Utilization of NKX3.1, P501S, Prostate-Specific Antigen, and Steroidogenic Factor 1 to Distinguish Malignant Leydig Cell Tumor From Metastatic Prostatic Adenocarcinoma to the Testis.

CONTEXT.­: A recent study demonstrated that NKX3.1-positive staining can uncommonly be seen in testicular Sertoli cell tumors (1 of 4 cases). Also, it was reported that 2 of 3 Leydig cell tumors of the testis showed diffuse cytoplasmic staining for P501S, although it was unclear whether it was specific granular staining that defines true positivity. However, Sertoli cell tumors do not typically pose a diagnostic dilemma with metastatic prostate carcinoma to the testis. In contrast, malignant Leydig cell tumors, which are exceedingly rare, can closely resemble Gleason score 5 + 5 = 10 prostatic adenocarcinoma metastatic to the testis. OBJECTIVE.­: To evaluate the expression of prostate markers in malignant Leydig cell tumors and steroidogenic factor 1 (SF-1) in high-grade prostate adenocarcinoma, as no data are currently published on these topics. DESIGN.­: Fifteen cases of malignant Leydig cell tumor were collected from 2 large genitourinary pathology consult services in the United States from 1991 to 2019. RESULTS.­: All 15 cases were negative immunohistochemically for NKX3.1, and all 9 with available additional material were negative for prostate-specific antigen and P501S and positive for SF-1. SF-1 was negative immunohistochemically in a tissue microarray with cases of high-grade prostatic adenocarcinoma. CONCLUSIONS.­: The diagnosis of malignant Leydig cell tumor and its distinction from metastatic adenocarcinoma to the testis can be made immunohistochemically on the basis of SF-1 positivity and negativity for NKX3.1.

A rare case of bilateral testicular metastasis from ileocecal NET: multiparametric US detection.

Testicular metastasis are rare findings and bilateral metastasis of testes are extremely rare. Here we are describing for the first time a case of bilateral testicular metastasis in a patient with a known ileocecal valve NET using an in-depth ultra-sound studying including microvascular flow imaging (MV-flow), ultra-sound new technique, able to detect small vessel slow-signal.

Paratesticular metastasis arising from colonic mucinous adenocarcinoma: a rare case report.

Colonic mucinous adenocarcinoma rarely metastasizes to the paratesticular region, highlighting the importance of a correct diagnosis. We herein present a case involving a 65-year-old man with paratesticular carcinoma associated with scrotal swelling 1 year after radical resection of colon cancer. Computed tomography revealed a low-density tumor in the right scrotum and mild enhancement of the mass after administration of a contrast agent. The patient underwent radical surgery to remove the right testis. Pathology and immunohistochemistry revealed mucinous adenocarcinoma of the paratesticular tissue. The patient was discharged from the hospital 6 days after surgery. We reviewed the recent literature to summarize the clinical manifestations, treatments, and prognosis of this disease.

A comparative study of peri-operative outcomes for 100 consecutive post-chemotherapy and primary robot-assisted and open retroperitoneal lymph node dissections.

PURPOSE: To describe and compare differences in peri-operative outcomes of robot-assisted (RA-RPLND) and open (O-RPLND) retroperitoneal lymph node dissection performed by a single surgeon where chemotherapy is the standard initial treatment for Stage 2 or greater non-seminomatous germ cell tumour. METHODS: Review of a prospective database of all RA-RPLNDs (28 patients) and O-RPLNDs (72 patients) performed by a single surgeon from 2014 to 2020. Peri-operative outcomes were compared for patients having RA-RPLND to all O-RPLNDs and a matched cohort of patients having O-RPLND (20 patients). Further comparison was performed between all patients in the RA-RPLND group (21 patients) and matched O-RPLND group (18 patients) who had previous chemotherapy. RA-RPLND was performed for patients suitable for a unilateral template dissection. O-RPLND was performed prior to the introduction of RA-RPLND and for patients not suitable for RA-RPLND after its introduction. RESULTS: RA-RPLND showed improved peri-operative outcomes compared to the matched cohort of O-RPLND-median blood loss (50 versus 400 ml, p < 0.00001), operative duration (150 versus 195 min, p = 0.023) length-of-stay (1 versus 5 days, p < 0.00001) and anejaculation (0 versus 4, p = 0.0249). There was no statistical difference in complication rates. RA-RPLND had lower median lymph node yields although not significant (9 versus 13, p = 0.070). These improved peri-operative outcomes were also seen in the post-chemotherapy RA-RPLND versus O-RPLND analysis. There were no tumour recurrences seen in either group with median follow-up of 36 months and 60 months, respectively. CONCLUSIONS: Post-chemotherapy RA-RPLND may have decreased blood loss, operative duration, hospital length-of-stay and anejaculation rates in selected cases and should, therefore, be considered in selected patients. Differences in oncological outcomes require longer term follow-up.

