Fine needle aspiration cytodiagnosis of Hodgkin's disease and its subtypes. I. Scope and limitations

The fine needle aspiration (FNA) smears and paraffin-embedded sections from 89 cases with a cytologic and histologic diagnosis of Hodgkin's disease (HD) and 27 cases with minor or major cytohistologic discrepancies were reviewed. The accuracy of the initial cytologic study was found to be 91.8% for diagnosing HD and 58.1% for classifying its subtypes. Following review, 87 of the 89 agreement cases remained classified as HD. Of the 27 cases with initial cytohistologic discrepancies, 12 were classified as HD and 10 were categorized as lymphocytic or non-Hodgkin's lymphoma by both cytology and histology upon review. Following review, the accuracy of FNA cytology for the diagnosis of HD improved to 98.0%, with 71.4% correct subtyping. The greatest limitation of cytologic subtyping was in cases of nodular sclerotic HD: only 3 of 17 cases could be subtyped even after review. The cytomorphologic features of the HD subtypes are described, and the difficulties encountered in the cytodiagnosis of HD are discussed at length. The results of this study indicate that FNA cytology is a useful tool not only for the diagnosis of HD, but also for its subtyping.     

Diagnosis of the rare solid and papillary epithelial neoplasm of the pancreas by fine needle aspiration cytology. Light and electron microscopic study of a case

A case of the rare solid and cystic papillary tumor of the pancreas in a young woman is described. The diagnosis was made by fine needle aspiration cytology, with electron microscopic examination of the needle washings. The preoperative cytologic diagnosis enabled appropriate surgical treatment to be planned and carried out without undue delay. It is important to distinguish this rare tumor from other pancreatic tumors with similar cytohistologic features since, if diagnosed correctly and managed surgically, this neoplasm is associated with a good prognosis.     

Fine needle aspiration cytology of parathyroid adenoma. A review of seven cases

The value of fine needle aspiration (FNA) cytology in the diagnosis of parathyroid adenomas was demonstrated by a cytohistologic review of seven cases. The cytologic patterns, which were characterized by numerous, mostly isolated epithelial cells and naked nuclei showing anisokaryosis and multiple nucleoli, were consistent with the histologic findings in this neoplasm, which should be considered in the differential (FNA) diagnosis of masses in the neck region. The only diagnostic problem is its differentiation from follicular thyroid neoplasms.     

Preoperative diagnosis of bilateral renal oncocytoma by needle aspiration cytology. A case report

The cytohistologic and ultrastructural findings in a case of bilateral renal oncocytoma diagnosed by needle aspiration cytology are presented. This case appears to be the first reported example in which the preoperative needle aspiration cytologic diagnosis of bilateral renal oncocytoma was made due to the presence of characteristic tumor cells that were seen singly or in small clusters with rounded polygonal shapes and abundant eosinophilic granular cytoplasm. The preoperative diagnosis of bilateral oncocytoma permitted a timely decision as to the appropriate management in this case.     

Giant cell carcinoma of the lung. Report of a case with cytohistologic and clinical correlation

BACKGROUND: Giant cell carcinoma (GCC) of the lung is an unusual tumor characterized by an aggressive outcome. CASE: A peripheral lung tumor was observed in an elderly male. At presentation the clinical symptoms were cough, thoracic pain and hemoptysis. Chest roentgenography showed a left pleural effusion and neutrophilia in the blood. Bronchoscopic examination showed a peripheral tumor mass that could not be biopsied. Bronchoalveolar lavage was negative. The patient underwent a cerebrovascular accident and died. The autopsy showed a peripheral giant cell tumor of the left lung that involved regional and mediastinal lymph nodes. Touch imprints showed tridimensional clusters of pleomorphic and large cells, some of which were multinucleated, containing leukocytes in their cytoplasm. CONCLUSION: This case illustrates the typical cytohistologic features of GCT of the lung, which should be considered in the differential diagnosis of any peripheral lung tumor composed of large cells. Clinical correlation is helpful in reaching the correct diagnosis.     

