Definition/General
Introduction:
Pure red cell aplasia (PRCA) is a rare hematological disorder characterized by selective failure of red blood cell production
The bone marrow shows marked reduction or absence of erythroid precursors with preservation of granulopoiesis and thrombopoiesis
It can be congenital or acquired and presents with severe anemia.
Origin:
Results from selective suppression of erythropoiesis at the level of committed erythroid progenitors
The disorder affects CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) cells
Myeloid and megakaryocytic lineages remain intact
The exact pathophysiology varies between congenital and acquired forms.
Classification:
Classified as congenital (Diamond-Blackfan anemia) or acquired PRCA
Acquired forms include primary idiopathic PRCA
Secondary PRCA associated with thymoma
Viral-induced PRCA (parvovirus B19)
Drug-induced PRCA
Autoimmune PRCA
Transient erythroblastopenia of childhood (TEC).
Epidemiology:
Rare disorder with incidence of 1-2 per million population annually
Acquired PRCA more common in adults aged 40-60 years
Slight female predominance in acquired cases
Congenital forms present in infancy or early childhood
Associated with thymoma in 30-50% of adult cases.
Clinical Features
Presentation:
Progressive fatigue and weakness due to severe anemia
Pallor and shortness of breath
Exercise intolerance
Absence of splenomegaly (unlike other bone marrow disorders)
No lymphadenopathy
Cardiac symptoms (palpitations, chest pain) in severe cases.
Symptoms:
Severe anemia symptoms
Fatigue and weakness
Dyspnea on exertion
Reticulocytopenia (hallmark feature)
Normal or low-normal white blood cell count
Normal platelet count
Absence of bleeding or infection tendency.
Risk Factors:
Thymoma (30-50% of adult cases)
Parvovirus B19 infection (especially in immunocompromised)
Drug exposure (phenytoin, azathioprine)
Autoimmune disorders
Chronic kidney disease
Pregnancy (rare cases)
Genetic predisposition in congenital forms.
Screening:
Complete blood count with reticulocyte count
Bone marrow examination
Parvovirus B19 serology
Thymoma screening (CT chest)
Drug history evaluation
Anti-erythropoietin antibodies in selected cases.
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Gross Description
Appearance:
Bone marrow aspirate shows reduced volume and pale appearance
Hypocellular aspirate with predominant myeloid cells
Absence of erythroid clusters
Normal megakaryocytes and granulocytic elements.
Characteristics:
Decreased bone marrow cellularity specifically affecting erythroid lineage
Normal trabecular bone architecture
Fatty replacement in areas of erythroid depletion
Preserved myeloid islands and megakaryocyte distribution.
Size Location:
Affects all active hematopoietic sites
Vertebral bodies, pelvis, ribs show changes
Peripheral bones may show fatty conversion
Spleen and lymph nodes typically normal in size.
Multifocality:
Diffuse involvement of all hematopoietic bone marrow sites
Uniform pattern of erythroid suppression
No focal lesions or infiltrates
Selective erythroid involvement maintains normal bone marrow architecture.
Microscopic Description
Histological Features:
Marked reduction or absence of erythroid precursors (<5% of nucleated cells)
Normal granulopoiesis with full maturation spectrum
Normal megakaryopoiesis with appropriate numbers
Increased myeloid-to-erythroid ratio (>10:1, normal 3-4:1).
Cellular Characteristics:
Erythroid precursors show maturation arrest at pronormoblast or basophilic normoblast stage
Giant pronormoblasts may be present (parvovirus infection)
Normal morphology of granulocytes and megakaryocytes
Absence of dysplastic changes in other lineages.
Architectural Patterns:
Preserved bone marrow architecture with selective erythroid depletion
Normal sinusoidal pattern
Increased fat content in erythroid areas
Maintained myeloid islands and megakaryocyte distribution
No fibrosis or infiltrates.
Grading Criteria:
Severity graded by erythroid percentage: Severe (<1% erythroid cells)
Moderate (1-5% erythroid cells)
Mild (5-10% erythroid cells)
Reticulocyte count consistently low (<1%)
Hemoglobin levels typically <7-8 g/dL.
