Nuclear Contours Research Articles

Variação entoacional no Português do Brasil: uma análise fonológica do contorno nuclear em enunciados declarativos e interrogativos

In this paper we present a phonological analysis of the nuclear contour of declarative and interrogative utterances in Brazilian Portuguese, as spoken in 7 regions, along the Atlantic Coast - Paraíba, Sergipe, Bahia (North); Minas Gerais, Rio de Janeiro (Center), Santa Catarina and Rio Grande do Sul (South). Declaratives present a falling contour, with phonetic differences across varieties. As for interrogatives, more variation was found. Namely, two types of nuclear contours were observed: a rising contour in the North and a rising-falling in the Center-South. Unlike declaratives, the two interrogative patterns display a phonological continuum, in which the Center-Southern pattern spreads towards the North.

Hyaline globules and papillary fragments in cytologic smears from two intra‐abdominal tumors (ovarian and hepatic) in female patients: A diagnostic pitfall with histologic correlation

Hyaline globules and papillary fragments in cytologic samples from two intra-abdominal tumors in young females are presented including the cytological features and the correlation with the histopathologic and immunohistochemical findings. In the first case a cytologic study from an ovarian mass showed papillary structures and isolated tumor cells with epithelioid morphology, irregular reniform-like nuclear contour, pale or vacuolated cytoplasm, abundant hyaline globules and occasional glomeruloid structures resembling Schiller-Duval bodies. Yolk sac tumor (YST) was the diagnosis on the histological slides. Tumor cells showed positivity for cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), alpha-fetoprotein (AFP) and Sal-like protein 4 (SALL4). In case number two the cytologic study from a liver metastasis displayed papillary and rosette-like clusters composed of uniform and bland cells showing occasional long cytoplasmic tails, hyaline globules and nuclear grooves. A diagnosis of hepatic metastasis from solid pseudopapillary neoplasm of the pancreas (SPNP) was rendered from the histology. Tumor cells revealed immunoreactivity for cytokeratin (AE1/AE3), Vimentin, Galectin-1 (GAL-1), Neuron specific-enolase, CD10, progesterone and β-catenin (nuclear stain). Regarding differential diagnosis, in the patient with the ovarian mass an ovarian clear cell carcinoma was considered, as well as other germ cell tumors or metastatic carcinoma, while in the patient with a liver metastasis a neuroendocrine carcinoma was taken into account. YST and SPNP share some cytological findings, including hyaline globules, papillary structures, clear cells and intercellular eosinophilic basement membrane deposits. Thus, a detailed study and careful interpretation of the cytological, histological and immunohistochemical findings may be worthwhile to avoid a potential misdiagnosis, particularly in the cytologic specimens of the ovarian and/or intra-abdominal mass, when involving young females. Diagn. Cytopathol. 2016;44:935-943. © 2016 Wiley Periodicals, Inc.

Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: A name change to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features would help prevent overtreatment

Encapsulated follicular variant of papillary thyroid carcinoma is a common thyroid gland cancer, with a highly indolent behavior. Recently, reclassification as a non-malignant neoplasm has been proposed. There is no comprehensive, community hospital based longitudinal evaluation of encapsulated follicular variant of papillary thyroid carcinoma. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma were identified in a review of all thyroid gland surgeries performed in 2002 within the Southern California Permanente Medical Group. All histology slides were reviewed and follow-up obtained. Seventy-five women and nineteen men, aged 20–80 years (mean 45.6 years), had a single (n=61), multiple (same lobe; n=20), or bilateral (n=13) tumor(s), ranging in size from 0.7 to 9.5 cm in diameter (mean 3.3 cm). Histologically, all cases demonstrated a well-formed tumor capsule, with capsular and/or lymphovascular invasion in 17 and no invasion in 77 cases. Lymph node metastases were not identified. The tumors had a follicular architecture, without necrosis or >3 mitoses/10 high-power fields (HPFs). Classical papillary thyroid carcinoma nuclear features were seen in at least three HPFs per 3 mm of tumor diameter, including enlarged, elongated, crowded, and overlapping nuclei, irregular nuclear contours, nuclear grooves, and nuclear chromatin clearing. Lobectomy alone (n=41), thyroidectomy alone (n=34), or completion thyroidectomy (n=19) was the initial treatment combined with post-op radioablative iodine in 25 patients. All patients were without evidence of disease after a median follow-up of 11.8 years. Encapsulated follicular variant of papillary thyroid carcinoma showed benign behavior, supporting conservative surgery alone and reclassification of these tumors to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).

