JPC SYSTEMIC PATHOLOGY

REPRODUCTIVE SYSTEM

January 2025

R-N12

 

Signalment:  A 10-month-old Fischer 344 rat

 

HISTORY: Incidental finding in an aging rat study.

 

HISTOPATHOLOGIC DESCRIPTION: Uterus: Originating from and markedly expanding the endometrial stroma up to 2.5mm, compressing the uterine lumen, and compressing the uterine wall, is a circumferential, densely cellular proliferation of cells with several different morphologies arranged in variably well demarcated zones. Peripherally and most prominently at the antimesometrial aspect of the uterus, extending a third of the way around the uterus, is the basal zone that separates the myometrium from the proliferative decidual cells and is composed of remnants of the endometrial stroma and glands and few scattered lymphocytes. The inner aspect of the basal zone merges with a thin capsule that separates it from the proliferative decidual cells; this capsule is composed of an indistinct, thin band of spindle cells. The antimesometrial region of proliferative decidual cells is composed of densely packed, polygonal cells separated into packets by small capillaries; these cells have abundant eosinophilic, microvacuolated cytoplasm, large, round, vesiculate nuclei with prominent nucleoli, and are often binucleate. Mitotic figures in this region average 1 per individual HPF (0.237 sq mm). The mesometrial region of proliferative decidual cells is composed of two cell populations: loosely packed spindle to stellate cells with prominent cytoplasmic processes ("spiny cells") and scattered round cells with prominent eosinophilic granules (granulated metrial gland cells) separated by clear space. Mitoses and binucleate cells are frequent in both cell populations. The glycogenic area lies between the antimesometrial and mesometrial regions and encircles the uterine lumen. Though not prominent in this section, it is composed of plump polygonal cells separated by prominent vascular sinuses and separated by clear space toward the periphery. Nuclei are vesiculate and cells are often binucleate, with prominent nucleoli and 1 mitotic figure per individual HPF (0.237 sq mm). 

 

Urinary bladder; kidney; ovary; oviduct; urethra; and vagina: No significant lesions.

 

MORPHOLOGIC DIAGNOSIS: Uterus: Decidual reaction, Fischer 344 rat, rodent.

 

SYNONYM: Deciduoma (obsolete term)

 

GENERAL DISCUSSION:

• Non-neoplastic proliferation of decidual tissue that resembles pregnancy implantation; usually in young pseudopregnant rats; occurs in response to nonspecific stimuli; mimics normal decidual implantation sites; has a high degree of structural organization 
• The National Toxicology Program recommends that the term “deciduoma” be discontinued and the lesion renamed “decidual reaction”
• Decidual cells are endometrial stromal fibroblasts that re-differentiate during pregnancy to allow for trophoblasts to survive and grow, forming deciduate placentas
• Composed of six distinct regions (not all may be discernible due to the cut or stage of development): Basal zone, capsule, antimesometrial region, mesometrial region, glycogenic region, and metrial gland area (see light microscopic findings)

 

PATHOGENESIS:

• The cause is unknown but it is believed to be associated with pseudopregnancy and nonspecific stimuli
• Sensitization to decidualizing stimuli occurs at day 3-4 of pseudopregnancy- there must be at least 48 hours of exposure to progesterone, followed by small amounts of estrogen; the luminal epithelium has the ability to proliferate when stimulated and induces stromal differentiation and decidual reaction 
• Nonspecific stimuli includes mechanical and electrical stimuli; endometrial trauma; intrauterine injections of various substances including balanced salt solutions, oily fluids, and air; vitamin E deficient diets
• This proliferative reaction has a defined, limited course; it ends in degeneration of decidual cells and spontaneous regression in about 12 days; the normal life span of rat decidual reaction is from day 4 until day 12-16 of pseudopregnancy
• Antimesometrial region develops first, followed by mesometrial region, and then metrial gland; decidual reaction regression occurs in the same order
• Low incidence of spontaneous decidual reactions

