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Microglandular adenosis (MGA) is an uncommon, benign breast lesion that is characterized by a proliferation of small uniform, round glands lined by a single layer of epithelial cells around open lumina with haphazard infiltrative growth in fibrous and fatty breast tissue. Although MGA usually has an indolent course, there is morphologic evidence that MGA can be a precursor for the development of intraductal and invasive ductal carcinoma. To investigate the possibility of such a transition, we studied 17 cases of MGA or atypical MGA some of which had given rise to carcinoma in situ (CIS) and/or invasive ductal carcinoma using the reticulin stain, immunohistochemistry (S-100, p63, Ki-67, and p53), and a molecular approach involving microdissection and high-resolution comparative genomic hybridization and MYC chromogenic in situ hybridization. MGA and carcinomas arising from MGA were typically negative for p63 and positive for S-100 and Ki-67 and occasionally positive for p53. High-resolution comparative genomic hybridization identified recurrent gains and losses in MGA (2q+, 5q-, 8q+, and 14q-) and atypical MGA (1q+, 5q-, 8q+, 14q-, and 15q-). Some examples of MGA and carcinomas arising from MGA harbored few gross chromosomal abnormalities whereas others had considerable genetic instability with widespread aberrations affecting numerous chromosomal arms. Such widespread genetic changes, together with recurrent loss of 5q and gain of 8q were reminiscent of those reported specifically for basal-like, estrogen receptor-negative, and BRCA1-associated breast tumors. Concordant genetic alterations were identified between MGA, atypical MGA, and higher risk lesions (CIS and invasive ductal carcinoma) and in some cases there was an accumulation of genetic alterations as cases “progressed” from MGA to atypical MGA, CIS, and invasive ductal carcinoma. The molecular data suggests that MGA, atypical MGA, and carcinoma arising in MGA in a single case were clonally related. This result implicates MGA as a nonobligate precursor for the development of intraductal and invasive ductal carcinoma. Copyright: © 2009 Lippincott Williams & Wilkins, Inc.

Context.—Vascular tumors comprise a minor subgroup of tumors arising in the breast and represent variants of hemangiomas and angiosarcomas. Diagnostic challenges may arise when differentiating hemangiomas from types I and II angiosarcomas. Ki-67 expression has been used as an adjunct to distinguish between benign and malignant lesions exhibiting histologic overlap at various anatomic sites. Objective.—To investigate the utility of Ki-67 and other cell cycle regulatory proteins (S-phase kinase-associated protein 2 [Skp2], p27, and cyclin D1) in the differential diagnosis of mammary vascular lesions. Design.—Thirty-four vascular tumors (21 hemangiomas and 13 angiosarcomas) of the breast were studied. The Ki-67 index and immunoreactivity for Skp2, p27, and cyclin D1 were determined in each case. Appropriate statistical methods were used. Results.—The mean value of Ki-67 index was statistically different when comparing hemangiomas and angiosarcomas (P < .001). Angiosarcomas were typically positive for Skp2, whereas hemangiomas were negative (P < .001). Sensitivity and specificity cutoffs for Ki-67 index to distinguish hemangiomas from angiosarcomas showed a candidate cutoff point of 175. The mean values of Ki-67 of low-grade angiosarcomas were significantly different from all hemangiomas (P < .001) and also different from the subset of atypical hemangiomas (P = .02). Sensitivity and specificity cutoffs for Ki-67 index to distinguish all hemangiomas from low-grade angiosarcomas showed a candidate cutoff point between 150 and 175. Among angiosarcomas, positivity for Ki-67 was inversely related to that of p27 but not to Skp2 or cyclin D1. This was also true among hemangiomas. Conclusions.—Ki-67 index can be used as a diagnostic tool to distinguish between benign and malignant vascular lesions of the breast. This can be particularly helpful in cases of histologic overlap such as low-grade angiosarcoma and hemangioma.

Nephrogenic systemic fibrosis, previously known as nephrogenic fibrosing dermopathy, is a newly recognized systemic fibrosing disorder primarily affecting patients with chronic renal failure. Patients with skin involvement often develop papules and plaques with peau d'orange surface changes. The lower extremities and trunk are most commonly affected. The most important histologic differential diagnosis is with scleromyxedema. To our knowledge, we report the first case of nephrogenic systemic fibrosis involving the breasts of a 61-year-old woman with end-stage renal disease, clinically mimicking inflammatory breast carcinoma. We propose that nephrogenic systemic fibrosis be considered in the differential diagnosis as a rare possibility when cutaneous changes in the breast suggest inflammatory breast carcinoma in a patient with renal failure.

Microglandular adenosis is a rare proliferative lesion of the breast that may mimic carcinoma grossly and histologically. Although the lesion in its simplest form is benign, it can give rise to carcinoma, which may be found at the time of diagnosis in a minority of cases. Limited follow-up data have indicated no predisposition to develop subsequent carcinoma in patients treated with excisional biopsy for microglandular adenosis when carcinoma was not initially present. Breast conservation has rarely been used in patients with carcinoma arising in microglandular adenosis. We report here the unique 10-year follow-up of a woman who underwent breast conservation treatment for carcinoma that arose in microglandular adenosis.

The success of needle core biopsy procedures and the validity of pathologic diagnoses made on material from the procedures are key determinants in planning the optimal management of a wide variety of breast diseases. The most common diagnostic problems encountered in these biopsy specimens include lobular and ductal proliferations, sclerosing and papillary lesions, cellular fibroepithelial tumors, and minimally invasive or microinvasive carcinoma. This review provides practical guidance to help narrow the differential diagnosis of lesions on needle core biopsies and offers guidelines for the pathologic reporting of these specimens.

Context.—Percutaneous image-guided core biopsy is increasingly becoming the method of choice to evaluate impalpable breast lesions presenting with mammographically detected calcifications or as a mammographically detected mass. Infrequently, a diagnosis of a primary lobular lesion is rendered by needle core biopsy. Although lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) are not themselves detectable by mammography, they can be associated with calcifications. The management of patients with a primary diagnosis of LCIS or ALH on needle core biopsy is uncertain. Recommendations include excisional biopsy, tamoxifen citrate therapy, mammographic surveillance, or a combination of these approaches. Objective.—The purpose of this study was to report the histologic findings of excisional biopsies performed after ALH or LCIS was found in a needle core biopsy. Design.—Hematoxylin-eosin–stained slides of 20 needle core biopsy specimens from patients with a primary diagnosis of LCIS or ALH were retrieved from the consultation and surgical pathology files of New York Presbyterian Hospital–Weill Medical College of Cornell University. Histologic diagnoses were confirmed in all cases. Results.—Fourteen cases of primary LCIS and 6 cases of ALH found on needle core biopsy were identified. Subsequent excisional biopsy of the 14 LCIS cases revealed the following: LCIS, ductal carcinoma in situ, invasive carcinoma (1 patient; 7%); LCIS, infiltrating lobular carcinoma (1 patient; 7%); LCIS, ductal carcinoma in situ (1 patient; 7%); LCIS (8 patients; 57%); and ALH with or without atypical ductal hyperplasia (3 patients; 21%). Among the 6 patients with ALH on needle core biopsy, 1 had infiltrating lobular carcinoma and LCIS and 2 had LCIS in subsequent excision; other excisions for ALH were benign. Overall, 3 (21%) of 14 patients with a primary diagnosis of LCIS on needle core biopsy had a more significant lesion (ductal carcinoma in situ or invasive carcinoma) in a subsequent excisional biopsy. Conclusions.—Data obtained in this study and in previously published reports lead us to conclude that excisional biopsy may be indicated and should be considered when LCIS is found on needle core biopsy in order to more fully examine the biopsy site for coexistent, clinically inapparent intraductal or invasive carcinoma that may be present in about 25% of these patients. The small number of ALH cases studied produced inconclusive results. We recommend that excisional biopsy be considered if atypical ductal hyperplasia is present with ALH in a needle core biopsy or if the diagnosis of the biopsy specimen is discordant with the mammographic findings.

