AFIP Wednesday Slide Conference - No. 19

March 05 1997

Conference Moderator: Dr. Steven E. Weisbrode
Diplomate, ACVP
College of Veterinary Medicine
The Ohio State University
1925 Coffey Road
Columbus, OH 43210-1093

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Case I - 94 1228 (AFIP 2547680)

Signalment: A 1½-year-old, intact, male Domestic Shorthair cat.

History: The cat was a "runt" which never grew properly and appeared now to have a large brachycephalic head with thickened mandible and short curved legs, difficult, noisy breathing and anorexia. The cat was treated symptomatically and euthanized when quality of life deteriorated.

Gross Pathology: Face distorted; no teeth erupted, all bones foreshortened and broadened without distortion of joints. Mandible 2 to 4 cm in diameter.

Laboratory Results: FeLV positive on ELISA and PCR on liver/spleen. Gradual development of non-regenerative anemia (PCV .21 reference (.24-.45 L/L). X-rays: Increased density and thickness of all bones

Contributor's Diagnosis and Comments: Osteopetrosis secondary to feline leukemia virus infection.

This kitten had the condition recognized at 3 months of age and lived with the progressive bone formation for over a year. The cat had neoplastic lymphocytes in the liver and intestine on post mortem but was not leukemic at the time of euthanasia.

AFIP Diagnosis: 1. Bone, site unspecified: Osteopetrosis, diffuse, severe, with failure of modeling, domestic shorthair, feline.
2. Bone, marrow: Hypercellularity, diffuse, moderate, with myeloid hyperplasia and erythroid hypoplasia (M/E= 4:1).

Conference Note: This is an excellent example of osteopetrosis which by definition is the accumulation of primary and secondary spongiosa due to a reduction in bone resorption caused by defective osteoclast function (failure to model). The primary and/or secondary spongiosa are retained and fill the diaphysis of tubular bones. Osteopetrosis secondary to FeLV infection has been reported in cats. C-type retrovirus particles consistent with FeLV were detected in association with the plasma membranes of osteocytes and osteoblasts and embedded in the osteoid. Virus particles were also found within megakaryocytes of the bone marrow.

Osteopetrosis has been reported in the rat, rabbit, mouse, dog, cat, sheep, horse, pig, ox, deer, and human. In humans and other animal species, osteopetrosis is generally a hereditary disease passed in an autosomal recessive manner. Osteopetrosis secondary to type-C retrovirus has been described in cats, mice, and chickens. In cats, there is defective osteoclasis, whereas in mice and chickens the disorder is primarily osteoblastic. Avian osteopetrosis is probably the best characterized example of a bone disorder caused by a type-C retrovirus; however, it is not a true osteopetrosis because the increased bone formation is subperiosteal rather that medullary and results from osteoblastic activity rather than defective osteoclasis.

The precise nature of osteoclast dysfunction in these disorders is unknown. Numerous functional defects have been observed in osteoclasts of osteopetrotic animals including:

1. Lack of hydrolytic enzymes in the bone-osteoclast interface or the inability of osteoclasts to discharge lysosomal and oxidative enzymes in the extracellular spaces.
2. Partial or complete absence of ruffled borders on the osteoclasts. The brush border is considered the cytoplasmic structure which allows bone resorption.
3. Reduction in the number of osteoclasts.

Experimental models in mice have shown that a mutation in the gene coding for macrophage colony stimulating factor (M-CSF), the C-src gene and the C-fos oncogene can result in osteopetrosis.

Conference participants were concerned that the open physis did not correspond with the age given in the signalment. Although we don't know from what bone this section was taken, it has been reported that the distal radial and ulnar physes can remain open up to 20 months of age in cats.

Contributor: Central Laboratory for Veterinarians, 5645 199th St., Langley, British Columbia, Canada V3A-1H9.

