Did you know this rare form of AML with visible goblet cells?

（），（），“”（29616，223）
。 

（），（），“”（29616，223）
。 

The leukemias with this morphological feature can be summarized as follows: ① Most of them are acute myeloid leukemias, ② The nuclei of the blast cells are significantly invaginated > 25% , or form a typical fish mouth shape, ③ M1 is more common in FAB classification in China.

And M2 type (more common in foreign countries in M4 and M5 ), ④ and acute myeloid leukemia with NPM1 mutation has obvious correlation .
Generally, the percentage of goblet cells in blast cells is ≥10% as positive .

The leukemias with this morphological feature can be summarized as follows: ① Most of them are acute myeloid leukemias; ② The nuclei of the blast cells are significantly invaginated > 25% of the leukemia , or form a typical fish-mouthed shape; ③ It is more common in FAB classification in China.
M1 and M2 types (more common in foreign countries are M4 and M5 ), ④ and acute myeloid leukemia with NPM1 mutation have obvious correlation .
Generally, the percentage of goblet cells in blast cells is ≥10% as positive .

However, last year we encountered a case with goblet cells, not AML with NPM1 mutation, but another type of AML with recurrent genetic abnormalities
.

Which disease is it? Let's take a look

However, last year we encountered a case with goblet cells, not AML with NPM1 mutation, but another type of AML with recurrent genetic abnormalities

case after

The patient is a 19 -year-old female with a fat body
.

He was admitted to hospital due to fever and leukocytosis

The patient is a 19 -year-old female with a fat body

Blood routine and scatter plot:

WBC 120.

95×109/L , unclassified, abnormal WDF scattergram (a piece of gray); hemoglobin 60g/L ; PLT 53×109/L

WBC 120.
95×109/L , unclassified, abnormal WDF scattergram (a piece of gray); hemoglobin 60g/L ; PLT 53×109/L

The most common blood routine manifestations of acute leukemia are one high and two low ( WBC ↑ , Hb and PLT ↓ ), this case is very consistent, is that right?

Morphology of peripheral blood cells:

Morphology of peripheral blood cells:

↑ Two lymphocytes and multiple blasts are seen, two of which have nuclear invagination (cup cells)

↑ Two lymphocytes and multiple blasts are seen, two of which have nuclear invagination (cup cells)

↑ Multiple blasts are seen, one reduced neutrophil

↑ Multiple blasts are seen, one reduced neutrophil

↑ Three blasts and one basophil are visible

↑ Three blasts and one basophil are visible

↑ Four blasts and one basophil are visible

↑ Four blasts and one basophil are visible

↑ Multiple blasts, one basophil, one reduced neutrophil, one lymphocyte seen

↑ Multiple blasts, one basophil, one reduced neutrophil, one lymphocyte seen

↑ Multiple blasts are seen (one of the group in the lower left has an invaginated nucleus), two neutrophils with reduced granules, one basophil

↑ Multiple blasts are seen (one of the group in the lower left has an invaginated nucleus), two neutrophils with reduced granules, one basophil

Peripheral blood classified blast cells accounted for 74% and basophils accounted for 10%
.

As indicated, the patient underwent bone marrow aspirate

Peripheral blood classified blast cells accounted for 74% and basophils accounted for 10%

Bone marrow cell morphology: Bone marrow cell morphology:

↑ A large number of blasts can be seen, and one blast in the center has an invaginated nucleus (cup cell)

↑ A large number of blasts can be seen, and one blast in the center has an invaginated nucleus (cup cell)

↑ Numerous blasts are seen, with reduced granulation of mature neutrophils

↑ Numerous blasts are seen, with reduced granulation of mature neutrophils

↑ A large number of primitive cells can be seen, and one of the primitive cells in the lower center has an invagination of the nucleus (cup cell)

↑ A large number of primitive cells can be seen, and one of the primitive cells in the lower center has an invagination of the nucleus (cup cell)

↑ A large number of blasts and several basophils can be seen, and the leftmost blast in the middle has nuclear invagination

↑ A large number of blasts and several basophils can be seen, and the leftmost blast in the middle has nuclear invagination

Bone marrow accounted for 69% of blast cells, 12% of basophils in all stages

Bone marrow accounted for 69% of blast cells, 12% of basophils in all stages

POX staining:

POX staining:

↑ POX of some primitive cells is granular positive 

↑ POX of some primitive cells is granular positive 

NAE+NaF staining:

NAE+NaF staining:

↑ The NAE of the original cells is positive, and some of them can be inhibited by NaF

↑ The NAE of the original cells is positive, and some of them can be inhibited by NaF

 

So far, this case can definitely be acute leukemia, and tend to myeloid
.

