Insight to neoplastic thyroid lesions by fine needle aspiration cytology.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a valuable adjunct to pre-operative screening in the diagnosis of thyroid nodules, and in most cases, it can distinguish between benign and malignant lesions. AIM: To study the cytology of neoplastic thyroid lesions to minimize surgical intervention and for confirmation of the diagnosis by histopathological study.
MATERIALS AND METHODS: 100 cases of thyroid FNAC smears were analyzed and cyto-histopathological correlation was done in 47 cases. Galen and Gambino's method was used to calculate the sensitivity and positive predictive value.
RESULTS: Of the 100 cases, 90 were diagnosed as neoplastic lesions by FNAC and ten cases as non-neoplastic lesions, which turned out to be neoplasms on histopathological study. Among 100 cases, 47 were biopsied and subjected to histopathological study. The sensitivity of FNAC was 75.60%, and positive predictive value was 83.78% for malignant lesions.
CONCLUSIONS: FNAC is a rapid, efficient, cost-effective, relatively painless procedure with a high diagnostic accuracy. It has high rate of sensitivity and positive predictive value in diagnosing thyroid neoplastic lesions. Hence, it is a valuable tool in the diagnosis and management of patients.

Introduction

Thyroid is a frequent site of disease in human body. Fine needle aspiration cytology (FNAC) is a simple, safe, rapid, cost-effective diagnostic method and is a valuable adjunct to pre-operative screening in the diagnosis of thyroid lesions and a valuable tool in the management of patients.[12] Lymphoma and undifferentiated carcinoma of thyroid can be treated with radiation or chemotherapy and do not need surgery. This study was undertaken to appreciate the cytology of neoplastic thyroid lesions to improve the diagnostic accuracy, to minimize surgical intervention, and for confirmation of the diagnosis by histopathology

Materials and Methods

FNAC of hundred cases of a suspected neoplastic thyroid were performed using 23-gauge needle by the non-aspiration technique. Ultrasound-guided FNACs were performed wherever necessary. In cases of cystic lesions, fluid was completely aspirated and was centrifuged. Subsequently sedimented material was examined. Re-aspiration was done in such cases. Slides were studied after staining with hematoxylin-eosin, Papanicolaou and May-Grünwald-Giemsa (MGG) stain. Cyto-histopathological correlation was done in 47 cases.

Inclusion criteria

Cases, which were diagnosed as neoplastic by cytology.

Those cases diagnosed as non-neoplastic by FNAC but turned out to be neoplastic by histopathology.

Exclusion criteria

Those cases, which were diagnosed as non-neoplastic lesions cytologically.

Cases with inadequate material for interpretation.

Statistical analysis

Galen and Gambino's method was used to calculate the sensitivity and positive predictive value.

Results

The present study was conducted prospectively from July 2008 to June 2010. During this period, 585 cases of thyroid FNACs were done. Hundred cases were diagnosed to have neoplastic lesions by FNAC, and histopathologic correlation was possible in 47 cases. Age ranged from 11-70 years, median age was 40.57 years, and majority of cases were clustered in third decade. Females [75 cases (75%)] were predominantly affected with male to female ratio of 1:3.

Majority of cases presented with solitary nodule while few cases presented with diffuse or nodular swelling. A few had difficulty during swallowing or breathing and change of voice. All the patients tolerated the procedure well without any complications. The aspirate was satisfactory for interpretation in majority. It was blood mixed to frankly hemorrhagic and in some cases, either brown or dark brown fluid was aspirated, ranging from 1 to 8 mL.

In our study, 100 suspected neoplastic cases were analyzed, and 90 cases were reported as neoplastic. Ten cases, diagnosed as non-neoplastic cytologically, turned out to be malignant by histopathology. Neoplastic lesions diagnosed cytologically were 56 cases of follicular neoplasm, 29 cases of papillary carcinoma, 2 cases of medullary carcinoma, 2 cases of anaplastic carcinoma, and 1 case of metastatic carcinoma.

