The indications, complications and outcomes of dogs undergoing partial penile amputation: 10 cases (2014-2021).

OBJECTIVES: To report the signalment, indications for surgery, postoperative complications and medium-/long-term outcomes in dogs undergoing partial penile amputation. MATERIALS AND METHODS: Retrospective case series. The electronic medical records of a single small animal referral hospital were searched between January 2014 and January 2021 for dogs that underwent a partial penile amputation. Data collected included signalment, presenting clinical signs, indication for partial penile amputation, surgical technique, postoperative complications and outcome. RESULTS: Ten dogs were included in the study. Indications for surgery were treatment of preputial neoplasia (n=5), penile neoplasia (n=1), idiopathic paraphimosis (n=3) and chronic urethritis (n=1). Five of five preputial tumours were cutaneous mast cell tumours, and the penile tumour was a squamous cell carcinoma. All dogs recovered uneventfully from surgery with a median postoperative hospitalisation time of 28.8 hours. Two of the three dogs treated for paraphimosis had major postoperative complications requiring further resection of the tip of the penis at 2 weeks and 24 months. Four dogs had minor complications managed without surgical intervention. The outcome was good to excellent in nine of nine dogs for which medium- or long-term follow-up data were available. CLINICAL SIGNIFICANCE: In this group of dogs, partial penile amputation, performed with or without concurrent resection of the prepuce, was a well-tolerated surgical procedure with low intraoperative and postoperative complication rates and good functional outcomes. Partial penile amputation should be considered for conditions affecting the distal penis and prepuce.

Multiple Simultaneous Proliferative Lesions on the Prepuce and Penis of a Gelding.

Skin lesions are among the leading diseases in equids, and the urogenital region is considered the third most frequently affected body location with tumors and tumor-like skin lesions in horses. Tumor-like skin lesions or multiple tumors of different types in the equine prepuce and penis are a challenging clinical presentation leading to misdiagnosis and subsequent ineffective treatment. An 18-year-old 395-kg male mixed-breed gelding was referred for evaluation of preputial enlargement. Clinical examination revealed a 2.5 × 2.0 × 0.8 cm proliferative ulcerated lesion on the penile mucosa, five ulcerated and circumscribed hardened wounds on the preputial skin fold from 2.0 to 6.0 cm in diameter, and multiple variable-sized raised exophytic lesions ranging from 2.0 mm to 2.3 cm cauliflower-like lesions throughout the prepuce and penis. Pathological and immunohistochemical findings confirmed the definitive diagnosis of three distinct proliferative lesions: squamous cell carcinoma, squamous viral papilloma and cutaneous habronemiasis. Additionally, we present features of concurrent habronemiasis and squamous cell carcinoma and highlight the importance of proper diagnostic approach in the prognosis and correct treatment selection.

Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment.

Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by Equus caballus papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas in situ, CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirmed EcPV-2-L1 DNA in 18/20 (90%) samples. L1 expression was instead retrieved in 13/20 cases (65%). The samples showed an increased infiltration of CD3+lymphocytes, macrophages (MAC387; IBA1), plasma cells (MUM1), and FoxP3+lymphocytes in the intra/peritumoral stroma when compared to extratumoral tissues (p < 0.05). Only MAC387+neutrophils were increased in EcPV-2high viral load samples (p < 0.05). IL12/p35 was differentially expressed in EcPVhigh and EcPVlow groups (p = 0.007). A significant decrease of IFNG and IL2 expression was highlighted in TGFB1-positive samples (p < 0.05). IBA1 and CD20 were intratumorally increased in cases where IL-10 was expressed (p < 0.005). EpSCCs may represent a good spontaneous model for the human counterpart. Further prospective studies are needed in order to confirm these preliminary results.

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions.

BACKGROUND: There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. The aim of this study was to identify histologic criteria and diagnostic markers allowing for a more accurate diagnosis of EcPV2-associated equine penile lesions. RESULTS: A total of 61 archived equine penile lesions were histologically re-assessed and classified as benign hyperplasia, papilloma, CIS or SCC. From these, 19 representative lesions and adjacent normal skin were comparatively analysed for the presence of EcPV2 DNA and transcripts using PCR and RNA in situ hybridisation (RISH). All lesional samples were positive by EcPV2 PCR and RISH, while adjacent normal skin was negative. RISH analysis yielded signal distribution patterns that allowed distinction of early (hyperplasia, papilloma) from late stage lesions (CIS, SCC). Subsequently, the 19 lesions were further assessed for expression of p53, Ki67, MCM7 and MMP1 by immunohistochemistry (IHC). All four proteins were expressed in both normal and lesional tissue. However, p53 expression was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs, as well as in upper keratinocyte layers of CIS and SCCs. MCM7 expression was only up-regulated in upper proliferating keratinocyte layers of papillomas, CIS and SCCs. CONCLUSION: This study proposes combining a refined histological protocol for analysis of equine penile lesions with PCR- and/or RISH based EcPV2-screening and p53/MCM7 IHC to more accurately determine the type of lesion. This may help to guide the choice of optimum treatment strategy, especially at early stages of disease.

