Three-dimensional analysis of junctions between efferent and epididymal ducts in the human caput epididymis.

BACKGROUND: Due to the scarcity of studies using human tissues, the limited information is currently available on the gross structure of the caput epididymis in humans, at which efferent ducts connect to the epididymal duct. OBJECTIVE: The present study investigated the three-dimensional structures of efferent and caput epididymal ducts in humans, with a focus on junctions between the former and the latter. MATERIALS AND METHODS: We examined three sets of human efferent and caput epididymal ducts in specimens obtained from prostatic carcinoma patients. They were reconstructed from serial paraffin sections using a segmentation model created by a deep learning protocol and high-performance three-dimensional reconstruction software. RESULTS: Serial sections and three-dimensional images of human efferent and caput epididymal ducts were combined to obtain the detailed anatomical information. When a single efferent duct was defined as a duct connecting to both the extra-testicular rete testis and epididymal duct, there were 14.7 efferent ducts with a total length of 3.0 m per specimen on average. The cranial portion of the efferent ducts joined to a single duct and terminated at the end of the epididymal duct, whereas other efferent ducts terminated independently on the side of the epididymal duct. These two types of junctions between the efferent and epididymal ducts differed in the patterns of the epithelial-type switch. The epididymal duct consisted of multiple segments, which were separated by a minimal amount of connective tissue septa or even without them. Efferent ducts occupied most of the volume of the caput epididymis. DISCUSSION AND CONCLUSIONS: By utilizing deep learning, we reconstructed human efferent and caput epididymal ducts and revealed their precise three-dimensional structures, which differed from those of rodents in several aspects. The present results may be useful for analyzing anatomical abnormalities related to some types of male infertility.

Cystic dysplasia of the rete testis accompanying ipsilateral renal agenesis in a young adult: a case report.

A 31-year-old man with left-sided testicular pain lasting a couple of months was referred to our urology department due to a suspected testicular tumor. Physical examination showed a hard, thickened, and small left testis on palpation with a diffuse, inhomogeneous ultrasonographic appearance. After a urologic examination, a left-sided inguinal orchiectomy was performed. The testis, epididymis, and spermatic cord were sent to pathology. Gross examination revealed a cystic cavity filled with brown fluid and the surrounding brownish parenchyma measuring up to 3.5 cm in diameter. Histologic examination showed a cystically dilated rete testis lined with cuboidal epithelium and a positive immunohistochemical reaction to cytokeratins. Microscopically, the cystic cavity was a pseudocyst filled with extravasated erythrocytes and abundant clusters of siderophages. The siderophages extended into the testicular parenchyma, surrounding the seminiferous tubules and spreading out around the ducts of the epididymis, which were also cystically dilated with siderophages inside their lumina. On the basis of clinical data, histological, and immunohistochemical analysis, the patient was diagnosed with cystic dysplasia of the rete testis. The literature shows an association between cystic dysplasia of the rete testis and ipsilateral genitourinary anomalies. Therefore, our patient underwent a multi-slice computed tomography scan, which revealed ipsilateral renal agenesis, a right seminal vesicle cyst reaching up to the iliac arteries, and a multicystic formation cranial to the prostate.

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.

[Clinicopathological features of adenocarcinoma of the rete testis].

Objective: To investigate the clinicopathological features, immunophenotype, and differential diagnosis of adenocarcinoma of the rete testis. Methods: Four adenocarcinoma cases of the rete testis diagnosed at West China Hospital, Chengdu, China (3 cases, including 2 consultation cases) and the First Affiliated Hospital of Fujian Medical University, Fuzhou, China (1 case) between January 2009 and December 2017 were included. Their clinical, morphologic and immunohistochemical features were analyzed using histological analysis and immunohistochemical staining. Related literature was reviewed to reveal the characteristics of this tumor. Results: The 4 patients' age range was 26-64 years. The maximum diameters of the tumors were 3.0 and 4.5 cm in 2 cases, respectively. On gross examination, adenocarcinomas of the rete testis appeared as a solid, white to gray or tan to yellow mass that raised at the hilum of the testis. Microscopically, all tumors showed multiple histologic patterns, including corded/trabecular (4/4), glandular, nested, sarcomatoid (3/4), solid (2/4), papillary, cribriform, and slit-like (1/4). Three types of adenocarcinoma cells included cuboidal to columnar (4/4), polygonal (4/4) and spindle-shaped (2/4) with pale eosinophilic and clear cytoplasm. The tumor cell nuclei appeared moderately to markedly atypical and pleomorphic, with a various number of mitoses. Transition from benign to malignant rete epithelium was seen in all cases. Eosinophilic hyaloid globules were found in 1 case. On immunohistochemical study, the tumor cells were diffusely, strongly positive for CKpan (4/4), EMA (4/4), Ber-EP4 (3/3) and CAⅨ(2/2), and focally positive for CK7 (4/4), vimentin (4/4), CD10 (4/4), PAX8 (3/3), PAX2 (3/3). The Ki-67 proliferative index was all>50% (4/4). The prognosis was poor. Two of the 3 patients died within 1 year after the surgical resection. Conclusions: Adenocarcinoma of the rete testis is a rare malignant tumor with several histologic patterns. Transition from benign to malignant rete epithelium is an important diagnostic clue. Detailed clinical history, tumor growth site and immunohistochemistry are helpful for its diagnosis and differential diagnosis.

