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CAP Home > CAP Reference Resources and Publications > CAP TODAY > CAP TODAY 2005 Archive > Anatomic Abstracts
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  Anatomic Abstracts

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November 2005
Feature Story

Significance of percentage of positive/ dissected axillary lymph nodes in breast cancer
Micrometastasis in breast carcinoma and complete axillary dissection
BCLIO or NF-kB in predicting H. pylori-independent status of MALT
Ki67 and p53 evaluation and assessment of Barrett’s esophagusMbr
Cytologic features of high-grade SIL in conventional slides
Benign breast disease and risk of breast cancer

Significance of percentage of positive/ dissected axillary lymph nodes in breast cancer

Adjuvant therapy for women with T1-T2 breast carcinoma and one to three positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence risks. This inconsistency has been attributed to variation in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes. The study cohort was composed of 542 women with pathologic T1-T2 breast carcinoma who had one to three positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, and overall survival rates stratified by the number of positive lymph nodes, number of dissected lymph nodes, and percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. The median followup was 7.5 years. Locoregional recurrence, distant recurrence, and overall survival rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in locoregional recurrence was observed was 25 percent positive lymph nodes. (The 10-year Kaplan-Meier locoregional recurrence rates were 13.9 percent and 36.7 percent in women with 25 percent or fewer and more than 25 percent positive lymph nodes, respectively; P<0.0001.) Higher distant recurrence rates and lower overall survival rates were observed among patients who had more than 25 percent positive lymph nodes compared with patients who had 25 percent or fewer positive lymph nodes (distant recurrence, 53 percent versus 30.3 percent, respectively; P<0.0001; overall survival, 43.4 percent versus 62.6 percent, respectively; P<0.0001). In the multivariate analysis, percentage of positive lymph nodes and histologic grade were significant, independent factors associated with locoregional recurrence, distant recurrence, and overall survival. The authors concluded that the presence of more than 25 percent positive lymph nodes was an adverse prognostic factor in patients with one to three positive nodes and may be used to identify patients at high risk of postmastectomy locoregional and distant recurrence who may benefit from adjuvant radiotherapy and more aggressive systemic therapy regimens.

Truong PT, Berthelet E, Lee J, et al. The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes. Cancer. 2005;103:2006–2014.

Reprints: Dr. Pauline T. Truong, British Columbia Cancer Agency, Vancouver Island Center, 2410 Lee Ave., Victoria, British Columbia, V8R 6V5, Canada; ptruong@ bccancer. bc.ca


Micrometastasis in breast carcinoma and complete axillary dissection

The decision whether to proceed with complete axillary node dissection based on sentinel node status is clear for patients with negative or macrometastatic disease. However, the course of action based on sentinel node micrometastasis remains controversial. The authors reviewed 358 cases from June 1999 to July 2003. They evaluated all sentinel nodes at three levels by frozen section, touch preparation, and scrape preparation. Micrometastasis was defined as tumor deposits between 0.2 mm and 2 mm. The authors recorded the size, grade, and lymphvascular invasion of the primary tumor, as well as the number, status, and size of metastatic disease, and presence of extranodal capsular extension of sentinel and nonsentinel nodes. Of the 358 cases, 89 had positive sentinel nodes, 29 of which represented micrometastases. Only one of the 29 (three percent) cases contained a nonsentinel node with macrometastasis. In 60 of the 89 (67 percent) cases, sentinel nodes contained macrometastases. Of these, 38 cases (63 percent) had metastatic tumor in nonsentinel nodes. Intraoperative consult was performed in 53 of the 89 cases with positive sentinel nodes. Only one of the 19 (five percent) intraoperative consult cases with micrometastatic sentinel nodes had positive nonsentinel nodes, while 21 of 34 (62 percent) of the macrometastatic sentinel nodes at intraoperative consult had tumor in nonsentinel nodes. No single variable studied discriminated between micro- and macrometastatic disease. At intraoperative consult, macrometastatic disease was present in all three diagnostic preparations, while diagnostic material in micrometastatic sentinel nodes was usually present in only one modality. This analysis suggests that the risk of finding tumor in nonsentinel nodes differs significantly between cases with micro- (three percent) versus macrometastatic (63 percent) disease in sentinel nodes. This holds true for cases assessed by intraoperative consult. Considering the known morbidity of complete axillary dissection, the authors concluded that clinicians should assess the risk versus benefit of undertaking this procedure on a case-by-case basis in patients with sentinel node micrometastases.

