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Atypical squamous metaplasia of seromas in breast needle aspirates from irradiated lumpectomy sites: a potential pitfall for false-positive diagnoses of carcinoma.

The presence of squamous metaplasic cells is an uncommon finding in fine-needle aspiration (FNA) biopsies of the breast. We report that FNA smears containing atypical squamous metaplastic cells derived from the lining of seroma-type cavities following lumpectomy and irradiation in patients with breast cancer can be a potential pitfall for a false-positive diagnosis of recurrent malignancy. Four fine-needle breast aspirates from two adult patients with previous histories of invasive breast carcinoma were retrieved. One specimen was from a 56-yr-old female, while the remaining three FNAs aspirates were from a 75-yr-old female. Both patients presented with indurated cystic lesions arising at irradiated lumpectomy sites. The cytospins from the 56-yr-old patient showed markedly atypical cells having enlarged, degenerating, hyperchromatic nuclei and surrounding dense cytoplasm with sharp borders that were suspicious for carcinoma. A mastectomy revealed irradiation changes and atypical squamous metaplastic cells lining a cystic cavity consistent with a seroma, but there was no evidence of residual cancer. After three aspirations yielded "atypical" diagnoses, the second patient underwent core needle biopsies that also revealed changes consistent with a seroma cavity lined by atypical squamous metaplastic cells. We believe this is the first report of squamous metaplasia occurring in a seroma cavity following lumpectomy and irradiation of the breast. The squamous metaplastic cells in aspirates of these cystic lesions may display significant cellular atypia that can potentially result in a false-positive diagnosis of malignancy.

Aged↗

Fine-needle aspiration cytology in pancreatic endocrine tumors.

Pancreatic endocrine tumors (PETs) are relatively uncommon neoplasms. Although their histologic patterns have been widely studied, their cytologic features as they appear in fine-needle aspiration (FNA) specimens have rarely been reported. In this study, aspirates of seven PETs, four primary and three metastatic lesions (two to liver and one to bone), are described. The tumors occurred in seven men ranging in age from 37 to 72 yr. Six tumors presented as nonfunctioning masses and one produced Zollinger-Ellison syndrome. Three were located in the head of the pancreas and four in the body and tail. The pancreatic and liver aspirations were performed under computed tomographic guidance and the bone lesion, under fluoroscopy. The aspiration specimens were hypercellular. The tumor cells occurred singly and in small clusters. In three cases, there was a tendency toward acinar formations. In two cases, there were prominent, thin-walled, branching blood vessels with tumor cells attached to the vascular walls. The cells were round or polygonal with a moderate amount of finely granular, well-defined cytoplasm. The nuclei were eccentrically located and round-to-oval--with one or two small nucleoli and finely granular, evenly-dispersed chromatin. The diagnosis was confirmed by immunocytochemistry (two cases) and electron microscopy (four cases) of the aspirated material and histology sections of the resected tumors (two cases). The results of this study demonstrate that FNA is a useful method to establish the diagnosis of PETs.

Adenoma, Islet Cell↗

Diagnosis of tuberculosis of bone and soft tissue by fine-needle aspiration biopsy.

Fine-needle aspiration biopsy is a well-established procedure in the detection of various neoplastic processes. However, there are only limited reports on the efficacy of this technique in nonneoplastic conditions. In this study, fine-needle aspiration cytology findings of bone and soft tissue lesions in 11 patients with tuberculosis are reported. Spine, scapula, chest wall, flank areas, tibia, ring, and index fingers were the sites of fine-needle aspiration biopsies. The age of the patients ranged from 21 to 65 years. Granulomatous reaction with or without caseation necrosis was seen in 73%. The aspirated material was acellular or predominantly composed of necrotic material and inflammatory infiltrates in 27%. Acid-fast bacilli (AFB) could be demonstrated in 64%. Culture for Mycobacterium tuberculosis was positive in 83%. This study supports previous suggestions that fine-needle aspiration biopsy is a simple alternative to open biopsy for the diagnosis of TB of bone and soft tissue lesions.

Adult↗

Diagnostic accuracy and clinical utility of fine-needle aspiration cytology in the diagnosis of clinically primary bone lesions.

