Carbimazole-induced atypia – A mimicker of malignancy in fine-needle aspiration cytology

A 20-year-old female presented with complaints of thyroid swelling and showed signs and symptoms of thyrotoxicosis and fine-needle aspiration cytology (FNAC) was requested by the surgeon. On examination of FNAC smear, it showed thyroid follicular cells with atypical features like bizarre giant cells, pseudo nuclear inclusions, and mitotic figure. Correlation between clinical history and cytomorphologic features was done and it was reported as atypical changes in thyroid probably due to carbimazole-induced changes. It helped the patient, as radical surgery and its untoward complications were avoided.

Risk of malignancy in thyroid nodules classified as Bethesda categories III, III - subcategories and IV: 2.5 years study

Introduction: Thyroid fine-needle aspiration cytology (FNAC) has gained significance as a quick, safe, and relatively simple method to differentiate malignant from benign thyroid nodules and is regarded as the gold-standard first-line diagnostic test in the evaluation of thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid FNAC with each category having an implied cancer risk. However, the optimal management of thyroid nodules in the Bethesda III and IV categories is controversial, given the variable malignancy rates. Aims/Objectives: (1) Analysis of the cytomorphological characteristics of patients with categories III and IV of “TBSRTC.” (2) Assessment of risk of malignancy of TBSRTC category III, IV, and substratification of TBSRTC category III. Materials and Methods: A retrospective and prospective study of cases categorized under TBSRTC as category III and IV at a tertiary-care center. Cytological along with their histological results were compared. Results: We identified an overall malignancy rate of 33% for nodules belonging to Bethesda category III and a malignancy rate between 19% and 33% for Bethesda category IV. Also, a significantly higher risk of malignancy in subcategories with nuclear and architectural atypia (66.6%) than only architectural atypia (28.7%). Conclusion: Although surgery is recommended in most of these cases, cytomorphology helps to predict the final histopathological findings with greater accuracy. Substratification of category III into subgroups may help reduce the heterogeneity of the atypia of undetermined significance/follicular lesion of undetermined significance category and more.

MSRSGC: A prospective study of heterogenous group atypia of undetermined significance

Context: Many standard books, literatures, and internet described the characteristic lineament of each salivary gland lesion. Nevertheless, there are dozens of disarray, confusion, and unmanageable morphological features regarding proper reporting. To fight with these issues, Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018, but still the third category, Atypia of undetermined significance (AUS), poses difficulties for the pathologists and clinicians for a definite interpretation. Aim: The aim is to analyze the risk of neoplasia (RON) and risk of malignancy (ROM) of Milan's category III (AUS) by subdividing into six groups based on cytolomorphology. Settings and Design: The duration of study was from March 2018 to may 2021 with the focus on ROM and RON of all Milan's categories with especial attention on AUS. Methods and Material: Result of total 329 Fine Needle Aspiration Cytology of salivary glands was categorized according to MSRSGC. On the basis of cytomorphology, further subtyping of AUS and its cytohistopathology correlation was done. The ROM and RON of each subtype was analyzed. Statistical Analysis: All data were calculated by existing formulas. Results: Out of 329 aspirates, 24 (07.29%) cases belong to AUS with availability of histology in 13 (54.17%) cases. RON and ROM was 84.62% and 53.85%, respectively. Cases of lymphocytes with nuclear atypia (L-NA) was the most prevalent (29.17%). The RON were 60.00%, 68.57,% 84.62%, 94.87%, 87.50%, 100%, 100% and the ROM were 20.00%, 11.42%, 53.85%, 05.13%, 43.75%, 83.33% and 100% in each Milan's categories I, II, III, IVa, IVb, V, and VI, respectively. ROM was the highest in cystic fluid with nuclear atypia (C-NA) (100.0%), followed by basaloid cells (75%), L-NA (66.675), and SC (50%), but ROM was zero in NA and oncocytic cells. Conclusions: Subgrouping of AUS helps to dissipate the muddiness and provide more exact and reproducible diagnostic and prognostic tool.

Automated grading of glioma based on density and atypia analysis in whole slide images / 生物医学工程学杂志

Glioma is the most common malignant brain tumor and classification of low grade glioma (LGG) and high grade glioma (HGG) is an important reference of making decisions on patient treatment options and prognosis. This work is largely done manually by pathologist based on an examination of whole slide image (WSI), which is arduous and heavily dependent on doctors' experience. In the World Health Organization (WHO) criteria, grade of glioma is closely related to hypercellularity, nuclear atypia and necrosis. Inspired by this, this paper designed and extracted cell density and atypia features to classify LGG and HGG. First, regions of interest (ROI) were located by analyzing cell density and global density features were extracted as well. Second, local density and atypia features were extracted in ROI. Third, balanced support vector machine (SVM) classifier was trained and tested using 10 selected features. The area under the curve (AUC) and accuracy (ACC) of 5-fold cross validation were 0.92 ± 0.01 and 0.82 ± 0.01 respectively. The results demonstrate that the proposed method of locating ROI is effective and the designed features of density and atypia can be used to predict glioma grade accurately, which can provide reliable basis for clinical diagnosis.

