Juan Rosai, MD (1940-2020) Klimstra, David S.; Young, Robert H.
The American journal of surgical pathology,
12/2021, Volume:
45, Issue:
12
Journal Article
Aims
Since the sclerosing stromal tumour (SST) of the ovary was first described in 1973, few studies have expanded upon its histological features or overlap with other tumours. We thus investigate ...these aspects based on our experience with 100 cases.
Methods and results
The patients, 14 of whom were pregnant, ranged from 12 to 63 years (median = 26 years). Ten patients had hormonal manifestations (seven oestrogenic, three androgenic). Bilateral ovarian involvement was present in two cases. Size ranged from 1 to 23 cm (mean = 8.4 cm). Most tumours were solid and white with focal yellow areas; oedema with cystic degeneration (seen in 25 cases) resulted in eight being predominantly cystic. On microscopic examination, alternating cellular and paucicellular areas (pseudolobulation) were prominent in 94 cases but seen to a limited degree in the remaining neoplasms. Admixed spindled and luteinised cells were present in all tumours, but 13 demonstrated mainly spindled cells and 19 demonstrated mainly lutein cells; 14 of the latter were from pregnant patients. The stroma was typically oedematous or collagenous, but in 14 cases was prominently hyalinised and, in four, myxoid. Prominent vascularity was present in most cases. The mitotic rate ranged from 0 to 8/10 high‐power fields (HPF), but most demonstrated <1/10 HPF.
Conclusions
The differential diagnosis of SST is broad, including fibromas, thecomas, solitary fibrous tumours, pregnancy luteomas, myxomas, other ovarian sex cord‐stromal tumours with sclerosis and, rarely, Krukenberg tumours. Strict adherence to the requirement of pseudolobulation, prominent (usually ectatic) vessels, and lutein cells and fibroblasts admixed in a jumbled manner, will distinguish the neoplasm from others in the differential.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Small RNAs--including piRNAs, miRNAs, and endogenous siRNAs--bind Argonaute proteins to form RNA silencing complexes that target coding genes, transposons, and aberrant RNAs. To assess the ...requirements for endogenous siRNA formation and activity in Caenorhabditis elegans, we developed a GFP-based sensor for the endogenous siRNA 22G siR-1, one of a set of abundant siRNAs processed from a precursor RNA mapping to the X chromosome, the X-cluster. Silencing of the sensor is also dependent on the partially complementary, unlinked 26G siR-O7 siRNA. We show that 26G siR-O7 acts in trans to initiate 22G siRNA formation from the X-cluster. The presence of several mispairs between 26G siR-O7 and the X-cluster mRNA, as well as mutagenesis of the siRNA sensor, indicates that siRNA target recognition is permissive to a degree of mispairing. From a candidate reverse genetic screen, we identified several factors required for 22G siR-1 activity, including the chromatin factors mes-4 and gfl-1, the Argonaute ergo-1, and the 3' methyltransferase henn-1. Quantitative RT-PCR of small RNAs in a henn-1 mutant and deep sequencing of methylated small RNAs indicate that siRNAs and piRNAs that associate with PIWI clade Argonautes are methylated by HENN-1, while siRNAs and miRNAs that associate with non-PIWI clade Argonautes are not. Thus, PIWI-class Argonaute proteins are specifically adapted to associate with methylated small RNAs in C. elegans.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CD8 T cell differentiation is orchestrated by dynamic metabolic changes that direct activation, proliferation, cytotoxic function, and epigenetic changes. We report that the BTB-ZF family ...transcriptional repressor Zbtb20 negatively regulates CD8 T cell metabolism and memory differentiation in mice. Effector and memory CD8 T cells with conditional Zbtb20 deficiency displayed enhanced mitochondrial and glycolytic metabolism, and memory CD8 T cells had enhanced spare respiratory capacity. Furthermore, Zbtb20-deficient CD8 T cells displayed increased flexibility in the use of mitochondrial fuel sources. Phenotypic and transcriptional skewing toward the memory fate was observed during the CD8 T cell response to
Memory cells mounted larger secondary responses and conferred better protection following tumor challenge. These data suggest that inactivation of Zbtb20 may offer an approach to enhance metabolic activity and flexibility and improve memory CD8 T cell differentiation, useful attributes for T cells used in adoptive immunotherapy.
