Tumours of the kidney

XVIII. Tumours of the kidney SVEND W. NIELSEN," L. J. MACKEY,2 & W. MISDORP3 The most frequent renal tumours of animals are renal cell carcinoma and nephro- blastoma. Renal cell carcinomas are seen mainly in dogs and cattle and nephroblastoma is encountered in pigs, puppies, and calves. Renal cell carcinomas are usually papillary in the dog. They show a markedpropensity for vascular invasion, penetration of the posterior vena cava, and subsequent pulmonary metastasis. Nephroblastoma, which is morphologi- cally identical to Wilms' tumour of children, is almost always a benign tumour in animals. It is one of the most frequent neoplasms ofpigs, possibly owing to the fact that most pigs are slaughtered (and examined) when a few months old. Lymphosarcoma involving the kidney is particularly frequent in the cat, but is also seen in other species as part of a generalized disease. The classification is based on a study of 200 cases of primary renal tumours, mainly from dogs, pigs, and cattle. Comparatively few renal tumours were found in cats, sheep, and horses. The two most important types are renal cell carcinoma and nephro- blastoma. Renal cell carcinomas were encountered most frequently in old dogs and cattle, whereas nephroblastoma occurred in pigs, puppies, and calves. Nephroblastoma and lymphosarcoma are the most frequently observed neoplasms of the pig, account- ing for approximately 40% of all porcine neoplasia. The predominance of these conditions may be due in part to the fact that the majority of pigs examined post-mortem are 5-6 months of age. HISTOLOGICAL CLASSIFICATION AND NOMENCLATURE OF TUMOURS OF THE KIDNEY I. EPITHELIAL TUMOURS OF RENAL PARENCHYMA A. ADENOMA B. CARCINOMA (RENAL CELL CARCINOMA) II. EPITHELIAL TUMOURS OF THE RENAL PELVIS A. TRANSITIONAL CELL PAPILLOMA B. TRANSITIONAL CELL CARCINOMA C. SQUAMOUS CELL CARCINOMA 1 Professor of Pathology and Director of the Northeastern Research Center for Wildlife Diseases, University of Con- necticut, Storrs, CT 06268, USA. ' Senior Lecturer, Department of Veterinary Pathology, University of Glasgow, Veterinary School, Bearsden, Glasgow G61 IQH, Scotland. 3 Veterinary Pathologist, Department of Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands. III. UNDIFFERENTIATED CARCINOMA IV. NEPHROBLASTOMA (EMBRYONAL NEPHROMA) V. MESENCHYMAL TUMOURS VI. LYMPHOSARCOMA VII. TERATOMA VIII. SECONDARY TUMOURS IX. UNCLASSIFIED TUMOURS X. TUMOUR-LIKE LESIONS A. WHITE SPOTTED KIDNEY OF CALVES B. GRANULOMAS OF FELINE INFECTIOUS PERITONITIS C. HAMARTOMA D. CYSTS 3434 237 BULL. WORLD HEALTH ORGAN., Vol. 53, 1976 S. W. NIELSEN ET AL. DESCRIPTION OF TUMOURS I. EPITHELIAL TUMOURS OF RENAL PARENCHYMA A. Adenoma This lesion is rare and is most often seen in cattle and horses. The uniform, usually cuboidal cells are arranged in tubules, papilliferous structures, or solid sheets. Areas showing these different pattems may be found within the same tumour. The cells are sup- ported by a sparse, delicate stroma, closely resem- bling the normal tubular basement membrane. They have well delineated cell borders, eosinophilic cyto- plasm, and round, hyperchromatic nuclei. It is not always possible to separate adenomas from adeno- carcinomas on a morphological basis, since imper- ceptible transitions exist between the two. Macro- scopically, the tumour is seen as a solitary, circum- scribed, expansively growing nodule, usually less than 2 cm across (Fig. 1-4). B. Carcinoma (renal cell carcinoma) These tumours may be subdivided according to their predominant histological pattern, which may be solid, tubular, or papillary, or according to their cytological characteristics, which may be clear cell, granular eosinophilic, or basophilic, and either cuboidal or columnar. These forms may be of uniform type, but not infrequently more than one histological pattern can be found in different areas of the same tumour. Papillary tumours are made up of uniform cu- boidal cells situated on thin stromal septa, and form- ing digitating papillary projections. The cells are small with somewhat basophilic, non-vacuolated cytoplasm