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Research Article: Cytomorphological spectrum of epididymal nodules: An institution's experience
Jyotsna Naresh Bharti, Biswajit Dey, Jenna Bhattacharya, Shyama Jain
CytoJournal 2017, 14:26 (12 October 2017)
DOI:10.4103/cytojournal.cytojournal_51_16  
Background: Epididymal lesions are uncommon in clinical practice. Few case series has been described in the literature documenting the role of cytology in the evaluation of epididymal nodules. This study was undertaken to analyze the cytomorphology of epididymal nodules and to evaluate role of fine-needle aspiration biopsy (FNAB) in early definitive diagnosis of epididymal nodules. Materials and Methods: A total of seventy cases of epididymal nodules were aspirated over a period of 6 years in the Department of Pathology. These cases were taken from the cytology record as a part of this study. The aspiration was performed using 22/23-gauge needle. Smears were stained with May-Grunwald-Giemsa and Papanicolaou stains. Special stains and immunocytochemistry were performed, wherever required. Results: The cytological features were adequate to establish the diagnosis in sixty cases. The lesions diagnosed were tuberculosis 16 (22.85%), spermatoceles 12 (17.14%), benign cystic lesion 8 (11.42%), encysted hydrocele 8 (11.42%), acute suppurative lesion 6 (8.57%), filariasis 4 (5.71%), chronic epididymitis 3 (4.28%), nodular fasciitis 1 (1.42%), epidermal inclusion cyst 1 (1.42%), and cystic adenomatoid tumor 1 (1.42%). Ten cases were inadequate to establish the diagnosis. FNAB was useful in diagnosis of 86% of cases. Infectious lesions of the epididymis were more common than neoplastic lesions. Patients with infection responded well to medical treatment. Conclusions: FNAB is an easily available technique for palpable lesions of epididymis, and it helps in making an early, near definitive diagnosis of epididymal lesions. It also helps to avoid unnecessary surgical interventions and helps in timely management.
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CytoJournal Quiz Case: A case of painful ankle swelling: Cytomorphological clues and pitfalls
Biswajit Dey, Archana Hemant Deshpande, Pushpanjali Ojha, Chitrawati Bal Gargade, Jitendra Singh Nigam, Amit Ray
CytoJournal 2017, 14:25 (12 October 2017)
DOI:10.4103/cytojournal.cytojournal_49_16  
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Case Report: Cytologic features of primary monophasic synovial sarcoma of the thyroid gland
Chang-Soo Park, Young Kim, Eun-Hui Jeong, Nah-Ihm Kim, Yoo-Duk Choi
CytoJournal 2017, 14:24 (12 October 2017)
DOI:10.4103/cytojournal.cytojournal_14_17  
Synovial sarcoma (SS) is a rare soft tissue tumor, commonly arising in para-articular areas of extremities, but can also present in the head and neck area. However, primary SS of the thyroid gland is an extremely rare tumor which has been reported only five times in previous English literatures. This report presents fine needle aspiration (FNA) cytology of primary monophasic SS of the thyroid gland. A 47-year- old woman incidentally detected thyroid nodule in the isthmus of right thyroid gland on an ultrasonography by regular health check-up. Because the possibility of malignancy could not be ruled out, FNA and surgical resection were performed. The cytological, histopathological, immunohistochemical, and molecular genetic study of SYT-SSX transcript were discussed. For the past 3 years of follow-up after surgery, no recurrence or metastasis has been identified.
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Case Report: 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
Yosep Chong, Young Sub Lee, Tae-Jung Kim, Woo-Chan Park, Chang Suk Kang, Eun Jung Lee
CytoJournal 2017, 14:23 (25 September 2017)
DOI:10.4103/cytojournal.cytojournal_3_17  
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.
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Research Article: Significance of finding benign endometrial cells in women 40–45 versus 46 years or older on Papanicolaou tests and histologic follow-up
Shanna M Colletti, Ghassan A Tranesh, Aziza Nassar
CytoJournal 2017, 14:22 (25 September 2017)
DOI:10.4103/cytojournal.cytojournal_16_17  
Background: The 2014 Bethesda System recommends reporting the finding of benign-appearing, exfoliated endometrial cells on Papanicolaou (Pap) tests in women aged 45 years and older. We aimed to determine the significance of normal endometrial cells on liquid-based Pap tests in women aged 40 years and older and to correlate this finding with clinical factors and cytologic/histologic follow-up. Materials and Methods: We retrospectively identified all women aged 40 years and older who had benign endometrial cells (BECs) on Pap tests at our institution during a 6-year period. Histologic follow-up and outcomes were evaluated. Results: Among 18,850 Pap tests during the study period, 255 (1.4%) had findings of BECs and 159 (62.4%) of these women had follow-up Pap tests or subsequent tissue sampling by surgical procedures. Of the 159 cases, only 4 (2.5%) had significant endometrial pathologic processes, all endometrial endometrioid adenocarcinoma (three women had postmenopausal bleeding and 1 was perimenopausal with menorrhagia). No women between ages 40 and 45 years had significant pathologic findings and only one woman between 46 and 50 years (47 years) had an endometrial endometrioid carcinoma (1.5%). Women older than 47 years have higher odds (5.38) of having a significant endometrial lesion (P = 0.029) than those who are ≤47. Conclusion: Clinically significant endometrial lesions occurred predominantly in women older than 50 years (4.6%) and in only one woman between ages 46 and 50 years (1.5%). Therefore, endometrial sampling should be performed in women aged 47 years and older with BECs, especially when additional clinical indicators (e.g., postmenopausal bleeding) are recognized.
