Patient: 59 y/o female.  
 
Amanesis: 4 years ago diagnosed with metastatic fallopian tube/ovarian serous carcinoma (BRCA1 positive). Received 6 courses of platinum based chemotherapy and maintenance therapy with bevacizumab. Had a recurrence and received 6 additional courses of platinum based chemotherapy and maintenance therapy with olaparib.  
Three years after the systemic treatment blood test showed thrombocytopenia (10 x109/l), anemia (84 g/l) and neutropenia (0,6 x109/l). 0,9% blasts in periheral blood . LDH 574 U/l. Deficiency of Vit. B12 (19,6 pmol/l).  
 
FIRST BONE MARROW BX AND ASPIRATE (biopsy photos 1-18):  
Bone marrow aspirate showed 7,5% blasts (myeloblasts) with phenotype: CD45+bl, CD34+, CD117+, HLA-DR+, CD7+bl, CD13+ryš, CD15+bl, CD33+, CD38+, CD96-/+, CD123+bl, cMPO+weak, CD3-, cCD3-, CD10-, CD11b-, CD11c-, CD14-, CD16-, CD19-, CD36-, CD56-, CD64-, cCD79a-, TdT-. It also detected 14% monocytoid cells with increased immature forms.  
Marrow touch imprint showed 18,5% blasts.  
 
Bone marrow trephine biopsy showed panhyperplasia with architecture distortion, trilineage dysplasia (hypolobated small megakarrhyocytes, left shifted granulopoiesis and megaloblastoid erythropoiesis), about 15% CD34+ blasts with microclasterisation, abundant immature monocytoid population (CD68/CD123/CD117+) and diffuse strong p53 expression in all of the hematopoietic tissue.  
The diagnosis of this first threpine biopsy was MDS/AML with probable TP53 mutation (most likely therapy associated).  
 
MOLECULAR ANALYSIS  
SNP: complex karyotype (4 aberrations) - del(3p), del(5q), del(9p).  
NGS showed TP53 mutation (VAF 84,8%;)  
 
The patient then received treatment: decitabine + venetoclax  
 
SECOND BONE MARROW BX AND ASPIRATE (biopsy photos 19-44):  
Just one month after the first bone marrow biopsy/aspiration the second one was performed.  
Aspirate flow cytometry detected 2,3% aberrant myeloblasts with the same phenotype as previously. It also detected 11% of cells with aberrant phenotype (CD45-/+, CD117+het, CD36+, HLA-DR-, CD96+, CD38+, CD13-/+het, CD33-, CD64-, CD14-, CD34- ) interpreted as erythroblasts or metastatic cells of solid tumor.  
Bone marrow trephine biopsy showed distorted architecture, serous degeneration, sparse NASDE+ granulopoietic elements and interstitial or focally clustered in sheets megaloblastoid infiltration with admixed giant anaplastic multinucleated/lobulated cells (E-Cadherin+).  
 
THE MAIN QUESTIONS:  
- Does the second biopsy qualify as AML M6?  
- Can the erythroblasts of M6 be that polymorphous/anaplastic? (or is it part of the MDS?)  
- Is the detection of CD34+ blasts excess in the first biopsy compatible with the diagnosis of AML M6 in the second biopsy (one month later)?  

tzankov 2024-02-27 17:35

Very interesting case.     According to the ICC, the unequivocal diagnosis is:   MDS/AML with mutated TP53 (because of the 15% blasts in the BMB), therapy-related     According to WHO-5, the diagnosis is:   post cytotoxic therapy MDS with biallelic TP53 inactivation     Since diagnostic criteria apply to pre-therapy states, I would not try to adjust the diagnosis based on what you have seen a month later. What we appreciate one month later is namely the natural history of persistent/progressive TP53 mutated MDS/AML, in this occasion with the rather inefficient but morphologically impressive imprint of decitabine + venetoclax, which you and me percept as anaplasia.

ugnius 2024-02-27 20:23

Thank you professor for the clear answer!     So acute erythroid leukemia can only derive de novo or after cytotoxic therapy, but without a preceding MDS TP53+ phase?     We got confused, because although the erythroid cytology in the 2nd BMB is highly pleomorphic (more suitable for MDS, with some "enhancement" due to therapy) there is a focus of more monotonous/conventional proerythroblast, forming almost sheets like pattern (esp. on E-Cadherin, fig. 30) - resembling AEL...       Gintarė