2009: Neoplasia of the reproductive tract of the male dog Neoplasia of the reproductive tract of the male dog 1 M. V. Root Kustritz 2 College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA 3 Abstract 4 A brief review of tumors of the male reproductive tract is provided. Diagnosis is 5 straightforward in most cases, with resolution of disease easily achieved. The exception 6 to the latter is prostatic neoplasia, a high morbidity, high mortality form of cancer to 7 which we may predispose dogs by castration. 8 Keywords: Neoplasia, penis, prostate, testes, transmissible venereal tumor 9 Introduction 10 Neoplasia of the male canine reproductive tract is uncommon and often easily 11 diagnosed. The most common reproductive tract tumor of male dogs worldwide is 12 testicular neoplasia, with transmissible venereal tumor also very common. The most 13 devastating cancer of the reproductive tract of male dogs is prostatic neoplasia. Less 14 common tumors include those of the soft tissues of the penis and prepuce, those of the os 15 penis, and those of the scrotal skin and mammary tissues. Excellent published reviews of 16 this topic exist.1,2 This manuscript will provide brief reviews of cancer biology and 17 updated information. 18 Testicular tumors 19 The three most common tumor types are seminomas, Leydig (interstitial) cell 20 tumors, and Sertoli cell tumors. In humans, testicular neoplasia is common in young men 21 and is aggressively malignant. In dogs, testicular neoplasia occurs in older individuals 22 93 and is malignant in 10% of cases at most. It is not uncommon for there to be more than 23 one tumor type in a given testes or between testes concurrently.3,4 24 Incidence of testicular neoplasia is higher in retained than in descended testes. 25 There is no research documenting increased risk of neoplasia in the descended testis of 26 unilateral cryptorchids.5 Controversy exists regarding whether or not the predisposition 27 to neoplasia in retained testes remains if the cryptorchid testis is surgically pulled down 28 and tacked into the scrotum. In human medicine, studies suggest increased incidence in 29 tumor incidence if orchiopexy is delayed until puberty or beyond.5,6 This may suggest 30 that medical therapies to induce testicular descent are beneficial in prepubertal dogs, both 31 by potentially decreasing tumor incidence and making castration of those dogs easier. 32 Dogs with testicular neoplasia may present with enlargement of one or both 33 testes. If neoplasia is unilateral, oftentimes there will be atrophy of the contralateral testis 34 due to increased intrascrotal temperature and possibly to hormone secretion by the 35 affected testis. Components of an associated paraneoplastic syndrome, most commonly 36 associated with estrogen secretion, include gynecomastia, attraction of male dogs, and 37 bilaterally symmetrical alopecia. Malignant tumors mestastasize locally and to the 38 regional lymph nodes and lungs, with occasional reports of hypertrophic 39 osteoarthropathy.7 A fair proportion of dogs (28.3% in one study) have inapparent 40 testicular neoplasia; these dogs may present for testicular atrophy, poor semen quality, or 41 infertility.3 42 Diagnosis is by inspection. For dogs with no overt change in testicular size or 43 consistency, testicular ultrasound is the preferred diagnostic technique. Fine-needle 44 aspirate (FNA) of the testes also may be used to identify abnormal cells. The dog is 45 94 sedated and the scrotal skin cleaned. A 20 ga needle is attached to a 12 cc or larger 46 syringe. The needle is introduced on or just lateral to the midline and redirected several 47 times, with suction at each location. Negative pressure is released and the needle 48 withdrawn. The sample is expelled onto a glass slide and submitted to a cytologist for 49 interpretation.8-10 50 Treatment is surgical. Bilateral castration is recommended. Caution during 51 surgery is recommended; there are reports of neoplastic tissue (n = 11 Sertoli cell tumors, 52 n = 1 Leydig cell tumor) arising in the spermatic cord, at the incision site, on the scrotal 53 skin, and in the inguinal canal, presumably due to transplantation of cells during 54 castration.11 In valuable breeding animals, one may consider removing only the affected 55 testis but the owners must be cautioned that spermatogenesis may be altered by 56 inapparent changes in the remaining testis. 