Intraductal Papillomatosis Research Articles

Use of fiberoductoscopy for the management of pathological nipple discharge: ten years follow up of a single center in China.

Pathological nipple discharge (PND) is usually associated with benign intraductal papilloma, which has a higher malignant rate than other benign tumors in most cases. Fiberoductoscopy (FDS) is an alternative possibility in diagnostic and finding lesions in PND patients. Previously, the bloody discharge was presumed to show papilloma or breast cancer. However, as we started using FDS, papilloma or cancer also can be found in the cases with a transparent or yellow discharge. This study investigated the value of FDS for the diagnosis and locating of intraductal lesions in cases with nipple discharge. A retrospective analysis of 3,696 cases that initially presented with pathologic nipple discharge was performed. There were 4,456 FDSs performed, and the correlations between the FDS findings for distinct types of lesions and the pathological diagnosis were determined. Among the 2,816 cases of elevated lesions, FDS confirmed 1,933 cases of intraductal papilloma, 584 cases of intraductal papillomatosis, and 299 cases of intraductal carcinoma. Among the 880 cases of non-elevated lesions, FDS confirmed 380 cases of duct dilation, 350 cases of duct inflammation, 136 cases of duct dilation and inflammation, and 14 cases of ductal carcinoma in situ (DCIS). All patients followed up 3 months to 12 years. There were 241 DCIS in total, and 8 cases had local recurrence, 2 cases had metastasis. Invasive ductal carcinoma, 41 cases, 3 had recurrence and 3 had metastases, and 1 for death. Invasive lobular carcinoma 23 cases, recurrence 2 cases, metastasis 1 case. FDS has a high positive predictive rate and correlates well with the results of the pathological examination. The advantage of FDS is that it can observe the lesions, increasing the detection rate of early stage breast cancer, simple to operate, low cost, and no need for the appointment, appropriate for Chinese conditions.

Breast papillary lesions: a retrospective analysis from oncology set up of Pakistan

Background: Papillary lesions of the breast are a heterogeneous group of breast lesions that are difficult to diagnose as benign or malignant. These lesions have varied morphologic features that carry differing prognostic implications for affected patients. Accurate diagnosis is required to ensure that effective treatment is achieved. Papillary lesions can have increased risk of carcinoma and recurrence, in these patients even for lesions yielding a benign concordant diagnosis of papilloma at percutaneous biopsy, surgical excision may be warranted. Malignant lesions are usually surgically treated. Depending on stage-adjuvant chemotherapy and/or radiation therapy is given.Methods: A retrospective study was conducted at Shaukat Khanum Memorial hospital and Research Centre Lahore Pakistan. We reviewed the electronic records of diagnostic and registered patients from January 2007 till December 2017 in women imaging section, in age range of 25 to 75 years. Total 150 diagnosed patients with benign or malignant breast papillary lesions were selected and their conventional breast imaging (mammography and ultrasound) and histopathology was retrospectively analyzed on SPSS.Results: Patients were predominantly asymptomatic or on follow-up to an abnormal mammogram. Of the 150 cases most of the patients had intra-ductal papilloma followed by invasive papillary carcinoma and intra cystic papillary carcinoma. Few patients had intra-ductal papillomatosis and invasive micro papillary carcinoma.Conclusions: Conventional breast imaging remains the first main stay and quite sensitive in detecting breast papillary lesions leading to early detection and management.

Assessment of the cytokine-producing resource of tumor biopsy samples from patients with invasive carcinoma of no special type and with non-malignant breast diseases

Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1β and the ratio of IL1β/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1β, as well as the ratio of IL1β/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.

Abstract 3703: SHetA2 decreases mitoses and growth, and alters pathology of MNU-induced rat mammary tumors.

