Decision analysis in cytopathology.
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Decision Making↗
Biomedical subjects
S S Raab
Publications and source records attributed to S S Raab.
p53 protein overexpression in smooth muscle tumors of the uterus.
p53 is a nuclear phosphoprotein whose overexpression may portend a poor prognosis in a variety of neoplasms. In this immunohistochemical study we examined p53 overexpression in a variety of uterine smooth muscle tumors (34 leiomyosarcomas, 18 leiomyomas, and six smooth muscle tumors of uncertain malignant potential [STUMPs]). p53 immunoreactivity was observed in none of 18 (0%) leiomyomas, one of six (17%) STUMPs, and 16 of 34 (47%) leiomyosarcomas. Reactivity was not observed in the surrounding nonneoplastic uterine smooth muscle. Strong p53 overexpression in the leiomyosarcomas was significantly associated with high grade morphology (P = .013) and a high stage at the time of presentation (P = .021). In 25 leiomyosarcoma patients with clinical follow-up, p53 overexpression was associated with shorter length of survival (P = 0.024). However, this effect was not independent of tumor stage or grade. A regression analysis showed that tumor stage was the only independent predictor of length of survival. Our study size is small, and further studies are warranted to determine the significance and replicability of these findings.
Female↗
Pathology and probability. Likelihood ratios and receiver operating characteristic curves in the interpretation of bronchial brush specimens.
Diagnoses in pathology often are qualitative, such as atypical or suspicious, and consequently are thought to have limited clinical value. To investigate the utility of a qualitative diagnostic system, seven pathologists retrospectively evaluated 100 bronchial brush specimens using the following categories: definitely benign, probably benign, possibly malignant, probably malignant, and definitely malignant. The likelihood ratio (LR) and receiver operating characteristic (ROC) curve, two statistical probabilistic measurements, were used to calculate diagnostic accuracy among individuals and groups. The results show: (1) the LR for individual diagnostic categories varied among observers, resulting in different clinically malignant probabilities; (2) observer experience did not appear to play a role in overall diagnostic accuracy, except in the diagnosis of small cell carcinoma; (3) observers operate at higher levels of diagnostic accuracy with, rather than without, clinical history. The authors conclude that qualitative diagnoses contain important information and can be interpreted effectively with LR and ROC.
Bronchi↗
Atypical glandular cells of undetermined significance. Cytologic criteria to separate clinically significant from benign lesions.
Histologic follow-up of the cervical-vaginal smear diagnosis of atypical glandular cells of undetermined significance (AGUS) shows a broad spectrum of clinically significant (preneoplastic or neoplastic) and benign lesions. There are few statistical studies that have attempted to separate these AGUS categories based on select cytologic criteria. The authors retrospectively reviewed 116 AGUS without concurrent squamous dysplasia smears (66 clinically significant and 50 benign lesions), and used logistic regression analysis to identify the cytologic criteria of irregular nuclear membranes, atypical single cells, and decreased cytoplasm as useful in separating clinically significant from benign lesions. Using contingency tables, these criteria in combination had a sensitivity 29% and a specificity of 94% in the diagnosis of clinically significant lesions. If any single criterion was present, the sensitivity and specificity were 100% and 28%, respectively. In conclusion, by using key cytologic criteria, a percentage of benign AGUS lesions can be separated from clinically significant AGUS lesions.
Diagnosis, Differential↗
Brush cytology of the extrahepatic biliary tract: comparison of cytologic features of adenocarcinoma and benign biliary strictures.
Malignant strictures of the extrahepatic biliary tract are difficult to discern from benign strictures solely by clinical and/or radiographic findings. Endoscopic retrograde wire-guided brushings of strictures have proven to be useful in evaluating such lesions. Because the reported sensitivity of diagnosing adenocarcinoma of the extrahepatic biliary tract by this technique has varied considerably (44 to 100%), we undertook a retrospective study to determine if the diagnostic accuracy could be increased by identifying key cytologic features by reviewing a series of 90 biliary tract brushings from 80 patients. The cytologic diagnosis was confirmed either by additional pathologic material and/or clinical follow-up. Utilizing a multiple logistic regression analysis, three key cytologic features were identified that were useful in separating benign from malignant strictures; these features included: nuclear molding, chromatin clumping, and increased nuclear-cytoplasmic ratio. The presence of two of these three features resulted in a sensitivity of 83%; the corresponding specificity was 98%. The use of these key features should aid the cytologist in better recognizing malignant cells in biliary tract brushings.