Malignancy Rate in Thyroid Nodules with Atypia or Follicular Lesion of Undetermined Significance

Abstract Introduction Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is one of the six diagnostic categories of the Bethesda System for Reporting Thyroid Cytopathology. The prevalence of malignancy among Bethesda category III cytology is variable, ranging from 5% to 37% in the literature. Objective To determine the rate of malignancy in thyroid nodules reported as Bethesda category III. Methods A total of 495 patients underwent surgical intervention for thyroid nodules from January 2015 to December 2017. The present study included 81 cases reported as Bethesda category III, and their medical records were reviewed. Results Out of 495 fine-needle aspiration cytology samples, 81 (16.4%) samples were labeled as AUS/FLUS. Among these 81 patients, the mean age was 43.0 years (±13.9), with only 11 (14%) patients older than 55 years of age.Most of our patients were female (n=69; 85.2%), and the rest were male. The rate of malignancy based on the final histology was of 33.3% (n=27). The majority were 17 cases (21%) of papillary carcinoma, followed by follicular carcinoma (n=6) (7.4%). Conclusion The risk of malignancy can be higher than it is commonly believed, and guidelines should be based on the data from the institutions themselves for a better assessment of the outcomes.

The usefulness of high-risk HPV hybrid capture in patients with squamous cell atypia in cervical cytological examination / A utilidade da captura híbrida para o HPV de alto risco em pacientes com atipia de células escamosas na colpocitologia

ABSTRACT Introduction: The cervical cytological examination and the investigation of high-risk human papillomavirus (HPV) deoxyribonucleic acid (DNA) are well-known valuable tools for screening of cervical lesions, since they allow the early diagnosis of cancer and its precursor lesions. Objective: This study aimed to evaluate the ability of high-risk HPV DNA detection by hybrid capture to predict intraepithelial lesions and cancer in patients with initial cervical cytological diagnosis of atypical squamous cells (ASC). Method: Retrospective analysis of histological or cervical cytological results after one-year follow-up from hybrid capture for high-risk HPV DNA research in patients with previous ASC diagnosis. Sensitivity, specificity and positive and negative predictive values of hybrid capture were calculated in relation to the identification of squamous intraepithelial lesions. Results: Among the 163 patients previously diagnosed with ASC and absence of high-risk HPV DNA, nine (5.5%) showed low-grade (LSIL) or high-grade squamous intraepithelial lesion (HSIL) during the follow-up. On the other hand, among the 110 patients presenting ASC and high-risk HPV DNA positivity, 43 (39%) showed cervical lesions within one year. Sensitivity and specificity values and positive and negative predictive values applied to hybrid capture for the identification of squamous intraepithelial lesions were 82.3%, 69.3%, 38.1%, and 94.4%, respectively. Conclusion: Our results showed a high negative predictive value of hybrid capture for cervical lesions detection, in patients with previous diagnosis of ASC, when the high-risk HPV DNA research was negative.

RESUMEN Introducción: La colpocitología y la investigación del ácido desoxirribonucleico (ADN) del virus del papiloma humano (VPH) de alto riesgo son herramientas bien conocidas para la detección de lesiones cervicales, puesto que permiten el diagnóstico precoz del cáncer y sus lesiones precursoras. Objetivo: El objetivo de este estudio es evaluar la capacidad de detección del ADN-VPH de alto riesgo por captura híbrida en predecir lesiones intraepiteliales y cáncer en pacientes con diagnóstico colpocitológico inicial de atipia de células escamosas (ASC). Método: Análisis retrospectivo de resultados histológicos y citológicos después de un año de seguimiento desde la captura híbrida para investigación de ADN-VPH de alto riesgo en pacientes con diagnóstico previo de ASC. Se calcularon sensibilidad, especificidad y valores predictivos positivo y negativo en relación con la identificación de lesiones intraepiteliales escamosas. Resultados: Entre las 163 pacientes con diagnóstico de ASC previo y ausencia de ADN-VPH de alto riesgo, nueve (5,5%) presentaron lesiones escamosas intraepiteliales de bajo grado (LEIBG) o alto grado (LEIAG) durante el seguimiento. Por otra parte, entre las 110 pacientes con ASC y positividad para ADN-VPH de alto riesgo, 43 (39%) presentaron lesiones cervicales en un plazo de un año. Los valores de sensibilidad y especificidad y los valores predictivos positivo y negativo empleados en la captura híbrida para identificar lesiones escamosas intraepiteliales fueron 82,3%, 69,3%, 38,1% y 94,4%, respectivamente. Conclusión: Nuestros resultados demostraron alto valor predictivo negativo de la captura híbrida para detectar lesiones cervicales en pacientes con diagnóstico previo de ASC, cuando la investigación de ADN-VPH de alto riesgo ha sido negativa.

