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Gastrointestinal lymphomas can be difficult to diagnose, particularly in small samples, when early in development, or when of unusual types. In this review, we describe lymphoid proliferations in the gastrointestinal tract in a location-based manner, including, mouth, esophagus, stomach, small intestine, and large bowel. For the purpose of differential diagnosis, benign mimics of lymphoma are also described. Lymphoma types that are specifically addressed include plasmablastic, extranodal natural killer/T-cell-nasal type, extranodal marginal zone lymphoma (eg, mucosa-associated lymphoid tissue lymphoma), diffuse large B cell, primary follicular of small intestine, enteropathy-associated T cell, and Burkitt and mantle cell. Immunohistochemical markers useful in the diagnostic approach are elaborated in detail., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We reviewed our institution's long-term experience treating patients diagnosed with ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine the impact of patient age on outcome over time. All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics (including age <45) and pathologic factors were analyzed for effect on outcomes including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included limited surgery (excisional biopsy or lumpectomy) followed by radiotherapy to the whole breast (median whole-breast dose: 50 Gy, median tumor bed dose: 60.4 Gy). One hundred and forty-five cases were evaluated; the median follow-up was 19.3 years. Twenty-five patients developed an IBTR, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. The 10-year ipsilateral rate of recurrence was 23.3% (<45 years) versus 9.1% (≥ 45 years) (p = 0.05). Younger patients more frequently developed invasive recurrences (20-year actuarial rates: 20.4% versus 12.8%, p = 0.22) and true recurrences/marginal misses of the index lesion (23.3% versus 9.7%, p = 0.04) with lower rates of contralateral breast cancer (0.0% and 0.0% versus 12.0% and 20.5%, p = < 0.01, at 10 and 20 years, respectively). Young women under the age of 45 diagnosed with DCIS have a greater risk of local recurrence with different patterns of failure following BCT, which is most notable within 10 years of diagnosis., (© 2013 Wiley Periodicals, Inc.)

Background: Management of mammographically detected ductal carcinoma in situ (DCIS) at a single institution was reviewed to determine long-term clinical outcomes after treatment with breast-conserving therapy (BCT)., Methods: Data from all patient-cases with DCIS who received BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for their effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included breast-conserving surgery followed by external-beam radiotherapy to the whole breast, with 86 % of patients receiving a lumpectomy cavity boost. The median dose to the whole breast was 50 Gy and 60.4 Gy to the lumpectomy cavity., Results: A total of 129 cases were evaluated; the median follow-up was 19.3 years. Twenty-one patients developed an ipsilateral breast tumor recurrence (IBTR), 76.2 % of which were invasive (n = 16). Fourteen recurrences (66 %) were within the same breast quadrant (true recurrence), while an additional 7 cases developed an IBTR elsewhere in the breast. True recurrences were more prevalent in women <45 years of age (20 %/24 % vs. 5.1 %/8 %) at 10 and 20 years (p = 0.02). The 5-, 10-, 15-, and 20-year actuarial rates of IBTR for this cohort were 8.7, 10.4, 12.1, and 16.3 % (IBTR), while overall survival at 5, 10, and 20 years was 97.6, 96.8, and 96.8 %, respectively., Conclusions: Mammographically detected DCIS remains a clinically distinct subset of noninvasive breast cancer. With 20 year follow-up, local control and overall survival are excellent after BCT.

Purpose: To determine 20-year rates of local control and outcome-associated factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy (BCT)., Methods and Materials: All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival., Results: One hundred forty-five cases were evaluated; the median follow-up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after diagnosis. Young age and cancerization of lobules predicted for IBTR at <10 years, and increased slide involvement and atypical ductal hyperplasia were associated with IBTR at later time points., Conclusions: Patients with DCIS treated with BCT have excellent long-term rates of local control. Predictors of IBTR vary over time, and the risk of recurrence seems highest within 10 to 12 years after diagnosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: It is generally believed that ipsilateral breast failures (IBFs) after breast-conserving therapy (BCT) develop from incompletely eradicated carcinoma. We previously suggested that monomorphic epithelial proliferations (MEPs) in the breast may be a pool of partially transformed clones from which breast carcinomas can arise and that radiation therapy (RT) may also reduce the risk of IBF by eradicating MEPs. We examined salvage mastectomy specimens in patients experiencing an IBF to define the relationship between MEPs and IBFs and an additional potential mechanism for IBF risk reduction by RT., Methods and Materials: The location, number, and distribution of radiation changes and MEPs relative to 51 IBFs were mapped in salvage mastectomy specimens from BCT patients with adequately excised, initial carcinomas (negative lumpectomy margins)., Results: All 51 salvage mastectomies had diffuse, late radiation changes. None had active fibrocystic lesions. MEPs were predominantly located in the immediate vicinity of the IBFs. A mean of 39% of MEP cases were located within the IBF, 46% were located within 2 cm of the IBF, and 14% were 2-3 cm from the IBF., Conclusions: MEPs appear to be a pool of partially transformed precursor lesions that can give rise to ductal carcinoma in situ and invasive carcinomas (CAs). Many IBFs may arise from MEPs that reemerge after RT. Radiation may also reduce IBF risk after BCT (including in patients with negative margins) by primarily eradicating MEPs., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Involvement of the upper gastrointestinal tract by inflammatory bowel disease was long held to be a feature of Crohn's disease, whereas ulcerative colitis was considered to be limited to the colon. It is now recognized that ulcerative colitis associated inflammation can involve the upper gastrointestinal tract, primarily the stomach. In addition to aphthoid esophageal ulcers in Crohn's disease, eosinophilic esophagitis and so-called lymphocytic esophagitis occur in association with ulcerative colitis and Crohn's disease. Possible immune mechanisms behind these conditions are presented. The differential diagnosis of inflammation in each site is discussed., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers., Methods: The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance., Results: Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria., Recommendations: The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

