Extent of Microinvasion in Ductal Carcinoma In Situ is not Associated with Sentinel Lymph Node Metastases

Background

Ductal carcinoma in situ with microinvasion (DCISM) is a rare diagnosis with a good prognosis. Although nodal metastases are uncommon, sentinel lymph node biopsy (SLNB) remains standard care. Volume of disease in invasive breast cancer is associated with SLNB positivity, and, thus we hypothesized that in a large cohort of patients with DCISM, multiple foci of microinvasion might be associated with a higher risk of positive SLNB.

Methods

Records from a prospective institutional database were reviewed to identify patients with DCISM who underwent SLNB between June 1997 and December 2010. Pathology reports were reviewed for number of microinvasive foci and categorized as 1 focus or ≥2 foci. Demographic, pathologic, treatment, and outcome data were obtained and analyzed.

Results

Of 414 patients, 235 (57 %) had 1 focus of microinvasion and 179 (43 %) had ≥2 foci. SLNB macrometastases were found in 1.4 %, and micrometastases were found in 6.3 %; neither were significantly different between patients with 1 focus versus ≥2 foci (p = 1.0). Patients with positive SLNB or ≥2 foci of microinvasion were more likely to receive chemotherapy. At median 4.9 years (range 0–16.2 years) follow-up, 18 patients, all in the SLNB negative group, had recurred for an overall 5-year recurrence-free proportion of 95.9 %.

Conclusions

Even with large numbers, there was no higher risk of nodal involvement with ≥2 foci of microinvasion compared with 1 focus. Number of microinvasive foci and results of SLNB appear to be used in decision making for systemic therapy. Prognosis is excellent.     

Ductal Carcinoma In Situ with Microinvasion

Abstract: The natural history of patients with ductal carcinoma in situ (DCIS) and microinvasion is poorly defined and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Studies addressing this lesion have used highly varied and sometimes arbitrary criteria for the evaluation of microinvasion. At the Armed Forces Institute of Pathology, we have defined microinvasion as a single focus of invasive carcinoma ≤ 2 mm or up to three foci of invasion, each ≤ 1 mm in greatest dimension. Such minuscule invasive carcinomas are apparently rare, accounting for considerably less than 1% of cases of breast carcinoma reviewed in consultation at our institution. To determine the frequency of axillary lymph node metastases associated with this lesion, we retrospectively reviewed 38 cases of DCIS with microinvasion (n= 29) or probable microinvasion (n= 9), all treated with mastectomy and axillary node dissection between 1980 and 1996. The foci of microinvasion ranged from 0.25 to 1.75 mm (mean 0.6 mm) in greatest dimension and were present adjacent to DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of foci of microinvasion. Axillary node dissections yielded a mean of 19.3 lymph nodes (range 7-38) and all lymph nodes were negative for metastatic tumor. None of 33 patients, followed for a mean of 7.5 years (range 1.0-14.4 years), developed local recurrence or metastasis. While the cases of microinvasive carcinoma evaluated in this study were not associated with axillary node metastases and appear to have an excellent prognosis, further study is indicated to determine the appropriate management and long-term prognosis of patients with this lesion.     

Associations Between Sentinel Lymph Node Biopsy and Complications for Patients with Ductal Carcinoma In Situ

Purpose

To examine the associations between sentinel lymph node biopsy (SLNB) and complications among older patients who underwent breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS).

Methods

We identified women from the Surveillance, Epidemiology, and End Results–Medicare dataset aged 67–94 years diagnosed during 1998–2011 with DCIS who underwent BCS as initial treatment. We assessed incidence of complications, including lymphedema, wound infection, seroma, or pain, within 9 months of diagnosis. We used Mahalanobis matching and generalized linear models to estimate the associations between SLNB and complications.

Results

Our sample consisted of 15,515 beneficiaries, 2409 (15.5%) of whom received SLNB. Overall, 16.8% of women who received SLNB had complications, compared with 11.3% of women who did not receive SLNB (p?<?0.001). Use of SLNB was associated with subsequent mastectomy but not radiotherapy. Multivariate analyses of the matched sample showed that, compared with no SLNB, SLNB use was significantly associated with incidence of any complication [adjusted odds ratio (AOR) 1.39; 99% confidence interval (CI) 1.18–1.63], lymphedema (AOR 4.45; 99% CI 2.27–8.75), wound infection (AOR 1.24; 99% CI 1.00–1.54), seroma (AOR 1.40; 99% CI 1.03–1.91), and pain (AOR 1.31; 99% CI 1.04–1.65). Sensitivity analyses excluding patients who underwent mastectomy yielded qualitatively similar results regarding the associations between SLNB and complications.

