Inquirement on the Morphological Classification of Acute Hypergranular Promeylocytic Leukemia and Its Clinical Characteristics*

WANG Xiao-hong HU Jian-gong WANG Ke-qiang

(1.The occupation college is nursed in Taishan，Taian 271000, China; 2.The Affiliated Hospital of Taishan Medical College, Taian 271000，China)

Author's brief introduction：WANG Xiao-hong (1958—)，Woman，born in Chengwu Shandong，Undergraduate course ，Associate professor.Corresponding author:HU Jian-gong.

In the Tianjin Symposium on the Classification and Typing of Leukemia[1]held in September 1986,the acute hypergranular promyelocytic leukemia (M3) was further divided into two subtypes: coarse granule subtype (M3a) and fine granule subtype (M3b). In the routine cytological practice, however, most M3cases have a mixture of coarse and fine granules, making the subtyping of them a difficult work. The criteria are not clear and the cytological diagnoses differ considerably from one cytologist to another. Che Chunlan[2], Li Shuenyi[3]and Huang Chuanying[4]have the same experience. Li et al[3]pointed out that the diagnosis of M3could be established whenever the hypergranular promyelocytes made up more than 30% of the total leukemic cells, and that there was no need for further subdividing them into M3aand M3b. Others analyzed 58 cases of M3, in which 28 were coarse granule subtype and 30 were fine granule subtype, and found that the M3acases had profound WBC and BPC reduction, severe hemorrhage, high DIC incidence; whereas the M3bpatients responded favorably to chemotherapy and had a longer survival time. It was concluded that subtyping M3was helpful to treatment and prognosis[5]. In order to find out a rational solution to the difficulty in subtyping M3due to the mixed-up of coarse and fine granules, so as to make an unified criteria for subtyping M3, we re-evaluated our M3blood and bone marrow smear archives and made a new set of M3subtyping criteria based on the percentage of coarse granules in the leukemic cells[6]. The relationship of the new system with clinic-pathologic characteristics was also analyzed.

1 Materials and Methods

208 well-stained and well-kept bone morrow smears with M3diagnosis from January 1980 to October 2013 were selected and reinterpreted.

1.1Overall Data of the 208 patients, 111 (53.37%) were men and 97 (46.63%) were women, with mean age of 28.6±8.16 years (range 5-64years).

1.2Methods For each bone marrow smear (Wright-Giemsa stain), 200 promyelocytes were counted and the percentage of coarse and fine granular promyelocytes was calculated. The following criteria were adopted:①. coarse granule subtype (M3a):more than 70% of promyelocytes had coarse granules;②.mixed granule subtype (M3b):30-70% of promyelocytes contained coarse granules; and ③. fine granule subtype (M3c): less than 30% of promyelocytes had coarse granules.

2 Results

2.1According to the above criteria , the 208 M3were subtyped into M3a88 (42.31%), M3b63 (30.29%), and M3c57 (27.40%) . The frequency was M3a>M3b>M3c.

2.2The age and sex distribution patterns of the three subtypes (see Table 1)

As it can be seen from Table 1, there was a distinct age and sex distribution pattern difference among the three subgroups. There were more male patients in M3asubtype (P<0.01) and more female patients in M3csubtype (P<0.01), but no significant sex distribution pattern in M3bsubtype (P>0.05). The age distribution pattern was that M3apatients were younger than M3bpatients, who were younger than M3cpatients (M3avs M3b, M3cvs M3a,P<0.01; M3bvs M3c,P<0.05).

