[Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases].

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 µg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

Paraneoplastic Progressive Downbeat Nystagmus, Ataxia and Sensorineural Hearing Loss due to the ANTI-Kelch-11 Protein Antibody.

ABSTRACT: A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic-cochleovestibular syndrome.

Robotic Assisted Retroperitoneal Lymph Node Dissection for Small Volume Metastatic Testicular Cancer.

PURPOSE: Robotic assisted retroperitoneal lymph node dissection in patients with testicular cancer is controversial. Lately, unusual recurrence patterns with adverse outcomes after robotic assisted retroperitoneal lymph node dissection have been published. In this report we determine the feasibility, safety and early oncologic outcome of robotic assisted retroperitoneal lymph node dissection in patients with small volume metastatic testicular cancer. MATERIALS AND METHODS: We retrospectively evaluated 27 consecutive patients with small volume metastatic testicular cancer (October 2010 to November 2019) who underwent robotic assisted retroperitoneal lymph node dissection (unilateral modified template). Intraoperative and postoperative complications as well as early oncologic outcomes are reported. Surgery was performed in the primary metastatic setting in 22 (81%), post-chemotherapy in 4 (15%) and for late relapse in 1 patient (4%). Initial clinical stage was IIA for 14 (52%), IIB for 12 (43%) and III for 1 (4%) patient. RESULTS: Median operative time, blood loss and length of hospital stay were 175 minutes, 50 ml and 4 days, respectively. Expectedly, viable tumor was found in 21/27 patients (78%) and 6 patients (22%) showed fibrosis, necrosis or no tumor. Overall 3 (11%) patients experienced intraoperative (Satava II) and 1 (4%) postoperative (Clavien-Dindo IIIb) complications, respectively. Median followup was 16.5 months (3-69), and 3 (11%) patients experienced relapse outside of the surgical field after 12, 22 and 36 months. CONCLUSIONS: In highly selected patients with low volume metastatic testicular cancer robotic assisted retroperitoneal lymph node dissection may be indicated, and appears to be technically feasible and comparable with open surgery in terms of complications and early oncologic safety. Prospective data collection in larger series is necessary to clarify the role and specific indications of this approach.

Contemporary North-American population-based validation of the International Germ Cell Consensus Classification for metastatic germ cell tumors of the testis.

BACKGROUND: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus. MATERIALS AND METHODS: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates. RESULTS: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups. CONCLUSIONS: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

The Clinical Significance of Seminoma Component in Testicular Mixed Germ Cell Tumour.

BACKGROUND: The aim of this study was to examine clinical/pathological characteristics, prognosis and tendency to metastasis of mixed germ cell tumours (MGCTs) that contain a seminoma component. METHODS: A total of 111 MGCT cases between 2008 and 2018 were retrospectively enrolled. The patients were divided into 2 groups according to the absence (group 1) or presence (group 2) of seminoma component in MGCTs. Patients' age, complaints at admission to our clinic, primary tumour localization, primary tumour size, preoperative testicular tumour markers, MGCT histopathological components and percentages, lymphovascular invasion, pathological tumour stage, postoperative testicular tumour markers, presence of lymph node involvement in abdominal tomography, lung metastasis based on thorax tomography, clinical tumour stage, adjunctive therapies performed, state of recurrence and survival were compared in 2 groups. RESULTS: The mean age of the patients was 24.51 ± 4.79 years. The mean age, initial complaint rates, primary tumour size, postoperative testicular tumour markers, presence of lymphovascular invasion, presence of lymph node involvement and lung metastasis were found to be higher in group 2 than in group 1, although these differences were not statistically significant. Especially, it was found that a seminoma component rate of 30% and higher had a higher tendency for a poor prognosis. CONCLUSION: Although the word "seminoma" may be initially interpreted as an indication of good prognosis, a seminoma component in MGCTs is actually not a good prognostic factor. MGCTs that contain a seminoma component (especially 30% and higher) can have a higher tendency for occult metastatic disease.

Reclassification of good-risk seminoma: prognostic factors, novel biomarkers and implications for clinical management.

Germ cell tumors represent 11% of the cancers diagnosed in adolescent males and are the most common solid tumors in adult men between the ages of 20 and 35. Pure seminoma accounts for around 50% of all testicular germ cell tumors. The prognostic classification of the International Germ Cell Cancer Collaborative Group for good-prognosis seminoma includes both nodal disease and pulmonary visceral metastases. In this article, we analyzed recent data on prognosis and outcome of good-prognosis seminoma to revise the traditional classification of the disease and improve tailored treatment.

Serum Levels of MicroRNA371a-3p: A Highly Sensitive Tool for Diagnosing and Staging Testicular Germ Cell Tumours: A Clinical Case Series.

