Role of biliary brush cytology in primary sclerosing cholangitis

OBJECTIVE: To assess the role of brush cytology in the routine evaluation of patients with primary sclerosing cholangitis (PSC). STUDY DESIGN: From January 1995 to June 2000, 64 brush cytology specimens were obtained from 21 patients who had at least one cytologic sample obtained during endoscopic retrograde cholangiography. All patients had a diagnosis of primary sclerosing cholangitis. Cases were classified as benign, atypical or malignant according to major cytologic criteria (nuclear contour and chromatin irregularities) and minor cytologic criteria (polarity, cellularity, nuclear enlargement, mitosis, increased nuclear/cytoplasmic ratio) used by us to diagnose biliary brush cytology. Follow-up was available in all cases. RESULTS: Diagnoses were benign (13), atypical (5) and malignant (3) on cytology. Follow-up of the 13 benign cases showed bile duct stones (2), gallbladder adenocarcinoma at cholecystectomy (1), ascending cholangitis (1) and clinically/cytologically by benign follow-up (9). Five of 13 benign cases had subsequent liver transplantation for liver failure, with explants showing changes of primary sclerosing cholangitis. Of the 3 malignant cases, 1 had carcinoma in situ on biopsy, with the explanted liver showing high grade dysplasia; the second patient had cholangiocarcinoma on explant; and the third had hepatocellular carcinoma on liver five needle aspiration. The 5 patients with atypical cytology were reclassified on review as reactive (3) and atypical not otherwise specified (2). Follow-up showed benign disease in 3 of 3 atypical cases reclassified as reactive; 2 of 2 reclassified as atypical not otherwise specified showed low grade dysplasia in the explant. CONCLUSION: The overall incidence of malignancy was low (3 of 21) in patients with PSC. Bile duct brushing is a sensitive method of detecting neoplasia in the setting of PSC when well-defined cytologic criteria are applied.     

Cytologic diagnosis of intraocular lymphoma in vitreous aspirates

OBJECTIVE: To evaluate the cytologic findings of vitreous fluids with atypical, suspicious for malignancy or malignant lymphoid cells to assess cytologic parameters that may help in reaching the diagnosis of intraoclular lymphoma. STUDY DESIGN: Vitreous aspirates with a malignant, suspicious for malignancy or atypical lymphoid population were identified from the files of Barnes-Jewish Hospital during the previous 11 years. Cytologic preparations were reviewed. Pertinent clinical information was obtained from medical records. RESULTS: Thirteen vitreous aspirates from 12 patients were included. The chief complaints included floaters, blurred vision and decreased visual aculity. Bilateral ocular involvement was present in 8 (67%) patients. Three patients had a history of an extraocular lymphoid malignancy. All patients underwent pars plana vitrectomy and collection of the vitreous aspirate. Cytologic diagnoses included: malignant lymphoma (9 of 13), suspicious for malignant lymphoma (3 of 13) and atypical lymphoid population (1 of 13). Most samples had high cellularity (11 of 13) and necrosis (9 of 13). Abnormal lymphoid cells were large (2-4 times the size of a lymphocyte) and had a high nuclear/cytoplasmic ratio, prominent nucleoli, irregular nuclear contours and a fine to coarse chromatin pattern. All cases with malignant cytology had abundant abnormal lymphoid cells; inconclusive cases had few. Immunocytochemistry for CD20 and CD45RO was performed on 9 of 13 samples and was conclusive in 6 of 9. CONCLUSION: Cytologic analysis of vitreous aspirates can be useful in diagnosing intraocular involvement by malignant lymphoma. Sparse cellularity is the main factor leading to inconclusive diagnoses. Immunostaining can be useful in confirming the lymphoid nature of the malignant cells.     

