Abnormal ultrasonic pattern in contralateral testes in patients with unilateral testicular cancer

Summary Ultrasound examination and biopsy of the nonaffected testis was performed in 78 men with a unilateral testicular cancer. Each testis was measured in three planes and the volume was calculated using the formula of an ellipsoid. The ultrasonic texture of each testis was given a score ranging from 1 to 5 as follows: 1, very regular; 2, slightly irregular; 3, irregular with small echogenic points; 4, very irregular or with coarse echogenic points; and 5, irregular with demarcated areas raising suspicion of tumor. Biopsies were examined for the presence of tubules with carcinoma in situ (CIS), germinative epithelium, Sertoli cell only, and obliterations; the thickness of tubular membranes and the amount of Leydig cells were registered. The mean ultrasonic testicular volume was 12.88 ml (range 3–24 ml), which was smaller than that previously reported for normal men and larger than that previously reported for infertile men. The ultrasonic testicular volume was inversely correlated to the score. Score 4 was given to 46% of the testes (median score, 4), and the score distribution was different from that reported in normal men (median, 2) and in infertile men (median, 3). In all, 9 testes contained CIS tubules, and 8 of these were given score 4; 1 testis with CIS in only 5% of the tubules was given score 3. The predictive value of score 4 for the testis to contain CIS was 22.2%, and the predictive value of a score different from 4 that the testis would not contain CIS was 97.6%. We conclude that a large percentage of contralateral testes in men with unilateral testicular cancer have an abnormal echotexture and that CIS is most likely found in testes given score 4 by ultrasound.     

Early detection of a contralateral second carcinoma in patients with testicular tumors caused by testicular carcinoma in situ

Carcinoma in situ (CIS) of the testis is considered to be a precursor of germ cell cancer. Diagnosis is made by the conventional biopsy technique. Only for patients at risk is a screening biopsy justifiable. This group includes patients with testicular cancer in whom the incidence of contralateral second germ cell tumors is increased. In a prospective study we found three cases of testicular CIS in biopsies from the contralateral testes of 61 such patients. All cases with a diagnosis of CIS presented with testicular atrophy (volume less than 12 ml), associated with necrozoospermia in one patient and with azoospermia in two patients. Treatment consisted in local irradiation (20 Gy) of the remaining testis to preserve Leydig cell function. In control biopsies no evidence of CIS or germ cells was found. More than 3 months after therapy, plasma testosterone levels were normal and LH and FSH levels were increased. None of the patients with negative biopsy (n = 49) who were followed up was found to have a second cancer of the contralateral testis. The average observation time so far is 17.2 months.     

Noninvasive detection of testicular carcinoma in situ in semen using OCT3/4

OBJECTIVE: Carcinoma in situ (CIS) is accepted as the precursor of the germ cell tumors of the adult testis. CIS cells are located within the seminiferous tubules and can be exfoliated into semen. We performed a study to detect CIS cells in semen using the highly specific immunohistochemical marker OCT3/4, potentially a method for noninvasive diagnosis. MATERIAL AND METHODS: In 2006, 41 men at risk for CIS of the testis were found eligible for this study. Indications for inclusions were a suspicious lesion on scrotal ultrasound investigation (n=14), patients on surveillance after a history of a testicular tumor (n=14), and 13 patients with bilateral testicular microlithiasis (TM). RESULTS: Three of the 13 men (23%) who underwent testicular biopsies for bilateral TM were histologically diagnosed with CIS (two bilateral), and their semen showed OCT3/4-positive cells in all cases. Twelve of the 14 patients (86%) with a solid mass were diagnosed with a TGCT with adjacent CIS in the parenchyma, and in 9 cases (75%) OCT3/4-positive cells were present in the semen. No OCT3/4-positive cells were found in patients with biopsies who did not show any evidence of malignancy. CONCLUSION: This study demonstrates that OCT3/4-positive cells can be found in semen from the majority of patients with CIS. The observations indicate that there is probably a time window in which the CIS cells are exfoliated, which gives an opportunity for early detection of CIS cells in semen of men at risk for TGCT.     