1. Hoover EA, Kociba GJ: Bone lesions in cats with anemia induced by feline leukemia virus, J Nat'l Cancer Inst, 53(5):1277-1279, 1974.
2. Zenoble RD, Rowland GN: Hypercalcemia and proliferative, myelosclerotic bone reaction associated with feline leukovirus infection. JAVMA 175:6:591-595, 1979.
3. Cotran RS, Kumar V, Robbins SL (eds): Robbins, Pathologic Basis of Disease, 5th ed., WB Saunders, pp. 1222-1223, 1994.
4. Jubb KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic Animals, Vol. 1, Academic Press, pp. 39-42, 1993.
5. Kramers P, et al: Osteopetrosis in cats, J Small Anim Pract 29:153-164, 1988.
6. Marks SC: Osteopetrosis, multiple pathways for the interception of osteoclast function, Appl Pathol 5:172-183, 1987.
7. Naito M, et al: Abnormal differentiation of tissue macrophage populations in osteopetrosis (Op) mice defective in the production of macrophage colony-stimulating factor, Amer J Pathol 139(3):657-667, 1991.

International Veterinary Pathology Slide Bank:
Laser disc frame #4020, 4593, 7431, 12850, 20367, 20369, 20370, 21230.


Case II - 10621-96 (AFIP 2550849)

Signalment: 75-day-old, 24 kg, Suffolk ewe-lamb.

History: In early April, this lamb was observed to walk with a stiff gait. Despite treatment with selenium ("BoSe"), amoxicillin, and banamine, she became depressed and died two days later. Other lambs in the flock were not affected.

Gross Pathology: Pale gray streaks and white foci were disseminated in most skeletal muscles and throughout the ventricular myocardium. The lungs were diffusely swollen, dark red, and wet (congested and edematous).

Laboratory Results: None relevant.

Contributor's Diagnosis and Comments: Skeletal muscle: Degeneration and necrosis of myofibers, multifocal-coalescing, with myofiber calcification (mineralization) and regeneration, "satellite" cell proliferation, and macrophage infiltration.

Etiology: Selenium-Vitamin E deficiency.

Lesions in the submitted section of skeletal muscle (from a pelvic limb) are typical of nutritional myopathy (so-called "White muscle disease") in lambs. Except for a lack of myofiber regeneration, myocardial lesions were similar to those in the skeletal muscles and, when considered with the finding of diffuse pulmonary edema, provided evidence that heart failure secondary to nutritional cardiopathy resulted in the death of this lamb. Monensin toxicosis was considered as a differential diagnosis because this lamb had access to feed containing monensin, but the extreme degree of myofiber calcification seen in tissue from this lamb was not typical of ionophore-induced myopathy.

AFIP Diagnosis: Skeletal muscle, pelvic limb (per contributor): Degeneration and necrosis, multifocal to coalescing, with regeneration, fibrosis, mineralization, and histiocytic inflammation, Suffolk, ovine.

Conference Note: The conference participants agreed with the contributor's diagnosis and comments. The differential diagnosis for this lesion includes vitamin E/selenium deficiency, toxic myopathies caused by the systemic effects of plant toxins (Cassia sp., Karwinskia sp., gossypol), feed additives (monensin), and metallic or nonmetallic toxins (copper, cobalt, iron, silver, cadmium, zinc, thallium, mercury, selenium, tellurium, and sulfur), the local action of injected toxic substances (chloramphenicol, oxytetracycline and iron preparations), bluetongue virus, and exertional rhabdomyolysis. One characteristic finding in vitamin E/selenium deficiency is the presence of a fine stippling of mineral in less affected myofibers which can be better visualized with a Von Kossa stain.

Contributor: Animal Disease Diagnostic Laboratory, Purdue University, West Lafayette, IN 47907-1175.

Hulland TJ: Muscle and Tendon. In: Pathology of Domestic Animals, ed. Jubb KVF, Kennedy PC, Palmer N, 4th ed., Vol. 1, pp. 228-238. Academic Press, 1993.

International Veterinary Pathology Slide Bank:
Laser disc frame #1045.


