Cyto-histopathological and outcome features of the prepuce squamous cell carcinoma of a mixed breed dog
© Yaghoobi Yeganeh Manesh et al.; licensee BioMed Central Ltd. 2014
Received: 22 April 2014
Accepted: 2 June 2014
Published: 6 June 2014
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.
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.
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.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5748771971272873
KeywordsHistopathology Cytology Dog Prepuce Tumour
The prepuce, or sheath, is a voluminous, folded “sleeve” of integument covering the mobile portion of the quiescent penis. The prepuce consists of the haired external lamina, which is continuous with the skin of the abdominal wall and an internal lamina which is in contact with the penis. Neoplasms of the penis and prepuce include squamous papillomas, squamous cell carcinomas, sarcoids, melanomas, mastocytomas, and hemangiomas[2–4]. The penis is covered with skin and can thus be affected by tumours of epithelial or mesenchymal origin. Squamous cell carcinomas in this region frequently cause discomfort but can also lead to more severe squeal and even result in death.
Cutaneous squamous cell carcinomas (SCCs) are malignant epidermal neoplasms of humans and animals. Squamous cell carcinoma of the penis and prepuce is demonstrated in horses, dogs and bulls. In dogs, squamous cell carcinoma located in the penis or prepuce is similar to horse neoplasm, but keratinization is poor or absent. Metastases take place in over 25% of cases, usually in inguinal lymph nodes[5, 6]. Primary SCC may occur at any anatomic site on the penis. It most often occurs on the glans although it may also develop on the prepuce, both the glans and the prepuce, the coronal sulcus, and the shaft. Invasion of the shaft by a tumor originating from more distant sites may also be observed. Squamous cell carcinoma (SCC) accounts for at least 95% of all penile malignancies. It represents approximately 2% of all cancers of the male genitalia and comprises 0.3-0.5% of the cancer-bearing male population[7, 8].
In man, infection with papilloma viruses (HPV) has been reported to be a risk factor for the development of SCC, but secondary factors must also be[9, 10]. Squamous cell carcinomas (SCCs) are the most common form of penile and preputial neoplasia; however, squamous cell papillomas, melanomas, fibromas, fibrosarcoma and haemangiomas have been reported[11, 12]. Penile and/or preputial neoplasia may cause discomfort and in advanced cases can result in systemic disease[13, 14]. In addition, SCCs are the commonest neoplasm involving the penis, prepuce or both. Moreover, prepuce SCC is considered a loco-regional disease with a fairly predictable pattern of progression. Widespread dissemination occurs in at least one-third of the patients. Local recurrence (defined as the presence of tumor after a primary treatment affecting any remainder tissue, including skin, erectile corpora, or urethra) present in up to 30% of the patients increases the risk of regional inguinal and pelvic lymph nodes metastases. Papillomaviruses (PVs) are a diverse group of viruses that cause the mouth and genitalia SCCs of people. Additionally, some evidence suggests that PVs may act as a cofactor with ultraviolet (UV) light to promote the development of human cutaneous SCCs[17, 18]. However, regarding nonhuman species, evidence suggesting a causal association between PVs and cutaneous SCCs, which has been reported in cats, rabbits, horse, bandicoots and some rodents. In dogs, seven papillomavirus (PV) types have been completely described[20, 21]. Of these, Canis familiaris papillomavirus 2 (CfPV 2), CfPV 3 and CfPV 7 have been previously detected in canine cutaneous SCCs.
The diagnosis of cancer is usually confirmed by a histologic examination. Histopathologic examination is essential to establish the diagnosis and to provide information about the extension of the tumour in deeper tissues. Upon microscopy, squamous cell carcinoma (SCC) may have different histologic features according to the degree of differentiation. The histological evidence of PV infection within the SCCs could support a causative association between PVs and a proportion of canine cutaneous SCCs[16–19, 22]. The aim of the study was to evaluate cytopathological and outcome features of squamous cell carcinoma of the prepuce.
This study was approved by the Animal Ethics Committee at Tehran University (Ethics code permit no. TU2013-1-11-007Y). The animal was placed in shade, in standard conditions, water ad libitum, and without restriction of movement according to the guidelines of the Institutional Animal Ethical Committee of the Tehran University of Animal Science, Iran. Surgery was performed under aseptic conditions and sedation by injection of xylazine hydrochloride (0.05 mg/kg) followed by 2% lignocaine hydrochloride.
Clinical case reports
The present study was carried out on a terrier dog. This animal was admitted to Tehran Veterinary Teaching Hospital of the Faculty of Veterinary Medicine, Tehran University, Tehran, Iran. Diagnosis was based on history of the case and clinical examination of each mass including location, size and age as well as histopathological examinations.
Clinical examination was performed of the penis and prepuce. Examination of the penis itself and the internal fold of the prepuce required sedation with intravenous detomidine 1% (Domosedan, Pfizer) 0.01 mg/kg body weight. Furthermore, superficial inguinal lymph nodes were examined.
In April 2012, a 8-year-old, 9 kg, intact male, terrier mix breed dog was examined because of multiple, 10 × 8 × 9 mm in diameter, round, extradermal nodule around the prepuce with history of two months difficulty in retraction of the prepuce. Firstly, only a slightly scaly, erythematous patch had been noted. At our initial evaluation, an erythematous and focally ulcerated plaque and evidence of ulceration and bleeding was noted on manipulation. Inguinal lymph nodes, abdominal and respiratory system revealed normal upon examination. Furthermore, owner complained from foul-smelling discharge from the ulcer. Moreover, clinical examination revealed an infiltrated porcelain white plaque over the mucosal surface of the prepuce along with a soft friable, red colored erythematous plaque over the penis glans, the surface of which was covered by a necrotic discharge.