Proffered papers 14.00–15.00 Tuesday 16 September 2003

Background  ERCP-directed brush cytology is used to sample lesions of the pancreatic and biliary ducts and the ampulla of Vater. With conventional preparations, the sensitivity and specificity range from 44% to 63% and 80% to 98%, respectively, and increased N : C ratio, nuclear molding and loss of honeycombing are reliable features of malignancy. The performance and morphology of specimens prepared by ThinPrep, a liquid-based cytology technique is mostly unknown.
Methods  The laboratory information system was searched for all cases prepared by ThinPrep. Patient disease classification of benign or malignant was determined by linkage with the provincial cancer registry and was the gold standard against which sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. True positives and negatives were reviewed to identify predictive cytomorphologic features.
Results  Between 1996 and 2001, there were 149 ThinPrep specimens; 55 (37%) were reported as positive for malignancy and 94 (63%) as negative. Disease was classified as malignant in 86 (58%) patients and benign in 63 (42%). There were 42 false negative, 11 false positive, 52 true negative, and 44 true positive cytology results. Sensitivity was 51.2% (CI; 40.2 : 62.0), specificity 82.5% (CI; 70.5 : 90.6), and PPV and NPV 80.0% (CI; 66.6 : 89) and 55.3% (CI; 44.7 : 65.5), respectively. Cell groups with crowded, enlarged, irregular nuclei and nuclear features of vesicular chromatin and large, multiple irregular nucleoli correlated with malignant disease, while monolayered sheets of uniform columnar cells, regular nuclei and a finely granular chromatin correlated with benign disease.
Conclusions  The performance of ThinPrep brushings from this anatomic site equals conventional preparations. Cytomorphologic features of malignancy are more frequent and pronounced with ThinPrep.     

Proffered papers 14.00–15.00 Tuesday 16 September 2003 8 Ampullary,pancreatic and biliary duct exfoliative brush cytology prepared by the thinprep method: performance and morphology

Background ERCP‐directed brush cytology is used to sample lesions of the pancreatic and biliary ducts and the ampulla of Vater. With conventional preparations, the sensitivity and specificity range from 44% to 63% and 80% to 98%, respectively, and increased N : C ratio, nuclear molding and loss of honeycombing are reliable features of malignancy. The performance and morphology of specimens prepared by ThinPrep, a liquid‐based cytology technique is mostly unknown. Methods The laboratory information system was searched for all cases prepared by ThinPrep. Patient disease classification of benign or malignant was determined by linkage with the provincial cancer registry and was the gold standard against which sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. True positives and negatives were reviewed to identify predictive cytomorphologic features. Results Between 1996 and 2001, there were 149 ThinPrep specimens; 55 (37%) were reported as positive for malignancy and 94 (63%) as negative. Disease was classified as malignant in 86 (58%) patients and benign in 63 (42%). There were 42 false negative, 11 false positive, 52 true negative, and 44 true positive cytology results. Sensitivity was 51.2% (CI; 40.2 : 62.0), specificity 82.5% (CI; 70.5 : 90.6), and PPV and NPV 80.0% (CI; 66.6 : 89) and 55.3% (CI; 44.7 : 65.5), respectively. Cell groups with crowded, enlarged, irregular nuclei and nuclear features of vesicular chromatin and large, multiple irregular nucleoli correlated with malignant disease, while monolayered sheets of uniform columnar cells, regular nuclei and a finely granular chromatin correlated with benign disease. Conclusions The performance of ThinPrep brushings from this anatomic site equals conventional preparations. Cytomorphologic features of malignancy are more frequent and pronounced with ThinPrep.     

The gray zone in breast fine needle aspiration cytology. How to report on it?

OBJECTIVE: To study the "gray zone" in breast fine needle aspiration cytology in which an unequivocal diagnosis cannot be reached with fine needle aspiration cytology findings. STUDY DESIGN: This study compared cytology and histopathology of 72 breast lesions in which an initial cytologic diagnosis of atypia was given. RESULTS: There were 36 benign (50%) and 36 malignant (50%) histologic biopsy cases in the cytologic atypia group. Anisonucleosis, chromatin and nuclear membrane irregularity, and presence of myoepithelial cells were significantly different in benign and malignant cases. CONCLUSION: The gray zone in breast fine needle aspiration cytology is a broad spectrum that changes from proliferative fibrocystic disease to sclerosing adenosis to malignancy. Diagnosing gray zone pathology as atypical in fine needle aspiration cytology causes no delay in treatment as excisional biopsy is recommended for all equivocal cases.     

