Eosinophilic esophagitis: a paradigm shift for pathology.

BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized disease only reported in the adult literature since 1993. Our facility has the opportunity to evaluate steroid-naive EoE patients since 1988, allowing us to describe the evolution of the histologic diagnosis of EoE. METHODS: This retrospective study analyzed 95 patient charts with initial diagnosis of congenital esophageal stenosis/EoE from 1988 to 2012. Patients had dysphagia and met endoscopic criteria consistent with current EoE histologic criteria while on chronic proton-pump inhibitor therapy. Histologic slides were obtained for only 10 patients because of limited slide availability; and the slides were reviewed by a single pathologist. EoE is defined as ≥1 biopsy specimens demonstrating >15 eosinophils/HPF. RESULTS: Following review of histologic analysis reports, pathologists in our 2 academic hospitals began recognizing EoE as separate disease entity starting in 2007, coincidental with first EoE guidelines. After 2007, there was a clear surge in histologic diagnosis of EoE. Slides from 10 patients from 1988 to 2012 were reviewed. Of 35 biopsy sets, 19 were previously interpreted as reflux esophagitis (RE) or acute/chronic inflammation, 3 as RE with eosinophils, 2 as normal, and 11 as EoE. Reevaluation revealed EoE in 79% specimens with RE/inflammation and 100% with RE and eosinophils; remaining specimens had confirmed original diagnosis. All 10 patients had at least one set of slides meeting current EoE histologic criteria. CONCLUSIONS: EoE as a disease has been present for at least 2 to 3 decades. This is the first report of a clearly demarcated time point reflecting a paradigm shift in the histologic diagnosis of EoE as a distinct entity resulting from a seminal consensus report.

Breast epithelial cells in dermal angiolymphatic spaces: a manifestation of benign mechanical transport.

Evidence suggesting that breast epithelial cells may reach axillary lymph nodes by benign mechanical transport (BMT), rather than metastatic means, has been recently reported. We report a case of a patient with ductal carcinoma in situ of the breast, who had displaced epithelial elements in the mastectomy specimen, dermal angiolymphatic spaces, and a sentinel lymph node. We attribute the epithelial aggregates in the dermal angiolymphatic spaces and a single cell in the sentinel lymph node to BMT, based on the clinicopathological findings of the case. We, therefore, suggest that the effects of BMT be considered in the differential diagnosis of epithelial aggregates in dermal angiolymphatic spaces in the appropriate clinicopathological setting.

Benign mechanical transport of breast epithelial cells to sentinel lymph nodes.

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

Significance of sentinel lymph node micrometastases in human breast cancer.

BACKGROUND: The significance of micrometastatic disease in the sentinel lymph nodes (SLN) of patients with invasive breast cancer has been questioned. The objective of our study was to review the impact of micrometastatic carcinoma detected by SLN biopsy. STUDY DESIGN: Between January 1997 and May 2004, 2,408 patients with invasive breast cancer and an SLN with micrometastatic (N0[i+], N1mi) or no metastatic (N0[i-]) disease were identified through our breast database. Slide review was performed and reclassified by the 6(th) edition of the American Joint Committee on Cancer Staging Manual. Of these, 27 were excluded from analysis because of evidence of macrometastatic disease on slide review or enrollment in the American College of Surgeons Oncology Group Z10 study. RESULTS: Of 2,381 patients, 2,108 were N0(i-), 151 were N0(i+), and 122 were N1mi. Overall and disease-free survivals of patients with an N1mi SLN were substantially worse than those in patients with an N0(i-) SLN (p < 0.001 and p=0.006, respectively). Additional positive non-SLNs were identified in 15.5% (15 of 97) of N1mi patients and 9.3% (10 of 107) of N0(i+) patients undergoing completion axillary lymph node dissection. Overall survival of the N0(i+) SLN patients not undergoing axillary dissection was substantially less than those undergoing axillary dissection (p=0.02). CONCLUSIONS: Detection of micrometastatic carcinoma (N1mi) in the SLNs of invasive breast cancer patients is a major indicator of poorer survival compared with N0(i-) patients. Although survival of patients with an N0(i+) SLN does not statistically differ from that of N0(i-) patients, 9.3% of these patients had additional axillary nodal disease on axillary dissection, and N0(i+) patients had a decreased survival when axillary dissection was omitted.

