A neuroendocrine carcinoma of undetermined origin in a dog

In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-like structures. Scattered small necrotic foci and invasion to fibrous septa were typically observed. Neoplastic cells showed round to oval-shaped nuclei with prominent nucleoli and abundant eosinophilic cytoplasm that were positive for Grimelius' silver impregnation staining and immunostaining with cytokeratin, synaptophysin, vasoactive intestinal peptide and chromogranin A, indicative of the development of a neuroendocrine carcinoma. However, judging from the distribution of tumors lacking the portion suggestive of the primary site in any organ examined, as well as no further indication of differentiation potential of neoplastic cells, this tumor has so far been diagnosed as neuroendocrine carcinoma of undetermined origin.     

A Case of Metastatic Adrenocortical Carcinoma Diagnosed with Steroidogenic Factor-1 in a Sprague-Dawley Rat

This report describes the morphological and immunohistochemical characteristics of an adrenocortical carcinoma with distant metastasis in a Sprague-Dawley rat. Macroscopically, a single large mass was observed in the adrenal gland, and multiple nodules were noted in the lung, liver and thyroid. Histologically, the adrenal tumor consisted of a solid growth of eosinophilic round cells with nuclear atypia. Vascular invasion was present, and multiple metastatic lesions were also observed in the lungs, liver, and mediastinal lymph nodes. Immunohistochemically, the nuclei of these tumor cells were positive for Steroidogenic Factor-1 (SF-1). In the thyroid, tumor cells histologically resembling adrenal cells were immunohistochemically negative for SF-1 but positive for calcitonin; thus the lesion was diagnosed as thyroid C-cell carcinoma. From these results, the present case was diagnosed as adrenocortical carcinoma with distant metastases. SF-1 could be a valuable marker for the differential diagnosis of adrenocortical tumors versus other endocrine tumors such as C-cell carcinoma.     

Thyroid C-cell carcinoma with amyloid in a red fox (Vulpes vulpes schrenchki).

An amyloid-producing medullary thyroid carcinoma (MTC) in a red fox (Vulpes vulpes schrenchki) bred in a zoo was examined using histopathologic and immunohistochemical techniques. The neoplastic cells had an ill-defined cytoplasmic membrane and abundant, finely granular eosinophilic cytoplasm, containing numerous argyrophilic granules. The neoplastic tissues were divided into various sizes by a vascular connective stroma, which was partly fibrovascular with broad areas of hyalinization containing varied amounts of amyloid. Immunohistochemically, neoplastic cells showed reactivity to anti-calcitonin, neuron-specific enolase, somatostatin, and keratin antibodies. However, amyloid in the stroma did not show immunoreactivity to the antibodies used. Histologic and immunohistochemical features of MTC in the present animal were analogous to those of the C-cell carcinoma derived from thyroid C cells (parafollicular cells) reported in humans and dogs.     

What Is Your Diagnosis?

A fine needle aspirate was taken from an enlarged prescapular lymph node from an 8-year-old male Doberman Pinscher. Squash preparations were prepared for cytologic examination by air-drying and staining with Wright's stain (Hema-Tek Stainer:Ames Laboratories). Cytologically, the mass consisted of a population of non-cohesive, variably sized (15 to 30 μ m) round to oval cells enmeshed in a background of eosinophilic finely fibrillar extracellular matrix material. The cells contained slightly oval to round nuclei which were occasionally eccentric in location. The chromatin was moderately hyperchromic and most nuclei contained a single prominent round nucleolus. A few cells contained multilobulated nuclei or were multinucleate. Cytoplasm was abundant, lightly to deeply basophilic and moderately granular (Figs.1&2).     

Cytologic appearance of a keloidal fibrosarcoma in a dog

A 5-year-old neutered male, mixed-breed dog was presented with a single 4-mm, nodular, firm, haired subcutaneous mass on the left flank that had been present for approximately 2 weeks. Cytologic preparations of the mass revealed many spindle cells, few mast cells, rare eosinophils, rare macrophages, abundant hyalinized collagen, and moderate numbers of erythrocytes. The spindle cells were oval to fusiform, with oval nuclei, finely stippled to lacy chromatin, 1-5 variably sized prominent nucleoli, and moderate to abundant cytoplasm with indistinct cell borders, wispy cytoplasmic extensions, and occasionally, fine magenta granulation. The cell population exhibited moderate anisocytosis, moderate anisokaryosis, and rare binucleation. The eosinophilic material occurred both in large angular aggregates with blunt ends and in amorphous aggregates with fine wispy projections. Histologic findings were consistent with a keloidal fibrosarcoma. To the authors' knowledge, this report is the first to describe the cytomorphologic characteristics of a keloidal fibrosarcoma in a dog.     

