The term malignant fibrous histiocytoma (MFH) has been supplanted by undifferentiated pleomorphic sarcoma (UPS). Even now, however, a number of pleomorphic neoplasms are classified as UPSs when in ...fact at least a subgroup of these can be more precisely classified as a pleomorphic sarcoma with a specific line of differentiation. Still others are pseudosarcomas, most commonly sarcomatoid carcinomas. This review will discuss historical aspects of MFH/UPS as well as provide an approach to the pleomorphic malignant neoplasm with a discussion of useful ancillary techniques in the evaluation of such cases.
Background & Aims Although several classification systems have been proposed for characterization of Barrett’s esophagus (BE) surface patterns based on narrow-band imaging (NBI), none have been ...widely accepted. The Barrett’s International NBI Group (BING) aimed to develop and validate an NBI classification system for identification of dysplasia and cancer in patients with BE. Methods The BING working group, composed of NBI experts from the United States, Europe, and Japan, met to develop a validated, consensus-driven NBI classification system for identifying dysplasia and cancer in BE. The group reviewed 60 NBI images of nondysplastic BE, high-grade dysplasia, and esophageal adenocarcinoma to characterize mucosal and vascular patterns visible by NBI; these features were used to develop the BING criteria. We then recruited adult patients undergoing surveillance or endoscopic treatment for BE at 4 institutions in the United States and Europe, obtaining high-quality NBI images and performing histologic analysis of biopsies. Experts individually reviewed 50 NBI images to validate the BING criteria, and then evaluated 120 additional NBI images (not previously viewed) to determine whether the criteria accurately predicted the histology results. Results The BING criteria identified patients with dysplasia with 85% overall accuracy, 80% sensitivity, 88% specificity, 81% positive predictive value, and 88% negative predictive value. When dysplasia was identified with a high level of confidence, these values were 92%, 91%, 93%, 89%, and 95%, respectively. The overall strength of inter-observer agreement was substantial (κ = 0.681). Conclusions The BING working group developed a simple, internally validated system to identify dysplasia and EAC in patients with BE based on NBI results. When images are assessed with a high degree of confidence, the system can classify BE with >90% accuracy and a high level of inter-observer agreement.
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a ...disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.
Perivascular epithelioid cell neoplasms (PEComas) include the common renal angiomyolipoma, pulmonary clear cell sugar tumor, lymphangioleiomyomatosis, and less common neoplasms of soft tissue, ...gynecologic, and gastrointestinal tracts. Recently, aberrant immunoreactivity for TFE3 protein (a sensitive and specific marker of neoplasms harboring TFE3 gene fusions) has been reported in as many as 100% of PEComas; however, TFE3 gene status in these neoplasms has not been systematically investigated. We used a fluorescence in situ hybridization (FISH) break-apart assay to evaluate for evidence of TFE3 gene fusions in archival material from 29 PEComas. These cases included 2 earlier published TFE3 immunoreactive nonrenal PEComas, 14 additional nonrenal PEComas, and 13 renal angiomyolipomas with predominantly spindle or epithelioid morphology. Four nonrenal PEComas (mean patient age 24 y) showed TFE3 gene rearrangements by FISH, and all 4 of these showed strong positive (3+) TFE3 immunoreactivity using the original validated overnight incubation protocol. Two of these cases had adequate mRNA for RT-PCR analysis, but neither harbored the PSF-TFE3 gene fusion reported earlier in 1 PEComa. In addition, a lung metastasis of a uterine PEComa showed TFE3 gene amplification, an earlier unreported phenomenon. None of the other 24 PEComas (mean patient age 54 y) showed TFE3 gene alterations, though 4 exhibited moderate positive (2+) TFE3 immunoreactivity. In contrast, using an automated stainer, 2 of these 4 cases exhibited strong (3+) TFE3 immunoreactivity. All PEComas with TFE3 genetic alterations immunolabeled strongly for Cathepsin K, similar to other PEComas. In conclusion, a subset of lesions currently classified as PEComas harbors TFE3 gene fusions. Although numbers are small, distinctive features of these cases include a tendency to young age, the absence of association with tuberous sclerosis, predominant alveolar architecture and epithelioid cytology, minimal immunoreactivity for muscle markers, and strong (3+) TFE3 immunoreactivity. Despite significant morphologic and immunohistochemical overlap with other PEComas, PEComas harboring TFE3 gene fusions may represent a distinctive entity.
Undifferentiated carcinoma of the esophagus and gastroesophageal junction is a recently recognized entity in the fifth edition of the World Health Organization Classification of Digestive Tumors and ...is diagnostically challenging, particularly on small biopsies. SMARCA4 and SMARCA2 are chromatin remodeling genes with key roles in oncogenesis. We retrieved 14 cases of SMARCA4/SMARCA2-deficient undifferentiated carcinoma of the gastroesophageal junction and esophagus from the authors’ institutions. The tumors showed similar histologic findingsthe sheet-like proliferation of tumor cells characterized by discohesion, large nuclei, and prominent macronucleoli with many tumor cells exhibiting a rhabdoid appearance. In 8 cases, adjacent specialized intestinal metaplasia was noted and 3 cases exhibited adjacent high-grade dysplasia. Immunohistochemically, tumors variably expressed keratins and disclosed loss of expression of SMARCA4 in 12 and SMARCA2 in 7 cases. In 2 cases SMARCA2 alone was lost without SMARCA4 loss. A mutant p53 immunohistochemical pattern was seen in 4 of 4 cases, 3 of which showed diffuse, strong nuclear expression, and 1 case displayed a complete loss of nuclear expression of p53, including invasive carcinoma and associated dysplasia, when present. Limited clinical follow-up was available, but 3 patients died of disease within 0.6, 2, and 7 months of diagnosis. We present the first series of undifferentiated carcinoma of the esophagus and gastroesophageal junction with this characteristic morphology associated with loss of SMARCA4 and/or SMARCA2 expression. This tumor type likely arises from dedifferentiation of a lower grade carcinoma in some cases, and Barrett esophagus and appears to be associated with an aggressive clinical course.