Conclusions

Among older women with DCIS who received BCS, SLNB use was associated with higher risks of short-term complications. These findings support consensus guidelines recommending against SLNB for this population and provide empirical information for patients.

     

Utilization of Sentinel Lymph Node Biopsy in Patients with Ductal Carcinoma In Situ Undergoing Mastectomy

Background

Current guidelines suggest consideration of sentinel lymph node biopsy (SLNB) for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy. Our objective was to identify factors influencing the utilization of SLNB in this population.

Methods

We used the Surveillance Epidemiology and End Results database to identify all women with breast DCIS treated with mastectomy from 2000 to 2008. We excluded patients without histologic confirmation, those diagnosed at autopsy, those who had axillary lymph node dissections performed without a preceding SLNB, and those for whom the status of SLNB was unknown. We used multivariate logistic regression reporting odds ratios (OR) and 95 % confidence intervals (CI) to evaluate the relationship of patient- and tumor-related factors to the likelihood of undergoing SLNB.

Results

Of 20,177 patients, 51 % did not receive SLNB. Factors associated with a decreased likelihood of receiving a SLNB included advancing age (OR 0.66; 95 % CI 0.62–0.71), Asian (OR 0.75; CI 0.68–0.83) or Hispanic (OR 0.84; 95 % CI 0.74–0.96) race/ethnicity, and history of prior non-breast (OR 0.57; 95 % CI 0.53–0.61). Factors associated with an increased likelihood of receiving a SLNB included treatment in the east (OR 1.28; 95 % CI 1.17–1.4), intermediate (OR 1.25; 95 % CI 1.11–1.41), high (OR 1.84; 95 % CI 1.62–2.08) grade tumors, treatment after the year 2000, and DCIS size 2–5 cm (OR 1.54; 95 % CI 1.42–1.68) and >5 cm (OR 2.43; 95 % CI 2.16–2.75).

Conclusions

SLNB is increasingly utilized in patients undergoing mastectomy for DCIS, but disparities in usage remain. Efforts at improving rates of SLNB in this population are warranted.     

Sentinel Node Biopsy in Ductal Carcinoma In Situ Patients

Background: Sentinel lymph node (SLN) mapping is an effective and accurate method of evaluating the regional lymph nodes in breast cancer patients. The SLN is the first node that receives lymphatic drainage from the primary tumor. Patients with micrometastatic disease, previously undetected by routine hematoxylin and eosin (H&E) stains, are now being detected with the new technology of SLN biopsy, followed by a more detailed examination of the SLN that includes serial sectioning and cytokeratin immunohistochemical (CK IHC) staining of the nodes.Methods: At Moffitt Cancer Center, 87 patients with newly diagnosed pure ductal carcinoma in situ (DCIS) lesions were evaluated by using CK IHC staining of the SLN. Patients with any focus of microinvasive disease, detected on diagnostic breast biopsy by routine H&E, were excluded from this study. DCIS patients, with biopsy-proven in situ tumor by routine H&E stains, underwent intraoperative lymphatic mapping, using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. All SLNs that had only CK-positive cells were subsequently confirmed malignant by a more detailed histological examination of the nodes.Results: CK IHC staining was performed on 177 SLNs in 87 DCIS breast cancer patients. Five of the 87 DCIS patients (6%) had positive SLNs. Three of these patients were only CK positive and two were both H&E and CK positive. Therefore, routine H&E staining missed microinvasive disease in three of five DCIS patients with positive SLNs. In addition, DCIS patients with occult micrometastatic disease to the SLN underwent a complete axillary lymph node dissection, and the SLNs were the only nodes found to have metastatic disease. Of interest, four of the five nodepositive patients had comedo carcinoma associated with the DCIS lesion, and one patient had a large 9.5-cm low grade cribriform and micropapillary type of DCIS.Conclusions: This study confirms that lymphatic mapping in breast cancer patients with DCIS lesions is a technically feasible and a highly accurate method of staging patients with undetected micrometastatic disease to the regional lymphatic basin. This procedure can be performed with minimal morbidity, because only one or two SLNs, which are at highest risk for containing metastatic disease, are removed. This allows the pathologist to examine the one or two lymph nodes with greater detail by using serial sectioning and CK IHC staining of the SLNs. Because most patients with DCIS lesions detected by routine H&E stains do not have regional lymph node metastases, these patients can safely avoid the complications associated with a complete axillary lymph node dissection and systemic chemotherapy. However, DCIS patients with occult micrometastases of the regional lymphatic basin can be staged with higher accuracy and treated in a more selective fashion.Presented at the 52nd Annual Meeting of Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Outcome of Patients with Ductal Carcinoma In Situ and Sentinel Node Biopsy