Squamous Cell Carcinoma of the Penis with Pulmonary Metastasis and Paraneoplastic Hypertrophic Osteopathy in a Dog.

Squamous cell carcinoma of the penis was diagnosed by incisional biopsy of a penile mass in a 12 yr old intact male beagle dog presenting with hemorrhagic discharge from the prepuce. Penile amputation, orchiectomy with scrotal ablation, and scrotal urethrostomy were performed. Hypertrophic osteopathy secondary to pulmonary metastatic disease occurred 10 mo after the surgery. Palliative treatment with piroxicam was administered and led to complete resolution of the clinical signs of the pain. Sixteen months following surgery, the dog presented with significant dyspnea and anorexia and was euthanized due to poor prognosis. This case report describes a rare penile tumor, squamous cell carcinoma. Consequent paraneoplastic hypertrophic osteopathy and its palliative treatment are also reviewed.

Myxoma of the penis in an African pygmy hedgehog (Atelerix albiventris).

A penile tumor (4 × 2.5 × 1 cm) was surgically removed from an African pygmy hedgehog (Atelerix albiventris) aged 3 years and 5 months. The tumor was continuous with the dorsal fascia of the penile head. Histopathologically, tumor cells were pleomorphic (oval-, short spindle- and star-shaped cells) with low cell density. Abundant edematous stroma was weakly positive for Alcian blue staining and positive for colloidal iron reaction. Tumor cells displayed no cellular atypia or karyokinesis. Tumor cell cytoplasm was positive for vimentin antibody, while cytoplasm and nuclei were positive for S-100 protein antibody. Tumor cell ultrastructure matched that of fibroblasts, and the rough endoplasmic reticulum was enlarged. The tumor was diagnosed as myxoma. This represents the first report of myxoma in a hedgehog.

Plasmocitoma extramedular em bulbo peniano de cão: relato de caso / Extramedullary plasmacytoma in the penile bulb of a dog: case report

O objetivo deste relato de caso é descrever a ocorrência de plasmocitoma em bulbo peniano de um cão, classificado como uma doença extramedular não cutânea de localização rara e casuística inédita. Um cão, sem raça definida, com sete anos de idade e pesando 15kg, não castrado, apresentou histórico clínico de anorexia, vômitos, anúria e constipação. Ao exame específico da genitália externa, foi encontrada uma massa em bulbo peniano durante a inspeção do prepúcio, aderida à pele e encapsulada, extremamente firme e arredondada, medindo cerca de 6cm de diâmetro. Por meio da ultrassonografia dessa estrutura, foi observado aumento do volume regional com ecotextura heterogênea e ecogenicidade mista, além de neovascularização tecidual ao Doppler colorido. Foi realizada biópsia da massa, sendo verificada a presença de neoplasia de células redondas. A caracterização do tumor foi realizada pela imuno-histoquímica, e as células neoplásicas foram imunoexpressas para CD79a e MUM1, indicando o diagnóstico de plasmocitoma extramedular. Embora os tumores penianos em cães sejam os predominantemente venéreos transmissíveis (TVT), e os plasmocitomas sejam neoplasias raras nessa localização, este relato de caso fornece com ineditismo a ocorrência de plasmocitoma extramedular em bulbo peniano de cão, condição ainda não descrita em veterinária.