Are tyrosine kinase inhibitors an effective treatment in testicular metastases from kidney cancer? Case report.

Testicular metastases from renal cell carcinoma (RCC) are extremely rare. Tyrosine kinase inhibitors (TKI) are the cornerstone of systemic therapy for metastatic RCC. We report a case of testicular metastasis in a 72-year-old patient with RCC that developed 17 years after nephrectomy and response to TKI treatment, a retrospective literature search on testicular metastases from RCC, and the indirect evidence described in the literature on the efficacy of chemotherapy and target therapy on testicular lesions.

Expression of programmed death ligand-1 (PD-L1) in metastatic and postchemotherapy viable testicular germ cell tumors.

INTRODUCTION: Chemotherapy for testicular germ cell tumors (GCT) is highly effective, with few patients who do not respond. Clinical studies to evaluated novel treatments are challenging given the rarity of these patients. Therefore, we sought to evaluate PD-L1 staining on metastatic and postchemotherapy viable testicular GCTs as a surrogate for potential benefit for immunotherapy targeting the PD-1/PD-L1 axis. METHODS: Ethics research committee approval for this retrospective study was obtained by four participating institutions (CHU de Québec, St. Joseph's Health Care, Halifax Health Science Centre, Johannes Gutenberg University). Patients with viable metastatic testicular GCTs pathology samples were included. Patients with pure teratoma were excluded. PD-L1 staining with the 22C3 clone was evaluated on samples with >100 viable tumor cells using the combined positive score (CPS). RESULTS: From 51 patients identified at participating institutions, 24 postchemotherapy and 18 chemotherapy-naive metastatic samples were available for PD-L1 staining, with 9 matched prechemotherapy samples and 7 matched orchiectomy pathology samples, respectively. The median CPS score was 55.6 (IQR 16-100) for all metastatic samples, 44.9 (IQR 13-100) for postchemotherapy metastatic samples, and 68.8 (IQR 38-100) for chemotherapy-naïve metastatic samples, with the median number of viable tumor cells at 545, 500, and 550, respectively. Differences were not significant between chemotherapy-naïve and postchemotherapy samples (P = 0.07), though among non-seminoma GCT metastatic samples, CPS scores were significantly lower postchemotherapy (P = 0.02). Significant differences among postchemotherapy metastatic tumors were also seen according to predominant subtype, with lower CPS scores for predominant yolk sac and higher values for predominant seminoma and choriocarcinoma. In 7 patients with matched specimens pre- and postchemotherapy, a significant increase in CPS was observed for seminoma (26.7 vs. 81.7, P = 0.045), but not nonseminoma GCTs. Comparing all chemotherapy naïve-samples, PD-L1 expression was higher in metastatic samples versus testicular samples (mean CPS 68.8 vs. 39.8, P = 0.02). This was also seen in matched chemotherapy-naïve samples (mean CPS 77.9 vs. 33.1, P = 0.01). CONCLUSION: Our results suggest that most patients with refractory GCTs postchemotherapy will not benefit from PD-1/PD-L1 immunotherapy. However, the high PD-L1 expression in patients with predominant or pure seminoma post-chemotherapy suggests this may represent a subgroup for whom further trials may be considered.

