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.     

Surgery of metastatic anal sac adenocarcinoma in five dogs

OBJECTIVE: To identify survival and morbidity information after surgery for metastases from apocrine gland anal sac adenocarcinomas (AGACA). STUDY DESIGN: Retrospective study. ANIMALS: Five dogs with AGACA. METHODS: Medical records of dogs that had surgery for treatment of metastatic AGACA between 1993 and 2003 were reviewed. Criteria for inclusion required that dogs had lymphadenectomy, with or without further debulking, as part of their treatment for metastatic AGACA and that the tissue was histologically confirmed as consistent with the primary AGACA. Signalment, history, physical examination findings, clinicopathologic data, imaging findings, surgical complications, number of surgeries, survival times, and cause of death were recorded. All dogs had a complete blood count, serum biochemical profile, serum electrolytes, 3-projection thoracic radiographs, abdominal radiographs and/or abdominal ultrasonography, and histologic confirmation of metastatic AGACA invading the regional lymph nodes and caudal abdomen. RESULTS: No surgical complications occurred. Three dogs were euthanatized; median survival, 20.6 months. One dog was alive for 19 months postoperatively. One dog had 5 sequential surgical procedures: 1 iliac lymphadenectomy and 4 debulking procedures of metastatic neoplastic tissue around and dorsal to the iliac vessels extending into the pelvic cavity, and was alive 54 months after initial surgery. CONCLUSION: Dogs with anal sac adenocarcinoma metastases to the iliac lymph nodes can experience long-term survival after surgical excision of the metastatic lesion. CLINICAL RELEVANCE: Lymphadenectomy may afford long-term survival to patients with metastatic anal sac adenocarcinoma.     

Anal sac tumours of the dog and their response to cytoreductive surgery and chemotherapy

A retrospective study of anal sac tumours without pulmonary metastases, from the author's clinical records for the period July 1989 to July 2002, was conducted to establish the response to treatment with surgery and melphalan chemotherapy. Of 21 dogs with tumours of the anal sacs 19 had apocrine gland adenocarcinomas of anal sac origin, one had a benign papillary cystadenoma and another had a malignant melanoma. Two of the 19 dogs had bilateral anal sac adenocarcinomas. Ten of the 19 dogs with apocrine gland adenocarcinomas of anal sac origin had sublumbar lymphadenopathy. Five dogs were excluded by their owners from recommended treatment. Fourteen dogs with apocrine gland adenocarcinomas of anal sac origin were treated by surgical cytoreduction and chemotherapy with melphalan. Seven of the 14 dogs had regional lymph node metastases. Cytoreduction was by local excision of the anal sac in all 14 dogs and concurrent removal of the sublumbar retroperitoneal lymph nodes in the seven dogs with regional lymph node metastases. The median survival time of dogs with sublumbar nodal metastasis was 20 months and for dogs with tumour localised to the anal sac the median survival time was 29.3 months. There was no difference in median survival of those dogs with sublumbar metastases compared to those without. This study suggests there is a role for melphalan in the treatment of dogs with anal sac adenocarcinoma when combined with cytoreductive surgery, with treatment survival times and the local recurrence rate of the primary tumour comparing favourably with previously published treatment regimes.     

Sentinel lymph node mapping of the canine anal sac using lymphoscintigraphy: A pilot study

Sentinel lymph node mapping and biopsy are important parts of oncologic staging in human medicine. Sentinel lymph node mapping enables identification of the first lymph node to receive lymphatic drainage while avoiding unnecessary lymph node dissection. Anal sac adenocarcinoma is the most common malignant neoplasm of the canine perineal area. For dogs with anal sac adenocarcinoma, lympadenectomy and metastasis to the iliosacral lymphocentrum are negative prognostics indicators. The objectives of this prospective, two by two, crossover pilot study were to establish the feasibility of lymphoscintigraphy using Technetium‐99 sulfur colloid of the canine anal sac of healthy dogs, compare two injection techniques, and the time for identification of sentinel lymph nodes using each technique. We hypothesized that both intramural and perimural injections of the canine anal sac would identify similar sentinel lymph node drainage. The sentinel lymph node was identified in all dogs using either technique. Intramural injection of the canine anal sac showed radiopharmaceutical uptake faster than perimural injection technique (P = 0.040). There was concordance between intramual and perimural techniques for the sentinel lymph node identified in 50% of cases. A sacral lymph node was identified as sentinel in three of eight dogs (37.5%). Lymphoscintigraphy of the canine anal sac is safe and feasible in normal dogs; however, the method of injection technique seems to have a significant effect on the sentinel lymph node identified.     

