Abstract. Emperipolesis of hematopoietic cells within megakaryocytes was found in rats. The incidence was less than 0.3% in young rats (2 to 12 months old) but increased to 2-5% among the aging rats (1 8 to 24 months old). The incidence increased markedly in hyperplastic bone marrow secondary to chronic suppurative or neoplastic lesions. Mature neutrophils appeared to be the most common marrow cell engulfed by megakaryocytes. By light microscopy, engulfed cells were separated from megakaryocyte cytoplasm by a narrow pencellular space. By electron microscopy, marrow cells engulfed by megakaryocytes were located in the open canalicular system. Cell membranes of both engulfed cells and megakaryocytes were intact, and there was no fusion of cell membranes or phagosome formation in the megakaryocytes.Emperipolesis, a word of Greek derivation, was defined as "the active penetration of one cell by another which remains intact" by Humble et al.4 It differs from phagocytosis in that an engulfed cell only temporarily exists within another cell and remains viable with intact normal structure. Emperipolesis has been recognized in association with human lymphocyte^,^ tumor cells, Sternberg-Reed cells, and r n e g a k a r y~c y t e s .~~~~~~~ Recently, Chiu2 described briefly the light microscopic observation of megakaryocytes containing marrow cells in rats that had been used for toxicity or chemical carcinogenicity testing. Under experimental conditions, megakaryoblasts or leukemic blast cells containing blood cells were observed incidentally in bone marrow of rats with experimentally induced-myelogenous leukemia.6 Megakaryocytic emperipolesis was also observed in bone marrow of rats under experimentally induced-blood loss. l o Since little information is available about the diagnostic significance or ultrastructure of spontaneously occurring megakaryocytic emperipolesis in animals, ultrastructural observations of this phenomenon in the bone marrow of rats are described. Materials and Methods AnimalsIn addition to 435 male and 148 female rats (Crl : CDBR) from 2 to 12 months old, 456 male and 467 female rats between 18 and 24 months old were selected at random to study megakaryocytic emperipolesis. These rats were used in experiments to evaluate the safety of chemicals between 1980 and 1987 at Haskell Laboratory, but hematopoietic organs of these rats were not affected by any of the compounds tested. The rats were obtained from a commercial breeder (Charles River Breeding Laboratories, Wilmington, MA and Kingston, NY), were housed in suspended stainless steel cages, and were fed a basic diet of ground Purina Laboratory Chow (Ralston Purina Co., St. Louis, MO). Some rats also received 1% corn oil that was added as a vehicle in selected studies. Food and water were provided ad libitum in climate controlled rooms (23 ? 2 C, 50% f 20 relative humidity). Animal rooms were maintained on a timer-controlled, 12 hour light/l2 hour dark cycle. Tissue preparationAfter rats were killed by chloroform euthanasia, two sternebrae from each...

Pigmented male rats were administered a suspension of 0, 25, or 100 mg/kg 2-phenyl-APB-144 in corn oil by gavage. The rats were killed at 4 and 12 h, and at 1, 2, 4, 7, 14, 28, 57, or 84 days after a single oral administration. The primary site of retinopathy appeared to be the retinal pigment epithelial (RPE) cells. The RPE cells showed necrosis within 12 h post-exposure (PE) at 25 mg/kg and within 4 h PE at 100 mg/kg. Subsequently, photoreceptor outer segments (POS) were disrupted with a hyperplastic RPE cell response within 2 days PE. Intact photoreceptor inner segments (PIS) and RPE cells apposing closely with distal POS were important determinants for reversibility of the damaged POS. The damaged RPE cells were regenerated prior to restoration of normal POS. At 25 mg/kg, both the RPE cells and POS were damaged, but PIS were intact. The damaged POS were regenerated from intact PIS with closely apposing RPE cells. By 14 days PE, the damaged POS had partially regenerated and attained approximately one third to one half of their normal length. By 57 and 84 days PE, the damaged retina had regained an essentially normal structure. In contrast, at 100 mg/kg, the POS and PIS were extensively disrupted, with marked RPE cell hyperplasia after 7 days PE resulting in the formation of multiple retinal arcades (foldings), and rosettes by 14 days PE. Subsequently, retinal arcades and rosettes gradually disappeared as the result of extensive loss of PIS and POS with progressive migration of photoreceptor nuclei toward the Bruch's membrane after 28 days PE. Focal regeneration of POS was observed by 57 days PE where intact PIS and a single layer of regenerated RPE cells were apposed closely with distal POS. The POS regeneration did not occur where the RPE cells were denuded or hyperplastic RPE cells were present. The hyperplastic RPE cells were devoid of slender apical processes, closely enclosing the distal POS. Approximately 20-30% of the retina had partially regained a normal structure by 84 days PE.