Case III - W928/89 (AFIP 2506867), 2 photos

Signalment: Adult male dromedary camel (Camelus dromedarius).

History: This adult male camel (Camelus dromedarius) was one of a group of camels grazed on irrigated pastures of Werribee Open Range Zoo (southern Victoria). He developed chronic progressive multiple limb lameness and stiffness which was unresponsive to treatment with oral phenylbutazone and necessitated euthanasia with intravenous barbiturate. No other clinical signs were noted.

Three non-breeding female camels 2-12 years of age and grazed in the same environment developed similar disease during the subsequent 4 years. Other male camels and zoo-type herbivores grazed in the same environment seemed to be unaffected.

Each of the affected camels had been raised naturally by their parent. They were grazed at Werribee (temperate, predominantly winter rainfall climate) on a variety of pasture types which appeared to provide a balanced mineral diet. Supplemental feeding with pellets and lucern/meadow hay was provided whenever pasture was inadequate.

This camel had been kept on lush irrigated pasture consisting of mixed grasses and some lucern and was reported to have had irregular but frequent episodes of "loose feces". Subsequently, camels were moved to drier enclosures where diarrhea did not occur. The three other camels developed lameness etc. on these drier pastures.

Gross Pathology: The carcass was relatively fresh and in good body condition with ample fat in depots; no abnormalities were detected in visceral organs.

Prominent almost symmetrical bulges were present on each side of the face in front of the eyes. On cross-section of the nose there was a large tumor-like mass of firm, cream-white, fibrous-like tissue within each nasal cavity. Each mass occupied almost the entire nasal cavity and compressed the nasal turbinates dorsally. There was moderate thickening of the horizontal portion of both rami of the mandible. The teeth seemed normal, held firmly within alveoli and had no obvious abnormal alignment of wear. The oral cavity was otherwise unremarkable.

Several joints, especially the hip, stifle, shoulder and elbow, had mild thickening of their joint capsules and small depressions, wrinkles and/or erosions in their articular cartilages. Otherwise the long bones and joints, especially those of the lower limbs, seemed normal. Thoracic and lumbar vertebrae seemed normal.

Laboratory Results: None available for this camel. Three non-breeding female camels grazed in the same environment developed similar disease in subsequent years. Laboratory results of these (Cases 2,3 and 4) together with similar results from 2 male camels grazed on the same pastures and published "normal values" are included in the table.


mmol/L Albumin
g/l Adjusted
mmol/L P
mmol/L ALP
Case 2 2.3 28 2.4 2.53 124 250
Case 3



Case 4



Male 1 2.44 40 2.32 1.09 236 89


Male 2 2.1 33 2.15 2.38 607 68

2.75@ 30
44@ 2.30
2.19@ 43


@ Reported by Higgins and Kock (1986)
+ Beef Cattle Normals (Trube pers. comm.)
* Reported by Calgiuri et al. (1989)

Contributor's Diagnosis and Comments: Nasal cavity, osteodystrophia fibrosa,
cause not determined, probably due to nutritional hyperparathyroidism.

The sections are from samples of the mass of tissue in the nasal cavity and
demonstrate very marked proliferation of fibrous tissue around/within remnants of the
maxilla etc. Numbers of large prominent osteoclasts occur throughout the tissue
particularly around fragments of residual bone. Trabeculae of apparently newly formed
bone occur throughout the mass of fibrous tissue. The overlying nasal epithelium etc.
appears to be normal.

Sections of visceral organs including kidney contained no significant lesions.
There was mild to moderate eosinophil and mononuclear leucocyte infiltration of the
lamina propria etc. of some areas of forestomach, gastric acid secreting and intestinal
mucosae suggesting mild/moderate gastro-enteritis possibly associated with nematode
parasitism. Parathyroids were not available for examination.