Assessment of Cytomorphometric Features of Oral Squames from Buccal Mucosa of Tobacco Users using Oral Brush Biopsy: An Exfoliative Cytological Study

Background: Tobacco comprises of one of the most common addiction in the society. All the forms of the tobacco are harmful, causing alterations in the cellular parameters of the oral mucosal cells. A number of techniques and methods are available along with chair side examination for supplementing the diagnosis of tobacco induced premalignant lesions. Exfoliative cytology is one such technique, which is non-invasive and can be used for mass screening. Therefore, we evaluated the cytological and cytomorphometric changes in the oral squames using brush biopsy from buccal mucosa of tobacco users. Methods: A total of 300 patients with age group of 25 to 60 years were included in the study. Detailed history of the patients were taken to known the method (smoking, smokeless or both) and frequency of tobacco intake. Scrapings from the buccal mucosal scrape were obtained, smeared on slides and were subsequently stained with Hematoxylin and Eosin staining. Observation and analyses of the smears was done under microscope followed by analysis in the computer using software Dewinter Biowizard version 3.0. various cellular parameters were assessed and compared in between different groups. Patients were divided into two major groups- Habituers and Nonhabituers. The habituers were again divided into: Tobacco smokers, Tobacco chewers and patients having combined habit. Independent-Samples T Test and One-Way ANOVA were used to assess the level of significance. Results: Significant results were obtained while comparing nuclear parameter, cellular area, cellular perimeter, cell contour and nucleo-cytoplasmic ratio in between lesional group and tobacco smoking group. While comparing between tobacco smoking group and Non habituers group, significant results were obtained in all the parameters except for cell contour and N/C ratio. Significant results were obtained while comparing between lesions and combined habit groups. While comparing between habituers and non- habituers group, except for cell contour significant results were obtained in all other cellular parameters. Conclusion: Early changes detection in clinically normal oral mucosa of tobacco users is possible by using non-invasive, painless procedures like oral brush biopsy and cytomorphometry. Further studies recommended.

Abstract P6-04-10: Clinicopathological and molecular characteristics of pleomorphic invasive lobular carcinoma of breast

