Atypical Germ Cells Research Articles

Interesting case series on distinct histopathological findings of six cases of epididymo-orchitis

Several clinicopathological illnesses impact the testis and paratesticular area, which are divided into non-neoplastic and neoplastic diseases. Despite the availability of imaging and tumor marker testing, histopathological examination is the primary method for diagnosing testicular lesions. Common indications of orchidectomy for non-neoplastic lesions are cryptorchidism, epididymitis and testicular torsion. Few non- neoplastic lesions present as mimickers of neoplasm with commonest being granulomatous orchitis and AFB positivity detected only in 2.1% of cases with bilateral presentation being rarest. We report here a series of six cases of epididymo-orchitis to discuss the histopathological spectrum with varied etiologies. Age of the patients ranged between 33-65yr old males. Amongst six cases, two of them were clinically and radiologically suspected as neoplastic lesions, which were histopathologically diagnosed as granulomatous epididymo-orchitis with one among it showing strong positivity for AFB, and two cases as testicular torsion with orchitis and one of the case was diagnosed as cryptorchid testis with foci of atypical germ cell and last case was reported as mild non-specific orchitis, for surgical castration. In this study, we also noted unilateral presentation being the commonest, specifically of Right side. Knowledge of histopathological spectrum of epididymo-orchitis is of prime importance to detect underlying specific etiology for targeted therapy and prevent undue orchidectomy.In this study, two cases which were clinically suspected as neoplastic lesions, were confirmed as granulomatous epididymo-orchitis on histopathological examination with one case showing strong AFB positivity.In this study, we noted late presentation (5th decade) of cryptorchidism with some atypical germ cells which are forerunner of malignancy.

Моlecular mechanisms of initiation of carcinogenesis in the testis.

In this review, literature data on the study of precancerous changes in testicular tissue and molecular changes, as well as the influence of environmental factors that can initiate carcinogenesis, were analyzed and summarized for the future determination of early diagnosis of germ cell tumors of the testis and the development of preventive measures. The review also discusses the significant new changes presented in the Fourth Edition of the World Health Organization Classification of Urogenital Tumors, published in2016, and modern concepts of the etiology and pathogenesis of these diseases. Among the environmental factors that can initiate carcinogenesis, the most noteworthy are the biological effects of low doses of ionizing radiation, such as the effect of radiation-induced genome instability, which increases the risk of carcinogenesis, the "bystander effect", and chronic oxidative stress. Disruption of ubiquitin-proteasomal proteolysis, impaired molecular-level components of the blood-testis barrier, and impaired regulatory action of TGF-β on the cell cycle can play a crucial role in the pathogenesis of male infertility and the initiation of carcinogenesis in the testis. The effect of low doses of ionizing radiation as an additional etiological factor leads to changes in the structural, as well as molecular, components of the testis, including epigenetic changes, which can be characterized as environmental pathomorphosis, which leads to impaired spermatogenesis and increased risk of malignancy. Summarizing the literature review data, we can state that patients with blocked spermatogenesis, in which atypical germ cell neoplasia in situ cells are detected in testicular tissue, constitute a group at increased risk of testicular carcinogenesis. The presence of additional etiological factors, such as chronic low doses of ionizing radiation, can initiate the progression of carcinogenesis in the testicle.

Positive Oct -3/4 and D2-40 Immunohistochemical Expression in Germ Cells and Suspected Histology Pattern of Intratubular Germ Cell Neoplasia in Boys with Cryptorchidism Vanish after the Age of 2 Years.