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CytoJournal Quiz Case: Perihepatic cystic mass: Zebra or horse?
Alan Marcus, June Koizumi, Brian Robinson, Tamara Giorgadze
CytoJournal 2017, 14:21 (25 September 2017)
DOI:10.4103/cytojournal.cytojournal_16_16  
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Research Article: Can an inadequate cervical cytology sample in ThinPrep be converted to a satisfactory sample by processing it with a SurePath preparation?
Sveinung Wergeland Sorbye, Mette Kristin Pedersen, Bente Ekeberg, Merete E. Johansen Williams, Torill Sauer, Ying Chen
CytoJournal 2017, 14:20 (22 August 2017)
DOI:10.4103/cytojournal.cytojournal_34_16  PMID:28900466
Background: The Norwegian Cervical Cancer Screening Program recommends screening every 3 years for women between 25 and 69 years of age. There is a large difference in the percentage of unsatisfactory samples between laboratories that use different brands of liquid-based cytology. We wished to examine if inadequate ThinPrep samples could be satisfactory by processing them with the SurePath protocol. Materials and Methods: A total of 187 inadequate ThinPrep specimens from the Department of Clinical Pathology at University Hospital of North Norway were sent to Akershus University Hospital for conversion to SurePath medium. Ninety-one (48.7%) were processed through the automated “gynecologic” application for cervix cytology samples, and 96 (51.3%) were processed with the “nongynecological” automatic program. Results: Out of 187 samples that had been unsatisfactory by ThinPrep, 93 (49.7%) were satisfactory after being converted to SurePath. The rate of satisfactory cytology was 36.6% and 62.5% for samples run through the “gynecology” program and “nongynecology” program, respectively. Of the 93 samples that became satisfactory after conversion from ThinPrep to SurePath, 80 (86.0%) were screened as normal while 13 samples (14.0%) were given an abnormal diagnosis, which included 5 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 2 atypical glandular cells not otherwise specified, and 1 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion. A total of 2.1% (4/187) of the women got a diagnosis of cervical intraepithelial neoplasia 2 or higher at a later follow-up. Conclusions: Converting cytology samples from ThinPrep to SurePath processing can reduce the number of unsatisfactory samples. The samples should be run through the “nongynecology” program to ensure an adequate number of cells.
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Case Report: Cytologic features of tubular adenoma of ampulla causing distal common bile duct stricture: A case report and review of the literature
Sangeeta Mantoo, Madhusudhan R Sanaka, Deborah J Chute
CytoJournal 2017, 14:19 (22 August 2017)
DOI:10.4103/cytojournal.cytojournal_2_17  PMID:28900465
Adenomas of the ampulla of Vater are distinctly rare, representing <10% of periampullary neoplasms. Very few reports of the cytologic features of ampullary adenomas are present in literature, particularly in bile duct brushing samples. A case report and review of the literature is presented. The typical cytologic features of ampullary adenomas on cytologic preparations include tall, thin columnar cells with mildly hyperchromatic elongated nuclei and nuclear pseudostratification, in a relatively clean background. The key differential diagnostic entities include invasive adenocarcinoma, thermal artifact, and reactive atypia.
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CytoJournal Quiz Case: A diagnostically difficult case of a cellular pleural fluid: Morphology, immunohistochemistry, and fluorescence in situ hybridization study
Minhua Wang, Shabnam Samankan, Amarpreet Bhalla, N Paul Ohori, Nora K Frisch
CytoJournal 2017, 14:18 (24 July 2017)
DOI:10.4103/cytojournal.cytojournal_54_16  PMID:28828031
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Research Article: Interobserver reproducibility of the Paris system for reporting urinary cytology
Theresa Long, Lester J Layfield, Magda Esebua, Shellaine R Frazier, D Tamar Giorgadze, Robert L Schmidt
CytoJournal 2017, 14:17 (24 July 2017)
DOI:10.4103/cytojournal.cytojournal_12_17  PMID:28828030
Background: The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm). Methods: Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management. Results: The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact. Conclusions: Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.
