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OBJECTIVE: To review the morphologicalaspects (classical and molecular) of the natural history oftesticular germ cell tumors that have an impact ontreatment.METHODS: Data available in the literature publishedduring the last 10 years and the experience of the PathologyDepartment of the Puigvert Foundation over the last 20years were reviewed.RESULTS/CONCLUSIONS: Intratubular germ celltumor is the precursor lesion of testicular germ celltumors. Its classification into seminoma and nonseminomatous lesions continue to be useful for practicalpurposes. All available data indicate that an intermediateform of seminoma may exist. AFP production is morerelevant in tumors of the vitelline sac, thereforedetermination of AFP in blood could indicate a tumor withthis component. Furthermore, vitelline sac tumors mayhave morphological expressions (epithelial andmesenchymal) that could be the origin of many of themetastases that look like teratoma. One must be cautiousin the biological evaluation of teratomas since nuclearatypias are common in the mature teratoma and celldensity in the immature teratoma. Evidence of infiltrativegrowth is the only sign that indicates malignant teratoma.Retroperitoneal germ cell tumors are testicular metastasesunless demonstrated otherwise, whereas mediastinallesions are usually primary tumors.
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OBJECTIVE: The present study reviewsthe diagnostic criteria of testicular ultrasonography.METHODS: Our experience and data available at ourinstitution and in the literature were reviewed. The USpatterns directly or indirectly related to testicular tumorsand the lesions that may mimick these tumors are analyzed.The utility of CT and MRI is also discussed.RESULTS: The sensitivity of US in testicular tumorswas 100%. Its specificity was lower and was limited by thetechnique which is operator-dependent. Most of thetesticular tumors were hypoechoic and this was a commonfeature of seminoma.CONCLUSIONS: The rational use of the US patternstogether with the clinical and biological findings areuseful in making the diagnosis in tumors with atypicalpatterns or those found in special groups of patients.
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OBJECTIVE: To review the current use of fine needle aspiration in the diagnosis of intratubular germ cell tumor and other testicular pathology. METHODS: The Medline database was accessed to review the literature on fine needle aspiration. Journal articles, monographs and books on the subject were also reviewed. RESULTS: The cytological findings on fine needle aspiration were not found to be conclusive in the diagnosis of intratubular germ cell tumor. CONCLUSIONS: Surgical testicular biopsy is currently considered to be the only reliable diagnostic method for intratubular germ cell tumor and in the determination of the pathogenesis of male infertility. However, conventional open surgical biopsy and thru-cut biopsy are not atraumatic procedures and cause injury to the testis. The sensitivity of fine needle aspiration as a diagnostic procedure has not yet been established, probably due to the lack of information or consensus on the characteristic findings on which to establish the diagnosis of intratubular germ cell tumor, or for application in the diagnosis and follow-up of testicular tumors and the study of testicular physiopathology.
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OBJECTIVE: To review the diagnosticand therapeutic aspects of carcinoma in situ of the testis,the preinvasive stage of testicular germ cell tumors.METHODS: The indications for performing testicularbiopsy in patients with a higher incidence of testicularcarcinoma in situ (patients with infertility, cryptorchidismand / or testicular atrophy, gonadal dysgenesis and aprevious diagnosis of testicular or extragonadal germ celltumor) are discussed, with special reference to thecontroversy of whether biopsy of the contralateral testis isnecessary in patients with primary testicular tumor. Theadvantages and disadvantages of the noninvasivediagnostic techniques as an alternative to biopsy are alsodiscussed.RESULTS/CONCLUSIONS: Testicular biopsy is themain diagnostic procedure. Testicular ultrasonography isthe most useful noninvasive diagnostic technique and canbe considered in areas with a low incidence of tumor of thecontralateral testis. Orchidectomy and radiotherapy arethe two main therapeutic options for testicular carcinomain situ. The choice between one or the other approachdepends basically on whether the testicular involvement isunilateral or bilateral.
