Canine Apocrine Gland Anal Sac Adenocarcinoma: A Review.

Apocrine gland anal sac adenocarcinoma (AGASAC) is a relatively uncommon tumor in the dog and comprises approximately 17% of perianal malignancies; however, it is one of the most common causes of paraneoplastic hypercalcemia. Clinical signs in affected dogs most commonly are associated with mechanical obstruction caused by the primary tumor or enlarged regional metastatic lymph nodes and the effects of paraneoplastic hypercalcemia when present. Surgical excision of the primary tumor and metastasectomy of affected locoregional lymph nodes is the preferred initial treatment option for most dogs, although radiation therapy and adjuvant chemotherapy are commonly incorporated into multi-modality treatment plans. A significant role for the use of adjuvant chemotherapy has not been clearly demonstrated. Prolonged survival times are possible, especially for dogs with smaller primary tumors and for dogs that undergo further treatments for recurrent disease. In this article, we review the clinical signs, diagnosis, staging, treatment, and prognosis of AGASAC in the dog.

Basal cell enumeration does not predict malignancy in canine perianal gland tumor cytology.

BACKGROUND: Perianal (hepatoid) gland tumors are common in dogs, and the distinction between the benign and malignant forms is clinically important. Cytology of these tumors typically contains many large hepatoid cells and fewer small basal cells. OBJECTIVES: The objective of this study was to determine whether the proportion of the smaller basaloid reserve cells in cytologic samples from perianal tumors correlates with malignancy. METHODS: Eighty-three cases of cytologically diagnosed perianal gland tumors with corresponding histopathologic sections were identified from two separate institutions and included six (7.2%) malignant tumors and 77 (92.8%) benign tumors. The proportion of basal cells from each sample was evaluated. RESULTS: No difference between these groups was found, although the study was sufficiently powered to detect an approximately 1.5-fold change in basal cell proportion. CONCLUSIONS: This report found no evidence that the proportion of basal cells in canine perianal tumor cytology is an indication of the potential for malignancy. We, therefore, do not recommend citing this feature in cytologic reports or when communicating with clinicians.

Metastatic disease in a dog with a well-differentiated perianal gland tumor.

Fine-needle aspirates from a perianal mass on an 8-year-old, intact male, Miniature Poodle presenting for tenesmus showed a uniform population of well-differentiated hepatoid cells with no notable criteria of malignancy. The cytologic diagnosis was a perianal gland tumor, with adenoma likely given the cytomorphology. The abdominal ultrasound revealed multiple, markedly enlarged, intra-abdominal lymph nodes. LN aspirates also showed well-differentiated polygonal, hepatoid cells displaying no notable cellular atypia. The presence of the metastasis led to the interpretation of a well-differentiated, malignant perianal gland tumor despite the benign cellular appearance. Histopathology of the surgically excised perianal mass and one enlarged abdominal lymph node revealed lobules of uniform polygonal hepatoid cells arranged in organized islands and trabeculae surrounded by a single layer of uniform reserve cells. Few mitotic figures were present. The only histopathologic indication of malignancy within the primary mass was the presence of small islands of well-differentiated hepatoid cells infiltrating into adjacent tissue and possible lymphatic invasion. The histopathologic diagnosis was perianal gland adenocarcinoma. Most textbooks describe perianal gland adenocarcinomas as showing increased cellular atypia including pleomorphism, disorganization of hepatoid cells, and increased numbers of pleomorphic reserve cells with mitotic figures. This case is an example of the occurrence of a well-differentiated perianal gland tumor with metastasis and highlights the importance of realizing that with these tumors, a benign cytologic and histologic appearance may not correlate with biologic behavior. To the authors' knowledge, this is the first case reporting both the cytologic and histologic appearance of a well-differentiated metastatic hepatoid gland tumor.

Prognostic significance of histopathology in canine anal sac gland adenocarcinomas: Preliminary results in a retrospective study of 39 cases.

