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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 3  |  Page : 144-147

The distribution of parafollicular cells (C cells) in adult cadaveric thyroid gland: An immunohistochemical study


1 Associate Professor, Department of Anatomy, Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Chennai, Tamil Nadu, India
2 Professor and HOD, Department of Anatomy, Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Chennai, Tamil Nadu, India
3 Assistant Professor, Department of Microbiology, Sri Lalithambigai Medical College, Chennai, Tamil Nadu, India

Date of Submission04-Feb-2021
Date of Decision16-May-2021
Date of Acceptance07-Jun-2021
Date of Web Publication30-Jul-2021

Correspondence Address:
Kafeel Hussain
Door No: 11, Plot No: 58, 5th Cross Street, Rajalakshmi Nagar, Velachery, Chennai - 600 042, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/NJCA.NJCA_19_21

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  Abstract 


Background: The population of parafollicular cells or C cells in the normal thyroid has subjective variation. These variations in cadaveric thyroid gland are primarily attributed to ethnicity, gender, underlying pathologies, and sampling technique or approach. The lack of homogenous C cell dispersal poses a challenge in the diagnosis and interpretation of C cell hyperplasia. The aim of the study is to analyze the C cell distribution in various parts of the cadaveric thyroid. Methodology: This study was performed with 56 thyroid glands acquired from adult human cadavers (37 males and 19 females). Calcitonin polyclonal antibody was employed to identify the C cells. C cells in tissue sections from the isthmus, upper, middle, and lower regions of the thyroid gland were examined. Results: The number of C cells in the section from the thyroid ranged between 0 and 5/low-power field (LPF) in the upper region, 0 and 12/LPF in the middle region, and 0 and 3/LPF in the lower region. The mean number of C cells displayed in the section from the upper third region of the thyroid was 9 ± 1.92 C cells (range 6–12 C cells). The mean number of C cells quantified in the section from the middle third region was 25 ± 3.34 cells (range 19–30 C cells). The mean number of C cells in the section from the lower third was 3 ± 1.88 C cells (range 0–6 C cells). Sexual dimorphism in the mean total number of C cells in the section from the midzone of the gland was statistically significant. Conclusion: The midzone of thyroid gland has more population of C cells than other region. A significantly higher number of C cells were observed in males. This nonuniform distribution of C cells could result in conflicting reports, especially during the assessment of C cell hyperplasia.

Keywords: C cell hyperplasia, parafollicular cells, thyroid


How to cite this article:
Hussain K, Sathialakshmi V, Fathima S. The distribution of parafollicular cells (C cells) in adult cadaveric thyroid gland: An immunohistochemical study. Natl J Clin Anat 2021;10:144-7

How to cite this URL:
Hussain K, Sathialakshmi V, Fathima S. The distribution of parafollicular cells (C cells) in adult cadaveric thyroid gland: An immunohistochemical study. Natl J Clin Anat [serial online] 2021 [cited 2021 Sep 21];10:144-7. Available from: http://www.njca.info/text.asp?2021/10/3/144/322800




  Introduction Top


The microscopic section of the thyroid gland displays follicular cells and parafollicular cells, which are embryologically derived from two different sources. The follicular cell population makes up the major portion of it. The follicular cells have been considered to be endodermal in origin, whereas the cells of the neural crest contribute to the genesis of C cells.[1] Both the cells vary in their microscopic structure and function. C cells are concerned with the synthesis of “calcitonin,” which decreases the level of calcium in the blood. There have been disagreements among authors regarding the number and distribution of C cells.[2],[3] This inconsistency could arise from the associated pathology, gender, or variations in sampling methods. Interpretation of C cell hyperplasia is difficult owing to the uneven pattern in which the parafollicular cells are distributed.[4],[5] C cells are characteristically 2–3 times larger than follicular cells but stain palely with hematoxylin and eosin (H/E). The lack of certainty in localizing C cells with the customary H/E stains makes the task of quantification even more difficult. This warrants the need of an immunohistochemical study to revisit the distribution of C cells and quantify them in sections from the thyroid.

Hence this study aimed to study the distribution of the C cells in various regions of the normal thyroid gland acquired from adult human cadavers.

Aim

The aim is to study the distribution of the C cells in various regions of the normal thyroid gland acquired from adult human cadavers.


  Materials and Methods Top


This is an observational, cross-sectional study undertaken with 56 thyroid glands sourced from adult human cadavers (37 males and 19 females) at Shri Sathya Sai Medical College and Research Institute (SSSMCRI). The normal thyroid glands obtained from adult human cadavers received in the department of anatomy from 2015 to 2019 were included in this study.

Glands with autolytic alterations and any gross or histopathological evidence of thyroid diseases were excluded from the study. A total of 64 thyroid glands were examined out of which five glands were excluded due to histopathological features of multinodular goiter and three were excluded due to autolytic changes. The autolyzed glands were determined based on the altered histoarchitecture of tissues that was unrelated to any pathology, failure to take up the stain, intracytoplasmic vacuolation, the absence of a nucleus, and cellular edema.

The permission to conduct this study was obtained from the Institutional Ethical Committee (IEC) of SSSMCRI, Chennai. IEC clearance number was 2014/186. This study undertaken is in compliance with the principles enunciated in the Declaration of Helsinki.

The thyroid lobe was slit longitudinally and sliced into superior, mid, and inferior zones. The isthmus was also isolated. The gland was then fixed in formalin for 72 h and subjected to routine tissue processing. A prediluted calcitonin polyclonal antibody (Bio SB Catalog No. 5114) was employed to identify the C cells. In this study, indirect method of streptavidin immunoperoxidase staining procedure and diaminobenzidine chromogen was used. The staining protocol encompassed heat-induced epitope retrieval with an antigen retrieval solution (1.21 g of Tris buffer and 0.37 g of EDTA mixed in 1 l of distilled water), followed by application of chromogen to visualize the antibody/antigen complex and finally counterstaining with hematoxylin.

The immunostained sections from the isthmus, superior, mid, and inferior zones of the thyroid gland were visualized under a Binocular light microscope with APCAM-5 USB 2 Digital Camera (Model AP40 Cat. No. 112 AP40). The number of C cells in each low power field (LPF, ×10) was counted by moving each section orthogonally in the microscope. The C cells were quantified by summing up the number of C cells encountered in each LPF. The C cells in both the sexes were compared and statistically analyzed using two-tailed Student's t-test. The C cells were also compared between the respective regions of the two lobes and statistically analyzed using independent sample t-test.


  Observation and Results Top


The mean number of C cells displayed in the section from the upper third region of the thyroid was 9 (±1.92) (range 6–12 C cells). The mean number of C cells quantified in the section from the middle third region was 25 (±3.34) C cells (range 19–30 C cells). The mean number of C cells in the section from the lower third was 3 (±1.88) (range 0–6 C cells) [Chart 1]. C cells were not observed at the isthmus.



It was observed that not all LPFs which were orthogonally scanned demonstrated C cells. The number of C cells in the section from the thyroid ranged between 0 and 5/LPF in the upper region [Figure 1], 0 and 12/LPF in the middle region [Figure 2], and 0 and 3/LPF in the lower region [Figure 3].
Figure 1: Improved C cells in the upper one-third of normal thyroid (calcitonin, ×10)

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Figure 2: C cells in the middle one-third of normal thyroid (calcitonin, ×10)

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Figure 3: C cells in the lower one-third of normal thyroid (calcitonin, ×10)

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The difference in the C cell number between the two lobes was not statistically significant on applying independent sample t-test (upper region [P = 0.79], middle region [P = 0.259], and lower region [P = 0.6990]).

Sexual dimorphism of C cells

The C cells were markedly increased in number in males than in females. The mean number of C cells in a section of the middle third of the thyroid gland was 27 (±3.39) (range: 23–31) in males and 21 (±2.92) (range: 19–24) in females. The difference was statistically significant (P < 0.001) [Table 1].
Table 1: Comparison of the mean number of C cells between the two sexes in the normal thyroid gland

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  Discussion Top


The C cells in the current study were maximally concentrated in the “middle third” of the gland. Nevertheless, studies by previous authors have demonstrated C cells in the “upper” as well as the “middle third” of the gland.

