Evaluation of tumour size and rete testis invasion in progression free survival of our patients with stage i testicular seminoma. A retrospective observational study of a reference hospital center and literature review.

INTRODUCTION: The aim of this study was to evaluate the impact of tumour size and rete testis invasion in progression free survival of our patients with stage I testicular seminoma. A literature review is also made. MATERIAL AND METHODS: A retrospective observational study was performed. We included patients with stage I seminoma between January 2010 and July 2022. Patients without factors of poor prognostic -Group A- were compared with patients with factors of poor prognostic -Group B-. Kaplan-Meier curves and log-rank testing were used to compare progression free survival (PFS) between these groups. Statistical significance was considered at P≤.05. RESULTS: 55 patients were included in this study. 20 patients (36.4%) were of good prognostic -Group A- and 35 (63.6%) had factors of poor prognostic -Group B-. The mean age was similar in both groups (mean±standard deviation), 38.62±9.04 years. The mean follow-up time was 63.5±33.6 months. All the patients in group A and 25.7% of the patients in group B underwent active surveillance (AS). 26 patients (74.3%) of the patients in Group B were treated with one cycle of adyuvant carboplatin. Three patients suffered a relapse with retroperitoneal lymph nodes (10.3%), all of them were treated with three cycles of BEP, with a complete response of the disease. No statistical significant differences were found in PFS between Group A and B (log Rank P=.317). CONCLUSION: Individualization of adjuvant treatment in stage I seminoma is important, avoiding the adverse effects derived from them.

KMT2C mutation in a Chinese man with primary multidrug-resistant metastatic adenocarcinoma of rete testis: a case report.

BACKGROUND: Adenocarcinoma of the rete testis (AORT) is an extremely rare malignant tumor with poor prognosis and limited responsiveness to traditional chemotherapy. Few previous studies have focused on the molecular mechanisms underlying therapy resistance in AORT and further scrutiny is required to enable searches for targeted drugs to guide treatment selection. CASE PRESENTATION: The current case concerns a 55-year-old man with AORT who presented with isolated bone metastasis at initial diagnosis and experienced rapid disease progression after multi-line platinum-based combination chemotherapy. Next-generation sequencing revealed a novel somatic lysine methyltransferase 2C (KMT2C) c.5605 T > C mutation in exon 36 with an abundance of 49.27%. The patient received antiangiogenic drug treatment for 2 months but this was discontinued due to unacceptable anorexia and nausea. He survived for 12 months after diagnosis. CONCLUSION: A potential correlation between AORT primary multi-drug resistance and KMT2C mutations is implied. Further studies are needed to determine the efficacy of PARP1/2 inhibitors for tumors with KMT2C mutations.

Clinicopathologic features and proposed grossing protocol of orchiectomy specimens performed for gender affirmation surgery.

Gender affirmation surgery performed for gender dysphoria is increasing to instigate changes more closely approximating gender identity. We investigated the clinicopathologic features of gender-affirming orchiectomies performed at our institution and devised a grossing protocol for these increasingly encountered specimens. We obtained 45 orchiectomies from 23 patients and reviewed clinicopathologic features. The number of sections per case was noted and reviewed to devise an optimal grossing protocol to assess pathologic findings. Twenty-three patients had bilateral orchiectomy with 1 unilateral. The average patient age was 39.4 years (range, 21-71 years); all received hormones for a mean of 66.1 months (range, 12-348 months). The average number of slides per orchiectomy was 8 slides (range, 1-11). Aspermatogenesis occurred in 32 (71%), hypospermatogenesis in 8 (18%), and normal spermatogenesis in 5 (11%) testes. Twenty-five (56%) exhibited scattered cells with nuclear cytomegaly, concerning for germ cell neoplasia in situ (GCNIS), but OCT4 negative. Six (13%) had multinucleated stromal cells. Leydig cells were markedly reduced/absent in 38 testes (85%). Epithelial hyperplasia was identified in 15 rete testes (33%) and 24 epididymes (53%), while 18 (40%) showed periepididymal muscular hyperplasia. All findings were identified in the initial 2 slides including rete testis/epididymis, except for 3 cases, missing only focal tubular sclerosis. Despite all received treatment, only a subset showed changes of exogenous hormone therapy. The presence of nuclear cytomegaly can mimic GCNIS and may be a potential pitfall. Two sections to include rete testis/epididymis and a third of cord margin are sufficient to identify the relevant pathology and germ cell tumors overall are uncommon in orchiectomies performed for gender affirmation.

Molecular analysis of adenocarcinomas of the rete testis demonstrates frequent alterations in genes involved in cell cycle regulation.