Metastatic rates and survival times of canine anal sac gland adenocarcinomas (ASGACs) vary among studies, making prognostication difficult. Little is known about the prognostic significance of histopathology of ASGACs. This retrospective study investigated associations between histological features, clinical presentation and outcome for 39 ASGACs. Most tumours were incompletely excised (62%) and had moderate to marked peripheral infiltration (74%). The predominant growth pattern was solid, tubules/rosettes/pseudorosettes and papillary in 49%, 46% and 5% of the cases, respectively. Nuclear pleomorphism was either moderate (77%) or mild (23%). Necrosis and lymphovascular invasion were present in 54% and 10% of the cases, respectively. All histological features except mitotic count and necrosis were associated with nodal metastasis at presentation. A statistically significant poorer outcome was identified for tumours with a solid growth pattern, moderate or marked peripheral infiltration, necrosis and lymphovascular invasion. These results need further validation in a larger cohort of dogs.

Malignant collision tumors in two dogs.

CASE DESCRIPTION A 13-year-old Labrador Retriever with a 4-cm-diameter ulcerated perianal mass and a 12-year-old Golden Retriever with a 5-cm-diameter ulcerated caudolateral abdominal mass were brought to a referral oncology practice for evaluation of the dermal masses. Both masses were resected with wide margins without reported postoperative complications. For both dogs, a diagnosis of collision tumor was made. The database of the Veterinary Diagnostic Laboratories at Colorado State University was searched for other examples of collision tumors in dogs. CLINICAL FINDINGS Histologic assessment of the masses revealed collision tumors in both patients. The perianal mass was diagnosed as a perianal gland carcinoma with adjacent hemangiosarcoma. The flank mass was diagnosed as a fibrosarcoma with an adjacent mast cell tumor. The university database search of sample submissions in 2008 through 2014 for the keywords collision, admixed, or adjacent yielded 37 additional cases of dogs with malignant nontesticular collision tumors. TREATMENT AND OUTCOME Both dogs were treated with surgery alone and received no adjunctive treatments. Both tumors were completely excised. There was no evidence of either local tumor recurrence or metastasis in the Labrador Retriever and the Golden Retriever at 1,009 and 433 days after surgery, respectively. CLINICAL RELEVANCE Collision tumors are rare, and there is minimal information regarding treatment recommendations and outcome for animals with collision tumors. On the basis of the 2 cases described in this report, the outcome associated with treatment of collision tumors may be similar to the expected outcome for treatment of any of the individual tumor types in dogs.

Malignant anal sac melanoma in dogs: eleven cases (2000 to 2015).

OBJECTIVES: To report the signalment, clinical presentation, treatments pursued and outcomes of dogs with malignant anal sac melanoma. METHODS: Medical records from five institutions from January 2000 through December 2015 were reviewed and dogs with cytologically- or histologically-confirmed malignant anal sac melanoma were identified. Signalment, clinical signs, staging, cytology, histopathologic analysis, surgical and non-surgical treatments were extracted from the medical records. The referring veterinarians and owners were contacted for follow-up data. RESULTS: Eleven dogs were included and survival data was available for all. The most common clinical signs were bloody anal sac discharge and perianal licking. Initial treatments pursued included surgery (n=8), chemotherapy (n=1), and palliative treatment with pain medications and stool softeners (n=2). In an adjuvant setting, melanoma vaccine was pursued following surgery in three dogs and chemotherapy in one dog. Regardless of treatment, progression-free survival (mean 92 · 5 days) and overall survival times (median 107 days) were short. CLINICAL SIGNIFICANCE: Dogs in this case series had a guarded to poor prognosis regardless of treatment. Ten of 11 dogs were euthanased due to local or distant disease progression. Only 1 of 11 dogs was alive one year after diagnosis. An understanding of tumour behaviour in this location could lead to improved survival times with earlier diagnosis and treatment.

Utility of Computed Tomography versus Abdominal Ultrasound Examination to Identify Iliosacral Lymphadenomegaly in Dogs with Apocrine Gland Adenocarcinoma of the Anal Sac.

