Pathologic, immunohistochemical, and molecular features of benign and malignant phyllodes tumors of the breast.

The histologic distinction between benign and malignant Phyllodes tumors (PT) is often difficult and arbitrary. We analyzed a group of benign and malignant PT to determine whether specific histologic features and expression of Ki-67 and p53 could be useful in distinguishing benign PT from malignant tumors. We also determined whether deletions in Chromosome 3p at the FHIT and hMLH1 loci are common abnormalities in PT. Twenty PT were histologically classified as benign (7) or malignant (13). Seven of the malignant PT were low grade, and six were high grade. Ki-67 and p53 immunohistochemistry was performed on all tumors and analyzed for the stromal and for the epithelial component. PCR-based loss of heterozygosity analyses were performed with the following markers on Chromosome 3p: D3S1478 (3p21.2--21.3), D3S1289 (3p21.1--21.2), and D3S1295 (3p14.3--21.1). The distribution of immunoreactivity for Ki-67 was analyzed by quantifying the percentage of positive nuclei and expressed as the labeling index (LI). Patients' ages ranged from 13 to 71 years (median: 51 y). After a mean follow-up period of 8 years, none of the PT metastasized, whereas three recurred locally. Although malignant PT were larger than benign PT (means, 7.1 versus 4.3 cm), this difference was not statistically significant. Five tumors had infiltrating margins, and 14 were circumscribed. The Ki-67 LI in low-grade malignant PT (16 +/- 25.5) was significantly higher than that in benign PT (3.6 +/- 4.8), whereas the LI in the high-grade malignant PT group (50 +/- 21.9) was significantly higher than that in low-grade malignant tumors (P =.012). The Ki-67 LI in the three tumors that recurred was less than 10%. Two of seven (29%) benign PT were focally positive for p53, whereas four of seven (57%) low-grade malignant and three of six (50%) high-grade malignant PT were diffusely positive for p53. The three tumors that recurred initially were histologically benign, as were two of the recurrences. One recurrent tumor evolved to a high-grade malignant PT. Margins were greater than 1 cm in all tumors except four, three of which recurred locally. No allelic loss of 3p was found. In summary, Ki-67 expression may assist in distinguishing benign from malignant PT in diagnostically difficult cases. 3p deletions do not play a significant role in the development of these tumors. Neither Ki-67 nor p53 can reliably predict recurrence. Histologically high-grade malignant PT have a favorable prognosis if widely excised. We emphasize the importance of adequate margins in the treatment of benign and malignant PT.

Relationship between mammographic screening intervals and size and histology of ductal carcinoma in situ.

OBJECTIVE: The objective of this study was to determine how the length of time between mammographic screenings is related to the size, grade, and histology of mammographically detected ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: We retrospectively reviewed 166 consecutive mammograms of women evaluated for DCIS with (n = 24) and without (n = 142) microinvasion. The size of the DCIS was determined by the maximum diameter as measured on the mammogram. After pathologic analysis, DCIS was classified by histologic architecture, nuclear grade, presence of microinvasion, and presence of multifocality. Four screening intervals were defined: annual (6-17 months), biennial (18-29 months), triennial (> or = 30 months), and first time. Patients were grouped according to screening intervals. The average age of all groups was 55 years. RESULTS: The annual group (mean size of DCIS, 1.69 cm) had significantly smaller DCIS than did the biennial (mean size, 2.27 cm), triennial (mean size, 3.49 cm), or first time groups (mean size, 3.29 cm) (p = .003). Comedo histology was more frequently observed in patients screened biennially (73.7%) than in those screened annually (46.8%) (p = .05). High-grade nuclear histology was more commonly seen in the biennial (76.3%) than in the annual (48.1%) screening group (p = .008). We found no significant correlation between screening interval and the incidence of microinvasion and multifocality. CONCLUSION: Small, low-grade noncomedo DCIS was more common in the annual mammographic screening group than in the biennial screening group. A direct relationship was found between DCIS size and length of screening interval: DCIS detected at annual screening was smaller than that found at biennial screening, which in turn was smaller than DCIS revealed at triennial screening. This study provides inferential support for annual screening mammography for DCIS detection and management.

