Pathology of the Equine Penis and Prepuce

by Rob Foster

OVC Pathobiology

University of Guelph

Table of Contents

Disease of the penis and internal sheath of the prepuce

Disease of the external sheath of the prepuce

 


One of the conundrums of reviewing diseases from the perspective of a surgical pathologist is that the prevalence of diseases as represented by the submission of biopsies, is very different from the prevalence seen by or theriogenologists (who are also clinicians!). The bias here will be toward what you will see as a pathologist, but many diseases simply are not biopsied. One of the most common diseases is nonspecific posthitis of geldings, yet I have never seen a biopsy of this condition. The listing of diseases is done with the view to the perceived clinical prevalence!

Functional abnormalities

Functional abnormalities of the penis are clinical problems, so the only time a pathologist becomes involved is to exclude causes, or to confirm the presence of some underlying problem. A pathologist should know the terminology so that they can help the clinician should the occasion arise.

Phimosis is the inability to extrude the penis. It is the opposite of paraphimosis, which is the inability to retract the penis. Persistent erection, which can lead to paraphimosis, is priapism

Phimosis

Paraphimosis

Paraphimosis, or inability to retract the penis, is a particular problem in the stallion. It is commonly called penile prolapse, paralysis or (incorrectly) priapism.

Administration of phenothiazine tranquilizers was a common cause but once veterinarians were aware of this complication, other causes such as trauma, are more likely.

Severely debilitated stallions or horse suffering from local neurologic disorders will develop this too. Metastatic melanoma and squamous cell carcinoma will lead to this if the weight is excessive or there are local neuromuscular dysfunction.

(JAVMA 211 (5) 587 J Equine Sci 8: 101-107

Priapism

Priapism has several definitions. These include persistent erection of the penis, an erection lasting longer than 4 hours without sexual stimulation, or continuous, usually nonsexual erection of the penis, especially due to disease. Persistently erect penises become traumatised, dry, or undergo necrosis. Little is reported about the pathogenesis in dogs. In humans, there is a nonischemic form due to increased arterial flow, and an ischemic form with reduced venous outflow.

Physiochemical injury (including trauma) to the penis and prepuce.

Erosion and ulceration

Foreign bodies

Trauma

Disturbances of Growth

Neoplasia

Valentine (2006) published the results of a survey of cutaneous neoplasms and reported multiple cases of squamous cell carcinoma of the penis and prepuce.

van den Top et al (2008) reported on 114 cases and 97 cases were examined histologically. 77 were squamous cell carcinomas, 6 were melanomas, 1 was an adenocarcinoma, 1 was a fibrosarcoma, one was a basal cell carcinoma and one was a neurofibroma.

Rizk et al (2013) reported on the surgical treatment of stallions with penile or preputial neoplasia and found 15 squamous cell carcinomas, 4 sarcoids, a fibrosarcoma and a melanoma.

 

Valentine BA. Survey of equine cutaneous neoplasia in the Pacific Northwest. J Vet Diagn Invest. 2006 Jan;18(1):123-126.

Rizk A, Mosbah E, Karrouf G, Abou Alsoud M. Surgical Management of Penile and Preputial Neoplasms in Equine with Special Reference to Partial Phallectomy. J Vet Med. 2013; 2013 article 891413.

van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008; 40: 528-532.

Epithelial neoplasia

 

Adenocarinoma

van den Top et al (2008) reported finding one adenocarcinoma of the penis.

van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008; 40: 528-532.

Basal cell carcinoma

van den Top et al (2008) reported finding one basal cell carcinoma of the penis.

van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008; 40: 528-532.

Squamous Papilloma and plaque

Squamous cell carcinoma

Squamous cell carcinoma is a very important neoplasm of the penis of the horse. It occurs with increasing age and is causally linked with the Dyoiotapapillomavirus 1 (Equus caballus papillomavirus-2 [EcPV2]) because viral DNA is found in the cells of squamous cell carcinoma. No evidence of the virus was found in adjacent tissue, equine ocular SCC, or nasal carcinomas. None was found in most smegma samples obtained from tumour-free horses. In a second study, 9 of 20 horses with penile SCC had EcPV 2 DNA sequences and 1 of 20 with non SCC penile disease has the sequences.

In the study by van den Top et al (2008) of 97 cases where confirmatory histology was done, there were 77 SCC. These were in the head of the penis. 5 of 28 had metastasis to the superficial inguinal lymph node.

Newkirk et al (2014) found EcPV2 in the penile SCC of 10 of 22 horses. No evidence of EcPV-2 was seen in periocular SCC.Van den Top et al (2015) found that horses with poorly differentiated tumors did much worse than those with well differentiated squamous cell carcinoma. They found that 89% of horses with SCC had EcPV-2 whereas only 1.5% had EcPV-3.