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Research Article: Metastatic neoplasms to the thyroid diagnosed by fine-needle aspiration/core needle biopsy: Clinicopathologic and cytomorphologic correlation
Mobeen Rahman, Ashley Rae Okada, Kevin Guan, Pamela Tauchi-Nishi
CytoJournal 2017, 14:16 (20 June 2017)
DOI:10.4103/cytojournal.cytojournal_50_16  PMID:28694837
Background: Although thyroid fine-needle aspiration (FNA) and core needle biopsy (CNB) are commonly utilized modalities in the evaluation of thyroid nodules, metastatic tumors to the thyroid are only rarely encountered. We aspired to determine the incidence and primary origin of metastases to the thyroid at our institution and to examine their clinicopathologic and cytomorphologic features. Materials and Methods: A search of our database was undertaken to review all thyroid FNA and/or CNB examined between January 2004 and December 2013. Results: During our 10 year study period, 7497 patients underwent 13,182 FNA and/or CNB. Four hundred sixty one (6%) patients were diagnosed with neoplasms. Only five (1.1%) were found to have metastatic tumors to the thyroid involving three females and two males. Two were diagnosed by FNA, one by CNB, and two by both FNA and CNB, with rapid on-site evaluation (ROSE) employed in all cases. The primary malignancies in the five cases were pulmonary and nasopharyngeal squamous cell carcinomas, renal cell carcinoma, pancreatic adenocarcinoma, and olfactory neuroblastoma. The cytomorphologic features of these metastases to the thyroid aided in their distinction from primary thyroid carcinoma. Two of these metastases, a renal cell carcinoma and pancreatic adenocarcinoma, were the first clinical manifestations of cancer. Conclusion: Metastases to the thyroid diagnosed by FNA and/or CNB are exceedingly rare in our institution, comprising only 0.04% of total FNA/CNB and only 1.1% of all thyroid neoplasms. We report the first known case of metastatic olfactory neuroblastoma to the thyroid diagnosed by aspiration cytology. In addition, an occult primary may present as a thyroid mass on FNA or CNB as occurred with two of our cases. FNA/CNB proved to be highly effective in the diagnosis of metastases to the thyroid, with ROSE proving valuable in assuring specimen adequacy. Thyroid FNA and CNB demonstrated great utility in the setting of metastatic disease, obviating the need for more invasive procedures.
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Case Report: Metastatic prostatic stromal sarcoma: A challenging diagnosis on fine-needle aspiration with broad differential diagnosis
Muhammad Siddique Khurram, Ghassan Tranesh, Ramen Sakhi, Ameer Hamza, Warda Ibrar, Roohi Bano
CytoJournal 2017, 14:15 (20 June 2017)
DOI:10.4103/cytojournal.cytojournal_46_16  PMID:28694836
Prostatic stromal sarcomas (PSS) are rare solid organ mesenchymal sarcomas. PSS may pose difficult diagnostic challenges on fine needle aspiration biopsy. We report a 48-year-old man diagnosed with metastatic high grade prostatic stromal sarcoma by a CT-scan guided fine needle aspiration (FNA) biopsy of a right lower lung lobe nodule. We reviewed the literature on the epidemiologic, cyto-histological, and immunophenotypic findings and discussed the differential diagnosis for this rare entity.
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CytoJournal Quiz Case: Myoepithelioma of soft tissue in the gluteal region: Diagnostic pitfall in cytology
Viral M Bhanvadia, Neeru M Agarwal, Alpesh D Chavda, Bharat V Bhetariya
CytoJournal 2017, 14:14 (20 June 2017)
DOI:10.4103/cytojournal.cytojournal_45_16  PMID:28694835
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Research Article: “Low-grade squamous intraepithelial lesion, cannot exclude high-grade:” TBS says “Don't Use It!” should I really stop it?
Jeanine M Chiaffarano, Melissa Alexander, Robert Rogers, Fang Zhou, Joan Cangiarella, Melissa Yee-Chang, Paul Elgert, Aylin Simsir
CytoJournal 2017, 14:13 (26 May 2017)
DOI:10.4103/cytojournal.cytojournal_48_16  PMID:28603542
Background: The Bethesda System uses a two-tiered approach in the diagnosis of cervical squamous intraepithelial lesions (SILs). Occasionally, Papanicolaou (Pap) tests with evident low-grade SIL (LSIL) also have some features suggestive but not diagnostic of high-grade SIL (HSIL). This study reviews our experience with “Low-grade Squamous Intraepithelial Lesion, Cannot Exclude High-grade” (LSIL-H) and discusses the best approach to report such Paps if the LSIL-H interpretation is abandoned. Methods: Abnormal Paps were identified between January and December 2014 that had surgical follow-up within 6 months. Their biopsy outcomes were compared. Statistical analysis was performed using Pearson's Chi-square and McNemar tests in SPSS software version 23. Statistical significance was defined as P ≤ 0.05. Results: There were a total of 1049 abnormal Paps with follow-up. High-grade dysplasia/carcinoma (HGD+) was found in 8% of LSIL, 30% of LSIL-H, 52% of atypical squamous cells (ASCs), cannot rule out HSIL (ASC-H), and 77% of HSIL Paps. The detection rate of HGD+ for LSIL-H was between that of LSIL (Pearson's Chi-square test, P = 0.000) and ASC-H (P = 0.04). If LSIL-H cases are reported as ASC-H, the rate of HGD+ for the ASC-H category would decrease from 51.5% to 37.4% (McNemar test, P = 0.000). Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7.7% to 10.4% (McNemar test, P = 0.000). Nearly 86.7% of LSIL-H cases were positive for high-risk HPV (HR-HPV) in comparison to 77.5% of LSILs, 100% of ASC-Hs, and 75% of HSILs. The sample size for HR-HPV and LSIL-H was too small for meaningful statistical analysis. Conclusions: “LSIL-H” category detects more HGD+ than LSIL, and fewer than ASC-H and HSIL. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy since management of LSIL Paps depends on multiple factors (age, HPV status, etc.).
