Primitive Neuroectodermal Tumor as the Second Malignant Neoplasm in a Long-Term Survivor Child of Acute Lymphoblastic Leukemia: A Case Report.

Acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The second malignant neoplasms (SMNs) in long-term survivors of pediatric ALL are relatively rare. Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor (PNET) 5 years after the initial diagnosis of ALL with radiotherapy-free treatment. PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL. It is predisposed to be misdiagnosed and the pathogenesis is unclear. The outcome is poor. Long-term follow-up is necessary for the survival children of ALL.

[Clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma involving bone marrow].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma (SMZL) involving bone marrow. METHODS: The clinical and pathologic features of 22 patients with SMZL were retrospectively studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. Immunoglobulin heavy chain rearrangement study was performed using polymerase chain reaction-based method. RESULTS: Villous lymphocytes were found in peripheral blood smears of 11/18 of the patients. In bone marrow aspirates, lymphocytosis (> 20%) was demonstrated in 15 cases (15/18) and villous lymphocytes in 6 cases (6/18). Flow cytometry showed CD19(+) CD20(+) FMC7(+) CD22(+) CD10(-) CD2(-) CD3(-) CD7(-) in 18 cases. Bone marrow biopsies of all the 22 patients revealed various degrees and patterns of neoplastic infiltration, as follows: mild (4 cases, 18.2%), moderate (11 cases, 50.0%) or severe (7 cases, 31.8%); intrasinusoidal (16 cases, 72.7%), interstitial (14 cases, 63.6%), nodular (11 cases, 50.0%) or diffuse (1 case, 4.5%). Reactive germinal center formation (CD23(+) bcl-2(-)) was found in 2 cases (91.0%). Immunohistochemical study showed the following results: CD20(+) PAX5(+) CD3(-) CD5(-) CD10(-) cyclin D1(-) CD23(-) CD43(-) Annexin A1(-) CD11C(-) CD25(-) in all the 22 cases, CD38(+) in 2 cases (9.1%) and CD138(+) in 2 cases (9.1%). CONCLUSIONS: Different and overlapping patterns of bone marrow involvement are observed in SMZL. As the histologic and immunophenotypic features are not specific to SMZL, distinction from other types of mature B-cell lymphomas is necessary.

[Hematopathologic features of T-cell large granular lymphocytic leukemia].

OBJECTIVE: To explore the hematopathologic features of T-cell large granular lymphocytic leukemia (T-LGLL). METHODS: A retrospective analysis of the clinical presentation, bone marrow morphology, immunophenotyping and T-cell receptor gene rearrangement status were performed in 19 patients with T-LGLL. RESULTS: Of 19 patients, the most frequent hematological abnormalities were anemia and neutropenia (16/19 and 17/19 patients, respectively). Large granular lymphocytes (LGLs) were observed in 17 of 19 peripheral blood smears and 15 of 19 bone marrow aspirate specimens. Lymphocytosis (> 0.2) was present in 17 of 19 patients in their bone marrow aspirate specimens. Bone marrow biopsy specimens revealed lymphocytosis in 16 cases, with a mild to moderate increase of lymphocytes observed in 12 cases (12/16). The pattern of lymphoid distribution was interstitial in bone marrow sections. Intravascular distribution was seen in 8 cases. Lymphoid nodules were present in 4 cases. Flow cytometery showed an immunophenotype of CD3(+) CD4(-) CD8(+) CD56(-) CD57(+) of the tumor cells in 13 cases. Of the other 6 cases, the immunophenotypes included CD8(-) (1 case), CD56(+) (2 cases) and CD57(-) (3 cases). Immunohistochemistry showed CD3+ (10/10), CD57+ (3/3), CD8+ (6/7), TIA-1+ (6/7), granzyme B+ (4/7), perforin + (1/7), CD4- (4/4) and CD56- (9/9). Clonal T-cell receptor γ gene rearrangement by PCR was detected in 12 cases (12/17). CONCLUSIONS: Hematopathologic features of most T-LGLL are distinct. Morphologic, immunophenotypic and molecular analysis of both peripheral blood and bone marrow specimens are essential and complementary in the diagnosis and differential diagnosis of T-LGLL.

[Clinicopathologic features of aggressive natural killer cell leukemia].