Combined hepatocellular-cholangiocarcinoma. Diagnostic challenge in hepatic fine needle aspiration biopsy

OBJECTIVE: To study the cytohistologic features of combined hepatocellular-cholangiocarcinoma (CHCC-CC) in fine needle aspiration biopsy (FNAB) material. STUDY DESIGN: Six hepatic FNAB cases with cell blocks (five) and hepatic resections (two) were analyzed cytohistologically and immunohistochemically. RESULTS: The six cases were diagnosed as CHCC-CC based on clinicopathologic correlation. Unequivocal hepatocellular carcinoma (HCC) cells corresponding to Edmondson and Steiner's grade 3 lesions were identified in the FNAB in three instances. Adenocarcinoma, represented by cohesive columnar cells with ovoid, basal nuclei displaying nuclear palisading, acini and/or papillary structures with variable intracytoplasmic intraacinar or brush border mucin production, was identified in all cases. Intermediate cells with hybrid/polymorphic cytologic features straddling malignant hepatocytes and glandular cells were identified in five instances. Tissue alpha-fetoprotein was negative. There was brush border and/or diffuse cytoplasmic p-carcinoembryonic antigen immunoreactivity in the glandular elements. CONCLUSION: FNAB diagnosis of CHCC-CC is possible if the clinical, cytohistologic and immunohistochemical findings support the presence of HCC and adenocarcinoma. Intermediate cells pose a great challenge to recognize and define: they tend to lose the classic cytologic features of malignant hepatocytes and acquire glandular characteristics. At the very least, there should be a high index of suspicion. These cases underscore the necessity for clinicopathologic correlation in enhancing the precision of FNAB diagnoses.     

Correlation of immunocytochemical and immunohistochemical determination of estrogen and progesterone receptors in breast cancer

OBJECTIVE: To evaluate prospectively the degree of correlation between immunocytochemical (ICC) and immunohistochemical (IHC) determination of estrogen (ER) and progesterone receptors (PR) in breast cancer. STUDY DESIGN: Fine needle aspiration cytology (FNAC) of 101 primary breast cancers were immunostained for ER and PR. They were compared with similar determinations in formalin-fixed paraffin sections of biopsies from the same patients. In cases of discrepancy, the histologic result was considered the gold standard. RESULTS: For ER a cytohistologic correlation of 94%, with a sensitivity of 96.1% and specificity of 86.9%, was found. For PR the cytohistologic correlation was 71.2%, with a sensitivity of 65.7% and specificity of 83.8%. CONCLUSION: ICC determination of hormone receptors in routinely fixed smears obtained by FNAC is a simple method that correlates adequately with the results of IHC determinations, especially for ER.     

Fine needle aspiration of toxoplasmic (Piringer-Kuchinka) lymphadenitis: a cytohistologic correlation study

OBJECTIVE: To define the cytomorphologic features of toxoplasmic lymphadenitis (TL) and to establish the diagnostic sensitivity and specificity of the cytologic diagnosis. STUDY DESIGN: A cytohistologic correlation study of 11 patients in which a histologic diagnosis of TL was available. These cases were analyzed in a blind study among other cases of nonneoplastic lymphadenopathies. The results of the study are expressed in terms of diagnostic sensitivity and specificity. Although not included in the study, 3 other cases of TL with serologic confirmation were also reviewed. RESULTS: Microgranulomas were a characteristic finding in TL. They consisted of small clusters of epithelioid histiocytes, each with abundant cytoplasm and an eccentric, oval nucleus. Diff-Quik-stained smears had cytoplasm with particularly pale staining and a homogeneous appearance. Most microgranulomas had a monotonous appearance with a few, small lymphocytes accompanying the epithelioid cells. No necrosis, suppurative changes or giant cells were present. Blind examination by 4 reviewers led to a correct diagnosis of TL in 9 of the 11 cases. Eight of the 9 cases were recognized by each of the 4 reviewers. One false positive diagnosis was made by 1 of the reviewers. The sensitivity of the diagnosis was 72.7-81.8% and the specificity 98.8-100%. CONCLUSION: This study showed high sensitivity and specificity for the cytologic diagnosis of TL. Given the appropriate clinical context, the presence of characteristic epithelioid microgranulomas permits a diagnosis of TL. The cytologic diagnosis can be easily confirmed with serologic studies, thereby avoiding biopsy.     

