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Activating mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer predicts a significantly higher clinical response rate to tyrosine kinase inhibitors targeting EGFR, and it is currently recommended that patients under consideration for EGFR TKI as first-line therapy be tested for such mutations to determine the appropriateness of treatment. For lung cancer patients who present with advanced stage disease where surgical treatment is not indicated, cytology specimens obtained through bronchoscopy, drainage of body fluid, or fine-needle aspiration are the only means to obtain tumor cells for tissue diagnosis and EGFR gene mutation testing. We reviewed the experience of 1,410 consecutive EGFR mutation testing requests at a single institution in Hong Kong that comprised 269 cytology specimens and 1,141 surgical specimens. The material inadequacy issue in cytology specimens may be overcome by tumor cell enrichment strategies and employment of mutation detection techniques with increased analytical sensitivity. The use of cytology specimens to test for predictive molecular cancer biomarkers is without a doubt expected to increase, and cytopathologists should be closely engaged with the clinicians in the therapeutic process and become acquainted with new technology in order to directly participate in personalized oncology care., (Copyright © 2012 S. Karger AG, Basel.)

Objective: This study evaluated the impact of the Bethesda System (TBS) 2001 in reporting of atypical glandular cells (AGC) when using conventional Pap smears (CS) and liquid-based cytology preparations (LBC)., Study Design: Follow-up information for all atypical glandular cells of undetermined significance (AGUS)/ AGC cases encountered in Queen Mary Hospital from July 2000 to June 2004 was analyzed. The difference in percentages associated with certain end points when using different reporting systems and preparation methods were compared. The age trends and time interval between cytologic diagnosis and detection of positive end points were studied., Results: More than half of these cases turned out to be "negative." The majority with "negative" end points belonged to the "not otherwise specified" (NOS) groups (including atypical endometrial cells) in TBS 2001. The connotation of "favor neoplastic" carried a high positive predictive value for significant lesions. Most of the significant outcomes were discovered within the subsequent 6 months. A decreased reporting of "AGC, NOS" and an increased reporting of "atypical endocervical cells, NOS" were noted when using LBC., Conclusion: Subcategorization of AGC in TBS 2001 according to cellular origin and risk of malignancy, which is further enhanced by application of LBC, is useful.

Background: Since the first description of extranodalfollicular dendritic cell sarcoma in 1994, there has been a gradual increase in understanding of the morphologic features and clinical presentation of this tumor. However, difficulties persist in making cytologic diagnosis., Cases: Two cases of follicular dendritic cell sarcoma with fine needle aspiration cytology (FNAC) findings were reported. The first patient was a Chinese woman who presented with a right tonsillar mass, which was followed by right submandibular recurrence. The second patient was a Chinese man with known history of Castleman's disease of the nasopharynx complicated by follicular dendritic cell sarcoma, followed by tumor recurrence in cervical lymph nodes. FNAC of both recurrent cases showed isolated or syncytial sheets of tumor cells containing eosinophilic granular cytoplasm, ill-defined cell borders, round to oval nuclei, solitary round eosinophilic nucleoli and fine chromatin., Conclusion: The tumor cells in follicular dendritic cell sarcoma show cytologic features reminiscent of native follicular dendritic cells but with a greater than expected cell number and nuclear pleomorphism. These cells may be immunohistochemically inert for follicular dendritic cell markers CD21 and CD35. A presumptive diagnosis on the basis of cytologic examination is possible when paying attention to the subtle morphologic features.

Objective: To develop a local quality assurance program in cytopathology based on circulation of patient specimens on glass slides, with limited resources., Study Design: A working group was set up for design and running of the program. Participation is on a laboratory basis. The scope and frequency of testing are defined. Well-documented cases (including gynecologic, nongynecologic and fine needle aspiration cytology) with commonly encountered diagnoses are collected. Consensus concerning the diagnosis, interpretive menu and scoring system is sought before the actual slide circulations using express mail. After returning their answers to the program organizer, the participating laboratories receive immediate feedback on their scores, with reference answers, explanatory notes, "whole-mount" images of glass slides and cumulative responses of peer laboratories for on-site checking. At the end of each year, an electronic file containing representative photomicrographs of all cases examined is provided to individual laboratories for their permanent records and training purposes., Results: The program was launched in mid-2003. There were 24 and 27 participating laboratories from Hong Kong (and Macau) in 2003 and 2004, respectively. To date, >150 well-documented cytology cases are available in the slide pool and ready for circulation. As the revenue is mainly to cover the expenses of express mail, the program can be carried out at a relatively low cost., Conclusion: In order to have any cytology quality assurance program accepted by local laboratories, it has to be fair and practical. Strict confidentiality needs to be observed throughout the process. This program emphasizes both performance assessment and educational value. Adequate representation from experienced local cytology workers, detailed documentation support from authorities and assistance from dedicated staff are essential to the success of any external proficiency testing scheme. Regular review and evaluation are also necessary for continuous improvement. The Hong Kong experience can serve as an example of running a glass slide-based cytology quality assurance program in a small region with limited resources.