Chronic intestinal inflammation and impaired tissue repair leading to intestinal fibrosis are a commonly observed complication in inflammatory bowel disease. This is particularly true for small bowel ...Crohn's disease. However, the development of fibrosis in ulcerative colitis has remained largely unexplored. This is surprising, given knowledge about its prevalence for decades, well described histopathologic features of fibrotic and stricturing ulcerative colitis, the relevance of the extracellular matrix for intestinal inflammation and fibrosis, and the clinical impact of fibrosis on stricture formation, motility, and the necessary discrimination from colonic malignancy. This systematic review summarizes the current knowledge of ulcerative colitis-related fibrosis, including epidemiology, basic mechanisms, histopathology, and clinical implications.
AIM： To evaluate how proximal colon polyps interpreted as hyperplastic polyps in 2001 would be interpreted by expert pathologists in 2007.
METHODS： ≥ 5 mm in interpreted pathologists 2007 by 3 GI ...Forty consecutive proximal colon polyps size, removed in 2001, and originally as hyperplastic polyps by general at Indiana University, were reviewed in pathologists.
CONCLUSION： Many polyps interpreted as hyperplastic in 2001 were considered sessile serrated lesions by GI pathologists in 2007, but there is substantial inter-observer variation amongst GI pathologists.
Cutaneous myxoma (CM) is an uncommon benign neoplasm of skin, which may be sporadic or arise in association with syndromes such as Carney complex. There has been only one large case series describing ...CM. We report 54 additional cases of CM; patients had a mean age of 55 years (range = 7–91), with a female-to-male ratio of 1.3. Most occurred on the trunk (n = 19), with the back being the most common site. The remainder presented on the lower extremity (n = 18), head and neck (n = 10), and arm (n = 7). Histopathologically, they were relatively circumscribed, nodular, and centered in the dermis. All had abundant myxoid stroma, a thin, arborizing vascular network, and spindled to stellate cells with no to mild atypia without mitotic activity. Follicular induction, stromal neutrophils, and intranuclear inclusions were present in 35%, 25%, and 61% of cases, respectively. Collagen trapping, splitting of collagen fibers, and encircling of hair follicles or eccrine glands were encountered in a subset. Thirty-nine cases were treated with shave excision, whereas 12 cases underwent wide local excision. Follow-up data were available for 28 of 54 cases (mean = 50 months). Only one case recurred at 36 months. This study suggests CM has a lower risk of local recurrence than previously reported.
•Cutaneous myxoma is a benign myxoid neoplasm of skin•This is the largest clinicopathologic study of cutaneous myxoma till date.•We compared the clinicopathologic features of the cases in our series with the features described in the previous studies and also with a pooled data group of case reports of cutaneous myxoma between 1996-2020.•This study revealed a lower local recurrence rate in cutaneous myxoma compared to previous studies.
Gene rearrangements involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase gene have been identified in various neoplasms, including inflammatory myofibroblastic tumor and ...epithelioid fibrous histiocytoma. We present an ALK-rearranged cutaneous soft tissue tumor with unique morphologic and immunophenotypic features that are not shared by other entities with ALK rearrangements. The six cases involved two females and four males, aged 18–84 (mean 51) years old. Three tumors were on the back and three on the lower extremities (thigh, knee, shin); ranging from 0.5 to 5.6 (mean 2.1) cm. Four were confined to the dermis; two involved the subcutis. All six cases were characterized by the presence of spindled to ovoid cells arranged in concentric whorls and cords against a myxoid to myxohyaline stroma and relatively cellular aggregates of plump ovoid to epithelioid cells. Four cases showed distinct hyalinized blood vessels. Both cases that involved the subcutis showed peripheral lipofibromatosis-like areas. Tumor-infiltrating lymphocytes were absent to moderate. Severe cytologic atypia or conspicuous mitotic activity was not identified. Immunohistochemically, all tumors diffusely expressed ALK (D5F3) and CD34. All but one tumor was diffusely positive for S100 protein. All tumors were negative for EMA, AE1/AE3, SMA, and SOX10. Next-generation sequencing revealed ALK fusions with FLNA (3 cases), MYH10 (2 cases), and HMBOX1 (1 case) as the partner genes. In all six cases, the breakpoints involved exon 20 of ALK, which preserves the receptor tyrosine kinase domains of ALK in the fusion product. Of the four cases with limited follow-up information (2–18 months), none recurred. In conclusion, we report an ALK-rearranged cutaneous soft tissue tumor characterized by the presence of myxoid spindle cell whorls and cords, and co-expression of ALK, CD34, and frequently S100 protein, we term “superficial ALK-rearranged myxoid spindle cell neoplasm”.
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