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  Table of Contents    
LETTER TO EDITOR  
Year : 2021  |  Volume : 64  |  Issue : 2  |  Page : 434-436
Myelodysplastic syndrome/myeloproliferative neoplasm – ring sideroblast with myelofibrosis – A diagnostic dilemma/? A distinct entity


1 Department of Pathology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
2 Department of Pathology-Haematopathology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
3 Department of Medical Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
4 Department of Haemato-Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India

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Date of Submission10-Feb-2020
Date of Decision10-Mar-2020
Date of Acceptance24-Mar-2020
Date of Web Publication9-Apr-2021
 

How to cite this article:
Talwar A, Bansal S, Bapna A, Sharma U. Myelodysplastic syndrome/myeloproliferative neoplasm – ring sideroblast with myelofibrosis – A diagnostic dilemma/? A distinct entity. Indian J Pathol Microbiol 2021;64:434-6

How to cite this URL:
Talwar A, Bansal S, Bapna A, Sharma U. Myelodysplastic syndrome/myeloproliferative neoplasm – ring sideroblast with myelofibrosis – A diagnostic dilemma/? A distinct entity. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 8];64:434-6. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/434/313267




Dear Editor,

Myelodysplastic Syndrome with Ring Sideroblast (MDS-RS) is characterized by cytopenias, morphological dysplasia and RS usually constituting ≥15% of the bone marrow erythroid precursors; secondary causes of RS must be excluded. There is associated SF3B1 mutation in most cases, and in the presence of such mutation, diagnosis can be made with ≥5% marrow RS.

A 57-year-male presented with history of recurrent fever for 1 year, generalized weakness, fatigue, and weight loss. Computed tomography examination of whole abdomen revealed gross hepatosplenomegaly (liver-21.4 cm, spleen-21.6 cm). Renal and liver function tests were within normal limits; however, there was an increase in Lactate Dehydrogenase levels-506 U/l.

Hemogram revealed haemoglobin-9g/dl, total leucocyte count-21.35×109/l, platelet count-123×109/l. Differential count revealed polymorphs 83%, lymphocytes 12%, eosinophils 1%, basophils 1%, monocytes 1%, and metamyelocytes 2%. Peripheral smear showed normocytic normochromic red cells with moderate to marked anisopoikilocytosis, tear drop cells, and neutrophilic leucocytosis [Figure 1].
Figure 1: Peripheral blood smear, Leishman stain, ×40 view showing ringed neutrophils, demonstrating feature of dysmyelopoiesis. Numerous tear drop cells also seen, a feature of myelofibrosis

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Bone marrow was very hypercellular for age with overall cellularity >95%. Myelogram revealed blast-0.4%, myelocytes-11.6%, metamyelocytes-10.4%, neutrophils-22.4%, eosinophils-0.6%, basophils-0.6%, lymphocytes-18.2% and erythroid precursors-35.8%. Hematopoietic series displayed features of multilineage dysplasia. In view of anemia and dyserythropoiesis, iron study was performed which revealed bone marrow iron 3+ with numerous RS (>15%). Reticulin stain revealed myelofibrosis of grade I (WHO 2017) [Figure 2] and [Figure 3].
Figure 2: (a and b) Bone marrow aspiration, May-Grunwald-Giemsa stain, ×10 and ×40 view respectively. Smear is hypercellular with a hypercellular particle. Megakaryocytic series displaying features of dysmegakaryopoiesis with the presence of hypolobated, dysplastic bizarre forms. (c) Bone marrow aspiration, May-Grunwald-Giemsa stain, ×100 view showing features of dyserythropoiesis (nuclear budding)

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Figure 3: (a) Perl's stain for bone marrow iron, ×100 view, showing numerous ring sideroblasts. (b) Bone marrow biopsy, Haematoxylin and Eosin stain, ×40 view, hypercellular marrow seen with proliferation of dysplastic megakaryocytes. (c)Reticulin stain ×40 view: showing myelofibrosis of grade I

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Molecular study (MPN reflex panel) revealed positivity for JAK2V617F mutation, however was negative for BCR-ABL1 and calreticulin mutation. There is a well-known association between SF3B1 mutation and RS, but next generation sequencing and cytogenetic study was not done in our case due to financial constraints.[1],[2]

