Automated Quantitative CD8+ Tumor-Infiltrating Lymphocytes and Tumor Mutation Burden as Independent Biomarkers in Melanoma Patients Receiving Front-Line Anti-PD-1 Immunotherapy.

BACKGROUND: CD8+ tumor-infiltrating lymphocyte (TIL) predicts response to anti-PD-(L)1 therapy. However, there remains no standardized method to assess CD8+ TIL in melanoma, and developing a specific, cost-effective, reproducible, and clinically actionable biomarker to anti-PD-(L)1 remains elusive. We report on the development of automatic CD8+ TIL density quantification via whole slide image (WSI) analysis in advanced melanoma patients treated with front-line anti-PD-1 blockade, and correlation immunotherapy response. METHODS: Seventy-eight patients treated with PD-1 inhibitors in the front-line setting between January 2015 and May 2023 at the University of Pittsburgh Cancer Institute were included. CD8+ TIL density was quantified using an image analysis algorithm on digitized WSI. Targeted next-generation sequencing (NGS) was performed to determine tumor mutation burden (TMB) in a subset of 62 patients. ROC curves were used to determine biomarker cutoffs and response to therapy. Correlation between CD8+ TIL density and TMB cutoffs and response to therapy was studied. RESULTS: Higher CD8+ TIL density was significantly associated with improved response to front-line anti-PD-1 across all time points measured. CD8+ TIL density ≥222.9 cells/mm2 reliably segregated responders and non-responders to front-line anti-PD-1 therapy regardless of when response was measured. In a multivariate analysis, patients with CD8+ TIL density exceeding cutoff had significantly improved PFS with a trend toward improved OS. Similarly, increasing TMB was associated with improved response to anti-PD-1, and a cutoff of 14.70 Mut/Mb was associated with improved odds of response. The correlation between TMB and CD8+ TIL density was low, suggesting that each represented independent predictive biomarkers of response. CONCLUSIONS: An automatic digital analysis algorithm provides a standardized method to quantify CD8+ TIL density, which predicts response to front-line anti-PD-1 therapy. CD8+ TIL density and TMB are independent predictors of response to anti-PD-1 blockade.

Successful use of montelukast in eosinophilic gastroenteritis: a case report and a literature review.

BACKGROUND: Eosinophilic gastrointestinal disorders, also known as eosinophilic gastroenteritis, are rare inflammatory conditions characterized by eosinophilic infiltration of different parts of the gastrointestinal tract, along with peripheral eosinophilia in most cases. Other known causes for gut eosinophilic infiltration must be excluded to confirm the diagnosis of eosinophilic gastroenteritis. Symptoms of the disorder depend on the affected gastrointestinal tract segment and depth of involvement. Treatment includes systemic glucocorticoids and/or dietary therapy with an empiric elimination diet. Second line therapies include the leukotriene receptor antagonist montelukast, and other anti-allergy drugs such as mast cell stabilizers (including cromolyn and the H1-antihistamine ketotifen), suplatast tosilate which is a selective Th-2 cytokines (IL-4 and IL-5) inhibitor, and the monoclonal anti-IgE antibody omalizumab. We report a case of eosinophilic gastroenteritis who was successfully treated and achieved remission with montelukast as an initial monotherapy. Upon extensive literature review, this represents the second reported adult case of eosinophilic gastroenteritis who responds to montelukast alone as a first line therapy. CASE PRESENTATION: A 49-year-old female presented with recurrent abdominal pain, vomiting, diarrhea and unexplained eosinophilia. She was diagnosed with eosinophilic gastroenteritis and was successfully treated with montelukast monotherapy. After 7 days of therapy, the patient responded well and had complete resolution of her gastrointestinal symptoms and peripheral eosinophilia. Patient remained in remission on follow-up after 12 months. We reviewed the literature for leukotriene antagonist use in the treatment of eosinophilic gastroenteritis and included the cases treated with the leukotriene antagonist montelukast as an initial therapy or as a second line therapy for refractory disease. CONCLUSION: Montelukast may be an effective treatment for eosinophilic gastroenteritis, either alone or in combination with systemic steroids or ketotifen. Our patient is the second reported adult case of eosinophilic gastroenteritis who responded to montelukast alone as a first line therapy. Further studies and clinical trials are required to confirm efficacy compared to standard therapy.

