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CytoJournal 2015,  12:10

Thyroid gland and adjacent lesions: Cytomorphological clues!

Department of Pathology, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI, USA

Date of Submission10-Apr-2015
Date of Acceptance11-Apr-2015
Date of Web Publication21-May-2015

Correspondence Address:
Amarpreet Bhalla
Department of Pathology, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1742-6413.157497

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How to cite this article:
Bhalla A, Meijas-Badillo L, Jencks A, Shidham VB. Thyroid gland and adjacent lesions: Cytomorphological clues!. CytoJournal 2015;12:10

How to cite this URL:
Bhalla A, Meijas-Badillo L, Jencks A, Shidham VB. Thyroid gland and adjacent lesions: Cytomorphological clues!. CytoJournal [serial online] 2015 [cited 2019 Dec 6];12:10. Available from: http://www.cytojournal.com/text.asp?2015/12/1/10/157497

Editorial/Peer Review Statement
To ensure the integrity and highest quality of CytoJournal publications, all Quiz cases are reviewed by Quiz case section team prior to be accepted for publication.

A 65-year-old female presented for evaluation of hypertension. Physical examination revealed a painless lump in the neck. Ultrasound examination of the thyroid showed a posteriorly located, hypervascular, single hypoechoic, solid lesion, measuring 1.4 cm, near the upper pole of the left thyroid gland. [Figure 1]a-d shows the cytomorphological features of the fine needle aspirate in Diff-Quik stained smears. Papanicolaou (Pap) stained smears were suboptimal with scant cellularity.
Figure 1: Fine-needle aspiration of neck lesion (Diff-Quik stained preparation). (a) Mildly cellular smear without colloid (×4). (b) Showing small groups of cells forming syncitia, admixed with a few bare nuclei (arrowheads). Inset of "b" (×40 Zoomed) shows occasional fragment of capillary stroma with loosely attached cells (yellow arrows) (×10). (c and d) The cells showed solitary paranuclear intracytoplasmic vacuoles (arrows) without paravacuolar granules. A few bare nuclei are seen at the periphery of the groups (arrowheads). Inset of "d" (×40 Zoomed) highlights the paranuclear intracytoplasmic vacuoles indenting the nuclei (arrows) in many intact cells (×40)

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 » What is Your Interpretation? Top

  1. Follicular lesion with Hurthle cell change
  2. Hyperplastic thyroid nodule
  3. Parathyroid gland tissue
  4. Thyroiditis with Hurthle cell change.

Click here to view answer. View Answer

 » Additional Quiz Questions Top

Q1. Which of the following cytomorphological features is highly reproducible for parathyroid gland tissue in Diff-Quik stained preparations?

  1. Intracytoplasmic lipid vacuoles, indenting the nucleus
  2. Bare nuclei
  3. Para vacuolar granules
  4. Oncocytic cytoplasm

Q2. Which of the following cytomorphological features favor parathyroid neoplasms over thyroid follicular neoplasms?

  1. Regimented pattern of palisading nuclei along branching network of delicate capillaries
  2. Bare nuclei
  3. Cytoplasmic vacuoles, indenting the nucleus
  4. All of the above

Q3. Which of the following features does not favor parathyroid lesions?

  1. Intracytoplasmic lipid vacuoles
  2. Immunoreactivity for calcitonin
  3. Oncocytic cytoplasm
  4. Metachromatic neurosecretory granules

Answers to additional quiz questions

1.a; 2.d; 3.b

1. (a): [Figure 1]c and d the fat vacuoles appear as discrete, round to oval intracytoplasmic spaces with a sharp outline, and a tendency to indent a portion of nucleus, touching it, subtly. They are a hallmark of parathyroid gland cells and are most numerous in normal parathyroid glands. [3]

Both intercellular and intracellular lipid vacuoles decrease in parathyroid hyperplasia and adenoma. The intracytoplasmic fat vacuoles may also be seen in the setting of lipoadenoma and parathyroid hamartoma. Imprint smears preserve the cytoplasm of individual fragile cells better than scrape smears (and hypothetically conventional smears of FNA aspirates), permitting better visualization of intracytoplasmic fat vacuoles [3],[5],[6] [Figure 1]c-d. Some studies do not describe the vacuoles, but they are observed in their published Diff-Quik images of FNA of parathyroid lesions [[Figure 2] pg. 409]. [7] Rarely nonspecific vacuoles may be present in other neck lesions. However, they may not be solitary, paranuclear, and do not indent the nucleus.

Bare nuclei, devoid of cytoplasm may be dispersed singly [arrow heads in [Figure 1]b-d]. They may also be observed in aspirates from thyroid lesions, lymphoid neoplasms, and metastatic small cell carcinoma.

