Ossifying fasciitis of the proximal lower extremity.

Ossifying fasciitis is a rare benign tumor of heterotopic bone formation within fascial tissue. We present a case of a 23-year-old female with a nontraumatic painful mass of the left proximal thigh identified as ossifying fasciitis, a lesion that must be considered in the differential diagnosis of soft tissue tumors.

Correlation of spontaneous radiographic cranial tibial translation with complete cranial cruciate ligament rupture and medial meniscal tears in dogs.

The primary objective of our study was to determine the prevalence of cranial tibial translation on a single unstressed, standing angle, mediolateral radiograph of the stifle and the accuracy of diagnosing complete cranial cruciate ligament rupture in dogs with this finding using a previously published method. The secondary objective was to determine if there was a higher incidence of meniscal injuries associated with spontaneous radiographic cranial tibial translation as previously proposed. Medical records were reviewed for client owned dogs with cranial cruciate ligament rupture that underwent surgical stabilization with intra-operative evaluation of the stifle joint via arthrotomy between June 2013 to January 2022 and had pre-operative radiographs performed within 60 days prior to surgery. Pre-operative radiographs were evaluated for cranial tibial translation via the previously published method. Three hundred twenty-three dogs met the inclusion criteria for the study. Intra-operative findings and radiographic assessments were evaluated for correlations. Cranial tibial translation on pre-operative standing angle radiographs detected cranial cruciate ligament tears in 24.8% of cases but had a positive predictive value of 97.5% for diagnosing complete cranial cruciate ligament rupture with a specificity of 95.4% and an overall accuracy of 36.8%. Meniscal tears were present in 58.75% of cases with radiographic cranial tibial translation and 41.25% of cases without. There was no significant increase in the incidence of meniscal tears between the two groups. The presence of radiographic cranial tibial translation in dogs on an unstressed, standing angle, mediolateral radiograph of the stifle is diagnostic for cranial cruciate ligament rupture, but cannot be used to determine the presence of a meniscal tear.

Calcified Chondroid Mesenchymal Neoplasm: Exploring the Morphologic and Clinical Features of an Emergent Entity With a Series of 33 Cases.

Calcified chondroid mesenchymal neoplasm is a term proposed for tumors with a spectrum of morphologic features, including cartilage/chondroid matrix formation, that frequently harbor FN1 gene fusions. We report a series of 33 cases of putative calcified chondroid mesenchymal neoplasms, mostly referred for expert consultation out of concern for malignancy. Patients included 17 males and 16 females, with a mean age of 51.3 years. Anatomic locations include the hands and fingers, feet and toes, head and neck, and temporomandibular joint; 1 patient presented with multifocal disease. Radiologic review showed soft tissue masses with variable internal calcification, which occasionally scalloped bone but in all cases appeared indolent/benign. Tumors had a mean gross size of 2.1 cm and a homogenous rubbery to fibrous/gritty tan-white cut surface. Histology demonstrated multinodular architecture with a prominent chondroid matrix and increased cellularity towards the periphery of the nodules. The tumor cells were polygonal with eccentric nuclei and bland cytologic features and showed a variable amount of increased spindled / fibroblastic forms in the perinodular septa. The majority of cases had notable grungy and/or lacy calcifications. A subset of cases demonstrated at least focal areas of increased cellularity and osteoclast-like giant cells. Herein, we confirm the distinct morphologic and clinicopathologic features associated with this entity with the largest series to date, with a focus on practical diagnostic separation from similar chondroid neoplasms. Awareness of these features is critical in avoiding pitfalls, including a malignant diagnosis of chondrosarcoma.

Surgical treatment of persistent right aortic arch with combined ligamentum arteriosum transection and esophageal diverticulum resection in three dogs.

OBJECTIVE: To describe the treatment of persistent right aortic arch (PRAA) in dogs with combined ligamentum arteriosum (LA) transection and esophageal diverticulum resection. ANIMALS: Three client owned dogs. STUDY DESIGN: Short case series. METHODS: Medical records were reviewed for clinical signs, diagnostic procedures, surgical treatment, post-operative therapies including medications and feeding regime, outcomes, and follow-up imaging. RESULTS: Esophageal resection was performed using a thoracoabdominal (TA) stapler with suture overlay. All dogs recovered well from surgery and did not experience any peri- or post-operative complications. The last follow-up was performed between 64 and 1004 days post-operatively. In all cases, regurgitation resolved and did not recur in any dogs. No dogs required medical therapy or dietary modifications. In two cases, follow-up imaging was performed that revealed marked improvement of esophageal dilation. CONCLUSION: Resection of esophageal diverticulum secondary to PRAA utilizing a TA stapler with suture overlay was technically feasible and did not seem associated with early or late complications.

