Clinical Management of Mucocele-Like Lesions of the Breast with Limited or no Epithelial Atypia on Core Biopsy: Experience from Two Institutions.

PURPOSE: Mucocele-like lesions of the breast identified on core biopsy are rare high-risk lesions associated with variable upgrade rates to carcinoma on excision. We aimed to identify the clinicoradiopathological features that can help optimize management of this lesion. METHODS: We evaluated 50 mucocele-like lesions identified on core biopsies from two institutions, including 36 with no atypia and 14 with limited atypia. Outcome data from excision or clinicoradiological follow-up were reviewed with core biopsy results. RESULTS: Radiological targets were calcifications in 74% of cases, calcifications with associated mass or density in 16%, and mass in 10%. One of the 16 excised lesions without atypia on core biopsy, which was a mass lesion, was upgraded to mucinous carcinoma on excision. Of the 12 excised lesions with limited atypia, none were upgraded on excision. Among the lesions not excised, 20 without atypia had a median follow-up of 61 months, and 2 with limited atypia had follow-up of 97 and 109 months. None of these 22 patients had new development of their lesions on follow-up. The upgrade rate was 2% in our entire cohort, 3% for lesions without atypia, and 0% for lesions with limited atypia. CONCLUSIONS: Clinicoradiological surveillance can be appropriate when a mucocele-like lesion without atypia is identified on core biopsy for a non-mass lesion with pathological-radiological concordance. For mucocele-like lesions with limited atypia, a nonsurgical approach could be considered if the atypia by itself does not warrant excision. The latter recommendation requires careful clinicopathological correlation and support from additional studies.

Atypical ductal hyperplasia in directional vacuum-assisted biopsy of breast microcalcifications: considerations for surgical excision.

BACKGROUND: Our goal was to analyze clinicopathologic features of patients with atypical ductal hyperplasia (ADH) diagnosed on directional vacuum-assisted biopsy (DVAB) targeting microcalcifications to identify factors predicting the presence of carcinoma. MATERIALS AND METHODS: We retrospectively evaluated the clinical, mammographic, and histologic features of 140 patients with DVAB-diagnosed ADH who underwent either segmental excision (86.4%) or mammographic follow-up (≥2 years; 13.6%). Cases with mass lesions or ipsilateral cancer were excluded. RESULTS: In 16 cases, carcinoma was found on excision. All cases without excision showed no new abnormalities on mammographic follow-up. Only the amount of calcifications removed (≤95%) significantly correlated with the rate of upgrade of ADH to carcinoma (P = .037). Significant histologic predictors of upgrade to carcinoma included number of terminal duct-lobular units (TDLU; >2) involved (P = .0306), presence of significant cytologic atypia suspicious for intermediate or high-grade carcinoma (P < .0001), and necrosis (P = .0006). Among ADH cases without significant atypia and/or necrosis, the extent of ADH (≤2 vs. >2 TDLU involved) was not a significant predictor of carcinoma (P = 1.0000). CONCLUSIONS: ADH associated with calcifications in the absence of a mass lesion can be categorized into different risk groups using a multidisciplinary approach with correlation of histologic and mammographic findings. ADH lesions with significant cytologic atypia and/or necrosis are most likely to be associated with carcinoma and should be excised. ADH without these features, regardless of extent of involvement, and with >95% removal of the targeted calcifications, is associated with a minimal risk (<3%) of carcinoma and may undergo mammographic follow-up only.

Rosai-Dorfman disease confined to the breast.

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is an uncommon, idiopathic, benign histiocytic lesion. It usually involves the cervical lymph nodes and, less commonly, extranodal sites. Involvement of the breast is rare, with only 17 cases reported in the English literature to date. Here we describe 3 new patients with extranodal Rosai-Dorfman disease in the breast. All 3 patients-aged 45, 53, and 54 years-presented with solid breast lesions that were detected on screening mammography and had no clinical history of Rosai-Dorfman disease or radiographic evidence of extramammary involvement. Initial diagnoses were accomplished by needle core biopsy in the one case and excisional biopsy in the other two. We present the histopathologic findings and follow-up of each patient and conduct a literature review of mammary Rosai-Dorfman disease with emphasis on its differential diagnosis. Because Rosai-Dorfman disease frequently mimics invasive breast carcinoma in its clinical presentation and radiographic appearance-and can mimic other benign or malignant histiocytic lesions microscopically-awareness and appropriate diagnosis of this entity are essential for proper treatment.

Pleomorphic ductal carcinoma of the breast: predictors of decreased overall survival.