Purpose: The goal of the current study is to help refine guidelines for the need for re-excision and the appropriate amount of breast tissue to re-excise in patients with early breast cancer following excisional breast biopsy when treated with breast-conserving therapy (BCT)., Patients and Methods: The study population consisted of 441 patients derived from a dataset of 607 consecutive cases of stage I and II breast cancer treated with BCT, in which patients underwent primary excisional diagnostic biopsy and subsequent re-excision prior to the initiation of radiation therapy (RT). A single pathologist reviewed all specimens. Re-excision was indicated because tumor was found close to or involving the resection margin. In 333 of the 441 cases, it was possible to measure the extension of carcinoma into the re-excision specimen. Margins were classified as negative (carcinoma>4.2 mm from the margin), near (<4.2 mm from the margin) or positive. Any carcinoma identified near the final margin was quantified by width of invasive carcinoma and number of ductal carcinoma in situ (DCIS) ducts near the margin and subdivided into three distinct groups: least, intermediate, and greatest amount. These factors were then analyzed to determine the likelihood and extent of residual carcinoma in re-excision specimens. Statistical analysis was performed using Systat version 10 (SPSS Inc., Chicago, IL)., Results: The quantity of carcinoma near the initial biopsy margin and the invasive carcinoma-to-specimen dimension ratio demonstrated a significant association with increasing amounts of residual carcinoma at re-excision. Combination of these two variables allowed for a statistically significant (P<0.001) calculation of risk index for identifying significant residual invasive carcinoma or DCIS in the adjacent breast parenchyma at re-excision, and yielded stratification into low- (6%), intermediate- (27%), and high-risk (44%) groups. In re-excision specimens, the observed distance of carcinoma extension into adjacent breast tissue was associated with a statistically significant decrease in the ratio of the initial excisional biopsy specimen dimensions and invasive carcinoma dimensions. Combining the initial margin status with the specimen-to-invasive carcinoma maximum dimension ratio yielded an accurate predictor of the maximum distance of tumor extension., Conclusions: Evaluation of the initial excisional biopsy margin status in correlation with the invasive carcinoma-to-specimen maximum dimension ratio may be helpful for (1) identifying patients who require re-excision prior to RT and (2) predicting the quantity of additional breast tissue to excise to ensure adequate surgical margins with BCT.

Purpose: To examine 10-year results of a single institution's experience with radiotherapy limited to the region of the tumor bed (i.e., accelerated partial breast irradiation, [APBI]) in selected patients treated with breast-conserving therapy (BCT) and compare them with results of matched BCT patients who underwent whole-breast irradiation (WBI)., Patients and Methods: A total of 199 patients with early-stage breast cancer were treated prospectively with BCT and APBI using interstitial brachytherapy. To compare potential differences in local recurrence rates on the basis of the volume of breast tissue irradiated, patients in the APBI group were matched with 199 patients treated with WBI. Match criteria included tumor size, nodal status, age at diagnosis, margins of excision, estrogen receptor status, and use of adjuvant tamoxifen therapy. Local-regional control, disease-free survival, and overall survival were analyzed between treatment groups., Results: Median follow-up for surviving patients was 9.6 years (range, 0.3-13.6 years). Eight ipsilateral breast tumor recurrences (IBTRs) were observed in patients treated with APBI. The cumulative incidence of IBTR at 10 years was 5%. On matched-pair analysis, the rate of IBTR was not statistically significantly different between the patient groups (4%, 95% confidence interval [CI] 1.3-6.7% for WBI therapy patients vs. 5%, 95% CI 1.5-8.5% for APBI patients; p = 0.48)., Conclusions: Radiation therapy limited to the region of the tumor bed (APBI) produced 10-year local control rates comparable to those from WBI in selected low-risk patients.

Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomarker that determines breast cancer prognosis after treatment with endocrine therapy. Although immunohistochemistry has been widely viewed as the gold standard methodology for ER testing in breast cancer, lack of standardized procedures, and lack of regulatory adherence to testing guidelines has resulted in high rates of "false-negative" results worldwide. Standardized testing is only possible after all aspects of ER testing--preanalytical, analytical, and postanalytical, have been closely controlled. A meeting of the "ad-hoc committee" of expert pathologists, technologists, and scientists, representing academic centers, reference laboratories, and various agencies, issued standardization testing recommendations, aimed at optimization of clinical ER testing environment, as a step toward improved standardized testing.

Purpose: To examine the clonality relationships among initial invasive breast carcinoma (IBC), ipsilateral breast failure (IBF), and distant metastasis (DM) to determine the effect of local tumor recurrence on the development of DMs., Methods and Materials: A total of 18 patients treated with breast-conserving therapy who developed an IBF followed by DMs were studied using a 20 informative-marker, polymerase chain reaction-based allelic imbalance clonality assay., Results: Four relationships were identified. First, in 7 cases, the IBF and DMs were clonally related to the initial IBC as one progressively genetic unstable process. Second, in 3 cases, the IBF and DMs were each clonally related to the IBC but clonally distinct from each other. Third, in 3 cases, the IBC and the IBF were clonally related and the DMs were clonally related to the IBFs, with a weak relationship to the initial IBC. Finally, in 5 cases, the IBF was clonally distinct from the initial IBC (new second primary) and the DMs were clonally related to the IBF and clonally distinct from the initial IBC., Conclusion: These findings provide molecular evidence demonstrating that some DMs can directly develop from IBFs and support the importance of local tumor control in the overall treatment of breast cancer patients.

We studied whether precursor lesions (monomorphic epithelial proliferations [MEPs]) contributed to ipsilateral breast failures (IBFs; local recurrences). Margin status and MEPs near (within 4.2 mm) of the initial excision margin in 70 carcinoma patients with IBFs and allelic imbalance clonality data were recorded. Of the IBFs, 46 (66%) were clonal and 24 (34%) were second primary carcinomas. Control cases were 2 matching non-IBF cases for each study case. MEP lesions were predominantly single-cell layered, slightly overcrowded, monomorphic, clonallike luminal cell proliferations that unfolded terminal duct lobular units (TDLUs) in an overgrowth extension pattern. MEPs often extended into TDLUs involved by hyperplasia of usual type. Clonal IBF cases had a mean of 6.24 MEPs near the initial excision margin compared with 3.85 MEPs in matched non-IBF control mples (P < .001). In the negative-margin subset, clonal IBF cases had mean of 7.82 MEPs near the margin, which was significantly greater than 4.26 in the distinct IBF group (P = .012) and 2.85 in the non-IBF matched control group (P < .001). MEPs seem to be the pool of partially transformed precursor lesions for most invasive carcinomas. Radiation therapy may reduce the IBF rate by eradicating these precursor lesions and preventing new carcinomas from emerging rather than eradicating microscopic residual disease.

