Primary lymphoma of breast: a clinicopathologic and prognostic study of 40 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and prognosis of primary lymphoma of breast.</p><p><b>METHODS</b>Forty cases of primary breast lymphoma, diagnosed according to the 2008 World Health Organization classification of hematopoietic and lymphoid tumors, were retrospectively studied. Immunohistochemistry was performed by SP method. The follow-up data were analyzed.</p><p><b>RESULTS</b>(1) All the patients were females and the median age was 47 years. Unilateral and bilateral breast involvement were noted in 36 and 4 patients, respectively. The number of tumor were 31 cases (77.5%, 31/40) less than 3, and 9 cases (22.5%, 9/40) were 3 and more than 3. According to Ann Arbor staging system, 33 cases (82.5%) were in stage I to II and 7 cases (17.5%) in stage III to IV. The level of LDH in 9 cases (24.3%, 9/37) went up. For ECOG scores, 34 cases (85.0%) were 0 to 1 score and 6 cases (15.0%) were more than 2 scores. With respect to international prognostic index, 83.8% (31/37) were of score 0 to 2 and 16.2% (6/37) were of score 3 and more than 3. The axillary lymph nodes of 21 patients (53.8%, 21/39) were involved by the malignancy. (2) Histologically, 38 cases (95.0%, 38/40) were classified as B-cell lymphoma [including 27 cases (67.5%) of diffuse large B-cell lymphoma, 8 cases (20.0%) of mucosa-associated lymphoid tissue lymphoma, 2 cases of follicular lymphoma and 1 case of lymphoplasmacytic lymphoma]. The remaining cases included one case of peripheral T-cell lymphoma and one case of lymphoblastic lymphoma. Immunohistochemically, expression of CD20+/- CD79a were demonstrated in the 38 cases (95.0%) of B-cell lymphoma. The staining for CK was negative in all cases. In 33 cases, the positive rates of MUM-1, bcl-6 and bcl-2 were 57.6% (19/33), 30.3% (10/33) and 72.7% (24/33), respectively. Three cases were germinal center B cell phenotype and 21 cases were non-germinal center B cell phenotype. (3) Follow-up information was available in 37 patients (92.5%, 37/40). Twenty-three patients (62.2%, 23/37) were still alive and fourteen ones (37.8%, 14/37) died. For the 27 cases with diffuse large B-cell lymphoma, the five-year and disease-free survival rates were 48.0% and 36.0%, respectively.</p><p><b>CONCLUSIONS</b>Primary breast lymphoma is a rare disease entity. Diffuse large B-cell lymphoma is the commonest histologic type and the majority show a non-germinal center B cell phenotype. The level of LDH, number of tumor and international prognostic index are of prognostic significance.</p>

Breast magnetic resonance imaging in patients with occult breast carcinoma: evaluation on feasibility and correlation with histopathological findings / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As an uncommon presentation, occult primary breast cancer remains a diagnostic and therapeutic challenge in clinical practice. This study aimed to retrospectively assess the feasibility of breast magnetic resonance imaging (MRI) in patients with malignant axillary lymphadenopathy and unknown primary malignancy, and correlation with histopathological characteristics.</p><p><b>METHODS</b>A total of 35 women with occult breast carcinoma were evaluated with dynamic contrast-enhanced breast MRI. Whole seriate section was used in all cases. MRI performance was assessed and correlated with histopathological findings.</p><p><b>RESULTS</b>Twenty-one of 35 patients were found to have primary breast carcinoma histologically. Twenty of the 21 patients had abnormal MR findings and 1 patient had a normal MRI study. Of the remaining 14 patients, 10 were negative on both MRI and surgery. Four had suspicious enhancement on MRI and no corresponding tumor was found. Lesions with mass enhancement were found in 55% (11/20) and ductual and segmental enhancement in 45%. The average diameter of the primary tumors was 15 mm. Invasive ductal carcinomas were found in 81% (17/21). One of 17 invasive ductual carcinomas was too small to be graded. Fourteen of the remaining 16 were classified as grade II and 2 as grade I. Thirty-two of the 35 patients had received estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 examinations and the 12 of 32 were triple-negative breast carcinoma.</p><p><b>CONCLUSIONS</b>Mass lesions with small size and lesions with ductal or segment enhancement are common MRI features in patients with occult breast cancer. The dominant types of primary tumors are invasive ductal carcinoma with moderate histopathological grade. The rate of triple-negative breast carcinoma may be higher in occult breast cancer.</p>