Seventy thecomas of the ovary were evaluated to ascertain their histopathologic spectrum. The tumors occurred over a wide age range (average 49.6 y). Presentation in the form of pelvic or abdominal ...pain was uncommon, but postmenopausal bleeding was relatively frequent. All the tumors were unilateral, ranging up to 22.5 cm (average 4.9 cm) in greatest dimension. They were typically intact, uniformly solid, and yellow. Microscopic examination usually showed a predominant diffuse growth but was altered to varying degrees by hyaline plaques (37 cases), nodular growth (20 cases), calcification (20 cases), and keloid-like sclerosis (12 cases). Forty percent of the tumors had a minor component of fibroma. Reticulin stains typically showed an investment of single cells. The tumor cells characteristically had ill-defined cytoplasmic membranes and distinctive pale gray cytoplasm. Two tumors had degenerative so-called bizarre atypia. Fifteen tumors had nuclear grooves, but they were rarely conspicuous. The differential diagnosis is primarily with other sex cord-stromal neoplasms, particularly sclerosing stromal tumor, microcystic stromal tumor, steroid cell tumor, and adult granulosa cell tumor. The nodules of the first have a more heterogenous morphology than the uniform cell type of thecomas, and microcystic stromal tumors are distinguished because of microcysts and differing character of the tumor cells. Steroid cell tumors also have contrasting cytoplasmic features. Granulosa cell tumor with a prominent thecomatous component is the most clinically important differential and is largely solved by thorough sampling. Our experience indicates a relatively distinctive appearance of thecomas, which contrasts with the lipid-rich character often emphasized in the literature. Awareness of this and a spectrum of other findings should enable accurate interpretation of an almost invariably benign tumor.
Learning and memory rely on long-lasting, synapse-specific modifications. Although postsynaptic forms of plasticity typically require local protein synthesis, whether and how local protein synthesis ...contributes to presynaptic changes remain unclear. Here, we examined the mouse hippocampal mossy fiber (MF)-CA3 synapse, which expresses both structural and functional presynaptic plasticity and contains presynaptic fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein involved in postsynaptic protein-synthesis-dependent plasticity. We report that MF boutons contain ribosomes and synthesize protein locally. The long-term potentiation of MF-CA3 synaptic transmission (MF-LTP) was associated with the translation-dependent enlargement of MF boutons. Remarkably, increasing in vitro or in vivo MF activity enhanced the protein synthesis in MFs. Moreover, the deletion of presynaptic FMRP blocked structural and functional MF-LTP, suggesting that FMRP is a critical regulator of presynaptic MF plasticity. Thus, presynaptic FMRP and protein synthesis dynamically control presynaptic structure and function in the mature mammalian brain.
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•Mossy fiber boutons (MFBs) contain ribosomes and synthesize protein locally•Local presynaptic translation is increased by in vitro and in vivo GC activity•MFB structural plasticity relies on de novo protein synthesis•Presynaptic FMRP is required for MF-CA3 structural and functional plasticity
Monday, Kharod et al. report that neuronal activity regulates presynaptic FMRP function and the local synthesis of β-actin. In vitro activity and in vivo experience engage the FMRP-dependent spatiotemporal regulation of protein synthesis that is required for presynaptic remodeling and long-term changes in neurotransmitter release.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Here, we report that kinase-dead IKKα knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKα downregulation and marked pulmonary inflammation. IKKα reduction ...upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKαlowK5+p63hi cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing transgenic K5.IKKα, depleting macrophages, and reconstituting irradiated mutant animals with wild-type bone marrow (BM) prevented SCC development, suggesting that BM-derived IKKα mutant macrophages promote the transition of IKKαlowK5+p63hi cells to tumor cells. This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs.
