Abstract. Tissue sections and records of 56 rats with chordoma, identified in the National Toxicology Program's (NTP) data base of approximately 1 15,000 rats, were examined to determine morphological characteristics, incidence, and aspects of biological behavior. Chordomas occurred in aged rats, originated predominantly in lumbosacral vertebrae, were highly malignant, occurred three times more often in male versus female rats, and commonly produced bilateral posterior paresis, paralysis, and/or distention of the colon and rectum.Chordomas are uncommon axial skeletal neoplasms that arise from residual foci of primitive notochord.8,20In humans, residual notochord has been identified in the nucleus pulposus of the intervertebral discs, peripheral zones of vertebral bodies, including the sacrum, and the spheno-occipital region of the sku1L2J0 Chordomas may arise anywhere along the vertebral column, but most commonly involve the cranial and caudal limits of the axial skeleton. The approximate distributions of chordomas in humans are: sacrococcygeal, 50%; vertebral, 15%; and sphenoid region of the cranium, 35%.19 Chordomas have been reported in human^,^.^ r a t~,~~J~J~ mice,5 dogs,24 and mink.7Chordomas in humans are highly infiltrative, grow slowly, produce bone destruction, and frequently extend into soft tissue. The most common symptom is pain, secondary to destruction of bone and/or to pressure on nerves or adjacent organs. Sacral pain, incontinence, constipation, bladder dysfunction, and lower extremity weakness are commonly reported symptoms in humans with sacrococcygeal or vertebral chordomas.I9Previous reports of three chordomas in Fischer 344 rats describe the light and electron microscopic feat u r e~.~~,~' ,~~ These features are similar to those in humans. The rats in these reports were over 2 years old; two were female and one was a male. One chordoma originated in a lumbar vertebra,I8 one in a sacrococcygeal vertebra,17 and one in the posterior neck.12 One of these chordomas was locally destructive, having invaded surrounding muscles and nerves.I8 There were no reported metastases in any of these three cases, although one report did mention a metastatic chordoma in the lung of another rat.I8 Clinical signs in these rats were not reported. This is the first report concerning incidence and aspects of biological behavior of chordoma from a large data base of Fischer 344 rats. Materials and MethodsHematoxylin and eosin (HE)-stained tissue sections and individual animal records were obtained from all animals identified in the National Toxicology Program's data base for the following diagnoses: chordoma; metastatic pulmonary liposarcoma, chondroma, or chondrosarcoma, including those of unknown or uncertain origin; and axial skeletal, subcutaneous, or cervical vertebral liposarcomas, chondromas, or chondrosarcomas. These neoplasms were chosen because of similar histologic and gross characteristics to chordomas. Tissue sections were then examined by light microscopy to confirm the presence of a chordoma. Data fr...

We describe the effects of tissue preservation, fmtion time, and hydrolytic treatment on the detection of proliferating cell nuclear antigen (PCNA) by immunoperoxidase staining with three commercial anti-PCNA antibodies (19A2, l9F4, PClO). Our goal was to provide guidelines for PCNA immunohistochemistry in formalin-fued, paraffin-embedded specimens. In proliferative cell compartments, nudear staining was achieved with all three antibodies. In some cases PCNA was also expressed in non-proliferative, histologically normal tissues associated with tumors or other lesions elsewhere. In most autopsy specimens PNCA immunoreactivity was markedly diminished as compared with similar surgical specimens. Incubation overnight with primary antibody at 4°C enhanced PCNA immunoreactivity over incubation at 421C for 45 min. Pre-treatment with 2 N HCI did not increase staining. Staining with the PClO antibody was much better preserved than staining with the antibodies 19A2 and 19F4 after prolonged formalin fmtion of surgical specimens and in tissues obtained at autopsy. With all three antibodies, however, PCNA immunoreactivity was well preserved during formalin fmtion for 8-24 hr and during fmtion delays for 8 hr at room temperature. This indicates that PCNA is stable under conditions routinely encountered in diagnostic surgical pathology and facilitates its potential use as a diagnostic proliferation marker. ( J His-

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Abstract. Ninety-six primary cardiac neoplasms were identified from 79,97 1 Fischer 344 (F344) rats used in chronic toxicity and carcinogenicity studies by the National Toxicology Program (NTP) and National Cancer Institute (NCI), for an overall incidence of 0.1%. Neoplasms were classified as: 60 endocardial schwannomas, 23 intramural schwannomas, eight atriocaval mesotheliomas, three paragangliomas, one pericardial mesothelioma, and one hemangioma. Metastases occurred in four rats with endocardial schwannoma. Histological appearance of the endocardial and intramural schwannomas was consistent with origin from nerve sheath. Two of six endocardial schwannomas available for immunohistochemical staining were weakly positive for S-100 antigen. The atriocaval mesotheliomas, while morphologically resembling adenocarcinoma, were positive for vimentin and keratin, indicating mesothelial origin. Seventy of the 96 cardiac neoplasms occurred in rats 2 years of age or older at time of death. There were no sex or treatment-related differences in the incidence of these neoplasms, with the exception of atriocaval mesothelioma, which was more common in males.Spontaneous primary cardiac neoplasms are rare in rats with the exception of congenital atriocaval mesothelioma, which occurs in 20% of NZWGd inbred albino rats.13 Because of this low incidence, many documented cardiac neoplasms are individual case reports or incidental findings in publications on another subject. The literature on rat cardiac neoplasms is complicated by different terminology and by disagreement about cell of origin. Endocardia1 neoplasm^^^,^^ of rats have previously been referred to as endocardial disease,4 sub-endocardial endocardial mesenchymal neoplasm,2o endocardial ~c h w a n n o m a ,~.~~ neur i n o r n a~,~~ n e u r i l e m~m a s ,~~ neurosar~ornas,~~ and Anitschkow cell sarcomas.36 Intramural schwanno ma^^,^^ have also been reported as neurilemoma2* and fibroma.38 Atriocaval neoplasm^^^-^^ have previously been reported in NZWGd rats as epithelial or mesothelial neoplasms. Paragangliomas ("chemodecto ma^"),^.^^ pericardial m e s o t h e l i o m a~, I~,~~,~~ and hemangioma~~~.~* have also been reported in rats. Terminology used in this report is based on that used in a recent review of comparative pathology of cardiac neoplasms in humans and laboratory rodents.2o Although many previous reports of rat cardiac neoplasms contain detailed accounts of light and electron microscopic morphology, they are generally confined to a single neoplasm type, and it is seldom possible to assess neoplasm incidences, as the total population at risk is not stated.The purpose of this paper is to establish the incidence of cardiac neoplasms in a large population of Fischer 344 rats, to compare and contrast morphological and immunohistochemical features, and to clarifL the controversial origin of these neoplasms. Materials and MethodsNeoplasms were identified by histological examination of Fischer 344 (F344) rats from over 300,2-year toxicology and carcinogenicity studies ...