Suspected Autosomal Recessive Polycystic Kidney Disease but Cerebellar Vermis Hypoplasia, Oligophrenia Ataxia, Coloboma, and Hepatic Fibrosis (COACH) Syndrome in Retrospect, A Delayed Diagnosis Aided by Genotyping and Reverse Phenotyping: A Case Report and A Review of the Literature.

The clinical features of cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis (COACH) characterize the rare autosomal recessive multisystem disorder called COACH syndrome. COACH syndrome belongs to the spectrum of Joubert syndrome and related disorders (JSRDs) and liver involvement distinguishes COACH syndrome from the rest of the JSRD spectrum. Developmental delay and oculomotor apraxia occur early but with time, these can improve and may not be readily apparent or no longer need active medical management. Congenital hepatic fibrosis and renal disease, on the other hand, may develop late, and the temporal incongruity in organ system involvement may delay the recognition of COACH syndrome. We present a case of a young adult presenting late to a Renal Genetics Clinic for evaluation of renal cystic disease with congenital hepatic fibrosis, clinically suspected to have autosomal recessive polycystic kidney disease. Following genetic testing, a reevaluation of his medical records from infancy, together with reverse phenotyping and genetic phasing, led to a diagnosis of COACH syndrome.

Utilizing digital pathology and immunohistochemistry of p53 as an adjunct to molecular testing in myeloid disorders.

TP53 mutation status guides early therapeutic decisions in the treatment of clonal myeloid disorders and serves as a simple means of monitoring response to treatment. We aim here to develop a standardized protocol for evaluating TP53 mutation status in myeloid disorders using immunohistochemistry assisted by digital image analysis and further compare this approach to manual interpretation alone. To accomplish this, we obtained 118 bone marrow biopsies from patients with hematologic malignancy and molecular testing for mutations associated with acute myeloid leukemia was performed. Clot or core biopsy slides were stained for p53 and digitally scanned. Overall mutation burden was assessed digitally using two different metrics to determine positivity, compared to the results of manual review, and correlated with molecular results. Using this approach, we found that digital analysis of immunohistochemistry stained slides performed worse than manual categorization alone in predicting TP53 mutation status in our cohort (PPV 91%, NPV 100% vs. PPV 100%, NPV 98%). While digital analysis reduced inter- and intraobserver variability when assessing mutation burden, there was poor correlation between the quantity and intensity of p53 staining and molecular analysis (R2 = 0.204). Therefore, digital image analysis of p53 immunohistochemistry accurately predicts TP53 mutation status as confirmed by molecular testing but does not offer a significant advantage over manual categorization alone. However, this approach offers a highly standardized methodology for monitoring disease status or response to treatment once a diagnosis has been made.

Strong Annexin A10 Expression Supports a Pancreatic Primary and Combined Annexin A10, Claudin 18, and SOX2 Expression Supports an Esophagogastric Origin in Carcinomas of Unknown Primary.

Primary tumor site determination for gastrointestinal (GI) tract and pancreaticobiliary (PB) tree carcinomas that present as metastasis of unknown primary can be problematic. Annexin A10 (ANXA10), claudin 18 (CLDN18), and trefoil factor 1 (TFF1) have been identified through expression profiling as markers of gastric lineage commitment; sex-determining region Y (SRY)-box transcription factor 2 (SOX2) expression has been reported in several tumor types, including gastric adenocarcinomas. We evaluated the diagnostic utility of immunohistochemistry for ANXA10, CLDN18, SOX2, and TFF1 for determining the site of origin for GI/PB adenocarcinomas. Immunohistochemistry for all 4 markers was performed on tissue microarrays including 559 GI/PB tumors and 421 other tumors. H-scores were calculated as the product of the intensity (0 to 3) and extent (percentage, 0% to 100%) of staining. Positive staining was defined as >5% staining. ANXA10 expression was most frequent in pancreatic adenocarcinomas when compared with all other GI/PB tumors (96.4% vs. 43.5%, P <0.001). Strong staining for ANXA10 (H-score ≥200) distinguished pancreatic ductal adenocarcinoma from intrahepatic cholangiocarcinoma and adenocarcinomas of the gallbladder and colorectum (69.6% vs. 0%, P <0.001). Triple positivity for ANXA10, CLDN18, and SOX2 was more frequent in esophagogastric tumors than in other GI/PB tumors (22.6% vs. 4.1%; P <0.001). TFF1 expression was observed in nearly all tumor types. Staining for ANXA10, CLDN18, and SOX2 as part of a panel may aid in distinguishing esophagogastric adenocarcinomas from lower GI/PB tumors. ANXA10 staining may be particularly useful in distinguishing pancreatic adenocarcinomas from intrahepatic cholangiocarcinoma and adenocarcinomas of the gallbladder and colorectum.

