Hepatobiliary neuroendocrine carcinoma in cats: a clinicopathologic, immunohistochemical, and ultrastructural study of 17 cases.

Hepatobiliary neuroendocrine carcinoma was diagnosed in 17 cats in a period of 10 years. Seven tumors were of intrahepatic origin, one of which was a composite containing components of epithelial and neuroendocrine carcinoma. Nine tumors were of extrahepatic origin, and one tumor was located in the gall-bladder. The cats were adult and geriatric, and the male : female ratio varied according to tumor group. Hepatomegaly, anorexia, weight loss, and vomiting were the most common clinical signs observed in the cats with hepatic neuroendocrine carcinoma. The cats with extrahepatic neuroendocrine carcinoma showed these signs plus icterus (5/9) and high concentrations of hepatic enzymes. Histologically, the hepatic neuroendocrine carcinomas had two patterns, one with acinar structures separated by vascular stroma lined by cuboidal or columnar cells and the other solid with groups of anaplastic cells separated by vascular stroma. The composite tumor consisted of both bile duct carcinoma and neuroendocrine carcinoma. The extrahepatic neuroendocrine carcinomas and the gallbladder neuroendocrine carcinoma were characterized by solid sheets or groups of round to oval cells with vascular or fibrovascular stroma. Immunohistochemical examination of 10 of the neuroendocrine carcinomas revealed that all 10 stained with neuron-specific enolase; one bile duct carcinoma and the gallbladder carcinoma stained with chromogranin; four of five bile duct carcinomas and the gall bladder carcinoma stained with synaptophysin; and one bile duct carcinoma stained with gastrin. One cat with hepatic carcinoma had duodenal ulcer; in this cat, ultrastructural studies showed neurosecretory granules leading to the diagnosis of Zollinger-Ellison syndrome. In four cats in which necropsy was permitted, carcinomatosis (4/4), lymph nodes (4/4), lungs (2/4), and intestines (1/4) were the metastatic sites. Fourteen of the 17 cats were euthanatized during or immediately after surgery.

Canine hepatic neuroendocrine carcinoma: an immunohistochemical and electron microscopic study.

Ten dogs with neuroendocrine carcinoma of the liver were selected for inclusion in the study. Clinical signs were anorexia (7), vomiting (5), polydipsia/polyuria (3), icterus (2), lethargy (2), weight loss (2), paresis (1), ataxia (1), weakness (1), collapse (1), and urinary tract infection (1). Hematologic and biochemical abnormalities included anemia (2/8), leukocytosis (4/8), high liver enzyme activity (serum alkaline phosphatase, 7/9; alanine transaminase, 7/9; aspartate transaminase, 8/9), and high total bilirubin (6/9). Grossly, the tumors were diffuse, involving all liver lobes in six dogs, and two dogs had various-sized nodules in addition to diffuse involvement. Histologically, there were eight tumors with solid or trabecular pattern (group A), one tumor with cords or rows of neoplastic cells (group B), and one tumor with multiple rosette-like structures (group C). Immunohistochemical studies revealed that all 10 neoplasms were positive for at least one of the endocrine markers used: neuron-specific enolase (NSE; 8/10), synaptophysin (5/10), and chromogranin-A (3/10). A panel of NSE, chromagranin-A, and synaptophysin detected 100% of the tumors in our series. Electron microscopy confirmed the diagnosis by the presence of intracytoplasmic neurosecretory granules in the two examined cases. Our results show that neuroendocrine markers commonly used in humans can be used for the diagnosis of hepatic neuroendocrine carcinoma in dogs, preferably a panel of synaptophysin, chromagranin-A, and NSE because chromogranin-A alone is not as useful in dogs as in humans.

Feline cystic thymoma: a clinicopathologic, immunohistologic, and electron microscopic study of 14 cases.