Purpose: We present our ongoing clinical experience utilizing three-dimensional (3D)-conformal radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer treated with breast-conserving therapy., Methods and Materials: Ninety-one consecutive patients were treated with APBI using our previously reported 3D-CRT technique. The clinical target volume consisted of the lumpectomy cavity plus a 10- to 15 -mm margin. The prescribed dose was 34 or 38.5 Gy in 10 fractions given over 5 consecutive days. The median follow-up was 24 months. Twelve patients have been followed for > or =4 years, 20 for > or =3.5 years, 29 for >3.0 years, 33 for > or =2.5 years, and 46 for > or =2.0 years., Results: No local recurrences developed. Cosmetic results were rated as good/excellent in 100% of evaluable patients at > or = 6 months (n = 47), 93% at 1 year (n = 43), 91% at 2 years (n = 21), and in 90% at > or =3 years (n = 10). Erythema, hyperpigmentation, breast edema, breast pain, telangiectasias, fibrosis, and fat necrosis were evaluated at 6, 24, and 36 months after treatment. All factors stabilized by 3 years posttreatment with grade I or II rates of 0%, 0%, 0%, 0%, 9%, 18%, and 9%, respectively. Only 2 patients (3%) developed grade III toxicity (breast pain), which resolved with time., Conclusions: Delivery of APBI with 3D-CRT resulted in minimal chronic (> or =6 months) toxicity to date with good/excellent cosmetic results. Additional follow-up is needed to assess the long-term efficacy of this form of APBI.

Background: The molecular classification system categorizes invasive breast carcinomas according to their key driving biomarkers. In the current study, the authors evaluated whether response to neoadjuvant chemotherapy was correlated with the molecular classification groups., Methods: Using immunohistochemistry, the molecular classification group (luminal-A, luminal-B, HER-2-variant, HER-2-classic, and basal phenotype) was retrospectively determined in 68 breast cancer patients who received neoadjuvant treatment., Results: A total of 28 carcinoma patients (41.2%) achieved a compete pathologic response (CPR), including 2 of 15 patients classified as having luminal-A (13.3%), 4 of 16 patients classified as having luminal-B (25.0%), 10 of 12 patients classified as having HER-2-classic (83.3%), none of the 4 patients classified as having HER-2-variant, and 12 of 21 patients classified as having basal phenotype (57.1%) neoplasms. The CPR rate among patients with the HER-2-classic and basal neoplasms was 67% (22 of 33 neoplasms), compared with 17.1% (6 of 35 neoplasms) in the non-HER-2-classic/basal combined group (P < .001). Eleven carcinomas were initially diagnosed as invasive lobular carcinomas (pleomorphic and classic), 4 of which were luminal-A, 4 of which were luminal-B, 2 of which were HER-2-classic, and 1 of which was basal. On review, only 3 of these 11 cases remained classified as classic lobular carcinoma, all of which were classified as luminal-A, and none of these patients achieved a CPR. Four of the other 8 patients achieved a CPR., Conclusions: The molecular classification system is useful for identifying carcinoma patients who are most likely and those who are least likely to achieve a CPR. In the current study, all the morphologically classic lobular carcinomas were classified as luminal-A neoplasms, which may explain the low rate of CPR reported.

Purpose: To determine the gross tumor volume (GTV) to clinical target volume margin for non-small-cell lung cancer treatment planning., Methods: A total of 35 patients with Stage T1N0 adenocarcinoma underwent wedge resection plus immediate lobectomy. The gross tumor size and microscopic extension distance beyond the gross tumor were measured. The nuclear grade and percentage of bronchoalveolar features were analyzed for association with microscopic extension. The gross tumor dimensions were measured on a computed tomography (CT) scan (lung and mediastinal windows) and compared with the pathologic dimensions. The potential coverage of microscopic extension for two different lung stereotactic radiotherapy regimens was evaluated., Results: The mean microscopic extension distance beyond the gross tumor was 7.2 mm and varied according to grade (10.1, 7.0, and 3.5 mm for Grade 1 to 3, respectively, p < 0.01). The 90th percentile for microscopic extension was 12.0 mm (13.0, 9.7, and 4.4 mm for Grade 1 to 3, respectively). The CT lung windows correlated better with the pathologic size than did the mediastinal windows (gross pathologic size overestimated by a mean of 5.8 mm; composite size [gross plus microscopic extension] underestimated by a mean of 1.2 mm). For a GTV contoured on the CT lung windows, the margin required to cover microscopic extension for 90% of the cases would be 9 mm (9, 7, and 4 mm for Grade 1 to 3, respectively). The potential microscopic extension dosimetric coverage (55 Gy) varied substantially between the stereotactic radiotherapy schedules., Conclusion: For lung adenocarcinomas, the GTV should be contoured using CT lung windows. Although a GTV based on the CT lung windows would underestimate the gross tumor size plus microscopic extension by only 1.2 mm for the average case, the clinical target volume expansion required to cover the microscopic extension in 90% of cases could be as large as 9 mm, although considerably smaller for high-grade tumors. Fractionation significantly affects the dosimetric coverage of microscopic extension.

Purpose: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience., Methods and Materials: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for >or=10 years., Results: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients., Conclusions: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.

Immunohistochemistry (IHC) continues to suffer from variable consistency, poor reproducibility, quality assurance disparities, and the lack of standardization resulting in poor concordance, validation, and verification. This document lists the recommendations made by the Ad-Hoc Committee on Immunohistochemistry Standardization to address these deficiencies. Contributing factors were established to be underfixation and irregular fixation, use of nonformalin fixatives and ancillary fixation procedures divested from a deep and full understanding of the IHC assay parameters, minimal or absent IHC assay optimization and validation procedures, and lack of a standard system of interpretation and reporting. Definitions and detailed guidelines pertaining to these areas are provided.