Abstract Background: SHetA2 (NSC721689) is a non-toxic chemoprevention drug that has completed pre-clinical testing by the NCI-RAID and RAPID programs and will be evaluated in a Phase 0 clinical trial under development. Previous studies found that SHetA2 reversed the cancerous phenotype and prevented carcinogenesis in organotypic cultures of human ovarian cancer and endometrial cells. The objective of this project was to evaluate the effects of oral SHetA2 on histologic features of tumors induced by the nitrosomethylurea (MNU) carcinogen in Sprague-Dawley rats. Methods: SHetA2 was administered to 3 treatment groups of 15 animals each in a Teklad diet formulated to contain doses of 0 (control), 25 (low dose) and 50 (high dose) mg/kg/day. Five days after initiation of treatment, each rat was injected with 11.25 mg of MNU into the peritoneum and the animals were continued on their respective diets. The first palpable tumors were noted 48 days after MNU injection. Tumors volumes were measured weekly. Four animals in the control group were euthanized early on days 58, 63, 78 and 82, one animal in the low dose group was euthanized on day 78 and one animal in the high dose group was euthanized on day 74 due to the excessive sizes of their tumors. The remaining animals were euthanized on day 85 and the tumors were collected for histologic evaluation. H&E stained slides of the tumors were reviewed for histologic features in a blinded manner. A linear mixed model was used to compare the growth rate of tumor volumes. The fixed effects included treatment group and days. An unstructured covariance matrix was used in the model. The numbers of mitoses in the tumors of the different treatment groups were compared using a linear mixed model. Results: Tumor growth rate was significantly lower in the high dose group in comparison to the control group (p=.004) and the low dose (p=.003). No significant difference (p=.716) in growth rate was observed between low dose and control groups. The number of mitoses counted in the tumors was significantly smaller in the high dose than in the control group (p=.004), but no significant difference was observed between low dose and control groups (p=.945). The histology of the tumors included fibrocystic disease, intraductal papillomatosis, adenoid cystic carcinoma, papillary carcinoma, papillary and adenoid cystic carcinoma and carcinoma. When compared per animal, there were no significant differences in the histologies between the treatment groups, however when each tumor was considered an individual data point, there was a statistical trend that both doses of SHetA2 decreased the percentage of papillary carcinoma and increased the percentages of adenoid cystic carcinoma, (high dose vs control: p=.058; low dose vs control: p=.058). Conclusion: SHetA2 administered in the diet reduced cell proliferation, growth and aggressiveness of the pathologic diagnosis of mammary tumors in MNU-treated rats. Citation Format: Stan Lightfoot, Daniel Zhao, Elangovan Thavathiru, Doris Mangiaracina Benbrook. SHetA2 decreases mitoses and growth, and alters pathology of MNU-induced rat mammary tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3703. doi:10.1158/1538-7445.AM2013-3703

Intraductal papillomatosis of the breast in adolescents

Intraductal papillomatosis of the breast in adolescents

Is Further Diagnostic Surgery Necessary for the Benign Papillary Lesions that Are Diagnosed by Large Volume Vacuum Assisted Breast Biopsy?

papillary carcinoma in situ), 침습적유두상암(invasive papPurpose: There is ongoing controversy regarding the management of papillary lesions that are diagnosed by core needle biopsy (CNB). The development of vacuum assisted biopsy now permits non-operative removal of papillary breast lesions. Our aim was to evaluate whether the papillary lesions diagnosed by vacuum assisted breast biopsy (VABB) can be followed up without further diagnostic excision. Methods: From January 2003 to July 2009, a total of 4,655 US-guided mammotome excision were performed in 3,714 patients at Kangnam CHA Hospital. Out of 4,655 lesions, 156 lesions were proved to be papillary lesions. Among these, 82 lesions that had histologic findings that were consistent with benign papillary lesions and that were followed up for more than 2 years without further diagnostic surgical excision were collected and retrospectively analyzed. Ultrasonographic followup was done at 3-6 month intervals to assess for recurrence. The mean follow up period was 49.6 months. Results: The pathologic diagnoses for the 82 lesions obtained via VABB were benign intraductal papilloma and papillomatosis. Half of the lesions were palpable and 50.0% (41 cases) were nonpalpable. Twenty eight lesions (34.1%) were classified as BIRADS category 3, 50 lesions (61.0%) were category 4A, 3 lesions (3.7%) were category 4B and only 1 lesion (1.2%) was category 5 according to the ultrasound exams. No local recurrence developed during the follow up period that needed surgical re-excision or rebiopsy. None of those diagnosed as benign lesions at VABB were upgraded to a more advanced lesions. Conclusion: The benign papillary lesions that are diagnosed and excised by mammotome may not need further diagnostic surgical re-excision if surgeons are sure that the targeted lesions were excised completely.

