Testicular Nubbins Research Articles

Testicular Regression Syndrome: Histopathological Evaluation of 20 cases from Rural India with Review of Literature

ABSTRACT Context: Testicular regression syndrome (TRS), clinically termed “vanishing testes,” is a condition with atrophy of testes in late fetal or early neonatal life. The spermatic cord ends blindly or into a small fibrovascular nubbin. Histopathology reveals a fibrovascular nodule with associated hemosiderin-laden macrophages and dystrophic calcification. Few cases show the presence of seminiferous tubules and germ cells. The presence of germ cells is associated with the risk of developing a testicular germ cell tumor. Aims: To study the histopathological features of testicular nubbins and to determine the presence of germ cells and associated neoplasm. Settings and Design: It is a retro-prospective observational study carried out on patients referred to a pediatric surgical pathology center in Miraj, who were clinically diagnosed with undescended testis, over a period of 1 year. Data were collected after the study was approved by the IEC-MGCH on December 19, 2022. Materials and Methods: Twenty patients diagnosed with cryptorchidism, undescended testis, or atrophic testis were included. Findings of hematoxylin and eosin-stained slides of each case were noted, and Prussian Blue (special staining) was performed in four cases. Statistical analysis used: As this is a descriptive observational study, simple arithmetic calculations were performed. No unique statistical analysis was performed. Results: Among twenty cases of vanishing testes syndrome, 20 cases showed fibrovascular tissue only, and 1 case showed the presence of seminiferous tubules with Sertoli cells. Conclusions: Vanishing testes syndrome is a rare condition that is difficult to diagnose on clinical examination, and a definitive diagnosis may be missed if the pathologist is unaware of the condition. Also, there is a risk of germ cell tumor if there are residual germ cells in the testicular nubbin.

Testicular regression syndrome: A series of 22 cases at a tertiary care hospital

Testicular regression syndrome (TRS) represents a congenital condition in which no normal testicular tissue can be identified following exploration for a clinically impalpable testis. It is seen in less than 5% of cryptorchidism cases, however accounts for 35-60% of clinically impalpable testis. To study the Clinicopathological spectrum of Testicular regression syndrome (TRS) and review the literature. Study design: The study included 22 patients with nonpalpable testis, who had undergone resection of testicular nubbins. Original diagnosis was studied in context of pathological recognition of TRS and additional sections and stains were examined. Pathological assessment included identification of epididymis and vas deferens, vascularised fibrous nodule (VFN), dystrophic calcification, hemosiderin and pampiniform plexus like veins. Stain for iron and calcium were performed. On secondary review, 21 out of 26 cases of undescended testis (UDT) showed features consistent with the diagnosis of TRS. On microscopy, VFN was observed in 17 (77.3%), calcification in 4 (18.2%), hemosiderin in 15 (68.2%), vas deferens in 13 (59%), epididymis in 11 (50%), prominent vessels in 21 (95.4%) and seminiferous tubules in 6 (27.3%) cases. The presence of dystrophic calcification and hemosiderin deposition with absent viable tissue points to the hypoxic injury to the testis. TRS theoretically carries a long-term risk for malignant degeneration therefore In the typical situation in which a blind-ending spermatic cord without viable testis is submitted for tissue analysis, it is imperative to characterize such cases as consistent with regressed testis thus eliminating the need for further surgical intervention.

Is excision of testicular nubbin necessary in vanishing testis syndrome?

Background/PurposeVanishing Testes Syndrome11VTS: Vanishing Testes syndrome (VTS) is one of the most common causes of impalpable testes in children. The role of removal of testicular nubbins owing to malignant potential in VTS is unclear. We sought to evaluate whether testicular nubbins need to be excised owing to this potential. MethodsWe conducted a retrospective review of children with a clinical diagnosis of impalpable testes aged 0–18 who presented to our tertiary hospital between 2007 and 2017. VTS was defined as the presence of hypoplastic vas entering a closed internal inguinal ring or remnants of gonadal tissue distally. Data collected included: age at operation, need for laparoscopy, location of nubbin and histopathological findings. ResultsWe identified 50 consecutive children (mean age 2.4 years, range: 7 months to 12 years) with a clinical diagnosis of impalpable testis. Forty-eight of the 50 underwent laparoscopy with no testicle palpable when examined under anesthesia. Thirty-three children had VTS confirmed at laparoscopy and testicular nubbins identified with three of these being bilateral. Thirty-two children had these nubbins excised with histopathology available for 31 individual testes. Thirty were confirmed testicular nubbins with no viable testicular tissue. No malignancies were identified. ConclusionResults from this study show that testicular nubbins do not have viable germ cells and therefore do not need to be excised on the basis of malignant potential of residual testicular tissue. Level of evidenceLevel IV treatment study.

