Journal of Pathology and Translational Medicine

Volume 18(1); March 2007

Review

Cervical Cancer Prevention for the Future: the Complimentary Roles of Cytology Screening and HPV Vaccination.: Euphemia McGoogan; Korean J Cytopathol. 2007;18(1):1-12.

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Abstract PDF: Approximately 70% of cervical cancers are caused by HPV types 16/18 and thus the implementation of vaccination programmes ith vaccines against HPV types 16/18 will have a major impact on the incidence of cervical cancer worldwide. However, this reduction will not be seen until several decades after full implementation of such vaccination programmes since the vaccines must be given to young adolescents before exposure to the virus and women who are already sexually active are not likely to be protected. Both GSK and Merck insist that even vaccinated women must continue to participate in regular cervical screening by the most sensitive method available since the vaccine can only give protection against up to 70% of cervical cancers. It is unlikely that the current vaccines will be modified to include additional high risk HPV types in the foreseeable future. While HPV testing is highly sensitive, it is not recommended for women under 30 years of age nor for vaccinated women. Additionally, HPV testing has poor specificity. The Digene Hybrid Capture 2 test is licensed for use only in conjunction with a cytology test, not as a stand-alone test, and the high risk panel has recognised cross reactivity with low risk HPV types. None of the other HPV test methods currently commercially available are FDA approved and all must be internally validated before use. This makes comparison of test results between laboratories difficult. The most sensitive and specific screening test currently available for women of all ages is the Cytyc ThinPrep(R) System consisting of the ThinPrep(R) Pap Test (TPPT) and the ThinPrep(R) Imaging System (Imager). The TPPT was the first LBC system approved by the US FDA in 1996 and there are about 4,000 processors in use worldwide. The Imager was FDA approved in 2003 and over 350 systems are in routine use, mainly in the US. 40% of TPPT in the US are processed on Imager. There is clear evidence in peer reviewed literature that the Imager increases laboratory productivity by 100% and growing evidence that Imager detects more high grade SIL than the conventional smear or manual evaluation of TPPT. This aspect is particularly important since the number of cytological abnormalities will decrease as vaccination programmes are implemented. Cytotechnologists will see fewer and fewer abnormal smears and their skills will be put at risk. By doubling throughput, Imager will allow cytotechnologists to maintain their skills.

Original Articles

Misinterpretation of Pregnancy Related Changes: Effect on the Postpartum Regression Rate of Abnormal Cervical Smears in Pregnancy.: Hye Sun Kim; Korean J Cytopathol. 2007;18(1):13-19.

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Abstract PDF: An aim of this study was to evaluate an effect of misinterpretation of pregnancy related cellular changes on the postpartum regression rate of abnormal cervical smears in pregnancy. A series of 265 cases with abnormal cervical smears in pregnancy were selected from a database of cervical smear results. The selected cases were classified as regression, persistence, and progression based on the results of postpartum cervical smears and histology. Of the selected cases, 162 cases were classified as regression and the postpartum regression rate was 61.1% (162/265). We reviewed abnormal cervical smears in pregnancy these cases. The primary cytologic diagnoses of these cases were ASCUS (118 cases), AGUS (2 cases), ASCUS/AGUS (1 case), LSIL (25 cases), LSIL R/O HSIL (2 cases), and HSIL (14 cases). With information of the pregnacy, we identified decidual cells in 24 cases, but cells identified by the Arias-Stella reaction and trophoblasts were not found. Sixteen cases out of 162 cases were reclassified as a pregnancy related change rather than an abnormal. Desidual cells were considered as ASCUS in 15 cases and as LSIL in one case. The revised postpartum regression rate was 55.5%(147/265) and was lower than the original. Consequently, misinterpretation of the pregnancy related cellular changes has an effect on a rise of the postpartum regression rate of the abnormal cervical smear in pregnancy. Pathologists may diagnose pregnancy related cellular changes as abnormal findings if they do not have information regarding the pregnancy. Therefore, clinical information of pregnancy and knowledge about the pregnancy related cellular changes are essential to prevent misinterpretation.