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Case Report: Cytological features of adenocarcinoma admixed with small cell neuroendocrine carcinoma of the uterine cervix
Naoshi Shimojo, Yoshifumi S Hirokawa, Kazuki Kanayama, Misao Yoneda, Ryotaro Hashizume, Akinobu Hayashi, Katsunori Uchida, Hiroshi Imai, Yuji Kozuka, Taizo Shiraishi
CytoJournal 2017, 14:12 (26 May 2017)
DOI:10.4103/1742-6413.207139  PMID:28603541
Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis, and few reports have described the cytological features of this carcinoma. To characterize the cytological features of this malignancy in cervical smears, we report a case of a 52-year-old Japanese woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma (SCNEC). Cytologically, there were two types of cells with different sizes. The smaller cells formed clusters, which showed a partially Indian file pattern, a high nuclear/cytoplasmic ratio, and hyperchromatic nuclei. In contrast, the larger cells showed cytological features of adenocarcinoma, indicating a glandular-like pattern. Histological examination of biopsy specimens revealed that the tumors were composed of almost equal areas of SCNEC and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for synaptophysin and CD56. Thus, when adenocarcinoma cells are detected in smears, attempts to search for SCNEC cells should be made by combined cytological and histological analyses in order to reach an accurate diagnosis of the carcinoma in the uterine cervix.
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CytoJournal Quiz Case: An elderly man with a solitary liver lesion
Lisa Barton, Lichao Zhao, Jessica N Doty, Thomas Stasko, Rachel Conrad
CytoJournal 2017, 14:11 (26 May 2017)
DOI:10.4103/1742-6413.207138  PMID:28603540
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Research Article: Cytomorphologic features distinguishing Bethesda category IV thyroid lesions from parathyroid
Simon Sung, Anjali Saqi, Elizabeth M Margolskee, John P Crapanzano
CytoJournal 2017, 14:10 (28 April 2017)
DOI:10.4103/1742-6413.205313  PMID:28567111
Background: Thyroid follicular cells share similar cytomorphological features with parathyroid. Without a clinical suspicion, the distinction between a thyroid neoplasm and an intrathyroidal parathyroid can be challenging. The aim of this study was to assess the distinguishing cytomorphological features of parathyroid (including intrathyroidal) and Bethesda category IV (Beth-IV) thyroid follicular lesions, which carry a 15%–30% risk of malignancy and are often followed up with surgical resection. Methods: A search was performed to identify “parathyroid” diagnoses in parathyroid/thyroid-designated fine-needle aspirations (FNAs) and Beth-IV thyroid FNAs (follicular and Hurthle cell), all with diagnostic confirmation through surgical pathology, immunocytochemical stains, Afirma® analysis, and/or clinical correlation. Unique cytomorphologic features were scored (0-3) or noted as present versus absent. Statistical analysis was performed using R 3.3.1 software. Results: We identified five FNA cases with clinical suspicion of parathyroid neoplasm, hyperthyroidism, or thyroid lesion that had an eventual final diagnosis of the parathyroid lesion (all female; age 20–69 years) and 12 Beth-IV diagnoses (11 female, 1 male; age 13–64 years). The following cytomorphologic features are useful distinguishing features (P value): overall pattern (0.001), single cells (0.001), cell size compared to red blood cell (0.01), nuclear irregularity (0.001), presence of nucleoli (0.001), nuclear-to-cytoplasmic ratio (0.007), and nuclear chromatin quality (0.028). Conclusions: There are cytomorphologic features that distinguish Beth-IV thyroid lesions and (intrathyroidal) parathyroid. These features can aid in rendering correct diagnoses and appropriate management.
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Case Report: Indian visceral leishmaniasis with extensive lymphadenopathy – An unusual presentation: A case report with literature review
Poojan Agarwal, Vijay Kumar, Manju Kaushal, Manju Kumari, Arvind Chaudhary
CytoJournal 2017, 14:9 (28 April 2017)
DOI:10.4103/1742-6413.205312  PMID:28567110
Visceral leishmaniasis (VL), also known as kala-azar, is a life-threatening systemic disease caused by the obligate intracellular protozoan, Leishmania, and transmitted to humans by the female phlebotomine sand fly (Phlebotomus argentipes). The disease is fatal, if left untreated. We report a case of a patient clinically suspected of disseminated tuberculosis, but fine needle aspiration cytology of cervical and axillary lymph nodes yielded a diagnosis of leishmaniasis. Diagnosis of VL was challenging as the disease closely mimicked tuberculosis in the setting of extensive lymphadenopathy including conglomerate of mesenteric lymph nodes, on and off fever, and granulomatous lymphadenitis on aspiration. Bone marrow examination was further performed. A detailed workup revealed patient to be severely immunocompromised and newly diagnosed human immunodeficiency virus (HIV) positive. Worldwide, India has the largest number of VL cases, accounting for 40%–50% of world's disease burden and the second largest HIV-infected population, accounting for approximately 10% of the global disease burden. HIV increases the risk of developing VL by 100–2320 times in endemic areas and concurrently VL promotes the clinical progression of HIV disease. Co-infection with HIV alters the body's immune response to leishmaniasis thus leading to unusual presentations. This case highlights the diagnostic problem in the aforesaid setting. Moreover, co-infection with HIV in VL can be a potential source of drug resistance. An early diagnosis and intensified treatment is the key to patient management.
