Fine needle aspiration cytology of the thyroid: a comparison of 5469 cytological and final histological diagnoses.

OBJECTIVE: We evaluated the efficacy of fine needle aspiration cytology (FNAC) of the thyroid in a series of 5469 lesions with histological control and studied the causes of, and the possibility of reducing the limitations of the method. METHODS: FNAC was always performed by a pathologist under the guidance of a clinician, using a 22-gauge needle. Generally two aspirations were carried out, and usually four slides were obtained for each nodule; they were then stained with May-Grünwald-Giemsa and with Papanicolaou. The cytological diagnoses were classified in four groups: inadequate, benign, suspicious and malignant. RESULTS: We obtained a complete sensitivity of 93.4%, a positive predictive value of malignancy of 98.6%, and a specificity of 74.9%. At histological control, the cytological diagnosis of Hurthle cell neoplasm corresponded to a significantly higher incidence of malignant neoplasms than the diagnosis of non-Hurthle cell follicular neoplasm (32.1% versus 15.5%). There were 66 false-negative findings, the main cause of diagnostic error (24 cases) being failure to recognize the follicular variant of papillary carcinoma. The number of inadequate FNACs was low (4.2%). CONCLUSION: Our study confirmed the great efficacy of thyroid FNAC. A cytological diagnosis of Hurthle cell neoplasm should be considered an indicator of high risk. Awareness that failure to recognize the follicular variant of papillary carcinoma was the main problem in the interpretation of thyroid FNAC should lead to a decrease of false-negative diagnoses. The inadequate rate was very low, as it was the pathologist personally who performed the needle aspiration.

Fine needle aspiration cytology of primary lymphoma of the thyroid: a report of 17 cases.

Between 1980 and 1998, 4272 thyroid surgical specimens with a preoperative fine needle aspirate were sent to our Anatomical Pathology Department. Among these cases there were 17 primary thyroid lymphomas, which constituted 0.3% of all the thyroid lesions and 2.3% of the thyroid malignancies. Seven cases were diffuse large B-cell (DLBC) lymphomas and 10 were MALT lymphomas. Of the DLBC lymphomas six were correctly diagnosed by fine needle aspiration cytology (FNAC) and one was diagnosed as positive for malignancy, and among MALT lymphomas four were diagnosed as lymphoma, four as suspicious for lymphoma, and three as Hashimoto's thyroiditis (HT). Our data indicate that the diagnosis of primary thyroid lymphoma of high grade is easy, and immunocytochemistry (ICC) can confirm suspicious cases. The diagnosis of MALT lymphoma is more difficult; ICC can confirm suspicious cases, and false-negative results seem to be caused by sampling error, because HT usually coexists with MALT lymphoma.

Multivariate analysis of patients with medullary thyroid carcinoma. Prognostic significance and impact on treatment of clinical and pathologic variables.

BACKGROUND: The prognostic significance of the histologic and clinical features of medullary thyroid cancer (MTC) and their impact on therapy and outcome have been evaluated infrequently in the same series. METHODS: Fifty-tree patients with MTC (32 females, 21 males; 44 sporadic, 9 familial MTC [4 families]; mean age: 46.11 +/- 14.04 years) who were operated on consecutively between 1970 and 1992 were studied. All pathology slides were reviewed. Patients were followed with clinical examination, serum calcitonin (CT), and carcinoembryonic antigen (CEA) assay, and imaging procedures (median follow-up: 4 years; mean: 5.66 +/- 4.85 years; range: 0-19 years). Impact on survival was evaluated with Kaplan-Meier survival curves compared with the log rank test for these variables: familiarity, sex, age, pT, N, M, stage, histotype, necrosis, calcitonin, gene-related peptide (CGRP), CT, CEA, thyroglobulin, chromogranin A, chromogranin A PHE5, neuron-specific enolase, amyloid, argyrophilia, synaptophysin Y38, external radiotherapy, chemotherapy, 131I therapy, postsurgical serum CT, and postsurgical serum CEA, Multivariate analysis was performed using Cox's proportional hazards model for statistically significant factors (P < 0.05). RESULTS: Ten- and 15-year cause-specific survival were 71% and 54%. Nineteen patients (35.8%) appeared to be cured and 8 (15.1%) were alive with high serum CT levels but no proven metastases. Eight recurrences as distant sites and four at the cervical region were diagnosed. Stage M, N, necrosis, and postsurgical CT and CGRP were significant prognostic factors for survival by univariate analysis, but only the stage was significant by multivariate analysis. CONCLUSIONS: Stage and postsurgical serum CT level are the most powerful and the most useful prognostic factors for MTC, while survival did not correlated significantly with the majority of available immunohistochemical markers.