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OBJECTIVE: The present article reviews the different aspects of "burned out" testicular tumor.METHODS: A survey of the literature on "burned out" testicular tumor in Medline 1980-1999 was performed. The selected articles referenced in the present study were reviewed.RESULTS: The "burned out" phenomenon is the regression of a testicular tumor focus after distant metastasis whose cause is unknown. However, characteristic histological lesions have been identified, such as lesions comprised of collagen tissue containing neoplastic cells. The diagnosis is based on the anatomopathological study of the orchidectomy specimen, which should be performed in patients with extragonadal germ cell tumor and alterations detected on physical or ultrasound examination.CONCLUSIONS: "Burned out" testicular tumor should be taken into account in patients with extragonadal germ cell tumor. The importance of a thorough physical examination and testicular ultrasound evaluation is emphasized. Chemotherapy may not be effective. Orchidectomy may improve the outcome in these tumors.
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OBJECTIVE: To review our experiencewith Leydig cell tumor of the testis and compare ourfindings with those reported in the literature.METHODS: The clinical records of patients with Leydigcell tumor of the testis that were treated in our hospitalwere reviewed. This study analyzed patient age, reason for consultation, previous history of testicular pathology, sizeand location of the tumor, US pattern, histological findings,hormone analysis, semen analysis, treatment and clinicalcourse.RESULTS: 7 patients had Leydig cell tumor of thetestis, accounting for 2.1% of the testicular tumors treatedin our hospital. The mean age at the time of diagnosis was40 years. The presenting features were enlarged testis,gynecomastia, sexual dysfunction or incidental findingduring testicular US assessment for cryptorchidism. Mostof the tumors were hypoechoic and showedhypervascularization. Hormone analysis was abnormal in4 patients and showed reduced testosterone and increasedserum estradiol levels. The initial semen analysis showedazoospermia, severe oligozoospermia or cryptozoospermiain 4 patients. Six patients had previously undergoneorchidectomy via the inguinal approach and one patienthad undergone tumor resection. At 41 months meanfollow-up, the tumor has been demonstrated to be benign.CONCLUSIONS: Leydig cell tumor of the testis usuallypresents as a testicular mass, accompanied or preceded byhormonal changes in 20% of the cases, with feminizationin the adult and masculinization in the child. The lesionsare always benign in children and in 90% of the adultpatients. The US features are usually hypoechoic. Thehistological criteria for malignancy do not always correlatewith the clinical features. Malignancy is established by the presence of metastasis at the time of diagnosis orduring follow-up. There is currently no effective treatmentfor the metastasis. Following orchidectomy, the clinicalhormonal manifestations return/remit in 90% of the cases.
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OBJECTIVE: To review the utility of tumormarkers in the treatment of germ cell testicular tumors.METHODS: The literature on this subject was reviewed.RESULTS/CONCLUSIONS: The tumor markers alphafetoprotein, beta-HCG and LDH are essential in themanagement of germ cell tumors. They are useful for theinitial diagnosis and postoperatively, particularly in thedetection of residual disease following surgery in stage Itumors. Their role as a prognostic marker has been clearlyestablished in the IGCCCG classification. Furthermore,these markers are useful for follow-up, detection of tumorrecurrence and for monitoring response to therapy.Spurious increases of marker levels unrelated withtumor progression may occur and should be recognized.The increase in alpha-fetoprotein levels can be caused byliver damage and tumor lysis, and the increase in betaHCG levels can be caused by hypogonadism, tumor lysis,or may be a discordant increase or hook effect.
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OBJECTIVE: To describe 11 cases ofmetastatic carcinoma of the testicular parenchymapresenting as a scrotal mass.METHODS: A descriptive and retrospective study ofmetastatic carcinoma of the testis was performed. Elevencases of testicular metastasis from prostate cancer (7),renal adenocarcinoma (2), bladder carcinoma (1) andcarcinoma of the pancreas (1) are presented.RESULTS: All the patients had multiple disseminateddisease from their underlying condition, which is a sign ofpoor prognosis.CONCLUSIONS: Testicular metastasis from carcinoma is rare and frequently arises from adenocarcinoma ofthe prostate. Clinically, testicular metastases cannot bedistinguished from primary tumors and generally affectmales over 60 years old.