Introduction Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen in boys younger than the age of 2 years, where most orchiopexies are performed. The aim of the study was to evaluate the diagnostic challenge to differentiate between a histological pattern of ITGCN and a histological pattern with some atypical germ cells and all positive cancer immunohistochemical markers, but no increased risk of malignancy. Materials and Methods Histology sections from 373 testicular biopsies from 289 boys aged 1 month to 2 years operated for cryptorchidism were incubated with primary antibodies including anti-placental-like-alkaline phosphatase, antiOct-3/4, anti-C-kit, anti-D2-40, and in case of repeat biopsy with anti-stem cell factor (SCF) receptor. Results The prevalence of Oct-3/4 and D2-40-positive staining of germ cells in testicular biopsies were in age groups less than 6 months, 100% and 50%; 6-12 months, 60% and 17%; and 1-2 years, 12% and 4%. A 1 year, 1-month-old boy with Prader-Willi syndrome treated with growth hormone had ITGCN in both cryptorchid testes. In another three bilateral nonsyndromic cases, 8 months, 8 months and 1-year-old, a histological pattern in accordance with ITGCN was found. These three boys had a repeat biopsy from both testes performed at the age of 3 years, 4 months, 3.5 years, and 3 years, 10months, respectively. In all cases, the Oct-3/4 and D2-40 positive germ cells turned negative and the histological pattern normalized completely. The primary biopsies had SCF negative germ cells. Conclusion This study is valuable in identifying the age-related change in Oct-3/4 or D2-40 immunopositive germ cells in seminiferous tubules. An ITGCN-like histological pattern in nonsyndromic cryptorchidism will vanish after the age of 3 years. Even when immunohistochemistry is applied, prepubertal ITGCN is so rarely demonstrated in cryptorchid testes, that it is not plausible that ITGCN generally originates during fetal development in cryptorchidism.

Histopathological features and protein ubiquitin immunohistochemical expression in peritumoral tissue of the testicular germ cell tumors

Aim. For the purpose of determination of characteristic morphological changes as well as the immunohistochemical protein Ubiquitin expression in peritumoral testicular tissue, which could be characterized as precancer lesions, the 40 patients with testicular germ cell tumors (TGCT) were investigated.Methods and results. Peritumoral testicular tissue in patients with the spermatogenesis alteration (that was detected in 95% of cases) demonstrated: 1) the dramatic increase of ubiquitination processes in seminiferous tubules, confirming the intensive proteolysis of the damaged intracellular proteins, 2) occurrence of atypical germ cells (TIN), which differ from the normal spermatogenesis cells by the authentically lower levels of the nuclear and cytoplasmatic protein Ubiquitin expression, 3) alteration of ubiquitination processes in Leydig cells with the significant increase of the protein Ubiquitin cytoplasmatic expression and the total disappearance of protein Ubiquitin nuclear expression.Conclusion. Our results show the important role of the structural and functional ubiquitin-proteolysis system components alterations at the initial stages of the testicular tissue carcinogenesis.

Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology

Patients with complete androgen insensitivity syndrome are at an increased risk for the development of gonadal germ cell cancer. Residual androgen receptor (AR) activity and abnormal gonadal location may influence the survival of atypical germ cells and the development of other histopathological features. To assess this, we evaluated 37 gonads from 19 patients with complete androgen insensitivity (ranging in age from 3 months to 18 years). Histological abnormalities were examined using hematoxylin and eosin-stained sections and sections stained for POU5F1 and KITLG, markers of early changes in germ cells at risk for malignant transformation. Hamartomatous nodules (HNs), Leydig cell hyperplasia (LCH), decreased germ cells, tubular atrophy and stromal fibrosis were more pronounced as age increased (P<0.001). Expected residual AR activity acted as a positive predictor only for non-malignant germ cell survival in (post)pubertal patients (P<0.05). Immunohistochemical studies indicated that delayed maturation of germ cells was present in three patients, whereas intermediate changes that occurred between delayed maturation and intratubular germ cell neoplasia, designated pre-intratubular germ cell neoplasia, were identified in four cases. Intratubular germ cell neoplasia was observed in one patient. Neither POU5F1 nor KITLG expression was dependent on expected residual AR activity. An independent effect of inguinal versus abdominal position of the gonads was difficult to assess because inguinal gonads were present primarily in the youngest individuals. In conclusion, many histological changes occur increasingly with age. Expected residual AR activity contributes to better survival of the general germ cell population in (post)pubertal age; however, it did not seem to have an important role in the survival of the germ cells at risk for malignant transformation (defined by POU5F1 positivity and KITLG overexpression) in complete androgen insensitivity. Comparison of the high percentage of patients in our study that were carrying germ cells with delayed maturation or pre-intratubular germ cell neoplasia with previously reported cumulative risk of tumor development in adult patients indicates that not all such precursor lesions in complete androgen insensitivity will progress to invasive germ cell cancer.