Optimal treatment of primary bone sarcomas requires minimal disturbance of the tumor prior to preoperative radiation and chemotherapy. Currently, carefully planned incisional or cutting needle biopsies are the favored methods for procurement of specimens. Recently, fine-needle aspiration has gained favor as the initial diagnostic procedure at some centers. We investigated the diagnostic accuracy and the effects of errors in diagnosis and of complications on the patient's course in a series of 101 patients presenting with lesions clinically believed to have arisen in bone. We found that 29% of aspirates were insufficient for the diagnosis; 41% of aspirates yielded a correct diagnosis that had a significant favorable impact on the patient's course, while 20% of aspirates gave a correct diagnosis that did not significantly influence therapy. In 7% of cases, the aspirates were associated with an incorrect diagnosis that negatively influenced therapy, and in an additional 3% of cases an incorrect diagnosis was obtained that had no impact on patient outcome. No complications were encountered in this series of patients.

Biopsy, Needle↗

Fine-needle aspiration of histiocytic necrotizing lymphadenitis (Kikuchi's disease).

Fine-needle aspiration (FNA) of the lymph node was done in five patients with histiocytic necrotizing lymphadenitis (Kikuchi's disease). In four patients, the aspirates were found to have many small and large atypical lymphocytes, some reactive, phagocytic histiocytes, and intense extracellular debris. Neutrophils, plasma cells, or multinucleated giant cells were not seen. These cytologic findings were considered diagnostic for Kikuchi's disease. In one patient, the aspirate did not show significant histiocytosis or tissue necrosis and was considered nondiagnostic. In patients with both typical clinical features and characteristic cytologic findings in the lymph node aspirates, FNA of the lymph node alone will suffice for diagnosis. In those patients with typical clinical features but nondiagnostic findings in the FNA aspirates, the diagnosis of Kikuchi's disease may have to be established either on repeated nodal FNA or on lymph node biopsy.

Adolescent↗

Fine-needle aspiration cytology of extramedullary hematopoiesis (myeloid metaplasia).

Myeloproliferative disease may be associated with extramedullary hematopoiesis (EH). Clinically, however, the differential diagnosis of solid masses in these patients includes not only EH but also inflammatory lesions and malignant neoplasms, including granulocytic sarcoma. We report the fine-needle aspiration (FNA) cytology of extramedullary hematopoiesis in five patients with a history of myeloproliferative disease. All of the masses developed subsequent to the diagnosis of myeloproliferative disease. Two of the patients had chronic myelogenous leukemia, one had essential thrombocythemia, and two had an unspecified chronic myeloproliferative disorder. The patients ranged in age from 50 to 88 years, and all presented with solid masses involving the kidney (two aspirates), liver (one aspirate), and lymph nodes (three aspirates). One of the lymph node aspirates was from a paratracheal lymph node. Cytologically, the lesions were composed of varying numbers of hematopoietic cells from all three hematologic cell lines. The Diff-Quik stain was especially helpful in the recognition of the hematopoietic cells such as granulocytic precursors, eosinophils, and megakaryocytes. In several cases, the megakaryocytic component was particularly prominent. In one case, the Factor VIII immunoperoxidase stain was used to confirm the megakaryocytic lineage of the multinucleated cells. The cytologic differential diagnosis, which includes granulocytic sarcoma, inflammatory disorders, and other lesions containing multinucleated giant cells, is discussed.

Aged↗

Fine-needle aspiration biopsy of vertebral body lesions: cytologic, pathologic, and clinical correlations of 57 cases.

We reviewed 57 cases of fine-needle aspiration biopsy (FNAB) specimens of vertebral body lesions at our institutions and sought correlations between clinical histories, aspirates, and tissue specimens. Patients' ages ranged from 10-86 yr (mean 62 yr). Previous clinical histories included malignancy (n = 33), osteomyelitis or systemic infection (n = 18), and nonspecific (n = 6). FNAB diagnoses were rendered in 81% of cases (n = 46) and were correlated with previous clinical history (P < 0.004). Tissue diagnoses were also correlated with previous clinical history (P < 0.02). In 19% of cases (n = 11), FNAB was unsatisfactory; of these, tissue specimens were diagnostic for five cases. In 19% of cases (n = 11), both aspirates and tissue specimens were available, and the diagnoses coincided in all cases; tissue specimens did not enhance the results of aspirates which produced positive results. Aspirates which showed normal bone marrow elements appeared to effectively rule-out metastatic malignancy based on clinical follow-up (mean 3.7 yr).

Adenocarcinoma↗

Utility of polyclonal and monoclonal antibodies against carcinoembryonic antigen in hepatic fine-needle aspirates.

