What is the likelihood of a patient with Immune Thrombocytopenic Purpura (ITP) co-occurring with a bone marrow malignancy like Myelodysplastic Syndrome (MDS)?

Co-occurrence of ITP and MDS: Clinical Reality and Diagnostic Challenges

ITP and MDS can co-occur, and this represents a critical diagnostic pitfall—MDS with isolated thrombocytopenia (MDS-IT) is frequently misdiagnosed as refractory ITP, with studies showing that a significant proportion of presumed ITP cases are actually MDS. 1

Frequency and Clinical Context

The exact prevalence of true co-occurrence is not well-established in the literature, but the diagnostic confusion between these entities is well-documented:

• MDS presenting as isolated thrombocytopenia occurs in a meaningful minority of cases, and these patients are commonly misdiagnosed as having ITP 1
• Cytogenetic abnormalities are found in approximately 3% of patients initially diagnosed with ITP, suggesting underlying MDS or clonal hematopoietic disorders 2
• Autoimmune phenomena, including secondary ITP, are well-described in myelodysplastic disorders, particularly in chronic myelomonocytic leukemia (CMML) 3

Key Distinguishing Features of MDS-IT

When MDS presents with isolated thrombocytopenia mimicking ITP, it typically has specific characteristics:

• MDS-IT patients often present with multilineage dysplasia, normal karyotype, and low-risk prognostic scores based on IPSS-R 1
• Minimal morphological dysplasia is common, making diagnosis particularly challenging—MDS with isolated del(20q) frequently presents with thrombocytopenia and minimal dysplasia that may be indistinguishable from ITP on morphology alone 4
• Increased megakaryocytes in bone marrow without obvious dysplasia can be seen in both conditions 2

Critical Red Flags for MDS Rather Than ITP

Refractory ITP should always trigger reconsideration of the diagnosis:

• Lack of response to standard ITP therapies (glucocorticoids, TPO-receptor agonists, rituximab) strongly questions the ITP diagnosis and necessitates thorough re-evaluation 1
• Development of additional cytopenias, monocytosis, or hepatosplenomegaly during follow-up suggests evolution to MDS/CMML 3
• Accidental discovery of thrombocytopenia without bleeding symptoms is more typical of MDS-IT than ITP 2

Mandatory Diagnostic Approach

For any adult patient with isolated thrombocytopenia, especially if refractory to treatment, the following must be performed:

• Conventional cytogenetic analysis is mandatory—specific clonal chromosomal abnormalities (such as del(20q), der(1;7), or other MDS-associated changes) can establish MDS diagnosis even with minimal morphological dysplasia 2, 4
• Bone marrow aspiration and biopsy with differential count of 500 cells to evaluate for dysplasia and enumerate blasts 5
• Peripheral blood smear evaluation for dysplastic changes, hypersegmented neutrophils, or morphologic abnormalities 6
• Somatic mutation analysis (TET2, SF3B1, ASXL1, TP53, RUNX1) may demonstrate clonal disease when morphology is equivocal 5

Common Diagnostic Pitfalls

The most critical error is diagnosing ITP based solely on clinical presentation and platelet count:

• Flow cytometry alone should never be used to diagnose or exclude MDS—phenotypic abnormalities suggest MDS but are not diagnostic without conclusive morphological or cytogenetic features 5
• Assuming ITP in the absence of obvious dysplasia is dangerous—MDS with del(20q) and other subtypes can have minimal dysplasia indistinguishable from ITP 4
• Failing to perform cytogenetic analysis in adult thrombocytopenia leads to missed MDS diagnoses that require different treatment approaches 2, 4

Clinical Implications for Management

When cytogenetic abnormalities are found in presumed ITP:

• Diagnosis should be revised to presumptive MDS or idiopathic cytopenia of undetermined significance (ICUS) according to WHO 2008 classification 2
• Close follow-up is essential as these patients may have indolent disease but require monitoring for progression 2, 4
• Treatment approach differs fundamentally—ITP treatments (steroids, TPO-agonists, rituximab) versus MDS treatments (hypomethylating agents, lenalidomide, supportive care) 1

Rare but Documented: Other Hematologic Malignancies with ITP

Multiple myeloma can also co-occur with ITP, though this is rare:

• IgG lambda types show marked predominance when MM and ITP appear simultaneously 7
• This represents true co-occurrence rather than misdiagnosis, as both conditions respond to appropriate combined therapy 7