Adenocarcinomas of the rete testis (ACRT) are rare and aggressive testicular neoplasms that present predominantly in older men and have a tendency for early systemic spread. Their morphology spans a wide spectrum, including tumors with glandular, solid, papillary, micropapillary, glomeruloid, cribriform, and sarcomatoid growth patterns, or a combination thereof. The genomic alterations associated with these tumors have not been studied previously. We assessed eight ACRT published in prior clinicopathologic series using a solid tumor DNA sequencing panel. Pathogenic variants were identified in 6/8 cases. More specifically, four cases demonstrated inactivation of genes involved in cell cycle regulation, including CDKN2A, BAP1, TP53, and RB1. CDKN2A was the only recurrently affected gene, with pathogenic variants detected in 3/8 cases. One of these three cases had molecular evidence of concurrent homozygous (i.e. biallelic) NF2 inactivation by a frameshift variant and loss of the wildtype copy of the gene. One case had an internal tandem duplication in AKT, which has been previously described in juvenile granulosa cell tumor and sclerosing pneumocytoma and results in downstream activation of PI3K signaling. The remaining case with positive molecular findings harbored two concurrent truncating SETD2 variants. Multiple arm-level and chromosome-level copy number events were present in 3/8 cases, all of which harbored variants in genes involved in cell cycle regulation. In summary, ACRT are rare tumors with frequent inactivation of genes that play a major role cell cycle regulation, and a subset harbors variants that are potentially amenable to targeted therapy.

[ADENOCARCINOMA OF THE RETE TESTIS WITH METASTASIS OF THE PENILE AND LUNG: A CASE REPORT].

Adenocarcinoma of the rete testis is a rare malignant tumor with poor prognosis. We report a case of adenocarcinoma of the rete testis. A 55-year-old man became aware of discomfort in the right scrotum. Negative results were obtained for the serum markers AFP, ß-human chorionic gonadotropin (ß-HCG), and LDH. Computed tomography (CT) showed enhancement of the right testis. Radical orchiectomy was performed. Immunohistochemical examination of the resected specimen showed positive results for CEA, and adenocarcinoma of the rete testis was diagnosed. Serum CEA level was elevated. CT showed swelling of the para-aortic lymph nodes. Retroperitoneal lymph node dissection (RPLND) was performed, and serum CEA then normalized. The patient developed penile metastases 4 months after RPLND, and serum CEA level again increased. Total penile resection was performed. TIP (Paclitaxel, Ifosfamide, Cisplatin) therapy was started after lung metastasis and increased serum CEA were identified. CT after 2 cycles of TIP therapy revealed disappearance of lung metastasis and normalization of serum CEA. Five months later, CT showed recurrence of lung metastases.

Tubular ectasia of the rete testis in an Angus bull.

An 18-month-old Angus bull presented to Auburn University College of Veterinary Medicine for a routine breeding soundness evaluation and lameness evaluation. He was classified as deferred potential breeder due to a lameness and was donated to the university. Following treatment, the bull's lameness resolved. He passed the breeding soundness examination in accordance with the Society for Theriogenology standards. However, avascular dilated areas at the level of the mediastinum testis of the right testicle were detected via Doppler ultrasonography. A high level of vascularity is routinely seen with neoplasia, such as teratomas. Due to the lack of vascularity, a presumptive diagnosis of tubular ectasia of the rete testis was made. The bull was castrated. The right testicle was submitted for histopathology revealing a definitive diagnosis of tubular ectasia of the rete testis.

Carcinoma of the rete testis: A rare testicular tumor.

Carcinoma of the rete testis is a rare malignant tumor which frequently occurs in middle-aged to older patients and has an aggressive biological behavior. We present the case of a 57-year-old man who presented with an ill-defined mass in the right testicle. The patient underwent a radical orchidectomy. Microscopic evaluation showed a neoplasm displaying a complex papillary-cystic architecture, infiltrating the testicular parenchyma. An in situ proliferation of neoplastic cells, with nuclear stratification and scanty cytoplasm was seen at the periphery, within the channels of the rete testis. The tumor infiltrated the tunica albuginea focally without disrupting it completely. Immunohistochemistry was positive for AE1/AE3, CK7, CK34ßE12, D2-40, and PAX8. Imaging studies presented no evidence of metastatic disease. These findings are those of a primary rete testis carcinoma. The transition between benign and neoplastic rete testis epithelium served as a helpful diagnostic clue. Metastatic carcinomas from other sites were considered in the differential diagnosis.

Patterns of relapse and treatment outcome after active surveillance or adjuvant carboplatin for stage I seminoma: a retrospective study of the Spanish Germ Cell Cancer Group.