Osteodystrophia fibrosa is a lesion associated with excessive secretion of
parathyroid hormone over prolonged periods resulting in extensive osteoclastic
resorption of bone and replacement by proliferation of fibro-osseous tissue. Though
long bones are frequently affected resulting in defects in articular cartilages due to
collapse of underlying supportive bone structure, in many animals the lesion is most
severely expressed in the bones of the face and mandible. In horses enlargement of
these bones associated with the proliferation of fibro-osseous tissue often results in the
clinical syndrome of "bighead". In domestic animals, the lesion is usually due to
disturbances of calcium/phosphorus metabolism of dietary or renal origin.

No significant lesions could be demonstrated in the kidneys of this camel thus
suggesting a nutritional cause for the problem. Though there was evidence of
mild/moderate gastro-enteritis, maldigestion/malabsorption did not seen to be a major
contributing factor as the camel was otherwise in reasonably good nutritional condition
("in good hump").

Fibrous osteodystrophy with multiple limb lameness and facial deformity has been
described previously in 2 dromedary camels associated with feeding a predominantly
grain/concentrate diet. This camel grazed a mixed species pasture with very little
supplementary feeding. Analysis of pastures at a later date suggested adequate
calcium availability (calcium 0.36 - 0.44%, phosphorus 0.23 - 0.35%). Phosphate levels
in drinking water were low (1 mg/L). Examination of pastures failed to identify significant
numbers of plants known to contain oxalates which might have affected calcium
availability. Ruminants are known to be less susceptible than monogastric animals to
the calcium binding effects of plant oxalates because of breakdown of oxalates by
rumen microflora. Though of somewhat different structure to that of domestic
ruminants, the camel's forestomach has been shown to function in a similar manner.
Presumably they therefore have a similar tolerance of dietary oxalates. Vitamin D
availability should have been adequate as the camel continuously grazed pasture with
plentiful exposure to sunlight.

Intermittent diarrhea associated with grazing lush pastures has been suggested
as a possible cause of defective calcium absorption. While this may possibly have
contributed to cause the condition in this animal, the subsequent 2 cases occurred after
the camels had been moved to drier pastries where periodic diarrhea or "loose feces"
was no longer evident.

The exact cause(s) of this problem has not been determined.

AFIP Diagnosis:
1. Maxilla; nasal turbinates: Osteodystrophy, fibrous, diffuse,
severe, dromedary camel (Camelus dromedarius), camelid.
2. Nasal turbinate: Rhinitis, subacute, multifocal, mild.

Conference Note: The conference participants agreed with the contributor's
diagnosis. Fibrous osteodystrophy describes the skeletal lesions that occur in primary
or secondary hyperparathyroidism. This is a generalized process that is characterized
by widespread increased osteoclastic resorption of bone and replacement by fibrous
tissue. In domestic animals, secondary hyperparathyroidism is most common and may
be nutritional or renal.

Nutritional secondary hyperparathyroidism is caused by factors that tend to lower
the levels of serum ionized calcium and to increase the output of parathormone (PTH).
It is most common in young, rapidly growing animals that are fed rations low in calcium
and relatively high in phosphorous. This metabolic disorder is a compensatory
mechanism directed against a disturbance in mineral homeostasis induced by nutritional
imbalances, ie. low serum calcium, excessive phosphorus with normal or low calcium,
inadequate amounts of vitamin D3. The significant end result is hypocalcemia which
result in parathyroid stimulation. Parathyroid glands undergo cellular hypertrophy and
hyperplasia. Increased levels of PTH result in a poorly understood interaction between
osteoclasts and osteoblasts. PTH secretion results in hyperplasia and activation of
osteoclasts. Osteoclasts do not have PTH receptors. Their resorptive activity is
probably controlled by a complex system that involves the response of undifferentiated
cells of osteoblastic lineage which possess receptors for to PTH. These
undifferentiated cells may interact with osteoclasts through a paracrine effect resulting
in stimulation of osteoclastic bone resorption. Increased levels of PTH also cause
diminished renal tubular reabsorption of phosphorus and increased reabsorption of
calcium. Bone resorption is accelerated and release of calcium elevates blood calcium
levels to the low-normal range. Continued ingestion of the imbalanced diet sustains the
state of compensatory hyperparathyroidism, which leads to progressive development of
the metabolic bone disease. There is increased resorption of cancellous bone and
cortical bone, together with the proliferation of fibrous tissue (fibroblasts have PTH
receptors). New bone is formed in a radial fashion by the periosteum, increasing the
size of the bone. The spaces between the trabeculae are constantly filled with
connective tissue. The new trabeculae may remain mineralized or may partially
mineralize only to be again resorbed and replaced, repeatedly and irregularly. A similar
process occurs in the endosteum, replacing the medulla and marrow with fibrocellular
tissue that contains irregular trabeculae. As the original compact bone is broached from
both surfaces, it is steadily and completely replaced by fibrous tissue causing
enlargement of bones such as those of the skull or mandible. Subperiosteal cortical
bone resorption results in bowing deformities and multiple folding fractures of affected
bones, articular collapse and deformity of structures such as the vertebrae and ribs.