Association of HER2 genetic heterogeneity with clinicopathological characteristics in breast cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To introduce the College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee criteria for genetic heterogeneity (GH) in HER2 testing, and investigate the clinicopathological significance of HER2 genetic heterogeneity in invasive breast cancer.</p><p><b>METHODS</b>The clinical parameters of 100 cases of invasive breast carcinomas were collected. HER2 expression level and HER2 gene copy number in formalin-fixed and paraffin embedded tumor samples were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and the relationship between HER2 gene GH and clinicopathological characteristics were analyzed.</p><p><b>RESULTS</b>Among the 100 patients, HER2 gene GH was observed in 20 (20%) cases. When the number of HER2 amplified cells was more than 25%, the frequencies of FISH positive were higher than those cases with less than 25% HER2 amplified cells. The results showed that HER2 gene GH was associated with the degree of HER2 protein expression (P=0.004), and ER expression (P=0.002).</p><p><b>CONCLUSION</b>HER2 gene GH may be correlated with the HER2 protein IHC 1+/2+, and ER expression in breast carcinoma. It is important for doctors to avoid ignoring or only counting FISH positive cells leading to incorrect diagnosis for these patients.</p>

Significance of interleukin-1beta expression and microvascular density in invasive micropapillary carcinoma of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the significance of interleukin-1beta (IL-1beta) expression and microvascular density (MVD) in invasive micropapillary carcinoma (IMPC) of breast.</p><p><b>METHODS</b>Immunohistochemical study for IL-1beta and CD34 was performed on 100 cases of IMPC and 97 cases of invasive ductal carcinoma (IDC). The relationship between IL-1beta expression, MVD and various pathologic parameters (estrogen and progesterone receptor status, Ki-67 proliferative index, histologic grade and lymph node metastasis) in IMPC was analyzed.</p><p><b>RESULTS</b>There was no significant difference in expression of IL-1beta between IMPC and IDC (P = 0.924). The expression of IL-1beta positively correlated with proliferative index (P = 0.023), histologic grade (P = 0.038) and lymph node metastasis (P = 0.008), and negatively correlated with estrogen receptor expression (P = 0.035). The MVD in IMPC was significantly higher than that in IDC (66.4 versus 60.0, P = 0.003). The mean MVD in node-positive IMPC was higher than that in node-negative IMPC (68.8 versus 54.4, P = 0.001). In IMPC, the MVD in histologic grade II and III tumors was much higher than that in histologic grade I tumors (68.3 versus 59.9, P = 0.025). It had no relationship with hormonal receptor status and proliferative index.</p><p><b>CONCLUSION</b>Overexpression of IL-1beta and high microvessel density may have important roles in tumor cell proliferation and lymph node metastasis in IMPC.</p>

Significance of expression of stromal cell derived factor 1 and CXCR4 in invasive breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of stromal cell derived factor 1(SDF-1)/CXCR4 and their association with clinicopathologic features and lymph node metastasis in invasive breast carcinoma.</p><p><b>METHODS</b>The expression of SDF-1 was studied by immunohistochemistry and in-situ hybridization. Immunohistochemical study for CXCR4 was also performed. The correlation with various clinicopathologic parameters was analyzed.</p><p><b>RESULTS</b>(1) SDF-1 was mainly expressed in tumor cells and the level of its expression (both membranous and cytoplasmic) in lymph node-positive group was higher than that in lymph node-negative group (P = 0.033). Only cytoplasmic expression correlated with the number of positive lymph node involved by metastasis, TNM tumor stage, histologic grade, tumor dimension and estrogen receptor status (P < 0.05). (2) SDF-1 protein was also detected in the endothelial cells, although its mRNA was rarely detected. SDF-1 staining in lymphatics was associated with positive lymph node (P = 0.005) and SDF-1 staining in blood vessels correlated with stromal lymphocytic reaction (P = 0.001). The extent of nodal involvement was higher in the group with positive SDF-1 staining in blood vessels and with prominent lymphocytic reaction than that in other groups with one or neither of the two features (P < 0.05). (3) On the other hand, CXCR4 was mainly expressed in tumor cells (both nuclear and cytoplasmic); and the level of its expression in lymph node-positive group was higher than that in lymph node-negative group (P = 0.005). Only cytoplasmic expression correlated with the number of positive lymph node involved by metastasis, TNM tumor stage, histologic grade, tumor dimension and HER2 status (P < 0.05). The nuclear expression of CXCR4 was only correlated with progesterone receptor status (P < 0.01). The cytoplasmic expression CXCR4 also positively correlated with SDF-1 expression (P = 0.001).</p><p><b>CONCLUSIONS</b>SDF-1 and CXCR4 can serve as biomarkers for diagnosis and prediction of lymph node metastasis, as well as potential therapeutic targets in invasive breast carcinoma. The difference in localization and staining patterns may also carry different significance.</p>