We noticed that the percentage and intensity of estrogen receptor (ER) antibody (Ab) AB ER 1D5 immunohistochemical (IHC) staining was altered by Ab incubation time and the type of chromogen detection system in invasive breast carcinomas. We studied the impact of these 2 factors on Ab ER 1D5 immunoreactivity. Serial sections from 22 strongly ER-positive invasive breast carcinomas were immunohistochemically stained with Ab clone ER 1D5 using 3 IHC protocols. One IHC protocol used a 12-hour Ab incubation and a supersensitive, labeled streptavidin-biotin chromogen detection system (12 h-Standard), the second IHC protocol used a 2-hour Ab incubation and a supersensitive, labeled streptavidin-biotin chromogen detection system (2 h-SS), and the third protocol used a 2-hour Ab incubation and a polymer-based detection system (2 h-Env). Twenty identical fields on each slide stained with each IHC protocol were evaluated and staining was quantified using image analysis. The mean staining percentages using the 12 h-Standard, 2 h-SS, and 2 h-Env IHC staining protocols were 89%, 72%, and 47%, respectively (P<0.001). Three of the 22 cases (14%) were ER negative (<10% stained area) with the 2 h-Env IHC protocol. Stain intensity was significantly stronger with the 12 h-Standard Ab incubation IHC protocol than either 2-hour Ab incubation protocol (P<0.001). Twelve cases stained with 2-hour Ab incubation IHC protocols had weak visually seen staining: 7 were Allred total score 2 (ER negative) and 5 were Allred total score 3. Ab ER 1D5 avidity is directly related to factors that impact electrostatic forces, one of which is Ab incubation time. Standard automated stainer Ab incubation times of less than 1 hour may be of insufficient duration and result in artificially low levels of ER immunoreactivity. The chromogen detection system in association with the ER 1D5 Ab also alters levels of immunoreactivity. Optimization of IHC staining protocols should include evaluating the Ab incubation time and chromogen detection system. These factors can substantially alter the extent and intensity of ER IHC staining.

Interpreting immunohistochemical stains of metastatic adenocarcinoma in small needle core biopsy specimens is not always straightforward. We studied the effects of small specimen size on immunohistochemical stain results in 20 colorectal adenocarcinoma hepatic resection specimens stained with cytokeratin (CK)7 and CK20. We superimposed 18- and 20-gauge needle core biopsy computer images. The results in needle core biopsy specimens correlated best with resection specimen results when immunoreactivity was assessed using the 3 images with the highest percentage of immunoreactive cells. CK7- and CK20+ needle core biopsy specimens correlated best when a higher percentage cut point was used. Immunohistochemical stains in small needle core biopsy specimens should be based on the regional area with the greatest immunoreactivity. The positive result cut point should increase as the amount of stainable carcinoma available for interpretation decreases.

Purpose: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients., Methods and Materials: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years., Results: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p=0.04). On multivariate analysis, positive margin (p<0.01), positive/no reexcision (p=0.04), and presence of LCIS (p=0.02) remained independently associated with IBTR; positive margin (p<0.01) and LCIS (p=0.04) were also associated with TR/MM failure. When examining only cases with negative final margins, the presence of LCIS remained associated with higher IBTR and TR/MM rates (p<0.01)., Conclusion: The presence of LCIS was independently associated with higher rate of IBTR and TR/MM after BCT for invasive breast cancer. LCIS may have significant premalignant potential and progress to an invasive IBTR at the site of index lesion. The adequacy of excision of LCIS associated with invasive carcinoma should be considered in patients undergoing BCT.

Purpose: We performed a complete pathologic analysis examining extracapsular extension (ECE) and microscopic spread of malignant cells beyond the prostate capsule to determine whether and when clinical target volume (CTV) expansion should be performed., Methods and Materials: A detailed pathologic analysis was performed for 371 prostatectomy specimens. All slides from each case were reviewed by a single pathologist (N.S.G.). The ECE status and ECE distance, defined as the maximal linear radial distance of malignant cells beyond the capsule, were recorded., Results: A total of 121 patients (33%) were found to have ECE (68 unilateral, 53 bilateral). Median ECE distance=2.4 mm [range: 0.05-7.0 mm]. The 90th-percentile distance = 5.0 mm. Of the 121 cases with ECE, 55% had ECE distance>or=2 mm, 19%>or=4 mm, and 6%>or=6 mm. ECE occurred primarily posterolaterally along the neurovascular bundle in all cases. Pretreatment prostrate-specific antigen (PSA), biopsy Gleason, pathologic Gleason, clinical stage, bilateral involvement, positive margins, percentage of gland involved, and maximal tumor dimension were associated with presence of ECE. Both PSA and Gleason score were associated with ECE distance. In all 371 patients, for those with either pretreatment PSA>or=10 or biopsy Gleason score>or=7, 21% had ECE>or=2 mm and 5%>or=4 mm beyond the capsule. For patients with both of these risk factors, 49% had ECE>or=2 mm and 21%>or=4 mm., Conclusions: For prostate cancer with ECE, the median linear distance of ECE was 2.4 mm and occurred primarily posterolaterally. Although only 5% of patients demonstrate ECE>4 to 5 mm beyond the capsule, this risk may exceed 20% in patients with PSA>or=10 ng/ml and biopsy Gleason score>or=7. As imaging techniques improve for prostate capsule delineation and as radiotherapy delivery techniques increase in accuracy, a posterolateral CTV expansion should be considered for patients at high risk.

This study evaluated 28 patients to characterize the morphologic features associated with typical Crohn disease (CD). All patients had similar complaints, an endoscopically normal colon, and small isolated, aphthoid erosions in the terminal ileum. The mean length of follow-up was 5.8 years. Of 28 patients, 25 (89%) were female (mean age, 32.3 years). Four patients were ingesting nonsteroidal anti-inflammatory drugs. All 28 lesions were morphologically similar, with focal lamina propria edema, mild active inflammation, and crypt disarray. Most had a lymphoid aggregate within the region of edema. Erosion was identified histologically in 21 cases. Following colonoscopy, symptoms resolved in all 28 patients. Typical, full-blown CD developed in 8 patients (29%) after a mean interval of 3.6 years. CD lesions were morphologically identical to non-CD lesions. Most focal ileal erosions in patients with mildly altered bowel habits are idiopathic and clinically insignificant. They represent early CD in approximately 30% of patients. The interval between initial examination and typical CD can be long. Pathologists should remain diagnostically vigilant when examining ileal biopsy specimens obtained from patients with previous abnormal ileal biopsy findings, regardless of the interval. Persistent, mild morphologic abnormalities have a high likelihood of being CD.

