A stepwise approach to fine needle aspiration cytology of lymph nodes.

The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

The Efficacy and Safety of 'Inverted Omega En-bloc' Holmium Laser Enucleation of the Prostate (HoLEP) for Benign Prostatic Hyperplasia: A Size-Independent Technique for the Surgical Treatment of LUTS.

PURPOSE: To evaluate the safety, efficiency, and size-dependency of the 'Inverted omega En-bloc (Ʊ)' holmium laser enucleation of the prostate (HoLEP) in benign prostate hyperplasia (BPH) with lower urinary tract symptoms. MATERIALS AND METHODS: A retrospective analysis of 716 consecutive patients who underwent HoLEP under the care of a single surgeon from 2014-2021. These patients were treated using the 'Inverted omega En-bloc' HoLEP technique for BPH. The patients were divided into 3 groups: Group 1 (<40 mL, n=328), Group 2 (40-60 mL, n=221), and Group 3 (≤60 mL, n=167). Perioperative parameters, safety, and functional outcomes were assessed and analyzed. RESULTS: The perioperative parameters, like enucleation time (45.8±26.9 min), morcellation time (13.2±47.5 min), and catheterization duration (1.6±1.2 d) significantly differed to favor smaller prostate sizes (p<0.01). Significant improvements in the IPSS (total, voiding, storage, and quality of life), post-void residual urine, and maximum flow rate were observed 3 months post-HoLEP and continued during the 1-year follow-up period in all groups (p<0.01). The postoperative complications included urethral stricture in 11 patients (1.5%), bladder neck contracture in 12 (1.7%), urinary incontinence in 14 (2.0%), and bladder injuries in 4 (0.6%). Bladder neck contractures occurred only in Group 1. The postoperative surgical management for complications included urethral sounding (n=9, 1.3%), endoscopic internal urethrotomy (n=2, 0.3%), and re-HoLEP for bladder neck contractures in (n=12, 1.7%). The rate of re-HoLEP for regrowing adenomas was 15 (2.1%). Postoperative medications exceeding 6 months were α-blocker (n=22, 3.1%), cholinergics (n=16, 2.2%), anticholinergics (n=58, 8.1%), antidiuretics (n=18, 2.5%), and daily PDE5 inhibitor (n=38, 5.3%). Thirty-four patients (4.7%) had postoperative incidental prostate cancer. CONCLUSIONS: The inverted omega En-bloc HoLEP technique is safe and effective for the treatment of BPH. Moreover, 'Inverted omega En-bloc' HoLEP is a size-independent and effective method for all prostate sizes.

Identification of Torque Teno Virus/Torque Teno-Like Minivirus in the Cervical Lymph Nodes of Kikuchi-Fujimoto Lymphadenitis Patients (Histiocytic Necrotizing Lymphadenitis): A Possible Key to Idiopathic Disease.

Kikuchi-Fujimoto disease (KFD) is rare, and many infectious agents have been suspected for its etiology. This report presents an interesting case of KFD found with torque teno virus/torque teno minivirus (TTV/TTMV), which closely resembles the circovirus that causes necrotizing lymphadenitis in pigs. Three Korean patients showed several enlarged lymph nodes in their neck. Quantitative polymerase chain reaction (qPCR) and subsequent DNA sequencing for TTV/TTMV using formalin-fixed paraffin-embedded tissue were performed. Histologic examination demonstrated typical features of KFD. qPCR showed successful amplification of TTV/TTMV, and DNA sequencing confirmed the results. It is the first report of TTV/TTMV presence in three patients with KFD.

Prognostic significance of stem cell/ epithelial-mesenchymal transition markers in periampullary/pancreatic cancers: FGFR1 is a promising prognostic marker.

BACKGROUND: Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs. METHODS: Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed. RESULTS: A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. CONCLUSIONS: In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.

Strong association of Torque teno virus/Torque teno-like minivirus to Kikuchi-Fujimoto lymphadenitis (histiocytic necrotizing lymphadenitis) on quantitative analysis.