Adenocarcinoma of the Lung With Initial Presentation as Painful Testicular Metastasis: 18F-FDG PET/CT Findings in an Unusual Case.

ABSTRACT: Testicular metastasis is rare, with prostate cancer followed by lung cancer being the commonest primary site. Usually these are incidentally detected and are rarely symptomatic. We present an unusual case of adenocarcinoma lung, presenting initially with right testicular pain. Further workup with 18F-FDG PET/CT demonstrated primary malignancy of the left lung with nodal and right testicular metastasis.

Lymph node density in retroperitoneal lymph node dissection as a novel marker for predicting recurrence in patients with germ cell testicular cancer: A case-control study and long-term clinical experience of a tertiary referral hospital. / La densidad de los ganglios linfáticos en la linfadenectomía retroperitoneal como marcador novel para predecir la recurrencia en pacientes con cáncer testicular de células germinales: estudio de casos y controles y experiencia clínica a largo plazo de un hospital de referencia terciario.

INTRODUCTION AND OBJECTIVES: In this retrospective study, we aimed to evaluate lymph node (LN) density in retroperitoneal lymph node dissection (RPLND) to analyze whether residual mass after chemotherapy might behave as predicting factor for recurrence in patients with germ cell testicular cancer (GCTC). MATERIALS AND METHODS: The data of 185 patients that were operated between 12/2004 and 02/2017 because of GCTC were reviewed retrospectively. LN density was calculated. The patients were compared statistically in terms of demographic features, tumor characteristics, serum tumor marker levels, treatment strategies, and pathological results according to GCTC subtypes. Correlation analysis was performed to determine the parameters related to recurrent disease. RESULTS: The median follow-up was 79 (31-179) months and the median age of the patients was 23 (16-71). The median tumor size was 4 (1-18) cm. Five (2.7%) patients had metastatic disease at initial diagnosis. Seminoma, non-seminomatous-GCT and mix type-GCTC was detected in 62 (33.5%), 60 (32.4%) and 63 (34.1%) patients, respectively. Following inguinal orchiectomy, 48 (25.9%) patients underwent follow-up, 126 (68.1%) patients underwent chemotherapy and 11 (5.9%) patients underwent radiotherapy. A total of 21 (11.4%) patients underwent post-chemotherapy RPLND. Early and late recurrence was seen in 3 (1.6%) and 2 (1.1%) of the patients, respectively. A mild to moderate, negative, but significant correlation was found between the recurrence and the number of LNs containing metastatic deposits and LN density (r= -0.490, P=.024 and r= -0.450, P=.041, respectively). CONCLUSIONS: There was a negative correlation between the number of LNs containing metastatic deposits and LN density and recurrent disease.

Thoracic Metastasectomy in Germ Cell Tumor Patients Treated With First-line Versus Salvage Therapy.

BACKGROUND: Outcomes after thoracic metastasectomy in patients with testicular germ cell tumors (GCTs) who received first-line chemotherapy alone versus salvage chemotherapy remain unexplored. METHODS: We conducted a retrospective review of patients who underwent thoracic metastasectomy for residual GCT between 1997 and 2019 at a single tertiary center. Factors associated with progression-free survival (PFS) and overall survival (OS) were assessed using multivariable Cox regression. RESULTS: Of 251 patients, 191 received only first-line chemotherapy (76%) and 60 received salvage chemotherapy (24%). Median follow-up was 3.45 years (interquartile range, 1-7.93 years). Among first-line patients without teratoma in the primary tumor, with necrosis in the retroperitoneal nodes and normalized or decreasing serum tumor markers, 17 of 20 had intrathoracic necrosis (85%). Among first-line and salvage patients, respectively, 5-year OS was 93% (95% confidence interval [CI], 89%-98%) versus 63% (95% CI, 51%-78%; P < .001), and 5-year PFS was 69% (95% CI, 62%-77%) versus 40% (95% CI, 29%-56%; P < .001). On multivariable analysis, multiple lung lesions (hazard ratio [HR] = 3.01; 95% CI, 1.50-6.05; P = .002) and brain metastasis (HR = 4.51; 95% CI, 2.34-8.73; P < .001) at diagnosis, salvage chemotherapy (HR = 1.85; 95% CI, 1.10-3.13; P = .021), teratoma (HR = 2.68; 95% CI, 1.50-4.78; P = .001), and viable malignancy (HR = 4.34; 95% CI, 2.44-7.71; P < .001) were associated with worse PFS. CONCLUSIONS: Although GCT patients treated with salvage chemotherapy followed by thoracic metastasectomy have more aggressive disease and poorer PFS, they can achieve encouraging OS. Our findings highlight the integral role of aggressive thoracic metastasectomy in the treatment of GCT patients with residual thoracic disease after first line-only or salvage chemotherapy.