However, I have two questions

So far, this case can definitely be acute leukemia, and tend to myeloid

1.
The increase of basophils in this case may be AML from CML ? 

2.

It is easy to see cup cells in this case.
Could it be the familiar AML with NPM1 mutation?

2.
It is easy to see cup cells in this case.
Could it be the familiar AML with NPM1 mutation?

Immunotyping : 

Immunotyping : Immunity 

   

      

↑ Blast cells express HLA-DR , CD13 , CD33 , CD34 , CD38 , CD117 , CD123

↑ Blast cells express HLA-DR , CD13 , CD33 , CD34 , CD38 , CD117 , CD123

 So far, this case can definitely be AML , but the blast cell immunophenotype of this case is different from typical AML with NPM1 mutation, this disease generally does not express stem cell markers ( CD34 and HLA-DR ), and CD13 is often negative or low expression
.

 So far, this case can be definitely AML , but the blast cell immunophenotype of this case is different from typical AML with NPM1 mutation, this disease generally does not express stem cell markers ( stem cell CD34 and HLA-DR ), and CD13 is often negative or low .
express
.

Cytogenetics:

Cytogenetics:

Ph chromosome was not detected , but t(6;9)(p23;q34) translocation was detected

Ph chromosome was not detected , but t(6;9)(p23;q34) translocation was detected

molecular biology:

molecular biology:

 

 

BCR-ABL1 was not detected , but DEK-CAN fusion gene was detected 

BCR-ABL1 was not detected , but DEK-CAN fusion gene was detected 

High levels of FLT3-ITD mutation and WT1 mutation detected, but no NPM1 mutation 

High levels of FLT3-ITD mutation and WT1 mutation detected, but no NPM1 mutation 

To sum up, this case does not consider CML blast, and it is indeed not AML with NPM1 mutation, but AML with t(6;9)(p23;q34);DEK-CAN , which is also recognized by WHO Genetically abnormal AML
.
 

To sum up, this case does not consider CML blast, and it is indeed not AML with NPM1 mutation, but AML with t(6;9)(p23;q34);DEK-CAN , which is also recognized by WHO Genetically abnormal AML
.
 

case analysis

case study case study

1.
AML with t(6;9)(p23;q34);DEK-NUP214

1.
AML with t(6;9)(p23;q34);DEK-NUP214

In the 2016 edition of the WHO classification of hematopoietic and lymphoid neoplasms, acute myeloid leukemia with recurrent genetic abnormalities has the following types:

In the 2016 edition of the WHO classification of hematopoietic and lymphoid neoplasms, acute myeloid leukemia with recurrent genetic abnormalities has the following types:

AML with t(6;9)(p23;q34), DEK-NUP214 (also known as CAN ) is a type of AML that may have monocytic features, often combined with basophilia and multilineage dysplasia , accounting for AML .
0.
7-1.
8% (relatively rare), the median age of onset in children is 13 years, and the median age of onset in adults is about 35-44 years .  

AML with t(6;9)(p23;q34), DEK-NUP214 (also known as CAN ) is a type of AML that may have monocytic features, often combined with basophilia and multilineage dysplasia , accounting for AML .
0.
7-1.
8% (relatively rare), the median age of onset in children is 13 years, and the median age of onset in adults is about 35-44 years .  

The disease is mostly anemia and thrombocytopenia, often pancytopenia
.
The peripheral white blood cell count in adult patients is generally lower than that of other types of acute myeloid leukemia at initial diagnosis, with a median white blood cell count of 12x109/L , but the white blood cell count in patients with FLT3-ITD is usually higher
.

The disease is mostly anemia and thrombocytopenia, often pancytopenia
.
The peripheral white blood cell count in adult patients is generally lower than that of other types of acute myeloid leukemia at initial diagnosis, with a median white blood cell count of 12x109/L , but the white blood cell count in patients with FLT3-ITD is usually higher
.