Adenocarcinoma↗
Pediatric thyroid nodules: disease demographics and clinical management as determined by fine needle aspiration biopsy.
OBJECTIVE: The prevalence of thyroid nodularity in children has been estimated to be 1.8%. The reported prevalence of specific diseases which comprise these nodules is conflicting as evidenced by a reported range of malignancy of 2 to 50% in solitary nodules. In order to better classify pediatric (< 18 years old) thyroid disease and evaluate the utility of fine needle aspiration biopsy (FNAB) in this patient population, we retrospectively reviewed 66 FNABs from 64 thyroid nodules and 2 perithyroid lymph nodes from 57 patients. METHODOLOGY PATIENTS: The study was composed of 8 males and 49 females who ranged in age from 1 to 18 years old (mean = 13.1). DESIGN: Surgical and/or clinical follow-up was obtained in all patients. The 66 FNAB diagnoses were initially classified into specific diseases. However, for the purpose of this review, the cases were classified as: 3 insufficient, 51 benign, 8 suspicious, and 4 malignant. RESULTS: There were no "false positives" and one "false negative" (a papillary carcinoma was misdiagnosed as a benign nodule). Overall, 10 patients (18%) had malignant thyroid lesions, including 8 papillary carcinomas and 2 follicular carcinomas. Benign diagnoses included benign nodule, cyst, lymphocytic thyroiditis, granulomatous thyroiditis, hyperplasia, and abscess. CONCLUSIONS: The prevalence of malignancy in pediatric patients with thyroid nodules was 18%. We conclude that, because of its high diagnostic accuracy and minimal invasiveness, FNAB is useful in the management of pediatric thyroid nodules.
Adolescent↗
Fine needle aspiration biopsy of proliferative breast disease.
Proliferative breast disease (PBD) is a well-recognized histologic entity that has received increasing attention in the cytologic literature. We have attempted to prospectively identify and subclassify PBD by fine needle aspiration biopsy since 1987 using criteria we developed through our experience. Over 2800 breast FNABs were performed on breast lesions from 1987 to mid-1992; 257 were cytologically diagnosed as PBD with or without atypia. Eighty-four were significantly worrisome clinically to warrant surgical excision. Forty of these were designated PBD without atypia by cytology; 23 (58%) were in agreement with histology; three (8%) were PBD with atypia by histology; five (13%) were cancers; and nine (22%) were nonproliferative. Forty-four cases were designated PBD with atypia; 24 (55%) were in agreement with the histologic diagnosis; 12 (27%) proved to be PBD without atypia; six (13%) were carcinoma; and two (5%) were nonproliferative. After 1991 we employed stricter criteria for PBD, improving on the results from 1991-1992. During this period, there were 53 diagnoses of PBD with or without atypia and 34 were excised. Nine of the 10 (90%) aspirates designated as PBD without atypia were in agreement with histologic findings. The other case was nonproliferative. Fifteen of the 24 cases diagnosed as PBD with atypia were in concordance with histologic findings (63%), one was nonproliferative, seven were PBD without atypia (29%), and one (4%) proved to be carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Low grade transitional cell carcinoma of the bladder. Cytologic diagnosis by key features as identified by logistic regression analysis.
BACKGROUND: Bladder cytology is being used increasingly to detect and monitor early stage bladder cancer. Because of the lack of significant cytomorphologic atypia in low grade transitional cell carcinomas (TCCs), there often is great difficulty in separating these neoplastic cells from benign urothelial cells. METHODS: In an attempt to increase diagnostic sensitivity, 82 bladder wash specimens, which included 33 low grade TCCs and 49 nonneoplastic lesions, were reviewed retrospectively. With a stepwise logistic regression analysis, three key cytomorphologic criteria useful in the separation of low grade TCC from benign urothelium were identified. RESULTS: The key cytologic criteria were increased nuclear/cytoplasmic ratios, irregular nuclear borders, and cytoplasmic homogeneity. By using contingency tables, these three criteria combined had a sensitivity of 45% and a specificity of 98% in the diagnosis of low grade transitional cell carcinoma. If any two of the criteria were present, there was a sensitivity of 85% and a specificity of 96%. CONCLUSIONS: By using these three criteria, the diagnosis of TCC can be made with a high degree of accuracy in bladder wash specimens.
Adult↗
Diagnostic accuracy in cytopathology.