BACKGROUND: Apocrine gland adenocarcinoma of the anal sac (AGAAS) is associated with high rates of iliosacral lymph node metastasis, which may influence treatment and prognosis. Magnetic resonance imaging (MRI) recently has been shown to be more sensitive than abdominal ultrasound examination (AUS) in affected patients. OBJECTIVE: To compare the rate of detection of iliosacral lymphadenomegaly between AUS and computed tomography (CT) in dogs with AGAAS. ANIMALS: Cohort A: A total of 30 presumed normal dogs. Cohort B: A total of 20 dogs with AGAAS that underwent AUS and CT. METHODS: Using cohort A, mean normalized lymph node : aorta (LN : AO) ratios were established for medial iliac, internal iliac, and sacral lymph nodes. The CT images in cohort B then were reviewed retrospectively and considered enlarged if their LN : AO ratio measured 2 standard deviations above the mean normalized ratio for that particular node in cohort A. Classification and visibility of lymph nodes identified on AUS were compared to corresponding measurements obtained on CT. RESULTS: Computed tomography identified lymphadenomegaly in 13 of 20 AGAAS dogs. Of these 13 dogs, AUS correctly identified and detected all enlarged nodes in only 30.8%, and either misidentified or failed to detect additional enlarged nodes in the remaining dogs. Despite limitations in identifying enlargement in all affected lymph nodes, AUS identified at least 1 enlarged node in 100% of affected dogs. CONCLUSION AND CLINICAL IMPORTANCE: Abdominal ultrasound examination is an effective screening test for lymphadenomegaly in dogs with AGAAS, but CT should be considered in any patient in which an additional metastatic site would impact therapeutic planning.

Squamous cell carcinoma of the anal sacs in three dogs.

Anal sac squamous cell carcinoma is rare in dogs. Five cases have been previously reported, treatment of which involved surgery alone. This report describes three further cases of canine anal sac squamous cell carcinoma which underwent medical (meloxicam) management alone, resulting in survival of up to seven months. No metastases were identified. Squamous cell carcinoma, although extremely uncommon, should be considered as a possible differential diagnosis when a dog is presented for investigation of an anal sac mass.

Comparison of abdominal ultrasound and magnetic resonance imaging for detection of abdominal lymphadenopathy in dogs with metastatic apocrine gland adenocarcinoma of the anal sac.

Imaging studies in humans with anal and rectal cancer indicate that magnetic resonance imaging (MRI) is a more sensitive technique than abdominal ultrasound (AUS) for the detection of abdominal lymphadenopathy. The purpose of this retrospective study was to directly compare the efficacy of these two techniques in detecting abdominal lymphadenopathy in dogs with apocrine gland adenocarcinoma of the anal sac (AGAAS). Six dogs with histologically confirmed AGAAS and histopathologic confirmation of metastasis to abdominal lymph nodes (LNs) had AUS and abdominal MRI. AUS identified lymphadenopathy in two of six dogs, whereas MRI identified lymphadenopathy in all the six dogs. Lymphadenopathy was predominantly sacral in location, with involvement of the medial iliac and hypogastric LNs in only two cases. These data suggest that MRI is more sensitive than AUS for detecting sacral abdominal lymphadenopathy in dogs with AGAAS. As such, MRI could be considered in any patient with AGAAS for initial staging of this disease.

Diagnostic and prognostic value of cellular proliferation assessment with Ki-67 protein in dogs suffering from benign and malignant perianal tumors.

In the perianal region of carnivores, skin consists of modified sebaceous glands called perianal glands. Tumors originating from perianal glands are the third most frequent type of neoplasm in male dogs after neoplastic diseases of testes and skin. Ki-67 is a nuclear non-histone protein considered a proliferation marker in normal and neoplastic proliferating cells. Previous investigations revealed that Ki-67 expression may be used as a prognostic factor for breast cancer in humans. Thus, the aim of this study was to estimate the diagnostic and prognostic value of Ki-67 evaluation in dogs suffering from benign and malignant perianal tumors. The highest value of the Ki-67 index was obtained in the carcinoma group (18.50% ± 2.68), significantly higher compared to the values obtained in the control tissue (7.63% ± 2.12) and adenoma (7.33% ± 1.06; all P < 0.05). Statistically significant differences in the Ki-67 index were not found between the epithelioma group (11.95% ± 1.96) and all other groups (P < 0.05). This investigation on dogs with perianal gland tumors has shown significantly increased expression of Ki-67 antigen in carcinoma cells, while the expression of this protein was similar in the case of control tissues, adenoma and epithelioma. Thus, it may be postulated that Ki-67 evaluation in perianal gland tumors in dogs may serve as a useful marker possessing high diagnostic and prognostic value and enabling differentiation of malignant and benign tumors.