Wilms' tumor. Role of fine needle aspiration and DNA ploidy by image analysis in prognostication

OBJECTIVE: To evaluate the utility of cytomorphologic features and DNA ploidy estimation in fine needle aspirates (FNAs), from Wilms' tumors for prognostication. STUDY DESIGN: Twenty-three cases of Wilms' tumor having FNA and follow-up data were selected. Cytomorphology was analyzed by two observers. DNA ploidy was determined in 19 cases by image cytometry by destaining Papanicolaou-stained slides and restaining with Feulgen stain. Various parameters and patient outcomes were compared, and statistical evaluation was done. RESULTS: Poor outcome (12/23 cases) was associated with age < 2 years (P = .01), severe pleomorphism of blastemal cells (4/23 cases, P < .05), very large nucleoli (5/23 cases, P = .075), atypical mitosis (6/23 cases, P = .032) and aneuploidy/tetraploidy of tumor cells (6/29 cases, P = .005). Term unfavorable cytology is proposed when a combination of severe pleomorphism, very large nucleoli and atypical mitosis is seen in FNA smears. Four Wilms' tumor FNAs were characterized as showing unfavorable cytology, and all had a poor outcome (P = .0351). Three of the six cases with aneuploid/tetraploid features also showed unfavorable cytology. CONCLUSION: Unfavorable cytology and aneuploidy/tetraploidy in FNA smears of Wilms' tumor are associated with a poor prognosis.     

Warty (condylomatous) carcinoma of the cervix. A review of 3 cases with emphasis on thin-layer cytology and molecular analysis for HPV

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.     

Müllerian carcinofibroma of the uterus. A case report.

BACKGROUND: Müllerian carcinofibroma is composed of malignant epithelial tumor (cancer) and benign mesenchymal tumors. It is the least frequent among mixed müllerian tumors. There are eight reported cases of carcinofibroma or cases showing similar histology, with only two of these cases recurrent. CASE: A case of müllerian carcinofibroma arose in the uterine body. The patient was an 83-year-old, postmenopausal female whose endometrial cytology revealed cell clusters of adenocarcinoma and scattered nonepithelial cells with enlarged nuclei without nuclear atypism or mitosis. Histology of the resected uterus showed a mixture of well to poorly differentiated adenocarcinoma, and fibromatous and leiomyomatous nonepithelial tumors without a transition between them. There was no sign of recurrence nine months after hysterectomy. CONCLUSION: Müllerian carcinofibroma seems to have a better prognosis than malignant mixed müllerian tumor. When both cancer cells and an abundance of nonepithelial cells are seen on gynecologic cytology, it may be important to consider mixed müllerian tumor and to differentiate müllerian carcinofibroma from malignant mixed Müllerian tumor by careful observation of the nuclear size, nucleoli, nuclear atypism and mitosis of the nonepithelial cells.     

Follow-up study of atypical glandular cells in gynecologic cytology using conventional Pap smears and liquid-based preparations: impact of the Bethesda System 2001

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.     

The cytopathologic diagnosis of esophageal adenocarcinoma

The diagnostic cytologic features were analyzed in 18 cases of histopathologically proven esophageal adenocarcinoma accessioned at the Johns Hopkins Hospital between 1975 and 1988 for which cytologic material was available. Primary esophageal adenocarcinoma was diagnosed in 15 of 18 cytologic specimens (83%); in 3 cases (17%), carcinoma was suspected, but the changes were nondiagnostic. The most consistent cytologic changes included both architectural features (loss of orientation and nuclear crowding) and criteria of malignancy (high nuclear/cytoplasmic ratios and prominent nucleoli). In the 15 diagnostic cases, the nucleoli were small in 8 and round in 11; in the majority of these cases, the nuclei contained one to three nucleoli. In addition, nuclear and cytoplasmic molding was seen in 9 of these 15 cases, hyperchromasia was present in 8, coarse chromatin clumps were seen in 5, and tissue fragments tended to be multilayered. Review of the three nondiagnostic cases showed that scant material was present in two; the third case had abundant material, but only nondiagnostic changes, suggesting a sampling error. Barrett mucosa was seen in 7 of the 18 cases. These cases show that esophageal adenocarcinoma can be reliably diagnosed on cytologic preparations, based on the consistent architectural features and the usual cellular criteria of malignancy.     

