Hidden Monocytosis Clue Reshapes Rare Leukemia Diagnosis in 88-Year-Old Patient

An 88-year-old Chinese man whose blood disorder was first classified as myelodysplastic neoplasm with increased blasts has been retrospectively reclassified as chronic myelomonocytic leukemia, after clinicians reviewing his records discovered that elevated monocyte counts had been present for more than a year before his initial bone marrow examination. The case, published in Frontiers in Oncology, also documents an unusual expansion of mature plasmacytoid dendritic cells alongside the underlying myeloid cancer, a combination that complicated the diagnostic picture from the outset and offers a cautionary lesson about how easily one rare feature of a blood malignancy can obscure another.

The patient was admitted to Dazhou Second People’s Hospital in August 2025 with two weeks of worsening constipation and fecal impaction. Testing on admission revealed circulating blasts, prompting a hematology consultation. Laboratory work showed a white blood cell count of 11.67 × 10⁹ per liter, an absolute monocyte count of 4.12 × 10⁹ per liter, hemoglobin of 74 g/L, and platelets of 79 × 10⁹ per liter. He was also found to have a pulmonary infection, with elevated inflammatory markers including C-reactive protein at 39.20 mg/L, and was treated with piperacillin and tazobactam. Physical examination showed no skin lesions, no swollen lymph nodes, and no enlargement of the liver or spleen, findings that would later matter when doctors weighed alternative explanations for the strange cells in his marrow.

Bone marrow examination revealed a hypercellular sample for his age, with dysplastic changes across multiple blood cell lineages and myeloblasts accounting for 13.5 percent of nucleated cells. Alongside these abnormal precursors, roughly 13 percent of marrow cells displayed the appearance of plasmacytoid dendritic cells, with pale blue cytoplasm, occasional cytoplasmic extensions, and prominent nucleoli. Cytochemical staining helped separate the two populations: peroxidase activity was present in about 26 percent of the myeloblasts but absent in the dendritic-like cells. Flow cytometry then drew an even sharper line, identifying a distinct plasmacytoid dendritic cell population of 8.60 percent that expressed bright CD123, HLA-DR, CD4, and CD303, with partial CD304 expression, while lacking CD34, CD117, and CD56. A separate aberrant immature myeloid population, 3.54 percent of gated cells, expressed CD117 with the myeloid markers CD13 and CD33.

Genetic testing added to the picture of an aggressive clonal disease. Conventional cytogenetics revealed a complex karyotype with multiple structural and numerical abnormalities, including monosomy 7, which supported the clonality of the myeloid neoplasm but was not disease-specific. A targeted next-generation sequencing panel covering 24 myeloid genes identified a TP53 mutation, c.404G>A causing a cysteine-to-tyrosine substitution at position 135, at a variant allele frequency of 36.50 percent, along with a low-level ASXL1 nonsense variant detected at 1.36 percent. Tests for several recurrent fusion genes, including DEK::NUP214, RUNX1::MECOM, and BCR::ABL1, were negative. On the basis of the prominent dysplasia and the 13.5 percent marrow myeloblast count, which falls within the World Health Organization fifth edition range for myelodysplastic neoplasm with increased blasts-2, the team initially diagnosed MDS-IB2 accompanied by mature plasmacytoid dendritic cell proliferation.

The reclassification hinged on history rather than on any new test. When the patient’s white cell count surged in February 2026, reaching 99.35 × 10⁹ per liter with an absolute monocyte count of 36.76 × 10⁹ per liter, the clinicians went back through his earlier records. They found that absolute and relative monocytosis had been documented well before the initial marrow examination: an absolute monocyte count of 0.82 × 10⁹ per liter, or 12.1 percent of white cells, in May 2024, and 1.16 × 10⁹ per liter, or 12.6 percent, in January 2025. At those earlier visits, his anemia had been attributed to iron deficiency, supported by low serum iron, low ferritin, and a positive fecal occult blood test, and he received intravenous iron. The mild monocytosis, composed mainly of mature monocytes, drew no further attention, and chronic myelomonocytic leukemia was never considered at the time.

Under the WHO fifth edition classification, persistent absolute monocytosis of at least 0.5 × 10⁹ per liter together with relative monocytosis of at least 10 percent is a prerequisite criterion for diagnosing chronic myelomonocytic leukemia. When the absolute monocyte count sits between 0.5 and 1.0 × 10⁹ per liter, both dysplasia and an acquired clonal cytogenetic or molecular abnormality are required as supporting criteria; at counts of 1.0 × 10⁹ per liter or above, one supporting criterion suffices. Both of the patient’s earlier blood counts met the monocytosis thresholds, and because the monocytosis predated his August 2025 pulmonary infection, infection could have accentuated the finding at presentation but could not explain the preceding abnormalities. Marrow dysplasia, increased blasts, and clonal genetic changes occur in both MDS and chronic myelomonocytic leukemia and cannot by themselves separate the two, so the longitudinal monocytosis became the decisive piece of evidence. The authors note that a recent reclassification study found a substantial proportion of patients previously diagnosed with MDS met the 2022 chronic myelomonocytic leukemia criteria once the revised monocytosis thresholds were applied, underscoring how much diagnostic overlap persists between the entities.

