Massive localized lymphedema is a monstrous tumefactive pseudosarcoma seen in middle-aged morbidly obese adults. Since its initial description in 1998, the etiology remains unknown, although associations with trauma, surgeries, and hypothyroidism have been reported. Herein, we report the largest study of massive localized lymphedema and expand upon its clinicopathologic features. Fifty-four cases from 46 patients were retrospectively identified from the institutional archives of The Ohio State University Wexner Medical Center between 2002 and 2015. Forty-six patients (21 males and 25 females, mean age 50 years) presented with large masses developing over a 5-60-month period. The majority of patients were Caucasian (n = 39). All patients were obese with a mean weight of 384.7 lb and a mean body mass index of 59.6 kg/m 2 . Thirty-six patients had a history of atherosclerotic cardiovascular disease and diabetes mellitus type 2 was present in 22 patients. Eight patients had multifocal massive localized lymphedema. The sites included thigh (n = 33), abdomen (n = 17), suprapubic region (n = 1), mons pubis (n = 6), scrotum (n = 2), perianal region (n = 1), and right flank (n = 1). Mostly, the clinical impression was benign processes, including pannus or lymphedema pseudotumor. Grossly, the mean weight was 8237 g and the mean size was 53.2 cm. Histologically, eight cases showed a unique pattern of dystrophic calcifications mimicking hyperchromatic, atypical nuclei that might lead to misdiagnosis of liposarcoma, four cases showed focal metaplastic ossification, and three cases showed multinucleated cells in addition to prototypic features of massive localized lymphedema. We report that this is the largest series of massive localized lymphedema. This is a lesion mostly seen in morbidly obese patients and the thigh is the most common site of involvement. We note a marked racial predilection for Caucasians and a tendency towards multiplicity. We suggest that obesity itself and the related metabolic syndrome have an important role in its pathogenesis.

Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in bone mineralization and motor function, but it is unclear whether the medication can affect fracture healing in adult HPP patients. We present the course of fracture healing in two adults with HPP on enzyme replacement. Case 1 is a 41‐year‐old female with infantile‐onset HPP who was wheelchair‐bound due to a nonhealing tibial fragility fracture sustained 3 years before and also had nonhealing femoral pseudofracture sustained 17 years before starting asfotase alfa therapy in December 2015. One month after medication initiation, she underwent elective osteotomy of tibia and fibula with intramedullary nail fixation. After 3 months of enzyme replacement, she was full weight‐bearing and radiographs demonstrated callus formation at osteotomy sites, and at 11 months of therapy, radiographs showed union of the osteotomies. By 11 months of asfotase alfa therapy, there was near resolution of the femoral pseudofracture without interval surgery at this site. Case 2 is a 61‐year‐old male who showed nonunion of a fragility fracture of the right femur 8 years prior, intramedullary nail fixation 6 years prior, and stress fracture of the left femoral diaphysis sustained 1 year before starting asfotase alfa in October 2015. A trial of teriparatide was unsuccessful in healing of these fractures. On asfotase alfa, radiographs revealed interval healing of the left femur fracture after 12 months and complete healing of the right femur fracture and near resolution of the left femur fracture after 16 months of medical therapy. These two adult patients with HPP showed significant clinical and radiographic improvements in a total of four recalcitrant fractures on enzyme replacement therapy with asfotase alfa. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Manganese/ligand association dynamics were studied using a series of structurally related anionic phosphorus ester ligand probes [CH(3)OP(O)(X)(Y)(-), where X = CH(3)O, CH(3)CH(2), or H and Y = O, S, or BH(3)]. Reactions of the probe ions with Mn(H(2)O)(6)(2+) and a manganese(III) porphyrin (Mn(III)TMPyP(5+)) were studied in aqueous solution by paramagnetic (31)P NMR line-broadening techniques. A satisfactory linear free energy relationship for reactions of the probe ions with Mn(H(2)O)(6)(2+) and Mn(III)TMPyP(5+) required consideration of both the basicity and solvent affinity of the probe ligands: log(k(app)) = log(k(0)) + alpha pK(a) + beta log(K(ext)), where k(0), alpha, and beta are metal complex dependent parameters and pK(a) and K(ext) represent the measured Bronsted acidity and water/n-butanol extraction constant for the probe anions, respectively. Reactions of Mn(H(2)O)(6)(2+) were relatively insensitive to changes in ligand basicity (alpha = -0.04) and favored the more hydrophilic anions (beta = -0.54). These observations are consistent with a dissociative ligand exchange mechanism wherein the outer-sphere complex is stabilized by hydrogen bonding between Mn(H(2)O)(6)(2+) and the incoming ligand. In contrast, reactions with Mn(III)TMPyP(5+) are accelerated by decreases in both the basicity (alpha = -0.43) and the hydrophilicity (beta = +0.97) of the probe. We conclude that reactions of Mn(III)TMPyP(5+) are also dissociative but that the aromatic groups of the porphyrin provide a hydrophobic environment surrounding the ligand binding site in Mn(III)TMPyP(5+). Thus, the probe/water solvent interactions must be significantly weakened in order to form the outer-sphere complex that leads to ligand substitution. This work demonstrates the utility of phosphorus relaxation enhancement (PhoRE) techniques for characterizing the second coordination sphere environment of metal complexes leading to ligation and will allow comparison of the second coordination spheres of Mn(H(2)O)(6)(2+) and Mn(III)TMPyP(5+) to those of other metal complexes.