Staged marginal contoured and central excision technique in the surgical management of perianal Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is an adenocarcinoma of the apocrine glands with unknown exact prevalence and obscure etiology. It has been divided into primary EMPD and secondary EMPD, in which an internal malignancy is usually associated. Treatment for primary EMPD usually consists of wide lesion excision with negative margins. Multiple methods have been proposed to obtain free-margin status of the disease. These include visible border lesion excision, punch biopsies, and micrographic and frozen-section surgery, with different results but still high recurrence rates. METHODS: The investigators propose a method consisting of a staged contoured marginal excision using "en face" permanent pathologic analysis preceding the steps of central excision of the lesion and the final reconstruction of the surgical defect. RESULTS: Advantages of this method include adequate margin control allowing final reconstruction and tissue preservation, while minimizing patient discomfort. CONCLUSIONS: The staged contoured marginal and central excision technique offers a new alternative to the armamentarium for surgical oncologists for the management of EMPD in which margin control is imperative for control of recurrence rates.

Temporally separated bilateral anal sac gland carcinomas in four dogs.

Anal sac gland carcinoma arising from the apocrine secretory epithelium in the anal sac wall, is locally invasive and highly metastatic. The majority of anal sac gland carcinomas are unilateral on presentation, but bilateral tumours have been identified. This case series presents the outcome of four unique cases of unilateral anal sac gland carcinoma which subsequently developed contralateral anal sac gland carcinoma 50 to 390 days after removal of the initial tumour. Median survival was 1035 days after initial diagnosis and 807 days after diagnosis of the second anal sac gland carcinoma.

Evaluation of an anal sac adenocarcinoma tumor in a Spitz dog.

A 9-year-old emasculated male Spitz with tenesmus and constipation had a subcutaneous mass at the left ventral aspect of the anus with history of polyuria and polydipsia. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Abnormalities in the serum biochemistry panel included a mildly elevated serum cholesterol concentration (7.28 mmol/L; reference interval, 2.70-5.94 mmol/L), increased serum alkaline phosphatase activity (184 U/L; reference interval, 9-90 U/L), alanine transaminase (122 U/L; reference interval, 5-60 U/L) activity and aspartate aminotransferase (80 U/L; reference interval, 5-55 U/L) activity, severe increased total calcium concentration (16.3 mg/dL; reference interval, 8.2-12.4 mg/dL or 9.3-11.4 mg/dL), and decreased total calcium concentration (3.4 mg/dL, reference interval, 2.5-5.6mg/dL). Furthermore, testing revealed an increased intact parathyroid hormone concentration (38.6 pmol/L; reference interval, 3-17 pmol/L). On cytologic and histopathologic examinations, various types of cells were observed. Most of the cells were oval to polygonal and had elliptical or elongate nuclei and a moderate amount of pale to basophilic cytoplasm. The remaining cells had round to oval nuclei and pale to basophilic cytoplasm. Cells of both types were loosely adhered to each other and were arranged in rosette-like structures. Both neoplastic cell types had fine homogenous chromatin and either a small indistinct nucleolus or no visible nucleolus. Mild anisokaryosis and anisocytosis were observed. Histologically, the mass consists of glandular structures formed by cuboidal cells admixed with bundles of spindle cells. Based on location and histologic features, the final diagnosis was adenocarcinoma of the apocrine gland of the anal sac, which should be included as a cytologic differential diagnosis when spindle cells and typical epithelial cells are observed in masses in the region of the anal sac of dogs.

Ki-67 labeling in canine perianal glands neoplasms: a novel approach for immunohistological diagnostic and prognostic.

BACKGROUND: The antibody Ki-67 is a reliable and easy tool to accurately assess the growth fraction of neoplasms in humans and animals, and it has been used to predict the clinical outcome. Therefore, the aim of the present study was to investigate the immunohistochemical expression pattern of Ki-67 in normal and neoplastic perianal glands of dogs to evaluate the possible use of this proliferation marker as an ancillary method of perianal tumor diagnosis. We studied 42 cases of perianal gland neoplasms including adenomas (n = 15), epitheliomas (n = 15), and carcinomas (n = 12). As controls, 13 tissue samples from normal perianal glands were used. A Ki-67 index was established by a computer-assisted image analysis and compared with manual counting. RESULTS: Out of the 42 cases of perianal gland neoplasms, 34 were from males and eight from females. Recurrence was reported in 14 cases, being higher (8/12) in carcinomas. Immunostaining for Ki-67 revealed that the carcinomas showed a higher proliferation rate (9.87%) compared to groups of epitheliomas (2.66%) and adenomas (0.36%). For adenomas and epitheliomas of the perianal glands the computer-assisted counting and the manual counting gave similar results; however, only the computer-assisted image analysis was efficient to predict the perianal gland carcinoma recurrence. CONCLUSION: Since there were significant differences in the number of Ki-67-positive nuclei, this marker proved to be effective in helping the classification of perianal gland neoplasms and to refine the diagnosis criteria, especially in those samples with high variation in morphology/area. Also, higher Ki-67 index is related to recurrence in cases of perianal gland carcinomas. Further, the computer-assisted image analysis proved to be a fast and reliable method to assess the Ki-67 index in perianal gland neoplasms.

