Porcine Multisystemic Wasting Syndrome – PCV-2

Whats your diagnosis #3

Porcine Multisystemic Wasting Syndrome – PCV-2

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History: A feeder pig was found dead in the morning, it was thinner than its penmates.

Gross Necropsy: (no photos)

The lungs were loosely adhered to the thoracic body wall by multiple strands of fibrin. The lungs were diffusely edematous and firm.

The pericardium contained approximately 200 mls of fluid. The right ventricle was severely enlarged and the pulmonary trunk was dilated.

There was diffuse serous atrophy of fat.

Histopathology:

Lungs: Alveolar septa contain large numbers of lymphocytes, macrophages, plasma cells and lesser numbers of neutrophils and eosinophils. Small bronchioles and a few alveoli contain neutrophils. There are perivascular infiltrates of lymphocytes and macrophages. Within the walls of arterioles there are neutrohilic and lymphocytic infriltrates and there is vacuolar degeneration of the tunica media. There is proliferation of fibrous tissue which occludes the lumens of multifocal small arterioles and bronchioles.

Lung: Vasculitis and perivasculitis, proliferative, and bronchointerstitial pneumonia

Kidneys: The renal interstitium is infiltrated with large numbers of lymphocytes, macrophages, and plasma cells with lesser numbers of neutrophils and eosinophils. There are macrophages containing multiple basophilic round cytoplasmic inclusions.

Kidney: Interstitial nephritis, eosinophilic and granulomatous

Kidney, renal cortical tubule: Sloughed necrotic epithelial cells with basophilic cytoplasmic inclusions in epithelial cells and macrophages

Lymph nodes: There is diffuse lymphoid depletion characterized by loss of lymphoid follicles and germinal centers. There are moderate numbers of multinucleated giant cells in the medullary sinuses along with moderate numbers of lymphocytes, neutrophils, macrophages, and some eosinophils.

Lymph node: Granulomatous lymphadenitis- Macrophages and multinucleated giant macrophages replace normal architecture

Spleen: There is diffuse lymphoid depletion in the spleen similar to the lymph node.

Ileum: There is diffuse lymphoid depletion in the Peyer’s patches of the ileum, and there are large numbers of macrophages and lymphocytes infiltrating the submucosa along with small numbers of neutrophils.

Brain: There are a few foci of perivascular histiocytic and lymphocytic infiltrates in the brain stem.

Kidney, PCV-2 IHC: Strong immunoreactivity in tubular epithelial cells

Lung, PCV-2 IHC: Strong immunostaining in macrophages around blood vessels

Lymph node, PCV-2 IHC: The centers of follicles are devoid of lymphocytes and macrophages/ dendritic cells stain strongly with PCV-2 antigen

Diagnosis:

1. Lungs: Interstitial pneumonia, granulomatous, severe, diffuse, with arteritis, perivasculitis, and multifocal proliferation of vascular fibrous tissue

2. Kidneys: Interstitial nephritis, granulomatous, multifocal, moderate, with intrahistiocytic basophilic cytoplasmic inclusions.

3. Brain: Perivasculitis, granulomatous, mild, multifocal

4. Spleen/Lymph nodes/ Ileum: Diffuse lymphoid depletion

5. Lymph nodes: Granulomatous lymphadenitis, moderate, diffuse

6. Ileum : Granulomatous enteritis, mild, multifocal

A feeder pig was presented for necropsy 12/8/08. This pig is thinner than its pen mates. It was found

dead 12/08/08 in the morning. The farm has had APP and Strep on the premises.

Comment:

The gross and microscopic lesions are consistent with PMWS, and PCV- 2 was detected in pooled tissues by PCR. No significant bacterial agents were isolated from the lymph node or intestines, and no bacteria were isolated from the lung. The PCR test for PRRSV was negative. An ELISA for swine flu was negative as well.

This case demonstrates the usefulness of histopathology as a diagnostic tool.  The gross lesions alone suggest polyserositis such as would be caused by Streptococcus suis or Haemophilus parasuis.  The histopathologic lesions of granulomatous inflammation with multinucleated giant macrophages and intracytoplasmic basophilic inclusions are specific for PCV-2 associated disease.  Immunohistochemistry and PCR confirmed the presence of PCV-2 antigen in the affected tissues, and other viruses (PRRS and Influenza) were ruled out by PCR and ELISA tests.

A diagnosis of PMWS is made based on 1) clinical signs of failure to grow, weight loss, and pneumonia, 2) typical histologic lesions including granulomatous lymphadenitis/ lymphoid depletion, and 3) detection of the virus in tissues by IHC or ISH.  Affected pigs are 5-18 weeks old and may have gastric ulcers, pleural and perioneal effusions and diarrhea.