Intraepidermal cytokeratin 7 immunoreactive cells in the non-neoplastic nipple may represent interepithelial extension of lactiferous duct cells Aims: The interpretation of cytokeratin 7 (CK7)-positive cells in the epidermis of the nipple has been controversial. These cells have been described in Paget's disease of the nipple, and they have also been cited as benign `Toker' cells or as Merkel cells. Having observed CK7+ cells in histologically unremarkable nipple biopsies, we sought to assess the distribution of CK7+ cells in Paget's disease of the nipple and in histologically unremarkable nipple. Methods and results: Representative sections from 37 cases of Paget's disease of the nipple and 32 cases of histologically unremarkable nipple were obtained. The histologically unremarkable nipple sections were taken from prophylactic mastectomies (n=17) and from autopsies of patients who did not have breast cancer (n=15). CK7 immunostaining was performed on sections from formalin-fixed paraffin blocks. Sequential sections were immunostained with antibodies to low-molecular weight cytokeratin-CAM 5.2 and HER-2/neu. CK7+ cells were present in the epidermis around the opening of the lactiferous ducts in Paget's disease (95%) and in histologically unremarkable nipple (45%) cases. CK7+ cells diminished in number with increasing distance from the orifice of the lactiferous ducts. The lactiferous duct epithelium in Paget's disease and in histologically unremarkable nipple was CK7+ in all specimens when this element was present. CAM5.2 immunostaining had a similar but weaker pattern of reactivity. HER-2/neu reactivity was seen in 68% cases of Paget's disease and was negative in all cases of histologically unremarkable nipple. Tumour cells in two cases of Paget's disease were CK7−. In one of these, the underlying breast carcinoma was also CK7−, the only CK7− tumour in this series. In the other case, the normal lactiferous duct was CK7+ and no underlying carcinomatous tissue was available to study. Conclusions: The presence of CK7+ cells does not equate to Paget's disease of the nipple. Intraepidermal CK7+ cells in the non-neoplastic nipple can be a manifestation of interepithelial extension of benign lactiferous duct cells. The increased presence of CK7+ cells in Paget's disease probably results either from neoplastic transformation of native intraepithelial lactiferous duct cells or form direct extension/migration of neoplastic cells into the nipple. The distribution of CK7 immunoreactive cells in the nipple epidermis can be helpful in the diagnosis of Paget's disease of the nipple.

So-called acinic cell carcinoma of the breast arises from microgladular adenosis and is not a distinct entity

BACKGROUND To the authors' knowledge, there are no long-term cohort studies of lymphedema, despite the substantial morbidity of arm swelling. The goal of this study was to identify prevalence of breast carcinoma–related lymphedema, time of onset, and associated predictive factors. METHODS A cohort of 923 women consecutively treated with mastectomy and complete axillary dissection at our center between 1976 and 1978 was observed intensively for 20 years. Two hundred sixty-three study subjects (28.5%) who were alive and recurrence free constituted the cohort for the current study. A subset of 52 women (20% of study population) with contralateral mastectomy was analyzed separately. Subjects reported circumferential arm measurements taken using a validated instrument. In addition to providing analysis of clinical and treatment variables, this study is the first to the authors' knowledge to analyze possible etiologic factors in the posttreatment years, such as occupation, general physical activity, and sports/leisure activities. Univariate and multivariate analytic methods were used. RESULTS At 20 years after treatment, 49% (128 of 263) reported the sensation of lymphedema. Arm swelling measurements were severe (≥ 2.0 in [5.08 cm]; patients reported measurement in inches) for 13% (33 of 263 women). Seventy-seven percent (98 of 128) noted onset within 3 years after the operation; the remaining percentage developed arm swelling at a rate of almost 1% per year. Of the 15 potential predictive factors analyzed, only 2 were statistically significantly associated with lymphedema: arm infection/injury and weight gain since operation (P < 0.001 and P = 0.02, respectively). CONCLUSIONS This defined cohort, treated by axillary dissection 20 years ago, documents the high prevalence of lymphedema and its time course. Two significantly associated factors, both potentially controllable, are identified. The current study provides further support for treatments that limit lymph node dissection. The authors are prospectively evaluating patients undergoing sentinel lymph node biopsy. Cancer 2001;92:1368–77. © 2001 American Cancer Society.

We report a case of mammary carcinoma with striking cytoplasmic pigmentation in a 60-year-old Japanese woman who presented with a self-evident nodular lesion in the left breast. Methods and results: After a fine needle aspiration revealing atypical clusters of cells, an excisional biopsy was performed. Histologically, a partially cystic 18 mm lesion containing a 5-mm mural nodule was present. The mural nodule and adjacent thickened epithelium were comprised of atypical cells focally invading into the cyst wall. Striking abundant granular brown pigment resembling melanin was present in some of the neoplastic cells. The differential diagnosis included metastatic melanoma and mammary carcinoma with melanocytic differentiation. After a series of special stains and immunohistochemical studies, the diagnosis of mammary carcinoma with extensive cytoplasmic lipofuscin pigment was rendered. Conclusion: Mammary carcinoma with lipofuscin pigment to the degree seen in this case which mimics melanocytic differentiation has not, to our knowledge, previously been documented.

Small cell carcinoma of the breast is an uncommon neoplasm that has been reported rarely in the literature. The aim of this study was to characterize better the pathologic and immunohistochemical features of this neoplasm. Nine examples of mammary small cell carcinoma were retrieved from the authors' consultation files and reviewed. The patients ranged in age from 43 to 70 years. Two patients had a previous history of cutaneous malignant melanoma and one had prior lobular carcinoma in situ and atypical duct hyperplasia in the same breast as the small cell carcinoma. Eight patients presented with a mass in the breast; one patient had an axillary tumor. Tumor size ranged from 1.3 to 5.0 cm (mean, 2.6 cm). Histologically, the nine tumors had characteristics of small cell carcinoma with high mitotic activity and necrosis. A dimorphic histologic appearance was observed in four tumors. In one instance, this consisted of small cell carcinoma merging with invasive lobular carcinoma. In three cases, small cell carcinoma was present together with invasive, poorly differentiated duct carcinoma; invasive carcinoma with "lobular and gland-forming elements"; and focal squamous differentiation, respectively. Lymphatic tumor emboli were identified in four instances. An in situ component was seen in seven tumors; five were of the small cell type in ducts and two were of the ductal type with high nuclear grade. Immunohistochemical analysis showed consistent staining for cytokeratin markers but variable staining with neuroendocrine markers. Sixty-six percent of the tumors (six of nine) were reactive for chromogranin, synaptophysin, or peptide hormones, including four positive for chromogranin and synaptophysin, one positive for synaptophysin and calcitonin, and one positive for calcitonin alone. One tumor that was reactive for chromogranin and synaptophysin also contained calcitonin immunoreactive cells, whereas gastrin-releasing peptide was present in two other tumors that were also positive for chromogranin. Leu 7 was positive in three cases that were reactive for either chromogranin or synaptophysin. Five tumors were estrogen and progesterone receptor-positive. All tumors were positive for bcl-2 and negative for HER2/neu. Patients were treated by mastectomy (n = 3) or lumpectomy (n = 6). Eight underwent an axillary dissection that revealed metastatic carcinoma in four patients. Seven patients received adjuvant chemotherapy and four patients received radiation. Two patients also received tamoxifen treatment. Metastases developed in two patients (22%) with a follow-up period of 11 and 32 months. All patients were alive at last follow up 3 to 35 months after treatment. When compared with published reports of mammary small cell carcinoma, our results show that the prognosis in these patients may not be as poor as previously suggested.

