JPC SYSTEMIC PATHOLOGY

HEMOLYMPHATIC SYSTEM

February 2024

H-M03 (NP)

 

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 10-15µm in diameter, with brightly eosinophilic cytoplasm, a single round 4-5µm nucleus with clumped to condensed nuclear chromatin (erythroid series: rubricyte or late rubricyte); cells are occasionally binucleate or pleomorphic; there are also smaller cells with hyperchromatic nuclei and eosinophilic cytoplasm (metarubricytes). Multifocally, there are many 60-70 µm 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.

2. 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

 

GENERAL DISCUSSION: 

• A syndrome characterized by anemia, progressive alopecia, and dyskeratosis 
• Identified in polled Herefords; slowly progressive and often fatal disease

 

PATHOGENESIS:

• Unknown but thought to be related to impaired cytokinesis during terminal cell division
• Erythropoiesis is ineffective; maturation is arrested at the late rubricyte stage

 

TYPICAL CLINICAL FINDINGS:

• Persistent non-regenerative, normocytic to macrocytic, normochromic anemia with spherocytosis; WBC number and distribution normal

• Mild reticulocytosis, inappropriate for severity of anemia

• Hypoproteinemia (both albumin and globulin fractions are low)
• Hyperferremia: Increased saturation of serum total iron binding capacity (rules out iron deficiency)

 

TYPICAL GROSS FINDINGS:

• 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
• Pale mucous membranes, subcutaneous tissues, and kidneys

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Bone marrow:  

• 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

Skin:

• 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

 

ADDITIONAL DIAGNOSTIC TESTS:

• Hematological evaluation, skin biopsies and bone marrow aspirate

• Erythroid precursors have abnormalities associated with the nucleus including frequent binucleation and mitotic nuclei

• Cats: Acquired dyserythropoiesis is a cause of visible (stainable) iron stores on bone marrow cytology, which is an abnormal finding in cats

 

DIFFERENTIAL DIAGNOSIS:

• 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

 

COMPARATIVE PATHOLOGY:

 

REFERENCES:

1.  Durham AC, Boes KM. Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:843.

2.   Haddad JL, Roode SC, Grindem CB. Bone Marrow. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:480-483.

3.   Mauldin E, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 1. St. Louis, MO: Elsevier limited; 2016:539. 

5. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013:167.

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