Histopathological and immunohistochemical findings of primary and metastatic medullary thyroid carcinoma in a young dog

This report describes the gross, histological, and immunohistochemical features of medullary thyroid carcinoma (MTC) with pulmonary metastases in a young dog. Sheets of pleomorphic cells supported by fibrous stroma characterized the primary mass, while metastatic nodules had a neuroendocrine pattern. Despite differing histologic features, all masses showed marked immunoreactivity against calcitonin and multiple neuroendocrine markers consistent with MTC. Although MTC is a well-recognized entity, it may be difficult to distinguish this mass from other thyroid neoplasms, necessitating immunohistochemical characterization.     

Cytologic, histologic, and immunohistochemical features of lingual liposarcoma in a dog

A 9-year-old female spayed mixed-breed dog was presented to the referring veterinarian with a history of decreased appetite and difficulty with prehension and swallowing because of a firm oval mass in the tongue. On cytologic evaluation of a fine-needle aspirate of the mass there were numerous round to polygonal cells organized individually or in loose clusters with rare branching capillaries. The cells had eosinophilic granular cytoplasm, round to oval nuclei, and occasionally indistinct borders. The cytologic diagnosis was granular cell tumor (GCT) of the tongue. Impression smears of a biopsy sample of the lingual mass contained similar eosinophilic granular cells with variable numbers of clear vacuoles in the background, numerous perivascular arrangements, and occasional lipoblasts, suggestive of liposarcoma. On histologic examination the tumor was composed of numerous lipocytes with rare foci of round eosinophilic granular cells without evidence of vacuolation; occasionally, atypical mitotic figures were seen. Immunohistochemically, the cells were uniformly negative for periodic acid-Schiff and did not express smooth muscle actin, desmin, or cytokeratin but were immunoreactive for vimentin and S100. A diagnosis of well-differentiated liposarcoma was made on the basis of morphologic and immunohistochemical results. Eosinophilic granular cells may be a component of well-differentiated liposarcoma and are not limited to GCT. Liposarcoma should be considered in the differential diagnoses of lingual tumors in the dog when cytological evaluation reveals eosinophilic granular cells consistent with GCT.     

Cranial mediastinal carcinomas in nine dogs*

Nine dogs were diagnosed with cranial mediastinal carcinomas. Based on histological and immunohistochemical analysis, four dogs were diagnosed with ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with anaplastic carcinomas. Clinical signs and physical examination findings were associated with a space‐occupying mass, although one dog was diagnosed with functional hyperthyroidism. Surgical resection was attempted in eight dogs. The cranial mediastinal mass was invasive either into the heart or into the cranial vena cava in three dogs. Resection was complete in six dogs and unresectable in two dogs. All dogs survived surgery, but four dogs developed pulmonary thromboembolism and two dogs died of respiratory complications postoperatively. Adjunctive therapies included pre‐operative radiation therapy (n = 1) and postoperative chemotherapy (n = 3). Three dogs had metastasis at the time of diagnosis, but none developed metastasis following surgery. The overall median survival time was 243 days. Local invasion, pleural effusion and metastasis did not have a negative impact on survival time in this small case series.     

Histopathological and Immunohistochemical Characterization of Spontaneously Occurring Uterine Deciduomas in Young Adult Rats