Cystic thymoma was diagnosed in 14 cats in a period of 6 years. The most common clinical sign was laboured breathing. The tumours were characterized by various-sized cystic spaces with central vessels. The epithelial cells varied from oval to spindle to polygonal cells enclosing cystic spaces or in pure epithelial cell components. The nuclei of the neoplastic cells had scattered chromatin and small nucleoli. The cytoplasm was pale eosinophilic. The concentration of mature lymphocytes varied from area to area with rare germinal centres. Immunohistochemically, the epithelial cells stained only with AE(1)/AE(3). The central vessels were positive for vimentin, smooth muscle actin, and factor VIII antigen. Electron microscopy revealed that the cyst walls were lined by epithelial cells that were joined by desmosomes, and the walls were well separated from the cystic spaces by a well-defined basement membrane. The neoplastic epithelial cells contained scattered tonofilaments. Three of the cats had metastasis to the lymph nodes and lungs. Two novel cases of ectopic cystic thymoma have also been described. Results of this study reveal that cystic thymoma is uncommon in cats, and that the histomorphologic, immunohistochemical, and electron microscopic features are similar to those of cystic thymoma in humans.

Neuroendocrine carcinoma of the nasopharynx in a dog.

Neuroendocrine carcinoma of the nasopharynx was diagnosed in a 9-year-old male Golden Retriever. The mass was identified by computed tomography of the nasal cavity and nasopharyngoscopy, and it was surgically excised. Histologic, cytochemical, and electromicroscopic examination of specimens confirmed the type of tumor. The dog was clincally improved for 150 days but was then reexamined because of respiratory difficulty and poor appetite. Thoracic radiographs revealed multiple nodules in all lung lobes, and ultrasonography revealed a mass in the spleen. The dog died the next day.

Malignant nerve-sheath tumor with divergent and glandular differentiation in a dog: a case report.

Malignant nerve-sheath tumor with divergent differentiation including epithelial components was diagnosed in an 8-year-old Labrador retriever. The myelographic, morphologic, and immunohistochemical findings confirmed the diagnosis. The tumor was located in the peripheral nerve roots at the first and second lumbar vertebrae. The dog survived for 161 days after resection of the tumor.

Clinicopathologic and electron microscopic study of cutaneous neuroendocrine (Merkel cell) carcinoma in a cat with comparisons to human and canine tumors.

Malignant neuroendocrine carcinoma of the skin (Merkel cell tumor) was diagnosed in an 18-year-old spayed female Maine Coon Cat. The diagnosis was made on the basis of morphologic and electron microscopic findings. The cat was euthanatized 321 days after surgical excision of the tumor. The tumor's malignancy contrasted with the benign nature of Merkel cell tumors reported in dogs and was consistent with the malignancy of Merkel cell tumors reported in humans.

Prognostic factors in dogs with urinary bladder carcinoma.

Medical records and biopsy specimens were retrospectively reviewed from 25 dogs diagnosed with unresectable urinary bladder carcinoma and treated with chemotherapy. Our intention was to identify clinical, histologic, and immunohistochemical indicators of prognosis. Immunohistochemical stains for P-glycoprotein, glutathione-S-transferase pi, and factor VIII-related antigen were applied to archived tissue. There were more spayed female dogs than castrated male dogs (76% versus 24%). Transitional cell carcinoma was the most common tumor (88%, n = 22), followed by undifferentiated carcinoma (8%, n = 2) and squamous cell carcinoma (4%, n = 1). Overall median survival was 251 days. Histologic diagnosis and immunohistochemical characteristics did not correlate with prognosis. Spayed females survived significantly longer than castrated males (358 days versus 145 days, P = .042). Dogs that received either doxorubicin or mitoxantrone in addition to a platinum-based chemotherapeutic (either cisplatin or carboplatin) lived significantly longer than those that received only a platinum compound (358 days versus 132 days, P = .042).

Radiation treatment for incompletely resected soft-tissue sarcomas in dogs.