Due to the ubiquitous presence of PCV-2 in swine herds and the broad variety of diseases that can involve PCV-2 it is proposed to introduce the term Porcine Circovirus Associated Disease (PCVAD).   PCVAD  can  be  subclinical  or  include  one or more of the following:  multisystemic disease with weight loss,  respiratory  signs,  PDNS,  diarrhea, and reproductive disorders.

Other proposed systems of classification of  PCVAD   includes: systemic infection (such as PMWS),  PCV2-associated  pneumonia,  PCV2-associated enteritis,  PCV2-associated  reproductive  failure,  and PCV2-associated  PDNS.

References:

Opriessnig T,  Xiang-Jin M, Halbur  P G.  2007. Porcine circovirus type 2–associated disease: Update on current terminology, clinical manifestations, pathogenesis, diagnosis, and intervention strategies.  J Vet Diagn Invest 19:591–615.

Luteinizing follicular cyst in a dog

History: Tissue from an 11 month old female Great Dane.  The tissue was removed during a routine spay surgery and submitted for histopath due to abnormal appearance.

Ovary: Large corpus luteum at the top of the image and a smaller luteinizing follicle in the center

Ovary: Below the solid corpus luteum is a large cyst lined by granulosa cells with a focal area of luteinization (foamy vacuolated cells)

Ovary: Higher magnification of the luteinizing cells lining the cyst

Ovary:  In each section examined there are primary follicles present in a fibrovascular stroma.  There are two normal corpora lutea present consisting of a large solid mass ofpolygonal cells with large intracytoplasmic lipid vacuoles (luteinized cells). In addition there are two large cystic follicles partially lined by luteinized cells and partially lined by follicular epithelium.

Comment:

Luteinized ovarian cysts are derived from anovulatory Graffian follicles and can cause hyperestrogenemia in some cases and are associated with cystic endometrial hyperplasia and development of pyometra in dogs.

Tissue from an 11 month old female Great Dane was submitted for histopathology.  During the spay

surgery the submitting veterinarian noticed an abnormal anatomical arrangement of the reproductive

tract and requests identification of the submitted tissue to see if it is ovarian or lymphoid.

Whats Your Diagnosis #3

History: A feeder pig was found dead in the morning, it was thinner than its penmates.

Gross Necropsy: (no photos)

The lungs were loosely adhered to the thoracic body wall by multiple strands of fibrin. The lungs were diffusely edematous and firm.

The pericardium contained approximately 200 mls of fluid. The right ventricle was severely enlarged and the pulmonary trunk was dilated.

There was diffuse serous atrophy of fat.

Histopathology:

Lung:

Differential Diagnoses for interstitial pneumonia and vasculitis in a pig:

1. PRRS virus

2. Porcine Circovirus-2-

3. Classical Swine Fever (Pestivirus)

To Be Continued….

What other tissues would you examine?   What histologic lesions do you expect to find with each of the differentials above?

To see our diagnosis and discussion click here

Uterine Adenocarcinoma in a Rabbit

 

History:  An 11 year old intact female rabbit  had a chronic history of Pasteurella multocida snuffles and head tilt which had resolved.   Her owner noticed she started to have increased abdominal component of respiration which progressed to open mouth breathing.  A mass was palpated in the caudal abdomen during examination. 

 

Gross Necropsy: 

The lungs were almost completely replaced by large numbers of individual to coalescing firm white nodules ranging in size from 0.5 cm to 3 cm in diameter and projecting 1-2 cm from the lung surface. On cut surface the nodules were firm and homogeneously white.

 

Lungs. liver, in situ: Multifocal tan firm nodules replace most of the lung tissue

Lungs, liver, closer view

 

Lungs (with pluck) removed

A 3.5 cm x 2 cm x 1 cm elliptical mass was present in the wall of the right uterine horn located approximately 1 cm from the ovary. The mass was irregular and composed of firm white nodules and softer grey areas.

 

Uterus and uterine horns: One horn is enlarged with a transmural mass

Uterine horn: Closer view of mass

 

Uterine horn: Lumen opened showing thickened uterine wall

 

 

 

The liver had multifocal firm white nodules (1.5 cm to 0.5 cm in diameter) scattered throughout the parenchyma.

An 11 year 9 month old intact female rabbit was presented for necropsy on 9/19/08. This doe had a

chronic history of Pasteurella multocida snuffles and head tilt which had resolved. On 9/18/08 her

owner noticed she started to have increased abdominal component of respiration which progressed to

open mouth breathing on 9/19/08. She had no previous indication of respiratory distress. A mass

palpated in the caudal abdomen during examination. She was euthanized at 2:10 pm and sent in for

necropsy.