Abstract Background: Pleomorphic invasive lobular carcinoma (PILC) is described as a distinct morphological variant of invasive lobular carcinoma (ILC) but its clinical behavior is not well characterized. PILCs have loss of E-cadherin similar to ILCs but have distinct morphological features like nuclear contour irregularity, a single prominent nucleolus, increased hyperchromasia and more frequent mitoses. In addition, some studies have reported that PILCs have acquired further molecular alterations such as gain of HER2/neu, amplification of c-myc and loss of p53. To the best of our knowledge there have been no studies evaluating Phosphoinositide 3 kinase/Akt/mammalian (or mechanistic) target of rapamycin (PI3K/Akt/mTOR) pathway in PILC. We hypothesize that there is increased activation of PI3K/Akt/mTOR pathway in PILC compared to ILC. Activation of the PI3k/Akt/mTOR pathway was evaluated by quantifying protein expression of phosphatase and tensin homolog (PTEN) and phosphorylated-S6 kinase1 (p-S6K1). PTEN is a negative regulator of the PI3K pathway and its loss/decreased expression (by mutation or allelic imbalance) activates downstream signaling. Loss (or decrease) of PTEN expression has been reported to be associated with PI3K pathway activation in more than 50% of ER+ breast tumors. Since PI3K pathway can be activated by other mechanisms in addition to PTEN loss, we hypothesized that evaluation of pS6K1 may predict activation of this pathway more than PTEN protein expression alone. Methods: We conducted a retrospective translational study at the University of Arizona Cancer Center. Our Pathology database was searched to identify PILCs from 2012-2014. Two investigators reviewed the pathology reports independently and abstracted clinocopathological data. Formalin-fixed paraffin embedded (FFPE) primary PILCs were stained for PTEN and pS6K1 expression. Expression of PTEN and pS6K1 was quantified by long score methodology as low (≤ 10), moderate (11-50) or high (≥ 50) expression. Results: We identified 19 patients with PILC. All tumors were either moderately (n=10) or poorly differentiated (n=9). Estrogen receptor (ER) was positive in all, progesterone receptor (PR) was positive in 11(52%) and HER2 was negative in all tumors. Proliferation index (Ki67) was elevated in all tumors (median 32%, range 20-70%). Lymph nodes were involved with metastatic carcinoma in 7 patients (negative in 9 and unknown in 3). The 21-gene recurrence score assay (Oncotype Dx) was performed in 10 patients and demonstrated higher scores (median 23, range 6-36) with the majority being in the intermediate or high range (8/10). Expression of PTEN and p-S6K1 was quantified on 10 FFPE tumor tissues. PTEN expression was high in all while pS6K1 was high in 8 and low in 2 tumors. Conclusion: PILCs are a biologically distinct group of ILC. Clinicopathological characteristics suggest they would have a more clinically aggressive behavior (higher grade, high proliferative index and 21 gene recurrence score). In addition, our results indicate that PI3k/Akt/mTOR pathway in activated in majority of these tumors and that PTEN is not the key regulator of this pathway. Genomic profiling is currently underway to further analyze other causes of pathway activation. Citation Format: Segar J, Baker AF, MacKerricher W, Nagle R, Livingston R, Clarke K, Ley M, Viscusi R, Gonzalez V, LeBeau L, Chalasani P. Clinicopathological and molecular characteristics of pleomorphic invasive lobular carcinoma of breast. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-04-10.

A clinicopathologic study of malignant melanoma based on cytomorphology.

Melanoma accounts for 1-3% of all malignancies. It is usually diagnosed as metastasis in the draining lymph nodes, that is inguinal lymph node. Due to paucity of cytological studies on melanoma in India, the present study was undertaken. To study the cytomorphology of malignant melanoma and to correlate the cytological diagnosis with histopathology and clinical details. Sixteen cytomorphological features were studied and analysed from the cases diagnosed as melanoma on cytology with histopathological correlation. Thirty patients diagnosed with malignant melanoma on fine-needle aspiration cytology (FNAC) were studied over a period of 10 years and compared by histopathology. Papanicolaou (Pap)- and May Grunwald Giemsa (MGG)-stained smears were studied and analysed for the cytomorphological spectrum of melanoma. Among the 30 patients studied, males were 19 and females were 11 (M:F:1.7:1) with a mean age of 49.3 years. The commonest primary site was foot followed by maxilla and thigh. The most common site for metastasis was inguinal lymph node. All 30 cases had histopathological correlation. Pigmented melanophages (83%) was the predominant feature followed by presence of melanin pigment (77%) and pseudo-inclusions (73%). Condensed chromatin was observed in the majority of the patients (53%). Smooth and irregular nuclear contours were seen in combination in 37% of the cases. A combination of nuclear placement, that is eccentric and central was observed as a predominant feature (53%). Spindle cell pattern was the predominant shape. Among cytoplasmic features, melanin granules and vacuoles were equally distributed (50%). Mixed pattern, that is singly scattered plasmacytoid cell pattern and cell clusters was the predominant cell architecture. A spectrum of cytomorphological features in correlation with clinical details leads to greater precision in diagnosis and helps to avoid pitfalls in diagnosing melanoma.

Variação entoacional no Português do Brasil: uma análise fonológica do contorno nuclear em enunciados declarativos e interrogativos

In this paper we present a phonological analysis of the nuclear contour of declarative and interrogative utterances in Brazilian Portuguese, as spoken in 7 regions, along the Atlantic Coast - Paraiba, Sergipe, Bahia (North); Minas Gerais, Rio de Janeiro (Center), Santa Catarina and Rio Grande do Sul (South). Declaratives present a falling contour, with phonetic differences across varieties. As for interrogatives, more variation was found. Namely, two types of nuclear contours were observed: a rising contour in the North and a rising-falling in the Center-South. Unlike declaratives, the two interrogative patterns display a phonological continuum, in which the Center-Southern pattern spreads towards the North.