INTRODUCTION: MicroRNA (miR)371a-3p was suggested to be a sensitive and specific new serum biomarker of germ cell tumours (GCTs); however, its clinical usefulness remains unproven. PATIENTS, METHODS: In 312 consecutive cases with various testicular diseases, serum levels of miR371a-3p were measured. Measurement results became available only after completion of treatment. Five patients with testicular seminoma were selected for review because of unanticipated clinical courses. RESULTS: In each two patients, elevated miR levels heralded undetected primary testicular GCT and metastases despite inconclusive radiological findings. In one case, a normal miR371a-3p level correctly pointed to the absence of metastases contrary to clinical assessment. In all cases, knowledge about the miR371a-3p levels would have altered the clinical management. CONCLUSIONS: These cases highlight the exceptional usefulness of the new GCT biomarker. In contrast to classical markers, miR371a-3p can identify primary testicular GCT. The marker can aid in clinical decision making in cases with ambiguous clinical findings.

Burned-out seminoma revealed by solitary rib bone metastasis.

Burned-out tumor is a rare phenomenon in which a testicular tumor regresses in the primary lesion and progresses in a metastatic lesion. We report the case of a 30-year-old male with burned-out seminoma revealed by open biopsy of solitary 10th rib bone metastasis. He underwent inguinal orchiectomy, which revealed hyalinization, indicating a spontaneously regressed testicular tumor. Chemotherapy for seminoma was administered in three cycles of bleomycin + etoposide + cisplatin therapy. The chemotherapy was effective, and wide resection of the rib was subsequently performed. No postoperative chemotherapy was performed, and there has been no evidence of recurrence for 3 years postoperatively.

[Granulomatous slack skin associated with metastatic testicular seminoma]. / Mycosis fongoïde chalazodermique associé à un séminome testiculaire métastatique.

BACKGROUND: Granulomatous slack skin (GSS) is an extremely rare subtype of T-cell lymphoma, a variant of mycosis fungoides (MF). Herein, we describe the first reported case of GSS associated with metastatic testicular seminoma. PATIENTS AND METHODS: A 28-year-old male patient presented with circumscribed erythematous loose skin masses, especially in the body folds and which had been relapsing for 4years. Skin biopsy showed a loss of elastic fibers and an atypical granulomatous T-cell infiltrate with epidermotropism, enabling a diagnosis of GSS to be made. A biopsy of a retroperitoneal lymphadenopathy showed testicular seminoma metastasis. DISCUSSION: Patients suffering from GSS have a statistically higher risk of developing a second primary cancer, especially Hodgkin's lymphoma. The association found between GSS and a lymphoproliferative malignancy requires long-term follow-up and determines the patient's prognosis. CONCLUSION: It is not possible to prove a formal link between GSS and testicular seminoma. However, this case illustrates the value of screening for a second cancer, particularly where extra-cutaneous lesions appear during GSS treatment. Lymph node biopsy should be performed routinely in the event of GSS with possible lymph node involvement.

Sick leave and disability pension among Swedish testicular cancer survivors according to clinical stage and treatment.

PURPOSE: To investigate if testicular cancer survivors (TCSs) have a higher incidence of work loss compared with the population, accounting for stage, treatment and relapse. MATERIAL AND METHODS: A cohort of 2146 Swedish TCSs diagnosed 1995-2007 (seminoma n = 926, non-seminoma n = 1220) was identified in the SWENOTECA (Swedish-Norwegian Testicular Cancer Group) register, and matched 1:4 to population comparators. Prospectively recorded work loss data (both before and after diagnosis) were obtained from national registers through September 2013. Adjusted relative risks (RR) and 95% confidence intervals (CI) of sick leave and/or disability pension were calculated annually and overall with Poisson- and Cox regression, censoring at relapse. The mean number of annual work days lost was also estimated. RESULTS: TCSs were at a modestly increased annual risk of work loss up to the third year of follow-up (RR3rd year 1.25, 95% CI 1.08, 1.43), attributed to a more pronounced risk among extensively treated patients (4 chemotherapy courses: RR3rd year 1.60, 95% CI 1.19, 2.15; > 4 courses: RR3rd year 3.70, 95% CI 2.25, 6.11). Patients on surveillance or limited treatment (radiotherapy, 1-3 chemotherapy courses) did not have an increased risk of work loss beyond the first year. TCSs receiving > 4 chemotherapy courses had higher mean number of annual days of work loss up to the 10th year post-diagnosis, and a five-fold risk of disability pension (RR 5.16, 95% CI 2.00, 10.3). CONCLUSION: Extensively treated TCSs, but not those on surveillance or limited treatment, are at increased risk of work loss long-term, not explained by relapse. These patients may benefit from early rehabilitation initiatives.

