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* Context.--Next-generation sequencing-based approaches using RNA have increasingly been used by clinical laboratories for the detection of fusion genes, intragenic rearrangements, and exon-skipping events. Correspondingly, the College of American Pathologists (CAP) has advanced RNA sequencing proficiency testing (PT) to ensure optimal performance of these assays. Objective.--To report on laboratory performance and practices of RNA sequencing for the detection of fusion genes, intragenic rearrangements, and exon-skipping events using CAP PT data from 8 mailings (2018-A through 2021-B). Design.--CAP PT RNA sequencing program results from 153 laboratories across 24 proficiency test specimens, interrogating 22 distinct engineered fusion transcripts, were analyzed for correct identification of the fusion event, associated performance variables, and laboratory practices. Results.--Overall, the 4-year program detection rate (sensitivity) was 95.5% (1486 of 1556 results). False-negative rates were 3.6% (53 of 1463) and 18.3% (17 of 93) for fusion gene and intragenic rearrangement/exon-skipping events, respectively. Only 19 false-positive results were reported among the 8 PT mailings, and most were likely the result of preanalytical or postanalytical errors. There were no practice characteristics (eg, instrumentation, sequencing method) significantly associated with the fusion detection results. Conclusions.--These data reveal a high overall sensitivity and specificity for fusion gene detection by participating laboratories using clinical RNA sequencing. Performance was comparable across all laboratories, regardless of methodology. The fraction of false-negative results for intragenic rearrangement/exon-skipping events was greater than that for the chimeric fusion genes. False-negative results could not be attributed to any specific practice characteristics., Fusion oncogenes represent valuable biomarkers that aid in diagnostic classification and prognostication, as well as serving as therapeutic targets. (1-4) Examples of structural alterations/mutations that may lead to chimeric fusions [...]

Context.--Detection of high-risk human papillomavirus (HR-HPV) in squamous cell carcinoma is important for classification and prognostication. In situ hybridization (ISH) is a commonly used HR-HPV-specific test that targets viral RNA or DNA. The College of American Pathologists (CAP) provides proficiency testing for laboratories performing HR-HPV iSh. Objective.--To compare the analytical performance of RNA- and DNA-based ISH methods on CAP HR-HPV proficiency tests. Design.--Data from the 2016-2018 CAP HPV ISH proficiency testing surveys were reviewed. These surveys consist of well-characterized samples with known status for HR-HPV, including 1 to 2 copies, 50 to 100 copies, 300 to 500 copies, and no copies of HR-HPV per cell. Results.--Ninety-five participants submitted 1268 survey results from 20 cores. Overall, RNA ISH had a significantly higher percentage of correct responses than DNA ISH: 97.4% (450 of 462) versus 80.6% (650 of 806) (P < .001). This disparity appears to be the consequence of a superior sensitivity of rNa ISH compared to DNA ISH for samples with 1 to 2 and with 50 to 100 copies of HRHPV per cell: 95.2% (120 of 126) versus 53.8% (129 of 240), P < .001, respectively, and 100% (89 of 89) versus 76.3% (119 of 156), P < .001, respectively. Conclusions.--An assessment of CAP HR-HPV proficiency test performance indicates that RNA ISH shows significantly higher accuracy than DNA ISH owing to higher analytical sensitivity of RNA ISH in tumors with low (1-2 copies per cell) to intermediate (50-100 copies per cell) HR-HPV viral copy numbers. These data support the use of RNA over DNA ISH in clinical laboratories that perform HR-HPV testing as part of their testing algorithms. (Arch Pathol Lab Med. 2020;144:344-349; doi: 10.5858/arpa.2019-0093-CP), High-risk human papillomavirus (HR-HPV) causes HPV-positive squamous cell carcinomas (SCCs) at multiple anatomic sites including the oropharynx, anus, and urogenital tracts. The detection of HR-HPV in tissue samples containing SCC [...]