INTRODUCTION: Kikuchi-Fujimoto disease (KFD) is a rare benign lymphadenitis that mainly involves cervical lymph nodes of young Asian women with unknown etiology. Recently, we experienced a case of KFD found with Torque teno virus/Torque teno-like mini virus (TTV/TTMV) from a 26-year-old woman. TTV/TTMV is a genus of Circoviridae that causes necrotizing lymphadenitis in pigs, which shares the key histologic finding of KFD. The purpose of this study is to investigate the pathogenic role of TTV/TTMV in KFD by quantitative polymerase chain reaction (qPCR) analysis. METHOD: We performed two-step qPCR specific to TTV/TTMV with formalin-fixed paraffin-embedded tissue of sequentially selected 100 KFD patients and 50 randomly selected, matched normal controls. Consequent direct sequencing was done for confirmation with PCR products. RESULTS: PCR amplification of TTV and TTMV was found in a significantly higher proportion in KFDs than normal controls (TTV, 85% vs. 18%, p < 0.000; TTMV, 91% vs. 24%, p < 0.000). After the sequencing, KFD samples showed more sequence matching than control samples for TTMV (94% vs. 30%, p < 0.000). CONCLUSION: This finding strongly suggests the possible implication of TTV/TTMV in the pathogenesis of KFD. Animal or in vivo experimental design should be followed in the future.Key Points• Kikuchi-Fujimoto disease (KFD) is rare and its etiology is still unclear.• Torque teno/Torque teno-like minivirus (TTV/TTMV) is a recently introduced virus in the Circoviridae family that causes necrotizing lymphadenitis in pigs, histologically similar to KFD.• We discovered the significantly increased TTV/TTMV viral loads in the KFD patients than normal controls, which implicates TTV/TTMV in the pathogenesis of KFD.

Expression of Müllerian-Inhibiting Substance/Anti-Müllerian Hormone Type II Receptor in the Human Theca Cells.

Context: Müllerian-inhibiting substance/anti-Müllerian hormone (MIS/AMH) is produced in the ovarian granulosa cells, and it is believed to inhibit ovarian folliculogenesis and steroidogenesis in women of reproductive age. Objective: To investigate the expression of MIS/AMH type II receptor (MISRII/AMHRII) that binds MIS/AMH in the ovaries of reproductive-age women; to identify the exact targets of MIS/AMH. Design: Laboratory study using human ovarian tissue. Setting: University hospital. Patients: Tissue samples from 25 patients who had undergone ovarian surgery. Interventions: The segregation of ovarian granulosa and theca cells by laser microdissection was followed by RT-PCR, analyzing MISRII/AMHRII mRNA expression. Afterward, in situ hybridization and immunohistochemistry were performed to determine the localization of MISRII/AMHRII mRNA and protein expression. Main Outcome Measures: MISRII/AMHRII mRNA expression by RT-PCR, in situ hybridization, and immunohistochemistry. Results: MISRII/AMHRII were expressed in granulosa and theca cells of preantral and antral follicles. The granulosa cells showed stronger MISRII/AMHRII expression than theca cells. MISRII/AMHRII mRNA staining of granulosa and theca cells in large antral follicles, early atretic follicles, and corpus luteum waned but were still detected weakly, showing higher expression in theca cells than in granulosa cells. However, MISRII/AMHRII protein in the granulosa layer of the atretic follicle and corpus luteum could not be assessed. Conclusions: As MISRII/AMHRII is expressed in both granulosa and theca cells, this indicates that MIS/AMH, produced in the granulosa cells, is active in the theca cells as well. MIS/AMH is most likely actively involved not only in the autocrine and endocrine processes but also in the paracrine processes involving theca cells.

Can liquid-based preparation substitute for conventional smear in thyroid fine-needle aspiration? A systematic review based on meta-analysis.