57 In humans, incidence of testicular neoplasia is increasing. This same trend 58 appears to be true in veterinary medicine, with incidence of testicular tumors increased in 59 one study from that described in 1962.12 The primary theory explaining this in human 60 medicine is increase in exposure to environmental toxins. 61 Transmissible venereal tumor 62 Transmissible venereal tumor (TVT) is a cellular transplant containing an average 63 of 59 chromosomes, rather than a transformed canine cell, which would contain 78 64 chromosomes. Analysis of TVTs from five continents showed that all are genetically 65 similar, suggesting that all arose from a single mutation. That mutation is believed to 66 have arisen 250 to 2500 years ago in a wolf or east-Asian breed of dog.13 67 95 Incidence of TVT in one study was 5.4%; this incidence varies greatly by region.4 68 TVT is most common in young, sexually intact, free-roaming dogs, and so is primarily a 69 problem in sub-tropical and tropical areas of the world. 70 Most TVTs invade only locally and so usually are not considered malignant. The 71 tumor is a meaty and irregular, and is easily ulcerated. Lesions may be noted on the 72 mouth and nose; this is from transplantation of cells by licking of the genitalia. 73 Occasionally tumor will spread to regional lymph nodes and the internal organs.14 74 Metastasis is more common in very young animals and immunosuppressed animals.15 75 Diagnosis is by cytology. TVT is easily identified as round cells with abundant 76 cytoplasm and an eccentrically placed round to oval nucleus. 77 Chemotherapy with vincristine is the recommended treatment. Surgical debulking 78 may be required in some cases. Vincristine treatment has been demonstrated to cause 79 resolution of clinical signs with minimal side-effects within 4 treatments in most dogs, 80 and to decrease semen quality in breeding dogs for only up to 15 days after treatment is 81 completed.16,17 Treatment failure is more likely if tumors are large, the affected animal is 82 old or immunosuppressed, and if the treatment is performed during hot or rainy months.18 83 Prostatic neoplasia 84 The most common prostatic neoplasm reported is adenocarcinoma. It is 85 considered to have metastasized by the time of diagnosis in the majority of cases. It is a 86 disorder of older male dogs and may occur in either intact or castrated dogs. It is the only 87 prostatic disorder commonly seen in castrated dogs. Overall incidence of prostatic 88 neoplasia is reported as 0.4 to 0.7%.19,20 It is a high mortality disorder; in one survey of 89 96 72 affected dogs, 58 were euthanized at the time of diagnosis and mean survival for those 90 who survived more than one week from diagnosis was 30 days.21 91 In humans, prostatic neoplasia is hormone-dependent. That is not true in dogs. In 92 fact, castration, and subsequent removal of testosterone, appears to predispose dogs to 93 prostatic neoplasia, with increased risk of 2.8 to 4.3 times reported.22,23 Castrated dogs 94 tend to develop more poorly differentiated tumors than intact dogs, suggesting that 95 testosterone has a protective effect.24 Number of androgen receptors is decreased in the 96 prostates of dogs with neoplasia compared to dogs with normal prostates or benign 97 prostatic hypertrophy, again suggesting loss of a protective effect of testosterone.25 In 98 one survey of 56 affected dogs, time from castration to onset was variable and there was 99 no difference in mean age at time of diagnosis between intact and castrated dogs, 100 suggesting that castration does not favor tumor initiation but may favor tumor 101 progression.20 102 It has been shown in dogs that castration leads to an increase in number of 103 receptors for endothelin on the prostate; endothelin increases mitogenic responses and 104 uncontrolled cell growth.26 Endothelin also supports osteoblastic function and stimulates 105 bony growth at areas of metastasis from prostatic neoplasia in dogs.27 106 Dogs may present with signs of prostate disease, such as dripping of bloody fluid 107 from the penis unassociated with urination, hematuria, and passage of ribbon-shaped 108 stools. Commonly, dogs also present with stranguria and signs referable to sites of 109 metastasis including stiff gait or ataxia, coughing, and cachexia. 