Bone marrow biopsy for the staging of non-Hodgkin's lymphoma: bilateral or unilateral trephine biopsy?

AIM: The occurrence of unilateral involvement in bilateral bone marrow trephine biopsies in non-Hodgkin's lymphomas (NHL) at disease onset (10-20% of cases) has been reported since the early 70s. Therefore, although these studies were based on small series, the use of bilateral bone marrow biopsies has become the rule. However, the clinical value of this procedure has never been clearly established. The aim of the present study was to ascertain the true value of bilateral bone marrow biopsy in the staging of NHL. STUDY DESIGN: We examined 368 cases of NHL (A-H according to the Working Formulation) (WF), without leukemic involvement of the peripheral blood, in order to evaluate: 1) the incidence of unilateral bone marrow involvement; 2) the percentage of patients who, as a result of unilateral bone marrow involvement, changed from stages I-II to stage IV; 3) assessment of response to therapy for patients with both bilateral or unilateral bone marrow involvement. RESULTS: In the A-C NHL groups of WF there was a unilateral bone marrow involvement of 8.8%. Overall, bone marrow involvement induced a change from clinical stages I-II to stage IV in 5.6% of cases, a figure which would correspond to a false negative rate of 2.8%, if unilateral bone marrow biopsy was performed. In the D-F and G, H groups of WF, unilateral involvement was 10.1% and 8.5% respectively; the change in stage from I-II to IV by unilateral bone marrow involvement respectively amounted to 1.4% and 2.8%, which correspond to respective false negative rates of 0.7% and 1.4%. CONCLUSIONS: On the basis of these results and of the present therapeutic strategies, we propose: bilateral bone marrow biopsy for clinical stages I-II of all NHL; no bone marrow biopsy at disease onset for clinical stages III and IV of A to H histologic subtypes of the WF; unilateral bone marrow biopsy (A-C subtypes of the WF) or bilateral (D-H of the WF), after the regression of extramedullary localizations.

Epidemiology of human toxocariasis in northern Italy.

Sera from both clinically healthy adults (2112) and adult patients (471) were tested to assess the main risk factors for Toxocara infection in humans in Northern Italy. The patient group included 257 adult epileptics, 76 Strongyloides stercoralis-infected adult patients and 142 institutionalized mentally retarded adult patients. The overall seroprevalence in healthy population was 3.98%. No significant differences in seroprevalence were observed for sex, residence (urban or rural) or dog ownership, while seroprevalence significantly increased with age (18- greater than 51 years). Highest seroprevalence values were found in outdoor or soil-related workers. The seroprevalence was 4.35% in adult epileptics, 9.21% in Strongyloides stercoralis-infected patients and 14.47%-10.61% among institutionalized mentally retarded patients. These findings suggest that the prevalent source of human toxocariasis is the environmental contamination by infectious eggs of the parasite.

Percutaneous alcohol injection of portal thrombosis in hepatocellular carcinoma: a new possible treatment.

Hepatocellular carcinoma (HCC) with portal thrombosis is usually regarded as a contraindication for surgery and for percutaneous alcohol injection (PAI). For palliative purposes we used PAI in 4 patients with infiltrative HCC and segmental portal thrombosis. Ethanol, injected directly into the thrombus, diffused mostly along it. No complications emerged after 20 injections. In the first patient, who later received a liver transplant, the thrombus was completely necrotic. In the other patients, biopsies yielded only necrotic material: in two cases, progression of the thrombus was stopped at 4 and 12 months of follow-up, and in one case the thrombus shrank and remained as such 13 months later. This preliminary experience might broaden the scope of treatment for HCC.

Fine needle biopsy of hepatocellular carcinoma: improvement in diagnosis by microhistology.

Percutaneous liver biopsies with fine aspirating and cutting needles were performed under ultrasound guidance to diagnose hepatocellular carcinoma in 112 cases. All the specimens were examined partially with cytologic methods and partially with microhistology. Cytology established the diagnosis of hepatocellular carcinoma in 83 cases and of generic malignancy in 12, with 9 false-negatives and 8 inadequates. Microhistology established the diagnosis of hepatocellular carcinoma in 92 case and of generic malignancy in 2, with 3 false-negatives and 15 inadequates. In all, the combined retrieval rate was 98% with only 2 cases of inadequate material and the diagnosis of hepatocellular carcinoma was possible in 105 cases (93.7%).

