Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Tuesday, December 15, 2020

Clinical performance of the aptima HPV assay

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Abstract

Background

Despite Aptima assay as the latest US Food Drug Administration (FDA)‐approved high‐risk human papillomavirus (hrHPV) test has been implemented as an adjunct in cervical cancer screening for years, histological follow‐up data remain limited with respect to its performance in women with ASC‐US Pap tests and positive hrHPV results.

Methods

Cases with results of ASC‐US cytology and positive hrHPV by Aptima assay during the period 06/ 2015–02/2017 were retrieved from archived pathology reports. Immediate histological follow‐up results were analyzed within 6 months interval after cotesting.

Results

Among 4196 women with ASC‐US Pap tests and positive hrHPV, 51.1% of them had the immediate histological follow‐up within 6 months. With positive Aptima hrHPV as the adjunct, 46.5% (95%CI 46.2–46.8) of ASC‐US women were found to have cervical intraepithelial neoplasia type 1 (CIN1); 8.8% (95%CI 8.1‐9.5) women were detected CIN2+ lesion including eight adenocarcinoma in‐situ (AIS)s. CIN2+ detection rates were highest in women under 25 (15.4%, n = 65), when comparison with different age cutoffs, younger age women had higher CIN2+ lesion detection rate than that in older group (P <.01).

Conclusion

This is by far one of the largest retrospective studies to analyze the histological follow‐up results of ASC‐US women with positive hrHPV tested by Aptima hrHPV mRNA assay. The results indicated that younger women with ASC‐US and positive hrHPV testing have highest risk of developing high grade CIN lesions as compared to the older women. Lastly, with positive HPV as the adjunct, 55.3% (1186/2145) of ASC‐US women will result in the positive finding on histological follow‐up.

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Cytologic features of angiolymphoid hyperplasia with eosinophilia: Highlighting the diagnostic clues

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Abstract

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign, inflammatory disorder involving the skin and microvasculature with an undetermined etiopathogenesis. Although the histopathology is well‐characterized, the cytologic features of this entity have been rarely described in literature. This study was conducted to describe in detail the cytomorphologic features of ALHE and to identify the characteristic features that can help in establishing a correct diagnosis of this entity. This was a retrospective study conducted over a period of 3 years, wherein the corresponding cytologic smears of histopathologically diagnosed cases of ALHE were retrieved and reviewed. All the cytologic features were recorded to identify characteristic features that can be used to differentiate ALHE from other cytologic mimics. On histopathologic examination, 15 cases were reported as ALHE. Corresponding cytologic samples were available for three cases. All the three cases were males who were 21, 22 and 52 years old, respectively. The sites of the swellings were scalp, orbital and preauricular. The most consistent cytologic findings were the presence of eosinophilia, scattered plump endothelial cells and a reactive lymphoid background. We believe that a thorough cytologic examination for the presence of plump to spindle‐shaped cells in smears with eosinophilia and reactive lymphoid tissue, can help in reaching to a cytologic diagnosis of ALHE in suspected cases.

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A novel combined animal tissue model for freehand and ultrasound‐guided fine needle aspiration biopsy and smear preparation techniques training

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Abstract

Objective

A variety of models are used for fine needle aspiration biopsy (FNAB) and smear preparation techniques training: human, animal and silicon models or combined models. We present fresh animal tissues as models for freehand and ultrasound (US)‐guided FNAB technique training, enabling an integrated approach from tumour detection to smear evaluation.

Methods

We introduced a novel combined animal tissue model using dietary animal meat with covering skin as a substrate. Animal liver tissue of various sizes, representing tumour, was inserted into the various layers of the substrate (subcutaneous fat, muscle tissue, proximity of bone). Freehand and US‐guided FNAB smear preparation, including fixation, was then performed and assessed.

Results

The use of a combined animal tissue model for 6 freehand and 3 US‐guided FNAB sessions showed a statistically significant improvement in the US‐guided FNAB retrieval of liver tissue (Fisher's exact test, p =  .0216), in smear preparation technique reflected in a decrease in the number of too thick smears after freehand FNAB (Fisher's exact test, p  =  .0070), in the overall number of smears satisfactory for evaluation by US‐guided FNAB (Fisher's exact test, p =  .0206) and in the number of flawless smears obtained in the freehand FNAB training sessions (Fisher's exact test, p =  .0020).

Conclusions

A unique advantage of the presented model encompassing various layers of animal tissues with covering skin, offers an integrated approach for FNAB training from "tumour" detection, puncture precision, to smear preparation and cytological evaluation for a wider audience and does not compromise patient safety.