Manipulation of Redox Metabolism Using Pharmacologic Ascorbate Opens a Therapeutic Window for Radio-Sensitization by ATM Inhibitors in Colorectal Cancer.

PURPOSE: Ataxia telangiectasia mutated kinase (ATM) inhibitors are potent radiosensitizers that regulate DNA damage responses and redox metabolism, but they have not been translated clinically because of the potential for excess normal tissue toxicity. Pharmacologic ascorbate (P-AscH-; intravenous administration achieving mM plasma concentrations) selectively enhances H2O2-induced oxidative stress and radiosensitization in tumors while acting as an antioxidant and mitigating radiation damage in normal tissues including the bowel. We hypothesized that P-AscH- could enhance the therapeutic index of ATM inhibitor-based chemoradiation by simultaneously enhancing the intended effects of ATM inhibitors in tumors and mitigating off-target effects in adjacent normal tissues. METHODS AND MATERIALS: Clonogenic survival was assessed in human (human colon tumor [HCT]116, SW480, HT29) and murine (CT26, MC38) colorectal tumor lines and normal cells (human umbilical vein endothelial cell, FHs74) after radiation ± DNA repair inhibitors ± P-AscH-. Tumor growth delay was assessed in mice with HCT116 or MC38 tumors after fractionated radiation (5 Gy × 3) ± the ATM inhibitor KU60019 ± P-AscH-. Intestinal injury, oxidative damage, and transforming growth factor ß immunoreactivity were quantified using immunohistochemistry after whole abdominal radiation (10 Gy) ± KU60019 ± P-AscH-. Cell cycle distribution and ATM subcellular localization were assessed using flow cytometry and immunohistochemistry. The role of intracellular H2O2 fluxes was assessed using a stably expressed doxycycline-inducible catalase transgene. RESULTS: KU60019 with P-AscH- enhanced radiosensitization in colorectal cancer models in vitro and in vivo by H2O2-dependent oxidative damage to proteins and enhanced DNA damage, abrogation of the postradiation G2 cell cycle checkpoint, and inhibition of ATM nuclear localization. In contrast, concurrent P-AscH- markedly reduced intestinal toxicity and oxidative damage with KU60019. CONCLUSIONS: We provide evidence that redox modulating drugs, such as P-AscH-, may facilitate the clinical translation of ATM inhibitors by enhancing tumor radiosensitization while simultaneously protecting normal tissues.

Education Case: Hereditary Thrombophilia With Double Heterozygous Factor V Leiden and Factor II c.*97G>A Mutations.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Markers of Follicular Helper T Cells Are Occasionally Expressed in T-Cell or Histiocyte-Rich Large B-Cell Lymphoma, Classic Hodgkin Lymphoma, and Atypical Paracortical HyperplasiaA Diagnostic Pitfall For T-Cell Lymphomas of T Follicular Helper Origin.

OBJECTIVES: Follicular helper T cell (TFH) markers are expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma of the TFH phenotype (PTCL-TFH). However, differential expression and coexpression of these markers in benign and other malignant lymphoid proliferations have not been well studied. METHODS: We performed programmed death-1 (PD-1), C-X-C motif chemokine ligand 13 (CXCL13), inducible costimulator (ICOS), CD10, and B-cell lymphoma 6 protein (BCL-6) immunohistochemistry on AITL, PTCL not otherwise specified (PTCL-NOS), PTCL-TFH, T-cell or histiocyte-rich large B-cell lymphoma (THRLBCL), classic Hodgkin lymphoma (CHL), atypical paracortical hyperplasia (PCH), progressive transformation of germinal centers (PTGC), and reactive follicular hyperplasia (RFH). RESULTS: CXCL13 and ICOS were more sensitive but less specific for AITL than PD-1, CD10, and BCL-6. Moreover, 74% of AITL (none of PTCL-NOS or PTCL-TFH) coexpressed more than 2 TFH markers. In background T cells of THRLBCL, 70% of cases coexpressed more than 1 marker. The background T cells of CHL expressed all TFH markers except CD10 in all cases. In addition, 13% of PCH cases coexpressed more than 1 marker. In RFH and PTGC, all markers were expressed mainly in germinal centers with rare extrafollicular staining. CONCLUSIONS: AITL, PTCL-NOS, and PTCL-TFH show differential expression of TFH markers. AITL frequently coexpresses more than 2 TFH markers. TFH markers can be expressed in PCH and in background T cells of THRLBCL and CHL. Consequently, caution should be used before a diagnosis of AITL is established, particularly with limited samples.