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CytoJournal Quiz Case: Ultrasound-guided fine-needle aspiration of hyperenhancing lesion suspicious for pancreatic neuroendocrine tumor in the tail of pancreas-potential pitfalls
Kinda Hayek, Tatyana Kalinicheva, Vinod B Shidham
CytoJournal 2017, 14:8 (28 April 2017)
DOI:10.4103/1742-6413.205311  PMID:28567109
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Research Article: Next-generation sequencing of non-small cell lung cancer using a customized, targeted sequencing panel: Emphasis on small biopsy and cytology
David M DiBardino, David W Rawson, Anjali Saqi, Jonas J Heymann, Carlos A Pagan, William A Bulman
CytoJournal 2017, 14:7 (20 March 2017)
DOI:10.4103/1742-6413.202602  PMID:28413430
Background: Next-generation sequencing (NGS) with a multi-gene panel is now available for patients with lung adenocarcinoma, but the performance characteristics and clinical utility of this testing are not well-described. We present the results of an extended 467 gene panel in a series of advanced, highly selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens, including predominantly small biopsy and cytology specimens. Materials and Methods: A retrospective review of 22 NSCLC biopsies sent for NGS using an extended gene panel from January 2014 to July 2015. The customized NGS panel sequences 467 cancer-associated genes with exonic and intronic sequences obtained from purified tumor DNA. Genomic alterations, patient characteristics, and success of testing were determined. Results: The majority of samples tested were metastatic lung adenocarcinoma on final pathology. Of the 22 specimens tested, 5 (22.7%) were surgical resections and 17 (77.3%) were small biopsy and cytology specimens. Twenty-one (95%) of the specimens were adequate for full sequencing and yielded a total of 204 genomic alterations (average 8.9 per tumor), of which 17 (average 0.81 per tumor) were actionable and/or clinically relevant. Genomic alterations were found most commonly in the TP53, EGFR, EPHB1, MLL3, APC, SETD2, KRAS, DNMT3A, RB1, CDKN2A, ARID1A, EP300, KDM6B, RAD50, STK11, and BRCA2 genes. Conclusions: NGS using a comprehensive gene panel was performed successfully in 95% of all NSCLC cases in this series, including 94% small biopsy and cytology specimens and 100% surgical resections. This custom assay was performed on a range of tumor specimens and demonstrates that small specimens are able to provide a similar depth of information as larger ones. As many patients present at an advanced stage and only small specimens are obtained, the information these provide has the potential for guiding treatment in highly selected patients with advanced lung adenocarcinoma.
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Case Report: Falling under the umbrella cells: A single institutional experience and literature review of urothelial carcinoma presenting as a primary pancreatic mass on endoscopic ultrasound-guided fine-needle aspiration
Michael Chambers, Konrad Krall, Shantel Hébert-Magee
CytoJournal 2017, 14:6 (20 March 2017)
DOI:10.4103/1742-6413.202601  PMID:28413429
Metastases to the pancreas are much less common than primary pancreatic lesions, and there are few reports in the literature of metastatic urothelial carcinoma (UC) found in the pancreas. We report two cases of metastatic UC mimicking a primary pancreatic lesion. Two female patients, aged 48 and 83 years, presented with isolated pancreatic lesions causing obstructive jaundice suspicious for pancreatic adenocarcinoma and underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with rapid on-site evaluation (ROSE). On cytopathology, the lesions were found to be UC, confirmed with immunohistochemical (IHC) staining. UC rarely metastasizes to the pancreas, and diagnosis through EUS-FNA can be challenging. However, the utilization of ROSE, dedicated cell block passes, and IHC have proved to be effective in obtaining this unusual pancreatic diagnosis by EUS-FNA.