To assess the usefulness of polyclonal and monoclonal antibodies against carcinoembryonic antigen (CEA) in the differential diagnosis of hepatocellular carcinoma (HCC) vs. metastatic adenocarcinoma (MA), we studied 25 cases of fine-needle aspirates (FNA) of hepatic lesions. The material consisted of 9 primary HCCs, 8 MAs, and 8 benign hepatic aspirates. For immunostaining, the avidin-biotin complex technique was performed on paraffin sections of cell blocks, using a standardized automatic immunostainer. Specific bile canalicular immunostaining with polyclonal CEA (pCEA) antibody was present in five of eight (5/8) benign hepatic aspirates and eight of nine (8/9) HCCs. Diffuse cytoplasmic immunostaining with pCEA antibody was present in four of eight (4/8) MAs. None of the aspirates showed any positive immunostaining with monoclonal CEA (mCEA) antibody. We conclude that: (1) pCEA antibody is useful in the evaluation of hepatic FNAs. Diffuse cytoplasmic staining is seen in MAs, whereas canalicular immunostaining pattern is an indication of benign or malignant hepatocytes. (2) Paraffin-embedded cell blocks made from hepatic aspirate material are suitable for immunostaining with polyclonal CEA antibody. (3) mCEA antibody has no value in the diagnosis of HCC.

Adenocarcinoma↗

Value of ancillary studies in fine-needle aspiration biopsy.

With growing interest in the application of fine-needle aspiration biopsy (FNAB) in primary diagnosis of benign and malignant lesions, there has been a significant increase in the use of ancillary studies in the aspirated material. To assess the value of such studies, we reviewed 254 morphologically difficult aspiration biopsy cases obtained from different sites that underwent ancillary studies which included microbiology (MC), special stains (SS), immunocytochemistry (ICC), electron microscopy (EM) and flow cytometry (FC). Correlation with available histologic material and/or pertinent clinical information was used as a "gold" standard. In some cases, more than one ancillary study was performed on a single aspirate. According to the impact of the ancillary studies on the final diagnosis, these studies were divided into three categories: confirmatory/diagnostic (22%), helpful (41%), and non-helpful (37%). Overall, more studies had positive contributory effect to the diagnosis (63%) than those with non-helpful results (37%). Among these adjunct testings, ICC were the most commonly used tests (135/296, 46%), while the EM studies had more positive impact in establishing the diagnosis. These findings emphasize the usefulness of ancillary testings in FNAB and justify the more selective use of these studies in the aspirated material.

Adolescent↗

Estimation of estrogen receptor content in fine-needle aspirates from breast cancer using the monoclonal antibody 1D5 and microwave oven processing: correlation with paraffin embedded and frozen sections determinations.

We describe a method of immunocytochemically assessing estrogen receptor (ER) status on alcohol-fixed smears obtained by fine-needle aspiration (FNA) from breast cancer patients, using a commercially available monoclonal antibody (1D5) with microwave oven processing. A series of 31 cases of aspirates from breast cancer were analysed and the results were compared with assessment by ER immunocytochemical assay using the same procedure on formalin-fixed tissue and with assessment by ER-ICA assay on frozen sections. The results were scored semiquantitatively using a five grade scoring system. Of the 31 cases examined, 21 were positive at least by two methods and 10 were negative for all three determinations. The results obtained in the ER immunocytochemical assay on aspirates and paraffin-sections using the antibody 1D5 and those obtained on frozen sections using the antibody H222 were closely similar. In only one case was it not possible to interpret the reaction in the cytological specimen because there was a strong background in the smear. In general, we obtained more intense positivity with the antibody 1D5 in aspirates and formalin-fixed material than with the antibody H222 in frozen sections. The scoring results of the three methods were almost identical. We conclude that the application of ER method on alcohol-fixed smears will eliminate the need for using a special fixation procedure and will provide several advantages, such as: improvement in morphological concomitant analysis, utilization whenever malignancy is found without necessity to re-aspirate the patient, and adequacy of archival material.

Adult↗

Value of fine-needle aspiration in the diagnosis of Hürthle cell neoplasms.

The cytologic and histologic slides on all patients with a diagnosis of Hürthle cell tumor at Mount Sinai Hospital during the last 12 years were reviewed. There were 67 Hürthle cell tumors of which 15 (22%) were malignant. Four carcinomas (27%) occurred in a background of thyroiditis. Forty-three patients with Hürthle cell tumors had undergone preoperative fine-needle aspiration, of which 31 had satisfactory aspirates. For Hürthle cell neoplasia, fine-needle aspiration cytology had a sensitivity of 83.8% (26 of 31) and positive predictive value of 93% (26 of 28), provided that the aspirate was of adequate cellularity. All 3 cases predicted as Hürthle cell carcinoma on the basis of cellular and nuclear atypia were correctly predicted, but 3 carcinomas composed of bland cells were incorrectly predicted as adenomas. We conclude that aspiration cytology can differentiate nonneoplastic from neoplastic Hürthle cell lesions with high accuracy, but that the differentiation between benign and malignant lesions is less reliable.