RESUMO Introdução: O exame colpocitológico e a investigação do ácido desoxirribonucleico (DNA)-papilomavírus humano (HPV) de alto risco são ferramentas bem conhecidas para o rastreamento das lesões cervicais, pois permitem o diagnóstico precoce do câncer e suas lesões precursoras. Objetivo: Este estudo tem o objetivo de avaliar a capacidade da detecção do DNA-HPV de alto risco pela captura híbrida em predizer lesões intraepiteliais e câncer em pacientes com diagnóstico colpocitológico inicial de atipia de células escamosas (ASC). Método: Análise retrospectiva de resultados histológicos e colpocitológicos após um ano de seguimento a partir da captura híbrida para pesquisa de DNA-HPV de alto risco em pacientes com diagnóstico prévio de ASC. Sensibilidade, especificidade e valores preditivos positivo e negativo da captura híbrida foram calculados em relação à identificação de lesões intraepiteliais escamosas. Resultados: Entre as 163 pacientes com diagnóstico de ASC prévio e ausência do DNA-HPV de alto risco, nove (5,5%) apresentaram lesões intraepiteliais escamosas de baixo grau (LIEBG) ou alto grau (LIEAG) durante o acompanhamento. Por outro lado, das 110 pacientes com ASC e positividade para o DNA-HPV de alto risco, 43 (39%) apresentaram lesões cervicais em até um ano. Os valores de sensibilidade e especificidade e os valores preditivos positivo e negativo aplicados à captura híbrida para a identificação de lesões intraepiteliais escamosas foram 82,3%, 69,3%, 38,1% e 94,4%, respectivamente. Conclusão: Nossos resultados mostraram alto valor preditivo negativo da captura híbrida para detecção de lesões cervicais em pacientes com diagnóstico prévio de ASC, quando a pesquisa do DNA-HPV de alto risco foi negativa.

Bocio multinodular tóxico por intoxicación con monóxido de carbono / Toxic multinodular goiter due to poisoning by carbon monoxide

RESUMEN Paciente masculino de 53 años con antecedentes de alergia, trabajador artesanal que realiza serigrafías, con alta exposición a productos químicos que, al someterse a altas temperaturas desprenden gran cantidad de vapor. Acude a consulta refiriendo que desde aproximadamente 2 meses antes presenta decaimiento con calambres musculares, palpitaciones, enrojecimiento de la cara y, aumento de tamaño de la glándula tiroides. Se diagnostica un bocio multinodular tóxico, por cifras hormonales elevadas. Se realiza ultrasonido de tiroides que informa bocio multinodular, una biopsia por aspiración con aguja fina, con atipia de significado incierto, y lesión folicular del tiroides. Se separa de su centro de trabajo y se logra revertir la sintomatología a los 15 días del tratamiento. Frecuentemente aparecen enfermedades asociadas a intoxicaciones por químicos y medicamentos, donde la presencia de hipertiroidismo no es habitual. Se requiere una anamnesis exhaustiva y exámenes complementarios específicos para un diagnóstico y tratamiento adecuados(AU)

ABSTRACT 53 years old male patient with a history of allergy; he works as a craft worker (producing serigraphs) very exposed to chemicals, which when subjected to high temperatures emit large amount of steam. The patient attends to the consultation referring that from approximately 2 months before he has been presenting weakness with muscle cramps, palpitations, flushing of the face and, increase in the size of the thyroid glands. It is diagnosed by the high hormonal figures a toxic multinodular goiter. Thyroid ultrasound is performed that shows multinodular goiter; it is also conducted a biopsy by fine-needle aspiration resulting in atypia of uncertain significance, and follicular lesion of the thyroid. The patient was separated from his workplace and there were reversed the symptoms after 15 days of treatment. Frequently appear diseases associated to poisonings caused by chemicals and medicines, where the presence of hyperthyroidism is not usual. It requires a comprehensive anamnesis and complementary tests that are specific for a proper diagnosis and treatment(AU)

