The recognition and classification of lymphoproliferative disorders of the gut.

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.

Long-term impact of young age at diagnosis on treatment outcome and patterns of failure in patients with ductal carcinoma in situ treated with breast-conserving therapy.

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.

Twenty-year outcomes after breast-conserving surgery and definitive radiotherapy for mammographically detected ductal carcinoma in situ.

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.

Long-term outcome in patients with ductal carcinoma in situ treated with breast-conserving therapy: implications for optimal follow-up strategies.

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.

Monomorphic epithelial proliferations of the breast: a possible precursor lesion associated with ipsilateral breast failure after breast conserving therapy in patients with negative lumpectomy margins.

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.

Optimal use of re-excision in patients diagnosed with early-stage breast cancer by excisional biopsy treated with breast-conserving therapy.

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.

Differences in patterns of failure in patients treated with accelerated partial breast irradiation versus whole-breast irradiation: a matched-pair analysis with 10-year follow-up.

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.

Consensus recommendations on estrogen receptor testing in breast cancer by immunohistochemistry.

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.

Molecular evidence demonstrating local treatment failure is the source of distant metastases in some patients treated for breast cancer.

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.

Monomorphic epithelial proliferations: characterization and evidence suggesting they are the pool of partially transformed lesions from which some invasive carcinomas arise.

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.

Interim cosmetic results and toxicity using 3D conformal external beam radiotherapy to deliver accelerated partial breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy.

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.

Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy.

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.

Clinicopathologic analysis of microscopic extension in lung adenocarcinoma: defining clinical target volume for radiotherapy.

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.

Estrogen receptor antibody incubation time and extent of immunoreactivity in invasive carcinoma of the breast: the importance of optimizing antibody avidity.

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.

Long-term efficacy and patterns of failure after accelerated partial breast irradiation: a molecular assay-based clonality evaluation.

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.

An approach to interpreting immunohistochemical stains of adenocarcinoma in small needle core biopsy specimens: the impact of limited specimen size.

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.

The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy.

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.

Clinicopathologic analysis of extracapsular extension in prostate cancer: should the clinical target volume be expanded posterolaterally to account for microscopic extension?

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.