Rare Breast Cancer Subtypes.

PURPOSE OF REVIEW: Breast cancer is a collection of diseases including the more common invasive ductal and lobular carcinomas and rarer subtypes of breast cancer. This review summarizes the features of rare breast cancers. RECENT FINDINGS: Each of the rare tumors has defined pathological and clinical features that impact treatment recommendations. In this review, we summarize these for each rare type of breast cancer and where available we include molecular features of each tumor. Rare subtypes of breast cancer each have unique features. In many cases, data is limited for the optimal treatment approaches.

Classification of Trauma-Associated Invasive Fungal Infections to Support Wound Treatment Decisions.

To evaluate a classification system to support clinical decisions for treatment of contaminated deep wounds at risk for an invasive fungal infection (IFI), we studied 246 US service members (413 wounds) injured in Afghanistan (2009-2014) who had laboratory evidence of fungal infection. A total of 143 wounds with persistent necrosis and laboratory evidence were classified as IFI; 120 wounds not meeting IFI criteria were classified as high suspicion (patients had localized infection signs/symptoms and had received antifungal medication for >10 days), and 150 were classified as low suspicion (failed to meet these criteria). IFI patients received more blood than other patients and had more severe injuries than patients in the low-suspicion group. Fungi of the order Mucorales were more frequently isolated from IFI (39%) and high-suspicion (21%) wounds than from low-suspicion (9%) wounds. Wounds that did not require immediate antifungal therapy lacked necrosis and localized signs/symptoms of infection and contained fungi from orders other than Mucorales.

Elucidating encounters of atypical ductal hyperplasia arising in gynaecomastia.

AIMS: Atypical ductal hyperplasia (ADH) rarely arises in gynaecomastia. We set out to understand more clearly the clinical, histological and immunohistochemical features of ADH in this setting. METHODS AND RESULTS: Twenty-five cases of ADH arising in gynaecomastia, nine cases of ductal carcinoma in situ (DCIS) and 36 cases of gynaecomastia with usual ductal hyperplasia (UDH) were studied. Reviews of clinical, morphological and immunohistochemical findings were performed. The extent of cytokeratin 5/6 (CK5/6) luminal epithelial cell staining was assessed (0% = 0, < 10% = 1, 10-50% = 2 and > 50% = 3). Oestrogen receptor (ER) was evaluated using the H-scoring system. The average age of ADH patients was 35 years (range 14-78). ADH was bilateral in 20% and less frequent in active gynaecomastia (24%). ADH often showed a cribriform pattern (72%), with less nuclear variation/size and similar frequency of mitoses than UDH cells. CK5/6 luminal epithelial staining was decreased in ADH (68%) versus UDH (11%). ADH showed high ER expression compared to UDH (H score > 270 in 88% and 14%, respectively). CONCLUSIONS: ADH in gynaecomastia can be distinguished from UDH by morphological and immunohistochemical features. We also identified a subset of young patients (< 25 years) with extensive bilateral ADH. More studies are needed to characterize this patient subset more clearly.

Heritability of Low ER Staining/HER2-Breast Tumors: Are We Missing an Opportunity for Germline Testing?

In 2010, the genetic testing criteria was changed to allow women diagnosed ≤ 60 years old with triple negative breast cancer (TNBC) to undergo germline testing. In the same year, estrogen receptor (ER) positivity was defined as having ≥1% ER staining cells. While tumors with 1-10% ER staining cells and HER2 negative (HER2-) status share characteristics with TNBC, the utility of germline testing in women with ER low positive/HER2- (ERLP/HER2-) tumors is not well-understood. To this end, all patients with hormone receptor positive staining cells ≤ 10% and negative HER2 status were identified. Clinical genetic test results were extracted for patients who underwent testing. Panel testing was performed for those women who had genomic DNA available for research purposes. ERLP/HER2-tumors constituted 2.7% of all tumors in the database. Patients did not differ significantly from those with TNBC by age at diagnosis, ethnicity, family history or tumor size, stage or grade (p > 0.05). Mutation frequency did not differ significantly (p = 0.757) between groups (ERLP/HER2- 16.1%; TNBC 16.7%). Hereditary forms of breast cancer were similar in both ERLP/HER2- and TNBC, thus current guidelines may result in the under testing of women with low ER tumors, resulting in missed opportunities to improve patient management.

Evaluating the utility of trefoil factor 1 as a mammary-specific immunostain compared and in conjunction with GATA-3 and mammaglobin in the distinction between carcinoma of breast and lung.

OBJECTIVES: The distinction between metastatic breast carcinomas (BCs) and primary lung carcinomas (PLCs) can be difficult. This study tested the utility of trefoil factor 1 (TFF1) for this purpose and compared it with mammaglobin and GATA protein binding 3 (GATA-3). METHODS: Tissue microarrays containing 365 BCs and 338 PLCs were stained with TFF1, mammaglobin, and GATA-3, and an H-score was calculated. Sensitivity, specificity, and accuracy were calculated, and logistical regression analysis was performed. RESULTS: Accuracy of correctly classifying the tumor type was 81.9%, 71.3%, and 64.0% for GATA-3, mammaglobin, and TFF1, respectively. Odds ratios for selecting BCs were 25.69, 93.15, and 4.17, respectively, with P values less than .001. With a single exception, the best immunopanel included GATA-3 and mammaglobin in all comparisons. CONCLUSIONS: TFF1 demonstrated breast specificity but was inferior to mammaglobin and GATA-3. Therefore, its routine clinical use may not be justified. TFF1 showed little benefit when added to an immunopanel.

Are renal reference intervals required when screening for plasma cell disorders with serum free light chains and serum protein electrophoresis?

Renal impairment and polyclonal hypergammaglobulinemia may abnormally increase the serum free light chain (sFLC) ratio, giving false-positive results with current reference intervals. We measured sFLCs with concomitant serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) in 281 patients. Results were interpreted relative to renal function (serum creatinine concentrations) and polyclonal hypergammaglobulinemia. Overall, 78 plasma cell disorders (PCDs) were detected with the serum panel of SPEP/sFLC vs 76 with SPEP/UPEP. In 13 samples with negative SPEP/UPEP, mildly increased ratios up to 3.1 (normal, 0.26-1.65) were observed: 10 were associated with increased serum creatinine and 1 with polyclonal hypergammaglobulinemia; 2 were unassociated with either condition. In 2 samples, decreased kappa/lambda ratios were identified that were clinically significant despite normal SPEP/UPEP. Two monoclonal gammopathies were identified with UPEP and sFLC, but samples were normal with SPEP. Screening for PCDs with a serum panel consisting of SPEP and the sFLC assays is a highly sensitive approach that could eliminate the need for UPEP. A mildly increased kappa/lambda ratio up to 3.1 was observed with increased serum creatinine and/or polyclonal hypergammaglobulinemia that was consistent with pathophysiologic changes, and, therefore, renal reference intervals are recommended.