Endometrial Carcinosarcoma in a Sow: An Immunohistochemical Study

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2. Bjorklund NE, Hogsved O, Lindahl O, Sallvik K: 1972, Manure gas poisoning in a herd of calves. Sven Veterinartidning 24:616– 619. 3. Blaxland JD, Shemtob J, Francis GH, Jones GE: 1978, Mortality in a battery of laying hens attributed to the presence of noxious gases from slurry. Vet Rec 103:241–242. 4. Cummings BA, Gould DH, Caldwell DR, Hamar DW: 1995, Ruminal microbial alterations associated with sulfide generation in steers with dietary sulfate-induced polioencephalomalacia. Am J Vet Res 56:1390–1395. 5. Dahme E, Bilzer T, Dirksen G: 1983, Neuropathology of manure gas poisoning (H2S intoxication) in cattle. Dtsch Tiera¨rztl Wochenschr 90:316–320. 6. Dirksen G, Dahme E: 1982, Neuere beobachtungen zur klinik und pathologie der jauchegasgiftung. Proc XIIth World Congr Dis Cattle 2:1135–1140. 7. Donham KJ, Yeggy J, Dague RR: 1988, Production rates of toxic gases from liquid swine manure: implications for workers and animals in swine confinement buildings. Biol Wastes 24: 161–173. 8. Feilden NEH: 1982, Toxic gases from slurry. Farm Build Progr 68:7–10. 9. Gerber DB, Manci KM, Veenhuizen MA, Shurson GC: 1991, Ammonia, carbon monoxide, carbon dioxide, hydrogen sulfide, and methane in swine confinement facilities. Compend Cont Ed Pract Vet 13:1483–1488. 10. Gould DH, Cummings BA, Hamar DW: 1997, In vivo indicators of pathologic ruminal sulfide production in steers with diet-induced polioencephalomalacia. J Vet Diagn Invest 9:72–76. 11. Gould DH, McAllister MM, Savage JC, Hamar DW: 1991, High sulfide concentrations in rumen fluid associated with nutrition-

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ally induced polioencephalomalacia in calves. Am J Vet Res 52: 1164–1169. Hall AH, Rumack BH: 1997, Hydrogen sulfide poisoning: an antidotal role for sodium nitrite? Vet Hum Toxicol 39:152–154. Hays FL, Goret E, Johnson HD, Hahn L: 1972, Hydrogen sulfide (H2S) exposure in ruminants. J Anim Sci 35:189. Kandylis K: 1984, Toxicology of sulfur in ruminants. J Dairy Sci 67:2179–2187. Lawson GHK, McAllister JVS: 1966, Toxic gases from slurry. Vet Rec 79:274. Miniats OP, Willoughby RA, Norrish JG: 1969, Intoxication of swine with noxious gases. Can Vet J 10:51–53. O’Donoghue JG: 1961, Hydrogen sulphide poisoning in swine. Can J Comp Med Vet Sci 25:217–219. Osweiler GD, Carson TL, Buck WB, Van Gelder GA: 1985, Toxic gases. In: Clinical and diagnostic veterinary toxicology, ed. Osweiler GD, Carson TL, Buck WB, van Gelder GA, 3rd ed., pp. 369–377. Kendall/Hunt, Dubuque, IA. Pickrell J: 1991, Hazards in confinement housing—gases and dusts in confined animal houses for swine, poultry, horses and humans. Vet Hum Toxicol 33:32–39. Raisbeck MF: 1982, Is polioencephalomalacia associated with high-sulfate diets? J Am Vet Med Assoc 180:1303–1305. Short SB, Edwards WC: 1989, Sulfur (hydrogen sulfide) toxicosis in cattle. Vet Hum Toxicol 31:451–453. Sivertsen T, Overnes G, Karlsen B, Soli N: 1992, Poisoning of domestic animals in Norway in 1990. Nor Veterina¨rtidsskr 104: 173–182. Van t’Veld PT: 1992, Poisoning incident in finishing pigs by hydrogen sulfide from a slurry pit. Tijdschr Diergeneeskd 117: 13–14.

