JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 1949421): 23-month-old male Fischer 344 rat
HISTORY: Not provided
HISTOPATHOLOGIC DESCRIPTION: Testis: There are two neoplasms within this tissue section. Expanding and replacing 95% of testicular architecture and compressing adjacent seminiferous tubules is a well demarcated, unencapsulated, multilobular neoplasm composed of cords and vague nests of polygonal cells supported by a fine fibrovascular stroma. Neoplastic cells have variably distinct cell borders, abundant eosinophilic vacuolated cytoplasm, round to oval nuclei with finely stippled chromatin and one variably distinct nucleolus. There is mild anisocytosis and anisokaryosis. Mitotic figures are less than 1 per 10 HPF. The neoplasm is punctuated by few, up to 1mm diameter lakes of eosinophilic, flocculent material (cystic degeneration) or hemorrhage. The remaining seminiferous tubules are atrophied, with irregular, undulant basement membranes, lined by a single layer of Sertoli cells, devoid of germ cells, spermatocytes and spermatids, and contain variable amounts of a fibrillar to homogeneous eosinophilic material. Extending from the tunica vaginalis is a second neoplasm composed of arborizing papillary projections lined by cuboidal cells that often pile up to three cell layers thick supported by a loose collagenous core. Neoplastic cells have variably distinct cell borders, small amounts of homogenous to finely granular eosinophilic cytoplasm, round to oval nuclei with finely stippled chromatin and a single distinct nucleolus. Mitotic figures are less than 1 per 10 HPF. There is mild anisocytosis, few infiltrating hemosiderin-laden macrophages and mast cells, and moderately ectatic lymphatics.
- Testis: Interstitial cell tumor, Fischer 344 rat, rodent.
- Testis, tunica vaginalis: Mesothelioma.
- Testis, seminiferous tubules: Atrophy diffuse, severe with aspermatogenesis.
- Interstitial cell tumor (ICT; Leydig cell tumor; interstitial cell adenoma)
- Most common testicular tumor of rats; also seen in the bull and dog
- F344 rats, incidence approaches 100%
- Often multiple, bilateral
- Usually benign, difficult to differentiate from hyperplasia
- Hyperplasia usually more diffuse, often entraps seminiferous tubules, and does not compress peripheral testicular tissue
- In rats, about 10% are malignant; features of malignancy include invasion of the epididymis and (rarely) pulmonary metastasis
- Associated with concurrent hypercalcemia in rats
- Third most common testicular tumor of rats after interstitial cell tumor and mononuclear cell leukemia; not uncommon to see ICT and mesothelioma co-occurring
- Tunica vaginalis is the most common site
- Rare in female rats; may arise in the ovarian bursa
- All mesotheliomas considered malignant; spread by direct extension or implantation throughout the peritoneum, with invasion of subjacent tissue
- Some metastasize through lymphatics; strangulation of the intestines may occur with abdominal mesotheliomas
- F344 rats exposed to vinylidene chloride resulted in marked increase in malignant mesothelioma
- Must differentiate from reactive mesothelium
TYPICAL GROSS FINDINGS:
- Interstitial cell tumors:
- Circumscribed, lobulated, yellow-white, multiple, bilateral masses
- Larger tumors may be hemorrhagic, necrotic or mineralized
- Multiple firm sessile or pedunculated nodules, villous projections, or plaque like with fibrous adhesions
- Gelatinous or white fibrous proliferations partially surrounding the testis
- Shaggy yellow-tan to red-brown growths on serosal surfaces of the peritoneal cavity, tunica vaginalis propria, or both
- Ascites and scrotal edema (can be severe)
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Interstitial cell tumors:
- Sheets of polyhedral to elongate cells; granular or vacuolated cytoplasm
- Admixed with smaller cells with scant cytoplasm and hyperchromatic nuclei
- Extend between, compress and often replace tubules