Clinicopathological and biological features of breast cancer in young females and their relationship with prognosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the relationship between clinicopathological and biological characteristics and prognosis in young females with breast cancer.</p><p><b>METHODS</b>The clinicopathological data of 99 young patients (< or =35years) with primary breast cancer were analyzed retrospectively. All the 99 patients were followed up for 5 years. The histological specimens were reviewed. The expression of ER, PR, AR, c-erbB2, ki67, p53 and BRCA1 were assessed by immunohistochemistry in 63 carcinomas.</p><p><b>RESULTS</b>The lymph node involvement, 5-year metastasis and 5-year survival rate were 59.6% (59/99), 28.0% (26/ 93) and 72.7% (72/99), respectively. The univariate analysis showed that the survival was related to lymphatic vessel invasion, fat involvement, node-positive status, EIC, AR and c-erbB2 expression. The COX multivariate analysis identified that only node-positive status, AR negativity and c-erbB2 overexpression were independent prognostic factors.</p><p><b>CONCLUSION</b>Our data demonstrated that the lymph node status and c-erbB2 expression are strong prognostic factors in young patients with breast cancer. AR may be an adjuvant prognostic factor. The therapeutic measurement could not benefit the outcome radically.</p>

Diagnosis and prognosis study of breast carcinoma with micropapillary component / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the diagnostic criteria, clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma (IMPC) of breast.</p><p><b>METHODS</b>All cases of breast carcinoma diagnosed during the period from 1989 to 2001 were retrospectively reviewed. One hundred examples with IMPC component, according to the 2003 World Health Organization classification of breast tumors, were identified. The clinicopathologic features and follow-up data of these cases were analyzed.</p><p><b>RESULTS</b>Amongst the 100 cases of IMPC studied, 69% (69/100) had evidence of lymphovascular invasion. The incidence of regional lymph node metastasis was 84.8% (84/99). Follow-up information was available in 98 patients (mean of follow-up duration = 60.1 months). Eleven patients (11.2%) had local recurrence within a mean of 26.4 months after the operation, while 38 patients (38.8%) had distant metastases within a mean of 36.0 months. Thirty-six patients (36.7%) died of the disease. The overall 5-year survival rate was 59% and the 10-year survival rate was 48%. Univariate and multivariate analysis showed that the prognosis of patients was adversely affected by the presence of lymphovascular invasion and family history of breast cancer. On the other hand, tamoxifen therapy and adjuvant chemotherapy improved survival.</p><p><b>CONCLUSIONS</b>Breast carcinoma with IMPC component is associated with poor prognosis, despites the relative proportion of this architectural pattern. The overall prognosis is related to the presence of lymphovascular invasion and family history of breast cancer. Hormonal therapy and individualized chemotherapy can improve the survival rate.</p>