Background

In sentinel node biopsy (SNB), tumor-positive findings, mainly micrometastases and isolated tumor cells (ITC) have been found in up to 8%?C16% of patients with pure ductal carcinoma in situ (DCIS) or microinvasive DCIS (DCISM). The prognostic significance of such findings is largely unknown. The aim of this study is to examine the outcome of DCIS and DCISM patients with SNB.

Methods

A total of 280 breast cancer patients with pure or microinvasive DCIS underwent SNB between April 2001 and December 2010 at the Breast Surgery Unit of Helsinki University Central Hospital. Patient, tumor, SNB procedure, and follow-up data were gathered. The median follow-up was 50?months (range 7?C123?months).

Results

Altogether, 21 patients had tumor-positive sentinel node findings. Of these, 14 were in pure DCIS patients (1 macrometastasis, 1 micrometastasis, 12 ITC) and 7 in DCISM patients (1 macrometastasis, 2 micrometastases, 4 ITC). Also, 16 patients, 10 with pure DCIS and 6 with DCISM, underwent completion axillary lymph node dissection (ALND). Only 1 of them, a patient with DCISM, had additional tumor positive finding in the ALND. During a median follow-up of 50?months (range 7?C123?months) there were 5 local recurrences. One patient with pure DCIS and tumor-negative SNB developed overt axillary metastases and later also distant metastases.

Conclusions

DCIS and DCISM patients do have tumor positive findings, but a majority of these are ITC or micrometastases. In light of this study, these findings do not affect the outcome of DCIS or DCISM patients.     

Predictors of Treatment with Mastectomy, Use of Sentinel Lymph Node Biopsy and Upstaging to Invasive Cancer in Patients Diagnosed with Breast Ductal Carcinoma In situ (DCIS) on Core Biopsy

Background

There are few established indications for sentinel lymph node biopsy (SLNB) in breast ductal carcinoma in situ (DCIS). This study examines factors contributing to the high rate of SLNB in DCIS in Alberta, Canada.

Methods

Patients who underwent definitive surgery from January 2009 to July 2011 for DCIS diagnosed on preoperative core-needle biopsy were identified using a provincial synoptic operative report database (WebSMR). The relationship between baseline patient and tumor characteristics and treatment with total mastectomy (TM), use of SLNB, and upstaging were examined.

Results

There were 394 patients identified in the study cohort. Mean age was 57 years, and average preoperative tumor size was 3 cm. Overall, 148 patients (37.6 %) underwent TM; predictors were preoperative tumor size [odds ratio (OR), 1.92 per 1-cm increase in size; 95 % CI 1.65–2.24] and surgeon. Upstaging to invasive cancer at surgery occurred in 23 %, predicted only by preoperative tumor size (OR 1.14 per 1 cm; 95 % CI 1.03–1.27). SLNB was performed in 306 patients overall (77 %) and 140 of those treated with BCS (61 %). Predictors of SLNB were larger preoperative tumor size (OR 1.55 per 1 cm; 95 % CI 1.18–2.04) and the surgeon. In patients treated with BCS, 3 patients who were upstaged had positive SLNs (>0.2 mm), and no patients with DCIS had a positive SLN.

Conclusions

SLNB use is high in patients undergoing BCS for DCIS. Tumor size and the operating surgeon predicted SLNB use. Despite a 23 % upstaging rate, the rate of clinically significant positive SLNs in patients treated with BCS is low, supporting omission of upfront SLNB.     