Testicular hypertrophy as a predictor for contralateral monorchism: Retrospective review of prospectively recorded data

Testicular hypertrophy has previously been evaluated as a predictor of monorchism. However, its implication in clinical practice is not well evaluated. The aim of the present study was to examine its value in planning the operative time. Medical charts of prospectively recorded data of 76 consecutive patients with unilateral impalpable testis from 2011 to 2014 were reviewed at the present institute. Inclusion criteria included prepubertal patients with non-palpable testes by examination under anesthesia. Contralateral testes were prospectively measured using a Takihara orchidometer. Orchiectomy or orchiopexy was performed according to the viability of the undescended testis (UDT). Collected data included age of surgery, contralateral testicular size, surgical time and laparoscopic findings. A ROC curve was used to define the best cut-off volume of the contralateral testis that can predict ipsilateral testicular viability. The Student's t-test was used to examine if this cut-off volume would be useful in allocating the operative time. Of 76 patients, four palpable testes by examination under anesthesia were excluded. The remaining 72 patients were included in the study. Ipsilateral normal viable testes were found in 26 (36.1%) patients, while 46 (63.9%) had non-viable testes (testicular nubbins or vanishing testes) (Figure). A contralateral testicular volume > 2 ml was significantly predictive for monorchism with 71.7% sensitivity and 100% specificity (P < 0.001). The mean operative time for management of UDT with a contralateral size >2 ml was 50 min, which was significantly shorter than that for UDT with a contralateral size ≤ 2 ml, which was 88 min (P < 0.001). In previously published reports, the cut-off value for testicular hypertrophy that predicts monorchism greatly varied. This is likely due to the different methods used for testicular measurements that make it impractical to make a direct comparison. The usefulness of predicting monorchism before surgery has not previously been used as a guide for allocating operative time in the management of a unilateral non-palpable testicle. This study had some limitations, including a relatively small sample size and involvement of different surgeons, which may have affected the operative time. Using the cut-off volume of a contralateral testis >2 ml as a predictor for monorchism can reduce the allocated operative time by approximately one third.

The Prevalence of Bell Clapper Anomaly in the Solitary Testis in Cases of Prior Perinatal Torsion

Bell clapper anomaly is associated with an increased risk of intravaginal testicular torsion. However, perinatal torsion is thought to be secondary to an extravaginal process. We quantified the contralateral prevalence of bell clapper anomaly in children found to have atrophic testicular nubbins secondary to presumed torsion during gestation to better define the subsequent risk of metachronous testicular torsion. Inspection results for the presence of contralateral bell clapper anomaly was recorded by a single surgeon in 50 consecutive cases in which exploration for nonpalpable testes revealed a testicular nubbin. For comparison data were collected in 27 consecutive cases of acute testicular torsion. Anatomy of the normal contralateral testis was compared between the 2 groups. Average age at surgery in the perinatal torsion group was 15 months vs 12.7 years in the acute torsion group. One case of partial contralateral bell clapper anomaly was discovered in the perinatal torsion group but no complete anomaly was found. In contrast, in older boys with acute testicular torsion complete bell clapper anomaly was found in 21 of the 27 contralateral testes (78%). In older boys with acute testicular torsion contralateral bell clapper anomaly is highly prevalent, supporting the standard practice of contralateral testicular fixation in this clinical situation. However, the prevalence of contralateral bell clapper anomaly is exceedingly small in cases of monorchism after perinatal torsion, substantiating an insufficient risk of subsequent torsion to justify routine fixation of the solitary testis.

