|Year : 2020 | Volume
| Issue : 1 | Page : 25-31
The cytomorphological spectrum of Hashimoto thyroiditis and its correlation with serological parameters: A study in the coastal region
Nibedita Sahoo1, Sujata Naik1, Pranita Mohanty1, Pradeep N Sahoo2, Prateek Das1
1 Department of Pathology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
2 Department of Internal Medicine, AMRI Hospital, Bhubaneswar, Odisha, India
|Date of Submission||26-Dec-2019|
|Date of Acceptance||10-Mar-2020|
|Date of Web Publication||14-May-2020|
Dr. Nibedita Sahoo
Department of Pathology, IMS and SUM Hospital, Bhubaneswar, Odisha-19
Source of Support: None, Conflict of Interest: None
Objective: To analyse the detailed cytomorphological spectrum in Hashimoto thyroiditis (HT), cytological grading and its significance with the hormonal and antibody status
Methods: This is both a prospective and retrospective study of 102 cases of HT in a tertiary care institute of the eastern part of India. Detailed cytological parameters were observed, graded and correlated with the serological parameters.
Results: The majority of patients were females with a younger age group (21–30 years) and diffuse thyromegaly was the common presentation. A good number of cases showed neutrophilic infiltration, background colloid and follicular hyperplasia. Among the cytological parameters, Hurthle cell change was correlated with hypothyroidism (P < 0.05) but there was no significant correlation with the anti-TPO antibody. Statistical correlation of different cytological grades with the anti-TPO antibody was significant (P < 0.05), however the thyroid hormone profile with cytological grade and TPO level were not significant (P > 0.05).
Conclusion: A younger age of presentation in a coastal area with iodine sufficiency and supplementation needs further epidemiological studies. Fine-needle aspiration cytology is superior to other sophisticated methods in diagnosing HT, even in seronegative cases. A good number of cases displaying folliculolysis by neutrophils needs to be corroborated by larger studies. One should be vigilant while examining slides to rule out associated malignancy.
Keywords: Anti TPO antibody, autoimmune thyroiditis, cytomorphology, neutrophils, thyroid function test
|How to cite this article:|
Sahoo N, Naik S, Mohanty P, Sahoo PN, Das P. The cytomorphological spectrum of Hashimoto thyroiditis and its correlation with serological parameters: A study in the coastal region. J NTR Univ Health Sci 2020;9:25-31
|How to cite this URL:|
Sahoo N, Naik S, Mohanty P, Sahoo PN, Das P. The cytomorphological spectrum of Hashimoto thyroiditis and its correlation with serological parameters: A study in the coastal region. J NTR Univ Health Sci [serial online] 2020 [cited 2020 Jul 10];9:25-31. Available from: http://www.jdrntruhs.org/text.asp?2020/9/1/25/284312
| Introduction|| |
Hashimoto thyroiditis (HT) is an autoimmune disease, destroying the thyroid gland and progressive thyroid function failure. It is the most common cause of hypothyroidism in iodine sufficient areas., The disease was first reported by Hakaru Hashimoto in 1982 and termed as struma lymphomatosa. Synonymously chronic lymphocytic thyroiditis, autoimmune thyroiditis are used for the disease. The disease is prevalent between 45 and 65 years of age with a female predominance and female to male ratio of 10:1 to 20:1. The entity most commonly manifests in the form of diffuse thyromegaly, though asymmetrical enlargement and nodular presentation are also seen and may mimic as a malignant lesion.,,, Ultrasonographically, the reduction of thyroid echogenicity is a strong predictor of autoimmune thyroiditis.
The characteristic cytological findings in HT are increased mature and transformed lymphocytes impinging and destroying the thyroid follicular cells with Hurthle cell change of the follicular epithelial cells. Although, the combined approach of serology with cytomorphology is being highlighted in the literature for diagnosis of HT, fine-needle aspiration cytology (FNAC) is a reliable, cost-effective procedure for diagnosis even in seronegative cases.,, First cytological grading of thyroiditis was done by Bhatia et al. with some predefined parameters and it correlated the different grades with clinical, biochemical, ultrasonographic, radionuclide parameters and serum trimethylamine (TMA) levels.