Background: Glassy cell carcinoma is a rare form of poorly differentiated carcinoma of the cervix with no obvious squamous or glandular differentiation. Its liquid-based cytology findings have not been described before., Case: A 46-year-old Filipina presented with vaginal bleeding due to a bulky cervical tumor. The liquid-based cytology preparation was of moderate cellularity and contained small clusters of polygonal to elongated tumor cells admixed with amphophilic, granular, necrotic debris. The malignant cells possessed round to oval nuclei; a thin nuclear membrane; finely dispersed chromatin; prominent, solitary nucleoli; abundant, cyanophilic cytoplasm; and discrete cell borders. Occasional tumor cells showed phagocytosis of polymorphs. The background contained a mixed population of inflammatory cells. Eosinophils, though present, were not readily identified in the cytologic specimen. There was no evidence of dyskeratosis, cytoplasmic vacuolation or koilocytosis. Histologic and ultrastructural examination of the tumor biopsy showed classic features of glassy cell carcinoma. Molecular analysis using polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus (HPV) DNA in the liquid-based cytology sample. The HPV genotype, however, did not belong to any of the commonly encountered prototypes., Conclusion: Glassy cell carcinoma of the cervix may show distinct, though subtle, cytomorphologic features in liquid-based preparations. The findings, however, are slightly different from those in conventional cervical smears. Awareness of this rare entity is important, as glassy cell carcinoma is often associated with more aggressive clinical behavior.

Background: Cytoplasmic eosinophilia in breast tumors is due mainly to abundance of secretory granules, lysosomes and/or mitochondria. Diffuse cytoplasmic hyalinization caused by intermediate filaments has not been described before., Cases: Two cases of pure mammary mucinous carcinoma occurred with marked cytoplasmic hyalinization among 556 wide excision/mastectomy specimens of mammary ductal carcinoma, either in situ or invasive, encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the period from 1994 to the end of 2001. Preoperative fine needle aspiration cytology was available in 1 case, showing cohesive clusters and micropapillae of tumor cells in abundant background mucin. The tumor cells had low mitotic activity and possessed round to oval nuclei, solitary macronucleoli; ample, eosinophilic cytoplasm and discrete cell borders. Cytoplasmic granularity, intracytoplasmic vacuoles or "cometlike" cells were not found. Histologic examination of the surgical specimens in both cases revealed pure mucinous carcinoma with diffuse and marked cytoplasmic hyalinization. There was no evidence of peritumoral lymphovascular permeation or regional lymph node metastasis. Ultrastructural examination showed minimal secretory activity, with abundant, loose aggregates of intermediate filaments in the cytoplasm. There was a relative paucity of other organelles., Conclusion: Diffuse cytoplasmic hyalinization is a peculiar morphologic change in mammary ductal carcinoma and apparently unique to pure mucinous carcinoma. Recognition of this phenomenon may help to avoid misdiagnosis of other types of ductal carcinoma with cytoplasmic eosinophilia, such as apocrine carcinoma and ductal carcinoma with neuroendocrine differentiation, which sometimes are also associated with pools of extracellular mucin.

