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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  
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  
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  
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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  
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  
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  
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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
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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Research Article: Prognostic markers in smear preparations for pancreatic endocrine neoplasms: A cytomorphologic study and statistical analysis of 20 potential prognostic features
Lester J Layfield, Robert L Schmidt, Jack Campbell, Magda Esebua
CytoJournal 2016, 13:22 (20 September 2016)
DOI:10.4103/1742-6413.190915  PMID:27729936
Background: Papanicolaou Society of Cytopathology guidelines place low- and intermediate-grade pancreatic endocrine tumors into the "neoplastic, other" category whereas high-grade pancreatic endocrine tumors are placed in the "malignant" category. No attempt was made to stratify pancreatic endocrine tumors in the "neoplastic, other" category by likelihood for metastases. Histologically, pancreatic endocrine tumors are divided into well, intermediate, and poorly differentiated examples based on mitotic count and Ki-67 proliferation index (PI). PI has been used in the evaluation of cytologic specimens utilizing cell block material. Unfortunately, cell block material may not always be available for analysis, and little data exists as to cytomorphologic features in smear preparations which might distinguish between low- and intermediate-grade endocrine neoplasms and predict metastases. Methods: We studied 36 cases of Diff-Quik stained smear preparations for 20 morphologic features to determine which best-classified cases into poor and not poor outcome categories. Hierarchical logistic regression analysis was used to determine associations between the morphologic features and outcomes. Results: Absolute agreement between raters ranged from 51% to 97% across the 20 morphologic features. About 12 of the 20 morphologic features showed statistically significant associations with poor outcome. Mitoses, irregular nuclear membranes, and 3-fold variation in nuclear size are the best discriminators between poor and not poor outcomes. Conclusions: A scoring system was developed utilizing mitoses, irregular nuclear membranes, and 3-fold variation in nuclear size to divide smears of pancreatic endocrine tumors into poor and not poor outcome groups. The scoring system achieved 84% accuracy in separating cases into poor and not poor outcomes.
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Case Report: A case of S-100 negative melanoma: A diagnostic pitfall in the workup of a poorly differentiated metastatic tumor of unknown origin
Anna Biernacka, Konstantinos D Linos, Peter A DeLong, Arief A Suriawinata, Vijayalakshmi Padmanabhan, Xiaoying Liu
CytoJournal 2016, 13:21 (20 September 2016)
DOI:10.4103/1742-6413.190914  PMID:27729935
When confronted with a metastatic poorly differentiated tumor of unknown origin, the initial workup includes the standard panel of immunostains to rule out carcinoma, sarcoma, lymphoma, and the greatest mimicker in pathology - malignant melanoma. Although not specific, the S-100 protein is expressed in over 95% of malignant melanomas. Herein, we present a case of multiorgan metastatic malignancy with a dominant hilar and mediastinal mass in a current smoker; clinically, highly suggestive of widespread primary lung cancer. This case was eventually classified as malignant melanoma, despite a significant diagnostic challenge due to lack of prior history, unusual cytomorphology, and S-100 protein negativity. A battery of immunostains was performed and the addition of other melanocytic-associated markers confirmed the melanocytic lineage of the neoplasm. This case highlights the pitfalls in the differential diagnosis of a metastatic tumor of unknown origin by fine needle aspiration cytology due to the significant morphologic overlap of poorly differentiated malignancies. We emphasize that, albeit rare, malignant melanomas can be completely negative for S-100 protein and the use of additional melanocytic-associated markers in the differential workup maybe critical in arriving promptly at a proper diagnosis. We also briefly discuss other currently available immunohistochemical markers that can assist in the identification of the S-100 negative melanoma.
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Research Article: Stromal tissue as an adjunct tool in the diagnosis of follicular thyroid lesions by fine-needle aspiration biopsy
Kien T Mai, Kevin Hogan
CytoJournal 2016, 13:20 (31 August 2016)
DOI:10.4103/1742-6413.189639  PMID:27651822
Background: The stroma in fine-needle aspiration biopsy (FNAB) of thyroid lesions has not been well investigated. Design : We studied 256 consecutive cases of thyroid FNAB prepared with traditional smear technique. The stroma was categorized: Type 1a consisted of long (more than 3 mm), broad bands composed of mesh containing collagen fibrils thickened by entrapped blood components and follicular cells. Type 1b consisted of dense strands/bands. Type 2 was similar to Type 1a but with shorter (<2 mm) and looser stromal strands. Results : Types 1a and b showed straight/curved/circular branching patterns suggestive of incomplete frameworks of nodular/papillary architectures or fragments of capsule. Type 1b stroma likely represented thick/collagenized fibrous septae. Incomplete or complete rings of small encapsulated tumor were occasionally identified. These frameworks of stroma were frequently associated with multinodular goiters (MNGs) which are often hypocellular and follicular neoplasms/papillary thyroid carcinoma with increased cellularity. Type 2 was associated with microfollicles in encapsulated neoplasms or with macrofollicles in MNG. Follicular lesions of unknown significance (n = 41) either negative (n = 26) or positive (n = 15) for carcinoma in subsequent follow-up were frequently associated with stroma characteristic of MNG and carcinoma, respectively. Conclusion : The preservation of the in vivo architecture of Type 1 is likely due to its elasticity. Recognition of the stromal architecture will likely facilitate the diagnosis.
