Hematopathological profile of plasmacytoid dendritic cell proliferation associated with non‐myeloid acute leukemia

Two types of plasmacytoid dendritic cell (pDC) proliferation disease are acknowledged so far by the 5th edition of the World Health Organization Classification of Haematolymphoid Tumors: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and mature pDC proliferation associated with myeloid neoplasms (MPDCP) in which pDC is part of the malignant clone. We aim to investigate pDC proliferation associated with non‐myeloid acute leukemia (AL). A retrospective analysis of all cases admitted in our center with a diagnosis of non‐myeloid AL from September 2020 to April 2023 was performed to select cases with pDCs greater than 2% of bone marrow by flow cytometry (FCM). We conducted comprehensive analyses encompassing FCM immunophenotyping, histopathological examination, morphological assessment, cytogenetic studies, and molecular genetic profiling across all cases. Proliferation of pDCs was detected in 10 (0.88%) out of 1140 non‐myeloid AL patients by FCM, including 4/944(0.42%) cases of B lymphoblastic leukemia (B‐ALL), 3/95 (3.16%) cases of T lymphoblastic leukemia (T‐ALL) and 3/101 (2.97%) cases of acute leukemia of ambiguous lineage (ALAL) ( p = 0.009). The 4 cases of B‐ALL were all Philadelphia Chromosome positive (Ph+). PDCs in 3 out of 10 patients expressed CD56 (37.5%), 8/10 expressed CD7 (80%), 9/10 expressed CD303 (90%), all expressed CD304 (100%), and 5 of 8 evaluable cases were positive for CD34 (62.5%). In cases in which pDCs expressed CD7 and/or CD56, the blast cells all expressed CD7 and/or CD56 as well; the pDCs in all B‐ALL patients expressed CD19. FCM dot plot in 2 of the B‐ALL‐pDC showed a spectrum from blast cells to pDCs: CD303 and CD304 gradually emerged as CD34 disappeared. Among the 8 patients who underwent bone marrow biopsy, pDCs exhibited two distinct distribution patterns: pure interstitial infiltration in 6 cases (75%) and focal/scattered clusters against an interstitial background in 2 cases (25%). NRAS showed recurrent mutations at identical genomic positions. Each NRAS variant (c.35G>A and c.38G>T) was detected twice across three patients. FCM could effectively detect pDC proliferation in non‐myeloid leukemia, which occurred at a significantly higher incidence in T‐ALL and ALAL than in B‐ALL. In B‐ALL, it was associated with the Ph + subtype. PDCs and blast cells shared some lymphoid antigens that were uncommon in AML‐pDC or BPDCN. In the bone marrow, pDCs were predominantly characterized by an interstitial infiltration pattern.