JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

December 2023

U-N06 (NP)

 

SIGNALMENT: 9-month-old female Fisher 344 rat.

 

HISTORY: This rat received a single injection of dimethylnitrosamine at one day of age.

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Effacing and replacing approximately 70% of the cortex and medulla is an unencapsulated, infiltrative, poorly differentiated neoplasm composed of spindle to stellate cells. Spindle cells are arranged in streams and tightly packed whorls surrounding and entrapping tubules, glomeruli and cystic spaces, and infiltrate adjacent normal cortex on a fine collagenous to myxomatous matrix. Stellate cells are arranged in loose streams, widely separating and replacing preexisting tubules, glomeruli and cystic spaces, and extend to the renal pelvis. Neoplastic cells have indistinct cell borders, scant to moderate eosinophilic fibrillar, occasionally vacuolated cytoplasm, an oval to elongate nucleus with vesiculate chromatin and 1-2 variably distinct nucleoli. Mitoses average 1 per 2.37mm² and there is occasional single cell necrosis characterized by shrunken cells with hypereosinophilic cytoplasm and pyknosis. Entrapped glomeruli are atrophied and surrounded by a dilated Bowman’s space. Entrapped tubules scattered throughout the neoplasm are variably dilated and cystic, lined by epithelium that is either attenuated or hyperplastic, and multifocally contain homogenous eosinophilic material (proteinaceous fluid) or basophilic granular material (mineral) and occasionally neutrophils and cellular debris (cellular casts). Within the adjacent renal cortex, tubules contain one or more of the following changes: degeneration, characterized by swollen vacuolated cytoplasm and faded nuclei; or regeneration, characterized by basophilic nuclei and rare mitotic figures. Multifocally, there are moderate numbers of mildly dilated tubules, and the interstitium is mildly expanded by small numbers of lymphocytes and plasma cells (interstitial nephritis).

                                                                                              

MORPHOLOGIC DIAGNOSIS: Kidney: Renal mesenchymal tumor (RMT), Fisher 344 rat, rodent. 

 

SYNONYMS: Renomedullary interstitial cell tumor, malignant mesenchymal tumor

 

GENERAL DISCUSSION:

• In man and laboratory rodents, there are mesenchymal tumors in the kidney that display multiple patterns of differentiation, suggesting transformation of pluripotential mesenchymal cells; these tumors have not been recognized, to date, in domestic animals
• This is an entity of young rats of either gender, and is frequently experimentally induced by the introduction of genotoxic carcinogens at an immature age
• Second most common chemically-induced renal tumor of rats (spontaneous cases are rare) after epithelial tumors (adenoma, adenocarcinoma)
• Rapidly growing, locally invasive into adjacent abdominal wall, with metastasis in only a few cases (lung and mesentery) 
• The hallmark of these tumors is the heterogeneous range of connective tissue cell types that constitute the differentiative capacity of the stem cell of origin, and which typically are represented within a single tumor; the predominant cell type is a fibroblastic spindle cell with predisposition to encircle sequestered preexisting tubules; smooth muscle fibers, vascular structures, and occasionally striated muscle and cartilage can be found in these tumors
• Characteristically, the tumors have poorly cellular myxomatous areas and densely cellular areas that contain entrapped tubules, glomeruli, or cystic spaces, and/or nests of urothelium which represent remnants of preexisting nephrons, dilated tubules, or epithelial lining
• Spindle cells aggregate in sheets forming a herring-bone pattern as well as stratified whorls around sequestered tubules
• Sometimes smooth muscle in swirling patterns is so profuse that it forms large areas of leiomyosarcoma which merge into areas of fibrosarcoma
• At least one-third of tumors develop conspicuous abnormal vascular structures which can be identified as hemangioma, hemangiopericytoma, or hemangiosarcoma
• May grow large enough to fill the abdominal cavity
• In chemically-induced renal tumors of rats, it is not unusual to have two types of tumor arise and collide, giving the appearance of one tumor (renal adenocarcinoma with renal mesenchymal tumor)

 

PATHOGENESIS:

• Unknown for spontaneously arising tumors
• These neoplasms arise from primitive pluripotential mesenchymal cells in the cortical interstitium and the outer stripe of the medulla
• Dimethylnitrosamine, dimethyl hydrazine, cycasin, and methylnitrosourea are toxins known to induce renal mesenchymal tumors

 

TYPICAL GROSS FINDINGS:

• Single or multiple, unilateral or bilateral, white, infiltrative lesion that is usually of the outer cortex, at one pole of the kidney
• Small tumors are typically fibrous
• Larger tumors are multiloculated, with cysts, hemorrhage, necrosis and gelatinous tissue

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Contain cytoplasmic lipid droplets
• Heterogenous range of connective tissue cell types
• Spindle cell areas that are densely cellular
• Stellate cell areas that are poorly cellular and myxomatous
• Extensive collagen deposition is a feature of this tumor
• Sequestration of pre-existing tubules, glomeruli, urothelial nests
• Cystic spaces in large tumors

 

ULTRASTRUCTURAL FINDINGS:

• Spindle cells resemble fibroblasts with abundant, anastomosing channels of rough endoplasmic reticulum and bundles of actin-like myofilaments
• Stellate cells resemble fibrocytes

 

DIFFERENTIAL DIAGNOSIS:

• Nephroblastoma: RMT most commonly misdiagnosed as nephroblastoma; purely epithelial neoplasm with a uniform histologic pattern and hallmark neoplastic blastema; develops mainly in circumscribed fashion as an epithelial tumor by expansion, without engulfment of pre-existing tubules from adjacent parenchyma; also, nephroblastoma originates from the cortex proper
• Renal fibrosarcoma: An infrequent, uniform, highly basophilic spindle cell neoplasm with none of the heterogeneity of the renal mesenchymal tumor; also, no entrapped surviving remnants of preexisting nephrons; absent to minimal collagen deposition 
• Hemangiosarcoma: RMT may have a frank vascular component; could represent variants of renal mesenchymal tumors
• Renal liposarcoma: Characterized by sheets of mature lipocytes infiltrating between preexisting renal tubules and glomeruli; Adipocytes are not found in renal mesenchymal tumors
• Renal cell carcinoma: Predominantly a cortical tumor that is composed of atypical, pleomorphic epithelial cells arranged in tubules, islands, nests, or papillary projections, which can resemble primitive glomeruli, supported by variable amounts of stroma

 

COMPARATIVE PATHOLOGY:

 

REFERENCES:  

1. Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. 6th ed. Vol 2. Philadelphia, PA: Elsevier Saunders;2016:447.
2. Hard GC, Seely JC, Betz LJ. A survey of mesenchyme-related tumors of the rat kidney in the National Toxicology Program Archives, with particular reference to renal mesenchymal tumor. Toxicol Pathol. 2016;44(6):848-855.
3. Khan KNM, Hard GC, Li X, Alden CL. Urinary system. In: Wallig MA, Haschek WM, Rousseaux CG, Bolon B, Mahler BW, eds. Fundamentals of Toxicologic Pathology. 3^rd ed. San Diega, CA: Elsevier; 2018:226
4. Meuten DJ, Meuten TLK. Tumors of the urinary system. In: Meuten DJ, ed. Tumors in Domestic Animals. 5^th ed. Ames, IA: Wiley Blackwell; 2017:650-651.
5. Meuten DJ, Everitt J, Inskeep W, Jacobs RM, Peleteiro M, Thompson KG. Histological classification of tumors of the urinary system of domestic animals. In: Schulman FY, ed. World Health Organization International Histological Classification of Tumors of Domestic Animals. Vol. XI. Second Series. Washington, DC: Armed Forces Institutes of Pathology; 2004:22-23. 
6. Murphy WM, Grignon DJ, Perlman EJ. Kidney tumors in adults. In: Tumors of the kidney, bladder, and related urinary structures, AFIP Atlas of Tumor Pathology. Fascicle 1. Fourth Series. Washington, DC: American Registry of Pathology; 2004:194-195. 
7. Sula MM, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:744.

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