Is mammography useful in screening for local recurrences in patients with TRAM flap breast reconstruction after mastectomy for multifocal DCIS?

BACKGROUND: Skin-sparing mastectomy with immediate transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction is being used more often for the treatment of breast cancer. Mammography is not used routinely to evaluate TRAM flaps in women who have undergone mastectomy. We have identified the potential value of its use in selected patients. METHODS AND RESULTS: We report on four women who manifested local recurrences in TRAM flaps after initial treatment for ductal carcinoma in situ (DCIS) or DCIS with microinvasion undergoing skin-sparing mastectomy and immediate reconstruction. All four patients presented with extensive, high-grade, multifocal DCIS that precluded breast conservation. Three of four mastectomy specimens demonstrated tumor close to the surgical margin. Three of the four recurrences were detected by physical examination; the remaining local recurrence was documented by screening mammography. The recurrences had features suggestive of malignancy on mammography. CONCLUSION: We conclude that all patients undergoing mastectomy and TRAM reconstruction for extensive, multifocal DCIS should undergo regular routine mammography of the reconstructed breast. Our experience with this subgroup of patients raises concern about the value of skin-sparing mastectomy with immediate reconstruction for therapy. Adjuvant radiation therapy should be recommended for those patients with negative but close surgical margins.

Adenoid cystic carcinoma of the breast: value of histologic grading and proliferative activity.

Adenoid cystic carcinoma of the breast is an uncommon carcinoma with a distinctive histology. Prognosis is favorable, although recurrence and distant metastases have been described. We assessed whether histologic features and proliferative activity can identify aggressive neoplasms. We studied 31 cases of adenoid cystic carcinoma (age range of patients, 33 to 74 years). Three histologic grades were defined: grade I: completely glandular; grade II: < 30% solid areas, and grade III: > or = 30% solid pattern. In 19 of 31 cases, immunohistochemical stains for estrogen receptor were available. Twelve of 31 cases were immunohistochemically stained for Ki-67 antigen using MIB1 antibody. Ten of 20 tumors were subareolar. All tumors were grossly circumscribed; however, 12 of 20 (60%) had focal infiltration peripherally. Five of 19 tumors were estrogen receptor positive. There was no statistical correlation between MIB1 score and histologic grade, nuclear grade, infiltration of the adjacent fat or breast parenchyma, or estrogen receptor status. All patients were alive with no evidence of disease after a median follow-up of 7 years. Neither histologic or nuclear grading nor proliferative activity were useful prognosticators. None of the tumors had lymph node metastases. Therefore, axillary lymph node dissection may not be necessary. Because more than half of adenoid cystic carcinomas are infiltrative focally, the most important therapeutic goal is complete tumor removal with uninvolved margins of excision.

Nationwide survey of home transfusion practices.

BACKGROUND: Limited information exists on home transfusion practices. STUDY DESIGN AND METHODS: In 1995, a survey requesting data for 1994 was sent to 1273 American Association of Blood Banks (AABB) institutional members and 113 non-AABB home health care agencies that provide out-of-hospital transfusions. RESULTS: Of 943 respondents, 102 provide blood to a home transfusion program, 37 provide blood and run a home transfusion program, and 13 run a home transfusion program only, for a total of 152 (16%) with some involvement in home blood transfusions. Most of the 50 respondents with a home transfusion program are licensed by their state and accredited by the Joint Commission on Accreditation of Healthcare Organizations. All respondents have written policies for home transfusion, and 90 percent require a signed informed-consent document before initiating transfusions in the home. Most have policies requiring that there be a second adult and a telephone in the home, that the home be deemed safe for transfusion, that the patient's physician be readily available, and that the patient have had prior transfusions. The most common component issued by the blood providers was red cells, followed by platelets. White cell-reduced components were always provided by 36 percent of respondents. The most common patient diagnosis was cancer. Home transfusions were provided primarily by registered nurses. Only 14 percent of respondents indicated that the medical director of the blood bank is responsible for approving a patient for home transfusion. A posttransfusion visit is performed by 46 percent of respondents. CONCLUSION: Although most facilities have policies for the administration of home transfusions, there remains marked heterogeneity among blood providers and transfusionists regarding home transfusion practices.