Cytological diagnosis of follicular neoplasm [56 cases] included a single case of Hurthle cell adenoma [Figure 1]. Histopathological correlation was done in 21 cases with a diagnostic accuracy of 76.19%. Six cases proved to be wrong, which included colloid goiter [4 cases], follicular variant of papillary carcinoma [1 case], and follicular carcinoma [1 case].

Figure 1

(a) Follicular neoplasm: Cellular smear with cells arranged in microfollicular pattern with anisokaryosis (MGG, ×200); (b) Follicular carcinoma: Tissue section showing vascular invasion (H and E, ×100); (c) Hurthle cell neoplasm: Cellular smear with sheets of oxyphilic cells having abundant granular cytoplasm and eccentrically placed nucleus (Pap, ×200); (d) Papillary carcinoma: Smear showing tumor cells with chewing gum colloid and psamomma body (H and E, ×200)

Twenty-nine cases of papillary carcinoma were diagnosed by FNAC, of which 2 had metastatic cervical lymphadenopathy. Histopathology was done in 15 cases, and diagnosis was confirmed in 14 cases, which included 3 cases of follicular variant with diagnostic accuracy of 93.33%. One case was diagnosed as colloid goiter with papillary hyperplasia.

Two cases of medullary carcinoma were diagnosed by FNAC in a 63-yr-old male and 51-yr-old female, but histopathological correlation was not possible [Figure 2]. FNAC diagnosis of spindle cell variant of anaplastic carcinoma was offered in two elderly female patients. However, histopathological correlation was not available.

Figure 2

(a) Medullary carcinoma: Cellular smear showing poorly cohesive cells with a plasmacytoid appearance and moderate anisokaryosis. Occasional binucleate cells seen (Pap, ×400); (b) Anaplastic spindle cell carcinoma showing cluster of pleomorphic plump spindle cells with hyperchromatic nuclei (Pap, ×400); (c) Metastatic renal cell carcinoma: Sheets of clear cells having hyperchromatic nucleus (MGG, ×400); (d) Metastatic renal cell carcinoma in thyroid: Section showing a clear cell lesion with adjacent normal looking thyroid tissue (H and E, ×100)

Single case of metastatic carcinoma was diagnosed cytologically in a 65-yr-old female with past history of surgery for renal cell carcinoma ten years back. This was confirmed histopathologically.

Non-neoplastic by FNAC but neoplastic by histopathology

Out of 100 cases, ten cases were non-neoplastic lesions by cytology, but were neoplasms on histopathology. Nine cases were diagnosed as colloid/adenomatoid goiter by cytology, out of which six cases were follicular adenoma, two were follicular variant of papillary carcinoma, and one was a case of papillary carcinoma. Lastly, single case was diagnosed as lymphocytic thyroiditis on cytology, but turned out to be papillary carcinoma by histopathology [Table 1].

Table 1

Cyto-histopathological correlation of neoplastic and non-neoplastic lesions

Present study showed a sensitivity of 75.60% and a positive predictive value of 83.78% by Galen and Gambino's method. As benign lesions were not taken in the study, no true negatives were considered, and hence other statistical parameters like specificity, negative predictive value and efficacy could not be deduced.

Discussion

FNACs were done in 100 patients followed by excision biopsy in 47 cases. Age distribution and median age was comparable to Hawkins et al.[1] In the present study, median age was lower when compared to Pandit et al.[2] Majority were females [75%], and males were 25%. Sex distribution was similar to studies done by Bagga et al,[3] but female patients were less compared to studies of Hawkins et al.[1] Pandit et al.[2] Since thyroid is a highly vascular organ, non-aspiration technique was used without any complications.[4-6] We felt 5-6 groups of well preserved cells with each group consisting of 10 or more cells was adequate material for reporting.