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Endometrial carcinosarcoma in a sow: an immunohistochemical study Daniela Bedenice, Joseph Alroy, Mary Rose Paradis Endometrial malignancy occurs rarely in most animals,5,7 except in rabbits and cattle,4 and is extremely rare in the sow.10 The following report concerns a case of carcinosarcoma in a sow. A 10-year-old Landrace sow was presented to Tufts University School of Veterinary Medicine with a 2-week history of a chronic weight loss and inappetence. The owner had noted a 15-cm-diameter enlargement on the animal’s lateral abdomen 1 week prior to admission. On physical examination, the sow was depressed, nonambulatory, tachycardiac, and cachectic and appeared to be moderately dehydrated, with slightly pale mucous membranes and prolonged capillary refill time. A firm 15-cm mass was palpated in the right From the Large Animal Hospital, School of Veterinary Medicine, Tufts University, North Grafton, MA 01536 (Bedenice, Paradis), and the Department of Pathology, Schools of Medicine and Veterinary Medicine, Tufts University, 136 Harrison Avenue, Boston, MA 02111 (Alroy). Received for publication July 14, 1998.

Figure 1. sow.

Tumor mass filling the uterine lumen of a domestic

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Figure 2. Diaphragmatic lung lobe of a domestic sow with multiple metastatic nodules attached to the visceral pleura.

abdominal region posterior to the last rib. On auscultation, lung sounds were dull. A complete blood count revealed moderate anemia (hematocrit 5 28%, 4.6 3 103 red blood cells/ml), poikilocytosis, and absolute lymphopenia (528 lymphocytes/ml). A chemistry profile revealed mild hypoglycemia (62 mg/dl), low sodium (130 meq/liter), and low chloride levels (83 meq/liter) compatible with third compartment fluid losses. Calculated bicarbonate level was slightly decreased (22.5 meq/liter), with concurrent moderately increased unmeasured anions (anion gap 5 29), suggestive of mild metabolic acidosis. Elevated creatine phosphokinase (8,212 U/liter) and lactate dehydrogenase (728 U/liter) were attributed to prolonged recumbency. Because of a poor prognosis, the sow was euthanized, and a postmortem examination was performed. At the necropsy, the pertinent findings include 10 liters of clear thoracic fluid and 4 liters of clear ascites. The uterus was enlarged, and the uterine wall was diffusely thickened up to 10 cm in greater dimension (Fig. 1). Multiple nodular masses were attached to the uterine wall, mesosalpinx, 1 ovary, visceral (Fig. 2) and parietal pleura, and liver. The nodular masses ranged in size from 1 to 10 cm in greater dimension. The mesenteric and thoracic lymph nodes were enlarged, lobulated, and firm. Representative samples of all tissues were fixed in 10% buffered formalin, embedded in paraffin, sectioned at 5 mm, and stained with hematoxylin and eosin (HE). Microscopic examination of the uterus revealed massive infiltration of the endometrium by neoplastic cells (Fig. 3), invading the myometrium and the associated blood vessels and the adjacent lymph nodes. The neoplastic cells formed pleural nodules associated with dilated lymphatics and edema but did not invade the lung parenchyma (Fig. 4). In the uterus, clusters neoplastic cells separated the endometrial glands (Fig. 5) and were surrounded by fine fibrovascular network (Fig. 6). These cells had moderate eosinophilic to amphophilic cytoplasm and large oval, open-faced nuclei with occasional prominent nucleoli. In the metastases, however, the neoplastic cells were more pleomorphic and often larger, with abundant cytoplasm and large and occasionally multiple nuclei.

Figure 3. Uterus; domestic sow. Endometrium (top), myometrium (bottom). The endometrium is replaced by neoplastic cells. HE. 253.

Figure 4. Lung (bottom) of a domestic sow, with edematous visceral pleura and metastatic nodule (top). HE. 253.

