Testicular Mass in Children: A Case Report

Testicular sarcomas constitute only 1–2% of all testicular tumors and are mostly associated with germ cell tumor. Primary intratesticular rhabdomyosarcoma is rare and only 14 cases have been reported in the literature till date. It should be differentiated from germ cell tumor with sarcomatous component, other intratesticular spindle-cell sarcomas and paratesticular rhabdomyosarcoma. Accurate diagnosis and early treatment is essential as it is an aggressive tumor with high metastatic potential and poor prognosis. Orchidectomy is the treatment of choice. Chemo-radiotherapy is recommended in case of recurrence and metastasis.

ImportanceTesticular cancer is the most common solid malignancy among males aged 15 to 40 years in the US, with approximately 10 000 new cases diagnosed each year. Between 90% and 95% of testicular cancers are germ cell tumors (GCTs).ObservationsThe mean age at diagnosis for testicular cancer is 33 years. GCTs are categorized as seminomas and nonseminomatous GCTs (NSGCTs) based on their embryonic origins and path of differentiation. Risk factors include cryptorchidism, family history of testicular cancer, gonadal dysgenesis, infertility, cannabis use, and genetic conditions such as Klinefelter syndrome. The most common presenting symptom of testicular cancer is a painless testicular mass. History, physical examination, scrotal ultrasound, laboratory assessment of GCT-associated serum tumor markers (α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase), and prompt referral to a urologist are indicated when testicular cancer is suspected. Early diagnosis and treatment, starting with a radical inguinal orchiectomy, are important to optimize outcomes. At diagnosis, GCT is stage I (localized to the testicle) in 70% to 75% of patients, stage II (metastatic only to the retroperitoneal lymph nodes) in 20%, and stage III (widely metastatic) in 10%. Treatment of GCTs is guided by histology, clinical staging, and risk classification, with 5-year survival rates of 99%, 92%, and 85% for those diagnosed at stages I, II, and III, respectively. Optimal treatment often involves a multidisciplinary team at high-volume, experienced medical centers and may include surveillance (serum tumor markers [α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase] and imaging of the chest, abdomen, and pelvis), surgery (retroperitoneal lymph node dissection), chemotherapy, and/or radiation. Treatment decisions should consider long-term survivorship concerns, including body image, fertility, hypogonadism, mental health, financial cost, adherence to follow-up, and late adverse effects of therapy such as cardiovascular disease, secondary malignancies, and potential psychosocial effects such as anxiety, depression, and social isolation.Conclusions and RelevanceTesticular cancer is the most common solid malignancy in young men in the US, and 90% to 95% are GCTs. Patients with testicular GCT have a 5-year survival rate of 99%, 92%, and 85% for stages I, II, and III, respectively. Prompt diagnosis and treatment are important to optimize outcomes, and treatment decisions should balance oncologic control with survivorship concerns to minimize long-term adverse effects of treatment.

Testicular and Paratesticular Neoplasms in Prepubertal Males

Testicular seminoma and non-seminoma: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up

To clarify the significance of the International Germ Cell Cancer Collaborative Group classification in the 2000s, especially in intermediate- and poor-prognosis testicular germ cell tumor in Japan. We retrospectively analyzed 117 patients with intermediate- and poor-prognosis testicular non-seminomatous germ cell tumor treated at five university hospitals in Japan between 2000 and 2010. Data collected included age, levels of tumor markers, spread to non-pulmonary visceral metastases, treatment details and survival. The median follow-up period of all patients was 57months. A total of 50 patients (43%) were classified as having intermediate prognosis, and 67 patients (57%) as poor prognosis according to the International Germ Cell Cancer Collaborative Group classification. As first-line chemotherapy, 92 patients (79%) received bleomycin, etoposide and cisplatin. Of all patients, 74 patients (63%) received second-line chemotherapy. The most commonly used second-line chemotherapy regimens were a combination of taxanes, ifosfamide and platinum in 49 cases (66%). Overall, 33 patients (28%) received third-line chemotherapy. A total of 88 patients (75%) underwent post-chemotherapy surgery. The 5-year overall survival for intermediate (n=50) and poor prognosis (n=67) was 89% and 83% (P=0.21), respectively. In poor prognosis patients, patients with two or more risk factors (any of high lactic dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin levels, and presence of non-pulmonary visceral metastases) had significantly worse survival than those with only one risk factor (71% and 91%, respectively, P=0.01). The 5-year overall survivals of poor-prognosis testicular non-seminomatous germ cell tumor patients reached 83%. Further stratification of poor-prognosis patients based on a number of risk factors has the potential to further identify those with poorer prognosis.

Nonseminomatous mixed germ cell tumor of the testis: Case report.