Cytopathologic diagnoses play an important role in clinical decision making. As a result, the tests that produce material for cytopathologic interpretation must be evaluated critically and carefully. One way to evaluate these tests is by the assessment of diagnostic accuracy. The commonly used sensitivity and specificity format dichotomizes the data set and often loses or misinterprets important diagnostic information, especially the data which is semiquantitative. In addition, sensitivity and specificity do not allow the clinician to revise the probability of disease depending upon the test result. The LR and ROC analysis are two methods that systematically measure the diagnostic accuracy of tests, including those that produce semiquantitative data. LR and ROC measurements incorporate the concepts of sensitivity and specificity, but, in addition, provide a way to assess the clinical utility of a test by estimating the post-test probability of disease. These methods are related to other techniques in medical decision making such as decision analysis and information theory, and are straightforward and easily utilized by clinicians and pathologists.
Biopsy, Needle↗
Clinical utility of cytologic typing of lung tumors.
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Cytodiagnosis↗
Fine-needle aspiration biopsy of salivary gland mycoses.
This report details the fine-needle aspiration biopsy (FNAB) cytomorphologic features of two cases of salivary gland mycosis. Both patients had acquired immunodeficiency syndrome (AIDS) and presented with parotid gland masses. The first patient had Histoplasmosis with secondary infection by Candida. Cytopathologically, the FNAB smears showed classic features of a deep-seated mycosis characterized by necrosis and scattered fungal forms. The second patient had a colonizing sialadenitis caused by either Asperigillus or Fusarium. Cytopathologically, the findings were similar to those seen in aspergillomas of the lung or paranasal sinuses with numerous hyphal forms and an absence of an inflammatory response. Because mycotic disease can induce a wide spectrum of pathogenic change, other benign or malignant, solid or cystic lesions enter into the differential diagnosis.
AIDS-Related Opportunistic Infections↗
Is the fine-needle aspiration biopsy diagnosis of proliferative breast disease feasible?
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Biopsy, Needle↗
Fine-needle aspiration cytology of hepatic leiomyosarcoma.
Hepatic leiomyosarcoma is a rare malignancy to involve the liver, occurring as a primary liver sarcoma in patients without an underlying medical disorder, as a metastatic malignancy, and with increasing incidence, as a primary tumor in AIDS patients. A series of hepatic leiomyosarcomas diagnosed by FNA biopsy, including the first reported case in an adult AIDS patient, were reviewed with respect to cytomorphologic features. The series consisted of five men and two women ranging from 24 to 72 years of age. One case was a primary hepatic lesion in a 24-yr-old man with AIDS and six were metastatic from a number of sites (stomach, small bowel, retroperitoneum, vena cava, and seminal vesicle). Two cytologic patterns were identified. Aspirates of spindle-cell leiomyosarcomas (six cases) generally produced hypocellular smears composed primarily of small irregular clusters of cells with blunt-ended, uniform, overlapping nuclei. The differential diagnosis included benign reactive processes and other benign and malignant spindle-cell neoplasms. The aspirate of an epithelioid leiomyosarcoma (one case) revealed a second pattern characterized by highly cellular smears with many single polygonal cells having eccentric, malignant nuclei and a characteristic clear quality to the cytoplasm in Papanicolaou-stained material. This epithelial appearance generated a differential diagnosis that included hepatocellular carcinoma, metastatic carcinoma, and melanoma. Careful integration of clinical information, cytomorphologic features, and ancillary studies will allow specific FNA diagnosis of hepatic leiomyosarcoma in most cases.
Acquired Immunodeficiency Syndrome↗
Utility of Gomori methenamine silver stains in bronchoalveolar lavage specimens.
Bronchoalveolar lavage (BAL) with Gomori methenamine silver (GMS) stain is commonly used to detect Pneumocystis carinii and fungal organisms as causes of infectious pulmonic disease in immunosuppressed patients. However, several reports have indicated that GMS stains are not any more sensitive than conventional cytologic stains in detecting Pneumocystis organisms in select patient populations, such as those with acquired immunodeficiency syndrome (AIDS). To examine the utility of GMS stains in our laboratory, we retrospectively reviewed 243 BALs from 188 patients. Sensitivity of the GMS stain for Pneumocystis and for fungi detection was 100%. Sensitivity for Pneumocystis and for fungi detection by Papanicolaou stain alone was 79% and 88%, respectively; by Diff-Quik stain alone it was 68% and 88%, respectively; and by combined Papanicolaou and Diff-Quik stains it was 79% and 100%, respectively. In four additional cases, fungi were detected by other methods (culture, biopsy) and not by BAL. The GMS stain result was correlated with a number of risk variables to determine which variables were associated with GMS positivity. Using stepwise logistic regression, Pneumocystis positivity by GMS stain correlated (P < 0.0001) only with the variable of history of AIDS or AIDS risk factors. Fungal organism positivity by GMS stain correlated (P = 0.02) only with the variable of history of BAL positivity for fungus. Cost savings analyses were performed, estimating the cost of the GMS stain at $45 (total cost of GMS in 243 BALs was $10,935).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Technology assessment in anatomic pathology. An illustration of test evaluation using fine-needle aspiration biopsy.