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Letter to Editor: Diagnostic relevance of cell block procedure in secondary tumors of the pancreas
Antonio Ieni, Valeria Barresi, Giovanni Tuccari
CytoJournal 2016, 13:19 (31 August 2016)
DOI:10.4103/1742-6413.189638  PMID:27651821
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Review Article: Fine-needle aspiration and core biopsy in the diagnosis of breast lesions: A comparison and review of the literature
Suvradeep Mitra, Pranab Dey
CytoJournal 2016, 13:18 (31 August 2016)
DOI:10.4103/1742-6413.189637  PMID:27651820
In recent times, the diagnosis of breast lesions has mostly become dependent on core needle biopsies (CNBs) with a gradual reduction in the rate of performing fine-needle aspiration cytology (FNAC). Both the procedures have their pros and cons and outsmart each other taking into account different parameters. Both the methods are found to be fraught with loopholes, taking into account different performance indices, diagnostic accuracy and concordance, patient benefit, and cost-effectiveness. Unlike the popular belief of an absolute superiority of CNB over FNAC, the literature review does not reveal a very distinct demarcation in many aspects. We recommend judicious use of these diagnostic modalities in resource-limited settings and screening programs taking into account parameters such as palpability and availability of an experienced cytopathologist.
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Research Article: Tuberculous lymphadenitis: Comparison of cytomorphology, Ziehl-Neelsen staining, and rapid mycobacterial culture at a pediatric superspecialty hospital Highly accessed article
Sonam Mahana, Reena Tomar, Rawi Agrawal, Rushika Saksena, Vikas Manchanda, Ruchika Gupta
CytoJournal 2016, 13:17 (27 July 2016)
DOI:10.4103/1742-6413.187070  PMID:27563340
Background: To evaluate and compare the role of Ziehl-Neelsen (ZN) staining and mycobacterial culture in diagnosis of tuberculous lymphadenitis. Materials and Methods: A total of 56 fine needle aspirations (FNAs) from patients who were clinically suspected to have tuberculous lymphadenitis were included. Acid-fast Bacilli detection was attempted by ZN staining on smears as well as culture on Middlebrook 7H9 broth. Percentage positivity of both smears and culture was calculated. Results: Of the 56 cases, 46 showed cytomorphological features consistent with tuberculosis (TB). The most common pattern was only necrosis in 37 cases followed by necrotizing granulomas in 13 cases. ZN-stained smears were positive in 40 cases while culture was positive in only 27 cases. The highest smear and culture positivity was noted in cases with only necrosis. In six cases, diagnosis of TB was made on culture alone since smear was negative in these cases. Conclusion: FNA is a reliable technique for early and accurate diagnosis of tuberculous lymphadenitis in many cases. Mycobacterial culture by newer rapid techniques can assist in bacillary detection in smear-negative cases and also allows for drug sensitivity testing. Hence, culture should be resorted to in such cases.
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Case Report: Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor
Longwen Chen, Kristina A Butler, Debra A Bell
CytoJournal 2016, 13:16 (27 July 2016)
DOI:10.4103/1742-6413.187052  PMID:27563339
Serous borderline tumor (SBT) involving a cervical lymph node is extremely rare. In addition, fine needle aspiration (FNA) cytology of the involved cervical lymph node shares tremendous morphologic similarity with other low-grade papillary carcinomas. Thus, it can be easily misdiagnosed as metastatic carcinoma. A 42-year-old female had a history of bilateral SBT and postbilateral salpingo-oophorectomy. She presented with left cervical lymphadenopathy 6 months later. FNA cytology showed a low-grade papillary neoplasm with psammoma bodies. Needle core biopsy along with immunostains was diagnostic of cervical lymph node involvement (LNI) of SBT. although extremely rare, cervical LNI can be found in patients with SBTs. FNA cytology, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or needle core biopsy is essential to make the correct diagnosis.