Adenoma↗

Fine-needle aspiration biopsy for the measurement of hepatic iron concentration.

The potential application of fine-needle aspiration liver biopsy in the documentation of hepatic iron overload has been assessed in iron-loaded rats. Fine-needle aspiration and standard liver biopsy specimens were obtained from three groups of animals supplemented with oral and parenteral iron for 2 to 6 mo. The mean dry weights of standard and fine-needle biopsy specimens were 7.41 +/- 0.77 (+/- S.E.M.) and 0.57 +/- 0.54 mg, respectively. Hepatic iron in fine-needle aspiration biopsy specimens correlated significantly with hepatic iron in standard liver biopsy specimens as measured by biochemical determination, computerized image analysis and histological grading (r greater than 0.9, p less than 0.001). In conclusion, we have shown that fine-needle aspiration biopsy of the liver can obtain sufficient tissue for biochemical measurement of the hepatic iron concentration in an animal model of iron overload. The clinical applications of fine-needle aspiration liver biopsy in human beings with iron overload is currently being investigated.

Analysis of Variance↗

Aberrant promoter methylation of p16(INK4a), RARB2 and SEMA3B in bronchial aspirates from patients with suspected lung cancer.

Aberrant promoter methylation of normally unmethylated CpG-islands offers a promising tool for the development of molecular biomarkers. We investigated bronchial aspirates of patients admitted for suspected lung cancer with regard to the prevalence of aberrant methylation of potential marker genes. Applying quantitative methylation specific PCR (QMSP) we analyzed bronchial aspirates from 75 patients with primary lung cancer and 64 bronchial aspirates of patients diagnosed with benign lung disease for promoter methylation of 3 candidate marker genes (p16(INK4a), RARB2 and SEMA3B). Hypermethylation of p16(INK4a) detected 18/75 (24%) cases with primary lung cancer and was present predominantly in squamous cell carcinomas (14/25; 56%). RARB2 QMSP at an assay threshold greater than 30 was found in 42/75 (56%) patients with lung cancer without relation to histological subtype. Patients with benign lung disease showed methylation of p16(INK4a) and a RARB2 QMSP at an assay threshold greater than 30 in 0/64 (0%) and 8/64 (13%) cases, respectively. Combining the 2 methylation markers, p16(INK4a) and RARB2, yielded a sensitivity of 69% and a specificity of 87% for the diagnosis of pulmonary malignancy. In contrast, SEMA3B displayed frequent promoter methylation (around 90%) both in bronchial aspirates of tumor and nontumor cases and thus was not suited as a biomarker. The results of this study indicate that QMSP analysis of p16(INK4a) and RARB2 may aid the diagnosis of primary lung cancer in bronchial aspirates. In particular, detection of p16(INK4a) methylation by QMSP may serve as a highly specific marker of pulmonary squamous cell carcinoma.

Adult↗

Detection of small-cell-lung-cancer cells in bone-marrow aspirates by monoclonal antibodies NCC-LU-243, NCC-LU-246 and MLuC1.

We have used immunocytochemistry to identify tumor cells in bone-marrow aspirates of patients with small-cell lung cancer and we have compared the results with conventional histomorphology. The monoclonal antibodies (MAbs) used were NCC-LU-243 and NCC-LU-246 (cluster 1) and MLuC1 (cluster 6); 108 slides (52 patients) incubated with NCC-LU-246, 106 (51 patients) with NCC-LU-243 and 69 with MLuC1 (36 patients) were evaluated. Bone-marrow biopsies (83) were also obtained from 50 of these patients; 48/108 bone marrow aspirates were positive for cluster-1 antigen and 22/69 were positive for MLuC1. Immunocytochemistry with anti-NCAM MAbs detected bone-marrow localization in 38/83 bone-marrow aspirates compared with 9/83 bone-marrow biopsies, while MLuC1 was positive in 18/60 and bone-marrow biopsies in 6/60. Moreover, bone-marrow aspirates were positive for cluster-1 antigen in 7/17 patients with limited disease at diagnosis. Patients with positive bone-marrow biopsies had significantly shorter survival. No differences were found between patients with positive and those with negative marrow aspirates.