In the present study, the emphasis was given to the detailed cytomorphological spectrum in HT, cytological grading and its significance with the hormonal and antibody status.
| Methods|| |
This is both prospective and retrospective study, carried out from January 2017 to January 2019 in a tertiary care institute of eastern India. Around 102 cases diagnosed as Hashimoto/autoimmune thyroiditis in cytology formed the study population. The clinical details of all patients including age, sex, type of thyroid swelling with a drug history, biochemical parameters and ultrasonographic findings wherever available were recorded. The study protocol was approved (Ref : IMS/IEC/IWF-101/2020 with IEC registration number ECR/627/Inst/OR/2014/RR-17) by the ethical committee of our institution and informed consent was obtained from patients of the prospective study group.
FNAC was done by non-aspiration and aspiration technique by using 24 and 23 gauze needle. In one case, due to barely visible swelling with strong clinical suspicion of thyroiditis ultrasound-guided FNAC was done. Smears were stained by Diff Quik, Hematoxylin and Eosin and Papanicolau stain.
The diagnostic criteria for HT for our study were increased lymphoid cells in the background with lymphoid cells impinging the follicles. Besides, in our study special emphasis was given to other inflammatory cells such as plasma cells, neutrophils, eosinophils, histiocytes, giant cells, epithelioid cell aggregates and also to the background. The polymorphs impinging and/or very close to the follicular clusters were considered as significant and rests were considered as blood-derived.
In all the cases the severity of thyroiditis was graded according to Bhatia et al. For grade I or mild thyroiditis the criteria were few lymphoid cells infiltrating the follicles or increased lymphocytes in the background. In grade II or moderate thyroiditis: moderate lymphocytic infiltration or mild lymphocytic infiltration with Hurthle cell change/giant cells/anisonucleosis. Florid lymphocytic infiltration with the germinal center formation with very few left out follicular cells was considered as severe or grade III thyroiditis.
The thyroid function test was done using electrochemiluminescence immunoassay from Cobase 411 analyser with a normal reference range of T3 (84.63–201.08 ng/dL), T4 (5.13–14.06 μg/dL) and TSH (0.270–4.2 μIU/mL). The anti-TPO antibody was measured by the enzyme-linked immunosorbent assay (ELISA) method with the normal reference value of <50 IU/mL.
The different cytological grades were correlated with the serological parameters using the χ test in Microsoft XL software where P value ≤0.05 was considered as statistically significant.
| Results|| |
Out of 102 patients, 96 (94.11%) were female and rest 06 (5.88%) were male with an F:M ratio of 16:01. The age ranged from 11 to 70 years with a mean age of 38.83. The mean age for females was 39.07 with SD of 12.83 and males were 35.33 with SD of 13.41. A maximum number of patients were in the age range of 21 to 30 for either sex. The thyroid swelling was diffuse in 90 (88.23%) cases, among which symmetrical in 54 (52.94%) and asymmetrical (either more prominent in left or right) in 36 (35.29%) several cases. Solitary thyroid nodule was seen in 6 (5.8%) cases and multinodular enlargement observed in 6 (5.8%) in several cases. Barely visible swelling was observed in one (0.98%) case.
Out of these, 85 number of cases were having thyroid hormone profile and anti-Thyroid peroxidase (TPO) antibody. According to the biochemical parameters, hypothyroidism was noted in 39 (45.88%) cases of which, overt hypothyroidism was observed in 10 (11.76%) and subclinical hypothyroidism in 29 (34.11%); 32 (37.64%) cases were euthyroid and 14 (16.47%) were hyperthyroid. The thyroid antibody (anti-TPO) antibody was elevated in 67 (78.82%) cases.
