Clinicopathologic management of tumors of the thyroid gland in an endemic goiter area. Combined use of preoperative fine needle aspiration biopsy and intraoperative frozen section

In total, 15,325 fine needle aspiration (FNA) biopsies of the thyroid were examined in the Department of Pathology of the University of Innsbruck, Austria, between 1976 and 1985, with the cytologic results histologically verified in 3,112 cases. Since (1) it is frequently impossible to distinguish benign from malignant encapsulated follicular thyroid tumors by cytologic criteria and (2) there is a high level of follicular thyroid carcinoma in our endemic goiter area, we have adopted a diagnostic strategy that accepts a high percentage of false-positive cytologic results in order not to miss highly differentiated follicular carcinoma. To avoid unnecessarily extensive surgical treatment, 1,079 intraoperative frozen section examinations of the thyroid were performed in the same time period in (1) patients with preoperative suspicious or positive FNA cytologic findings, (2) cases with suspicious clinical and anamnestic data and (3) tumors with a suspicious macroscopic appearance without preoperative FNA or with negative or unsatisfactory cytologic findings. In 48 cases (4.5%), the frozen section diagnosis had to be revised after examination of paraffin-embedded tissue. An intraoperative false-positive diagnosis was obtained in 3 cases (0.3%) while a false-negative diagnosis was made in 45 cases (4.2%). The main effort in examining frozen sections should be concentrated on avoiding false-positive errors, which can lead to unnecessary thyroidectomies.     

Metastatic tumors in fine needle aspiration biopsy of the thyroid

A series of almost 25,000 thyroids examined by fine needle aspiration (FNA) biopsy was reviewed to ascertain the incidence and presentation of metastatic cancers in thyroid FNA samples. Metastatic cancers in FNA samples from the thyroid were identified in 25 cases (0.1%); the primary tumors were carcinomas of the kidney (8 cases), lung (7 cases), breast (5 cases), cervix uteri (1 case) and colon (1 case) and 1 case each of malignant melanoma, malignant pleural mesothelioma and rhabdomyosarcoma. FNA cytology was positive in all 25 cases. In 11 cases, the primary tumor was clinically known at the time of FNA biopsy; of the other 14 cases, cytology suggested that the malignancy was metastatic in only 5. Metastases of renal and mammary adenocarcinomas were almost indistinguishable from follicular and papillary thyroid carcinomas on cytologic grounds. The results demonstrate the rarity of this finding and the difficulty of diagnosing a metastatic tumor in the thyroid by FNA biopsy, in the absence of a clinical history of a prior primary neoplasm.     

Necrosis of thyroid nodules after fine needle aspiration

In a series of 200 fine needle aspirations (FNA) of the thyroid, necrosis around the needle tract was histologically evident in 2 of 30 cases with surgical follow-up. In one case of a differentiated thyroid carcinoma, necrosis with involution of the nodule was the dominant finding. This suggests that FNA can induce necrosis and apparent clinical regression of thyroid neoplasms. We believe, however, that a positive cytologic diagnosis coupled with a clinical suspicion of neoplasm should lead to surgical intervention, despite clinical regression following FNA.     

Usefulness of light microscopy in lymph node fine needle aspiration biopsy

OBJECTIVE: To evaluate light microscopic examination of lymph node fine needle aspiration biopsy (FNAB) in order to determine the indications for ancillary procedures and biopsy. STUDY DESIGN: Reports and smears from 693 consecutive lymph node FNABs were reviewed. Fifty-five cases were excluded because of inadequacy of the material, and another 26 were excluded because follow-up information was not available. RESULTS: Cytologically, 220 cases were diagnosed as positive for malignancy and 392 as negative. Global sensitivity was 94.1% and specificity 96.9%. Sensitivity was higher for nonlymphoid neoplasms (98.2%) than for lymphoproliferative disorders (82.8%). CONCLUSION: Lymph node FNAB is a cost-effective procedure, and with adequate cytologic examination and follow-up, a large number of biopsies and time-consuming ancillary techniques can be avoided.     

