JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

January 2024

U-N07 (NP)

 

Signalment (JPC # 2020925): An 18-month-old Sprague Dawley rat

 

HISTORY: A CRCD Sprague Dawley rat with a renal mass

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Affecting over 40% of the section, effacing the renal pelvis, infiltrating the adjacent medulla and cortex, separating, surrounding and replacing tubules and glomeruli, and extending through the capsule is an unencapsulated, poorly demarcated, densely cellular, infiltrative neoplasm composed of pleomorphic polygonal to spindle cells that are densely packed or arranged in short streams on a fine fibrovascular stroma. Neoplastic cells have variably distinct cell borders and moderate amounts of pale eosinophilic cytoplasm that contain either: multiple variably-sized clear vacuoles (lipoblast); one large vacuole that peripheralizes the nucleus (lipocyte); or are unvacuolated (undifferentiated mesenchymal cell). Nuclei are round to oval to elongate with coarsely stippled chromatin and 1-2 distinct nucleoli. There are 5 mitotic figures per 2.37mm^2 and are higher in the undifferentiated population of cells. Multifocally within the neoplasm are linear to round foci of proliferating transitional epithelial cells that often form lumina. There is focally extensive lytic necrosis with abundant eosinophilic cellular and karyorrhectic debris admixed with large numbers of degenerate neutrophils and abundant hemorrhage, fibrin, and edema. Scattered throughout the neoplasm are aggregates of few lymphocytes and neutrophils. Multifocally within the cortex and medulla, there are occasional dilated tubules that contain eosinophilic homogeneous proteinaceous material (proteinosis). Occasionally within the interstitium there are low numbers of lymphocytes and plasma cells. Rarely glomeruli are expanded by eosinophilic homogenous material.   

 

MORPHOLOGIC DIAGNOSIS: Kidney: Liposarcoma, CRCD S/D rat, rodent.

 

GENERAL DISCUSSION:  

• Lipomatous renal neoplasms are generally uncommon; however they are the most common primary renal neoplasm of the aging Fischer 344 and Osborne-Mendel rat strains (highly malignant in Osborne-Mendel strain and frequently metastasize to the lungs); may also occur in other strains such as Sprague-Dawley
• Cell of origin and etiology have not been determined; interstitial growth suggests intertubular mesenchymal origin
• Liposarcoma occur mostly in male rats as part of mesenchymal-related tumors in rat kidney
• May be a sex predilection for males

 

TYPICAL CLINICAL FINDINGS:  

 

 TYPICAL GROSS FINDINGS:  

• Lipomas:  
  1. Usually solid and unilateral

  2. Generally <5mm in diameter

  3. Well circumscribed, unencapsulated, yellow to white mass, indistinguishable from fat

  4. Commonly located within the outer medulla at the corticomedullary junction

• Liposarcomas:  

  1. Usually single and unilateral

  2. Generally >5mm in diameter

  3. Poorly demarcated with irregular outline, substantial loss of the renal parenchyma and often distortion of the kidney

  4. Often located at a pole of the kidney, may grow large enough to obliterate the kidney

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Lipomas:  

  1. Monomorphic population of mature adipocytes or lipocytes within the interstitium

  2. May surround and separate tubules

  3. No capsular reaction, hemorrhage or necrosis

• Liposarcomas:  

  1. Sheets of mature lipocytes infiltrating between preexisting tubules and glomeruli

  2. Immature fat cells, lipoblasts, and islands of primitive mesenchymal cells may be present

  3. Nuclei are larger compared to lipomas, with varying degree of pleomorphism

  4. Anaplastic or pleomorphic variant:  variable morphology mixed with large, bizarre multinucleated cells; intracytoplasmic fat vacuoles present in only small percentage of cells; may resemble histiocytic sarcoma or malignant fibrous histiocytoma

  5. Areas of hemorrhage and necrosis in large tumors   

 

ULTRASTRUCTURAL FINDINGS:

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemistry: MDM2 or CDK4 for confirming diagnosis of well-differentiated & de-differentiated liposarcoma
• p53 expression in canine liposarcoma correlates with myxoid variant and higher proliferative activity

 

DIFFERENTIAL DIAGNOSIS:

• Lipoma vs. Liposarcoma: Size, cellular features and tissue invasiveness differentiate lipomas from liposarcomas
• Renal mesenchymal tumor: Generally in young rats (<12 months old) and do not contain lipid
• Fatty infiltration: Mature adipocytes with infiltrative pattern, may be difficult to differentiate from renal lipoma

 

COMPARATIVE PATHOLOGY:  

• Uncommon in most species
• Liposarcoma is a rare primary bone tumor in animals, resembling its soft tissue counterpart but forming osteolytic bone lesions.
• Dog – Predilection for subcutis and deeper soft tissues (axial most common); viscera also reported
• Cat - Have been associated with retrovirus infection and with vaccination sites
• Rats – Most commonly in subcutis or in fatty tissues of the abdominal cavity; more common in males
• Human – Predilection for deeper soft tissues including gluteal region, thigh, lower extremities, and retroperitoneum 

 

REFERENCES:  

1. Avallone G, Muscatello LV, Leoni A, Roccabianca P, Lepri E, Crippa L, Bacci B. p53 Expression in Canine Liposarcoma Correlates With Myxoid Variant and Higher Proliferative Activity. Vet Pathol. 2020;57(5):620-622.
2. Brannick, EM, Newkird, KM, Schaefer, DMW.  Neoplasia and Tumor Biology, In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:385-387.
3. Craig LE, Dittmer KE, Thompson KG. Bones and Joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals  6th ed. vol 1. St. Louis, MO: Elsevier; 2016: 123.
4. Hard GC, Seely JC, Betz LJ. A Survey of Mesenchyme-related Tumors of the Rat Kidney in the National Toxicology Program Archives, with Reference to Renal Mesenchymal Tumor, Tox Pathol., 2016, Vol 44(6):848-855.
5. Mauldin EA, Peters-Kennedy, J. Integumentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals  6th ed. vol 1. St. Louis, MO: Elsevier; 2016: 726.
6. Meuten DJ. Tumors in Domestic Animals. 5th ed., Ames, IA: Iowa State University Press;2017:158-159.
7. Mohr U. Urinary System. In: Mohr U, ed. International Classification of Rodent Tumors, Part 1-The Rat. New York, NY: Oxford University Press; 1992:10-11.
8. Seely JC, Hard, GC, Blankenship B. In: Boorman’s Pathology of the Rat. Cambridge, MA: Elsevier Academic Press, 2018: 149-150.

Click the slide to view.

---