Background: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoma typically occurs in extranodal sites, such as nasal cavity, nasopharynx, gastrointestinal tract, skin, testis and salivary gland. Secondary lymph node involvement is rarely encountered until late in the disease course. The fine needle aspiration cytology of NK/T-cell lymphoma with a nodal presentation has not been described before., Cases: Two cases of nasal-type (extranasal) NK/T-cell lymphoma with a nodal presentation were seen at Pamela Youde Nethersole Eastern Hospital, Hong Kong. Both patients presented with submandibular lymph node enlargement but unremarkable peripheral blood and bone marrow findings. Fine needle aspiration cytology was available in both cases, showing a heterogeneous population of small to medium-sized lymphoid cells, follicular center cells, plasma cells, eosinophils and some histiocytes. The medium-sized lymphoid cells showed readily discernible nuclear atypia with an irregular nuclear outline. Cell block sections revealed occasional lymphoid cells with pleomorphic nuclei. Immunocytochemical study confirmed the presence of CD56-positive lymphoma cells. In situ hybridization for EBV-encoded RNA also revealed positive nuclear signals. Histologic examination of the surgical biopsies showed interfollicular expansion by malignant lymphoid cells. Immunoglobulin heavy chain gene and T-cell receptor gene rearrangement studies demonstrated a germline pattern, confirming the putative NK (natural killer cell), non-B and non-T lineage of the lymphoma cells., Conclusion: Nodal presentation of NK/T-cell lymphoma, though rare, is diagnosable on the basis of fine needle aspiration biopsy alone, especially in view of its distinctive immunophenotype and EBV association. Recognition of the subtle but definite cytologic atypia of malignant lymphoid cells and presence of an appropriate background (including more eosinophils than usual), together with proper application of ancillary techniques, is crucial to arriving at a correct diagnosis.

Background: Papillary squamotransitional cell carcinoma of the lower female genital tract is a rare form of malignancy with distinctive histologic features. To my knowledge, its adenosquamous counterpart has not been reported before., Case: A 69-year-old woman presented with postmenopausal bleeding due to a bulky cervical tumor. The thin-layer cytology preparation (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) was of high cellularity and contained multiple small, papillary clusters of basaloid to columnar cells. Discernible fibrovascular cores were noted. In the background were many loosely dispersed, bland-looking columnar cells as well as cells of high grade squamous intraepithelial lesion (CIN 3). On a diligent search, scattered adenocarcinoma cells containing distinct intracytoplasmic vacuoles were found. There were a small number of dyskaryotic squamous cells with bizarre shapes, assuming "tadpolelike" morphology. Histologic examination of the tumor biopsy showed a papillary tumor with central fibrovascular cores covered with mitotically active, poorly differentiated squamous cells that imperceptibly merged with abortive glandular structures. Molecular analysis using the polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus type 16 DNA in the liquid-based cytology sample., Conclusion: Papillary adenosquamous carcinoma of the cervix shares some morphologic and even histogenetic overlaps with papillary squamotransitional cell carcinoma and, to a lesser extent, conventional endocervical adenocarcinoma. It may pose certain diagnostic dilemmas for the unwary. In view of its distinctive cytohistologic features, this tumor warrants greater recognition in gynecologic pathology.

Objective: To describe and reevaluate the fine needle aspiration cytology findings of pseudoangiomatous stromal hyperplasia (PASH) of the breast, with histologic, immunohistochemical and ultrastructural correlation., Study Design: The authors reviewed the clinical features, fine needle aspiration cytology, histology and immunohistochemical results in all cases of mammary PASH encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period from January 1998 to May 2002. Ultrastructural examination was carried out in a selected example. The findings were compared with those in the literature., Results: Four cases of PASH of the breast were encountered during the study period. The ages of the patients ranged from 34 to 56 years. One of them was a male presenting with gynecomastia. Only 2 cases had fine needle aspiration biopsies with a satisfactory cellular yield available for review. The cytospin preparations were of moderate cellularity and showed cohesive clusters of bland-looking ductal cells in a background of single, naked nuclei and some spindle cells containing fine chromatin and a discernible amount of cytoplasm. Occasional ductal cell clusters assuming a "staghorn" pattern, a feature commonly seen in fibroadenoma, were noted. Besides, there were scantly, loose and hypocellular stromal tissue fragments that contained spindle cells and occasional paired, elongated nuclei embedded in a fibrillary matrix. Histologic examination of the excisional biopsies confirmed the presence of PASH. It was characterized by many slitlike spaces rimmed by CD34-positive myofibroblasts/fibroblasts in a focally hyalinized stroma. Sometimes, ill-formed, fusiform aggregates of fibroblasts were also observed. Their fibroblastic nature was confirmed by electron microscopy., Conclusion: Fine needle aspiration cytology of PASH closely resembles that of fibroadenoma. Though subtle differences do exist, a definitive diagnosis is unlikely on the basis of the cytologic examination alone. PASH needs to be distinguished from borderline lesions, such as phyllodes tumor, and more sinister conditions, which sometimes have a similar cytologic appearance.

