benign in: untreated retroperitoneal lymph node dissection with clinical suspicion (13% increase), postchemotherapy retroperitoneal lymph node dissection (7%), and untreated retroperitoneal lymph node dissection without suspicion (4%). However, no patient with an entirely negative dissection specimen was reclassified as positive. OCT4 immunohistochemistry detected scattered seminoma cells and small clusters of seminoma cells in lymph nodes previously considered to be benign for an overall increase of 8%, greatest in the setting of untreated retroperitoneal lymph node dissection with clinical suspicion. However, immunohistochemistry did not convert any entirely negative specimen to positive. Future studies will be useful to determine whether the small volume of disease detected by immunohistochemistry has the same impact as routinely detected lymph node metastases.

Prediction of Retroperitoneal Histology in Metastatic Nonseminomatous Testicular Cancer Patients after Chemotherapy Based on Clinical and Radiological Parameters

Introduction: We retrospectively analysed the predictive value of numerous clinical and radiological parameters to identify a predictor for either necrosis or residual tumors found by retroperitoneal lymph node dissection (RPLND) histology in a collection of nonseminomatous germ cell tumor (NSGCT) patients. Materials and Methods: A database was created containing detailed clinical, radiological and histological information of all consecutive NSGCT patients, who underwent post chemotherapy RPLND between 1984 and 2007. According to the histology of the RPLND specimen, patients were assigned to the “necrosis-only” group or the “residual tumor” group. Associations between clinical and radiological parameters and histology of RPLND were analyzed. Results: Histology of dissected masses showed complete necrosis in 57.4% of patients and residual tumors in 42.6% (3.1% viable cancer and 39.5% teratoma). Univariate analysis showed significant correlation of RPLND histology and the following parameters: teratoma-positive primary tumors, pre-chemotherapy α-fetoprotein (AFP) and – less pronounced – human chorionic gonadotropin levels, size of metastatic mass, total volume of metastatic retroperitoneal lymph nodes, and percentage of volume reduction. The best prediction for necrosis in RPLND histology was in patients with no evidence of teratomatous elements in primary tumors and with normal pre-chemotherapy AFP levels and small lymph nodes. Stepwise multivariate logistic regression analysis confirmed AFP < 10 ng/ml as the best independent predictor for only necrosis in RPLND histology. Conclusions: At the present time we still consider all patients with metastatic NSGCT as candidates for a post-chemotherapy RPLND, arguing that in experienced hands mortality is negligible and morbidity is low and therefore not relevant compared to the risk of missing a residual tumor.

Differentiated rhabdomyomatous tumors after chemotherapy for metastatic testicular germ-cell tumors: a clinicopathological study of seven cases mandating separation from rhabdomyosarcoma

To gain insight concerning prognosis, we investigated seven cases of post-chemotherapy retroperitoneal lymph-node dissections from patients with testicular germ-cell tumors that contained sizable nodules of differentiated skeletal muscle, but that lacked both a primitive cellular component and mitotic activity. The patients were 18–28 years old at the time of retroperitoneal lymph-node dissection. All had a previous non-seminomatous germ-cell tumor of the testis, five of which had a teratoma component. In one the testicular tumor had foci of embryonal rhabdomyosarcoma. The retroperitoneal lymph-node dissections were performed 0.2–4.7 years after orchiectomy, all following cisplatin-based chemotherapy, and contained rhabdomyomatous tumors that ranged from 0.8–5 cm. These consisted of nodular to diffuse aggregates of fetal-type rhabdomyocytes with central to peripheral nuclei and abundant, eosinophilic, fibrillary cytoplasm with occasional cross striations. Elongated myotubes with multiple nuclei in a common sarcoplasm occurred at least focally in all cases. Mild to moderate nuclear atypia, including nuclear enlargement and nucleolar prominence, was present, but mitotic activity, necrosis, and a primitive cellular component were absent. All but one retroperitoneal lymph-node dissection also contained other teratomatous elements. Follow-up in six patients showed three were disease free at 2.2–3.4 years; two developed recurrent teratoma at 1.3–3.7 years; and a sixth developed recurrent teratoma at 0.5 and 2 years, followed at 17 years by progressive tumor with elevated α-fetoprotein. No patient with available follow-up developed progressive sarcoma. We conclude that rhabdomyomatous tumors in retroperitoneal lymph-node dissection specimens after chemotherapy for metastatic testicular germ-cell tumors show clinical behavior similar to teratoma rather than rhabdomyosarcoma. We believe the most likely explanation for the finding of pure rhabdomyomatous tumors in this setting, a phenomenon sometimes termed ‘cytodifferentiation,‘ is selective persistence of differentiated tumor cells because of chemotherapy.