Sistema antioxidante enzimático en mujeres con diagnóstico de Atipias celulares y Neoplasia Intraepitelial Cervical grado I / Enzymatic antioxidant system in women diagnosed with cell atypia and grade I cervical intraepithelial neoplasia

Introducción: El virus de papiloma humano per se no es capaz de desarrollar todas las transformaciones neoplásicas en el cérvix uterino, de manera que factores de riesgo como los genéticos, ambientales, estilo de vida sexual y el desbalance oxidativo podrían contribuir a la enfermedad. Objetivo: Determinar el comportamiento del sistema enzimático antioxidante en mujeres con atipia de células escamosas de significado indeterminado y neoplasia intraepitelial cervical grado I. Métodos: Se conformaron tres grupos de estudio: el primero incluyó 30 mujeres con diagnóstico de atipias, el segundo se constituyó con 40 mujeres con neoplasia intraepitelial grado I y el tercero consistió en 30 mujeres con citología negativa tomadas como control, provenientes de la consulta de Patología de Cuello del Agustín Gómez Lubián de Santa Clara. Mediante métodos espectrofotométricos se determinaron los niveles de actividad enzimática superóxido dismutasa y catalasa así, como las concentraciones de glutatión reducido. Las comparaciones se realizaron con el programa SPSS, versión 18. Resultados: En el grupo de atipias aunque los tres parámetros tuvieron una tendencia a la disminución no hubo diferencias significativas con respecto al control. Mientras que el grupo de neoplasia grado I evidenció disminución significativa de los tres indicadores estudiados al ser comparados con el grupo control. Conclusiones: Se constató afectación del sistema antioxidante enzimático en el grupo de neoplasia grado I, lo cual podría considerarse un cofactor importante en la progresión de las lesiones en el cérvix uterino(AU)

Introduction: Human papillomavirus per se can not carry out all the neoplastic transformations occurring in the uterine cervix. Genetic and environmental risk factors as well as sexual behavior and oxidative imbalance may also play a role. Objective: Determine the behavior of the enzymatic antioxidant system in women with squamous cell atypia of indeterminate significance and grade I cervical intraepithelial neoplasia. Methods: Three study groups were formed. The first group included 30 women diagnosed with atypia, the second group was made up of 40 women with grade I intraepithelial neoplasia, and the third or control group consisted of 30 women with negative cytology from Agustín Gómez Lubián Cervical Pathology service in Santa Clara. Spectrophotometric methods were used to determine the levels of superoxide dismutase and catalase enzymatic activity, as well as the concentrations of reduced glutathione. Comparisons were made with the SPSS software, version 18. Results: In the atypia group the three parameters showed a decreasing tendency, but differences with respect to the control group were not significant. In the grade I neoplasia group, however, a significant reduction was found of the three study indicators when compared with the control group. Conclusions: Damage to the enzymatic antioxidant system was observed in the grade I neoplasia group. This could be considered to be an important cofactor in the progress of uterine cervix lesions(AU)

Risk of malignancy in Thyroid “Atypia of undetermined significance/Follicular lesion of undetermined significance” and its subcategories – A 5-year experience

Context: Atypia of undetermined significance/Follicular lesion of undetermined significance [AUS/FLUS] is a heterogeneous category with a wide range of risk of malignancy [ROM] reported in the literature. The Bethesda system for reporting thyroid cytopathology [TBSRTC], 2017 has recommended subcategorization of AUS/FLUS. Aims: To evaluate the ROM in thyroid nodules categorized as AUS/FLUS, as well as separate ROM for each of the five subcategories. Settings and Design: Retrospective analytic study. Methods and Materials: A retrospective audit was conducted for all thyroid fine-needle aspiration cytology (FNAC) from January 2013 to December 2017. Slides for cases with follow-up histopathology were reviewed, classified into the five recommended subcategories, and differential ROM was calculated. Statistical Analysis Used: z test for comparison of proportions was done to evaluate the difference in ROM among different subcategories of AUS/FLUS. The P value of less than 0.05 was taken as statistically significant. Results: Total number of thyroid FNACs reported was 1,630, of which 122 were AUS/FLUS (7.5%). Histopathology was available in 49 cases, out of which 18 were malignant (ROM = 36.7%). The risk of malignancy (ROM) for nodules with architectural and cytologic atypia was higher (43.8%) than ROM for nodules with only architectural atypia (16.7%). Conclusions: The sub-classification of AUS/FLUS into subcategories as recommended by TBSRTC, 2017 may better stratify the malignancy risk and guide future management guidelines.