Objective: To evaluate MR features and clinical course of malignant melanotic nerve sheath tumor (MMNST), previously known as melanotic schwannoma and considered indolent and rarely metastasizing. Materials and methods: This IRB-approved retrospective study searched 31 patients (20 male: 11 female, mean age 48; range 15–76) with histologically confirmed MMNST in a single tertiary cancer center over 22 years. Pre-treatment MR was available in 12 patients and evaluated by two radiologists in consensus regarding lesion location, size, morphology, signal characteristics, contrast enhancement, local invasion, and presence of classic signs of peripheral nerve sheath tumors. Clinical outcomes, including local recurrence, metastasis, and survival, were examined in 12 patients for whom follow-up was available. Results: The spine was the most frequent site (13/31) among all identified cases. In 12 cases with MR, lesions were well-circumscribed in 11/12 cases, with a mean size of 4.5 cm (2.3–13.0 cm). Ten of 12 cases showed T1 hyperintensity. In 5/9 spinal MRI, tumor involved multiple levels. All lesions showed contrast enhancement, and local bone invasion in > 50%. A dumb-bell shape was common to all spinal lesions. Classical signs of nerve sheath tumors were uncommon. Among 12 patients with a mean follow-up of 4.8 years (range 1.3–10.2 years), six were disease-free, while two had recurrence or metastases, and four had died of metastases. Conclusion: MMNST usually presents as a T1 hyperintense enhancing dumb-bell shaped mass in the spine. Multi-level involvement and bone invasion are common. MMNST is clinically aggressive with high rates of metastases and death. [ABSTRACT FROM AUTHOR]

Atypical lipomatous tumor/well-differentiated liposarcoma is the most common sarcoma of soft tissue in adults. We describe the clinical, radiologic, and pathologic features of an atypical lipomatous tumor arising within the soft tissue of the left hand of a 68-year-old female that underwent transformation to dedifferentiated liposarcoma and eventually metastasized. At initial presentation, imaging demonstrated an extensively calcified fatty soft tissue mass with displacement of the digits. Following biopsy and staged debulking, the patient subsequently developed local recurrence, dedifferentiation, and widespread metastases to the lungs, pancreas, bone, and soft tissues. To our knowledge, this is the first case of a cytogenetically proven atypical lipomatous tumor of the hand that has undergone dedifferentiation with widespread metastases. [ABSTRACT FROM AUTHOR]

Objective: To determine the imaging features of hemosiderotic fibrolipomatous tumor (HFLT), which has a propensity towards local recurrence and the potential to transform into myxoinflammatory fibroblastic sarcoma (MIFS). Materials and methods: The study included 8 patients with a diagnosis of HFLT and imaging at a tertiary cancer center. Imaging studies included radiographs ( n = 2), ultrasound ( n = 3), and MRI ( n = 16). Imaging features were evaluated including location, calcification, sonographic echogenicity, vascular flow, size, border, signal characteristics, contrast enhancement, and blooming on MRI. Results: The HFLT was located in the ankle/foot in 4 out of 8 and was subcutaneous in 8 out of 8, ranging in size from 2 to 18 cm. Histology at initial diagnosis was HFLT in 5 out of 8 and HFLT with MIFS in 3 out of 8. None was calcified on radiography. On ultrasound 2 out of 3 were heterogeneously echogenic with ≥10 foci of vascular flow. Two out of 8 patients had MRI only at local recurrence. The tumor border was infiltrative in 4 out of 6 at initial diagnosis and in 2 patients with MRI at recurrence only. Fat and septae were present in 7 out of 8 at initial diagnosis and at recurrence. Signal intensity was iso-/hypointense to muscle on T1-weighted sequences in more than two thirds of the tumor in 4 out of 7 and hyperintense to muscle in at least one third of the tumor on fluid-sensitive sequences in 6 out of 8. Contrast enhancement was heterogeneous in 7 out of 7; blooming in two thirds of the tumor on gradient-echo sequence MRI indicated hemorrhage. Conclusion: The HFLT commonly presents as a mass with an infiltrative border, interspersed fat and septations at initial diagnosis and local recurrence on MRI regardless of histology of HFLT alone or with MIFS. Hemosiderin deposits may be detected as blooming on gradient-echo sequences. [ABSTRACT FROM AUTHOR]