Results of retroperitoneal lymph node dissection after chemotherapy in patients with pure seminoma in the orchidectomy specimen but elevated serum α‐fetoprotein

To determine the incidence of necrosis, teratoma, and active cancer in specimens at retroperitoneal lymph node dissection (RPLND) after chemotherapy in patients who presented with a pure seminoma primary tumour and an elevated serum alpha-fetoprotein (AFP) level at diagnosis who underwent surgery. A retrospective review of the Indiana University testis cancer database from 1980 to 2004 was performed to identify all patients with metastasic germ cell cancer, pure seminoma in the orchidectomy specimen, and an elevated AFP level. In all, 42 patients were identified; two with nonseminomatous germ cell cancer in the contralateral testicle were excluded. RPLND pathology in the 40 patients showed necrosis in 13 (32.5%), teratoma in 12 (30%), and cancer in 15 (37.5%). The histological subtype of the 15 cancer specimens at RPLND was pure seminoma in two, embryonal in three, yolk sac in seven, variant in one, and mixed elements in two (one with seminoma and yolk sac, and one with embryonal and variant). In all, 20 patients presented with a serum AFP level of <1000 microg/mL with nine (45%) having teratoma only in the retroperitoneum in contrast to 20 patients with an AFP level of >1000 microg/mL with three (15%) having teratoma only in the retroperitoneum (P = 0.04). The level of serum AFP did not predict for active cancer in the retroperitoneum (P = 0.5). RPLND in patients after chemotherapy who presented with pure seminoma in the orchidectomy specimen and an elevated AFP do not have a high probability of finding necrosis only in the RPLND specimen. In fact, the prevalence of persistent cancer is higher compared with the general group of patients that have RPLND after chemotherapy.

Results of Bilateral Nerve Sparing Laparoscopic Retroperitoneal Lymph Node Dissection for Testicular Cancer

We evaluated the feasibility and early oncological outcome of a laparoscopic nerve sparing bilateral retroperitoneal lymph node dissection. The surgical technique is described. From July 2004 to December 2007 a total of 42 patients with nonseminomatous germ cell tumor (21 with stage I, 2 with stage IIA marker negative and 19 with post-chemotherapy stage IIB disease) underwent transperitoneal bilateral laparoscopic retroperitoneal lymph node dissection. The sympathetic trunk and postganglionic nerves were identified, and lymphatic tissue was dissected between the nerves. Patients with clinical stage I and IIA disease that was lymph node positive at laparoscopic retroperitoneal lymph node dissection did not receive additional chemotherapy. Surgery was successfully completed in all patients and no conversion to open surgery was necessary. Mean operative time was 323 minutes. No intraoperative complications occurred. Of patients with stage I and marker negative stage IIA disease active tumor was found in 5 retroperitoneal lymph node dissection specimens, and no patients had recurrence. Of 19 patients with post-chemotherapy stage IIB disease teratoma was found in the lymphatic tissue in 4 (21.0%). No retroperitoneal recurrence was observed. Pulmonary metastases developed 9 months after surgery in 1 patient with stage I disease and negative retroperitoneal histology, and were treated successfully. All patients are currently free of disease at a mean followup of 17.2 months. Antegrade ejaculation was preserved in 36 patients (85.7%). Bilateral nerve sparing laparoscopic retroperitoneal lymph node dissection is feasible and associated with low morbidity if performed by experienced hands. The oncological efficacy of this approach is promising and currently under evaluation.