Sentinel Lymph Node Biopsy as a Tool for the Staging of Ductal Carcinoma In Situ in Patients with Breast Carcinoma

Purpose. Ductal carcinoma in situ (DCIS) of the breast is defined as stage 0 disease, but its diagnosis is subject to sampling errors. This study was conducted to assess the usefulness of sentinel lymph node biopsy (SLNB) for furnishing indirect evidence of the invasion of tumors diagnosed as DCIS. Methods. A total of 201 SLNB procedures performed using a peritumoral tracer, being either dye alone or dye plus ^99mTc-labeled colloidal albumin, were reviewed. The cases of DCIS were selected for analysis, and the results were compared with published data. Results. Among ten cases of DCIS studied by SLNB, only one had micrometastatic nodal involvement, which was revealed by cytokeratin immunostaining, and was limited to the sentinel node. This was a large intermediate-grade micropapillary/cribriform-type DCIS. Conclusion. These findings indicate that while SLNB may be a valuable tool for the staging of tumors diagnosed as DCIS, it should not be performed in all cases, but probably restricted to large, high-grade, or comedo-type intraductal carcinomas. Received: February 5, 2001 / Accepted: September 11, 2001     

Sentinel Node Biopsy is Important in Mastectomy for Ductal Carcinoma In Situ

Background There is uncertainty about the utility of sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) and its potential to avoid axillary lymph node dissection (ALND) in patients undergoing mastectomy for DCIS. Methods A review was conducted of 179 patients who underwent mastectomy with sentinel node biopsy for DCIS without invasion or microinvasion on premastectomy pathology review. Results The sentinel node identification rate was 98.9% (177/179). Twenty (11.3%) of 177 mastectomies for DCIS had a positive SNB: two micrometastasis (pN1mi) and 18 isolated tumor cells [pN0(i+)]. Unsuspected invasive cancer was found in 20 (11.2%) of 179 mastectomies, eight T1mic, five T1a, three T1b, and four T1c tumors. Sentinel nodes were identified in 19 of 20 patients with invasive cancer and four were positive: one pN1mi and three pN0(i+). Eighteen of 19 patients with unsuspected invasive cancer were able to avoid axillary dissection on the basis of SNB results. Of the 159 patients whose final pathology revealed DCIS without invasion, a sentinel node was identified in 158 (99.4%). The SNB was positive in 16 patients (10.1%): one pN1mi and 15 pN0(i+). Three patients underwent ALND on the basis of positive SNBs and in each the SNB was the only positive node. Conclusions 11% of patients undergoing mastectomy for DCIS were found to have invasive cancer on final pathology. The use of SNB during mastectomy for DCIS allowed nearly all such patients to avoid axillary dissection. These results support routine use of SNB during mastectomy for DCIS.     

Incidence and Clinical Significance of Lymph Node Metastasis Detected by Cytokeratin Immunohistochemical Staining in Ductal Carcinoma In Situ

Background This study explored the long-term prognosis of patients with ductal carcinoma-in-situ (DCIS) and lymph node metastasis detected by cytokeratin immunohistochemical stains (CK-IHC).Methods Using the Columbia University breast cancer database, we identified all DCIS patients who had eight or more axillary nodes dissected and free of metastasis. Five-micrometer sections from all paraffin blocks containing lymph node tissue were stained with an anticytokeratin antibody cocktail (AE1/AE3 and KL1). The results of the CK-IHC and updated database were anonymized and merged. Survival of CK-IHC–positive and –negative patients was compared by using Kaplan-Meier curves and log-rank tests.Results CK-IHC was performed on 301 DCIS patients, who had an average of 16.7 axillary nodes dissected. Eighteen (6%) of 301 patients tested positive by CK-IHC. Seventy patients with bilateral breast cancer and 2 patients without any follow-up data were excluded, for a final study population of 229 patients. Among the 216 patients with negative CK-IHC, 18 patients died, compared with 1 of 13 patients with positive CK-IHC. The median follow-up for the study group was 127 months. Kaplan-Meier overall and breast cancer–specific survival estimates were similar for CK-IHC–positive and –negative patients (P = .81 and P = .73, respectively).Conclusions CK-IHC increases the incidence of positive nodes by 6% in DCIS patients. A positive node by CK-IHC does not seem to affect survival in these patients. These results raise concerns regarding the clinical significance of positive nodes by CK-IHC in DCIS patients.     

Sentinel Lymph Node Biopsy is Associated with Improved Survival in Merkel Cell Carcinoma

Background

Although sentinel lymph node biopsy (SNB) has become a standard for Merkel cell carcinoma (MCC), the impact on survival is unclear. To better define the staging and therapeutic value of SNB, we compared SNB with nodal observation.

Methods

Patients with clinical stage I and II MCC in the Surveillance, Epidemiology, and End Results (SEER) registry undergoing surgery between 2003 and 2009 were identified and divided into two groups—SNB and observation.

