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Transthyretin cardiomyopathy (ATTR-CM) is a cardiac condition caused by the deposition of transthyretin (TTR) fibrils in cardiac tissue. Recent studies have shown that ATTR amyloidosis may be present in a significant proportion of patients with heart failure, transcatheter aortic valve repair, and hypertrophic cardiomyopathy. The prevalence of ATTR-CM may be even higher among Black Americans due to a specific genetic variant. This article proposes the possibility of using prostate samples to screen for amyloid deposits as a potential method for early detection of ATTR-CM. Several studies have shown that a percentage of prostate samples contain amyloid deposits, and a significant proportion of these patients may develop cardiac involvement. However, further research is needed to accurately distinguish TTR amyloid from other types and to determine the clinical relevance of prostatic amyloid deposits. [Extracted from the article]

Introduction Despite the fact that the characteristic translocation of myxoid round cell liposarcoma (MRCLS) that results in the fusion protein TLS:CHOP was characterized almost 20 years ago (1, 2), the [...], Myxoid round cell liposarcoma (MRCLS) is a common liposarcoma subtype characterized by a translocation that results in the fusion protein TLS:CHOP as well as by mixed adipocytic histopathology. Both the etiology of MRCLS and the mechanism of action of TLS:CHOP remain poorly understood. It was previously shown that ET743, an antitumor compound with an unclear mechanism of action, is highly effective in patients with MRCLS. To identify the cellular origin of MRCLS, we engineered a mouse model in which TLS:CHOP was expressed under the control of a mesodermally restricted promoter (Prx1) in a p53-depleted background. This model resembled MRCLS histologically as well as functionally in terms of its specific adipocytic differen tiation based response to ET743. Specifically, endogenous mesenchymal stem cells (MSCs) expressing TLS: CHOP developed into MRCLS in vivo. Gene expression and microRNA analysis of these MSCs showed that they were committed to adipocytic differentiation, but unable to terminally differentiate. We also explored the method of action of ET743. ET743 downregulated TLS:CHOP expression, which correlated with CEBP α expression and adipocytic differentiation. Furthermore, PPAR £ agonists enhanced the differentiation process initiated by ET743. Our work highlights how clinical observations can lead to the generation of a mouse model that recapitulates human disease and may be used to develop rational treatment combinations, such as ET743 plus PPAR £ agonists, for the treatment of MRCLS.

The skeleton is affected by many nonneoplastic processes that may be interpreted clinically and radiographically as either benign or malignant primary bone tumors. Even if a benign or nonneoplastic process [...], Context.--The skeletal system may be affected by a variety of nonneoplastic lesions, which may potentially be confused with primary bone tumors on clinical, radiologic, and pathologic grounds. These conditions include fractures, infections, and reactive and degenerative processes, as well as an array of quasineoplastic entities, such as intramedullary cystic lesions like unicameral and aneurysmal bone cysts; fibro-osseous lesions, such as fibrous dysplasia; and exophytic entities, like osteochondromas. Objective.--To review clinical, radiographic, and histologic features of nonneoplastic lesions of bone, discussing the difficulties in diagnosis and the differential diagnosis with primary neoplasms of bone. Data Sources.--The sources include the more relevant medical literature on the different subjects and case-derived material. Conclusions.--Because many nonneoplastic bone lesions may require biopsy or resection, the general surgical pathologist must be familiar with these lesions and be aware that review of hematoxylin-eosin slides is only one of the many steps in the diagnostic process, which also includes review of imaging studies and all available clinical information. Morphologic analysis disconnected from the clinical and radiographic context may lead to misinterpretation. (Arch Pathol Lab Med. 2012; 136:772-788; doi: 10.5858/arpa.2011-0557-RA)

