CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

• MeSH
• buněčné jádro patologie   MeSH
• folikulární adenokarcinom * patologie   epidemiologie   diagnóza   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé MeSH
• nádory štítné žlázy * epidemiologie   patologie   diagnóza   MeSH
• papilární karcinom štítné žlázy epidemiologie   patologie   diagnóza   MeSH
• papilární karcinom patologie   epidemiologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Oceánie MeSH
• Severní Amerika MeSH

Acinic cell carcinoma (AciCC) is a common salivary gland malignancy, typically composed of neoplastic acinic cells with zymogen granules. The vast majority of cases are driven by a t(4;9)(q13;q31) leading to enhancer hijacking and upregulation of the NR4A3 gene. However, a minority of cases do not display NR4A3 overexpression on immunohistochemical examination and are negative for the rearrangement involving the NR4A3 gene when tested by FISH. Such cases overexpress NR4A2, and the protein product is detectable by immunohistochemistry. In this study, we aimed to assess the utility of NR4A2 and NR4A3 immunohistochemistry in the differential diagnosis of salivary gland tumors. Eighty-five cases of classic low-grade ACiCC, as well as 36 cases with high-grade transformation (HGT) and 7 high-grade AciCC cases were included in the analysis. NR4A3 was at least focally positive in 105/128 (82%) cases. Out of the 23 cases that were immunohistochemically negative for NR4A3, 6 displayed nuclear immunopositivity with the NR4A2 antibody. The NR4A3 rearrangement was confirmed by FISH in 38/52 (73%) cases. In addition, this is the first report of an NR4A2 rearrangement being detected by FISH in 2 AciCC cases that were negative for the NR4A3 rearrangement. Our analysis confirms that the majority of AciCC, including high-grade cases and cases with HGT, are immunopositive for NR4A3, and suggests that NR4A3 immunohistochemistry is a powerful tool in the differential diagnosis of salivary gland tumors. However, its utility is limited in sub-optimally fixed samples which often display weaker and focal positivity. Our study also indicates that in a minority of cases, AciCC might be negative for NR4A3 immunostaining, because the pathogenic genetic event in these cases is instead a rearrangement involving the NR4A2 gene.

• MeSH
• acinární karcinom * diagnóza   genetika   metabolismus   MeSH
• buněčné jádro patologie   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• imunohistochemie MeSH
• jaderné receptory - podrodina 4, skupina A, člen 2 metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinných žláz * diagnóza   genetika   patologie   MeSH
• receptory thyreoidních hormonů metabolismus   MeSH
• slinné žlázy patologie   MeSH
• steroidní receptory * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Leiomyoma with bizarre nuclei (LBN) is an uncommon variant of uterine smooth muscle neoplasm. Involvement of fumarate hydratase (FH) has been suggested in the pathogenesis of a subset of LBN. The goal of our study is to assess the clinicopathological, morphological, immunohistochemical and molecular findings focusing on FH in LBNs (n = 108) and compare it with the findings in usual leiomyomas (UL; n = 50) and leiomyosarcomas (LMS; n = 42). Immunohistochemically, loss of FH expression was found in 67/108 of LBN, 1/50 of UL and in no LMS. Class 4/5 FH mutations were detected in 15/53 LBN with sufficient DNA quality for molecular analysis. Pathogenic variants of the FH gene were detected in neither UL nor LMS. Local recurrence after surgery was present in 18/92 of LBN patients, 7 of which were histologically verified and 2 of which were found to be LBN. Our results confirmed that LBN behave in a benign fashion, although they may relapse. FH gene mutations were a common finding only in LBN, but not in UL and LMS. Immunohistochemistry with an antibody against FH seems to have a good sensitivity (87%) and moderate specificity (58%) with regard to predicting FH gene mutations and could be used as a screening method in tumors with features suggestive of FH alterations to identify patients who are at risk for the FH aberrations.

• MeSH
• buněčné jádro patologie   MeSH
• dospělí MeSH
• fumarasa genetika   MeSH
• leiomyom genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• nádory dělohy genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation of lamin A, which contributes to nuclear architecture and the spatial organization of chromatin in the nucleus. The expression of a lamin A mutant, named progerin, leads to functional and structural disruption of nuclear organization. Since progerin lacks a part of the actin-binding site of lamin A, we hypothesized that nuclear actin dynamics and function are altered in HGPS cells. Nuclear F-actin is required for the organization of nuclear shape, transcriptional regulation, DNA damage repair, and activation of Wnt/β-catenin signaling. Here we show that the expression of progerin decreases nuclear F-actin and impairs F-actin-regulated transcription. When nuclear F-actin levels are increased by overexpression of nuclear-targeted actin or by using jasplakinolide, a compound that stabilizes F-actin, the irregularity of nuclear shape and defects in gene expression can be reversed. These observations provide evidence for a novel relationship between nuclear actin and the etiology of HGPS.