and hyperchromatic nuclei; mitoses may be infrequent. Despite its well differentiated appear- ance and lack of anaplastic changes, this tumour is highly malignant in the dog and has a great propen- sity for vascular invasion. Pulmonary metastases were present in approximately half of the canine cases investigated. Clusters of tumour cells grow along the renal vein and form emboli with frequent metastases to the lungs and often to other organs, particularly the brain, heart, and skin. In general, the skin is an extremely rare site for metastatic tumours in all animal species. Three dogs were exam- ined in which cutaneous tumours initially thought to be apocrine sweat gland carcinomas proved to be metastases of renal adenocarcinomas (Fig. 5-7). In tubular carcinomas, the tumour cells are usu- ally cuboidal or columnar, but are sometimes of uneven size and shape, forming irregular tubular structures, which are surrounded by a fibrous stroma. The nuclei may be irregular in size and are often vesicular; mitoses are usually frequent (Fig. 8). In clear cell carcinomas, the tumour cells are large and have clear cytoplasm in H & E stained sections. They are arranged mainly in solid masses and may in places show a tubular pattern. The cells have well delineated borders and small, round, dense nuclei, often at the base of the water-clear cytoplasm. The stroma is scant but carries many tiny vessels. Because it bears some resemblance to adrenal cortical tissue, this form of renal carcinoma has sometimes been termed " hypernephroma" (Fig. 9, 10). Carcinomas composed of cells with eosinophilic granular cytoplasm are uncommon. The cells are usually closely packed and arranged in an ill-defined trabecular pattern with or without lumen formation. The cytoplasm is abundant, dense, non-vacuolated, strongly eosinophilic, and slightly granular. Often small, spherical, eosinophilic intracytoplasmic inclu- sion bodies can be seen. The nuclei tend to be hyper- chromatic and several multinucleate giant cells occur (Fig. 11). Macroscopically, renal cell carcinomas are white, lobulated, and usually well delineated ovoid or round masses, often located near one pole of the kidney. The tissue may be discoloured by haemor- rhage and infarction. Despite apparent encapsulation on macroscopic examination, these tumours grow invasively. II. EPITHELIAL TUMOURS OF THE RENAL PELVIS A. Transitional cell papilloma (Fig. 12) Papillomas of the renal pelvis are rare. They are composed of cuboidal or tall cylindrical cells, arran- ged as transitional epithelium and supported by thin fibrous tissue septa, which may contain foci of lymphocytes. Macroscopically, they are seen as papil. liform nodules projecting into the pelvic cavity. B. Transitional cell carcinoma Transitional cell carcinomas may originate in either the renal pelvis or ureter and appear as papil- liferous growths or invasive carcinomas of the same 238 KIDNEY 239 morphology as the transitional cell tumour of the urinary bladder described elsewhere.a Foci of squamous metaplasia may be seen, and occasionally glandular elements occur. C. Squamous cell carcinoma (Fig. 13) The squamous cell (epidermoid) tumours are rare and have the characteristic morphological appear- ance of such tumours elsewhere in the body with intercellular bridges and/or keratinization. III. UNDIFFERENTIATED CARCINOMA (Fig. 14, 15) This category is used to designate carcinomas that are so poorly differentiated that the cell type is not apparent. They consist of pleomorphic cells, which can range from round to fusiform, forming solid masses without tubules and showing frequent mi- toses. The stroma varies and ischaemic necrosis may be present. IV. NEPHROBLASTOMA (EMBRYONAL NEPHROMA) (Fig. 16, 17, 18, 19) This tumour is described as a frequent tumour in young, immature animals. It is most often diagnosed in pigs, puppies, and calves before the animal is 1 year of age. It is most frequently encountered in young pigs slaughtered for bacon at the age of 5-6 months. However, it has also been seen in older breeding sows where the tumours may reach ex- tremely large sizes (up to 