Adenomatous hyperplastic nodules in the cirrhotic liver: a therapeutic approach. Work in progress.

Adenomatous hyperplastic nodules (AHNs) in the cirrhotic liver may be precurosors of hepatocellular carcinoma. These nodules have been demonstrated more frequently because of the increased use of ultrasonography (US) in the screening of high-risk patients. Treatment is a problem because surgical resection of a precancerous lesion is considered by some to be unadvisable in patients with high surgical risk. The authors used percutaneous ethanol injection with US guidance in five patients with AHNs that measured 1.4-2.6 cm. A total of 30 injections were performed, without complications. Lesions were undetectable or were reduced in size on follow-up US scans. All biopsies yielded necrotic material. No recurrences have been demonstrated with US after 9-21 months. Percutaneous ethanol injection is therefore proposed as a therapeutic alternative for small AHNs.

Fine aspiration versus fine cutting needle, and comparison between smear cytology, inclusion cytology and microhistology in abdominal lesions.

Two hundred patients underwent ultrasound guided percutaneous fine needle biopsy of focal solid abdominal lesions using 22 gauge aspiration and cutting needles. The material obtained by aspiration needle was treated by smear cytology and by inclusion cytology, and that obtained by cutting needle by microhistology. The retrieval rate was 89% for aspiration needle (smear cytology = 89%, inclusion cytology = 83.5%) and was 83% for cutting needle; the combined diagnostic accuracy was 98%. The typing accuracy was 76% for smear cytology, and was 84% for inclusion cytology and microhistology. We conclude that: 1. to obtain the highest retrieval rate (98%) both aspiration and cutting needles are necessary, because the aspiration needle is more likely to secure necrotic or soft tissue, and the cutting needle, fibrous or hard tissue; 2. histologic treatment of the samples yields a higher typing accuracy: 84% vs 76%; however, smear cytology remains essential because it permits a much faster evaluation of the adequacy of the sample and because it may avoid histologic methods in 76% of cases; 3. the smear cytology + microhistology combination seems to be the best solution (retrieval rate = 97.5%), but the costs are much higher because the cutting needle is somewhat expensive. The best solution would be to use the combination smear + inclusion cytology (retrieval rate = 89%) and to reserve the cutting needle for when aspiration needle material proves to be inadequate.

240 hepatocellular carcinomas: ultrasound features, tumor size, cytologic and histologic patterns, serum alpha-fetoprotein and HBs Ag.

Two hundred and forty cases of hepatocellular carcinomas (HCC), diagnosed by ultrasonography and fine needle biopsy, were studied. The following parameters were investigated: 1. echo features (240 cases) - hypoechoic, 54; hyperechoic, 56; complex, 112; isoechoic with halo, 18; 2. tumor size (240 cases) - single tumor under 4.5 cm, 30; single tumor over 4.5 cm, 74; multiple masses or diffuse, 136; 3. cytologic pattern (240 cases) - well and medium differentiated, 144; pleomorphic, 43; poorly differentiated, 28; unclassified, 25; 4. histologic pattern (157 cases) - trabecular, 74; solid, 42; acinar, 1; mixed, 2; unclassified, 38; 5. alpha-fetoprotein (AFP) level (185 cases) - under 20 ng/ml, 79; between 20 and 320 ng/ml, 40; over 320 ng/ml, 66; 6. HBs Ag (208 cases) - present in 56 cases; 7. cirrhosis (102 cases) - present in 79 cases. Some of the above parameters were correlated with one another. There was: 1. a highly significant frequency of the hypoechoic feature among small HCC; 2. a percentage of AFP-producing tumors increasing with tumor size; 3. no relationship between AFP production and cytologic or histologic pattern; 4. no relationship between tumor size and cytologic or histologic pattern. However, among the small HCC, all the 9 HCC with a diameter of less than 3 cm showed a trabecular pattern and well-differentiated cells. Cirrhosis was present in every patient with a small HCC. Since the discovery of a small HCC is an incidental ultrasonographic finding in the context of severe liver disease, ultrasonographic monitoring of cirrhotic patients is the best available strategy to screen for small HCC.

Primary mediastinal embryonal carcinoma and choriocarcinoma. A case report.

