This case seems to be compatible with CMPD in fibrotic stage, most probably IMF or PV spent phase . Dysplastic changes may be of iatrogenic origin or due to the clonal progression of disease.

Exactly the same idea was formulated. But after clinicians, there is acute onset without signs of MF. I hope they join us with clinical argues. Thank you.

The patient is a 63-year-old male who presented with anemia related symptoms in June that had developed over 3 week period . The patient received RBC transfusions at another hospital.  
The patient had been trated for laryngeal ca in 2000 with surgery and radiotherapy. He had a normal blood count in Aug 2006.  
On presentation no splenomegaly was present. There was slight hepatomegaly.  
CBC: WBC 2.98x109/l, Eos 1%, Baso 1%, segm 32%, bands 7%, metamyeloc 3%, myeloc 1%, blasts 3%, monoc 13%, lymph 39%, normoc. 3-100, Hb 73 g/l, MCV 86, PLT 49 x 109/l. Hyposegmentation, dyserythropoietic normocytes.  
Bone marrow asp. - dry tap. Treph biopsy imprints - cell lysis.  
PB cytogenetics - pending.  
JAK2V617 - neg., bcr/abl - neg.  
The patient appears to have a short standing hematological disorder. I would favor acute panmyelosis with MF dif with MDS with MF, radiotherapy related?

Mega morphology looks quite different from IMF. I think that and lack of splenomegaly rules IMF out.  
 
CD34+ blasts seem to be a constant feature of acute panmyelosis. I don't know if there has been some shift in diagnostic cryteria, but somehow AMF doesn't seem probable without CD34 or CD117 blast population.  
 
Fibrotic MDS or even AML-M6 could be an option. Cytogenetics would be of great help, let's wait for results.  
 
On the other hand, there is a rather prominent population of lymphocyte-like cells. Well, TdT is negative, but did you check the lymphoid population in other ways? The whole thing could theoretically be secondary to some lymphoid tumour.

It is easier to comment on the case knowing the clinical data. Given the short clinical evolution, the fact that the patient had radiotherapy for laryngeal carcinoma and the lack of splenomegaly, makes the DD: MDS with fibrosis versus acute panmyelosis with myelofibrosis the most likely, both therapy related.  
Morphologic arguments are: dysplasia of megakaryocytes, but mostly small forms, no large and bizzare megas as in ET or CIMF and extensive predominantly reticulin fibrosis.  
Please do inform us about the results of cytogentics.

I agree with much of the above opinion, in that this is probably Acute panmyelosis with fibrosis (APF), rather than Chronic idiopathic myelofibrosis (CIM).  
The differentiation between these two conditions is probably easier on the peripheral blood morphology than on BM examination. In CIM there is always (unless post-splenectomy)  
prominent red cell poikilocytosis, tear drop formation (dacrocytes) with clear leucoerythroblastosis. In APF there is little or no red cell abnormality, with minimal leucoerythroblastosis. I would be interested in seeing a blood film, preferably pre-transfusion.

I agree that MDS with fibrosis versus acute panmyelosis with myelofibrosis is a basic differential. The blasts may not be CD34+ and therefore may not be easy to find if good imprints are not made. One could try to search with megakaryocyte markers for clusters of immature looking cells. Sometimes CD117 helps identify CD34-neg blasts. However, it is worth mentioning that I have seen a very similar case and even made a diagnosis of AP with myelofibrosis, but it turned out that the patient had widely metastatic clear cell sarcoma and the changes in the bone marrow were rather paraneoplastic than a separate synchronous disorder. As much as it is not very likely, I agree that it would be wise to check with few markers like S-100, panCK, CD20, CD30, and CD3 if there is another hidden component that is missed due to complex morphology.

Please allow me to comment as a new member of your group. I agree with the others and the differential diagnosis. In MPD (including CIMF), the spleen is typically enlarged; in MDS (including acute MDS with fibrosis, known under many names), it is typically small. The abnormal bone, dense reticulin fibers, and prominence of abnormal megakaryocytes suggest MPD, probably CIMF in view of the absence of preceding recognized PV or ET. The lack of splenomegaly and rapid development of pancytopenia favor MDS with fibrosis. I agree that PB smear exam is very helpful; if no teardrop RBCs are present, MDS is by far more likely. Numerous cytogenetic abnormalities would favor MDS. On the whole, I favor MDS with fibrosis, but it's a tough call.

