Clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma involving bone marrow / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma (SMZL) involving bone marrow.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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%).</p><p><b>CONCLUSIONS</b>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.</p>

The role of bone marrow pathology in diagnosis and differential diagnosis of refractory cytopenia of children / 中华血液学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Hematopathologic features of T-cell large granular lymphocytic leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the hematopathologic features of T-cell large granular lymphocytic leukemia (T-LGLL).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Clinicopathologic features of aggressive natural killer cell leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of aggressive natural killer cell leukemia (ANKL).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Clinicopathologic features of lymphoplasmacytic lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the clinicopathologic features of lymphoplasmacytic lymphomas (LPL).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Clinicopathologic study of 15 splenectomy specimens of patients with hairy cell leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features, diagnosis, differential diagnosis and the prognosis of hairy cell leukemia (HCL).</p><p><b>METHODS</b>Fifteen splenectomy specimens of HCL patients were investigated retrospectively using HE and immunohistochemistry in correlation with the follow-up information.</p><p><b>RESULTS</b>(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.</p><p><b>CONCLUSIONS</b>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.</p>

Clinical significance of ZAP-70 protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and prognostic significance of ZAP-70 protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).</p><p><b>METHODS</b>The histologic features of 52 cases of CLL/SLL with lymph node and/or bone marrow biopsies performed were retrospectively reviewed. Immunohistochemical study using EliVision for ZAP-70 protein was adopted.</p><p><b>RESULTS</b>The lymph nodes of the 12 cases studied showed effacement of the nodal architecture and was replaced by a monotonous infiltration of small lymphoid cells. Among them, proliferation centers were identified in 6 cases. Similar morphologic pattern was seen in the 40 bone marrow biopsy samples, but no proliferation center formation obtained. The infiltration pattern of tumor cells in the bone marrow were further subdivided into nodular (n = 9), interstitial (n = 3), mixed (n = 9) and diffuse types (n = 19). There was no significant difference found on survival rates between the diffuse infiltration and non-diffuse infiltration groups (Fisher's exact test, P = 0.199). ZAP-70 protein was mainly located in the cytoplasm and nuclei of lymphoma cells. There were 21 cases (40.4%) positive for ZAP-70 and among them, 11 died of this disease or the related infections. On the other hand, ZAP-70 was negative in 31 cases (59.6%) and only 4 of them died of this disease or related infections. The overall survival in ZAP-70-negative group was higher than that of the ZAP-70-positive group (59 months versus 39 months, chi(2) = 6.991, P = 0.008). Follow-up information was available in 51 patients. Among the 21 dead cases, 15 died of CLL/SLL or the related infection.</p><p><b>CONCLUSION</b>A positive expression of ZAP-70 protein in CLL/SLL suggests a poor prognosis.</p>

Clinicopathologic features of peripheral T-cell lymphoma, unspecified with follicular pattern / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of peripheral T-cell lymphoma, unspecified (PTL-U) with follicular pattern.</p><p><b>METHODS</b>The clinical data, hematoxylin and eosin-stained sections of lymph node biopsies and follow-up data of 18 cases of PTL-U associated with follicular growth pattern were reviewed and studied. Eight cases of reactive lymphoid hyperplasia were used as controls. Semi-quantitative observation by retiform micrometer rule was carried out. Immunohistochemical study was also performed in all cases. T-cell receptor and immunoglobulin heavy chain gene rearrangement studies were conducted by polymerase chain reaction-based method.</p><p><b>RESULTS</b>The median age of the patients was 53 years. The male-to-female ratio was 1.57:1 in lymphoma group. All of the lymphoma patients presented with superficial lymphadenopathy, with (8/18) or without B symptoms. Histologically, the lymphoma was characterized by follicles of various sizes and shapes. The T zones were expanded by medium-sized lymphoma cells which contained clear cytoplasm and irregular nuclei. Mitotic figures were commonly identified. Immunohistochemical study confirmed that the lymphoma cells were of T-lineage. The proliferative index, as highlighted by Ki-67, was higher [average = (38.24 +/- 13.42)%/mm2] than that in the control group. T-cell receptor gene rearrangement was demonstrated in 71.4% (10/14) of the lymphoma cases.</p><p><b>CONCLUSIONS</b>A definitive diagnosis of PTL-U with follicular pattern can be made on the basis of morphologic examination, immunohistochemical assessment and clinical features. Cases with atypical features can further be delineated by molecular analysis. Long-term follow up of these patients is prudent.</p>

