Purpose: A comprehensive comparison of biomarker expression between patients' primary breast carcinoma (PBC) and their metastatic breast carcinomas (MBC) has not been done. Experimental Design: We did rapid autopsies (postmortem intervals,1-4 hours) on10 consenting patients who died of MBC.We constructed single-patient tissue microarrays from the patients' archived PBC and multiple different MBCs harvested at autopsy, which were immunohistochemically labeled for multiple biomarkers. Methylation of multiple gene promoters was assessed quantitatively on dissected PBC and MBC samples. Results: Extensive heterogeneity was observed between PBC and their paired MBC, as well as among multiple MBC from the same patient. Estrogen and progesterone receptors tended to be uniformly down-regulated in metastases. E-cadherin was down-regulated in a subset of the MBC of one case.Variable overexpression in MBC compared with the PBC was observed for cyclooxygenase-2 (five cases), epidermal growth factor receptor (EGFR; four cases), MET (four cases), and mesothelin (four cases). No case strongly overexpressed HER-2/neu by immunohistochemistry, but eight cases showed variable protein expression ranging from negative to equivocal (2+) in different MBC. In one case, variable low-level HER-2/neu gene amplification was found. EGFR and METoverexpression were restricted to the four basal-type cancers. EGFR protein overexpression did not correlate with EGFR gene amplification. Multigene promoter hypermethylation of RASSF1a, HIN1, cyclin D2,Twist, estrogen receptor a, APC1, and RARb was overall very similar in the PBC and all MBCs in all cases. Conclusions: Therapeutic targets identified in the PBC or even some MBC may not reflect targets present in all metastatic sites.

Nodular fasciitis (NF) is a clonal self-limited neoplastic proliferation characterized by rearrangements of the USP6 locus in most examples. To our knowledge well-documented malignant behavior has never been previously observed in NF. In this report we present an unusual case of NF with classical histologic features that showed a protracted clinical course characterized by multiple recurrences and eventual metastatic behavior over a period of 10 years. Molecular analyses revealed the presence and amplification of the novel PPPR6-USP6 gene fusion, which resulted in USP6 mRNA transcriptional upregulation. These findings further support the oncogenic role of the USP6 protease in mesenchymal neoplasia and expand the biologic potential of NF. © 2016 Wiley Periodicals, Inc.

Mucin dissecting stroma suggests the presence of an invasive mucinous (colloid) carcinoma. However, in virtually every organ in which invasive mucinous carcinoma exists, there exist benign mimickers associated with dissecting mucin. This article reviews diagnostic criteria for the differential diagnosis of mucinous lesions of the breast, pancreas, biliary tract, colon, appendix, and bladder, emphasizing practical points, which we find helpful in daily diagnostic surgical pathology practice.

Three pediatric patients presented with histologically confirmed osteolysis after limb lengthening with a magnetic, telescoping, stainless-steel device. The first patient's findings were discovered radiographically before routine removal of the device. In all cases, intraoperative histologic specimens taken from around the modular junction demonstrated particle-laden macrophages with suspicion for metal debris. Silicone debris was also identified. We found definitive osteolysis secondary to metal at the modular junction of three stainless-steel lengthening implants. This process is not well-understood in the setting of limb lengthening and should be examined further.