Paraneoplastic leukemoid reaction: Case report and review of the literature.

OBJECTIVES: We recently encountered a patient with unexplained hyperleukocytosis (105.4 K/µL at presentation), subsequently found to have colon cancer with a marked tumor-associated neutrophilic infiltrate; the leukocytosis abruptly improved after tumor removal. Paraneoplastic leukemoid reaction (PLR) is a rare entity, occurring due to tumor cytokine secretion (typically granulocyte-colony stimulating factor [G-CSF]). We describe a case and aggregate results of previously published cases. METHODS: We reviewed the English-language literature for all prior reports of PLR, recording age, gender, histologic diagnosis, WBC count, G-CSF level, and overall survival. We analyzed clinicopathologic variables' impact on survival. RESULTS: We identified 179 cases (mean age 64; 72 % M). Adeno-, squamous cell, sarcomatoid, and undifferentiated carcinomas accounted for >70 %. Esophagus, gallbladder, lung, liver, and pancreas were the most common primaries. At time of publication 81 % of patients had died, with mean overall survival of 4 months. There was no correlation between WBC count and G-CSF level. On univariate analysis, WBC count was the only variable associated with survival (P = 0.03). Patients with WBC counts >100 K/µL were twice as likely to die as those with counts from 11 K to 40 K/µL. CONCLUSIONS: PLR, typically carcinoma-associated, is characterized by dismal prognosis. The WBC count is inversely related to survival. Knowledge of this phenomenon militates against protracted, expensive work ups. In malignant neoplasms with prominent neutrophilic stroma, the pathologist should correlate with the WBC count and, if markedly elevated (>40 K/µL), raise consideration for PLR.

Case of a Large Pedunculated Biliary Cholesterol Polyp With Osseous Metaplasia.

Cholesterol polyps are the most common benign gallbladder polyps and are usually seen in a background of cholesterolosis. Rarely, they can harbor foci of osseous metaplasia, which is an event of uncertain clinical significance that might be confused with cholelithiasis clinically or radiologically. Herein we report the case of a 78-year-old female with a 1.8-cm pedunculated polyp arising in the gallbladder body. Histologic examination showed microscopic foci of osseous metaplasia, characterized by heterotropic bone trabeculae rimmed by osteoblasts and surrounded by osteoclast giant cells. To the best of our knowledge, this case is the third case report of a cholesterol polyp with osseous metaplasia in the English literature. We also review the relative pathogenesis, clinical and pathologic findings, and previous reports.

Paraneoplastic leukemoid reactions induced by cytokine-secreting tumours.

Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone marrow infiltration by that solid tumour. The clinical presentation is widely variable, and therefore challenging. If the underlying malignancy is not clinically apparent, PLR could be mistaken for myeloproliferative neoplasms, altering the patient's management. CSTs are highly aggressive tumours associated with a poor prognosis due to multiple mechanisms. Localising and treating the underlying malignancy is the mainstay of treatment. Both the treating clinician and the pathologist should keep a high level of suspicion for this entity in patients having unexplained leukocytosis. We herein discuss the underlying mechanisms, clinical presentation, pathological features, differential diagnosis and prognosis of this rare entity. An emphasis on the role of the pathologist is provided since the lack of knowledge on this entity can lead to dramatic effects on the patient, including unnecessary diagnostic testing and treatments.

Vertebral hemangiomas: Diagnosis and management. A single center experience.

