Unusual US Findings of Diffuse Large B-Cell Lymphoma of the Breast: A Case Report.

Lymphoma is an uncommon type of breast malignancy, with low prevalence. The ultrasonographic findings of breast lymphoma have been described as nonspecific. Breast lymphoma most commonly appears as a solitary hypoechoic mass on US, and usually shows hypervascularity on color Doppler US. Herein, we report an unusual case of breast lymphoma that presented as multiple bilateral hyperechoic nodules on US.

Intratumor Heterogeneity of Synchronous In Situ and Invasive Breast Carcinoma Revealed Using Multi-region Exome Sequencing.

BACKGROUND/AIM: Intratumor heterogeneity (ITH), defined as a tumor composed of multiple subclones with different characteristics, is widely reported in invasive breast carcinoma (IBC) and ductal carcinoma in situ (DCIS). This study aimed to assess the extent of ITH in synchronous DCIS-IBC at the genetic level. MATERIALS AND METHODS: A total of 17 lesions from 5 patients were subjected to whole-exome sequencing. Nonsynonymous mutations and copy number aberrations were visualized to assess ITH. RESULTS: The most commonly mutated cancer-related genes in IBC and DCIS were RUNX1 (35.3%), PIK3CA (29.4%), and GATA3 (29.4%). There were no universally mutated cancer-related genes in all IBCs. All lesions harbored private mutations restricted to each lesion. Several DCIS lesions displayed a greater amount of genetic aberrations than the accompanying IBC, implying that a subset of DCIS was as advanced or more advanced than the synchronous IBC. CONCLUSION: We herein demonstrated genetic ITH in DCIS lesions coexisting with IBC.

Prognostic value of tumor budding in gallbladder cancer: application of the International Tumor Budding Consensus Conference scoring system.

Tumor budding (TB), a histopathological manifestation of epithelial-mesenchymal transition, is an important step in cancer invasion and metastasis development. TB has been considered a strong prognostic indicator in colorectal cancer. The International Tumor Budding Consensus Conference (ITBCC) scoring system is the standardized method used for patient outcome prediction in several human tumors. We investigated the clinicopathological implications and applicability of TB measured using the ITBCC scoring system in gallbladder cancer (GBC). The TB grades assigned to the 78 GBC patients were as follows: Bd1 (low TB), 41 (52.6%) patients; Bd2 (intermediate TB), 22 (28.2%) patients; and Bd3 (high TB), 15 (19.2%) patients. A higher TB grade correlated with a poorer histological differentiation (P < 0.000), higher pT category (P < 0.000), the involvement of surgical resection margin (P = 0.005), presence of nodal metastasis (P < 0.000), lymphatic and venous invasion (P < 0.000), and perineural invasion (P = 0.004). Univariate Cox regression analysis revealed that a poor histological grade, high pT category, lymphatic invasion, perineural invasion, and intermediate to high TB grades were associated with worse 5-year overall survival and disease-free survival. TB was not significantly associated with death or recurrence risk in multivariate Cox analysis. The interobserver agreement of TB grading was substantial. This study is the first to apply the ITBCC scoring system and suggest the prognostic value of TB in GBC.

Clonality analysis of multifocal ipsilateral breast carcinomas using X-chromosome inactivation patterns.

The definition of multifocal breast cancer is ambiguous, and its incidence varies depending on the definition and detection methods. Multifocal breast cancers either have the same clonal origin or arise from completely distinct progenitor cells. The current American Joint Committee on Cancer Staging system and College of American Pathologists breast tumor guidelines state that only the largest tumor needs to be staged and studied immunohistochemically, on the assumption that they are of the same origin. However, some multifocal tumors have been proved to have arisen from different clones. In the present study, 71 cases of surgically resected multifocal breast cancers were selected. To detect and characterize the tumors of each clonal origin, a human androgen receptor gene (HUMARA) assay to compare the X-chromosome inactivation patterns of multiple tumors was conducted. Twenty-nine of 71 (40.8%) patients were revealed to be heterozygous for HUMARA. Sixty-four (90.1%) patients had the same X chromosome inactivated in different tumors. Seven (9.9%) cases had different inactivated X chromosomes between multifocal tumors, indicating that those tumors were from separate progenitor cells. Five (7.0%) cases showed identical histologic features but had different inactivated HUMARA alleles. According to these results, 2 separate tumors might be synchronous primary tumors, although their histopathologic characteristics are similar. Furthermore, multifocal tumors can be of different origins despite being closely located to each other. These findings suggest that separate grouping of multiple breast tumors based on their clonal origin is needed for future studies.