Uterine deciduomas were found in two female virgin rats, a 15-week-old Lewis rat and a 7-week-old Sprague-Dawley rat. The firm white nodules were located at the base of unilateral uterine horns and were approximately 6 mm and 4 mm in diameter. Histopathologically, the nodules were composed of three areas, each with a distinct type of proliferating cells: large epithelioid decidual cells with round nuclei, prominent nucleoli and abundant eosinophilic cytoplasm (antimesometrial region); compact spindle-shaped cells with oval nuclei and vacuolar cytoplasm (transitional region); and pleomorphic and spiny cells with round to oval nuclei and compact eosinophilic cytoplasm (mesometrial region). These cells proliferated in sheet-like arrangements and transformed into the other types of cells located in surrounding regions. Immunohistochemically, proliferating cells in all regions were strongly positive for proliferating cell nuclear antigen. The proliferating cells were positive for vimentin, and large decidual cells were positive for common acute lymphoblastic leukemia antigen 10, a marker of uterine interstitial cells. Large decidual cells were positive for α-smooth muscle actin and desmin, suggesting differentiation into muscular cells. Progesterone receptor was expressed in all cell types; however, estrogen receptor α was not expressed in the antimesometrial region. These extremely rare tumor-like nodules represent nonneoplastic lesions referred as decidual reactions of endometrial interstitial cells, and their biological behavior is that of a space-occupying benign tumor in young rats. Our cases might provide information as a historical control in toxicity and pharmacological studies in rats.     

What is your diagnosis? Shoulder mass in a dog with lameness

Abstract: An adult castrated male Golden Retriever of unknown age was presented with a history of weight loss and progressive left thoracic limb lameness. On physical examination, a solid mass was palpated on the left scapula that had areas of lysis on radiographs and an area of cortical bone loss on ultrasound. Hepatomegaly, abdominal distension, and numerous intra‐abdominal soft tissue masses were also found. Fine‐needle aspirates of the scapula and several abdominal masses contained numerous free nuclei mixed with fewer individualized, intact cells that were round in shape and rarely formed small sheets. The cells had high nuclear to cytoplasmic ratios, central nuclei, coarsely stippled chromatin, 1–2 prominent nucleoli, and basophilic cytoplasm with indistinct cell borders. The cytopathologic interpretation was neuroendocrine neoplasia, either metastatic or multicentric. The dog was subsequently euthanized and based on gross and histologic findings at necropsy, a diagnosis of pheochromocytoma with multiple metastases was made. The neoplastic cells stained positive with Grimelius stain and were immunoreactive for synaptophysin and chromogranin A. Pheochromocytomas are rare tumors in dogs and uncommonly undergo distant metastasis, especially to bone.     

Cytologic variants of γδ T cell lymphoma in cattle

Two cytologic variants of γδ T cell lymphoma are described. Case 1 represented a giant cell variant found in a 5-year-old Holstein cow, which had large tumor masses in the pelvic cavity. This variant consisted of very large lymphoid cells with round to oval nuclei, medium-sized nucleoli and abundant cytoplasm. Case 2 was an aborted 7-month-old female Holstein fetus, which represented an immature cell variant. Most of the neoplastic lesions were located in the skin and pleural and peritoneal submesothelial tissues. The neoplastic tissues were composed of homogeneous growth of lymphoma cells characterized by inconspicuous nucleoli and finely dispersed chromatin. Both cases demonstrated CD3, CD8 and WC1 immunoreactivity. The current study revealed that there are 4 cytologic variants (common, giant cell, hypergranular and immature cell) in bovine γδ T cell lymphomas.     

COMPUTED TOMOGRAPHIC FEATURES OF BASIHYOID ECTOPIC THYROID CARCINOMA IN DOGS

Eight dogs with a firm, nonpainful swelling in the ventral laryngeal region and with a final diagnosis of ectopic thyroid carcinoma were investigated by Computed Tomography (CT) at six different institutions. Computed Tomography findings were reviewed, focusing on lesion volume, shape, margins, relationship with surrounding structures and adjacent vessels, attenuation characteristics, and presence of metastases. Ectopic thyroid carcinomas were seen as oval‐to‐bilobed masses centered on the basihyoid bone with associated bone lysis, highly vascularized capsules with central poorly contrast enhancing areas. In all cases there was laryngeal wall infiltration, in two dogs invasion of the laryngeal lumen and in one case invasion of the ventral muscular and subcutaneous plane. Metastases were found in retropharyngeal lymph nodes (three cases) and in the lung (two cases). Ectopic thyroid carcinoma should be considered in the differential diagnosis when a mass in the basihyoid region is present. Described CT features may be typical for ectopic thyroid neoplasia and could be used to help decide the therapeutic plan.     