The value of finding a closed internal ring on laparoscopy in unilateral nonpalpable testis

PurposeThere is an ongoing debate about whether initial laparoscopy is as efficient as initial extra-abdominal exploration for unilateral nonpalpable testis. The aim of this study was to clarify whether the finding of a closed internal ring on laparoscopy accurately predicts extra-abdominal findings in unilateral nonpalpable testis. MethodsBoth laparoscopy and subsequent extra-abdominal exploration were prospectively performed in consecutive patients with unilateral nonpalpable testis. Laparoscopic findings were reviewed with respect to the status of the vas deferens, spermatic vessels, and the appearance of the internal ring. Except for patients with an abdominal testis, all patients underwent subsequent open exploration regardless of the laparoscopic findings. Open explorations were primarily performed by scrotal incision. During open exploration, any testicular remnants were removed and evaluated histologically. ResultsA total of 100 patients with unilateral nonpalpable testis were evaluated, of whom 15 had an abdominal testis. Of the 85 patients without an abdominal testis, an open internal ring was recognized in only 8. Of the remaining 77 with a closed internal ring, subsequent open exploration revealed testicular nubbins in all patients (100%), regardless of the laparoscopic findings of the vessels and vas. Nine nubbins were associated with intra-abdominal vanishing vessels above the closed internal ring. All nubbins were confirmed by histological findings, and the incidence of viable germ cell elements was 7.4%. ConclusionsWhen laparoscopy demonstrates no abdominal testis in patients with unilateral nonpalpable testis, the finding of a closed internal ring on laparoscopy is always associated with the presence of an extra-abdominal nubbin, regardless of the status of the vessels and the vas at the internal ring. Subsequent extra-abdominal exploration can be obviated in this circumstance if nubbin excisions are skipped. Initial diagnostic laparoscopy for unilateral nonpalpable testis provides not only the intra-abdominal findings, but also exact prediction of the extra-abdominal findings in patients with a closed internal ring.

Feasible etiology of vanishing testis regarding disturbance of testicular development: Histopathological and immunohistochemical evaluation of testicular nubbins

To identify the causes of vanishing testis besides vascular events secondary to testicular torsion. A total of 102 boys with vanishing testis were treated in our hospital from 1984 to 2011. Of these cases, 91 testicular nubbins were excised. Immunohistochemical analysis of testicular nubbins was carried out using anti-Wilms tumor 1 antibody, which is a stable marker of Sertoli cells. Reverse transcription polymerase chain reaction was also carried out using Wilms tumor 1-specific primers. Most testicular nubbins were associated with inguinal lesion (51 patients, 56.0%). Light microscopy showed that 11 patients (12.5%) had seminiferous tubules (with germ cells in three patients [3.4%]), and 77 patients lacked seminiferous tubules, some of which had calcification (26 patients, 29.5%), and/or deposition of hemosiderin (21 patients, 23.9%). Immunohistochemical analysis showed Wilms tumor 1 expression not only in the Sertoli cells of the seminiferous tubules in the seminiferous tubule-positive patients, but also in the interstitium of testicular nubbins in the seminiferous tubule-negative patients. Reverse transcription polymerase chain reaction showed Wilms tumor 1 messenger ribonucleic acid expression in the testicular nubbins of both seminiferous tubule-positive and tubule-negative patients. The presence of Wilms tumor 1-positive cells in the interstitium of vanishing testis lacking seminiferous tubules suggests that the disturbance of testicular development after Sertoli cell differentiation and during testicular tubule formation might be involved in the etiology of vanishing testis.

