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ORIGINAL ARTICLE
Year : 2016  |  Volume : 13  |  Issue : 1  |  Page : 15-18

Papillary microcarcinoma in clinically benign thyroidology


Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Web Publication5-Jan-2016

Correspondence Address:
Divya Rabindranath
Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh - 202 002, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-0354.159530

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  Abstract 

Context: Multi-nodular goitre (MNG) is one of the most common presentations of thyroid diseases. Although a benign entity, MNG has recently been associated with a significant risk of malignancy, as Papillary Thyroid Microcarcinoma (PTMC) is often an incidental finding in such patients. Aim: The objective of this study was to highlight the value of mandatory and diligent gross as well as histopathological examination in clinically benign thyroid specimens. Materials and Methods: This was a prospective study which included all the resected thyroid specimens of provisionally diagnosed MNG cases received in the histopathology laboratory of our department over a period of 6 months. Result: The microscopic examination showed a predominant picture of MNG along with foci of PTMC in 3 cases. Conclusion: All the patients with MNG who are treated conservatively need a close and careful follow-up for malignancy. In case of surgical treatment, careful grossing and histopathological examination of thyroid specimens is of utmost importance to identify minute foci of Papillary Thyroid Microcarcinoma (PTMC).

Keywords: Benign, foci, Multi-nodular goitre, Papillary thyroid microcarcinoma


How to cite this article:
Jain A, Alam K, Maheshwari V, Rabindranath D, Narula V, Khan AA, Khan R. Papillary microcarcinoma in clinically benign thyroidology. Thyroid Res Pract 2016;13:15-8

How to cite this URL:
Jain A, Alam K, Maheshwari V, Rabindranath D, Narula V, Khan AA, Khan R. Papillary microcarcinoma in clinically benign thyroidology. Thyroid Res Pract [serial online] 2016 [cited 2019 Oct 14];13:15-8. Available from: http://www.thetrp.net/text.asp?2016/13/1/15/159530


  Introduction Top


Thyroid nodules are reported to be found in 4–7% of the population on neck palpation and in 30–50% of the population by ultrasonography (USG). Multi-nodular goitre (MNG) is one of the most common presentations of thyroid diseases. Although considered to be a benign entity in the past, MNG has recently been associated with a significant risk of malignancy.[1] The most common variety of malignancy documented in the literature is papillary thyroid carcinoma (PTC).[2] Papillary Thyroid Microcarcinoma (PTMC) is a thyroid tumor measuring 10 mm or less in maximum diameter and comprises up to 30% of all PTC. Most PTMC are not palpable and are detected incidentally on postoperative pathological examination of surgical specimens resected for benign diseases like MNG.[3] Through the present study, we aim to emphasize the fact that all resected surgical specimens should be submitted for histopathological examination. Careful grossing and histopathological examination of thyroid specimens resected for seemingly benign conditions, is an absolute necessity for identifying small foci of malignancy that are often missed in such patients.


  Materials and Methods Top


This was a prospective study which included all the resected thyroid specimens of provisionally diagnosed MNG cases received in the histopathology laboratory of our department over a period of 6 months. Clinical details along with radiological and cytological findings were documented wherever available. These specimens were thoroughly examined grossly; and multiple representative sections including sections from capsule were submitted for histopathological examination. Any areas of discoloration, cystic change, papillary formation or calcification seen on gross examination were especially sampled. The sections were stained routinely with hematoxylin and eosin (H and E) stain and examined under microscope.


  Results Top


Out of a total of 35 thyroidectomy specimens, after detailed histopathological examination, we found three cases having foci of PTMC. The clinical details, USG and gross findings of these patients are given in [Table 1].
Table 1: Comparison of clinical, USG and gross findings in 3 cases

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On retrospective analysis of the fine needle aspiration smears of these cases, we found that they predominantly had blood mixed smears with moderate to abundant colloid material. Benign follicular thyroid epithelium in sheets and small clusters was seen. No definite or suspicious cellular morphology suggestive of malignancy was appreciated.

These patients were offered surgery for cosmetic reasons as well as to relieve the pressure effects. The preferred modality was total thyroidectomy.