A Comparision of Surepath(TM) Liquid-Based Smear with a Conventional Smear for Cervicovaginal Cytology-with Reference to a Histological Diagnosis.: Kyung Chul Lee, Chan Kwon Jung, Ahwon Lee, Eun Sun Jung, Yeong Jin Choi, Jong Sup Park, Kyo Young Lee; Korean J Cytopathol. 2007;18(1):20-28.

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Abstract PDF: This study was performed to compare Surepath(TM) liquid-based smear and a conventional cervicovaginal smear with reference to a histological diagnosis. A hybrid capture test (HCII) was also performed and analyzed. We collected matched cases for cervicovaginal cytology- histology: 207 cases for conventional cytology (CC) and 199 cases for liquid-based cytology (LBC). HCII was performed in 254 patients. When a cytological diagnosis of ASCUS or above (ASCUS+) is classified as positive and a histological diagnosis of LSIL+ is classified as positive, the sensitivity and specificity for LBC was 91.7% and 75.9%, respectively and the sensitivity and specificity for CC was 62.6% and 96.1%, respectively. When a cytological and histological diagnosis of LSIL+ is classified as positive, the sensitivity and specificity for LBC was 77.5 and 96.6%, respectively and the sensitivity and specificity for CC was 49.7% and 100%, respectively. When a histological diagnosis of LSIL+ is classified as positive, the sensitivity and specificity for HCII was 78.9% and 78.1%, respectively. The concordance ratio between the cytological and histological diagnosis was 80.4% (kappa=76.0) for LBC and 56.5% (kappa=55.1) for CC. LBC is more sensitive and less specific then CC, as a cytological cutoff level of ASCUS, but more sensitive and equally specific, as a cytological cutoff level LSIL or HSIL. LBC is more reliable with a high concordance ratio between the cytological and histological diagnosis.

Cytologic Evaluation of CellPrep(R) Liquid-based Cytology in Cervicovaginal, Body Fluid, and Urine Specimens: Comparison with ThinPrep(R).: Jae Soo Koh, Soo Yeon Cho, Hwa Jeong Ha, Jung Soon Kim, Myung Soon Shin; Korean J Cytopathol. 2007;18(1):29-35.

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Abstract PDF: This study purposed to evaluate a CellPrep(R) (CP) of liquid-based cytology (LBC) to search for a less expensive and automated alternative cytologic preparation technique applicable to usually encountered cytologic specimens. Cervicovaginal direct-to-vial split samples from 457 gynecologic patients, 40 body fluid samples, and 34 urine samples were processed with the CP technique and the results were compared with those of currently used ThinPrep(R) (TP) method. Both CP and TP methods provide evenly distributed thin layers of cells with little cellular overlaps or significant obscuring elements in most of cases. Staining quality of both preparations showed a little difference due to the difference of fixative solutions without significant distractions in cytologic interpretation. On the supposition that TP was a gold standard, sensitivity, specificity, positive predictive value, and negative predictive value of CP cytology were 89%, 98%, 86%, and 99% in the cervicovaginal smear, 89%, 82%, 80%, and 90% in body fluid, and all of these values were 100% in urine samples. To testify the availability of immunohistochemistry on CP preparations, cytokeratin, vimentin, and Ki-67 were applied on body fluid specimens, and all of these antibodies were specifically stained on targeted cells. Conclusively, the CP method gave comparable results to those of TP in terms of smear quality and cytologic diagnostic evaluation, and was available on immunohistochemistry. The CP method could offer a cost-effective and automated alternative to the current expensive techniques of liquid- based cytology on popular cytologic materials including cervicovaginal, body fluid, and urine specimens.

Cytologic Evaluation of Adenocarcinoma and its Mimics in Sputum and Bronchial Washings.: Young Chae Chu, In Suh Park, Suk Jin Choi, Lucia Kim, Jee Young Han, Joon Mee Kim, Jung Ae Park; Korean J Cytopathol. 2007;18(1):36-45.