The mechanisms underlying the pathogenesis of estrogen-induced breast carcinogenesis remain unclear. The present study investigated the roles of estrogen metabolism and oxidative stress in estrogen-mediated mammary carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated with 17β-estradiol (E2), the antioxidant vitamin C, the estrogen metabolic inhibitor α-naphthoflavone (ANF), or cotreated with E2 + vitamin C or E2 + ANF for up to 8 months. E2 (3 mg) was administered as an subcutaneous implant, ANF was given via diet (0.2%) and vitamin C (1%) was added to drinking water. At necropsy, breast tumor incidence in the E2, E2 + vitamin C and E2 + ANF groups was 82, 29 and 0%, respectively. Vitamin C and ANF attenuated E2-induced alterations in oxidative stress markers in breast tissue, including 8-iso-prostane F2α formation and changes in the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase. Quantification of 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) formation in breast tissue confirmed that ANF inhibited 4-hydroxylation of E2 and decreased formation of the highly carcinogenic 4-OHE2. These results demonstrate that antioxidant vitamin C reduces the incidence of estrogen-induced mammary tumors, increases tumor latency and decreases oxidative stress in vivo. Further, our data indicate that ANF completely abrogates breast cancer development in ACI rats. The present study is the first to demonstrate the inhibition of breast carcinogenesis by antioxidant vitamin C or the estrogen metabolic inhibitor ANF in an animal model of estrogen-induced mammary carcinogenesis. Taken together, these results suggest that E2 metabolism and oxidant stress are critically involved in estrogen-induced breast carcinogenesis. [ABSTRACT FROM AUTHOR]

This report describes the clinicopathologic and immunohistochemical findings in 21 cases of a highly distinctive tumor with a strong predilection for the lower neck region of adult males. Our study group consisted of 20 males and one female. The patients were 28 to 79 years old (mean age, 47 years; median age, 40 years), and they presented with solitary, lobular or multilobular masses ranging in size from 2.0 to 19.0 cm in greatest dimension (mean size, 5.1 cm; median, 4 cm). The tumors principally involved the lower neck region, usually in close proximity to the sternoclavicular joint. The preoperative duration of the lesions ranged from 2 months to 30 years. Histologically, the tumors were typically well marginated and composed of plump spindled cells, delicate spindled cells, mature adipose tissue, and epithelial cells, including both squamous and glandular elements. Epithelial-lined cysts were a focal finding in most cases and measured up to 2 cm in greatest dimension. Mitotic counts for the tumors ranged from 0 to 7 mitotic figures per 50 high power fields (mean mitotic count, 1.1 mitotic figures per 50 HPFs). Our immunohistochemical analysis revealed a complex immunophenotype with a diverse keratin profile. The plump spindled cells had a myoepithelial phenotype, as evidenced by the coexpression of keratins (5, 5/6, and 14), alpha-smooth muscle actin, CD10, and to a lesser extent, calponin. No compelling evidence for thymic differentiation was observed. The patients were initially managed by biopsy or partial resection (n = 4), simple local excision (n = 16), or an unspecified procedure (n = 1). Clinical follow-up of > or =3 years was available for 10 patients (48%). Two patients had recurrent disease, but there were no metastases or tumor-related deaths. A derivation from sequestered branchial epithelium is likely, but evidence for a thymic component is tenuous, at best. Our data support reclassification of this distinctive process as a branchial anlage mixed tumor. The differential diagnosis includes conventional mixed tumors of skin adnexal or salivary gland origin, synovial sarcoma, a peripheral nerve sheath tumor variant, and cystic teratoma.

Tenosynovial chondromatosis is a multinodular cartilaginous proliferation that arises from the tenosynovial membranes. This report describes the clinical, radiologic, and histopathologic findings in 37 cases of this uncommon entity. There were 17 males and 20 females, ranging in age from 20 to 86 years (mean and median age, 46 years). The process involved tenosynovium of the fingers (n = 19), feet (n = 8), wrists (n = 4), ankles (n = 2), hand, not otherwise specified, or palm (n = 2), knee (n = 1), and forearm (n = 1). Signs of disease or symptoms were present for 5 weeks to 18 years (median duration, approximately 2 years) before surgical excision. The two most common complaints were a painless mass and a mass that was mildly tender with pressure. None of the tumors had clinical, radiologic, or histopathologic evidence of articular or bone involvement. Histologically, all tumors consisted of a multinodular cartilaginous proliferation involving tenosynovium and/or subsynovial connective tissue. Mild or moderate atypia, as encountered in chondroma of soft parts and synovial chondromatosis, was a frequent finding. Follow-up information was available for 16 patients (43%). Only two patients with follow-up information remained disease free after their initial surgical procedure. Seven patients had one recurrence and seven patients had two or more recurrences. Tenosynovial chondromatosis appears to be an extraarticular counterpart of synovial (intraarticular) chondromatosis. Our review indicates this process is often confused with chondroma of soft parts, in part, because both entities have a predilection for the hands and feet. Diagnosis of this underrecognized entity is of clinical importance because of the high local recurrence rate.