The purpose of this study was to review surgical histologic findings in women with lobular carcinoma in situ (LCIS) at percutaneous breast biopsy.Retrospective review was performed of 1315 consecutive lesions that underwent percutaneous breast biopsy. Percutaneous biopsy yielded LCIS in 16 (1.2%) lesions. Subsequent surgical biopsy was performed in 14 lesions in 13 women. Histologic findings were reviewed.In five of the 14 lesions, percutaneous biopsy yielded LCIS and a high-risk lesion (radial scar in three and atypical ductal hyperplasia in two); in one (20%) of these five lesions, surgery revealed ductal carcinoma in situ (DCIS). In four of the 14 lesions, the LCIS in the percutaneous biopsy had features that overlapped with those of DCIS; in two (50%) of these four lesions, surgery revealed DCIS (n = 1) or infiltrating lobular carcinoma (n = 1). In the remaining five of the 14 lesions, surgery revealed no DCIS or infiltrating carcinoma. Five (38%) of 13 women with LCIS lesions had synchronous or metachronous infiltrating carcinoma (three ductal, one lobular, one mixed) in the ipsilateral (n = 1) or contralateral (n = 4) breast.Surgical excision was warranted in lesions in which LCIS was found at percutaneous breast biopsy when the percutaneous biopsy histologic features overlapped with those of DCIS, when a high-risk lesion was present, or when there was imaging-histologic discordance. LCIS without these factors was not shown to require surgical excision in our small series, but a larger study is needed. Diagnosis of LCIS at percutaneous biopsy is a marker for women who are at increased risk of ductal or lobular carcinoma in either breast.

To determine the technical success rate of sentinel lymph node biopsy in women with nonpalpable infiltrating breast cancer diagnosed by using percutaneous core biopsy and to determine the frequency with which sentinel lymph node biopsy obviated axillary dissection.Retrospective review revealed 33 women who underwent sentinel node biopsy after percutaneous core biopsy diagnosis of nonpalpable infiltrating breast cancer. Sentinel nodes were identified with radioisotope and blue dye; the procedure was technically successful if sentinel nodes were found at surgery. All sentinel nodes were excised. Axillary dissection was performed if tumor was present in sentinel nodes.Sentinel nodes were found at surgery in 30 women (91%). Sentinel nodes were identified with both radioisotope and blue dye in 22 (73%) of these women, with only radioisotope in six (20%), and with only blue dye in two (7%). Sentinel nodes were found in 12 (80%) of 15 women in the first half of the study versus all 18 (100%) women in the second half (P = .08). Sentinel nodes were free of tumor in 23 (77%) of 30 women. In six (86%) of seven women with tumor in sentinel nodes, the sentinel nodes were the only nodes with tumor.Sentinel node biopsy was successful in 30 women (91%) with nonpalpable infiltrating carcinoma diagnosed with percutaneous core biopsy and obviated axillary dissection in 23 women (70%). Using both radioisotope and blue dye may increase the success rate. A learning curve exists, and success improves with experience.

This study was undertaken to assess the accuracy of percutaneous large-core biopsy in evaluating papillary breast lesions.A retrospective review of imaging-guided large-core breast biopsy of 1077 consecutive lesions revealed that papillary lesions were diagnosed in 34 (3%) cases. Surgical correlation (n = 22) or minimum 2 years' mammographic follow-up (n = 4) were available for 26 papillary lesions. Mammographic and histologic findings in these 26 cases were reviewed.Percutaneous biopsy histology had benign findings in nine lesions, atypical in 10, and malignant in seven. Of seven lesions yielding benign papilloma at percutaneous biopsy, none (0%) had carcinoma at surgery or mammographic follow-up. Surgery revealed carcinoma in one of two lesions yielding papillomatosis at percutaneous biopsy. This lesion was a spiculated mass; surgical biopsy, recommended because of mammographic-histologic discordance, revealed a radial sclerosing lesion and ductal carcinoma in situ (DCIS). Of 10 papillary lesions with atypical ductal hyperplasia at percutaneous biopsy, surgery revealed DCIS in three (30%). Of seven lesions in which percutaneous biopsy yielded papillary DCIS, surgery revealed DCIS in all seven; three (43%) also had invasive carcinoma.Among our patients, diagnosis by percutaneous core biopsy of benign papillary lesions proved to be accurate when concordant with imaging findings. Surgical excision was indicated when diagnosis by percutaneous biopsy revealed atypical papillary lesions or papillary DCIS. A larger series with longer follow-up is required to assess the clinical course of benign papillary lesions without atypia that are not excised after percutaneous large-core breast biopsy.

The optimal treatment of ductal carcinoma in situ (DCIS) is one of the most controversial issues in the management of breast cancer. Identification of factors that affect the risk of local recurrence is very important as the incidence of DCIS increases and the use of breast conservation becomes more widespread. Because the extent of resection may affect the relapse rate, we hypothesized that larger volumes of resection (VR) may account for the lower local recurrence rates we have previously found in elderly patients.Between 1978 and 1990, 173 cases of histologically confirmed DCIS were treated at MSKCC with breast conservation therapy. Of these, complete VR data were available for 126 cases. The VRs thus obtained were divided into two groups,60 cm3 andor =60 cm3, and were evaluated for correlating factors. The patients were divided into three groups by age at diagnosis: younger than 40 years, 40 to 69 years, and 70 years or older.The eldest group had a significantly greater proportion of large VRs (30%) as compared to the middle group (11%) and the youngest group (9%) (P=.03, chi2). Although not statistically significant, the large VR group had a lower 6-year actuarial local recurrence rate (5.6%) than did the small VR group (21.3%) (P=.16, log-rank test). This trend was observed even though adjuvant radiotherapy was used less often in patients who had large VRs.Breast conservation surgery for DCIS in elderly patients is more likely to employ a large VR. This may explain, at least in part, the observation that elderly patients have a lower local recurrence rate.

To determine the frequencies of calcification retrieval and histologic underestimates at stereotactic, 11-gauge, directional, vacuum-assisted breast biopsy.Retrospective review of records revealed 112 calcific lesions in 80 women (aged 31-85 years) who underwent stereotactic, 11-gauge, directional, vacuum-assisted biopsy; a mean of 14 specimens per lesion were obtained. Calcification retrieval was defined as identification of calcifications on radiographs of specimens. Atypical ductal hyperplasia (ADH) underestimates were lesions that yielded ADH at stereotactic biopsy and carcinoma at surgery. Ductal carcinoma in situ (DCIS) underestimates were lesions that yielded DCIS at stereotactic biopsy and infiltrating carcinoma at surgery. Mammograms, stereotactic images, radiographs of specimens, and histologic findings were reviewed.Stereotactic, 11-gauge, directional, vacuum-assisted biopsy removed all calcifications in 51 (46%) lesions, some calcifications in 55 (49%) lesions, and no calcifications in six (5%) lesions. Failure to retrieve calcifications was significantly more likely in lesions 5 mm or smaller (12% [five of 43] vs 1% [one of 69], P = .03), in calcifications with amorphous morphology (21% [three of 14] vs 3% [three of 98], P.03), or if the probe was fired outside the breast (12% [five of 40] vs 1% [one of 72], P = .02). Surgery revealed DCIS in one (10%) of 10 lesions that yielded ADH at stereotactic biopsy. Surgery revealed infiltrating carcinoma in one (5%) of 21 lesions that yielded DCIS at stereotactic biopsy. No underestimation occurred when all calcifications were removed.Stereotactic, 11-gauge, directional, vacuum-assisted biopsy resulted in successful calcification retrieval in 106 (95%) of 112 cases. Histologic underestimation was infrequent.

