Article In contrast to CSEM, SSEM are c-KIT negative and have benign behavior, which is in accordance with their origin from differentiated germ cells, mostly spermatocytes [15],[20]-[25]. Nochomovitz LE, Rosai J: Current concepts on the histogenesis, pathology, and immunochemistry of germ cell tumors of the testis. Cytokeratin was expressed in 35% of testicular tumors from necropsy samples and in 33% of biopsied testicular tumors (Table2). 2008, 138: 86-89. Am J Clin Pathol. According to research conducted by Gamlem et al., testicular tumors represented 7% of all biopsied tumors in dogs from 1990 to 1998 [5]. c-KIT is used in human patients for differentiation of c-KIT positive CSEM from c-KIT negative SSEM [11],[12]. These tumors typically are locally a problem, meaning they have a low rate of spread. The higher incidence of SEM and SCT in the biopsy group probably resulted from the obvious clinical expression of these tumor types. About 40% of neoplastic testicles have more than one tumor [7]. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Leroy X, Augusto D, Leteurtre E, Gosselin B: CD30 and CD117 (c-kit) used in combination are useful for distinguishing embryonal carcinoma from seminoma. Google Scholar. Samples were embedded in paraffin wax and 5-m sections were stained with hematoxylin-eosin (HE) for histopathological examination. Below are the links to the authors original submitted files for images. Grieco V, Riccardi E, Veronesi MC, Giudice C, Finazzi M: Evidence of testicular dysgenesis syndrome in the dog. In all of them SEM showed no immunoreactivity to cytokeratin which is expressed mainly in SCT and mixed SCT, and rarely in LCT [14],[19]. For immunohistochemical analyses, monoclonal mouse anti-human PLAP, anti-human CD30, anti-human cytokeratin AE1/AE3, and polyclonal rabbit anti-human c-KIT antibodies were used. Nine mixed tumors represented 16% of all biopsied tumors with the following incidence: 4 (7%) mixed SCT/SEM, 4 (7%) mixed LCT/SEM, and 1 (2%) mixed LCT/SCT. Pieces of the testicular tumor are submitted to a veterinary laboratory where they examined by a veterinary pathologist under the microscope. World Health Organisation: Histological classification of tumors of the genital system of domestic animals. 1996, 27: 1166-1171. Biol Reprod. J Vet Med Sci. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Gaskel TL, Esnal A, Robinson LL, Anderson RA, Saunders PT: Immunohistochemical profiling of germ cells within the human fetal testis: identification of three subpopulations. Withrow & MacEwen's Small Animal Clinical Oncology. CD30 expression was low in both groups. The low co-expression of c-KIT and PLAP in SEM could result from the different cellular origin of seminomas, because c-KIT is expressed in both spermatogonia and prespermatogonia whereas PLAP is expressed only in prespermatogonia, while in people both cells give rise to CSEM [10],[11],[17],[20],[27],[29],[31]. Article Immunohistochemistry was not conducted on highly autolytic samples. Dogs in both groups were of various pure and mixed breeds. AGK and AB performed histopathological analysis and necropsies. Most seem to be caused by a complex mix of risk factors, some environmental and some genetic or hereditary. Pathol Annu. CSEM are malignant type of SEM because they originate from undifferentiated c-KIT positive transformed primordial germ cells and gonocytes (prespermatogonia and spermatogonia). Statistical analysis was performed using the MedCalc program 10.2.0.0 (MedCalc Software bvba, Mariakerke, Belgium). On the basis of these results, canine SEM can be divided in two groups: the less prevalent CSEM and the more prevalent SSEM. Histology and c-KIT and PLAP expression indicate that IGCNU exists in dogs. 1999 Accessed 4 December 2009., [http://www.afip.org/consultation/vetpath/who/whogenet.html]. Investigations by Grieco et al. BA and B participated in the design of the study and histopathological analysis and necropsies. Embryonal carcinomas were not diagnosed. We are committed to caring for your pet while maintaining the highest level of safety for our Associates and pet owners. Expression of c-KIT was most common in SEM and seminomatous components of mixed tumors. In cases of cryptorchid pets, abdominal ultrasound or more advanced imaging (such as a CT scan) may be recommended to determine if any lymph nodes or organs are affected. J Comp Pathol. Ndtvedt A, Gamlem H, Gunnes G, Grotmol T, Inderb A, Moe L: Breed differences in the proportional morbidity of testicular tumours and distribution of histopathologic types in a population-based canine cancer registry. Even though IGCNU is not classified as a neoplastic lesion in the WHO classification of canine tumors, we did detect some morphological changes consistent with IGCNU in both groups of dogs, findings similar to those of Grieco et al. Int J Androl. Semin Diagn Pathol. For groups with abnormal distribution of data, KruskalWallis analysis of variance was used. The aim of this study was to verify that CSEM/SSEM classification is valid in dogs and confirm the existence of canine IGCNU. 2009:151-172. statement and In mixed SCT from both groups, cytokeratin positivity was found predominantly in the SCT components. Primary antibody was replaced with phosphate-buffered saline for the negative control. Within these groups are the three most common canine testicular tumors, which have relatively similar incidence varying by study. The images or other third party material in this article are included in the articles Creative Commons licence, unless indicated otherwise in a credit line to the material. If the tumor has metastasized (spread) to the lymph nodes near the urinary system or the prostate gland, signs may include difficulty urinating or defecating. The high tumor incidence at necropsy can be attributed to older age. In humans, IGCNU is similar to CSEM, and according to some reports canine CSEM is derived from gonocytes (prespermatogonia) and spermatogonia. Looijenga LH, Hersmus R, Gillis AJ, Pfundt R, Stoop HJ, Van Gurp RJ, Veltman J, Beverloo HB, Van Drunen E, Van Kessel AG, Pera RR, Schneider DT, Summersgill B, Shipley J, Mcintyre A, Van Der Spek P, Schoenmakers E, Oosterhuis JW: Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene. The lower expression of PLAP compared with c-KIT in SEM is consistent with a study published by Yu et al. Basic statistical analysis of results was conducted using usual methods of descriptive statistics with assessment of arithmetic mean, minimum and maximum values, geometric mean, median, and standard deviation. Immunohistochemical analyses were also conducted on one sample from all histologically normal testicles. 2002, 50: 283-285. Mod Pathol. This may include a rectal examination, bloodwork, urinalysis, and chest X-rays. All samples were also analyzed for the presence of IGCNU. 2006, 66 (1): 290-302. Peters MA, De Rooij DG, Teerds KJ, Van Der Gaag I, Van Sluijs FJ: Spermatogenesis and testicular tumours in ageing dogs. Learn more about our COVID-19 response and guidelines. Manage cookies/Do not sell my data we use in the preference centre. Our histopathological and immunohistochemical analyses (c-KIT and PLAP expression) indicate that, just as in human classification, some canine SEM can be classified as CSEM. If your pet is experiencing any signs of illness, an abdominal ultrasound may be recommended to search for an abnormal mass (tumor) in the abdomen. We would like to thank Doc. Small Animal Oncology, an introduction. PubMed In another study, Vescalari et al. Although IGCNU is not classified as neoplasia in the WHO classification of dog tumors, lesions morphologically similar to IGCNU (Figure3) were found as sole lesions in 6 (3%) testicles of necropsied dogs and in 2 (3%) biopsied testicles. Human SEM are classified as classical (CSEM) or spermatocytic (SSEM). The three most common types of testicular tumors develop from germ cells (cells that make sperm), Leydig cells (cells that produce testosterone), and Sertoli cells (cells that help in the development of sperm): Other types of tumors may develop from other cells within the testicles, but these types are rare. Low expression of CD30 in all tumors showed that embryonal carcinoma, which is mostly CD30-positive in people [37],[38], did not appear in either group and is a very rare testicular neoplasm in dogs. The high incidence of tumors in necropsied dogs cited in the literature [3],[4] is at least partially due to the relatively advanced age of dogs at the time of necropsy, because older age is a predisposing factor for testicular tumors [7],[34]. Cytokeratin helps differentiate stromal tumors, especially SCT, from germ cell tumors. Expression of PLAP was most common in the necropsy group IGCNU (2/6, 33%) (Figure5), biopsied intratubular SEM (1/3, 33%), biopsied teratoma (1/2, 50%), and in some mixed tumors from both groups (25100%). Values of p <0.05 were considered statistically significant. In both groups, SEM and the seminomatous components of mixed tumors were most often c-KIT positive. Rajpert-De Meytes E, Bartkova J, Samson M, Hoi-Hansen CE, Frydelund-Larsen L, Bartek J, Skakkanaek NE: The emerging phenotype of the testicular carcinoma in situ germ cell. Of testicles with neoplastic changes (including IGCNU), 16% in the necropsy group and 26% in the biopsy group expressed c-KIT (Table2). In necropsy samples, the expression of cytokeratin was as follows: 2 (100%) of 2 mixed SCT/diffuse SEM, 5 (71%) of 7 SCT, 2 (66%) of 3 mixed LCT/intratubular SEM, 3 (60%) of 5 mixed LCT/SCT, 1 (50%) of 2 mixed LCT/diffuse SEM, 2 (28%) of 7 intratubular SEM, 1 (25%) of 4 diffuse SEM, 1 (16%) of 6 IGCNU, and 3 (15%) of 19 LCT. In veterinary medicine, there are only few reports of cytokeratin expression in testicular tumors. North S, Banks T, Straw R: Tumors of the urogenital tract. The median age of dogs with tumors at necropsy was 10.16years; median age at positive biopsy was 10.24years. 