Histopathological evaluation of the sections revealed colloid rich follicles lined by flattened, inactive epithelium and areas of follicular hyperplasia. Sections from the whitish and calcified areas showed small papillary and follicular foci measuring less than 10 mm [Figure 1]. The lining epithelium contained cells with high nucleocytoplamic ratio. The nuclei were optically clear with finely dispersed chromatin with intranuclear inclusions and grooving present in some [Figure 2]. The diagnosis of PTMC -usual morphology was made in two cases and follicular variant in one case. Sections from the capsule did not show any signs of invasion.
Figure 1: Section showing colloid filled follicles along with a focus of follicular variant of Papillary Microcarcinoma Thyroid (Haematoxylin and Eosin stain, original magnification ×:100)

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Figure 2: Section showing cells with optically clear nuclei and intranuclear grooving (Haematoxylin and Eosin stain, original magnification ×:400)

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Follow up of these patients for 1 year did not reveal any lymphadenopathy, or evidence of local recurrence or distant metastases in two patients. However, one of the patients presented with a recurrent solitary thyroid nodule after 6 months. This was about 2 cm in diameter. USG revealed non specific findings. Fine needle aspiration cytology (FNAC) and histopathological examination revealed the diagnosis of papillary carcinoma.


  Discussion Top


MNG is defined as the palpation of multiple distinct nodules in the enlarged thyroid gland. The etiopathogenesis of MNG is not very clear. A mild dietary deficiency of iodine, slight impairment of hormone synthesis, increased iodide clearance from the kidneys and the presence of thyroid stimulating immunoglobulins have been suggested as the various causes.[4]

A long standing and hitherto unresolved issue is whether MNG is significantly associated with malignancy.[4] MNG had been traditionally thought to be at a low risk for malignancy as compared to a solitary nodule thyroid.[5] However, various studies have reported a 7–17% incidence of malignancy in MNG.[5],[6] A relatively recent multi- institutional trial identified an incidental cancer rate of 18%.[7]

The most common variety of malignancy which has been documented in the literature is papillary thyroid carcinoma.[2] The recent use of USG screening and USG guided fine-needle aspiration biopsy (FNAB) have facilitated the frequent detection and diagnosis of PTC. Patients with PTC have an excellent prognosis with a 10-year survival rate of 93% which is one of the best in the field of oncology.[8] Among prognostic factors, the most debated is tumor size; and in many studies, it represents a factor which correlates with recurrence and mortality in PTC.[9],[10]

According to World Health Organization (WHO) classification, PTMC is defined as tumors smaller than 1 cm in diameter. Most of these tumors are nonpalpable and cannot be identified clinically. In the past, most of the PTMCs were diagnosed in thyroidectomy specimens resected because of benign pathologies or in autopsies of patients who died because of nonthyroid causes.[11] The clinical importance of PTMC is debatable. Some authors have observed that PTMCs have a benign behavior and do not progress over a mean follow-up period of 3.8 years. In contrast, other authors have reported cases of PTMC with local lymph node and distant metastases at the time of diagnosis and during follow-up evaluation. We also report similar findings with one of our patients progressing to papillary carcinoma after 6 months. Multifocality is common in PTMC and is observed in 20–46% of cases. Occasionally, PTMC causes cancer-related death.[12]

In view of all these features, it is very important to identify PTMC in patients with clinically palpable thyroid. FNAC is a fast and inexpensive investigation which can be done to obtain cellular samples. However, a negative FNAC report does not exclude with certainty the possibility of a carcinoma, especially in MNG, where the error in sampling the right area is greater.[1] Also, FNA's are often very hemorrhagic due to high vascularity of thyroid tissue/lesion; and aspiration of blood may obscure neoplastic cells. It should be understood that excessively blood stained smears are not necessarily related to poor technique but may signal the possibility of a neoplasm. Repeat needling through multiple sites after a gap of a week or two often yields diagnostic material. FNAC of a suspicious nodule under USG guidance is of great help.[13]

The use of USG examination of the thyroid gland has greatly increased the number of small benign and malignant nodules diagnosed before surgery. Some characteristics of the thyroid nodules on USG appear suspicious for malignancy. Microcalcifications are one of these features and have been observed in many studies. Irregular margins of the nodules and hypoechogenicity are two other such features suggestive of malignancy. A taller-than wider dimension and antero-posterior diameter larger than the transverse diameter of nonpalpable thyroid nodules have also been suggested as a diagnostic feature for the presence of malignancy. An increase in the size of small thyroid nodules at USG follow-up was not a reliable marker in the differential diagnosis between malignant and benign nodules.[14]

Many times, due to a benign diagnosis, the resected thyroid specimens are not submitted for histopathological examination by the surgeons. However, we found that careful grossing and histopathological examination of thyroid specimens is of prime importance in identifying minute foci of malignancy in thyroid specimens which have been excised for benign diseases. Any areas of discoloration or calcification should always be sampled as they frequently harbor such foci. Sections from the capsule are also of eminent importance to rule out any signs of invasion.