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Fine needle aspiration of an intrathyroidal parathyroid carcinoma mimicking a primary thyroid anaplastic carcinoma: A case report with review of the literature

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Abstract

Intrathyroidal parathyroid carcinoma is an uncommon malignancy. A 46‐year‐old male presented with a left neck mass. Computed tomography (CT) scan revealed a hypodense mass in the left thyroid lobe along with evidence of metastatic lymphadenopathy. Aspiration of the left thyroid nodule was performed, and a diagnosis of malignancy was rendered, favoring a primary anaplastic carcinoma. Based on the cytologic diagnosis, the patient underwent a total thyroidectomy. Before the surgery, intact parathyroid hormone (PTH) and calcium level (PTH = 78 pg/mL; Calcium = 10.6 mg/dL) were found to be minimally elevated. On gross examination, a 3.2 cm mass within the left inferior thyroid lobe was seen. Histopathologic examination and ancillary studies supported the diagnosis of a parathyroid carcinoma. We, hereby present, an exceedingly rare presentation of an intrathyroidal parathyroid carcinoma with only minimal elevation of PTH and calcium, mimicking a primary anaplastic thyroid carcinom a on cytologic examination.

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How useful are cervical Pap smears in detecting endometrial carcinomas?

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Abstract

Objective

To determine the role of routine cervical Pap smears in detecting endometrial carcinomas.

Method

A retrospective study was carried out from the histopathology archives for cases diagnosed as endometrial carcinomas with Pap smears within 6 months before histological diagnosis. The demographic details, reports of Pap smears and other tumor parameters on histopathology were noted.

Results

We identified 380 of 482 cases of endometrial carcinoma with a documented Pap smear within 6 months before histopathogical diagnosis. Out of 380 cases, 187 cases (49.2%) had shown abnormalities on Pap smear of which 80 cases (42%) were diagnosed as atypical glandular cells and 78 cases (41.7%) were diagnosed as adenocarcinoma. The presence of glandular abnormality on Pap smear significantly correlated with the tumor type, myometrial invasion and cervical involvement on histopathology (P < .05). Cases which had higher FIGO staging also had a higher detection rate on Pap smear (P < .05).

Conclusion

The Pap smear may help in detection of endometrial carcinoma especially in cases with type 2 endometrial carinomas, tumor with cervical involvement and/or advanced FIGO stage.

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Secretory carcinoma of salivary type in a lymph node presenting as a neck cyst diagnosed by cytology: A case report

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Abstract

Secretory carcinoma (SC) is a relatively recently described salivary gland adenocarcinoma characterized by ETV6‐NTRK3 gene fusion and, in most cases, indolent clinical behavior. Morphologically, the tumor shows a glandular architecture and the presence of monophasic tumor cells with vacuolated cytoplasm, low‐grade nuclear atypia, and mucin production, with possibly a tubular, papillary, or cystic arrangement. In this article, we describe a case of a 52‐year old man with SC involving a neck lymph node clinically manifesting as a slowly growing cystic neck mass without recent proof of the primary tumor, but with a history of a parotid gland "cystadenopapilloma," which had been removed 35 years prior. A fine‐needle aspiration biopsy revealed a diagnosis of SC. Subsequent histopathological examination after lymph node dissection confirmed the diagnosis. The tumor showed typical features of SC, including immunohistochemical positivity for NTRK and NTRK3 gene rearra ngement, detected using in situ hybridization. We discuss that the tumor may be a late metastasis occurring 35 years after resection of undiagnosed salivary SC or a primary SC arising from heterotopic salivary tissue within a lymph node. Differential diagnostic considerations and review of relevant literature are included.

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The role of cytology in endobronchial ultrasound‐guided transbronchial needle aspiration:

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Abstract

Background

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is a minimally invasive technique for cytological and histological diagnosis. The objective of this study was to explore the role of cytological diagnosis in EBUS‐TBNAs.

Methods

Eight hundred and thirteen consecutive cases performed EBUS‐TBNA with both cytological and histological diagnoses were retrospectively reviewed. All patients were followed up for clinical data.

Results

Before immunohistochemical examination, the cytological sensitivity, specificity, and diagnostic accuracy of EBUS‐TBNAs were 92.9% (421/453), 98.9% (348/352), 95.5% (769/805), respectively. After immunohistochemical examination, the sensitivity, specificity, and diagnostic accuracy were 93.0% (423/455), 99.4% (348/350), 95.8% (771/805), respectively. The majority of false‐negative were cases whose cytological diagnosis was "atypical" or the cytological diagnosis suggested "inadequate." "Neoplastic" were also prone to false‐negative cytology. The diagnostic accordance rate of cytological subtyping was 90.3% for squamous‐cell carcinoma, 99.2% for adenocarcinoma, and 98.1% for small‐cell carcinoma before immunohistochemical examination, and became 85.9%, 98.5%, and 98.2% after immunohistochemical examination, respectively.

Conclusion

Cytological diagnosis in EBUS‐TBNAs had a good sensitivity and high specificity. The sensitivity and specificity of cytological diagnosis were proved to be higher after the immunohistochemical examination. At the same time, cytology had high accordance rate in subtype diagnosis. False‐negative results occurred more commonly in cases whose cytological diagnosis was "atypical" or the cytological diagnosis suggested "inadequate" or the corresponding histological diagnosis was "Neoplastic."

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Fine needle aspiration cytology of primary neuroendocrine tumor of the breast and it's differential diagnosis

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A second endoscopic ultrasound with fine‐needle aspiration for cytology identifies high‐risk pancreatic cysts overlooked by current guidelines

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Abstract

Background

Endoscopic ultrasound with fine‐needle aspiration (EUS‐FNA) is recommended for diagnosis of pancreatic cystic lesions (PCLs). Its role in surveillance is unclear. Our goal was to determine if a second EUS‐FNA changes diagnosis or management of PCLs.