Papillary Lesions of the Breast at Percutaneous Core-Needle Biopsy

To retrospectively review the imaging and histologic findings in patients in whom a benign papillary lesion was diagnosed at core-needle breast biopsy. This retrospective study was approved by the institutional review board at each institution; patient consent was not required. The study was HIPAA compliant. The authors reviewed the findings from 42 patients (age range, 26-76 years; mean age, 54.3 years) with 43 benign papillary lesions diagnosed at core-needle biopsy. Thirty-six (84%) of the 43 lesions were surgically excised, and seven (16%) were followed up with long-term imaging. The authors assessed the radiographic findings, the histologic findings at core-needle biopsy, and the findings at subsequent surgical excision or imaging follow-up. Statistical analysis was performed on a per-patient basis and included the Blyth-Still-Casella procedure to construct exact 95% confidence intervals (CIs) and the Fisher exact test. At core-needle biopsy, lesions were diagnosed as papilloma (n = 29), sclerosing papilloma (n = 8), and benign papillary lesions not otherwise specified (n = 6). For the 36 lesions that were surgically excised, histologic follow-up showed no residual lesion in 10, intraductal papilloma in 14, intraductal papillomatosis in two, papilloma with adjacent foci of atypical ductal hyperplasia (ADH) in eight, and well-differentiated papillary ductal carcinoma in situ (DCIS) in two. Mammographic follow-up in the remaining seven lesions revealed stable calcifications in five (at 28-55 months) and no residual lesion in two (at 26-29 months). In nine of the 42 patients (21%), the diagnosis was upgraded to either ADH or DCIS (exact two-sided 95% CI = 11.4%, 36.4%). The results strongly suggest that papillary lesions diagnosed as benign at core-needle biopsy should be surgically excised because a substantial number of lesions were upgraded to ADH and DCIS at excision.

Mammary lesions diagnosed as "papillary" by aspiration biopsy: 70 cases with follow-up.

The authors reviewed smears from fine-needle aspiration biopsies (FNAB) diagnosed as "papillary lesions" and correlated the cytologic findings with the final diagnoses at excision. The objective of the current study was to determine the accuracy of FNAB diagnosis of a papillary lesion in distinguishing true papillary from nonpapillary proliferations and to evaluate cytologic criteria for the distinction of papillomas from true papillary malignancies and their cytologic look-alikes. The cytopathology database at the New York University Medical Center was searched for women who underwent surgical excision after a breast FNAB diagnosis of a papillary lesion. The FNAB smears and corresponding slides from excisional biopsies were reviewed. The smears were evaluated and graded for the following features: cellularity, architecture, presence of fibrovascular cores, single cells, columnar cells, cellular atypia, myoepithelial cells, foamy histiocytes, and apocrine cells. The F test was used to determine the statistical significance of differences between true benign papillary lesions (papilloma) and adenocarcinomas (in situ and invasive). At the time of excision, 46 (66 %) cases were benign (23 solitary intraductal papillomas, 6 intraductal papillomatosis, 11 examples of fibrocystic change, and 6 fibroadenomas) and 24 (34 %) were malignant (1 low-grade phyllodes tumor [PT], 23 ductal in situ and invasive carcinomas). Of the 23 carcinomas, 3 (13 %) were classified as benign papillary lesions on FNAB and 19 (86 %) were classified as either atypical or suspicious. One case of low- grade PT originally was classified as benign on FNAB. There were four false-negative diagnoses; two were due to sampling and two to interpretative errors. A portion of the lesions classified as papillary were fibroadenomas and examples of fibrocystic change on excision and all of these were correctly classified as benign on FNAB. Of the histologically proven papillomas, 62% were correctly classified as benign on FNAB and none were designated as being positive for malignancy. Statistically significant features of distinction between papillomas and carcinomas included cellularity (P = 0.016), cellular atypia (P = 0.0053), and the presence of cytologically bland columnar cells (P = 0.04). Low-grade ductal carcinoma in situ (cribriform and micropapillary types) and tubular carcinoma represented the most difficult differential diagnostic problems. A significant portion of lesions displaying a papillary pattern on FNAB are nonpapillary on follow-up. Among benign processes, fibrocystic change and fibroadenoma may closely simulate papilloma on cytology. However, in spite of the overlapping features of true papillary lesions and their cytologic look-alikes, the majority can be classified accurately into benign or atypical (and above) categories by FNAB. Lesions that fall short of a definitive benign diagnosis should be placed into an indeterminate category. This approach will guide the surgeon to provide better patient management.