OBJECTIVE: Conventional smear (CS) using fine-needle aspiration cytology (FNAC) has been established as the test of choice for diagnosing thyroid lesions, despite low sample adequacy and inter-individual variations. Although a liquid-based preparation (LBP) technique has been recently applied to overcome these limitations, its clinical utility and its accuracy over CS are controversial. This study aimed to determine the true sensitivity and specificity of LBP in thyroid FNAC by meta-analysis. DESIGN: Systematic review with meta-analysis. METHODS: We searched major electronic databases (MEDLINE, EMBASE, Cochrane library, Google Scholar) with queries of 'thyroid', 'LBP' and 'liquid-based cytology'. Original articles including cytohistologic correlation data comparing the accuracy of any LBP technique, such as ThinPrep, SurePath and Liqui-Prep, with CS were included for qualitative meta-analysis and preparation of synthesized reporter-operating curves (sROC). RESULTS: A total of 372 studies were screened and 51 original articles were eligible for full-text review; finally, 24 studies were chosen for the meta-analysis. Average sample inadequacy was significantly lower in two mainstream LBP methods (ThinPrep and SurePath) than CS. Specificity and sensitivity by sROC were similar or slightly superior for LBP vs CS. Various cytomorphologic changes by each method have been reported. CONCLUSIONS: Although a learning curve is essential for adapting to the cytomorphologic features of the LBP technique, our results support the use of two mainstream LBPs alone in thyroid FNAC that LBP will increase the sample adequacy and reduce the workload with similar accuracy. More data and further evaluation are needed for the other LBP methods.

Fine needle aspiration of spindle cell ductal carcinoma in situ of the breast: A case report and the use of ancillary tests for the differential diagnosis of metaplastic carcinoma.

Spindle cell ductal carcinoma in situ (DCIS) is a recently recognized subtype of DCIS, which is associated with a very rare and unique morphology. Although the histologic features have been relatively well described in a few reports, the cytologic features have not. Even though the distinction of this lesion from usual DCIS is not crucial clinically, it should be noted that this lesion might simulate the features of metaplastic carcinoma on fine needle aspiration cytology. Here, we report a case of spindle cell DCIS in a 45-year-old female, with the detailed cytologic features, both on conventional and liquid-based preparations, along with some useful immunohistochemical staining markers for the differential diagnosis.

Comparison of EASYPREP(®) and SurePath(®) in thyroid fine-needle aspiration.

BACKGROUND: While fine-needle aspiration cytology (FNAC) using conventional smear has been widely accepted as the primary diagnostic tool for thyroid lesions, liquid-based preparations (LBPs) are increasingly replacing it. A new automated LBP method, EASYPREP(®) (EP), was recently introduced and has shown relevant diagnostic efficacy in gynecologic samples. We compared the diagnostic utility of EP and SurePath(®) (SP), a more widely established LBP method, in thyroid FNAC. METHODS: Under the ultrasonographic guidance, 253 thyroid FNAC samples were collected by sample-splitting manner. Three pathologists made cytologic diagnoses of EP and SP according to the Bethesda system independently and compared the cytomorphologic parameters. Cytohistologic correlation was performed in 30 resected cases. RESULTS: Fifteen (5.9%) and 21 (8.3%) samples were unsatisfactory in SP and EP, respectively, owing to the unequal sample-splitting. Cytologic diagnoses of SP and EP were consistent in 228 cases (90.1%), and inconsistent in remainder mostly owing to the unequal distribution of pathognomic cells. While cytomorphologic parameters were not significantly different between two methods, EP showed less three-dimensional configuration in benign lesions. Cytohistologic correlation showed no significant differences in sensitivity (100% vs. 95.5%) and specificity (100% vs. 100%) between SP and EP. Labor time for processing 48 cases was 42% shorter with EP than with SP (28 min vs. 48 min). CONCLUSIONS: The diagnostic utility of EP in thyroid FNAC was comparable to that of SP. EP allowed better visibility owing to better fragmentation of follicular clusters. The automated system of EP has the advantages of a shorter labor time for batch processing. Diagn. Cytopathol. 2016;44:283-290. © 2016 Wiley Periodicals, Inc.

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Intramural florid cystic endosalpingiosis of the uterus: a case report and review of the literature.

