Paula S. Ginter

Tumor Microenvironment of Metastasis and Risk of Distant Metastasis of Breast Cancer

BACKGROUND Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer. We prospectively examined the association between TMEM score and risk of distant metastasis and compared risk associated with TMEM score with that associated with IHC4. METHODS We conducted a case-control study nested within a cohort of 3760 patients with invasive ductal breast carcinoma diagnosed between 1980 and 2000 and followed through 2010. Case patients were women who developed a subsequent distant metastasis; control subjects were matched (1:1) on age at and calendar year of primary diagnosis. TMEM was assessed by triple immunostain and IHC4 by standard methods; slides were read by pathologists blinded to outcome. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for clinical variables. A Receiver Operating Characteristic analysis was performed, and the area under the curve was estimated. All statistical tests were two-sided. RESULTS TMEM score was associated with increased risk of distant metastasis in estrogen receptor (ER)(+)/human epidermal growth factor receptor (HER2)(-) tumors (multivariable OR high vs low tertile = 2.70; 95% CI = 1.39 to 5.26; P trend = .004), whereas IHC4 score had a borderline positive association (OR10 unit increase = 1.06; 95% CI = 1.00 to 1.13); the association for TMEM score persisted after adjustment for IHC4 score. The area under the curve for TMEM, adjusted for clinical variables, was 0.78. Neither TMEM score nor IHC4 score was independently associated with metastatic risk overall or in the triple negative or HER2(+) subgroups. CONCLUSIONS TMEM score predicted risk of distant metastasis in ER(+)/HER2(-) breast cancer independently of IHC4 score and classical clinicopathologic features.

Diagnostic utility of MYC amplification and anti-MYC immunohistochemistry in atypical vascular lesions, primary or radiation-induced mammary angiosarcomas, and primary angiosarcomas of other sites

Breast cancer patients who receive radiation therapy or develop chronic lymphedema following axillary dissection can develop secondary mammary angiosarcomas (ASs) and, additionally, atypical vascular lesions (AVLs) in the former group. Recently, MYC amplification by fluorescence in situ hybridization (FISH) has been identified in secondary mammary AS but not in AVL and most primary mammary AS as well as AS of other sites. We studied MYC amplification and MYC protein expression in 7 radiation-induced AVLs, 9 secondary mammary ASs, 17 primary mammary ASs, and 20 primary ASs of other sites by FISH analysis and immunohistochemistry. All 9 secondary mammary ASs showed gene amplification and protein expression, whereas neither was found in any of 7 AVLs. No MYC amplification or protein expression was identified in any of the 17 primary mammary ASs. Among primary ASs of other sites, 1 cardiac AS and 1 skin AS showed gene amplification and protein expression. The remaining 18 did not show amplification (90%), but some demonstrated protein expression (39%). We conclude that MYC amplification by FISH is present in secondary mammary AS but not in AVL. We also found MYC amplification in 1 primary skin AS and 1 primary cardiac AS. There was 100% concordance between MYC amplification and protein expression in all AVL, primary mammary AS, and secondary mammary AS, whereas only 65% concordance was found in AS of other sites. MYC protein expression in AS can be helpful in certain diagnostic scenarios in the breast but not in other sites.

A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples

Inflammatory and reactive lesions of the breast are relatively uncommon among benign breast lesions and can be the source of an abnormality on imaging. Such lesions can simulate a malignant process, based on both clinical and radiographic findings, and core biopsy is often performed to rule out malignancy. Furthermore, some inflammatory processes can mimic carcinoma or other malignancy microscopically, and vice versa. Diagnostic difficulty may arise due to the small and fragmented sample of a core biopsy. This review will focus on the pertinent clinical, radiographic, and histopathologic features of the more commonly encountered inflammatory lesions of the breast that can be characterized in a core biopsy sample. These include fat necrosis, mammary duct ectasia, granulomatous lobular mastitis, diabetic mastopathy, and abscess. The microscopic differential diagnoses for these lesions when seen in a core biopsy sample will be discussed.

Cystic hypersecretory (in situ) carcinoma of the breast: a clinicopathologic and immunohistochemical characterization of 10 cases with clinical follow-up.

