Abstract | | |
Coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular variant of papillary carcinoma is described in the same thyroid, with study of p53 expression. A 72-year-old woman presented to the endocrinology out-patient unit for a routine follow-up visit. Patient underwent a total thyroidectomy. Histological examination revealed a solid nodular neoplasm with the longest diameter of 0.8 cm in the upper pole of the left lobe. The neoplasm showed the histological features of follicular variant of papillary carcinoma with moderate diffuse immunoreactivity for p53. The lower pole of the right lobe showed two adjacent nodules with histological features respectively of atypical adenoma and adenoma with bizarre nuclei, with strong diffuse immunoreactivity for p53. Keywords: Adenoma with bizarre nuclei, atypical adenoma, follicular variant of papillary carcinoma of the thyroid, simultaneous neoplasms of the thyroid
How to cite this article: Pusiol T, Zorzi MG, Morichetti D. Coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular variant of papillary carcinoma of the thyroid. Indian J Pathol Microbiol 2013;56:399-401 |
How to cite this URL: Pusiol T, Zorzi MG, Morichetti D. Coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular variant of papillary carcinoma of the thyroid. Indian J Pathol Microbiol [serial online] 2013 [cited 2023 Jan 27];56:399-401. Available from: https://www.ijpmonline.org/text.asp?2013/56/4/399/125342 |
Introduction | |  |
Two variant of follicular adenoma (FA) has been characterized by nuclear atypia: atypical adenoma and adenoma with bizarre nuclei. Atypical adenoma show high cellularity, nuclear atypia or unusual histologic patterns (such as spindle cell fascicles), but lacking vascular and capsular invasion on thorough sampling. Despite the histologically worrisome appearance, this tumour pursues a benign course. Adenoma with bizarre nuclei is characterized by scattered bizarre nuclei with huge size, irregular shape and striking hyperchromasia. These nuclei tend to occur in clusters. They are analogous to nuclei seen in many other endocrine tumors and should not be taken by themselves as a sign of malignancy. Papillary carcinoma is the most common type of thyroid cancer. In the present report, we describe the coexistence of atypical adenoma, adenoma with bizarre nuclei and follicular variant of the papillary thyroid carcinoma (PTC) with study of p53 expression in all three lesions.
Case Report | |  |
A 72-year-old woman presented to the endocrinology out-patient unit for suspected hyperthyroidism. Patient underwent a total thyroidectomy. Histological examination of the thyroid gland revealed a solid nodular neoplasm with the longest diameter of 0.8 cm in the upper pole of the left lobe. The neoplasm was characterized by an almost exclusively follicular pattern of growth. Capsule formation was absent. Regardless of follicle size, the nuclei of the lining cells have features analogous to those to conventional papillary carcinoma. Immunostaining for p53 showed moderate diffuse immunoreactivity of neoplastic cells. Diagnosis of follicular variant of PTC was made [Figure 1]. The lower pole of the right lobe showed two adjacent nodules [Figure 2]. The first had a maximum diameter of 0.9 cm; histologically, the lesion was encapsuled by fibrous tissue with extensive calcification and was composed by microfollicular pattern with scattered clusters of bizarre nuclei [Figure 3] and [Figure 4]. Follicular cells with bizarre nuclei were strong diffuse immunoreactive with antibody against p53, whereas follicular cells with unremarkable nuclei (typical cells) were not stained [Figure 5]. The diagnosis of adenoma with bizarre nuclei was made. The second nodule measured 0.8 cm in diameter maximum and showed complete capsule of fibrous tissue. The lesion was composed by closely packed follicles lucking lumina, atypical bizarre cells of irregular shape and with hyperchromatic nuclei. The capsular or vascular invasion was absent. Immunostaining for p53 showed strong diffuse immunoreactivity of atypical bizarre cells. | Figure 1: Follicular variant of papillary carcinoma of the left lobe (H and E, × 4 and× 40 in insert). Immunostaining for p53 showed moderate diffuse immunoreacti vity of neoplasti c cells (p53× 20 in insert)
Click here to view |
 | Figure 3: The nodules were separated by a thick fi brous and calcifi ed capsule (a) the smaller nodule (b) the largest nodule (H and E, × 10)
Click here to view |
 | Figure 4: The largest nodule (a) the smaller nodule was interely composed by atypical, bizarre cells (b) a patt ern microfollicular with typical cells (§) and a component with scatt ered atypical cells (# and insert). (H and E, × 20 and × 40 in insert)
Click here to view |
 | Figure 5: The p53 staining was intensely positi ve in atypical bizarre cells whereas was negati ve in typical follicular cells (H and E, × 10)
Click here to view |
Discussion | |  |