Evaluation of efficacy of stereoscopic location and whole serial sections of margin status in breast conservation therapy specimens / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of different methods in pathologic assessment of margin status in breast conservation therapy specimens.</p><p><b>METHODS</b>Assessment of margin status in breast conservation therapy specimens by stereoscopic location and whole serial sections (SLWS) and selective margin sections (SMS) was compared. The margin status was evaluated with intraoperative frozen sections either by SLWS (145 cases) or SMS (79 cases). On the other hand, with formalin-fixed specimens, the margin status of 84 cases was assessed by SLWS and that of another 226 cases by SMS. Follow-up data of all patients were analyzed.</p><p><b>RESULTS</b>The rate of detection of positive margin by SLWS (24.1%, 35/145) was significantly higher than that by SMS (6.3%, 5/79) during frozen section setting. Similarly, the rate of detection of positive margin by SLWS (34.5%, 29/84) was also higher than that by SMS (12.0%, 27/226) when applied in formalin-fixed specimens. The duration of follow-up ranged from 2 to 46 months. None of the patients with margin status assessed by SLWS developed local recurrence. This was in contrast to 3 cases with tumor recurrence (6 months, 15 months and 28 months after the operation respectively) in SMS group.</p><p><b>CONCLUSIONS</b>Assessment of margin status by SLWS in breast conservation therapy specimens can reduce the chance of missing underlying minute foci of margin involvement and help to localize the exact site of positive margin. It thus reduces the overall risk of local recurrence and the need of a second operation.</p>

Relationship between lymph node metastasis and pathologic features of invasive micropapillary carcinoma of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between lymph node metastasis and pathologic features of invasive micropapillary carcinoma (IMPC) of the breast.</p><p><b>METHODS</b>Histopathologic features and status of lymph node metastasis of fifty-one cases of IMPC were studied by microscopic examination, immunohistochemical staining (VEGF-C and VEGFR-3) and analysis of lymphatic vessel density.</p><p><b>RESULTS</b>(1) The number of positive lymph nodes in histologic grade II/III IMPCs was significantly higher (mean 12.5) than that in histologic grade I tumors (mean 4.0). (2) The incidence of nodal metastases in IMPCs with lymphocyte infiltration (+)/(++) was significantly higher (27/28, 96.4%) than that in tumors with no or minimal lymphocyte infiltration (-)/(+/-) (14/23, 60.9%), and the number of positive nodes was also higher (mean 14.4) in tumors with lymphocyte infiltration compared with those without (mean 4.6). (3) In IMPCs with histologic grade II/III, the expression of VEGF-C was significantly higher than that of histologic grade I tumors (P = 0.03). VEGF-C expression was in positive correlation with lymph node metastasis (P = 0.006) and lymphatic vessel density (P = 0.009). Lymph node metastasis was also correlated with lymphatic vessel density (P = 0.007). (4) The percentage of IMPC component in the tumor did not correlate with nodal metastasis. The metastatic foci in lymph node were all IMPC or mainly IMPC. (5) Fourteen of twenty-eight cases (14/28, 50%) of IMPC containing ductal carcinoma in-situ (DCIS) were DCIS of micropapillary type.</p><p><b>CONCLUSIONS</b>The histologic grade, lymphatic vessel density and lymphocyte infiltration are key histological features that are correlated with lymph node metastasis of IMPC. The expression of VEGF-C and VEGFR-3 may play an important role in the development of lymph node metastasis of IMPC. Micropapillary type DCIS may be the early stage of IMPC.</p>

Relationship between expression of cell adhesion molecules and metastatic potential in invasive micropapillary carcinoma of breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of cell adhesion molecules and Their significance in invasive micropapillary carcinoma (IMPC) of the breast.</p><p><b>METHODS</b>Immunohistochemical study for E-cadherin was performed on 64 cases of IMPC and 57 cases of invasive ductal carcinoma (IDC).</p><p><b>RESULTS</b>E-cadherin was mainly expressed on the cell membrane of tumor cells. The expression of E-cadherin in IMPC (85.9%, 55/64) was significantly higher than that in IDC (43.9%, 25/57). E-cadherin expressed in the intercellular contact surface of IMPC cells. In contrast, it was weakly positive/not expressed on the outer membranous surface of the tumor clusters in IMPC. The rate of lymph node metastasis in IMPC (85.9%, 55/64) was significantly higher than that in IDC (52.6%, 30/57), the rate of alpha-catenin and beta-catenin coexpression in IMPC (45.1%, 26/51) with lymph node metastasis and E-cadherin normal expression was also significantly higher than that in IDC (15.4%, 2/13).</p><p><b>CONCLUSION</b>Weak cell adhesion molecule expression on the outer surface of IMPC cell clusters, in contrast to strong cohesion in intercellular contact surface, may help to explain the high metastatic potential of this type of breast cancer.</p>