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OBJECTIVE: To review the advantages,disadvantages and efficacy of the different therapeuticoptions for stage I seminoma and nonseminomatous germcell testicular tumors.METHODS: The literature on the treatment of stage Igerm cell testicular tumors was reviewed.RESULTS/CONCLUSIONS: Germ cell tumors of thetestis constitute 1-1.5% of neoplasms in the male,accounting for 95% of testicular neoplasms, and is themost common solid tumor in men aged 20-35 years.Currently, 70% of the patients with seminoma and 50% ofthe patients with nonseminomatous germ cell testiculartumors are diagnosed in stage I.Radiotherapy following orchidectomy has classicallybeen utilized in the treatment of stage I germ cell testiculartumors. Postoperative radiation therapy is currently beingreplaced by close patient follow-up in many centers.Retroperitoneal lymphadenectomy post-orchidectomy isthe standard treatment for stage I nonseminomatous germcell testicular tumors. Today, however, the foregoingapproach is also being replaced by close postoperativefollow-up.
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OBJECTIVE: To review the treatment ofstage I nonseminomatous germ cell testicular tumor withadjuvant chemotherapy.METHODS: The literature on this subject was reviewed.RESULTS/CONCLUSIONS: Overall, 30% of stage Inonseminomatous germ cell testicular tumors that arefollowed recur within two subsequent years. Several factorsassociated with a higher risk have been described. Themost important are the presence of venous or lymphaticinfiltration, the presence of a carcinoembryonic componentand the absence of tumor of the endodermal sinus. Patientswith the foregoing characteristics have a recurrence rateof approximately 50%. Over the last few years, someexperience using two cycles of BEP adjuvant chemotherapyin patients at a higher risk have shown that this recurrencerate can be reduced to less than 5% with minimal latetoxicity.
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To analyze the current roleof surgery in the treatment of stage I testicular germ celltumors.METHODS: We reviewed the literature on stage Itesticular germ cell tumors. The technique of orchidectomy,the arguments in favor of retroperitoneallymphadenectomy, the evolution of this technique and theprognostic factors that might be useful in determining thetherapeutic approach to stage I testicular germ cell tumorsare analyzed.RESULTS/CONCLUSIONS: Treatment of testiculargerm cell tumors should be performed in specializedcenters that can offer all the therapeutic possibilities witha maximum guarantee so that the patient can decide on thetreatment after receiving all the information on theadvantages and disadvantages of each modality.Retroperitoneal lymphadenectomy with preservation ofsympathetic innervation preserves ejaculation. Its curerate is similar to that of other therapeutic options, itcarries a minimum morbidity, follow-up is simplified,patient anxiety is reduced and there are long-term savingson costs.
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OBJECTIVE: To review the role oflaparoscopic lymphadenectomy for stage Inonseminomatous germ cell tumor of the testis.METHODS: The current literature on this subject isreviewed and the advantages and disadvantages of thistechnique are discussed.RESULTS/CONCLUSIONS: Although there is noagreement on the management of nonseminomatous germcell tumors of the testis, some groups advocate performingretroperitoneal lymphadenectomy after orchidectomy,particularly for tumors with a high risk of dissemination.The laparoscopic approaches that were introducedbasically in the 90’s, have permitted performing surgicaltechniques with a low morbidity and a shorter recoverytime. Laparoscopic retroperitoneal lymphadenopathy isone such technique. According to the experience of severalgroups, this technique has an acceptable operating time(approximately 5 hours), low complication rate and shorthospital stay (2-5 days according to the different series).For those with experience in performing the laparoscopicapproach, it is a therapeutic alternative that should beconsidered for this type of testicular tumor.
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OBJECTIVE: Conventional treatment oftesticular seminoma has been orchiectomy followed byadjuvant lymph node irradiation. Over the last 10 yearsthe role of postoperative elective radiotherapy has beenquestioned. This paper reviews the role of radiotherapy inthe treatment of seminoma of the testis.METHODS: The literature is reviewed with specialreference to the results achieved in the treatment oftesticular seminoma with and without radiotherapy. Theadvantages and disadvantages of postoperativeradiotherapy, the techniques and dose administered arediscussed.RESULTS/CONCLUSIONS: The results obtained withradiotherapy postorchidectomy in stage I seminoma of thetestis are excellent, with a disease free survival of 95%-100%. The use of more limited fields of irradiation andlower dose has reduced the radiation-induced toxicity.Currently, many centers have opted for clinical surveillanceafter orchiectomy. Their experience have permittedidentification of the risk factors and there have beenattempts to identify the group of patients that benefit fromadjuvant therapy.The low incidence of stage II tumors has not permittedperforming randomized studies to determine the benefitsof adjuvant therapy and its comparison with chemotherapy.Consolidation radiotherapy for bulky stage II and stage III and IV tumors continues to be a controversy, although itspotential value in carefully selected patients is recognized.