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Editorial: CytoJournal Quiz Cases: Publishing open-access, PubMed-searchable cytopathology cases with educational messages
Katherine G Akers, Vinod B Shidman
CytoJournal 2016, 13:15 (27 July 2016)
DOI:10.4103/1742-6413.187015  PMID:27563338
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Research Article: Unsatisfactory rate in liquid-based cervical samples as compared to conventional smears: A study from tertiary care hospital
Nalini Gupta, Vikrant S Bhar, Arvind Rajwanshi, Vanita Suri
CytoJournal 2016, 13:14 (10 June 2016)
DOI:10.4103/1742-6413.183831  PMID:27382408
Background: Developed countries adopted liquid-based cytology (LBC) cervical cytology, partly because of its lower proportions of unsatisfactory (U/S)/inadequate samples. This study was carried out to evaluate effect on the rate of U/S samples after introduction of LBC in our laboratory. Materials and Methods: An audit of U/S cervical samples was performed, which included split samples (n = 1000), only conventional Pap smear (CPS) smears (n = 1000), and only LBC samples (n = 1000). The smears were reviewed by two observers independently, and adequacy for the samples was assessed as per The Bethesda System 2001. The reasons for U/S rate in split samples were categorized into various cytologic and/or technical reasons. Results: U/S rate was far less in only LBC samples (1.2%) as compared to only CPS (10.5%) cases. Cases in the satisfactory but limited category were also less in only LBC (0.4%) as compared to only CPS (3.2%) samples. The main reasons for U/S smears in split samples were low cell count (37.2% in CPS; 58.8% in LBC). The second main reason was low cellularity with excess blood and only excess blood in CPS samples. Conclusion: There was a significant reduction of U/S rate in LBC samples as compared to CPS samples, and the difference was statistically significant. The main cause of U/S samples in LBC was low cellularity indicating a technical fault in sample collection. The main cause of U/S rate in CPS was low cellularity followed by low cellularity with excess blood. Adequate training of sample takers and cytologists for the precise cell count to determine adequacy in smears can be of great help in reducing U/S rate.
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Case Report: Pleural fluid metastases of myoepithelial carcinoma: A case report and review of the literature
Alicia Calderon Bhambra, Yanhong Zhang, Eric C Huang, John Bishop, Mahan Matin, Alaa Afify
CytoJournal 2016, 13:13 (10 June 2016)
DOI:10.4103/1742-6413.183829  PMID:27382407
Myoepithelial carcinoma (MECA) is one of the rarest salivary gland neoplasms, which may either arise de novo or develop within a preexisting pleomorphic adenoma or benign myoepithelioma. The tumor occurs mainly in the parotid gland followed by minor salivary glands and other body sites. As a result of their morphologic heterogeneity, they can be confused easily with many tumors. Awareness of their unique cytoarchitectural patterns and immunohistochemical profile is crucial for accurate identification. Herein, we report a rare case of a 51-year-old female patient with MECA of the maxillary sinus that metastasized to the pleural fluid. To the best of our knowledge, this is the first case of pleural fluid involvement by MECA reported in the literature.
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Case Report: Cytomorphological features of papillary cystadenocarcinoma of parotid gland: A case report with review of literature
Usha Joshi, Sanjay Singh Chufal, Naveen Thapliyal, Harsh Khetan
CytoJournal 2016, 13:12 (25 May 2016)
DOI:10.4103/1742-6413.182955  PMID:27298629
Papillary cystadenocarcinoma is a very rare slow growing malignant neoplasm characterized by cysts and intraluminal papillary projections. It is defined by WHO as a separate entity. On FNA, cytological features can mimic with various papillary and cystic neoplasms of salivary gland. It is also difficult to distinguish from benign salivary gland neoplasms as it has bland nuclear features. Thus we present cytomorphological features and discuss its differential diagnosis with neoplasms having prominent papillary architecture with review of literature.
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Methodology Article: The role of intraoperative scrape cytology in vertebroplasty
Renuka Venkata Inuganti, Rami Reddy Mettu, Harsha Vardhan Surath, Amarnath Surath
CytoJournal 2016, 13:11 (25 May 2016)
DOI:10.4103/1742-6413.182954  PMID:27298628
Aims: To assess the adequacy of intraoperative scrape cytology during percutaneous vertebroplasty by correlating results with corresponding histopathology. Settings and Design: Vertebroplasty is a procedure increasingly used to treat painful vertebral compression fractures. The history and presentation of osteoporotic fractures are straightforward, but difficulty arises in differentiating infective from neoplastic lesions, especially in cases where the magnetic resonance imaging is equivocal. The procedure involves injection of polymethyl methacrylate (bone cement) into the pathological vertebral body and gives dramatic pain relief. It is indicated in osteoporotic and neoplastic lesions but contraindicated in infections. Hence, intraoperative evaluation of a specimen is essential to aid in the decision of performing vertebroplasty. Subjects and Methods: A total of 128 patients with vertebral lesions underwent core biopsy and scrape cytology from June 2006 to June 2015. Based on the findings of cytological examination, malignant lesions were subjected to vertebroplasty. In lesions with infective etiology, vertebroplasty was abandoned and antibiotic or antituberculous therapy started. Results: The overall diagnostic accuracy of scrape cytology was excellent with 97.58% cases correlating with the final histopathological diagnosis. Specificity was 100%, positive predictive value was 100% and negative predictive value was 33.33%. Conclusion: Scrape cytology is a simple, rapid, accurate cytodiagnostic technique and should be routinely utilized in vertebral lesions for intraoperative consultation and decision making during vertebroplasty.
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