AFIP Wednesday Slide Conference - No. 23
- April 09 1997
- Conference Moderator: Major Mark Martinez
U.S. Army Medical Research Institute of Infectious Disease
Fort Detrick, MD 21702-5011
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Case I - 96N377 (AFIP 2550229)
- Signalment: 2-day-old, female, Quarterhorse, equine.
- History: Mild scours developed 24 hours prior to death,
and progressed to severe colic. Then, no more feces passed. Radiograph
revealed gas distended small and large intestines.
- Gross Pathology: Turbid, flocculent, yellow fluid
in peritoneal cavity. At least two areas (10-12 cm) of dark red
to black discoloration of the small intestine with severe hemorrhage
and congestion in the local mesentery. Mucosa of the affected
bowel is dull, brown and roughened. Mesenteric lymph nodes are
enlarged and hemorrhagic.
- Laboratory Results: Neutropenia with degenerative
left shift reported.
Microbiology: Clostridium perfringens isolated in heavy
growth from intestine.
Contributor's Diagnosis and Comments: Acute, severe, diffuse,
- Examined is a section of jejunum taken from the most severely
affected area identified at the gross exam. In both sections,
there is severe, diffuse, acute necrosis of the intestinal mucosa.
Small remnants of intestinal epithelium remain, usually in the
base of the intestinal crypts. The outline of the intestinal
villi remains as blunted, short folds of necrotic tissue. The
surface of these necrotic folds of epithelium is consistently
covered by a thin dense line of bacteria. Bacteria are basophilic,
long, and rod-shaped, and are aligned perpendicular to and in
close contact with the tissue surface. Abundant degenerative
neutrophils fill the lamina propria and the submucosa. There
is marked diffuse congestion of the large and small vessels throughout
the intestinal wall.
- The findings in this foal are consistent with the history
and clinical signs for acute bacterial enteritis and colitis
with peritonitis and sepsis. Histologic picture of large gram-
positive bacilli adhered in a "picket fence" fashion
to the necrotic mucosa is classic for acute clostridial enteritis.
The culture results confirm the identity of these organisms.
- AFIP Diagnosis: Small intestine: Enteritis, necrotizing,
acute, diffuse, severe, with necrotizing vasculitis, fibrin thrombi,
diffuse transmural edema, and myriad mucosal adherent bacilli,
- Conference Note: The conference participants agreed
with the contributor's diagnosis and comments.
- Hemorrhagic necrotizing enteritis in newborn foals has been
reported to be caused by the following Clostridium species: Clostridium
perfringens type C, Clostridium perfringens type B, Clostridium
sordelli, and Clostridium difficile. Culture and identification
cytotoxins allows definitive diagnosis.
- Clostridium perfringens is a gram-positive, spore-forming,
anaerobic bacterium. The species is divided into 5 types, designated
A-E, based on exotoxin production. There are four major antigenic
lethal exotoxins. Alpha toxin is a lecithinase which acts on
cell membranes to produce necrosis or hemolysis. Beta toxin,
the most important toxin elaborated by Cl. perfringens types
B and C, causes necrosis, decreases mobility of intestinal villi,
and enhances bacterial attachment to the villi. Epsilon is also
a necrotizing toxin which is produced as an inactive prototoxin
and activated by enzymatic digestion (ex: trypsin in the intestine).
Iota toxins increase the capillary permeability, and are produced
as prototoxins which are activated by proteolytic enzymes in
the intestine. In addition to these four major toxins, there
are eight minor toxins produced by C. perfringens.
- Types and toxins of Clostridium perfringens:
Toxin Alpha Beta Epsilon Iota
Type A ++ - - -
B + ++ + -
C + ++ - -
D + - ++ -
E + - - ++
++ = significant toxin; + = small amount; - = none detected
- Diseases associated with the 5 types of Cl. perfringens include
1. Type A - gas gangrene, food poisoning (humans), necrotic enteritis
2. Type B - dysentery (lambs, calves), hemorrhagic enteritis
3. Type C - hemorrhagic enteritis (calves, lambs, foals, piglets,
4. Type D - enterotoxemia (sheep, goats, calves), focal symmetric
5. Type E - rare; hemorrhagic enteritis (calves, rabbits)
- The sequence of events leading clostridial overgrowth and
toxin production in
neonates is not well elucidated. Because B toxin is trypsin labile,
factors such as low
levels of the enzyme in young animals, trypsin inhibitors, and
high toxin concentrations
may play a role in the disease process. Clostridia initially
attach to the tips of the villi
and produce toxin. Toxin production results in damage to absorptive
epithelial cells. The
epithelial cells degenerate and slough beginning at the villar
tips and extending
progressively downward. Edema and transient leukocytosis occur
in the lamina propria
followed by necrosis. After 6-8 hours, one third or more of the
length of the villi is
damaged leading to an outpouring of serum, inflammatory cells
- Contributor: Department of Pathology, Colorado State
University, Fort Collins,
1. Jones RL, et al: Hemorrhagic necrotizing enterocolitis
Clostridium difficile infection in four foals. JAVMA 193(1):76-79,
2. Drolet R, et al: Necrohemorrhagic enterocolitis caused by
perfringens type C in a foal. Can Vet J 31:449-450, 1990.