Microsurgical testis biopsy: a novel technique for retrieval of testicular tissue

PURPOSE: In vitro fertilization with intracytoplasmic sperm injection has resulted in a dramatic increase in the need for diagnostic and therapeutic testis biopsies. We developed a microsurgical testis biopsy technique which allows identification of testicular vessels and individual seminiferous tubules. We compare the results of this technique to our prior series of nonmicroscopic biopsies. MATERIALS AND METHODS: A retrospective study of 226 consecutive patients who had undergone open testes biopsy with or without an operating microscope was performed. Between 1988 and 1994 standard open testis biopsy was performed without a microscope in 119 patients and a single sample of testicular tissue was taken. After 1994 microsurgical biopsy was performed under 6 to 25x magnification in 107 patients, nearly half of whom had multiple biopsies of each testis. The complication rates of the 2 procedures were compared. RESULTS: Scrotal hematoma required surgical drainage in 3 of the 119 standard testis biopsy cases and testis atrophy was noted in 1, for a total complication rate of 3.4%. There were no episodes of clinically detectable testicular atrophy or scrotal hematoma requiring surgical drainage in the 107 microsurgical biopsy cases (p<0.05). In 2 men the microscope allowed identification of larger tubules that contained sperm. CONCLUSIONS: Use of the operating microscope for testicular biopsy allows identification and avoidance of testicular vessels, minimizing complications. It also may allow selection of seminiferous tubules more likely to contain sperm.     

Pattern of Sertoli cell degeneration in cryptorchid prepubertal tests

Seventy-three testicular biopsies from 54 children (aged 2 months-14 years) with undescended testes were examined by light and electron microscopy. The biopsies included abdominal, inguinally fixed, inguinally moveable, and retractile testes. Alterations in Sertoli cell morphology were found in all biopsies. The alterations included dilated elements of rough endoplasmic reticulum, vacuolization of the cytoplasm, mitochondria with poorly preserved cristae, increase in electron density of the matrix, elongation of the nuclei, and irregularities of the nuclear membrane. According to the numerical appearance of these cells and to the extent of lesions in single Sertoli cells, seven phases in the continuous process of tubular alteration were distinguished. The most severe tubular damaged (phase VII) occurred when the seminiferous epithelium consisted exclusively of necrotic cells. All phases of tubular alterations were seen regularly in each of the biopsies investigated. Germ cells occurred only in phases I-IV and were never observed in tubules in phases V-VII. Significant differences became evident between inguinal and retractile testes by morphometric evaluation. It was demonstrated that the number of germ cells per cross-sectioned tubule (S/T value) correlated negatively with the percentage of tubules in phases V-VII. In contrast to inguinal testes, a complete absence of Sertoli cells and an S/T value less than 0.1 were never found in retractile testes and the percentage of tubules in phases V-VII was reduced significantly compared with inguinal testes. Our findings indicate that (i) maldescended testis in patients between 1 and 15 years-of-age is associated with a special pattern of Sertoli cell degeneration; (ii) Sertoli cell degeneration is a continuous process, which can lead eventually to complete dissolution of the seminiferous epithelium; (iii) total degeneration is not related to age but is dependent on testicular position; (iv) a defined phase of degeneration excludes germ cell development, and therefore enhanced Sertoli cell degeneration in cryptorchid testes must also account for the reduction in germ cell number.     

Further practical experiences in the recognition and management of carcinoma in situ of the testis.

99 biopsies from the contralateral testis in patients with unilateral germ cell tumor were investigated using the semithin section technique. Four cases (4%) revealed a carcinoma in situ (CIS) pattern. Two patients underwent a local radiation (20 Gy), 2 patients received combination chemotherapy (cisplatin, etoposide and bleomycin; PEB). No tumor cells were found in control biopsies 4-8 months after therapy. Both biopsy specimens taken from radiated patients lacked also germ cells. In contrast, 1 patient who was treated with PEB and also another 1 presenting with a teratocarcinoma of apparently retroperitoneal origin and unilateral CIS revealed germ cells after chemotherapy. The present data suggest radiation therapy to be the first line treatment for CIS-bearing testes. In order to get informations about the distribution of CIS cells in the affected testes, one or two biopsies were additionally taken from macroscopically unsuspicious tissue surrounding various solid germ cell tumors (74 patients). 56 cases (76%) revealed CIS. Even considering the possibility of missing CIS, a screening biopsy is actually the only method for detecting early manifestations of germ cell tumors and should be performed routinely in contralateral testes of patients with germ cell tumors.     