Laparoscopic Management of Nonpalpable Testis: New Treatment Strategy

We established a new strategy for nonpalpable testis, including intra-abdominal testis, testicular nubbins, and intracanalicular testis, to correct these conditions by laparoscopic procedures. Of the 53 boys (mean age, 24.5 months), nonpalpable testis was on the right side in 13, on the left in 34, and bilateral in 6. Three boys with nonpalpable testis involved contralateral palpable undescended testis. We applied only laparoscopic treatment without open inguinal incision for all cases. After laparoscopic orchiopexy and orchiectomy, we performed subsequent laparoscopic inguinal ring and/or peritoneal defect closure to prevent postoperative inguinal hernia formation, and concurrent laparoscopic repair for cases of contralateral undescended testes and open processus vaginalis under the same anesthesia. All boys underwent laparoscopic treatment immediately after laparoscopic evaluation. We performed laparoscopic orchiopexy for 22 cases with intra-abdominal testes. Twenty-seven boys underwent laparoscopic groin exploration, and 24 underwent subsequent laparoscopic orchiectomy for testicular nubbins, and 3 underwent subsequent laparoscopic orchiopexy for intracanalicular testes. In two boys with testicular nubbin, an open processus vaginalis was present. Forty-nine boys underwent laparoscopic inguinal ring and/or peritoneal defect closure after orchiopexy or orchiectomy to prevent inguinal hernia formation or hydrocele testis. Concurrent laparoscopic contralateral inguinal closure was performed for two cases with opened contralateral processus vaginalis. Our new strategy is useful because all patients with nonpalpable testis could be treated successfully by only laparoscopic management, avoiding open inguinal incision, preventing inguinal hernia formation, and enabling the concurrent repair of contralateral undescended testis and open processus vaginalis.

Findings of fat‐suppressed T2‐weighted and diffusion‐weighted magnetic resonance imaging in the diagnosis of non‐palpable testes

To evaluate the magnetic resonance imaging (MRI) findings, diagnostic accuracy and clinical usefulness of fat-suppressed T2-weighted and diffusion-weighted imaging (DWI) in the management of non-palpable testes. In all, 56 children (63 non-palpable testes) aged 8 months-11 years (mean 24.7 months) with non-palpable testes were enrolled. T1- and T2-weighted imaging, as well as fat-suppressed T2-weighted imaging and DWI were performed during MRI examination, and the imaging results were compared with surgical findings. In the 63 non-palpable testes, MRI identified 22% (14/63) as intra-abdominal, 20% (13/63) as intra-canalicular, 29% (18/63) as testicular nubbins, and 29% (18/63) as unidentifiable. Although it was difficult to confirm their presence in the abdominal cavity using T1- and T2-weighted imaging alone, additional assessment, including fat-suppressed T2-weighted imaging and DWI facilitated the detection of intra-abdominal testes more easily because they were imaged at a markedly higher signal intensity. The sensitivity, specificity and positive and negative predictive values for the MRI vs the operative findings were 100, 97.3, 96.3, and 100%, respectively. The overall prediction accuracy was 98.4%. Additional MRI assessments, fat-suppressed T2-weighted imaging and DWI are useful examinations to improve the preoperative diagnostic accuracy of non-palpable testes.

Magnetic Resonance Arteriography/Venography is Not Accurate to Structure Management of the Impalpable Testis

Recent studies have shown that magnetic resonance arteriography/venography is a highly sensitive tool to identify impalpable testes in young boys. Due to this and the low risk of cancer in testicular nubbins observation has been proposed after the identification of nubbins by magnetic resonance arteriography/venography. We prospectively examined the accuracy of magnetic resonance imaging and magnetic resonance imaging with magnetic resonance arteriography/venography for identifying impalpable testes in a younger cohort of patients typically seen at a pediatric institution in the United States. We prospectively studied 26 infants and boys with impalpable testes. Conventional magnetic resonance imaging or magnetic resonance imaging with magnetic resonance arteriography/venography was performed in all patients. All patients subsequently underwent surgical exploration. Surgical and radiological findings were then evaluated for concordance. A total of 26 boys (29 impalpable testes) with a median age of 13 months were evaluated. A subset of 14 boys (14 impalpable testes) also underwent magnetic resonance arteriography/venography. Standard magnetic resonance imaging correctly identified 10 of 12 intra-abdominal testes, 4 of 6 intracanalicular testes, 4 of 10 testicular nubbins and 0 of 1 scrotal testis. Magnetic resonance arteriography/venography correctly identified 4 of 5 intra-abdominal testes, 2 of 3 intracanalicular testes, 2 of 5 testicular nubbins and 0 of 1 scrotal testis. The overall accuracy of magnetic resonance imaging alone and magnetic resonance arteriography/venography for identifying a viable testis or testicular nubbin was 62% and 57%, respectively. The accuracy of magnetic resonance imaging and magnetic resonance arteriography/venography for identifying a viable testis was 74% and 67%, respectively. Preoperative magnetic resonance imaging or magnetic resonance arteriography/venography does not accurately identify or localize impalpable testes in the age group typically presenting to pediatric urologists. Accuracy at our institution is discrepant with that in previous studies. We do not recommend using magnetic resonance imaging or magnetic resonance arteriography/venography for the possible observation of vanishing testes or nubbins and we recommend surgical exploration in all individuals.