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Figure 5. Uterus; domestic sow. Section through the endometrium illustrating neoplastic cells, nonneoplastic endometrial glands, and stromal cells. The cytoplasm of the neoplastic and glandular cell stained positive with anti-cytokeratin but stromal cells did not. 1923.

A few cells had vacuolated cytoplasm and eccentric nuclei and resembled lipocytes (Fig. 6), and rare cells resembled ‘‘strap’’ cells, with elongated and moderately wide cytoplasm but lacking cross-striations (Fig. 7). The number of mitotic figures differed according to site. Mitoses were relatively rare in the uterus (Fig. 6) but were more common in metastatic sites, such as peritoneum or pleura. In the uterus, the extracellular matrix between the neoplastic cells was slightly basophilic and associated with mild desmoplasia. The neoplastic cells were accompanied by small infiltrates of lymphocytes (Fig. 6) and a few neutrophils. In contrast, necrotic foci in the metastases were associated with moderate neutrophilic infiltration and more prominent desmoplasia. To further characterize the neoplastic cells, sections were stained with periodic acid–Schiff (PAS), mucicarmine, and Masson’s trichrome and were processed for immunohisto-

chemistry. The following antibodies were used: low- and high-molecular-weight cytokeratins,a vimentin,b desmin,b and smooth muscle actin.c The avidin–biotin–peroxidase method was used to visualize the reaction product. Negative controls consisted of similarly treated sections that were not exposed to primary antibodies. The vacuoles in the neoplastic cells did not stain with PAS or mucicarmine. The cytoplasm of the neoplastic cells stained positively with both cytokeratin (Fig. 6) and vimentin (Fig. 7) but not with desmin or smooth muscle actin. These data in conjunction with the histologic appearance of the neoplasm confirm the diagnosis of carcinosarcoma. Carcinosarcoma is a mixed tumor in which both the epithelial and mesenchymal components are histologically malignant. It is also known as malignant mixed mesodermal tumor or malignant mixed muellerian tumor. Carcinosarcoma is a rare uterine malignancy in humans and is the largest

Figure 6. Uterus; domestic sow. Endometrium with pleomorphic neoplastic cells, separated by blood capillaries, presence of lipocytelike cells (arrowheads), mild lymphocytic infiltration, and abnormal mitotic figure (arrow). 1863.

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Figure 7. Lymph node; domestic sow. Neoplastic cells showing a few elongated ‘‘strap’’ cells (arrowheads) that are stained positively with anti-vimentin. 4483.

of any uterine tumor.9 Cytokeratin and vimentin are intermediate filaments; cytokeratin is a marker for epithelial cells,6 and vimentin is a mesenchymal cell marker.1 In synovial sarcomas, epithelioid sarcomas, tibial adamantinomas, and chordomas, the neoplastic cells express both cytokeratin and vimentin.1 Carcinosarcomas are subclassified into homologous and heterologous subtypes. In the homologous tumors, the sarcomatous element consists predominantly of spindle, round, or giant cells, whereas the heterologous tumors include foci of rhabdomyosarcoma, chondrosarcoma, osteosarcoma, or liposarcoma.9 In humans, immunohistochemical studies are instrumental in the diagnosis of carcinomasarcoma of the female genital tract.2,3,8,9 In this sow, the mesenchymal component contained cells that resembled lipocytes and others that resembled ‘‘strap’’ cells; therefore, this neoplasm could be considered a heterologous type of carcinosarcoma.9 There are 3 hypotheses regarding the histogenesis of carcinosarcoma of the female genital tract. The majority of investigators have proposed that the neoplastic cells arise from a single primitive or reserve cell of the endometrial stroma.3 The other hypotheses are the collision tumor (i.e., 2 stem cells) theory3 and the conversion tumor theory (i.e., metaplastic transformation of 1 neoplastic cell type into another).2 Immunohistochemical techniques were useful in the diagnosis of a carcinosarcoma in this sow. Acknowledgement. We thank Mrs. L. Duhamel for her assistance with immunohistochemistry.