Production and perception of contrast: The case of the rise-fall contour in German.

This study investigates the phonetics of German nuclear rise-fall contours in relation to contexts that trigger either a contrastive or a non-contrastive interpretation in the answer. A rise-fall contour can be conceived of a tonal sequence of L-H-L. A production study elicited target sentences in contrastive and non-contrastive contexts. The majority of cases realized showed a nuclear rise-fall contour. The acoustic analysis of these contours revealed a significant effect of contrastiveness on the height/alignment of the accent peak as a function of focus context. On the other hand, the height/alignment of the low turning point at the beginning of the rise did not show an effect of contrastiveness. In a series of semantic congruency perception tests participants judged the congruency of congruent and incongruent context-stimulus pairs based on three different sets of stimuli: (i) original data, (ii) manipulation of accent peak, and (iii) manipulation of the leading low. Listeners distinguished nuclear rise-fall contours as a function of focus context (Experiment 1 and 2), however not based on manipulations of the leading low (Experiment 3). The results suggest that the alignment and scaling of the accentual peak are sufficient to license a contrastive interpretation of a nuclear rise-fall contour, leaving the rising part as a phonetic onglide, or as a low tone that does not interact with the contrastivity of the context.

Biliary stent–related alterations can be distinguished from adenocarcinoma on bile duct brushings using a limited number of cytologic features

Although it is widely accepted that cytologic alterations secondary to a biliary stent can be difficult to distinguish from adenocarcinoma in pancreatobiliary exfoliative cytology, no systematic study has been undertaken to identify the cytologic features that best distinguish these entities. A training set of 29 bile duct brushings (14 with biliary stents, originally classified as atypical or suspicious, with >6 months of benign clinical follow-up; and 15 diagnosed as adenocarcinoma with histologic confirmation) was evaluated for the following: nuclear enlargement, nuclear contour, nuclear overlap, chromatin distribution, nuclear-cytoplasmic ratio, anisonucleosis, macronucleoli, mitoses, acute inflammation, disorganization, necrosis, cell borders, single atypical cells, and 2 distinct cell populations. A distinct validation set of 31 equivocal stented brushings-13 later diagnosed with carcinoma and 18 with ≥6 months of benign follow-up-were similarly evaluated. Cases were categorized as benign or malignant using a scoring algorithm based on statistically significant features. Five features achieved statistical significance: atypical single cells (P = 0.0001), 2 distinct cell populations (P = 0.0007), and anisonucleosis (P = 0.0422) favored malignancy; distinct cell borders (P = 0.0018) and acute inflammation (P = 0.0035) favored benign. The algorithm correctly classified 12 of 14 benign and 15 of 15 malignant cases in the training set and 16 of 18 benign and 7 of 13 malignant cases in the validation set. Most bile duct brushings from patients with biliary stents could be definitively and correctly classified as either benign or malignant using 5 morphologic features: single atypical cells, binary cell population, anisonucleosis, distinct cell borders, and acute inflammation.

A Pilot Study Evaluating Fine-Needle Aspiration Cytology of Clear-Cell Renal Cell Carcinoma: Comparison of Ancillary Immunocytochemistry and Cytomorphological Characteristics of SurePath™ Liquid-Based Preparations with Conventional Smears

Objective: Fine-needle aspiration cytology (FNAC) based on a liquid-based preparation is a safe and valuable diagnostic tool. However, due to unfamiliarity with this method and the considerably altered morphology that is associated with it, diagnosing renal cell carcinoma (RCC) from this type of preparation remains a challenge for cytopathologists. The aim of this study was to evaluate the cytomorphological characteristics of SurePath™ (SP)-based preparations compared with conventional smear (CS), and also the role of SP-based FNAC in the diagnosis of clear-cell RCC (CRCC), the most common primary renal malignancy. Study Design: Ex vivo FNAC of both tumors and normal renal parenchyma was prepared from 73 cases. Comparative cytomorphological analysis between liquid-based cytology (LBC) and CS as well as Fuhrman nuclear grading (FNG) was carried out. Immunocytochemistry was performed from normal and CRCC cytology specimens. Results: Normal renal cytology (NRC) showed no significant morphological differences between LBC and CS. For CRCC, LBC showed small, fragmented cell clusters, a 3-dimensional configuration, distinct cytoplasmic vacuoles, and irregular nuclear contours when compared with CS. FNG was overgraded with LBC compared to with CS. AMACR was the most valuable immunocytochemical marker for distinguishing CRCC from NRC. Conclusion: Once cytopathologists become familiar with the altered cytomorphological features of CRCC, FNAC, along with immunocytochemistry, may prove helpful for diagnosis.