PURPOSE: Active surveillance (AS) and adjuvant chemotherapy (AC) with carboplatin are valid alternatives for managing stage I seminoma, and most relapses can be cured with cisplatin-based chemotherapy. However, some reports suggest that AC may modify the classical pattern of recurrences. METHODS: We analyzed all relapses observed in a series of 879 patients with stage I seminoma included in 4 consecutive studies of the Spanish Germ Cell Cancer Group. After a median follow-up of 67 months, recurrences were detected in 56/467 (12%) low-risk cases on AS and 13/412 (3%) high-risk cases after AC (p < 0.001). The objective was to describe clinical features, treatment and outcome. Univariate comparisons were performed between both groups. RESULTS: No significant differences were found between relapses on AS and those after AC in terms of time to relapse (13 vs 17 months), size (26 vs 27 mm), location (retroperitoneum in 88% vs 85%), and method of detection (computed tomography in 77% vs 69%). Treatment consisted of chemotherapy (etoposide + cisplatin ± bleomycin) in 89% and 92%, respectively. Late relapses (after > 3 years) were seen in 11% vs 7.7% (p = NS) and second or successive recurrences in 1.8 vs 23% (p < 0.05). With a median follow-up of 130 moths, two patients died of seminoma-unrelated causes (AS group) and the rest are alive and disease-free. CONCLUSION: In the setting of a risk-adapted treatment of stage I seminoma, the administration of two courses of AC in patients with tumor size > 4 cm and/or rete testis invasion is associated with a higher incidence of second recurrences but does not significantly modify the pattern of relapses or their outcome.

[Secondary pseudopriapism after lymphatic invasion in a patient with adenocarcinoma of the rete testis]. / Seudopriapismo secundario a invasión linfática en paciente con adenocarcinoma de rete testis.

We present a case, the first ever published to our knowledge, of penile metastasis from rete testis adenocarcinoma. 62 years old male, who underwent orchiectomy for left testicular mass. Pathology results reveal rete testis adenocarcinoma. Ten months after chemotherapy, show up a pseudopriapism as a consequence of lymphatic infiltration from low differentiated carcinoma in the biopsy of the glans and foreskin taken during shunt surgery and circumcision. Immunohistochemistry revealed that was a primary testicular tumor metastasis, positivity for EMA, negativity for AFP, PLAP, CD117 and CD30 was seen, supporting the diagnosed of metastatic rete testis adenocarcinoma and excluding other tumors. Rare but highly aggressive tumor, poor prognosis because late diagnosis and bad response to adjuvant surgical or chemotherapeutic treatment. The patient dies one month after the surgery.

Adenocarcinoma of the Rete Testis: Clinicopathologic and Immunohistochemical Characterization of 6 Cases and Review of the Literature.

Adenocarcinoma of the rete testis is rare and its etiological and pathologic characteristics are not well studied. We therefore investigated the clinical, morphologic, and immunohistochemical features of 6 cases diagnosed at our institution and conducted a detailed review of the literature. The mean age was 64 years. All patients presented with testicular masses; 4 were right-sided. On gross examination, all tumors were centered in the hilum and had solid and cystic cut surfaces. Microscopically, all had intrarete and invasive growth and showed multiple patterns, with a variable proportion of papillary, solid and glandular morphology, the latter varying from slit-like lumens to well-formed glands and tubules. Less common patterns included corded/trabecular (n=3), cribriform (n=3), glomeruloid (n=3), nested (n=2), and micropapillary (n=2). Discrete nests of eosinophilic and clear cells were a distinctive feature in 3 cases. Geographic necrosis occurred in 3 cases. All showed at least moderate nuclear pleomorphism with ovoid nuclei. Transition from benign to malignant rete epithelium was seen in all cases. The stroma was hyalinized to partially fibrotic. On immunohistochemical study, the tumor cells were positive for CK7 (5/5), AE1/AE3 cytokeratin (5/5), EMA (5/5), vimentin (5/5), EpCAM (detected by BerEP4 anitbody) (4/5), CK5/6 (4/5), nuclear Wilms Tumor-1 (4/5), epithelial specific antigen (detected by MOC31 antibody) (3/4), PAX8 (3/5), and calretinin (2/5). OCT3/4, SALL4, CD30, NKX3.1, PSA, α-inhibin, CK20, and S100 protein were negative. Ki-67 proliferative index ranged from 5% to 60% (mean: 40, median: 43). At presentation, 5 patients had retroperitoneal lymph node metastasis and one of these also had pulmonary metastases. The sixth patient developed pulmonary metastasis within 15 months of diagnosis. Three died within 4 years of diagnosis. In summary, adenocarcinoma of the rete testis is a rare malignant tumor with poor survival and a high propensity for retroperitoneal lymph node metastasis that must be distinguished from other testicular neoplasms and metastasis to the testis. Hilar localization, transition from benign to malignant rete epithelium, and supportive immunostains aid its accurate diagnosis.