Accuracy of cytologic diagnosis of central nervous system neoplasms in sterotactic biopsies

The cytohistologic correlation is reported for 112 of the 128 consecutive sterotactic aspiration biopsies performed on patients with clinical and neuroradiologic evidence of brain tumors investigated at the Neurosurgery Department, Karolinska Hospital, from 1976 to 1979. The cytodiagnostic accuracy of benign and malignant tumors was 87% when adequate cell material was obtained. In 17 benign tumors of the sellar region, the diagnostic rate was 88%; cytologic examination independent of histologic biopsy is feasible in this area. The cytodiagnostic accuracy for 95 malignant central nervous system (CNS) tumors was 87% after adjusting for the appreciable sampling error inherent in the use of a stereotactic procedure during the early phase of the study. Two histopathologically proven infectious lesions were reported cytologically as benign. The main microscopic problems were the recognition of highly differentiated astroglial neoplasms and the differential diagnosis between poorly differentiated brain neoplasms and metastases to the CNS. Cytodiagnostic accuracy of CNS tumors can be increased by technical improvements in the stereotactic device, diagnostic experience and immunochemical staining.     

Cystoscopic biopsy supernate. A new cytologic approach for diagnosing urothelial carcinoma in situ

The examination of cystoscopic biopsy supernates is a new cytologic procedure that can aid the urologist in the differential diagnosis of urothelial carcinoma in situ (CIS) and cystitis. Within the past two years, the Cytodiagnostic Urinalysis Laboratory has received 79 cystoscopic biopsy supernate specimens from 29 patients; these were prepared using a membrane filtration technique and stained with a modified Papanicolaou method. Positive diagnoses were rendered on 17 (21.5%) specimens, including 7 (41%) CIS and 10 (59%) papillary neoplasms. An 87% cytohistologic correlation was seen. Of the 17 cases with biopsy specimens that were denuded and thus nondiagnostic, 11 had negative supernate cytologies and 6 had positive cytologic diagnoses. Half of these positive specimens were diagnosed as CIS. Because urothelial CIS is often a friable lesion that yields denuded bladder biopsies, the cytologic examination of cystoscopic biopsy supernates offers a valuable adjunctive method for diagnosing urothelial CIS on otherwise lost cellular material.     

Atypical glandular cells of undetermined significance on cervical smears. A study with cytohistologic correlation.

OBJECTIVE: The incidence of endocervical adenocarcinoma has increased steadily over the past two decades. Since the Bethesda System was introduced, the diagnosis of atypical glandular cells of undetermined significance (AGUS) has also risen and now accounts for 0.46-1.83% of all cervical (Pap) smears. The purpose of this study was to evaluate the significance of a diagnosis of AGUS using cytohistologic correlation. STUDY DESIGN: A retrospective review of archival material from 1993 through 1996 identified 64 patients who had smears diagnosed as AGUS and had a subsequent surgical biopsy. The smears were reviewed and cytologic features analyzed and correlated with the histologic diagnosis. RESULTS: On biopsy, 3 (5%) of the 64 cases showed endocervical adenocarcinoma in situ (AIS) (1 case with invasive adenocarcinoma also), 14 (22%) had a benign glandular lesion (endocervical polyp, tubal metaplasia, microglandular hyperplasia, reactive changes), 35 (54%) had squamous intraepithelial lesion (SIL) (15 diagnosed on the original smear), and 12 (19%) had no abnormality. Among the cytologic criteria evaluated, feathering (P = .01), palisading (P < .001) and chromatin clearing (P = .002) were shown to have a significant association with the histopathologic diagnosis of AIS/adenocarcinoma. These features were also useful in distinguishing AIS/adenocarcinoma from SIL and benign glandular changes from AIS/adenocarcinoma but not benign/reactive glandular changes from SIL. CONCLUSION: A diagnosis of AGUS correlated with a clinically significant lesion in the majority of cases. Squamous dysplasia (SIL) was the most common lesion identified. The presence of feathering, nuclear palisading and chromatin clearing increased the likelihood of a histologic diagnosis of AIS/adenocarcinoma.     