Estrogens and development of the rete testis, efferent ductules, epididymis and vas deferens.

Estrogen has always been considered the female hormone and testosterone the male hormone. However, estrogen's presence in the testis and deleterious effects of estrogen treatment during development have been known for nearly 90 years, long before estrogen receptors (ESRs) were discovered. Eventually it was learned that testes actually synthesize high levels of estradiol (E2) and sequester high concentrations in the reproductive tract lumen, which seems contradictory to the overwhelming number of studies showing reproductive pathology following exogenous estrogen exposures. For too long, the developmental pathology of estrogen has dominated our thinking, even resulting in the "estrogen hypothesis" as related to the testicular dysgenesis syndrome. However, these early studies and the development of an Esr1 knockout mouse led to a deluge of research into estrogen's potential role in and disruption of development and function of the male reproductive system. What is new is that estrogen action in the male cannot be divorced from that of androgen. This paper presents what is known about components of the estrogen pathway, including its synthesis and target receptors, and the need to achieve a balance between androgen- and estrogen-action in male reproductive tract differentiation and adult functions. The review focuses on what is known regarding development of the male reproductive tract, from the rete testis to the vas deferens, and examines the expression of estrogen receptors and presence of aromatase in the male reproductive system, traces the evidence provided by estrogen-associated knockout and transgenic animal models and discusses the effects of fetal and postnatal exposures to estrogens. Hopefully, there will be enough here to stimulate discussions and new investigations of the androgen:estrogen balance that seems to be essential for development of the male reproductive tract.

Spontaneous regression of cystic dysplasia of the rete testis in an 18-month-old boy: the key role of ultrasonography.

Cystic dysplasia of the rete testis (CDT) is a rare cause of scrotal swelling in children. It is a congenital disorder and it can be associated with other genitourinary abnormalities. At present, there is no clear consensus on treatment. Surgical approach has traditionally been the treatment of choice, while, more recently, conservative approach has been applied, justified by the benign nature of the lesion and after few cases of spontaneous regression have been documented. Ultrasonography, supported by negative tumor markers, plays a key role in the diagnostic work up and during observational follow-up. We report a further case of spontaneous regression of suspected CDT in an 18-month-old boy, who has been followed with clinic and ultrasonographic checks.

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.

Cystic Dysplasia of the Rete Testis: Does Pathophysiology Guide Management?

Cystic dysplasia of the rete testis (CDT) is a rare, benign, cause of testicular mass in the pediatric population. The mass appears on sonography as multiple small cysts of varying size surrounded by normal or compressed testicular tissue. CDT is often associated with other genitourinary anomalies, commonly presenting with agenesis or dysplasia of the ipsilateral kidney. The pathophysiology and the management remains controversial. We report a case of a 3-year-old presenting with an enlarged testicular mass later presumed to be CDT associated with ipsilateral renal agenesis, review the literature, and propose an evaluation and management algorithm.

What Is the Significance of Rete Testis Invasion by Malign Germ Cell Tumor and Does Hilum Predict Metastasis?

BACKGROUND: The significance of hilar soft tissue invasion of rete testis in malign germ cell tumors is still controversial on current guidelines. OBJECTIVES: We aimed to investigate the importance of hilar soft tissue involvement in germ cell tumors and evaluated the possibility of a risk factor such as rete testis. METHOD: Totally, 59 radical orchiectomy specimens operated between 2007 and 2015 at our clinics. All records were retrospectively researched. Patients' age, level of tumor markers, tumor size, histological subtype, clinical stage, presence or absence of carcinoma in situ, vascular/lymphatic and/or hilar soft tissue invasion, tumoral necrosis, number, site and diameter of metastasis, type of further treatment (radiotherapy or chemotheraphy) and follow-up period were recorded and evaluated for all patients. RESULTS: Twenty-six of totally 59 malign germ cell tumors were seminomatous and 33 were nonseminomatous (NS). Mean patients age was 38.54 years (range 17-89 years). Mean follow-up duration was 39.84 months (range 3-96). Serum tumor marker levels were found associated with rete testis invasion (p = 0.035). Hilar soft tissue invasion was significantly associated with vascular invasion (p = 0.001). As it was expected, vascular invasion was significantly associated with metastasis (p = 0.024). CONCLUSIONS: We concluded that there is a strong association between hilar soft tissue invasion and vascular invasion. Especially in NS germ cell tumors, hilar soft tissue involvement a risk factor for prognosis and to determine the need for additional treatment. According to our study, hilar soft tissue status should be reported on routine pathology report.

[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.