Fenugreek seed extract attenuates cisplatin‐induced testicular damage in Wistar rats

Cisplatin (CIS) provides oxidative stress and inflammations in testicular tissues. Fenugreek seed extract (FSE) is a widely used herbal medicine with potent antioxidant and anti‐inflammation properties. The purpose of this study was to investigate the protective effects and the possible mechanisms of FSE against CIS‐induced testicular damage in rats. Adult male Wistar rats were given vehicle, single dose of CIS alone (10 mg kg^?1), single dose of FSE alone or single dose of CIS followed by FSE (50, 100 or 200 mg kg^?1) every day for 5 days. On day 6, oxidative stress and apoptotic testicular toxicity were evaluated. FSE attenuated both germ cell degenerations and apoptosis in seminiferous tubules in CIS‐treated rats. Furthermore, FSE counteracted CIS‐induced oxidative stress in rats as assessed by the restoration of superoxide dismutase and catalase activities and reduction in the myeloperoxidase activity and malondialdehyde levels in testes. CIS increased expressions of inducible nitric oxide synthase and nuclear factor‐kappa B in testicular tissues. Importantly, treatment with FSE at all doses effectively alleviated all of these inflammatory parameters in testes. Based on these results, we concluded that FSE reduces CIS‐induced reproductive toxicity in rats by the suppression of testicular oxidative stress, apoptosis and inflammations.     

Mechanism of alcoholic testicular damage]

To observe the mechanism of alcoholic testicular damage, in a previous experiment we used weanling male SD rats aged 45 days, weighing about 200 g, and fed a liquid diet (Lieber's) containing 5% ethanol. The latter accounted for 36% of total caloric intake for 7 weeks, but did not result in testicular atrophy. In a later experiment, we used a liquid diet in which ethanol accounted for 46% of the total calorie count. It provided a high-fat, low-protein content which simulated the nutritional background of patients with alcoholic liver diseases. This diet resulted in testicular atrophy. Histological and biochemical changes accompanying this experimental testicular atrophy included the following: 1) The testes of alcohol-fed animals contained smaller seminiferous tubules with reduced numbers of total cells, but no degeneration was seen in the spermatids. 2) In the peritubular wall of the seminiferous tubules, we observed curvature, irregularities, infolding of the basement membrane, and lamellation of the lamina densa, as well as hyperplasia of collagen fibers in the tunica propria. 3) In the cytoplasm of the Sertoli cells, deposits of gigantic fat droplets and stratification of the mitochondria were observed. The permeability of the Sertoli cell tight junction was confirmed using the Lanthanum method. 4) Testosterone levels in both the serum and testes declined. 5) Lactate dehydrogenase-X (LDH-X) activity in the testes declined. 6) Low Km alcohol dehydrogenase (ADH) activity localized in the testicular interstitial tissue was increased. These results indicate that the composition of three major nutritional elements as well as alcohol concentration are important in the mechanism of alcoholic testicular damage, and this damage affects both the testicular interstitial cell and the seminiferous tubules, particularly the Sertoli cells and peritubular wall of the latter. In addition, the findings suggest that ADH is involved in alcohol metabolism in the interstitial cells of the testes.     

Sonographic testicular microlithiasis as an indicator of premalignant conditions in normal and infertile men.