Metastatic seminoma to the ureter.

We present a case report of testicular seminoma with intraluminal metastasis to the ureter causing obstruction and hydronephrosis. To our knowledge, this is the fourth case to be reported in the world literature of metastatic tumor to the ureter from a primary testicular seminoma.

Duodenal involvement by seminomatous tumors.

Testicular germ cell tumors, though rare (1%), represent the most common neoplasm among young men. Gastrointestinal involvement from these malignancies usually presents as bowel obstruction and digestive bleeding, but their frequency is low (5%). The patterns of this involvement are: infiltration from affected retroperitoneal lymph nodes or, less frequently, by peritoneal seeding and direct hematogenous spread. Particularly, infiltration of duodenum is also rare, though its real frequency is not well defined. Moreover, the affinity for GI tract differs among the histological types of GCT, being seminomatous tumors an exceedingly unfrequent cause of duodenal infiltration. We herein present a recent case in our institution of severe anemia due to gastrointestinal bleeding in the context of giant retroperitoneal bulky metastatic mass infiltrating duodenum as first manifestation of a testicular pure seminoma.

[Testicular tumor with opposite inguinal lymph node metastasis in a patient with prior orchiopexy for undescended testis].

The patient was a 54-year-old man. At age 6 years, he had undergone orchiopexy for left undescended testis. Six months prior to the current presentation, he visited our hospital with a chief complaint of painless enlargement of the left testis. Left high orchiectomy was performed under a diagnosis of left testicular tumor. Histopathological examination determined the tumor to be a seminoma (pT2). Postoperatively, the patient was placed on surveillance without preventive radiation treatment. He visited our hospital six months after surgery due to a painless mass in the right inguinal region. All tumor markers (AFP, HCG-ß, and LDH) were within normal ranges. However, based on ultrasound and CT scan findings, lymph node metastasis was suspected and a right inguinal lymph node excision was thus performed. Histopathological examination led to the diagnosis of seminoma.

Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS.

BACKGROUND: We aimed to better discriminate (occult) metastasised from non-metastasised seminoma based on transcriptional changes of small RNAs in the primary tumour. METHODS: Total RNAs including small RNAs were isolated from five testicular tumours of each, lymphogenic, occult and non-metastasised patients. Next-generation sequencing (SOLID, Life Technologies) was used to examine transcriptional changes. Small RNAs showing ⩾50 reads and a significant ⩾2-fold difference using non-metastasised tumours as the reference group were examined in univariate logistic regression analysis and combinations of two small RNAs were further examined using support vector machines. RESULTS: On average, 1.3 × 10(7), 1.4 × 10(7) and 1.7 × 10(7) small RNA reads were detectable in non-metastasised, occult and lymphogenic metastasised seminoma, respectively, of which 30-32% remained after trimming. Between 59 and 68% represented annotated reads and between 8.6 and 11% were annotated small RNA tags. Of them, 137 small RNAs showed>50 reads and a two-fold difference to the reference. In univariate analysis, 32-38 small RNAs significantly discriminated lymphogenic/occult from non-metastasised seminoma, and among these different comparisons, it were the same small RNAs in 51-88%. Many combinations of two of these small RNAs allowed a complete discrimination of metastasised from non-metastasised seminoma irrespective of the metastasis subtype. CONCLUSIONS: Metastasised and non-metastasised seminoma can be completely discriminated with a combination of two small RNAs.

A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic non-seminomatous germ cell tumor.

BACKGROUND: Approximately a quarter of men with metastatic non-seminomatous germ cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after chemotherapy. The management of small residual masses (≤1 cm) is controversial, with good outcomes seen with either post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) or surveillance. We sought to review our experience of surveillance and synthesize the cumulative findings with the current literature in the form of a meta-analysis. PATIENTS AND METHODS: We searched PubMed, EMBASE and abstracts from ASCO and AUA to identify relevant, English-language studies for the meta-analysis. The DFCI (Dana Farber Cancer Institute) database was constructed from a database of men undergoing cisplatin-based chemotherapy for metastatic NSGCT. The outcomes of interest were the proportion with necrosis, teratoma or active cancer on histology at PC-RPLND (literature) and the total number of relapses, RP-only relapses and overall survival in men undergoing surveillance (literature and DFCI cohort). RESULTS: Three of 47 men undergoing post-chemotherapy surveillance at our institution relapsed over a median follow-up of 5.4 years. All three were alive at a median of 4.2 years after relapse. On meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in the 588 men who underwent PC-RPLND were 71, 24 and 4%, respectively. Of the combined 455 men who underwent surveillance, the pooled estimate of the relapse rate was 5%, with an RP-only relapse rate of 3%. Of the 15 men who suffered an RP-only relapse on surveillance, two died of disease. CONCLUSION: Surveillance is a reasonable strategy for men with minimal residual RP disease after chemotherapy and avoids an RPLND in ∼97% of men who are cured with chemotherapy alone.