Carcinoma of the anal sac glands in ranch mink

During a 14-year period, carcinoma of the anal sac apocrine glands was found in 52 pastel and 8 sapphire mink (Mustela vison) kept for studies on slow viral diseases. The pastel mink varied in age from 72 to 135 months (mean age 108 months), the sapphire mink from 63 to 100 months (mean age 81 months). All but one pastel mink were females. The primary tumor varied in size from masses that caused bulges in the perineum to those that were found only after microscopic examination of the anal sac glands. Although the primary tumor grew mainly by expansion with little local infiltration, 41 of the 60 tumors had metastasized to the regional lymph nodes and sometimes also to more distant sites. The striking propensity of the carcinoma to metastasize while still small, even microscopic, often resulted in massive secondary growths, notably in the iliac lymph nodes. Hypercalcemia did not accompany the carcinoma. Its varied microscopic appearance included solid, glandular, squamous cell, and spindle or round cell components. Combinations of them formed mixed or complex histologic patterns, no doubt largely attributable to neoplastic proliferation of myoepithelial cells and squamous metaplasia of the apocrine gland epithelium. Although its cause remains obscure, the carcinoma appeared to arise from small foci of hyperplastic apocrine glands, sometimes in relation to both anal sacs. The tumor is a common and distinctive expression of neoplasia in older ranch mink.     

Canine anal sac adenocarcinomas: clinical presentation and response to therapy

A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was performed to characterize the clinical presentation and response to treatment. Clinical signs at presentation varied considerably, with signs related either to sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria-polydipsia and anorexia) being the most frequent findings. At the time of presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis. A variety of chemotherapeutic agents were administered, with partial remission (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%) dogs treated with carboplatin. The median survival for all dogs was 6 months (range, 2 days-41 months). There was no statistical association between the presence of hypercalcemia and survival, although the power of the study to detect an increase in survival of 3 months was low (.33). We conclude that platinum chemotherapy has antitumor activity in canine apocrine gland carcinoma and that further study of these agents is warranted.     

Quantification of the effect of various patient and image factors on ultrasonographic detection of select canine abdominal organs.

We assessed factors that affected ultrasonographic visualization of the pylorus, duodenal papilla, pancreas, adrenal glands, and jejunal and medial iliac lymph nodes in the dog. An abdominal ultrasonographic examination was performed on 100 canine patients, equally divided between two facilities. The pylorus was visible in 64% of the dogs, the major duodenal papilla in 42%, the left pancreatic lobe in 56%, the body of the pancreas in 60%, the right pancreatic lobe in 87%, the left adrenal gland in 91%, the right adrenal gland in 86%, the medial iliac lymph nodes in 54%, and the jejunal lymph nodes in 51%. The parameters that negatively influenced the visibility of these organs were the presence of air or food in the gastrointestinal tract (pancreas, duodenal papilla), age (lymph nodes), and body weight (pancreas, duodenal papilla). The parameters that positively influenced their visibility were the presence of air or food in the gastrointestinal tract (lymph nodes), body weight (lymph nodes), body condition score (right adrenal gland), and inherent image quality (left pancreatic lobe). There was a significant difference between the two institutes for the visualization of the pylorus, pancreas, and lymph nodes, which was probably related to different body positions used for scanning in each institution.     

SONOGRAPHIC CHARACTERISTICS OF PRESUMPTIVELY NORMAL CANINE MEDIAL ILIAC AND SUPERFICIAL INGUINAL LYMPH NODES

The medial iliac and superficial inguinal lymph nodes are not routinely palpable in the dog, and ultrasound imaging provides an alternate noninvasive technique to assess these lymph nodes, as well as to guide needle aspiration. Herein we describe the ultrasound characteristics of the medial iliac and superficial inguinal lymph nodes in 50 healthy dogs, as well as frequency and ease of node detection. The relationship between the size of the lymph nodes and the following variables was assessed: age, gender, body weight, body condition score, body length, and thoracic height and width. Right and left medial iliac lymph nodes were detected in 50 (100%) dogs, right superficial inguinal lymph node(s) in 49 (98%) dogs, and left superficial inguinal lymph node(s) in 47 (96%) dogs. In >90% of both sets of lymph nodes, the echogenicity was hypoechoic or isoechoic to surrounding tissues, with a corticomedullary or homogenous echotexture, smooth, clearly defined margins, and a fusiform shape. Increasing weight, distance from the sternal manubrium to the ischium, and thoracic height and width were associated with increased lymph node size (P‐values<0.05). Average lymph node sizes and range of sizes provide preliminary reference values for the medial iliac and superficial inguinal lymph nodes in normal dogs.     