Surveillance of postchemotherapy subcentimeter residual retroperitoneal mass in metastatic nonseminomatous germ cell tumor: Does how you measure matter?

BACKGROUND: Approximately 70% to 80% of patients with metastatic nonseminomatous germ cell tumor (NSGCT) treated with cisplatin-based chemotherapy achieve a complete response, defined as normalization of serum tumor markers and either no residual retroperitoneal mass (RRM) or an RRM <1.0 cm. While there is universal agreement that patients with an RRM ≥1.0 cm should undergo retroperitoneal lymph node dissection (RPLND), many institutions including ours recommend surveillance for patients who achieve a complete response. However, studies have not defined which axis of the RRM should be considered when deciding between surveillance and RPLND. PATIENTS AND METHODS: Good-risk metastatic NSGCT patients treated with cisplatin-based chemotherapy who achieved a complete response and underwent surveillance were identified using our institution's electronic medical records. A post-hoc review was performed by a blinded radiologist. The RRM dimensions in the transaxial short axis (TSA), transaxial long axis (TLA), and craniocaudal axis (CCA) were recorded. Differences in the frequency of recurrence between groups with an RRM <1.0 cm and ≥1.0 cm in the TLA and CCA were assessed using the Fisher exact test. RESULTS: Thirty-nine patients who met study criteria were included. At a median follow-up of 63.8 months, 2 patients (5.1%) recurred. Both were successfully treated with salvage chemotherapy and RPLND. Thirteen (33%) and 27 (69%) patients had an RRM ≥1.0 cm in the TLA and CCA, respectively. There were no statistically significant differences in the risk of recurrence between patients with an RRM <1.0 cm and ≥1.0 cm in the TLA (P = 0.54) or CCA (P = 0.53). CONCLUSIONS: Surveillance is an effective strategy in good-risk NSGCT patients with a postchemotherapy RRM <1.0 cm in the TSA. Our study suggests referencing the TSA and not the TLA or CCA may avoid unnecessary postchemotherapy RPLNDs.

Burned-out testicular germ cell tumour presenting as acute inferior vena cava syndrome.

Germ cell tumours (GCT) are the most common testicular neoplasms, seen mainly in young adults. Rarely they can affect extragonadal tissues, either as primary tumours or as metastases, most commonly to retroperitoneal lymph nodes. A 'burned-out' testicular tumour is a metastatic GCT with a relatively occult primary testicular tumour, which has histologically spontaneously regressed. We report a case of a 26-year-old man who presented with an acute history of lower back pain and leg swelling. CT demonstrated a large retroperitoneal soft tissue mass causing right-sided hydronephrosis with inferior vena cava and iliofemoral vein thrombosis. Although clinical examination of the testis was normal, ultrasound imaging of the scrotum identified a burned-out testicular primary. Orchiectomy confirmed the diagnosis and the patient responded well to chemotherapy, with no viable residual tumour on follow-up imaging. However, despite nephrostomy insertion, a dimercaptosuccinic acid (DMSA) scan demonstrated loss of function of the right kidney after treatment.

Mechanism of metastasis to the spermatic cord and testis from advanced gastric cancer: a case report.