OBJECTIVE: To evaluate efficacy of radiation for treatment of incompletely resected soft-tissue sarcomas in dogs. DESIGN: Prospective serial study. ANIMALS: 48 dogs with soft-tissue sarcomas. PROCEDURE: Tumors were resected to < 3 cm3 prior to radiation. Tumors were treated on alternate days (three 3-Gy fractions/wk) until 21 fractions had been administered. Cobalt 60 radiation was used for all treatments. RESULTS: Five-year survival rate was 76%, and survival rate was not different among tumor types or locations. Four (8%) dogs developed metastases. Eight (17%) dogs had tumor recurrence after radiation. Development of metastases and local recurrence were significantly associated with reduced survival rate. Median survival time in dogs that developed metastases was 250 days. Median disease-free interval for all dogs was 1,082 days. Median time to recurrence was 700 days. Dogs that developed recurrence after a prolonged period responded well to a second surgery. Acute radiation toxicosis was minimal; osteosarcoma developed at the radiation site in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: An excellent long-term survival rate may be achieved by treating soft-tissue sarcomas in dogs with resection followed by radiation. Amputation is not necessary for long-term control of soft-tissue sarcomas in limbs. Development of metastases and recurrence of local tumors after radiation treatment are associated with decreased survival rate. Acute and delayed radiation toxicosis was minimal with the protocol used in this study.

Comparison of needle-core (Trucut) biopsy and surgical biopsy for the diagnosis of cutaneous and subcutaneous masses: a prospective study of 51 cases (November 1997-August 1998).

Cutaneous or subcutaneous masses in 51 dogs and cats were examined by needle-core (i.e., Trucut) biopsy, and results were compared to results of surgical biopsy to assess the accuracy of the former. Needle-core specimens obtained before surgical biopsy were submitted to a single pathologist who evaluated both samples and was blinded to the results of surgical biopsy when evaluating the Trucut specimen. The results indicate that needle-core biopsy can accurately predict surgical biopsy. Thus, needle-core biopsy performed before surgical excision of masses can facilitate planning and reduce the need for numerous surgical procedures. Needle-core biopsy can direct appropriate treatment of nonmalignant masses.

Ectopic lingual thyroid tissue in a cat.

Ectopic thyroid tissue was identified at the base of the tongue in a 9-year-old, euthyroid, domestic shorthair cat. The lingual submucosa and the muscles were replaced by thyroid tissue, which consisted of various-sized follicles each lined by a row of cuboidal epithelium. Many follicles contained eosinophilic, periodic acid Schiff-positive, colloid material. Imunohistochemically, the epithelial cells stained positive for AE(1)/AE(3)and thyroglobulin. No calcitonin positive cells or parathyroid tissue was seen. The cat has been followed for 1018 days after surgery, is clinically well and remains euthyroid.

Hypoadrenocorticism as the primary manifestation of lymphoma in two cats.

Hypoadrenocorticism secondary to bilateral lymphomatous invasion of adrenocortical tissue was diagnosed in 2 adult castrated domestic shorthair cats. In both cats, findings during initial physical examination (ie, lethargy, anorexia, weight loss, and severe weakness) were consistent with severe hypoadrenocorticism. Hyperkalemia, hyponatremia, and azotemia were also detected, which were consistent with hypoadrenocorticism. Hypoadrenocorticism was documented on the basis of finding low baseline and ACTH-stimulated serum cortisol concentrations. The cats initially responded well to treatment, but both owners chose to have the cat euthanatized. Multicentric lymphoma with infiltration and destruction of the adrenal glands was confirmed during necropsy.

Malignant colonic neoplasia in cats: 46 cases (1990-1996).

OBJECTIVE: To evaluate a group of cats with malignant colonic neoplasia and to identify factors related to survival time. DESIGN: Retrospective study. ANIMALS: 46 cats with malignant colonic neoplasia. PROCEDURE: Information on signalment, diagnostic findings, histopathologic diagnosis, surgical procedure performed, identification of nodal metastasis at surgery, type of chemotherapy administered, and survival time was obtained from the medical record of each cat. A diagnosis of malignant colonic neoplasia had been established by histologic examination of endoscopic biopsy specimens (3 cats), biopsy specimens obtained during laparotomy (38), or necropsy specimens (5). RESULTS: Mean age of cats was 12.5 years (range, 6 to 18 years). Ultrasonography was useful 84% of the time in localizing the mass to the intestine. Three cats had endoscopic biopsy, 9 had incisional biopsy, 21 had mass resection, and 8 had subtotal colectomy performed. Histopathologic diagnoses included adenocarcinoma (21 cats), lymphoma (19), mast cell tumor (4), and neuroendocrine carcinoma (2). CLINICAL IMPLICATIONS: Obtaining clean margins at surgery seems to increase survival time in cats with malignant colonic neoplasia. Metastasis at the time of surgery decreases survival time. Data from this study indicate that the survival time of certain cats with colonic lymphoma may not be affected by chemotherapy. Cats with an unidentified colonic mass should receive a subtotal colectomy to increase survival time. Cats with colonic adenocarcinoma should receive a subtotal colectomy with consideration of doxorubicin administration to increase survival time.

