To be hematopoietic, or not to be: That is the neoplastic cell's question.

A 60-year-old woman was referred for investigation of unexplained chronic anemia. Her medical history included adenocarcinoma of the breast, without lymph node involvement, diagnosed 7 years previously and treated by mastectomy without radiotherapy, followed by 1 year of paclitaxel plus trastuzumab and 5 years of tamoxifen. The patient was asymptomatic, although she had experienced chest pain for a 2-week period 6 months previously, which had since resolved. She was considered to be in ongoing remission. Clinical examination was normal. The blood count showed normocytic normochromic anemia (hemoglobin concentration 88 g/L) with a normal reticulocyte count (67.6 × 109/L) and mild neutropenia (1.3 × 109/L). Microscopy of the blood film revealed 21% nucleated red blood cells but no granulocyte precursors. There were no morphological abnormalities in platelets, leucocytes, or erythrocytes. Biochemical tests were normal and tumor markers (ACE, CA15-3, CA19-9) measured 3 months previously had been negative. A bone marrow aspirate showed decreased cellularity without excess blasts but with marked dyserythropoiesis including nuclear budding, vacuolization, and basophilic stippling (top left, all images May-Grünwald-Giemsa ×100 objective). It also revealed isolated atypical large cells with an eccentric oval non-lobulated nucleus, clumped chromatin, no distinct nucleoli, and abundant gray–pink cytoplasm (top right and lower images), which resembled atypical megakaryocytes as observed in myelodysplastic syndrome (MDS) with isolated del(5q) but could also have been nonhematopoietic neoplastic cells. Cytogenetic analysis was normal, and no mutation was identified by next-generation sequencing. A bone scan indicated the presence of post-traumatic rib fracture sequelae, and positron emission tomography showed supradiaphragmatic lymphadenopathy with a diffuse heterogeneous pattern. Bone marrow trephine biopsy was performed, showing bone marrow relapse of the ER−, PR−, and HER2+ breast adenocarcinoma. Immunostaining of bone marrow aspirate films showed expression of cytokeratins AE1AE3 and CK7, confirming the nonhematopoietic origin of the atypical cells. Finally, the diagnosis of MDS could be excluded, and treatment for the bone marrow relapse of the breast carcinoma could be initiated. Distinguishing nonhematopoietic neoplastic cells from atypical hematopoietic cells in bone marrow aspirate examination can be challenging, particularly when there are no clinical or peripheral blood features suggesting bone marrow infiltration and cells are dispersed. Associated dysplasia can suggest MDS but it should be noted that dyserythropoiesis is a common, non-specific feature, seen in many conditions. This case highlights the importance of distinguishing these nonhematopoietic neoplastic cells from hypolobulated megakaryocytes indicative of MDS with isolated del(5q). It also underscores the value of immunostaining of bone marrow aspirate films when clinical, hematological, and cytological features are potentially misleading. The authors declare no conflict of interests.