Anal sac gland carcinoma in a cat

A perianal mass in a 15-year-old domestic shorthair cat with a history of a firm, painful swelling in the left ventrolateral perianal region was surgically excised and submitted for light microscopic evaluation. Histologically, this was a poorly demarcated, unencapsulated, multilobulated neoplasm that invaded surrounding perirectal skeletal muscle bundles. Lobules were composed of sheets and acinar arrangements of cuboidal to round neoplastic epithelial cells with scant to moderate eosinophilic to amphophilic cytoplasm and a round or oval nucleus with coarse chromatin. Mitotic figures were 2 per 40 x objective field. Acinar lumina sometimes contained eosinophilic proteinaceous material or cell debris. These microscopic features are consistent with anal sac gland carcinoma. This is the second report of this neoplasm in a cat.     

What is your diagnosis? Preputial mass in a ferret

Abstract: A 7‐year‐old neutered male polecat‐type ferret (Mustela putorius furo) was presented for evaluation of a cutaneous mass close to the preputial orifice. Cytologic examination of a fine‐needle aspirate revealed numerous large clumps of amorphous pink mucinous material and numerous large clumps of slightly pleomorphic epithelial cells. The cells were arranged in papillary structures, palisades, and loosely cohesive sheets with a vaguely honeycomb appearance. Occasional acinar formations were also seen. The cells had moderate to large amounts of finely granular gray to gray–blue cytoplasm. The cells were round to wispy and elongated, with indistinct borders. Often, anuclear cytoplasmic clumps were seen free in the background or adjacent to intact cells. Nuclei were round to oval and usually off‐center. Chromatin was finely stippled and contained 1–3 indistinct nucleoli. Anisokaryosis and anisocytosis were moderate. Binucleated cells were noted occasionally. The cytologic features were consistent with a carcinoma of probable apocrine origin. Histopathologic examination supported a diagnosis of secretory apocrine adenocarcinoma of the preputial skin. Secretory apocrine adenocarcinomas of the prepuce are seen relatively frequently in ferrets, although their cytologic appearance has not been described widely. These neoplasms carry a poor prognosis although prompt surgical removal with wide and deep surgical margins and adjunctive radiotherapy may improve survival.     

Immunohistochemical evaluation of a malignant intestinal carcinoid in a dog

An intestinal carcinoid with multiple metastases was identified in a 5-year-old male Shih Tzu with a clinical history of anemia, fatigue, anorexia, vomiting, intermittent diarrhea, intestinal bleeding, and progressive emaciation. There was a yellowish-white mass 15 mm in diameter in the anterior jejunum and white nodules consistent with metastases in many organs. Histopathologically, the mass consisted of neoplastic cells arranged in lobules, trabeculae, or closely interdigitating islands of cells. Neoplastic cells were generally polygonal with round hyperchromatic nuclei, modest amounts of eosinophilic cytoplasm, and eosinophilic cytoplasmic granules. Mitoses were common. Rosette formations of tumor cells were apparent in metastatic tumors. Immunohistochemically, tumor cells stained positive for cytokeratin 13, synaptophysin, protein gene product 9.5, neuron-specific enolase, chromogranin A, calcitonin gene-related peptide, serotonin (5-HT), and Leu-7. Serum 5-HT concentrations for this dog were increased 10-fold compared with those of normal dogs. All findings were consistent with a diagnosis of a malignant intestinal carcinoid.     

Thyroid follicular adenocarcinoma in a ferret

A 5-year-old male castrated ferret was presented to the Washington State University College of Veterinary Medicine for evaluation of progressive hair loss and a large, rapidly growing ventral neck mass. The patient had been diagnosed previously with an insulinoma, which was managed medically. Fine-needle aspirates of the neck mass were performed. The cytologic results were most consistent with epithelial neoplasia, likely a carcinoma; thyroid origin was considered likely based on tumor location and cell morphology. The tumor grew rapidly, and the owners elected euthanasia 1 week after examination. At necropsy, a circumscribed, ovoid mass disrupted the right cervical musculature next to the right lobe of the thyroid gland. Histopathologic evaluation revealed an infiltrative mass consisting of cuboidal cells arranged in solid sheets and irregular follicles enclosing colloid. The cells were large, with prominent nucleoli, and had a high mitotic rate. The histopathologic diagnosis was consistent with thyroid follicular adenocarcinoma. Immunochemical findings confirmed thyroglobulin production by neoplastic cells, but to a lesser extent than in normal ferret thyroid tissue. To our knowledge, this is the first case of thyroid follicular adenocarcinoma to be reported in a ferret, with only 1 other case of thyroid carcinoma, a C-cell carcinoma, described previously.     