Blastic plasmacytoid dendritic cell neoplasm: a case report and review of literature

Objective To investigate the feature, pathological diagnosis and differential diagnosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN). Methods The clinical and histological findings, immunophenotype, treatment and prognosis of one case with BPDCN were evaluated with review of the relevant literature. Results The female patient with age of 32 years presented as cutaneous lesions. Pathologic findings showed skin and bone marrow were involved. Microscopically, the tumors were composed of diffuse blasts with small to medium size, scant cytoplasm, highly irregular nuclear contours, dispersed nuclear chromatin and faint indistinct nucleolus. Immunohistochemical characteristics of the tumors were the positive expression of CD4, CD56 and CD123, and negative expression of CD3, CD20, CD34, TdT, MPO. Conclusion BPDCN is a rare and highly aggressive hematopoietic neoplasm. Except for the skin, bone marrow and lymph node can also be involved. The differential diagnosis is necessary from other haematopoietic and lymphoid tumors. Key words: Blastic plasmcytoid dendritic neoplasm; Immunophenotype; Bone Marrow biopsy

Diffuse pulmonary meningotheliomatosis: A diagnostically challenging entity on fine‐needle aspiration cytology

Diffuse pulmonary meningotheliomatosis (DPM) is an exceedingly rare entity consisting of multiple minute pulmonary meningothelial-like nodules profusely involving the lungs. To the best of our knowledge, we present the first cytologic description of this uncommon lesion from a 57-year-old nonsmoking woman. Computerized tomographic-guided fine-needle aspiration cytology from a left upper lobe nodule showed whorled/nested clusters of elongated cells with oval nuclei, clear pseudonuclear inclusions, nuclear grooves/indentations, smooth nuclear contours, fine granular chromatin, inconspicuous nucleoli, and abundant fibrillary cytoplasm with indistinct cell borders. The subsequent pulmonary wedge resections confirmed the diagnosis of DPM. As this condition is exceptionally rare, familiarity with these cytologic features is of the essence to accurately establish this challenging diagnosis.

Abstract P1-07-08: TP53 alteration in morphologically benign breast tissue in patients with ER/PR negative high grade breast carcinomas: Marker for early detection of high risk patients for high grade carcinomas?

