A Perplexing Predominance of Plasmacytoid Dendritic Cells: Chronic Myelomonocytic Leukemia Initially Considered on a Lymph Node Biopsy

A 54-year-old man with an apparently unremarkable previous medical history presented from an outside hospital with abdominal pain and unintentional weight loss. A computerized tomography scan revealed splenomegaly and generalized lymphadenopathy. The clinical impression of lymphoma led to a cervical lymph node (LN) biopsy. Hematoxylin and eosin-stained histological images of this biopsy demonstrated distortion of architecture by interfollicular vaguely nodular expanses (evident on low power, indicated by white circles) of small to medium-sized cytologically monotonous cells with moderately dispersed chromatin (high-power inset) (Figure 1). These cells were surrounded by a heterogeneous mixture of lymphocytes and non-lymphoid hematopoietic elements, including megakaryocytes (labeled EMH, extramedullary hematopoiesis). The nodular infiltrates expressed CD123 and TCL1, indicating that they were plasmacytoid dendritic cells (pDCs). Extraneous to the nodules, CD163 decorated monocytes while myeloperoxidase, E-cadherin, and CD61 highlighted myeloid, erythroid, and megakaryocytic cells, respectively, indicative of EMH. Next-generation sequencing on the LN revealed NRAS, ZRSR2, and biallelic TET2 disease-associated variants. Following the LN biopsy, the full blood count (FBC) and differential became available, showing an absolute (8.5 × 109/L) and relative (28.3%) monocytosis in the setting of anemia (hemoglobin 100 g/L) and thrombocytopenia (platelets 90 × 109/L). A follow-up in-house bone marrow aspirate and biopsy revealed marked hypercellularity with an increased myeloid:erythroid ratio (6.7:1), monocytosis (12%), myeloid left shift with increased blasts and promonocytes (8%), and trilineage cytologic atypia. There was no abnormal increase in reticulin fibrosis. Bone marrow flow cytometry showed increased monocytes (10.1%) that co-expressed CD56, and a minor but discrete population of myeloblasts (2.3%). Cytogenetics showed a normal male karyotype. This case demonstrates a mature pDC proliferation associated with chronic myelomonocytic leukemia (CMML), a diagnosis initially, and somewhat unusually, considered on this LN biopsy. Extramedullary involvement by CMML can be seen and may include LN involvement or nodal extramedullary hematopoiesis [1]. CMML is frequently associated with the presence of nodules of mature pDCs, both in the marrow and when it presents in LNs [2-4]. This seems particularly common in RAS-mutated CMML [2, 3], as is evident in this case. The TET2 mutations (occurring in ∼60% of cases) and RAS pathway mutations (occurring in ∼30% of cases) seen in our case are supportive of the diagnosis [5]. Biallelic TET2 mutations, as in this case, are particularly frequent in CMML [6]. The pDC nodules were the prominent morphological feature in the LN in this case, which was performed before bone marrow studies (and prior to knowledge of the FBC) and prompted consideration of CMML on the LN biopsy. Mature pDC proliferations are important to recognize in LNs and may provide morphological insights into the underlying diagnosis, in this case CMML. Additional diagnostic considerations and differential diagnoses should broadly include mature pDC proliferations associated with non-neoplastic conditions (such as hyaline-vascular Castleman disease, Kikuchi Fujimoto disease, Kimura disease, granulomatous lymphadenitis, dermatopathic lymphadenopathy), and those associated with other myeloid neoplasms. Jaryse Harris: conceptualization, writing original draft. Elena Fenu: conceptualization, writing original draft. Adam Bagg: conceptualization, writing original draft, supervision. The authors have nothing to report. The authors have nothing to report. Jaryse Harris: None. Elena Fenu: None. Adam Bagg: (1) Scopio Labs: Consultant; (2) ASCO: Educational Honorarium; (3) Recordati Rare Diseases: Speakers Bureau. The authors have nothing to report.