20 kg). Metastasis is infre- quent in pigs and calves, even in large tumours, whereas it is present in over half of canine nephro- blastomas reported in the literature. This tumour may show neoplastic growth of both epithelial and vatious mesenchymal elements, such as fibrous tis- sue, fat, bone, cartilage, and muscle-hence the terms adenosarcoma, sarcocarcinoma, mixed tu- mour, etc. have been used previously. A great variety of morphological patterns exist. The epithelial portion of the tumour may dominate, with neo- plastic tubules and embryonic glomerular structures surrounded by only scant fibromatous tissue. A very typical pattern is one of islands consisting of epi- thelial cells in the centre undergoing differentiation into tubules or glomerulus-like structures, surrounded by a peripheral zone of stroma. If mesenchymal tis- sue constitutes the major part of the tumour, neo- a PAMUKCU, A. M. International histological classifi- cation of tumours of domestic animals. IV. Tumours of the urinary bladder. Bulletin of the World Health Organization, 50: 43-52 (1974). plastic fibrous, myxoid, lipoid, myoid, chondroid, and osteoid tissues may be seen. These components may be present singly or in several combinations and different proportions. Cyst cavities and ischae- mic necroses are frequent in large tumours. V. MESENCHYMAL TUMOURS The most frequent renal stromal tumours are fibroma and fibrosarcoma, followed by vascular tumours, haemangiomas, and haemangiosarcoma. Primary leiomyomas, lipomas, and their malignant counterparts occur rarely. All the tumours have the same histological patterns as the corresponding tumours seen elsewhere in the body. VI. LYMPHOSARCOMA Involvement of kidneys as part of a generalized lymphosarcoma is common in most animals. How- ever, the cat appears to be more frequently affected than other species and, in addition, it may have apparently primary renal lymphosarcomas without visible infiltration of other organs. The renallesions in the cat often appear as bilateral, grey-white, multi- focal, spherical nodules affecting the cortices, and eventually progress to diffuse infiltration. VII. TERATOMA This tumour is extremely rare. It may have com- ponents of hair, bone, and cystic spaces lined with stratified squamous epithelium, with areas ofsarcoma or carcinoma. VIII. SECONDARY TUMOURS Metastasis to the kidney is not infrequent in animals, especially in cases of severe involvement of the lungs with either primary or secondary tumours. The epithelial tumours in animals that most fre- quently metastasize to the kidney are pulmonary, mammary, ovarian, and prostatic carcinomas, in addition to osteosarcomas, mastocytomas, and lym- phosarcomas. One particular tumour of the dog deserves men- tion here, as it may present a difficult problem for the pathologist if only a few tissues are available to him. It can be difficult to distinguish primary pulmonary adenocarcinoma with renal metastasis from primary renal adenocarcinoma with pulmon- ary metastasis, since their histological features in the dog may be similar. S. W. NIELSEN ET AL. IX. UNCLASSIFIED TUMOURS These are tumours that cannot be placed in any of the above categories. X. TUMOUR-LIKE LESIONS A. White spotted kidney of calves This lesion occurs in young calves, frequently as an incidental finding in the abattoir; occasionally, however, it may progress to such an extent that renal function is impaired and may contribute to the demise of the animal. The kidneys are bilaterally involved with grey-white, small (1 cm) spherical nodules, often raised over the renal surface, which on cutting show uniform, white, poorly demarcated, wedge-shaped tissue. Histologically, there is a focal interstitial infiltration of histiocytes, lymphocytes, and plasma cells. The lesion has the appearance of a reactive process, and may regress spontaneously. It is of unknown causation but is believed by some pathologists to be related to previous infection with bacteria, notably Corynebacterium renale. It is im- portant for the pathologist to differentiate it from lymphosarcoma of the kidney, which macroscopi- cally