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  Anatomic Abstracts

 

 

 

 

March 2011

Editors:
Michael Cibull, MD
Melissa Kesler, MD
Rouzan Karabakhtsian, MD
Megan Zhang, MD

Usefulness of detecting lymphovascular invasion in lymph node-positive patients with primary operable breast cancer Usefulness of detecting lymphovascular invasion in lymph node-positive patients with primary operable breast cancer

Lymphovascular invasion is a widely recognized prognostic factor in lymph node-negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node-positive patients. To investigate its significance in the latter group, the authors conducted a study on 931 patients who underwent surgery and were monitored at the authors’ institution for an invasive breast carcinoma between 1989 and 1992. All 374 lymph node-positive breast cancers during that time were entered in the study (median followup, 126 months). The authors found that lymphovascular invasion (LVI) was present in 46 percent of the tumors and was associated with age of not more than 40 years (P=0.02), high histological grade (P=0.01), and negative estrogen receptor status (P=0.032), but not with tumor size, number of involved lymph nodes, or HER2/neu status. LVI was an independent prognostic factor for distant metastases (P=0.002). Furthermore, in HER2/neu-negative/hormone receptor-positive tumors (n=287), the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a five-year metastasis-free survival ranging from 100 percent with no factors (n=25), to 89 percent plus or minus two percent with one or two factors (n=186), to 67 percent plus or minus six percent with three to five factors (n=76). The authors concluded that LVI is an independent prognostic factor in lymph node-positive breast cancer and merits further prospective investigation as a decision tool in the adjuvant chemotherapy setting.

Ragage F, Debled M, MacGrogan G, et al. Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer? Cancer. 2010; 116(13): 3093–3101.

Correspondence: Dr. Marc Debled at debled@bergonie.org
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Comparison of classification systems in melanoma sentinel lymph nodes Comparison of classification systems in melanoma sentinel lymph nodes

Various classification systems for melanoma have been proposed to predict overall survival and recurrence-free survival based on findings in the sentinel lymph node. The authors conducted a study in which they compared the recurrence-free survival (RFS) and overall survival (OS) rates for 697 melanoma patients as predicted by various classification systems. They studied the Rotterdam system (based on the greatest dimension of the largest tumor cell deposit), Augsburg S-classification (based on tumor penetrative depth [TPD]), and Hannover system (based on a combination of tumor load, TPD, and invasion of the capsule). The study focused on 697 consecutive melanoma patients who underwent SLN biopsy at the authors’ center. In univariate analyses, the Rotterdam and Hannover systems, but not the S-classification, identified one group of SLN-positive patients who had OS and RFS similar to the OS and RFS of SLN-negative patients. The intermediate groups from all classification systems did not differ significantly from the adjacent groups with regard to RFS or OS, or both. In multivariate analysis using a Cox model, the greatest dimension of the largest tumor cell deposit (cutoff point, less than 0.1 mm versus 0.1 mm or more), TPD (cutoff point, 2 mm or less versus more than 2 mm), and capsular involvement represented independent parameters for RFS. TPD and capsular involvement were also independent parameters for OS. On the basis of these three parameters, the authors proposed a new scoring system for risk assessment in patients with melanoma that can distinguish three separate groups of patients that differ significantly in OS and RFS. The authors concluded that different parameters of independent prognostic significance were identified in SLNs from patients with melanoma. Combining these parameters, the prognosis for patients with melanoma was predicted more precisely by the new scoring system than by current classification systems.

Meier A, Satzger I, Volker B, et al. Comparison of classification systems in melanoma sentinel lymph nodes—an analysis of 697 patients from a single center. Cancer. 2010; 116(13): 3178–3188.

