122例不育症睾丸活检病理学观察

对122例不育症睾丸活检标本进行观察分析。结果表明，病变累及的部位主要为曲细精管生精上皮（122／122），依次为曲细精管界膜（78／122）、睾丸间质（68／122）。病理组织学分类为生精细胞脱落管腔雍塞50例（40．9％），生精障碍26例（21．3％），生精功能低下18例（14．8％），生精细胞发育不全17例（14．0％）．曲细精管透明变性7例（5．8％），克氏征3例（2．5％），混合病变1例。睾丸活检对男性不育症的诊断、分型、治疗及预后判断均具有重要价值。本文亦对精索静脉曲张致使不育进行了讨论。     

The role of testicular biopsy in the modern management of male infertility.

PURPOSE: We evaluate the traditional role of isolated testicular biopsy as a diagnostic tool, as opposed to the value as a therapeutic procedure for azoospermic men. MATERIALS AND METHODS: The medical records of azoospermic patients who were evaluated, and treated between 1995 and 2000 were retrospectively analyzed for history, physical examination findings, endocrine profiles, testicular histology and sperm retrieval rates. Based on these parameters, cases were placed into diagnostic categories that included obstructive or nonobstructive azoospermia. Diagnostic parameters used to distinguish obstructive from nonobstructive azoospermia were subjected to statistical analysis with the t-test, analysis of variance and receiver operating characteristics curve. RESULTS: A total of 153 azoospermic men were included in our analysis. Of men with obstructive azoospermia 96% had follicle-stimulating hormone (FSH) 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. Conversely, 89% of men with nonobstructive azoospermia had FSH greater than 7.6 mIU/ml., or testicular long axis 4.6 cm. or less. Receiver operating characteristics analysis revealed that FSH, testicular long axis, and luteinizing hormone were the best individual diagnostic predictors, with areas 0.87, 0.83 and 0.79, respectively. CONCLUSIONS: In the vast majority of patients obstructive azoospermia may be distinguished clinically from nonobstructive azoospermia with a thorough analysis of diagnostic parameters. Based on this result, we believe that the isolated diagnostic testicular biopsy is rarely if ever indicated. Men with FSH 7.6 mIU/ml. or greater, or testicular long axis 4.6 cm. or less may be considered to have nonobstructive azoospermia and counseled accordingly. These men are best treated with therapeutic testicular biopsy and sperm extraction, with processing and cryopreservation for usage in in vitro fertilization and intracytoplasmic sperm injection if they accept advanced reproductive treatment. Diagnostic biopsy is of no other value in this group. Men with FSH 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. may elect to undergo reconstructive surgery with or without testicular biopsy and sperm extraction, or testicular biopsy and sperm extraction alone depending on their reproductive goals.     

Detection of testicular ultrasonographic lesions in severe male infertility

PURPOSE: We retrospectively assessed the number and histology of testicular lesions diagnosed clinically and by ultrasonography in a population of infertile men. MATERIALS AND METHODS: From October 2000 to January 2003, 560 infertile men underwent physical examination, hormonal assessment (follicle-stimulating hormone, luteinizing hormone, testosterone) and scrotal ultrasonography. Eight men were diagnosed with focal testicular ultrasonographic lesions. In 4 cases there was a palpable lesion and in the other 4 cases the lesion was not palpable, diagnosed by ultrasonography (1 was cryptorchid). Only cases of lesions with clear-cut ultrasonographic edges and no history of recent genital infections were considered for explorative surgery through the groin. Microcalcifications were reported if present. The testicle was only preserved when frozen section examination revealed a benign lesion and the margins were negative. RESULTS: Gynecomastia was not present in any patient. No microcalcifications were observed. Follicle-stimulating hormone was high in all patients (range 19.8 to 66.0 mUI/ml, mean 34.4). Luteinizing hormone levels were variable (range 1.32 to 28 mUI/ml, mean 12.3). Testosterone was normal in all cases (range 2.82 to 6.25 ng/ml, mean 4.2). Ultrasonographic features of the lesions were hypoechoic area (6 patients) and mixed hyper-hypoechoic area (2 patients). Histological outcomes of Leydig cell tumor (in 3 patients), focal Leydig cell hyperplasia (1 patient), fibrosis (1 patient), diffuse Leydig cell hyperplasia (1 patient), classic seminoma (1 patient) and embryonal carcinoma (in 1 patient) were observed. CONCLUSIONS: Of 560 infertile patients 8 (1.4%) showed focal testicular lesions, 2 (0.4%) were diagnosed with germ cell tumors and 3 (0.5%) with interstitial cell neoplasms. The malignant tumors were both palpable and in 2 of 3 cases Leydig cell tumors were diagnosed only with ultrasonography.     