Rete Testis Invasion Is Consistent With Pathologic Stage T1 in Germ Cell Tumors.

OBJECTIVES: Rete testis invasion by germ cell tumors is frequently concomitant with lymphovascular or spermatic cord invasion (LVI/SCI); independent implications for staging are uncertain. METHODS: In total, 171 seminomas and 178 nonseminomatous germ cell tumors (NSGCTs; 46 had 1%-60% seminoma component) came from five institutions. Metastatic status at presentation, as a proxy for severity, was available for all; relapse data were unavailable for 152. Rete direct invasion (ReteD) and rete pagetoid spread (ReteP) were assessed. RESULTS: ReteP and ReteD were more frequent in seminoma than NSGCT. In seminoma, tumor size bifurcated at 3 cm or more or less than 3 cm predicted metastatic status. Tumors with ReteP or ReteD did not differ in size from those without invasions but were less than with LVI/SCI; metastatic status or relapse did not show differences. In NSGCT, ReteP/ReteD did not correlate with size, metastatic status, or relapse. CONCLUSIONS: Findings support retaining American Joint Committee for Cancer pathologic T1 stage designation for rete testis invasion and pT1a/pT1b substaging of seminoma.

A Risk-Adapted Approach to Patients with Stage I Seminoma according to the Status of Rete Testis: The Fourth Spanish Germ Cell Cancer Group Study.

OBJECTIVE: The aim of this study was to assess a risk-adapted strategy for stage I seminoma guided by the presence of rete testis invasion. METHODS: Between January 2013 and December 2015, a total of 135 consecutive patients with stage I seminoma from 18 Spanish tertiary hospitals were included in a prospective multicenter study. Median patient age was 38 years (range 22-60). Preoperative beta-human chorionic gonadotropin was elevated in 9.6% of patients. Rete testis invasion was present in 47.4% of patients. After orchiectomy, subjects with rete testis invasion were treated with 2 courses of adjuvant carboplatin (area under the curve of 7, with 21-day interval). Those without this risk factor were managed by surveillance. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method. RESULTS: After a median follow-up time of 33 months, only 6 relapses were recorded (5 on surveillance, 1 after carboplatin). These cases were rescued with BEP or EP chemotherapy, and all 135 patients are currently disease free without sequelae. Three-year DFS was 92.0 and 98.2% for patients on surveillance and after carboplatin, respectively. Three-year OS was 100%. CONCLUSION: A risk-adapted approach based on rete testis invasion as a single risk factor is feasible and yielded an excellent outcome with a 3-year DFS of 94.9%.

Acquired adenomatous hyperplasia of the rete testis: an immunohistochemical study of its pathogenesis.

Adenomatous hyperplasia of the rete testis (AHRT) is an uncommon abnormality first described by Nistal and Paniagua in 1988. Congenital and acquired forms of AHRT are recognized. We present a case of AHRT in a patient who underwent bilateral orchiectomy for penile carcinoma; he had received chemotherapy for Hodgkin lymphoma 18 years prior. Proposed causes for this disorder include developmental, hormonal, and paracrine induction by adjacent testicular tumors and exposure to chemicals, based on clinical contexts but without experimental support. We performed immunohistochemical studies using markers of cell cycle (cyclin D1, p16), proliferation (Ki-67), apoptosis (bcl2), senescence (γ-H2AX), and androgen receptors to try to provide scientific support for or refute existing hypotheses. Our results indicate that, in this case of acquired AHRT after chemotherapy, the process is neither adenomatous nor hyperplastic but rather represents abnormal accumulation of rete testis cells with acquired senescence.

The Morphologic Spectrum of Sertoliform Cystadenoma of the Rete Testis: A Series of 15 Cases.