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions
This paper reports the cytological findings based on air-dried smears in a retrospective series of 143 cases of endocervical adenocarcinoma, combined adenocarcinoma-squamous carcinoma and adenosquamous carcinoma drawn from the files of the BC Cancer Registry. Cervical cytology smears were available before biopsy in 131 patients, but in 18 cases the cytology showed no abnormality. Malignant changes or high-grade atypia of glandular and/or squamous cells (defined as moderate or severe dyskaryosis) were detected in 103 cases. In 46 cases, only a high-grade squamous abnormality was detected. Low-grade glandular and/or squamous lesions were detected in nine cases and one showed atypical endometrial-type glands. The cervical smears of 64 cases were reviewed in detail to determine the important cytomorphological criteria of in situ and invasive adenocarcinoma in air-dried smears, the technique used for preparing PAP smears in British Columbia. Endocervical cells were absent in four cases. Numerous (>10) groups of glandular cells were present in 51 cases. Important clues to the diagnosis of adenocarcinoma included crowding of nuclei, stratification of nuclei, loss of polarity, syncytial balls and papillary groups of glandular cells, nuclear enlargement, nuclear pleomorphism, and the presence of free-lying atypical glandular cells. Nuclear hyperchromatism, chromatin pattern, nuclear borders, nuclear membranes, and numbers and morphology of nucleoli were not helpful criteria in our material. Criteria enabling reliable distinction between in situ and invasive adenocarcinoma and/or mixed adenocarcinoma-squamous carcinoma could not be established.     

Calculus artifact. A challenge in urinary cytology.

OBJECTIVE: To retrospectively review calculus artifact and compare it with instrument artifact and papillary transitional cell carcinoma (TCC). STUDY DESIGN: Voided urine specimens from patients with calculi (65), TCC (low grade, 10, high grade, 34) and history of prior instrumentation (12) were studied. RESULTS: Nineteen specimens of calculus artifact had unremarkable cytology. Forty-six specimens had abnormal single cells or papillary clusters and cell balls or a mixture of both. The papillary groups had smooth as well as irregular borders, a cytoplasmic collar and cells with occasional cytoplasmic vacuoles, slightly increased nuclear/cytoplasmic (N/C) ratio and inconspicuous nucleoli. Squamous preponderance and birefringent crystals were seen. In instrumentation artifact, papillary clusters or three-dimensional cell balls had smooth borders, cytoplasmic collars, an occasional cytoplasmic vacuole, normal N/C ratio, regular nuclear membrane and finely granular nuclear chromatin. In TCC, papillary clusters with loss of polarity and irregular borders were present in both grades but were predominant in low grade TCC. No cytoplasmic collar was noted. In high grade TCC, single cells and nuclear alterations were more pronounced, with increased N/C ratio, hyperchromasia, coarse chromatin, irregular nuclear envelopes, prominent nucleoli and rare mitosis. CONCLUSION: Calculus artifact can produce papillary clusters masquerading as papillary TCC. Unlike instrument artifact, there may be significant nuclear atypia, which could be reversible. To avoid diagnostic pitfalls, further investigation is suggested after removal of calculus.     