Single Circulating Blast in the Peripheral Blood Film in Normal Individuals and Patients of Non-neoplastic Haematological Disorders and Non-hematological Neoplasms/Disorders- A Study at a Tertiary Care Centre

Introduction: The blasts in the peripheral blood is usuallyassociated with a haematological disorder. Study aimed tosee if a single blast seen in a peripheral blood film of healthyindividuals and patients of non-neoplastic haematologicaldisorders and non-hematological neoplasms/disorders didhave any clinical significance.Material and Methods: The period of study was from 2014to 2018 conducted at a tertiary care hospital. The study wasdone exclusively on Peripheral Blood Films. The films werestained with Leishman stain. An occasional blast was detectedin some healthy subjects and patients of non-neoplastichaematological disorders and non-hematological neoplasms/disorders.Result: The routine smears were analyzed with caution afterthe first case of a patient of Iron Deficiency Anemia revealeda clear-cut Blast. In the period of 4 years from 2014 to 2018,a total of 23 cases of apparently normal individuals or patientswith non neoplastic haematological disorders and nonhematological neoplasms/disorders showed at least 1% on oneseparate occasion.Conclusion: A careful morphological examination in theperipheral smears of few normal individuals and individualswith non neoplastic haematological disorders and nonhematological neoplasms/disorders showed at least 1%Blast on one separate occasion. The cells were clear cutblasts with a large size, fine nuclear chromatin, one to twonucleoli with round to slightly irregular nuclear contours anda mild amount of pale agranular cytoplasm. On thoroughinvestigations of these individuals there was no evidence ofa neoplastic haematological disorder. Therefore a single blastin a peripheral blood seen in a healthy individuals or patientswith benign haematological disorder and non-neoplasticneoplasms/disorders may not always indicate a neoplasticprocess.

Malignization of Oral Leukoplakia and the Need for Early Excisional Biopsy / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cancer of the oral cavity is a disease of the head and neck that is difficult to treat. Periodic observation and biopsy are important for its early diagnosis once a premalignant lesion in the oral cavity is confirmed. The purpose of this study was to determine the importance of early excisional biopsy by investigating the histological features of oral leukoplakia and the rate of malignant change in the oral cavity. SUBJECTS AND METHOD: A total of 327 patients who underwent punch biopsy of oral cavity from January 2011 to December 2017 were reviewed retrospectively for the presence of initial gross lesions and for their biopsy results. The histological findings of 6 initial gross lesion groups were compared. Additional excisional biopsies were performed in the seven oral cavity subsites. RESULTS: There were 33 cases of oral leukoplakia. The punch biopsies of 3 of these cases (9.1%) showed malignancy. Additional excisional biopsies were performed in 6 cases, 4 of which were malignant (66.7%). Additional excisional biopsies of the tongue were performed in 14 cases (9.0%), 5 of which (35.7%) were malignant. The rate of atypia in leukoplakia (9.1%) was higher than in other atypia groups. Additional excisional biopsies were performed in 3 cases (100%) of atypia of leukoplakia, all of which were assessed to be malignant. CONCLUSION: For tongue leukoplakia, performing an early excisional biopsy rather than an incisional biopsy is recommendable. Moreover, additional excisional biopsies are needed when the initial biopsy is suggestive of hyperkeratosis, parakeratosis, or atypia.

Analysis of inconclusive cytology reports on fine needle aspiration samples – A descriptive five-year study in Medical College Hospital in Southern India

Background: Reactive lymphocytes can be presented with a different number of morphologies. The significance of evaluation of lymphocytes on peripheral smear tests and its clinical correlation are still neglected. Materials and methods: Clinical details along with other clinical investigations like cell counter results of patients presented with lymphocytosis and other hematological parameters including hemoglobin, total WBC count and platelet count, were collected from Department of Pathology, Dhanalakshmi Srinvasan Medical College and Hospital, India. Results: A total number of 120 cases were studied, out of which 82 patients showed absolute lymphocyte count more than 4000/ul. Out of the 120 patients, a total of 31 patients had history of smoking/tobacco chewing. 18(58%) of them showed reactive/ atypical lymphocyte morphology and 13(41%) of them showed mature lymphocytes. Of the 10 patients with alcoholism history, only 4 of them showed a normal morphology of lymphocytes, other 6 patients showed reactive lymphocyte morphology. Only one patient in the study population showed atypical lymphocytes and in peripheral smear and subjected to lymph node biopsy and rest of the patient failed to follow up after advised biopsy. Conclusions: Current study also reports that, lymphocytosis with reactive lymphocytes have a correlation with acute stress, smoking, and other ailments.