Correspondence: Dr. Imke Satzger at satzger.imke@mh-hannover.de
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Ovarian frozen sections: Use of whole-slide imaging to show correlation between a virtual slide and original interpretation Ovarian frozen sections: Use of whole-slide imaging to show correlation between a virtual slide and original interpretation

The authors conducted a study to test the reproducibility and accuracy of ovarian frozen section interpretation using whole-slide imaging, in lieu of routine analog interpretation, to better understand the technology limits and unique interpretive pitfalls of such imaging. A sequential series of ovarian frozen section slides, representative of routine practice, were converted into whole-slide images for the study. The images were examined by two pathologists, masked to all prior results. Correlation characteristics among the images, the original, and the final interpretations were analyzed. A total of 52 cases, consisting of 71 frozen section slides, were included: 34 cases (65 percent) were benign and 18 cases (35 percent) were malignant, borderline, or of uncertain potential (nine [17 percent], seven [13 percent], and two [four percent] of 52 cases, respectively). The correlation between whole-slide imaging and frozen section interpretation was 96 percent (50 of 52) for each pathologist for benign versus malignant, borderline, and uncertain entities. Each pathologist undercalled two borderline malignant cases (four percent) as benign cysts on whole-slide imaging. There were no overcalls of benign cases. Specific issues within the benign and malignant groups involved endometriosis versus hemorrhagic corpora lutea, and granulosa cell tumor versus carcinoma, respectively. The authors concluded that correlation between original frozen section and whole-slide imaging interpretations was very high. The few discordant cases represented recognized differential diagnostic issues. The ability to examine gross pathology and real-time consultations with surgeons might be expected to improve performance. Ovarian frozen section diagnosis by whole-slide imaging is accurate and reproducible. Therefore, remote interpretation, teaching, and digital archiving of ovarian frozen section specimens by this method can be reliable.

Fallon MA, Wilbur DC, Prasad M. Ovarian frozen section diagnosis: Use of whole slide imaging shows excellent correlation between virtual slide and original interpretations in a large series of cases. Arch Pathol Lab Med. 2010;134(7):1020–1023.

Correspondence: Dr. David C. Wilbur at dwilbur@partners.org
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Factors that predict lymph node yield from surgical specimens in colorectal cancer Factors that predict lymph node yield from surgical specimens in colorectal cancer

The National Quality Forum endorses the recommendation of examining at least 12 lymph nodes from colorectal cancer specimens. However, heterogeneity in lymph node harvest exists. The authors conducted a study to investigate the clinicopathologic factors that influence lymph node yield. They used the National Cancer Institute’s Surveillance, Epidemiology, and End Results database to identify patients who were diagnosed with stage I, II, or III colorectal cancer between 1994 and 2005. Poisson regression was used to model the number of lymph nodes examined as a function of individual clinicopathologic factors, including age, gender, race, year of diagnosis, geographic region, anatomic site, preoperative radiation, tumor size, tumor classification, tumor differentiation, and lymph node positivity. The authors identified 153,483 patients with colorectal cancer. The mean number of lymph nodes examined (+/– standard deviation) was 12 (+/–9.3). Separate multivariate analyses revealed that age, year of diagnosis, tumor size, and tumor classification were significant predictors of lymph node yield for colon and extraperitoneal rectal cancers (P<0.01 for all covariates). Tumor location and radiotherapy were significant predictors of lymph node yield in patients with colon cancer and rectal cancer, respectively. Overall, lymph node yields increased between two percent and three percent annually. The authors concluded that despite the increasing yields observed over time, patients with rectal cancer and older patients who had distally located early colon cancer were less likely to meet the benchmark yield of 12 lymph nodes. Further investigation into how lymph node yield is influenced by alterable factors, such as the extent of mesenteric resection and pathologic technique, as well as nonalterable factors, such as patient age and tumor location, may reveal innovative ways to improve staging methods.

Chou JF, Row D, Gonen M, et al. Clinical and pathologic factors that predict lymph node yield from surgical specimens in colorectal cancer: a population-based study. Cancer. 2010; 116: 2560–2570.

Correspondence: Dr. Martin R. Weiser at weiser1@mskcc.org
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Gleason score of tumor at the margin in radical prostatectomy as a predic-tor of biochemical recurrence Gleason score of tumor at the margin in radical prostatectomy as a predictor of biochemical recurrence