Antibodies, Monoclonal↗

Mammogram-directed fine-needle aspiration of nonpalpable breast lesions.

A prospective study was undertaken to evaluate the effectiveness of mammogram directed fine-needle aspiration cytology in women with nonpalpable abnormalities detected on mammogram. Seventy patients were entered into the research protocol, with 61 patients undergoing mammogram directed fine-needle aspiration. Forty-three of the aspirates were adequate for diagnosis. Fine-needle aspiration yielded an accurate diagnosis in 12 of the 14 carcinomas in which the sample was considered adequate, for a sensitivity of 87%. No patients were falsely diagnosed with malignant disease, a specificity of 100%. The predictive value of a positive test was 100%, and that of a negative test was 93%. We conclude that fine-needle aspiration cytology can aid in making a diagnosis when nonpalpable breast abnormalities are detected on mammogram.

Biopsy, Needle↗

Needle aspiration biopsy of thyroid nodules.

Needle aspiration biopsies for cytology were performed on 224 patients with thyroid nodules. Diagnosis was confirmed by surgical exploration in 134 patients. Twenty-four biopsies were reported positive for malignancy; 23 were confirmed at operation and there was 1 false positive. Forty-one biopsies were reported benign. Three of these lesions were found to be malignant, representing false negatives. Sixty-nine biopsies were in the questionable category; 16 (23%) of these were malignant. None of the patients suffered complications from the biopsies. Routine employment of needle aspiration biopsy on our service has resulted in a marked increase in the incidence of carcinoma in thyroid nodules selected for surgery. This has resulted from detection of otherwise unsuspected malignancy, as well as avoidance of surgery in patients with benign lesions. Needle aspiration is not a substitute for surgery. It is a valuable diagnostic procedure, and should be performed in the evaluation of essentially all thyroid nodules. We continue to use radioiodine scanning to evaluate our patients, but have found the routine use of ultrasonography unnecessary when needle aspiration is employed. The ultimate decision regarding surgical exploration is based on a combination of factors including history, physical findings, radioiodine scan and needle aspiration biopsy.

Biopsy, Needle↗

Fine needle aspiration biopsy cytology as an adjunct in the diagnosis of childhood sarcoidosis.

Fine needle aspiration biopsy cytology performed in three children with sarcoidosis expedited clinical investigation and diagnosis of their disease. Each patient had a different clinical presentation; in two of them lymphoma was part of the initial differential diagnosis. Aspiration cytology in all cases revealed collections of epithelioid histiocytes, and multinucleate foreign body-type giant cells, without accompanying necrosis or acute inflammation. A diagnosis of non-caseating granulomas consistent with sarcoidosis was made in all aspirates. Special stains for identification of organisms performed on the smears of one case, and culture of aspirate material from one case were negative. Subsequent serum angiotensin converting enzyme levels in all patients were elevated. Chest x-ray films in all patients showed mediastinal and hilar lymphadenopathy. One patient had an interstitial pulmonary infiltrate. All patients responded to steroid therapy. Fine needle aspiration biopsy can be a useful diagnostic tool in the evaluation of children with suspected sarcoidosis.

Adolescent↗

DNA amplification of nasopharyngeal aspirates in rats: a procedure to detect Pneumocystis carinii.

The diagnosis of Pneumocystis carinii pneumonia (PCP) requires invasive methods of bronchoalveolar lavage and lung biopsy. In this study, we examined efficacy of polymerase chain reaction (PCR) compared to Giemsa and silver ammoniacal staining to detect P. carinii in easily accessible extrapulmonary sites as well as lung. Samples were collected from lung, nasal and pharyngeal aspirates, gastric contents, urine and blood from dexamethasone treated or untreated virus-free Sprague-Dawley rats. All immunosuppressed lung samples were P. carinii positive by PCR analysis and both stains. Respectively DNA fragments of P. carinii were found in 93%, of nasal and 75% of pharyngeal aspirates, and 0% of sera, urine or gastric aspirates from immunosuppressed rats. However, no P. carinii cysts or trophozoites were found in nasal and pharyngeal aspirates (extrapulmonary sites) by silver ammoniacal or Giemsa staining. In comparison, none of the specimens from immunocompetent rats were PCR positive at any sites tested including the lungs. Therefore, PCR amplification products of nasal and pharyngeal aspirates showed that immunosuppressed rats with PCP can carry P. carinii DNA fragments in their upper respiratory tracts, but immunocompetent animals without PCP, are free of the organism and this suggests an approach to be investigated in humans with PCP.

Animals↗