Primary testicular lesions in the twisted testis*

Urology-andrology FERTILITY AND STERILITY

Vol. 57, NO.2, February 1992

Copyright Q 1992 The American Fertility Society

Printed on acid-free paper in US.A.

Primary testicular lesions in the twisted testis*

Manuel Nistal, M.D.t:J: Candido Martinez, M.D.t Ricardo Paniagua, Ph.D.§ Autonomous University of Madrid, School of Medicine; La Paz Hospital; and University of Alcala de Henares, Madrid, Spain

Objective: To investigate primary lesions in twisted testes. Design: The histologic study of testicular specimens obtained from men who had suffered testicular torsion. Setting: The conditions required for material selection were the knowledge of the exact time of torsion and the presence of recognizable seminiferous epithelium cells. Patients: Two hundred eighteen testicular torsions treated in La Paz Hospital, Madrid, Spain, from 1970 to 1990. Main Outcome Measures: After rejection of specimens that did not fulfill the conditions for selection, 109 biopsy and orchidectomy specimens from pubertal and adult males were studied to determine if primary lesions are superimposed to lesions secondary to anoxia. Results: The following primary tubular lesions were found: (1) focal hypospermatogenesis (5 biopsies and 1 orchidectomy specimen; these testes showed degree I, II, or III anoxic lesions); (2) hypoplastic zones with only immature and hyperplastic Sertoli cells (3 orchidectomy specimens with degree III lesions); (3) zones of Sertoli-cell-only tubules that only contained a normal amount of mature appearing Sertoli cells (5 orchidectomy specimens with degree III lesions); and (4) intratubular calcifications (1 orchidectomy specimen with degree III lesions). In two cases with degree III lesions, more than one primary testicular lesion could be observed. Conclusions: An important number of twisted testes bear primary lesions that might had been involved in torsion development. The real percentage is probably even higher than that found in this study (14%) because the material obtained (biopsies) in many cases was insufficient to ensure complete exploration and because primary lesions are not recognizable in areas with pronounced anoxic lesions. Fertil Steril1992;57:381-6 Key Words: Testis, testicular lesions, testicular torsion, hypospermatogenesis, hypoplastic seminiferous tubules, Sertoli -cell-only tubules, intratubular calcifications

Testicular torsion, if it is not immediately repaired, results in serious and irreversible lesions leading to hemorrhagic infarct and necrosis of the

Received June 7, 1991; revised and accepted October 8, 1991.

* Supported in part by grants from the "Fondo de Investigaciones Sanitarias de la Seguridad Social" y "Caja Madrid", Madrid, Spain. t Department of MOrPhology, School of Medicine, Autonomous University of Madrid, and Department of Pathology, La Paz Hospital. :\: Reprint requests: Manuel Nistal, M.D., Department of Morphology, Autonomous University, School of Medicine, Calle Arzobispo Morcillo 2, E-28029 Madrid, Spain. § Department of Cell Biology and Genetics, University of Alcala de Henares.

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testis. In recent years, the testicular torsion has acquired great interest because of the following features: 1. The increase in its frequency which, in a general hospital, has risen from 4 to 9 to 15 to 20 patients/year (1-6). 2. Although a correlation betwe~n the time elapsed after torsion and the severity of the lesions is usually observed, there are also exceptions to this rule: whereas some patients present minimal lesions several hours after torsion, other patients show pronounced lesions shortly after torsion (7). This observation is corroborated by experimental studies on laboratory animals. The results of these studies showed pronounced differences among subjects, even

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381

Table 1

Distribution of Cases According to Their Age, and the Degree of the Lesion Caused by Anoxia Degree of lesion caused by anoxia a Degree I

Age

Biopsy specimen

Orchidoectomy

Degree II

Degree III

Biopsy specimen

Orchidoectomy

Biopsy specimen

Orchidoectomy

y

9 to 13 14 to 19 21 to 60

15 5

10 8 4

2 4 1

2 1

19 19 8

All ages

31

22

7

3

46

a

11

Mikuz's classification.