Although anatomic pathology diagnoses are the standard on which treatments often are based, many facets of anatomic pathology have not been rigorously examined. These areas include the evaluation of a procedure's technical and diagnostic characteristics, clinical utility, and cost. Technology assessment is the disciplined scientific and systematic evaluation of a test or procedure, and it can be used to evaluate these areas in anatomic pathology. To illustrate and promote the use of technology assessment in anatomic pathology, we show examples in fine-needle aspiration biopsy, which is a subspecialty of cytopathology. We discuss some of the more commonly encountered problems and misconceptions of test evaluation and also the need for further fine-needle aspiration biopsy evaluation. We conclude that technology assessment is a powerful but underutilized tool for test evaluation in fine-needle aspiration biopsy and in anatomic pathology.
Biopsy, Needle↗
Fine-needle aspiration cytology of primary large-cell lymphoma of the mediastinum: cytomorphologic findings with potential pitfalls in diagnosis.
We report the fine-needle aspiration (FNA) cytomorphologic features of six cases of primary mediastinal large-cell lymphoma with sclerosis. The series consisted of three men and three women with a median age of 36 yr. All the patients presented with a large anterior or superior mediastinal mass with no evidence of peripheral lymphadenopathy or hepatosplenomegaly. Two of the cases showed typical findings of lymphoma, characterized by hypercellular specimens with numerous individually scattered markedly atypical lymphoid cells present, demonstrating nuclear irregularity with the presence of nucleoli and surrounding scant to slight amount of cytoplasm. Numerous lymphoglandular bodies were seen in the background. Both cases were correctly diagnosed as representing non-Hodgkin's large-cell lymphomas. Two other cases had slight cellularity with the presence of a few scattered atypical lymphoid cells. Although a definite diagnosis was not rendered in either case, the possibility of malignant lymphoma was considered. Two other cases consisted predominantly of microtissue fragments with some associated scattered individual atypical cells. Within the microtissue fragments, the cells were distorted with a tendency to elongate and spindle in a prominent fibrous matrix. Our experience demonstrates that FNA cytology of primary mediastinal diffuse large cell lymphoma with sclerosis can be challenging, with a potential for a false-negative diagnosis due to limited cellularity secondary to the sclerosis or a misdiagnosis as a spindle cell neoplasm due to distortion of these cells by the fibrous matrix. To the best of our knowledge, we believe this is the first FNA series of primary mediastinal diffuse large cell lymphoma with sclerosis.
Adult↗
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↗
Adenocarcinoma in the lung in patients with breast cancer. A prospective analysis of the discriminatory value of immunohistology.
In some patients with a history of breast cancer who also have masses in the lung, making a clinical distinction between primary pulmonary neoplasia and pulmonary metastasis of mammary carcinoma may be impossible. To ascertain whether immunohistologic studies could contribute to resolving this problem, the authors undertook a prospective study of 30 cases showing synchronous or metachronous adenocarcinomas in these two sites. A predefined panel of antibodies--as derived from published antigenic catalogs for breast and lung cancer--was applied to each case. Tumors were interpreted as metastases if they were positive for gross cystic disease fluid protein-15, estrogen receptor protein, or S-100 protein. Conversely, primary adenocarcinomas of the lung were defined by their expression of carcinoembryonic antigen and a lack of the other three determinants. Using these criteria, 15 lesions were classified as metastatic; 11 were categorized as primary pulmonary adenocarcinomas; and 4 cases were indeterminate in origin. Responses to corresponding therapeutic protocols generally supported the validity of the immunohistologic diagnoses; 8 of 15 patients treated for metastatic breast cancer were well at least contact, as were 5 of 11 patients who received therapy for primary carcinoma of the lung. These data suggest that immunohistology plays a useful role in distinguishing mammary from pulmonary adenocarcinomas.
Adenocarcinoma↗