Infiltrating micropapillary carcinoma of the breast. Cytologic findings

OBJECTIVE: To examine the cytologic features of infiltrating micropapillary carcinoma (IMPC). METHODS: Using the histopathology files of one of the authors (I.J.B.), we retrospectively identified 20 IMPC cases (pure, 12; partial micropapillary carcinoma differentiation, 8) with corresponding cytology. We evaluated the cases for cellularity, atypia, architecture and background. RESULTS: All cases were diagnostic of malignancy, characterized by atypical cells present predominantly in three-dimensional clusters and single cells, facilitating the diagnosis. The clusters had cell ball and papillarylike arrangements, like the morular growth pattern seen on histopathology. Apocrine cytology was present in 12 cases, focal mucin background in 5 and psamomma bodies in 2. The differential diagnosis includes primary papillary neoplasms of the breast, metastatic ovarian papillary serous carcinoma, apocrine and colloid carcinoma of the breast, and intraductal carcinoma (micropapillary type). CONCLUSION: As in histopathology, the cytologic features of IMPC are unique and should be recognized due to its aggressive behavior.     

Immunocytochemical detection of prognostic markers in breast cancer; technical considerations

The purpose of this study was to establish a good technical procedure for immunocytochemical (IC) staining of prognostic markers in breast cancer specimens. The influence of various preparation, fixation and storage methods on ER, P53 and Ki-67 IC staining was assessed, using cells of two breast cancer cell lines T47D (ER/P53+) and ZR-75-ER (ER+, P53-). In addition we searched for a suitable transport medium. Depending on the technical procedure, great variations in expression of the tested antigens were found. Cytospins fixed and stored according to the Abbott method gave the best results. Histocon appeared to be the medium of choice. A good concordance of IC and immunohistochemical (IH) results was found when the adopted method was tested on material of 10 breast cancers. This study underlines the importance of quality controlled standardization of cell processing, fixation and storage of fine needle aspiration (FNA) aspirates in order to obtain reproducible and consistent IC results.     

Papillary carcinoma of the breast. Cytologic study of nine cases.

OBJECTIVE: To study the cytologic findings of papillary breast carcinoma by fine needle aspiration. STUDY DESIGN: The study group consisted of fine needle aspiration (FNA) specimens of breast tumors from nine patients performed during the period 1988-1997. Eight were female, and one was male. The FNA results were compared with the final histologic diagnosis. RESULTS: The tumor sizes were 4-6.5 cm. The aspirations yielded a good amount of bloody material. The smears revealed high cellularity, papillary clusters, isolated low-to-tall columnar cells, mild to moderate atypia, hemorrhagic background, foam and hemosiderin-laden macrophages, calcification, rare mitoses, palisading row of cells and bipolar cytoplasmic eosinophilic granules. The smears were diagnosed as either suspicious or suggestive of papillary carcinoma. The histologic examination revealed invasive papillary carcinoma. CONCLUSION: Papillary carcinoma of the breast can be diagnosed by using a panel of cytologic findings that includes hypercellularity, papillary clusters, hemorrhagic background, palisading rows of tall columnar cells, cellular atypia and calcification. The interesting finding in this study was the presence of eosinophilic bipolar cytoplasmic granules, which has not been reported before.     

Expression and prognostic role of SKIP in human breast carcinoma

Ski-interacting protein (SKIP) is a nuclear hormone receptor-interacting cofactor, interactions with the proto-oncogene Ski, appears to modulate a number of signalling pathways involved in control of cell proliferation and differentiation, and may play a critical role in oncogenesis. In the present study, to investigate the potential roles of SKIP in breast cancer, expression patterns, interaction and the correlation with clinical/prognostic factors of SKIP and Ki-67 were examined among patients with breast cancer. Immunohistochemistry and Western blot analysis were performed for SKIP in 85 breast carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. We found that SKIP was over expressed in breast carcinoma as compared with the adjacent normal tissues. High expression of SKIP was positively associated with histological grade (P = 0.01) and Ki-67 (P = 0.004). Univariate analysis showed that SKIP expression was associated with a poor prognosis (P = 0.006). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of SKIP was up-regulated, whereas p27 was down-regulated. In addition, we employed small interfering RNA (siRNA) technique to knock down SKIP expression and observed it effects on MDA-MB-231 cells growth. SKIP depletion by siRNA inhibited cell proliferation, blocked S phase and decreased cyclin A and cyclin B levels. On the basis of these results, we suggested that SKIP overexpression was involved in the pathogenesis of breast cancer, which might serve as a future target for breast cancer.     

Cytologic characteristics of endocrine ductal carcinoma in situ of the breast. A case report

BACKGROUND: Endocrine ductal carcinoma in situ is a rare form of ductal carcinoma in situ. It is regarded as a distinct subgroup of mammary carcinoma. However, the cytologic features of endocrine ductal carcinoma in situ have not been previously reported. CASE: A case of endocrine ductal carcinoma in situ exhibited characteristic cytologic findings on a specimen obtained by the scrape method (stained with hematoxylin and eosin and Diff-Quik). CONCLUSION: The cytologic criteria for endocrine ductal carcinoma in situ are sufficiently distinct and are useful for making the diagnosis on fine needle aspiration.     