Fibrous Dysplasia at Unusual Anatomic Sites: A Series of 86 Cases With Emphasis on Histologic Patterns.

Aims. Fibrous dysplasia (FD) is a benign fibro-osseous neoplasm that most commonly arises in the ribs, femur, and craniofacial bones. We analyzed features of FD arising in the spine/short tubular/small bones of the hands/feet (STSBHF), specifically assessing for pattern of bone formation (conventional, complex/anastomosing, psammomatoid/cementum like), myxoid change, and presence of osteoclast-type giant cells. Materials and methods. A total of 1958 cases of FD were reviewed, of which 131 arose in the spine/STSBHF representing 2.5% of institutional and 10% of consultation cases, respectively. Eighty-six cases had material available for review. Anatomic sites included vertebrae (n = 58, 67%), short tubular bones (n = 20, 23%), and small bones of the hands/feet (n = 8, 9%). The most common morphologic pattern of bone identified was conventional (n = 77, 90%), followed by complex/anastomosing (n = 22, 26%) and psammomatoid/cementum like (n = 22, 26%). Eighteen cases (21%) had matrix-poor areas. Hypercellular areas were identified in 6 cases, 2 cases of which showed matrix-poor areas. Osteoclast-type giant cells were noted in 9 cases and myxoid change was present in 3 cases. Radiologic imaging studies available for 41 cases nearly all demonstrated features typical of FD, but the diagnosis was not predicted due to the unexpected location. Conclusions. FD arising in the spine/STSBHF is rare and frequently results in expert consultation. A significant number of cases exhibited less commonly recognized patterns of bone formation, and stromal changes including osteoclast-type giant cells, and matrix poor areas. Furthermore, imaging features in the STSBHF are often less specific. Awareness of the morphologic spectrum at these locations coupled with radiologic correlation should aid in accurate classification.

MyoD1 expression in fibroepithelial stromal polyps.

Fibroepithelial stromal polyps (FESPs) are benign polypoid mesenchymal lesions thought to arise from desmin-positive specialized stromal cells of the female genital tract. Although most cases are easily diagnosed by morphology alone, the morphology of FESPs is variable and in some instances can contain hypercellular stroma with numerous atypical desmin-positive cells, simulating botryoid embryonal rhabdomyosarcoma (ERMS). Recently, we encountered a cellular FESP showing desmin expression as well as nuclear immunoreactivity for the skeletal muscle-associated transcription factor MyoD1. Although these lesions are widely known to express desmin, there are very few studies examining expression of the more specific markers of skeletal muscle differentiation, myogenin and MyoD1. The aim of our study was to examine desmin, MyoD1, and myogenin expression in a series of 25 FESPs. Of the 25 cases, desmin expression was present in 23 (92%), at least focal MyoD1 expression was present in 10 (40%), and all cases were negative for myogenin. Follow-up data were available for all 25 cases, and none recurred or behaved in a malignant fashion. Awareness of this potential immunohistochemical pitfall and careful morphologic evaluation should allow for the confident distinction of MyoD1-positive FESP from botyroid ERMS in almost all instances.

Molecular Characterization of a Rare Dedifferentiated Liposarcoma With Rhabdomyosarcomatous Differentiation in a 24 Year Old.

Aims. The aim of this study was to identify potential driver genetic alterations in a dedifferentiated liposarcoma (DDLPS) with rhabdomyosarcomatous differentiation. Methods and Results. A 24-year-old female underwent resection of an abdominal mass, which on a previous biopsy demonstrated rhabdomyosarcomatous differentiation concerning for embryonal rhabdomyosarcoma. Histologically the resected tumor displayed a high-grade sarcoma with rhabdomyosarcomatous differentiation in the background of well-differentiated liposarcoma consistent with DDLPS. Fluorescence in situ hybridization confirmed MDM2 amplification, as did array-based copy number profiling. Whole-exome sequencing revealed a somatic FGFR1 hotspot mutation and RNA sequencing an LMNB2-MAP2K6 fusion only within the dedifferentiated component. Conclusions. This study represents an in-depth examination of a rare DDLPS with rhabdomyosarcomatous differentiation in a young individual. Additionally, it is also instructive of a potential pitfall when assessing for MDM2 amplification in small biopsies. Despite exhaustive analysis, mutation and gene copy number analysis did not identify any molecular events that would underlie the rhabdomyoblastic differentiation. Our understanding of what causes some tumors to dedifferentiate as well as undergo divergent differentiation is limited, and larger studies are needed.