Testicular nubbins and prosthesis insertion: is it all just in the timing?

I was interested to read Emir et al’s [1] article on the histological evaluation of testicular nubbins in boys with an impalpable testis. At a mean age of 4.1 years 44 testicular nubbins were examined in 40 boys. Of these, only five were found to contain seminiferous tubules and none showed evidence of malignant degeneration. The authors then used this argument to propose that exploration for a testicular nubbin via an inguinal approach and its removal might therefore be postponed until the time of testicular prosthesis insertion, normally during late adolescence. But is it all simply in the timing of surgery? The authors’ contention raises a number of issues, not all of which they address in their article. First, deferring any inguino-scrotal surgery until completion of puberty potentially exposes the boy with a presumed single testis to some additional risk of loss of that testis through torsion. Whilst the risk is very low and ideal management controversial, many would advise prophylactic fixation of the contralateral remaining testis at the same time as excision of a testicular nubbin [2–4]. Secondly, the authors’ article implies that insertion of a testicular prosthesis represents routine practice and should therefore be another reason to safely defer exploration and removal of a testicular nubbin late in adolescence [1]. Insertion of such a prosthesis, however, would not represent standard practice at my institution. There remains considerable evidence from the literature to suggest potential long-term adverse consequences in a young adult, including local tissue reactions, particle migration, rupture and immunological sequelae [5–8]. These risks require careful evaluation by the surgeon, parent and patient on an individual basis prior to insertion, which should therefore never be regarded as ‘routine’.

Histological evaluation of the testicular nubbins in patients with nonpalpable testis: assessment of etiology and surgical approach

There is a controversy in the literature whether testicular nubbins carry malignancy risk and excision of the nubbin is necessary in patients with nonpalpable testis. It is also controversial whether vanishing testis has the same etiopathogenesis and risk with true undescended testis. The aim of this study is to investigate the histological findings of testicular nubbins in patients with nonpalpable testis and to question etiology and surgical indications for vanishing testis. We reviewed the histopathological results of 44 testicular nubbins in 40 patients (mean age: 4.1 years, range 1-13 years) with nonpalpable testis between 1992 and 2004, retrospectively. Exploration revealed 5 intraabdominal and 39 inguinal testicular nubbins. Of 44 specimens only 5 (11.3%) from inquinal testicular nubbins were found to have seminiferous tubules. Two of the five had seminiferous tubule structures with viable germ cells showing maturation correlating with age. The other two with scarce seminiferous tubules were seen on only a single area and one had Sertoli cells only. None of the excised tissue had malignant degeneration. The vas deferens was identified in 23 (52.2%), vessels in 26 (59%), calcification in 14 (31.8%) and hemosiderin in 12 (27.2%) of excised tissue. Presence of calcification in one-third of the nubbins supports vascular accident thesis in the etiopathogenesis of vanishing testis. The possibility for the presence of seminiferous tubules and viable germ cells in the testicular nubbin is low. These facts decrease theoritical risk of malingnancy. Therefore, an inguinal exploration for testicular nubbin in patients with vas deferens and vessels entering into the inquinal canal diagnosed at laparoscopy can be postponed untill testicular prosthesis implantation and the nubbin can be removed at this operation.

MAGNETIC RESONANCE ANGIOGRAPHY FOR THE NONPALPABLE TESTIS: A COST AND CANCER RISK ANALYSIS

For the unilateral nonpalpable testis standard management is open surgical or laparoscopic exploration. An ideal imaging technique would reliably identify testicular nubbins and safely allow children to forgo surgical exploration without compromising future health or fertility. Our goal was to perform a cost and risk analysis of magnetic resonance angiography (MRA) for unilateral nonpalpable cryptorchid testes. A search of the English medical literature revealed 3 studies addressing the usefulness of MRA for the nonpalpable testicle. We performed a meta-analysis and applied the results to a hypothetical set of patients using historical testicular localization data. Analysis was then performed using 3 different management protocols-MRA with removal of testicular nubbin tissue, MRA with observation of testicular nubbin tissue and diagnostic laparoscopy. A cancer risk and cost analysis was then performed. MRA with observation of testicular nubbin tissue results in 29% of patients avoiding surgery without any increased cost of care. Among the 29% of boys with testicular nubbins left in situ and observed the highest estimated risk was 1 in 300 of cancer developing, and 1 in 5,300 of dying of cancer. A protocol using MRA with observation of inguinal nubbins results in nearly a third of boys avoiding surgical intervention at a similar cost to standard care without any significant increased risk of development of testis cancer.