Objective: To describe the thin-layer cytology and diagnostic pitfalls of papillary squamotransitional cell carcinoma of the cervix, with clinical and histologic correlation., Study Design: The author reviewed the clinical findings, thin-layer cytology and histologic features of papillary squamotransitional cell carcinoma of the cervix encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period January 1998-March 2002. Strict histologic criteria (basaloid/transitional cell-like cells constituted > 70% of the tumor cell population and papillary/anastomosing, frondlike structures seen in > 70% of tumor tissue in superficial biopsies) were employed in defining this entity., Results: During the study period, 10 biopsy cases of carcinoma of the lower female genital tract (9 in cervix and 1 in vagina) fulfilled the above histologic criteria. Six of them had thin-layer cytology performed The preparations were often of moderate to high cellularity and contained three-dimensional, arborizing, papillary clusters of basal/parabasal cells. Discernible fibrovascular cores were sometimes identified. Occasionally at the papillary surface, the basaloid cells were aligned horizontally. High-power cytology of the tumor cells ranged from bland-looking to high grade squamous intraepithelial lesions (HSILs) and sometimes squamous cell carcinoma. Mitotic figures were commonly identified. Tumor diathesis and dyskeratotic cells were occasional. Koilocytosis was not observed. Subsequent tumor biopsies showed evidence of stromal invasion in 3 cases., Conclusion: Papillary squamotransitional cell carcinoma has a distinctive appearance in thin-layer cytologic preparations. The predominance of bland-looking basaloid cells or HSIL cells, together with scantiness of tumor diathesis and carcinoma cells, may lead to underdiagnosis. Recognition of the subtle cytologic features and clinical correlation are essential in arriving at a correct diagnosis.

Objective: To describe the thin-layer cytology (if available) and histologic findings of warty (condylomatous) carcinoma of the cervix, with molecular analysis for HPV screening., Study Design: The authors reviewed the clinical features, thin-layer cytology (if available) and histologic findings of all cases of warty carcinoma of the cervix encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period January 1998-April 2002. Molecular techniques for HPV screening using polymerase chain reaction were carried out on thin-layer cytology specimens or paraffin-embedded tumor tissue., Results: Three cases of warty carcinoma of the cervix were encountered during the study period. Thin-layer preparations (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) were available for 2 of them, and both were of moderate cellularity. There were small, cohesive clusters and syncytial sheets of tumor cells with vague papillary configurations. Dispersed squamous carcinoma cells and necrotic tumor debris (diathesis) were focally present in the background. The tumor cells were polygonal to elongated and contained oval nuclei, coarse chromatin and sometimes distinct nucleoli. Dyskeratotic tumor cells with bizarre shapes were also noted. Characteristically, there were also many koilocytes demonstrating extreme nuclear atypia and increased nuclear/cytoplasm ratio. These koilocytic cells possessed pleomorphic nuclei, distinct nucleoli and perinuclear cytoplasmic halos. Histologic examination of the tumor biopsies showed classic features of warty carcinoma, with papillary architecture, obvious koilocytic cytopathic change and focal stromal invasion. Molecular analysis confirmed the presence of HPV DNA in all the samples., Conclusion: Although koilocytes are rarely found in cervical cytology specimens of conventional squamous cell carcinoma, they are characteristically observed in warty carcinoma. A correct cytologic diagnosis is possible if one pays attention to the extreme koilocytic atypia, focal papillary configurations and otherwise classic features of squamous cell carcinoma. Abundance of koilocytes does not necessarily rule out invasive malignancy.

