Milicent L. Cranor

Pseudoangiomatous stromal hyperplasia (PASH) : a mammary stromal tumor with myofibroblastic differentiation

Pseudoangiomatous stromal hyperplasia (PASH) is frequently a microscopic incidental finding in breast biopsies performed for benign or malignant disease. However, it may also produce a mass lesion. We reviewed PASH seen first as a tumor in 40 women aged 14 to 67 years (mean, 37 years). All but one lesion were clinically palpable. The exceptional tumor was found by mammography. The mass, typically unilateral, was usually diagnosed clinically as a fibroadenoma. Most specimens contained a well-circumscribed tumor with a firm white-gray cut surface. In six cases, there was no discrete gross lesion in the surgical specimen. Microscopically, there was a spectrum of pathological stromal changes ranging from classical PASH with anastomosing slit-shaped spaces outlined by flat, bland spindle cells to more proliferative lesions composed of bundles of plump spindle cells that obscured the underlying pseudoangiomatous architecture in the most florid lesions. The spindle cells were vimentin and CD34 positive and factor VIII negative. In more cellular fascicular lesions, the stromal cells acquired desmin and actin positivity. These immunohistochemical features were consistent with myofibroblastic histogenesis of PASH. Reactivity for progesterone receptor (PR) typically exceeded estrogen receptor (ER) in the nuclei of stromal and glandular cells. In most lesions, the nuclei of stromal spindle cells were ER negative. The majority of the patients were treated by excisional biopsy. One lesion, incompletely excised, spontaneously regressed. One patient had bilateral mastectomies. Follow-up was 0.6–11 years (mean, 4.5 years). Five patients had ipsilateral recurrences, and two had subsequent contralateral PASH. The morphological spectrum of cellular proliferation and staining qualities indicates that the myofibroblast plays a major role in the histogenesis of PASH. The pathogenesis of PASH remains uncertain, but aberrant reactivity of myofibroblasts to endogenous or exogenous hormones is likely to be an important factor. Simple excision is adequate treatment initially and for infrequent recurrences. Diffuse PASH occasionally presents a difficult management problem that may necessitate mastectomy.

Immunohistochemical detection of HER2/neu in patients with axillary lymph node negative breast carcinoma : a study of epidemiologic risk factors, histologic features, and prognosis

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.

Mammary mucocele-like lesions benign and malignant

In 1986 mucocele-like lesions (MLL) were described as benign tumors; subsequent reports identified MLL associated with ductal hyperplasia or carcinoma (CA). To characterize MLL further, we studied 53 lesions from 49 patients, in whom 25 MLL were benign and 28 were malignant (14 in situ, 14 invasive). Two had bilateral benign MLL, and two had bilateral MLL with CA. Patients ranged in age from 24 to 79 years (mean, 48 years). There were no appreciable differences in age, tumor size, or laterality between patients with benign or malignant MLL, although MLL with CA had coarse calcifications more often than benign MLL and were more likely to be detected mammographically. Intraductal carcinoma was micropapillary or cribriform, and invasive carcinoma was usually mucinous. Fewer of the benign lesions were estrogen and progesterone receptor positive. HER2/neu positivity was more common in MLL with CA. Known treatment was as follows: for benign MLL, excisional biopsy was done in 22 patients (one with axillary dissection) and total mastectomy in one patient; for MLL with CA, excisional biopsy was done in 17 patients, biopsy followed by wider excision in four patients (three of whom had axillary dissection), and mastectomy and axillary dissection in five patients (one also had radiotherapy). Follow-up ranged from less than a 1 year to 15 years (mean and median, 3.7 years). Two patients had recurrences in the breast (one benign MLL and one MLL with CA). At the time of this report, all were alive without evidence of disease. We conclude that MLL with CA is a low-grade neoplasm with few clinical differences from benign MLL except for more prominent calcifications, leading to mammographic detection. Excisional biopsy is recommended for benign MLL. Breast-conserving surgery is appropriate therapy for MLL with CA. Radiotherapy is indicated if CA involves margins or if extensive intraductal carcinoma is present.

Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements.

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.

Low-grade adenosquamous carcinoma of the breast. A clinocopathologic study of 32 cases with ultrastructural analysis.

Low-grade adenosquamous carcinoma of the breast is an uncommon neoplasm of uncertain pathogenesis, clinical behavior, and malignant potential. This report describes the clinical and pathologic features of 32 cases of lowgrade adenosquamous carcinoma. All patients presented with palpable tumors ranging from 0.6 to 8.6 cm (mean, 2.8 cm). Origin from an intraductal papillary tumor was found in 12 cases, including three with adenomyoepitheliomatous features. Electron microscopy disclosed glandular and squamous differentiation; the squamous cells often lined ducts that were structurally analogous to the acrosyringium of the eccrine sweat gland. Treatment consisted of mastectomy (13 patients) or excisional biopsy (19 patients). A single lymph node in one patient with a 3.5-cm primary carcinoma harbored metastatic adenocarcinoma. Axillary dissection revealed no metastases in 11 other patients. Another patient with an 8.0-cm breast tumor had metastatic adenosquamous carcinoma in the lung at initial diagnosis. After follow-up of 12 to 124 months, 20 of 25 patients had no recurrence. Five women treated by excisional biopsy had local recurrences in the breast. In one patient, the local recurrence was ultimately fatal due to invasion of the hemithorax. Estrogen and progesterone receptor studies were negative in 13 of 15 cases studied by biochemical analysis. The two tumors that were hormone-receptor positive were histologically associated with a papilloma and an adenomyoepithelioma, respectively. In the latter case, immunohistochemical studies showed the carcinoma to be hormone-receptor negative. Hormone receptor activity was limited to the adenomyoepitheliomatous component. This study confirms the largely indolent, but locally aggressive, clinical course of low-grade adenosquamous carcinoma of the breast. Although complete limited excision of small lesions may be curative, tumors greater than 3.0 cm may require more aggressive therapy