Sarcomatoid carcinomas of the prostate are rare malignancies composed of carcinomatous and sarcomatous elements. Their etiology is uncertain and may represent a single malignant process or a mixture of two distinct malignancies. We report a clinical case of a patient who presented with locally advanced disease and was treated with hormonal and cytotoxic chemotherapy, but ultimately developed distant metastasis and died of the disease. A loss-of-heterozygosity analysis of the primary and metastatic tissues provided compelling evidence that the carcinomatous and sarcomatous elements are clonally related, supporting the hypothesis that a single malignant process underlies the etiology of sarcomatoid carcinoma of the prostate.

Eight sessile serrated adenoma (SSA), right colon polypectomies with focal invasive adenocarcinoma or high-grade dysplasia were studied to identify features indicating a high risk of transformation and characterize the morphologic features of serrated dysplasia; 6 cases had invasive adenocarcinoma; 2 were high-grade dysplasia. All 8 were microsatellite unstable-high and had absent hMLH1 nuclear immunoreactivity. The mean patient age at polypectomy was 69.5 years (range, 57.1-83.9 years). Mean polyp maximum dimension was 8.5 mm (range, 6-12 mm). The majority of each polyp was nonmalignant SSA. All 8 cases had an abrupt transition from benign to high-grade in situ or invasive malignancy. In the 6 invasive adenocarcinomas, the neoplasm extended directly down into the submucosa without lateral intramucosal spread. The mean maximum dimension of the invasive adenocarcinoma was 2.9 mm (range, 2-4 mm). All 8 cases had high-grade serrated-type dysplasia. The nonmalignant SSAs had marked expansion of the proliferative zone. Crypts adjacent to malignancy had moderately enlarged nuclei, irregular nuclear membranes, and overly prominent nucleoli. SSA crypts were lined by a variety of gastric-type cells; no cell type predominated. Foci of adjacent crypts had similar cytologic features. Small proximal SSAs can transform into adenocarcinoma without a component of adenomatous dysplasia.

This review addresses the genetic mutations and cell signaling pathway alterations in colorectal premalignant polyps, focusing on the link between molecular changes and morphologic features. Biallelic APC (adenomatous polyposis coli) mutations are directly responsible for the specific and characteristic cytologic features of dysplastic cells in conventional tubular adenomas. Sessile serrated adenomas (SSAs) are the precursor lesions of the serrated neoplasia pathway. The BRAF activating mutation and hypermethylation of SLC5A8, which mediates short chain fatty acid transport, may be the important events in the genesis of SSAs. Intracellular butyrate inhibits histone deacetylase, allowing histone hyperacetylation and, eventually, transcriptional activation of specific genes. Decreased p21(WAF1/CIP1) and activation of the mitogen-activated protein kinase pathway may be the key intermediary alterations. Progressive loss of cell cycle control and decreased and altered cytoplasmic differentiation produce the characteristic constellation of morphologic changes of SSAs and traditional serrated adenomas.

We studied the clonality relationships in invasive breast carcinomas, ipsilateral breast failures (IBFs), and distant metastases (DMs) using a polymerase chain reaction-loss of heterozygosity (LOH) clonality assay to determine whether IBFs can be the source of DMs. Six cases of initial carcinomas, IBFs, and DMs were identified. Carcinoma DNA was extracted from paraffin blocks and analyzed with 20 markers. In 2 cases, the LOH pattern suggested the DM directly resulted from the IBF. In 2 cases, the initial carcinoma, IBF, and DM were one progressive, genetically unstable process. Separate subclones in the initial carcinoma gave rise to the IBF and DM in 1 case, and the DM derived from a second IBF in 1 case. The relationships of initial carcinomas, IBFs, and DMs are complex. DMs seem to be the direct result of IBFs in some cases. Some carcinomas seem to be composed of subclones with different and unrelated IBF and DM potential.

Introduction: Esophageal food impaction is a common presentation of eosinophilic esophagitis. The prevalence of eosinophilic esophagitis among patients with food impaction is unknown. To address this, we evaluated clinicopathologic features of adults with food impaction., Methods: For a 3-year period, patients from a single, adult, community-based gastroenterology practice with esophageal food impaction were evaluated. Histories were assessed and esophageal biopsy specimens were evaluated by routine and immunohistochemical techniques., Results: Thirty-one patients with food impaction were evaluated. Seventeen of 31 patients had >20 eosinophils/high power field (HPF) without gender predilection. Thirteen of these 17 patients had been treated with proton pump inhibitors at the time biopsy specimens were obtained. Patients with >20 eosinophils/HPF were significantly younger (mean age 42 +/- 4 years) than patients with <20 eosinophils/HPF (mean age 70 + 3 years). Superficial white exudates and eosinophilic microabscesses in the squamous epithelium were features observed only in patients with >20 eosinophils/HPF. Immunopathologic analysis demonstrated increased CD8 lymphocytes and major basic protein deposition in their squamous epithelium., Conclusions: More than half of patients with esophageal food impaction in a primary gastroenterology practice have >20 eosinophils/HPF. Based on clinicopathologic features, a significant number likely have eosinophilic esophagitis.

We established clonality relationships between invasive ipsilateral breast failures (IBFs; local recurrences) and initial invasive carcinomas using a molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26 patients treated with breast-conserving therapy for invasive carcinoma with no distant metastases (DMs) before the IBE LOH was +/- 50% allelic loss. Eighteen IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally distinct, second primary carcinomas. IBFs and initial invasive carcinomas were morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF classification and molecular assay results differed in 11 cases (42%). The mean intervals to IBF were 4.7 years in related and 8.7 years in different cases (P = .013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases, the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs was 18.9% compared with 7.6% in cases unassociated with DMs (P = .004). Molecular assays can accurately establish the clonality of most IBFs. Morphologic comparison and clinical IBF classification are unreliable methods of determining clonality. Clonally related IBFs occurred sooner than clonally different IBFs. Patients with clonally related IBFs are the main pool in which DMs occur Not all clonally related IBFs have the same DM association; those with large FAL gains were associated with DMs. Molecular clonality assays may provide a reliable means of identifying patients who might benefit from systemic chemotherapy at the time of IBF.