OBJECTIVE: To study the clinicopathologic features of aggressive natural killer cell leukemia (ANKL). METHODS: The clinical and pathologic features were analyzed in 10 patients with ANKL. The complete blood count, peripheral blood smears, bone marrow aspirates and bone marrow biopsies were studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. T-cell receptor (TCR) γ gene rearrangement was studied by PCR method. RESULTS: The most frequent hematologic abnormalities observed were anemia (7 cases) and thrombocytopenia (9 cases). Large granular lymphocytes were found on peripheral blood smears of 6 patients. In bone marrow aspirates, lymphocytosis (> 20.0%) was demonstrated in 8 cases and large granular lymphocytes in 6 cases. Bone marrow biopsies revealed various degrees of neoplastic infiltration, as follows: mild (5 cases), moderate (3 cases) and severe (2 cases). The neoplastic cells were mainly interstitial in distribution in 8 cases and diffuse in 2 cases. Hemophagocytosis was observed in 4 cases. Flow cytometry showed CD2+ sCD3- CD4- CD56+ CD57- in all cases, CD7+ in 9 cases, CD16+ in 5 cases, CD8+ in 4 cases and CD5+ in 1 case. Immunohistochemistry performed in 8 cases showed the following results: cCD3+ in 4 cases, CD56+ in 6 cases, TIA-1+ in 6 cases, granzyme B+ in 4 cases and perforin+ in 2 cases. PCR study revealed germline TCRγ gene configuration in all cases. CONCLUSIONS: ANKL is a highly aggressive NK cell-derived lymphoid neoplasm. Comprehensive morphologic, immunophenotypic and molecular analysis are essential in arriving at a correct diagnosis. ANKL needs to be distinguished from other types of NK-cell and T-cell lymphomas.

[Clinicopathologic features of lymphoplasmacytic lymphoma].

OBJECTIVE: To explore the clinicopathologic features of lymphoplasmacytic lymphomas (LPL). METHODS: Routine histological examination was performed on hematoxylin-eosin stained sections of 24 bone marrow biopsies and available 6 concurrent lymph node specimens. Immunohistochemistry study was performed using EliVision methods. RESULTS: Among 24 cases, the male-to-female ratio was 2.4:1 and the median age was 59.5 years (42 - 75). The most common symptom was weakness (83.3%, 20/24). Hyperviscosity and "B" symptoms occurred in 20.8% (5/24) and 8.3% (2/24) respectively. 41.7% (10/24) patients presented with lymphadenopathy. Anemia, leukocytosis and thrombocytopenia were seen in 79.2% (19/24), 8.3% (2/24) and 37.5% (9/24) respectively. Monoclonal Ig light chain expression was detected by serum immunofixation electrophoresis in 23 cases (95.8%), including IgM (20 cases), IgG (2 cases) and IgA (1 case). Basing on the histology and immunohistochemistry findings, the diagnosis was made in 22 bone marrow and 2 lymph node biopsies, respectively. Histologically, the bone marrow and lymph node specimens composed of small lymphocytes, plasmacytoid lymphocytes and plasma cells. The most frequent pattern of bone marrow involvement was diffuse in appearance (63.6%, 14/22), while nodular and interstitial patterns were less common (22.7%, 5/22 and 13.6%, 3/22, respectively). Lymph node involvement was also to be diffuse in pattern. The proliferative cells expressed Pax5, CD20, CD38 and CD138, but were negative for CD5, CD10, CD23, CyclinD1, CD3, CD7 and MPO. CONCLUSIONS: LPL has distinct clinicopathological features. Histological and immunohistochemistry findings are important for its differential diagnosis with chronic lymphocytic leukemia/small lymphocytic lymphoma, splenic marginal zone lymphoma and follicular lymphoma. Waldenström macroglobulinemia is LPL.

[Clinicopathologic study of 15 splenectomy specimens of patients with hairy cell leukemia].