OBJECTIVE: We report a case of intramural florid cystic endosalpingiosis in the lower uterine segment of the uterus. CASE REPORT: A 43-year-old female presented with vaginal bleeding. Abdominal computed tomography suggested a leiomyoma with cystic degeneration. A total hysterectomy revealed a 4.0 cm × 3.8 cm cystic mass in the lower uterine segment. The cystic space microscopically was lined with a single layer or stratified layer of ciliated columnar cells that resembled tubal epithelium without cytologic atypia. The glandular spaces were surrounded by normal myometrium with no evidence of periglandular endometrial stroma, which was consistent with the diagnosis of florid cystic endosalpingiosis. CONCLUSION: Florid cystic endosalpingiosis involving the uterus is a rare and clinically unexpected finding; however, it should be considered in the differential diagnosis of a uterine mass.

Imaging features of bilateral breast plasmacytoma as unusual initial presentation of multiple myeloma: case report and literature review.

Breast plasmacytoma (BP) is an extremely rare extramedullary manifestation of multiple myeloma (MM). We report the imaging findings of an unusual case in which BP was the initial presentation of MM. A 53-year-old woman with no contributory medical history underwent chest computed tomography to evaluate intermittent nocturnal anterior chest pain, and bilateral multiple breast masses were found. Following an ultrasound-guided core needle biopsy, these lesions were confirmed to be BP.

Pancreatic adenocarcinosarcoma of monoclonal origin: a case report.

Adenocarcinosarcoma, a neoplasm containing both carcinomatous and sarcomatous components, is a rare form of a cancer and the pathophysiology is currently poorly understood. Moreover, definitive treatment guidelines for this disease have not yet been established. Pancreatic adenocarcinosarcoma is even more rare and the prognosis is fatal. Here, we report a case of a 77-year-old male with pancreatic adenocarcinosarcoma and metastasis to the liver. The patient presented at our hospital with uncontrolled glucose levels and diabetes mellitus. The patient's laboratory findings were unremarkable with the exception of elevated carbohydrate antigen 19-9 levels. Biopsies of the tumors in the pancreas and the liver revealed two types of tumors: pancreatic adenocarcinoma and a poorly differentiated sarcoma. To determine if KRAS mutations were present, we performed a peptide nucleic acid (PNA) clamp PCR-based assay. DNA sequencing by PNA clamp PCR identified a point mutation in codon 12 of exon 2 within KRAS from both tumor types. Because the KRAS mutation is observed in both tumor components, our findings support a monoclonal tumor origin followed by subsequent divergent differentiation into the sarcomatous and carcinomatous tumor populations. After we considered the patient's status and the late stage of tumor detection, gemcitabine chemotherapy was administered.

Causative agents of Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis): a meta-analysis.

OBJECTIVE: Kikuchi-Fujimoto disease (KFD) is a self-limiting disorder characterized by histiocytic necrotizing lymphadenitis in the cervical lymph nodes of young women. Although an infectious etiology has been postulated, a definitive causative agent has not been identified. The few dozens of published studies are limited by small sample size and poorly structured study designs. The purpose of this study is to evaluate the association of each infectious agent to KFD that has been studied. METHODS: We performed metaanalysis using major electronic database (MEDLINE (PubMed), Cochrane library, Embase, Web of Science, NML gateway, LILACS, and Google Scholar). Cross-sectional studies on the positivity of each agent in clinicopathologically diagnosed KFD and normal controls by polymerase chain reaction (PCR) or in situ hybridization (ISH) were carefully retrieved. The included infectious agents were herpes simplex virus (HSV) type 1, 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus (EBV), human herpes virus (HHV) 6, 7, 8, parvovirus B19, human papilloma virus, hepatitis B virus, human T-lymphotropic virus 1, Brucella, and Bartonella henselae. RESULTS: After an exclusion process of 2491 studies, five, two, four, two, two, and three studies on EBV-PCR, EBV-ISH, HHV6-PCR, HHV8-PCR, parvovirus B19-PCR and HHV7-PCR, respectively, were suitable for quantitative meta-analysis. CONCLUSION: The most suspected pathogen, EBV was not associated to KFD than normal controls (odds ratio=0.28, p=0.005), while the HHV8 positivity was more likely to be associated (odds ratio=8.24, p=0.003) although it still needs further verification. None of other viruses was associated to KFD although the results are limited by small sample size. More studies with large sample size and strict sample selection criteria are necessary in future.