Synchronous Pulmonary Adenofibroma and Solitary Fibrous Tumor: Case Report and Review of the Literature.

Pulmonary adenofibroma (PAF) is a rare neoplasm that may be related to solitary fibrous tumor (SFT). A subset of PAFs harbor the NAB2-STAT6 fusion that is typical of SFT, but a significant proportion do not. Their distinction is clinically important as SFTs can potentially have an aggressive clinical course, while there has been no report of a PAF behaving in a malignant fashion. We report a case of a 60-year-old male who developed a SFT and PAF in the same lung. The SFT harbored a NAB2-STAT6 fusion, while the PAF did not have any identifiable fusion. This case represents the first instance of a single patient with both of these tumors occurring simultaneously in the same lung.

A novel case of an aggressive superficial spindle cell sarcoma in an adult resembling fibrosarcomatous dermatofibrosarcoma protuberans and harboring an EML4-NTRK3 fusion.

A subset of soft tissue sarcomas often harbors recurrent fusions involving protein kinases. While some of these fusion events have shown utility in arriving at a precise diagnosis, novel fusions in otherwise difficult to classify sarcomas continue to be identified. We present a case of a 40-year-old female who noted a lower back nodule in 2010 that was initially labeled as a dermatofibrosarcoma protuberans with fibrosarcomatous transformation. The lesion recurred the following year and metastasized to the groin 6 years later. Because of some morphologic peculiarities, molecular characterization was pursued in the metastatic focus, which revealed the neoplasm was negative for the COL1A1-PDGFB fusion. However, anchored multiplex polymerase chain reaction for targeted next-generation sequencing (Archer Dx) detected an EML4-NTRK3 fusion, which was confirmed by reverse transcription-PCR, Sanger sequencing and RNA sequencing analysis of the recurrent and metastatic specimens. Although various soft tissue neoplasms involving fusions with NTRK genes are well-reported, the current case could not be easily classified in any of the established entities. Nevertheless, it raises interesting questions regarding the importance of classification, prognosis, and treatment for some of these tyrosine kinase fusion-driven sarcomas.

Dedifferentiated Solitary Fibrous Tumor: A Concise Review.

Solitary fibrous tumor (SFT) is a unique mesenchymal neoplasm that was originally believed to be of submesothelial origin. Eventually, SFT expanded to include what was previously called hemangiopericytoma in other regions of the body that had similar immunohistochemical and morphologic features. Although most are benign, many studies have tried to identify histologic features that predict which tumors will behave in an aggressive manner. Recently, dedifferentiation has been described in rare cases of SFT and does appear to correlate with a more aggressive clinical course. Dedifferentiated SFT occurs in a similar age range and location as conventional SFT and can resemble multiple different malignant entities. Utilization of ancillary studies and thorough tissue sampling is important to reach the correct diagnosis. The morphologic features, immunohistochemistry, molecular alterations, and prognosis will be discussed.

Central xanthoma of the jaw in association with Noonan syndrome.

Xanthomas are histiocytic lesions of the skin, soft tissue, and bone and are generally considered to be reactive in nature. When they arise in the bones of the jaw, they are referred to as central xanthomas. New evidence supports the hypothesis that central xanthomas are a separate and distinct entity from their extragnathic counterparts. Noonan syndrome (NS) is an autosomal dominant disorder that has been associated with giant cell lesions, which also commonly occur in the jaw. We present a case of a 15-year-old boy with NS who presented with a radiolucent lesion of the mandible that on excision was found to be a central xanthoma. Although giant cell lesions have been well described in NS, xanthomas of the jaw have not been reported. We will also discuss the entities that must be excluded before making a diagnosis of central xanthoma, as this can affect both treatment and follow-up.

Factor V Inhibitors: A Diagnostic and Therapeutic Challenge.