Table 1 Age and sex distribution patterns of 208 cases of M3 leukemia patients

▲M3avs M3b；△M3bvs M3c；▼M3cvs M3a

2.3Clinical symptoms and signs of the three subtypes (see Table 2 )

Symptoms and signs at initial presentation, including fever, hemorrhage symptoms (including petechiae, ecchymoses, mouth mucosa membrane bleeding, oozing gums, menorrhagia, hematuria and hematochezia) stern tenderness were summarized in Table2, and other signs including hepatomegaly, splenomegaly and enlagrged lymph nodes were summarized in Table 3. It could be seen that a majority of M3patients had fever on first presentation, with M3bcases had the most fever, followed by M3a, and M3chad few fever cases M3bvs M3a, and M3bvs M3c,P<0.01; M3cvs M3aP<0.05). M3apatients had the most frequent hemorrhage symptoms, followed by M3band M3c(M3avs M3c,P<0.01), which is in keeping with other report[5,7]that suggested that coarse granule subtype had more severe hemorrhage symptoms than the fine granule subtype. Some patients in the M3aand M3bsubgroups also had profound stern tenderness, which was not found in M3cpatients. Some M3apatients had hepatomegaly, but M3band M3chad no enlarged liver. Splenomegaly was present in M3a, M3b, and M3c, and no difference was found among them (P>0.05). For lymph node enlargement, M3b>M3a, and M3chad no enlarged lymph nodes.

Table 2 Fever, hemorrhage and stern tenderness at presentation among 208 M3 cases

▲M3asvs M3b；△M3bvs M3c；▼ M3cvs M3a

Table 3 Hepatomegaly, splenomegaly and lymph nodes at presentation among 208 M3 cases

▲M3asvs M3b；△M3bvs M3c；▼M3cvs M3a

2.4Peripheral blood (see Table 4 )

The peripheral blood Hb, RBC, WBC and the percentage of promyelocytes were summarized in Table 4. In all the three subtypes, the mean values of HGB and RBC were much lower than normal. It was especially severe with M3aand M3b, and less severe in M3c. Significant differences in Hb values were found when M3cwas compared with M3aand M3bsubgroups (P<0.01). RBC reductions were all statistically significant among all the three subgroups (P<0.01). For BPC reduction M3a>M3b, but in M3cthe mean BPC value was within normal range (P<0.01). M3chad a significantly higher WBC, but the WBC in M3aand M3bwere within normal value with mean WBC value of M3b>M3a(P<0.01). The peripheral blood promyelocyte counts were M3c>M3a>M3b, with significant statistical difference among the three subtypes (M3avs M3b, and M3bvs M3c,P<0.01; M3cvs M3a,P<0.05).

Table 4 Peripheral blood features of 208 M3 patients at presentation

▲M3avs M3b;△M3bvs M3c;▼M3cvs M3a

2.5Bone marrow features (see Table 5 )

Myeloproliferation features of the three subtypes at presentation were summarized in Table 5, and the granulocyte/erythrocyte ratio, percentages of coarse granule promyelocytes and the presence of Auer bodies were summarized in Table 6. It could be seen that myeloproliferation was extremely active in M3a, much more hypercellular than M3band M3c(P<0.01). In all the three subtypes the granulocyte/erythrocyte ratio were high, with the pattern of M3a>M3b>M3c( M3cvs M3a,P<0.01). For the percentage of promyelocyte, M3a>M3c>M3b, the difference was statistically significant (M3avs M3b, M3avs M3c,P<0.01; M3bvs M3c,P<0.05). The percentage of coarse granule promyelocytes were also different statistically (P<0.01), with M3a>M3b>M3c. For Auer bodies, M3b>M3c>M3awas also observed (P<0.01).

Table 5 Myeloproliferation of 208 M3 cases at presentation

Table 6 Bone marrow features of 208 M3 cases at presentation

3 Discussion

According to the above set criteria, 208 M3cases were further subtyped into three groups. These subtypes each had different characteristics in their age and sex distributions, clinical symptoms, peripheral and bone marrow features. This new classification system is of vital practical significance for treatment and prognosis. The new system based upon the percentage of coarse granular promyelocytes has solved the difficulty in subtyping. It will be helpful to exchanging academic findings based on the same criteria.

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