Background Testicular cancer remains one of the most common malignant diseases in young men. The highest incidence was seen in the ages of 25-29 years. A significant part of them come from germ cell tumors, which are divided into seminoma and non-seminoma. Although the aggressiveness of tumors with germ cells remains high, it should be noted that there is a very high response to surgical and chemotherapeutic treatment, where a 5-year disease-free survival is evident in more than 95% of cases. The metastatic spread of these tumors follows the lymphatic drainage of the testes. The retroperitoneal and pre-aortocaval spread, which are resistant to chemotherapy, requires the intervention of an extended surgical procedure, which consists in the removal of the lymph nodes in these regions. The purpose of this procedure is the resection of pre-aortocaval lymph nodes remaining after orchidectomy, a procedure which represents one of the major components of the curative treatment. Case presentation There are three cases of patients, aged 37/32/39-years-old, who have undergone the surgical procedure of right orchidectomy. The biopsy obtained after the surgical intervention showed grade II seminoma. All three patients, who underwent orchidectomy in different years, were subjected to chemotherapeutic treatment with the 3 preparations bleomycin, etoposide and cisplatin. After that, for a period of 1.5-2 years, they carried out occasional checks, which they then stopped. The lack of control for a 5-year period, as well as the limitation of the surgical procedure only in the right orchidectomy, has led to the metastasis of the seminoma in the pre-aortocaval region. In this study, we consider the fact of performing the retroperitoneal lymphatic drainage procedure according to the lymphatic drainage route of the tests, in the cases of the biopsy result "Seminoma grade II" and above, as one of the major components of the curative treatment in addition to Chemotherapeutic treatment. Discussion The implementation of retroperitoneal, pre-aortocaval lymphadenectomy is considered mandatory, especially in the results of "Seminoma grade II" biopsy. In cases where laboratory and imaging examinations indicate residual retroperitoneal, pre-aortocaval masses, the surgical procedure of lymphadenectomy should be performed as soon as possible. The principle of the lymphadenectomy according to the way of drainage of the testes is important when we talk about oncological principles. Statistical data show the advantage of the extended surgical procedure, consisting of a disease-free survival period of 5 years at a rate of 95%. The choice of the retroperitoneal lymphadenectomy procedure has resulted in the normalization of tumor markers for at least a 2-year period after the intervention, also showing an improvement in the patient's prognosis. Conclusion In cases of histopathological response, where the result of Seminoma grade II and above is concluded, the surgical procedure should not be limited to simple orchidectomy or radical inguinal orchidectomy with the aim of avoiding metastatic spread along the lymphatic drainage route. Keywords: General surgery, Testicular cancer, Seminoma, Para-aortocaval retroperitoneal lymphatic resection, RPLND. DOI: 10.7176/ALST/95-06 Publication date: November 30 th 2022

SEXUAL FUNCTIONING AFTER MULTIMODALITY TREATMENT FOR DISSEMINATED NONSEMINOMATOUS TESTICULAR GERM CELL TUMOR

About 40 % of testicular germ-cell tumours are seminomas, and most of them are clinical stage Ⅰ . For a long time, the standard treatment approach for stage Ⅰ testicular seminoma has been radical inguinal orchiectomy followed by radiotherapy to the para-aortic and ipsilateral pelvic lymph nodes. In recent years, many oncologists indicate that the effect of the adjuvant postoperative para-ortic lymph nodal irradiation and chemotherapy using carboplatin is equivalent to para-aortic and ipsilateral pelvic irradiation post orchiectomy for patients with Stage Ⅰ seminoma of the testis, and the side effects is obviously declined, but the long-term side effects are still indefinite. This review presents the treatment development of the stage Ⅰ testicular seminoma after radical inguinal orchiectomy. Key words: Seminoma; Radiotherapy dosage; Drug therapy,combination

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the ‘‘Surgical Pathology Cancer Case Summary (Checklist)’’ portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents.

Aim: This study reports surgical treatment and its outcome for boys with a testicular tumor, in order to analyze the considerations of testis-sparing surgery (TSS) and investigate whether, in retrospect, treatment was according to a recently developed algorithm. Methods: We retrospectively reviewed boys with testicular tumors who underwent surgical treatment between January 2000 and June 2020 at the Wilhelmina’s Children’s Hospital and the Princess Máxima Center for Pediatric Oncology, The Netherlands. Medical records were searched for clinical characteristics and outcome. Results: We identified 31 boys (median age = 5.5 years) with a testicular tumor, 26 germ cell tumors (GCTs), four sex cord-stromal tumors, and one gonadoblastoma. Seventeen boys (median age = 1.5 years) had malignant and 14 (median age = 3.6 years) had benign tumors. Four boys with benign GCTs were treated with TSS, 25 with radical inguinal orchiectomy (RIO), and 2 with scrotal orchiectomy. No recurrence or testicular atrophy was reported. All boys with benign testicular tumors were treated as suggested by the algorithm, except for one boy treated with RIO. Conclusion: Retrospective analysis of surgical treatment of prepubertal boys with benign testicular tumors showed that TSS appears to be safe, and should be considered based on clinicoradiological data, in line with our algorithm.