We examined 46 nonalcoholic steatohepatitis (NASH) and 52 hepatitis C virus (HCV) biopsy specimens to determine the magnitude of fibrosis heterogeneity and minimum length for accurate fibrosis staging. Three fibrosis scores were recorded: lowest regional, highest regional, and most common overall. Mean specimen lengths were 1.6 and 1.8 cm in NASH and HCV, respectively (P = .283). Mean (highest minus lowest) fibrosis heterogeneity scores (highest regional fibrosis - lowest regional fibrosis) were 3.7 and 2.0 in NASH and HCV, respectively (P < .001). Of 36 NASH specimens longer than 1.0 cm, 31 (86%) had the highest regional fibrosis in the deepest sampled parenchyma. Shorter specimens were associated significantly with greater fibrosis heterogeneity in NASH (coefficient, -1.3; P < .001) but not in HCV (P = .901). NASH specimens longer than 1.6 cm had significantly lower mean heterogeneity scores than specimens 1.6 cm or shorter (1.2 vs 3.4; P = .012). In NASH, fibrosis heterogeneity can be substantial and is greater than in HCV, and parenchymal injury, fibrosis, and healing might vary in different regions of the liver. The fibrosis stage in patients with NASH might not be assessed accurately in short specimens. Individual needle cores should be longer than 1.6 cm in NASH for accurate fibrosis staging.

We studied outcomes of 147 patients with stage I/II grade 1 (32 pure tubular, 115 ductal) carcinoma treated with breast-conserving therapy to evaluate the prognostic usefulness of standard and recently proposed revised criteria for tubular (tubularity percentage [proportion of neoplastic cells adjacent to open lumens], nuclear grade, and mitoses) and ductal carcinoma. Carcinomas with less than 70% tubularity were ductal. Carcinomas with 70% or more tubularity were divided into those with occasional grade 2 nuclei and mitoses and those with pure grade 1 nuclei and rare or no mitoses. The 10-year disease-free survival for patients with pure ductal vs pure tubular carcinoma was 91% vs 96% (P = .036). Overall survival rates were similar (85% vs 89%; P = .161). With the recently proposed criteria, neoplasms with less than 70% tubularity; 70% or more tubularity and occasional grade 2 nuclei and mitoses; and 70% or more tubularity, pure grade 1 nuclei, and rare mitoses had 10-year disease-free survival rates of 88%, 93%, and 100% (P < .001) and 10-year overall survival rates of 85%, 88%, and 94%, respectively (P < .001). Tubular carcinoma as a distinct morphologic entity should be restricted to neoplasms with 70% or more tubularity, pure grade 1 nuclei, and rare mitoses. Other definitions of tubular carcinoma do not guarantee the excellent prognosis.

Background: This pathologic analysis was conducted to help define the clinical target volume (CTV) for partial breast irradiation (PBI) by analyzing the amount and distance of residual disease found at reexcision after an initial lumpectomy., Materials and Methods: The study population consisted of 441 patients derived from a dataset of 607 consecutive cases of Stage I and II breast cancer (reviewed by one pathologist) who underwent reexcision (after lumpectomy) before radiation therapy (RT) as part of their standard breast-conserving therapy (BCT). The assumption in this analysis was that the maximal measured extension distance from the initial excision specimen margin (in the reexcision specimen) represents the minimum distance that needs to receive full-dose RT for PBI to be successful. In 333 of the 441 cases, it was possible to measure this distance. Margins were classified as negative (carcinoma > 1/2 low-power field [LPF] from the margin), near (< 1/2 LPF from the margin), or positive. The amount of carcinoma near the final margin was quantified as the width of invasive carcinoma and number of ductal carcinoma in situ (DCIS) ducts near the margin and divided into three groups: least, intermediate, and greatest amount., Results: Of the 333 cases, 119 (35.7%) had no residual carcinoma in the reexcision specimen, 67 (20.1%) had maximum extension (invasive carcinoma or DCIS) distances of >0<5 mm beyond the initial excision cavity edge, 83 (24.9%) extended 5 to <10 mm, 34 (10.2%) extended 10 to <15 mm, and 30 (9.0%) extended > or =15 mm. In 90% of 134 patients with negative initial lumpectomy margins (per National Surgical Breast and Bowel Project criteria) at lumpectomy, if any residual disease was present (38.2% of cases), it was limited to <10 mm from the edge of the original lumpectomy margin. The initial lumpectomy margin status was then combined with the invasive carcinoma: specimen maximum dimension ratio to determine if these two criteria (when combined) could better identify patients with residual disease limited to <10 mm from the initial margin. Analyzed in this fashion, all 13 of the reexcision specimens (9.7%) with >10 mm of maximum extension by carcinoma beyond the edge of the initial excision specimen cavity could be identified., Conclusions: A margin of 10 mm around the tumor bed should be adequate in covering disease remaining in the breast after lumpectomy in >90% of patients treated with PBI. However, it is possible to accurately identify all patients with disease extending beyond 10 mm using more restrictive pathologic selection criteria. These results can also be used as a guide for defining the CTV for boost treatment after whole-breast RT and the amount of breast tissue to remove at reexcision.

The location, amount, and anatomic relationships of adenocarcinoma in situ (AIS) in 5 delayed second cone biopsy excision specimens and 21 definitive-therapy hysterectomy specimens were measured in relation to the neosquamocolumnar junction (nSCJ). All 5 biopsy specimens had 1 to 2 mm of AIS situated at the nSCJ. None had AIS in the proximal endocervix, despite positive or extremely close biopsy margins. Residual AIS in hysterectomy specimens was located proximal to the nSCJ in 19 (90%) of 21 cases. The mean distance between AIS and the nSCJ was 4.9 mm in 12 (86%) of 14 hysterectomy specimens. The mean maximum length of AIS was 4.6 mm in hysterectomy specimens and 1.1 mm in biopsy specimens. Some postbiopsy failures might be de novo neoplasms that begin at the nSCJ rather than recrudescence of persistent AIS. Small amounts of residual AIS following cone biopsy excision might be eradicated by the healing process. These 2 factors might underlie the disparate rates of residual AIS in hysterectomy specimens and postbiopsy excision failures and also explain the poor correlation between biopsy margin status and clinical failure. Factors that impact postbiopsy AIS eradication might be unrelated to de novo AIS beginning at the nSCJ.