Spinal tumors in 37 dogs: clinical outcome and long-term survival (1987-1994).

The current management of dogs with spinal canal neoplasia in a large veterinary institution was evaluated. Postoperative survival time and prognostic indicators for survival were examined. Spinal neoplasms in dogs and humans also were compared. Thirty-seven cases with histologically confirmed spinal tumors were included in the study. The cervical region was affected most commonly, and 23 (62%) of 37 cases had extradural tumors. A hemilaminectomy or a dorsal laminectomy was performed in each case; three cases received adjuvant treatment. Twelve (32%) cases were euthanized at the time of surgery, and two died immediately after surgery. One dog was euthanized 20 days after surgery because of persistent clinical signs. Twenty-two cases were followed postoperatively; nine different types of primary tumors were confirmed by histological examination of tissue specimens from these 22 cases, and three cases had metastatic lesions. The median survival time of these 22 cases was 240 days. Twelve (32%) of the 37 cases had nerve-sheath tumors; the median survival time for these 12 cases was 180 days. No prognostic indicators were identified. However, median survival times of cases with benign versus malignant tumor types were 1,410 days and 180 days, respectively (p of 0.07). Four cases each had a myxoma/myxosarcoma, a tumor previously unreported in the spinal canal in dogs.

Nonlymphoid vertebral canal tumors in cats: 11 cases (1987-1995).

OBJECTIVE: To determine outcome of cats with nonlymphoid tumors of the vertebral canal that undergo surgery. DESIGN: Retrospective study. ANIMALS: 11 cats. PROCEDURE: Information obtained from the medical records included signalment, tumor location, gross evaluation of completeness of surgical excision, histologic diagnosis, and survival time. RESULTS: Median age of cats was 12 years: all cats had negative FeLV and feline immunodeficiency virus test results. All cats underwent a hemilaminectomy or dorsal laminectomy. The tumor was located in the thoracic portion of the vertebral column in 6 cats. Six cats had intradural-extramedullary tumors. Tumors included meningioma (n = 5), malignant nerve sheath tumors (2), and meningeal sarcoma, chondrosarcoma, lipoma, and osteosarcoma (1 each). One cat was lost to follow-up, 1 cat with meningioma was alive 1,400 days after surgery, and 1 cat with a nerve sheath tumor was alive 2,190 days after surgery. Median survival time for the other 4 cats with meningioma was 180 days (range, 30 to 600 days). CLINICAL IMPLICATIONS: Cats with nonlymphoid vertebral canal tumors that undergo surgery may have a good prognosis.

A prospective study of radiation therapy for the treatment of grade 2 mast cell tumors in 32 dogs.

Surgery, chemotherapy, and irradiation have been used singly or in combination to treat dogs with cutaneous grade-2 mast cell tumors (MCT). However, optimal treatment has not been established. At The Animal Medical Center, 32 dogs with grade 2, stage 0 MCT received cobalt radiation treatment to a dose of 54 Gy; 94% had a disease-free interval of 1 year. The 2-,3-,4-, and 5-year disease-free intervals were 86%. Survival rates were 100% for 1 year and 96% for 2 to 5 years, with only 1 death caused by MCT. Primary site was not a prognostic factor for survival in this study. Minimal toxicity was observed and was limited to acute cutaneous reactions. Late-term reactions to radiation therapy were mild and considered acceptable in all cases. No deaths occurred due to treatment, and no dog was eliminated from the study because of radiation therapy toxicity. Radiation therapy appears to be an effective treatment for dogs with grade 2, stage 0 MCT.

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.

A clinicopathologic, histologic, and immunohistochemical study of mixed germ cell-stromal tumors of the testis in 16 dogs.