Historically, inhibitors to coagulation factor V (FV) most often have developed in patients treated with bovine thrombin, a topical hemostatic agent used during surgical procedures. With the advent of newer hemostatic agents, and the concurrent diminished use of bovine thrombin, the incidence of FV inhibitors has fallen. Nevertheless, FV inhibitors are occasionally seen on an idiopathic basis as well as in association with medications, malignancies, autoimmune disorders, pregnancy, and infections. Factor V inhibitors may present with life-threatening bleeding or thrombosis, or they may be discovered incidentally as a coagulation screening test abnormality. Management of patients with FV inhibitors is challenging and consists of control of bleeding and eradication of the inhibitor. In this short overview we review the role of platelet and plasma FV in hemostasis and discuss the unique characteristics, clinical features, diagnosis, treatment, and prognosis associated with FV inhibitors.

Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein.

Germline mutations in the Folliculin (FLCN) tumour suppressor gene result in fibrofolliculomas, lung cysts and renal cancers, but the precise mechanisms of tumour suppression by FLCN remain elusive. Here we identify Rab7A, a small GTPase important for endocytic trafficking, as a novel FLCN interacting protein and demonstrate that FLCN acts as a Rab7A GTPase-activating protein. FLCN-/- cells display slower trafficking of epidermal growth factor receptors (EGFR) from early to late endosomes and enhanced activation of EGFR signalling upon ligand stimulation. Reintroduction of wild-type FLCN, but not tumour-associated FLCN mutants, suppresses EGFR signalling in a Rab7A-dependent manner. EGFR signalling is elevated in FLCN-/- tumours and the EGFR inhibitor afatinib suppresses the growth of human FLCN-/- cells as tumour xenografts. The functional interaction between FLCN and Rab7A appears conserved across species. Our work highlights a mechanism explaining, at least in part, the tumour suppressor function of FLCN.

Nodular Fasciitis of the Posterior Chest Wall With Bone Invasion Mimicking a Malignant Neoplasm.

Nodular fasciitis is a self-limiting benign fibroblastic/myofibroblastic proliferation, which typically presents as a rapidly growing mass resembling an aggressive lesion clinically. It can also mimic a sarcoma histologically, hence the frequent characterization as "pseudosarcoma." We describe a case of a 53-year-old man who presented with a posterior chest wall mass that on imaging showed erosion into the adjacent ribs. After resection, the diagnosis of nodular fasciitis was rendered. Bone erosion by nodular fasciitis is extremely rare and can resemble a malignant neoplasm radiologically.

Scleromatous Changes in an Abdominal Wall Graft: Graft-Versus-Graft Disease, or Chronic Graft Rejection?

Abdominal wall transplants are relatively new procedures that are frequently performed in conjunction with multivisceral transplants. The skin of the abdominal wall transplant is often the first site for graft rejection to manifest itself. Prompt recognition can lead to appropriate treatment before the involvement of the underlying viscera. However, the signs of graft rejection are nonspecific and can overlap with other entities. We present a case of a patient who received a multivisceral and abdominal wall transplant from 2 different donors, who presented with acute and eventually chronic graft rejection of the abdominal wall graft. Serial biopsies performed during the course of her treatment demonstrated progressive sclerotic changes in the dermis. Because these changes were confined to the abdominal wall graft, they could represent either chronic graft rejection or graft-versus-graft disease. To date, graft-versus-graft disease has not been documented in these patients. This case illustrates the possibility that patients with multidonor transplants may be at an increased risk for graft failure secondary to multiple potential etiologies.

Successful use of cryocrit for monitoring response to therapeutic plasma exchange in type 1 cryoglobulinemia.

Waldenstrom macroglobulinemia (WM) is a clinical syndrome that is defined as lymphoplasmacytic lymphoma with bone marrow involvement and IgM monoclonal gammopathy of any level. In some instances WM can result in a type I cryoglobulinemia with very high cryocrits, which is unusual in type II and III cryoglobulinemia. We describe a case of an 80 year old male with WM, severe type I cryoglobulinemia, and an extremely elevated cryocrit (69%). Over the course of five weeks we performed nine therapeutic plasma exchanges (TPE), and after seven treatments his cryocrit had decreased to 6% with improvement in his symptoms. By monitoring his cryocrit throughout his TPE sessions, we were able to assess his response to treatment, determine the ideal length of treatment in addition to his symptomatic improvement. J. Clin. Apheresis 31:403-404, 2016. © 2015 Wiley Periodicals, Inc.