[Clinicopathologic study of centrally necrotizing carcinoma of breast].

OBJECTIVE: To study the clinicopathologic features and immunophenotype of centrally necrotizing carcinoma (CNC) of breast; and to study its relationship with basal-like breast cancer. METHODS: The clinical and pathologic characteristics of 35 cases of CNC were analyzed. Immunohistochemical study for estrogen receptor, progesterone receptor, HER2, CK8/18, 34betaE12, CK5/6, CK14, CK17, smooth muscle actin, p63, vimentin and epidermal growth factor receptor was performed using EnVision method. The surival information of 10 case were obtained. RESULTS: The age of patients with CNC ranged from 30 to 82 years (mean = 54.2 years). Macroscopically, all tumors were relatively circumscribed, with a mean diameter of 2.4 cm. Histologically, there was a prominent central, necrotic or acellular zone surrounded by a narrow rim of viable tumor cells. The central necrotic foci had the following morphologic patterns: (1) coagulative tumor necrosis associated with various degree of fibrosis or hyaline degeneration (24 cases), (2) predominance of fibrous and scar tissue, with small amount of necrotic debris (8 cases), and (3) infarction (3 cases). The peripheral zone of tumor cells showed features of grade 3 invasive ductal carcinoma in 32 cases and grade 2 in 3 cases. Twenty cases of CNC were associated with ductal carcinoma in-situ. A component of invasive micropapillary carcinoma was identified in 5 cases. Peripheral lymphocytic infiltrates were seen in 17 cases. Immunohistochemical study of 31 cases showed that the expression rate of basal-like markers (83.9%, 26 cases) was higher than that of myoepithelial markers (38.7%, 12 cases). The percentage of basal-like subtype (64.5%, 20 cases) was higher than luminal-A (9.7%, 3 cases), luminal-B (9.7%, 3 cases), HER2 over-expression (12.9%, 4 cases) and null (3.2%, 1 case) subtypes. In 20 cases of basal-like carcinoma, the expression ratio of CK5/6 was highest amongst basal-like markers (18 cases), the other markers ratios of CK17, CK14 and epidermal growth factor receptor were 8/10, 14/19 and 8/16, respectively. Follow-up data were available in 10 patients. The follow-up duration ranged from 15 to 42 months (mean = 21.5 months). The median disease-free and overall survivals were 14.0 and 18.0 months, respectively. Disease progression (as defined by the presence of recurrence, metastasis or tumor-related death) occurred in 9 patients. The mean and median time to disease progression was 16.6 and 13.0 months, respectively. CONCLUSIONS: CNC is a rare subtype of breast carcinoma and has distinctive, easily discernible morphologic features. The majority of CNC exhibits basal-like immunophenotype and carries a poor prognosis. CNC is the typical representative of basal-like breast cancer.

[High incidence of t (11; 18)/API2-MALT1 and BCL10 aberrant nuclear expression in pulmonary mucosa-associated lymphoid tissue lymphomas].

OBJECTIVE: To detect the BCL10 expression and chromosomal translocations in pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas, including t (11; 18)/API2-MALT1; t (1; 14)/IgH-BCL10 and t (14; 18)/MALT1-IgH, and to determine if aberrant nuclear BCL10 expression is related with chromosomal translocations. METHODS: Twenty-three cases of pulmonary MALT lymphomas were collected from Cancer Hospital of Fudan University. BCL10 was detected by immunohistochemistry of EnVision method, and API2-MALT1, BCL10, MALT1, IgH chromosomal abnormalities were detected by fluorescent in situ hybridization (FISH) technique. RESULTS: BCL10 was expressed in 82.6% (19/23) of the pulmonary MALT lymphomas. Among those cases, 9 of 23 (39.1%) were expressed in the cytoplasm, and 10 of 23 (43.5%) were in the nucleus. In the FISH results, 9 cases (39.1%, 9/23) showed API2-MALT1 fusion gene, 1 case with possible BCL10-IgH abnormality, but none showed chromosomal abnormalities related with MALT1 and IgH gene simultaneously. Among 10 BCL10 nuclear expressive cases only 5 harbored genetic abnormalities. There was no correlation between BCL10 aberrant nuclear expression and chromosomal translocations (chi(2) = 0.306, P = 0.685). Follow-up of 10 cases for a period of 7 to 35 months showed that all the patients were alive. Because different treatments applied in different patients (chemotherapy only, surgery with chemotherapy or surgery only), best available treatment could not be confirmed in this study. CONCLUSIONS: t (11; 18)/API2-MALT1 was the most common chromosomal abnormality in pulmonary MALT lymphomas, but t (1; 14)/BCL10-IgH and t (14; 18)/MALT1-IgH were rare. Pulmonary MALT lymphomas also had higher nuclear BCL10 expression, which was not correlated with chromosomal abnormalities. As a result, BCL10 nuclear expression and cytogenetic aberration may be helpful in the diagnosis, especially for small biopsy specimens.