Hiperplasia endometrial simple con complejo focal y sin atipia, en una paciente de 23 años de edad. A propósito de un caso y revisión de la literatura / Simple endometrial hyperplasia with focal complex without atypia, in a patient of 23 years old. A case presentation and literature review

Resumen Se presenta el caso de una paciente de 23 años de edad, previamente sana, G1P0A1, con cuadro clínico de hemorragia uterina anormal, a quien se le realizó ecografía transvaginal que reportó embarazo molar, sin embargo tras realizar la medición sérica de B-HCG, fue de 0.00 mUI/ml, por lo que requirió realización de legrado y biopsia para establecer diagnóstico histológico. El resultado evidenció hiperplasia simple, con complejo focal y sin atipia. Se destaca la importancia de la comunicación de este caso, debido a que a esta edad, la presentación de esta patología es infrecuente. Se hace una revisión de los artículos publicados en los últimos 10 años en las bases de datos Medline vía PubMed, y en LILACS en español, inglés y francés. Se tuvo como referencia además textos clásicos. La hiperplasia endometrial simple en pacientes menores de 30 años es poco frecuente, se debe tener en cuenta la presencia de atipias en la histología pues de ser positivo, es mayor el riesgo de transformación maligna.

Abstract A case of a 23-year-old patient, previously healthy, G1P0A1, with clinical symptoms of abnormal uterine bleeding. The patient was underwent transvaginal ultrasound that reported molar pregnancy, however after making the measurement of serum B-HCG was 0.00 mIU/ml. It was necessary curettage and biopsy to establish histological diagnosis. The result showed simple hyperplasia endometrial with focal complex without atypia. The importance of communication in this case, because at this age, the presentation of this disease is uncommon. The literature published in English, Spanish and French during the last 10 years in the Medline database were reviewed via Pubmed and LILACS. Besides, classical texts was referenced in this article. Simple endometrial hyperplasia in patients under 30 years old is rare. It should be taken into account the presence of atypia on histology, because the risk is greater of malignant transformation.

BRAF(V600E) Mutation is a Strong Preoperative Indicator for Predicting Malignancy in Thyroid Nodule Patients with Atypia of Undetermined Significance Identified by Fine Needle Aspiration / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study aimed to identify a reliable preoperative predictive factor for the development of thyroid cancer in patients with atypia of undetermined significance (AUS) identified by fine needle aspiration biopsy (FNAB). SUBJECTS AND METHOD: This was a retrospective cohort study. Two hundred and ninety-nine patients diagnosed with AUS by preoperative FNAB who underwent curative thyroid surgery at our institution between September 2005 and February 2014 were analyzed. Clinical, radiological and molecular features were investigated as preoperative predictors for postoperative permanent malignant pathology. RESULTS: The final pathologic results revealed 36 benign tumors including nodular hyperplasia, follicular adenoma, adenomatous goiter, nontoxic goiter, and lymphocytic thyroiditis, as well as 263 malignant tumors including 1 follicular carcinoma and 1 invasive follicular carcinoma; the rest were papillary thyroid carcinomas. The malignancy rate was 87.9%. The following were identified as risk factors for malignancy by univariate analysis: BRAFV600E gene mutation, specific ultrasonographic findings including smaller nodule size, low echogenicity of the nodule, and irregular or spiculated margin (p < 0.05). Multivariate analysis revealed that only BRAFV600E mutation was a statistically significant risk factor for malignancy (p < 0.05). When BRAFV600E mutation was positive, 98.5% of enrolled patients developed malignant tumors. In addition, the diagnostic rate of malignancy in these cases was approximately 16-fold higher than BRAF-negative cases. CONCLUSION: Patients with AUS thyroid nodules should undergo BRAFV600E gene mutation analysis to improve diagnostic accuracy and if the mutation is confirmed, surgery is recommended due to the high risk of malignancy.

Clinicopathological Study of 18 Cases of Inflammatory Myofibroblastic Tumors with Reference to ALK-1 Expression: 5-Year Experience in a Tertiary Care Center

BACKGROUND: Inflammatory myofibroblastic tumor is a histopathologically distinctive neoplasm of children and young adults. According to World Health Organization (WHO) classification, inflammatory myofibroblastic tumor is an intermediate-grade tumor, with potential for recurrence and rare metastasis. There are no definite histopathologic, molecular, or cytogenetic features to predict malignant transformation, recurrence, or metastasis. METHODS: A 5-year retrospective study of histopathologically diagnosed inflammatory myofibroblastic tumors of various anatomic sites was conducted to correlate anaplastic lymphoma kinase-1 (ALK-1) expression with histological atypia, multicentric origin of tumor, recurrence, and metastasis. Clinical details of all the cases were noted from the clinical work station. Immunohistochemical stains for ALK-1 and other antibodies were performed. Statistical analysis was done using Fisher exact test. RESULTS: A total of 18 cases of inflammatory myofibroblastic tumors were found during the study period, of which 14 were classical. The female-male ratio was 1:1 and the mean age was 23.8 years. Histologically atypical (four cases) and multifocal tumors (three cases, multicentric in origin) were noted. Recurrence was noted in 30% of ALK-1 positive and 37.5% of ALK-1 negative cases, whereas metastasis to the lung, liver, and pelvic bone was noted in the ALK-1 positive group only. CONCLUSIONS: Overall, ALK-1 protein was expressed in 55.6% of inflammatory myofibroblastic tumors. There was no statistically significant correlation between ALK-1 expression, tumor type, recurrence and metastasis. However, ALK-1 immunohistochemistry is a useful diagnostic aid in the appropriate clinical and histomorphologic context.