Metaplastic carcinoma of the breast: mammographic appearance with pathologic correlation.

OBJECTIVE: The objective of this study was to describe the mammographic appearance with pathologic correlation of metaplastic carcinoma of the breast. CONCLUSION: Metaplastic carcinomas of the breast are masses with mammographic characteristics of low suspicion because of their histologic appearance. Metaplastic carcinoma should be included in the differential assessment of predominately circumscribed, noncalcified masses revealed on mammography. One salient feature that may distinguish metaplastic carcinomas is the occurrence of a circumscribed portion with a spiculated portion, which is seen in carcinomas that have a significant mixture of metaplastic and invasive carcinoma growth patterns.

Hypotensive reactions: a previously uncharacterized complication of platelet transfusion?

BACKGROUND: In 1993, the American Association of Blood Banks (AABB) received reports of severe hypotensive reactions associated with platelet transfusions. The question arose as to whether these reports were indicative of a previously uncharacterized platelet transfusion reaction. STUDY DESIGN AND METHODS: To further characterize these reactions, the AABB Transfusion Practices Committee developed a series of three questionnaires. The initial questionnaire was sent to all AABB institutional members; the two subsequent questionnaires were sent to those institutions reporting severe and/or unusual platelet transfusion reactions. This report focuses on the 24 responses to the third and most detailed questionnaire, which specifically addressed reactions that were characterized by hypotension and/or unexplained respiratory failure. RESULTS: Of the 24 detailed responses received, 4 were not considered to represent unusual reactions to platelet transfusion, 3 described reactions consistent with a (presumably unrecognized) diagnosis of transfusion-related acute lung injury, and 17 described reactions that were primarily characterized by hypotension. The majority of the hypotensive reactions occurred within 1 hour of the beginning of the transfusion (88%), were associated with respiratory distress (82%), and resolved rapidly after cessation of the transfusion (82%). Eighty-eight percent of implicated components had been white cell reduced by filtration. CONCLUSION: The hypotensive platelet transfusion reactions that were described appear to represent a previously uncharacterized complication of platelet transfusion. However, the nature of the questionnaires used in this investigation does not allow the drawing of firm conclusions as to the frequency or the cause of these reactions.

Blood utilization in adult patients undergoing extracorporeal membrane oxygenated therapy.

BACKGROUND: The impact of extracorporeal membrane oxygenation (ECMO), performed on adult patients, on the blood transfusion service of a tertiary-care hospital was assessed. The quantity and pattern of blood component utilization by these patients were compared to those in a previous evaluation of neonatal patients receiving similar treatment. STUDY DESIGN AND METHODS: The records of blood component transfusion to 74 adult patients, treated with ECMO within a 6-year period, were reviewed. This information was correlated with the clinical indication for ECMO and duration of ECMO treatment. In addition, daily use of components for these patients was studied to ascertain whether the blood requirements were predictable and uniform. RESULTS: Over 15,000 units of blood components, with platelet concentrates making up the largest portion, were transfused to these patients while they were undergoing ECMO. The duration of ECMO varied from less than 1 day to 53 days. However, the length of treatment could not uniformly be correlated with blood utilization or with survival. Daily blood transfusion needs often could not be anticipated, which meant that the transfusion service frequently had to respond to urgent requests for transfusion support. The provision of platelet concentrates proved to be the most difficult part of the maintenance of this program. CONCLUSION: Whereas ECMO treatment of neonatal patients has a relatively minor impact on a transfusion service, the same is not true for a program that uses this form of treatment for adults as well.

Microscopic extracapsular extension in the axilla: is this an indication for axillary radiotherapy?