A case of primary malignant germ-cell tumor of the mediastinum is presented. The diagnosis was suggested by a fine needle aspiration biopsy and confirmed by alpha-fetoprotein and human chorionic gonadotropin demonstration in the patient's serum. The cytologic, gross and microscopic findings are described.

Inclusion-cytology versus smear-cytology in fine needle abdominal biopsy.

1568 patients underwent percutaneous fine needle biopsy (22-23 g. Chiba). 761 of these had histologic type confirmation of malignant disease. Among the latter, 313 cases had adequate samples retrieved from the same lesion for smear cytology (SC) and inclusion cytology (IC), 400 for SC alone (378 performed before the use of IC) and 48 for IC alone. SC was stained by Papanicolaou and MGG, IC by haematoxylin-eosin technique. In SC + IC group typing accuracy was 0.64 for SC and 0.86 for IC, in SC group was 0.66, in IC group was 0.87. IC permitted an easier preparation and interpretation of special stains. In conclusion, IC routine is recommended. Some interesting observations were possible because material was collected from three hospitals.

Smear and inclusion cytology in Chiba-needle aspiration biopsy of hepatic tumors.

183 patients underwent fine-needle liver biopsy with a Chiba 22-gauge needle for suspected neoplasia, and the specimens were prepared for smear and inclusion cytology. 149 patients were controlled and 106 were true positives. Of these, 79 yielded material suitable for both methods, which could thus be compared. The results showed that inclusion cytology improves the typing accuracy for the diagnosis of well-differentiated primary liver tumors. Further, specimens for embedding can be obtained with ordinary Chiba 22-gauge needles which are normally used only for obtaining material for smear cytology.

Focal fatty liver change by sonography.

Focal fatty liver change (FFLC) is a poorly characterized entity whose ultrasound pattern has not yet been properly defined. From our experience based on 12 cases and from the few cases reported in the literature, the following conclusions can be made: (1) FFLC can be of increased and decreased echogenicity with map-like or clearcut margins; (2) rounded lesions with defined margins are indistinguishable from other focal pathology; according to the case, fine needle biopsy, arteriography, computed tomography or nuclear scan should be used; (3) FFLC can change in size or disappear in a short span of time, and (4) a hypoechogenic area with map-like margins in the quadrate lobe (even if it turns out to be a false focal defect in that it corresponds to residual normal liver tissue) of a patient with abnormal values for gamma-glutamyltransferase (GGT) and serum glutamic oxaloacetic transaminase (SGOT) is reasonably indicative of FFLC.

Fine needle biopsy of a patent umbilical vein thrombus demonstrates hepatocellular carcinoma.

An umbilical vein thrombosis was shown to be neoplastic by fine needle biopsy. The aspirated material permitted to trace the primary tumor, a hepatocellular carcinoma, not diagnosed by ultrasonography.

Alpha 1-antitrypsin in patients with hepatocellular carcinoma and chronic active hepatitis.

Forty-seven Italian patients suffering from hepatocellular carcinoma (HCC) and 58 patients with chronic active hepatitis (CAH) were screened for alpha 1-antitrypsin (alpha 1 AT) levels and types and compared with a previously screened healthy Italian population. Serum alpha 1 AT concentrations were significantly raised among the HCC patients compared to the controls, whereas the CAH group showed no differences. The incidence of non-M phenotypes (MS, MZ and S) is significantly higher in patients with HCC than in the CAH group and the controls. The mean age of HCC patients with a non-M phenotype is significantly lower than the mean age of HCC patients with an M phenotype.

Evaluation of T and B lymphocytes in liver infiltrates of patients with chronic active hepatitis.

The proportions of T and B lymphocytes in the liver infiltrates of 23 patients with chronic active hepatitis have been determined. The results were compared with the values obtained from peripheral blood and with the presence of HB virus markers and alpha-fetoprotein in liver tissue. A group of patients with chronic liver disease other than chronic active hepatitis were studied as controls. In chronic active hepatitis the percentage of hepatic T cells was 49 +/- 8 SD (control patients 61 +/- 8) (P less than 0.01), whereas the percentage of B cells was 40 +/- 10 (control patients 18 +/- 8) (P less than 0.01). No correlation was observed between hepatic T and B cells and the presence of HB virus. The numbers of T cells in liver tissue was significantly higher, the numbers of B cells lower, in patients whose biopsies were positive for alpha-fetoprotein than in those whose biopsies were negative. In peripheral blood, only the patients with chronic active hepatitis and established cirrhosis presented lower absolute values of T cells, whereas surface immunoglobulin-positive lymphocytes were within the normal range.