Cytologic evaluation of low grade transitional cell carcinoma and instrument artifact in bladder washings

OBJECTIVE: To identify key cytologic features for the separation of low grade transitional cell carcinomas (TCCs) from nonneoplastic lesions in bladder washings. STUDY DESIGN: The cytomorphologic features of 95 bladder washing specimens showing papillary fragments, which included 50 low grade TCCs and 45 nonneoplastic lesions, were reviewed retrospectively. RESULTS: Bladder washings from low grade TCCs showed papillary and irregular groups of cells with ragged borders, cytoplasmic homogeneity and subtle nuclear changes, such as increased nuclear/cytoplasmic ratio and irregular nuclear border. Bladder washings after instrumentation from nonneoplastic lesions of the bladder showed cellular specimens with cohesive, ball-shaped and papillary clusters with smooth borders lined with a denser-staining cytoplasmic collar. Reactive urothelial cells often displayed loose aggregates with irregular borders but no cytoplasmic collar. CONCLUSION: In bladder washing cytology, nuclear changes and cytoplasmic homogeneity play a major role in the diagnosis of carcinoma.     

Cytologic appearances in invasive lobular carcinoma of the breast. A study of 21 cases

OBJECTIVE: To examine the fine needle aspiration cytologic features of invasive lobular carcinoma of breast and to discuss problems that may occur in cytodiagnosis. STUDY DESIGN: Fine needle aspiration cytologic smears from 21 cases of invasive lobular carcinoma (ILC) of breast were subjected to detailed cytomorphologic analysis. Features studied included pattern of cells, size of cells, nuclear placement, pleomorphism, presence of intracytoplasmic lumina (ICL) and signet ring cells. RESULTS: Cellularity was generally moderate or high, and the pattern was predominantly or partly dissociated in 86% of cases. Rosettelike pattern was discerned in alveolar-type ILC. Cell size was usually small or intermediate, with nuclei placed eccentrically in most cases. ICLs with or without signet ring cells were present in 12 cases (57%). CONCLUSION: A cytologic picture consisting of predominantly dissociated small or intermediate-sized tumor cells with eccentric nuclei, with some of the cells showing ICLs, is highly suggestive of ILC. Indian file pattern, another characteristic feature of ILC, is, however, focal and inconsistent. Variant patterns of ILC may show other cytologic features, such as rosettelike pattern (alveolar variant of ILC) or large cell pattern (pleomorphic variant of ILC) and may consequently be difficult to categorize on cytologic smears.     

MIB1 proliferation index in breast infiltrating carcinoma: comparison with other proliferative markers and association with new biological prognostic factors

AIMS: In breast invasive carcinoma our objectives were I) to compare cellular proliferation determined by MIB1 index with S-phase fraction (SPF) assessed by flow cytometry and with mitotic index, and II) to examine the association of MIB1 index with classical and with new biological prognostic factors [bcl-2, p53, c-erbB-2 and cathepsin D (CD)]. METHODS AND RESULTS: From 102 cases of breast invasive carcinoma, 5-microm thick serial sections were cut from formalin-fixed, paraffin-embedded tissue blocks, and processed for detection of CD, c-erbB-2, p53, bcl-2, Ki-67 antigen MIB-1 and estrogen receptors (ER) and progesterone receptors (PR). SPF was measured by flow cytometry in fresh-frozen tissue samples taken from the carcinoma in each patient. MIB1 index was correlated with SPF (rho=0.45, p<0.0001) and with mitotic index (rho=0.42, p<0.0001). The MIB-1 index was positively associated with the histological grade (p=0.001), tumor size (p=0.04) and the presence of metastases in axillary lymph nodes (p=0.01). MIB1 was associated directly with p53 (p=0.045) and inversely with bcl-2 (p=0.0002). The MIB-1 index was not statistically associated with c-erbB-2. There was a weak association between MIBI index and stromal cell CD. The median MIB1 index was higher in tumors with moderate to strong CD staining of stromal cell, but the difference did not reach statistical significance (p=0.09). CONCLUSIONS: MIB1 index correlates with well established methods for assessing tumor proliferation and with parameters of an aggressive phenotype of tumor. MIB1 index is an effective and readily accessible method for assessing tumor proliferation in breast carcinoma.     

Medullary breast carcinoma: prognostic implications of p53 expression

Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.     

Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer

To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.     

Cytologic grading and DNA image cytometry of breast carcinoma on fine needle aspiration cytology smears

OBJECTIVE: To correlate the cytologic grade of breast carcinoma with DNA image cytometry (ICM) and nuclear area on fine needle aspiration cytology (FNAC) smears. STUDY DESIGN: In this prospective study, FNAC material from 28 breast carcinomas were studied for cytologic grade and DNA ICM. Breast carcinomas were classified as grade 1-3 (low to high). DNA histograms were classified by the modified Auer method. Degree of hyperploidy (DH), ploidy balance (PB) and nuclear area (NA) were measured on Feulgen-stained smears by a CAS 200 image cytometer. Cytologic grade was correlated with DNA ICM findings and NA. RESULTS: There were 3 cytologic grade 1, 13 grade 2 and 12 grade 3 breast carcinomas. Seven of eight cases of hypertetraploid aneuploidy were grade 3 tumors. All cytologic grade 1 tumors were diploid. There were significant differences in DH, PB and NA in different grades of breast carcinoma (one-way ANOVA). CONCLUSION: DNA image cytometry in combination with cytologic grading might offer additional information for the characterization of breast carcinomas diagnosed by FNAC. These observations are of particular interest with the introduction of preoperative chemotherapy.