2. (d): [[Figure 1]b - Inset] regimented pattern of palisading nuclei along branching network of delicate capillaries is typically seen in parathyroid lesions and differentiates it from thyroid nodules. [1],[2],[3],[4] However, similar features may also be seen in carotid body tumors (paraganglioma), metastatic tumors and other neuroendocrine lesions.

3. (b): Chief cells of the parathyroid gland show cytoplasmic lipid, better observed in Romanowski stained preparations such as Diff-Quik stained smears [[Figure 1]d - Inset]. Hyperplastic and neoplastic glands tend to have less cytoplasmic lipid and smaller droplets than normal or atrophic parathyroid cells.

Glycogen may be present in clear cells and stains with periodic acid-Schiff.

Neurosecretory granules may be seen as metachromatic inclusions in the cytoplasm, stained with Romanowsky stains. [2]

Immunoreactivity for calcitonin is a specific feature of parafollicular cells (C cells) and medullary carcinoma thyroid.

 » Brief Review of the Topic Top

Awareness of cytomorphological features of parathyroid and other anatomical structures in the vicinity, inclusive of lymph nodes, thyroid, and branchial cleft remnants is important to make a definitive diagnosis.

Cytomorphological features suggesting parathyroid gland lesion may be encountered in the following clinical scenarios:

  • Suspected parathyroid lesion.
  • Intraoperative consultation: Frozen section evaluation of tissues in the vicinity of thyroid gland including thyroidectomies and parathyroid gland surgeries.
  • Evaluation of hyperparathyroidism.
  • Incidental finding on FNA, as in intrathyroidal parathyroid or ectopic parathyroid.
  • FNA of hypoechoic thyroid nodules.
  • FNA of parathyroid cyst.
  • FNA of ectopic parathyroid while evaluation of neck nodule.
  • FNA of thyroid bed, status post thyroidectomy.

Clinical associations

  • Hypercalcemia
  • Nephrolithiasis
  • Bone lesions (brown tumors)

Radiological correlation [1],[7]

  • Normal parathyroid glands are not visualized by ultrasonography.
  • Parathyroid adenomas are usually hypervascular, hypoechoic, ovoid or lobulated lesions, associated with extrathyroidal feeding artery and one or more vascular pedicles.
  • They may show cysts and calcifications.

Fine-needle aspiration biopsy

Fine-needle aspiration biopsy of parathyroid lesions is a challenging procedure, with variable yield of diagnostic material. The inadequacy rates, range from 8.3% to 28.1%. The rate of contamination with thyroid follicular epithelial cells varies from 8.3% to 31.5%. [7]

 » Focused differential diagnosis of PArathyroid gland lesions Top

Normal parathyroid glands

  • Architectural patterns: Solid sheets, branching anastomosing cords and acinar structures with rich vascularity.
  • Cellularity: Admixture of parenchyma and adipose tissue.
  • Cell types: Chief cells, oncocytic/oxyphilic cells, and water clear cells.
  • Cell size: Slightly smaller than follicular epithelial cells from thyroid.
  • Cytoplasm: Moderate amount of pale granular cytoplasm with small intracytoplasmic lipid vacuoles with a tendency to indent the nucleus [Figure 1]c and d
  • Oxyphil cells are slightly larger and have abundant oncocytic cytoplasm. The nuclei are round, central to eccentric, with dense chromatin, and prominent dark nucleoli.
  • Water clear cells are rarely seen in normal parathyroid glands. They have faintly eosinophilic to clear cytoplasm with abundant glycogen deposits and sharply defined cell membranes. [1],[2],[9]
  • Immunohistochemistry: Cytoplasmic immunoreactivity for keratin, chromogranin A, and parathormone. Lack of immunoreactivity for vimentin, glial fibrillary acidic protein, neurofilament, and chromogranin B. [10]

Parathyroid cysts

  • Derived from embryologic remnants, coalescence of microcysts or degeneration of an adenoma.
  • Contents of parathyroid cyst: Clear, watery; occasionally golden brown. The fluid is acellular or hypocellular.
  • Cytoarchitecture: Tissue fragments, honeycomb sheets or microfollicles.
  • Cells: Small, cuboidal, with round nuclei and granular to compact chromatin.
  • Background: Proteinaceous debris.
  • Differential diagnosis: Cystic degeneration of nodular goiter, branchial cleft cyst, thymic cyst, and thyroglossal duct cyst.