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Research Article: KRAS detection on archival cytological smears by the novel fully automated polymerase chain reaction-based Idylla mutation test
Caterina De Luca, Elena Vigliar, Melania d'Anna, Pasquale Pisapia, Claudio Bellevicine, Umberto Malapelle, Giancarlo Troncone
CytoJournal 2017, 14:5 (24 February 2017)
DOI:10.4103/1742-6413.200936  PMID:28331530
Background: Molecular techniques are relevant to modern cytopathology, but their implementation is difficult without molecular expertise and infrastructure. The assessment of KRAS mutational status on cytological preparations may be useful either to refine uncertain diagnoses on pancreatic aspirates or to yield predictive information to plan targeted treatment of metastatic colorectal cancer (mCRC). The novel test Idylla™ enables fully automated KRAS genotyping in approximately 2 h, even in less experienced hands. Materials and Methods: This study aims to validate this methodology to detect KRAS mutations on archival cytological preparations of pancreatic cancer (n = 9) and mCRC (n = 9) by comparing the Idylla™ performance to that of standard real-time polymerase chain reaction. Results: The same 11 mutations (n = 4: p.G12D; n = 2: p.G12V; n = 2: p.A59E/G/T; n = 1: p.G12R; n = 1: p.G13D; n = 1: p.Q61H) were detected by both techniques. Conclusion: Even in less experienced laboratories, a cytopathologist may easily integrate morphological diagnostic report with accurate KRAS mutation detection, which is relevant for diagnostic and treatment decisions.
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Research Article: Detection of BRAF mutation in the cytocentrifugation supernatant fluid from fine-needle aspiration of thyroid lesions may enhance the diagnostic yield
Ashley E Brown, Khin Sandar Lim, George Corpus, Martha T Hustek, Tien Anh N Tran, Chung-Che Chang
CytoJournal 2017, 14:4 (24 February 2017)
DOI:10.4103/1742-6413.200935  PMID:28331529
Objective: BRAF mutations using cellular DNA from fine-needle aspiration (FNA) specimens are commonly used to support the diagnosis of papillary thyroid carcinoma (PTC). The goal of this study was to preliminarily evaluate the diagnostic utility of detecting BRAF mutations in the routinely discarded FNA specimen supernatant fluid. Materials and Methods: Seventy-eight FNAs of thyroid lesions were evaluated for BRAF mutations using both cellular and supernatant DNA. BRAF mutation data were correlated with cytology and surgical pathology. Results: Of the 78 samples evaluated, 68 (87%) had amplifiable DNA in the supernatant with 2 (3%) positive for BRAF mutations. These two samples showed no mutations in the cellular counterpart. Among the 11 samples showing morphologic findings (FNA/surgical pathology) suspicious/diagnostic of PTC, 6 (55%) samples (one supernatant and five cellulars) were positive for BRAF mutations. This suggests that testing supernatant DNA in FNA specimens may increase the diagnostic yield by 1/11 (9%) in this setting. Conclusions: The vast majority of routinely discarded FNA supernatants contain amplifiable DNA. In addition, profiling the mutations of BRAF and other genes using supernatant DNA may provide valuable diagnostic information to assist the diagnosis of PTC in patients with clinical/morphologic findings suspicious for malignancies and cellular DNA showing no mutations.
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CytoJournal Quiz Case: Thyroid fine-needle aspiration of an immunocompromised patient: Cytomorphological clues
Longwen Chen, Nirvikar Dahiya, Matthew A Zarka
CytoJournal 2017, 14:3 (24 February 2017)
DOI:10.4103/1742-6413.200934  PMID:28331528
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CytoJournal Quiz Case: Primary orbital mantle cell lymphoma: Flow cytometric immunophenotyping as an adjunct to fine-needle aspiration cytology for diagnosis
Sangeeta Verma, Nalini Gupta, Satyawati Mohindra, Manupdesh Singh Sachdeva, Arvind Rajwanshi
CytoJournal 2017, 14:2 (20 January 2017)
DOI:10.4103/1742-6413.198816  PMID:28217141
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Research Article: Evaluation of polymerase chain reaction in space-occupying lesions of liver reported as granulomatous inflammation/tuberculosis on fine-needle aspiration cytology
Kusum Sharma, Nalini Gupta, Kapil Goyal, Ajay Kumar Duseja, Aman Sharma, Arvind Rajwanshi
CytoJournal 2017, 14:1 (20 January 2017)
DOI:10.4103/1742-6413.198815  PMID:28217140
Background: Tubercular involvement of the liver is uncommon, but is a serious consideration in differential diagnosis of granulomatous conditions, especially in endemic regions like India. Objective: To assess the role of polymerase chain reaction (PCR) done on archival cytological material in diagnosing tuberculosis (TB) in cases reported as granulomatous inflammation/TB in liver lesions. Materials and Methods: This was a retrospective study including a total of 17 cases of liver space-occupying lesions (SOLs) reported as granulomatous inflammation (n = 12) and TB (n = 5). The smears were retrieved from the archives of the department and were reviewed for the cytomorphologic features. Air-dried smears stained with May–Grünwald–Giemsa (MGG) stain were assessed for the representative material in the form of epithelioid granulomas and giant cells. One/two MGG smears from each case were destained and the material was used for performing PCR for Mycobacterium tuberculosis by amplification of 123 bp fragment of the IS6110 insertion element. Results: The age of the patients ranged from 3 to 61 years. There were 12 females and 5 males. The patients presented with solitary/multiple liver SOLs. DNA could be extracted from 10/17 cases from archival MGG smears. PCR positivity was noted in 8/10 cases (including four acid-fast bacilli smear-positive cases), confirming a diagnosis of TB. Conclusion: Cytomorphology alone may not be sufficient for differentiating various granulomatous lesions reported in liver SOLs. DNA can be extracted from the archival cytological MGG-stained smears. PCR should be carried out if Ziehl–Neelsen staining is negative in granulomatous lesions, especially when material has not been submitted for culture.