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OBJECTIVE: To discuss briefly the newtherapeutic strategies for poor-prognosis testicular germcell cancer.METHODS: The use of new drugs in first linechemotherapy, intensive alternating and sequentialchemotherapy and high dose chemotherapy with autologousbone marrow or stem cell transplantation are brieflydiscussed.RESULTS/CONCLUSIONS: Despite the currentadvancements in the treatment of germ cell tumors,approximately 50% of patients with poor-prognosis germcell tumors according to the IGCCCG classification diefrom their disease. In order to improve the results in thisgroup of patients, new therapeutic strategies are currentlybeing investigated, such as the introduction of new drugsto the first line chemotherapeutic regimen. However,randomized studies have shown no benefit from the use ofifosfamide. Phase II trials have shown promising resultswith intensive alternating and sequential chemotherapy,although the only phase III randomized trial that has beenconducted comparing BOP-VIP with BEP showed noadvantages. Some phase II trials using high-dosechemotherapy with hematopoietic support in first linetreatment of poor-prognosis germ cell tumors have shownpromising results. Randomized trials are necessary in thisgroup of patients in order to achieve therapeuticadvancements.
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OBJECTIVE: To review the classificationsof the risk groups of different prestigious institutions andcollaborative groups that have had a major impact on ourknowledge and therapeutic approach to germ cell tumorsof the testis.METHODS: We reviewed the different classificationsof renowned institutions and collaborative groups and theliterature published over the last 15 years that provideevidence for the optimal therapeutic approach for eachsubgroup at risk.RESULTS/CONCLUSIONS: Germ cell testicular tumorsis the paradigm of curable tumors of the adult. Patientswith stage I tumors have an excellent prognosis with morethan 98% probability of cure. The prognosis for theadvanced stage tumors is superior to that of other solidtumors with a similar volume due to their exquisitechemosensitivity. Patients with advanced disease can bedivided into two or three groups (low and high, or low,intermediate and high risk) with different probability ofcure after treatment with cisplatin-based regimens,according to the location of the primary tumor, extent ofthe disease and serum levels of the markers. The standardtreatment for the advanced disease consists of first linechemotherapy with cisplatin, etoposide and bleomycin(BEP) followed by surgery in cases with residual tumor.Approximately 10% of the patients with good-prognosisfactors and 30%-50% of those with poor-prognosis factorswill not cure after first line chemotherapy, althoughrescue with second line chemotherapy can be utilized insome of these patients. The search for more effectivechemotherapeutic regimens for high risk patients andregimens with a lower toxicity for the low risk patients hasbeen hampered by the lack of consensus among theworking groups on the criteria for the classification ofthese patients into subgroups according to prognosis. Therecent International Germ Cell Consensus Classificationwill permit studies on homogeneous risk groups of patientsand will allow us to obtain reliable and reproducibleresults.
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OBJECTIVE: Surgical treatment of the residual retroperitoneal mass is indicated in 30% of germ cell testicular tumors with lymph node involvement after chemotherapy. This approach is reviewed in the present article.METHODS: We reviewed the literature on the surgical treatment of the residual retroperitoneal mass.RESULTS: CT is reported to be the most sensitive in detecting the nodes, but no diagnostic method can predict the histological characteristics. Surgery of the residual tumor mass demonstrated tumor in 20% of the cases and necrosis (40%) or teratoma (40%) in the rest of the cases. Patients with active tumor benefit from a second course of chemotherapy, which achieves a cancer-specific survival of 63%. If surgery is incomplete, the second course of chemotherapy only achieves 25% remission. Non-responders to the second course of chemotherapy require another surgical procedure, which only achieves 30%remission. Teratoma is chemotherapy- resistant, therefore complete resection is required, which achieves a survival of 94%. Patients with necrosis have 14% extraperitoneal recurrence. Surgical treatment of the residual retroperitoneal mass has a 21% complication rate. Ejaculation is preserved in 76% of the patients by sympathetic nerve-sparing techniques which does not affect survival.CONCLUSIONS: Surgical treatment of the residual retroperitoneal mass is necessary in patients with recurrence post-chemotherapy. It selects the patients with active cancer that require a second course of chemotherapy and permits cure in patients with teratoma.