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Abstract PDF: OBJECTIVE: To identify key cytologic features for diagnosis of adenocarcinoma and morphologic differentiation from reactive/reparative respiratory epithelium. STUDY DESIGN: The cytomorphologic features of 145 pulmonary cytology specimens (sputum and bronchial washing), which included 117 histologically proven adenocarcinomas and 28 non-neoplastic lesions, cytologically diagnosed as atypia and suspicious for malignancy (adenocarcinoma) were reviewed retrospectively. We analyzed 11 morphologic criteria in pulmonary cytologic specimens.
RESULTS
Over 110 of 117 cases of adenocarcinomas revealed nuclear membrane irregularities, non-cohesive cells, single atypical cells, moderate to markedly enlarged nuclei and an increased nuclear/cytoplasmic (N/C) ratio. Chromatin clearing, chromatin heterogeneity and hyperchromasia were seen in 102, 99 and 97 cases, respectively. All 28 cases involving non-neoplastic lesions revealed hyperplastic reactive pneumocytes, hyperplastic reactive bronchial epithelium, or degenerating macrophages. The non-neoplastic lesions revealed a small number of atypical cell clusters and paucity or absence of atypical single cells.
CONCLUSION
The most important morphologic features for diagnosis of adenocarcinoma are nuclear membrane irregularities, non-cohesive cells, single atypical cell, moderate to markedly enlarged nuclei and increased N/C ratio. Chromatin clearing, chromatin heterogeneity and hyperchromasia were also helpful features, while pleomorphism and prominent nucleoli were less valuable.

Evaluation for Cytopreservability of Manual Liquid-Based Cytology Liqui-PREP(TM) and its Application to Cerebrospinal Fluid Cytology: Comparative Study with Cytospin.: Gyeongsin Park, Kyungji Lee, Chan Kwon Jung, Dae Hyoung Lee, Bin Cho, Youn Soo Lee, Sang In Shim, Kyo Young Lee, Chang Suk Kang; Korean J Cytopathol. 2007;18(1):46-54.

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Abstract PDF: Cerebrospinal fluid (CSF) cytology is an effective tool for evaluating diseases involving the central nervous system, but his technique is usually limited by its low cellularity and poor cellular preservation. Here we compared the manual liquid-base Liqui-PREPTM (LP) to the cytospin (CS) with using a mononuclear cell suspension and we applied both methods to the CSFs of pediatric leukemia patients. The cytopresevability, in terms of cell yield and cell size, and the clinical efficacy were evaluated. When 2000 and 4000 mononuclear cells were applied, LP was superior to CS for the cell yield, 16.8% vs 1.7% (P=0.001) and 26.2% vs 3.5% (P=0.002), respectively. The mean size of the smeared cells was 10.60 micrometer in the CS, 5.01 micrometer in the LP and 6.50 micrometer in the direct smear (DS), and the size ratio was 1.7 (CS to DS), 0.8(LP to DS) and 2.1 (CS to LP), respectively. As compared to the cells in the DS, the cells in the CS were significantly enlarged, but those in the LP were slightly shrunken. Upon application to 109 CSF samples, 4 were diagnosed as positive for leukemia (positive), 4 had atypical cells and 101 were negative by CS; 6 were positive, one had atypical cells and 102 were negative by LP. For six cases, in which 4 were positive for leukemia and 2 of 4 had atypical cells by CS, they were positive by LP and they were also confirmed as positive according to the follow-up study. Three cases diagnosed as atypical cells (two by CS and one by LP), were confirmed as negative. In conclusion, these results suggest that LP is superior to CS for the cytopresevability and for rendering a definite diagnosis of cerebrospinal fluid.