This study was designed to describe and correlate the major clinical and histopathological characteristics of canine genital SCC, similar to that reported in the human literature[24, 25]. Cutaneous neoplasms occur in veterinary medicine in distributions similar to those seen in human subjects. Squamous cell carcinoma is the most common tumor seen in the genitalia, accounting for 45% of the tumours seen in the male genitalia and 12% in the female perineum.
Preoperative pathological evaluation of the primary tumour is required to classify the tumour and design a treatment plan. This may be performed by fine needle aspiration biopsy (FNAB) or by punch or excisional biopsy[26, 27]. Fine needle aspiration biopsy can be utilized to identify cells with malignant features, but it is not a reliable means of assessing SCC, because early neoplastic, hyperplastic or dysplastic keratinocytes can appear similar cytologically. Tumour architecture and depth of invasion can only be assessed by evaluating a full thickness biopsy; therefore a full thickness biopsy of the lesion is more reliable than FNAB. Independent of the type of tumour, the lesion can be so severe that complete excision is necessary in any case. In such cases, surgical removal or debulking can be combined with harvesting material for histopathological examination. In this study, the malignant squamous cells were pleomorphic, round to caudate in shape exhibiting prominent anisokaryosis and anisocytosis. Anisokaryosis characterised by nuclei, varying from pyknotic to large type, variable nuclear to cytoplasmic ratio, binucleation and multinucleation and perinuclear vacuolation were observed such observations were in line with the previous observations[28–30].
Histologically, the prepuce erythematous plaques (PEP) have been reported to contain mild to moderate epidermal hyperplasia and orthokeratosis[31–33]. In contrast, the epidermis in the presently described plaques was often markedly thickened with prominent folds. While large keratohyaline granules have been previously described in PEP[31, 32], the number and size of the granules in the present case was greater than in previous descriptions. The PEP in the presently reported dog underwent malignant transformation more rapidly and more frequently than in previous reports. Additionally, this is the first report of malignant transformation of multiple PEP in a dog without detectable immunodeficiency. Since there are few reports describing the malignant transformation of canine PEP, prediction of which plaques will become neoplastic is difficult. However, results from the present case suggest that larger PEP that contains greater histological changes may be predisposed to malignant transformation. The present dog was anaesthetized to remove ulcerated masses during a 1-day period. Although masses were confirmed histologically to be SCC, all the masses had a similar gross appearance, suggesting that all were likely to be neoplastic. Therefore, the PEP in the presently reported dog underwent malignant transformation more rapidly and more frequently than in previous reports. In the presently reported dog, erythematous plaques frequently and rapidly progressed to SCC within sun-exposed skin. Additionally, although histology revealed only rare foci of koilocytosis, epidermal hyperplasia was prominent, and one section contained bands of keratinocytes with increased quantities of pale cytoplasm and vacuolated nuclei with marginated chromatin within the superficial layers of the epidermis.
In our case most of the lesions were proliferative and were often ulcerated as previously reported in the cutaneous different regions. Ulceration is observed in advanced human SCCs and SCC in human patients usually presents as an indurated, non-healing ulcer. Furthermore, infiltration by lymphocytes has been described in numerous human tumours, the presence of such cell often being associated with an improved prognosis[37–39] that these observations are in agreement with our study. Moreover, the amount of keratin was abundant in our case. The proliferating cells revealed moderate cellular pleomorphism, large vesicular nuclei, prominent nucleoli and variable mitotic activity. Similar microscopic observations have been reported[40–47].
In conclusion, squamous cell carcinoma can occur on virtually all keratinizing surfaces of the skin. The present study describes for the first time several histological diagnosis of SCC affecting the prepuce of dogs. Although the prognostic value of histological classification of prepuce SCC remains a controversial topic in human medicine, this should be further evaluated in dogs, as there may be differences in the biological behaviour of canine prepuce SCC. The clinical presentation of a well-demarcated scaling erythematous plaque can be altered when it appears in moist, intertriginous, or hyperkeratotic sites. Because little is known about the behaviour of SCC on the external genitalia of the male dog, deciding on the most appropriate treatment is difficult. Poorly differentiated SCC on the external genitalia of the male horse seem to metastasis relatively frequently, but prospective research on the relationship between tumour grade, treatment performed and incidence of recurrence is needed to confirm this clinical impression. So the system proposed in this study, admittedly not based on large case series and entirely open to any modification or improvement, is offered as a first step in this direction.
In conclusion, the presently described case was unusual owing to the extensive development and frequent malignant transformation of the erythematous plaques. To the authors’ knowledge, this is the first time that multiple erythematous plaques have undergone malignant transformation in a terrier mix dog. Finally, the histopathologic features coupled with the cytopathology findings led to a diagnosis of squamous cell carcinoma.
Written informed consent was obtained from the dog owner for publication of this Case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Squamous cell carcinomas
Herpes papilloma viruses
Haematoxylin and eosin
Five high power fields.
The authors thank Dr.M.aghamohammad Hassan for his help with this manuscript.
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