Chemosensitivity and stratification by a five monoclonal antibody immunohistochemistry test in the NSABP B14 and B20 trials.

PURPOSE: To test the association between risk stratification and outcome in a prospectively designed, blinded retrospective study using tissue arrays of available paraffin blocks from the estrogen receptor-expressing, node-negative samples from the National Surgical Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and chemotherapy trials. EXPERIMENTAL DESIGN: Tissue arrays were stained by immunohistochemistry targeting p53, NDRG1, SLC7A5, CEACAM5, and HTF9C. Risk stratification was done using predefined scoring rules, algorithm for combining scores, and cutoff points for low-risk, moderate-risk, and high-risk patient strata. RESULTS: In a univariate Cox model, this test was significantly associated with recurrence-free interval [HR, 1.3 (95% confidence interval, 1.1-1.6); P = 0.006]. In a multivariate model it contributed information independent of age, tumor size, and menopausal status (P = 0.007). The Kaplan-Meier estimates of the proportion of recurrence-free after 10 years were 73%, 86%, and 85% for the high-risk, moderate-risk, and low-risk groups (P = 0.001). The Kaplan-Meier estimates of the breast-cancer-specific-death rate were 23%, 10%, and 9% (P < 0.0001). Exploratory analysis in patients >/=60 years old showed Kaplan-Meier estimates of the proportion of recurrence-free of 78%, 89%, and 92%. Both high-risk and low-risk groups showed significant improvement on treatment with cytotoxic chemotherapy. CONCLUSIONS: Immunohistochemistry using five monoclonal antibodies assigns breast cancer patients to a risk index that was significantly associated with clinical outcome among the estrogen receptor-expressing, node-negative tamoxifen-treated patients. It seems that the test may be able to identify patients who have greater absolute benefit from adjuvant chemotherapy compared with unstratified patient populations. Exploratory analysis suggests that this test will be most useful in clinical decision making for postmenopausal patients.

Technology insight: Application of molecular techniques to formalin-fixed paraffin-embedded tissues from breast cancer.

Breast cancer is a heterogenous disease in terms of both clinical behavior and molecular characteristics. To develop prognostic and predictive markers for breast cancer, it would be useful to be able to analyze formalin-fixed paraffin-embedded tissue (FPET) collected and banked from completed clinical trials. RNAs extracted from FPETs are chemically modified and fragmented, and are therefore not ideal substrates for gene-expression profiling assays. However, methods are being developed to optimize the use of such RNAs for high-throughput gene expression profiling assays. For microarray analysis, existing methods may be adequate for fresh FPET, but they do not work well with older FPET. For older samples, real-time reverse transcription-polymerase chain reaction is the method of choice for gene-expression profiling.

Transthoracic fine needle aspiration and core biopsy of pulmonary lesions. A study of 296 patients.

OBJECTIVE: To retrospectively investigate and compare the usefulness of transthoracic fine needle aspiration (FNA), core biopsy and a combination of the two in the diagnosis of pulmonary lesions. STUDY DESIGN: Two hundred ninety-six patients who had undergone FNA, core biopsy or both for lung lesions were divided into malignant and benign groups according to the final diagnoses, which were based on the cytologic and histopathologic findings combined with clinical features. In each group, the diagnostic usefulness of FNA, core biopsy and a combination of the two were evaluated by comparing the results of each with the final diagnoses. RESULTS: In the malignant group, FNA was diagnostically helpful in 188 of 205 patients (91.7%) and core biopsy in 158 of 180 patients (87.8%). The combination of the two methods improved the result to 172 of 178 patients (96.6%). The sensitivities were 94.6%, 88.3% and 97.2%, respectively, for each result. In the benign group, 71.1% (64/90), 70.1% (47/67) and 74.2% (49/66) of cases received specific or nonspecific diagnoses by FNA, core biopsy and their combination, respectively. The rates of specific diagnoses were 20.1%, 21.0% and 31.8%, respectively. CONCLUSION: The combination of FNA and core biopsy markedly improved the diagnostic yields in the malignant group and, to a lesser degree, also in the benign group.