Analysis of histological findings of testicular biopsies in male infertility

Histological findings of testicular biopsy were studied following the Johnsen's score count method in 68 cases of idiopathic male infertility, and the relation between serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T) and histological findings were analyzed in the same cases. In oligozoospermia, there were no cases showing a Johnsen's score lower than 4. The score counts ranged widely from 1 to 9 in azoospermia. The cases with the Johnsen's score count lower than 4 revealed high values of serum LH and FSH and a low level of serum T. There was no relationship between Leydig cell accumulations or thickness of the seminiferous tubular walls and score values. Further examination using ABC (avidin biotin complex) method was carried out to find the localization of FSH and T in the testicular tissues. Immunohistochemical localization FSH was not noted in normal testicular tissues obtained the autopsy cases and testicular biopsy specimens of idiopathic male infertility. The localization of T was found in the Leydig cells and the Sertoli cells of normal and infertile testes. In the cases with the thickness of tubular walls, Sertoli cells were not stained. This fact might indicate that absence of T in Sertoli cells is related to spermatogenetic maturation only with the thickness of seminiferous tubular walls.     

Metachronous bilateral testicular tumors in a case of male infertility

A 42-year-old man referred to our hospital with the chief complaint of a solid mass of right scrotal contents. As ultrasonography revealed a right testicular tumor, right high orchiectomy was performed and the pathlogical diagnosis was testicular seminoma. At the age of 35-year-old, he was admitted to another hospital for male infertility due to azoospermia. Because left testicular tumor was found, left high orchiectomy was performed, with right testicular biopsy and testicular sperm extraction of the right testis at the same time. Pathological diagnosis revealed left testicular seminoma and no malignancy of the right testicular biopsy specimen. After the second operation, he has been receiving androgen replacement therapy, with no evidence of tumor recurrence.     

Atypical germ cells in testicular biopsy in male sterility

Of 2178 patients who underwent testicular biopsy for the investigation of male sterility between 1950 and 1979 at Zürich University, 10 cases with atypical germ cells (AGC) could be demonstrated (corresponding to 0.46%). Based on the clinical course, the cases are subdivided in three groups: 1) subsequent development of a testicular germ cell tumour within the period of a few months (2 patients), 2) development of germ cell tumour following a tumour-free interval of several years (2 patients) and 3) no tumour development up to the present (6 patients).
The presence of AGC, therefore, is of quite varied significance. The possibilities whether they represent a precancerous lesion, a reactive alteration, intratubular spread of frank tumour cells, or stem cells of all kinds of testicular neoplasms, are discussed.     

Mast cells and fibrosis on testicular biopsies in male infertility

Testicular dysfunction correlates with increased testicular mast cells. Mast cells can activate fibroblasts and promote collagen synthesis. The aim of the study was to examine testicular mast cells containing tryptase, and the relationship between mast cells and different fibrosis stages of interstitium and peritubular region of testes. Testicular biopsies obtained from 33 infertile men were assigned to 2 groups: normal spermatogenesis (n = 10) and defective spermatogenesis (n = 23). Total, interstitial, and peritubular mast cells were examined immunohistochemically using antihuman tryptase. The fibrosis stage was evaluated using vimentin and alpha-smooth muscle actin. The ratio of tubules with sclerosis to total tubules was also calculated. In all cases, mast cells were mainly localized in the interstitium. The number of total mast cells was significantly higher in defective spermatogenesis than in normal spermatogenesis (p = .048). In both groups, interstitial mast cells were higher than peritubular mast cells. However, the increase in peritubular region was much higher than the increase in interstitium. Total, peritubular, and interstitial mast cell counts were not different from each other, according to the changing fibrosis stages. Total and interstitial mast cells were significantly higher in the cases with sclerosing seminiferous tubules than in the cases with no sclerosis (p = .04 and p = .024, respectively). The mast cells and the mast cell product tryptase could be involved in the etiology of defective spermatogenesis, especially whenever the last stage (tubular hyalinization and sclerosis) takes place.     