Abstract Background: TP53 alterations have been identified in approximately 20% of breast carcinomas, especially in ER/PR negative high grade carcinomas. It is believed that TP53 alteration is an early event in the carcinogenesis of high grade breast carcinomas. TP53 alteration could even be identified in morphologically "benign" appearing breast tissues. Nevertheless, the precursor lesion of high grade ductal carcinoma in situ and/or invasive carcinoma is not well recognized morphologically. Design: We retrospectively analyzed the TP53 status of 108 cases with high grade (modified Bloom-Richardson grade 3) invasive ductal carcinoma, 51 cases with non-high grade invasive ductal carcinoma, and 50 cases with benign breast from mammoplasty. The high grade carcinomas were all estrogen receptor (ER) and progesterone receptor (PR) negative and 96.3% of them were HER-2 negative. The non-high grade carcinomas were all ER and/or PR positive, 92.2% Her2 negative. Blocks with tumor and/or benign tissue were selected from each case. Immunohistochemical stain for p53 was performed. TP53 gene sequencing was performed on selected tumors with inconclusive p53 staining. Further ER and Ki67 immunohistochemical stains were performed on the blocks with p53 positive benign tissue. Results: Of the 108 high grade carcinomas, 48 (44%) were positive for TP53 alteration. Seventeen of the 48 (35.4%) cases also showed focal p53 staining in the adjacent benign appearing tissue. Only one case was negative for TP53 alteration in tumor but with focal p53 staining in benign tissue. Of the non-high grade carcinomas, 5 (9.8%) were positive for TP53 alteration, one of which had focal p53 staining in adjacent benign breast tissue. No p53 staining positivity was identified in the mammoplasty specimens. The p53 staining positive benign glands were ER negative, and did not show an increase in Ki67 labeling index. The morphology of these cells appeared to be slightly enlarged nuclei, with a mildly increased nuclear/cytoplasm ratio, slightly irregular nuclear contours, open chromatin, and prominent nucleoli, but still within the limits of "benign" glands. Conclusion: TP53 is already altered in "benign" appearing breast glands in patients with high grade breast carcinomas. These glands show the same ER status as their counterpart carcinomas, but remain inactive with low Ki67 labeling index, indicating further genetic changes are needed to trigger the unlimited tumor growth and fully malignant transformation. The special morphology and p53 positivity of the "benign" appearing cells could serve as an indicator for future potential risk of TP53 positive high grade breast carcinoma. Citation Format: Xi Wang, Moritz Stolla, Todd S Laughlin, Paul G Rothberg, Kristin Skinner, David G Hicks. TP53 alteration in morphologically benign breast tissue in patients with ER/PR negative high grade breast carcinomas: Marker for early detection of high risk patients for high grade carcinomas? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-08.

Cytopathology of pulmonary adenocarcinoma with a single histological pattern using the proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification.

Guidelines for histological subtyping in patients with surgically resected lung adenocarcinoma (ADC) were recently proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. The objective of the current study was to investigate the cytomorphology of these subtypes of ADC in cases with matched histology specimens demonstrating a single pure subtype. The authors reviewed their database for patients with histological diagnoses of primary lung ADC with a single histological pattern observed on surgical resection and investigated the cytological findings in 18 matched cytology specimens to eliminate sampling issues in cases of mixed ADC. Resections were classified as acinar (7 specimens), solid (6 specimens), lepidic (2 specimens), mucinous (2 specimens), and papillary (1 specimen). Cytology specimens demonstrating a solid pattern had a predominance of 3-dimensional clusters (5 of 6 vs 0 of 12 specimens) (P = .0007, Fisher exact test), necrotic background (3 of 6 vs 0 of 12 specimens) (P = .02), pleomorphic nuclei (6 of 6 vs 1 of 12 specimens) (P = .0004), irregular nuclear contours (6 of 6 vs 3 of 12 specimens) (P = .009), and nuclear enlargement (5 of 6 vs 2 of 12 specimens) (P = .01) compared with the nonsolid patterns. Nuclear pseudoinclusions were present only in nonsolid patterns (5 of 12 specimens), although this finding was not statistically significant (P = .05) CONCLUSIONS: Cytological features of lung ADC subtypes proposed by the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification overlap. However, architectural and nuclear features may be helpful, particularly in distinguishing the prognostically adverse solid pattern from other patterns.

Morphometric Characterization of Marginal Zone Lymphoma

Abstract The morphometry in histopathology is used to characterize cell populations belonging to different tissues and to identify differences in their parameters with prognostic implications. To achieve morphometric examination were selected 6 of 8 cases identified as marginal zone lymphoma. For each case analysis was done on five fields, for each field measuring the parameters of 20 cells. The studied parameters were for cytoplasm: cytoplasmic area, maximum and minimum cytoplasmic diameter, cytoplasmic perimeter; for nucleus were measured: nuclear area, minimum and maximum nuclear diameter, nuclear perimeter, nuclear contour index, nuclear ellipticity index, nuclear irregularity index. Also the nucleo-cytoplasmic ratio was calculated in all studied cases. Marginal zone lymphoma is characterized in terms of morphometric parameters by small cytoplasmic and nuclear area, and small nucleo-cytoplasmatic ratio of about 1:1. Nuclear contour index is small, accompanied by a large ellipticity index and an small index of nuclear irregularity. Standard deviations for measured morphometric parameters are variable, having high values for cytoplasmic and nuclear area, highlighting the polymorphic nature of the cells. Morphometric aspects, with corresponding microscopic aspects of large and small lymphocyte proliferation with cleaved and uncleaved nuclei, fit this form of lymphoma in terms of clinical outcome in indolent lymphomas category.