Sonographic detection of multiple, small hyperechogenic lesions in the testis (testicular microlithiasis; TM) can indicate germ cell tumors. However, it has not been well established whether this finding signifies a risk factor for development of testicular neoplasm in all cases or whether it indicates premalignant changes only in those men with additional risk factors for germ cell cancer, such as infertility, a history of testicular maldescent, or the presence of an atrophic testis. In a retrospective analysis of 1701 consecutively performed scrotal sonographies of patients with (n = 1399) and without (n = 219) infertility or with contralateral testicular tumors (n = 83), the prevalence of TM was compared with that in 198 healthy men who volunteered for different clinical trials. TM was equally frequent in all groups (2.3% [32/1399] of infertile patients, 2.3% [5/219] of other patients without infertility, and 1.5% [3/198] of healthy men). Results of testicular biopsies were available for a subgroup of infertile men. Carcinoma in situ (CIS) was present only in cases with TM (2/11). In addition, sonographic follow-up examinations were performed in another 14 men with TM. Testicular tumors had developed in 2 patients, one whom was infertile and one in the control group. None of these patients had a history of testicular maldescent but all testes affected either by CIS or tumors were reduced in volume. We conclude that diagnosis of TM, especially if it is present in an atrophic testis, demands a diagnostic biopsy or at least sonographic follow-up examinations.     

Lipoprotein lipase and endothelial lipase in human testis and in germ cell neoplasms

The aim of this study was to investigate endothelial lipase (EL, LIPG) and lipoprotein lipase (LPL) mRNA and protein expression in normal human testis and testicular germ cell tumours (GCT). Both EL and LPL were expressed in normal seminiferous tubules and in the interstitial compartment. EL mRNA and protein were found in all germ cells as well as in Sertoli and Leydig cells. EL mRNA was abundant in pre-invasive carcinoma in situ (CIS) cells and GCTs, and EL protein was present in the cytoplasm of these cells. LPL mRNA was also relatively abundant in germ cells, Sertoli cells, CIS cells and GCTs. The LPL protein, however, was restricted to the cell membranes of pachytene spermatocytes and spermatids in normal tubules, absent from CIS cells and scarcely represented in tumours. The distribution of LPL protein in non-seminomas resembled the distribution of OCT3/4, a marker of embryonal carcinoma. The results suggest that both EL and LPL participate in the supply of nutrients and steroidogenesis in the testes, and that especially EL may be important for the supply of cholesterol for testosterone production in the Leydig cells. The partial cellular separation of the expression of the two lipases in normal testis suggests the existence of distinct biological roles, perhaps developmentally regulated, as indicated by the LPL expression in GCTs with embryonic features. A high expression of EL and abundance of lipid in tubules with CIS may have a diagnostic value.     

Macrophages Lysing Seminoma Cells in Patients with Carcinoma-In-Situ (CIS) of the Testis/Makrophagen, die Seminomzellen lysieren, bei Patienten mit Carcinoma-In-Situ (CIS) des Hodens

Testicles of 15 subfertile men who underwent orchidectomy because of intratubular seminoma cells resp. carcinoma-in-situ (CSI) pattern in testicular biopsy were examined by semithin sections as well as by ultrathin sections. With one exception the volume of the testicles was reduced (means = 16 ml). 6 cases (= 40%) had exclusively intratubular seminoma cells, 4 cases (= 26.6%) intratubular and interstitial seminoma cells and 5 cases (= 33.3%) a solid seminoma near the rete testis. In all patients an interstitial inflammatory infiltration as well as tubular shadows of various degree could be observed. Some tubular shadows contained macrophages in the center heavily loaded with lipid droplets. Furthermore, in two cases many seminiferous tubules could be detected which contained activated macrophages in the lumen lysing tumor cells. One of the patients had only intratubular tumor cells, whereas the other patient had a solid seminoma near the rete testis. Our data suggest that activated macrophages killing intratubular tumor cells in patients with CIS pattern of the testis resp. with an early stage of a seminoma represent a physiological immunological reaction of the host in preventing further invasive tumor growth. Tubular shadows represent the final process of macrophage activity and may explain the reduced testicular volume in patients with CIS. However, the density of the inflammatory reaction and the extent of intratubular macrophages lysing tumor cells does not correlate with a low or high risk of tumor growth.     