Diagnostic value of qualitative and quantitative variables in thyroid lesions

Two hundred and thirty-three thyroid lesions were studied by fine needle aspiration (FNA) cytology using standard cytologic criteria available in the literature. These included 114 cases of nodular colloid goitre (NCG), 47 cases of Hashimoto's thyroiditis (HT), 12 follicular adenomas (FAd), five cases of subacute thyroiditis and three cases of thyrotoxicosis among the benign lesions. The malignant lesions seen were 30 cases of papillary carcinoma (PCa), 16 follicular carcinomas (FCa), three cases with double lesions, e.g. papillary carcinoma with coexisting NCG, and three of papillary carcinoma with HT. Emphasis was given to eight qualitative and quantitative (morphometric) variables in these various thyroid lesions. Cell measurements were done using a Visopan Lux projection microscope. The three qualitative variables included type of nuclear membrane (regular/irregular), type of nuclear chromatin and the presence or absence of conspicuous nucleoli. The quantitative variables studied were nuclear diameter, nuclear area, cytoplasmic diameter, cytoplasmic area & N/C ratio. Statistical analysis was performed in order to know whether the standard cytologic criteria used at FNA cytology in the literature (increased cellularity, microfollicles, increased N/C ratio, absence of significant haemosiderin-laden macrophages and scanty colloid) could differentiate a follicular adenoma from a follicular carcinoma. A statistical analysis was also performed to establish the utility of the qualitative and quantitative variables. The results showed that none of the standard cytologic criteria applied could differentiate follicular adenoma from a follicular carcinoma. With regard to qualitative variables, irregularity of nuclear membrane and presence of conspicuous nucleoli were most significant in papillary carcinoma, followed by follicular carcinoma, then by follicular adenoma; these features being hardly evident in nodular colloid goitre and Hashimoto's thyroiditis. A coarse nuclear chromatin was most significant in follicular carcinomas followed by follicular adenomas. It was less obvious in the benign conditions, but more prominent in Hashimoto's thyroiditis compared with a goitre. It was also not obvious in a papillary carcinoma. Of the quantitative variables, all measurements were greatest in PCa > FCa > FAd > NCG = HT. When differentiating follicular adenoma from follicular carcinoma the qualitative variables of significance were the presence or absence of nucleoli, the chromatin pattern and regularity/irregularity of nuclear membrane; the nuclear area was the most important feature among quantitative variables.     

Fine needle aspiration cytology of hepatoblastoma. Recognition of subtypes on cytomorphology

OBJECTIVE: To delineate the cytomorphologic appearances of hepatoblastoma (HBL) in the largest series to date and to evaluate the feasibility of subtyping on fine needle aspiration cytology (FNAC). STUDY DESIGN: Papanicolaou- and May-Grünwald-Giemsa-stained smears of aspirates from 26 cases of HBL were analyzed by 2 observers. Histologic material, available in 15 cases, was correlated. A cytology grouping system was proposed on the basis of which all cases were classified. RESULTS: The ages of the patients ranged from 4 months to 9 years. Twenty-five cases were categorized as epithelial HBL, with epithelial fragments showing a trabecular arrangement and acinar formation in all, and extramedullary hemopoiesis in 20 cases. It was possible to differentiate fetal and embryonal areas on FNAC. Six cases showed only fetal elements (cytology group F), characterized by cells with abundant cytoplasm and a small, rounded nucleus resembling a normal fetal hepatocyte. The chromatin was finely granular, with a single, central nucleolus. Pleomorphism and mitoses were not seen, and the nuclear/cytoplasmic ratio was < or = 1/3. Fourteen cases showed, in addition to fetal elements, an embryonal component characterized by cells with scant cytoplasm, a pleomorphic nucleus, N/C ratio of > or = 3/1, coarsely granular chromatin and 2-4 angulated nucleoli. Mitoses were seen in these cells (1-4/1,000 cells). Of these 14 cases, 6 showed predominantly fetal and scant embryonal cells, while 8 cases showed fetal and embryonal components in equal amounts (cytology groups Fe and FE, respectively). Four cases showed predominantly embryonal cells (cytology group E). One case was unclassifiable (U). On histology, 8 of 14 cases were of mixed epithelial and mesenchymal type, but mesenchymal tissue was not seen on the corresponding cytology. The cytology grouping system correlated well with histology. One case was small cell undifferentiated HBL and resembled a round cell tumor without differentiation. Macrotrabecular arrangement was not seen on cytology but was seen on histology in 1 case. CONCLUSION: Epithelial HBL can be easily diagnosed in aspirates further classified into fetal and embryonal subtypes, which may be of prognostic relevance. The proposed cytology grouping system is effective in semiquantification of the observed subtypes.     