BACKGROUND: The spermatic cord and testis are very rare sites for metastasis from gastric cancer. Although several mechanisms have been suggested to explain this unusual metastasis, the actual mechanism remains unclear. We report a case of right spermatic cord and testicular metastasis, review its imaging findings, and suggest a mechanism of tumor spread. CASE PRESENTATION: A 61-year-old man complained of a palpable mass in the right inguinal area. He had been treated with distal gastrectomy with chemotherapy for advanced gastric cancer 5 years ago. Computed tomography, ultrasound, and magnetic resonance imaging showed a mass surrounding the right spermatic cord, involving the right testis. Another mass was observed in the aortocaval space, presumed to be a metastatic lymph node. The imaging features of the right testicular lesion were different than those of the primary testicular cancer. The lesions at both sites showed similar radiologic features of abundant internal necrosis, which is consistent with metastatic lesions. Pathology confirmed metastatic adenocarcinoma. He underwent a series of chemotherapy sessions, and all metastatic masses had partially decreased in size at the 5-month outpatient follow-up. CONCLUSIONS: The imaging features of testicular mass and spermatic cord involvement are important clues for accurate differential diagnosis of metastasis from other primary tumors in patients with a history of stomach cancer. This unusual metastasis can be explained via retrograde tumor spread along the lymphatic channels in terms of concurrent aortocaval lymph node metastasis. A suspicion of metastasis should not be overlooked, even if a patient has undergone curative treatment, including surgery and adjuvant chemotherapy, many years ago.

[Symptomatic testicular metastasis of acinar adenocarcinoma of the prostate]. / Symptomatische Hodenmetastase eines azinären Adenokarzinoms der Prostata.

We report about the rare occurrence of symptomatic testicular metastasis of an acinar adenocarcinoma of the prostate. Testicular metastases are usually incidentally detected in patients treated with bilateral orchiectomy or more often during autopsy. In the literature, there are only a few clinical cases describing symptomatic testicular metastases. However, the possibility of such metastases should be considered in patients diagnosed with advanced prostate cancer. Testicular examination should be performed regularly, even in patients with low prostate-specific antigen levels.

Clinical outcome of post-chemotherapy retroperitoneal lymph node dissection in metastatic nonseminomatous germ cell tumour: A systematic review.

Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an important element of the management of patients with residual tumour after chemotherapy for disseminated nonseminomatous germ cell tumour (NSGCT). This is a challenging procedure and the outcome varies widely between institutions. There is much debate concerning the anatomical extent of the dissection and the literature is conflicting regarding the outcome of this procedure. In this systematic review we aim to summarise the literature on the relapse rate of PC-RPLND. We performed a search of the literature of the PubMed/MEDLINE and Embase databases, in accordance with the PRISMA guidelines. Studies reporting on the relapse rate of PC-RPLND in NSGCT patients with residual tumour were eligible for inclusion. We calculated the weighted average relapse rates of included studies and assessed the risk of bias using the Newcastle-Ottawa scale. A total of 33 studies, reporting on 2,379 patients undergoing open PC-RPLND (O-RPLND) and 463 patients undergoing minimally invasive PC-RPLND (MI-RPLND) were included. The weighted average relapse rates were 11.4% for O-RPLND, and 3.0% for MI-RPLND. The rates of retroperitoneal relapse were 4.6% and 1.7% after O-RPLND and MI-RPLND, respectively. For O-RPLND specifically, the average retroperitoneal relapse rate was 3.1% after modified dissection and 6.1% after bilateral dissection. We conclude that modified template dissection is oncologically safe in carefully selected patients. Minimally invasive procedures are feasible but long-term data on the oncological outcome are still lacking. PC-RPLND is a complex and challenging procedure, and patients should be treated at high-volume expert centres.

Simultaneous Vs Sequential Retroperitoneal, Thoracic and Cervical Resection of Post Chemotherapy Residual Masses in Patients With Metastatic Nonseminomatous Germ Cell Tumors of the Testis.