- Hemorrhage, necrosis, mineralization, inflammation, cystic degeneration, tubular atrophy may occur
- Diffuse or nodular foci or complex papillary structures
- Prominent stratification and associated stromal proliferation
- Polyhedral to cuboidal cells; abundant eosinophilic, often finely vacuolated cytoplasm
- Round to oval nuclei; single or multiple nucleoli
- Mitotic rate usually low
- Interstitial cell tumor:
- Lipid droplets, lipofuscin, abundant smooth endoplasmic reticulum, abundant mitochondria with tubulovesicular cristae and desmosomes
- Tubulovesicular mitochondrial cristae are characteristic of interstitial cell
- Other cells of the testis and epididymis have lamellar mitochondrial cristae
- Microvillous cell membrane, junctional complexes between cells, pinocytotic vesicles, distinct basal lamina
- Microfilaments often abundant, may be difficult to differentiate from endothelial cells
ADDITIONAL DIAGNOSTIC TESTS:
- Interstitial cell tumors:
- Immunohistochemistry: GATA 4 positive; other such as inhibin α also reported positive in some cases
- Elevated plasma inhibin levels
- Cytoplasmic mucopolysaccharides stain weakly positive with PAS and keratin; strongly positive with alcian blue, colloidal iron, and vimentin
- Immunohistochemically usually positive for vimentin and cytokeratin
- Interstitial cell tumor:
- Interstitial cell hyperplasia: Proliferative cell growth dispersed between the tubules rather than displacement/destruction, size less than the diameter of a seminiferous tubule
- Interstitial cell carcinoma: Invasion, hemorrhage, increased pleomorphism and mitotic activity
- Sertoli cell tumor: Usually forms tubules and has a prominent fibrous stroma; IHC positive for AMH and inhibin, among others
- Villous hyperplasia (mesothelial hyperplasia): No fibrovascular stalk; often associated fibrosis
- Chronic peritonitis, which may be secondary to experimental manipulation
- Mononuclear leukemia
- Scrotal hemorrhage seen in Kilham’s rat virus (parvovirus)
- Interstitial cell tumor: Most common testicular neoplasm of the dog, cat, and bull (primarily Guernsey breed), and in the Guernsey is associated with a high incidence of telangiectasia of the liver, thyroid C-cell (parafollicular) tumors, and infertility; also develops almost exclusively in cryptorchid stallions; rare in birds, rabbits, mice and man
- Mesothelioma: Reported in man and laboratory animals exposed to asbestos; rare in domestic animals, most commonly reported in the bull, calf, and dog. In dogs (as in humans) three types of mesotheliomas are described- epithelioid type, sarcomatoid type, biphasic or combination type
- Blackshear P, Pandiri A, Nagai H, et al. Gene expression of mesothelioma in vinylidine chloride-exposed F344/N rats reveal immune dysfunction, tissue damage, and inflammation pathways. Toxicol Pathol. 2015; 43:171-185.
- Blackshear P, Pandiri A, Ton T, et al. Spontaneous mesotheliomas in F344/N rats are characterized by dysregulation of cellular growth and immune function pathways. Toxicol Pathol. 2014; 42:863-876.
- Canadas A, Romão P, Gärtner F. Multiple cutaneous metastasis of a malignant interstitial cell tumour in a dog. J Comp Pathol. 2016 Aug-Oct;155(2-3):181-184.
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 2. 6th St. Louis, MO: Elsevier; 2016: 523.
- Foster RA. Male reproductive system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1204, 1211.
- Foster RA. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:474, 492-495.
- Lopez A, Martinson SA. Respiratory system, mediastinum, and pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:559.
- Murakami T, Sassa Y. Pleomorphic malignant mesothelioma in a broiler breeder infected with avian leucosis virus subgroup J. J Comp Pathol. 2018; 160:50-55.
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits, 4th ed. Ames, IA: John Wiley & Sons, Inc.; 2016:169-170.
- Uzal FA, Plattner BL, Hostetter JM. Alimentary system In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:256-257.