within the same species and following the same protocol (8-10), and suggest that the time elapsed after torsion repair is not the sole factor involved in the testicular lesions related with torsion. 3. In spite of antecedents of testicular torsion usually not being mentioned in the histories of men consulting for infertility (11), a follow-up study of patients who had suffered testicular torsion revealed subfertility in many of them (12-15). This subfertility has been explained on the basis that the contralateral testis would either be the bearer of primary lesions (16-18) or develop a sympathetic orchidopathy (19). Testicular atrophy and/or high antibodies rates have been reported in some of these contralateral testes. The purpose of this paper is to investigate whether the twisted testis bears primary lesions that predispose it to torsion and, therefore, whether saving a twisted testis with doubtful viability is advisable. MATERIALS AND METHODS

A total of 218 testicular biopsies or orchidectomy specimens were obtained from males with testicular torsion in La Paz Hospital during 1970 to 1990. The material comprised 63 newborn testes, 17 testes from infants or children < 9 years of age; 53 testes from boys between 9 and 13 years of age; 61 testes from young adult men from 14 to 19 years of age; and 24 testes from men > 20 years of age. The testes were fixed in formaldehyde (prepubertal testes) or Bouin's fluid (postpubertal testes) and fixed in paraffin. Several 6-JLm thick sections from each testis were stained with hematoxylin and eosin (H and E), Mason trichrome, periodic acid-Schiff, and orcein for elastic fibers. After light microscopy examination of the histologic specimens, all the testes from males < 9 years of age were excluded because the necrosis of testicular parenchyma impeded clear recognition 382

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Primary lesions in the twisted testes

of histologic features. In addition, 29 adult testes were also precluded because either the exact time of torsion (including intermittent or recurrent testicular torsions) was not precisely stated in the clinical histories or the testicular material available (small biopsy specimen) was insufficient to evaluate the characteristics of the testicular parenchyma. Therefore, the material selected for the study comprised 109 testes (42 testes from boys between 9 and 13 years of age; 48 testes from young adult men between 14 and 19 years of age, and 19 testes from men between 21 and 60 years of age) (Table 1). In all cases the torsion was intravaginal. The highest incidence of testicular torsion was found at 13 years of age. The three degrees of testicular lesions secondary to torsion-caused anoxia proposed by Mikuz (7) were evaluated. In addition, the following focal primary testicular lesions were considered: 1. Focal hypospermatogenesis. Groups oftubules showing a thin seminiferous epithelium in which the average number of each germ cell type (from spermatogonia to elongated spermatids) was half of the normal number or less. According to Nistal et al. (20), the following germ cell numbers per cross-sectioned tubule were assumed as normal numbers: 17 ± 0.3 spermatogonia, 25 ± 0.5 primary spermatocytes, 31 ± 0.6 round spermatids, and 21 ± 0.4 elongated spermatids. For each twisted testis, the average number of each germ cell type was calculated on at least 20 randomly selected cross-sectioned tubules. 2. Hypoplastic zones. According to Hedinger et al. (21), groups of tubules consisted of Sertoli cells only with an immature prepubertal pattern (round to avoid, regularly outlined nuclei displaying a pseudostratified distribution) and pronounced hyperplasia. 3. Groups of tubules with Sertoli cells only that had a mature, adult appearance (irregularly outlined Fertility and Sterility

Figure 1 Degrees of lesions caused by anoxia. (A), First degree lesions in a twisted testis from a 15-year-old boy. The seminiferous tubules showed complete spermatogenesis with spermatid sloughing (star). The basal compartment is not altered. Hand E was X250. (B), Second degree lesions in a twisted testis from a 16-year-old boy showing sloughing of all germ cell types (star) and interstitial hemorrhage (asterisk). Hand E was X125. (C), Twisted testis from a 16-year-old boy showing second degree lesions in the center of the testicular parenchyma (star) and second degree lesions in the periphery (asterisks). Hand E was X60. (D), Twisted testis from a 15-year-old boy showing third degree lesions with necrosis of the seminiferous epithelium and interstitial hemorrhage (star). The subalbugineal region only shows second degree lesions (asterisk). Hand E was X60.

nuclei with a prominent and centrally located, tripartite nucleolus) and that were present in normal numbers. 4. Groups of tubules containing intratubular calcifications. RESULTS