The literature provides us with conflicting information regarding the prognosis and the management of these lesions. Recent studies have suggested that the PTMC classically progress to a clinically evident disease if they are left untreated. This is evident by our findings also. The treatment of PTMC should be similar to that of PTC.[15]


  Conclusion Top


In conclusion; due to the risk of occult malignancy, all the patients with MNG who have been treated conservatively, need a close follow-up for malignancy. This may be clinical and/or by using USG which is becoming quite handy in detection of malignant foci. Also, multiple site sampling should be done while doing FNAB so as to reduce the risk of missing any small focus of malignancy. As PTMC is being diagnosed with increasing frequency, careful grossing and histopathological examination of all thyroidectomy specimens (especially the ones resected for non-malignant reasons) has proved to be of utmost importance in ruling out these lesions. Although there are conflicting data regarding the progression of PTMC to papillary carcinoma, our study included a patient who progressed to papillary carcinoma within a period of 6 months of detection of PTMC. Hence, based on our experience, we propose that all thyroid lesions (including the ones resected for benign diagnosis) should undergo careful histopathological examination in order to detect any minute foci of PTMC.

 
  References Top

1.
Hanumanthappa MB, Gopinathan S, Rithin S, Guruprasad Rai D, Shetty G, Shetty A, et al. The incidence of malignancy in multi-nodular goitre: A prospective study at a tertiary academic centre. J Clin Diagn Res 2012;6:267-70.  Back to cited text no. 1
    
2.
Pedamallu R, Pedamallu SB, Rama Rao K, Pedamallu CS. Incidence of occult carcinoma in multi-nodular goitre which was diagnosed on the basis of the histopathological findings. The Intern J Surg 2007;17.  Back to cited text no. 2
    
3.
Ertorer ME, Tutuncu NB, Ozyilkan O. Incidental papillary microcarcinoma of the thyroid. Asian Pac J Cancer Prev 2007;8:631-4.  Back to cited text no. 3
    
4.
Abu-Eshy SA, Khan AR, Khan GM, Al-Humaidi MA, Al-Shehri MY, Malatani TS. Thyroid malignancy in multi-nodular goitre and in a solitary nodule. JR Coll Surg Edinburg 1995;40:310-2.  Back to cited text no. 4
    
5.
Gandolfi PP, Frisina A, Raffa M, Renda F, Rocchetti O, Ruggeri C, et al. The incidence of thyroid carcinoma in multi-nodular goitre: A retrospective analysis. Acta Biomed 2004;75:114-7.  Back to cited text no. 5
    
6.
Sachmechi I, Miller E, Varatharajah R, Chernys A, Carroll Z, Kissin E, et al. Thyroid carcinoma in the single cold nodules and in the cold nodules of multi-nodular goitres. Endocr Pract 2000;6:5-7.  Back to cited text no. 6
    
7.
Smith JJ, Chen X, Schneider DF, Broome JT, Sippel RS, Chen H, et al. Cancer after thyroidectomy: A multi- institutional experience with 1,523 patients. J Am Coll Surg 2013;216:571-9.  Back to cited text no. 7
    
8.
Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53.856 cases of thyroid carcinoma treated in the US.,1985-1995. Cancer 1998;83:2638-48.  Back to cited text no. 8
    
9.
Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994;97:418-28.  Back to cited text no. 9
    
10.
Baudin E, Travagli JP, Ropers J, Mancusi F, Bruno-Bossio G, Caillou B, et al. Microcarcinoma of the thyroid gland: The Gustave-Roussy Institute experience. Cancer 1998;83:553-9.  Back to cited text no. 10
    
11.
Gulben K, Berberoğlu U, Celen O, Mersin HH. Incidental papillary microcarcinoma of the thyroid factors affecting lymph node metastasis. Langenbecks Arch Surg 2008;393:25-9.  Back to cited text no. 11
    
12.
Roti E, Rossi R, Trasforini G, Bertelli F, Ambrosio MR, Busutti L, et al. Clinical and histological characteristics of papillary thyroid microcarcinoma: Results of a retrospective study in 243 patients. J Clin Endocrinol Metab 2006;91:2171-8.  Back to cited text no. 12
    
13.
Jayaram G, Orell SR. Thyroid. In Fine Needle Aspiration Cytology. Orell SR, Sterrett GF, 5th edition. Churchill Livingstone, Elsevier; 2012. p. 118-156.  Back to cited text no. 13
    
14.
Roti E, degli Uberti EC, Bondanelli M, Braverman LE. Thyroid papillary microcarcinoma: A descriptive and metaanalysis study. Eur J Endocrinol 2008;159:659-73.  Back to cited text no. 14
    
15.
Kucuk NO, Tari P, Tokmak E, Aras G. Treatment for micro-carcinoma of the thyroid— Clinical experience. Clin Nucl Med2007;32:279-81.  Back to cited text no. 15
    


    Figures

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    Tables

  [Table 1]



 

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