Fine needle aspiration cytology in the management of male breast masses. Nineteen years of experience.

OBJECTIVE: To determine the utility and accuracy of fine needle aspiration cytology (FNAC) as well as its sensitivity, specificity and predictive value in the diagnosis of male breast masses. STUDY DESIGN: Data on male breast FNAC done between 1978 and 1997 were retrieved from the records of the cytopathology laboratory. FNAC diagnoses were categorized as positive, negative, inconclusive or unsatisfactory. Cytohistologic correlation was done with data from histopathology records. Sensitivity, specificity, diagnostic accuracy and predictive values of FNAC were calculated using standard statistical methods. RESULTS: Five hundred seven of 13,175 patients undergoing breast FNAC were males. Of them, 393/507 had satisfactory aspirates. Of these, 70 were positive (13.8%), 295 were negative (58%), and 29 were inconclusive (5.7%). A total of 114 FNACs (22.5%) were unsatisfactory. Histopathology was available in 97/507 cases. There were no false positive or false negative diagnoses. FNAC had a sensitivity, specificity and diagnostic accuracy of 100% for male breast lesions. CONCLUSION: This large study shows that FNAC is a very accurate tool for diagnosis of male breast lesions. It is highly sensitive and specific, with good cytohistologic correlation. FNAC should therefore be an integral part of the primary assessment of breast lumps in males.     

Fine needle aspiration cytology, immunocytochemistry and electron microscopy in a rare case of carcinoma of the breast with malignant epithelial giant cells

The cytohistologic findings in a fine needle aspirate from a case of the rare breast carcinoma with bizarre tumor giant cells are described, along with the results of immunocytochemical and ultrastructural studies. The observations in this case suggest that the bizarre malignant giant cells in this type of breast cancer are of an epithelial origin, rather than a histiocytic-stromal origin. The other conditions that may yield giant cells in needle aspirates of breast masses are briefly discussed.     

Comparison of cytohistologic techniques in diagnosis of gastroesophageal malignancy

OBJECTIVE: To evaluate the diagnostic performance of various endoscopic cytologic techniques, namely, brushing cytology, touch smear cytology and crush cytology, and comparison with concurrent biopsy results in diagnosis of gastroesophageal malignancy. STUDY DESIGN: This prospective study was conducted on 100 patients, with 78 clinically suspected cases of esophageal malignancy and 22 cases of gastric malignancy. RESULTS: The diagnostic accuracy of touch smear in esophageal malignancy was significantly higher (94.12%) than brushing and crush smears (89.71% each), and endoscopic biopsy had the diagnostic accuracy of 88.24%. The diagnostic accuracy of combined brushing and biopsy was 100%; it was 97.06% for touch smears combined with biopsy. In comparison, the diagnostic accuracy in gastric malignancy was 75% for brushing alone, which was significantly lower than touch smear (87.5%) and endoscopic biopsy (87.5%). The diagnostic yield for crush smear was 81.25%. A combination of touch smears and biopsy had a diagnostic yield of 100%; it was 93.75% for combined brushings and biopsy. CONCLUSION: A combination of cytohistologic techniques resulted in a statistically significant increase in the diagnostic yield of gastroesophageal malignancies and thus cytologic techniques may act as adjunct to biopsy histology to increase the diagnostic efficiency.     

Fine needle aspiration cytology of breast fibroadenoma. A cytohistologic correlation study of 405 cases.