Rutledge H, Davis J, Chiu R, et al. Sentinel node micrometastasis in breast carcinoma may not be an indication for complete axillary dissection. Mod Pathol. 2005;18: 762–768.

Reprints: Dr. H. Rutledge, Dept. of Pathology, University of Kentucky, Suite MS 117, 800 Rose St., Lexington KY 40536-0001; hlr1998@aol.com


BCLIO or NF-kB in predicting H. pylori-independent status of MALT

The t(11;18)(q21;q21) translocation is a specific marker for Helicobacter pylori-independent status of low-grade gastric lymphoma of mucosa-associated lymphoid tissue, or MALT. However, 30 percent to 50 percent of H. pylori-independent low-grade gastric MALT lymphomas lack this aberration. No reliable markers have been identified to predict tumor response to H. pylori eradication in patients without the translocation. The authors investigated whether nuclear expression of BCL10 and nuclear factor kB, or NF-kB (found to correlate with H. pylori-independent status in gastric high-grade MALT lymphoma), would predict H. pylori-independent status in low-grade gastric MALT lymphomas lacking t(11;18) (q21;q21). Sixty patients who underwent successful H. pylori-eradication for low-grade gastric MALT lymphoma were included in the study. Forty-seven lacked t(11;18) (q21;q21). Of these, 36 were H. pylori-dependent and 11 were H. pylori-independent. In the translocation-negative patients, nuclear expression of BCL10 was significantly higher in H. pylori-independent than in H. pylori-dependent tumors (72.7 percent versus 8.3 percent; P<.001). Nuclear expression of NF-kB was also significantly higher in H. pylori-independent than in H. pylori-dependent tumors (63.6 percent versus 8.3 percent; P<.001). Of the 13 patients with the t(11;18) (q21;q21), 12 showed nuclear expression of BCL10 and NF-kB. All 12 were H. pylori-independent. One case with the t(11;18)(q21;q21) was H. pylori-dependent; it showed cytoplasmic localization of BCL10 and NF-kB. The authors concluded that nuclear expression of BCL10 or NF-kB is predictive of H. pylori-independent status in low-grade gastric MALT lymphomas with or without t(11;18) (q21;q21).

Yeh KH, Kuo SH, Chen LT, et al. Nuclear expression of BCL10 or nuclear factor kappa B helps predict Helicobacter pylori-independent status of low-grade gastric mucosa-associated lymphoid tissue lymphomas with or without t(11;18)(q21;q21). Blood. 2005;106(3):1037–1041.

Reprints: Ann-Lii Cheng, Dept. of Internal Medicine and Dept. of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan S Rd., Taipei, Taiwan; andrew@ ha.mc.ntu.edu.tw; and Li-Tzong Chen, Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan; leochen@ nhri.org.tw


Ki67 and p53 evaluation and assessment of Barrett’s esophagus

The authors conducted a study to devise clinically applicable methods for assessing p53 and Ki67 immunohistochemical reactivity in Barrett’s esophagus and to compare the interobserver agreement between these methods and routine hematoxylin-and-eosin evaluation. One hundred and fifteen biopsies diagnosed as Barrett’s esophagus, selected from the files of the University Hospital MAS, Malmö, were re-evaluated for dysplasia by three pathologists. For immunohistochemical analysis, areas with the most prominent positivity were evaluated. The mean of p53+ epithelial nuclei/high-power field (HPF) was obtained by counting between one and five HPFs per biopsy. A proliferation quotient was obtained by dividing the number of Ki67+ epithelial nuclei in the upper half by the lower half of the mucosa using two HPFs. Mean k values were 0.24, 0.71, and 0.52 for hematoxylin and eosin, p53, and Ki67 evaluations, respectively. A correlation was noted between increasing severity of dysplasia, immunohistochemical measurable overexpression of p53, and shift of the mucosal proliferation zone towards the surface, measured as a proliferation quotient. The authors concluded that these methods for p53 and Ki67 evaluation were more reproducible than routine hemotoxylin-and-eosin evaluation of Barrett’s esophagus. Furthermore, the immunohistochemical methods correlate with the severity of dysplasia and are useful supplementary prognostic markers.