The clinicopathologic features of 32 metaplastic carcinomas with heterologous osteocartilaginous elements are reported. Each neoplasm consisted of invasive adenocarcinoma accompanied by a cartilaginous or osseous component. In 10 neoplasms, this consisted of cartilage and in 2 the heterologous element was osteoid or bone exclusively. The remaining 20 neoplasms contained a mixture of cartilaginous and osseous components. All patients were women; mean age was 56 years. Twenty-four patients were treated using mastectomy and eight by local excision. Twenty-six patients underwent axillary lymph node dissection. Lymph node metastases were detected in 6 of the 26 (23%) patients who underwent axillary dissection. Clinical follow-up was available for 29 of 32 patients (91%). Local recurrence or distant metastases developed in 6 patients (21%) within 2 years of initial treatment, and 4 of these patients died of metastatic carcinoma. The overall 5-year survival rate was 60%. When compared with control patients with infiltrating duct carcinoma, the group with metaplastic carcinoma tended to have a more favorable prognosis after adjustment for nodal status and tumor size. The prognosis of patients with metaplastic mammary carcinoma with heterologous osteocartilaginous elements is dependent on tumor stage at diagnosis. Immunohistochemical studies for 34BE12, p53, retinoblastoma protein, HER/2neu (polyclonal), epidermal growth factor receptor, and cyclin D1 were performed in 18 cases. Positive immunohistochemical staining was found as follows: 34BE12: n = 13 (72%); p53: n = 11 (61%); retinoblastoma protein: n = 12 (66%); HER2/neu: n = 2 (11%); epidermal growth factor receptor: n = 7 (38%); and cyclin Dm: n = 5 (28%). Positive staining for 34BE12 was observed in the carcinomatous component in 5 (38%) of the neoplasms, in the metaplastic component in 2 (15%), and in both elements in 6 (64%). A p53 staining was observed in the carcinomatous component exclusively in 4 (36%) of 11 p53-positive tumors. No disparity in p53 staining was noted between the epithelial and metaplastic elements in the other p53-positive tumors. Expression of these markers did not correlate with clinicopathologic features such as patient age, tumor size, tumor type, relative proportion of metaplastic elements, and axillary nodal status and was not predictive of disease-free survival.

To assess accuracy and usefulness of placement of a localizing clip after stereotactic, vacuum-assisted breast biopsy.Retrospective review was performed of 57 lesions that underwent placement of a localizing clip after stereotactic vacuum-assisted biopsy with an 11-gauge (n = 42) or 14-gauge (n = 15) probe. The clip was placed when images obtained after stereotactic biopsy suggested that the lesion seen at mammography was removed. Coordinates of the clip on stereotactic images obtained after placement were compared with lesion coordinates determined before biopsy. Surgery was performed in 25 cases. Mammographic and histopathologic findings were reviewed.The distance from clip to lesion site was less than 1 cm in 40 (95%) of 42 lesions that underwent clip placement with the 11-gauge probe versus 11 (73%) of 15 lesions that underwent clip placement after 14-gauge biopsy (P.04). The biopsy site was identified in the surgical specimen in 19 (100%) lesions with clips after 11-gauge biopsy and five (83%) of six lesions with clips after 14-gauge biopsy. No complications occurred.A localizing clip can be placed in proximity to the stereotactic biopsy site through an 11-gauge probe. Clip placement can enable accurate localization for surgical excision.

Tubular carcinoma is a distinctive subtype of invasive, well-differentiated mammary ductal carcinoma that has a good prognosis when treated by modified radical mastectomy. Little is known about tubulolobular carcinoma. The purpose of this study was to compare the frequency of prognostic factors in pure tubular carcinoma (PTC) and tubulolobular carcinoma (TLC). We studied 90 cases of pure PTC and 17 cases of TLC. The following results were found for PTC: size 0.5 to 1.8 cm (mean, 1.2 cm); multifocality in 18 of 90 cases (20%); axillary lymph-node dissection performed in 51 patients; positive axillary lymph nodes in six of 51 cases (12%); recurrences in one of 90 cases (1%), local. The following results were found for TLC: size 0.6 to 2 cm (mean, 1.3 cm); multifocality in five of 17 cases (29%); axillary lymph-node dissection performed in 14 patients; positive axillary lymph nodes in six of 14 cases (43%); recurrences in two of 17 cases (12%); one local and one systemic, each after mastectomy. The relationship between multifocality and positive axillary lymph nodes was as follows: In PTC, the percentage of positive axillary lymph nodes in multifocal cases was 33%, and in nonmultifocal cases, 7%; in TLC, the percentage of positive axillary lymph nodes in multifocal cases was 60% and in nonmultifocal cases, 33%. In conclusion, multifocality and positive axillary lymph nodes were more frequent in TLC than in PTC. Multifocality appeared to predispose to positive lymph nodes in both PTC and TLC. The distribution of prognostic factors suggest that TLC is a higher-grade lesion than PTC. Long-term follow-up is needed to correlate multifocality with recurrence after breast conserving therapy.

To evaluate mammographic findings after stereotactic 14-gauge vacuum biopsy.Retrospective review was performed of results at stereotactic 14-gauge vacuum biopsy in 108 lesions in 100 women. The median number of specimens obtained per lesion was 12 (mean, 14; range, 1-50). In all cases, mammography was performed immediately after vacuum biopsy. Pre- and postbiopsy mammograms were reviewed.Postbiopsy mammograms depicted air at the biopsy site in 78 (72%) of 108 lesions and hematoma in 65 (60%) of 108 lesions. Of 55 lesions depicted as calcifications, postbiopsy mammograms depicted a decrease in the number of calcifications in 45 (82%), including nine cases in which all calcifications were removed. No residual lesion was identified on postbiopsy mammograms in 14 (13%) of 108 lesions; 11 (58%) of 19 mammographic lesions that measured 0.5 cm or less in maximal dimension were completely removed. Nineteen patients underwent a needle localization procedure, at a median 14 days (range, 6-51 days) after vacuum biopsy. In one patient a hematoma was depicted at mammography 10 days after biopsy; in the remaining 18 (95%) patients, mammograms obtained during needle localization depicted no hematoma or air.Air and hematoma were often present on mammograms immediately after stereotactic vacuum biopsy, but these changes resolved rapidly. Stereotactic vacuum biopsy provided wide sampling of calcifications and allowed complete removal of the mammographic lesion in some cases.

The purpose of this study was to evaluate the role of core biopsy in the diagnosis of multiple synchronous ipsilateral breast lesions and to determine the impact of this information on patients' management.Of 371 patients who underwent core-needle breast biopsy under stereotaxic (n = 278) or sonographic (n = 93) guidance, 20 (5%) underwent core biopsy of two mammographically separate lesions in the ipsilateral breast on the same date. Fourteen of these 20 patients subsequently underwent surgery. We retrospectively reviewed the medical, radiographic, and histopathologic records in these 14 patients and in 91 patients with single mammographic lesions diagnosed as carcinoma by means of core biopsy during the same period.In 11 patients, core biopsy revealed two sites of carcinoma. Core biopsy findings in these 11 patients were two areas of infiltrating ductal carcinoma (n = 5), one infiltrating ductal carcinoma and one infiltrating lobular carcinoma (n = 2), one infiltrating ductal carcinoma and one ductal carcinoma in situ (n = 1), and two foci of ductal carcinoma in situ (n = 3). All 11 patients with two core biopsy-proven foci of carcinoma underwent mastectomy. Patients were significantly more likely to be treated with mastectomy if core biopsy revealed two rather than one site of carcinoma (100% versus 38%, p.001).Core-needle biopsy is useful in diagnosing multiple synchronous ipsilateral breast lesions. By showing whether carcinoma is present in one or more sites in the breast, core biopsy can provide information of critical importance in making treatment decisions.