Albino and pigmented strains of rats were administered 0, 5, 25, 100 or 500 mg/kg 2-phenyl-APB-144 by gavage and were killed 14 days later. Although no ocular lesions were found in rats dosed at 5 mg/kg, similar dose-related retinopathy was found at 25, 100, or 500 mg/kg in both albino and pigmented rats. The primary target site appeared to be retinal pigment epithelial (RPE) cells and photoreceptor outer segments (POS). At 25 mg/kg or greater, multifocal retinal detachment with disrupted POS occurred where the RPE cells showed necrotic changes and contact loss with POS due to fragmentation of apical processes in the RPE cells. Also, RPE cells showed hyperplasia, migration, and phagocytic activity toward disrupted POS. The photoreceptor nuclei (outer nuclear cells) were displaced into the areas occupied by disrupted POS. At 100 or 500 mg/kg, multifocal or diffuse disruption of POS and photoreceptor inner segments (PIS) was observed with markedly proliferating RPE cells. The photoreceptor nuclei were disorganized, less numerous, and necrotic. Some photoreceptor nuclei directly apposed the RPE cells or Bruch's membrane due to the absence of both POS and PIS. The cytoplasm of RPE cells was loaded with phagosomes, disrupted lamellar discs, myelin bodies, and lysosomal residual bodies. The morphological changes appeared to be related to lysosomal dysfunction of the RPE cells. The presence of melanin pigment in the RPE cells did not appear to be the primary factor in the development of the retinopathy.

An external ear lesion designated as auricular chondropathy in aging Crl:CD rats was reported. One hundred eighty (180) of 4,876 rats (3.7%) had ear deformity. Grossly, the ears were thickened, nodular, or disfigured. Both ears were affected in most rats. The lesions primarily involved the cartilaginous plate and were associated with two processes--chondrolysis and granulomatous inflammation. The detailed morphogenesis of the lesions is described, but the etiology of the lesions is unknown. Auricular chondropathy in rats and relapsing polychondritis in man are compared.

Abstract. The incidence of peliosis hepatis-like lesions in two-year-old Charles River-CD Sprague-Dawley rats (Charles River Breeding Laboratories, Wilmington, MA) was almost twice as high in males as females. Blood lakes developed from progressive expansion of sinusoids with destruction of the hepatic cell cords. The endothelial processes of the blood lakes had edematous swelling, vesiculation, and denudation. The microvilli of hepatocytes became swollen, blunted, and sloughed where the endothelial processes were disrupted. Subsequently, the hepatocytes were exposed directly to circulating blood cells and had degenerative changes with accumulation of red blood cells in the cytoplasm.The membrane-bound cysts were observed with the blood lakes and were bounded with atrophic hepatocytes or membranous wall extending to the Disse's space of adjacent hepatocytes. The cysts were filled with proteinaceous fluid, fibrin, and a few red blood cells. The wall of membrane-bound cysts consisted of endothelial processes extending from the endothelial cells of adjacent hepatocytes. The wall appeared to develop from adhesion of endothelial processes surrounding sinusoidal spaces of the hepatocytes following lysis of atrophic hepatocytes.Peliosis hepatis in the liver of man is a rare lesion characterized by multiple cystic spaces filled with blood. Gross diagnosis is simple due to the unique appearance of the lesion which contains tiny dark-red spaces filled with fluid or clotted blood. The lesion can be recognized readily through the intact capsule as well as on the cut surface [22]. The condition also has been called "telangiectasia hepatis disseminata" [ 171, "Leberblutung" [27], "multiple Leberblutung" [3 11, and "angiomatosis hepatis" [2 11. Peliosis hepatis has been observed in patients with chronic wasting diseases such as tuberculosis or cancer [7,15,22, 391. Recently, the incidence of peliosis hepatis has increased significantly in patients who developed hepatic neoplasms after taking oral contraceptives or anabolic androgenic steroids for long periods of time [ 16, 23, 28, 301. A few reports described extrahepatic peliosis in the spleen [ 15, 241, lymph nodes [22], and bone marrow [22].A peliosis hepatis-like lesion has been described in experimental animals exposed to virus [4] [35]. Peliosis and telangiectatic lesions were relatively common in the liver of old rats [5, 111 but etiology and pathogenesis are unknown. In an attempt to elucidate the morphogenesis of peliosis hepatis and membrane-bound cysts containing proteinaceous fluid, the livers of old rats were examined in detail by electron microscopy. Materials and MethodsTwo-year-old control rats (Charles River-CD Sprague-Dawley), which were used in experiments for safety evaluation of chemicals between 1968 and 1980 at Haskell Laboratory, were selected randomly to study peliosis hepatis. The rats, obtained as weanlings from a commercial breeder (Charles River Breeding Laboratories, Wilmington, MA), were housed two to a suspended stainless steel cage and fed a b...