The blast count carried its own subtleties. Chronic myelomonocytic leukemia-2 is defined by 5 to 19 percent blasts and blast equivalents in peripheral blood, or 10 to 19 percent blasts in bone marrow, with blast equivalents including myeloblasts, monoblasts, and promonocytes. The patient’s 13.5 percent marrow myeloblast count therefore fit the CMML-2 range, while flow cytometry’s 3.54 percent immature myeloid population, obtained by a different method, was not interchangeable with the morphologic count. In February 2026, peripheral blood morphology showed 3 percent myeloblasts, 1 percent monoblasts, and 13 percent promonocytes, a combined blast-equivalent proportion of 17 percent, still below the 20 percent threshold conventionally marking transformation to acute myeloid leukemia. The authors caution that monoblasts and promonocytes may lack CD34 expression, so immunohistochemistry cannot replace morphologic enumeration, and that the plasmacytoid dendritic cell population, being morphologically distinct, had to be excluded from the blast count to avoid inflating it.

The dendritic cell proliferation itself posed a separate diagnostic problem. Mature plasmacytoid dendritic cell proliferation, formally recognized in the WHO fifth edition as an accompaniment of myeloid neoplasms and seen most often with chronic myelomonocytic leukemia, must be distinguished from blastic plasmacytoid dendritic cell neoplasm, reactive plasmacytoid dendritic cell hyperplasia, and acute myeloid leukemia with plasmacytoid dendritic cell expansion. All of these can share expression of CD4, CD123, CD303, and CD304, so no single marker is diagnostic. In this patient, the mature appearance of the cells, the absence of skin lesions, the lack of CD56, and the presence of an underlying clonal myeloid neoplasm favored mature plasmacytoid dendritic cell proliferation. Even so, the authors acknowledge that CD56-negative blastic plasmacytoid dendritic cell neoplasm has been documented, and an extended panel including TCF4, TCL1, SOX4, and TdT was unavailable, so the distinction rested on combined morphologic, immunophenotypic, and clinical findings rather than any single negative result. Reactive expansion driven by his concurrent pulmonary infection also could not be entirely excluded.

One limitation looms over the clonal story: the molecular testing was performed on unsorted marrow, so neither the TP53 mutation nor monosomy 7 could be assigned specifically to the plasmacytoid dendritic cell population. Prior studies have demonstrated shared RAS-pathway mutations in sorted plasmacytoid dendritic cells and monocytes from patients with chronic myelomonocytic leukemia, and shared ASXL1 and CBL mutations in a patient with nodal proliferation, supporting a common clonal origin in some cases. Demonstrating such shared clonality here would have required sequencing purified cell populations, lineage-specific fluorescence in situ hybridization, or single-cell genomic analysis, none of which was performed. The authors are careful to separate clinicopathologic association from molecularly proven clonal identity, a distinction they argue is essential when interpreting these proliferations.

The clinical course underscored the stakes of the reclassification. The patient and his family declined chemotherapy, and management focused on treating the pulmonary infection, nutritional support, and symptomatic care. As his white cell count climbed through October 2025 and into February 2026, crossing the 13 × 10⁹ per liter threshold that defines the proliferative subtype of chronic myelomonocytic leukemia under WHO criteria, he received hydroxyurea, which reduced the white cell count to 20.72 × 10⁹ per liter, though the monocyte count remained elevated at 7.87 × 10⁹ per liter. Retrospective risk assessment using the CPSS, CPSS-Mol, and Mayo Molecular Model concordantly placed him in the high-risk category. He died in April 2026. The authors emphasize that his short survival should be interpreted in the context of high-risk chronic myelomonocytic leukemia, advanced age, comorbidities, infection, severe cytopenias, and limited disease-directed treatment, rather than attributed solely to the initial MDS-IB2 classification, and that whether earlier recognition would have altered his outcome cannot be determined. What the case does establish, they conclude, is the value of longitudinal blood counts and of parallel evaluation of both the dendritic cell population and the underlying myeloid disorder when the two collide in a single marrow.

Subject of Research: Retrospective reclassification of a myelodysplastic neoplasm case as chronic myelomonocytic leukemia with mature plasmacytoid dendritic cell proliferation

Article Title: Case Report: Chronic myelomonocytic leukemia with mature plasmacytoid dendritic cell proliferation initially classified as MDS-IB2

Article References: Chen, J., Liu, J., & Ren, Y. (2026). Case Report: Chronic myelomonocytic leukemia with mature plasmacytoid dendritic cell proliferation initially classified as MDS-IB2. Frontiers in Oncology, 16, Article 1961676. https://doi.org/10.3389/fonc.2026.1961676

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1961676

Keywords: chronic myelomonocytic leukemia, CMML, MDS, plasmacytoid dendritic cells, MPDCP, monocytosis, TP53 mutation, monosomy 7, flow cytometry, WHO classification, case report, hematologic malignancies