Bone Marrow Biopsy Report

Final Diagnosis

A. BONE MARROW, POSTERIOR ILIAC CREST, BIOPSY AND ASPIRATE: Involvement by Mast Cell Leukemia (Aleukemic Variant).

• Hypercellular marrow (90%) extensively infiltrated by atypical mast cells (>20% of all nucleated cells).
• Immunophenotype consistent with neoplastic mast cells (CD117+, Tryptase+, CD25+).
• KIT D816V mutation not detected.

Clinical History

23-year-old female with a diagnosis of Aggressive Systemic Mastocytosis (January 2025) with C-findings (hepatosplenomegaly, elevated liver enzymes, malabsorption). Presents with complex history including flushing, urticaria, anaphylaxis, asthenia, bone pain, history of hyperviscosity, and significant weight loss. Patient laboratory findings include chronic normocytic anemia and markedly elevated serum tryptase (257 ng/mL). Peripheral blood smear shows no increase in circulating mast cells or blasts. Bone marrow evaluation is performed for disease staging.

Microscopic Description

Aspirate Smears:

The aspirate smears are hypercellular. Evaluation reveals a marked, diffuse infiltration by atypical mast cells, comprising approximately 25% of total nucleated cells. These cells are pleomorphic, with many exhibiting immature, spindle-shaped morphology, bilobed nuclei, dispersed chromatin, and hypogranular to agranular basophilic cytoplasm. Metachromatic granules are sparse but identifiable with Giemsa stain. Myeloid and erythroid maturation appears orderly but markedly reduced. Megakaryocytes are present and appear adequate in number.

Biopsy Sections:

The core biopsy is adequate and demonstrates hypercellularity for age (approximately 90%). The normal marrow architecture is largely effaced by a dense, diffuse infiltrate of atypical mast cells, both interstitially and in large aggregates. Significant reticulin fibrosis is present. Trilineage hematopoiesis is severely suppressed.

Ancillary Studies

Immunohistochemistry (IHC):

Immunohistochemical stains performed on the core biopsy show the atypical cell infiltrate is strongly and diffusely positive for Tryptase and CD117 (KIT). The cells show aberrant co-expression of CD25. They are negative for CD34, MPO, CD3, and CD20.

Flow Cytometry:

Multi-parameter flow cytometry performed on the bone marrow aspirate identifies an abnormal mast cell population comprising 22% of total non-erythroid events. This population displays the following immunophenotype:

• Positive: CD117 (bright), CD25 (aberrant), CD33
• Negative: CD2, CD34, HLA-DR

Molecular Studies:

Test: KIT Mutation Analysis by PCR
Result: Negative for the D816V point mutation in exon 17.

Comment

The combined morphologic and immunophenotypic findings are diagnostic of Mast Cell Leukemia (MCL). The patient's bone marrow is extensively infiltrated by a neoplastic mast cell population, which comprises over 20% of the total nucleated cells. The diagnosis is supported by aberrant co-expression of CD25 on the mast cells. According to 2022 WHO Classification, this case meets the criteria for Mast Cell Leukemia. As circulating mast cells constitute less than 10% of peripheral blood leukocytes, this is classified as the aleukemic variant of MCL.

Notably, the common activating KIT D816V mutation was not detected. While this mutation is found in the vast majority of systemic mastocytosis cases, its absence does not preclude the diagnosis. Other mutations in KIT (such as those in exons 8, 9, or 11) or in other genes (e.g., SRSF2, ASXL1, RUNX1) can also be disease drivers and may warrant further investigation. The overall findings confirm disease progression and are consistent with the patient's severe clinical presentation.