HISTOLOGICAL EVALUATION OF THE TESTICULAR NUBBIN IN THE VANISHING TESTIS SYNDROME

We reviewed histopathological studies of the testicular nubbins associated with the vanishing testis syndrome, and determined whether surgical removal is indicated based on the histological findings. Between 1983 and 1997 a unilateral testicular nubbin consistent with a vanishing testis was excised in 29 patients an average of 28.6 months old. We retrospectively reviewed the gross pathology reports and microscopic slides, and prospectively performed histochemical stain analysis. Gross evaluation of the specimens revealed an identifiable cord structure in the majority of cases with the vas deferens most commonly identified in 72.4%. No recognizable testicular elements were present in any nubbin. In 3 cases the original pathology report identified cells with features consistent with Leydig cells, which immunohistochemical staining revealed to be atrophied cremasteric muscle fibers. In this series testicular nubbins in vanishing testes contained no viable testicular tissue. Since the risk of testicular cancer in an undescended testis is 8 to 10% and the incidence of viable testicular tissue in these nubbins ranges from 0% in our series to 11% in others, there is only a 0 to 1.1% risk of testicular cancer in the nubbin. Thus, surgical removal may not be warranted.

HISTOLOGICAL EVALUATION OF THE TESTICULAR NUBBIN IN THE VANISHING TESTIS SYNDROME

Purpose We reviewed histopathological studies of the testicular nubbins associated with the vanishing testis syndrome, and determined whether surgical removal is indicated based on the histological findings. Materials and Methods Between 1983 and 1997 a unilateral testicular nubbin consistent with a vanishing testis was excised in 29 patients an average of 28.6 months old. We retrospectively reviewed the gross pathology reports and microscopic slides, and prospectively performed histochemical stain analysis. Results Gross evaluation of the specimens revealed an identifiable cord structure in the majority of cases with the vas deferens most commonly identified in 72.4%. No recognizable testicular elements were present in any nubbin. In 3 cases the original pathology report identified cells with features consistent with Leydig cells, which immunohistochemical staining revealed to be atrophied cremasteric muscle fibers. Conclusions In this series testicular nubbins in vanishing testes contained no viable testicular tissue. Since the risk of testicular cancer in an undescended testis is 8 to 10% and the incidence of viable testicular tissue in these nubbins ranges from 0% in our series to 11% in others, there is only a 0 to 1.1% risk of testicular cancer in the nubbin. Thus, surgical removal may not be warranted.

Laparoscopy for Nonpalpable Testes in Childhood: Is Inguinal Exploration also Necessary When Vas and Vessels Exit the Inguinal Ring?

Laparoscopy has proved to be a safe method for determining the status for nonpalpable testes. In a combined series 52 boys with 57 nonpalpable testes were evaluated laparoscopically. Of the 57 nonpalpable testes 26 were located above the internal inguinal ring (abdominal), 4 were found more distally, and blind-ending vas and vessels terminated in the abdomen in 3, and beyond the internal ring (vanished testes) in 24. Of 29 abdominal testes primary orchiopexy was performed in 15, 4 were removed, the vessels were transected (Fowler-Stephens) in 5, stage 1 of staged repairs was done in 2, distinct laparoscopic evidence of blind-ending vessels and vas obviated further surgery in 2, and testis was not identified either laparoscopically or by abdominal exploration. Finally, inguinal exploration in 28 children in whom vas and vessels were found to exit the internal ring resulted in localization of 4 testes that were brought into the scrotum. Removal of 23 testicular nubbins and their evaluation histologically resulted in identification of viable tubular structures in 3. We recommend inguinal exploration in all children who on laparoscopy are found to have vas and vessels exit the internal ring, and removal of testicular nubbins.