The World Health Organization recommends the Gleason grading system for grading prostate carcinoma. The Gleason score of the main tumor in prostate carcinoma is a powerful predictive factor for biochemical recurrence, but the significance of the Gleason score of tumor at the margin is unknown. The authors investigated this subject in 336 patients (mean age, 61 years; median, 61 years; range, 39 to 80 years; mean followup, 41 months; median, 32 months; range, one to 202 months) with a positive surgical margin in radical prostatectomy. The mean preoperative prostate-specific antigen level was 8.2 ng/mL (median, 5.8; range, 0.9–85). The pathologic stage was T2, T3a, and T3b in 185, 127, and 24 patients, respectively. The Gleason score of the main tumor was six, seven, eight, and nine in 70 (all 3+3), 242 (3+4 in 186 and 4+3 in 56), eight (5+3 in one and 4+4 in seven), and 16 (4+5 in 12 and 5+4 in four) patients, respectively. The Gleason score of tumor at the margin was six in 220 (66 percent, all 3+3), seven in 88 (26 percent, 3+4 in 59 and 4+3 in 29), eight in 19 (six percent, all 4+4), nine in seven (two percent, 4+5 in four and 5+4 in three), and 10 in two (one percent) cases, respectively. The Gleason score concordance rate between the main tumor and tumor at the margin was 69 out of 70 (99 percent), 83 out of 242 (34 percent), five out of eight (63 percent), and six out of 16 (38 percent) in cases in which the main tumor had a Gleason score of six, seven, eight, and nine, respectively. The Gleason score of tumor at the margin was lower, equal to, and higher than that of the main tumor in 160 (48 percent), 163 (49 percent), and 13 (four percent) cases, respectively. The Gleason score of tumor at the margin was strongly correlated with preoperative prostate-specific antigen, pathologic stage, Gleason score of the main tumor, lymph node status, and linear length of tumor at the margin (P<0.05 for all). On univariate and multivariate analysis, the Gleason score of tumor at the margin was a strong predictive factor for biochemical recurrence (P<0.05). Among those patients with the same Gleason score in their main tumors (seven or above), those with a higher Gleason score of tumor at the margin were more likely to have had biochemical recurrence than those with a lower score. The authors concluded that reporting the Gleason score of tumor at the margin can improve the predictive accuracy of biochemical recurrence. The authors advocate reporting the Gleason score of tumor at the margin in radical prostatectomy.

Cao D, Kibel AS, Gao F, et al. The Gleason score of tumor at the margin in radical prostatectomy is predictive of biochemical recur-rence. Am J Surg Pathol. 2010;34(7):994–1001.

Correspondence: Dr. Dengfeng Cao at dcao@path.wustl.edu
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Diagnostic evaluation of papillary lesions of the breast on core biopsy Diagnostic evaluation of papillary lesions of the breast on core biopsy

Management of asymptomatic intraductal papillary lesions of the breast diagnosed on core biopsy poses a challenge for patients and clinicians as the distinction between common benign lesions and atypical or malignant varieties may be difficult without formal excision. The authors conducted a study to determine whether a combination of histopathologic and biomarker features could be used to identify benign papillary lesions on core biopsy. They characterized an inclusive group of 127 excised papillary lesions by detailed histopathologic review and immunohistochemical staining for the basal markers cytokeratin 5/6 (CK5/6) and P63 and the proliferation marker Ki67. Comparison of benign, atypical, and malignant lesions revealed that the combination of broad, sclerotic fibrovascular cores and epithelial CK5/6 staining was most commonly seen in benign papillomas. Ki67 staining revealed striking intralesional heterogeneity, but there was no difference between the high scores of benign, atypical, or malignant lesions (P=0.173). In a non-overlapping set of 42 cases, a binary classifier specifying benign lesions on the basis of thick fibrovascular cores and epithelial CK5/6 staining on core biopsy gave an overall misclassification rate of four of 42 (10 percent) when compared with the final excision diagnosis. Misclassified cases included two of 27 lesions ultimately diagnosed as benign and two of two atypical papillomas. All malignant lesions (n=13) were assigned correctly. The combined assessment of fibrovascular core thickness and CK5/6 staining on core biopsy distinguished benign from malignant papillary lesions but did not separate benign from atypical cases. The authors concluded that this approach may be a useful addition to the clinicopathologic evaluation of papillary lesions of the breast.

Pathmanathan N, Albertini AF, Provan PJ, et al. Diagnostic evaluation of papillary lesions of the breast on core biopsy. Mod Pathol. 2010;23:1021–1028.

Correspondence: Dr. N. Pathmanathan at nirmala.pathmanathan@swahs.health.nsw.gov.au
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.