Asking or Telling--Real-time Processing of Prosodically Distinguished Questions and Statements.

We introduce a targeted language game approach using the visual world, eye-movement paradigm to assess when and how certain intonational contours affect the interpretation of utterances. We created a computer-based card game in which elliptical utterances such as "Got a candy" occurred with a nuclear contour most consistent with a yes-no question (H* H-H%) or a statement (L* L-L%). In Experiment I we explored how such contours are integrated online. In Experiment 2 we studied the expectations listeners have for how intonational contours signal intentions: do these reflect linguistic categories or rapid adaptation to the paradigm? Prosody had an immediate effect on interpretation, as indexed by the pattern and timing of fixations. Moreover, the association between different contours and intentions was quite robust in the absence of clear syntactic cues to sentence type, and was not due to rapid adaptation. Prosody had immediate effects on interpretation even though there was a construction-based bias to interpret "got a" as a question. Taken together, we believe this paradigm will provide further insights into how intonational contours and their phonetic realization interact with other cues to sentence type in online comprehension.

Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia

AimsNear-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics and therefore, presumed to have an unfavourable prognosis. Our aim is to...

Chromatin Association with the Nuclear Envelope Supports Stable Nuclear Mechanics

Although the nuclear lamina is considered to be the primary mechanical defense of the nucleus, lamins are part of an integrated network of lipids, proteins, and chromatin. Here, we isolate the contribution of chromatin to nuclear mechanics by employing fission yeast, which lack a nuclear lamina. We have combined a quantitative imaging platform capable of measuring 3D nuclear contours in vivo with an in vitro optical tweezers assay to probe the mechanical properties of S. pombe nuclei. In live cells, we find that association of chromatin with the inner nuclear membrane (INM) through integral membrane proteins is required for a normal mechanical response to microtubule (MT) forces. Increasing loss of integral INM proteins results in highly deformable nuclei specifically in response to exogenous MT forces. These nuclei also show a decreased capacity to recover from mechanical stress. Using optical tweezers, we find that nuclei lacking integral INM proteins are less stiff than wild type nuclei and have increased chromatin flow, particularly when force is applied at rates that recapitulate the kinetics of MT dynamics in vivo. Wild type mitotic nuclei, in which chromatin is globally released from the INM, are extremely soft and also display increased chromatin flow compared to interphase nuclei. Interestingly, decreasing the chromatin to nuclear volume ratio without altering the association of chromatin with the INM has only a slight effect on stiffness and does not alter chromatin flow. Together, these findings suggest that association of chromatin with the nuclear envelope underlies nuclear stiffness. Further, release of chromatin from the INM allows chromatin to flow into MT-dependent fluctuations of the nuclear envelope, leading to larger, longer-lasting nuclear deformations. Lastly, these results suggest that chromatin association with the lamina may contribute to the mechanical behavior of metazoan nuclei.

Poorly Differentiated Squamous Cell Carcinoma in an Atomic Bomb Survivor.

