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Neal S Goldstein

Publications and source records attributed to Neal S Goldstein.

At least 19 recordsLinked to original sources
PubMed2007

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.

Adenocarcinoma↗
PubMed2006

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.

Adult↗
PubMed2006

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.

Aged↗
PubMed2006

Clonality of sarcomatous and carcinomatous elements in sarcomatoid carcinoma of the prostate.

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.

Carcinoma↗
PubMed2006

Isolated ileal erosions in patients with mildly altered bowel habits. A follow-up study of 28 patients.

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.

Adolescent↗
PubMed2006

Small colonic microsatellite unstable adenocarcinomas and high-grade epithelial dysplasias in sessile serrated adenoma polypectomy specimens: a study of eight cases.

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.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Serrated pathway and APC (conventional)-type colorectal polyps: molecular-morphologic correlations, genetic pathways, and implications for classification.

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.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Association of eosinophilic inflammation with esophageal food impaction in adults.

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.

Abscess↗
PubMed2005

Molecular clonality relationships in initial carcinomas, ipsilateral breast failures, and distant metastases in patients treated with breast-conserving therapy: evidence suggesting that some distant metastases are derived from ipsilateral breast failures and that metastases can metastasize.

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.

Aged↗
PubMed2005

Fibrosis heterogeneity in nonalcoholic steatohepatitis and hepatitis C virus needle core biopsy specimens.

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.

Biopsy, Needle↗
PubMed2005

Molecular clonality determination of ipsilateral recurrence of invasive breast carcinomas after breast-conserving therapy: comparison with clinical and biologic factors.

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.

Adenocarcinoma↗
PubMed2004

Defining the clinical target volume for patients with early-stage breast cancer treated with lumpectomy and accelerated partial breast irradiation: a pathologic analysis.

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.

Breast Neoplasms↗
PubMed2004

Use of pathologic factors to assist in establishing adequacy of excision before radiotherapy in patients treated with breast-conserving therapy.

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.

Breast Neoplasms↗
PubMed2004

Changes in management techniques and patterns of disease recurrence over time in patients with breast carcinoma treated with breast-conserving therapy at a single institution.

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.

Adult↗