Objective: To describe the thin-layer cytology findings of small cell carcinoma of the low female genital tract, with histologic correlation and human papillomavirus (HPV) genotyping., Study Design: The authors reviewed the clinical findings, thin-layer cytology and histologic features of small cell carcinoma of the lower female genital tract (cervix or vagina) occurring in three postmenopausal Chinese women at Pamela Youde Nethersole Eastern Hospital, Hong Kong, over a four-year period, from January 1998 to December 2001. Molecular techniques for HPV screening and genotyping using the polymerase chain reaction and restriction fragment length polymorphism were employed on the cytologic specimens., Results: The thin-layer preparations were of moderate to high cellularity. There were loose aggregates of or isolated small round cells with a high nuclear/cytoplasmic ratio, thin but irregular nuclear membrane, hyperchromatic nuclei, inconspicuous nucleoli and scanty cytoplasm. Tumor cell cannibalism was commonly found. Small groups of tumor cells with nuclear molding were noted. There was also obvious tumor diathesis in the background. The necrotic debris was admixed with isolated small round cells, apoptotic bodies and nuclear dust. Associated koilocytosis or squamous intraepithelial lesions were not seen. Histologic examination of the tumor biopsies showed classic features of small cell carcinoma associated with squashing artifacts and vascularized stroma. Molecular analysis revealed the presence of HPV DNA (either type 18 or 16) in all the three liquid-based cytology samples., Conclusion: While the cytomorphologic features of small cell carcinoma of the cervix or vagina in thin-layer preparations are slightly different from those in conventional smears, due mainly to the absence of smearing effect, recognition of the subtle but characteristic appearance can enhance the accuracy of the cytologic diagnosis. The association between HPV and primary small cell carcinoma of the lower female genital tract was confirmed by this study.

Objective: To delineate the significance of detecting squamous cells in fine needle aspiration biopsy of breast lesions., Study Design: The authors reviewed 15 cases of fine needle aspiration cytology of the breast with a discernible number of squamous cells from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a seven-year period from the start of 1994 to the end of 2001. The cytologic features were correlated with clinical, radiologic and histologic findings, if any., Results: Among the 15 fine needle aspirates of the breast with a discernible number of squamous cells, 5 of them represented metaplastic carcinoma. The remaining consisted of 3 cases of fibroepithelial tumors, 1 case of duct ectasia, 3 cases of subareolar abscess, 2 cases of sclerosed intraduct papilloma and 1 case of benign breast cyst. In general, benign squamous cells were bland looking and often associated with anucleated squames. They were mitotically inactive and could show a good maturation pattern. Tumor cell cannibalism was rare. The presence of abundant, foamy macrophages in the background suggested a benign lesion. The primary diagnosis could be deduced by recognition of other features, such as the presence of myxoid stromal tissue and papillary structures. In contrast, malignant squamous cells in metaplastic carcinoma were more pleomorphic and mitotically active. Dyskeratosis and tumor cell cannibalism were obvious. Tumor diathesis and bizarre-shaped cells were sometimes found., Conclusion: Squamous cells occur in fine needle aspirates from a number of benign and malignant breast lesions. Benign conditions with abundant squamous cells may sometimes mimic malignant squamous lesions and vice versa. Careful assessment of the cytologic features of squamous cells and background appearance is crucial for achieving a correct diagnosis.

Background: Clear cell change, which may occur in a variety of thyroid neoplasms, is an uncommon finding. A fine needle aspirate of a follicular neoplasm showing extensive clear cell morphology is even more rarely described in the literature., Case: We report the fine needle aspiration cytology of a case of follicular neoplasm undergoing clear cell change due to intracellular accumulation of lipid and mucin. The cytology showed cohesive sheets of nondescript, round to oval cells having ample, pale-staining cytoplasm. Many of the tumor cells tended to cluster around branching capillaries. Adipocytelike cells with discrete cell borders, eccentric nuclei and cytoplasm distended by fat globules were frequently found. The cell block sections also showed scattered ghost outlines of these adipocytelike cells in a mucoid background. Similar findings were noted in the crush preparation of the freshly excised surgical specimen. Histologic examination confirmed the presence of a minimally invasive follicular carcinoma with clear cell change., Conclusion: Though the cytologic features of this peculiar morphologic variant of follicular neoplasm may mimic those of mesenchymal lesions or metastatic tumors, recognition of other subtle changes, together with ancillary investigations, is useful in arriving at a correct preoperative diagnosis.