Sertoliform cystadenoma of the rete testis (SCRT) is rare with only 9 cases reported to date in the literature, none with follow-up. Four large genitourinary pathology consult services were searched. We identified 15 cases of SCRT. Men were 21 to 84 years old (mean, 46 y) and had testicular discomfort or mass. Other findings were seminoma (n=1), spermatocele (n=2), hydrocele (n=1), varicocele (n=1), and scrotal hematoma (n=1). Eight had preoperative serum tumor markers, which were normal. Tumors ranged from 0.3 to 4 cm (mean, 1.5 cm). All of them were well circumscribed with solid and cystic features and occupied on average, 73% of the rete (20% to 100%). The tumors were mostly confined within dilated channels of the rete testis and showed classic features consisting of: (1) tubules with well-formed lumina in 87% of cases; (2) well-formed tubules with no lumina in 87% of cases; and (3) cords/nests in hyalinized or myxoid stroma in 73% of cases. Other patterns included: (1) solid/sheet growth in 26% of cases; (2) individual cells in 13% of cases; (3) festoons in 13% of cases; (4) branching tubules in 7% of cases; and (5) papillary in 7% of cases. Cells were cuboidal with round to oval nuclei with small nucleoli, except at the periphery where projections into rete tubules had a more columnar appearance. In the festooning pattern, nuclei were pseudostratified and columnar with prominent nucleoli and nuclear grooves. In 4 cases, tumor extended into adjacent seminiferous tubules surrounded by dense peritubular fibrosis, with in some cases small cysts lined by flattened epithelium containing pale lightly granular material. All cases lacked necrosis and significant atypia. Mitoses ranged from 0 to 2 per 10 high-power field. Follow-up ranged from 4 to 170 months with mean of 97 months. For the 13 cases with information, all patients were alive, except for 3 who died of either unrelated causes (9.2 and 10 y) or of unknown cause (4.8 y at age 89 y). We performed immunohistochemistry for steroidogenic factor 1 and inhibin in 4 of our cases, where 3 (75%) were positive for both markers. We also describe 2 additional cases which morphologically resembled SCRT but had more atypical features. This study highlights that SCRT has variable morphology. We also verify the benign nature of the lesion and its lack of association with any syndromes.

Sertoliform Cystadenoma of the Rete Testis: Report of a Case and Review of the Literature.

Sertoliform cystadenoma is a rare benign tumor of the rete testis with 8 previously reported cases and an additional 14 cases reported in an abstract form. It usually presents with a unilateral scrotal mass, clinically and radiologically indistinguishable from malignant testicular tumors. We report a 39-year-old man who presented with a right testicular mass. The patient underwent radical inguinal orchiectomy. Grossly, no masses were appreciated. After histologic examination with subsequent immunohistochemical staining, a sertoliform cystadenoma of the rete testis was diagnosed.

Adenomatous hyperplasia of the rete testis: A rare intrascrotal lesion managed with limited testicular excision.

INTRODUCTION: Testicular cancer is one of the most frequent in young men and its incidence is increasing in recent years because of incidental finding during routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of the benign and rare pathological types incidentally detected and very few cases are described in the literature. CASE REPORT: A 40 years old man come to our attention for a balanoposthitis without testicular pain. During andrological examination we performed palpation of the testes and we noticed a palpable nodule of hard consistency in the left testicle. We then performed an ultrasound exam of the testis which highlighted the presence of an intra-didymus neoformation with diameters of 1.2 x 1.6 cm and with the presence of cysts inside. We also performed blood tests to check tumor markers alpha fetoprotein, beta hCG and LDH which resulted inside the normal range. We then conducted a chest and abdomen CT scan that showed no pathological elements. Therefore, as we suspected that this tumor was benign, we performed an enucleation of the neoplasm. The definitive histological examination revealed the presence of dilated ducts lined with epithelial cubic-columnar cells with clear cytoplasm rich in glycogen and the pathologist so concluded that the tumor could be classified as adenomatous hyperplasia of the rete testis. At three months of follow up, the patient doesn't have any recurrent lesion to either testicles. DISCUSSION: Adenomatous hyperplasia of the rete testis is a very rare intrascrotal lesion. This histological type is the most frequent between benign lesion of the ovary, but few works in literature reported this histological type in the male gonad and, in most of these works, authors described these lesion at epididymis. CONCLUSION: We believe that a conservative approach must be considered mandatory in case of testicular lesions 1.5 cm in diameter. A radical approach might have alterate fertility of the patient and also have caused psychological trauma more than an enucleation. However a longer follow up is needed to understand if this was the right decision for the oncological point of view.

Primary clear cell carcinoma of the rete testis: 1st report.

Primary tumours of the rete testis, either benign or malignant, are very rare. Such lesions require careful scrutiny including immunohistochemical analysis to exclude malignant lesions such as mesothelioma or papillary serous carcinoma. To the best of our knowledge this is the first report of a primary clear cell carcinoma of the rete testis. The possibility of a primary renal cell carcinoma or other primary site with metastatic spread to rete testis was excluded by thorough clinical and radiological work-up.