OBJECTIVE: Vertebral hemangiomas (VH) are common benign lesions involving the spine. Owing to the multiplicity of treatments, the management of VH has not always been consistent. In this retrospective review of a single center experience, indications and options available for the treatment of VH are outlined. PATIENTS AND METHODS: This is a retrospective review of 71 cases of VH managed at our institution between 2005 and 2019. Sixty of these cases were managed non-operatively, with 11 cases undergoing operative intervention. Of the 11 cases that underwent surgery, there were 2 cervical cases and 9 in the thoracic spine. Ten cases were symptomatic, and 1 incidental. Three patients presented with localized pain, and the remaining 7 had neurological deficit. Decompression with maximal resection of the hemangioma was undertaken in 10 cases, and vertebroplasty in 1. RESULTS: Of the 60 patients who were managed non-operatively, 13 patients had presented with back/neck pain, with the remaining 47 patients being asymptomatic and diagnosed incidentally. Among the 13 symptomatic patients, all were offered surgical intervention for pain management, but given lack of severity of symptoms, all had opted for conservative approaches of pain control. In the 11 patients who underwent surgery, the preoperative diagnosis of VH was accurate in all but 1 case. There were 2 cervical cases treated with corpectomy. One patient was treated with vertebroplasty, and the remaining 8 with decompression. Radiation was used in 2 cases. Of the 10 patients undergoing decompression, 7 patients had improvement of the neurologic deficit, with resolution of pain in the remaining 3. None of our cases demonstrated deterioration. CONCLUSION: VH are often discovered incidentally during evaluation of spinal pain. Except in rare cases, the diagnosis of VH is made correctly from the radiographic and MRI studies. Observation for the asymptomatic lesion is appropriate. For VH presenting with deficit or intractable pain, decompressive surgery is recommended. Radiation is appropriate in cases of recurrent VH.

Survival and metastasis in muscle-invasive bladder cancer patients who present with indeterminate pulmonary nodules before treatment.

BACKGROUND: Indeterminate pulmonary nodules (IPNs) are common during initial evaluation of bladder cancer patients. Their significance is still unknown. OBJECTIVE: Determine the significance of indeterminate pulmonary nodules, including their size and number, in muscle-invasive bladder cancer patients before definitive local therapy by surgery or chemo-radiotherapy. DESIGN: Retrospective review, single-center descriptive study. SETTINGS: A tertiary cancer center. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent definitive local therapy of bladder cancer by either radical cystectomy and lymph node dissection or with chemo-radiotherapy between January 1997 and December 2015. We identified patients with baseline CT scans done during staging work-up prior to definitive treatment. Patients with proven clinical metastasis at pre.sentation were excluded, while patients who had IPNs without features suggesting metastasis were included. MAIN OUTCOME MEASURES: Disease-free survival and overall survival. SAMPLE SIZE: 168 patients. RESULTS: The median age of patients at diagnosis was 66 years; 92% were males and 56% were smokers. IPNs (3 cm or less) were present in 74 patients (44.0%). Median follow-up was 24 months. IPNs were associated with decreased disease-free survival while IPNs did not affect the overall survival (HR=1.9; 95% CI: 1.1-3.4); P=.01 and HR=1.5; 95% CI: 1.0-2.5); P=.07, respectively. In addition, nodules greater than 1 cm had reduced disease-free survival (HR=2.5; 95% CI: 1.1-5.9); P=.04. In the surgery group (n=126), the median number of lymph nodes excised was 14, with no association between lymph nodes status and the presence of IPNs (P=.08). CONCLUSION: The presence of IPNs, especially nodules greater than 1 cm had a negative effect on disease-free survival. Tailored postoperative follow-up of these patients may impact disease outcomes. LIMITATIONS: The retrospective nature, the lack of standardized preoperative imaging protocols, the lack of a central radiology review and the small number of patients. CONFLICT OF INTEREST: None.

Trends of partial and radical nephrectomy in managing small renal masses.