Non-cutaneous extramedullary plasmacytomas are relatively rare in dogs, affecting mainly the oral cavity and bowel loops. The involvement of the penile bulb has not been described, a fact of great importance for obstetric and veterinary oncology. The aim of this case report is to describe the occurrence of plasmacytoma in a dog's penile bulb, classified as a non-cutaneous extramedullary disease of rare location and unpublished casuistry. A non castrated dog of undefined breed, with seven years of age and weighing 15kg, presented clinical history of anorexia, vomiting, anuria and constipation. By specific examination of the external genitalia, a penile bulb mass was found in the preputial inspection, which was adhered to the encapsulated skin, extremely firm and rounded, measuring approximately 6 cm in diameter. By ultrasound evaluation of the structure in the penile bulb an increase of regional volume with heterogeneous echotexture and mixed echogenicity and tissue neovascularization upon color Doppler was observed. Incisional biopsy of the mass was performed and showed the presence of neoplasia of round cells. The characterization of the tumor was performed by immunohistochemistry and the neoplastic immuno cells were expressed CD79a and MUM1, indicating the diagnosis of extramedullary plasmacytoma. Although the penile tumors in dogs are predominantly transmissible venereal tumors (TVT) and plasmocytomas are rare neoplasms in this location, this case report provides a novel occurrence of extramedullary plasmacytoma in the penile bulb of a dog, a condition not yet described in veterinary.

Equine Genital Squamous Cell Carcinoma: In Situ Hybridization Identifies a Distinct Subset Containing Equus caballus Papillomavirus 2.

Equus caballus papillomavirus 2 (EcPV2) has been proposed as an etiologic agent for genital squamous cell carcinoma (SCC), the most common malignant tumor of the horse penis. EcPV2 is commonly detected by polymerase chain reaction (PCR) on normal horse genitalia; therefore, unraveling the virus' role in oncogenic transformation requires other methods of detection. In this study, a highly sensitive multiple-probe chromogenic in situ hybridization (ISH) technique was designed to recognize the E6/E7 oncogenes of EcPV2. ISH demonstrated abundant virus within 6 of 13 penile and preputial SCCs, whereas evidence of solar damage was found in 6 cases that were negative for EcPV2 by ISH. The ISH technique is valuable for studies of pathogenesis, since it demonstrates for the first time that the vast majority of neoplastic cells contain virus. Moreover, hybridization was present in all metastases examined, implying stability of E6/E7 expression in these clonal populations of neoplastic cells. This study contributes to the accumulating evidence for a causal role of EcPV2 in a subset of genital SCCs in horses.

Penile amputation and scrotal urethrostomy followed by chemotherapy in a dog with penile hemangiosarcoma.

A 7 yr old castrated male standard poodle weighing 25 kg was presented with a 5 day history of hematuria, dysuria, and the presence of a 2.5 cm, firm swelling within the prepuce. Abdominal radiographs revealed a soft-tissue mass on the distal prepuce and lysis of the cranial margin of the os penis. The patient was sedated and an ulcerated hemorrhagic mass was identified at the tip of the penis. The mass was diagnosed as hemangiosarcoma via incisional biopsy. A penile amputation with scrotal urethrostomy was performed followed by chemotherapy with doxorubicin.

Primary penile adenocarcinoma with concurrent hypercalcaemia of malignancy in a dog.

A 13-year-old male neutered Siberian husky crossbreed dog was presented with a 3-week history of haematuria and penile swelling. Clinical examination and computed tomography demonstrated a soft-tissue mass located at the base of the penis without signs of other primary tumours or metastasis. Clinicopathological findings revealed paraneoplastic hypercalcaemia. Fine-needle aspiration cytology of the mass suggested an epithelial tumour with several criteria of malignancy present. Following surgical excision of the mass, the hypercalcaemia resolved. Histopathology and immunohistochemistry revealed features consistent with an adenocarcinoma. Despite thorough examination, no perineal or anal sac tumour was found. To the authors' knowledge, this is the first reported case of a penile adenocarcinoma with hypercalcaemia of malignancy.

Cyto-histopathological and outcome features of the prepuce squamous cell carcinoma of a mixed breed dog.

BACKGROUND: Squamous cell carcinomas (SCCs) are uncommon, high-grade tumors, predominantly composed of round cells in the prepuce. The aim of this study is to better define the clinicopathologic features of this neoplasm. CASE REPORT: We conducted cyto-histopathologic analysis on the manifestations of the prepuce SCC by H & E staining in a terrier mix dog. Grossly, tumor was large, multiple erythematous patch, and ulcerated masses frequently affecting the prepuce and deeply invading to distal prepuce out from the ventro-lateral of penis and the tumor covered by a necrotic discharge. Cytological evaluation of fine-needle aspirates from the cutaneous mass from the prepuce comprised of round nuclei, coarse chromatin pattern, distinct nucleoli and nuclear pleomorphism. Furthermore, the neoplastic cells were pleomorphic, round to caudate in shape, exhibiting prominent anisokaryosis and anisocytosis with rare mitotic features. Microscopically, the lesions were predominantly composed of atypical round cells disposed in interlacing fascicles. Frequent findings include keratin formation, horn pearls, mitoses and cellular atypia. The cells showed distinct borders, ranged from polygonal to round or elongate and had moderate amounts of eosinophilic cytoplasm. CONCLUSION: The histopathologic features coupled with the cytopathology findings led to a diagnosis of squamous cell carcinoma. To the authors' knowledge, this is the first time that multiple erythematous plaques have undergone malignant transformation in a terrier mix dog. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5748771971272873.

