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Notes: Abstract: Traditionally, estrogen and progesterone receptor levels have been determined by biochemical ligandbinding assays, but more recently immunohistochemical techniques have become available. They have gained popularity due to their low cost, smaller sample size requirements, and direct visualization capability of reaction location. Several antibody clones are commercially available and antibodies directed against the estrogen receptor (ER) are supplied by Ventana Medical Systems (Tucson, AZ), Abbott Laboratories (Abbott Park, IL), and lmmunotech Westbrook, ME). Antibodies directed against the progesterone receptor (PgR) are supplied by Ventana Medical Systems (Tucson, AZ), lmmunotech (Westbrook, ME), and Becton-DickinsonKelI Analysis Systems (San Jose, CA). Computer-assisted image analysis using the CAS ZOOTM (Becton-DickinsonKIS, San Jose, CA) allows quantitation of immunohistochemically determined receptor levels. Correlation of quantitated immunohistochemical ER levels with values determined by ligand-binding assay revealed the Ventana antibody to most closely predict the ligand-binding results (wk = .667). The Ventana anti-progesterone antibody quantitation most closely correlated with the ligand-binding results (wk = 435) for determination of PgR. Progesterone receptor level as determined by any of the tested methods did not stratify patients into favorable and unfavorable prognostic groups. Estrogen receptor level as determined by the Ventana antibody was the most predictive of patient outcome but this relationship did not reach statistical significance (p = .09). Most discrepancies between the ligand-binding assay and the immunohistochemical assays were associated with one of three factors: (a) low volume of neoplastic cells present due either to small sample size or high stromal content, (b) premenopausal status with circulating endogenous estrogens potentially occupying receptor sites, (c) presence of benign breast epithelium resulting in a false-positive ligand-binding assay.

Notes: Abstract: Several clinicopathologic variables influence prognosis in breast cancer, including stage, histologic grade, nodal status, and tumor size. Multiple studies have shown an independent value of proliferation index as a prognostic variable for the stratification into favorable and unfavorable groups. The monoclonal antibody MIB-1 reacts with the same antigen site, not epitope, as recognized by the Ki-67 antibody. Like Ki-67, MIB-1 reacts with cells in the late G1, S, M and G2 phases of the cell cycle, but MIB-1 has the advantage of reacting with formalin-fixed, paraffin-embedded material. The authors investigated the feasibility of using image analysis to quantitate the MIB-1 antibody staining (proliferation index [PI]) and predict survival in a series of 230 patients with stage I and stage II breast cancer. In a univariate Cox regression model, larger values of MIB-1 were related to shorter survival times (p 〈 0.001). Exploratory statistical procedures were used to categorize the patients into good, intermediate, and poor survival groups using the following proliferation indices as cut-points: 〈5%, 5–11%, and 〉11 %, respectively. Higher clinical stage was associated with higher MIB-1 values and shorter survival (p = 0.01, and p = 0.003, respectively). Tumor size (p = 0.02) and nodal status (p = 0.05) were also associated with higher values of MIB-1. After adjusting for age, clinical stage, nodal status, and tumor size in a multivariate analysis, MIB-1 retained its prognostic significance (p 〈 0.0001) when considered as either a continuous or categorical variable. There were no significant associations between MIB-1 determined proliferation index and age (p = 0.54), histologic grade (p = 0.69), nuclear grade (p = 0.06) or the presence of vascular invasion (p =.66). There is a strong statistical relationship between cell proliferative activity, as determined by MIB-1 expression, and survival in early stage breast cancer.

Notes: Abstract: Heterotopic squamous-lined cysts and ductal epithelium occurring in an intramammary lymph node from a 23-year-old woman are described. The lesion presented as a 3 cm × 2 cm well-circumscribed mass lying anterior to the left anterior axillary line. Careful examination of the breast revealed no other clinically apparent lesions. The nodule was thought to represent a benign neoplasm and excisional biopsy was performed. Pathologic examination revealed a lymph node whose architecture was distorted by multiple squamous-lined cysts. The squamous epithelium demonstrated a prominent granular cell layer. No evidence of nuclear atypia was found within the squamous lining. Only rare cases of epithelial inclusions within axillary lymph nodes have been described. The majority have been unrelated to a breast malignancy and have followed a benign clinical course. Because these inclusions may lead to significant axillary or intramammary lymphadenopathy, they may be mistaken clinically for metastatic carcinoma. Disclosure of intranodal epithelial deposits on pathologic examination may result in an incorrect diagnosis of metastatic disease. However, careful evaluation of the epithelial nests will establish their benign character. Benign epithelial deposits within intramammary and axillary lymph nodes must be added to the list of heterotopic benign epithelial structures found in lymph nodes.