Histopathology:

Uterus:  The myometrium was infiltrated by a neoplasm composed of epithelial cells forming tubules and acini.  

 

Uterine wall: The myometrium is invaded by a neoplasm forming acini (neoplastic endometrial glands)

 

Uterus: Closer view of neoplastic endometrial glands, the neoplastic cells are separated by fibrous tissue

 

Uterus: Close up of neoplastic cells

 

 

 

 

Lung and Liver:  The neoplastic cells in the lung and liver resembled those in the uterus, however they formed solid sheets rather than acini and were more anaplastic with marked anisocytosis and anisokaryosis. 

 

Lung: Low power view showing multiple individual nodule of metastatic uterine adenocarcinoma

 

Liver: A nodule of metastatic neoplastic cells compresses adjacent liver tissue

 

 

 

Comment:

Uterine adenocarcinoma arises from endometrial glands, and is the most common spontaneous neoplasm in Rabbits.  The incidence of this neoplasm increases to 80% of animals 5-6 years and older in Oryctolagus cuniculus.   The etiology of the neoplasm is unknown, however some reports implicate estrogen as a related factor.  These tumors usually are multinodular and involve both uterine horns.  They may metastasize to the lung and liver most commonly and become  implanted on serosal surfaces of the abdominal organs.

Reference:

Percy, DH and Barthold, SW. Chapter 6 Rabbit in Pathology of Laboratory rodents and rabbits, 3rd edition.  p 253.  Blackwell Publishing, 2007.

Epidural steatitis and vertebral osteomyelitis in a dog

 

History:  A 1 year old spayed female bulldog mix canine became acutely non-ambulatory, and both rear limbs were hyporeflexive.

Gross Necropsy:

There was a 7 cm x 3 cm x 3 cm abscess in the epaxial musculature of the lumbar spine containing red-brown purulent fluid. The muscles surrounding the abscess including the epaxial and hypaxial musculature was pale, and there was a focal area of lysis of the ventral cortex of vertebral bodies L2 and L3.

Lumbar epaxial muscles: Abscess over spinal column

The dura of the spinal cord from vertebral bodies L2-L5 was covered with a thick layer of organized fibrin and suppurative material causing compression of the spinal cord. There were no gross lesions in the intervertebral discs and spinal cord.

Spinal cord: There is a thick mat of fibrinous and suppurative exudate lying on the spinal cord

There were multifocal 3-5 mm round red nodules diffusely throughout the

lung.

There was a 7 cm x 3 cm x 3 cm abscess in the epaxial musculature of

the lumbar spine containing red-brown purulent fluid. The muscles

surrounding the abscess including the epaxial and hypaxial musculature

was pale, and there was a focal area of lysis of the ventral cortex of

vertebral bodies L2 and L3. The dura of the spinal cord from vertebral

bodies L2-L5 was covered with a thick later of organized fibrin and

suppurative material causing compression of the spinal cord. There were

no gross lesions in the intervertebral discs and spinal cord.

There were multifocal 3-5 mm round red nodules diffusely throughout the lung.

 

Lung: Multifocal embolic pneumonia

 

 

Histopathology:

Epidural adipose:  The epidural fat is infiltrated by large numbers of neutrophils, macrophages, lymphocytes and plasma cells with large amounts of fibrin and fibrous tissue.  There are multiple bacterial colonies.

 

Spinal cord, dura and epidural adiopse- Suppurative steatitis

 

Vertebrae:  The cortical bone is infiltrated and lysed by a large amount of neutrophils, macrophages and fibroblsats.  There are large numbers of neutrophils surrounding bacterial colonies in the bone marrow of several vertebrae.

 

Vertebrae: Suppurative osteomyelitis with bacterial colonies

 

Bacterial colonies are composed of mixed gram positive rods and gram negative bacteria with the gram positive rods predominating.  Similar bacterial colonies are present in the lungs and valvular thrombus.

 

Gram stain of bacteria- Large numbers of gram positive rods consistent with Campylobacter spp

Aerobic culture:  A swab from the exudate covering the spinal cord grew Corynebacterium spp and an unidentified bacteria.

 

Lung: Embolic suppurative pneumonia with bacterial colonies

 

Diagnosis:

1. Spinal Cord: Fibrinosuppurative epidural steatitis, chronic, focally extensive with compression of spinal cord 

2. Vertebral body:  Suppurative osteomyelitis with bacterial colonies

3. Lung: Multifocal suppurative pneumonia

4. Heart, right AV valve: Focal valvular endocarditis (not pictured)

 

Comment:

Microscopically the spinal column lesions are more chronic as evidenced by increased numbers of macrophages, lymphocytes, and fibroblast proliferation.  Epidural steatitis can occur through direct extension of bacteria into the epaxial musculature or through hematogenous bacterial emboli.  The infection spread into the vertebrae and epidural adipose tissue causing spinal cord compression and the neurologic signs noted in the history.  Secondary bacteremia caused valvular endocarditis and embolic pneumonia.