Predictive Factors for Upgrading Patients with Benign Breast Papillary Lesions Using a Core Needle Biopsy / 한국유방암학회지

PURPOSE: Intraductal papilloma (IDP) is a benign breast disease with malignant potential, for which complete surgical excision is usually recommended. The aim of the present study was to investigate predictive factors for upgrading patients with a benign papillary lesion (BPL). METHODS: This study was an observational study using a prospectively collected cohort. In total, 13,049 patients who underwent a core needle biopsy (CNB) for a breast lesion between January 2009 and May 2015 were enrolled. We reviewed all patients with pathologically confirmed BPL from a CNB. RESULTS: Surgical treatment was performed for 363 out of a total of 592 lesions. According to the pathological differences, the lowest upgrade rate was shown in IDP without atypia (without atypia, 6.0%; with atypia, 26.8%; papillary neoplasm, 31.5%; p54 years and lesion size >1 cm were significantly associated with upgrade to malignancy (odds ratio [OR]=4.351, p=0.005 and OR=4.236, p=0.001, respectively). CONCLUSION: The indications for surgical treatment can be defined as age >54 years and mass size >1 cm, even in IDP without atypia in the CNB results; this also includes cases of IDP with atypia or papillary neoplasm. Therefore, we suggest that close observation without surgery is sufficient for younger women with a small IDP without atypia.

Morphometric Analysis of Thyroid Follicular Cells with Atypia of Undetermined Significance

BACKGROUND: Atypia of undetermined significance (AUS) is a category that encompasses a heterogeneous group of thyroid aspiration cytology. It has been reclassified into two subgroups based on the cytomorphologic features: AUS with cytologic atypia and AUS with architectural atypia. The nuclear characteristics of AUS with cytologic atypia need to be clarified by comparing to those observed in Hashimoto thyroiditis and benign follicular lesions. METHODS: We selected 84 cases of AUS with histologic follow-up, 24 cases of Hashimoto thyroiditis, and 26 cases of benign follicular lesions. We also subcategorized the AUS group according to the follow-up biopsy results into a papillary carcinoma group and a nodular hyperplasia group. The differences in morphometric parameters, including the nuclear areas and perimeters, were compared between these groups. RESULTS: The AUS group had significantly smaller nuclear areas than the Hashimoto thyroiditis group, but the nuclear perimeters were not statistically different. The AUS group also had significantly smaller nuclear areas than the benign follicular lesion group; however, the AUS group had significantly longer nuclear perimeters. The nuclear areas in the papillary carcinoma group were significantly smaller than those in the nodular hyperplasia group; however, the nuclear perimeters were not statistically different. CONCLUSIONS: We found the AUS group to be a heterogeneous entity, including histologic follow-up diagnoses of papillary carcinoma and nodular hyperplasia. The AUS group showed significantly greater nuclear irregularities than the other two groups. Utilizing these features, nuclear morphometry could lead to improvements in the accuracy of the subjective diagnoses made with thyroid aspiration cytology.