Objective: To describe the fine needle aspiration cytology findings of fibroadenoma with multinucleated stromal giant cells, with histologic correlation., Study Design: The author reviewed the cytologic findings of two cases of fibroadenoma with multinucleated stromal giant cells from the file of Pamela Youde Nethersole Eastern Hospital in a six-year period from 1995 to the end of 2000. The diagnosis was confirmed by histologic examination of the lumpectomy specimens., Results: The two cases had similar cytologic findings. The direct smears contained cohesive clusters of bland-looking ductal cells arranged in a "staghorn" pattern. Numerous naked nuclei were also seen in the background. Also, there were occasional multinucleated giant cells in isolation. These giant cells contained 5-10 randomly arranged, round to oval nuclei, fine chromatin and sometimes distinct nucleoli. The cytoplasm was abundant and pale staining, and the cell border was ill defined. Associated epithelioid histiocytes and foamy macrophages were not seen. Histologic examination of the lumpectomy specimens showed architectural features of fibroadenoma with pericanalicular and intracanalicular patterns. In addition, scattered multinucleated giant cells with focal degenerative change were noted in the tumor stroma. Their stromal nature was confirmed by immunohistochemical study., Conclusion: Multinucleated stromal giant cells are rarely identified in fine needle aspiration biopsies of fibroadenoma. Recognition of this peculiar finding may help to avoid misdiagnosis of other, more sinister conditions, such as phyllodes tumor and metaplastic carcinoma.

Objective: To describe the fine needle aspiration cytology findings of apocrine carcinoma of breast and correlate them with the histologic appearance., Study Design: The author reviewed the fine needle aspiration cytology findings of two cases of pure apocrine carcinoma of the breast in the files of Pamela Youde Nethersole Eastern Hospital during a three-year period, 1998-2000., Results: The cytologic findings in both cases were similar. The smears were of moderate to high cellularity, consisting of predominantly dispersed or loosely cohesive tumor cells in a focally granular background. The carcinoma cells contained abundant, dense to granular cytoplasm; round or oval and sometimes eccentrically located nuclei; a smooth nuclear outline; evenly dispersed chromatin; and solitary macronucleoli. The cell borders were mostly discrete. In contrast to benign apocrine cells, the malignant cells showed nuclear overlapping, more frequent nuclear pleomorphism, increased nuclear/cytoplasmic ratios and occasional mitotic figures. Histologic examination of the excised specimens showed extensive, solid apocrine carcinoma in situ with focal stromal invasion., Conclusion: Apocrine carcinoma, a subtype of breast carcinoma characterized mainly by its cytologic features, needs to be distinguished from benign apocrine lesions or other eosinophilic and granular cell tumors of the breast. Recognition of the subtle cytologic differences renders a definitive preoperative diagnosis possible.

Objective: To describe the fine needle aspiration cytology findings of ductal breast carcinoma with neuroendocrine differentiation and correlate them with the histologic appearance., Study Design: We reviewed the cytologic features of eight cases of ductal carcinoma with neuroendocrine differentiation in the files of Pamela Youde Nethersole Eastern Hospital during the three-year period 1998-2000. Immunohistochemical study for neuroendocrine markers was performed, with ultrastructural correlation., Results: All cases showed similar cytologic features. The smears were of moderate to high cellularity with predominantly dispersed or loosely cohesive tumor cells. The carcinoma cells were mostly of low cytologic grade. They possessed round and relatively uniform, eccentric nuclei; finely stippled chromatin; sometimes small, distinct nucleoli; and discrete cell borders. Abundant eosinophilic and focally granular cytoplasm was a common finding. In some of the cases there was accentuation of staining in the paranuclear region; it correlated with aggregates of dense core neurosecretory granules seen ultrastructurally. Mucoid substance was seen in the background in some of the aspirates. Histologic examination of the tumors showed invasive ductal carcinoma with an organoid growth pattern and sometimes mucinous component. The neuroendocrine differentiation was confirmed immunohistochemically., Conclusion: Although this subtype of ductal carcinoma probably carries no significant prognostic value per se, it has distinct cytologic features, rendering preoperative diagnosis possible. Recognition of this entity is important in order to avoid the misdiagnosis of neuroendocrine tumor metastatic to the breast.