Plasma concentrations of parathyroid hormone-related protein in dogs with potential disorders of calcium metabolism

The plasma concentrations of total calcium, ionised calcium, albumin, parathyroid hormone and parathyroid hormone-related protein (PTHrp) were measured in 25 dogs with lymphoma, nine dogs with primary hyperparathyroidism and seven dogs with adenocarcinoma of the apocrine gland of the anal sac. Plasma total calcium, ionised calcium, albumin and parathyroid hormone-related protein were measured in 18 clinically normal control dogs. The concentration of PTHrp was high in 12 of the 14 dogs that were hypercalcaemic because of an underlying malignancy but was within the reference range in all the control dogs, in the 17 normocalcaemic dogs with lymphoma and in the seven dogs which were hypercalcaemic because of a parathyroid adenoma.     

Ultrasonographic assessment of abdominal lymph nodes in puppies

The jejunal and medial iliac lymph nodes of 53 clinically normal dogs between the age of 4 and 6 weeks were examined ultrasonographically. At least two jejunal and both left and right medial iliac lymph nodes were seen in all dogs. One hundred forty‐five jejunal, 53 right medial iliac and 53 left medial iliac lymph nodes in six litters of dogs, for a total of 251 lymph nodes, were measured for cross sectional maximum diameters. Mean jejunal lymph node length was 16.4 mm (range 6.4–34.9 mm) and mean width was 6.0 mm (range 2.3–15.7 mm). The mean medial iliac lymph node length was 13.6 mm (range 7.2–27.8 mm) and mean width was 4.4 mm (range 1.9–8.2 mm). Significant differences of lymph node size, noted between and within breeds, may not be of clinical significance. The mean size of the combined left and right medial iliac nodes was within previously published ranges for normal adult dogs. Lymph nodes were described in four litters of dogs (162 lymph nodes). Lymph nodes were either uniformly hypoechoic (108/163, 66%) or centrally hyperechoic with a hypoechoic rim (55/163, 34%). Although most (60%) lymph nodes were oval, a variety of shapes were seen, including vermiform and complex branching shapes. We concluded that in 4‐ to 6‐week‐old dogs, medial iliac lymph nodes are similar in size to adult dogs and jejunal lymph nodes are multiple, routinely seen, are larger than in adults and often have unconventional shapes.     

Hypercalcaemia associated with a retroperitoneal apocrine gland adenocarcinoma in a dog

A seven-year-old, entire female golden retriever was presented with a history of polyuria/polydipsia and progressive dysuria. Clinical examination, radiography and ultrasonography demonstrated urinary retention due to a large soft tissue mass in the retroperitoneal space. Laboratory findings revealed paraneoplastic hypercalcaemia. Fine-needle aspiration cytology of the mass suggested an epithelial tumour, resembling an apocrine gland carcinoma of the anal sac. Following euthanasia and necropsy, the histopathological diagnosis of the retroperitoneal mass was apocrine gland adenocarcinoma. Despite ante- and postmortem examination, no perineal or anal sac tumour was found. The retroperitoneal tumour in this case could be a very large lymph node metastasis from an occult primary apocrine carcinoma of the anal sacs, or it could represent the first case of an ectopic apocrine gland carcinoma of the retroperitoneal space in a dog.     

Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs

There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post‐operative management of ASAGAC. Seventy‐four dogs with naturally occurring ASAGAC underwent surgery. Forty‐four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC.     

Frequency of an accessory popliteal efferent lymphatic pathway in dogs

Staging and therapeutic planning for dogs with malignant disease in the popliteal lymph node are based on the expected patterns of lymphatic drainage from the lymph node. The medial iliac lymph nodes are known to receive efferent lymph from the popliteal lymph node; however, an accessory popliteal efferent pathway with direct connection to the sacral lymph nodes has also been less frequently reported. The primary objective of this prospective, anatomic study was to describe the frequency of various patterns of lymphatic drainage of the popliteal lymph node. With informed client consent, 50 adult dogs with no known disease of the lymphatic system underwent computed tomographic lymphography after ultrasound‐guided, percutaneous injection of 350 mg/ml iohexol into a popliteal lymph node. In all 50 dogs, the popliteal lymph node drained directly to the ipsilateral medial iliac lymph node through multiple lymphatic vessels that coursed along the medial thigh. In 26% (13/50) of dogs, efferent vessels also drained from the popliteal lymph node directly to the internal iliac and/or sacral lymph nodes, coursing laterally through the gluteal region and passing over the dorsal aspect of the pelvis. Lymphatic connections between the right and left medial iliac and right and left internal iliac lymph nodes were found. Based on our findings, the internal iliac and sacral lymph nodes should be considered when staging or planning therapy for dogs with malignant disease in the popliteal lymph node.     