PURPOSE: Although the axilla is often treated with radiotherapy (RT) postoperatively when microscopic extracapsular extension (ECE) of lymph nodal metastases is present, little data are available to assess axillary failure in the absence of such treatment. As it has been the practice at this institution to withhold axillary irradiation in the presence of microscopic extracapsular spread, we retrospectively analyzed our results for axillary recurrence, disease-free survival (DFS), and overall survival (OS). METHODS AND MATERIALS: Clinical records were reviewed of 82 women with Stage II node positive breast cancer treated with lumpectomy, axillary dissection, and RT in addition to systemic chemo/hormonal therapy. Axillary surgery consisted of a level I, II, +/- III dissection, with a median of 16.5 nodes removed. Tangential radiotherapy fields were used to treat the breast. All patients were also treated with an abbreviated supraclavicular field with the lateral border medial to the humeral head. Pathological sections were available for review in 72 of the 82 women. RESULTS: Twenty-seven of 72 (37.5%) had evidence of ECE; 45 of 72 (62.5%) had metastatic carcinoma confined within the nodal capsule. Clinical characteristics were comparable between the patients with and without ECE with the exception of (a) pathologic subtype, with a greater percentage of infiltrating ductal tumors associated with ECE (p = 0.044), and (b) number of positive lymph nodes, with 93% of patients without ECE having one to three positive nodes vs. only 56% among patients with ECE (p < 0.001). With a median follow-up of 40 months, 1 of 27 patients (4%) with ECE experienced an axillary failure as a component of first failure compared to 0 of 45 patients without ECE (p = 0.4). There were no isolated axillary failures. Five-year disease-free survival (72% without ECE vs. 57% with ECE, p = 0.12) and overall survival (83% vs. 53%, respectively, p = 0.068) suggested a less favorable outcome for patients with ECE. CONCLUSIONS: Microscopic ECE appears to be associated with increased axillary involvement and decreased survival rather than subsequent axillary failure. Our data suggest that radiotherapy to a dissected axilla may be omitted for the sole indication of microscopic extracapsular disease.

Pure and mixed mucinous carcinoma of the breast: pathologic basis for differences in mammographic appearance.

OBJECTIVE: It is important to differentiate pure and mixed mucinous carcinomas of the breast because the former have a more favorable prognosis. We correlate histopathologic findings with mammographic findings for 20 patients with pure or mixed mucinous carcinomas to determine differential characteristics and their pathologic basis. MATERIALS AND METHODS: We searched our pathology database of 2219 consecutive women with a diagnosis of breast cancer and found that 31 (1.4%) had mucinous carcinomas. Eleven women were excluded because the mammograms (n = 6) or the microscopic slides (n = 5) were not available. The remaining 20 women, who were 37-92 years old (mean, 64 years), were the subjects of the study. Their clinical records, mammograms, and microscopic slides were reviewed. Tumor size was based on the maximum mammographic diameter or measured diameter of the excised tumor. RESULTS: Seventeen patients (85%) had tumors that were mammographically apparent. Histopathologic review confirmed 15 pure mucinous tumors and five mixed mucinous tumors having an overall mean diameter of 3.4 cm. The pure-tumor group contained three incidentally detected tumors (all < or = 0.8 cm in diameter); six that had a circumscribed, lobular contour on mammograms (mean diameter, 3.6 cm); and six that had a poorly defined, irregular contour (mean diameter, 1.2 cm). One of the mammographically apparent small pure tumors contained histologically confirmed psammomatous microcalcifications. All pure tumors had microscopically evident circumscribed margins that could have accounted for the circumscribed mammographic appearance of the larger masses. All mixed tumors had mammographically and histologically evident irregular margins because of the associated fibrosis and infiltrative margins of the nonmucinous component (mean diameter, 5.3 cm). CONCLUSION: There are differences in the mammographic appearances of pure and mixed mucinous carcinomas that have a histopathologic basis. Circumscribed, lobular margins on mammograms are characteristic of large pure tumors and are the result of their microscopically evident circumscribed margins and expansile growth pattern. Irregular margins on mammograms are more characteristic of mixed mucinous tumors, regardless of tumor size, and are attributable to the fibrotic and infiltrative nature of the nonmucinous component.