OBJECTIVE: Use of partial nephrectomy (PN) for renal tumors appears to have relatively lower incidence rates in Jordan. We sought to characterize its trend at King Hussein Cancer Center for the last 10 years. MATERIAL AND METHODS: A retrospective review of our renal cell cancer data was performed. We identified 169 patients who had undergone surgery for renal tumors measuring ≤7 cm between 2005 and 2015. We characterized tumor size, pathology, type of surgery and clinical outcomes. Factors associated with the use of PN were evaluated using univariable and multivariable logistic regression models. RESULTS: Of the 169 patients, 34 (20%) and 135 (80%) had undergone partial and radical nephrectomy (RN) respectively for tumors ≤7 cm in diameter. Total number of 48 patients with tumors of ≤4 cm in diameter had undergone either PN (n=19; 40%) or RN (n=29; 60%). The frequency of PN procedures steadily increased over the years from 6% in 2005-2008, to 32% in 2013-2015, contrary to RN which was less frequently applied 94% in 2005-2008, and 68% in 2013-2015. In multivariable analysis, delayed surgery (p=0.01) and smaller tumor size (p=0.0005) were significant independent predictors of PN. During follow-up period, incidence of metastasis was lower in PN versus RN (13% and 32%, respectively, p=0.043). Local recurrence rates were not significantly different between PN (6.9%) and RN (7.2%) (p=0.99). The mean tumor sizes for patients who had undergone PN and RN were 4.1 and 5.5 cm respectively, (p<0.0001). The mean follow-up period for PN was 20 months, and for RN 33 months, (p=0.0225). CONCLUSION: Partial nephrectomy for small renal tumors is relatively less frequently applied in Jordan, however an increase in its use has been observed over the years. Our data showed lower rates of distant metastasis and similar rates of local recurrence in favor of PN.

Clinicopathologic Features of Translocation Renal Cell Carcinoma.

BACKGROUND: Translocation renal cell carcinomas (TFE3 RCC) are associated with variable genetic rearrangements of the TFE3 gene on chromosome Xp11.2. Translocation tumors represent 1% to 5% of all cases of RCC, with the greatest frequency among children and young adults. We sought to characterize the clinicopathologic features of translocation RCC at a Middle Eastern institution. MATERIALS AND METHODS: The clinical and pathologic data from a single institution were retrospectively reviewed. A total of 14 patients with translocation RCC had been diagnosed from 2005 to 2014. The outcome measures included patient characteristics, clinical manifestations, pathologic features, treatment outcomes, cancer-specific survival, and progression-free survival. RESULTS: The mean age at diagnosis was 35 years. Of the 14 patients, 5 were female. Translocation RCC was an incidental diagnosis for all but 2 of the 14 patients. The mean tumor size was 9 cm; 1 patient had bilateral tumors, and 3 presented with positive lymph nodes. Three patients underwent partial nephrectomy. Three patients had developed metastasis at 4 months, 5 months, and 3 years after diagnosis. One patent had died 4 months after surgery and one had died 21 months after surgery (both of metastases). The disease-free survival rate was 71% at a mean follow-up of 31 months. CONCLUSION: Translocation RCC is a rare and potentially aggressive subtype of kidney cancer. An overall survival of > 3 years has been noted, unless metastasis is present at diagnosis.

Clinico-pathological outcomes of post- primary and salvage chemotherapy retroperitoneal lymph node dissection for mixed germ cell tumors, King Hussein Cancer Center experience.

OBJECTIVE: We sought to characterize clinical and pathologic outcomes of advanced mixed germ cell tumors after retroperitoneal lymph node dissection for post-chemotherapy residual masses. MATERIAL AND METHODS: Between January 2006 and November 2015, 56 patients underwent retroperitoneal lymph node dissection (RPLND) for residual masses of greater than 1 cm after receiving either primary chemotherapy or salvage chemotherapy. Retrospective review of the patients' characteristics, clinical, pathological, and treatment outcomes were performed after institutional review board (IRB) and ethics committee approval. RESULTS: The mean age at diagnosis was 30 years. Ninety percent of the patients received 3-4 cycles of BEP (bleomycin/etoposide/cisplatin) as primary chemotherapy, and 29% of them salvage chemotherapy prior to lymph node dissection. The mean size of the residual masses after chemotherapy was 6 cm. The histological findings were necrosis in 30%, viable tumor in 34% and teratoma in 36% of the retroperitoneal masses. The mean time to relapse after RPLND was 11 months, out of 9 relapses, 6 were in the retroperitoneum, 1 in the lung and 1 in the kidney and 1 in the contralateral testicle. CONCLUSION: Our results indicated higher incidence of viable germ cell tumor in the retroperitoneal residual masses after primary and salvage chemotherapy when compared with previously reported global incidence rates.