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Case Report: An unexpected diagnosis of ectopic liver diagnosed by fine needle aspiration
Gonzalo Barazza, Douglas G Adler, Rachel E Factor
CytoJournal 2016, 13:29 (20 December 2016)
DOI:10.4103/1742-6413.196239  PMID:28105065
The differential diagnosis of perigastric masses is broad, ranging from benign to malignant entities. Among the benign entities, accessory liver lobes and ectopic liver are unusual and often incidentally discovered. Here, we report a patient with malignant melanoma who was clinically suspected to have a perigastric metastasis or a gastrointestinal stromal tumor but was ultimately diagnosed by fine needle aspiration (FNA) to have benign ectopic liver. A 47-year-old male was diagnosed with malignant melanoma of the scalp in May 2015 at a tertiary care hospital. He was found to have a 2.6 cm enhancing mass adjacent to the fundus of the stomach and below the diaphragm by computed tomography imaging. To exclude metastasis, the patient was referred to endoscopy, and an endoscopic ultrasound-guided FNA was performed with rapid on-site evaluation (ROSE) by a cytopathologist. A relatively new FNA needle (Shark Core) was used, which produced useful core biopsy material. Cytopathology demonstrated flat sheets, single cells, and small clusters of polygonal cells. There was abundant granular cytoplasm, often containing pigment. Cells lacked pleomorphism. The smear findings appeared consistent with hepatocytes. The cell block demonstrated small core fragments of hepatic parenchyma with portal tracts. Immunohistochemistry for arginase-1 confirmed that this was hepatic tissue. ROSE was useful for communicating with the endoscopist that the mass was both far from, and not connected to, the liver. This is the first documented account of perigastric ectopic liver diagnosed by FNA. This entity should be considered in the differential of perigastric masses.
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Research Article: Detection of in situ and invasive endocervical adenocarcinoma on ThinPrep Pap Test: Morphologic analysis of false negative cases Highly accessed article
Michael Chaump, Edyta C Pirog, Vinicius J. A. Panico, Alexandre Buckley d Meritens, Kevin Holcomb, Rana Hoda
CytoJournal 2016, 13:28 (20 December 2016)
DOI:10.4103/1742-6413.196237  PMID:28105064
Background: The goal of this study was to calculate the sensitivity and false negative (FN) rate of ThinPrep Pap Test (TPPT) and carefully analyze missed cases for educational purposes. Materials and Methods: Patients with histologically proven adenocarcinoma in-situ (AIS) or invasive endocervical adenocarcinoma (EAC) over a 17-year-period (1998-2015) were identified. The TPPT immediately preceding the histological diagnosis of AIS/ECA was designated as index Pap (IP). Paps up to 122 months before histologic diagnosis of AIS/ECA were considered for this study. All available negative and unsatisfactory TPPT were re-reviewed. Results: There were 78 patients with histologically-proven AIS (56) or ECA (22) with 184 TPPTs, and 95 of these TPPTs were abnormal. Of the abnormal cases, 55.7% TPPTs were diagnosed as endocervical cell abnormality (atypical endocervical cells/AIS/ECA). Notably, 44.2% of abnormal TPPTs were diagnosed as squamous cell abnormality (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion/high grade squamous intraepithelial lesion). Including the diagnoses of squamous cell abnormality, the sensitivity of index TPPT for histologically-confirmed AIS/ECA was 88%. Eighty-eight of 184 TPPT, including 10 IP, were negative = 87, or unsatisfactory = 1. Forty-two of these slides were available for re-review. Upon review, 21 TPPT (50%) were confirmed negative and 21 TPPT (50%) were reclassified as abnormal = 20, or unsatisfactory = 1. Of the FN cases, the main difficulty in correct diagnosis was the presence of few diagnostic cell clusters which had less "feathering," and consisted of smaller, rounder cells in small and tighter clusters, with nuclear overlap. In particular, nuclear overlap in three-dimensional groups precluded the accurate diagnosis. Rare FN cases showed squamous cell abnormality on re-review, and rare cases showed obscuring blood or inflammation. Conclusion: A significant proportion of AIS/EAC is discovered after Pap showing squamous cell abnormality. FN cases were most commonly related to nuclear overlap in tight three-dimensional clusters.
