Extranodal non-Hodgkin’s lymphoma (NHL) is a rare breast disease. Here we report three cases of primary NHL of the breast. The first patient was a 29-year-old woman with a firm mass in her right ...breast with ipsilateral axillary lymphadenopathy. An excisional biopsy revealed NHLs. Clinical stage was IIAE. The tumor and enlarged lymph nodes had successfully been treated following the combination therapy. The second patient was a 70-year-old women with an elastic hard mass in her left breast. An excisional biopsy revealed NHLs and clinical stage was 1AE. The tumor disappeared following the combination therapy. The third patient was a 67-year-old women with a hard mass in her left breast. Core needle biopsy revealed NHLs and clinical stage was 1AE. The tumor disappeared following chemotherapy. All patients are alive with no evidence of recurrence 4–8 years after the initial treatment. Although a standard treatment has yet to be established, an initial treatment with combination therapy without surgical intervention including axillary dissection appears to be appropriate for this rare disease.
There is no predictive biomarker for response to 5‑fluorouracil (5FU)‑based neoadjuvant chemotherapy (NAC) in rectal cancer. In the present study, we examined potential long non‑coding RNAs (lncRNAs) ...linked to the susceptibility to 5FU in cultured colorectal cancer cells, and in biopsy and resected tissues of 31 human rectal cancer cases treated with NAC. Candidate lncRNAs for the prediction of susceptibility to 5FU were investigated by comprehensive analysis of expression profiles of 84 lncRNAs in cultured cells using PCR array. Bioinformatic analysis identified H19 and urothelial cancer associated 1 (UCA1) as candidate biomarkers for 5FU susceptibility. Quantitative PCR of H19 and UCA1 in cultures of colorectal cancer cells demonstrated the notable variation in expression. The ratios of changes of H19 and UCA1 expression in response to 5FU were low in cells resistant to 5FU, whereas ratios were high in cells susceptible to 5FU. In 5FU‑susceptible cells, cell proliferation was inhibited by 5FU. Upregulation of H19 and UCA1 were associated with the reduction in target molecule expression, including retinoblastoma and p27kip1. In 31 cases of rectal cancer, H19 and UCA1 expression levels in biopsy and resected tissue were comparable. The ratios of H19 and UCA1 expression in resected tissue compared with biopsy samples were low in 17 cases, whereas the ratios were high in 14 cases; 11 of the 17 cases (65%) with low ratios exhibited poor response to NAC, whereas 4 of the 14 cases (29%) with high ratios showed poor response (P=0.045). The increase in H19 and UCA1 expression may represent the response to impaired cell cycle in cells susceptible to 5FU. Our results indicate that changes in H19 and UCA1 expression may be considered for predicting the susceptibility to 5FU‑based NAC in rectal cancer.
Background and Objectives
Emerging evidence suggests that the presence of atypical mitoses is associated with poor prognosis in some types of cancer, but its clinical significance remains uncertain. ...Here, we investigated the occurrence of atypical mitoses in breast cancers.
Methods
Mitotic figures, including normal and atypical mitoses, were assessed in resected histological sections from 109 patients with invasive carcinoma of no special type (ICNST). Comparisons with clinicopathological features and biomarkers such as Ki67 and phosphohistone H3 (PHH3) were performed.
Results
The total number of mitotic figures, including atypical mitoses, was higher in situ and invasive ductal carcinoma components than in normal ducts. Morphological characteristics of atypical mitoses included multipolar, lagged, ring, asymmetrical mitoses, and anaphase bridge. Patients with higher total mitoses and PHH3, and the presence of atypical mitoses showed reduced overall survival (OS), compared to those with lower total mitoses and PHH3, and without atypical mitoses (P = 0.03, 0.02, and <0.001, respectively). In multivariate analysis, the presence of atypical mitoses alone attained significant correlation with shorter OS (P < 0.001).
Conclusions
Atypical mitoses in routinely resected specimens have a robust prognostic value for ICNST of the breast, but its clinical utility remains to be validated in a multicenter large material.