Immunohistochemistry
Positive Markers:
Glycophorin A highlights residual erythroid cells
CD71 (transferrin receptor) marks erythroid precursors
Hemoglobin A in mature erythroid cells
CD34 may show normal stem cell population
MPO highlights preserved myeloid cells.
Negative Markers:
Viral capsid proteins (except in parvovirus cases)
Lymphoid markers (CD20, CD3) typically negative
Plasma cell markers (CD138) usually negative
CD117 shows normal pattern in stem cells.
Diagnostic Utility:
Confirms selective erythroid depletion
Helps identify residual erythroid cells
Excludes infiltrative processes
Quantifies erythroid percentage accurately
Helps distinguish from aplastic anemia
Identifies viral inclusions in parvovirus cases.
Molecular Subtypes:
Congenital forms (genetic mutations)
Parvovirus-associated (viral genome detection)
Autoimmune forms (anti-EPO antibodies)
Thymoma-associated (immune-mediated)
Drug-induced (reversible pattern).
Molecular/Genetic
Genetic Mutations:
RPS19 mutations (Diamond-Blackfan anemia, 25% cases)
RPS26, RPS24, RPL5 mutations (ribosomal protein genes)
GATA1 mutations (X-linked form)
KLF1 mutations (erythroid transcription factor)
EPO receptor antibodies (acquired cases).
Molecular Markers:
Erythropoietin levels markedly elevated (>100 mU/mL)
Anti-EPO antibodies in some acquired cases
Parvovirus B19 DNA (by PCR)
HLA associations in autoimmune cases
Ribosomal protein defects in congenital forms.
Prognostic Significance:
Congenital forms require lifelong management
Parvovirus-induced usually self-limiting in immunocompetent
Thymoma-associated may improve with thymectomy
Drug-induced reversible with drug withdrawal
Idiopathic cases variable prognosis with immunosuppression.
Therapeutic Targets:
Corticosteroids (first-line therapy)
Immunosuppressive agents (cyclosporine, ATG)
Erythropoiesis-stimulating agents (limited efficacy)
Thymectomy for thymoma cases
IVIG for viral cases
Rituximab for refractory cases.
Differential Diagnosis
Similar Entities:
Aplastic anemia (pancytopenia, hypocellular marrow)
Myelofibrosis (fibrosis, teardrop cells)
Myelodysplastic syndrome (dysplastic changes, blasts)
Acute leukemia (blasts, infiltration)
Transient erythroblastopenia of childhood (age-specific).
Distinguishing Features:
PRCA: Selective erythroid aplasia
PRCA: Normal granulopoiesis and thrombopoiesis
Aplastic anemia: Pancytopenia
Aplastic anemia: Hypocellular marrow all lineages
MDS: Dysplastic changes
MDS: Increased blasts
Leukemia: Blast infiltration
Leukemia: Abnormal cell morphology.
Diagnostic Challenges:
Distinguishing congenital from acquired forms
Identifying underlying thymoma
Detecting parvovirus infection in immunocompromised
Ruling out drug-induced causes
Differentiating from early aplastic anemia
Age-related considerations in diagnosis.
Rare Variants:
Transient erythroblastopenia of childhood (self-limiting)
X-linked PRCA (GATA1 mutations)
Late-onset Diamond-Blackfan anemia
Pregnancy-associated PRCA
Post-transplant PRCA (ABO incompatibility).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Bone marrow aspirate and biopsy from [site], adequate for evaluation
Diagnosis
Pure Red Cell Aplasia
Classification
Classification: [congenital/acquired] pure red cell aplasia
Bone Marrow Cellularity
Cellularity: [X]% for age, with selective erythroid depletion
Lineage Assessment
Erythropoiesis: markedly reduced ([X]% of nucleated cells). Granulopoiesis: normal. Megakaryopoiesis: normal
Morphological Features
Shows [erythroid precursor pattern] with myeloid-to-erythroid ratio of [X]:1
Special Studies
Glycophorin A: highlights residual erythroid cells
Flow cytometry: [if performed]
Molecular studies: [if performed]
Clinical Correlation
Findings consistent with pure red cell aplasia. Recommend [specific investigations]
Final Diagnosis
Bone marrow showing pure red cell aplasia, [severity grade]