Expression of PDGFR-β and Kit in canine anal sac apocrine gland adenocarcinoma using tissue immunohistochemistry

Canine anal sac apocrine gland adenocarcinoma (ASAGAC) is an uncommon but highly invasive and metastatic malignancy. Toceranib phosphate (Palladia) is a receptor tyrosine kinase (RTK) inhibitor that targets several members of the split kinase RTK family. These membrane receptors are important for cell cycling, apoptosis and angiogenesis, all of which can contribute to carcinogenesis. The objective of this study was to evaluate archived, paraffin-embedded canine ASAGAC and normal canine anal sacs for immunohistochemical detection of Kit and platelet-derived growth factor receptor beta (PDGFR-β). Two of 77 neoplasms (2.6%) expressed Kit. Fifteen of the neoplasms (19.5%) were positive for PDGFR-β expression. None of the normal canine anal sac epithelium expressed Kit or PDGFR-β. Because of these results, further investigation should be considered to determine the role of RTKs in the clinical course and treatment of canine ASAGAC.     

Squamous cell carcinoma of the anal sac in five dogs

Tumors of the perianal area of dogs are common and include multiple tumor types. Whereas perianal adenomas occur often, adenocarcinomas of the apocrine glands of the anal sac occur less frequently. A review of the literature revealed no reports of squamous cell carcinomas arising from the epithelial lining of the anal sac. Squamous cell carcinomas originating from the lining of the anal sac were diagnosed in five dogs. Microscopically, the tumors consisted of variably sized invasive nests and cords of epithelial cells displaying squamous differentiation. Four of the five dogs were euthanatized because of problems associated with local infiltration by the tumors. In the fifth dog, there was no evidence of tumor 7 months after surgical removal, but further follow up was not available.     

CONTRAST‐ENHANCED HARMONIC ULTRASONOGRAPHY OF MEDIAL ILIAC LYMPH NODES IN HEALTHY DOGS

Herein, we describe the normal contrast‐enhanced harmonic, color, and power Doppler ultrasonographic characteristics of the medial iliac lymph nodes in healthy dogs. Contrast‐enhanced harmonic ultrasonography of the medial iliac lymph nodes was performed on 14 healthy dogs after intravenous administration of the lipoprotein‐bound inert gas‐filled microbubble contrast media Definity^®. Time–pixel intensity curves were generated for 1‐min postinjection. Quantification of these curves was performed using Philips QLab software. Non‐contrast‐enhanced power and color Doppler examinations were performed in each node to assess vascular patterns subjectively. Normal lymph nodes exhibited a mean contrast wash‐in phase beginning at 6.3 s from the time of injection with mean peak pixel intensity at 12.1 s. Angioarchitecture was best visualized with contrast‐enhanced harmonic ultrasound compared with power and color Doppler. Normal lymph nodes in dogs have a central artery with a centrifugal and uniform branching pattern. Contrast‐enhanced harmonic ultrasonography is a noninvasive examination that demonstrates improved visibility of the intranodal architecture of healthy medial iliac lymph nodes in dogs compared with conventional, non‐contrast‐enhanced Doppler methods that may have future clinical applications.     

Hypercalcaemia in the dog: a study of 40 cases

Forty dogs referred to the University Department of Clinical Veterinary Medicine, Cambridge for medical and oncological conditions between 1985 and 1990 were found to be hypercalcaemia In 18 cases the primary or underlying condition was diagnosed as lymphoproliferative disease with multicentric lymphoma occurring most commonly. Ten dogs were suffering from hypoadrenocorticism (Addison's disease) and two had adenocarcinomas of the apocrine glands of the anal sac. In three dogs a clinical diagnosis of renal dysplasia was made, this diagnosis being confirmed at post mortem examination in one dog. In the remaining cases hypercalcaemia was associated with a primary lung tumour, a thymoma, an osteosarcoma with widespread skeletal metastases, primary hyperparathyroidism due to a parathyroid adenoma, chronic panniculitis, iatrogenic hypoadrenocorticism following mito-tane therapy (one case each] and, in a further case, no diagnosis was reached. The most common clinical signs were inappetence, polyuria/ polydipsia, weakness, vomiting, lethargy and depression. As a group, the dogs with lymphoproliferative disease had a significantly higher mean plasma calcium concentration (4-3 ± 0–7 vs 3–5 ± 0–4 mmol/litre), a significantly lower mean plasma inorganic phosphate concentration (1–5 ± 0–5 vs 2–4 ± 09 mmol/litre) and were significantly older (5-5 ± 2–4 vs 3-3 + 1–8 years) than the dogs with hypoadrenocorticism.