PURPOSE Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185HER2). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185HER2 and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk. RESULTS Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients. Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months. CONCLUSION rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent.

To analyze the mammographic, ultrasonographic (US), and clinical patterns of pseudoangiomatous stromal hyperplasia (PASH).Preoperative mammographic and US images, clinical records, and histologic assessments were reviewed in seven cases of PASH as the sole component or dominant stromal component of a clinically or mammographically defined mass lesion. In five, a PASH tumor was diagnosed at image-guided 14-gauge core-needle biopsy; in two, it was diagnosed at surgical excisional biopsy.Four women were premenopausal, two were postmenopausal, and one 40-year-old patient had iatrogenic primary amenorrhea. Four of seven masses were palpable; three were discovered at mammography. Four masses enlarged over 6 months to 5 years. At mammography, all masses lacked calcifications; six were well defined, and one was spiculated. One was inapparent at US; the remaining six were well defined and hypoechoic.The diagnosis of this rare lesion with image-guided breast biopsy or surgical biopsy is consistent with a well-defined uncalcified mass at mammography and a solid hypoechoic mass at US, usually in a premenopausal woman.

To evaluate the utility of stereotaxic core biopsy (SCB) in diagnosing recurrent carcinoma after breast-conserving therapy (BCT).Of 316 patients evaluated with SCB, 17 (5%) had nonpalpable lesions in breasts previously treated with BCT. Surgical correlation was obtained in 14 patients. SCBs were performed with digital stereotaxic equipment, with patients prone.Carcinoma detected at SCB in 11 (79%) of 14 patients included infiltrating ductal carcinoma (IFDC) in five, ductal carcinoma in situ (DCIS) in five, and infiltrating lobular carcinoma (ILC) in one. Surgical histopathologic findings agreed with core biopsy findings in 10 of these patients. In one patient with two SCB-proved foci of IFDC, one IFDC was identified at mastectomy. In two (14%) patients, SCB revealed atypical ductal hyperplasia; however, DCIS was found at surgical biopsy. In one patient, the SCB finding of fat necrosis was confirmed at surgical biopsy.These data suggest that SCB may be useful in diagnosing recurrent carcinoma in the conservatively treated breast.

The role of stereotaxic core biopsy in evaluating mammographically detected lesions that have a high probability of being malignant is still debated. This study was undertaken to assess the use of stereotaxic core biopsy in evaluating spiculated masses, by determining the frequency with which core biopsy reduced the number of surgical procedures performed in the management of these highly suspicious lesions.Forty-three impalpable spiculated breast masses in 43 patients were sampled with stereotaxic core biopsy. All patients underwent surgery. Patient charts were reviewed to determine the histopathologic findings at stereotaxic core biopsy and at surgery, and the number and type of surgeries performed.Invasive carcinoma was identified at stereotaxic core biopsy in 40 (93%) of 43 patients. Therapeutic surgical procedures were lumpectomy in 28 patients (22 with axillary dissection) and mastectomy in 12. The presence of tumor at the lumpectomy margins led to subsequent mastectomy in one case. One lesion yielded atypical ductal hyperplasia at core biopsy; surgical biopsy revealed ductal carcinoma in situ. Surgical biopsy was recommended in two lesions yielding benign histologies at core biopsy and revealed invasive ductal carcinoma in one. Thirty-three (77%) of 43 patients had the number of surgical procedures reduced by stereotaxic core biopsy; these were patients with carcinoma diagnosed at core biopsy who underwent one-stage lumpectomy with axillary lymph node dissection or mastectomy.Stereotaxic core biopsy reduced the number of surgical procedures in most women with impalpable spiculated breast masses. These data suggest that stereotaxic core biopsy is a valuable diagnostic technique for assessing these lesions, which are likely to represent carcinoma.

Thirteen carcinomas of the breast having in common neoplastic cells with granular to foamy cytoplasm are described. These cells exhibit apocrine differentiation as demonstrated by immunocytochemical and in situ hybridization studies. These tumors can be easily misinterpreted as either fibrohistiocytic or myoblastomatoid (granular cell) tumors. Therefore, the designation of myoblastomatoid (histiocytoid) invasive carcinomas seems the most appropriate for this specific group of apocrine carcinomas.

PURPOSE The present study explores p53 in relation to the following four aspects of node-negative breast carcinoma: epidemiologic risk factors, tumor histopathology, prognosis, and HER2/neu (HER) expression. MATERIALS AND METHODS Immunohistochemical (IH) staining for p53 was performed on formaldehyde-fixed, paraffin-embedded primary invasive carcinomas from 440 node-negative patients with a median follow-up duration of 119 months. RESULTS The IH expression, or lack thereof, of p53 separately or in combination with HER did not prove to be prognostically significant and there was no consistent association of p53 with epidemiologic risk factors. p53 was expressed in 68% of medullary carcinomas (MEDs), which is a significantly higher frequency (P < .001) than in lobular (9%) and duct (23%) carcinomas. p53 was not found in some types of low-grade carcinomas (tubular and papillary), and was observed in a minority of mucinous carcinomas. p53 was present significantly more often in carcinomas with high-grade or poorly differentiated nuclear grade than in low- or intermediate-grade tumors. There was an inverse statistically significant relationship between estrogen receptor (ER) positivity and p53 expression. Tumors with the p53(+)/HER(-) immunophenotype tended to be MEDs or duct carcinomas with a marked lymphoplasmacytic reaction. Infiltrating lobular carcinomas (IFLCs) were largely p53(-)/HER(-). p53(+)/HER(+) carcinomas had the best prognosis. The poorest outcome was associated with the p53(-)/HER(+) immunophenotype. This trend was statistically significant for recurrence-free and overall survival in patients with T1NOMO infiltrating duct carcinoma (IFDC). CONCLUSION The IH demonstration of p53 was not a reliable prognostic indicator in the node-negative breast carcinoma patients studied and it was not associated with major epidemiologic risk factors. The combined immunophenotypic expression of p53 and HER was significantly associated with some histologic types of breast carcinoma and with prognosis in T1NOMO breast carcinoma.

Background. Numerous studies have examined the prognostic significance of HER2/neu(HER) expression in patients with axillary lymph node negative breast carcinoma. Although some investigations suggest that the presence of the altered expression of HER is prognostically unfavorable, the subject remains controversial. This study explores the interaction of HER with three aspects of axillary lymph node negative breast carcinoma: epidemiologic risk factors, tumor histopathology, and prognosis. Methods. Immunohistochemical staining for HER was performed on 10% formalin fixed paraffin embedded primary carcinomas from 440 patients with negative axillary lymph nodes with a median follow-up of 119 months. Results. The immunohistochemical expression, or lack thereof, of HER did not prove to be prognostically significant in this group of patients with axillary lymph node negative breast carcinoma. There was also no consistent association with epidemiologic risk factors. The most striking results concerned the relationship of HER to histopathologic features of the carcinomas. Medullary carcinoma differed from other tumor types because it was HER(+) substantially less often (10%) than were other ductal (49%) or lobular (43%) carcinomas. Conclusion. The results obtained in this study suggest that the immunohistochemical demonstration of HER is not a reliable prognostic indicator for patients with axillary lymph node negative breast carcinoma. This marker was not associated with major epidemiologic risk factors; however, there was a significant correlation between HER and the phenotypic features of breast carcinoma because medullary carcinoma is rarely HER(+). Although the associations may not be a strong enough basis for refining the classification of breast carcinoma, they could be useful for diagnosing individual patients. The changes in HER that are detectable by the immunohistochemical methods used in this study probably do not occur in the earliest stages of mammary carcinogenesis. Cancer 1995;75:1320-6.