Degree I lesions were found in 31 cases (28.5%); all corresponded to testicular biopsies (Table 1). The lesion was principally interstitial and consisted of edema, congestion, and limited hemorrhages. In addition, the seminiferous epithelium showed sloughing of mature germ cells (spermatids and occasionally spermatocytes) without alterations in either the Sertoli cells or spermatogonia (Fig. lA). Other minor alterations observed were: vacuolation of the adluminal compartment of seminiferous tubules; focal dilation of the tubular lumen; and extremely dilated interstitial lymphatic vessels. Degree II lesions were found in 29 cases (26.5%) (Table 1). These testes showed interstitial hemorrhage with variable impairment of Leydig cells and germ cell sloughing by all germ cell types (Fig. IB). In 23 of these testes (biopsies and orchidectomy specimens), the lesions were more or less uniformly Vol. 57, No.2, February 1992

distributed through the testis. In the other 6 testes (only orchidectomy specimens), the severity of the lesions decreased from the center of the testicular parenchyma toward the periphery where the lesions corresponded to degree I. In these testes, the severity of lesions also differed from one to another testicular lobule (Fig. lC). Degree III lesions or hemorrhagic infarct appeared in 49 cases (45%) (Table 1). These testes showed a diffuse interstitial hemorrhage and necrosis of the seminiferous epithelium. A subalbugineal crescent of the testicular parenchyma showing milder lesions (degree II lesions) could be observed in 26 orchidectomy specimens (Fig. ID). The relationship between the degree of the lesion secondary to anoxia and the time elapsed after torsion is shown in Table 2. Focal primary lesions were found in 17 cases: 6 cases with hypospermatogenesis (Fig. 2A); 3 cases with hypoplastic tubules showing hyperplasia of immature Sertoli cells (Fig. 2B); 5 cases showing tubules with mature Sertoli cells only (Fig. 2C); 1 case with intratubular calcifications (Fig. 2D); 1 case with both hypospermatogenesis and hypoplastic tubules; and 1 case with hypoplastic tubules and tubules with mature Sertoli cells only. The source of these specimens and the relationship between the focal primary lesions and the degree of lesion secondary to anoxia is shown in Table 3. DISCUSSION

Most studies on testicular torsion have addressed three points: (1) the knowledge ofthe peculiar characteristics of these testis lesions and their possible reversibility to prevent orchidectomy; (2) a search for the anatomic anomalies in the supportive mechanisms of the twisted testis that might explain the causes of torsion (22); and (3) the exploration ofthe Table 2 Relationships Between the Time Elapsed After Torsion and the Degree of the Lesion Caused by Anoxia No. of testes showing each lesion degree a Time after torsion

Total no. of testes

Degree I

Degree II

Degree III

4 to 8 8 to 12 12 to 24 >24

31 23 6 20 29

22 9 0 0 0

9 14 5 1 0

0 0 1 19 20

All times

109

31

29

49

h

o to 4

a

Mikuz's degrees of lesion. Nistal et al.

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383

r

Figure 2 Primary lesions in twisted testes. (A), Tubules with hypospermatogenesis (star) among normal tubules (asterisk) in a twisted testis from a 15-year-old boy. Hand E was X125. (B), Zone of hypoplastic tubules with only hyperplastic immature Sertoli cells (star) among tubules with degree III lesions (asterisk) in a twisted testis from a 13-year-old boy. Hand E was X60. (C), Tubules with only Sertoli cells with a mature appearance (star) besides tubules with third degree lesions (asterisk) in a twisted testis from a 13-year-old boy. Hand E was X125. (D), Intratubular calcifications (star) in tubules with third degree lesions in a twisted testis from a 15-year-old boy. Hand E was X125.

contralateral testis to learn if this testis might be damaged by the noxious effects of the antigens produced by the twisted testis and thus explain the subfertility of many men who have suffered testicular torsion (16-18). The conclusions of these studies are important because surgeons are often doubtful whether a twisted testis should or should not be removed.