Objective: To determine common imaging features of low-grade fibromyxoid sarcoma (LGFMS), a rare subtype of fibrosarcoma with a benign histological appearance but with a propensity for local recurrence and metastasis. Materials and methods: By review of medical records, 29 patients (14 males, 15 females) with mean age of 41 years (range, 11-64 years) with diagnosis of LGFMS and imaging available in PACS were identified. The study included radiography (9/29), ultrasound (1/29), CT (14/29), and MRI (22/29). Imaging features evaluated included anatomic site, and lesion size, number, location, US echogenicity, CT attenuation, calcifications, MR signal intensity pattern, and contrast enhancement. Results: Twenty-two patients had imaging at initial diagnosis, and seven had imaging only at local recurrence. The majority of tumors (27/29) were deep in tissue, with mean size of 6.2 cm (range, 1.4-19.0 cm). Tumor was single at initial diagnosis and multiple at local recurrence; lower extremity was the most common site. On radiographs, tumor was visible in four of nine without bone erosion or calcification. Areas of CT attenuation hypodense to muscle were seen in 13/14 patients. Calcification was uncommon (3/14). On fluid-sensitive MRI sequences, the predominant signal intensity was hyperintense to muscle in 11/21 patients. In 13/21 patients, tumor displayed either a brain gyriform pattern of alternating hypointense and hyperintense signal intensity (9/13) or intralesional nodules (3/13); 1 case had both patterns. On US tumor was solid with heterogeneous echogenicity. Conclusion: LGFMS is commonly single at initial diagnosis and multiple at local recurrence. LGFMS frequently shows areas of CT attenuation hypodense to muscle and gyriform patterns of signal intensity and contrast enhancement at MRI. [ABSTRACT FROM AUTHOR]

Intraosseous benign notochordal cell tumor is a presumably benign, intravertebral lesion of notochord origin, which can be found incidentally on removal of the vertebra for unrelated lesions or during an autopsy. The notion of a larger benign notochordal cell tumor that is macroscopic, occasionally symptomatic, and seen radiologically was recently introduced, and described as giant vertebral notochordal rest, giant notochordal hamartoma of intraosseous origin, and benign chordoma. Because of the location, size, and similar histologic and immunohistochemical characteristics, larger benign notochordal cell tumors are easily misdiagnosed as the malignant notochord- type of tumor/chordoma, with critical implications. In this review, we attempt to shed light on the major differences between benign notochordal cell tumors and chordoma and other related notochord lesions, such as notochordal vestiges of the intervertebral disk and ecchordosis physaliphora. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to delineate the magnetic resonance (MR) appearance of a granular cell tumor (GrCT) of the extremity and to correlate the imaging appearance with the microscopic findings.Design and Patients: A retrospective review of five patients with a histopathologic diagnosis of GrCT and pre-operative MR imaging of the neoplasm was done. The images were reviewed by two musculoskeletal radiologists in a consensus fashion. Lesion location, size, shape, margination, and signal intensity characteristics were assessed. MR findings were correlated with histopathological examination.Results: The benign subtype of GrCT is usually isointense or brighter than muscle on T1-weighted sequences, round or oval in shape, superficial in location, and 4 cm or less in size. On T2-weighted sequences, benign lesions may demonstrate a high peripheral signal, as well as a central signal intensity that is isointense to muscle or suppressed fat. A significant stromal component in the tumor and, hypothetically, a ribbon-like arrangement of tumor cells may influence the signal intensity demonstrated on the T1 and T2-weighted sequences. The malignant subtype may demonstrate signal intensity characteristics and invasion of adjacent structures often seen with other aggressive neoplasms; sizes larger than 4 cm and association with major nerve trunks can be seen.Conclusion: Benign GrCT has imaging characteristics which may distinguish this tumor from other soft tissue neoplasms, as well as the malignant type of this tumor. [ABSTRACT FROM AUTHOR]

The overexpression of HER-2/neu and p53 has been associated with poor outcome in many neoplasms. Their role in patients with osteosarcoma is unclear. We studied the expression of HER-2/neu and p53 in 22 osteosarcoma samples (from 20 patients—2 had locally recurrent disease) biopsied at the University of Medicine and Dentistry of New Jersey (UMDNJ) from 1996-2000 using both immunohistochemical (THC) and fluorescence in situ hybridization (FISH) analysis. Fourteen patients (14 samples) presented with Stage II and 6 patients (8 samples) presented with Stage III disease. Median follow-up is two years (range one year to five years). Four of 22 (18%) samples showed focal membranous or cytoplasmic positivity for HER-2/neu and six of 22 samples (27%) showed nuclear positivity for p53 by THC analysis. In contrast, none of 22 tested samples showed gene amplification for HER-2/neu by FISH analysis. Seven of 13 HER-2/neu and p53 negative patients (54%) are currently disease free (between one year to five years). In this sample of patients, the HER-2/ neu oncogene is not overexpressed or amplified in osteosarcoma; six of 22 samples (27%) showed overexpression of p53 by THC analysis. By FISH, none of the samples demonstrated deletion of p53. Neither HER2/neu nor p53 expression was important for the biology of osteosarcoma in this population. [ABSTRACT FROM AUTHOR]