[Frequency of genetic aberrations in mucosa-associated lymphoid tissue lymphoma of different sites].

OBJECTIVE: To study the frequency of certain specific genetic aberrations, including t (11; 18)/API2-MALT1, t (1; 14)/IgH-bcl-10 and t (14; 18)/IgH-MALT1, in mucosa-associated lymphoid tissue (MALT) lymphoma of different sites. METHODS: One hundred and ninety-six cases of MALT lymphoma from Cancer Hospital of Fudan University were enrolled into the study. The samples consisted of MALT lymphomas from stomach (53 cases, including 44 cases of low-grade MALT lymphoma and 9 cases of MALT lymphoma with diffuse large B-cell lymphoma component), ocular adnexa (50 cases), salivary gland (20 cases), lung (20 cases), intestine (17 cases), skin (17 cases), liver (8 cases), thyroid (5 cases) and other sites (2 cases from tongue, 1 case from pancreas, 1 case from larynx, 1 case from vocal cords and 1 case from kidney). Fluorescence in-situ hybridization for API2-MALT1 fusion gene, bcl-10, MALT1 and IgH genes was performed on paraffin sections. RESULTS: Among the 196 cases of MALT lymphoma, 25 cases (12.8%) possessed API2-MALT1 fusion gene. The positive rates in various sites were significantly different (P = 0.002), as follows: 45.0% (9/20) in lung, 22.7% (10/44) in stomach (without large cell component), 15.0% (3/20) in salivary gland, 2 of 17 cases in intestine and 2.0% (1/50) in ocular adnexa. The fusion gene was not detected in the 9 cases of gastric MALT lymphoma with large cell transformation. It was also negative in the MALT lymphomas from skin, thyroid and other sites. One of the pulmonary MALT lymphoma cases showed simultaneous aberrations of IgH and MALT1 genes, such as t (14; 18)/IgH-MALT1. Two of the gastric MALT lymphoma cases without large cell transformation and one of the pulmonary MALT lymphoma cases showed aberrations in both IgH and bcl-10 genes, such as t (1; 14)/IgH-bcl-10. Six cases of MALT lymphoma, including 2 cases from salivary gland, 2 cases from liver, 1 case from thyroid and 1 case from stomach (large cell transformation), showed trisomy 18. On the other hand, 3 cases, including 2 cases from stomach and 1 case from intestine, showed MALT1 gene amplification. CONCLUSIONS: In general, specific genetic aberrations have a relatively low frequency of occurrence in MALT lymphomas. The positive rates however show a remarkable difference in tumors of different anatomic sites. This phenomenon may suggest that MALT lymphomas in different sites, though sharing similar morphologic features, may have a divergent tumorgenesis.

[Abnormal BCL10 nuclear expression and chromosomal translocation in ocular adnexal mucosa-associated lymphoid tissue lymphomas].