Squamous cell carcinoma of the anal sac in a spotted hyena (Crocuta crocuta).

A 25-yr-old spayed female spotted hyena (Crocuta crocuta) developed intermittent right pelvic limb lameness that persisted following conservative medical therapy. No obvious musculoskeletal lesions were noted on initial physical exam; however, spinal radiography was suspicious for possible intervertebral degenerative joint disease or discospondylitis. Despite prolonged medical therapy, the lameness progressed to minimal weight bearing and marked muscle atrophy of the right pelvic limb. Electromyography showed spontaneous activity in the muscles of right sciatic nerve distribution. Sensory and motor nerve conduction velocities in the right tibial and peroneal nerves were undetectable and markedly reduced, respectively. A magnetic resonance imaging (MRI) scan revealed a large, space-occupying mass on the right side of the sacrum and pelvis. Antemortem fine-needle aspiration of the mass and postmortem histopathology resulted in diagnosis of a high-grade squamous cell carcinoma of the anal sac. Squamous cell carcinoma of the anal sac is very rare in domestic dogs and previously unreported in spotted hyenas.

Multiple perianal infundibular follicular cysts in a dog.

This case report describes a 7-year-old male cocker spaniel dog with multiple perianal infundibular follicular cysts. Clinically the dog had moderate anal sacculitis, peri-anal pruritus causing it to 'scoot' and lick the area. On examination of the perianal area, there were over 100 firm, well circumscribed papules, ranged from 0.2 to 0.5 cm in diameter with a central pore, and were found in the perianal region. Alopecia was present in the perianal region. The skin tissue in the perianal region resected surgically was submitted for histological examination. Microscopically, the tissue revealed multiple dilated cysts filled with keratins and the papules corresponded to infundibular follicular cysts. The affected dog showed moderate anal sacculitis. Anal sacculitis commonly causes repeated scooting or licking the area around the anus. Therefore, the multiple follicular cysts in the present case appear to be primarily a sequela to chronic external trauma to the perianal area, probably in response to anal sacculitis. To the best of the authors' knowledge, the present report is the first documented case of multiple perianal infundibular follicular cysts in a dog.

Retrospective--systematic study and quantitative analysis of cellular proliferation and apoptosis in normal, hyperplastic and neoplastic perianal glands in dogs.

Neoplasms in the perianal region are frequently diagnosed in dogs. The aetiology is unknown, and most of them are benign. In this study, 240 neoplasms of the perianal glands of dogs were retrieved from the Department of Pathology archives of the Faculty of Veterinary Medicine and Zootechny of University of São Paulo (FMVZ/USP), from 1984 to 2004. All 240 cases were re-examined by two pathologists. Nine cases (4%) were diagnosed as hyperplasia, 49 (20%) as group I adenoma, 81 (34%) were classified as moderately differentiated adenomas of the group II, 46 (19%) were poorly differentiated adenomas of group II, 48 (20%) were carcinoma of the group III according to the classification proposed by Berrocal, and 7 (13%) were other kind of tumours. Males over 8 years of age were predominantly affected. Cell proliferation was quantified by counting proliferating cell nuclear antigen (PCNA) positive nuclei, and apoptosis was quantified by counting fluorescent eosin-stained apoptotic corpuscles (AC) in normal tissue, hyperplasia and in different histologic types of neoplasia of these glands. A parallel pattern of increase in both parameters (cell proliferation and apoptosis) was obtained. The net growth index (NGI), represents how much a cell population is proliferating or dying and was achieved by dividing the mean PCNA count in 1000 cells by the mean AC stain count in 1000 cells. NGI was different between hyperplasia and neoplasia; group I adenomas have a much higher potential of growth, and NGI decreases from benign towards malignant lesions. These results show up the importance of studying cell proliferation and apoptosis to understand the carcinogenesis of dog perianal gland.