In Vivo Actions of the Sertoli Cell Glucocorticoid Receptor

We determined the functional role of the Sertoli cell glucocorticoid receptor (GR) in vivo using a transgenic Cre-loxP approach to conditionally disrupt GR expression. Sertoli cell GR knockout (SCGRKO) was shown by absent Sertoli cell-specific GR immunolocalization and reduced levels of glucocorticoid-responsive Stc1 and Tsc22d3 mRNA in SCGRKO relative to control testes. Adult SCGRKO testes exhibited distinct morphological changes, including reduced seminiferous tubular lumen formation, decreased total Sertoli cell numbers, and parallel reductions in meiotic spermatocyte and postmeiotic spermatid numbers. Conversely, tubular diameter was increased and testis size was normal in SCGRKO males. Decreased serum FSH and testicular Fshr mRNA levels were consistent with reduced Sertoli cell number. Adult SCGRKO testes also displayed atypical germ cells and interstitial focal accumulations of hypertrophic lipid-laden, immature-like Leydig cells. Circulating LH, and testicular Lhr mRNA, testosterone, dihydrotestosterone, and 3α/3β-diol levels were all reduced in mature SCGRKO mice, whereas serum testosterone and dihydrotestosterone levels remained normal. Moreover, Sertoli cell GR disruption caused differential changes to steroidogenic enzyme transcripts, with down-regulated testicular Cyp11a1 contrasting with up-regulated Hsd17b3 expression. Reduced SCGRKO testicular expression of Hsd11b2, encoding an enzyme for corticosterone inactivation, supports a dynamic coupling between Hsd11b and androgen production. Our novel SCGRKO model has revealed that Sertoli cell-mediated GR actions support normal testicular function. Sertoli cell GR is required to maintain normal testicular Sertoli/germ cell numbers and circulating gonadotropin levels, as well as optimal Leydig cell maturation and steroidogenesis, providing new insight into gluocorticoid-mediated impact on male reproduction.

Difficult Differential Diagnoses in Testicular Pathology

Although relatively rare, testicular cancer is the most common solid organ malignancy in young men and remains a leading cause of cancer death in this population. Different types of testicular tumors are treated differently, with an overall very high cure rate with proper management. Pathologists must, therefore, be familiar with important diagnostic pitfalls in testicular pathology, particularly those that result in different treatments or prognoses. To summarize key diagnostic features and useful ancillary tools for the most frequently encountered problems in testicular tumor pathology. Current texts, PubMed (National Library of Medicine) articles, and archives at Indiana University School of Medicine and Beth Israel Deaconess Medical Center were all reviewed. Problematic differential diagnoses include seminoma versus nonseminomatous germ cell tumors, germ cell tumors versus non-germ cell tumors, intratubular germ cell neoplasia versus atypical germ cells with maturation arrest, pseudolymphovascular invasion versus real lymphovascular invasion in germ cell tumors, and macroscopic Sertoli cell nodules versus Sertoli cell tumors. In almost all cases, awareness of the differential diagnostic possibilities based on routine light microscopic features permits application of either additional, directed observations or immunohistochemical studies that lead to an accurate diagnosis.

Does Intratubular Germ Cell Neoplasia, Unclassified Type Exist in Prepubertal, Cryptorchid Testes?

