Publications by authors named "B Rubin"

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PRRX1-NCOA1 rearranged fibroblastic tumor: Clinicopathologic, immunohistochemical and molecular genetic study of 6 cases of a potentially under-recognized, distinctive mesenchymal tumor.

Histopathology 2021 Jul 17. Epub 2021 Jul 17.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.

Aims: PRRX1-NCOA1 rearranged fibroblastic tumor is a recently described, rare mesenchymal tumor. Only 4 cases have been previously reported. We report 6 additional cases of this unusual mesenchymal neoplasm with emphasis on its differential diagnosis.

Materials And Results: The six cases were from 3 females and 3 males (aged 20-49 years; median 42). Three tumors were located on the abdominal wall; two from the shoulder/axillary areas; one on the lateral hip. All presented as slow-growing subcutaneous nodules, ranging from 2.6 to 5.5 cm (median 4.0 cm). The tumors consisted of circumscribed, variably cellular nodules composed of relatively bland plump spindled to epithelioid cells arranged singly, in cords, and occasionally in nests, embedded in hyalinized and collagenous stroma. Small hypocellular myxoid zones with ropey collagen fibers were present, as were irregularly dilated, "gaping", "crescent-shaped" or "staghorn-like" thin-walled vessels, best appreciated at the periphery. Immunohistochemistry for CD34, S100 protein, MUC4 and STAT6 was consistently negative. RNA-sequencing revealed PRRX1-NCOA1 fusions in all cases. Of the 4 cases with limited follow-up (1.5-4 months), none recurred following local surgical excision.

Conclusions: The morphologic features of PRRX1-NCOA1 rearranged fibroblastic tumor overlap with those of RB1-deficient soft tissue tumors, solitary fibrous tumor, and low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma. This differential diagnosis can be resolved with a combination of careful morphologic study and application of a panel of immunostains, although molecular genetic study is most definitive. The natural history of PRRX1-NCOA1 rearranged fibroblastic tumor appears quite favorable, although longer term study of larger number of cases is warranted.
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http://dx.doi.org/10.1111/his.14454DOI Listing
July 2021

10 Years of belimumab experience: What have we learnt?

Lupus 2021 Jul 8:9612033211028653. Epub 2021 Jul 8.

GlaxoSmithKline, Collegeville, PA, USA.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting both adults and children. Belimumab is the only biologic approved for SLE, and the first in a class of drugs known as B-lymphocyte stimulator-specific inhibitors. The introduction of intravenous belimumab in 2011 was a major advance, being the first new therapy approved for SLE in over 50 years. As of April 2021, more than 7200 people with SLE have received belimumab in clinical studies, and it is approved in over 75 countries for the treatment of adults with SLE. A subcutaneous, self-injectable belimumab formulation was licensed in 2017 by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Belimumab was then approved for use in children in Europe, the USA and Japan in 2019, and China and Brazil in 2020. Recently, belimumab became the first FDA-approved drug for the treatment of adults with active lupus nephritis (LN), the most-common severe manifestation of SLE.Over the past 10 years, belimumab has established its position as a disease modifier in the SLE treatment paradigms. Robust evidence from randomised clinical studies and observational, real-world studies has demonstrated the tolerability and efficacy of belimumab for reducing disease activity and the risk of new, severe SLE flares. This enables patients to taper their glucocorticoid use, which limits damage accumulation. Significantly more patients with active LN met the criteria for renal responses and were at less risk of a renal-related event or death after receiving belimumab plus standard therapy, compared with standard therapy on top of mandatory steroid reduction. Ongoing clinical studies are evaluating belimumab's effectiveness in various indications beyond SLE. Post-marketing and registry studies are gathering additional data on key areas such as pregnancy outcomes after belimumab exposure and belimumab co-administration with other biologics.
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http://dx.doi.org/10.1177/09612033211028653DOI Listing
July 2021

Imazapic Herbigation for Egyptian Broomrape () Control in Processing Tomatoes-Laboratory and Greenhouse Studies.

Plants (Basel) 2021 Jun 10;10(6). Epub 2021 Jun 10.

R.H. Smith Institute of Plant Science & Genetics in Agriculture, R.H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel.