In a review of 262 neoplasms in 225 dogs, 18 tumors in 16 dogs were mixed germ cell-stromal tumors containing intimately admixed germ cells and Sertoli cells in tubular structures of various sizes. Seven of the 18 neoplasms were predominantly composed of germ cells, and 11 were predominantly composed of Sertoli cells. In 15 neoplasms, the germ cells were more anaplastic than the Sertoli cells, and in three neoplasms, both cell types were anaplastic. Five of the seven mixed-cell tumors with predominantly germ cells had germ cells infiltrating the adjoining tissues. Immunocytochemical studies of all 18 mixed-cell tumors, testes from five clinically normal dogs, six seminomas, and six Sertoli cell tumors revealed that neuron specific enolase (NSE) and vimentin were useful in demonstrating the dual population of the mixed cell tumors by differential staining of the germ cells and Sertoli cells. Half of the tumors stained differentially with desmin. In the normal testes, seminomas, and Sertoli cell tumors, parallel staining of germ cells and Sertoli cells by NSE and vimentin was seen, but only the appropriate tissues stained with desmin. The mixed-cell tumors in this study had morphologic features in common with mixed germ cell-sex cord stromal tumors and gonadoblastomas of human beings; clinically, they had more in common with the former. These mixed cell tumors in dogs should be classified separately.

Histologic and immunohistochemical studies of granular cell tumors in seven dogs, three cats, one horse, and one bird.

In a retrospective study, granular cell tumors in six dogs (Nos. 1-6), three cats (Nos. 1-3), one horse (No. 1), and one cockatiel (Nymphicus hollandicus) (No. 1) and a meningioma with a granular cell component in one dog (No. 7) were examined histologically and immunohistochemically. These tumors were identified by histologic examination of surgical biopsy specimens, except in the horse, in which the tumor was an incidental finding at necropsy. These diagnoses were initially made by more than one pathologist. Five of the six granular cell tumors in the dogs were in the oral cavity; one of these was in the maxillary gingiva of a 6-month-old puppy. The tumors in the cats were located in the tongue, vulva, and digit. The tumor in the horse was in the lung, and the tumor in the cockatiel was in the periocular tissue. Histologically, all granular cell tumors were characterized by oval to polygonal cells of various sizes. The cells had abundant, pale, eosinophilic cytoplasm with distinct intracytoplasmic granules, distinct cell margins, and mostly central nuclei. In the dogs, the gingival tumor had a large amount of collagen tissue, the tumor in the tongue had dilated blood vessels, and the maxillary tumor in the puppy was more cellular than the other tumors. The tumors in the cats were more anaplastic than the other tumors; one, located in the digit, was considered malignant. The granules in all of the tumors stained with periodic acid-Schiff and were diastase resistant. On staining with Luxol fast blue, the granules of all tumors stained different shades of pink, with the exception of the tumor in the tongue of a cat, which stained bluish green. Immunocytochemically, all tumors except the tumor in the cockatiel reacted against antibodies to vimentin. The granular cell tumor in the lung of the horse and the intracranial meningioma in a dog reacted to the antibody S-100 protein; the tumor in the horse reacted to neuron-specific enolase; tumors in two dogs (gingiva and skin) reacted to L-antitrypsin, and the maxillary tumor also reacted to lysozyme; the malignant tumor in the digit of a cat and the periocular tumor in the cockatiel reacted to muscle common actin and actin; the tumor in the cockatiel also reacted to desmin. Results of these immunocytochemical studies suggest that granular cell tumors, like tumors composed of rhabdoid cells, clear cells, and oncocytes, can have similar morphologic features but be of different cellular origins.

Correlation between yield and biochemical parameters in the mulberry silkworm,Bombyx mori L.

A detailed study was carried out on six biochemical parameters and four yield attributes using multiple regression analysis to investigate their relationship in the mulberry silkworm,Bombyx mori. The study generated new information on the importance of digestive amylase activity for the survival of the silkworm and revealed the inability of other enzymes to affect this relationship. Data also substantiate the observations made earlier on the genetic variability of amylase in the mulberry silkworm. Analyses extend the positive role of alkaline phosphatase and invertase in the expression of the other yield traits studied and indicate the definite possibility of using biochemical markers for silkworm breeding.