Coccidiosis in a Chukar

History:   The flock is healthy in the brooder house, but 3-4 weeks after being turned out 2-5% of the birds get weak, thin, and listless.

Gross Lesions:  The two birds were in good body condition with no pectoral muscle atrophy.  No lesions of any significance were found.

Histopathology:

Small intestine:  There are abundant intracellular coccidia in varying stages of development in the enterocytes of multiple small intestinal sections. There is also segmental enterocyte necrosis with villous blunting in several sections of small intestine. In some sections coccidian oocytes are seen in the lumen of the small intestine among sloughed epithelial cells and necrotic debris.

 

Small Intestine: Numerous villous enterocytes contain large coccidial organisms

Small Intestine: Closer magnification, showing more detail of the coccidia

 

Small Intestine: High power view showing different stages of coccidia

 

Small Intestine: High power view

Morphologic diagnosis:  

Small Intestine: Villous enterocyte necrosis and villous blunting, severe,  segmental with intralesional intracellular coccidia

Comment:

We considered these birds to be in the early stages of coccidiosis, since there was no obvious weight loss, diarrhea or enteritis.  The infection was localized to small sections of the small intestine, but was severe in those sections.

Coccidiosis in Chukars can be caused by  Eimeria legionensis.

Life cycle of Eimeria:

visual aid

biology

another helpful visual aid

yet another visual aid

Also helpful

Trophoblast Emboli in a Chinchilla

 

History:   An 8-11 month old female intact Chinchilla had given birth to 3 baby Chinchillas 2 weeks prior.   Without any premonitory signs she “had a spasm, fell to the side and died ½ hour later”.

Gross findings:

The lungs were mottled red and pink, wet and heavy. The right cranial lung lobe was most affected.

The uterine horns contained three ½ cm round white foci that expanded the uterine wall consisting of a semi-soft material (involution of placental sites).

Histopathology:

Lungs:   There was diffuse congestion, and multifocal suppurative bronchopneumonia with edema and hemorrhage filling alveoli.  There were multifocal alveolar capillaries with 100-200 um trophoblast cells occuring singly or multiply.  The cells had abundant cytoplasm and 50-100 um diameter nuclei.   Trophoblasts were present in normal lung as well as pneumonic lung.

Lung: trophoblast embolus, H&E stain

Lung: trophoblast embolus, close up

Lung: Tropholbast embolus PAS stain

Lung: Trophoblast embolus, PAS stain, close up

Lung: trophoblast embolus, PAS stain

Uterus:  Trophoblasts were present within blood vessels of the myometrium in the uterus.

Uterus: Trophoblast embolus in myometrium, PAS stain

PAS staining has been used to outline the basement membranes of the alveolar cappillaries to demostrate the intravascular nature of the trophoblast emboli.

Comment:

The cause of death was attributed to pneumonia.  Most trophoblast emboli were present in areas with no inflammation.  In other reports of this condition in hamsters, chinchillas, and porcupines these are considered incidental findings.  In humans they have been linked to life threatening conditions.   Hemochorial placentation is common to all these species.

References:

 Hamir,  A. N. and  Rupprecht, C. E.  Trophoblast-like Cells in the Tissues of Porcupines (Erethizon dorsatum), Vet Pathol 45:409–411 (2008).

Billington, W.D. Vascular Migration of Transplanted Trophoblast in the Golden Hamster. Nature 211: 988-989 (1966).

 da Silva Ilha, M.R. et al.  Trophoblastic Pulmonary Embolism in Chinchillas (Chinchilla laniger). Ciência Rural, Santa Maria, v. 30, n.5, p.903-904, 2000.

J. D. Burek, B. Goldberg, G. Hutchins and J. D. Strandberg.  The pregnant Syrian hamster as a model to study intravascular trophoblasts and associated maternal blood vessel changes.  Veterinary Pathology, Vol 16, Issue 5 553-566, Copyright © 1979.  

Orsini MW: The trophoblastic giant cells and endovascular cells associated with pregnancy in the hamster, Cricetus auratus. Am J Anat 94:273–331, 1954.

Tvedten HW, Langham RF: Trophoblastic emboli in a chinchilla. J Am Vet Med Assoc 165:828–829, 1974.

 

Habek D, Janculjak D, Cerkez Habek J, Jalsovec D. Sudden death because of massive pulmonary thromboembolism and concomitant cerebrovascular trophoblastic embolism following artificial abortion. Fetal Diagn Ther. 2005 Sep-Oct;20(5):390-2.