The disease can have morphological features other than M3 and M7 , the most common are M2 and M4 , about 1/3 of the cases have Auer bodies, 44%-62% of patients have basophilia, most Developmental abnormalities were present in the case .
Our case did have basophilia and myeloid dysplasia .

The disease can have morphological features other than M3 and M7 , the most common are M2 and M4 , about 1/3 of the cases have Auer bodies, 44%-62% of patients have basophilia, most Developmental abnormalities were present in the case .
Our case did have basophilia and myeloid dysplasia .

The blast cells express MPO, CD13, CD33, CD38, CD123 , HLA-DR , CD117 , CD34 and CD15
.
Some cases expressed monocytic lineage markers CD14 and CD64
.
Basophils can be a separate cell population, expressing CD123 , CD33 and CD38 , but not HLA-DR
.

The blast cells express MPO, CD13, CD33, CD38, CD123 , HLA-DR , CD117 , CD34 and CD15
.
Some cases expressed monocytic lineage markers CD14 and CD64
.
Basophils can be a separate cell population, expressing CD123 , CD33 and CD38 , but not HLA-DR
.

t(6;9)(p23;q34.
1) results in the fusion of DEK on chromosome 6 and NUP214 ( also known as CAN) on chromosome 9 .
The resulting nucleoporin fusion protein can act as aberrant transcription factors, altering nuclear transport by binding to soluble transport factors .
Due to the small size of this translocation, routine karyotyping may sometimes fail to detect it .  

t(6;9)(p23;q34.
1) results in the fusion of DEK on chromosome 6 and NUP214 ( also known as CAN) on chromosome 9 .
The resulting nucleoporin fusion protein can act as aberrant transcription factors, altering nuclear transport by binding to soluble transport factors .
Due to the small size of this translocation, routine karyotyping may sometimes fail to detect it .  

In the vast majority of cases, t(6;9) was the only clonal abnormal karyotype, often with a FLT3-ITD mutation, found in 69% of children and 78% of adults ( the frequency of FLT3-ITD in this disease).
about 3 times that of other AMLs ) .
The prognosis of this disease is poor, with a 5 -year survival rate of less than 30% .

In the vast majority of cases, t(6;9) was the only clonal abnormal karyotype, often with a FLT3-ITD mutation, found in 69% of children and 78% of adults ( the frequency of FLT3-ITD in this disease).
about 3 times that of other AMLs ) .
The prognosis of this disease is poor, with a 5 -year survival rate of less than 30% .

The diagnosis of this disease is relatively simple: if the myeloid blasts in peripheral blood / bone marrow are more than 20% , and t(6;9)(p23;q34) and (or) DEK-NUP214 can be detected , the disease can be diagnosed .

 

The diagnosis of this disease is relatively simple: peripheral blood diagnosis / myeloid blasts in bone marrow ≥ 20% , and t(6;9)(p23;q34) and (or) DEK-NUP214 can be detected , which can be diagnosed as this disease
.
 

2.
Why do cup cells appear in this disease? Is it an example?

2.
Why do cup cells appear in this disease? Is it an example? 2.
Why do cup cells appear in this disease? Is it an example?

The author believes that there are two reasons for the presence of goblet cells in this disease: First, the disease often has FLT3-ITD mutation, which is also closely related to goblet cells; second, the nucleoporin fusion protein of the disease is located in the nucleus.
, which can alter nuclear transport by binding to soluble transport factors, thus potentially altering the morphology of the nucleus
.

The author believes that there are two reasons for the presence of goblet cells in this disease: First, the disease often has FLT3-ITD mutation, which is also closely related to goblet cells; second, the nucleoporin fusion protein of the disease is located in the nucleus.
, which can alter nuclear transport by binding to soluble transport factors, thus potentially altering the morphology of the nucleus
.

The presence of cup cells in this disease is not an isolated case.
This is a case report published in the British Journal of Hematology in 2018 :

The presence of cup cells in this disease is not an isolated case.
This is a case report published in the British Journal of Hematology in 2018 :

Two of the AML with t(6;9)(p23;q34), DEK-NUP214 cases showed typical goblet cells.
Case 1 in the left panel had no FLT3-ITD mutation, while case 2 in the right panel had FLT3-ITD mutation is present .