OBJECTIVE: To detect the BCL10 expression and several types of chromosomal translocations [including t (11;18)/API2-MALT1; t (1;14)/IgH- BCL10 and t (14;18)/MALT1-IgH] in ocular adnexal mucosa-associated lymphoid tissue lymphomas (OA-MALT lymphomas). METHODS: Sixty OA-MALT lymphomas were collected from Cancer Hospital of Fudan University. BCL10 was detected by immunohistochemical studies, and API2-MALT1 fusion gene, BCL10, MALT1 and IgH chromosomal abnormalities were detected by fluorescent in situ hybridization (FISH). Fisher's exact test was used to analyze the relation between nuclear BCL10 expression and chromosomal translocation. RESULTS: BCL10 expressed in 85.0% (51/60) OA-MALT lymphomas. Among these positive cases, 25 cases (41.7%) were expressed in the cytoplasm, and 26 cases (43.3%) were expressed in the nucleus. FISH results showed that no chromosomal abnormalities related with BCL10 and IgH genes, except 2 cases with API2-MALT1 fusion gene. Under statistic of Fisher exact test, nuclear BCL10 expression and API2-MALT1 fusion gene were two independent factors (P > 0.05). CONCLUSIONS: BCL10 nuclear expression is common in OA-MALT lymphomas and may be used as a potential marker for the diagnosis of MALT lymphomas arising from ocular adnexa. Aberrant chromosomal translocations reported in the other sites MALT lymphomas are rare in OA-MALT lymphomas.

[Abnormal expression of bcl-10 protein in extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue lymphoma type].

OBJECTIVE: To evaluate the diagnostic role of nuclear expression of bcl-10 protein in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. METHODS: One hundred and forty cases of MALT lymphoma were collected from Cancer Hospital of Fudan University (including 38 cases from stomach, 35 cases from ocular adnexa, 16 cases from intestine, 15 cases from skin, 15 cases from salivary gland, 14 cases from lung, 3 cases from thyroid and 4 cases from other sites). Ten cases of reactive follicular hyperplasia of tonsil, 5 cases of reactive lymphoid hyperplasia of orbit and 143 cases of non-Hodgkin's lymphoma other than MALT lymphoma (including 20 cases of NK/T cell lymphoma, 20 cases of follicular lymphomas, 20 cases of anaplastic large cell lymphomas, 20 cases of nodal diffuse large cell B-cell lymphoma (DLBCL), 10 cases of gastric diffuse large B-cell lymphoma, 13 cases of nodal marginal zone B-cell lymphoma, 12 cases of mantle cell lymphoma, 11 cases of splenic marginal zone B-cell lymphoma, 6 cases of angioimmunoblastic T-cell lymphoma, 6 cases of peripheral T-cell lymphoma, not otherwise specified, 3 cases of small lymphocytic lymphoma, 1 case of lymphoplasmacytic lymphoma and 1 case of plasmacytoma were used as controls. Immunohistochemical study for bcl-10, as well as dual staining with CD20, was performed by EnVision method in paraffin sections. RESULTS: In reactive follicular hyperplasia of tonsil, bcl-10 was moderately or strongly expressed in the cytoplasm of germinal center B cells, while the mantle cells were negative and the marginal zone cells and paracortical T cells showed weak staining. In the 5 cases of reactive lymphoid hyperplasia of orbit, 2 were bcl-10-negative and the remaining 3 expressed bcl-10 in the cytoplasm of germinal center B cells. As for non-MALT lymphomas, 3 gastric DLBCL showed nuclear expression. The remaining cases showed variable cytoplasmic staining. In some cases of lymphoma, bcl-10 was expressed in tumor cells but not in reactive lymphoid cells. On the other hand, 92.1% (129/140) of MALT lymphoma were bcl-10 positive. Among those cases, 54.3% (76/140) showed cytoplasmic positivity and 37.9% (53/140) showed nuclear positivity. The nuclear positivity rate of bcl-10 in different anatomic sites was different. The staining was most intense in MALT lymphoma of ocular adnexa. Dual staining with CD20 showed that the bcl-10-positive cells were also CD20-positive, though the number of bcl-10-positive cells were less than that of CD20-positive cells. CONCLUSIONS: Bcl-10 expression in lymphoid hyperplasia is a universal phenomenon. Cytoplasmic expression of bcl-10 is seen in many different kinds of non-Hodgkin's lymphoma and reactive lymphoid conditions. In some cases of lymphoma, bcl-10 is expressed in tumor cells but not in reactive lymphoid cells, suggesting a possible role of abnormal bcl-10 expression in tumorgenesis. Nuclear expression of bcl-10 is seen mainly in MALT lymphoma, especially when occurring in ocular adnexa and lung. This is in contrast to loss of bcl-10 expression in residual germinal center cells.