Notes: Abstract: The assessment of steroid hormone receptors in resected breast carcinoma tissue is currently the standard of practice. The traditional method for assessment of receptor status is the ligand binding assay. More recently, immunohistochemistry (IHC) has become a popular method for such testing. Despite the widespread use of IHC and the availability of many antibodies, standardization of quantitative IHC for assessment of estrogen and progesterone receptors has not been achieved. While the College of American Pathologists (CAP) offers a Quality Assurance (QA) program for IHC quantitation of estrogen receptor (ER) and progesterone receptor (PgR), no universal standard is currently recognized in assessment of ER and PgR by IHC. We surveyed 300 laboratories within the United States for their current practices regarding the assessment of ER and PgR status in breast cancer tissue specimens. Eighty usable responses were received. Forty-nine (61%) laboratories performed the assay in-house, while the remainder sent the material out for assay. All responding laboratories performing their steroid receptor analysis in-house used the IHC technique. Forty-three (80%) laboratories answering the question on material accepted for analysis performed the assay only on paraffin-embedded material, three (6%) used either paraffin block or frozen material, and two (4%) used only frozen material. Eighty-eight percent of laboratories performing steroid receptor analysis in-house used a manual quantitation technique. Four (8%) used computer-assisted image analysis, and a single laboratory used laser scanning cytometry. Eight different antibodies were used among the 44 laboratories documenting the antibody supplier, and for any given commercially prepared antibody a wide variety of dilutions were used, with the exception of the standard solution used with the Ventana antibody. Of the laboratories using manual estimation techniques, 61% simply estimated the percentage of positive cells, 29% evaluated both the intensity of staining and percentage of nuclei staining, 6% used formal H-score analysis, 2% evaluated only intensity of nuclear staining, and 2% mainly counted the percentage of nuclei staining for ER but used a formal H score in the assessment of PgR. Cutoff points for the separation of positive and negative results varied widely, with some laboratories assessing any demonstrable positivity as a positive result, while others required as many as 19% of the nuclei to stain before a specimen was declared positive. Standardization techniques differed considerably among laboratories. Eighty-six percent used the CAP program for QA. While all laboratories utilized some form of intralaboratory control for assessment of ER and PgR, the nature of that control varied from laboratory to laboratory. Our survey indicates that a majority of laboratories perform their steroid hormone receptor analysis in-house using IHC. There is considerable variability in the antibodies utilized, the dilutions applied, and the quantitation method and level of expression used to dichotomize specimens into positive and negative groups. Finally, no universal control for interlaboratory standardization appears to exist.

Notes: Abstract: Standard practice in surgical pathology dictates that random sections from the four quadrants of the breast be taken in mastectomy specimens. These sections are obtained in addition to sampling of any grossly visible lesions within the breast specimen. While tradition dictates the submission of these sections, we are unaware of any study supporting their efficacy. We have investigated the utility and significance of these random sections in a series of 78 mastectomy specimens. This retrospective study identified mastectomy specimens from pathology files of Magee Woman's Hospital, the University of Pittsburgh, and the University of Utah School of Medicine between 1997 and 2000. Clinical data (palpable versus nonpalpable), radiographic features (mammographic diagnosis, presence of mass density and/or calcification), and pathologic features (size, histopathologic type, etc.) were studied. The histologic sections of the cases were reviewed and the random sections were specifically studied for pathologic findings. Diagnosis and clinically significant features obtained from examining these random sections, but not demonstrable in grossly selected sections, were tabulated. A total of 78 mastectomy specimens were analyzed. Diagnoses rendered were infiltrating ductal carcinoma (23), infiltrating ductal carcinoma with ductal carcinoma in situ (DCIS) (16), DCIS (25), infiltrating lobular carcinoma (4), biopsy cavity with no residual malignancy (4), infiltrating lobular carcinoma with lobular carcinoma in situ (3), invasive ductal and lobular carcinoma (1), adenoid cystic carcinoma (1), and atypical ductal hyperplasia (1). The number of random sections ranged from 2 to 17 (mean 9). Random sections provided additional information in 21 of 78 mastectomies (27%). The multifocal/multicentric nature of the lesion was diagnosed in 20 cases: DCIS (6), lobular carcinoma in situ and invasive (2), invasive ductal carcinoma (6), invasive and in situ ductal carcinoma (5), invasive lobular carcinoma (1), invasive ductal and lobular carcinoma (1). Additional findings include lymphovascular invasion (2 cases), atypical ductal hyperplasia (1), DCIS at the operative margin (1), DCIS within less than 1 mm of an operative margin (1), and atypical lobular hyperplasia (1). In the remaining 57 cases, random sections did not provide any additional information. Histologic examination of random sections from breast quadrants yielded important information about the presence of multifocality, multicentricity, vascular invasion, and margin involvement by carcinoma in only a minority of cases, many of which had a lobular morphology. 