Six of 276 prepubertal testicular specimens had atypical germ cells. Specimens from 3 intersex patients met the criteria for intratubular germ cell neoplasia, unclassified type (IGCNU). Of the remaining 3 specimens (2 patients), 1 from a Down syndrome patient had centrally positioned germ cells with mild nuclear enlargement and hyperchromasia and expressed fetal germ cell markers (Oct3/4, placental alkaline phosphatase, CD117); it was classified as "delayed germ cell maturation". The remaining 2 specimens (1 patient) were diagnosed as IGCNU but, in retrospect, the patient had an undiagnosed intersex disorder. We therefore did not find a bona fide case of IGCNU in prepubertal testes apart from an intersex disorder.

Atypical Basal Ganglia Germ Cell Tumor Presenting as Cerebral and Brainstem Hemiatrophy

We describe a 20-year-old male patient with a germ cell tumor of the basal ganglia who presented with progressive hemiparesis and hemisensory loss. Initial computed tomography and magnetic resonance imaging showed ipsilateral cerebral and brain stem hemiatrophy predominantly in the left basal ganglia and thalamus, whereas no mass or enhancement was depicted. Single photon emission computed tomography revealed mild hypoactivity of the left cerebral hemisphere. Stereotactic biopsy was performed after a mass lesion became apparent, allowing histologic verification of germ cell tumor to be established.

Testicular microlithiasis and neoplastic lesions in wild eland (Tragelaphus oryx): Possible effects of exposure to environmental pollutants?

The purpose of the study was to compare wildlife in the proximity and away from the sources of known industrial pollution. Macroscopic, focal, gritty areas that appeared white were observed in the testes of all 24 South African eland (Tragelaphus oryx) culled in the Rietvlei Nature Reserve (RNR; n=17) between 2001 and 2003 and Suikerbosrand Nature Reserve (SNR; n=7) in 2004. Histopathological evaluation of testes showed multiple intratubular dystrophic calcifications, focal areas of sperm stasis and interstitial chronic cell infiltrates with fibrosis. Spermatogenesis was generally impaired; a few atypical germ cells were also encountered. Sertoli cell vacuolization and sloughing of the seminiferous epithelium were evident. Adenomatous changes of the rete testis, reflective of possible chronic estrogenic exposure, were found. In testes collected from three reference eland in 2007 from the Molopo Nature Reserve (MNR) in the Kalahari/Kgalagadi Desert, except for one focal area of sperm stasis and another with microcalcification, the seminiferous epithelium as well as collecting/rete tubules were normal. Analyses of fat tissue for environmental pollutants showed that 11 out of 17 RNR eland contained a detectable estrogenic chemical p-nonylphenol (mean+/-SD: 184.8+/-24.6 microg/kg fat); no organochlorine chemicals or polychlorinated biphenyls were detected. Of the 7 SNR eland, 5 had detectable octylphenol residues (50.2+/-30.9 microg/kg fat), 3 had detectable p-nonylphenol (137.8+/-77.9 microg/kg fat), 3 had o-p'-DDT (114.9+/-31.1 microg/kg fat), 3 had p-p'-DDT (127.3+/-49.9 microg/kg(79.5+/-30.4 microg/kg fat) and 5 contained o-p'-DDE (27.7+/-9.9 microg/kg fat). One eland from the MNR contained one 70.6 microg o-p'-DDT/kg fat and another p-p'-DDE 61.3 microg/kg fat. Therefore, in eland with testicular abnormalities, significant amounts of various estrogenic chemicals were bioaccumulated in fat samples. It therefore seems likely that the lesions found in RNR and SNR were associated with the relatively high body-burden of environmental pollutants (phenols), although the possibility of systemic infections cannot be ruled out. No testicular abnormalities were found in reference eland. These findings are the first indication of mammalian wildlife being affected by environmental pollution of endocrine disrupting chemicals in South Africa.

Morphological Findings

The pathogenesis of cryptorchidism is not known and likely to be multifactorial. On one hand, the extent of testicular changes—for example, the reduced number of spermatogones per tubular cross section, the reduced diameter of the tubuli, the fibrosis of the testes—depends on the position of the gonads. Intra-abdominal testicles have the most severe lesions. On the other hand, the patients’ age at the time of the operation is important. The older the boys are at the time of their surgery the more pronounced the changes. The unphysiological position of the gonads impairs normal testicular development in adolescence and results in an increase of existing lesions. The decrease in spermatogones is crucial as it may impair fertility at a later stage. Patients with unilateral cryptorchidism may also develop impaired fertility or even infertility. In unilateral testicular retention, the scrotal testicle will be affected by the same severe changes as the retained gonad in one third of cases. The “increase” in spermatogones after GnRH therapy probably only seems like an increase, because these cells are stimulated by hormone therapy and are thus more clearly visible. In so called testicular aplasia, no genuine aplasia is present; the term may be established but is erroneous. The primary embryonic gonads are subsequently partially or completely scarred, and the cause of this is usually not found. The cause of the increased incidence of germ cell tumors in cryptorchidism remains unexplained. The presence of atypical germ cells in retained prepubertal testicles has not been confirmed as far as we are aware.

A case of germinoma in a limpet ( Patella coerulea) ( Patellogastropoda)

Germinoma is a gonadal neoplasm originating from progenitor cells in germinal epithelium. Frequently described in some populations of bivalve molluscs, to our knowledge, germinoma has never been reported in gastropods so far. In this paper we describe the histopathological findings of some atypical cellular masses, originating in the undifferentiated germ cell layer in the male gonads of a limpet ( Patella coerulea), whose morphological appearance resembled that of a germ cell tumor. The abnormal, and independent growth with no evidence of maturation of the undifferentiated and atypical germ cells, the limited number of follicles involved ( n < 10%) and the absence of tissue invasion, supported a diagnosis of Stage 1 germinoma.

Intratubular germ cell tumours of pig testicles.

In the course for the histopathological examination of testicles of 30 castrated boars the authors have observed in 4 animals the intratubular growth of atypical germ cells. On the basis of the histological picture this change is equivalent to the human infertile testicles, observed as carcinoma in situ, resp. intratubular germ cell tumour. The described phenomenon occurred in atrophic testicles in 3 of the 4 old animals. The described change in the domestic pig, not known so far, raises the possibility of development of solid testis tumours in this species, as well.

Sequelae in male rabbits following developmental exposure to p, p′-DDT or a mixture of p, p′-DDT and vinclozolin: Cryptorchidism, germ cell atypia, and sexual dysfunction

Rabbit does (7–9 per group) were treated daily per orum from gestation day 15 through post-natal week 4 to provide per kg body wt 25 μmol (low) or 250 μmol (high) p, p′-DDT or a mixture of DDT and vinclozolin (12.5 and 125 μmol each). Developmental as well as post-pubertal reproductive sequelae of male progeny were studied. Testicular descent in some pups was impaired by DDT. Serum LH or testosterone was not affected. FSH was lower in mixture- but not in DDT-exposed rabbits. Lack of sexual interest, penile erection and ejaculation were observed in some mixture rabbits. Sperm counts were unaffected, but morphologically normal spermatozoa were fewer; nuclear and acrosomal morphogenesis was disrupted. Atypical germ cells resembling carcinoma in situ were found. Also considering data for vinclozolin [Veeramachaneni DNR, Palmer JS, Amann RP, Kane CM, Higuchi TT, Pau K-YF. Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide. Reproduction 2006;131:805–16], we concluded that DDT causes cryptorchidism and germ cell atypia, vinclozolin permanently disrupts FSH secretion and sexual function, and the mixture causes the full spectrum of dysgenesis.

Natural history of testicular regression syndrome and consequences for clinical management

Aims Testicular regression syndrome (TRS or ‘vanishing testis’) is a condition in which a testis is thought to have once existed but has atrophied and disappeared during early development. The natural history of TRS is in completely understood, due to the absence of any prospectively studied cohort of patients. This study aimed to quantify the cardinal features of the disease and correlate these with age. Materials and methods A total of 117 cases of TRS were submitted for histopathological examination. Patient age ranged from birth to 12 years, with a median age of 2 years. The proportion of each histological feature present was analysed according to age, using the χ 2 test. Birth Results The 117 cases accounted for 21% of the testicular/paratesticular specimens examined. Only 12 cases (10%) were found to contain testicular tissue, with no readily identifiable germ cells and in particular no atypical germ cells identified. Features such as haemosiderin-laden macrophages, calcification, the presence of a nodule, vas or epididymis were less prevalent amongst specimens from older boys. Conclusions This is the largest series studied to date. With only 10% of the removed specimens containing identifiable testicular tissue with no germ cells seen, a negligible risk of future germ-cell cancer on the affected side is implied. If the laparoscopic findings suggest a diagnosis of vanishing testis, we contend that a groin exploration may be no longer indicated.

Germ cell atypia in undescended testes hinges on the aetiology of cryptorchidism but not the abdominal location per se

Testicular carcinoma in situ (CIS), which precedes germ cell tumours, has been associated with coexistence or a history of testicular maldescent in 20-30% of human cases. The objective of this study was to determine if the abdominal location of the testis by itself affects differentiation of germ cells and why only some undescended testes manifest atypical germ cells. Groups (n = 4-6) of pregnant Dutch-Belted rabbits were treated on alternate days between gestation days 15 and 30 with anti-androgenic chemicals -- p,p' 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE; 100 mg/kg bw; oral), or flutamide (50 mg/kg; s.c.); oestrogenic chemical octylphenol (150 mg/kg; oral); or nothing. Groups (n = 4) of neonatal male pups from untreated litters were either implanted with oestradiol (0.5 mg; 60-day release), surgically rendered cryptorchid before testes transcended inguinal canal, or left untreated. Of the pups exposed in utero, four of the 12 DDE, two of the nine flutamide and one of the four octylphenol pups were unilaterally cryptorchid. All animals treated with oestradiol were bilaterally cryptorchid. Light and electron microscopic evaluation at 24-26 weeks revealed presence of atypical germ cells in the undescended testes of DDE-, octylphenol-, and oestradiol-exposed animals but not in flutamide-treated or surgical cryptorchids. These atypical cells exhibited morphological hallmarks of CIS, which included large nuclei with irregular contours, meandering nucleoli, swollen mitochondria, unusual cytoplasmic inclusions and occasional mitotic figures. As transformation of germ cells to CIS-like cells did not occur in flutamide or surgical groups, this phenomenon seems to be directly associated with the type of the chemical assault but not with the abdominal location of the testis per se.

Gonadotrophin-releasing hormone antagonist arrests premeiotic germ cell proliferation but does not inhibit meiosis in the male monkey: a quantitative analysis using 5-bromodeoxyuridine and dual parameter flow cytometry

