JPC SYSTEMIC PATHOLOGY
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. Spindles cells are arranged in streams and tightly packed whorls that surround and entrap 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 separate and replace 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, and oval to elongate nucleus that is vesiculate, and has 1-2 variably distinct nucleoli. Mitoses within the stellate cells average 1 per 10 HPF. Mitoses within the spindle cells average 1 per HPF 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 are 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
- 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 carcinogens at a very early age; experimentally, rats at 4 weeks of age are the most susceptible
- 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
- 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 basic stem cell is a spindle form, but other cell types present which are invariably present are stellate cells typifying mesenchyme and smooth muscle
- 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
- Other components not always present include neoplastic vascular tissue, striated muscle, cartilage, and osteoid
- 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)
- Unknown for spontaneously arising tumors
- These neoplasms arise from primitive pluripotential mesenchymal cells in the cortical interstitium and the outer stripe of the medulla
- Toxin-induced: Stages following single dose of dimethylnitrosamine: Acute phase: toxicity and inflammation in the outer cortex > latent phase: sporadic hypercellular foci of macrophages, lymphocytes and plasma cells in the cortical interstitium > 12-16 weeks post-inoculation: poorly differentiated neoplastic mesenchymal cells proliferate between and around tubules > progressive sequestration of tubules and glomeruli with extensive collagen deposition
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:
- 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
- Spindle cells resemble fibroblasts with abundant, anastomosing channels of rough endoplasmic reticulum and bundles of actin-like myofilaments
- Stellate cells resemble fibrocytes
- 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
- Hemangiosarcoma: RMT may have a frank vascular component; could represent variants of renal mesenchymal tumors
- Liposarcoma: 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
This tumor is found only in laboratory rodents and humans
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