Follicular neoplasm

Follicular neoplasm was commonest neoplastic lesion encountered in our study. Histopathological confirmation was achieved in 15 cases and differed in 6 cases, which included 4 colloid goiter, 1 follicular variant of papillary carcinoma, and 1 follicular carcinoma. The reason for misdiagnosis of four cases was high cellularity with predominant follicular pattern. Review of histopathology showed presence of nodular hyperplasia with focal crowding of epithelium, and aspiration was probably done from these hypercellular areas of colloid nodules. Suster et al,[7] Silverman et al,[8] Hall et al.[9] and Bommanahalli et al,[10] had similar observations in their study.

One case of follicular variant of papillary carcinoma was misdiagnosed as follicular neoplasm because of high cellularity, predominant follicular pattern and nuclear overlapping. Focal nuclear features like grooving were ignored in view of predominant follicular pattern. Diagnosis of this tumor by FNAC and frozen section is notoriously difficult and unreliable. A possible remedy is multiple aspirations from different sites, and many feel that nuclear features in more than 20 cells have a greater risk of papillary carcinoma, and typical nuclear features are always helpful.[89]

Misdiagnosis of follicular carcinoma as adenoma was because of high cellularity with follicular pattern and mild anisonucleosis. In well-differentiated follicular carcinoma, cellular atypia will be minimal and hence favors a benign lesion as suggested by Koss et al.[11] They felt that nuclear enlargements were not helpful in differentiating follicular carcinoma from adenomas. Moreover, less well-differentiated follicular carcinomas do not show marked nuclear atypia, but large nucleoli will be helpful.

Papillary carcinoma

FNAC diagnosis was offered in 28 cases. Histopathological confirmation was available in 14 cases. One case was misdiagnosed as colloid goiter with papillary hyperplasia. Smears in this case were cellular, arranged in papillary pattern with indistinct nuclear features. Kini et al,[12] and Silverman et al,[7] had similar problems. Important features like intra-nuclear inclusions can be found in colloid goiter, medullary carcinoma and follicular adenoma.[13] Powdery nuclear chromatin, papillary fronds, intra-nuclear inclusions and nuclear grooves were common findings. Psammoma bodies are seen rarely.[14] Das et al,[15] suggested that “cystic papillary carcinoma” is a common cause for false negative reports in cytology. Problems in diagnosing papillary carcinoma include cystic change, marked lymphocytic infiltration, mixed patterns of growth, papillary adenoma, hyalinizing trabecular adenoma and calcified debris.[16] Small lesions of papillary carcinoma should be aspirated under imaging guidance.

Medullary carcinoma

Two cases of medullary carcinoma were diagnosed by FNAC and showed tumor cells having plasmacytoid appearance with moderately pleomorphic nuclei, granular cytoplasm and occasional binucleated forms. Amyloid was not seen in both the cases in our study. Cyto-morphological features correlated with studies of Hawkins et al.[1]

Anaplastic carcinoma

Two cases of anaplastic carcinoma were highly cellular with marked pleomorphism. Clusters of spindle-shaped tumor cells having hyperchromatic nuclei with mitotic figures and occasional binucleate forms favored our diagnosis of spindle cell variant of anaplastic carcinoma. Zeppa et al,[17] stated that diagnostic reliability is limited, because these cases can be associated with inflammation, necrosis and hemorrhage.

Metastatic carcinoma

We diagnosed a single metastatic case cytologically, and smears showed tumor cells in sheets and singles with abundant clear cytoplasm, round to oval dark nuclei. Diagnosis was confirmed by histopathology. Prognosis of metastatic renal cell carcinoma is better than other metastases.

Conclusion

FNAC of thyroid lesions is a safe, simple, cost-effective and accurate method for management of palpable thyroid lesions. Misdiagnosis was more with follicular neoplasms compared to other lesions. The scope and limitations of FNAC should be fully realized, especially in the interpretation of adenomatous goiter and follicular neoplasms. We stress the importance of nuclear features in the diagnosis of papillary carcinoma and follicular variant of papillary carcinoma.