Benign heterotopic epithelial inclusions in axillary lymph nodes are an extremely rare condition that must be differentiated from metastatic carcinoma. We describe 2 histologically different examples of benign epithelial inclusions in nonsentinel axillary lymph nodes, each with an unusual clinical presentation.

Lesional breast tissue is often subjected to various needling procedures prior to resection and formal histologic examination. In this article, we describe a series of 29 surgical breast specimens in which histologic examination revealed fragments of benign or malignant epithelium displaced in breast stroma or in lymphovascular channels, associated with the traumatic effects of a needling procedure. Follow-up revealed that a variety of different interventions, including needle localization, fine-needle aspiration, infiltration with local anesthetic, core biopsy, and suture placement, preceded the surgical resection in these instances. The displaced epithelial fragments mimic stromal invasion to a variable degree and may represent a potential source of misdiagnosis. The incidence and biological significance of epithelial displacement in this context are as yet unknown.

Adipose differentiation is an uncommon stromal alteration in cystosarcoma phyllodes (CP). We have studied 14 lesions to define the structural variation and prognostic significance of these rare forms of CP. All patients were women between 17 and 71 years of age (mean 40 years; median 42 years). Most were first seen with a mass; three were pregnant. Grossly, the lesions were circumscribed with lobulated cut surfaces. Microscopically, the mesenchymal component showed adipose differentiation that ranged from mature fat to liposarcoma with well-differentiated, myxoid, or pleomorphic components. Six lesions were high-grade malignant CP with immature cellular mesenchyme, abundant mitoses, and areas of pleomorphic liposarcoma. Seven tumors were low-grade malignant CP with few mitoses, relatively low cellularity, and myxoliposarcoma. One tumor with slight periductal condensation and mature adipose tissue was a benign CP, which we named lipophyllodes tumor. Two patients had concurrent breast carcinoma, and two others subsequently had carcinoma. The follow-up was 8-90 months (mean 46 months; median 39 months). There was one recurrence among eight patients treated with simple excision and no recurrences in six treated with mastectomy. One woman died of metastatic breast carcinoma. All others are alive and free of disease. CP with adipose differentiation can be graded histologically on the basis of this component. Despite the high-grade histology in some instances, the patients had an excellent prognosis when the tumors were completely excised.

False-positive diagnosis of lymph nodes occurs when a benign element in a lymph node, or in its capsule, is interpreted as metastatic carcinoma. This report describes a patient with breast carcinoma who had megakaryocytes in axillary sentinel lymph nodes mimicking metastatic carcinoma. The patient had no history of a hematologic disease, and we found no evidence of a concurrent hematopoietic disorder. The megakaryocytes were reactive for CD31, CD61, and von Willebrand factor, but not for cytokeratin (AE1/AE3). Megakaryocytes should be added to the list of benign histologic abnormalities that may simulate metastatic carcinoma in a sentinel lymph node.

We report synchronous bilateral Paget disease derived from lobular carcinoma in situ in a 53-year-old woman who underwent bilateral mastectomy. The epidermis of both nipples contained small cells with a moderate amount of pale-staining cytoplasm. The nuclei had fine chromatin and identifiable nucleoli. The cells were strongly immunoreactive with cytokeratin 7 and displayed nuclear estrogen receptor reactivity. The underlying mammary gland showed involvement by lobular carcinoma in situ with pagetoid spread into lactiferous ducts, which was confirmed by lack of immunoreactivity for E-cadherin.

Breast carcinoma arose in or in conjunction with microglandular adenosis (MGA) in 14 of 60 (23%) patients with MGA listed in the authors' files. This article describes the clinicopathologic and immunohistochemical features and prognosis of these carcinomas. The median patient age was 47 years (range, 26-68 years). All patients had a mass. Six (43%) had a family history of breast carcinoma. Lymph node metastases were found in 3 of 11 axillary dissections. Ten patients treated by mastectomy were recurrence-free, with a median follow-up of 57 months (range, 3-108 months). Two of three patients treated by excisional surgery were recurrence-free 12 and 105 months later. The third woman had bone metastases at 51 months and was alive 98 months after treatment. Carcinoma arose in the MGA in 13 patients. In these patients, in situ carcinoma was found in expanded MGA glands composed of cells with vesicular poorly differentiated nuclei. One patient with benign MGA had carcinoma develop in the opposite breast that was not associated with MGA. When it arose in MGA, basement membranes were present in benign MGA and in situ carcinoma but tended to be disrupted in invasive foci that appeared to be formed by coalescent MGA glands. Strong immunoreactivity for cytokeratin, S-100, and cathepsin D was detected in carcinomas. Two carcinomas had nuclear progesterone receptors, and one of these had estrogen receptors. One carcinoma had positive findings for HER-2neu, and four had immunoreactivity for p53 protein. The following conclusions were drawn from these observations: (1) carcinomas arising in MGA have a distinctive histopathologic pattern; (2) the carcinomas are composed of epithelial cells (cytokeratin positive, actin negative) that are strongly immunoreactive for S-100 protein and cathepsin D; and (3) with a median follow-up of nearly 5 years, patients with these carcinomas had a relatively favorable prognosis, despite histopathologic and immunohistochemical features usually associated with a poor prognosis.

PURPOSE This study was undertaken to define prognostically favorable and unfavorable subgroups of node-negative breast carcinoma patients by employing conventional pathologic data. PATIENTS AND METHODS Seven hundred sixty-seven women with T1N0M0/T2N0M0 breast carcinoma treated consecutively from 1964 through 1970 by modified or radical mastectomy without systemic adjuvant therapy were analyzed at a median follow-up duration of 18 years. RESULTS Size and histologic type of the carcinoma were crucial discriminants of prognosis. We defined a prognostically favorable group of 219 patients (29%) with infiltrating duct or lobular carcinoma < or = 1.0 cm in diameter or special tumor types < or = 3.0 cm. This group had a relapse-free survival rate of 91% at 10 years and 87% at 20 years. The less favorable group (548 patients, 71%) with infiltrating duct or lobular carcinoma greater than 1.0 cm and special tumor types greater than 3.0 cm had relapse-free survival rates of 73% and 68% at 10 and 20 years, respectively. The frequency of nonmammary malignant neoplasms (NMMN) was similar to that of contralateral carcinoma. Deaths due to NMMN were seven times more frequent than deaths due to contralateral carcinoma. CONCLUSION Nearly 30% of these node-negative patients, identified on the basis of tumor size and type, had an extremely favorable prognosis. There is insufficient evidence to warrant the routine use of adjuvant therapy in this group unless new forms of treatment prove to be less toxic and/or more effective in enhancing relapse-free survival. Early detection of NMMN should be an important part of the follow-up of node-negative breast carcinoma patients.

Juvenile papillomatosis is a benign proliferative lesion, which may include atypical duct hyperplasia, that occurs most often in women 15 to 30 years of age. About one third of the patients have a positive family history of breast cancer. Breast carcinoma only rarely has been detected in patients with juvenile papillomatosis but long-term follow-up, which is not yet available, will be necessary to assess the precancerous risk of this condition.