Increased incidence of benign breast disease in female renal transplant patients receiving cyclosporin.

Unlike other cancers, breast cancer does not occur at increased frequency in renal transplant patients but fibroadenomata may be more common as a result of exposure to cyclosporin. In order to determine the incidence of benign breast disease in renal transplant patients at Monash Medical Centre, current female patients were studied. The study was divided into two parts: (i) a retrospective review of those who presented with clinically detectable breast lumps; and (ii) mammographic screening of current female transplant patients who had been transplanted for more than 1 year. In the retrospective study there were 11 patients with 16 breast lumps among a total of 85 patients. All were confirmed by biopsy. The mean age at diagnosis of breast lumps was 41.5 years (range 25-70 years). The mean time to presentation was 3.5 years after transplantation. Nine out of 11 patients had benign breast disease including fibroadenoma (six patients), fibrocystic disease (two patients) and intraductal papillomatosis (one patient). Two patients had breast cancer. Five of the patients with fibroadenoma had multiple lumps and a recurrent course. All patients with fibroadenomata had received cyclosporin. In the second part, 54 patients were further screened. The mean duration of transplantation was 6.4 years (range 1.25-18.5 years). Eighty-seven per cent of the patients had received cyclosporin, and 80% had a negative (normal) study. Seven of 54 had abnormalities including cysts and calcification, of whom two patients had fibroadenomata. Four patients had 'dense mammograms', all of whom received cyclosporin as a part of their immunosuppression. No breast cancer was detected during the study. The incidence of benign breast disease in the female transplant patients studied was far greater then the general population. The increase in fibroadenomata, in particular, may relate to the use of cyclosporin.

Three-Dimensional Breast Ultrasound Imaging in Patients with Nipple Discharge: A Pictorial Review of 27 Patients

Background High-resolution, high frequency, three-dimensional (3D) breast ultrasound can be used as the first-line, noninvasive imaging tool for the evaluation of patients with breast discharge. Patients and Methods From June 2000 to April 2001, the medical records of 27 consecutive patients with pathologic nipple discharge were evaluated using 3D breast ultrasound equipped with automatic volume scan. Four patients did not undergo surgery because only mild duct dilation, without any visible tumor or vessel structures (around the dilated duct), was found on sonography. Of the remaining 23 patients who subsequently had surgery, four had watery discharge, seven had bloody discharge, five had serous discharge and seven had serosanguineous discharge. Results The final diagnoses were based on determinate histopathology from surgical specimens: intraductal papillary carcinoma (one), intraductal papillomatosis (five), and intraductal papilloma (17). In one of the four patients who did not have surgery, the bloody discharge disappeared 2 months later without recurrence during subsequent follow-up. Conclusions The availability of high-frequency linear transducers now enables us to visualize the mammary duct in detail. The 3D volume images can be reviewed immediately in the bedside ultrasound machine or retrospectively in the computer, so that the relationships between nipple, duct and tumor can be clearly identified. This advantage is one that conventional 2D ultrasound cannot provide.