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Methodology Article: The effect of the small amount of formaldehyde in the SurePath liquid when establishing protocols for immunocytochemistry
Ellen Cathrine Bjonness-Jacobsen, Anne Kristine Kallevag Eriksen, Vidar Nylokken Hagen, Kirsten Margrethe Ostbye, Anna Witterso, Mette Kristin Pedersen, Torill Sauer
CytoJournal 2016, 13:27 (16 November 2016)
DOI:10.4103/1742-6413.194163  PMID:27994636
Background: SurePath® is an ethanol-based liquid fixative. In addition to ethanol, it also contains a small amount of formaldehyde (<0.2%). The aim of this study was to investigate the immunoreactivity of cells stored for different lengths of time in the SurePath liquid. Materials and Methods: Rest material from one malignant and three benign effusions were fixed in SurePath for 1-12 days. Cytospins were incubated with cytokeratin 7 antibody (AB) to evaluate the staining intensity of carcinoma cells and benign, reactive mesothelial cells. Protocols varied as to pretreatment and AB incubation time. Results: Reduced immunostaining intensity was seen within 5 days of storage in the SurePath liquid. It was restored when the pretreatment time was prolonged. Conclusions: The small amount of formaldehyde in the SurePath liquid seems to affect the immunoreactivity. Local immunocytochemistry protocols in the cytology laboratories should consider this when optimizing their procedures. Postfixation with formalin should be omitted.
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Case Report: Diagnostic utility of double immunostaining of a urine cytology preparation for cytokeratin 20/p53 expression in a young woman with micropapillary urothelial carcinoma of the renal pelvis presenting as an unknown primary malignancy
Hyun-Jung Kim, Lucky Sung, Jung-Yeon Kim, Kyeongmee Park
CytoJournal 2016, 13:26 (16 November 2016)
DOI:10.4103/1742-6413.194162  PMID:27994635
Atypical urine cytology (CYT) triggers a cystoscopic or another ancillary investigation that targets urothelial neoplasms. We report a case presenting as an unknown primary malignancy, which illustrated the diagnostic utility of direct double immunostaining for cytokeratin 20 (CK20)/p53 expression in a urine CYT specimen. A 42-year-old woman visited the emergency room for pain in her right lower abdominal quadrant. Computed tomography revealed postrenal obstructive hydronephrosis, and her urine CYT showed malignancy, type undetermined. Atypical cells that are positive for cytoplasmic expression of CK20 and nuclear expression of p53 could facilitate the decision to perform a nephroureterectomy for urothelial carcinoma.
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Erratum: Erratum: CytoJournal Quiz Cases: Publishing open access, PubMed searchable cytopathology cases with educational messages.

CytoJournal 2016, 13:25 (13 October 2016)
DOI:10.4103/1742-6413.192192  PMID:27761150
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Research Article: Endoscopic ultrasound-guided fine needle aspiration cytology of metastatic renal cell carcinoma to the pancreas: A multi-center experience
Rahul Pannala, Karyn M Hallberg-Wallace, Amber L Smith, Aziza Nassar, Jun Zhang, Matthew Zarka, Jordan P Reynolds, Longwen Chen
CytoJournal 2016, 13:24 (13 October 2016)
DOI:10.4103/1742-6413.192191  PMID:27761149
Introduction: The increasing use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology to examine pancreatic neoplasms has led to an increase in the diagnosis of metastases to the pancreas. Renal cell carcinoma (RCC) is the most common metastasis to the pancreas. Our study examines 33 cases of metastatic RCC to the pancreas sampled by EUS-FNA from four large tertiary care hospitals. Materials and Methods: We searched the cytopathology database for RCC metastatic to the pancreas diagnosed by EUS-FNA from January 2005 to January 2015. Patient age, history of RCC, nephrectomy history, follow-up postnephrectomy, radiological impression, and EUS-FNA cytologic diagnosis were reviewed. Results: Thirty-three patients were identified. The average age was 67.5 years (range, 49-84 years). Thirty-two patients had a previous documented history of RCC. One patient had the diagnosis of pancreatic metastasis at the same time of the kidney biopsy. Thirty-one patients had been treated with nephrectomy. Twenty-seven patients were being monitored annually by computed tomography or magnetic resonance imaging. Twenty-five patients had multiple masses by imaging, but 8 patients had a single mass in the pancreas at the time of EUS-FNA. EUS-FNA of 20 cases showed classic morphology of RCC. Thirteen cases had either "atypical" clinical-radiologic features or morphologic overlaps with primary pancreatic neoplasms or other neoplasms. Cell blocks were made on all 13 cases and immunochemical stains confirmed the diagnosis. Conclusions: EUS-FNA cytology is useful for the diagnosis of metastatic RCC to the pancreas. Cytomorphology can be aided with patient history, imaging analyses, cell blocks, and immunochemical stains.
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Case Report: Oncocytic variant of poorly differentiated thyroid carcinoma: "Is diagnosis possible by fine-needle aspiration?"
Mine Onenerk, Sule Canberk, Pembegul Gunes, Murat Erkan, Gamze Z Kilicoglu
CytoJournal 2016, 13:23 (13 October 2016)
DOI:10.4103/1742-6413.192188  PMID:27761148
Poorly differentiated thyroid carcinoma (PDTC) is a very rare entity, and the diagnosis can be made on histopathology specimens. However, recognition of characteristic features of PDTC is significant on fine-needle aspirations (FNAs) to differentiate this entity from well-differentiated and anaplastic thyroid carcinomas. Here, we present an FNA case concordant with "oncocytic variant of PDTC" and discuss whether definitive diagnosis can be given on FNAs to assess the prognosis in clinically inoperable patients.
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