Glomangiopericytoma: The sinonasal mimic of soft tissue hemangiopericytoma

@#A 42-year old Filipino male with a 10-month history of progressive left nasal obstruction and rhinorrhea and a clinical impression of nasal polyposis underwent endoscopic sinus surgery with partial ethmoidectomy and polypectomy. We received several dark-brown, irregular, rubbery tissue fragments with an aggregate diameter of 3 cm. Histopathologic examination shows sheets of spindly tumor cells beneath the respiratory epithelial lining. These spindle cells are closely packed and arranged in short fascicles and storiform clusters surrounding hyalinized large vessels or thin-walled submucosal blood vessels. (Figures 1 and 2) There is no atypia or necrosis. Immunohistochemical studies show strong immunoreactivity to muscle specific actin, and focal reactivity to S-100. (Figure 3) Stains for CD34, caldesmon, cytokeratin, and desmin, are negative. (Figure 4) Based on these features, we diagnosed the case as glomangiopericytoma. Glomangiopericytoma is a rare tumor arising from the pericytes surrounding capillaries, and accounts for less than 0.5% of all sinonasal tumors.1 It has a very slight female preponderance, with a peak incidence during the seventh decade of life. The most common symptom is nasal obstruction, or epistaxis, with accompanying difficulty breathing, sinusitis and headache. A mass, or polyp is the most common clinical finding.2 Hematoxylin–eosin staining shows a well-delineated but unencapsulated cellular tumor underneath the normal respiratory epithelium that effaces or surrounds adjacent normal structures.2 The tumor is composed of closely packed, uniform, oval to spindle-shaped cells, in short fascicles and in storiform, whorled or palisaded patterns. The cells surround numerous branching thin-walled, blood vessels, thus the morphologic resemblance to soft tissue hemangiopericytoma/solitary fibrous tumor. However, in contrast to hemangiopericytoma, glomangiopericytoma shows diffuse reactivity to muscle actins, and non-reactivity to CD34, while hemangiopericytoma shows the reverse reactions. Desmin and caldesmon are likewise non-reactive, distinguishing the tumor from leiomyomas or leiomyosarcomas of the upper aerodigestive tract. Cytokeratin non-reactivity distinguishes it from spindle cell carcinoma. S100, although typically negative, can be focally and weakly positive in a small percentage of tumor.3 Glomangiopericytoma is categorized as a borderline low malignancy tumor with an overall survival of >90% in 5 years but which tends to recur in up to 30% of cases. Strict follow-up is thus required, especially if complete resection is not achieved.1

Core Needle Biopsy Is a More Conclusive Follow-up Method Than Repeat Fine Needle Aspiration for Thyroid Nodules with Initially Inconclusive Results: A Systematic Review and Meta-Analysis

BACKGROUND: This study investigated the appropriate management of thyroid nodules with prior non-diagnostic or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) through a systematic review and meta-analysis. METHODS: This study included 4,235 thyroid nodules from 26 eligible studies. We investigated the conclusive rate of follow-up core needle biopsy (CNB) or repeat fine needle aspiration (rFNA) after initial fine needle aspiration (FNA) with non-diagnostic or AUS/FLUS results. A diagnostic test accuracy (DTA) review was performed to determine the diagnostic role of the follow-up CNB and to calculate the area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve. RESULTS: The conclusive rates of follow-up CNB and rFNA after initial FNA were 0.879 (95% confidence interval [CI], 0.801 to 0.929) and 0.684 (95% CI, 0.627 to 0.736), respectively. In comparison of the odds ratios of CNB and rFNA, CNB had more frequent conclusive results than rFNA (odds ratio, 5.707; 95% CI, 2.530 to 12.875). Upon subgroup analysis, follow-up CNB showed a higher conclusive rate than rFNA in both initial non-diagnostic and AUS/FLUS subgroups. In DTA review of followup CNB, the pooled sensitivity and specificity were 0.94 (95% CI, 0.88 to 0.97) and 0.88 (95% CI, 0.84 to 0.91), respectively. The AUC for the SROC curve was 0.981, nearing 1. CONCLUSIONS: Our results show that CNB has a higher conclusive rate than rFNA when the initial FNA produced inconclusive results. Further prospective studies with more detailed criteria are necessary before follow-up CNB can be applied in daily practice.

Neutrophil-lymphocyte and platelet-lymphocyte ratios in endometrial hyperplasia

OBJECTIVE: The purpose of present study was to evaluate association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) and endometrial hyperplasia (EH). METHODS: One hundred and ten women with abnormal uterine bleeding were included into the study. Blood samples were drawn from all patients to obtain complete blood cell counts, neutrophil-leukocyte ratio and platelet-leukocyte ratio before endometrial curettage procedure initiated. The patients were divided into three groups due to their pathological results: group 1, patients with EH without atypia (n=40); group 2, patients with EH with atypia (n=15); and group 3, patients with neither hyperplasia nor cancer as control group (n=55). Blood cell counts, NLRs and PLRs were compared among these groups. RESULTS: Based on hemoglobin and platelet counts, there was no significant difference among these groups (P>0.05). Leukocyte and neutrophil counts were higher in group 2 (EH with atypia) than group 1 and group 3 (P<0.01). NLR of group 2 was significantly elevated when compared to group 1 and group 3 (P=0.004). PLR was higher in group 1 and group 2 than control group (P=0.024). CONCLUSION: Non-specific inflammatory markers such as NLR and PLR were elevated in women with atypical EH. These markers may be used as a predictor of atypical EH in patients with abnormal uterine bleeding.