Prepuce and partial penile amputation for treatment of preputial gland neoplasia in two ferrets.

Preputial tumours in ferrets are frequently malignant and therefore warrant prompt investigation. As many cases do not respond favourably to surgery, even in combination with radiation therapy, wide surgical resection has been recommended. Such a procedure may necessitate partial or total penile resection but outcomes have thus far not been well described. The current case series describes two ferrets in which surgical resection, including penile amputation, was performed using 10 and 5 mm margins, respectively. In the first case, no recurrence of preputial gland adenocarcinoma was noted for 32 months postsurgery, whereas multiple attempts at surgery and radiation therapy were unsuccessful in the second. These cases suggest that margins of at least 1 cm may help achieve a better outcome. Penile amputation for the treatment of preputial tumours appears to be well tolerated by ferrets, as demonstrated by these cases.

Pollakiuria and stranguria in a Labrador retriever with penile HSA.

An approximately 8 yr old castrated male Labrador retriever presented for evaluation of weight loss, stranguria, and pollakiuria. Lysis of the proximal one-third of the os penis was diagnosed on abdominal radiographs, and a positive contrast urethrography revealed a smoothly marginated filling defect along the dorsal aspect of the urethra at the level of the radiographically observed osteolysis. Regional ultrasound revealed an echogenic mass at the proximal aspect of the os penis with a severely irregular and discontinuous periosteal surface. A penile hemangiosarcoma (HSA) was confirmed on histopathologic evaluation after a penile amputation and scrotal urethrostomy were performed. Although HSA is a common malignant neoplasm in dogs, lysis of the os penis has not previously been documented. Adjunctive chemotherapy, although recommended, was declined, and the patient survived 236 days postoperatively. That survival time is considerably longer than the average survival time for patients with HSA, other than cutaneous forms of HSA. Although an uncommon presentation, HSA of the penis should be considered a differential diagnosis in older canines with signs of lower urinary tract disease, especially in breeds that have been documented to be predisposed to HSA.

Detection of papillomavirus in equine periocular and penile squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common tumor arising in the periocular and penile areas of horses. Both ultraviolet radiation and papillomaviruses have been implicated in the pathogenesis of SCC in various species, including the horse. This retrospective study used polymerase chain reaction (PCR) to detect papillomavirus DNA in archival biopsy samples from equine periocular and penile SCC from 3 different geographic areas (northeast, southeast, and central United States). Forty-two periocular SCCs were tested; none contained papillomavirus DNA. Twenty-two penile SCCs were tested, and papillomavirus DNA was identified in 10 (43%) cases. Sequencing of the PCR products revealed homology with Equus caballus papillomavirus 2 (EcPV-2). No geographic distribution in the detection of papillomavirus was identified. Penile SCCs were significantly more likely to be papillomavirus positive than the periocular SCCs (P < 0.001). The role of papillomavirus in the development of penile SCC requires further investigation. The differing pathogeneses of periocular and penile SCC suggest that the tumors may respond differently to treatment.

Haemangiosarcoma of the os penis in a dog: The most common neoplasm of the canine penis.

A castrated 9-year-old intact male boerboel cross-breed dog was presented with a month-long history of stranguria. On physical examination, a mass was noted at the caudal extremity of the os penis. Haematology, serum chemistry and urinalysis were all unremarkable. Abdominal and urethral ultrasound demonstrated an enlarged bladder and a dilated urethra, which was followed to the caudal extremity of the os penis. A hyperechoic, roughly spherical,vascularised mass was noted at the caudal os penis, which resulted in obstruction of the penile urethra. Radiographs demonstrated a soft tissue mass with osteolysis of the os penis. Cytology suggested an osteosarcoma. Treatment included amputation of the penis and adjuvant doxorubicin with carboplatin. Histopathology of the penis confirmed a haemangiosarcoma. The patient survived for 20 months. This is only the second published case report describing a penile haemangiosarcoma, and the first published report demonstrating the treatment and outcome of a case of haemangiosarcoma of the os penis. Based on published and unpublished reports, haemangiosarcoma appears to be the most common neoplasm of the canine penis.