Two of the AML with t(6;9)(p23;q34), DEK-NUP214 cases showed typical goblet cells.
Case 1 in the left panel had no FLT3-ITD mutation, while case 2 in the right panel had FLT3-ITD mutation is present .

The author has also seen cases of cup-mouth cells (or invagination of nuclei) in this disease in the WeChat group.

The author has also seen cases of cup-mouth cells (or invagination of nuclei) in this disease in the WeChat group.

This is the case of Mr.
Fu Zhaoqiang from Shanghai Zhaxin Integrated Chinese and Western Medicine Hospital (the picture comes from the WeChat public account " Academic Exchange of Comprehensive Diagnosis of Hematology " ):

This is the case of Mr.
Fu Zhaoqiang from Shanghai Zhaxin Integrated Chinese and Western Medicine Hospital (the picture comes from the WeChat public account " Academic Exchange of Comprehensive Diagnosis of Hematology " ):

This is the case of Mr.
Huang Xingqin from the First Affiliated Hospital of Chongqing Army Military Medical University (Southwest Hospital):

This is the case of Mr.
Huang Xingqin from the First Affiliated Hospital of Chongqing Army Military Medical University (Southwest Hospital):

This is the case of Mr.
Qiang Xing from the Second Affiliated Hospital of Chongqing Army Military Medical University (Xinqiao Hospital):

This is the case of Mr.
Qiang Xing from the Second Affiliated Hospital of Chongqing Army Military Medical University (Xinqiao Hospital):

In conclusion, this is also a type of AML with visible goblet cells
.
 

In conclusion, this is also a type of AML with visible goblet cells
.
 

The author personally feels that compared with AML with DEK-NUP214 , the cup mouth cells in AML with NPM1 mutation are more typical and the proportion is more
.
But this needs more cases to confirm
.
 

The author personally feels that compared with AML with DEK-NUP214 , the cup mouth cells in AML with NPM1 mutation are more typical and the proportion is more
.
But this needs more cases to confirm
.
 

As mentioned earlier , we have reviewed several cases of AML with NPM1 mutation in cup-mouth cells that have been posted in the past by the official account of Laboratory Medicine .  

As mentioned earlier , we have reviewed several cases of AML with NPM1 mutation in cup-mouth cells that have been posted in the past by the official account of Laboratory Medicine .

 

The case of Mr.
Du Yongguang from Huaihe Hospital of Henan University:

The case of Mr.
Du Yongguang from Huaihe Hospital of Henan University:

 

 

The case of Mr.
Wu Zhenyong from Guangzhou Development District Hospital:

The case of Mr.
Wu Zhenyong from Guangzhou Development District Hospital:

The case of Mr.
Li Mengyang from the People's Hospital of Gongyi City, Henan Province:

The case of Mr.
Li Mengyang from the People's Hospital of Gongyi City, Henan Province:

 

 

And a case of Mr.
Zhu Qiuhong himself:

And a case of Mr.
Zhu Qiuhong himself:

experience 

experience 

1.
AML with basophilic granulocytosis is not necessarily from CML , it may also be AML with t(6;9)(p23;q34) ; DEK-NUP214 , acute basophilic leukemia ( ABL ), etc.
.

1.
AML with basophilic granulocytosis is not necessarily from CML , it may also be AML with t(6;9)(p23;q34) ; DEK-NUP214 , acute basophilic leukemia ( ABL ), etc.
.

 

 

2.
Goblet cells are not only found in AML with NPM1 mutation and/or FLT3-ITD mutation, but also in AML with t(6;9)(p23;q34); DEK -NUP214 .  

2.
Goblet cells are not only found in AML with NPM1 mutation and/or FLT3-ITD mutation, but also in AML with t(6;9)(p23;q34); DEK -NUP214 .  

3.
Some AMLs with recurrent genetic abnormalities have characteristic morphological manifestations, and we can speculate their possible genetic changes through morphology! For example, in AML patients with easy to see goblet cells , if there is multilineage dysplasia, basophilia, and the original cells express stem cell markers, it may be t(6;9)(p23;q34);DEK -NUP214 .