110 Because prognosis is grave, definitive diagnostics are required. Definitive 111 diagnosis requires collection of a sample directly from the prostate, either as FNA or 112 97 biopsy. Ultrasound guidance is recommended with either technique. For FNA, sedation 113 usually is not required. A 20 ga needle is attached to a 12 cc syringe. The needle is passed 114 into the prostatic parenchyma and negative pressure applied. Pressure is released and the 115 needle withdrawn. The sample is expelled onto a glass slide and submitted to a cytologist 116 for interpretation. For biopsy, sedation is required. Prepare the area over the prostate as 117 for sterile surgery and place a sterile sleeve over the ultrasound probe. Viewing the 118 prostate by ultrasound, trigger the biopsy instrument to see it pass within the prostatic 119 parenchyma. Withdraw the biopsy instrument and retrieve the sample; make sure you 120 have an adequate sample before reversing sedation. Samples should be submitted to a 121 pathologist for interpretation. A diagnostic sample is more commonly retrieved by biopsy 122 than by FNA. Side-effects include hematuria and hemospermia.28,29 In humans, seeding 123 of the abdomen with tumor cells and subsequent growth of transplanted cells is reported 124 to occur in 0.009% of cases after these techniques.30 This is less of a concern in dogs, 125 who rarely live long enough after diagnosis for significant secondary tumor development 126 to occur. 127 Treatment is palliative. Most dogs are treated with anti-inflammatory medications 128 (meloxicam, piroxicam) and antibiotics to control secondary infection. Prostatectomy 129 rarely is performed because it cannot cure disease and often causes urinary or fecal 130 incontinence. There are reports of transurethral resection of the prostate using 131 electrocautery, with or without associated radiation and chemotherapy,31 and subcapsular 132 prostatectomy using a laser.32 Some of the dogs in these studies showed a resolution of 133 clinical signs and had longer mean survival times than is commonly reported but other 134 dogs in those studies did not respond to treatment or died from complications of therapy. 135 98 That, coupled with the technical skill required to perform this work, makes them 136 unsuitable alternatives for most veterinarians and their patients. 137 Tumors of the penis, prepuce, scrotum, and mammary tissue 138 Tumors of the soft tissue of the penis and of the os penis are described in the 139 literature. Tumors of the soft tissue of the penis often are associated with preputial 140 extension and, along with tumors of the scrotum, are the common skin tumors seen 141 elsewhere including papillomas, squamous cell carcinoma, lymphosarcoma, and mast cell 142 tumors.33,34 Tumors of the os penis are less common and may be either benign or 143 malignant. Stranguria is a common presenting complaint with tumors of the os penis, 144 which may be confused with fracture of the os penis.34-38 Mammary neoplasia rarely is 145 reported in male dogs; one institution reported that male dogs at that institution were 62 146 times less likely to develop mammary neoplasia than female dogs in that population.39 147 Mammary tumors usually are benign and easily surgically removed. 148 References 149 1. Johnston SD, Root Kustritz MV, Olson PN: Canine and feline theriogenology. 150 Philadelphia: WB Saunders; 2001. 151 2. Ogilvie GK, Moore AS: Managing the veterinary cancer patient. Trenton NJ: 152 Veterinary Learning Systems; 1995. 153 3. Peters MAJ, De Rooij DG, Teerds KJ, et al: Spermatogenesis and testicular 154 tumors in ageing dogs. J Reprod Fertil 2000;120:443-452. 155 4. Ortega-Pacheco A, Rodriguez-Buenfil JC, Segura-Correa JC, et al: Pathological 156 conditions of the reproductive organs of male stray dogs in the tropics: 157 99 prevalence, risk factors, morphological findings and testosterone concentrations. 158 Reprod Dom Anim 2006;41:429-437. 159 5. Wood HM, Elder JS: Cryptorchidism and testicular cancer: separating fact from 160 fiction. J Urol 2009;181:452-461. 161 6. Walsh TJ, Dall’Era MA, Croughan MS, et al: Orchiopexy for cryptorchidism 162 may be associated with lower risk of testicular cancer. J Urol 2007;178:1440-163 1446. 164 7. Barrand KR, Scudamore CL: Canine hypertrophic osteoarthropathy associated 165 with a malignant Sertoli cell tumor. J Sm Anim Pract 2001;42:143-145. 