Lorinc E, Jakobsson B, Landberg G, et al. Ki67 and p53 immunohistochemistry reduces interobserver variation in assessment of Barrett’s oesophagus. Histopathology. 2005; 46(6):642–648.

Correspondence: Ester Lorinc, Division of Pathology, Dept. of Clinical Pathology and Cytology, University Hospital MAS, Malmö, Sweden; ester.lorinc@skane.se


Cytologic features of high-grade SIL in conventional slides

Previous studies have suggested that cases of high-grade squamous intraepithelial lesion in conventional smears and in ThinPrep specimens that are frequently misinterpreted as normal have relatively few small and hypochromatic dysplastic cells. The authors conducted a study to determine the cytologic differences between conventional Papanicolaou slides of high-grade squamous intraepithelial lesion that perform poorly and those that perform well. To this end, they compared the cytologic features of 22 cases of conventional smears with high-grade squamous intraepithelial lesion that performed poorly in the College of American Pathologists’ Interlaboratory Comparison Program in Gynecologic Cytology with 45 cases of conventional smears that performed extremely well. They found that cases that performed poorly were significantly more likely to have 50 or fewer single dysplastic cells (P=0.003) and to have only small dysplastic cells (P=0.01). Cases that performed well were also more likely to have more than 500 dysplastic cells (P=0.002), to exhibit the presence of large dysplastic cells (P<0.001), and to be keratinized (P=0.03). Hypochromasia and the number of groups of dysplastic cells were not correlated with performance. The authors concluded that conventional smears with high-grade squamous intraepithelial lesion with 50 or fewer single dysplastic cells, no large dysplastic cells, and lacking keratinization are highly associated with poor performance in this CAP program.

Renshaw AA, Prey MU, Hodes L, et al. Cytologic features of high-grade squamous intraepithelial lesion in conventional slides. What is the difference between cases that perform well and those that perform poorly? Arch Pathol Lab Med. 2005;129:733–735.

Reprints: Dr. Andrew A. Renshaw, Dept. of Pathology, Baptist Hospital of Miami, 8900 N. Kendall Drive, Miami, FL 33176-2197; andrewr@bhssf.org


Benign breast disease and risk of breast cancer

Benign breast disease is an important risk factor for breast cancer. The authors studied a large group of women with benign breast disease to obtain reliable estimates of this risk. They identified all women who received a diagnosis of benign breast disease at the Mayo Clinic between 1967 and 1991. Breast cancer events were obtained from medical records and questionnaires. To estimate relative risks, the authors compared the number of observed breast cancers with the number expected on the basis of the rates of breast cancer in the Iowa Surveillance, Epidemiology, and End Results registry. The authors followed 9,087 women for a median of 15 years. The histologic findings were nonproliferative lesions in 67 percent of the women, proliferative lesions without atypia in 30 percent, and atypical hyperplasia in four percent. At the time of the study, 707 breast cancers had developed. The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. Strength of family history of breast cancer, available for 4,808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history of breast cancer and nonproliferative findings. In the first 10 years after initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia. The authors concluded that risk factors for breast cancer after the diagnosis of benign breast disease include the histologic classification of a benign breast lesion and family history of breast cancer.

Hartmann LC, Sellers TA, Frost MH, et al. Benign breast disease and risk of breast cancer. N Engl J Med. 2005;353:229–237.

Reprints: Dr. L.C. Hartmann, Mayo Clinic College of Medicine, Rochester, MN 55905

 
 

 

 

   
 
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