The clinical and pathologic aspects of sentinel lymph node biopsy have generated much attention. Pitfalls in the pathologic handling of sentinel lymph node specimens have received little attention. We report a case in which a false-positive diagnosis might have been rendered on a sentinel lymph node because of an inadvertent immunostaining error. Attention was drawn to the problem by an unusual pattern of distribution of immunoreactive cells—which proved to be plasma cells rather than metastatic carcinoma cells.

We report the case of a 78-year-old man who developed a breast mass 12 months after hormonal therapy for palliation of prostatic adenocarcinoma. On histologic and immunohistochemical examination, the breast tumor revealed a unique collision tumor composed of metastatic prostatic adenocarcinoma and solid papillary breast carcinoma.

Background: Emerging data show that patients with operable, HER-2/neu overexpressed/amplified breast carcinomas have significantly better responses (more frequently obtaining pathologic complete response and greater percent disease-free survival) when treated with trastuzumab (Herceptin) simultaneously with neoadjuvant chemotherapy than with chemotherapy alone. With the increasing use of neoadjuvant therapies, clinicians require information on biomarkers including HER-2/neu status at the time of needle core biopsy. Concordance rates between fluorescence in situ hybridization (FISH)-determined HER-2/neu status on needle core biopsies and on subsequent excisional biopsies of the same tumor have not been well studied. Moreover, the practice of automatically performing ("reflexing") 2 + immunohistochemical (IHC) staining needle core biopsies for FISH analysis on the same sample needs to be validated. In this study, we set out to (1) determine the accuracy of HER-2/neu status as determined by FISH on needle core biopsy material compared with FISH on the subsequent excisional biopsy of the same tumor with special consideration of IHC 2 + staining cases and (2) determine the constancy of HER-2/neu status in pre-neoadjuvant and post-neoadjuvant chemotherapy-treated tumor in the form of needle core biopsy and excisional biopsy samples, respectively. Design: 100 patients whose needle core biopsies and subsequent excisional biopsy samples were pathologically evaluated at our institution were studied. For each patient, unstained sections from both specimens were prepared and used for IHC or FISH. IHC was carried out using the HercepTest kit (DAKO, Carpinteria, CA). Parallel unstained slides were used to carry out FISH (dual probe, Vysis). Statistical analyses were carried out on the resulting data generated after interpretation. Results: The concordance rate between FISH results determined on the needle core biopsy and subsequent excisional biopsy of the same tumor was 86% (κ = 0.56, P = 2 × 10 ―8 ). If equivocal FISH cases (≥ 1.8 to ≤2.2 amplification ratio) in a needle core biopsy or excisional biopsy specimen or both, were excluded, the concordance rate increased to 95% (κ coefficient = 0.86, P = 2 × 10 ―15 ). Fourteen of 100 (14%) cases showed 2+ IHC staining in the needle core biopsy specimen with good concordance of FISH-determined HER-2/neu status between the needle core biopsy and excisional biopsy specimens (79% agreement and κ = 0.512, P = 0.05). Nine, 3, and 2 cases of the 14 cases were amplified, equivocal, and negative on the excisional biopsy specimens, respectively. Of the 15 patients who received neoadjuvant chemotherapy, 93% and 87% had no change in HER-2/neu status as determined by IHC or FISH, respectively, in the excisional biopsy specimen when compared with that determined on the prior core biopsy sample. Conclusions: Excellent overall concordance was achieved between FISH-determined HER-2/neu status on the needle core biopsy and that determined on the subsequent excisional biopsy of the same tumor. These results suggest that intratumoral heterogeneity of HER-2/neu assessed by FISH is not a significant confounding factor when analyzing smaller sized samples. Furthermore, 79% of 2 + IHC staining needle core biopsy cases showed concordant FISH results in the needle core biopsy and subsequent excisional biopsy specimens. Our results show good concordance, however, larger cohorts need to be studied to verify this finding. HER-2/neu status remains unchanged in the majority of cases when comparing pre-neoadjuvant and post-neoadjuvant chemotherapy-treated specimens.

PURPOSE To characterize the clinical and pathologic features of patients who developed breast cancer (BC) after treatment for Hodgkin's disease (HD). Recent epidemiologic studies have shown that women who are cured of HD have an increased risk of developing BC. PATIENTS AND METHODS The clinical data, mammograms, and pathologic specimens of 37 women who developed 45 BCs (eight bilateral events), and had a prior history of treatment for HD were analyzed. RESULTS The median age at diagnosis of HD was 27 years (range, 11 to 60). All patients received radiotherapy (RT) to the upper part of their body, and 10 also had chemotherapy for HD. The median interval from the treatment of HD to the diagnosis of BC was 15 years (range, 8 to 34). The median age at diagnosis of BC was 43 years (range, 27 to 75), 41% of patients were 39 years old or younger. Most mammograms (81%) showed abnormal findings of mass and/or microcalcifications. Of the eight patients (22%) with bilateral tumors, four were synchronous and four were metachronous. Involvement of the medial half of the breast occurred more frequently than in patients with primary BC (39% and 21%, respectively; P < .002). But, the histologic types, grades, presence of lymphocytic reaction, and lymphatic invasion were similar to those observed in 935 primary BC patients who were previously analyzed at our center. The 6-year actuarial relapse-free survival (RFS) for node-negative BC after HD was 85%. Node-positive patients had a significantly lower RFS of 33% (P = .002). CONCLUSIONS In comparison to patients with primary BC, patients who develop BC after HD are more likely to be younger, have bilateral disease, and have their tumors more frequently involve the medial half of the breast. Pathologic characteristics, nodal involvement, and prognosis are similar to those of primary BC. BC in women who were treated for HD is becoming an increasing problem, as more patients cured of HD reach a follow-up time of 10 to 15 years. Breast examination and mammography at an early age should be part of the follow-up program for women who are cured of HD.

Atypical duct hyperplasia of the breast is an unusual finding in the adolescent or young adult female. We report nine young women, ages 18-26 years (mean 21) with atypical duct hyperplasia. Clinical presentation was either breast hypertrophy treated by reduction mammoplasty (five patients) or a thickening or mass that was examined via biopsy (four patients). No focal abnormalities were present on gross examination other than two fibroadenomas in one patient. Microscopically, isolated hyperplastic ducts were scattered in a background of prominent stromal collagenization. Each case showed a continuum of ductal changes, from partial to complete involvement by micropapillary and laciform epithelial hyperplasia, which was sometimes markedly atypical. In four, lobules were poorly developed or not present in the available sections. During a follow-up of 5-68 months (mean 39), none developed breast carcinoma. Much longer follow-up is needed to determine if young women with atypical duct hyperplasia are at increased risk for subsequent development of breast carcinoma. Presently, no surgical or medical intervention is recommended, but such patients should perform breast self-examination and be monitored regularly by a physician.

Benign glandular inclusions in axillary lymph nodes are very rare events that have to be distinguished from metastatic carcinoma. We report an exceptional instance in which a patient with invasive ductal carcinoma had benign glandular inclusions in the form of sclerosing adenosis in 2 sentinel lymph nodes. The lymph nodes did not contain metastatic carcinoma. Immunohistochemical studies facilitated the correct diagnosis.

