Kenneth J. Bloom

Laser therapy for small breast cancers

BACKGROUND Widespread mammography has resulted in the increased detection of breast cancer <1.5 cm. It may be possible to treat these small tumors with in-situ laser ablation. Prior to ablation tumor size is determined by ultrasound and mammogram. Histologic diagnosis and determination of prognostic factors are obtained from image-guided needle core samples. Invasive and in-situ tumors may be percutaneously ablated by a stereotactically guided laser needle and subsequently evaluated by imaging methods and needle biopsy. METHODS Fifty-four patients (50 invasive, 4 in-situ); 51 mass, 3 microcalcification; mean diameter 12 (5 to 23) mm were treated by a stereotactically guided 805 nm laser beam via a fiber in a 16G needle delivered to the cancer. One to 8 weeks later the coagulated lesions were surgically removed for pathologic evaluation. In 2 additional patients, the laser-treated tumors were not removed but were monitored by mammography, ultrasonography, and needle core biopsy. RESULTS None of the patients sustained any adverse effect. The average treatment time was 30 minutes. Pathology analysis revealed a 2.5 to 3.5 hemorrhagic ring surrounding the necrotic tumor. Under steady conditions, in two groups of 14 patients, 93% and 100% of the tumors showed complete destruction, with no residual cancer report. In the 2 unresected cases kept under surveillance for 6 to 24 months, the laser-treated tumors first showed shrinkage, followed by a 2 to 3 cm oil cyst. Fibrosis was demonstrated on needle core biopsies. CONCLUSIONS Laser energy delivered through a stereotactically guided needle appears to ablate mammographically detected breast cancer. A multicenter clinical trail is planned.

Status of HER-2 in male and female breast carcinoma

BACKGROUND HER-2 overexpression is seen in 20% to 30% of invasive female breast carcinomas. Besides being prognostic, HER-2 may also be predictive of response to therapy. Similar studies in male breast carcinoma are lacking. We compared the overexpression and amplification of HER-2 in female and male breast carcinoma. DESIGN Formalin-fixed, paraffin embedded archival material from 58 invasive male breast carcinomas and 202 invasive female breast carcinomas were immunostained for HER-2. Scoring was performed according to established guidelines. Each case was also assessed for HER-2 gene amplification by fluorescence in-situ hybridization (FISH) utilizing the PathVysion assay (Vysis corporation, Downers Grove, Illinois). RESULTS There were 58 male patients who ranged in age from 38 to 92 years (mean 63). Thirty-five (60%) were T1 lesions and 23 (40%) were T2 lesions. Twenty-five patients (43%) had positive lymph nodes. One (1.7%) of the 58 cases showed 3+ staining of HER-2. The remaining 57 cases did not show overexpression. There was no amplification of the HER-2 gene in any of the cases. There were 202 female patients who ranged in age from 26 to 96 years (mean 52). In all, 129 (64%) were T1 lesions, 61 (30%) were T2 lesions, and 13 (6%) were T3 lesions. Fifty-two (26%) showed positive staining with HER-2 (44 cases 3+, 8 cases 2+). The remaining 150 (74%) did not show overexpression. There was amplification of HER-2 gene in 55 (27%) of the cases. Two of the cases negative by FISH were 3+ positive by IHC. CONCLUSIONS HER-2 is overexpressed in approximately 27% of female breast carcinomas. A high level of correlation is demonstrated between IHC and FISH techniques. Gene amplification of HER-2 does not play a role in male breast carcinoma. The rate of single-copy overexpression of HER-2 appears identical in male and female breast carcinoma.

Fine-needle aspiration of clinically suspicious palpable breast masses with histopathologic correlation