Dear Editor: Many epidemiological studies of atomic bomb survivors in Japan demonstrate that exposure to radiation increases the risk of cancers, especially leukemia, in most organs1. The risk of non-melanoma skin carcinoma in atomic bomb survivors is elevated2, and the most common primary skin tumors among 152 skin tumors among patients exposed to atomic bomb radiation were basal cell carcinoma (42%), followed by squamous cell carcinoma (SCC) (26%), Bowen's disease (13%), and malignant melanoma (6%)3. Here, we report a case of poorly differentiated SCC in an atomic bomb survivor. An 86-year-old Japanese woman visited our hospital with a one-month history of subcutaneous tumor in the inguinal region. She noticed a tumor on her the left side of waist when she was 46 years old. She was exposed to atomic bomb radiation in Hiroshima at the age of 19 years. Physical examination revealed a 32×40-mm reddish dome-shaped tumor on her the left side of the waist (Fig. 1A) and a 65×72-mm painful subcutaneous tumor on her left inguinal region (Fig. 1B). Blood examination revealed no abnormal changes. Whole-body computed tomography revealed no remarkable changes. Fluorodeoxyglucose-positron emission tomography revealed abnormal uptake in the tumor of on the waist and left inguinal lymph nodes. Histopathological examination of the waist tumor demonstrated numerous tumor cells throughout the dermis and subcutis (Fig. 1C). Atypical large tumor cells had irregular nuclear contours and prominent nucleoli (Fig. 1D). Immunohistochemistry showed the tumor cells were positive for keratin, CK7, p63, p40, and NSE but negative for CK20, chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), CD56, Melan-A, S-100, and EBER (Fig. 2A~E). The results of the histological and immunohistochemical examinations of the inguinal tumor were same. On the basis of these findings, she was diagnosed with poorly differentiated SCC in the waist and metastasis in the inguinal lymph nodes. Tumors in the waist and inguinal regions were resected, and she was subsequently treated with electron beam radiation (total dose: 59 Gy). Eight months later, a metastatic lesion in the left lung was observed, but she refused additional treatment. Fig. 1 (A) Reddish dome-shaped tumor on the left side of the waist. (B) Painful subcutaneous tumor on the left inguinal region. (C, D) Histopathological examination of the waist tumor (HE C: ×40, D: ×1,000). (C) Numerous tumor cells ... Fig. 2 Immunohistochemical examination of the waist tumor. Tumor cells stained positive for (A) keratin and (B) CK7, and negative for (C) chromogranin A, (D) CK20, and (E) thyroid transcription factor-1 (A~E: ×400). Tumor cells were positive for keratin as well as squamous cell markers p63 and p40. The common markers of neuroendocrine carcinomas, including Merkel cell carcinoma, CK20, chromogranin A and synaptophysin, were negative. TTF-1, a marker of primary thyroid and lung carcinoma, was negative. These immunohistochemical results and the low differentiation pattern of tumors on hematoxylin & eosin staining lead to a final diagnosis of poorly differentiated SCC. Regarding the relationship between the extent of tumor differentiation and atomic bomb radiation exposure, the frequency of poorly differentiated adenocarcinoma of stomach in atomic bomb survivors is significantly higher than that in non-exposed individuals4. Nevertheless, the association between atomic bomb radiation exposure and poorly differentiated SCC in our patient is speculative. A recent study reports multiple basal cell carcinomas were developed in atomic bomb survivors more than 40 years after radiation exposure5. Thus, exposure to atomic bomb radiation might influence the risk of cancers; therefore, dermatologists should perform long-term surveillance for skin carcinomas in atomic bomb survivors.

Cytological Features of a Variant NUT Midline Carcinoma of the Lung Harboring the NSD3-NUT Fusion Gene: A Case Report and Literature Review.

Background. Nuclear protein in testis (NUT) midline carcinoma (NMC) is a very rare and aggressive malignancy. In more than two-thirds of these NMC cases, a fusion between NUT and BRD4 or BRD3 has been documented; other variants are rare. The cytology of NMC itself has been sparsely documented and that of variant NMC has never been reported. Case Presentation. A 36-year-old woman was admitted because of a rapidly progressing lung tumor with metastases to the breast and bone. We recently reported this patient as the first case of a variant NMC of the lung harboring an NSD3-NUT fusion, based on immunohistochemical and genetic analyses. Cytological material was available for the present review. A highly cellular smear contained a predominantly noncohesive pattern of monomorphic cells with diameters 2–2.5 times greater than those of small lymphocytes, with a round-to-oval nucleus, slightly irregular nuclear contours, variably prominent nucleoli, scant cytoplasm, and identifiable mitotic figures. Foci of stratification and overt pearl formation, including a dyskeratocyte, were occasionally observed. The necrotic background contained naked nuclei, karyorrhectic debris, apoptotic cells, and macrophages phagocytizing karyorrhectic debris; nuclear crushing was noted. Conclusion. The cytological features of a variant NMC of the lung are described for the first time.