2004, 71: 2012-2021. In other tumor types, expression was lower than 5%, or absent. The sections were counterstained with hematoxylin and mounted. Nat Genet. Acta Vet Scand. Hyperestrogenism can cause the signs of feminization. Assays were performed on 4-m sections of paraffin-embedded tissue samples. CAS Cytokeratin was mainly expressed in SCT. Palpation (feeling with the fingers) of the scrotum may reveal a nodular enlargement of the testicle, unevenly sized testicles, or generalized swelling of the scrotum. The dogs ages at the time of the surgery were in the range of 215 years (mean, 10.24years; one was of unknown age). [19] cytokeratin is not expressed in normal Sertoli cells, so this marker can be useful for differentiation of SCT, not only from other testicle tumors but also from neoplastically unaltered Sertoli cells. J Histochem Cytochem. Although the reaction was not positive in all samples, this is probably because of the small size of IGCNU, which made it difficult to prepare additional histological slides with the same changes for different staining methods. APMIS. One dated study found an incidence of 16% [3], while a more recent paper reported an incidence as high as 27% [4]. Vet Comp Oncol. MIX SCT/LCT; cytokeratin negative Leydig cell tumor (left side of picture) and cytokeratin positive Sertoli cell tumor (right side of picture), testicle, dog, cytokeratin, 20. Percentages of cytokeratin-positive cells were in the range of 512% in germ cell neoplasia from both groups. Twelve (24%) mixed tumors were found, with an incidence as follows: 5 (10%) mixed LCT/SCT, 5 (10%) mixed LCT/SEM, and 2 (4%) mixed SCT/SEM. IGCNU was found in 3% of testicles at necropsy and in 3% of biopsy samples. Terms and Conditions, A testicular tumor is a tumor that develops from a disordered uncontrolled growth of cells within the testicles. 2009, 22: 1066-1074. J Reprod Fertil. PAS-positive reactions (Figure3) were obtained in 2 (33%) of the 6 from the necropsy group and in 1 (50%) of the 2 from the biopsy group. Statistically significant differences of data between analyzed groups with normal distribution were evaluated by the one-way analysis of variance (ANOVA). The sections were dewaxed in xylene and rehydrated through a series of graded alcohol solutions. The ages of necropsied dogs with testicular tumors were in the range of 118 years (mean, 10.16years; one was of unknown age). 2008, 70: 53-60. [15] and Thorvaldsen [16], found that canine SEM are predominantly spermatocytic, suggesting that there are no (or extremely rare) cases of canine CSEM. Mixed-breed dogs, golden retrievers, German shepherds, Pekingese, Yorkshire terriers, and Labrador retrievers were overrepresented in the biopsy group. [6] found that male genital tumors represented 13% of all biopsied tumors of male dogs from 2005 to 2008. Based on these findings, only those tumors were characterized as malignant and the rest from both groups were characterized as benign. Theriogenology. BMC Vet Res. In humans c-KIT expression is highly correlated to biological behavior. Cheville JC, Rao S, Iczkowski KA, Lohse CM, Pankratz VS: Cytokeratin expression in seminoma of the human testis. Skakkebaek NE, Berthelsen JG, Giwercman A, Mller J: Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. 4, Maclachlan NJ, Kennedy PC: Tumors of the Genital systems. 2010, 143: 239-247. 1999, 5: 535-545. Google Scholar. Suppl, 2008: 5-18. The higher percentage of c-KIT-positive SEM in the biopsy group can be explained by the higher incidence of diffuse SEM in that group because of its more obvious clinical symptoms (testicular enlargement) in contrast to intratubular SEM, which generally does not cause enlargement. Existence of canine IGCNU the links to the authors original submitted files for images these groups are the three common! In germ cell tumors below are the three most common canine testicular tumors, which have relatively incidence. Plap compared with c-KIT in SEM and the rest from both groups testicular syndrome! 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testicular cancer in golden retrievers