Testicular biopsy and vasography in the evaluation of male infertility

Testicular biopsy is performed mainly to differentiate primary testicular failure from obstructive ductal lesions (usually occurring in the epididymis in azoospermic patients who have normal serum gonadotropins). Testicular biopsy may be performed easily on an outpatient basis with excision of a small piece of seminiferous tissue using a "no-touch" technique. Needle core biopsy and needle aspiration biopsy may become more widely used in the future. The role of flow cytometry for purposes of interpreting testicular specimens may be expanded in the future. Vasography should be performed only at the time of planned definitive correction of obstructive lesions of the genital duct system. Various techniques of performing vasography are discussed. Emphasis is placed on deferring vasography until the time that definitive surgery is performed to correct the patient's ductal obstruction. In that regard, vasography therefore generally is not performed as an isolated outpatient procedure.     

Color Doppler ultrasonography as a routine clinical examination in male infertility

AIM: We assessed the value of scrotal color Doppler ultrasonography as a routine examination in infertile men. METHODS: Color Doppler ultrasonography was performed in 545 infertile men with a mean age of 35.8 years to detect intrascrotal abnormalities. Findings were compared with those of physical examination. RESULTS: Intrascrotal abnormalities were detected by ultrasonography in 65.3% of patients. Of 374 abnormalities, 58.3% were undetected by physical examination. Left varicocele was found in 313 patients (57.4%); testicular microlithiasis in 30 (5.5%); epididymal cyst in 21 (3.9%); right varicocele in 4 (0.8%); and testicular cysts in 3 (0.6%). One occurrence each (0.2%) was found for testicular tumor, intrascrotal hemangioma, and hydrocele of the spermatic cord. Compared to ultrasonography, sensitivity in detecting left varicocele by physical examination was 58.4%; specificity, 79.3%; accuracy, 67.3%; and positive predictive value, 79.3%. Venous diameters in the pampiniform plexus were 3 mm or more in 61.5% of 130 subclinical left varicoceles. Of 30 patients with testicular microlithiasis, 14 had varicocele, 2 had epididymal cyst,s 3 had a history of mumps orchitis, 1 had retractile testis, and 1 had a history of orchiectomy for contralateral testicular tumor. CONCLUSIONS: The routine Color Doppler ultrasonography is valuable for diagnosing scrotal abnormalities in infertile men, frequently detecting non-palpable lesions.     

Molecular evaluation of CFTR sequence variants in male infertility of testicular origin

Although the involvement of the CFTR gene has been well established in congenital agenesia of vas deferens, its role in non-obstructive (NOb) infertility is still a matter of debate. In order to definitively define the involvement of the CFTR gene in spermatogenic impairment and a potential synergistic contribution to known genetic and clinical factors, genetic variants in the entire coding sequence and the immediately flanking regions of the CFTR gene, along with a thorough clinical evaluation, were analysed in 83 NOb infertile patients and 87 clinically well-defined fertile individuals as controls. The results of our study showed no statistical difference between CFTR carrier frequency in the infertile and fertile population. Specifically, the IVS8-6(5T) allele carrier frequency was similar in NOb infertile patients when compared with fertile men, but it is noteworthy that, when fertile men were classified into having optimal and suboptimal fertility, no 5T allele was found among the 35 men with optimal fertility parameters. In conclusion, extensive CFTR analysis in infertile individuals and fertile population as adequate control definitively excludes the involvement of the CFTR gene variants in sperm production and stresses the importance of carefully identifying those individuals with obstructive defects, in whom CFTR screening will be beneficial.     

不育睾丸活检病理,免疫组化及组织化学研究

为探讨男性不育原因，对４２例男性不育症患者的睾丸进行活检病理、免疫组化及组织化学研究，结果发现大部分病例睾丸间质及部分曲细精管内有免疫复合物ＩｇＧ、ＩｇＡ、ＩｇＭ沉积，部分曲细精管内有ＰＡＳ阳性物。认为体液免疫是导致男性不育的重要因素。     

Critical appraisal of routine supraclavicular lymph node biopsy in staging of testicular tumors.