 

TYPICAL CLINICAL FINDINGS: None

 

TYPICAL GROSS FINDINGS:

• Unilateral or bilateral, single or multiple nodules within the uterine horn that measure up to 4 mm in diameter; occasional diffuse uterine horn enlargement
• Endometrial ulceration
• Hyperemic mesometrial vessels within the broad ligament

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

High level of structural organization; composed of six layers:

• Basal zone: Outermost layer; separates decidual reaction from myometrium; remnants of endometrial stroma and glands
• Capsule: Luminal to the basal zone; band of flattened cells that blend gradually with the endometrial cells on the antimesometrial side
• Antimesometrial region: Densely packed polygonal, eosinophilic antimesometrial cells, often binucleate, separated by small, radially oriented and cross-linked capillaries
• Mesometrial region: Two cell types
  • Spiny mesometrial cells: Cytoplasm has long processes and abundant glycogen; cells are usually binucleate
  • Granulated metrial gland (GMG) cells: Large round cells that are up to 40 um in diameter and frequently binucleated; numerous PAS-positive, diastase-resistant eosinophilic cytoplasmic granules  
    • Glycogenic area: Transition between antimesometrial and mesometrial regions; stromal cells that have glycogen (but not large amounts) and resemble spiny mesometrial cells
• Metrial gland: Located within the mesometrial triangle (bordered by longitudinal muscle on two sides and circular muscle on the third side)
  • Granulated metrial gland (GMG) cells: Loosely arranged; whorl around vessels; natural killer (NK) cell lineage
  • Fibroblastic stromal cells: Adjacent to or surround the GMG cells

 

DIFFERENTIAL DIAGNOSIS:

Nodular lesions in the uterus of a rat:

• Decidual alteration: Occurs in aged rats secondary to endometrial irritation (i.e. endometrial or myometrial tumors); lacks well-defined structure
• Implantation site in pregnant uterus: Looks much like a decidual reaction but has a rapidly expanding implantation cavity
• Granular cell tumor: Polygonal cells with cytoplasmic granules; PAS +, diastase resistant
• Endometrial adenoma / adenocarcinoma: Polygonal cells arranged in acini and tubules, scirrhous response
• Endometrial stromal polyp: Polypoid mass protruding into the uterine lumen; edematous and collagenous stroma covered by endometrial epithelium; highly vascular; +/- cystic endometrial glands 
• Leiomyoma / leiomyosarcoma: Spindle cells; cigar-shaped nuclei; positive for smooth muscle immunohistochemical markers 

 

COMPARATIVE PATHOLOGY:

Decidual reaction: Reported in the mouse, hamster, rabbit, dog, guinea pig and monkey

• Guinea pig: Observed in 24% of female guinea pigs affected by uterine lesions (Pazdzior-Czapula, J Comp Pathol., 2024)
• Mouse: Similar pathology and histology as rats; induced on day 3-5 of pseudopregnancy; lasts 4 days; mouse GMG cells are twice as large as rat GMG cells, with larger granules
• Hamster: Decidual reaction does not produce a metrial gland, but a "vascular knot" within the mesometrial triangle develops instead
• Dog: Spontaneous pseudo-placentational endometrial hyperplasia (PEH; R-M08) which occurs in the luteal phase may be induced by bacteria from the vagina that stimulate the endometrium like a fertile ovum
• Other sterile material within the lumen of the uterus during the luteal phase of a bitch can induce decidual reactions

 

REFERENCES:

1. Katsuhhiko Y, Emoto Y, Kinoshita Y, et al. Histopathological and immunohistochemical characterization of spontaneously occurring uterine deciduomas in young adult rats. J Toxicol Pathol. 2013;26:61-66.
2. National Toxicology Program Nonneoplastic Lesion Atlas. https://ntp.niehs.nih.gov/nnl/female_reproductive/uterus/decreac/index.htm. Accessed 20 January 2020.
3. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier Saunders; 2016:383.

 

 

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