Results

A total of 1,193 patients met the inclusion criteria (SNB 474 and Observation 719). The median age was 78 years, and the majority were White (95.3 %), male (58.8 %), received radiation therapy (52.9 %) and had T1 tumors (65.3 %). Twenty-four percent had a positive SNB. SNB patients were younger (73 vs. 81 years; p < 0.0001), had T1 tumors (69.6 vs. 62.5 %; p = 0.04) and received radiotherapy (57.8 vs. 40 %; p < 0.0001). Among biopsy patients, a negative SNB was associated with improved 5-year MCC-specific survival (84.5 vs. 64.6 %; p < 0.0001). Univariate analysis demonstrated an increased 5-year MCC-specific survival for the SNB group versus the Observation group (79.2 vs. 73.8 %; p = 0.004), female gender (83.2 vs. 70.4 %; p = 0.0004), and lower T stage (p < 0.0001). On Cox regression, diminished survival was noted for the Observation group (risk ratio [RR] 1.43; p = 0.04), male gender (RR 2.06; p < 0.0001), and a higher T stage.

Conclusion

SNB for MCC provides prognostic information and is associated with a significant survival advantage.     

Predictive Factors of Level IIb Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma

Background  The extent of neck dissection (ND) appropriate for necks yielding clinical evidence of metastases of papillary thyroid carcinoma (PTC) is controversial. The need for Ievel IIb lymph node (LN) dissection is particularly uncertain in view of its association with postoperative shoulder dysfunction. In the present study, we examined the frequency, pattern, and predictive factors of level IIb LN metastases in PTC patients with clinically positive lateral neck nodes. Methods  We reviewed the medical records of 76 PTC patients who underwent therapeutic lateral ND for the treatment of clinically positive lateral neck nodes between March 2005 and July 2008. ND specimens were separately obtained for analyzing LN involvement with respect to neck level. Results  Metastatic disease at levels II, III, IV, and V, was seen in 40 (52.6%), 55 (72.4%), 52 (68.4%), and 12 (15.8%) of the patients, respectively. The metastasis rate in level IIb was 11.8% (9 of 76). By univariate analysis, the rate of level IIb LN metastasis was significantly higher in patients with positive level IIa LNs and positive LNs in all lateral neck levels (levels IIa + III + IV) (P < .05). Multivariate analysis showed that positive LN involvement in all lateral neck levels (IIa + III + IV) was an independent predictive factor of level IIb LN metastasis (P = .044, odds ratio = 9.692). Conclusions  Level IIb LN dissection may be omitted in the treatment of positive neck nodes in PTC patients if multilevel involvement including level IIa involvement is absent.     

乳头状甲状腺癌颈淋巴结转移方式及其相关影响因素的研究

目的评估乳头状甲状腺癌（PTC）颈淋巴结的转移方式及相关影响因素在颈部不同区域淋巴结转移中的意义。方法回顾性分析笔者所在医院甲状腺外科2008年12月至2011年12月3年期间行手术治疗的223例PTC患者的临床资料,就患者性别、年龄、术前TSH水平、肿瘤直径、是否为多灶、是否侵及甲状腺被膜及其周围组织、是否合并桥本甲状腺炎、是否合并结节性甲状腺肿以及肿瘤的T分期等因素与颈部不同区域的淋巴结转移之间的关系进行分析。结果单变量分析结果显示,年龄≥45岁及合并结节性甲状腺肿与中央区淋巴结转移有关（P〈0．05）,多发病灶与颈侧区淋巴结转移有关（P〈0．05）;多变量分析结果显示,年龄≥45岁及合并结节性甲状腺肿是中央区淋巴结转移的保护因素（P〈0．05）,多发病灶是颈侧区淋巴结转移的危险因素（P〈0．05）。Ⅱ-Ⅳ区是颈侧区淋巴结转移的常见区域,其中Ⅲ区转移率最高,达100％;当出现跳跃性转移时,Ⅱ-Ⅳ区是转移高发区域。结论对年龄〈45岁的PTC患者应常规进行中央区淋巴结清扫;如果患者同时合并结节性甲状腺肿,中央区淋巴结转移的风险会显著降低;当原发肿瘤为多发病灶时,应加强术中对Ⅱ-Ⅳ区淋巴结的探查,尤其是Ⅲ区淋巴结;当可疑跳跃性转移出现时,Ⅱ-Ⅳ区淋巴结应是常规清扫范围。     

Tumor Size and Depth Predict Rate of Lymph Node Metastasis and Utilization of Lymph Node Sampling in Surgically Managed Gastric Carcinoids

Background  

Radical resection with regional lymphadenectomy is recommended for all sporadic gastric carcinoids. Local resection, however, is accepted for some carcinoids from other gastrointestinal sites (i.e., appendix and rectum). We sought to examine the relation of tumor size and depth to lymph node metastasis to determine whether gastric carcinoids can be selected for endoscopic resection. We also sought to quantify the utilization of lymph node sampling.     