Sources and manufacturers a. Boehringer-Mannheim Corp., Indianapolis, IN. b. Dako Corp., Carpinteria, CA. c. Biogenex, San Ramon, CA.

References 1. Altmannsberger W, Osborn M: 1987, Mesenchymal tumor markers: intermediate filaments. In: Current topics in pathology, morphological tumor markers, general aspects and diagnostic relevance, ed. Seifert G, pp. 155–178. Springer-Verlag, Berlin, Germany. 2. de Brito PA, Orenstein JM, Silverberg SG: 1993, Carcinosarcoma (malignant mixed muellerian (mesodermal) tumor) of the female genital tract: immunohistochemical and ultrastructural analysis of 28 cases. Hum Pathol 24:132–142. 3. Geisinger KR, Dabbs DJ, Marshall RB: 1987, Malignant mixed muellerian tumors: an ultrastructural and immunohistochemical analysis with histogenesis considerations. Cancer 59:1781– 1790. 4. Jones TC, Hunt RD, King NW, eds.: 1997, Veterinary pathology, 6th ed., pp. 1170–1172, Williams and Wilkins, Baltimore, MD. 5. Kennedy PC, Miller RB: 1993, Neoplastic diseases of tubular genitalia. In: Pathology of domestic animals, ed. Jubb KVF, Kennedy PC, Palmer N, 4th ed., vol. 3, pp. 450–454. Academic Press, San Diego, CA. 6. Moll R: 1987, Epithelial tumor markers: cytokeratin and tissue polypeptide antigen (TPA). In: Current topics in pathology, morphological tumor markers, general aspects and diagnostic relevance, ed. Seifert G, pp. 71–102. Springer-Verlag, Berlin, Germany. 7. Nielsen SW, Kennedy PC: 1990, Tumors of the female tubular genital tract. In: Tumors in domestic animals, ed. Moulton JE, 3rd ed., pp. 508–517. University of California Press, Berkeley, CA. 8. Scully RF, Young RH, Clement PB: 1998, Tumors of the ovary, maldeveloped gonads, fallopian tube and broad ligament. In: Atlas of tumor pathology, ed. Rosai J, pp. 128–131. Armed Forces Institute of Pathology, Bethesda, MD. 9. Silverberg SG, Kurman RJ: 1992, Tumors of the uterine corpus and gestational trophoblastic disease. In: Atlas of tumor pathology, ed. Rosai J, pp. 166–178. Armed Forces Institute of Pathology, Bethesda, MD. 10. Werdin R, Wold K: 1976, Uterine carcinoma in a sow. Vet Pathol 13:451–452.

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Erratum Journal of Veterinary Diagnostic Investigation 24(4) 813 © 2012 The Author(s) Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1040638712450578 http://jvdi.sagepub.com

Corrigendum

Stegelmeier, BL, et al.: 2010, Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in goats. J Vet Diagn Invest. 22: 570–577

In the article “Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in goats” by Bryan L. Stegelmeier et al., the published mean body weight and the means and statistics of serum biochemistries were carried out on groups of 4 animals, not 3, as described in the Material and Methods section. The additional animal in each group was part of an auxiliary physiologic study and though the animals were dosed and treated the same, they were not necropsied and were not included in the histologic study. To correct this oversight, the corrected weight and chemistry table (shaded cells indicate corrected numbers) are listed below. The differences are minimal and do not alter the conclusions. In addition, reference 7 has been deleted. Material and Methods: “Fifteen, yearling, female Spanish goats weighing 29.4 ± 3.4 kg (mean ± standard deviation) were randomly divided into 5 groups with 3 animals per group.”

References: Reference 7 should be deleted Corrected Table 1. Selected mean serum biochemical data from groups of 3 goats dosed with rayless goldenrod (Isocoma pluriflora) to obtain benzofuran ketone doses of 0, 10, 20, 40, and 60 mg/kg body weight for 7 days.* Serum result (mean ± standard deviation) Serum test (reference range†) Creatinine kinase (< 350 U/l)         Cardiac troponin-I (