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Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade sarcoma that most often involves the distal extremities of adults. Some MIFSs have been reported to show TGFBR3 and MGEA5 rearrangements. TGFBR3 and MGEA5 rearrangements have also been reported in hemosiderotic fibrolipomatous tumor (HFLT), in pleomorphic hyalinizing angiectatic tumor (PHAT), and in rare tumors allegedly showing features of both HFLT and MIFS (hybrid HFLT-MIFS). These findings have led to speculation that HFLT, MIFS, PHAT, and hybrid HFLT-MIFS are closely related; however, areas resembling HFLTs are only very rarely encountered in previous series of MIFSs. We studied classic examples of these tumors with the goal of clarifying the relationship between MIFS and HFLT-MIFS. Cases of MIFS (n=31), hybrid HFLT-MIFS (n=8), PHAT (n=2), HFLT (n=1), and undifferentiated pleomorphic sarcoma (n=4) were retrieved from our archives, and the diagnoses were verified by 5 soft tissue pathologists. Using previously validated break-apart fluorescence in situ hybridization probes, we analyzed for TGFBR3 and MGEA5 rearrangements. Only 2 of 31 MIFSs harbored MGEA5 rearrangements; all lacked TGFBR3 rearrangements. Six of 8 hybrid HFLT-MIFSs harbored rearrangements of TGFBR3 and/or MGEA5. Both PHATs were positive for rearrangements of TGFBR3 and/or MGEA5. The HFLT was positive for rearrangements of both TGFBR3 and MGEA5. All undifferentiated pleomorphic sarcomas with focal myxoid change were negative. We conclude that (1) TGFBR3 and/or MGEA5 rearrangements are much more common in hybrid HFLT-MIFSs than in classic MIFSs, (2) HFLTs and MIFSs may be unrelated lesions, and (3) hybrid HFLT-MIFSs most likely represent HFLTs with sarcomatous progression, rather than tumors strictly related to classic MIFSs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In 2014, the American Board of Pathology, in response to the pathology community, approved a physician scientist research pathway (PSRP). This brief report summarizes the history of and objectives for creating the physician scientist research pathway and the requirements of the American Board of Pathology for the certification of physician scientist research pathway trainees., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Implant-associated mesenchymal tumors (IAMT) of the breast are rare, and most are fibromatoses. There has been no systematic analysis of IAMT to determine their full histologic spectrum, whether there is an association with implant type or rupture, and if evidence supports a causal or fortuitous relationship between tumor and implant. We, therefore, analyzed all mesenchymal tumors associated with breast implants from our soft tissue consultation database spanning a period from 1989 to 2005. Information regarding location, type, and integrity of implant and its temporal relationship to tumor was recorded. Eight IAMT were identified exclusively in female patients (ages 28-64 years; median, 38 years), all of whom presented with a palpable mass. Tumors developed after placement of either a silicone (n = 7) or saline (n = 1) implant (median, 2 years; range, 1.8-10 years), which was usually inserted for cosmetic purposes (n = 7). All tumors arose in or around the capsule of a grossly intact implant, and in one case, the tumor was confined exclusively to the implant capsule. In patients with silicone implants, silicone granulomas were identified within the capsule and associated neoplasm despite the integrity of the implant. Six cases were fibromatoses; one was a pleomorphic undifferentiated sarcoma; and one was a fibrosarcoma. None of the patients with fibromatosis was known to have familial adenomatous polyposis (FAP) or Gardner syndrome, although one had Poland syndrome (aplasia of the thorax). One patient with a sarcoma had received radiation 10 years previously for breast carcinoma. Six patients were treated with local excision, one with a wide excision, and one patient with fibromatosis was treated with medical therapy. Median follow-up was 3.2 years (range, 16-92 months). One of the 5 patients with fibromatosis developed 2 recurrences. Neither of the 2 patients with sarcomas has developed metastasis. No patient has died of disease. We conclude that IAMT comprise 2 distinct groups-fibromatosis and sarcoma. Surgical trauma, perhaps occurring in patients with a predisposition to develop desmoid tumors, could account for fibromatosis in this setting. The causal relationship between implants and sarcomas is difficult to assess given the rarity of these tumors and that some may be radiation induced. However, at present, there is insufficient evidence to claim that they are biomaterial related.