Objective: To describe the fine needle aspiration cytology findings of adenomyoepithelioma of the breast, with histologic correlation., Study Design: The author reviewed the cytologic findings of three cases of adenomyoepithelioma of the breast in the files of Pamela Youde Nethersole Eastern Hospital in a three-year period, 1998-2000. The diagnosis was confirmed by histologic examination, immunohistochemical study and electron microscopy., Results: All cases showed similar cytologic findings. The direct smears and cytospin preparations contained an obvious biphasic cell population. There were clusters and sheets of benign apocrine cells admixed with clumps of bland-looking oval to spindle cells. The apocrine cells contained larger, round nuclei; prominent solitary nucleoli; and ample eosinophilic, granular cytoplasm. In contrast, the spindle cells had oval nuclei, fine chromatin, inconspicuous nucleoli and scanty amphophilic cytoplasm. A small number of named nuclei and foamy macrophages was noted in the background. The characteristic stromal elements seen in fibroepithelial tumor of the breast were not found. The myoepithelial nature of the spindle cells was confirmed by immunohistochemical and ultrastructural studies. Subsequent simple mastectomy and wide local excision were performed on cases 1 and 2, respectively, revealing focal carcinomatous transformation in the adenomyoepitheliomas. The carcinoma cells, however, were not sampled in the initial cytologic specimens., Conclusion: The cytologic features of adenomyoepithelioma, though variable and subtle, are characteristic enough for diagnosis. Recognition of the peculiar combination of benign apocrine cells and clumps of nondescript spindle cells should alert the cytologist to this rare but distinct entity, which carries a propensity for malignant transformation.

Objective: To describe the fine needle aspiration cytology findings of invasive micropapillary carcinoma and correlate them with the histologic appearance., Study Design: We reviewed the cytologic features of three cases of pure invasive micropapillary carcinoma in the files of Pamela Youde Nethersole Eastern Hospital from 1998 through 2000. Immunohistochemical study for epithelial membrane antigen was performed retrospectively on the cell block sections. Ultrastructural examination was also carried out on one of the cases., Results: Two of the tumors were at pathologic stage II, and the remaining case was at stage III. Ipsilateral axillary lymph node metastases with similar morphology were seen in two of them. Cytologically, the smears were of moderate cellularity and composed of three-dimensional tumor cell balls, abortive and sometimes branching papillae, angulated tumor cell clusters, morules and occasional acini. Some of the tumor cell balls possessed scalloped borders. Focally, the tumor morules clustered together and were separated from each other by small, slitlike spaces. A small number of isolated malignant cells was also present in the background. The cell block sections showed mainly dispersed acini of tumor cells. The "reverse polarity" highlighted in histologic sections by immunohistochemical study for epithelial membrane antigen was not consistently demonstrated in the cell block material. Ultrastructural examination confirmed the focal presence of surface microvilli on the periphery of the tumor cell morules., Conclusion: Invasive micropapillary carcinoma of the breast possesses some subtle but distinctive cytologic features. With the help of cell block morphology and ancillary techniques, the preoperative suspicion of this rare subtype of ductal carcinoma, which carries a high propensity for lymphatic permeation, is possible.

Background: Nonneoplastic osteoclastlike giant cells are occasionally associated with carcinoma of the breast, pancreatobiliary and gastrointestinal systems. In the breast, this uncommon stromal response is seen mainly in invasive carcinoma with low grade cytology, among which invasive cribriform carcinoma is the classic example. Details of the fine needle aspiration cytology of this phenomenon, especially in thin-layer preparations, have been described rarely., Case: The fine needle aspiration cytology of an invasive cribriform carcinoma of the breast occurred in a 66-year-old woman. Cytology showed cohesive sheets and three-dimensional cribriform clusters of bland-looking and mitotically inactive ductal cells in a blood-stained background. Scattered multinucleated, osteoclastlike giant cells, some containing hemosiderin granules, were also seen. Myoepithelial cells and naked nuclei were not obvious. The cellular composition was more discernible in liquid-based cytologic preparations. Histologic examination of the excisional biopsy showed an invasive cribriform carcinoma associated with many osteoclastlike giant cells in a hypervascular stroma., Conclusion: In view of the extremely low grade cytology of the malignant ductal cells, invasive cribriform carcinoma may closely mimic benign proliferative breast diseases on fine needle aspiration biopsy. Recognition of this special relationship with osteoclastlike giant cells, which are rarely present in certain subtypes of breast cancer but not benign lesions, can help to arrive at a correct cytologic diagnosis.