Abstract: Periosteal chondroma is a rare benign tumor of hyaline cartilage. It develops adjacent to the cortex of the bone and is rimmed by an intact periosteal membrane. Periosteal chondromas are most common in the metaphyses of long bones followed by the small tubular bones of the hands and feet. Periosteal chondroma arising in the rib is an extremely rare event. We could only find 10 reported cases in the English literature. We present a case of periosteal chondroma in the rib discovered incidentally on chest x-ray of an 11-year-old girl. [Copyright &y& Elsevier]

To explore pre-treatment imaging findings of neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, an emerging group of molecularly defined soft tissue tumors and summarize the clinical course, including TRK inhibitor therapy response. This retrospective study included 8 women and 4 men with NTRK -rearranged spindle cell neoplasm (median age, 35.5 years, range, 0–66). Available pre-treatment MRI, CT, PET, and US imaging were reviewed. Tumor histology and the patients' clinical course were reviewed. Primary tumors were located within the soft tissue, lungs, kidney, and breast with soft tissue being the most prevalent site (n = 6). Pre-treatment MRI (n = 4) revealed linear hypointense signal foci and contrast enhancement in all patients with hemorrhage in half of the tumors. A tail sign (n = 1) and fluid levels (n = 1) were less frequent. Ultrasound showed well-marginated hypoechoic masses with internal flow. Primary tumors were all non-calcified on CT (4/4). Metastases were FDG-avid (4/4). Among the 8 patients who developed metastasis, 7 developed pulmonary metastases. All four patients who received NTRK inhibitor therapy showed an initial decrease in tumor size or FDG uptake. NTRK -rearranged neoplasms may occur as enhancing masses with linear hypointense signal foci on MRI and FDG avid metastases on PET. Pulmonary metastases were frequent in our study. Initial treatment response is observed in most patients. • NTRK -rearranged spindle cell neoplasms are an emerging group of soft tissue tumors in the 2020 WHO Classification of Tumors. • These tumors exhibit a wide spectrum of histologic morphology ranging from benign fat containing tumor to high grade sarcomas. • Primary tumors show linear hypointense signal and enhancement, without fatty components despite presence of fat in histology. • Metastases are FDG avid on PET and lungs were frequent sites for metastases. • Initial treatment response to NTRK inhibitors is observed in most patients with varying durations in our study. [ABSTRACT FROM AUTHOR]

: BackgroundEpithelioid sarcoma is a rare, yet aggressive soft tissue neoplasm that has not previously been reported to originate in the cervix.: CaseA 29-year-old woman was seen in consultation at our institution after having been diagnosed with a poorly differentiated carcinoma of the cervix, which was treated with radiation and chemotherapy. Examination of the original biopsy material with additional studies led to a diagnosis of epithelioid sarcoma of the cervix.: ConclusionEpithelioid sarcoma can occur in the cervix and should be included in the differential diagnosis of cervical neoplasms. Additional cases are needed to develop optimum treatment strategies and predict prognosis. [Copyright &y& Elsevier]

Abstract: The atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) is a locally aggressive subtype of liposarcoma unless dedifferentiation occurs. The mechanism driving this progression is not clear. Loss of p16 is believed to be an early and critical event in tumor progression. Gene silencing by methylation of p16INK4a gene promoter has been reported in several soft tissue sarcomas. The aim of this study is to study the role of p16INK4a gene promoter methylation and p16 expression in tumor progression (dedifferentiation) and recurrence of ALT/WDLPS. Four cases of dedifferentiated liposarcomas (DDLPS) and three cases of recurrent well-differentiated liposarcomas (WDLPS) were collected, and methylation status of p16INK4a gene promoter was analyzed using methylation-specific PCR (MSP) on DNA extracted from paraffin blocks. p16 expression was examined by immunohistochemistry on the same blocks. Methylation of p16INK4a gene promoter was seen in the dedifferentiated (DD) components only, in two out of four (2/4, 50%) DDLPS. The other two DDLPS and three recurrent WDLPS were not methylated. Both WD and DD components in all four DDLPS cases showed strong nuclear p16 expression. All three recurrent WDLPS showed positive p16 expression with similar intensity between primary and recurrent tumors. Even though linear correlation between p16 promoter hypermethylation and p16 protein expression was not present, there appears to be a role for p16INK4a gene promoter hypermethylation in DDLPS and not in recurrent WDLPS. [Copyright &y& Elsevier]