Testicular biopsy: clinical practice and interpretation

Testicular biopsy was considered the cornerstone of male infertility diagnosis for many years in men with unexplained infertility and azoospermia. Recent guidelines for male infertility have limited the indications for a diagnostic testicular biopsy to the confirmation of obstructive azoospermia in men with normal size testes and normal reproductive hormones. Nowadays, testicular biopsies are mainly performed for sperm harvesting in men with non-obstructive azoospermia, to be used for intracytoplasmic sperm injection. Testicular biopsy is also performed in men with risk factors for testicular malignancy. In a subgroup of infertile men, there is an increased risk for carcinoma in situ of the testis, especially in men with a history of cryptorchidism and testicular malignancy and in men with testicular atrophy. Ultrasonographic abnormalities, such as testicular microlithiasis, inhomogeneous parenchyma and lesions of the testes, further increase the risk of carcinoma in situ (CIS) in these men. For an accurate histological classification, proper tissue handling, fixation, preparation of the specimen and evaluation are needed. A standardized approach to testicular biopsy is recommended. In addition, approaches to the detection of CIS of the testis testicular immunohistochemistry are mandatory. In this mini-review, we describe the current indications for testicular biopsies in the diagnosis and management of male infertility.     

Stagnation of blood in the microvasculature of the affected and contralateral testes of men with short-term torsion of the spermatic cord

Bilateral testicular biopsies from four men with a short duration (3 hours 10 minutes to 4 hours 30 minutes) of unilateral spermatic cord torsion and testicular biopsies from six men with irreversible brain death were used for the present investigation. Extensive light and electron microscopic studies and quantitative analyses of all biopsy materials were performed. The torsioned testes revealed variable degrees of damage to the seminiferous tubules, including germ cell disorganization and sloughing of immature germ cells. Ninety-five percent of the blood vessels from the biopsied tissue specimens were clogged with blood cells. The seminiferous tubules of the contralateral testis had normal germ cell arrangements and counts. However, 88% of the microvessels from the tissue biopsied from the contralateral testes were packed with blood cells, whereas only 10% of the blood vessels in the control biopsy specimen were clogged with blood cells. At the electron microscopic level, fewer tight junctions and enlarged pores were found between the endothelial cells of the affected vessels, and microvilli were completely absent from these endothelial cells. The clogging caused by blood cells in the affected vessels was so severe that no space was found between the membrane of the endothelial cell and the membrane of the blood cells. It has been suggested that local clogging by blood is responsible for the initiation of degenerative changes in the testes of men with unilateral torsion of the spermatic cord.     

Testicular pathology in 46,XY dysgenetic male pseudohermaphroditism: an approach to pathogenesis of testis cancer.

Eleven children with dysgenic male pseudohermaphroditism (DMP) and 18 boys with isolated penile hypospadias, all with 46,XY karyotype, were studied. Testicular dysgenesis was associated with significantly lower testosterone response to human chorionic gonadotropin (0.9 +/- 0.2 ng/mL) than it was in hypospadias (3.3 +/- 0.1 ng/mL), and with significantly higher mean serum follicle-stimulating hormone (FSH) levels (8.4 +/- 2.3 IU/L vs 1.5 +/- 0.3 IU/L). Gonadoblastoma, a tumor that arises from the sex cords, was found in more than 1/4 of patients with DMP, whereas testicular carcinoma in situ (CIS) cells were present in all of these patients. Forty-two percent to 98% of CIS cells revealed an aneuploid pattern of nuclear DNA, indicating that most of them are neoplastic cells. In patients with hypospadias, CIS was not seen, and no other abnormalities were detected. In children with DMP, the percentage of tubules populated with germ cells was significantly lower than it was in those with hypospadias (48.3% +/- 10.6% vs 92.4% +/- 4.0%). The total number of germ cells (CIS cells + spermatogonia) did not differ significantly between the 2 groups, but the number of spermatogonia was significantly reduced in children with DMP (0.08 +/- 0.05 vs 3.65 +/- 0.2), suggesting impaired differentiation of gonocytes to spermatogonia. The following significant correlations were present with DMP: 1) the higher the seminiferous tubule cross-section area, the higher the number of CIS cells (r = 0.78); and 2) the higher the serum gonadotropin levels, the higher were tubular diameter (r = 0.93 for FSH and r = 0.75 for luteinizing hormone [LH]), area (r = 0.79 for FSH and r = 0.82 for LH), percentage of tubules populated with germ cells (r = 0.86 for FSH and r = 0.81 for LH), and number of CIS cells (r = 0.87 for FSH and r = 0.79 for LH). The results indicate that in intersex children with 46,XY karyotype, CIS occurs in dysgenetic testes in all cases and is frequently associated with gonadoblastoma. Impaired organogenesis of sex cords, relative inhibition of testosterone secretion, and the associated increased secretion of gonadotropins may create a milieu that induces or is favorable for the formation or maintenance of neoplastic lesions in dysgenetic testes early in childhood.     