Methods

A retrospective analysis of an EUS database, searching for EUS‐FNAs in PCLs from 2007 to 2017 was performed. Demographics, cyst characteristics, and FNA results were compared in patients under surveillance, performing a single or two consecutive EUS‐FNAs.

Results

Of 203 PCLs referred for EUS‐FNA, surveillance was decided in 128 (63%). Data of 105 (82%) patients with a single EUS‐FNA were compared with 23 (18%) with two EUS‐FNAs during surveillance. Patients were younger in this latter group (P = .055), whereas CEA levels were marginally higher (P = .078) and a mass/nodule were more frequent (P = .006). The mean time between EUS‐FNAs was 38 months (4.7‐118.8) for 18 patients maintaining surveillance vs 18 months (2.9‐56.9) in the four referred for surgery (P = NS) after two EUS‐FNAs (two NETs, one IPMN‐HGD, and one MCN‐LG). A high correlation in CEA level between consecutive EUS‐FNAs (r 2 = 0.945, P < .01) was present, with a change of category observed (cut‐off level = 192 ng/mL) in two patients only. Of four patients with a second EUS‐FNA with conclusive cytology, two had NETs confirmed on resection.

Conclusions

Repeating EUS‐FNA in surveillance of PCLs with clinical suspicion of malignancy increased neoplasm diagnoses, changing decision toward surgery in almost 20% of patients while excluding IPMNs with mucin nodules from unnecessary resections. A second EUS‐FNA for cytology appears justified in some PCLs, particularly for diagnosing NETs.

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Images in cytology: Fine needle aspiration cytology of BRAFV600E positive anaplastic thyroid carcinoma

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Conditions associated with the need for additional needle passes in ultrasound‐guided thyroid fine‐needle aspiration with rapid on‐site pathology evaluation

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Abstract

Background

Rapid on‐site evaluation (ROSE) is a valuable tool for specimen adequacy assessment in thyroid ultrasound (US)‐guided fine‐needle aspiration (US‐guided FNA). To reduce the risk of nondiagnostic samples, additional needle passes may be needed at ROSE to ensure adequate sampling. Recommendations regarding the number of aspirates to ensure specimen adequacy are not well defined. Furthermore, there are limited data regarding nodule characteristics that may require increased sampling. In this study, we investigate conditions associated with requiring more than three needle passes during ROSE.

Methods

A retrospective quality review of all patients who underwent US‐guided thyroid FNA by a single board‐certified radiologist over a 1‐year period was performed. A total of 122 patients were identified: 70 with three passes performed and 52 with more than three passes to achieve adequacy.

Result

Our data demonstrate that large nodules (≥3 cm) were more likely than small nodules (≤1.1 cm) to require more than three passes to achieve adequacy. If a nodule was predominantly cystic or mixed cystic and solid, the sample was often adequate with only three passes. In cases of thyroiditis or nodules suspicious or diagnostic of neoplasia, there is a trend to require only three passes for adequacy.

Conclusion

On the basis of the data presented in this study, cytopathologists should be prepared for the potential need to obtain additional needle passes in larger (≥3 cm) nodules and provide reassurance to patients that this is an anticipated finding for these larger nodules.

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DNA methylation patterns of RAR‐β2 and RASSF1A gene promoters in FNAB samples from Greek population with benign or malignant breast lesions

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Abstract

Background

Promoter hypermethylation is common in Breast Cancer (BC) with studies mainly in histological specimens showing frequent methylation of tumor suppressor genes (TSGs) compared with normal tissues. The aim of this study was to estimate the frequency of promoter methylation of RAR‐β2 and RASSF1A genes in breast FNAB material aiming to evaluate the methylation status of these two genes as biomarker for detecting BC in Greek population.

Methods

FNAB material from 104 patients was collected for cytological evaluation and epigenetic analysis. DNA was extracted and subjected to bisulfite conversion. A methylation‐specific PCR was carried out and the final products were separated with electrophoresis in 2% agarose gels.

Results

From 104 samples, RASSF1A hypermethylation was observed in 78 (75%) and RAR‐β2 hypermethylation in 64 (61.6%). 84% and 78% of the cases diagnosed with breast malignancy (n = 50) were methylated for RASSF1A and RAR‐β2, respectively. Methylated RASSF1A and RAR‐β2 were also detected in 88.3% and 76.5% in samples diagnosed as suspicious for malignancy (n = 17) and in 57.2% of samples diagnosed with atypia (n = 14). The Odds Ratio for breast malignancy was 4.545 in patients with RASSF1A hypermethylation and 9.167 in patients with RAR‐β2 hypermethylation underlying their promoter's methylation positive correlation with breast malignancy.

Conclusion

To optimize the sensitivity and specificity of this epigenetic setting, more TSGs related to BC should be gradually imported in our evaluated methylation panel and be validated in a larger study sample with the aim that the obtained epigenetic profiles will provide clinicians with valuable tools for management of BC patients in Greece.

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