166 8. Dahlbom M, Makinen A, Suominen J: Testicular fine needle aspiration cytology 167 as a diagnostic tool in dog infertility. J Sm Anim Pract 1997;38:506-512. 168 9. Romagnoli S, Bonaccini P, Stelletta C, et al: Clinical use of testicular fine needle 169 aspiration (FNA) cytology in oligozoospermic and azoospermic dogs. 170 Proceedings of the International Symposium on Canine and Feline Reproduction, 171 Vienna, Austria, 2008. 172 10. Masserdotti C, Bonfanti U, De Lorenzi D, et al: Cytologic features of testicular 173 tumours in dogs. J Vet Med A 2005;52:339-346. 174 11. Doxsee AL, Yager JA, Best SJ, et al: Extratesticular interstitial and Sertoli cell 175 tumors in previously neutered dogs and cats: a report of 17 cases. Can Vet J 176 2006;47:763-766. 177 12. Grieco V, Riccardi E, Greppi GF, et al: Canine testicular tumours: a study on 232 178 dogs. J Comp Path 2008;138:86-89. 179 100 13. Murgia C, Pritchard JK, Kim SY, et al: Clonal origin and evolution of a 180 transmissible cancer. Cell 2006;126:477-487. 181 14. Park M-S, Kim Y, Kang M-S, et al: Disseminated transmissible venereal tumor 182 in a dog. J Vet Diagn Invest 2006;18:130-133. 183 15. Mukaratirwa S, Gruys E: Canine transmissible venereal tumor: cytogenetic 184 origin, immunophenotype, and immunobiology. A review. Vet Q 2003;25:101-185 111. 186 16. Saratsis PH, Ypsilantis P, Tselkas K. Semen quality during vincristine treatment 187 in dogs with transmissible venereal tumor. Theriogenology 2000;53:1185-1192. 188 17. Nak D, Nak Y, Cangul IT, et al:. A clinicopathological study on the effect of 189 vincristine on transmissible venereal tumour in dogs. J Vet Med A 2005;52:366-190 370. 191 18. Scarpelli KC, Valladao ML, Metze K: Predictive factors for the regression of 192 canine transmissible venereal tumor during vincristine therapy. Vet J, In Press, 193 Corrected Proof, Available online 23 December 2008. 194 19. Merlo DF, Rossi L, Pellegrino C, et al: Cancer incidence in pet dogs: findings of 195 the animal tumor registry of Genoa, Italy. J Vet Intern Med 2008;22:976-984 196 20. Teske E, Naan EC, Van Dijk EM, et al: Canine prostate carcinoma: 197 epidemiological evidence of an increased risk in castrated dogs. Molec Cell 198 Endocrinol 2002;197:251-255. 199 21. Mann FA, Barrett RJ, Henderson RA: Use of a retained urethral catheter in three 200 dogs with prostatic neoplasia. Vet Surg 1992;21:342-347. 201 101 22. Sorenmo KU, Goldschmidt M, Shofer F, et al: Immunohistochemical 202 characterization of canine prostatic carcinoma and correlation with castration 203 status and castration time. Vet Comp Oncol 2003;1:48-56. 204 23. Bryan JN, Keeler MR, Henry CJ, et al: A population study of neutering status as 205 a risk factor for canine prostate cancer. Prostate 2007;67:1174-1181. 206 24. Lai C-L, Van den Ham R, Van Leenders G, et al. Histopathological and 207 immunohistochemical characterization of canine prostate cancer. Prostate 208 2008;68:477-488. 209 25. Gallardo F, Mogas T, Baro T, et al: Expression of androgen, oestrogen alpha and 210 beta, and progesterone receptors in the canine prostate: differences between 211 normal, inflamed, hyperplastic and neoplastic glands. J Comp Path 2007;136:1-8. 212 26. Padley RJ, Dixon DB, Wu-Wong JR: Effect of castration on endothelin receptors. 213 Clin Sci 2002;103(Suppl 48):442S-445S. 214 27. LeRoy BE, Sellers RS, Rosol TJ: Canine prostate stimulates osteoblast function 215 using the endothelin receptors. Prostate 2004;59:148-156. 216 28. Root Kustritz MV: Collection of tissue and culture samples from the canine 217 reproductive tract. Theriogenology 2006;66:567-574. 218 29. Powe JR, Canfield PJ, Martin PA: Evaluation of the cytologic diagnosis of 219 canine prostatic disorders. Vet Clin Path 2004;33:150-154. 220 30. Nyland TG, Wallack ST, Wisner ER: Needle-tract implantation following 221 ultrasound-guided fine-needle aspiration biopsy of transitional cell carcinoma of 222 the bladder, urethra and prostate. Vet Radiol Ultrasound 2002;43:50-53. 223 102 31. Liptak JM, Brutscher SP, Monnet E, et al: Transurethral resection in the 224 management of urethral and prostatic neoplasia in 6 dogs. Vet Surg 2004;33:506-225 516. 226 32. L’Eplattenier HF, Van Nimwegen SA, Van Sluijs FJ, et al: Partial prostatectomy 227 using Nd:YAG laser for management of canine prostate carcinoma. Vet Surg 228 2006;35:406-411. 