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...

A total of 121 spontaneous amelanotic melanomas of the skin were identified in 70 of 11,171

Abstract. Five intraocu lar amela notic melanomas were identified in the National Toxicology Program 's database consisting of records from more than 60,000 female and 60,000 male F344 rats, which were used as control and treated animals in 2-year carcinogenicity studies. The five spontaneous melanomas were grossly observed as white or yellow, unilateral nodules, which originated in the region of the iris and ciliary body, often also involving the choroid. These amelanotic melanomas were composed predomin antly of spindlecells arranged in a whorled pattern often with perivascular orientation. Mitotic figures were common in five tum ors. The spindle cells had a positive immunoreactivity for S-I00 protein but were negative for desmin. Electron microscopic studies provided clear evidence that these tum ors originated from the uveal melanocytes. Ultrastructurally, the spindle cells contained numerous cytoplasmic premelanosomes (stage II melanosomes) that were not associated with melanin . Special histochemical studies showed that the spindle cells had a negative reaction for melanin . Although electron microscopic features are critical in the diagnosis of amelanotic melanomas of the uveal tract, the whorled pattern of spindle cells is a useful histologic criterion in differential diagnosis of this tumor in F344 rats.Key words: Albino rat; amelanotic melanomas; uveal tract.Spo ntaneous intraocular tumors are extre mely rar e in rat s, altho ugh che m ica lly-ind uce d intraocul ar mela no mas ha ve been rep orted in both albi no and ho od ed ra ts .1.2. 10 In alb ino rat s, on ly two re po rts ofsponta neous intraocular me lano mas are available.7, 1 1 Origin of th ese intraocul ar tumors fro m uveal melan ocytes is controversial because ult ra structural or hi stochemical ev iden ce of melanocyti c origin has not been rep orted. A me lanotic malignant m ela noma occurring in th e cilia ry bodies o f both eyes was re po rted in a fem ale Sp ragu e-Dawley rat ;' however , this rep ort provided no in formation as to th e histopathologic methods and m orphol ogic fea tures used to ide ntify th is tumor. In 197 8, intraocular m elan omas were reported in eight Sprag ue -Dawley and Wi sta r ra ts. I I Of th e eight m ela no mas, five were see n in three of 1,790 male a nd two of 1,07 0 female Sprague-Dawley ra ts . The re m aini ng three melano m as were found in two of3 ,520 m ale and one of 1,7 60 female Wista r rats. T he eight melanomas were loca ted primarily in the regio n of the ciliary body a nd co nsisted pred ominantl y of spi nd le cells. T wo of the eight tumors were d iagnosed as a melano tic m elanomas based up on hematoxylin and eosin-a nd a rgyroph ilic-stain ed sectio ns. Diagnosis of a melano tic spi ndl e ce ll m el an oma s w it ho ut ultrastructural or immunoh istoch emical studies is usuall y difficult. 6 ,2 l ,22 The re main ing six tum ors were classified as melanotic m elanomas on th e ba sis o f th e presen ce of "yellowish brown pigm ent" found in occasion al cells on hematoxylin a nd eosin -s...

Spontaneous amelanotic melanomas in the eyelids of F344 rats were found in one of 1/926 (0.11%) male and 5/925 (0.54%) female F344 rats that were used as control and treated animals in five different carcinogenicity studies conducted by the National Toxicology Program (Research Triangle Park, NC). These melanomas were grossly recognized as single, tan or white, well-circumscribed masses of the right or left eyelid. These melanomas primarily occurred in the dermis of the skin of the eyelids and consisted of poorly differentiated spindle cells characteristically arranged in interlacing fascicles. Rarely, epithelioid tumor cells were also observed, and these tumor cells showed a negative histochemical reaction for melanin. The epidermis and dermal-epidermal junction were usually uninvolved. The diagnosis of amelanotic melanoma could only be established by electron microscopic examination. The most striking ultrastructural feature of the tumor cells was a large number of intracytoplasmic premelanosomes (stage II melanosomes without melanin), which nearly filled the cytoplasm of most tumor cells. Giant premelanosomes and melanophagosomes were also seen. The tumor cells did not possess the ultrastructural features characteristics of Schwann cells (thin, long cell processes and pericytoplasmic basal laminae). The histologic and ultrastructural features of these palpebral tumors were similar to those of cutaneous amelanotic melanomas of the pinna in F344 rats.