Parasitic plants belonging to the Orobanchaceae family include species that cause heavy damage to crops in Mediterranean climate regions. is the most common of the Orobanchaceae species in Israel inflicting heavy damage to a wide range of broadleaf crops, including processing tomatoes. is extremely difficult to control due to its minute and vast number of seeds and its underground association with host plant roots. The highly efficient attachment of the parasite haustoria into the host phloem and xylem enables the diversion of water, assimilates and minerals from the host into the parasite. Drip irrigation is the most common method of irrigation in processing tomatoes in Israel, but the delivery of herbicides via drip irrigation systems (herbigation) has not been thoroughly studied. The aim of these studies was to test, under laboratory and greenhouse conditions, the factors involved in the behavior of soil-herbigated imazapic, and the consequential influence of imazapic on and tomato plants. Dose-response Petri dish studies showed that imazapic does not impede seed germination and non-attached seedlings, even at the high rate of 5000 ppb. Imazapic applied to tomato roots inoculated with seeds in a PE bag system revealed that the parasite is killed only after its attachment to the tomato roots, at concentrations as low as 2.5 ppb. Imazapic sorption curves and calculated Kd and Koc values indicated that the herbicide Kd is similar in all soils excluding a two-fold higher coefficient in the Gadash farm soil, while the Koc was similar in all soils except the Eden farm soil, in which it was more than twofold lower. In greenhouse studies, control of was achieved at >2.5 ppb imazapic, but adequate control requires repeated applications due to the 7-day half-life (t) of the herbicide in the soil. Tracking of imazapic in soil and tomato roots revealed that the herbicide accumulates in the tomato host plant roots, but its movement to newly formed roots is limited. The data obtained in the laboratory and greenhouse studies provide invaluable knowledge for devising field imazapic application strategies via drip irrigation systems for efficient and selective broomrape control.
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http://dx.doi.org/10.3390/plants10061182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229561PMC
June 2021

YAP1-TFE3 Gene Fusion Variant in Clear Cell Stromal Tumor of Lung: Report of Two Cases in Support of a Distinct Entity.

Histopathology 2021 Jun 22. Epub 2021 Jun 22.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Ohio, USA.

Aims: Clear cell (hemangioblastoma-like) stromal tumor of the lung is a newly described, rare pulmonary neoplasm. Recurrent YAP1-TFE3 gene fusions have recently been reported in three cases. We describe two additional cases and confirm the characteristic YAP1-TFE3 gene fusion.

Methods And Results: Two mesenchymal tumors of lung were identified from our soft tissue pathology consultation service and RNA sequencing was performed. Both cases were in male patients, aged 35 and 77 years old. Both presented as solitary lung nodules measuring 3.9 and 7.5 cm in greatest dimension. Histopathologically, the tumors were composed of epithelioid to plump spindled cells arranged in packets and solid sheets. The cells showed fusiform to ovoid nuclei with open chromatin, variably prominent nucleoli, and scant to moderate, clear to eosinophilic cytoplasm. Cytologic atypia and significant mitotic activity were minimal. None of the tumors expressed lineage-specific immunophenotypic markers. Both cases were diffusely positive for nuclear TFE3. Unlike YAP1-TFE3 fused epithelioid hemangioendothelioma, for which the fusion breakpoint occurs in YAP1 exon 1 and TFE3 exons 4 or 6, the fusion breakpoints of these tumors are located in YAP1 exon 4 and TFE3 exon 7. Following complete surgical resection, neither of the tumors has recurred or metastasized (follow-up period 6-7 months).

Conclusions: We validate the presence of YAP1-TFE3 gene fusion in a unique primary mesenchymal tumor of lung, adding additional support for clear cell stromal tumor of the lung as a distinct entity.
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http://dx.doi.org/10.1111/his.14437DOI Listing
June 2021

CD34-negative Solitary Fibrous Tumor: A Clinicopathologic Study of 25 Cases and Comparison With Their CD34-positive Counterparts.

Am J Surg Pathol 2021 Apr 7. Epub 2021 Apr 7.

Department of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.

CD34-negative solitary fibrous tumors (SFTs) are rare and have not been comprehensively studied. We retrospectively reviewed all cases of SFT confirmed with STAT6 immunohistochemistry and/or STAT6 gene fusion between 2013 and 2020 and collected pertinent clinicopathologic parameters. Of a total of 244 cases, 25 (10%) lacked CD34 expression by immunohistochemistry. Compared with CD34-positive SFT, CD34-negative SFT are more likely to arise in the head and neck area (32% vs. 24%, P=0.02) and present as metastatic disease (28% vs. 1%, P<0.0001). A significantly higher percentage of CD34-negative SFT exhibit high-grade cytologic atypia (hypercellularity, round cell or anaplastic morphology, nuclear pleomorphism, etc.) (48% vs. 22%, P=0.0073). There are no significant differences in the distributions of age, sex, tumor size, mitotic count, tumor necrosis, or risk stratification between CD34-negative and CD34-positive SFT. In addition, only 56% of CD34-negative SFT display a typical hemangiopericytoma-like vascular pattern. Special histologic features among CD34-negative SFT include prominent alternating hypercellular or fibrous and hypocellular myxoid areas with curvilinear vessels mimicking low-grade fibromyxoid sarcoma, pulmonary edema-like microcystic changes, and prominent amianthoid collagen fibers. In conclusion, compared with their CD34-positive counterparts, CD34-negative SFT is more likely to present as metastatic disease, show high-grade nuclear atypia, and lack the characteristic hemangiopericytoma-like vasculature, posing a unique diagnostic challenge. The use of STAT6 immunohistochemistry and/or molecular studies may be prudent in soft tissue tumors that appear CD34 negative and lack conventional SFT histopathologic characteristics.
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http://dx.doi.org/10.1097/PAS.0000000000001717DOI Listing
April 2021
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