appears similar and which may occur in the same age group. B. Granulomas offeline infectious peritonitis This lesion, which may occur without the fre- quent peritoneal form of the disease, can produce changes that macroscopically closely resemble multi- focal lymphosarcomas of the kidney. Spherical, greyish-white nodules measuring from 2 to 10 mm elevate the renal surface and their cut surface is uniformly white. The histological appearance is that of a granuloma with histiocytes, plasma cells, and a few neutrophils. C. Hamartoma This congenital defect is of rare occurrence in the kidney and consists of a small mass of viable aber- rant tissue (cartilage, bone, etc.) without neoplastic transformation. D. Cysts Solitary renal cysts. The most frequently observed cyst is the solitary renal cyst, which occurs in most animals but most frequently in calves, pigs, and dogs. Its size may vary from a few millimetres to several centimetres. A large solitary renal cyst has been seen to occupy the entire posterior pole of a canine kidney. The cysts occur predominantly in the cortex and are often visible beneath the renal capsule. They con- tain a clear fluid, surrounded by a smooth glistening cyst wall. They are asymptomatic and are seen as incidental findings on laparotomy, radiography, or necropsy. Their origin is attributed to disturbed renal organogenesis and as such are considered to represent a congenital anomaly. Polycystic kidney. Clinically, the polycystic kidney represents a much more severe anomaly, which usually terminates in fatal uraemia within a short time when both kidneys are affected. This anomaly is sometimes associated with other malformations such as multiple biliary cysts. The polycystic kidney is enlarged and transformed into a greyish mass of fibrous tissue containing numerous cysts of different sizes with only minimal renal tissue present. Retention cysts. These are bilateral, multiple (1-3 mm), clear cysts of the renal cortex that are visible under the capsule and present in the fibrotic kidney, particularly in dogs. They appear to be caused by contraction of scar tissue with subsequent retention of urine and dilatation of nephrons. Hydronephrosis. The hydronephrotic kidney will show various degrees of dilatation of the renal pelvic cavity depending on the stage of development of the occlusion in the corresponding ureter. Unilateral hydronephrosis may be asymptomatic, as opposed to bilateral lesions due to lower tract obstruction which may be seen in rams and tomcats. In the final stage the kidney is transformed into a urine-filled cyst, the wall of which is composed of renal tissue undergoing various degrees of pressure atrophy. The causes are: (a) stricture of the ureter due to con- genital anomaly, traumatic injury, or infection; (b) compression of the ureter by a neoplasm or an aberrant branch of the renal artery; (c) blockage by urinary calculi in the pelvis, ureter, or urethra; and (d) kinking and adhesion of the ureter to the renal pelvis. 240 Fig. 1, 2. Renal adenoma with papillary pattern of cuboidal cells (horse). Fig. 3, 4. Renal adenoma showing solid and tubular patterns (cat). 20 lippr .... . Aj.. '830.0whm 1! -A Fig. 5,6. Renalcell carcMiow pia pog Fig. 5, 6. Renal cell carcinoma with papillary projections of cuboidal cells (dog). Fig. 8. Renal cell carcinoma showing solid strands and tubules (cow). Fig. 7. Renal cell carcinoma with papillary pattern showing pleomorphic cells on delicatesepta (cow). Fig. 9, 10. Renal cell carcinoma showing large clear cells arranged in solid masses or tubules with a few visible lumens (cow). Fig. 1r l'lF, cacnm wit e o enhc cels ( Fig. I11. Renal cell carcinoma with pleomorphic eosinophilic cells (cow). Fig. 12. Transitional cell papilloma of renal pelvis (horse). AAl Fig. 13. Squamous cell carcinoma of renal pelvis (dog). Fig. 14, 15. Undifferentiated carcinoma showing solid masses of pleomorphic tumour cells (dog). x" Fig. 16, 17, 18, 19. Nephroblastoma showing a mixture of tubular epithelial structures and young mesen- chymal tissue, which is differentiating into cartilage. 21 .1.1': ftw .:::