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OBJECTIVE: To review our series ofpatients with the growing teratoma syndrome (GTS) andto compare our results with those reported in the literature.METHODS: We reviewed the clinical records of ourseries of patients with GTS for age, location of the tumormass before and after chemotherapy, clinical stageaccording to the Royal Marsden Hospital Classification,histological pattern of the primary tumor, number andtype of surgical procedures performed and clinical course.RESULTS: There were 17 patients with GTS, accountingfor 4.9% of the patients with nonseminomatous germ celltesticular tumors treated in our hospital. The mean age atthe time of diagnosis was 23 years. The site of the lesions was the same as that of the prechemotherapy metastasis inall cases. Histological analysis of the primary tumorshowed mature teratoma in 11, ectodermal sinus tumor in8, and both histological types in 4. By stage, 11 patientswere stage II and 6 were stage IV. A total of 33 surgicalprocedures were performed: 25 retroperitoneallymphadenectomy (7 with retrocrural involvement), 4thoracotomy with segmental lung resection, 2 resection ofsupraclavicular adenopathy, 1 resection of liver metastasis,and 1 resection of inguinal adenopathy. The 25retroperitoneal lymphadenectomy performed due to GTSaccount for 16.2% of the 154 retroperitoneallymphadenectomies that were performed during the sametime period. Follow-up showed recurrence in 10 patients(58.8%); 7 had mature teratoma and 3 had malignanttumor.CONCLUSIONS: Mature teratoma lesions can appearin different sites, the most frequent being theretroperitoneum and lung. These lesions can appear beforeor during chemotherapy or after a disease-free interval.The treatment of choice is resection of the mass, if possiblein a single session to prevent malignant degeneration orcompression of the adjacent structures. We institutetreatment early since an increase in size will make surgicaltreatment difficult, compromise organs and favorrecurrence.
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OBJECTIVE: To review the differentsalvage chemotherapy regimens according to theprognostic factors based on the response to the differenttherapeutic alternatives.METHODS: The conventional rescue chemotherapyregimens, as well as the role of surgery, new drugs andtherapeutic modalities, particularly high dose second andthird line chemotherapy, were reviewed.RESULTS/CONCLUSIONS: Germ cell testicular tumor is the paradigm of curable tumors of the adult.Whereas the cure rate for stage I tumors is higher than98%, patients with advanced stage tumors have a lowercure rate. Approximately 10% of the patients with goodprognosis factors and 30%-50% of those with poorprognosis factors show tumor progression or recurrenceafter first line chemotherapy using cisplatin-basedcombinations. Patients who have recurrence after firstline chemotherapy have a 40% probability of achievingsecond complete remission with second line chemotherapy,but will be sustained in only 20% of the patients, althoughrare cases of advanced pure seminoma that recurred haveshown a cure rate of 55% with second line chemotherapy.New strategies have been developed using new drugs suchas taxanes or high doses of well-known chemotherapeuticagents with autologous hematopoietic rescue that havebeen utilized with success in patients with refractory germcell testicular tumors. A global analysis of the patientstreated with third line chemotherapy shows a sustainedcomplete remission rate of 22%. However, this percentagecan only be increased to up to 50% for patients with noadverse factors.
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OBJECTIVE: To review the advancements in basic molecular biology and current insight into the pathogenesis of germ cell tumors of the testis, as well as the utility of the different genetic and molecular markers in the management of these tumors.METHODS: The literature on this subject was reviewed. The epidemiological data related to the pathogenesis of this tumor type, the cytogenetic and molecular alterations that could serve as a prognostic factor in these tumors were analyzed.RESULTS/CONCLUSIONS: The prenatal estrogenic effect together with the pubertal hypergonadotrophism could be responsible for the pathogenesis of germ cell testicular tumors. The cytogenetic changes of chromosome 12, although typical of the phenotype of these tumors, do not appear to be useful as a prognostic factor. However, cell proliferation, particularly of Ki-67, appears to be useful as a prognostic factor, although further studies are warranted.