Contributor: School of Veterinary Science, University of Melbourne, Veterinary
Clinical Centre, Werribee 3030 Victoria, Australia.

1. Bhatia J S and Ghosal A K: Studies on fermentation in the camel (Camelus
dromedarius). Proceeding of the First International Camel Conference, Allen W R et al,
eds, R & W. Publications (Newmarket) Ltd, pp. 271-274, 1992.
2. Caliguri R, Kollias G, and Spencer C: Metabolic bone disease in dromedary
camels (Camelus dromedarius). J. Zoo Wildl. Med. 20: 482-487, 1989.
3. Englehardt W, Abbas A M, Mousa HM and Lechner-Doll M: Comparative
digestive physiology of the forestomachs in camelids. Proceeding of the First
International Camel Conference, Allen WR, et al (eds), R & W Publications (Newmarket)
Ltd, pp. 263-270, 1992.
4. Higgens AJ, Kock RA: A guide to the clinical examination, chemical restraint
and medication of the camel. In Higgins A. (ed): The Camel in Health and Disease.
Balliere Tindall, London, pp. 21-40, 1986.
5. Kock RA and Chapman JJ: Management, feeding and health of camels kept
under intensive husbandry. In Higgins A. (ed): The Camel in Health and Disease.
Balliere Tindall, London, pp. 149-163, 1986.
6. Lynch M, Slocombe RF and Harrigan KE: Metabolic bone disease in
dromedary camels (Camelus dromedarius). Proc Ann Conf Am Assoc Zoo Vets,
Lansing Michigan, 1995, in press.
7. Palmer N: Bones and Joints. In Jubb KVF., Kennedy PC and Palmer N (eds):
Pathology of Domestic Animals, 4th Ed., Academic press, Vol 1, pp. 72-77, 1993.
8. Walthall JC and Mackenzie RA: Osteodystrophia fibrosa in horses at pasture
in Queensland: Field and laboratory observations. Aust. Vet. J. 52:11-16, 1986.

International Veterinary Pathology Slide Bank:
Laser disc frame #5349, 444, 2071, 2589, 2590, 3692, 6097, 6305, 6310, 8133,
9411, 9488, 10267, 11059, 19388.


Case IV - D96-11790E (AFIP 2549551), 1 photo

Signalment: 1-day-old Thoroughbred cross, male equine.

History: This foal was born weak and did not stand on its own. The foal was
hypothermic (T=90 F), and had bradycardia (42 beats/minute) with weak heart
contractility and arrhythmia. Lung sounds were increased ventrally and a yellowish
nasal discharge was present. The foal had prognathism and contracted tendons.