Ultrasonography was done in 74 number of cases and diffuse hypoechoic, heterogenous echotexture was seen in 61 (82.43%); hypoechogenic goiter in 9 (12.16%), a hyperechoic dominant nodule in 4 (5.40%) of cases.
In cytomorphological findings, increase lymphocytes and folliculolysis by lymphocytes were taken as criteria for the diagnosis of autoimmune thyroiditis, hence it was noted in all cases. Grading of thyroiditis was done according to Bhatia et al. and most of the patients i.e. 60 patients (58.82%) fall in grade II [Figure 1]b, 27 patients (26.47%) in grade III [Figure 1]c ] and the least was grade I i.e. 16 patients (15.68%) [Figure 1]a.
|Figure 1: (a) Displaying folliculolysis by sparse lymphocyte over background containing lymphocytes (Diff Quik, 400×). (b) Follicle displaying Hurthle cell change with evidence of folliculolysis by a good number of lymphocytes (Diff Quik, 400×). (c) Smear showing mature and reactive lymphoid cells destroying the follicles (Diff Quik, 400×)|
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Hurthle cell change was noted in 89 (87.25%) cases, out of which 3 cases showed sudden anisonucleosis and nuclear atypia [Figure 2]a. Follicular cell hyperplasia was noted in 5 cases and few showing a microfollicular pattern [Figure 2]b, [Figure 2]c. Plasma cells were seen in 55 (53.92%) cases with 4 (3.92%) cases showed plenty of plasma cells with Mott cells [Figure 2]d -inset]. Significant eosinophilic infiltration seen in 8 (7.84%) cases and neutrophilic infiltration noted in 32 (31.37%) cases [Figure 3]a. Histiocytes and giant cells were seen in 54 (52.94%) and 30 (29.41%) cases respectively. In three cases classical Langhan type of giant cells was seen [Figure 3]b. Cystmacrophages were seen in one case. Hurthle cells with epithelioid cell morphology in aggregates forming granulomas were noted in 19 (18.62%) of cases [Figure 3]c. Reactive lymphoid cells were observed in 63 (61.76%) cases. Fire flare noted in 14 (13.72%) cases and background colloid seen in 30 (29.41%) [Figure 3]d cases and out of that 2 cases showed thick colloid. One case shows along with features of HT features of papillary carcinoma of thyroid with cervical node metastasis [Figure 4]. The presence of different cytological findings in our study was shown in the bar diagram [Figure 5].
|Figure 2: (a) Sudden anisonucleosis and nuclear atypia of Hurthle (Diff Quik, 400×). (b and c) Hyperplastic follicular cells arranged in papillaroid pattern (b) and microfollicles (c) (Papaniculao, 100×). d: Folliculolysis by plasma cells and presence of Mott cells (Diff Quik, 400×)|
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|Figure 3: (a) Displaying folliculolysis by neutrophils (Arrow) of HT (Inset shows intranuclear inclusion) (Papaniculao, 400×) (Diff Quik, 400×). (b) Langhan type of giant cell (Diff Quik, 400×). (c) Epithelioid cell granuloma (Diff Quik, 400×). (d) Displaying presence of small lymphocytes in the background of thin colloid (Diff Quik, 400×)|
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|Figure 4: A case of papillary thyroid carcinoma with a background of HT (Inset shows intranuclear inclusion) (Papaniculao, 400×)|
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|Figure 5: Displaying the presence of different cytological parameters (n = 102)|
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A comparison of cytological grade with thyroid hormone profile [Table 1] was not statistically significant (P = 0.5249). In grade II thyroiditis TPO was elevated in 86% (43/50) of cases, grade III in 72.27% (17/22) cases and grade I in 53.84% (7/13) cases [Figure 6]. Statistical correlation of different cytological grades with the anti-TPO antibody was significant (P < 0.05), but thyroid hormone profile with cytological grade and TPO level are not significant (P > 0.05)
| Discussion|| |
The pathogenesis behind HT breaks down of self-tolerance to thyroid auto-antigens leading to CD8 cytotoxic T cell-mediated, cytokine-mediated activation of macrophages and antibody-dependent cell-mediated death of thyrocytes. According to the spectrum of injury, there is an initial phase of hyperthyroidism followed by hypothyroidism. Antibody-dependent cell-mediated toxicity causes the binding of the various antibodies (anti-thyroglobulin, anti-TPO) to the cell surface of follicular cells.