Calcium oxalate crystals in thyroid fine needle aspiration cytology

OBJECTIVE: To determine the occurrence, distribution and location of calcium oxalate crystals (COCs) in thyroid fine needle cytology specimens. STUDY DESIGN: Thyroid tissues from 60 fine needle aspiration cytology specimens (31 benign and 29 malignant lesions) were reviewed. These lesions were also histologically examined, and their pathologic diagnosis was confirmed. The cytologic slides were examined by normal and polarized light microscopy to determine their size, shape, occurrence, distribution and location. RESULTS: The size and shape of COCs varied from case to case. The total incidence was 45% (benign diseases, 68%; malignant lesions, 21%). No significant relationship between age and occurrence of COCs was found. Benign diseases showed more multifocal than focal distribution of COCs, unlike malignant diseases. Twenty-three (85%) of 27 cases with COCs revealed background location of COCs, especially within thyroid colloid. CONCLUSION: The occurrence of COCs in thyroid fine needle cytology was lower than that in histologic specimens reported in the literature, and COCs were more often identified in benign than malignant lesions. The presence of COCs may be a clue to benign lesions if their distribution is taken into consideration.     

Comparative study of fine needle aspiration and fine needle capillary sampling of thyroid lesions

OBJECTIVE: To investigate whether fine needle capillary (FNC) sampling gives quantitatively and qualitatively superior cytologic material as compared to the conventional technique of fine needle aspiration (FNA) when performed by a single aspirator. STUDY DESIGN: Cross-sectional diagnostic test evaluation study. FNA and FNC were performed by a single operator on 200 diffuse and nodular thyroid lesions. RESULTS: A statistically significant difference in favor of FNC was observed for the parameter amount of cellular material. For the rest of the parameters--background blood or clot, degree of cellular degeneration, degree of cellular trauma and retention of architecture--the average score favored FNC but was not statistically significant--i.e., smears prepared from FNC displayed cellular material that was more concentrated, less damaged and less likely to be obscured by blood. CONCLUSION: Although FNC sampling was diagnostic in a greater number of cases than FNA sampling, this study did not prove a clear superiority of FNC over FNA. Until greater experience shows clear sampling superiority of FNC alone, rather than performing only FNA in diffuse or nodular thyroid lesions, incorporating FNC into the second puncture will definitely improve the quality and quantity of material at the patient's first visit.     

Value of repeated fine needle aspiration cytology in patients with nodular goiter

OBJECTIVE: To assess the value of reaspiration cytology in benign nodular thyroid disease. DESIGN: We prospectively studied 400 patients (365 women, 35 men) aged 46 years (18-89) with nodular thyroid disease and initial benign fine needle aspiration cytology (FNAC). Reaspiration of the same nodule was performed in a median follow-up time of 14 months (6-18). RESULTS: Repeat FNAC was benign in 346 patients (86.5%), insufficient for diagnosis in 42 (10.5%), suspicious in 16 (2.5%) and malignant in 2 (0.5%). All diagnostic changes to suspicious malignant cytology took place in patients with solitary nodules. Surgery confirmed thyroid cancer in the 2 patients with malignant cytology, in 5 of 10 patients with suspicious cytology and in none of 39 patients with benign cytology who underwent surgery for other reasons. Clinical changes (size increase or local symptoms) were not related to changes in cytologic diagnosis after a second aspiration, nor with the results of the biopsy. CONCLUSION: Repeat aspiration cytology of thyroid nodules may correct initial false negative results because of cytologic misdiagnosis, occurring in 1.75% of patients, whereas clinical changes did not contribute to diagnosis change. Repeat aspiration cytology is recommended in all patients with nodular goiter.     

Worrisome histologic alterations following fine needle aspiration of the thyroid

OBJECTIVE: To investigate worrisome histologic alterations following fine needle aspiration (FNA) of the thyroid (WHAFFT). STUDY DESIGN: Of 1,890 FNA thyroid cases, 265 underwent surgical excision. The histologic sections of these cases were studied for WHAFFT lesions. Thirty control cases were also studied. RESULTS: WHAFFT lesions were present in 38.49% of cases. Acute lesions were seen in 30 and chronic in 72 cases. Control cases did not show WHAFFT lesions. The common lesions were hemorrhage and fibrosis. Worrisome lesions, like nuclear atypia, vascular changes, capsular pseudoinvasion and metaplasia, were present in 32 (12.07%) cases. CONCLUSION: Considering the large number of FNAs and reduction in the number of thyroid excisions, the advantages of FNA are manifold as compared to the few diagnostic problems. Misdiagnosis can be avoided with awareness of WHAFFT lesions.     