Seasonal changes in testicular structure and function in the blue fox (Alopex lagopus), as quantified by morphometric analysis and measurement of adenylate cyclase activity

The volume of the blue fox testis showed 5-fold changes during the year, associated with considerable changes in cellular composition. The seminiferous epithelium was maximally regressed in August, when 94% of tubules contained only spermatogonia. By late October, approximately 6 months before the mating season, 40% of tubules contained primary spermatocytes. From the middle of January until the end of April all tubules contained spermatids or more advanced haploid cells. Tubular diameter increased by 73% during testicular re-development, and epithelial height increased 3-fold. Regression to the basal state occurred during May to July. The volume densities of the seminiferous epithelium and of interstitial tissue remained approximately constant throughout the year. Soluble Mn2+-dependent adenylate cyclase activity showed seasonal variations that paralleled those of the haploid germ cell population and testicular volume, whereas somatic cell adenylate cyclase activity was relatively constant.     

Testicular volume does not predict germ cell count in patients with cryptorchidism

PURPOSE: A germ cell count of less than 0.2 germ cell per tubule on the prepubertal biopsy of cryptorchid testes predicts abnormal spermiograms and decreased fertility in adulthood, and may be used to select patients for post-orchiopexy hormonal therapy. Testicular volume directly correlates with testicular function and spermiogenesis. We determined whether testicular volume would predict the total germ cell count accurately enough to replace testicular biopsy in the modern management of cryptorchidism. MATERIALS AND METHODS: At our hospital 723 patients younger than 9 years with cryptorchidism (unilateral in 619 and bilateral in 104) underwent orchiopexy and bilateral testicular biopsies. These patients had not undergone groin surgery or hormonal therapy previously and had at least 50 tubules in each testicular biopsy. Testicular volume and position, patient age and germ cell counts were analyzed. The generalized estimating equation was used to determine whether a correlation existed between testicular volume and germ cell count. RESULTS: The generalized estimating equation demonstrated a direct correlation between testicular volume and germ cell count. However, germ cell counts predicted from testicular volume varied widely within the 95% confidence intervals. Testes with less than 0.2 germ cell per tubule cannot be reliably distinguished from those with greater than 0.2 germ cell per tubule. CONCLUSIONS: Testicular volume does not accurately predict the germ cell count in patients with undescended testes, cannot be used to select patients for post-orchiopexy hormonal therapy and cannot replace testicular biopsy in the modern management of cryptorchidism.     

Obstruction of the tubuli recti and ductuli efferentes by dilated veins in the testes of men with varicocele and its possible role in causing atrophy of the seminiferous tubules

Hormone measurements, spermiograms and testicular biopsies studies were performed in young with varicocele. In addition, the testes and epididymides of 27 adults with varicocele were obtained from autopsies. Light and electron microscopic examination of biopsy and autopsy specimens revealed two types of lesions in testes with varicocele: 1) a diffuse lesion consisting of abnormal spermatozoa and spermatid morphology and sloughing of immature spermatozoa and spermatid; 2) focal lesion, distributed irregularly throughout the testicular parenchyma, affecting several small groups of seminiferous tubules. Each of these groups corresponded to a testicular lobule and showed different degrees of tubular atrophy, so that the focal lesions were distributed in a mosaic pattern. The testicular interstitium showed dilated veins and venules, and progressive collagenization. Some testes showed dilated veins in the rete testis, which compressed several tubuli recti and caused tubular atrophy in the seminiferous tubules opening into these tubuli recti. Other testes showed dilated young veins among the ductuli efferentes, and the rete testis channels appeared to be dilated. Among the different etiological mechanisms which have been suggested to for testicular lesions in varicocele, tubular obstruction at the level of either the tubuli recti or the ductuli efferentes might be responsible for lesions leading to testicular atrophy.     