We examined clinicopathologic associations and biopsy changes that suggested classic lymphocytic colitis (C-LC) but were less well developed in intensity or distribution in 19 cases, which we termed paucicellular LC (P-LC). We also studied clinicopathologic associations and prevalence of LC in 100 asymptomatic, non-gluten-sensitive adults who underwent screening surveillance colonoscopy for previous adenoma. The control group was 38 randomly selected morphologically C-LC cases. The features of P-LC were foci of mildly increased lamina propria lymphoplasmacytic inflammation and increased surface intraepithelial lymphocytes separated by foci or tissue fragments of normal mucosa. Mean age and rates of female sex, endoscopically normal appearing colon, abdominal pain, watery stools, weight loss, connective tissue diseases, and consistent ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) were similar for P-LC and C-LC patients. Of 100 asymptomatic patients, 26 (26%) had LC and 43 (43%) used NSAIDs daily. Of these 43 patients, 14 (33%) had P-LC or C-LC. Daily NSAID ingestion was associated significantly with LC (P = .024). P-LC patients had clinicopathologic relationships similar to those of C-LC patients, suggesting they should be considered part of the morphologic spectrum of LC. LC in asymptomatic adults might be more common than previously thought and might not be associated with watery diarrhea syndrome.

Background: We reviewed our experience in patients with early-stage breast carcinoma treated with breast-conserving therapy (BCT) to identify pathologic factors useful in defining the adequacy of excision before radiotherapy (RT)., Methods and Materials: All slides from 607 consecutively treated cases of Stage I-II breast carcinoma were reviewed by one pathologist. Numerous pathologic factors were evaluated for their association with ipsilateral breast failure (IBF). Margin distance was classified as negative, near (<0.50 low-power field), or positive. The amount of carcinoma near the final margin was measured as the width of invasive carcinoma and number of ducts with carcinoma in situ near the margin and divided into three groups: near-least, near-intermediate, and near-greatest amount. The median follow-up was 8.5 years., Results: Patients with negative, near-least, near-intermediate, and near-greatest amount of carcinoma near the margin, and positive final margins had a 12-year IBF rate of 9%, 6%, 18%, 24%, and 30%, respectively. On multivariate analysis, only the amount of carcinoma near the margin was independently associated with IBF (p <0.001). To help explain these observations, 441 initial and reexcision specimens were examined. The amount of carcinoma near the initial margin and the invasive carcinoma/specimen maximal dimension ratio were significantly associated with greater amounts of residual carcinoma in adjacent breast parenchyma., Conclusion: The amount of carcinoma near the margin, in addition to margin status, appears to be directly related to an increased risk of IBF in patients treated with BCT. Pathologic factors that incorporate the amount of excised breast parenchyma and amount of carcinoma near the margin may be useful to clinicians in deciding whether a patient has undergone adequate excision for BCT.

Background: The authors reviewed changes in the initial clinical presentation, management techniques, and patterns of disease recurrence over time (1981-1996) in patients with breast carcinoma treated with breast-conserving therapy (BCT) at a single institution. The goals of the current study were to determine the frequency and use of optimal local and systemic therapy techniques and to evaluate the impact of these changes on treatment efficacy., Methods: Six hundred seven patients with American Joint Committee on Cancer Stage I or II invasive breast carcinomas treated with BCT at William Beaumont Hospital (Royal Oak, MI) constituted the study population. All patients received at least an excisional biopsy of the primary tumor, an axillary lymph node staging procedure, and postoperative radiotherapy (RT) (a median tumor bed dose of 61 Gray [Gy] was administered). All sides were reviewed by one pathologist. Numerous clinicopathologic and treatment-related factors were analyzed to monitor changes that occurred over time. Changes in patterns of disease recurrence and treatment efficacy over time also were analyzed., Results: Over the time period analyzed, changes at initial presentation included an increase in the mean age at diagnosis (age 56.1 years vs. 61.4 years; P < 0.001), a decrease in the number of patients with clinically palpable tumors (78% vs. 36%; P < 0.001), a decrease in the mean tumor size (2.2 cm vs. 1.6 cm; P < 0.001), but no change in the percentage of patients with negative lymph nodes (79% vs. 78%; P = 0.83). No differences over time were observed in mean tumor grade (2.0 vs. 1.9; P = 0.2) or the presence of angiolymphatic invasion (27% vs. 26%; P = 0.25). Changes in surgical management and pathologic assessment included the more frequent use of reexcision (46% vs. 81%; P < 0.001), larger mean total volumes of breast tissue specimens excised (115 cm3 vs. 189 cm3; P = 0.001), a larger percentage of patients with final negative surgical margins (74% vs. 97%; P < 0.001), and a small increase in the mean number of lymph nodes excised (13.8 lymph nodes vs. 14.1 lymph nodes; P = 0.01). The only other significant change in the pathologic management of patients over time included a doubling in the mean number of slides examined (10.6 slides vs. 21.1 slides; P < 0.001). Changes in adjuvant local and systemic therapy included an increase in the percentage of patients treated with > 60 Gy to the tumor bed (66% vs. 95%; P < 0.001), a doubling in the mean number of days from the last surgery to the start of RT (24 days vs. 50 days; P < 0.001), and a decrease in the use of regional lymph node RT (24% vs. 8%; P < 0.001). The use of adjuvant tamoxifen increased from 10% to 61% (P < 0.001). Finally, improvements were observed in the 5-year and 12-year actuarial rates of local disease recurrence (8% vs. 1% and 21% vs. 9%, respectively; P = 0.001) and distant metastases (12% vs. 4% and 22% vs. 9%, respectively; P = 0.006). No changes in the mean number of years to ipsilateral (6.5 years vs. 6.4 years; P = 0.59) or distant disease recurrence (4.6 years vs. 3.8 years; P = 0.73) were observed., Conclusions: The impact of screening mammography and substantial changes in surgical, pathologic, RT, and systemic therapy recommendations were observed over time in the study population. These changes were associated with improvements in 5-year and 12-year local and distant control rates and suggested that improvements in outcome can be realized through adherence to best practice guidelines and continuous monitoring of treatment outcome data., (Copyright 2004 American Cancer Society.)