Use of a thin-layer technique in thyroid fine needle aspiration

OBJECTIVE: To investigate the efficacy of the ThinPrep Processor (Cytyc Corporation, Boxborough, Massachusetts, U.S.A) in fine needle aspiration (FNA) of thyroid gland lesions. STUDY DESIGN: This study included 459 thyroid FNA specimens obtained from patients who came to our endocrinology department with various thyroid disorders over 3 years. The cytologic material was prepared using both the conventional and ThinPrep method in the first 2 years (285 cases), while in the last one only the ThinPrep method was used (1 74 cases). The smears were stained using a modified Papanicolaou procedure and May-Grünwald-Giemsa stain. Immunocytochemistry was performed on thin-layer slides using specific monoclonal antibodies when needed. Thin-layer and direct smear diagnoses were compared with the final cytologic or histologic diagnoses, when available. RESULTS: Our cases included 279 adenomatoid nodules, 15 cases of Hashimoto thyroiditis, 45 follicular neoplasms, 14 Hürthle cell tumors, 58 papillary carcinomas and 1 5 anaplastic carcinomas. Thin-layer preparations showed a trend toward a lower proportion of inadequate specimens and a lower false negative rate. Cytomorphologic features showed some differences between the 2 methods. Colloid was less frequently observed on ThinPrep slides, while nuclear detail and micronucleoli were more easily detected with this technique. Moreover, ThinPrep appeared to be the appropriate method for the use of ancillary techniques in suspicious cases. CONCLUSION: Thin-layer cytology improves the diagnostic accuracy of thyroid FNA and offers the possibility of performing new techniques, such as immunocytochemistry, on the same sample in order to detect malignancy as well as the type and origin of thyroid gland neoplasms.     

Cytopathology of papillary carcinoma of the thyroid by fine needle aspiration

To delineate the cytologic presentation of papillary carcinoma of the thyroid, the fine needle aspiration smears were studied from 87 surgically proven cases. Six diagnostically useful findings were identified: papillary fronds, monolayered sheets, tissue fragments, intranuclear cytoplasmic inclusions, psammoma bodies and multinucleated giant cells. From 1,500 smears on "cold" nodules of the thyroid, 6 known false-negative and 4 false-positive diagnoses for papillary carcinoma were made. The estimated accuracy of the fine needle aspirate diagnosis of papillary carcinoma is 94%.     

Fine needle aspiration cytology and immunocytochemistry in a case of intrathoracic thyroid goiter

Fine needle aspiration (FNA) was performed in the case of a patient with an anterior mediastinal mass. Examination of the smears revealed individual and groups of benign nondiagnostic cells. Surgical removal and histologic examination indicated that the mass was a true intrathoracic thyroid goiter. Subsequent immunocytochemical studies on the FNA smears showed thyroglobulin in the cytoplasm of the aspirated cells. The cytologic findings are presented; while not diagnostic of a thyroidal origin in this case, they serve as a reminder of the wide range of cytologic appearances of colloid nodules and goiters. This case will hopefully heighten the awareness of cytologists and other physicians to the consideration of the possibility of intrathoracic goiter in the differential diagnosis of mediastinal lesions seen in fine needle aspirates.     

Thin layer compared to direct smear in thyroid fine needle aspiration

The efficacy of preparing thyroid fine needle aspirations (FNAs) by the thin layer as opposed to the direct smear method has not been evaluated sufficiently in a regional laboratory setting. At the Foothills Hospital (Calgary, Canada), the method of processing thyroid FNAs was changed from direct smear to thin layer in January 1996. The results of 327 patients who had direct smear from 1994 to 1995 were compared to 401 who had thin layer between 1996 and 1997. While there were no significant differences across a broad range of quality indicators, thin layer showed a trend towards a higher proportion of true benign diagnoses (31% vs 24%), a lower proportion of inadequate specimens (41% vs 50%) and, most importantly, a lower false negative rate (3% vs 9%). In conclusion, the changeover to thin layer did not compromise the interpretation of thyroid FNAs.     