OBJECTIVE: To evaluate the cytohistologic correlation of breast fibroadenoma (FA) in order to assess the value of cytology in the conservative management of this lesion. STUDY DESIGN: A retrospective analysis of all aspirates diagnosed as FA or fibroadenomatous lesion (n = 1,549) for which a histologic follow-up study was available (n = 362). Forty-three aspirates, including 14 nonrepresentative smears, from histologically proven FAs with a different cytologic report were also included in the study. RESULTS: Cytohistologic agreement was present in 287 of the 362 cytodiagnoses. Lack of correlation was observed in 75 cases. Most diagnostic errors accumulated in the older patient group. The sensitivity of the cytologic diagnosis of FA was 86.9% (90.8% excluding nonrepresentative cases), with a positive predictive value of 79.3%. In 43 cases a histologic diagnosis of FA was given after previous erroneous (n = 29) or nonrepresentative cytodiagnoses (n = 14). The specificity of the cytologic diagnosis of FA reached 93.8%, with a negative predictive value of 96.3% (97.5% excluding nonrepresentative cases). Regarding malignancy, five tumors were diagnosed as FA and were malignant. No false positive diagnoses of malignancy were given, but nine aspirates were included in the category "suspicious for carcinoma." CONCLUSION: FA of the breast remains a diagnostic challenge for the cytopathologist. A considerable amount of benign breast lesions can mimic FA on cytology, and such diagnostic categories as "fibroadenomatous lesion" or "consistent with FA" are associated with low diagnostic accuracy. While the cytologic requisites for entering a program of conservative management of FA are established, it seems that strict diagnostic criteria should be applied even at the expense of diminishing sensitivity.     

Cytohistologic correlation of cirrhosis and hepatocellular carcinoma. Pitfall in diagnosis?

OBJECTIVE: To compare the diagnostic criteria for cirrhosis and hepatocellular carcinoma (HCC) noted on liver fine needle aspirates (FNAs) and their corresponding liver needle core biopsies (NCBs). STUDY DESIGN: We reviewed FNA slides from 15 cases of cirrhosis and 6 cases of HCC and their corresponding NCBs. We compared a variety of specific nonarchitectural criteria, including small cell dysplasia (SCD) and large cell dysplasia (LCD), for distinguishing cirrhosis from HCC. RESULTS: FNA smears diagnostically correlated with NCBs. The cytologic criterion with the greatest correlation in predicting HCC on FNA was SCD. This was not noted in all the core biopsies, probably due to sampling error. LCD was seen more frequently in cirrhosis than HCC on both cytology and histology and therefore was not a criterion useful in establishing a diagnosis of malignancy. The remaining cytologic criteria had good correlations but did not aid in diagnosing HCC. CONCLUSION: FNA has good cytohistologic correlation with NCB for both cirrhosis and HCC. There is an association of SCD with HCC; however, LCD is not a reliable "precancerous" change as it is commonly seen in cirrhosis and HCC. Therefore, the presence of SCD on FNA should be reported and is an indication for close clinical follow-up to exclude HCC.     

Aspiration cytology of 147 adnexal cysts with histologic correlation.

OBJECTIVE: To assess the usefulness of cytology in the diagnosis of 147 histologically established adnexal cysts. STUDY DESIGN: Retrospective, macro-microscopic study based on fluid aspirated from 132 ovarian and 15 extraovarian cysts and projected as a cytohistologic correlation. RESULTS: Typical macroscopic features were identified in 76% of endometriotic cysts, in 53% of mucinous neoplasms and in 67% of dermoid cysts. Cytology helped to identify 67% of nonneoplastic and 56% of neoplastic cysts. The lowest diagnostic sensitivities were observed in functional cysts and benign serous neoplasms (50%), while the highest were shown by endometriotic cysts (76%) and malignant epithelial neoplasms (71%). Inadequate samples were obtained from all types of cysts, even malignant ones (two mucinous cystadenocarcinomas). Diagnostic cytology was useless in extraovarian cysts (33% sensitivity). An adult granulosa cell tumor was erroneously diagnosed as a follicular cyst by cytologic examination. CONCLUSION: Examination of the cyst fluids obtained by aspiration demonstrated low sensitivity, with 43% of inadequate samples obtained from all types of cysts. Malignant cystic neoplasms may be overlooked in inadequate samples. Our study also revealed that specificity in this type of analysis is high in inadequate samples, provided that the technique is carried out correctly.     