Ductal carcinomain situ of the breast

Objective: To investigate the clinical characteristics, treatment and prognosis of ductal carcinomain situ (DCIS) of the breast. Methods: Clinicopathological and follow-up data were collected in 52 patients with DCIS. Results: The clinic data showed that 50 patients had signs of breast lumps or/and nipple discharges, 2 patients presented abnormal mammography; 2 patients had lymph node involved; and 14 patients were accompanied with intraductal papillomatosis. All patients were received surgical therapy. The follow-up data showed 1 patient locally recurred after lumpectomy, and was underwent mastectomy again, then cured. There were no patients died of DCIS. Conclusion: Mastectomy should be a standard surgical mode, and the prognosis of DCIS was favorable, but mammography for screening of asymptomatic women should be strengthened to find DCIS.

Pitfalls in frozen section interpretation: a retrospective study of palpable breast tumors.

The use of frozen sections for purposes of diagnosis is recognized to involve a degree of uncertainty. A retrospective study of breast specimen frozen section diagnoses was undertaken in order to analyse the major pitfalls. Hard copy files from our archives relating to symptomatic (palpable) breast specimens obtained between 1983 and 1996 were reviewed. The review revealed 23 errors among the diagnoses on 2110 frozen specimens. Twenty-two of them were false-negative and 1 (a case of multiple intraductal papillomatosis with atypical ductal hyperplasia) was false-positive for malignancy. The factors contributing to the pitfalls were: 1) misinterpretation; 2) poor quality of the frozen sections (artifacts making the diagnosis difficult); 3) sampling errors during sectioning; 4) ignorance of the macroscopic features; 5) lesions difficult to interpret; 6) ductal carcinoma in situ as the only lesion in the specimen; and 7) sections not deep enough. Several of the factors sometimes occurred simultaneously. Although the number of errors is relatively low, more stress should be placed on the preoperative diagnosis of breast lesions. Breast surgery frozen section should be used as rarely as possible for diagnostic purposes, despite the generally good diagnostic accuracy. However, it is reasonable to use frozen sections widely until the given preoperative diagnostic tools allow an appropriate preoperative workup, because it is the only way to keep histopathologists trained to interpret frozen sections.

Preoperative Diagnosis of Breast Diseases by Dynamic MR Mammography:Cut-off Point Establishment for Signal Intensity Ratio.

We have demonstrated that the dynamic study for breast lesions by magnetic resonance imaging(MRI)can differentiate benign from malignant lesions objectively.The cases were 57 histopathologically appraised breast lesions, including 20 cases of breast cancer, 28 cases of mastopathy, 8 cases of fibroadenoma and 1 caseof intraductal papillomatosis. We plotted time-signal intensity ratio curves and then determined 95% confidence intervals, plotting the signal intensity ratio for both breast cancer and mastopathy every 30 seconds during dynamic magnetic resonance mammography(MRM)after gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)administration, and further established cut-off points to differentiate between them. We then tried of estimate objectively the benign-malignant differentiation to breast lesions by confirming their signal intensity ratio to be more or less than the cut-off points. We advocate this procedure, and call it the " dynamic ratio method. " As a result, we found highly significant differences between breast cancer and mastopathy at 30 and 60 seconds after Gd-DTPA administration(P < 0.0001). We also confirmed that the cut-off point for the dynamic ratio method was equivalent to 1.4 and 1.8 times the precontrast signal intensity value at30 and 60 seconds after administration of Gd-DTPA respectively. By performing this dynamic ratio method preoperatively we can assess objectively not only the malignancy of breast lesions, but also neighboring infiltration, extending intraductal component, and lymph node metastasis. Furthermore, the dynamic ratio method provides detailed information for selecting the appropriate region for breast conserving surgery preoperatively, and can be expected to reduce unnecessary biopsies of benign cases. The dynamic ratio method had a sensitivity of 95.0%, a specificity of 81.1% and a positive predictive value of 73.1%. Also, for detectinginvasive ductal carcinoma, the sensitivity of the dynamic ratio method was 100.0%.

Clinical and pathological features of breast disease in Cowden's syndrome: An underrecognized syndrome with an increased risk of breast cancer

Cowden's syndrome (CS), or multiple hamartoma syndrome, is an autosomal dominant disorder associated with benign skin tumors and an increased risk of breast cancer. In an effort to understand the basic mechanisms regulating the development of breast cancer in this patient population, as well as to define diagnostic aspects of the disorder, we describe for the first time the clinical and pathological spectrum of breast disease in CS. We obtained the clinical histories and examined the histopathology of 59 cases from 19 women with CS sent to us from a variety of institutions. The 19 women showed a spectrum of benign histopathological findings, including ductal hyperplasia, intraductal papillomatosis, adenosis, lobular atrophy, fibroadenomas, and fibrocystic change. Seventeen (89%) showed features suggestive of a breast hamartoma. Fourteen women (74%) showed malignant disease, most of which was ductal carcinoma. Twelve patients (86%) showed ductal carcinoma in situ (DCIS), and 12 (86%) showed infiltrating ductal carcinoma. One patient had only DCIS and another patient showed both infiltrating tubular carcinoma and lobular carcinoma in situ. Ten patients (71%) actually showed foci of tumor involving densely fibrotic, hamartomatous areas. In summary, we show that women with CS have a spectrum of exuberant benign and malignant breast pathology. A common benign breast lesion in CS is a densely fibrotic hyalinized nodule, whereas the most frequent breast malignancy is ductal carcinoma.

PREOPERATIVE DIAGNOSIS OF BREAST DISEASES BY DYNAMIC MR MAMMOGRAPHY

We have revealed that a dynamic study of the breast using MR Imaging technique can estimate objectively benign-malignant differentiative diagnosis. Subjects were 41 cases of breast lesion, including 13 cases of breast cancer, 21 cases of mastopathy, six cases of fibroadenoma and one case of intraductal papillomatosis, and the results of them were investigaged in comparison with histopathological diagnosis. As so the method, we drew up time-signal intensity ratio curve plotting signal intensity ratio at each 30 second of dynamic MR mammography after Gd-DTPA administration. We found a especially high significant difference between breast cancer and mastopathy, within 90 second after Gd-DTPA administration (p=0.0000). Still more, we established cut off point concerning with establishment of 95% confidence interval, that is, at 30 second after Gd-DTPA administration the point equivalent 1.53 at 60 second equivalent 2.00, at 90 second equivalent 2.47, and about this estimating maneuver using the cut off point we named Dynamic ratio method. We can estimate preoperatively not only benign-mallignent differentiative diagnosis with breast tumor, but also neighboring infiltration and lymph node metastasis of breast cancer using this Dynamic ratio method. Over again, Dynamic ratio method provides fine information to preoperative decision of resecting region for breast conserving surgery. The efficiency of this method is sensitivity=92.3%, specificity=89.3% and positive predictive value=80.0%

Frozen section diagnosis of breast cancer.