 
The clinical history of laryngeal carcinoma 7 years ago, short clinical evolution of bone marrow dysfunction, lack of splenomegaly, peripheral blood smear demonstrating leukopenia with left shift and 3% blasts, hyposegmentation, dyserythropoietic normocytes and thrombocytopenia, and bone marrow showing fibrosis, dysmegakaryopoiesis (large and medium sized dysplastic megakaryocytes), depressed granulopoiesis and erythropoiesis, with no appreciable increase in CD34/TdT/Bcl2/CD117+ blasts, CK-, are consistent with therapy related MDS with myelofibrosis. The number of blasts in t-MDS can be variable, and the blasts can be CD34(+) or CD34(-) plus t- MDS is often associated with fibrosis. The megakaryocytes in t-MDS can show particularly marked pleomorphism with both small dwarf dysplastic megakaryocytes as well as large atypical forms.  
 
T-MDS can fall into different morphologic categories, when applying WHO criteria for de novo MDS. In the recent studies of a large group of patients with t-MDS and t-AML at the University of Chicago (Am J Clin Path 2007; 127:1970295), the patients with t-MDS could be categorized according to WHO criteria for de novo MDS as RA, RCMD, RCMD RS , RAEB1 and RAB2, with most patients falling into the RCMD category. Importantly, these studies have shown that there is no differences in median survival among patients classified into the different WHO subgroups of de novo MDS nor their bone marrow blast percentage correlate with the uniformly poor outcome in t-MDS regardless of morphologic subclassification. The average latency period from the onset of therapy for the primary disease and initial diagnosis to the development of bone marrow dysfunction was 62 months for t-MDS and 63 months for t-AML.(t-AML with balanced translocations excluded). The latency period was not different between the patients with primary hematologic malignancies and non hematologic malignancies, nor was different among the patients who received chemotherapy only, radiotherapy only, or combined modality therapy. However, significant survival differences correlated with cytogenetic stratification according to IPSS guidelines and /or karyotypic complexity. There was only a borderline difference in median survival of patients with an initial t-MDS compared with an initial t-AML diagnosis.  
 
The latency period of 7 years from the initial diagnosis of this patient’s laryngeal carcinoma to the onset of t-MDS is within latency time observed of t-MDS after RTX. I agree that PB smear, preferable pre- transfusion, would be very helpful to have better understanding of dyshematopoiesis. Cytogenetic studies would be also of great importance in supporting the diagnosis of t-MDS and prognostic stratification.  

Thank you for all done. I hope dr.L.Griskevicius will provide us the additional data about this case soon.

We have finaly received PB cytogenetics showing: isolated del(20q) in 4, complex abnormalities in 18, predominant: ?del(5q) or t(5q;?), add(7q), monosomy 6 and 15, del(20q).  
There were numerous other cytogenetic abnormalities involving different chromosomes.

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I feel that the cytogenetic abnormalities are consistent with the diagnosis of acute myelodysplastic syndrome with fibrosis (previously termed malignant myelosclerosis), possibly therapy-related. This patient has a grave prognosis.
 

 

 

 

A carcinoma 7 Years ago followed by a progressive anaemia and thrombocytemia without any hyperplasia of a blood cell line and no splenomegaly lead us to the diagnosis of myelodysplastic sd.  
The analysis of bone morrow is in agreement with a diagnosis of "refractory cytopenia with multilineage dysplasia" secondary to carcinoma treatment. Fibrosis is not a rare event in MDS. Cytogenetic analysis is compatible with this diagnosis.  
It seems that you could not demonstrate an excess of blast cells in bone marrow and it was found 3% blasts in blood. So we could not say "refractory cytopenia with excess blasts".  
However, prognosis is poor due to thrombocytopenia even if there is not an increase in blast number.

Thank you for great job. Looking future.

Our diagnosis is MDS: RCMD, IPSS-2. Thank you very much for participation.