Clinical significance of a cytologic diagnosis of atypical glandular cells, favor endometrial origin, in Pap smears

OBJECTIVE: To evaluate the significance of a diagnosis of atypical glandular cells, favor endometrial origin (AGC-EM), using cytohistologic correlation. STUDY DESIGN: A retrospective search identified 90 cervicovaginal smears (vaginal pool) with a diagnosis of AGC-EM, in 2 tertiary care medical centers between January 1998 and December 2002. RESULTS: Forty-six (51%) were conventional preparations and 44 (49%) were liquid-based monolayers (SurePath, TriPath Imaging Inc., Burlington, North Carolina, U.S.A.). Follow-up biopsies were available in 55 of 90 (61%) cases, 15 of 90 (17%) cases had cytology follow-up, and 20 of 90 (22%) were lost to follow-up. The patients ranged in age from 30 to 86 years (mean, 56); 56 of 90 (62%) were > 50 years. Among the patients who underwent biopsy, 22 (40%) had a clinically significant lesion, including 10 (18%) endometrial adenocarcinomas, 8 (15%) endometrial hyperplasias and 4 (7%) high grade squamous intraepithelial lesion/squamous cell carcinoma, nonkeratinizing type. The remaining 33 patients had benign histology, including benign endometrium, endometrial polyp, tubal metaplasia, cystic endometrial atrophy and cervical microglandular hyperplasia. Of the patients with cytologic follow-up, 2 had Pap smears showing atypical squamous cells of undetermined significance, while the remainder had negative results. CONCLUSION: In our study population, 40% (22 of 55) of women who underwent biopsy following a diagnosis of AGC-EM had significant uterine lesions, with the majority of the lesions endometrial in origin. Patients with a diagnosis of AGC-EM, especially those > 50, should be followed closely, and endometrial sampling should be included in their initial workup.     

Phyllodes tumor of the breast. A cytohistologic study of 80 cases

OBJECTIVE: To study the cytologic features of phyllodes tumor (PT) of the breast and determine the accuracy of their subclassification in fine needle aspirates. STUDY DESIGN: Eighty cases of histologically diagnosed PT between 1982 and 1997 with a previous fine needle aspiration (FNA) were evaluated. The FNA smears of each case were reviewed without knowledge of the initial cytologic diagnosis and subclassified into benign, borderline or malignant PT. RESULTS: Benign PTs were characterized by a dimorphic mixture of stromal and epithelial cells. The stromal fragments showed mild to moderate cellularity with absent to minimal pleomorphism and no mitosis. There were occasional, if any, single stromal cells. Borderline PTs had stromal fragments with moderately cellular stroma exhibiting moderate pleomorphism. Two additional features were the presence of single stromal cells and an occasional mitosis in the stromal fragments/single cells. Aspirates from malignant PT were very cellular, with a high stromal/epithelial ratio and marked stromal cellularity. The stromal cells were highly pleomorphic, with frequent mitosis and atypical single stromal cells in the background. Fifty-seven of the 80 histologically documented cases (71.3%) were diagnosed as PT on FNA (40 benign, 10 borderline and 7 malignant). In 81% (46 of 57 PTs), good cytohistologic correlation (32 benign, 8 borderline and 6 malignant) was observed. In another eight cases, one grade differentiation between cytologic and histologic grade was observed. Six of the nine malignant PTs on histology were correctly subclassified on cytology. There were one false positive and two false negative cases. CONCLUSION: Cytologic diagnosis and grading of PT on FNA is possible. Special care should be undertaken in interpreting phyllodes fragments, cellularity of stroma, pleomorphism and mitosis. Single stromal cells are also important morphologic criteria for subclassification. Multiple-site aspiration is advisable to avoid diagnostic errors.