Lasho et al. specifically described the clinicopathological features associated with SF3B1 mutation in primary myelofibrosis (PMF). In total 10 out of 155 patients showed SF3B1 mutations with PMF, of which 6 patients also carried JAK2V617F and RS. Therefore, it demonstrates the infrequent occurrence of SF3B1 mutations in PMF and their apparently invariable association with high percentage of bone marrow RS.[2]

Leonardo et al. studied features of SF3B1-mutated myeloproliferative neoplasms (MPN). Of note, RS were present only in a subset of SF3B1+ cases (4 out of 10) without any other feature of erythroid or granulocytic dysplasia.[3]

Jekarl et al. studied JAK2V617F mutation in 43 patients with myeloid neoplasm. The mutation was identified in 6 out of 43 (13.9%). The incidence of the JAK2V617F mutation in various diagnostic groups was as follows: 8.3% MDS; 22.2% MDS/MPN-U; 14.3% RARS- T; and 13.3% AML.[4]

This case revealed the features of proliferation as well as dysplasia, placing this entity in MDS/MPN category with additional findings of RS and myelofibrosis.

Within the MDS/MPN category, chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia and atypical chronic myeloid leukemia were ruled out as there was no monocytosis or significant shift to the left.

MDS/MPN with RS and Thrombocytosis (MDS/MPN-RS-T) is a known entity as per latest WHO classification. Only few cases have been reported in the past under this category.[5],[6] Our case represents laboratory and morphological features that overlap with both MDS and MPN with significant RS without thrombocytosis, as the platelet count was below normal (123 × 109/l) [normal platelet count 280±130 × 109/l].

According to WHO 2017 classification, the case described here should be classified as either MDS/MPN, unclassifiable (MDS/MPN-U) or PMF. MDS/MPN-U is myeloid neoplasm with mixed MDS/MPN features at onset and they do not meet the WHO criteria for any other MDS/MPN, MDS or MPN. In all of the previous studies of MPN, no neutrophilic or erythroid dysplasia (in >10% of cells in any hematopoietic lineage) was appreciated in any of the cases, whereas in contrast, the case under study displayed dyserythropoiesis in >10% cells with RS, hence, the possibility of MDS/MPN-U was favored.

This case highlights the diagnostic dilemma where molecular and clinical data cannot resolve the differential diagnosis between entities showing overlapping features of PMF and MDS/MPN. However, whether both processes occur simultaneously or develop one after another or are a part of spectrum of one disease, itself is a matter of debate and needs to be investigated further.

As we know, that the removal of MDS/MPN-RS-T from the category of MDS/MPN-U was a change made from the original fourth edition of the WHO classification. This raises a suspicion of a rare possibility of an unusual novel combination entity which will include features of both MDS/MPN with RS and PMF (MDS/MPN-RS-PMF). However, it would be reasonable enough to raise the merits of the proposed diagnostic entity in the case discussions which needs to be validated further.

Hence, this case highlights the importance of morphological evaluation (including vigilant search for dysplasia and RS) even in an era of molecular testing to reach the correct diagnosis, which will ultimately guide the treatment strategies as well as the prognosis.

This case calls for a consensus to further validate the diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Issa S, Ingley K. A case of refractory anemia with ring sideroblasts and associated thrombocytosis. Blood 2013;121:4256.  Back to cited text no. 1
    
2.
Lasho TL, Finke CM, Hanson CA, Jimma T, Knudson RA, Ketterling RP, et al. SF3B1 mutations in primary myelofibrosis: Clinical, histopathology and genetic correlates among 155 patients. Leukemia 2012;26:1135-7.  Back to cited text no. 2
    
3.
Boiocchi L, Hasserjian RP, Pozdnyakova O, Wong WJ, Lennerz JK, Le LP, et al. Clinicopathological and molecular features of SF3B1-mutated myeloproliferative neoplasms. Hum Pathol 2019;86:1-11.  Back to cited text no. 3
    
4.
Jekarl DW, Han SB, Kim M, Lim J, Oh EJ, Kim Y, et al. JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia. Korean J Hematol 2010;45:46-50.  Back to cited text no. 4
    
5.
Reinig EF, He R. Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis with co-mutated JAK2 and SF3B1. Blood 2017;129:656.  Back to cited text no. 5
    
6.
Xu Z. MDS/MPN with ring sideroblasts and thrombocytosis masquerading as prefibrotic/early primary myelofibrosis. Blood 2017;129:657.  Back to cited text no. 6
    

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Correspondence Address:
Shashi Bansal
11/172 Kaveri Path, Mansarovar, Jaipur - 302 020, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_115_20

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    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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