- 3. Jubb, KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic
edition. Academic Press, Inc., Philadelphia, pp. 237-247, 1993.
- 4. Schulman FY, Montali RJ, Hauer PJ: Gastroenteritis associated
Clostridium perfringens type A in black-footed ferrets (Mustela
nigripes). Vet Pathol
- 5. Thomson, RG. Special Veterinary Pathology. BC Decker,
Toronto, 1988, pp.
- International Veterinary Pathology Slide Bank:
Laser disc frame #13894, 13895.
Case II - L33 (AFIP 2558677)
- Signalment: 9-month-old female Beagle dog.
- History: The lesion was an incidental finding at necropsy
in a 9-month-old Beagle
dog used in a toxicology study.
- Gross Pathology: Multifocal dark discoloration was
found in the jejunum.
- Laboratory Results: None.
- Contributor's Diagnosis and Comments: Jejunum: heterotopy,
- Gastric mucosa replaces intestinal mucosa multifocally. At
the base of gastric
mucosa, tubular structures comparable to intestinal glands are
present. The underlying
muscular wall is unchanged. In the segments of intestine adjacent
to the gastric
mucosa, there is a marked increase in the number of goblet cells.
In these areas, villi
are blunt and the lamina propria contains an increased number
of inflammatory cells,
predominantly lymphocytes and macrophages with fewer neutrophils
and plasma cells.
- At the interface with gastric mucosa, there is goblet cell
enterocytes. This could represent an adaptive response to the
peptic insult. The lack of
evidence for pre-existing mucosal or submucosal injury argues
for a congenital origin
rather than being the result of a reparative or metaplastic process,
from which it needs
to be differentiated.
- Gastric heterotopia in the intestinal tract was reported
to have an incidence
around 4% in laboratory Beagle dogs (Iwata et al.,1990). In one
instance, it has been
the site of development of a gastric adenocarcinoma (Panigrahi,
- AFIP Diagnosis: Jejunum: Heterotopic fundic gastric
mucosa, segmental, with
goblet cell hyperplasia, and mild multifocal subacute inflammation,
- Conference Note: Heterotopia of the gastric mucosa
is extremely rare in
animals, having been noted in the Beagle breed and the cat. Heterotopic
mucosa in Beagles has only been reported in the small intestine.
- In humans, heterotopic gastric mucosa can occasionally be
found in the intestinal
tract, most commonly in the duodenum, but also in the jejunum,
ileum, colon, and
rectum. In most cases, the heterotopic gastric tissue is identified
as an isolated finding
in the intestinal mucosa, but may be a component of more complex
as Meckel's and other small bowel diverticula, enteric duplications,
and various other
congenital malformations. In dogs, heterotopic gastric mucosa
has only been reported
in the jejunum.
- Contributor: Laboratories PFIZER, Centre de Recherche,
BP 159, Amboise
Cedex, 37401, FRANCE.
1. Iwata H, et al: Heterotopic gastric mucosa of the small
intestine in laboratory
beagle dogs. Toxicol Pathol 18(3):373-379, 1990.
- 2. Panigrahi D, Johnson AN, Wosu NJ: Adenocarcinoma arising
heterotopia in the jejunal mucosa of a beagle dog. Vet Pathol
- 3. Rest JR: Gastrointestinal anomalies in the dog - two case
reports. Vet Rec
- 4. Fenoglio-Preiser CM, Pascal R, Perzin KH: Tumors of the
27, Second Series, Atlas of Tumor Pathology, Armed Forces Institute
of Pathology, pp.
- International Veterinary Pathology Slide Bank: None.
Case III - S123/96 (AFIP 2549001)
- Signalment: 2.5-year-old female Labrador Retriever
- History: For four weeks, the owner noted lack of appetite.
There was one
episode of opisthotonos and tonic seizures in the forelegs. The
pressed its head against the wall. At presentation, it had stooped
severe tremors and was smacking its lips. At the owners request,
the dog was
euthanized due to poor prognosis.
- Gross Pathology: At necropsy, alterations were found
in the cerebellum. A 1x1
cm2 leptomeningeal area was thickened and grey at the lateral
surface of the left lobus
rostralis. The leptomeninx overlying the lobus caudalis (tuber
and folium vermis,
pyramis and uvula) was also thickened and light to dark grey.