Clinically, a female predominance was seen in our study with a female to male ratio of 16:01, which is seen in most of the studies in English literature. The 5th decade of life is the common age group in western populations but in Indian studies, the common age group is 3rd to 4th decade,,,, but in our study most common age group was 21–30 for either sex which is in accordance to study of Kumar et al. and Sood et al., As our state (Odisha) is a coastal area, probably iodine sufficiency is a risk factor for developing HT in the early age group.,,
Diffuse thyromegaly was the common observation in our cases with most of them is symmetrical. However solitary thyroid nodule and multinodular enlargement are also noted in 5.8% of cases each, which is almost in accordance with other studies.,
Seropositivity for anti-TPO antibody was seen in 78.82% of cases and the negative serology (21.18%) can be explainable, as localized immune destruction occurs much earlier before to serological findings.,, In this way, cytological evidence is more superior than hormonal and serological findings.
Cytological grading of thyroiditis was done according to the criteria proposed by Bhatia et al. and most of the cases belonged to grade II. In a comparison of cytological grading of our study with other studies [Table 2], our study result was almost close to the study by Singh et al. Statistical correlation of different cytological grades with the anti-TPO antibody was significant (P < 0.05), but the thyroid hormone profile with cytological grade and TPO level are not significant (P > 0.05).
|TABLE 2: Comparison of cytological grading of our study with other studies|
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Hurthle cell change was noticed in 87.25% of cases in our study and there was no correlation of Hurtle cell population with antibody status (P = 0.89), but there was a positive association with hypothyroidism (P = 0.027). This was in concordance with a study by Kumar et al. and Jayram et al.,
Though follicular hyperplasia is rare in HT, as there is immune-mediated destruction of follicular cells but was a frequent finding in the study by Kumar et al. It probably depends on coexisting colloid goiter with follicular hyperplasia, the technique of aspiration or stage of the disease. In our study, we found follicular hyperplasia in 4.9% of cases. This type of case the diagnosis may be missed for that emphasis should be given to the background lymphocytes, infiltrating lymphocytes and follow-up is needed.
Lympho epithelial ratio (L: E ratio) is characteristically high in HT ranging from 2:1–10:1 and smears of florid lymphocytic thyroiditis mimic reactive lymphoid hyperplasia.,,,,, Following grading of severity of thyroiditis according to Bhatia et al., all cases of florid lymphocytic thyroiditis fall in grade III. In our observation high L: E ratio was seen in all cases of grade III and most cases of grade II thyroiditis and was 67.3%. Earlier studies also highlighted the different incidence of high L: E cell ratio.,,,,
We found fire flare in 14 cases, out of which hormonal evidence of hyperthyroidism noted in 3 (21.42%) cases; this signifies cytomorphology may not reflect the hormonal status always.
Infiltration of epithelial cells by eosinophils and neutrophils was first described by Jayram et al. and they found it in 17% of cases. Ekambaram et al. counted the average number of eosinophils in 10 high power field and they found significant eosinophils in 84% of cases. In our study, eosinophilic infiltration in 7.84% of cases and a significant neutrophilic infiltration in 31.37% of cases but none of these were correlated with hormonal or serological parameters statistically (P > 0.05). Singh et al. in their study highlighted the coastal belt with iodine sufficiency as the cause of iodine-induced thyroiditis and significant eosinophils but we found rather a high proportion of neutrophils. Our study shows higher neutrophilic infiltration compared to other previous studies.,,
The detail cytomorphology is tabulated with a comparison of other studies [Table 3].
|TABLE 3: Comparison of cytological features of HT in various studies with the present study|
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Plasma cells help to solve the diagnostic dilemma especially in grade I or early stage of HT; which was highlighted by Jayram et al. and careful search of the periphery of the smears were suggested. We found plasma cells in 53.92% of cases and 4 cases with plenty of plasma cells and presence of Mott cells.
