Six-year-old female French Alpine goat, (Capra aegagrus hircus).This goat was
suspected to have aborted prior to necropsy, although no expelled fetus was
found. This goat also aborted last year, but had successfully kidded in the past.
uterine body contained two macerated fetuses with a crown to rump length of 16
cm and 10 cm. Within the uterus, all of the caruncles were enlarged (~4x2x1
cm), homogeneous, and pale tan.
uterine caruncular labyrinth is diffusely expanded by abundant pale
eosinophilic homogenous, extracellular material which is multifocally disrupted
by areas of blue granular mineralization. The interdigitating cotyledonary
villi are sparse, and the allantoic stroma is mildly expanded by edema. The
aforementioned interstitial eosinophilic material within the caruncles stains
orange/pink with Congo red and exhibits apple green birefringence with
polarized light, consistent with amyloid. The umbilicated surface of the
placentome is multifocally ulcerated and replaced by large aggregates of
neutrophils, lymphocytes, and histiocytes. Similar inflammatory cells extend
into the subepithelial stroma of the caruncle, endometrium, and minimally
throughout the labyrinth. The placental and endometrial stroma is expanded by
moderate amounts of edema, few scattered inflammatory cells, and multifocal
aggregates of mineral. There are also multifocal areas of mineralization
throughout the tunica media of medium-sized vessels within the placenta and
1. Uterus: Diffuse interstitial caruncular amyloid
2. Uterus and placenta: Chronic necrotizing placentitis and endometritis with mineralization
Bacterial culture and sensitivity (uterus):
growth of Brucella species
, PCR (uterus): Negative
burnetii, PCR (uterus): Negative
Bronchointerstitial pneumonia/Influenza virus
amyloidosis has been previously reported in a small number of goats in
California. Clinical presentation of such goats included mid-to-late term
abortion that often occurred repeatedly over multiple years which was attributed
to impaired gas exchange at the site of fetal attachment.2 Ages
ranged from 3-8, and breeds included Toggenburg, La Mancha, and Saan. Similar
to the California goats, this goat had no evidence of amyloid deposition in
other organs nor was there evidence of a systemic or chronic disease process.
Few bacteria were isolated from the inflamed region of the placentome but are
considered to be secondary to the retained fetuses. Bacterial culture did not
isolate Brucella abortus, and PCR was negative for Chlamidophila
species and Coxiella burnetti.
In general, amyloid is composed of insoluble aggregates of misfolded proteins, and deposition of amyloid can occur in a wide variety of localized or systemic diseases.8 Although the fibrillar component of amyloid is overall similar in composition, a diverse number of proteins with variation in sequence and structure are considered amyloidogenic.7,8 Common amyloid precursors include: serum amyloid A (SAA), amyloid light chain (AL), islet amyloid polypeptide (IAPP), mutated forms of transthyretin, and beta protein amyloid.7,8
In particular, SAA proteins comprise a family of apolipoproteins that can be synthesized hepatically and/or extrahepatically. Hepatic derived SAA (SAA1 and SAA2) can dramatically increase in response to inflammation. In mice, rats, cows, and rabbits SAA3 appears to be the most common extrahepatic SAA in addition to being produced hepatically.3 Increased production of SAA3 has also been described in bovine and human mammary gland epithelium in response to prolactin, and in uterine papillary cancer. In the goats in California increased levels of SAA3 were detected within the endometrium when compared to the liver, suggesting localized expression. The type and cause of the amyloid deposition in this case is currently unknown, but the localized caruncular involvement is similar to what has been previously described and may represent a new syndrome of goats.2
Placenta, caruncle: Amyloidosis, diffuse, marked, French
Alpine goat, Capra aegagrus hircus
The contributor provides an informative summary of the
pathogenesis of amyloidosis and review of previously reported cases of a unique
syndrome of caruncular amyloidosis causing abortion in goats. This excellent
case confounded conference participants on initial examination of the tissue
section. Virtually every attendee interpreted the amorphous, smudgy, homogenous
eosinophilic material that diffusely expands the uterine lattice as a
geographic area of coagulative necrosis admixed with multifocal mineralization
and mild inflammatory infiltrate in the subepithelial stroma of the caruncle
and endometrium; collectively, the findings were attributed to normal post
kidding involutional change, rather than caruncular amyloidosis. Similar to the
findings reported by the contributor, Congo red histochemical staining of
serial sections performed at the JPC demonstrates the eosinophilic
proteinaceous material is diffusely congophilic and displays bright apple-green
birefringence when viewed under polarized light.
Spirited discussion ensued among conference participants regarding the presence of concurrent diffuse necrosis, autolysis, or a combination of both admixed with the deposited amyloid in the tissue section. Most favored diffuse necrosis of both the epithelial and endothelial cells secondary to amyloid deposition, resulting in infarction of the placentome. Discord over the presence or absence of necrosis or autolysis nothwithstanding, this case nicely demonstrates a newly reported syndrome of reproductive failure in goats secondary to uterine amyloid deposition in the endometrium at the site of placental attachment.2 Accumulation of amyloid within the carucle markedly compromises blood flow and both gas and nutrient exchange between the doe and the fetus; this leads to fetal hypoxia and eventually death.2 Similar to previously reported cases of caruncular amyloidosis in goats2, amyloid is not present within the intercaruncular endometrium, myometrium, endometrial glands, or vessels in this doe.
Before discussing this case, participants reviewed the normal placentation in small ruminants. All ruminants have similar cotyledonary placentation composed of the fetal cotyledon and the maternal caruncle. The placenta contains the maternal endometrium and the fetal chorioallantoic membranes (CAM).1 Ruminant placentas are nondeciduate, indicating that the maternal endometrium and fetal CAM are in close contact, but they do not intimately fuse. In cotyledonary placentation, there are numerous areas where the fetal cotyledon villar attachments interdigitate with the crypts of the caruncular epithelium. The combination of the fetal cotyledon and maternal caruncle make up the placentome.1 In sheep and goats, the caruncles have a characteristic concave shape, nicely demonstrated in this case.1 Bovine placentomes are similar in structure and function, but are convex rather than concave.
Conference participants discussed various causes of abortion in small ruminants, to include infectious agents such as Chlamydophila abortus, Toxoplasma gondii, Brucella ovis, Campylobacter fetus, Coxiella burnetii, and Listeria monocytogenes. Non-infectious causes include plant toxins, such as locoweed poisoning, and nutritional factors including dietary deficiencies of copper, magnesium, vitamin A, and selenium.5,6 After reviewing this case, conference participants agreed that caruncular amyloidosis should be considered as an additional differential diagnosis of non-infectious abortion in the goat.
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