Correlation between the papanicolaou stain and the Wright-Giemsa stain in body fluids: a quality assurance study

OBJECTIVE: To compare the use of Papanicolaou and Wright-Giemsa stains for the evaluation of body fluids in cytology and hematology laboratories and determine whether other factors account for discrepancies in diagnosis. STUDY DESIGN: We retrospectively reviewed cytopathology reports of peritoneal, pleural, and cerebrospinal fluids received by hematology and cytology laboratories for 1 year. Cases were divided into 3 categories-benign, atypical, and malignant--and slides of discrepant diagnoses were reviewed. RESULTS: During this period, 198 of 3212 (0.61%) cases received by the hematology laboratory and 252 of 4402 (0.57%) cases received by the cytology laboratory were diagnosed as malignant or atypical. Of 3212 cases simultaneously received by the cytology and hematology laboratories, 17 diagnosed as malignant by hematology were diagnosed benign by cytology (sensitivity 96%). Sixteen cases diagnosed as malignant by cytology were diagnosed as benign by hematology (sensitivity 97%). No benign cases were diagnosed as malignant (specificity 100%). Review of the glass slides of the discrepant cases revealed 8 cases undercalled by hematology and 7 cases undercalled by cytology. CONCLUSION: Papanicolaou stain is superior for carcinoma and Wright-Giemsa stain for hematopoietic disorders, but used together they may reduce false negative results. Delays in processing, staining technique, and interobserver variability contribute to discrepancy.     

False positive diagnosis in conventional and liquid-based cervical specimens

OBJECTIVE: To examine conventional and liquid-based cervical smears falsely diagnosed as malignant at our institution and to investigate, through cytologic-histologic correlation, factors influencing false positive diagnoses. STUDY DESIGN: Cervical cytologic diagnoses of malignancy from May 1, 1995, to April 30, 2001, were retrieved through a computer search. A retrospective review of hospital records and pathology reports was performed. Cases identified as false positives were reviewed and correlated with histologic follow-up specimens. RESULTS: A group of 68 patients with malignancy reported on cervical smears and with histologic follow-up was identified. Conventional smears numbered 32 (47%); the remaining 36 (53%) were liquid-based samples. Of the total, 7 false positive cases (10.3%) were identified in 4 conventional and 3 liquid-based preparations. Cytologic diagnosis in these cases was squamous cell carcinoma in 5 and adenocarcinoma in 2. On histologic follow-up, all 7 patients were ultimately found to have high grade squamous intraepithelial lesions (HSILs) without invasion. Review of the original slides confirmed most, or all, of the following features in all cases: major cellular pleomorphism, extensive cytoplasmic keratinization, intense nuclear pyknosis, background necrosis and severe atrophy. CONCLUSION: There was no significant difference in rates of false positive diagnoses between conventional (12.5%) and liquid-based (8.3%) samples. The chief reason for overdiagnosis in this series was the capacity of HSIL to exfoliate cells mimicking invasive malignancy, particularly when keratinized and especially in an atrophic milieu. The other cause of false positivity was superimposition of inflammation and atypical reparative change on a background of HSIL, which then suggested invasion.     

Peripheral T-cell lymphoma not otherwise specified vs. Hodgkin's lymphoma on fine needle aspiration cytology

OBJECTIVE: To study the morphologic features of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) on fine needle aspiration cytology (FNAC) smears and to identify cytomorphologic features that would delineate them from features of cases of Hodgkin's lymphoma (HL). CONCLUSION: Fourteen cases each of PTCL, NOS, and HL with adequate FNAC smears were retrieved. These cases were analyzed for 12 cytomorphologic features: presence of atypical lymphoid cells, percentage of large lymphoid cells, lymphoid cells with cleaved/indented nuclei, typical Reed-Sternberg (RS) cells, mononuclear cells with prominent eosinophilic macronucleoli, mononuclear cells with prominent nucleoli, histiocytes, eosinophils, plasma cells, polymorphonuclear leukocytes, vessels and perivascular clustering of atypical mononuclear/atypical lymphoid cells. Each of these features was evaluated for its presence or absence and was semiquantitated on a scale from 0 to +3. RESULTS: The presence of atypical lymphoid cells with a spectrum ranging from small to intermediate and large was seen exclusively in cases of PTCL. Lymphoid cells with cleaved or indented nuclei, endothelium-lined vessels with perivascular clustering of tumor cells and absence of typical RS cells, and mononuclear cells with prominent eosinophilic macronucleoli emerged as the parameters significant in not only diagnosing cases of PTCL, NOS, but also in their delineation from cases of HL. CONCLUSION: A careful analysis of cytomorphologic features can be useful in at least suggesting a diagnosis of PTCL and help to distinguish that diagnosis from HL, which the features may mimic. Immunophenotyping and molecular studies are important in arriving at a definitive diagnosis.     