Gross Pathology: Necropsy revealed prognathism, contracted forelimb flexor
tendons, partial rupture of the common digital extensor tendon, immature carpal and
tarsal bones and bilaterally enlarged thyroid glands. The left thyroid was 12.7 gm and
4.6 x 2 x 2.5 cm while the right thyroid was 12.8 gm and 3.8 x 2.3 x 2.8 cm. The cut
surfaces of the thyroid glands were homogeneous light brown with a meaty texture.

Laboratory Results: Serum Triiodothyronine (T3) value was 284.2 ng/dl.
(Normal = 366.5 ±222.5 ng/dl) Serum Thyroxin (T4) value was 3.05 g/dl (Normal = 13.5
± 5.1 g/dl) Examination of aqueous humor from the eye was negative for nitrates.

Contributor's Diagnosis and Comments: Congenital hypothyroidism
associated with diffuse hyperplastic goiter and musculoskeletal deformity. Cause not
specifically determined.

This case represents a fairly typical example of congenital hypothyroidism and
dysmaturity syndrome in foals. Similar cases have been reported in western Canada,
the Pacific northwest and the Great Lakes area. A single foal or multiple foals born with
this condition have been seen on individual farms. The thyroid glands of affected foals
may be deceptively normal in size or grossly enlarged. Thus, microscopic examination
of the thyroid gland should be included in the diagnostic work up of foals. Also,
determining serum T3 and T4 levels is useful for assessing thyroid function.

Microscopically, the thyroid glands have a hyperplastic appearance with small to
compact follicles producing little to no colloid. Cause of this condition appears to evolve
around the diet of the pregnant mare where consumption of excess nitrates or
inadequate amounts of iodine in the diet have been documented. Similar cases have
been reported with a wide range of thyrotoxic agents during gestation. These include
iodine excess (as well as iodine deficiency), feed contamination with Acremonium
coenophialum or Claviceps purpurea and locoweed ingestion.

AFIP Diagnosis: Thyroid: Hyperplasia, follicular, diffuse, severe (hyperplastic
goiter), Thoroughbred-cross, equine.

Conference Note: The conference participants agreed with the contributor's
diagnosis. Clinical features common to affected foals include prognathism, ruptured
common digital extensor tendons, forelimb contracture, and severely retarded
ossification and crushing of the carpal and tarsal bones. Hypothyroid foals are typically
affected at birth, are often weak and require assistance to stand and may have a grossly
enlarged thyroid.

The conference participants and moderator discussed differentiation of thyroid
hyperplasia, adenoma, carcinoma and different types of goiter in animals.

Contributor: University of Minnesota, College of Veterinary Medicine,
Department of Veterinary Diagnostic Medicine, 1333 Gortner Ave., St. Paul, MN 55108.

1. Allen AL, Doige CE, Fretz PB, et al: Hyperplasia of the thyroid gland and
concurrent musculoskeletal deformities in Western Canadian foals: Reexamination of a
previously described syndrome. Can Vet J 35:31-38, 1994.
2. Allen AL: Hyperplasia of the thyroid gland and musculoskeletal deformities in
two equine abortuses. Can Vet J 36:234-236, 1995.
3. Hines MT, Doles J, Gay C et al: Thyroid hyperplasia and musculoskeletal
deformity in neonatal foals. Proc. 14th ACVIM Forum 544-545, 1996.
4. Allen L, Townsend HGG, Doige CE, Fretz PB: A case-control study of the
congenital hypothyroidism and dysmaturity syndrome in foals. Can Vet J 37:349-358,
5. Sojka JE: Hypothyroidism in Horses, Comp Cont Educ Pract Vet 17(6):845-
852, 1995.
6. Boosinger TR, et al: Prolonged gestation, decreased triiodothyronine
concentration, and thyroid gland histomorphologic features in newborn foals of mares
grazing Acremonium coenophialum-infected fescue, Am J Vet Res 56(1):66-69, 1995.

International Veterinary Pathology Slide Bank:
Laser disc frame #3305, 5545, 11213, 18102, 19081, 19614, 21340, 21341.

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 College of
Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The
C.L. Davis Foundation also provides substantial support for the Registry.

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