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.     

Three-dimensional cytomorphology in fine needle aspiration biopsy of medullary thyroid carcinoma.

OBJECTIVE: To elucidate three-dimensional (3-D) cytomorphology in fine needle aspiration biopsy (FNAB) of medullary thyroid carcinoma (MTC). STUDY DESIGN: ENAB was performed on tumors from five patients with MTC. The aspirate was stained and observed under a light microscope (LM). The aspirate was also fixed, dehydrated, critical point dried, spattered with gold ions and observed with a scanning electron microscope (SEM). For transmission electron microscopy (TEM), the specimen was fixed, dehydrated, embedded in an Epon mixture, cut with an ultramicrotome, mounted on copper grids, electron doubly stained with uranium acetate and lead citrate, and observed with TEM. Findings under SEM were correlated with those under LM and TEM. RESULTS: Under SEM, 3-D cytomorphology of MTC displayed a disorganized cellular arrangement with indistinct cell borders in three cases. The cell surface was uneven and had granular protrusions that corresponded to secretory granules observed under TEM. In one case with multiple endocrine neoplasia type IIB, there were abundant granules on the cell surface. In one case of sporadic MTC with multinucleated tumor giant cells and small cells, granular protrusions also were noted on the cell surface. CONCLUSION: Granular protrusion was a characteristic finding in FNAB of MTC tinder SEM and might be helpful in the differential diagnosis.     

Fine needle aspiration cytodiagnosis of anaplastic carcinoma and malignant haemangioendothelioma of the thyroid in an endemic goitre area

Between 1970 and 1987, 20,028 fine needle aspirates (FNA) of the thyroid have been examined in the Department of Pathology of the University of Innsbruck, Austria. During this period 92 cases of anaplastic carcinoma and 16 cases of malignant haemangioendothelioma (MHE) of the thyroid were diagnosed. Forty-three out of these 108 highly malignant tumours of the thyroid underwent FNA pre-operatively (39.1%). Thirty-seven FNA contained numerous cells of a highly malignant tumour. Five specimens (11.8%) contained only necrotic material and inflammatory cells. In one case of an anaplastic carcinoma no malignant cells could be demonstrated in FNA. We conclude that pre-operative FNA of highly malignant thyroid tumours may contribute substantially to subsequent clinical management.     

Association of different pathologic processes of the thyroid gland in fine needle aspiration samples

OBJECTIVE: To evaluate the possible significant association between different pathologic processes of the thyroid gland. STUDY DESIGN: From a series of 10,039 fine needle aspiration biopsies of the thyroid gland, a total of 1,330 cases were aspirated involving two or more palpable nodules. In 103 (1%) cases, two different pathologic processes were cytologically diagnosed. Statistical analysis was performed through four two-tailed chi 2 tests to evaluate the following events: (1) mononodularity and multinodularity vs. neoplasms, (2) colloid goiter and neoplasms, and (3) all neoplasms vs. colloid goiter and lymphocytic thyroiditis. All tests were performed using < .05 as the probability level. RESULTS: Simultaneous pathologic processes observed were: goiter and chronic lymphocytic thyroiditis (32), goiter and Hashimoto's thyroiditis (21), goiter and subacute granulomatous thyroiditis (8), goiter and follicular neoplasm (9), and goiter and papillary carcinoma (14). In 12 cases we found goiter and Hürthle cell tumor, goiter and medullary thyroid carcinoma (2), papillary thyroid carcinoma and Hashimoto's thyroiditis (2), Graves' disease and lymphocytic thyroiditis (2), and follicular neoplasm and lymphocytic thyroiditis (1). Statistical analysis showed significant association between multinodularity and neoplasms (P < .001), while the association between goiter and any type of neoplasia was not statistically significant. All the neoplasms taken together were associated with lymphocytic thyroiditis and goiter (P < .005). CONCLUSION: While there may be no statistically significant associations between the individual pathologies, it seems that having one pathology increases the risk of developing another. All the palpable nodules in the same gland should be investigated by fine needle aspiration in order to improve diagnostic sensitivity and to identify occult neoplasms.