Cytologic studies of the fallopian tube in patients undergoing salpingo-oophorectomy

Background

Mounting evidence suggests the fallopian tube as the origin for ovarian high grade serous carcinoma (HGSC). We attempted to identify the tubal cytological features that allow us to distinguish malignant from benign conditions.

Methods

Tubal specimens (n = 56) were collected from patients who underwent bilateral salpingo-oophorectomy (BSO) due to various clinical indications. A standard procedure to collect fallopian tube brushings from freshly received surgical specimens was developed. Cytological diagnoses were classified into three categories: benign, atypical, and suspicious for malignancy/malignant. Cytological variables of individual cells and epithelia were subjected to statistical analysis. The fallopian tube histology was used as diagnostic reference for confirmation of cytology diagnosis.

Results

Among the 56 fallopian tube specimens, 2 (3.7 %) showed inadequate cellularity preventing further evaluation, 11 (20.4 %) were diagnosed as malignant or suspicious of malignancy, 7 were atypical, and 36 were benign. The presence of three dimensional clusters (p < 0.0001, Fisher’s Exact Test), or prominent nucleoli (p = 0.0252, Fisher Exact test) was highly correlated with the diagnosis of malignancy. The suspicious malignant/malignant cytological diagnosis was also highly correlated with presence of HGSC with or without serous tubal intraepithelial carcinoma (STIC).

Conclusions

Tubal cytology may be useful for ovarian cancer screening and early detection.

     

Analysis of fine needle aspiration cytology of the breast: a review of 1,297 cases and correlation with histologic diagnoses

OBJECTIVE: To evaluate the accuracy of fine needle aspiration (FNA) cytology of the breast and to ascertain its usefulness. STUDY DESIGN: The authors reviewed 1,297 cases of FNA cytology of the breast which were performed at Chonnam National University Hospital from 1999 to 2002. Cytologic diagnoses were compared with histologic diagnoses in 457 cases that underwent both cytologic and histologic examination. RESULTS: Of 1,297 cases, 1,201 (92.6%) were satisfactory and 96 (7.4%) unsatisfactory. Subsequent histologic examination was performed on 291 cases (29.7%) out of 981 "benign" lesions, 28 (73.7%) of 38 "suspicious," 124 (68.1%) of 182 "malignant" and 14 (14.6%) of 96 "unsatisfactory." FNA cytology revealed 77.7% sensitivity, 99.2% specificity, 98.4% positive predictive value and 88.0% negative predictive value. Diagnostic accuracy was 91.1%. Of the 291 benign cases on cytology, 35 cases were malignancy on histology. Of the 124 cases reported as malignant, 2 were benign. Interpretive error was the leading cause of false positive diagnoses. CONCLUSION: Although FNA cytology is a useful diagnostic procedure for the evaluation of breast lesions, it should be combined with other diagnostic modalities, such as physical examination, ultrasonography and mammography.     

Spontaneous Infarction of an Intraductal Papilloma of the Breast: Cytological Presentation On Fine Needle Aspiration

A relatively rare case of spontaneous infarction of an intraductal papilloma of the breast is presented which was considered to be suspicious for malignancy on fine needle aspiration (FNA) cytology. The aspirate revealed several groups of atypical cells featuring a high nuclear-cytoplasmic ratio, coarsely granular chromatin, and somewhat prominent nucleoli. There was abundant necrotic cellular debris in the background. These cellular features were considered evidence of ductal carcinoma of the breast. The correct diagnosis was made by open biopsy which revealed necrosis involving the breast due to infarction of an intraductal papilloma.