Cystosarcoma phyllodes in adolescent girls and young women: a study of 45 patients.

Cystosarcoma phyllodes (CP) is an uncommon tumor in adolescent girls and young women. This study seeks to define the clinical and pathologic features of CP in this unusual clinical setting. Forty-five CPs (34 benign and 11 malignant) in prepubertal and adolescent girls and young women were studied. Classification of the tumors was based on the following morphologic features: stromal cellularity, nuclear atypia, mitotic activity, necrosis, and the nature of tumor borders. Surgical therapy was local excision or mastectomy. The age of the patients ranged from 10 to 24 years (mean 17.7). The tumors measured 1.4 cm to 10.2 cm at their widest point (mean 4.6). Both breasts were affected equally. Thirty-two patients were treated by local excision with or without reexcision and four patients by mastectomy. Follow-up was available for 36 patients for a mean of 58.4 months. Local recurrence was reported in six of the 36 cases (16%) (four benign and two malignant). The six patients with recurrent disease had infiltrative tumor borders and positive surgical margins microscopically. There was a single instance of systemic metastases from a high-grade malignant tumor with rhabdomyosarcomatous stromal differentiation and a high mitotic rate. At last follow-up, 34 patients were alive with no evidence of disease, one patient was alive with pulmonary metastases, and one patient died of an unrelated cause. We concluded that CP in adolescent girls and young women is not more aggressive than in older patients. Infiltrative tumor borders and positive surgical margins are the best histologic predictors for local recurrence. Mitotic activity is the most important criterion for assessing the metastatic potential. CP in this age group should be treated to maximize breast conservation. Mastectomy may be required to obtain clear margins for CPs that cannot be managed by excision because of large tumor size relative to breast volume.

Is pleomorphic lobular carcinoma really a distinct clinical entity

Attempts to define the clinical behavior of pleomorphic lobular carcinoma (PLC) have been limited to small series, and clinical management strategies have yet to be established. We describe our experience with PLC as compared to classic ILC and invasive ductal carcinoma (IDC).

A Tool for Predicting Breast Carcinoma Mortality in Women Who Do Not Receive Adjuvant Therapy

Among the several proposed risk classification schemes for predicting survival in women with breast carcinoma, one of the most commonly used is the Nottingham Prognostic Index (NPI). The goal of the current study was to use a continuous prognostic model (similar to those that have already been demonstrated to possess greater predictive accuracy than risk group–based models in other malignancies) to predict breast carcinoma mortality more accurately compared with the NPI.

Hemangiomas of the Breast With Atypical Histological Features Further Analysis of Histological Subtypes Confirming Their Benign Character

Eighteen patients with vascular tumors of the breast that exhibited characteristics raising the question of but not qualifying for a diagnosis of low-grade angiosarcoma were reviewed. We had previously referred to these lesions as “atypical” hemangiomas because of concern regarding the diagnosis and the risk for the later development of angiosarcoma. Significant features, variably present, included small size (<2.0 cm), relative circumscription, broadly anastomosing vascular channels, and endothelial hyperplasia. Destructive invasion, solid areas, and hemorrhage or necrosis unrelated to a needle localization procedure were absent. Four distinct histological patterns were observed: cavernous, compact capillary, capillary budding, and a combined cavernous and compact capillary type. The age of the patients varied from 19 to 82 years (mean 60 years). Eleven tumors were detected mammographically. The size of the lesion ranged from 0.4 to 2.0 (mean 0.9) cm. The diagnostic biopsy was the only treatment in nine (50%) cases. Reexcision was performed in seven and mastectomy was done in two cases. Follow-up ranged from 1 to 140 (mean 44) months. There have been no local or systemic recurrences. Hemangiomas with diverse histological patterns have been detected clinically with the increasingly widespread use of mammography. Further follow-up indicates that the lesions originally referred to as “atypical” are benign and not associated with an appreciable risk of the development of angiosarcoma. Complete excision alone is recommended to treat these tumors, which may be diagnosed as hemangiomas and subclassified according to growth pattern.

Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ treated with breast‐conserving therapy

Multiple clinicopathologic factors have been analyzed for their association with an increased risk of ipsilateral breast tumor recurrence (IBTR) after women receive breast‐conserving treatment (BCT) for ductal carcinoma in situ (DCIS). The reported incidence of proliferative lesions, such as atypical ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia associated with breast cancer, has been as high as 23%; however, the relevance of these lesions on the natural history of DCIS and the risk of IBTR remains unknown.