Change in tumor cellularity of breast carcinoma after neoadjuvant chemotherapy as a variable in the pathologic assessment of response.

BACKGROUND: Complete pathologic response of breast carcinoma to neoadjuvant chemotherapy is a well defined outcome that correlates with prolonged survival. Categorization of incomplete response depends on accurate measurement of residual tumor size but is complicated by the variable histopathologic changes that occur within the tumor bed. In the current study, the authors investigated the contribution of assessing tumor cellularity in the pathologic evaluation of response to chemotherapy. METHODS: The slides from diagnostic core needle biopsy and the subsequent matched resection specimens were examined in 240 patients with breast carcinoma: 120 "treated" patients who received neoadjuvant chemotherapy and 120 "control" patients who received primary surgical management within a few weeks of diagnosis. Clinical response and residual tumor size were evaluated in 108 treated patients who completed a clinical trial with paclitaxel and then received combined 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Tumor cellularity was assessed from hematoxylin and eosin-stained tissue sections as the percentage of tumor area that contained invasive carcinoma. RESULTS: After neoadjuvant chemotherapy, tumor cellularity decreased from a median of 40% in core needle biopsy to 10% in resection specimens (P<0.01; Wilcoxon signed rank test). The cellularity of core needle biopsy (median, 30%) tended to underestimate the cellularity of resection specimens (median, 40%) in the control group (P<0.01). Changes in cellularity varied within each clinical response category, particularly partial response and minor response. The greatest reduction was observed in the cellularity of residual primary tumors that measured < or =1 cm (pathologic T1a [pT1a] and pT1b tumors), but changes in cellularity varied in the pT1, pT2, and pT3 residual tumor categories. The shape of the distribution of tumor size, expressed as the greatest dimension in cm, was similar in the control group and the treatment group (excluding complete pathologic response); however, when residual tumor size and cellularity were combined, the distribution of pathologic response shifted left (toward complete response) with a steep decline, suggesting that many tumors had a large reduction in cellularity but little change in the tumor size. CONCLUSIONS: Cellularity of the tumor mass was reduced significantly by neoadjuvant chemotherapy, and the change varied widely in different categories of clinical response. Although residual tumors measuring < or =1 cm in greatest dimension had the most reduction in tumor cellularity, there was broad variability for all residual tumor groups (pT1-pT3). The frequency distribution of residual tumor size was altered markedly by the inclusion of tumor cellularity, indicating that the product of pathologic size and tumor cellularity may provide more accurate pathologic response information than tumor size alone.

Large-needle core biopsy in atypical intraductal epithelial hyperplasia including immunohistochemical expression of high molecular weight cytokeratin: analysis of results of a single institution.

The diagnosis of atypical intraductal epithelial hyperplasia (AIDH) constitutes 6.3% of the breast core biopsies performed at our institution. Seventy-nine cases that were diagnosed as AIDH on core biopsy and went through excisional biopsy were included. Sixty-four biopsies were performed by an image-guided 11-gauge vacuum device, 11 under sonographic guidance using 14-gauge needles and 4 by a sonographically guided 11-gauge vacuum device. The histopathology of the core biopsies and the surgical excisions were reviewed. Immunohistochemistry was performed on the consecutive sections of core biopsy specimens using high molecular weight cytokeratin (HMW-CK) (DAKO-Cytokeratin, 34betaE12). At interpretation of the stain, intensity and percentage of positive cells were taken into account. The immunoprofiles of AIDH were categorized into four groups showing negative (i.e., no staining) or low-, moderate-, high-, and very high-intensity staining. Surgical excision of the 79 lesions revealed carcinoma in only 3 cases (4%)-two infiltrating carcinomas and one intraductal carcinoma-residual AIDH in 44 cases (56%), and epithelial hyperplasia or other benign lesions without atypia in 32 cases (40%). The HMW-CK stain was performed retrospectively on all of the core biopsies and 66 of them contained residual areas with AIDH for staining. Forty-nine (74%) were CK negative or stained with low intensity, but 17 cases (26%) had a moderate- to high-intensity stain. Our study showed a lower incidence of carcinoma on surgical excision following core biopsy for AIDH than other studies. The HMW-CK stain helped to characterize the nature of the intraductal proliferation and to confirm the presence of atypia, as has been previously reported, but frequently was inconclusive. The low incidence of carcinoma brings into question the need for surgical excision of all cases of AIDH diagnosed by core biopsy.

Osseous metaplasia of the breast: diagnosis with stereotactic core biopsy.

There are approximately 200 reported cases of breast tumors containing areas of bone. The majority of the neoplasms are sarcomas, phylloides tumors, or fibroadenomata. We present a case of osseous metaplasia mammographically detected by clustered heterogeneous calcifications. Stereotactic core biopsy revealed the presence of well-formed bone tissue without associated neolplasia. The case represents the first reported case of mammographically detected osseous metaplasia confirmed by core biopsy.