Comparision of Effectiveness between the ThinPrep(R) and the Cytospin Preparations of the Repeated Urine Cytology.: Soon Won Hong, Hyun Kyung Kim, Ju Yeon Pyo, Yoonhee Lee, Woo Hee Jung, Se Hoon Kim; Korean J Cytopathol. 2007;18(1):55-61.

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Abstract PDF: Once diagnosed as "cell paucity" or "atypia" by the cytospin (CS) preparation, this CS preparation does not secure a precise diagnosis by repeated testing alone. Although the ThinPrep(R) (TP) preparation is acknowledged to show increased cellularity, performing the screening tests for the cases that have enough cellularity, according to CS, raises issues for the cost-effectiveness. To obtain a more precise diagnosis through increasing the cellularity by performing TP, we selected the cases that were diagnosed as "cell paucity" or "atypia" by CS, but they required a more precise diagnosis, and the samples were processed via both CS and TP to compare the results. 11 patients diagnosed as "cell paucity" and 22 patients diagnosed as "atypia" by CS participated in this study. When the detection rate of atypical cells in both preparations with repeated urine cytology was compared, the overall detection rate of TP (16cases, 48.5%) was superior than that of CS (11cases, 33.3%), with statistical significance. The cellularity of both preparations was compared on repeated urine cytology; the general cellularity of TP (29cases, 87.9%) was higher than that of CS (20cases, 60.6%), but there was no statistical significance. Particularly, we repeated the TP for the 1 case that was diagnosed as "atypia" and we performed polyoma virus immunohistochemical staining, which confirmed polyoma virus. In conclusion, we can avoid obtaining negative diagnosis from cases with uncertain "atypia" or "cell paucity" by performing repeated TP testing.

Fine Needle Aspiration Cytology of Invasive Micropapillary Carcinoma of the Breast.: Hyun Joo Choi, Ji Han Jung, Jung Ha Shin, Kiouk Min, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee; Korean J Cytopathol. 2007;18(1):62-68.

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Abstract PDF: Invasive micropapillary carcinoma (IMPC) of the breast is recently described rare variant of invasive ductal carcinoma. This variant has a distinctive histological features and aggressive biological behavior. We reviewed the cytologic features of eight cases of IMPC. The cytologic smears showed moderate to high cellularity and the tumor tissue was composed of atypical, angulated, cohesive clusters of neoplastic cells with a papillary to tubuloalveolar architecture, and a morular growth pattern without fibrovascular cores was seen on the histopathology. IMPC of the breast has distinctive cytologic features and it is important to make an early diagnosis via fine needle aspiration cytology due to this tumor's aggressive behavior.

Case Reports

Invasine Ductal Carcinoma with Osteoclast-Like Giant Cell in a Young Woman.: Hyun Jeong Kang, Jee Yeon Kim, Kyung Un Choi, Hee Suk Kwak, Mee Young Sol; Korean J Cytopathol. 2007;18(1):69-73.

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Abstract PDF: Mammary carcinoma with osteoclast-like giant cells is an unusual neoplasm characterized by giant cells, mononuclear stromal cells, and hemorrhage accompanying a low grade carcinoma. We present the cytological findings in a case of invasive ductal carcinoma with osteoclast-like giant cells that was initially confused with a fibroadenoma, due to its well-demarcated and soft mass and the young age of the patient. A 28-year-old female presented with a 4.5 cm, well demarcated, soft and nontender mass in the right breast. Fine needle aspiration cytology (FNAC) showed a combination of low grade malignant epithelial cell clusters and osteoclast-like giant cells. The atypical epithelial cells were present in cohesive sheets and clusters. Osteoclast-like giant cells and bland-looking mononuclear cells were scattered. An histological examination revealed the presence of an invasive ductal carcinoma with osteoclast-like giant cells. We report here the cytological findings of this rare carcinoma in a very young woman. The minimal atypia of the epithelial cells and its soft consistency may lead to a false negative diagnosis in a young woman. The recognition that osteoclastlike giant cells are rarely present in a low grade carcinoma, but not in benign lesion, can assist the physician in making a correct diagnosis.