High Expression of Angiopoietin-1 is Associated with Lymph Node Metastasis and Invasiveness of Papillary Thyroid Carcinoma

Background

We investigated the expression of angiopoietins in patients with papillary thyroid carcinoma (PTC) and the role of angiopoietins as biomarkers predicting the aggressiveness of PTC.

Methods

Expression of angiopoietins was evaluated by immunohistochemistry of tumor specimens from patients with PTC. We demonstrated potential correlations between expression of angiopoietins and clinicopathologic features.

Results

High expression of Ang-1 was positively correlated with a tumor size >1 cm, capsular invasion, extrathyroid extension, lymphovascular invasion, lymph node metastasis, and recurrence (P < 0.05). Moreover, multivariate analysis revealed that high expression of Ang-1 was an independent risk factor for lymph node metastasis (P < 0.001, odds ratio [OR] = 62.113) and lymphovascular invasion (P = 0.027, OR 4.405). However, there was no significant correlation between Ang-2 and clinicopathologic features.

Conclusions

Our results suggest that Ang-1 can serve as a valuable prognostic biomarker for lymph node metastasis and invasiveness in patients with PTC.

     

Ductal Carcinoma In Situ Arising in a Benign Phyllodes Tumor: Report of a Case

Malignant epithelial change within a phyllodes tumor (PT) is a rare event. To our knowledge, only six cases of ductal carcinoma in situ arising in a PT have been reported in English. We report a case of PT with an intraductal carcinoma component, which grew rapidly to a huge size in 3 months. Histologically, the stromal element showed mild to moderate cellularity with few mitoses and mild nuclear atypia. The epithelial element consisted of irregularly dilated ducts with a phyllodes structure that had moderate to severe epithelial hyperplasia, and foci of cribriform ductal carcinoma in situ with comedo necrosis.     

Mammographic Localization Biopsy for Ductal Carcinoma In Situ: A Simple Mapping Technique for Sampling and Size Estimation

Size, grade, margin status, and microscopic invasion are currently significant parameters for management of ductal carcinoma in situ (DCIS). Size estimation of DCIS is difficult or impossible if tissue is sampled haphazardly. Histologic examination of the entire biopsy to exclude microscopic invasion is cumbersome and expensive, and may not yield more information than less extensive but planned sampling. One hundred twenty-four mammographic localization biopsies with DCIS including 4 cases with 3 mm or less invasion are presented to address these issues. All were examined by a mapping technique utilizing specimen radiograph as a guide for sampling and a schematic drawing to record the sections. This involved sequential sampling of the entire tissue for smaller biopsies, and en bloc sampling of the mammographic abnormality and surrounding tissue with end-to-end sampling of the remaining tissue at regular intervals for larger biopsies. All tissue was examined histologically initially in 55 cases, while tissue away from the lesion was selectively omitted in 71 cases. To address the issue of occult invasion, all initially unsampled tissue of 44 biopsies was submitted for histologic examination after completion of the case and the findings were recorded separately. Size estimates ranged from 4 to 70 mm. The solitary focus of microscopic invasion in four cases was present in the initial sections at the site corresponding to the mammographic abnormality. No invasion was identified in the additional tissue in any of the 44 cases. Margin status did not change for any. Using specimen radiographs as a guide, all the necessary information for DCIS, including the size and microscopic invasion, can be obtained by a planned sampling of tissue with diagrammatic documentation. Sequential sections of the entire tissue for small biopsies and sampling at regular intervals to include tissue at and around the mammographic abnormality for larger biopsies is appropriate. Microscopic invasion, when focal, is likely to be identified at the site of mammographic abnormality in the initial en bloc sections.     

CpG Island Methylator Phenotype Associated with Tumor Recurrence in Tumor–Node–Metastasis Stage I Hepatocellular Carcinoma

Background  

CpG island methylator phenotype (CIMP), characterized by simultaneous methylation of multiple tumor suppressor genes (TSGs), has been reported to be associated with biological malignancy in many cancers. Whether CIMP is potentially predictive of clinical outcome in hepatocellular carcinoma (HCC) remains unknown.