Laparoscopic retroperitoneal lymph node dissection for nonseminomatous germ cell tumors: long-term oncologic outcomes

Laparoscopic retroperitoneal lymph node dissection was first described in 1992, and has become more commonly practiced at certain centers. Laparoscopic retroperitoneal lymph node dissection may be less morbid than open retroperitoneal lymph node dissection, but more costly. Controversy exists, however, regarding the oncologic adequacy of the procedure. The published literature regarding the oncologic outcomes of laparoscopic retroperitoneal lymph node dissection is reviewed herein. Laparoscopic retroperitoneal lymph node dissection has not been as widely adopted as other laparoscopic procedures for genitourinary malignancy. There have only been seven publications in the last 3 years, often coming from the same centers. Recently there has been a change in practice with a greater effort to perform therapeutic laparoscopic retroperitoneal lymph node dissection and not simply a staging procedure. Adjuvant chemotherapy is no longer routinely offered to all patients with positive nodes. The impressive cure rate and decreasing morbidity associated with conventional open retroperitoneal lymph node dissection are difficult to improve upon. While on par with open retroperitoneal lymph node dissection series, the current oncologic outcomes are difficult to attribute to successful laparoscopic retroperitoneal lymph node dissection alone. Most patients with viable tumor in the retroperitoneal lymph node dissection specimen received chemotherapy. Thus, we must await follow-up of the patients who declined adjuvant chemotherapy after laparoscopic retroperitoneal lymph node dissection or the results of more recent initiatives with laparoscopic retroperitoneal lymph node dissection alone.

Malignant transformation of testicular teratoma: A chemoresistant phenotype

Purpose To review our experience in the management of malignant transformation of teratoma (MTT). Materials and methods Nine patients with MTT were identified from January 1980 to August 2005, with all pathological specimens re-reviewed by a single genitourinary pathologist. Results Two patients presented with clinical stage I disease in which malignant transformation occurred within the primary testis tumor (rhabdomyosarcoma in 1 and adenocarcinoma in 1). These patients underwent a primary retroperitoneal lymph node dissection (RPLND). No viable tumor was identified in the specimen, and both patients were alive without disease at 16 months follow-up. Of the remaining 7 patients, the clinical stages were IIA (N = 1), IIB (N = 3), and III (N = 3), and all were treated with chemotherapy followed by RPLND. The MTT histology of these RPLND specimens consisted of adenocarcinoma (N = 3), rhabdomyosarcoma (N = 2), angiosarcoma (N = 1), and astrocytoma (N = 1). Following preoperative chemotherapy, a significant radiologic response (defined as more than a 25% reduction in maximum tumor circumferential diameter) was demonstrated in 1 patient, and normalization of serum tumor markers was demonstrated in 6. At a mean follow-up of 5 years, 3 of these 7 patients were alive with no evidence of disease, 1 had persistent disease, and 3 had died of disease, and their median disease-specific survival duration was 4.6 years. Conclusions In our experience, MTT is significantly resistant to current chemotherapeutic regimens, as demonstrated by its poor radiologic response to treatment. Alternative therapeutic strategies targeted to MTT are thus needed.

Surgical Management of Growing Teratoma Syndrome: The M. D. Anderson Cancer Center Experience

We defined the growth rate and reviewed our experience in the surgical management of growing teratoma syndrome in patients with nonseminomatous germ cell tumors. Nine patients were clinically diagnosed with growing teratoma syndrome at our center from 1980 to 2003. The defining criteria of growing teratoma syndrome were growing metastatic mass in the retroperitoneum or other site consisting entirely of mature teratoma detected on serial abdominal/pelvic imaging during chemotherapy, and a significant decrease in or normalization of tumor markers. Precise serial abdominal/pelvic radiological measurements of the retroperitoneal masses were available for 7 of 9 patients. The median growth rate of growing teratoma syndrome measured as the increase in diameter during chemotherapy was 0.7 cm per month. The median growth rate measured as the increase in tumor volume was 12.9 cc per month. Median time from the start of chemotherapy to retroperitoneal lymph node dissection was 5.4 months (range 2.7 to 21.6). Pathological evaluation of the retroperitoneal lymph node dissection specimen revealed teratoma with no viable tumor in all 9 cases. There were 2 intraoperative complications (1 aortic and 1 ureteral injury) and 4 postoperative complications (2 ileus, 1 acute pancreatitis and 1 chylous ascites). At a median followup of 2 years 7 patients were alive without disease, 1 died of postoperative sepsis and 1 died of an unknown cause. The growth rate of growing teratoma syndrome can vary significantly, which must be taken into account when evaluating cases. Retroperitoneal lymph node dissection is an effective treatment for growing teratoma syndrome, providing excellent local control and a low risk of progression.