The pathological diagnoses and classification schemes for thyroid carcinoma have changed over the past 20 years and continue to do so. New entities have been described and molecular analyses have suggested better characterisation and grouping of certain tumors. Some of the pathological studies have added confusion to the literature by classifying certain tumors with different names. [1],[2] Bizarre nuclei are found in different neoplastic lesions of the thyroid such as atypical adenomas, FAs with bizarre nuclei, hyperplastic lesions of adenomatous goiter. The biologic significance of atypical adenoma is controversial. For this reason atypical adenoma has become for too many pathologists, a wastebasket term in which any adenoma that looks peculiar or worrisome, even for spontaneous necrosis or unjustified mitotic activity is included. Chan et al. believed that the use of the term "atypical adenoma" should be discouraged. P53 is a well-characterized tumor suppressor gene. [3] Mutations of the p53 tumor suppressor gene represent the most common genetic alteration in human tumors. As far as the thyroid gland, Freeman et al. have described that p53 mutation is frequently detected in anaplastic and poorly differentiated carcinomas. [4] Tzen et al. have analyzed the p53 mutations in 2 atypical adenomas: [5] Mutations of p53 where detected in the bizarre cells but not in the bland-looking follicular cells. Tzen et al. have seen that atypical adenomas showed an identical point mutation in codon 273 (CGT-CAT), a common mutation in various human cancers, including anaplastic carcinoma of the thyroid. [5] This finding supports the view of Tzen et al. that atypical FA is a precursor of thyroid anaplastic carcinoma and suggests that the term "atypical adenoma" should not be used to express diagnostic uncertainty about the nature of the lesion. [5] Sato et al. have examined the immunohistochemical expression of p53 protein in the bizarre nuclei of thyroid adenomatous nodule with micro-and macrofollicular components, cystic degeneration, hyalinised region and papillary structure. [6] The bizarre cells diffusely expressed p53 protein, but the "usual follicular cells" were negative. In the study of Sato et al. no mutation of exons 5-9 of the p53 gene was detected in the bizarre nuclei. [6] Sato et al. believed that bizarre nuclei can be seen in benign thyroid lesions and over diagnosis should be avoided regardless immunohistochemical over expression of p53. [6] Kanthan and Radhi have examined the p53 expression in 25 cases of FAs with hurtle cells changes, both pure and focal. [7] The majority of the hurtle cells where p53 positive and adenomas with an increased number of hurtle cells had an a increased percentage of p53 staining. Othman et al. have studied the p53 protein expression in 52 cases of thyroid FAs and have found p53 positive in 6 case (11.5%). [8] Nasir et al. have studied p53 expression in 20 FAs and 21 follicular carcinomas (FCs) of the thyroid. [9] Nasir et al. found that 90% of FCs showed strong nuclear p53 expression. [9] P53 stain was seen in only 15% of FAs. Therefore, Nasir et al. believed that immunohistochemical detection of p53 with others markers (CD44V6 and CD57) may have practical utility in differential diagnosis of FCs from FAs in routine surgical pathology. [9] Liang et al. stated in their study that they found a significant p53 expression in the thyroid carcinomas compared with adenomas in 119 cases, including 45 PTC, 26FC and 48 FA. [10] In a study conducted by Kim et al. there was p53 expression in 1 of 40 PTC cases and no expression in 20 FC cases. [11]
Conclusion | |  |
p53 expression has been reported not helpful in neither subtype carcinomas nor differentiating adenoma from carcinoma. The present case is the first report of coexistence variant follicular of papillary carcinoma, atypical adenoma and adenoma with nuclei bizzarre in the same thyroid. The present case showed that expression of p53 is not useful in the diagnosis differentiation between atypical adenomas, adenoma with bizarre nuclei and follicular variant of papillary carcinoma.
References | |  |
1. | Baloch Z, Livolsi VA, Tondon R. Aggressive variants of follicular cell derived thyroid carcinoma; the so called 'Real Thyroid Carcinomas'. J Clin Pathol 2013;66:733-43.  |
2. | Chui MH, Cassol CA, Asa SL, Mete O. Follicular epithelial dysplasia of the thyroid: Morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis. Virchows Arch 2013;462:557-63.  |
3. | Chan JK, Hirokawa H, Evans H, Williams ED, Osamura Y, Cady B, et al. Tumours of Endocrine Organs. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. Lyon: World Health Organization Classification of Tumours IARC Press 2004. p 98.  |
4. | Freeman J, Carroll C, Asa S, Ezzat S. Genetic events in the evolution of thyroid cancer. J Otolaryngol 2002;31:202-6.  |
5. | Tzen CY, Huang YW, Fu YS. Is atypical follicular adenoma of the thyroid a preinvasive malignancy? Hum Pathol 2003;34:666-9.  |
6. | Sato K, Shimode Y, Hirokawa M, Ueda Y, Katsuda S. Thyroid adenomatous nodule with bizarre nuclei: A case report and mutation analysis of the p53 gene. Pathol Res Pract 2008;204:191-5.  |
7. | Kanthan R, Radhi JM. Immunohistochemical analysis of thyroid adenomas with Hurthle cells. Pathology 1998;30:4-6.  |
8. | Othman NH, Omar E, Mahmood MH, Madhavan M. RET and p53 expression in thyroid follicular adenoma: A study of 52 cases with 14 years follow-up. Malays J Pathol 2005;27:91-8.  |
9. | Nasir A, Catalano E, Calafati S, Cantor A, Kaiser HE, Coppola D. Role of p53, CD44V6 and CD57 in differentiating between benign and malignant follicular neoplasms of the thyroid. In Vivo 2004;18:189-95.  |
10. | Liang HS, Zhong YH, Luo ZJ, Huang Y, Lin HD, Luo M, et al. Comparative analysis of protein expression in differentiated thyroid tumours: A multicentre study. J Int Med Res 2009;37:927-38.  |
11. | Kim YW, Do IG, Park YK. Expression of the GLUT1 glucose transporter, p63 and p53 in thyroid carcinomas. Pathol Res Pract 2006;202:759-65.  |

Correspondence Address: Teresa Pusiol Institute of Pathology, S. Maria Del Carmine Hospital, Piazzale S. Maria 6, 38068 Rovereto (TN) Italy
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0377-4929.125342

[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5] |