Fine Needle Aspiration Cytology of Parathyroid Neoplasms: A Review of Three Cases.: Lucia Kim, Jee Young Han, In Suh Park, Suk Jin Choi, Joon Mee Kim, Young Chae Chu; Korean J Cytopathol. 2007;18(1):74-80.

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Abstract PDF: Parathyroid tumors may be difficult to distinguish from thyroid follicular lesions, especially when a tumor is nonfunctioning. We report here two cases of asymptomatic parathyroid carcinoma preoperatively misdiagnosed as thyroid follicular lesions, and one case of parathyroid adenoma showing hyperparathyroidism, and review the cytologic features favoring the diagnosis of parathyroid neoplasm. The cytologic findings that are characterized by clean background, monomorphic small cells, cohesive three-dimensional papillary clusters, small tight clusters with scattered naked nuclei, and well-defined clear cytoplasm favor a diagnosis for the parathyroid lesions. Cytologic findings such as macrofollicular structure, presence of colloid and macrophages, and presence of perivacuolar cytoplasmic granules on May-Grunwald-Giemsa stain support a diagnosis of a thyroid follicular lesion. The cytomorphology of parathyroid tumors is so variable that the distinction from a thyroid lesion cannot be based on the presence or absence of a single feature only but on the cytologic features as a whole.

Imprint Cytology of a Desmoplastic Small Round Cell Tumor: A Case Report.: Joon Hyuk Choi, Yong Jin Kim, Jae Hwang Kim; Korean J Cytopathol. 2007;18(1):81-86.

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Abstract PDF: Desmoplastic small round cell tumor (DSRCT) is a rare malignant mesenchymal neoplasm. It mainly involves the abdominal or pelvic peritoneum of male adolescents. We report here the imprint cytologic features of a case of DSRCT occurring in the intraabdominal cavity of a 21-year-old man. A microscopic examination showed moderate cellularity. The tumor cells were singly arranged and arranged in clusters. The cells had round to oval nuclei with finely granular chromatin, inconspicuous nucleoli and scanty cytoplasm. Some tumor cells showed nuclear molding, and some cells had an epitheloid appearance with a large amount of lightly eosinophilic cytoplasm. A rosette-like pattern was present. Spindle-shaped, fibroblastic stromal cells were occasionally found. The tumor cells were immunoreactive for the markers cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), desmin, vimentin and neuron specific enolase (NSE).

Fine Needle Aspiration Cytology of Langerhans Cell Histiocytosis in a Lymph Node: A Case Report.: Seung Yeon Ha, Min Jung Kim, Gou Young Kim, Hyun Yee Cho, Dong Hae Chung, Na Rae Kim; Korean J Cytopathol. 2007;18(1):87-91.

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Abstract PDF: Langerhans cell histiocytosis (LCH) is a pleomorphic disease entity characterized by local or disseminated atypical Langerhans cells (LCs) found most commonly in bone, lungs, mucocutaneous structures and endocrine organs. Among different sites, unifocal disease confined to a lymph node (LN) is rare. We report a case of LCH confined to a LN in a 38-year-old male who presented with a 2 cm-sized cervical mass. The fine needle aspiration (FNA) smears of cervical LN showed high cellularity having isolated LCs with contorted nuclei and nuclear grooves mixed in multinucleated giant cells, small lymphocytes and eosinophils. Charcot-Leyden crystals were also seen, as were a few dendritic-like cells and intranuclear inclusions. Confirmation of LCH was made by histopathologic studies, positive reactions for S-100 protein and CD1a immunohistochemical staining and by the demonstration of Birbeck granules on electron microscopy. The differentials to be considered include dermatopathic lymphadenitis, sinus histiocytosis with massive lymphadenopathy, Hodgkin's lymphoma and malignant histiocytosis. The characteristic cytomorphologic pattern of LCH in a LN FNA smear plays an important role in suggesting the diagnosis of LCH.

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