RISK ADAPTED MANAGEMENT WITH ADJUVANT CHEMOTHERAPY IN PATIENTS WITH HIGH RISK CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TUMOR

This study aims to identify novel therapeutic targets for nonseminomatous pediatric germ cell tumors (GCTs). GCTs are the most common cancer in young men, and affect both children and adolescents. They are histologically classified into two types: seminomatous GCTs (SGCTs), which are undifferentiated, and non-seminomatous GCTs (NSGCTs), which exhibit differentiation. Although cisplatin treatment is effective for many types of GCTs, cisplatin resistance, which is especially common in NSGCTs, confers poor prognosis for affected patients. However, because the signaling pathways and genes responsible for the development of different types of GCTs are not well-understood, few targeted therapies exist for GCTs, and no specific therapies exist for NSGCTs. Therefore, novel therapies to specifically target NSGCTs are needed. To determine a targetable pathway that is activated in GCTs, we used quantitative RT-PCR to measure the expression of growth factor receptors in pediatric GCTs, immunohistochemistry (IHC) on a panel of clinically annotated germ cell tumors, and Western blot as well as cell viability assays on NSGCT cell lines (NCCIT and NTERA-2) to determine the effect of inhibition of two signaling pathways on cell viability. Our RT-PCR results showed that multiple members of the EGF and FGF receptor families are expressed at higher levels in NSGCTs than SGCTs. In addition, we found that EGF and FGF2 stimulate Ras-MAPK as well as PI3K/mTOR signaling in NSGCT cell lines. Based on IHC staining of phosphorylated ERK1/2, mTOR, and S6 ribosomal protein, we showed that both the Ras-MAPK and PI3K-mTOR pathways are activated at higher levels in NSGCTs than SGCTs. The results suggested that inhibiting EGFR as well as mTORC1 may be effective in impairing the growth and survival of NSGCT cell lines. To test this hypothesis, we examined the effects of two small molecule inhibitors of EGFR and mTOR signaling, erlotinib and rapamycin, respectively, on the survival of NCCIT and NTERA-2 cell lines. We verified by Western blot that erlotinib inhibits components of the Ras-MAPK pathway in NSGCT cell lines, while rapamycin inhibits components of the PI3K-mTOR pathway. Cell survival experiments showed that while treatment with rapamycin or erlotinib alone decreased cell viability, sufficient reduction of survival could only be achieved with high concentrations that are not clinically feasible. However, a combination treatment of erlotinib and rapamycin synergistically inhibited the growth of the two NSGCT cell lines at clinically achievable concentrations. Our findings showed that NSGCTs are dependent on EGFR and mTOR signaling in vitro, and suggest that targeting these signaling pathways may be a promising therapy to specifically target chemoresistant NSGCTs. Citation Format: Albert Budhipramono, Dinesh Rakheja, Kenneth S. Chen, Nicholas Fustino, Abhay Shukla, Jonathan Wickiser, Theodore Laetsch, James F. Amatruda. EGFR and mTORC1 are novel therapeutic targets in nonseminomatous germ cell tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B03.

We analysed the treatment results of 52 children with testicular germ cell tumors. Histopathological diagnoses were endodermal sinus tumor (63.4%), embryonal carcinoma (28.8%), teratocarcinoma (5.7%), and mixed tumors (2.1%). Radical inguinal orchiectomy was performed in 42 patients and retroperitoneal lymph node dissection in 10 (3/10 positive). Overall survival rates were: whole group: 71.2%; stage I: 89.7%; II: 68.5%; III: 31.2%; IV: 30% (p= .001). Five-year overall survival rates were 85.8% and 100% for stage I patients who received chemotherapy or not (p= .27); BEP regimen: 85.7%; classical VAC: 67.9%; vinblastine + bleomycin: 63.6%. Chemotherapy is not required in stage I. BEP regimen is effective in testicular germ cell tumors.

Testicular tumors are uncommon in adults, accounting for <1% of all cancers, with testicular germ cell tumors (TGCTs) representing the majority (>95%) of reported cases. Adult and prepubertal TGCTs are fundamentally distinct and the latter is extremely rare, representing 1% of all pediatric solid tumors and having an annual incidence rate of 0.5-2/100,000 boys. Bilateral TGCTs (BTGCTs) account for 0.5-5% of all testicular tumors; the majority are metachronous, while the synchronous account for approximately 0.5-1%. A 16-month-old boy was admitted to our Urology Department with a 2-week history of a painless scrotal mass. Ultrasonography revealed a homogeneous hyperechoic solid mass with rich blood supply in the right testis, and no discernable testicular tissue. A well-delineated heterogeneous echo mass was found within the left testis. Contrast-enhanced computed tomography (CT) scan showed a significantly enhanced mass in the right testis and a mildly enhanced mass in the left testis. Serum alpha-fetoprotein (AFP) was 12,567 ng/mL, while β-human chorionic gonadotrophin (HCG) and total testosterone levels were normal. Accordingly, bilateral testicular tumors were the primary consideration. The patient underwent right radical inguinal orchiectomy with high ligation of the spermatic cord and left testicle-sparing surgery. Final pathology confirmed a pure yolk sac tumor (YST) from the right testis and a cystic mature teratoma from the left. The follow-up ultrasonography showed no recurrence, with serum AFP returned to normal by postoperative day 44. Synchronous primary BTGCT with teratoma and YST respectively can occur coincidently and successfully treated by testicle-sparing surgery.