Clinicopathologic studies of 13 cases of chronic eosinophilic leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of bone marrow biopsy (BMB) in diagnosis and differential diagnosis for chronic eosinophilic leukemia (CEL).</p><p><b>METHODS</b>Clinical and pathological features of thirteen CEL patients were analyzed retrospective. Routine histologic examination was performed on H-G-E, reticulin fiber and toluidine blue stained sections of plastic material emdedded samples of bone marrow biopsies.</p><p><b>RESULTS</b>(1)The male-to-female ratio was 12:1. The median age was 40 (23-67) years old. They presented as fever, anemia, hemorrhage and so on. Most of organs and tissues were also be involved. (2) Peripheral blood counts characterized by eosinophilia (18.1 +/-16.2) x 10(9)/L, (3) BMB showed eosinophils were predominant components, others such as neutrophils, erythrocytes, megakaryocytes were decrease. Degree of reticular fiber was from (1+) to (3+). (4) Follow-up information was available in only 4 patients, whose conditions were stable.</p><p><b>CONCLUSION</b>Combine with the clinical manifestations of CEL patients, it is important in diagnosis and differential diagnosis for CEL by observing the histomorphology features of bone marrow biopsy carefully.</p>

Study of 161 chronic idiopathic myelofibrosis patients for clinicopathological staging / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the significance of clinicopathological stage of chronic idiopathic myelofibrosis (CIMF) in WHO classification of 2001.</p><p><b>METHODS</b>Histopathological analysis of bone marrow biopsy plastic-embedded sections stained with H-G-E and Gomori's stains and clinical features of 113 cases previously diagnosed as primary myelofibrosis (PMF) and 48 cases MPD-U (total of 161 cases which including male 79 and female 82) were studied retrospectively.</p><p><b>RESULTS</b>There was no significant differences on the clinical features among the cellular phase, collagen fiber phase, sclerotic phase and osteomyelosclerosis of 113 previously diagnosed patients. According to WHO classification 2001 of CIMF, previously diagnosis in 48 cases with MPD-U was WHO pre-CIMF, and in 113 cases with PMF was WHO CIMF-Fs. There were significant differences between of WHO pre-CIMF and WHO CIMF-Fs about clinicopathological features except age. The percentage of immature granulocytes, normoblasts, lymphocytes in peripheral blood, the size of hepatosplenomegaly, and the percent age of tear drop-like red blood cells in pre-CIMF were significantly lower than those in CIMF-Fs (P < 0.05). However, the number of hemoglobin and platelets in patients with pre-CIMF were significantly higher than that with CIMF-Fs (P < 0.01).</p><p><b>CONCLUSION</b>pre-CIMF and CIMF-Fs in clinical and histopathological features were different development stage of CIMF, while osteomyelosclerosis is a variant of CIMF, but not an independent disease.</p>

Morphologic and clinical study of 131 cases of plasma cell myeloma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the characteristics histologic and cytologic features and clinical usefulness of plasma cell myeloma (PCM) subtyping according to WHO PCM classification.</p><p><b>METHODS</b>Bone marrow biopsy plastic-embedded sections were stained with H-G-E and Gomori's stains, and bone marrow aspirate smears were stained with Wright's stain. The clinicopathologic findings were then analyzed.</p><p><b>RESULTS</b>Of the 131 cases with PCM, three types of growth patterns were noted: interstitial (21 cases, 16.0%), nodular (46 cases, 35.1%) and packed (64 cases, 48.9%). Besides, there were three cytologic subtypes: mature plasma cell type (43 cases, 32.8%), immature (81 cases, 61.8%) and pleomorphic (7 cases, 5.3%) types. The age of patients with mature plasma cell type was significantly higher than that of immature type (P = 0.005); and the number of tumour cells in bone marrow smears was significantly higher than that of immature type (P = 0.003). The numbers of WBC and platelets in peripheral blood were also significantly higher than that of pleomorphic type (P = 0.024, P = 0.002, respectively). On the other hand, the number of platelets in peripheral blood of immature type was significantly higher than that of pleomorphic type (P = 0.019). Marrow fibrosis was more frequently observed in immature type than in mature plasma cell type (P = 0.000). The incidence of marrow fibrosis and osteolytic lesions was higher in high risk group than in low risk group (P = 0.000, P = 0.023 respectively). Twenty-one cases (56.8%) of the 37 cases treated with MP or MP and M2 chemotherapeutic regimens showed good response. However, there was no significant difference in treatment response and survival between different subtypes.</p><p><b>CONCLUSIONS</b>Each subtype of PCM carries different clinicopathologic features in some aspects. The classification carries important value in pathologic diagnosis and probably in predicting prognosis.</p>