3.
Some AMLs with recurrent genetic abnormalities have characteristic morphological manifestations, and we can speculate their possible genetic changes through morphology! For example, in AML patients with easy to see goblet cells , if there is multilineage dysplasia, basophilia, and the original cells express stem cell markers, it may be t(6;9)(p23;q34);DEK -NUP214 .

References

References

[1] Wang Yan, Qiao Chun, Guo Rui, et al .
Analysis of clinical and laboratory characteristics of AML-M1 / M2 patients with morphological manifestations of invaginated goblet cells [J].
Chinese Journal of Experimental Hematology, 2018 , 26(4):958-963.

[1] Wang Yan, Qiao Chun, Guo Rui, et al .
Analysis of clinical and laboratory characteristics of AML-M1 / M2 patients with morphological manifestations of invaginated goblet cells [J].
Chinese Journal of Experimental Hematology, 2018 , 26(4):958-963.

[2] Leukemia and Lymphoma Group of Hematology Branch of Chinese Medical Association .
Guidelines for the diagnosis and treatment of adult acute myeloid leukemia (non-acute promyelocytic leukemia) in China ( 2021 edition) [J].
Chinese Journal of Hematology, 2021, 42(8 ): 617-623.

[2] Lymphoma , Leukemia and Lymphoma Group , Hematology Branch of Chinese Medical Association .
Chinese Adult Acute Myeloid Leukemia (Non-Acute Promyelocytic Leukemia) Diagnosis and Treatment Guidelines ( Diagnosis and Treatment Guidelines 2021 Edition) [J].
Chinese Journal of Hematology , 2021 , 42(8):617-623.

[3] Lu Xingguo, Ye Xiangjun, Xu Genbo .
Bone marrow cells and histopathological diagnosis [M].
Beijing : People's Health Publishing House, 2020

[3] Lu Xingguo, Ye Xiangjun, Xu Genbo .
Bone marrow cells and histopathological diagnosis [M].
Beijing : People's Health Publishing House, 2020

[4] Gao Haiyan, Liu Yabo, Lv Chengfang, Chen Xueyan .
Clinical examination and diagnosis of blood diseases [M].
Beijing: China Medical Science and Technology Press, 2021.
3

[4] Gao Haiyan, Liu Yabo, Lv Chengfang, Chen Xueyan .
Clinical examination and diagnosis of blood diseases [M].
Beijing: China Medical Science and Technology Press, 2021.
3

[5] Tian Liang , Ma Ping , Liu Wei, etc.
Clinical characteristics and prognosis of patients with DEK-CAN fusion gene-positive acute myeloid leukemia [J].
Leukemia & Lymphoma , 2021, 30(8): 466-469

[5] Tian Liang , Ma Ping , Liu Wei, etc.
Clinical characteristics and prognosis of patients with DEK-CAN fusion gene-positive acute myeloid leukemia [J].
Leukemia & Lymphoma , 2021, 30(8): 466-469

[6]BoriesClaire,Boyer Thomas,t(6;9)(p23;q34.
1) acute myeloid leukaemia with cup-like blasts.
[J] .
Br J Haematol, 2018, 182: 9.

[6]BoriesClaire,Boyer Thomas,t(6;9)(p23;q34.
1) acute myeloid leukaemia with cup-like blasts.
[J] .
Br J Haematol, 2018, 182: 9.

[7] Fu Zhaoqiang et al .
Acute leukemia with basophilia and multilineage pathological hematopoiesis, AML with t(6;9)(p23;q34.
1); DEK-NUP214.
Comprehensive diagnosis of blood diseases Academic Exchange [ Public Account ] [Z/OL] ( 2021-06-22 ) .
https://mp.
weixin.
qq.
com/s/QMe4j8Wo9Mw9UAdfnZil-A

[7] Fu Zhaoqiang et al .
Acute leukemia with basophilia and multilineage pathological hematopoiesis, AML with t(6;9)(p23;q34.
1); DEK-NUP214.
Comprehensive diagnosis of blood diseases Academic Exchange [ Public Account ] [Z/OL] ( 2021-06-22 ) .
https://mp.
weixin.
qq.
com/s/QMe4j8Wo9Mw9UAdfnZil-A

 

leave a message here