Clinicopathological study of the testicular microlithiasis

PURPOSE: Testicular microlithiasis (TM) is a relatively rare condition characterized by calcific concref1p4 within the seminiferous tubules. Little has been reported on the incidence or the clinical implication of TM among Japanese. To address the problem, we evaluated pathologic specimens from biopsies and orchiectomies, of testes with various conditions. MATERIALS AND METHODS: Pathologic specimens of the testes of 200 cases, 56 from orchiectomy and 144 from testicular biopsy, were investigated. RESULTS: The pathological diagnosis of TM was confirmed in seven (3.5%) cases, four of which were associated with germ cell tumors and the other three were obtained from testicular biopsies performed for examination of infertile men. Of the 41 patients with germ cell tumors, four (9.8%) were found to have TM, and another three (2.5%) were identified among 122 patients with infertility. The prevalence of TM is significantly higher in specimen with germ cell tumors than those without germ cell tumors (p < 0.05). CONCLUSIONS: Although TM is rarely encountered, this condition is relatively often accompanied by testicular malignancy. Further investigation would be fundamental to ascertain the relationship between TM and testicular malignancy.     

Evaluation of testicular biopsies for carcinoma in situ: immunohistochemistry is mandatory

Carcinoma in situ (CIS) is the common precursor of all type II testicular germ cell tumors (TGCTs), i.e. seminomas and non-seminomas, which can be diagnosed using a surgical biopsy. The objective of this study was to investigate the additional value of immunohistochemistry for the diagnosis of CIS in assessing testicular biopsies taken in the context of infertility. A series of 21 infertile patients were retrieved from the Dutch pathological database (PALGA), being diagnosed with an invasive TGCT, while a matched previously obtained testicular biopsy was diagnosed as non-malignant. From 20 patients, both the invasive tumors as well as the biopsies were revised using morphology and immunohistochemistry for OCT3/4, placental-like alkaline phosphatase and c-KIT, all known established markers for CIS. The presence of CIS or invasive malignancies was scored. There are no interventions. Morphological criteria alone allowed an experienced pathologist in TGCTs to diagnose CIS in five and an invasive tumor in two cases (total n  = 7, 35%). Application of immunohistochemistry resulted in the identification of an additional four cases of CIS (total n  = 11, 55%, additional value of 20%). The initial correct diagnosis of CIS could have prevented a second gonadectomy in four patients (20%). This study, for the first time, really shows that time of progression from CIS to seminoma is longer than to non-seminoma. Our study demonstrates that immunohistochemistry should be performed for the diagnosis of CIS of the testis on single biopsies obtained because of infertility, resulting in an extra diagnostic yield of at least 20%. Application of this protocol will allow early diagnosis, and therefore prevent any adverse anti-cancer treatment sequelae including gonadectomy, and requiring life long androgen supplementation in some patients.     

Carcinoma in situ detected by contralateral testicular biopsy of 55 germ cell tumor patients

PURPOSE: We performed contra-lateral testicular biopsies in 55 testicular tumor patients when high orchiectomy was performed. In these cases, two cases developed invasive testicular tumor later although the biopsies had not revealed testicular CIS. Then we re-examined the sensitivity of biopsies and judged if our results are contradictory against Skakkebaek's theory. PATIENTS AND METHODS: The paraffin blocks of two cases who later developed testicular tumor were sliced again and re-examined by H/E staining and immunostaining with PLAP antibody (clone No. 8A9). The other 53 H/E samples were re-examined and the result of the contra-lateral testis was re-searched in the case that CIS was detected in the specimen. RESULTS: CIS was detected in one of the two cases who later developed contra-lateral testicular tumor and another case among the other 53 cases. We could not reveal the result of the testis of case No. 3 because of the patient's disappearance. CIS existed 3.6% (2/55) and two cases were found to have been false negative. CONCLUSION: It is important for both urologists and pathologists to know well about testicular CIS and to perform biopsy according to Skakkebaek's guidance for raising the sensitivity to detect testicular CIS.