Parathyroid adenoma and hyperplasia

  • Cellularity: Moderate cellularity.
  • Architecture/cellular distribution: Two- or three-dimensional clusters, papillary fragments, complex branching, follicular pattern, dispersed single cell pattern. A branching network of capillaries and neoplastic cells arranged alongside capillaries, in a regimented pattern, is characteristic.
  • Cell size and shape: Monomorphous round to oval cells that exhibit stippled nuclear chromatin and high nucleo-cytoplasmic ratio. Endocrine atypia may be pronounced. Spindle-shaped cells may be seen.
  • Background: Inspissated colloid like material may be present, either mixed with the cells or distributed separately within the vicinity of cells. Macrophages, fat globules, delicate branching, vascularized stromal tissue fragments may be present.
  • Bare nuclei: Seen commonly in abundance.
  • Nuclear morphology: Round to oval, uniform, smooth membrane, coarsely granular/stippled chromatin, with micronucleoli. Intranuclear inclusions, nuclear pleomorphism/endocrine atypia, nuclear moulding, single vacuoles may be present. Mitosis and karyorrhexis should typically be absent in adenoma.
  • Distinction of different parathyroid lesions (hyperplasia versus adenoma) may not be possible on cytomorphologic evaluation alone.


  • Multiple small nodules, containing bland cells are disseminated in the soft tissues of the neck.
  • They may be associated with Multiple Endocrine Neoplasia 1 (MEN 1) syndrome.

Parathyroid carcinoma

  • The lesions are extremely cellular
  • Cells: Small, medium, or large. Either monomorphic or pleomorphic in appearance. Cells with clear cytoplasm and tumor giant cells may be present. The cells are dyshesive with anaplasia, macronucleoli, typical and atypical mitoses, and necrosis.
  • High Ki-67 index, Cyclin D1 expression, and lower p27 indices indicate parathyroid carcinoma. Galectin-3 is expressed in parathyroid carcinomas and not in adenoma. [2],[9]

 » Competing interests statement by all authors Top

The authors declare that they have no competing interests.

 » Authorship statement by all authors Top

All authors of this article declare that we qualify for authorship as defined by ICMJE http://www.icmje.org/#author.

Each author has participated sufficiently in the work and takes public responsibility for appropriate portions of the content of this article.

 » Ethics statement by all authors Top

As this is a quiz case without identifiers, our institution does not require approval from Institutional Review Board (IRB) (or its equivalent).

 » List of abbreviations Top

FNA = Fine-needle aspiration

TTF-1 = Thyroid Transcription Factor-1

 » References Top

Kini S, editor. Thyroid and parathyroid. In: Color Atlas of Differential Diagnosis in Exfoliative and Aspiration Cytopathology. 2 nd ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams and Wilkins; 2011. p. 401-541.  Back to cited text no. 1
DeMay RM, editor. Head and neck. In: The Art and Science of Cytopathology. 2 nd ed. Chicago, IL: ASCP Press; 2012. p. 752-73.  Back to cited text no. 2
Shidham VB, Asma Z, Rao RN, Chavan A, Machhi J, Almagro U, et al. Intraoperative cytology increases the diagnostic accuracy of frozen sections for the confirmation of various tissues in the parathyroid region. Am J Clin Pathol 2002;118:895-902.  Back to cited text no. 3
Chan JK. Tumors of the thyroid and parathyroid gland. In: Fletcher CD, editor. Diagnostic Histopathology of Tumors. 4 th ed. Philadelphia, PA: Elsevier; 2013. p. 1177-250.  Back to cited text no. 4
Sasano H, Geelhoed GW, Silverberg SG. Intraoperative cytologic evaluation of lipid in the diagnosis of parathyroid adenoma. Am J Surg Pathol 1988;12:282-6.  Back to cited text no. 5
Dimashkieh H, Krishnamurthy S. Ultrasound guided fine needle aspiration biopsy of parathyroid gland and lesions. Cytojournal 2006;3:6.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
Agarwal AM, Bentz JS, Hungerford R, Abraham D. Parathyroid fine-needle aspiration cytology in the evaluation of parathyroid adenoma: Cytologic findings from 53 patients. Diagn Cytopathol 2009;37:407-10.  Back to cited text no. 7
Giorgadze T, Stratton B, Baloch ZW, Livolsi VA. Oncocytic parathyroid adenoma: Problem in cytological diagnosis. Diagn Cytopathol 2004;31:276-80.  Back to cited text no. 8
Rosai J. Parathyroid glands. In: Rosai and Ackerman′s Surgical Pathology. 10 th ed. Philadelphia, PA: Elsevier; 2011. p. 565-83.  Back to cited text no. 9
 Faquin WC, Michael CW, Renshaw AA, Vielh P. Follicular neoplasm, hurthle cell type/suspicious for a follicular neoplasm, hurthle cell type. In: Ali SZ, Cibas ES, editors. The Bethesda System for Reporting Thyroid Cytopathology. Definitions, Criteria, and Explanatory Notes. New York: Springer; 2010. p. 59-73. Based on NCI Thyroid Fine Needle Aspiration State of the Science Conference (Oct 22-23, 2007), Springer.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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