Cytologic and immunohistochemical characterization of a lung carcinoid in a dog

An 11-year-old neutered male Yorkshire Terrier was presented to the Haemaru Referral Animal Hospital with a history of unresponsive tracheal collapse and an incidental finding of a lung nodule in the left caudal lung lobe on radiography. Thorough physical examination and imaging studies revealed no other masses. Cytologic examination of C-arm mobile fluoroscopy-guided fine-needle aspirates revealed numerous free nuclei and a low number of small round cells with moderate to abundant pale basophilic cytoplasm. Some cells contained indistinct basophilic granules in their cytoplasm, and extracellular pink material was noted. A caudal lung lobectomy was performed, and histologic evaluation of the mass revealed round to polygonal cells with abundant eosinophilic granular cytoplasm and round nuclei with mild anisokaryosis and 0-3 mitotic figures per high-power field. Cells were arranged in packets separated by fine fibrovascular stroma, suggestive of a pulmonary neuroendocrine neoplasm, specifically a carcinoma/carcinoid. The cells were immunoreactive for chromogranin A and neuron-specific enolase, and negative for cytokeratin, synaptophysin, calcitonin, thyroglobulin, parathyroid hormone, CD79a, light lambda, and vimentin. With these findings the tumor was diagnosed as a primary lung carcinoid. Eleven months after resection, there was no evidence of tumor regrowth or metastasis. The absence of necrosis, few mitotic figures, minimal pleomorphism, and benign behavior of this tumor resembled those of a typical carcinoid in humans.     

Immunohistochemical characterization of a hepatic neuroendocrine carcinoma in a cat.

A hepatic mass was identified in a 5-year-old, female mixed-breed cat that died spontaneously after a clinical history of progressive emaciation, ptyalism, and persistent coryza. At necropsy, a 7-cm-diameter, yellow-brown, firm, multilobulated tumor was identified in the liver. Microscopically, the mass consisted of neoplastic cells arranged in small, closely packed nests within a thin fibrovascular stroma. These cells were of medium sized and polygonal, with fine argyrophilic cytoplasmic granules. Nuclei were predominantly round with finely stippled chromatin and indistinct nucleoli. Mitotic figures were numerous. Immunohistochemically, most of the neoplastic cells were immunoreactive for chromogranin A, neuron-specific enolase (NSE), and cytokeratin AE1/AE3 and weakly labeled for synaptophysin. The tumor was negative for glial fibrillary acidic protein (GFAP), vimentin, and cytokeratins 5, 6, 8, and 17. Vascular emboli and intrahepatic micrometastasis were also identified with chromogranin A. All these features were consistent with a hepatic neuroendocrine carcinoma and emphasized the importance of using a panel of antibodies to diagnose such rare tumors.     

A Comparison of Medullary Thyroid Carcinoma and Thyroid Adenocarcinoma in Dogs: A Retrospective Study of 38 Cases

The medical records of 38 dogs with thyroid neoplasia that were treated by surgical excision of the tumor, or had an incisional biopsy performed as a diagnostic procedure, were reviewed. Of the 38 dogs, 21 (55%) had resectable tumors, whereas 17 (45%) had an incisional biopsy as the tumors were nonresectable. All dogs had an initial diagnosis of thyroid carcinoma. The type of carcinoma was confirmed in 33 dogs by histological and immunohistochemical examination. Twelve dogs (36%) had medullary thyroid carcinoma, and 21 dogs (64%) had thyroid adenocarcinoma. Of the 12 dogs with medullary thyroid carcinoma, 10 (83%) had resectable tumors. Of the 10, three (30%) had at least a 1-year survival. None had radiographic evidence of metastasis at the time of surgery. Of the 21 dogs with thyroid adenocarcinoma, 11 (52%) had resectable tumors. Of the 11 dogs, five (45%) had at least a 1-year survival. Three dogs had radiographic evidence of metastasis at the time of surgery. Of 10 dogs with nonresectable thyroid adenocarcinoma, two dogs (20%) had at least a 1-year survival. In the dogs in this study, medullary thyroid carcinoma was more prevalent than previously reported. Most of the medullary thyroid carcinomas were well circumscribed and resectable. Medullary thyroid carcinoma may possess gross and histological characteristics of a less malignant nature when compared with other thyroid carcinomas.