OBJECTIVE: To compare a simultaneous vs sequential approach to residual post chemotherapy mass resections in metastatic testis cancer. METHODS: A retrospective review was performed of patients who underwent retroperitoneal and thoracic/cervical resection of post chemotherapy residual masses between 2002 and 2018. Group 1: "Simultaneous" (Combined Retroperitoneal and Thoracic/Cervical resections on the same date); Group 2: "Sequential" (Retroperitoneal and Thoracic/Cervical resections at separate dates). RESULTS: During the study period, 35 simultaneous and 17 sequential resections were performed. The median age at surgery was 28 years (Range 16-61). The median follow-up from last surgical procedure was 62.7 months (Range 0.4-194). Histology revealed teratoma in 38 (73.1%) patients, necrosis in 8 (15.4%) and viable tumor in 6 (11.5%). Discordant pathology findings between thoracic/cervical and abdominal resections were noted in 16 (30.8%) patients. No differences were observed between the simultaneous vs sequential groups in median operating time (585 minutes vs 545 minutes, P = .64), blood loss (1300 vs 1300 mls, P = .42), or length of stay (9 vs 11 days, P = .14). There was no difference between the 5-year (65.7% vs 68.6%) relapse-free survival between the 2 groups (P = .84) or the 5-year (88.6% vs 100%) overall and disease-specific survival (P = .25). CONCLUSION: Simultaneous resection of retroperitoneal and thoracic/cervical post chemotherapy metastases is a feasible in some patients. It requires multidisciplinary collaboration and a longer primary procedure.

[Ureteric and testicular mestastasis 25 years after nephrectomy : Long-term survival with metastatic renal cell carcinoma]. / Harnleiter- und Hodenmetastase 25 Jahre nach Nephrektomie : Langjähriges Überleben mit einem metastasierten Nierenzellkarzinom.

A 70-year-old man with multiple metastasized renal cell carcinoma (RCC) presented himself in our clinic 25 years after initial diagnosis with newly developed hematuria and conspicuous right testis. The biopsy of the left ureter taken by ureterorenoscopy and the right orchiectomy show metastases of a clear cell RCC. This special case shows rare metastases in different organ systems. The individualized multimodal treatment led to a long-term survival with this metastasized disease. The presented case shows that late recurrences of RCC can occur years after initial diagnosis and should be considered at any time.

Significance of 18F-FDG PET/CT in Characterization of Equivocal Lesions in High-Risk Testicular Carcinoma in Restaging Setting.

OBJECTIVES: The present study aims to evaluate the role of Positron emission tomography (PET) -computed tomography (CT) with 18F-fluorodeoxyglucose (18F-FDG) in the restaging of high-risk testicular cancer. METHODS: Forty-five patients (mean age of 38.1±11.3 years and range 23-81 years) with testicular carcinoma, underwent 18F-FDG PET-CT during their clinical course were prospectively selected. PET positivity was defined as a site of abnormal 18F-FDG uptake in tissue histologically proven or clinically or radiographically suspected to represent tissue involvement. The sites of disease were characterized as either nodal or extranodal. All patients were followed-up for at least 12 months with a diagnostic and/or functional imaging modality. RESULTS: Of the 45 patients 38 (84%) patient presented with seminoma and 7 (16%) were Non-seminomatous germ cell tumors. Analysis of secondary disease spectrum showed nodal involvement in 65%, osseous involvement in 23% and mixed visceral/soft tissue lesions in 12% of patients. Nineteen (42%) were negative for any metastatic disease. All negative patients remain disease free in the follow-up of one year. Out of the positive 26/45 patients, PET-CT showed progressive disease in 3/26, stable disease 1/26 and partial response in 2/26 and complete metabolic resolution in 20/26 patients. 18F-FDG PET-CT was able to characterize all patients leading to significant change of primary decision of wait and watch to go for treatment and vice versa. CONCLUSION: 18F-FDG PET-CT scan is potentially an excellent tool for characterization of equivocal lesions on CT scan in the restaging settings and follow up of high-risk testicular cancer patients.