Zhu et al (2015) found that 6 of 13 SCC had the EcPV2 E6/E7 proteins that are the oncogenic proteins. 3 of these 6 were metastatic. They found 7 SCC without E6/E7 protein and these had solar damage (dermal elastosis and hyalinisation of vessels).

Sykora and Brandt (2017) reviewed the evidence of EcPV2 and squamous cell carcinoma in horses. Most of the literature refers to the the disease in males.

Sykora et al (2017) used PCR to identify EcPV2 in papillomas and smegma - much of the latter contain virions.


Although exophytic masses do occur, the usual growth habit is infiltrative. These carcinomas induce abundant fibrous tissue, which results in an enlarged firm penis with focal ulcers. Microscopically, the neoplasm is well differentiated with the classic appearance of invasive nests, cords, and nodules of neoplastic epithelium with differentiation toward the stratum spinosum, often with well-developed keratin pearls or keratin squames mixed with neutrophils. The neoplastic cells are surrounded by fibrous tissue, as well as lymphocytes and plasma cells.

Metastasis is to the superficial inguinal (scrotal), deep inguinal, and medial iliac lymph nodes. The prepuce often becomes edematous because of lymphatic obstruction, and the preputial cavity becomes distended by retained smegma, inflammatory debris, and urine. Systemic metastases are reported occasionally (Nelson et al 2015).

Cramer SD, Breshears MA, and Qualls HJ. 2011 Pathology in Practice Journal of the American Veterinary Medical Association 2011, 238: 581-583.

Knight CG, Munday JS, Peters J, Dunowska M. Equine penile squamous cell carcinomas are associated with the presence of equine papillomavirus type 2 DNA sequences. Vet Pathol. 2011; 48: 1190-1194.

Lange CE, Tobler K, Lehner A, Grest P, Welle MM, Schwarzwald CC, Favrot C. (2013) EcPV2 DNA in Equine Papillomas and In Situ and Invasive Squamous Cell Carcinomas Supports Papillomavirus Etiology. Vet Pathol 2013; 50: 686-692

Nelson BB, Edmondson EF;, Sonis JM, Frank CB, Valdes-Martnez A, Leise BS. Multiple skeletal metastases from a penile squamous cell carcinoma in a horse Equ Vet Educ 2015; 27: 119-123

Newkirk KM, Hendrix DV, Anis EA, Rohrbach BW, Ehrhart EJ, Lyons JA, Kania SA. Detection of papillomavirus in equine periocular and penile squamous cell carcinoma. J Vet Diagn Invest 2014;26: 131-135

Scase T, Brandt S, Kainzbauer C, Sykora S, Bijmholt S, Hughes K, Sharpe S, Foote A. (2010) Equus caballus papillomavirus-2 (EcPV-2): An infectious cause for equine genital cancer? Equine Vet J 2010; 42: 738-745

Sykora S, Brandt S. Papillomavirus infection and squamous cell carcinoma in horses. The Vet J. 2017; 223: 48-54.

Sykora S, Jindra C, Hofer M, Steinborn R, Brandt S. Equine papillomavirus type 2: An equine equivalent to human papillomavirus 16?  The Vet J 2017; 225: 3-8

Taylor S and Haldorson G (2013) A review of equine mucocutaneous squamous cell carcinoma. Equine vet. Educ (2013) 25 (7): 374-378

van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008; 40: 528-532.

Van den Top JGB, Ensink JM, Barneveld A, van Weeren PR. (2011) Penile and preputial squamous cell carcinoma in the horse and proposal of a classification system. Equine vet. Educ. (2011) 23:(12) 636-64

van den Top JG, Harkema L, Lange C, Ensink JM, van de Lest CH, Barneveld A, van Weeren PR, Gröne A, Martens A. Expression of p53, Ki67, EcPV2- and EcPV3 DNA, and viral genes in relation to metastasis and outcome in equine penile and preputial squamous cell carcinoma. Equine Vet J 2015; 47: 188-195.

Zhu KW, Affolter VK, Gaynor AM, Dela Cruz FN Jr, Pesavento PA. Equine Genital Squamous Cell Carcinoma: In Situ Hybridization Identifies a Distinct Subset Containing Equus caballus Papillomavirus 2. Vet Pathol. 2015; 52(6): 1067-1072.

 

Mesenchymal neoplasms

Fibroma

De Meyer et al (2017) reported on a gelding with a proliferative fibrous lesion of the prepuce that they called a fibroma. It behaviour was of an infiltrative tumour such as desmoid or aggressive fibromatosis.


De Meyer A, Vandenabeele S, Ververs C, Martens A, Roels K, De Lange V, Hoogewijs M, De Schauwer C, Govaere J. Preputial fibroma in a gelding. Equine Vet Education 2016; 29: 7-9.