229 33. Cerundolo R, Rest J, Persechino A: What is your diagnosis? Cutaneous 230 lymphosarcoma of the scrotum. J Sm Anim Pract 2002;43:1-2. 231 34. Root Kustritz MV, Fick JL. Theriogenology question of the month: benign 232 mesenchyoma of the os penis. J Am Vet Med Assoc 2007;230:197-198. 233 35. Mirkovic TK, Shmon CL, Allen AL: Urinary obstruction secondary to an 234 ossifying fibroma of the os penis in a dog. J Am Anim Hosp Assoc 2004;40:152-235 156. 236 36. Michels GM, Knapp DW, David M, et al: Penile prolapse and urethral obstruction 237 secondary to lymphosarcoma of the penis in a dog. J Am Anim Hosp Assoc 238 2001;37:474-477. 239 37. Bleier T, Lewitschek HP, Reinacher M: Canine osteosarcoma of the penile bone. 240 J Vet Med A 2003;50:397-398. 241 38. Patnaik AK, Matthiesen DT, Zawie DA: Two cases of canine penile 242 neoplasms: Squamous cell carcinoma and mesenchymal chondrosarcoma. J Am 243 Anim Hosp Assoc 1988;24:403-406. 244 39. Saba CF, Rogert KS, Newman SJ, et al: Mammary gland tumors in male dogs. J 245 Vet Intern Med 2007;21:1056-1059. 246 103 << /ASCII85EncodePages false /AllowTransparency false /AutoPositionEPSFiles true /AutoRotatePages /All /Binding /Left /CalGrayProfile (Dot Gain 20%) /CalRGBProfile (sRGB IEC61966-2.1) /CalCMYKProfile (U.S. Web Coated \050SWOP\051 v2) /sRGBProfile (sRGB IEC61966-2.1) /CannotEmbedFontPolicy /Warning /CompatibilityLevel 1.4 /CompressObjects /Tags /CompressPages false /ConvertImagesToIndexed true /PassThroughJPEGImages true /CreateJobTicket false /DefaultRenderingIntent /Default /DetectBlends true /DetectCurves 0.0000 /ColorConversionStrategy /CMYK /DoThumbnails false /EmbedAllFonts true /EmbedOpenType false /ParseICCProfilesInComments true /EmbedJobOptions true /DSCReportingLevel 0 /EmitDSCWarnings false /EndPage -1 /ImageMemory 1048576 /LockDistillerParams false /MaxSubsetPct 100 /Optimize true /OPM 1 /ParseDSCComments true /ParseDSCCommentsForDocInfo true /PreserveCopyPage true /PreserveDICMYKValues true /PreserveEPSInfo true /PreserveFlatness false /PreserveHalftoneInfo false /PreserveOPIComments false /PreserveOverprintSettings true /StartPage 1 /SubsetFonts true /TransferFunctionInfo /Apply /UCRandBGInfo /Preserve /UsePrologue false /ColorSettingsFile () /AlwaysEmbed [ true ] /NeverEmbed [ true ] /AntiAliasColorImages false /CropColorImages false /ColorImageMinResolution 300 /ColorImageMinResolutionPolicy /OK /DownsampleColorImages false /ColorImageDownsampleType /Average /ColorImageResolution 300 /ColorImageDepth -1 /ColorImageMinDownsampleDepth 1 /ColorImageDownsampleThreshold 1.50000 /EncodeColorImages false /ColorImageFilter /DCTEncode /AutoFilterColorImages true /ColorImageAutoFilterStrategy /JPEG /ColorACSImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /ColorImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000ColorACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000ColorImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasGrayImages false /CropGrayImages false /GrayImageMinResolution 300 /GrayImageMinResolutionPolicy /OK /DownsampleGrayImages false /GrayImageDownsampleType /Average /GrayImageResolution 300 /GrayImageDepth -1 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages false /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict << /QFactor 0.76 /HSamples [2 1 1 2] /VSamples [2 1 1 2] >> /GrayImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000GrayACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000GrayImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasMonoImages false /CropMonoImages false /MonoImageMinResolution 1200 /MonoImageMinResolutionPolicy /OK /DownsampleMonoImages false /MonoImageDownsampleType /Average /MonoImageResolution 300 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages false /MonoImageFilter /FlateEncode /MonoImageDict << /K -1 >> /AllowPSXObjects false /CheckCompliance [ /None ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile () /PDFXOutputConditionIdentifier () /PDFXOutputCondition () /PDFXRegistryName () /PDFXTrapped /False /CreateJDFFile false /Description << /ENU ([Based on 'No Compression'] [Based on 'No Compression wbleeed'] [Based on '[High Quality Print]'] Use these settings to create Adobe PDF documents for quality printing on desktop printers and proofers. 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