Assessing invasion criteria in fine needle aspirates from breast carcinoma diagnosed as DICS or invasive carcinoma: can we identify an invasive component in addition to DCIS?

OBJECTIVE: To evaluate invasion criteria in fine needle aspiration cytology (FNAC) of histologically diagnosed breast ductal carcinoma in situ (DCIS) and invasive carcinoma and to evaluate their usefulness in identifying an invasive component in addition to DCIS. STUDY DESIGN: The material consisted of 331 smears diagnosed as suspicious for or consistent with DCIS and in which histology had shown either DCIS or invasive ductal carcinoma. All smears were reevaluated for the following invasion criteria: invasion of fat or fibrous tissue fragments, fibroblast proliferation, cell-poor elastoid tissue fragments, tubular structures and intracytoplasmic vacuoles. RESULTS: All invasion criteria except cytoplasmic vacuoles correlated with invasiveness, but none of them were found exclusively in invasive lesions. Pseudoinvasion in fibrous or fatty tissue fragments were found in 8 cases of histologic pure DCIS. One DCIS (0.4%) revealed > or = 2 invasion features as well as 22 invasive carcinomas (20.7%), representing 7.4% of all cases. CONCLUSION: Using established invasion criteria, practically no pure DCIS lesion will be diagnosed as invasive on FNAC, but one will identify only a subset of cases harboring an invasive component.

EGFR gene copy number heterogeneity in fine-needle aspiration cytology from breast carcinomas determined by chromogenic in situ hybridization.

Most studies have shown epidermal growth factor receptor (EGFR) overexpression to be associated with poor prognostic factors in breast carcinomas. The relationship to EGFR gene copy number is unclear. The aim of our study was to investigate the heterogeneity of the EGFR gene copy number in breast carcinomas. The material consisted of air-dried smears from 29 breast carcinomas and 3 breast cancer cell lines (MCF-7, SKBR3, and T47D). Chromogenic in situ hybridization (CISH) was done using chromogenic detection. The mean signal numbers for EGFR gene and chromosome 7 as well as the EGFR gene/chromosome 7 centromere probe (CEP7) ratio were recorded. Immunohistochemical (IHC) staining was done on the corresponding paraffin sections. The copy number of the EGFR gene in each tumor/cell line ranged from 1.2 to 5.6. The EGFR gene/CEP7 ratio showed a biological continuum ranging from 0.59 to 1.94 with a mean of 1.04. EGFR gene copy loss was found in 16.6% of cases whereas copy gain was demonstrated in 19.4%. There was no relationship between IHC protein expression of EGFR and EGFR gene copy number or EGFR gene/CEP7 ratio.In conclusion, most breast carcinomas had a balanced EGFR gene/CEP7 copy number with a mean ratio of 1.04. Almost equal subpopulations revealed limited copy gain and copy loss. EGFR high dosage amplification, like in HER-2, was not demonstrated. Demonstration of EGFR gene copy loss might have a potential as a surrogate marker for EGFR gene mutation and/or deletion.

Cytologic features of ductal carcinoma in situ in fine-needle aspiration of the breast mirror the histopathologic growth pattern heterogeneity and grading.

BACKGROUND: Approximately 20% of the breast carcinoma cases detected on mammography screening represent ductal carcinoma in situ (DCIS). Cytopathologists are exposed to cytologic material from DCIS when nonpalpable, mammographic lesions are aspirated during the workup of organized and opportunistic mammography screening. METHODS: The material in the current study was comprised of 225 representative fine-needle aspiration cytology (FNAC) smears from histologically confirmed DCIS of the breast that were diagnosed between 1990-2003. Smears were rescreened to search for the following features: nuclear size (grading), monolayer sheets, solid and cribriform epithelial aggregates, micropapillary and true papillary structures, comedo-type necrosis, microcalcifications, myoepithelial cells, and discohesion. RESULTS: There were 174 high-grade lesions (77% were Grade 3) and 51 nonhigh-grade lesions (Grades 1 and 2). The concordance between the cytologic and histologic grading was 97% in the Grade 3 lesions and 94% in the Grade 1/2 lesions. Smears from Grade 3 DCIS contained solid and/or cribriform epithelial aggregates in > 93%% of the cases, whereas smears from Grade 1/2 lesions were found to contain cribriform aggregates in 94% of the cases. Pure subtypes were virtually nonexistent. Monolayer sheets were found in 49% of nonhigh-grade DCIS and in 16% of high-grade DCIS. Myoepithelial cells were demonstrated in 51% of the nonhigh-grade DCIS lesions and 27% of the Grade 3 lesions. Microcalcifications were found on the smears from 96% of nonhigh-grade lesions and 84% of high-grade lesions. Approximately 47% of high-grade DCIS and 31% of nonhigh-grade DCIS were found to harbor a distinct single cell population. CONCLUSIONS: The findings on FNAC from DCIS of the breast completely mirror the histologic heterogeneity of growth pattern subtypes. Primary cytologic grading can effectively separate the high-grade lesions from the nonhigh-grade lesions.