As the disease progresses there is destruction of follicular epithelial cells, scanty or absent colloid is the feature of HT., But, various authors have reported the presence of moderate to abundant colloid,, We found colloid in 29.4% cases and also thick colloid in 2 cases. Cytopathologists should be cautious while reporting, as abundant background colloids may mask the lymphocytes, so careful search for folliculolysis by lymphocytes, reactive lymphoid cells and plasma cells should be done.
| Conclusion|| |
Younger age of presentation in coastal areas with iodine sufficiency and supplementation needs further epidemiological studies. Solitary thyroid nodule does not exclude HT and cytology is a reliable and cost-effective method of diagnosis of HT in comparison to sophisticated serological and radiological study. A good number of cases displaying folliculolysis by neutrophils in our study needs to be corroborated by larger studies. Cytopathologists should be cautious when background shows abundant colloid, as it does not rule out HT. One should be vigilant while examining slides to rule out associated malignancy with detail clinic-radiological correlation and USG-guided aspiration is to be done wherever required.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
“Data Availability Statement”: The data that support the findings of this study are openly available in [repository name e.g. “figshare”] at http://doi.org/[doi], reference number (CYT-2019-0170)
Conflicts of interest
There are no conflicts of interest.
| References|| |
Marwaha RK, Garg MK, Nijhavan VS, Dham DN, Dubey R, Amberdar V, et al
. Prevalence of chronic lymphocytic thyroiditis in adolescent girls. J Assoc Physicians India 1998;46:606-8.
Maitra A, Abbas AK. The endocrine system. In: Kumar V, Abbas AK, Aster JC, editors. Robbins and Cotran's Pathologic Basis of Diseases. 9th
ed. Philadelphia: Saunders; 2014. p. 1086-7.
Marshall SF, Meissner WA. Struma lymphomatosa (Hashimoto'sdisease) Ann Surg 1955;141:737-46.
Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N
Engl J Med 1996;335:99-107.
Nguyen GK, Ginsberg J, Crockford PM, Villanueva RR. Hashimoto's thyroiditis: Cytodiagnostic accuracy and pitfalls. Diagn Cytopathol 1997;16:531-6.
Fitzgerald PA. Endocrinology. In: Tireney LM, McPhee SJ, Papakadakis MA, editors. Current Medical Diagnostics and Treatment. 43rd
ed. New York: Lange; 2004. p. 1090-102.
Bhatia A, Rajwanshi A, Dash RJ, Mittal BR, Saxena AK. Lymphocytic thyroiditis: Is cytological grading significant? A correlation of grades with clinical, biochemical, ultrasonographic and radionuclide parameters. Cytojournal 2007;4:10.
] [Full text]
Chandanwale SS, Gore CR, Bamanikar SA, Gupta N, Gupta K. Cytomorphologic spectrum of Hashimoto's thyroiditis and its clinical correlation: A retrospective study of 52 patients. Cytojournal 2014;11:9.
] [Full text]
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al
. The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55-68.
Singh N, Kumar S, Negi VS, Siddaraju N. Cytomorphologic study of Hashimoto's thyroiditis and its serologic correlation: A study of 150 cases. Acta Cytologica 2009;53:507-16.
Anila KR, Nayak N, Jayasree K. Cytomorphologic spectrum of lymphocytic thyroiditis and correlation between cytological grading and biochemical parameters. J Cytol 2016;33:145-9.