Supraclavicular lymph node biopsy was performed as a staging procedure in 36 patients with germ cell tumors of the testis and nonpalpable supraclavicular nodes. Of 28 patients with clinical Stage A or B disease, 1 patient (4 per cent) was found to have supraclavicular metastases. Of 8 patients with clinical Stage C disease, 2 (25 per cent) had supraclavicular metastases. The apparent infrequency with which subclinical supradiaphragmatic disease is documented with this procedure and the current use of adjuvant systemic therapy in patients with pathologic Stage B nonseminomatous tumors suggest that supraclavicular lymph node biopsy should be abandoned as a routine staging procedure.     

A histochemical study of testicular mast cells from patients with male infertility

The proteoglycan of the mast cells from human testes was analyzed using histochemical techniques. Testicular biopsies were obtained from 50 with idiopathic male infertility, 13 with obstructive azoospermia, 6 with varicocele and 14 normal men. To identify the proteoglycan, nitrous acid treatment and chondroitinase ABC digestion were carried out in addition to specific staining procedures using Alcian Blue pH 1.0 and high iron diamine. In all clinical groups, the mast cells which contained heparin were predominant. However, in the idiopathic male infertility group, the mast cells which contained chondroitin sulfate increased significantly. This type of mast cells were rarely seen in normal testicular tissue, whereas in the testes of patients with idiopathic male infertility, 20 percent or more mast cells contained chondroitin sulfate. This observation demonstrates that a change in mast cell subclass occurs in the testes of the patients with idiopathic male infertility and implies that the mast cells play an important role in the etiology of this disorder.     

替代睾丸活检的新方法——精液细胞学研究

目的：寻找无创伤判断睾丸生精功能及输精管道梗阻的检查方法。方法：对１２２例无精子症病人及５０例生育男性同时进行睾丸活检和精液细胞学检查。结果：生育男性精液细胞学及睾丸活检生精细胞发育水平符合率为１００％,无精子症病人总符合率为９１％;经Ｋａｐｐａ检验两法呈高度相关,Ｐ＜０．０１。１４例睾丸活检见精子及各级生精细胞,精液细胞学检查未见生精细胞的病例,经精液生化指标证实１３例为输精管道梗阻,１例为逆行射精。结论：两种方法所反映的生精细胞水平完全一致,说明精液细胞学检查是一种比较理想的判断睾丸生精功能及输精管道梗阻的无创伤检查方法     

A hCG-secreting testicular seminoma revealed by male infertility: mechanism of hCG-evoked endocrine disturbances

Summary. We report a case of a hCG-producing testicular seminoma revealed by a male infertility due to oligozoospermia. No palpable tumour was found at clinical examination and the diagnosis was established on hormonal data and the echography of the testis. The endocrine patterns associated high levels of β-hCG and 17β-oestradiol contrasting with low levels of LH and FSH and normal levels of testosterone. Immuno-histochemical studies confirmed the ectopic production of hCG. Histological findings and the evolution of hormonal parameters suggested that hyperoestradiolaemia was probably the consequence of a hCG-evoked Leydig cells hyperplasia involving a paracrine mechanism. In fact, after removal of the tumour, a dramatic decrease of plasma sex steroid levels was observed before recovery of normal testicular endocrine and exocrine functions.     

Comparison of flow cytometry with static densitometry in papillary thyroid carcinoma

The prognostic accuracy of flow cytometric and static densitometric DNA analysis was compared in 31 patients who had undergone surgery for papillary thyroid carcinoma between 1959 and 1978 (median follow-up 18 years). There were five deaths from papillary thyroid carcinoma. Three of six patients with DNA aneuploid tumours on flow cytometry died (P greater than 0.05, Fisher's exact test) compared with four of eight patients whose tumours were found to be aneuploid by static densitometry (P less than 0.02). When quantitative analysis was applied to the static densitometry data, all five patients who died from papillary carcinoma were distinguished, with no false positives (P less than 0.002). The prognostic accuracy of flow cytometric DNA analysis is less than that of static densitometry in which morphological selection of malignant cells permits quantitative measurements. DNA analysis may add refinement to existing scoring systems in predicting the risk of death from papillary thyroid carcinoma. Such information could provide the basis for controlled prospective evaluation of bilateral resection as opposed to lobectomy in defined high risk patients. At present there is insufficient evidence upon which aneuploidy should be used as a determinant of the extent of operation for papillary thyroid carcinoma.