The World Health Organization classification of tumors of the breast includes a rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by definition, but often>10-fold) and characteristically contains multinucleated tumor giant cells. Approximately one-third of the cases in the initial series contained a focal spindle cell metaplastic component. The tumors are reported to have an aggressive behavior, but because some contain a spindle cell metaplastic component, it is unclear whether the metaplastic component or other clinicopathologic features account for the poor clinical outcome. We identified 37 cases of pleomorphic carcinoma of the breast and evaluated the association between clinical outcome and multiple clinicopathologic features. Patients with invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy before chemotherapy were excluded. Patients ranged in age from 23 to 78 years (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical follow-up was available for 36 patients (median, 17 mo). In multivariate analysis, when the 2 stage-IV patients were excluded, the presence of a spindle cell component and tumor size >5 cm were each independently associated with decreased overall survival. The actuarial 5-year overall survival for patients with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%, respectively. Poor clinical outcome, therefore, is associated with the subset of pleomorphic carcinomas with a spindle cell metaplastic component. As the morphologic features of pleomorphic carcinoma can be seen in primary tumors from other sites, it is important to recognize this tumor as a rare variant of invasive breast carcinoma.

Estrogen receptor immunohistochemistry for confirmation of sentinel lymph node metastasis in cases with equivocal cytokeratin positivity.

Differentiation of true metastases from cytokeratin (CK)-positive nonepithelial cells by immunohistochemistry occasionally may be difficult in the evaluation of sentinel lymph nodes (SLNs) for occult breast carcinoma metastases. In this study, we evaluated estrogen receptor (ER) immunostaining superimposed on CK as a method for the confirmation of metastasis when CK immunostaining alone was equivocal. We performed sequential ER staining on previously CK-stained slides on 15 axillary SLNs from breast cancer patients: 5 SLNs with known metastatic carcinoma (positive controls), 6 known negative SLNs (negative controls), and 4 test cases (3 SLNs in which CK-positive cells were equivocal for malignancy and 1 SLN in which metastasis was obvious, but contained focal weakly CK-positive signet ring cells). The primary tumor in all cases expressed ER in >50% of cells. Only 3 of 5 positive controls showed metastatic cells with dual CK/ER staining. CK-positive reticulum cells in all negative controls were ER negative. Three test cases showed dual CK/ER staining in the equivocal cells. The case with signet ring cells showed strong ER staining in the nonsignet ring cells and weaker staining in the signet ring cells. We conclude that dual CK/ER staining can be useful in SLNs when CK staining alone is equivocal, particularly when the primary tumor is known to have high expression of ER. Although dual ER/CK positivity helps to confirm metastasis, negative ER staining does not exclude metastatic disease.

Pulmonary epithelial-myoepithelial carcinoma: a clinicopathologic and immunohistochemical study of 5 cases.

Pulmonary epithelial-myoepithelial carcinomas are rare low-grade malignant neoplasms with histologic features similar to their salivary gland counterparts. We report a series of 5 cases and describe their clinical, morphological, and immunohistochemical features. The patients included 3 men and 2 women whose ages ranged from 38 to 56 years. All patients had obstructing endobronchial lesions that ranged from 2.5 to 5.0 cm in greatest dimension. The tumors were completely resected by simple lobectomy or pneumonectomy. In one patient, the tumor infiltrated perinodal soft tissue of a peribronchial lymph node with intranodal extension and metastasis within the same lymph node. The follow-up in these patients ranged from 4 to 12 months. The histologic appearance of these tumors varied, but all shared the common feature of a biphasic proliferation of epithelial (strong cytokeratin-positive; actin and S-100-negative) and myoepithelial (strong actin and S-100 and focal weak cytokeratin-positive) cells with formation of bilayered ductlike structures. The focal resemblance to other salivary gland-type tumors may cause diagnostic difficulties, particularly in small endobronchial biopsies. Although little is known about their biologic potential due to limited follow-up data, these tumors when in the lung clearly have the capacity to infiltrate and metastasize and therefore should be designated as epithelial-myoepithelial carcinoma. At present, it appears that treatment by complete surgical resection with negative margins alone is appropriate and adequate.

Is single-cell apoptosis sufficient for the diagnosis of graft-versus-host disease in the colon?

Low-grade lesions of graft-versus-host disease (GVHD) in the colon are not uncommon. To determine if minimal diagnostic criteria can be established in such biopsies, we correlated histologic findings with clinical history and investigated the role of endoscopy and electron microscopy in establishing GVHD. About 85 colonic biopsies that were histologically consistent with GVHD from 47 bone-marrow transplant recipients were reviewed retrospectively. Of nine cases showing only a single apoptotic cell in the intestinal epithelium, only four lacked any confounding factors of GVHD. These cases, while too few to assess the utility of finding one apoptotic cell with statistical significance, appear to support the idea that in the appropriate clinical setting, a single apoptotic cell could be reported as possibly representing early GVHD. Endoscopic findings did not reliably correlate with histology. Although electron microscopy can be a useful adjunct, it does not contribute to the diagnosis of GVHD.