There were focal
adhesions between the altered leptomeninx and dura mater. Sagittal
sectioning of the
brain revealed thickening of the leptomeninx, the fissura prima,
fissura secunda and fissura caudolateralis as well as in the
areas of the lobus
- Laboratory Results: None.
- Contributor's Diagnosis and Comments: Malignant meningioma,
meningiothelial and fibroblastic type.
- Histologically, there was a proliferation of mesenchymal
cells in the leptomeninx.
Cellular borders of neoplastic cells were not well delineated.
Nuclei were ovoid or
elongated and contained a moderate amount of chromatin. Moderate
numbers of mitotic
figures were found. Two types of growth pattern were observed:
- 1. There were areas with loosely arranged reticular neoplastic
cells growing in
whirling patterns. Cells were embedded in unbounded matrix and
few collagen fibers.
These areas contained numerous small blood vessels which stained
positively for factor-
VIII-related antigen. There were also numerous melanin-containing
2. Other areas were more cellular. The bundles of fibroblastic
embedded in a densely collagenous matrix.
- The neoplastic cells infiltrated into the parenchyma along
the spaces of Virchow
Robin and caused multifocal destruction of the grey and white
matter of the cerebellum.
By immunohistochemistry, neoplastic cells were positive for vimentin
and negative for
glial fibrillary acidic protein (GFAP). There were regional differences
in the percentage
of neoplastic cells that expressed vimentin.
- Canine meningiomas are quite common. Most of the features
described in the
presented case are characteristic for the canine meningiomas.
predominantly in mature and aged dogs, with a higher prevalence
in females. In dogs,
they are more common in the brain than in the spinal cord. The
meningiomas have favored localizations. They occur over the convexities,
in the midline
attached to the falx cerebri, below the brain stem, attached
to the tentorium cerebelli or
at an intraventricular localization associated with the choroid
plexus. As observed in this
case, meningiomas are regularly attached to the dura mater. Their
attachment to the
dura or leptomeninges may be broad, narrow or total (meningioma
Meningiomas show a high degree of histopathological diversity
with both mesenchymal
and epithelial patterns. The range of patterns in canine meningiomas
- 1. Meningiothelial or syncytial forms
2. Fibroblastic form
3. Transitional for (syncytial and fibroblastic)
4. Angioblastic form
5. Psammomatous form
6. Microcystic form
- Mixtures of the various forms are common. Canine meningiomas
vimentin intermediate filaments. Vimentin expression is important
for the differentiation
from other intracranial tumors.
- The histological pattern seems to be of little prognostic
meningiomas are benign. Presence of mitotic figures and brain
invasion, as observed in
this case, as well as areas of tumor necrosis are considered
as indicators of a poor
- A differential diagnosis is primary sarcoma of the meninges.
- AFIP Diagnosis: Brain, cerebellum: Malignant meningioma,
Labrador Retriever, canine.
- Conference Note: The presence of scattered melanin
containing cells within the
neoplasm generated considerable discussion among the conference
complicated determination of the diagnosis. Pigmented meningioma
has not been
reported in animals. In humans, pigmented meningiomas have been
reported in the
past; however, recent immunohistochemical and ultrastructural
studies have shown
these tumors to be melanocytic. The existance of true melanotic
meningioma has been
questioned. Primary melanocytic neoplasms of the meninges are
recognized in humans
and animals. In the present case, pigmented malignant meningioma
malignant melanoma were included in the differential diagnosis.
- To resolve the issue, tissue from the neoplasm was examined
microscopy. Ultrastructurally, there is extensive interdigitation
of slender cytoplasmic
processes of the neoplastic cells. Many desmosomal junctions
connect the processes.
The cytoplasm contains intermediate filaments. These findings
are diagnostic of
meningioma. Melanoma cells contain membrane-bound melanosomes
melanosomes and have dendritic processes but do not have interdigitating
processes with desmosomes. The interpretation of malignancy is
based on brisk mitotic
activity, areas of patternless growth and extensive perivascular
infiltration. By criteria
used in human meningiomas, this would be an atypical meningioma.
and brain invasion (as opposed to perivascular extension) are
required for the diagnosis
of malignant meningioma in humans. Canine meningiomas are often
than their human counterparts.
- Contributor: Institut für Pathologie, Tieräztliche
Bünteweg 17, 30559 Hannover, Germany.
1. Andrews, EJ: Clinicopathological characteristics of meningiomas
JAVMA 163:151-157, 1973.
- 2. Braund KG, Ribas JL: Central nervous system meningiomas.
Contin Ed 8:241-248, 1986.
- 3. Patnaik AK, Kay WJ, Hurvitz AI: Intracranial meningioma:
pathologic study of 28 dogs. Vet Pathol 23:369-373, 1986.