Meiosis constitutes a crucial phase of spermatogenesis since the recombination of genetic information and production of haploid round spermatids need to be achieved. Although it is well established that gonadotrophic hormones are required for completion of the spermatogenic process, little is known about the dynamic and kinetic aspects of development of spermatocytes into spermatids and its endocrine control in the primate. In this study, S-phase germ cells were labelled using 5-bromodeoxyuridine (BrdU) incorporation and were then followed throughout meiosis under normal conditions and following GnRH antagonist (ANT)-induced gonadotrophin withdrawal in a nonhuman primate model, the cynomolgus monkey (Macaca fascicularis). Adult animals received either vehicle (VEH, n = 4) or the ANT cetrorelix (n = 5) throughout 25 days. On day 7 all animals received a bolus injection of BrdU. A biopsy was performed after 3 h, one testis was removed 9 days later (day 16 of treatment) and the other testis after 18 days (day 25 of treatment). Serum testosterone and inhibin levels, and testis weight were reduced (P < 0.05) by ANT treatment. BrdU localized to pachytene spermatocytes 9 days after BrdU and to round spermatids 18 days after BrdU in both groups, demonstrating that BrdU-labelled pachytene spermatocytes had undergone meiosis. Flow cytometric analysis revealed that the relative number and number per testis of BrdU-tagged 2C and 4C cells were reduced significantly (P < 0.05) within 16 days of ANT treatment. Numbers of 1C cells were lowered by day 25. The cell ratio for 1C:4C was similar with VEH and ANT (P > 0.05). These findings indicate that ANT reduced the number of cells available for meiosis but did not alter the rate of transition into round spermatids. Unexpectedly, however, the stage-dependent progression of BrdU-tagged round spermatids was significantly (P < 0.05) retarded under ANT as seen from the frequency of tubules containing BrdU-labelled round spermatids. The average duration of spermatogenic cycle was slightly prolonged (9.8 days in the VEH group and 10.8 days in the ANT group (P = 0.09)). Since no atypical germ cell associations could be found, it remains unclear whether this slight prolongation is entirely due to altered spermatid progression or whether earlier phases are affected. We conclude for the nonhuman primate that (1) BrdU-labelling of premeiotic germ cells is suitable for tracing their meiotic transition into postmeiotic cells, (2) unlike in the rat, gonadotrophin suppression initially affects premeiotic cell proliferation and thus the number of cells available for meiosis, (3) the meiotic process continues quantitatively despite gonadotrophin deficiency and (4) prolonged gonadotrophin deficiency might alter the timing of germ cell development.

Carcinoma in situ and seminoma in equine testis

The presence of atypical germ cells resembling carcinoma in situ of human testis is reported for the first time in an unilaterally cryptorchid stallion. These cells were found in association with developing intratubular seminoma indicating they represented carcinoma in situ.

Intratubular Germ Cell Neoplasia (ITGCN) with p53 and PCNA Expression and Adjacent Mature Teratoma in an Infant Testis An Immunohistochemical and Morphologic Study with a Review of the Literature

Intratubular germ cell neoplasia (ITGCN) and mature teratoma of the testis are uncommon findings in children. We report a case of a 3-year-old boy with both ITGCN and mature teratoma--a unique finding in our experience. Immunohistochemical markers, including placental alkaline phosphatase (PLAP), 43-9F, p53, and proliferating cell nuclear antigen (PCNA), as well as the periodic acid-Schiff (PAS) stain, were applied to the ITGCN. PLAP and 43-9F were not detected, whereas p53 and PCNA nuclear expression was detected in approximately 5% of atypical germ cells. Abundant clumped intracytoplasmic glycogen deposits were identified within atypical germ cells. Our findings indicate that both PCNA and p53, in addition to a PAS stain, may be useful markers in detecting malignant intratubular germ cells.

Testicular Intratubular Germ Cell Neoplasia in Children and Adolescents with Intersex

In a review of 102 cases with various intersex states, the frequency of intratubular germ cell neoplasia (IGCN) unclassified in testes of children and adolescents was 6%. It was seen in 2 of 87 cases in the prepubertal age group and 4 of 23 cases in the pubertal age group. The frequency of IGCN was 0 of 23 in androgen insensitivity syndrome (testicular feminization), 3 of 38 in gonadal dysgenesis, 1 of 12 in true hermaphroditism, 1 of 22 in male pseudohermaphroditism, and 1 of 7 in the group with multiple congenital anomalies and ambiguous genitalia. Five cases showed unilateral and one showed bilateral IGCN. Three pubertal cases had unilateral gonadoblastoma associated with IGCN. Invasive germ cell tumor was absent in all six cases. The atypical germ cells in all testes with IGCN showed immunoreactivity with placental alkaline phosphatase. Review of the literature revealed 30 prepubertal and pubertal cases with IGCN. The median age of the combined series of 36 cases with IGCN was 13 years (range 1 month to 19 years). Concomitant invasive tumor was present in 3 of 14 cases with gonadal dysgenesis and IGCN and 2 of 18 cases with androgen insensitivity and IGCN.