Survival outcomes in node-negative breast cancer patients evaluated with complete axillary node dissection versus sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node (SLN) biopsy combined with microstaging-associated immunohistochemical staining for cytokeratin more accurately assigns patients to their corresponding diagnostic stage. The purpose of this study was to compare the survival outcomes of node-negative patients who received an SLN biopsy with historical control data of node-negative patients who received routine complete axillary lymph node dissection (CALND) in the pre-SLN biopsy era. METHODS: Under institutional review board approval, 2458 node-negative invasive breast cancer patients between the ages of 25 and 94 years (mean, 60 years) were treated at our institution from January 1986 to May 2004. Of these 2458 patients, 604 (25%) were evaluated with CALND, whereas 1854 (75%) were evaluated with SLN biopsy. All were treated according to the current stage-specific guidelines. Kaplan-Meier graphs of overall survival and disease-free survival were constructed for each group of patients, and the two groups were compared by using the log-rank test. RESULTS: Overall survival and disease-free survival for the CALND and SLN biopsy groups did not differ significantly (P = .98). The average number of lymph nodes extracted in the pre-SLN biopsy group was 18, whereas the average number of SLNs extracted in the post-SLN biopsy group was 3. CONCLUSIONS: The survival rate among node-negative breast cancer patients who received an SLN biopsy alone has proven to have no significant difference (P = .98) from the survival rate among node-negative patients who received a CALND. SLN biopsy alone should replace CALND as the primary tool for axillary staging of breast cancer in node-negative patients.

Modes of benign mechanical transport of breast epithelial cells to axillary lymph nodes.

The status of axillary lymph nodes is a key prognostic indicator available for the management of patients with breast cancer. Sentinel lymph node (SLN) evaluation as a predictor of lymph node status has led to increased use of ancillary methods, principally immunohistochemistry, to increase the sensitivity of the SLN biopsy. So-called "occult" micrometastases detected by such methods have led to speculation that some may have reached the SLNs by benign mechanical transport (BMT) rather than a metastatic process. We review evidence suggesting two potential modes of BMT: lymphatic transport of epithelial cells displaced by biopsy of the primary breast tumor and by breast massage-assisted SLN localization. The biopsy techniques under most scrutiny include fine needle aspiration and large-gauge core biopsy. The evidence implicating breast massage prior to SLN biopsy as a mode of BMT has been supported by statistical analysis; however, no method of distinguishing massage-associated cells in SLNs from true occult micrometastases is available. The significance of small epithelial clusters in SLNs is currently unknown. Thus, deviation from current biopsy and SLN-localizing practices is unwarranted.

Radioactive seed localization breast biopsy and lumpectomy: can specimen radiographs be eliminated?

BACKGROUND: Wire localization (WL) is the current standard for surgical diagnosis of nonpalpable breast lesions. Many disadvantages inherent to WL are solved with radioactive seed localization (RSL). This trial investigated the ability of RSL to reduce the need for specimen radiographs and operating room delays associated with WL. METHODS: A total of 134 women were entered onto an institutional review board-approved study. RSL was performed by placing a titanium seed containing.29 to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion. The surgeon used a handheld gamma detector to locate and excise the iodine-125 seed and the lesion. RESULTS: Specimen radiographs were eliminated in 98 (79%) of 124 patients. Surgical seed retrieval was 100% in 124 patients. No seed migration occurred after correct radiographical placement. A total of 26 (21%) of 124 patients required a specimen radiograph; 22 (85%) of these 26 were performed for microcalcifications. CONCLUSIONS: After surgical removal, RSL can eliminate specimen radiographs when the radiologist accurately places the seed and the pathologist grossly identifies the lesion. If small microcalcifications are noted before surgery, then specimen radiographs may be necessary. RSL reduced requirements for specimen radiographs, decreased OR time, improved incision placement, and improved resections to clear margins.