Notes: Abstract: The diagnostic accuracy of excisional biopsy is used as the “gold standard” for the diagnosis of breast nodules. In comparison studies involving the diagnostic accuracies of fine-needle aspiration cytology and cutting needle biopsy, the accuracy rate of open biopsy is often assumed to be 100%. While diagnostic accuracy rates are well reported for fine-needle aspiration (FNA) and large-gauge core needle biopsy, little data has been published documenting the accuracy of excisional biopsy. Hence, valid comparisons of relative diagnostic precision between the techniques are difficult to achieve. We report our experience with the sensitivity and specificity of open biopsy, cutting-needle biopsy and fine-needle aspiration biopsy over a three-year period. Between January 1992 and December 1994, histologic specimens from 412 open breast biopsies, and 17 non image guided Tru-cut® biopsies of palpable breast nodules were reviewed. These cases had either histologic follow-up (n= 388) or at least 2 years clinical follow-up (n= 25). Similarly, 450 FNAs were performed of which 215 had histologic study or cytologic follow-up. Within the 388 open biopsies with histologic follow-up, two false-negatives (sensitivity 99%) and one false-positive (specificity 99.5%) were detected based on subsequent biopsies or review of the initial material. No erroneous diagnoses were found in the 25 patients having only clinical follow-up. Among the 17 cutting needle-biopsies, two false-negatives (sensitivity 85%) were detected; no false-positives occurred (specificity 100%). One false-positive and five false-negatives were detected on follow-up of the 215 FNAs. This yielded a sensitivity of 96.2% and a specificity of 99.6%. Fine-needle aspiration compares favorably with both of these techniques, being inferior to open biopsy but of greater accuracy than cutting needle biopsy. These results demonstrate that care must be taken in using the histopathologic findings of open biopsy as the standard with which other methods of diagnosis are compared.

Notes: Abstract  Macrodystrophia lipomatosa (MDL) is a rare disease typically causing localized gigantism and is often associated with a fibrolipomatous hamartoma (FH) of the median or plantar nerve. A previously unreported case of MDL with associated FH of the median nerve is presented.

Notes: Abstract Interventional magnetic resonance imaging (MRI) is a newly established field, made possible by improvements in imaging times and the development of nonferromagnetic materials. Interstitial laser therapy (ILT) is a promising new technology in which laser energy is adininistered percutaneously via optical fibers. In this study, MRI was used to image acute experimental lesions induced nv ILT. Nine experimental lesions were induced in the musculature of an adult swine using an argon laser,' with output power of 1–4 watts, and exposure times of 10–40 s. T2-weighted images were obtained immediately after laser energy administration. The animal was then sacrificed and lesions were dissected and examined histologically. On MRI, target like lesions were seen with a high intensity center surrounded by two alternating concentric rings of low and high intensity. Histologically, concentric zones of tissue disruption were present. A center cavity was surrounded by a zone of coagulative necrosis, followed by a zone of vascuolated tissue abutting normal muscle. We conclude that MRI is capable of imaging acute histological changes. Appropriate development of a scale relating MR changes to acute and long-term histologic changes will allow us to optimize 3 D control and monitoring of ILT.