Amyloidosis is triggered by the truncation of amyloid precursor proteins, causing organ damages. While previous studies found the truncation of amyloid A (AA) and amyloid transthyretin (ATTR) occurs ...in C- and N-terminal, respectively, the detailed mechanism of the fibril formation remains unclear. Liquid chromatography mass spectrometry is usually applied for a qualitative purpose, and thus quantification of tryptic peptide residue is difficult. We therefore employed a mass spectrometry-based quantification by isotope-labeled cell-free (MS-QBIC) to analyze the truncation processes in amyloid fibrillogenesis of AA and ATTR using the formalin-fixed paraffin-embedded tissues of autopsy cases. In this study, the process of transthyretin from an 'early fibril state' consisting of full-length ATTR to a 'mature ATTR amyloid fibril' with a truncated low-amyloidogenic segment has been mathematically revealed. The amount of full-length ATTR was nine times higher than in mature fibers. Large cohort studies using MS-QBIC may shed light on the clinical significance of amyloid fibrils.
Aims
The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its ...clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections.
Methods and results
Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot‐spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method confidence interval (CI) = 0.87; 95% CI = 0.799–0.93 marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot‐spot method (0.83; 95% CI = 0.74–0.90) did not. Visually, interobserver concordance in location of selected hot‐spots varies between cases. The median times for scoring were 9 and 6 min for global and hot‐spot methods, respectively.
Conclusions
The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further.
The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic ...infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease characterized by the infiltration of OGCs in the tumor; however, cytological aspects of this tumor type remain elusive. We ...examined the cytological features in fine needle aspiration (FNA) biopsy smears obtained from 5 patients who were histologically diagnosed with breast carcinoma with OGCs. We compared FNA and clinicopathological findings with results from the published literature. Histological assessment of the resected samples showed that all tumors exhibited a histological grade 1 phenotype with a predominant cribriform architecture. Four patients were estrogen receptor positive, and 1 patient showed a triple negative phenotype. All patients survived without tumor recurrence. In the FNA smears, tumor cells were arranged in loosely cohesive clusters, characterized by varying degrees of OGCs infiltration and rare formation of solid tumor nests. Occasionally, 2- or 3-dimensional clusters of tumor cells were found, accompanied by OGCs at the peripheral regions. In all patients, tumor cells were small without severe nuclear atypia. None of the patients showed significant background necrosis. In summary, cytological features of breast carcinoma with OGCs are characterized by loose aggregates of low grade tumor cells, the presence of OGCs, and the absence of necrosis, all of which were consistent with features reported previously. This peculiar form of breast tumors should be included in the differential diagnosis, when physicians encounter FNA findings including low grade ductal carcinoma with the admixture of multinucleated giant cells or OGCs.
•Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease.•Cytohistological findings were assessed in 5 patients with this unusual tumor.•Most tumors histologically exhibited a cribriform pattern and low-grade atypia.•Cytologically, loosely cohesive clusters and OGCs were noted in all the cases.
Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare tumor; however, their clinicopathological aspects remain unclear. We described the clinicopathological characteristics of 8 patients ...with breast carcinoma with OGCs. Immuno-phenotypes of the OGCs were comparatively examined with that of foreign body giant cells (FBGCs) in 4 cases of granulomatous reaction (GR) without cancerous elements. In most cancers, tumors displayed cribriform and tubular growth patterns. Three cases showed moderate to high nuclear grade, while all the other tumors had low nuclear grade. Six patients were estrogen receptor (ER) positive, while triple negative phenotype was identified in 2 patients. During the follow-up period, 1 patient had local recurrence of the tumor, and all the patients remained alive. All OGCs and FBGCs expressed CD68, a pan-macrophage marker. OGCs in all the breast cancers showed moderate to high expression of CD163 — a marker of M2-macrophage with pro-tumoral function — whereas its expression in FBGCs was low to moderate (p=0.04). CD86 — a marker of M1-macrophage with a tumoricidal activity — was positive in the OGCs of 3 breast cancers, and in the FBGCs of 3 GR cases (p=0.15). The expression of CD163 was significantly higher than that of CD86 in the OGCs of breast cancer (p<0.001), whereas they were comparable in the FBGCs of GR (p=0.79). In summary, we found that breast carcinoma with OGCs mostly exhibited cribriform and tubular growth pattern, ER positivity, and predominantly possessed the M2-macrophage phenotype. However, the clinical significance of OGCs in breast cancer needs to be elucidated in further studies involving a larger number of cases.
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