] [Full text]
Shetty A, Chowdappa V. Cytomorphological spectrum of Hashimoto's thyroiditis and its correlation with hormonal profile and hematological parameters. J Cytol 2019;36:137-41.
] [Full text]
Kumar N, Ray C, Jain S. Aspiration cytology of Hashimoto's thyroiditis in an endemic area. Cytopathology 2002;13:31-9.
Sood N, Nigam JS. Correlation of needle aspiration cytology findings with thyroid function test in cases of lymphocytic thyroiditis. J Thyroid Res 2014;2014:430510.
Li Y, Teng D, Shan Z, Teng X, Guan H, Yu X, et al
. Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 2008;93:1751-7.
Baker JR, Saunders NB, Burman KD. Sero- negative Hashimoto's thyroiditis with thyroid antibody production localized to thyroid. Ann Int Med 1988;108:26-30.
Fisher DA, Oddie TH, Johnson DE, Nelson JC. The diagnosis of Hashimoto's thyroiditis. J Clin Endocrinol Metab 1975;40:795-801.
Amino N. Thyroid directed antibodies. In: Ingbar SH, Braverman LE, editors.
Werner's the Thyroid – A Fundamental and Clinical Text. Philadelphia: J B Lippincott Co; 1986. p. 546-59.
Saraf SR, Gadgil NM, Yadav S, Kalgutar AD. Importance of combined approach of investigations for detection of asymptomatic Hashimoto Thyroiditis in early stage. J Lab Physicians. 2018;10:294-8.
Jayaram N, Chetan M, Prasad SR. Thyroiditis: Thyroid function and cytologic correlation. A study of 66 cases. J Cytol 1996;13:21-4. [Full text]
Jayaram G, Marwaha RK, Gupta RK, Sharma SK. Cytomorphologic aspects of thyroiditis – A study of 51 cases with functional, immunologic and ultrasonographic data. Acta Cytol 1987;31:687-93.
Friedman M, Shimaoka K, Rao U, Tsukada Y, Gavigan M, Tamura K. Diagnosis of chronic lymphocytic thyroiditis (nodular presentation) by needle aspiration. Acta Cytol 1981;25:513-22.
Kini SR, Miller JM, Hamburger JI. Problems in the cytologicdiagnosis of the “cold” thyroid nodule in patients with lymphocytic thyroiditis. Acta Cytol 1981;25:506-12.
Bhalotra R, Jayaram G. Overlapping morphology in thyroiditis (Hashimoto's and subacute) and Grave's disease. Cytopathology 1990;1:371-2.
DeMay RM. The Art and Science of Cytopathology. Chicago: ASC Press; 1996. p. 718-21.
Jayaram G. Atlas and Text of Thyroid Cytology. New Delhi: Arya Publications; 2006. p. 24-30.
Jayram G, Iyengar KR, Sthaneshwar P, Hayati JN. Hashimoto's thyroiditis-A Malaysian perspective. J Cytol 2007;24:119-24.
Ekambaram M, Kumar B, Chowdhary N, Siddaraju N, Kumar S. Significance of eosinophils in diagnosing Hashimoto's thyroiditis on fine needle aspiration cytology. Indian J Pathol Microbiol 2010;53:476-9.
] [Full text]
Rathi M, Ahmad F, Budania SK, Awasthi S, Kumar A, Dutta S. Cytomorphological aspects of Hashimoto's thyroiditis: Our experience at a tertiary centre. Clin Med Insights Pathol 2014;7:1-5.
Sanchez MA, Stahl RE. The thyroid, parathyroid and neck masses other than lymphnodes. In: Koss LG, Melamed MR, editors. Koss's Diagnostic Cytology and Its Histopathologic Basis. 2nd
ed. New York: Lippincott Williams and Wilkins; 2006. p. 1155-7.
Poropatich C, Marcus D, Ortel YC. Hashimoto's thyroiditis: Fine-needle aspirations of 50 asymptomatic cases. Diagn Cytopathol 1994;11:141-5.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3]