• MeSH
• aktiny genetika   metabolismus   MeSH
• buněčné jádro genetika   metabolismus   patologie   MeSH
• buňky NIH 3T3 MeSH
• lamin typ A genetika   metabolismus   MeSH
• lidé MeSH
• myši MeSH
• oprava DNA * MeSH
• progerie genetika   metabolismus   patologie   MeSH
• signální dráha Wnt * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH

Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Together with actin, it has been shown to initiate and regulate transcription, it is part of the chromatin remodeling complex B-WICH, and is responsible for rearrangements of chromosomal territories in response to external stimuli. Here we show that deletion of NM1 in mouse embryonic fibroblasts leads to chromatin and transcription dysregulation affecting the expression of DNA damage and cell cycle genes. NM1 KO cells exhibit increased DNA damage and changes in cell cycle progression, proliferation, and apoptosis, compatible with a phenotype resulting from impaired p53 signaling. We show that upon DNA damage, NM1 forms a complex with p53 and activates the expression of checkpoint regulator p21 (Cdkn1A) by PCAF and Set1 recruitment to its promoter for histone H3 acetylation and methylation. We propose a role for NM1 in the transcriptional response to DNA damage response and maintenance of genome stability.

• MeSH
• apoptóza MeSH
• buněčné jádro účinky léků   genetika   metabolismus   patologie   MeSH
• buněčné linie MeSH
• buněčný cyklus MeSH
• epigeneze genetická MeSH
• etoposid toxicita   MeSH
• genetická transkripce * MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• inhibitor p21 cyklin-dependentní kinasy genetika   metabolismus   MeSH
• myosin typu I genetika   metabolismus   MeSH
• myši MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• poškození DNA * MeSH
• proliferace buněk MeSH
• restrukturace chromatinu * MeSH
• transkripční faktory p300-CBP genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In the present study, we investigated protein expression of the transcription factors mammalian doublesex and mab-3 related transcription factor 1 (DMRT1), basic helix-loop-helix transcription factor-like 5 (TCLF5), and octamer-binding transcription factor 4 (OCT4) in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor (MGC-SCST), spermatocytic tumor, and seminoma. In normal human spermatogenesis, DMRT1 is expressed in the nuclei of spermatogonia but not in those of more mature germ cells. By way of contrast, TCLF5 is expressed in the nuclei of some clusters of primary spermatocytes that have entered meiosis 1, in secondary spermatocytes, and in round (early) spermatids in the seminiferous tubules of adults during the reproductive years. OCT4 is expressed in primordial germ cells but not in the seminiferous tubules of the normal adult testis during the reproductive years. DMRT1 is expressed in the germ cells of both testicular MGC-SCST and spermatocytic tumor, whereas TCLF5 is not expressed in either neoplasm. These low-grade neoplasms, however, differ histologically in that all the germ cell nuclei of testicular MGC-SCST resemble spermatogonia, whereas in spermatocytic tumor, the nuclei of the medium-sized and large cells resemble those of primary spermatocytes. Both neoplasms lack expression of OCT4. By way of contrast, in seminoma, a fully malignant testicular germ cell tumor, the germ cell nuclei express OCT4 but do not express either DMRT1 or TCLF5.

• MeSH
• biopsie MeSH
• buněčné jádro chemie   patologie   MeSH
• germinální a embryonální nádory chemie   patologie   MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• oktamerní transkripční faktor 3 analýza   MeSH
• semenotvorné kanálky chemie   patologie   MeSH
• seminom chemie   patologie   MeSH
• spermatocyty chemie   patologie   MeSH
• spermatogeneze MeSH
• testikulární nádory chemie   patologie   MeSH
• transkripční faktory bHLH analýza   MeSH
• transkripční faktory analýza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after >3 years), and 8 metastases (3 were paired with primary adverse cases). The ratio of greatest dimensions of largest and smallest nuclei, in each of 5 "worst" high-power fields, excluding those with degenerative features, was designated variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean VNS measured in adverse primary and control primary tumors were 3.7 ± 0.5 and 2.4 ± 0.4 respectively (P < .001), and 3.4 ± 0.4 for metastases (P < .001). Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81, respectively. PMCs were 6.0 ± 3.0 for adverse group, 5.7 ± 2.7 for controls, and 4.1 ± 1.6 for metastases (P = NS). PD-L2 could not discriminate adverse versus good primary tumors (χ21.6, P = .2), but was higher in metastases (χ2 6.9, P < .01), or metastases plus adverse primary tumors (χ2 4.8, P = .03), compared to good-pathology primary tumors. In conclusion, VNS is an easily obtained measurement that can predict adverse behavior of chromophobe RCC, and may impart value for needle biopsy reporting and the choice of active surveillance. PD-L2 was elevated in metastases but was less useful for primary tumors.