In Savonlinna Central Hospital, Southeastern Finland, 371 frozen section examinations were made from September 1981 to December 1986 to detect breast cancer. There was one false positive diagnosis (0.7%) among the 147 lesions interpreted as carcinoma. Among the 224 biopsies, which were benign on frozen section investigation, four showed carcinoma in paraffin sections (1.8%). Thus, the diagnostic sensitivity of frozen section method was 97.3% (146/150) and the clinical diagnostic specificity 99.5% (220/221) when the diagnosis in the paraffin sections was used as reference. In the four false negative cases the tumour was small and limited to the breast without any evidence of metastases. Two of them were ductal carcinomas, one was microinvasive lobular carcinoma, and one intraductal non-invasive papillary carcinoma. The false positive case had benign intraductal papillomatosis. Our results suggest that the probability of a false diagnosis in frozen section examination increases with diminishing size of the lesion. We suggest that small lesions (less than 1 cm in diameter, or non-palpable) should not be subjected to frozen section examination to avoid unnecessary loss of neoplastic tissue during the preparation process. Instead surgically radical lumpectomy and careful investigation of paraffin-embedded tissue are recommended.

Expression of A and B tissue isoantigens in benign and malignant lesions of the breast.

AB isoantigens are widely distributed in human tissues and loss of AB isoantigen expression has been shown to be an early marker for carcinomatous transformation in some tissues. We therefore applied the Specific Red Cell Adherence Reaction (SRCA) for detection and localization of AB isoantigens in tissue to the study of benign and malignant proliferative lesions of the breast. Twenty-nine lesions in 19 patients were studied. AB isoantigen expression in normal breast tissue was found to be largely confined to the mammary duct system. Loss of AB isoantigen expression was a consistent feature of intraductal carcinoma (3 of 3 cases). Proliferative lesions associated with fibrocystic disease also demonstrated varying degrees of isoantigen loss (simple cystic disease, 3 of 8 cases; intraductal hyperplasia, 6 of 7 cases; sclerosing adenosis, 4 of 4 cases; and intraductal papillomatosis, 7 of 7 cases negative for isoantigen). In contrast to other systems, loss of AB isoantigen expression in the breast appears to be a consistent marker of apparently benign proliferative duct lesions associated with fibrocystic disease, as well as duct carcinoma. The early loss of AB isoantigen expression in these histologically benign lesions supports a possible link between fibrocystic disease and mammary carcinoma. In contrast to other tissues, loss of AB isoantigen expression in proliferative breast lesions is not necessarily evidence of malignancy.

Malignant and benign papillary lesions of the breast

This presentation describes criteria that we found most helpful in classifying the various proliferative changes of the breast and in separating papillary carcinoma from other benign papillary lesions. The criteria we used are easily understood and extremely reproducible. The true incidence of benign proliferative changes in fibrocystic disease and the significance of these lesions in later development of cancer were determined by studying 200 randomly selected cases of fibrocystic disease seen at least 10 years earlier. Of the 200 cases of fibrocystic disease, 40 showed intraductal papillomatosis or terminal duct hyperplasia. None of the patients with benign proliferative lesions for whom we have complete follow-up data (up to 14 years) developed cancer. In order to determine the type of proliferating cells in papillary carcinoma and benign proliferative lesions, some of the recently encountered cases were studied by transmission and scanning electron microscopy and histochemistry. Our ultrastructural and histochemical study suggests that both epithelial and myoepithelial cells participate in papillary lesions of the breast.

Benign human mammary myoepithelioma

A leiomyoma-like, multifocal tumour developed from intraductal papillomatosis in the breast of a 42 year old woman. The spindle-shaped tumour cells were examined by light, electron and polarizing microscopy, which revealed that they originated from immature "precursor" myoepithelial cells. The author suggests that the tumour be called "myoepithelioma". From the morphological characteristics of the tumour the myoepithelial cells appear to be capable of producing leiomyoma-like benign or malignant tumours. The role that has been attributed by some to the myoepithelial cell in the production of epithelial tumours is problematical, in the light of the present finding.

Intraductal papillomatosis of the breast. Report of a case in a ten year old girl: Edward B. Diethrich, Walter W. Hammond, Jr., and Fred Holtz. Amer. J. Surg. 112:80–82, July, 1966

Intraductal papillomatosis of the breast. Report of a case in a ten year old girl: Edward B. Diethrich, Walter W. Hammond, Jr., and Fred Holtz. Amer. J. Surg. 112:80–82, July, 1966