Biopsy Proven Focal Osteolysis in a Stainless-Steel Limb-Lengthening Device: A Report of Three Cases.

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.

PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis.

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.

Angiosarcoma arising in a patient with a 10-year-old hemangioma.

The transformation of a benign hemangioma into a malignant angiosarcoma has been rarely reported, with only 11 cases reported in the literature. There have been no reports of malignant transformation of hemangioma into angiosarcoma in association with epithelioid hemangioendothelioma, to our knowledge. The existence of precursor malignancies in the tumorigenesis of sarcomas is still not clearly defined. We describe the case of a 40-year-old woman with a preceding history of a suspected hemangioma for ten years, who upon resection was found on histology to have evidence of a hemangioma with an associated area of epithelioid hemangioendothelioma as well as areas of overt high grade epithelioid angiosarcoma. These findings raise the possibility of the evolution of hemangioma to epithelioid hemangioendothelioma, and the latter to overt angiosarcoma. The patient was managed as having a high grade sarcoma with wide resection and radiation. She declined systemic adjuvant chemotherapy after a thorough discussion about the risks and benefits of chemotherapy, and she currently remains disease free one year after the surgery.

Heterogeneity of breast cancer metastases: comparison of therapeutic target expression and promoter methylation between primary tumors and their multifocal metastases.

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) on 10 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 MET overexpression 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 alpha, APC1, and RARbeta 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.

Distinguishing benign dissecting mucin (stromal mucin pools) from invasive mucinous carcinoma.

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.

The source of corticocollicular and corticobulbar projections in area Te1 of the rat.

Cortical area Te1 in the rat commonly is associated with primary auditory cortex. It is the source of direct projections to the inferior colliculus (IC), superior olivary complex (SOC), and the cochlear nucleus (CN). A question that arises is whether these descending pathways derive from a common source or separate populations of cortical neurons. We addressed this question in seven rats by injecting either Diamidino yellow (DiY) or Fast blue (FB) into the IC and injecting the other tracer into the CN (n=4) or SOC (n=3). All injections were made on the left side of the brain. In a sample of sections through area Te1 in both hemispheres, we counted single- and double-labeled cells. We estimate that IC-projecting cells outnumber those projecting to the CN or SOC by at least a factor of ten. The source of corticofugal pathways to the left IC was heavily biased towards the same side of the brain (ipsi/contra ratio 8 +/- 2.5), whereas it was more equally distributed between the two hemispheres for the left CN and SOC (ipsi/contra ratios ranged from 0.7-2.3). Finally, we observed that only 10-20% of those cells filled with a tracer injection in the CN or SOC also contained the tracer injected into the IC. In a previous study, we observed a similarly small percentage of double labeled cells when FB and DiY were injected into the CN and SOC, respectively. Combined with the distinct laminar distribution of IC-, SOC-, and CN-projecting neurons within layer V, the results suggest that these three pathways largely derive from different populations of cortical neurons.