BACKGROUND The purpose of this study was to compare the diagnostic accuracy of fine-needle aspiration (FNA) of clinically suspicious palpable breast masses in women younger and older than 40 years of age. METHODS All women who had FNA biopsy with subsequent tissue biopsy were included. The cytologic diagnoses were classified into three groups: malignant, suspicious, or benign. Histopathologic correlation was based on either a needle core biopsy, an excisional biopsy, or a mastectomy specimen. RESULTS A total of 1,158 fine-needle aspirations performed between 1982 and 2000, on women being evaluated for a clinically palpable breast mass were included in the study. The patients were divided into two groups: group I consisted of 231 patients aged 40 years and younger, and group II consisted of 927 patients aged 41 years and older. In group I there were 117 (51%) malignant FNA diagnoses, and only 1 (1%) false-positive case, subsequently diagnosed on histopathologic material as an atypical papillomatosis. There were 20 (9%) cases diagnosed as suspicious on FNA. On histopathology 10 were malignant, and 10 were benign. Of the 91 (39%) cases interpreted as benign, only 1 (1%) was a false negative. In group II, which comprised 927 patients, there were 693 (74%) malignant FNA diagnoses, and 3 (less than 1%) false-positive cases, which on follow-up histopathologic examination revealed 2 atypical ductal hyperplasias and 1 atypical papilloma. There were 90 (10%) cases diagnosed as suspicious on FNA. On histopathology, 68 were malignant and 22 were benign. Of the 131 (14%) lesions interpreted as benign, there were 18 false-negative cases (14%), which included 17 infiltrating carcinomas and 1 ductal carcinoma in-situ. Twelve (1%) of the cases were inadequate for the study. CONCLUSIONS The sensitivity, specificity, and positive predictive values were remarkably high and comparable in both groups: group I had 99% sensitivity, 99% positive predictive value, 99% specificity, and 99% negative predictive value; and group II had 98% sensitivity, 97% specificity, 99% positive predictive value, and 86% negative predictive value. The overall rate of false-positive (less than 1%) and false-negative cases (9%) is comparable with published literature. Suspicious cases should be further evaluated, as our study revealed more than 50% to be malignant. The incidence of malignancy in patients presenting with a clinically palpable breast mass with follow-up biopsy was 51% in patients aged 40 years and younger and 74% in patients aged 41 years and older. Fine-needle aspiration is an excellent diagnostic tool in assessing clinically palpable breast masses.

Occult metastases in sentinel nodes of 200 patients with operable breast cancer.

Background:Up to 30% of patients with operable breast cancer and negative regional lymph nodes experience disease recurrence within 10 years. Serial sectioning and immunohistochemical staining of these nodes have revealed 9% to 30% occult metastases.Methods:Sentinel nodes from 200 patients with T1 and T2 invasive breast carcinoma were step-sectioned at 2- to 3-mm intervals, fixed in 10% formalin, and embedded in paraffin. Sections were taken from the face of the blocks and stained with hematoxylin and eosin (H&E). The blocks were then cut completely, and sections at .25-mm intervals were stained with cytokeratin and examined.Results:Tumor metastases were found in 34 patients when the sentinel nodes were examined at 2- to 3-mm intervals and in an additional 51 patients when the nodes were sectioned in their entirety at .25-mm intervals and stained with cytokeratin, bringing the total number of patients with metastases to 85. Of the 51 patients whose metastases were detected by 2- to 3-mm sectioning and cytokeratin staining, 27 had isolated tumor cells and 24 had clusters of innumerable malignant cells, all of which were visualized and confirmed by H&E staining of the adjacent sections.Conclusions:Histologic examination of sentinel nodes of patients with invasive breast cancer sectioned at 2- to 3-mm intervals and stained with H&E significantly underestimates nodal metastases. Sectioning of the entire sentinel nodes at .25-mm intervals and staining with cytokeratin detects metastases as either isolated cells or as clusters.

Cell-to-cell fusion of lens fiber cells in situ: correlative light, scanning electron microscopic, and freeze-fracture studies.

We have discovered cell-to-cell fusion between fiber cells of adult frog lenses in situ. Stereo scanning electron microscopy (SEM) revealed fusion between neighboring fiber cells in radial cell columns (RCCs) and in the same growth ring, respectively. Cell-to-cell fusion of fiber cells in the lens produced fusion zones that in cross-section were larger and of different polygonal shapes than unfused fiber cells. The shape and sizes of fiber cells surrounding fusion zones and the alignment of RCCs were also altered. Serial sectioning through fusion zones confirmed that they were areas of cell-to-cell continuity established by the union of neighboring fiber cells as seen by SEM. Fusion zones represent a previously unrecognized intercellular pathway in the adult frog lens. Although numerous fusion zones were seen throughout the lens cortex and nucleus, cell-to-cell fusion was rarely observed to have occurred between elongating fiber cells. Interestingly, communicating junctions with an unusual ultrastructure that closely resembles the appearance of membranes in the process of fusion demonstrated in other systems were frequently seen in the region of the superficial cortex where fusion zones were most numerous. The fact that such unusual communicating junctions were not found in any other region of the lens leads us to speculate that structural changes in fiber cell communicating junctions may herald the formation of fusion zones and that the initial site of cell-to-cell fusion between fiber cells may be within communicating junctional plaques.