OBJECTIVE: To investigate the clinicopathologic features, diagnosis, differential diagnosis and the prognosis of hairy cell leukemia (HCL). METHODS: Fifteen splenectomy specimens of HCL patients were investigated retrospectively using HE and immunohistochemistry in correlation with the follow-up information. RESULTS: (1) The male to female ratio was 2.75:1, age ranged from 36 to 68 years with a median of 47 years. The most consistent clinical feature at presentation was marked splenomegaly (100%). Other symptoms included anemia (80.0%), thrombocytopenia (60.0%), leucocytosis (53.3%), pancytopenia (20.0%) and the absence of B-symptom. (2) The proportion of hairy cells was (14.6 +/- 7.2)% in periphery blood and (47.3 +/- 23.8)% in bone marrow. The positive rate of TRAP assay was 62.5% in bone marrow; 85.7% for TPA test and the detection rate for RLC was 25% by transmission electric microscopy. The frequency of bone marrow involvement was 100%. (3) The average weight of 15 spleens was (3012 +/- 1974) g. The size of 6 spleens ranged from 16 cm x 10 cm x 5 cm to 32 cm x 20 cm x 14 cm. The white pulp of spleen showed a characteristic atrophy feature or even absent due to leukemic infiltration, predominantly involving the red pulp with some sinusoidal pattern. "Blood pool" change was an infrequent feature (3/15 cases). The nuclei of leukemic cells were round (13 cases) or bean-shaped (2 cases), nucleoli inconspicuous or disappeared. The abundant cytoplasm and prominent cell border resulted in a "fried egg" appearance. By immunohistochemistry, leukemic cells were positive for CD45RA, CD20, PAX-5, CD25, CD11c, Annexin A1 and cyclinD1, but negative for CD3 and CD43. (4) 13 cases (86.7%) have been followed-up and all are alive. Among them, 9 cases are living well more than 5 years and 7 more than 10 years. CONCLUSIONS: Splenomegaly is frequently the first manifestation of patients with HCL and occurred predominantly in the middle to elderly adults. Definite diagnosis of HCL requires a combined histological and immunohistochemical assessment of the splenectomy specimen, bone marrow biopsy and aspirate.

[The role of bone marrow pathology in diagnosis and differential diagnosis of refractory cytopenia of children].

OBJECTIVE: To explore the diagnosis and differential diagnosis of refractory cytopenia of children (RCC) according to WHO classification, and discuss the relationship between the cytology reviewed by hematologists and histology reviewed by pathologists. METHODS: We selected 50 non-severe aplastic anemia cases from 2007 - 2010 in our hospital and collected clinical data. Experienced hematologists and pathologists evaluated bone marrow biopsy and smear respectively. RESULTS: Of 50 cases, 23 were male and 27 female (M:F = 1:1.17), the median age at diagnosis was 9 years (ranged from 3 to 14 years). 5 patients had disagreement of diagnosis between hematologists and pathologists. In 3 cases hematologists diagnosed as aplastic anemia (AA) and pathologists as RCC, 2 cases vice versa. The final diagnoses of 50 patients reached consensus between hematologists and pathologists were AA 16 cases, RCC 34 cases including 8 refractory cytopenias with multilineage dysplasia (RCMD) cases. All 16 cases AA showed severe hypocellularity. Only 4 cases (25.00%) RCC showed severe hypocellularity, 19 cases (73.08%) RCC showed mild hypocellularity and 3 cases (11.54%) RCC were normal hypocellularity. CONCLUSION: Our results suggests that RCC was not rare in China. The main feature of RCC was dysplasia because of absence of increased blast. RCC was easily confused with AA. The main points of differential were present dysplastic changes of megakaryocyte best appreciated by the hematologists and morphologists and abnormal location of hematopoietic easily observed by pathologists. Overall, cytology and histology were complementary in the investigation of RCC and AA, because of sometimes one might give information that not be given from the other.

The ultrastructure of hybrid acute leukemia: a study of 15 cases.

The objective of this study was to investigate the ultrastructural characteristics of hybrid acute leukemia (HAL). Fifteen cases of HAL were studied by transmission electron microscopy (TEM), focusing on organelles and myeloperoxidase (MPO) reaction of leukemic cells. By TEM, 5 out 15 cases of HAL were consistent with immunophenotyping (3 cases of biphenotypic type, and 2 cases of biclonal type with granulocytes and lymphocytes); 2 cases were suspected as HAL. On other hand, 5 cases of HAL were assigned to ALL, and 2 cases were misinterpreted as M5a and 1 as M4b. Most of the blast cells of biphenotypic HAL showed lymphoid features, except some cases containing MPO positive granules in blasts, while a few cases exhibited monocytic or nonspecific features. TEM offers advantages in the diagnosis of biclonal type HAL and biphenotypic HAL positive for MPO. However, it is difficult to differentiate MPO-negative cases of biphenotypic HAL from ALL and a few cases may be misinterpreted as M5 by TEM.