Kracht et al.[6] found an increase in parafollicular cells in hyperparathyroidism restricted to the “upper third” region. De Lima et al.[7] quantified C cells from the thyroid aspirates, which were detected more so on the “right lobe” than the left. C cells were often detected in the “upper” zone closely followed by the middle third of the gland. However, the C cells in the samples taken by fine-needle aspiration cytology need not be representative of the entire region and hence make this study not completely reliable.

De Lima et al.[7] rarely found C cells in the isthmus in normal thyroid aspirates. Papi et al.[8] performed an immunohistochemical study on the isthmus of benign nodular thyroid disease and medullary thyroid carcinoma. The isthmus was free of C cells in either group. Autopsy studies on normal thyroids to demonstrate C cells by Guyétant et al.[4] never revealed any C cells in the isthmus sections.

They observed the C cells concentrated predominantly in the “middle third” zone with the peak density at 44% of the lobar length.[8] Gibson et al.[9] documented that C cells were crowded in the midzone, despite the disparateness in the denseness of C cells both within a gland and between subjects. Wolfe et al.[10] mapped the dispersion of C cells and localized it in the “middle third” of the gland by immunoperoxidase, biological, and radioimmunoassay. Inoue et al.[11] frequently encountered C cells in “middle one-third” both in normal subjects as well as in cases of Grave's disease and chronic thyroiditis. Gmünder-Lehner et al.[12] ruled out a uniform glandular dispersal of Cells but added that C cells were predominantly localized at the “upper and the middle third” region. However, in “hyperplasia,” the C cells were overwhelmingly confined to the “middle and lower third” region.

Hence, a dense population of C cells in normal as well as diseased and hyperplastic conditions has been documented only in the middle one-third of the thyroid. Therefore, it undoubtedly seems to be the best region to examine the thyroid for C cells.

C cells develop from neural crest cells and drift and relocate to ultimobranchial bodies (UBBs). UBBs arise from the IV to the V branchial pouch complex separated from the parathyroid IV and bring the neural crest cells to the region between the upper and middle zone of the thyroid. This explains the increased localization of the C cells in this part of the gland as observed in this study. The experimental works with quail chick[13] also supported this phenomenon by demonstrating the capacity of the neural crest cells to give rise to mesenchymal derivatives in the cephalic neural axis down to the level of the fifth somite in both chick and quail embryos.

Nilsson and Williams[14] and Kameda[15] challenged the long-accepted view of the origin of C cells from neural crest cells by stating that thyroid cells are endodermal in origin. However, their views cannot support and provide reason for increased localization of C cells in the mid zone. Moreover, the C cell-derived medullary thyroid carcinoma (MTC) functions like a “neuroendocrine tumor.” Further, there is little similarity in the profile of MTC and endodermal cell-derived cancers. According to Albores-Saavedra et al.,[16] Harach,[17] and Papotti et al.,[18] “stem endodermal cells” could give rise to a minor subset of C cells. Hence, it is more likely that C cells could primarily be neural crest in origin with a minor population of the C cells derived endodermally.

The C cell population portrayed sexual dimorphism. The gender-based difference in the C cells encountered in this current study could be explained by the usually higher basal and pentagastrin stimulated plasma calcitonin concentrations in males as reported by Zink et al.[19] Testosterone to a greater extent thus seems to influence the poststimulatory level of calcitonin, thereby emphasizing the part played by androgens in C cell “growth and regulation.[20],[21] Moreover, tumor-associated C Cell Hyperplasia (CCH) has also been associated with sex.[22] Hence, the gender-based variations in the C cells seem to be very much existent and cannot be overlooked or denied.


  Conclusion Top


C cells are predominantly localized in the midzone of the thyroid. Sexual dimorphism in the number of C cells was evident. The homogenous spread of C cells could result in conflicting reports, especially during the assessment of C cell hyperplasia. Hence, the region scrutinized is crucial during investigation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Das SS, Mishra S, Kaul JM. Development of parafollicular cells and their relationship with developing thyroid follicles in human foetuses. J Clin Diagn Res 2017;11:C01-4.  Back to cited text no. 1
    
2.
Papi G, Rossi G, Corsello SM, Corrado S, Fadda G, Di Donato C, et al. Nodular disease and parafollicular C-cell distribution: Results from a prospective and retrospective clinico-pathological study on the thyroid isthmus. Eur J Endocrinol 2010;162:137-43.  Back to cited text no. 2
    