Assessment of Her-2/Neu status by immunohistochemistry and fluorescence in situ hybridization in mammary Paget disease and underlying carcinoma.

HER-2/Neu overexpression is seen in 20% to 30% of invasive breast carcinomas and has been reported in as many as 80% of high-grade infiltrating carcinomas. Earlier studies have suggested that 100% of the tumor cells in mammary Paget disease show overexpression of HER-2 protein. We undertook this study to assess HER-2 status of mammary Paget disease and of the underlying breast carcinoma, when present, by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Formalin-fixed, paraffin-embedded tissue from 20 cases of mammary Paget disease were analyzed for HER-2 status by IHC and FISH. IHC for estrogen receptor (ER) was also performed. The patients ranged in age from 34 to 88 years, with a mean age of 62 years. Eighty percent of the cases showed strong overexpression (3+) of HER-2 protein by IHC, and all of these cases showed more than 5-fold amplification of the HER-2 gene by FISH. The remaining 4 cases, which were negative for HER-2/Neu by IHC, showed no amplification by FISH. All of the latter cases expressed ER, whereas no case that overexpressed HER-2 expressed ER. Sixteen cases had an underlying tumor, which was in situ in 6 cases. The underlying tumors were identical to the Paget disease with respect to their HER-2/Neu overexpression by both IHC and FISH. HER-2 overexpression was identified in 80% of our cases of Paget disease. There was 100% concordance between HER-2 protein overexpression by immunohistochemistry and gene amplification in both the Paget and the underlying tumor. Moreover, all of the cases negative for HER-2 overexpression expressed ER, whereas those positive for HER-2 did not.

Laser Therapy of Breast Cancer with 3-Year Follow-up

Abstract:  Breast cancer is the commonest female malignancy in the United States and is increasingly being detected at a non‐palpable stage by annual mammography. Minimally invasive methods of its local treatment have been recently introduced as alternative to its surgical removal. The case reported in this article illustrates the advantages of in‐situ ablation with minimal discomfort to the patient and deformity of the breast. More importantly, it demonstrates the absence of any adverse effect on health and survival of the patient during this intermediate period of follow‐up.

Fixation Time Does Not Affect the Expression of Estrogen Receptor

The purpose of this pilot study was to determine the impact of the length of fixation in 10% buffered formalin on the expression of estrogen receptor by immunohistochemical analysis. We studied tissue samples from 10 invasive breast cancer cases after fixation for 1, 3, 6, and 9 to 10 hours. The tissue was processed immediately after fixation, resembling routine practice. Then the 40 blocks were incubated with antiestrogen receptors SP1, 6F11, and 1D5. The stained slides were reviewed and scored. We found no significant difference in the intensity of the stain or the percentage of cells stained regardless of the time in fixation or the antibody used. Fixation times between 1 and 9 hours in 10% formalin do not seem to have an impact on the expression of estrogen receptor by immunohistochemical analysis, at least in these high-expressing tumors.

Stereotaxic Interstitial Laser Therapy of Early-Stage Breast Cancer

Abstract: Coagulation leading to fibrosis of mammo‐graphically detected breast cancers by interstitial laser therapy was tested as an alternative to surgical removal. Availability of computerized stereotaxic digital imaging allows the precise placement of laser and thermal needles into the target tumor and its controlled ablation by heat. The methodology of interstitial laser therapy (ILT), evolution of the subsequently removed tumors, and their histologic appearance are outlined.

Image-guided surgery of small breast cancers

BACKGROUND Widespread screening mammography has resulted in detection of many breast cancers smaller than one cm. Image-guided percutaneous needle sampling provides accurate diagnostic and prognostic information for adjuvant therapy. Less invasive methods based on imaging techniques are emerging as an alternative to wire localization and lumpectomy. DATA SOURCES Information presented in this overview was provided by seven investigators from five medical centers in the United States. These researchers are currently developing various techniques of image-guided percutaneous therapy of small (Tis, 1) breast cancers. CONCLUSIONS Several percutaneous treatment modalities for treatment of early breast cancer, either excisional or in-situ ablative, are described in this overview and their potential applications are discussed.