Survival analysis of pure seminoma at post-chemotherapy retroperitoneal lymph node dissection.

PURPOSE: Viable seminoma encountered at post-chemotherapy retroperitoneal lymph node dissection for pure testicular seminoma is rare due to the chemosensitivity of this germ cell tumor. In this study we define the natural history of viable seminoma at post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: The Indiana University testis cancer database was queried from 1988 to 2011 to identify all patients with primary testicular or retroperitoneal pure seminoma and who were found to have pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. Clinical characteristics were reviewed and survival analysis was performed. RESULTS: A total of 36 patients met the study inclusion criteria. All patients received standard first line cisplatin based chemotherapy and 17 received salvage chemotherapy. The decision to proceed to retroperitoneal lymph node dissection was based on enlarging retroperitoneal mass and/or positron emission positivity in the majority of cases. Seven patients had undergone previous retroperitoneal lymph node dissection. Additional surgical procedures were required in 19 patients to achieve a complete resection. The 5-year cancer specific survival rate was 54%. However, only 9 of 36 patients remained continuously free of disease and of these patients 4 received adjuvant chemotherapy. Mean time from post-chemotherapy retroperitoneal lymph node dissection to death was 6.9 months. Second line chemotherapy, reoperative retroperitoneal lymph node dissection and earlier era of treatment were associated with poorer cancer specific survival. CONCLUSIONS: A total of 36 patients with pure seminoma were found to have viable pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. While 5-year cancer specific survival was 54%, these surgeries are technically demanding and only a minority of patients achieves a durable cure from surgery alone.

Inferior vena cava prosthetic replacement in a patient with horseshoe kidney and metastatic testicular tumor: technical considerations and review of the literature.

BACKGROUND: Seminomatous and non-seminomatous Germ Cell Tumors (GCT) of the testis are a rare cancer, with an estimated incidence of 56.3 per million white males and 10 per million black males in the United States.The association between non-seminomatous GCT and horseshoe kidney is a rare event and is seen in about 1.3% of patients requiring retroperitoneal lymph node dissection. To our knowledge, no cases have been reported in which replacement of the IVC was also necessary. CASE PRESENTATION: We report the case of a 22-year-old man with horseshoe kidney and metastatic non-seminomatous germ cell tumor involving the wall of the inferior vena cava.Following post-chemotherapy retroperitonal lymph node dissection, the inferior vena cava was replaced with an expanded polytetrafluoroethylene graft.At 2-years follow-up, the patient was in good health and the graft was patent. No clinical or diagnostic signs of renal impairment or recurrence of neoplastic disease were noted. CONCLUSION: Radical surgery is warranted in patients with non-seminomatous germ cell tumor metastasizing to the retroperitoneal lymph nodes. When vena cava replacement is required, and the situation is further complicated by horseshoe kidney, as in this case, surgical technique will rely on multidisciplinary surgical treatment planning by a team composed of urologists, vascular surgeons and oncologists.

Metastatic testicular cancer presenting as lower back pain in a pilot.

BACKGROUND: Lower back pain is ubiquitous in the helicopter community and testicular cancer is the most common solid organ tumor that affects approximately 1% of men ages 15 to 35. However, rarely is lower back pain caused by testicular cancer and, in an otherwise healthy male, it is generally low on the differential diagnosis. Literature review discovered the most recent case report where lower back pain was the presenting symptom for testicular cancer was in 1987. CASE REPORT: A 26-yr-old male helicopter pilot presented to clinic complaining of lower back pain for greater than 1 yr for which conservative treatment had failed. The pain was so severe he was unable to sleep and had to remove himself from the flight schedule. The patient was seen by physical therapy and a chiropractor and treated with NSAIDs and other pain medications, including narcotics. After further investigation, it was discovered that the patient's lower back pain was a result of a retroperitoneal metastatic tumor originating from his right testicle. DISCUSSION: It is important to consider that, although most aviators in their twenties have been screened for chronic illness, they are still at risk for developing cancer. In this case, the patient never complained of testicular mass or pain and even denied symptoms during review of systems questioning. Proper education regarding the importance of self-examination and reporting of abnormalities is key to early detection and intervention. The 5-yr survival for metastatic testicular cancer is greater than 95%.