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Sami I. Abdullah, Abdul-Jabbar J. Al-Samarrae,Abdul-Karim S. Mahood, The Effect of Aging on Human Thyroid Gland: (Anatomical and Histological Study), Iraqi J Comm Med 2010;(3):158-64.  Back to cited text no. 3
    
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Stein T, Murugan P, Li F, El Hag MI. Can medullary thyroid carcinoma arise in thyroglossal duct cysts? A search for parafollicular C-cells in 41 resected cases. Head Neck Pathol 2018;12:71-4.  Back to cited text no. 4
    
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Montgomery G, Collins L, Coghlin C, Ullah R. Calcitonin negative medullary thyroid cancer in ectopic thyroid tissue: A rare diagnosis in an unusual location. BMJ Case Rep 2020;13:e236865.  Back to cited text no. 5
    
6.
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7.
De Lima MA, Santos BM, Tiveron FS, de Abreu ME. C cells in normal thyroid aspirates. Acta Cytologica 1999;43:558-62.  Back to cited text no. 7
    
8.
Guyétant S, Rousselet MC, Durigon M, Chappard D, Franc B, Guerin O, et al. Sex-related C cell hyperplasia in the normal human thyroid: A quantitative autopsy study. J Clin Endocrinol Metab 1997;82:42-7.  Back to cited text no. 8
    
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Gibson WG, Peng TC, Croker BP. Age-associated C-cell hyperplasia in the human thyroid. Am J Pathol 1982;106:388-93.  Back to cited text no. 9
    
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Wolfe HJ, Voelkel EF, Tashjian AH Jr. Distribution of calcitonin-containing cells in the normal adult human thyroid gland: A correlation of morphology with peptide content. J Clin Endocrinol Metab 1974;38:688-94.  Back to cited text no. 10
    
11.
Inoue S, Yokoyama S, Nakayama I, Noguchi S. An immunohistochemical study of calcitonin-containing cells in benign and malignant thyroid lesions. Acta Pathol Jpn 1990;40:187-92.  Back to cited text no. 11
    
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Gmünder-Lehner RB, Okamoto E, Hedinger C. Distribution of C cells in the human thyroid gland. Schweiz Med Wochenschr 1983;113:1385-94.  Back to cited text no. 12
    
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Kameda Y. Morphological and molecular evolution of the ultimobranchial gland of nonmammalian vertebrates, with special reference to the chicken C cells. Dev Dyn 2017;246:719-39.  Back to cited text no. 13
    
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Nilsson M, Williams D. On the origin of cells and derivation of thyroid cancer: C cell story revisited. Eur Thyroid J 2016;5:79-93.  Back to cited text no. 14
    
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Kameda Y. Cellular and molecular events on the development of mammalian thyroid C cells. Dev Dyn 2016;245:323-41.  Back to cited text no. 15
    
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Albores-Saavedra J, Gorraez de la Mora T, de la Torre-Rendon F, Gould E. Mixed medullary-papillary carcinoma of the thyroid: A previously unrecognized variant of thyroid carcinoma. Hum Pathol 1990;21:1151-5.  Back to cited text no. 16
    
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Papotti M, Volante M, Komminoth P, Sobrinho-Simões M, Bussolati G. Thyroid carcinomas with mixed follicular and C-cell differentiation patterns. Semin Diagn Pathol 2000;17:109-19.  Back to cited text no. 18
    
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Zink A, Blind E, Raue F. Determination of serum calcitonin by immunometric two-site assays in normal subjects and patients with medullary thyroid carcinoma. Eur J Clin Chem Clin Biochem 1992;30:831-5.  Back to cited text no. 19
    
20.
Filipović B, Sošić-Jurjević B, Ajdžanović V, Pantelić J, Nestorović N, Milošević V, et al. The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis. J Anat 2013;222:313-20.  Back to cited text no. 20
    
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Stuermer EK, Sehmisch S, Tezval M, Tezval H, Rack T, Boekhoff J, et al. Effect of testosterone, raloxifene and estrogen replacement on the microstructure and biomechanics of metaphyseal osteoporotic bones in orchiectomized male rats. World J Urol 2009;27:547-55.  Back to cited text no. 21
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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