Cystic hypersecretory carcinoma (CHC) is an uncommon variant of ductal carcinoma in situ characterized by, among other features, the presence of luminal secretion resembling thyroidal colloid. CHC is thought to behave in an indolent manner but has the potential to give rise to invasive carcinoma, which is often poorly differentiated. We studied the immunohistochemical, clinical, and morphologic features of 10 cases of CHC. All patients were women averaging 62.8 years in age (range, 47 to 79 y). The clinical/radiographic presentation was a mass (5/10), calcifications (3/10), bloody nipple discharge (1/10), and unknown (1/10). Microscopic size of CHC ranged from 0.2 to 2.7 cm (mean, 0.9 cm). Micropapillary growth was present in all cases. Nuclear grade was intermediate (5/10) or high (5/10). One case also showed microinvasive carcinoma. All cases arose in a background of cystic hypersecretory hyperplasia (CHH) and/or CHH with atypia. CHC was ER+ in 8/10 cases (ER+/PR+, 4/10; ER+/PR−, 4/10). Two cases were ER−/PR−, including the case with microinvasive carcinoma. All were HER2−. Androgen receptor was expressed in 3/10 (30%) cases. Myoepithelial stains p63, smooth muscle myosin, and CK5 showed circumferential staining in 9/10 (90%) cases, whereas 1 case was negative for p63, smooth muscle myosin, and CK5 in both CHC and adjacent CHH. Basal-like carcinoma markers EGFR, CK14, and CK5 were negative in all cases, with the exception of 1 case that was positive for EGFR. Four patients with follow-up information showed no evidence of disease (mean, 5.5 y). CHC is a distinct variant of ductal carcinoma in situ that arises in a background of CHH and is characterized by micropapillary growth, intermediate-grade to high-grade nuclei, and luminal colloid-like secretion. CHC is usually ER+ and HER2−. Negative or discontinuous reactivity with myoepithelial markers may be seen, despite its in situ nature. CHC usually behaves in a nonaggressive manner as was seen in our patients who were all free from disease at last follow-up.

Cystic apocrine hyperplasia is the most common finding in MRI detected breast lesions

MRI of the breast is an increasingly employed modality for breast imaging due to its relatively high sensitivity for the detection of breast carcinoma. Cumulative data indicate that MRI of the breast has relatively higher sensitivity, but lower specificity than mammography. However, data regarding the diagnostic yield for particular types of breast lesions detected via breast MRI remain scant. Over a 3.5-year period, we evaluated histological findings of 192 needle core biopsies of MRI detected breast lesions. In this series, the positive predictive value of MRI detected lesions for breast carcinoma was 20%. Invasive carcinoma was diagnosed in 16/192 (8%) and in situ carcinoma in 22/192 (11%). The most commonly detected histological finding was cystic apocrine hyperplasia (19%), a benign entity.

Folate Receptor Alpha Expression Is Associated With Increased Risk of Recurrence in Triple-negative Breast Cancer

Background: Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in breast cancer. The limited studies evaluating the role of FOLR1 in breast cancer have shown that FOLR1 protein expression is enriched in triple‐negative breast cancer (TNBC) and associated with poor prognosis in all breast cancer types. Newly developed anti‐FOLR1 therapy could potentially be used in patients with TNBC for whom few therapeutic options exist. We sought to evaluate FOLR1 protein expression in a cohort of patients with TNBC to determine its prevalence and prognostic value. Materials: Immunohistochemistry was performed for FOLR1 in 76 cases of primary TNBC. Membranous staining in ≥ 5% of cells was deemed positive in a given case. Statistical analyses correlating FOLR1 protein expression with clinicopathologic parameters and clinical outcome (disease‐free survival and overall survival) were performed. Results: A total of 76 cases of primary TNBC were studied. Most cases were negative for FOLR1 (80.3%; 61/76). FOLR1 expression did not correlate with any clinicopathologic parameters. FOLR1 expression was significantly correlated with decreased disease‐free survival (hazard ratio, 2.61; 95% confidence interval, 0.96–7.09; P = .0497 log‐rank test). Although FOLR1 expression trended towards decreased overall survival, it was not statistically significant (hazard ratio, 1.99; 95% confidence interval, 0.62–6.36; P > .05 log‐rank test). Conclusion: We found a lower incidence of FOLR1 expression in TNBC compared with other studies; however, these patients may benefit from anti‐folate therapy as other targeted therapies are not available. Although no correlation between FOLR1 expression and standard clinicopathologic parameters was identified, our findings suggest that FOLR1 expression is prognostically significant in TNBC. Micro‐Abstract: Treatment options for patients with triple‐negative breast cancer (TNBC) are limited. Folate Receptor Alpha (FOLR1) is a potential target, whereas overexpression has been associated with poor prognosis in all breast cancer subtypes. In 76 TNBCs, 20% demonstrated FOLR1 overexpression, which was significantly associated with decreased disease‐free survival. Although eligible for anti‐FOLR1 therapy, patients with FOLR1‐positive TNBC were found to have an increased risk of recurrence.