► We establish a robust mouse lung SCC model that resembles human lung SCCs ► IKKα reduction deregulates oncogenes, tumor suppressors, and stem cell genes ► Increased IKKα mutant macrophages promote the initiation of lung SCCs ► IKKα prevents the abnormality of squamous cells in multiple epithelial organs
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High-grade histologic transformation of low-grade endometrial stromal sarcoma (LGESS) is rare. Here, we describe the clinicopathologic features and gene fusion status of 12 cases (11 primary uterine ...corpus and 1 primary vaginal), 11 diagnosed prospectively from 2016, and 1 retrospectively collected. Targeted RNA sequencing and/or fluorescence in situ hybridization was employed in all cases. High-grade transformation was seen at the time of initial diagnosis in eight patients and at the time of recurrence in four patients, 4–11 years after initial diagnosis of LGESS. High-grade morphology consisted of generally uniform population of round to epithelioid cells with enlarged nuclei one to two times larger than a lymphocyte, visible nucleoli, and increased mitotic index (range, 6–30; median, 16 per 10 high-power fields); there was often an associated sclerotic and/or myxoid stroma. Estrogen receptor, progesterone receptor, and CD10 expression was absent or significantly decreased (compared with the low-grade component) in the high-grade foci of five tumors. One tumor demonstrated positive (diffuse and strong) cyclin D1 and BCOR staining. p53 staining was wild type in both components of all eight tumors tested. JAZF1-SUZ12 (n = 6), JAZF1-PHF1 (n = 3), EPC1-PHF1, (n = 1), or BRD8-PHF1 (n = 1) fusions were detected in 11 tumors; no fusions were found in one by targeted RNA sequencing. Patients presented with FIGO stages I (n = 4), II (n = 4), III (n = 1), and IV disease (n = 2). Median overall survival calculated from the time of histologic transformation was 22 months (range, 8 months to 8 years) with five patients who died of disease 8–18 months after transformation. High-grade transformation may occur in LGESS with JAZF1 and PHF1 rearrangements at the time of or years after initial diagnosis. Such high-grade transformation is characterized by nuclear enlargement, prominent nucleoli, and increased mitotic index compared with typical LGESS. Histologic high-grade transformation may herald aggressive behavior.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bulk‐heterojunction organic photovoltaic materials containing nonfullerene acceptors (NFAs) have seen remarkable advances in the past year, finally surpassing fullerenes in performance. Indeed, ...acceptors based on indacenodithiophene (IDT) have become synonymous with high power conversion efficiencies (PCEs). Nevertheless, NFAs have yet to achieve fill factors (FFs) comparable to those of the highest‐performing fullerene‐based materials. To address this seeming anomaly, this study examines a high efficiency IDT‐based acceptor, ITIC, paired with three donor polymers known to achieve high FFs with fullerenes, PTPD3T, PBTI3T, and PBTSA3T. Excellent PCEs up to 8.43% are achieved from PTPD3T:ITIC blends, reflecting good charge transport, optimal morphology, and efficient ITIC to PTPD3T hole‐transfer, as observed by femtosecond transient absorption spectroscopy. Hole‐transfer is observed from ITIC to PBTI3T and PBTSA3T, but less efficiently, reflecting measurably inferior morphology and nonoptimal energy level alignment, resulting in PCEs of 5.34% and 4.65%, respectively. This work demonstrates the importance of proper morphology and kinetics of ITIC → donor polymer hole‐transfer in boosting the performance of polymer:ITIC photovoltaic bulk heterojunction blends.
Three high‐fill‐factor OPV polymers, PTPD3T, PBTI3T, and PBTSA3T are paired with the high performance acceptor, ITIC. A maximum power conversion efficiency of 8.43% is achieved with PTPD3T:ITIC blends due primarily to increased short‐circuit current density. Ultrafast hole‐transfer from ITIC to PTPD3T is observed by femtosecond transient absorption measurements due to the superior blend morphology and improved charge transport versus PBTI3T:ITIC and PBTSA3T:ITIC blends.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Entomopathogenic fungi have potential as biocontrol agents against insect pests, and mycovirus-mediated hypervirulence may enhance their efficacy. Before initiating research on hypervirulence, the ...presence or absence of double-stranded (ds) RNA elements was determined in 94 Korean entomopathogenic fungi. dsRNA elements varying in size from
ca.
0.8 to 7 kbp were found in 14.9% (14/94) of the strains examined, including
Beauveria bassiana
,
Metarhizium pemphigi
,
M. pinghaense
,
M. rileyi
, and
Cordyceps fumosorosea
. This study provides information on the incidence and electrophoretic banding patterns of dsRNA elements and is the first report of mycoviruses entomopathogenic fungi in Korea.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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