As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Epithelioid sarcomas are soft tissue tumors with an indolent, but potentially aggressive, clinical behavior. Distinction from other benign and malignant entities may be a diagnostic dilemma. In this study, we evaluate the presence of loss of heterozygosity (LOH) of chromosome 22q in tumor DNA from 13 epithelioid sarcomas, four epithelioid angiosarcomas, and two epithelioid hemangioendotheliomas, and investigate its possible role in diagnosis. LOH was detected in 6 of 10 (60%) of the informative epithelioid sarcomas. No allele loss was detected in the informative vascular tumors, three angiosarcomas, and two hemangioendotheliomas. Chromosome 22q carries the locus of a tumor suppressor gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or mutated in some NF2-related tumors, sporadic meningiomas, and vestibular schwannomas, as well as a few other tumors. Our data suggest that a region of chromosome 22q may be the locus of a tumor suppressor gene involved in the tumorigenesis of these neoplasms. Genetic alterations of yet-unknown tumor suppressor genes in this region, or even the NF2 tumor suppressor gene, may play a role in epithelioid sarcomas tumorigenesis. The fact that LOH was only detected in epithelioid sarcomas and not in the vascular tumors studied suggests a possible role for this marker in diagnosis.

A case of crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma is presented. Unlike previous cases, this patient presented with signs and symptoms suggestive of Weber-Christian disease. Biopsy of subcutaneous nodules showed numerous deposits of crystal-storing histiocytes with lymphoplasmacytic cells, the latter exhibiting light chain restriction (lambda-chain) with a predominance of immunoglobulin (Ig)G heavy chain. Polymerase chain reaction (PCR) analysis of CDR-II* region of the immunoglobulin heavy chain locus confirmed monoclonality of the lymphoplasmacytic cells in the nodule. Electron microscopy showed polygonal-shaped amorphous crystals, characteristic of immunoglobulin in the histiocytic cells. Crystal-storing histiocytosis should be examined by immunohistochemical and DNA analysis to confirm or exclude the possibility of lymphoplasmacytic lymphoma.

Solitary fibrous tumors (SFTs) often involve the pleura and also may encompass the peritoneum and nonserosal sites. On occasion SFTs mimics other neoplasms, including desmoplastic mesothelioma. CD-34, initially characterized as a hematopoietic progenitor cell antigen, recently has been identified in a small number of SFTs. Based on this observation, we compared the keratin, vimentin, and CD-34 expression of 19 SFTs and eight desmoplastic mesotheliomas. Fifteen of 19 SFTs (78.9%) expressed CD-34, whereas keratin expression was absent in all SFTs. In contrast, none of the desmoplastic mesotheliomas expressed CD-34 and keratin expression was found in seven of eight (87.5%). Vimentin expression was noted in 18 of 19 SFTs and in seven of eight desmoplastic mesotheliomas. We conclude that CD-34 expression distinguishes SFT from desmoplastic mesothelioma. Additionally, the results of our study support the idea that SFT is not derived from or related to conventional mesothelium.

Four new cases of ectopic hamartomatous thymoma are presented. The tumor occurred either superficially or deep in the area of the sternoclavicular joint and consisted of solid islands of squamous epithelium which blended with spindled cells. Cysts lined by squamous epithelium, small glands, and fat also occurred in variable amounts. Both the spindled and epithelial regions of the tumor expressed keratin and muscle actin, but neither desmin nor S100 protein. The tumor probably originates from thymic anlage associated with the third pharyngeal pouch (thymus III), although origin from other structures such as thymus IV and the cervical sinus of His are discussed. Our experience indicates that the large size and extreme cellularity of the spindled portion of some tumors may result in the mistaken diagnosis of sarcoma.

Two infants with Turner's syndrome and an unusual vascular tumor or malformation of the feet are described. In one child, the lesion developed in the dorsal metacarpal area, whereas in the other, the lesion was located in a bilaterally symmetrical distribution over the dorsum of the feet. Both lesions were characterized by a proliferation of tortuous, thick-walled veins with imperfectly formed muscular walls. Redundancy of the endothelial lining leading to intimal "webs" and intraluminal vascular channels was prominent. The similarity of these two lesions clinically and histologically suggests that they do not represent a fortuitous occurrence, but an additional manifestation of Turner's syndrome. Furthermore, their existence indicates that the vascular abnormality in Turner's syndrome may be more generalized than previously recognized and may include abnormalities of peripheral blood vessels in addition to those of the heart and aorta.

Nine new cases of adamantinoma of long bone are presented. The age range, location, and symptomatology are similar to those in precious reports. Histologically most of the tumors have a "basaloid" or "spindled" pattern. A squamoid pattern with keratinization or an "angioblastic" pattern is seen less frequently. In all cases with adequate material there has been an associated frbrous dysplasia-like lesion is interpreted as being a part of the spectrum of mesenchymal differentiation of which the tumor is capable. Two cases in which metastasis occurred are compared to previously reported metastasizing cases. Few criteria are available that identify the potentially metastasizing tumor.