- 4. Schulman FY, Ribas JL, Carpenter JL, Sisson AF, LeCouteur,
meningioma with pulmonary metastasis in three dogs. Vet Pathol
- 5. Summers BA, Cummings JF, de Lahunta A: Veterinary Neuropathology,
355-362. Mosby, St. Louis, USA, 1995.
- 6. Dardick I, et al: Handbook of diagnostic electron microscopy
in-training. Igaku-Shoin Medical Publishers, New York, Section
4, pp. 42-45, 1996.
- 7. Limas C, Tio FO. Meningeal melanocytoma ("melanotic
melanocytic origin as revealed by electron microscopy. Cancer
- 8. Burger PC, Scheithauer BW. "Tumors of Meningothelial
"Melanocytic Tumors" In Tumors of the central nervous
system, Atlas of tumor
pathology, Third series, Fascicle 10, Armed Forces Institute
of Pathology, Washington,
DC, pp345-348, 1994.
- International Veterinary Pathology Slide Bank:
Laser disc frame #237, 2548, 2549, 5143.
Case IV - CP96-5002 (AFIP 2565951)
Signalment: Magellanic penguin, 2-years-old, male.
- History: Experienced some minor foot problems and,
thus, was in and out of
isolation and exhibit. Placed on preventative anti-malarial and
numerous times. Appetite began decreasing on June 6, 1996 while
on exhibit, put on
antibiotics and placed in isolation. Breathing was labored. Received
fluids, nebulized with antifungal medication and given oxygen
continued to worsen. Found dead on July 2, 1996.
- Gross Pathology: General appearance normal. Slightly
muscle mass. Air sacs appeared normal. There was a 5mm raised,
firm round nodule
on the serosal surface of the distal esophagus. The mass did
not extend through the
mucosal surface. Another small brownish mass was seen on the
ventral surface of the
caudal right side of the sternum. This mass was 7mm diameter,
and was easily removed from the sternum. Both lungs were extremely
diffuse firm nodules of varying sizes throughout the parenchyma.
These masses were
solid on cut sections and yellowish internally. All other organs
appeared within normal
limits. The trachea was free of any plaques or discharges.
- Laboratory Results: Fungal culture yielded a culture
of Rhizopus sp.
- Contributor's Diagnosis and Comments: Lung, bronchointerstitial
necrogranulomatous, hemorrhagic, diffuse, severe, mycotic.
- The lungs have severe necrosis with inflammation and hemorrhage.
inflammation consists of epithelioid macrophages, multinucleate
giant cells, and
degenerate heterophils with fewer lymphocytes and plasma cells.
There is moderate
fibrosis; hemorrhage and edema are also present. There are numerous,
approximately 10-15 µm diameter fungal hyphae which are
branching, septate, non-
dichotomous, with bulbous projections. Occasional vessels have
and luminal fungi with inflammation.
- The most likely cause of death was the combination of fungemia
and sepsis. The
cultures and histologic morphology are both consistent with Rhizopus.
- AFIP Diagnosis: Lung: Pneumonia, necrogranulomatous,
diffuse, severe, with necrotizing vasculitis and fungal hyphae,
Magellanic penguin, avian,
etiology consistent with a mucoraceous zygomycete.
- Conference Note: Penguins appear to be highly susceptible
infections. Infections caused by Aspergillus fumigatus are the
most common cause of
death in captive penguins. Rhizopus infections are rarely diagnosed
in birds and, to our
knowledge, have not been reported in penguins.
- The taxonomy of pathogenic Zygomycetes was discussed during
Rhizopus belongs to the Family Mucoraceae, Order Mucorales, and
is the most frequent
agent of mucormycosis in animals. Mucoraceous zygomycetes tend
to spread along
tissue planes and invade blood vessels, often causing thrombosis.
intravascular hyphae leads to disseminated infection, most frequently
lungs, central nervous system, kidneys, liver, gastrointestinal
tract, and heart.
- The hyphae of the zygomycetes are indistinquishable from
each other in
histologic section; specific identification requires fungal culture
or other special
- Contributor: University of Miami, School of Medicine,
Department of Pathology
(R-46), P.O. Box 16960, Miami, FL 33121.
1. Fowler ME (editor): Zoo and Wild Animal Medicine, second
Saunders, Co., pp. 294-313, 1986.
- 2. Chandler FW, Watts JC: Pathologic Diagnosis of Fungal
Press, Chicago, pp. 85-95, 1987.
- 3. Montali RJ, Migaki G (eds): Proceedings of a symposium
on the comparative
pathology of zoo animals held at the National Zoological Park,
Washington DC, October 2-4, 1978. pp. 277-281, 1980.
- International Veterinary Pathology Slide Bank:
Laser disc frame #11074, 20547.
- Lance Batey
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
- * The American Veterinary Medical Association and the American
Veterinary Pathologists are co-sponsors of the Registry of Veterinary
C.L. Davis Foundation also provides substantial support for the
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