Breast carcinoma presenting with axillary metastases and no clinically apparent primary tumor in the breast is an uncommon form of stage II disease. Published studies have been characterized by small numbers and/or limited follow-up information. Although these patients are often looked on individually as having advanced disease, several published reports suggest that their prognosis is not exceptionally grave. The present study evaluated the largest series thus far described, consisting of 48 patients with a median follow-up of 5 years. Each presented with an axillary mass which proved to be metastatic adenocarcinoma, consistent with mammary origin when examined histologically. No patient had a palpable breast tumor. Mammography was negative in 28 patients (76%), and suspicious or positive in nine (24%). Nine (35%) of 26 metastases were positive for estrogen (ER) and progesterone (PR) receptors, 10 (38%) were negative for both receptors, and seven (27%) were ER positive/PR negative. Primary treatment was mastectomy and axillary dissection in 38 cases, 21 with adjuvant chemotherapy. A primary tumor was found pathologically in the breast in 36 cases (75%). Among 34 reviewed primary lesions, 27 (79%) were invasive and seven (21%) were histologically “noninvasive.” Measured size was 0.1 to 6.5 cm (median, 1.5 cm). The number of involved lymph nodes was one to 65 with 20 cases having one to three positive and 20 having four or more positive. Follow-up ranged from 5 to 267 months (median, 60 months). Overall, 29 patients (60%) remained alive and disease free; two (4%) were disease free, but died of other causes; and the status of two (4%) was not known. Fifteen patients developed recurrent carcinoma, including 12(25%) who died of disease. When compared with a matched series of stage II patients with equivalent extent of disease who presented with palpable breast tumors, patients with occult lesions had a more favorable prognosis overall, as well as when stratified by tumor size and nodal status, but the differences were not statistically significant. These results probably reflect the fact that the majority of stage II patients with clinically occult breast carcinoma usually have a grossly measurable invasive tumor detected pathologically. Consequently, the actual pathologic stage, which takes tumor size into consideration, determines prognosis rather than the apparent clinical stage described when the patient is first examined.

Juvenile papillomatosis (JP) is a benign proliferative breast tumor rarely found in women older than 30 years of age that may exhibit considerable histologic atypia. Often these findings would be regarded as precancerous in older patients. Rarely, carcinoma and JP have been coexistent at diagnosis, but little is known about the risk for development of carcinoma after excisional biopsy of JP. To examine this issue, the authors reviewed a series of 41 patients with JP who had biopsies between 1960 and 1978 with a median follow-up of 14 years. Age at diagnosis ranged from 15 to 35 years (median, 19 years), whereas at last follow-up the patients were 22-48 years old (median, 36 years). Overall, 21 (58%) reported a positive family history for breast carcinoma, with mothers and maternal aunts being at highest risk. Six had bilateral JP. Subsequent breast carcinoma was diagnosed in four (10%) of the patients with JP. All of these patients were unusual because they had recurrent and bilateral JP. In two instances the changes were multifocal. Each had a positive family history for breast carcinoma. In this series, none of the patients with nonrecurrent unilateral, unicentric JP has thus far had subsequent mammary carcinoma develop. When counseling the JP patient one should take care not to exaggerate her near term risk for development of carcinoma. The present data suggest that concern should be greatest for women with a positive family history and recurrent bilateral JP.

A precise histologic and clinical delineation of infiltrating lobular carcinoma, including its variant forms, has been elusive. We studied 230 patients with stage I and II infiltrating lobular carcinoma treated by mastectomy and axillary lymph node dissection. Included were 176 patients with the "classical" or "Indian-file" pattern (IFL) of infiltrating lobular carcinoma, and 54 patients with variant (VAR) histology [solid (SOL), alveolar (ALV), and mixed (MIX) patterns]. IFL patients were younger than VAR patients (52 versus 57 years; p = 0.004), and IFL patients were more likely to be premenopausal (p = 0.013). Microscopic multifocality and intraepithelial ductular extension of LCIS were both more frequent in the IFL group (p = 0.008 and 0.03, respectively). There was no significant difference in tumor size (T1 versus T2), axillary lymph node status, or TNM stage at presentation. Median survival time and time to recurrence was similar in the two groups. Although it was not statistically significant, median survival for stage I and low-axillary lymph node positive stage II IFL patients was better than that of VAR patients. One hundred forty of our 176 IFL patients (80%) could be matched with infiltrating duct carcinoma (IFDC) patients of similar age at diagnosis, menstrual status, tumor size, and axillary lymph node involvement. When stratified by stage, stage I IFL patients had a significantly higher disease-free survival (p = 0.02) than comparable patients with IFDC. There was not a significant difference in disease-free survival when stage II IFL and IFDC patients were compared. The unmodified term "infiltrating lobular carcinoma" should be restricted to lesions exhibiting the classical or Indian-file (IFL) microscopic architectural pattern in approximately 85% of the tumor. Patients with VAR forms of IFL may have a less favorable prognosis and should be distinguished from those with classical IFL for further characterization.

Fibroepithelial lesions are uncommon in the male breast. Most published reports describe phyllodes tumors. Fibroadenomas are very common in female breasts, but are exceedingly rare in the male breast. Gynecomastia and/or lobular differentiation have been known to coexist in both types of fibroepithelial lesions in men. We report an exceptional case of recurrent, bilateral fibroadenomas in a man under treatment for prostatic carcinoma. Intracytoplasmic inclusion bodies in stromal cells identical to those seen in infantile digital fibromatosis were identified in one fibroadenoma. To the best of our knowledge, this is the first reported case of bilaterally occurring fibroadenomas in the male breast, one of which also contained digital fibroma– like inclusions, a second unreported phenomenon.

Background E-cadherin, a cell surface protein involved in cell adhesion, is present in normal breast epithelium, benign breast lesions, and in breast carcinoma. Alterations in the gene CDH1 on chromosome 16q22 are associated with changes in E-cadherin protein expression and function. Inactivation of E-cadherin in lobular carcinomas and certain diffuse gastric carcinomas may play a role in the dispersed, discohesive "single cell" growth patterns seen in these tumors. The molecular "signature" of mammary lobular carcinomas is the loss of E-cadherin protein expression as evidenced by immunohistochemistry, whereas ductal carcinomas are typically E-cadherin positive. Patients and methods We report on E-cadherin immunostaining patterns in five cases of invasive mammary carcinoma Results These were five exceptional instances in which the E-cadherin immunophenotype did not correspond to the apparent histologic classification of the lesion. These cases which are exceedingly rare in our experience are the subject of this report. Conclusion Findings such as those illustrated in this study occur in virtually all biologic phenomena and they do not invalidate the very high degree of correlation between the expression of E-cadherin and the classification of breast carcinomas as ductal or lobular type on the basis of conventional histologic criteria.

Juvenile xanthogranuloma (JXG) is a benign histiocytic disorder of infants and childhood. Approximately 15% of cases occur in adults. Adult JXG characteristically affect patients in their 20s and 30s; however, about 5% of patients are older than 60 years. Adult JXGs rarely regress spontaneously, and reports of concomitant extracutaneous lesions are rare. Herein, we report an exceptional case of adult xanthogranuloma in a 74-year-old woman who presented with ipsilateral breast masses and also found to have prior cutaneous lesions. This is the first reported case of cutaneous and extracutaneous adult JXG where the latter manifested in the breast as a spindle cell xanthogranuloma. Histologically, the lesion was composed predominantly of spindle cells with associated multinucleated giant cells and a chronic inflammatory cell infiltrate. Spindle cells were immunoreactive for various histiocytic markers and negative for cytokeratins, S-100, CD34, factor XIIIa, and CD1a. In the breast, the morphologic features of JXG evoked several entities in the differential diagnosis, including spindle cell metaplastic carcinoma, inflammatory pseudotumor, fibromatosis, myofibroblastoma, and phyllodes tumor. With the aid of immunohistochemical stains and appropriate clinical history, the correct diagnosis of extracutaneous adult JXG manifesting as a spindle cell xanthogranuloma can be made.