• MeSH
• antigeny CD273 metabolismus   MeSH
• buněčné jádro patologie   MeSH
• dospělí MeSH
• karcinom z renálních buněk patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• monoklonální protilátky MeSH
• myši MeSH
• nádory ledvin patologie   MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• velikost buněčného jádra * MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We report 50 cases of peculiar histiocytic proliferations occurring in diverse body sites that currently bear various names, including nodular mesothelial/histiocytic hyperplasia, nodular histiocytic aggregates, mesothelial/monocytic incidental cardiac excrescences, reactive eosinophilic pleuritis, histioeosinophilic granuloma of the thymus, and intralymphatic histiocytosis. They can sometimes cause considerable differential diagnostic difficulties by resembling a metastatic carcinoma or Langerhans cell histiocytosis. Several previous publications have established a link between some of these conditions, suggesting that these are merely variations within a histopathologic spectrum, affecting different organs and bearing different names based on a particular location. However, no publication has ever comprehensively addressed all of these lesions together in one study in an attempt to explain and discuss their striking analogy. Having studied a large series of cases we provide evidence that all these lesions share the same morphologic, immunohistochemical, and pathogenetic properties, thus they all represent the same pathologic process and should be referred to as such. Taking into account their typical nuclear features we propose a collective term "histiocytosis with raisinoid nuclei" for this spectrum of conditions.

• MeSH
• biologické markery analýza   MeSH
• buněčné jádro patologie   MeSH
• dospělí MeSH
• histiocytóza patologie   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The perinucleolar region represents a special nuclear compartment involved in the cell malignancy and the perinucleolar heterochromatin reflects the presence of silent genes. The present study was undertaken to provide complementary and missing information on the perinucleolar heterochromatin in differentiating neutrophils in the bone marrow of patients with the chronic myeloid leukemia. That lineage is a very convenient model because of the increased number of granulocytic precursors that is satisfactory for size as well as optical density measurements in single cells. Moreover, the differentiation stages of neutrophils are well defined and easily identified. According to diameter measurements the enlarged width of the perinucleolar heterochromatin shell accompanied the decreasing nucleolar size in advanced stages of the cell differentiation. Such trend was not influenced by the anti-leukemic therapy with imatinib. Thus the increasing size of the perinucleolar heterochromatin shell with silent genes might reflect the genomic stability of the perinucleolar region during the cell differentiation. On the other hand, the increased perinucleolar heterochromatin condensation after the specific anti-leukemic therapy with imatinib indicated a “premature terminal differentiation” of leukemic neutrophils.

• MeSH
• benzamidy terapeutické užití   MeSH
• buněčná diferenciace * genetika   imunologie   účinky léků   MeSH
• buněčné jádro * genetika   mikrobiologie   patologie   MeSH
• chronická myeloidní leukemie farmakoterapie   genetika   imunologie   MeSH
• heterochromatin * genetika   imunologie   patologie   MeSH
• kostní dřeň imunologie   účinky léků   MeSH
• lidé MeSH
• modely genetické MeSH
• neutrofily imunologie   patologie   účinky léků   MeSH
• piperaziny terapeutické užití   MeSH
• prekurzorové buňky granulocytů imunologie   patologie   účinky léků   MeSH
• pyrimidiny terapeutické užití   MeSH
• statistika jako téma MeSH
• struktury buněčného jádra genetika   imunologie   mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

INTRODUCTION: Nuclei of hairy cells (HC) are typically oval, round or indented, but atypical shapes are occasionally described in HCL and may lead to a provisional wrong diagnosis. METHODS: The aim of this study was to quantify HC nuclei shapes classified into 11 categories on diagnostic bone marrow smears of 38 consecutive patients with HCL. RESULTS: HC in all 33 patients with evaluable smears at diagnosis exhibited a round/oval nucleus in 60.8-95.8%, an indented nucleus in 3.4-24.5% and a kidney-shaped nucleus in 0.4-7.0%. Other shapes of HC nuclei were found only in a proportion of patients: nuclei with two indentations in 0.4-6.5% HC (28 patients), overlapped nuclei in 0.5-3.5% HC (17) and lobulated nuclei in 0.4-4.5% HC (15). Two per cent or less of HC had the following nuclear shapes: that of an opposite indentation and impression (14 patients), dumb-bell (13), ring (10), horseshoe (5), two nuclei (8 patients). CONCLUSION: Different shapes of HC nuclei similar to cells typical for other diagnoses are found usually in low frequencies. However, if their numbers are increased, they may cause diagnostic problems because cytology of blood and bone marrow smears is usually the first available diagnostic method.

• MeSH
• aplastická anemie diagnóza   patologie   MeSH
• B-lymfocyty patologie   MeSH
• buněčné jádro patologie   MeSH
• cytodiagnostika MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• granulocyty patologie   MeSH
• kostní dřeň patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myelodysplastické syndromy diagnóza   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tvar buněčného jádra MeSH
• vlasatobuněčná leukemie diagnóza   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH