JPC SYSTEMIC PATHOLOGY
Signalment: 4-month-old female polled Hereford calf
HISTORY: This calf had progressive seborrhea since one month of age. Samples include skin and diaphyseal bone marrow.
HISTOPATHOLOGIC DESCRIPTION: Bone marrow: Diffusely, there is a marked increase in bone marrow cellularity and the majority of cells are 10-15 um in diameter, with brightly eosinophilic cytoplasm, a single round 4-5um nucleus withclumped to condensed nuclear chromatin (erythroid series: rubricyte or late rubricyte); cells are occasionally binucleate or have irregular nuclear profiles; there are also smaller cells with hyperchromatic nuclei and eosinophilic cytoplasm (metarubricytes). Multifocally, there are many 60-70 um diameter multinucleated cells with eosinophilic cytoplasm (megakaryocyte hyperplasia). Frequently, macrophages contain golden-brown pigment (hemosiderin). There is a marked decrease in the M:E. There is an absence of adipose tissue and bony trabeculae are rare.
Haired skin: Diffusely, the epidermis is plicated and there is marked epidermal and follicular orthokeratotic hyperkeratosis that often fills and distends hair follicles. Within the epidermis at all levels and within the internal root sheath there are few individual keratinocytes that are detached from surrounding cells, have pyknotic nuclei and hyperchromatic, eosinophilic cytoplasm (dyskeratosis). Multifocally, the granular layer is prominent, and the internal root sheath is fragmented or disrupted, with missing or irregularly shaped hair shafts. Diffusely, periadnexal and perivascular connective tissues are expanded by few lymphocytes, macrophages, rare eosinophils, mildly ectatic lymphatics, and edema.
MORPHOLOGIC DIAGNOSIS: 1. Bone marrow: Erythroid hyperplasia, marked, with erythroid maturation arrest, polled Hereford, bovine.
- Haired skin: Dyskeratosis, epidermal and follicular, multifocal, moderate, with diffuse marked epidermal and follicular orthokeratotic hyperkeratosis and mild lymphohistiocytic perivascular and periadnexal dermatitis.
ETIOLOGIC DIAGNOSIS: Congenital dyserythropoiesis and dyskeratosis
SYNONYMS: Congenital anemia, dyskeratosis, and progressive alopecia syndrome; congenital dyserythropoiesis of Herefords
- A syndrome characterized by anemia, progressive alopecia, and dyskeratosis
- Identified in polled Herefords; slowly progressive and often fatal disease
- Thought to be a maturation defect of the erythroid series and epidermis
- Erythropoiesis is ineffective; maturation is arrested at the late rubricyte stage
- Likely due to a simple genetic defect or defects in two closely linked loci
- Gaps in the nuclear membrane of recently divided and binucleate rubricytes indicate possible delayed or inhibited post-mitotic nuclear membrane fusion
TYPICAL CLINICAL FINDINGS:
- Small birth weight, exercise intolerance
- Persistent non-regenerative, normocytic to macrocytic, normochromic anemia; WBC number and distribution normal
- Hypoproteinemia (both albumin and globulin fractions are low)
- Hyperferremia: Increased saturation of serum total iron binding capacity (rules out iron deficiency)
TYPICAL GROSS FINDINGS:
- Prominent forehead and hyperkeratotic muzzle
- Skin: Progressive alopecia and hyperkeratosis evident first over the bridge of the nose, lateral auricular margins and base of the ears, which slowly becomes generalized
- Thick, wrinkled skin over the head, face and neck; seborrhea
- Hair is wiry, kinked or tightly curled and easily epilates
- Bone marrow: Dark red erythropoietic marrow fills the metaphysis and diaphysis of the humerus and femur, replacing fatty marrow
- Liver: Marked subcapsular hepatic fibrosis, giving a mosaic appearance
- Pale mucous membranes, subcutaneous tissues, and kidneys
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Marked erythroid hyperplasia with a predominance of late rubricytes and metarubricytes; replacement of diaphyseal fatty marrow
- Significantly decreased M:E ratios (0.02:1 - 0.15:1) due to increased erythroid precursors (normal bovine M:E ratio is 0.3:1 - 3.3:1)
- Nuclear:cytoplasmic asynchrony is evident by the absence of cytoplasmic polychromatophilia; hemoglobinization precedes nuclear maturation; rubricyte cytoplasm is homogenous and eosinophilic, typical of fully hemoglobinized cells
- Features of dysplastic rubricytes include binucleation, abnormal chromatin patterns, irregular nuclear shapes, and irregular nuclear margins
- Hyperplasia of the megakaryocyte series; granulocytic series is normal
- Epidermal and follicular orthokeratotic hyperkeratosis and hypergranulosis
- There is dyskeratosis of epidermal keratinocytes and follicular keratinocytes in Huxley’s layer of the inner root sheath; individual keratinocytes become detached and have pyknotic/hyperchromatic nuclei and deeply eosinophilic cytoplasm
- Epidermal surface may be plicated; follicular density may be normal or increased
- Many follicles are in the telogen phase and contain club hairs or no hair shafts; internal root sheaths are keratinized prematurely
- Degenerated sebaceous glands; ectatic tubular glands
- Mild, perivascular, lymphocytic infiltrate; diffuse increase in mononuclear cells throughout the superficial dermis
- Erythroid precursors have abnormalities associated with the nucleus:
- Irregular nuclear outlines
- Double nuclei
- Nuclear blebs, indentations, or clefts
- Nuclear membrane gaps with protrusion of cytoplasmic material into nuclear areas
- Abnormally condensed and hyperosmiophilic chromatin
- Numerous nuclear vacuoles
ADDITIONAL DIAGNOSTIC TESTS:
- Hematological evaluation, skin biopsies and bone marrow aspirate
- Defective erythropoiesis
- Deficiencies: B12, folic acid, iron, copper
- Toxicities: Molybdenum, lead, chloramphenicol
- Dermatologic lesions similar to nutritional and chronic endocrine diseases
- Dyskeratosis: Lichenoid dermatoses; pemphigus; seborrheic complexes
- Alopecia: Congenital hypotrichosis (abnormal trichohyalin granules); baldy calf syndrome; lethal trait A-46
- Dog: Idiopathic dyserythropoiesis of English springer spaniel dogs causes polymyopathy with megaesophagus, varying degrees of cardiomegaly, and microcytic nonregenerative anemia with metarubricytosis and dysplastic erythroid changes
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