Comparison of the levels of Equus caballus papillomavirus type 2 (EcPV-2) DNA in equine squamous cell carcinomas and non-cancerous tissues using quantitative PCR.

Equus caballus papillomavirus type 2 (EcPV-2) infection has been associated with equine genital squamous cell carcinomas (SCCs). However, quantitative PCR (qPCR) has not been performed to determine viral copy numbers within these lesions. Additionally, the frequency with which EcPV-2 can be detected in other common sites of equine SCC development remains uncertain. The aim of this study was to develop a qPCR assay to estimate the viral load in a variety of equine tissue samples. These included 40 SCC lesions, 19 penile non-SCC or precursor disease lesions, and 222 tissues without observable lesions from SCC-prone sites on clinically normal horses. EcPV-2 DNA was present significantly more frequently, and in higher copy numbers, in equine penile SCC lesions than in either healthy penile mucosa or non-SCC penile lesions. This supports the hypothesis that EcPV-2 is involved in development of penile SCCs and suggests that penile EcPV-2 infection is rare in the absence of SCCs. Samples of normal vulval mucosa rarely contained EcPV-2 DNA and none of the nictitating membrane samples contained EcPV-2 DNA, indicating that asymptomatic EcPV-2 infection is uncommon at these sites. EcPV-2 DNA was detected in a proportion of both SCCs and normal samples from the oral cavity or pharynx, although there were no significant differences in the rate of infection or viral copy number between the SCCs and the normal mucosal samples. As such, the role of EcPV-2 in development of SCCs in this location remains to be established.

EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology.

Equine penile papillomas, in situ carcinomas, and invasive carcinomas are hypothesized to belong to a continuum of papillomavirus-induced diseases. The former ones clinically present as small grey papules, while the latter 2 lesions are more hyperplasic or alternatively ulcerated. To test the hypothesis that these lesions are papillomavirus-induced, samples of 24 horses with characteristic clinical and histologic findings of penile papillomas or in situ or invasive squamous cell carcinomas were collected. As controls, 11 horses with various lesions--namely, Balanoposthitis (6 cases), melanoma (3 cases), follicular cyst (1 case), and amyloidosis (1 case)--were included. DNA was extracted and polymerase chain reaction applied to amplify papillomavirus DNA. The respective primers were designed to amplify DNA of the recently discovered equine papillomavirus EcPV2. All tested papilloma and squamous cell carcinoma samples were found to contain DNA of either of 2 previously published EcPV2 variants. Among the other samples 6 of 11 were found to contain EcPV2 DNA. To further support the findings and to determine where the papillomavirus DNA was located within the lesions, an in situ hybridization for the detection of EcPV2 DNA was established. The samples tested by this technique were found to clearly contain papillomavirus nucleic acid concentrated in the nucleus of the koilocytes. The findings of this study support previous data and the hypothesis that papillomaviruses induce the described penile lesions in horses.

EcPV2 DNA in equine genital squamous cell carcinomas and normal genital mucosa.

Squamous cell carcinoma (SCC) represents the most common genital malignant tumor in horses. Similar to humans, papillomaviruses (PVs) have been proposed as etiological agents and recently Equine papillomavirus type 2 (EcPV2) has been identified in a subset of genital SCCs. The goals of this study were (1) to determine the prevalence of EcPV2 DNA in tissue samples from equine genital SCCs, penile intraepithelial neoplasia (PIN) and penile papillomas, using EcPV2-specific PCR, (2) to examine the prevalence of latent EcPV2 infection in healthy genital mucosa and (3) to determine genetic variability within EcPV2 and to disentangle phylogenetic relationships of EcPV2 among PVs. EcPV2 DNA was detected in all but one penile SCC (15/16), in all PIN lesions (8/8) and penile papillomas (4/4). Additionally, EcPV2 DNA was demonstrated in one of two metastasized lymph nodes, one contact metastasis in the mouth, two vaginal and one anal lesion. In healthy horses, EcPV2 DNA was detected in 10% (4/39) of penile swabs but in none of vulvovaginal swabs (0/20). This study confirms the presence of EcPV2 DNA in equine genital SCCs and shows its involvement in anal lesions, a lymph node and contact metastases. Latent EcPV2 presence was also shown in normal male genital mucosa. We found that different EcPV2 variants cocirculate among horses and that EcPV2 is related to the Delta+Zeta PVs and is only a very distant relative of high-risk human PVs causing genital cancer. Thus, similar viral tropism and similar malignant outcome of the infection do not imply close evolutionary relationship.