More than just metastases: a practical approach to solid mesenteric masses

The abdominal mesenteries are important peritoneal structures that give rise to a wide spectrum of abnormalities, including solid mesenteric masses. Despite similarities in appearance, solid masses in the mesentery may have diverse etiologies, ranging from benign to highly malignant. While metastases are the most common cause of solid masses in the mesentery, other less common conditions are also important diagnostic considerations. This article reviews four pathologic entities (sclerosing mesenteritis, carcinoid tumors, desmoids tumors, and gastrointestinal stromal tumors) that may be manifested on abdominal imaging examinations by one or more mesenteric masses. These four pathologic entities are used to present a systematic approach to the radiographic characterization of solid mesenteric masses based on the morphology of the lesions, locoregional effects, and distant findings on various abdominal imaging examinations.

Current Concepts in Diagnosis, Molecular Features, and Management of Lobular Carcinoma In Situ of the Breast With a Discussion of Morphologic Variants

CONTEXT - Lobular carcinoma in situ (LCIS) refers to a neoplastic proliferation of cells that characteristically shows loss of E-cadherin expression and has long been regarded as a risk factor for invasive breast cancer. Long-term outcome studies and molecular data have also implicated LCIS as a nonobligate precursor to invasive carcinoma. In the past few decades, pleomorphic and florid LCIS have been recognized as morphologic variants of LCIS with more-aggressive histopathologic features, less-favorable biomarker profiles, and more-complex molecular features compared with classic LCIS. There is still a lack of consensus regarding certain aspects of managing patients with LCIS. OBJECTIVES - To review recently published literature on LCIS and to provide an overview of the current morphologic classification of LCIS, recent molecular advances, and trends in patient management. DATA SOURCES - Sources included peer-reviewed, published journal articles in PubMed (US National Library of Medicine, Bethesda, Maryland) and published guidelines from the National Comprehensive Cancer Network (Fort Washington, Pennsylvania). CONCLUSIONS - Lobular carcinoma in situ represents a marker for increased risk of breast cancer, as well as a nonobligate precursor to invasive carcinoma. Morphologic variants of LCIS-florid and pleomorphic LCIS-are genetically more-complex lesions and are more likely to be associated with invasive carcinoma. Further investigation into which molecular alterations in LCIS are associated with progression to invasive carcinoma is needed to help guide medical and surgical management.

Papillary Thyroid Carcinoma With Nodular Fasciitis–Like Stroma A Usual Entity With Distinctive Morphology

Papillary thyroid carcinoma (PTC) is a common malignancy with multiple variants, some of which are rarely encountered in routine surgical pathology practice. PTC with exuberant nodular fasciitis–like stroma (PTC-NFS) or PTC with fibromatosis-like stroma (PTC-FMS) is one such variant. We report a case of PTC-NFS, a tumor characterized by an abundant stromal component with an intervening epithelial component with the typical morphologic features of conventional PTC. We review the literature on this rare variant, discuss the importance of a thorough search for epithelial components within any fibroproliferative lesion of the thyroid, and address the diagnostic difficulties created by the tumor’s extensive stromal component.

Pleomorphic Adenoma of Breast: A Radiological and Pathological Study of a Common Tumor in an Uncommon Location

Pleomorphic adenoma occurs commonly in the major salivary glands but is uncommonly encountered in the breast. In both of these locations, the tumor is typically grossly circumscribed and has a “mixed” histological appearance, being composed of myoepithelial and epithelial components amid a myxochondroid matrix. Herein, we report a case of pleomorphic adenoma of the breast which was preoperatively thought to represent a fibroadenoma on clinical and radiological grounds. It is the rarity of the tumor in the breast, rather than its histological appearance, that causes diagnostic difficulty.