Fibropapilloma

Horses can develop benign fibropapilloma which is distinct from sarcoid or squamous cell carcinoma. It is a polypoid lesion just like bovine papilloma. It can be single or multiple. EcPV-2 was identified in a case of multiple papillomas.

 

Gardiner DW, Teifke JP, Podell BK, Kamstock DA (2008) Fibropapilloma of the glans penis in a horse. J Vet Diagn Invest 2008 20: 816-819.

Knight CG, Munday JS, Rosa1 BV, Kiupel M (2011) Persistent, widespread papilloma formation on the penis of a horse: a novel presentation of equine papillomavirus type 2 infection. Veterinary Dermatology. 2011, 22: 570–574.


Fibrosarcoma

van den Top et al (2008) reported finding one fibrosarcoma of the penis.

van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008; 40: 528-532.

Haemangiosarcoma

Byrne et al (2016) reported on a stallion that had a haemangiosarcoma of the urethral process. Surgical excision was curative.

Byrne DP, Woolford L, Booth TM. Penile haemangiosarcoma in a breeding stallion. Equine Veterinary Education 2016; 28: 304-309

 

Lymphangioma

Gomes et al (2023) reported a single case of lymphangioma. Unfortunately there was insufficient description to confirm this as a lymphangioma rather than lymphangiosarcoma.

 

Gomes JE, Canadas-Sousa A, Guimarães T, Cunha R, Dias-Pereira P. Preputial lymphangioma in a stallion: First report. Reprod Domest Anim. 2023; 58: 1161-1163.

Malignant nerve sheath tumor (Neurofibromasarcoma?)

van den Top et al (2008) reported finding one neurofibromasarcoma of the penis.

van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008; 40: 528-532.

Round cell tumors

Lymphoma

Doyle et al (2013) described the treatment of a gelding with cutaneous lymphoma that involved the penis.

 

 

Doyle AJ, MacDonald VS, Bourque A. Use of lomustine (CCNU) in a case of cutaneous equine lymphoma. Can Vet J. 2013; 54: 1137-1141.

Other tumors

Melanoma

 

van den Top et al (2008) reported finding 6 melanomas of the penis. One was metastatic to the lymph node.

van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008; 40: 528-532.

 

Polyps and tags

Erectile dysfunction, failure of erection of the penis, is rare. Erection requires central nervous system control, local nervous control with contraction of the ischiocavernosus muscles and vasoconstriction of veins. This allows arterial input to the erectile tissue of the cavernosum and spongiosum but occludes venous drainage. Vascular defects of the penis that cause failure of erection are studied in the stallion and boar, but their precise diagnosis or requires injection of contrast material and radiography, or injection of plastic into vessels to form casts. Vascular shunts from the cavernosum to the spongiosum of the penis or to peripenile vasculature prevent effective erection. Congenital shunts from the cavernosum to neighboring veins in boars can be inherited. Immunohistochemical studies of impotence in the boar provided evidence that defective innervation contributes, with depletion of vasointestinal polypeptide (VIP) reactivity in penile nerves.

Penetrating injuries and traumatic fistulas of the erectile tissue and the urethra or external tissues leads to hemorrhage that can be life threatening. Rupture of the cavernosum outside an intact tunic (tunica albuginea) of the penis is more frequent; trauma is the likely cause. Other vascular lesions include varicosities of preputial veins in stallions that may lead to thrombosis, edema, and inflammation. In dogs, trauma to the cavernosum or root of the penis may occur during attempted copulation and results in hindquarter pain and/or lameness, dysuria, and >perineal edema but no obvious hematomas. Extensive thrombosis of the corpus cavernosum penis occurs in stallions, dogs and cats with priapism, and it was unclear whether the thrombi were the cause or result of pain and persistent erection. In separate stallions, concurrent nematodiasis and metastatic melanoma were considered the primary cause.

 

Prepuce

Stéphanie Muller, Marco Grzybowski, Heinz Sager, Valérie Bornand, Walter Brehm (2008). A nodular granulomatous posthitis caused by Halicephalobus sp. in a horse. Veterinary Dermatology 19 (1), 44–48.
Single case report

Nonspecific posthitis

Immune mediated

posthitis

Bacterial infection.

Mycoplasmal infection

Mycotic infection

Phalitis

Phalitis is inflammation of the penis. The penis proper can be affected and this section is dedicated to inflammatory disease of the root, body or head of the penis, apart from the penile epithelium (covered with posthitis)

Disturbances of growth

 

Miscellaneous masses

Vascular hamartoma

Arteriovenous fistula

Urethral prolapse

Congenital anomalies

Hypoplasia and hypertrophy

Hypospadias and fistulas

I have chosen to discuss these anomalies in the section on Disorders of Sexual Development

Balanopreputial fold or band (Persistent frenulum)