Background: Arias-Stella reaction is commonly encountered in the endometrium during the gestational period and puerperium. Similar changes in the tubal epithelium are exceedingly rare. The cytologic findings of this phenomenon have never been described before., Case: Cytologic findings of Arias-Stella changes in the lining cells of a left paratubal cyst in a 41-year-old woman were examined. The smears showed occasional small clusters or isolated tubal epithelial cells consisting of a mixture of ciliated and secretory cells. Some of the ciliated cells showed a marked increase in nuclear and cytoplasmic volume and possessed coarse chromatin, prominent, angulated nucleoli, dense, amphophilic cytoplasm; and a discrete cell membrane. The nuclear membrane was still thin and regular, and these cells were mitotically inactive. The preservation of apical cilia in some of them ensured their benign nature. In some areas, clusters of secretory cells with an increase in both nuclear and cytoplasmic volume and ample, clear cytoplasm were also found. There were small, monolayered sheets of regular and benign-looking epithelial cells with a honeycomb arrangement, suggesting that the Arias-Stella atypia was focal., Conclusion: In view of the presence of scattered giant cells with coarse chromatin and angulated macronucleoli, a false positive cytologic diagnosis of malignancy can be made if one does not pay attention to the coexistence of apical cilia and other subtle changes, including the usual nuclear/cytoplasmic ratio, thin and regular nuclear membrane and absence of mitotic activity.

Background: Epithelial-myoepithelial carcinoma is a rare, low grade malignant tumor of the salivary glands. Histologically, it has a biphasic cellular composition and exhibits a high degree of differentiation. The fine needle aspiration cytology of this rare tumor is rarely described in the literature., Cases: We report the fine needle aspiration cytology of three epithelial-myoepithelial carcinomas, arising in the right parotid, left parotid and minor salivary gland of the hard palate. Cytology showed a biphasic population consisting of cells of ductal epithelial and myoepithelial origin arranged in small clusters and sheets. The myoepithelial cells had small, uniform nuclei; ample, clear cytoplasm and distinct cell borders, while the ductal epithelial cells had larger, mildly pleomorphic nuclei and scanty cytoplasm. These ductal cells tended to form tubules among background sheets of clear myoepithelial cells. This feature, if present, was an important diagnostic clue. Hyaline material surrounding cell clusters and focal adenoid cystic carcinoma-like areas with orangeophilic globules were also not uncommon., Conclusion: While the cytologic appearance of epithelial-myoepithelial carcinoma may closely mimic that of other salivary gland tumors, such as adenoid cystic carcinoma, pleomorphic adenoma and basal cell adenoma, certain peculiar cytologic features may allow a distinction to be made on fine needle aspiration biopsy.

Background: Myxopapillary ependymoma is a variant of ependymoma that usually occurs in the sacrococcygeal region. Histologically, it is characterized by arborizing papillary fronds of capillaries with mucinous stroma rimmed by ependymal cells. The fine needle aspiration cytology of this rare tumor is rarely described in the literature., Case: We report the fine needle aspiration cytology of a primary sacrococcygeal myxopapillary ependymoma occurring in a 18-year-old female. Cytology showed "fernlike" papillae and globules of mucinous and myxoid substance containing central capillaries. These structures were rimmed by one to several layers of mitotically inactive, mildly pleomorphic cuboidal to columnar cells with occasional pseudonuclear cytoplasmic inclusions. Some of these ependymal cells sent fibrillary processes toward the capillaries, suggestive of perivascular pseudorosettes. There were also numerous isolated tumor cells in the background., Conclusion: Because of the prominent mucinous elements and papillary fronds, myxopapillary ependymoma may mimic other myxoid or papillary tumors cytologically. Recognition of the characteristic cytologic features may allow a distinction to be made on fine needle aspiration biopsy.

The relationship between plasma levels of protein C, protein S and antithrombin III was examined in a group of normal pregnant Chinese women with singleton pregnancies to study the changes in the anticoagulant system in relation to pregnancy, labour and the puerperium. A significant correlation was found between protein C and antithrombin III both before labour and postpartum, and the ratio was close to unity. When the two groups are combined, a highly significant correlation was found (r = 0.758; p less than 0.001). The correlation is not observed at delivery when the ratio becomes very variable and in general greater than unity. The correlation between protein S and antithrombin III was 0.592 before labour and -0.532 at delivery, but both failed to reach statistical significance because of the small numbers. When postpartum concentration of protein C, protein S and antithrombin III is related to interval between sampling and delivery, significant correlation was found only with protein S. The results of this study suggest that the plasma level of protein C and probably protein S is correlated with that of antithrombin III during pregnancy, labour and the puerperium.