Seven patients (mean age, 37.6 years; 5 women) had several weeks of gluten sensitivity (GS)-like symptoms; 2 had flu-like symptom prodromes. The 7 cases had morphologically similar biopsy specimens; all tissue fragments had uniform injury--increased lymphoplasmacytic lamina propria inflammation, moderate to complete villous flattening, numerous crypt mitoses, and markedly increased villous intraepithelial lymphocytes (IELs). All patients were diagnosed with GS and prescribed a gluten-free diet; all returned 9 to 38 weeks later questioning their diagnosis because symptoms had resolved substantially or completely. Clinical improvement was unrelated to gluten abstinence or ingestion. Repeated endoscopy and colonoscopy performed 4.1 to 16 months later showed normal mucosa in all 7 patients. Diseases other than GS can cause marked villous flattening and increased villous IELs in adults. The cause of small bowel mucosal injury is unknown. A similar non-GS-associated clinicopathologic complex, assumed to be due to a protracted viral enteritis or slow regression of a virus-induced immune reaction, occurs in children. The temporal aspects of symptom improvement and mucosal restitution in these 7 patients are similar to "acute self-limited colitis." An overly exuberant immune response to an infectious agent is possible.

Small-bowel biopsies are routinely obtained from adult patients as a screening tool to evaluate the possibility of gluten sensitivity (GS). Previous morphological criteria of GS including completely flattened villi are usually absent. In the context of screening for GS, an altered distribution density pattern of villous intraepithelial lymphocytes (IELs) is probably the most sensitive morphological feature to suggest the possibility of GS and prompt the initiation of further medical evaluation. Altered villous IEL density distribution is a more sensitive screening feature than villous IEL counts. With increased small-bowel GS screening biopsies, occasional adults without GS with complete villous flattening and numerous villous IELs are encountered. These patients are usually incorrectly diagnosed with GS. However, they do not respond to a gluten-free diet and slowly improve over months.

Purpose: We present our ongoing clinical experience utilizing 3D conformal radiation therapy (3D-CRT) to deliver partial-breast irradiation (PBI) in patients with early-stage breast cancer treated with breast-conserving therapy., Materials and Methods: Thirty-one patients referred for postoperative radiation therapy after lumpectomy were treated with PBI using our previously reported 3D-CRT technique. Ninety-four percent of patients had surgical clips outlining the lumpectomy cavity (mean: 6 clips). The clinical target volume (CTV) consisted of the lumpectomy cavity plus a 10-mm margin in 9 patients and 15-mm margin in 22 (median: 15 mm). The planning target volume consisted of the CTV plus a 10-mm margin for breathing motion and treatment setup uncertainties. The prescribed dose (PD) was 34 or 38.5 Gy (6 patients and 25 patients, respectively) in 10 fractions b.i.d. separated by 6 h and delivered in 5 consecutive days. Patients were treated in the supine position with 3-5 beams (mean: 4) designed to irradiate the CTV with <10% inhomogeneity and a comparable or lower dose to the heart, lung, and contralateral breast compared with standard whole-breast tangents. The median follow-up duration is 10 months (range: 1-30 months). Four patients have been followed >2 years, 6 >1.5 years, and 5 >1 year. The remaining 16 patients have been followed <12 months., Results: No skin changes greater than Grade 1 erythema were noted during treatment. At the initial 4-8-week follow-up visit, 19 patients (61%) experienced Grade 1 toxicity and 3 patients (10%) Grade 2 toxicity. No Grade 3 toxicities were observed. The remaining 9 patients (29%) had no observable radiation effects. Cosmetic results were rated as good/excellent in all evaluable patients at 6 months (n = 3), 12 months (n = 5), 18 months (n = 6), and in the 4 evaluable patients at >2 years after treatment. The mean coverage of the CTV by the 100% isodose line (IDL) was 98% (range: 54-100%, median: 100%) and by the 95% IDL, 100% (range: 99-100%). The mean coverage of the planning target volume by the 95% IDL was 100% (range: 97-100%). The mean percentage of the breast receiving 100% of the PD was 23% (range: 14-39%). The mean percentage of the breast receiving 50% of the PD was 47% (range: 34-60%)., Conclusions: Utilizing 3D-CRT to deliver PBI is technically feasible, and acute toxicity to date has been minimal. Additional follow-up will be needed to assess the long-term effects of these larger fraction sizes on normal-tissue sequelae and the impact of this fractionation schedule on treatment efficacy.

We studied 31 T1 N0 M0 peripheral adenocarcinomas diagnosed by wedge resection and treated by lobectomy. Factors recorded were pleural surface-based, gross cut-surface, and microscopic margin distances; morphologic features of the adenocarcinomas; microscopic extension distance of beyond gross perimeter of neoplasm; and presence of residual adenocarcinoma in the lobectomy specimen. All staple-line margins in the wedge and lobectomy specimens underwent complete histologic examination. The mean pleural surface-based, gross cut-surface, and microscopic margin distances in wedge resections were 13.1, 4.1, and 2.3 mm, respectively. The mean microscopic wedge resection margin distance was 11 mm smaller than the pleural surface-based measured margin. The mean microscopic lepidic growth beyond the gross perimeter of the neoplasm was 7.4 mm. Fourteen lobectomy specimens (45%) included adenocarcinoma. The mean microscopic wedge resection specimen margin distances in cases with and without residual adenocarcinoma in the lobectomy specimens were 0.7 and 2.4 mm, respectively (P < .001). Incomplete excision may contribute to higher locoregional recurrence rates following limited resection surgery. Two processes affected wedge resection margin distances: stapling-induced parenchymal stretching, resulting in overestimation of pleural surface-based distances, and microscopic extension of adenocarcinoma beyond the gross perimeter of the neoplasm.

All slides from 607 consecutive invasive breast carcinomas from 583 patients were reviewed. Margin distance, composite width of invasive carcinoma, and number of ducts with intraductal carcinoma within the one-half low-power field (LPF) adjacent to the final margin were recorded. Final margin groups were positive (carcinoma at margin), near (< or = 1/2 LPF of margin), and negative (> 1/2 LPF). There were 39 ipsilateral breast failures (IBFs), and 63 patients (10.8%) developed distant metastases (DMs). Decreasing margin distance and increasing amounts of carcinoma near the margin were associated with IBF and DM. The 5-tiered composite factor of margin distance and amount of carcinoma near margin (negative margins, near least amount, near intermediate amount, near greatest amount, and positive margins) resulted in 12-year IBF rates of 9%, 6%, 18%, 24%, and 30%, respectively (P < .001). The composite factor, margin amount of carcinoma near margin, and invasive carcinoma/initial excision specimen dimension ratio were the most precise parameters assessing excision adequacy and, ultimately, IBF risk. The amount of carcinoma near the margin and volume of excised parenchyma related directly to the amount of residual carcinoma in the adjacent breast parenchyma.