Table 3

In our first review of the testicular torsion cases treated in our hospital, we found that most neonatal torsions presented very evolved lesions that hindered recognition of seminiferous epithelium cells. In addition, there was usually a lack of precision in the history concerning the time of appearance of the first symptoms (in many cases the lesions were already present at birth). It is possible that both features might be related with the extravaginal location of the torsion in newborns. This torsion type may suffer a more severe testicular ischemia than the intravaginal torsion (observed in most boys and adult men) and facilitate the necrosis of testicular parenchyma. Testicular torsions in pubertal and adult males are often associated with anomalies in the suspensory mechanisms of the testis, principally with the anomaly designated "clapper" (3). The testicular lesions caused by infarct can be classified using the three degrees of Mikuz (7), although a correlation between these degrees and the time of the torsion may be established only for short «4 hours) and long (>12 hours) times. Whereas degree I lesions can be observed even 8 hours after torsion, degree III lesions may be present at between 8 and 12 hours. This suggests that there are additional factors involved in the development of the lesions. An interesting observation is the gradual decrease in the severity of the lesions from the center to the periphery of the testicular parenchyma. This finding led us to confer only a limited prognostic value to the testicular biopsy from these testes and explains that some twisted testes have undergone poor evo-

Focal Primary Lesions in Twisted Testes

Primary lesion

Age

Specimen

Mikuz (7) degree of lesion

Biopsy Biopsy Biopsy Biopsy Biopsy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy Orchidectomy

I I III I II III III III III III III III III III III III III

y

Hypospermatogenesis

Hypoplastic tubules with hyperplastic immature Sertoli cells

Tubules with mature Sertoli cells only

Intratubular calcifications Hypospermatogenesis and hypoplastic tubules Hypoplastic tubules and tubules with mature Sertoli cells only a

12 15 15 16 17 19 a 13 16 19 13 13 14 a 16 18 a 15 19 19

Cryptorchid testis.

384

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lution in spite of the minimal nature of the lesions observed in their biopsy. This gradual difference in the lesion severity might be related with the distribution pattern of testicular blood vessels (23). Whereas the center of the testis contains large centripetal veins that run to the mediastinum testis, the periphery of the testis is drained by smaller centrifugal veins. After testicular torsion, the large veins would be congested and their walls would rupture, giving rise to hematic extravasation, whereas the centrifugal veins would be damaged later. In testes with degree II lesions, differences in the severity of these lesions were also observed not only from the center to the periphery of the testis but also from one to another lobule within the central portion of the testis. These lesions (vacuolation of the adluminal compartment of the seminiferous epithelium and dilation of the tubular lumen) recall those observed in obstructive processes (24) and suggest that once testicular torsion has occurred, obstructive mechanisms may play some role in the development of the lesions. Another finding that has not been reported in previous literature is the presence of primary lesions in the seminiferous tubules of twisted testes. These primary lesions were focally distributed; each focus extended to several groups of tubules that suggested testicular lobules. The examination of these lesions is hampered by the following features: (1) biopsy usually provides insufficient material for focal lesions detection; in our study, primary lesions other than hypospermatogenesis were only observed in orchidectomy specimens; (2) the most frequent age of testicular torsion (excluding the neonatal torsions) is about 13 years when complete spermatogenesis has usually not yet been reached; and (3) the hemorrhagic infarct in many surgical specimens is so evolved than it is impossible to study the seminiferous tubule structure. In spite of these difficulties, in 18 (15.5%) of the 109 testes studied here, primary tubular lesions were clearly recognizable. In 3 of these testes, cryptorchidism might be responsible for the presence of the lesions, but in the other 15 no well-defined testicular disorder was apparent. Lobules with tubules showing hypospermatogenesis, in contrast with the adjacent tubules, suggest that only decreased sperm production is the primary deficiency in these lobules. The hypoplastic zones (also termed zones of nodular hyperplasia of Sertoli cells) (21) are clearly distinguishable from the other Sertoli -cell-only tubule zones. In both zones, the presence of tubules devoid of germ cells is common. However, the Sertoli cells in the hypoplastic zones

Vol. 57, No.2, February 1992

have a prepubertal pattern and are hyperplastic, whereas the other Sertoli-cell-only zones contain a normal number of adult mature Sertoli cells. The presence of hypoplastic zones has been reported in both cryptorchid testes and normal testes and is considered an unspecific lesion that is interpreted as a focal dysgenesis. In contrast, tubules with mature Sertoli cells only have been reported in a variety of primary testicular disorders such as cryptorchidism, Klinefelter's syndrome and Del Castillo's syndrome (25). The presence of more than one type of primary tubular lesion supports the primary nature of these lesions. The presence of primary testicular lesions in twisted testes suggests that these testes are congenitally damaged and that these lesions might be involved in the development of torsion. Acknowledgment. We thank Ms. Carol F. Warren for linguistic assistance.

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