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CASE REPORT
Ahead of print publication  

Role of cytology in differentiating anaplastic thyroid carcinoma with osteoclast like giant cells from giant cell variant of medullary thyroid carcinoma


1 Department of Lab Sciences and Mol Med, Army Hospital (R and R), Delhi, India
2 Department of Radiotherapy, Army Hospital (R and R), Delhi, India
3 Department of Graded Specialist, Department of ENT & HNS Base Hospital Delhi Cantt, India

Date of Submission17-Dec-2019
Date of Decision06-Feb-2020
Date of Acceptance19-Apr-2020
Date of Web Publication02-Sep-2020

Correspondence Address:
G P S Gahlot,
Department of Lab Sciences and Mol Med, Army Hospital (R and R),Delhi
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmms.jmms_85_19

  Abstract 


Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor and constitutes 2%–5% of all thyroid carcinomas. The cytological diagnosis of osteoclast giant cell variant of ATC is extremely rare, and only a few cases have been described in literature. A 67 - year-old female underwent fine-needle aspiration cytology from the thyroid nodule. Smears revealed hypercellular aspirate comprising of clusters and singly scattered atypical cells with few interspersed multinucleated tumor cells. Cytomorphological differential diagnosis of giant cell/pleomorphic variant of medullary carcinoma and anaplastic carcinoma was offered. Histomorphological features on cell block assisted with immunohistochemistry confirmed the diagnosis of ATC with osteoclastic-like giant cells. Computed tomography-guided right lung lesion aspirate was reported as metastasis of high-grade poorly differentiated carcinoma. The patient was managed with cisplatin-based chemotherapy. This case highlights the importance of cytological diagnosis of ATC to guide the treatment modality of chemotherapy thus avoiding surgery, especially in old moribund patient with lung metastasis.

Keywords: Anaplastic thyroid carcinoma, medullary thyroid carcinoma, osteoclast-like giant cells



How to cite this URL:
Gahlot G P, Chatterjee T, Tewari R, Singh V, Ahuja A, Singh K, Singh B. Role of cytology in differentiating anaplastic thyroid carcinoma with osteoclast like giant cells from giant cell variant of medullary thyroid carcinoma. J Mar Med Soc [Epub ahead of print] [cited 2020 Sep 19]. Available from: http://www.marinemedicalsociety.in/preprintarticle.asp?id=294200




  Introduction Top


Thyroid cancer is the most common endocrine malignancies and represents <1% of all human cancers.[1] It can be either follicular cell origin with well-differentiated papillary/follicular carcinoma or poorly differentiated thyroid carcinoma or anaplastic thyroid carcinoma (ATC) or medullary thyroid carcinoma (MTC) morphology. ATC is the most aggressive form of primary thyroid malignancies, which is composed of undifferentiated follicular thyroid cells.[2] ATC accounts for 2%–5% of all thyroid cancers with >90% mortality in 6 months. Three microscopic patterns of ATC occurring singly or in combination are sarcomatoid, giant cell, and epithelial ones. All these patterns usually exhibit necrosis, increased mitosis, and growth infiltration. We, hereby, present an extremely rare case of ATC with osteoclastic-like giant cells in an old lady using simple fine-needle aspiration cytology (FNAC) technique that determined the treatment modality.[3],[4],[5],[6],[7]


  Case Report Top


Our patient, a 67-year-old female presented with midline neck swelling which on ultrasonography revealed multiple nodules in bilateral thyroid lobes with compression of the trachea. FNAC smears showed hypercellular aspirate of clusters and singly scattered atypical cells having pale blue cytoplasm, eccentric nuclei, nucleomegaly, irregular nuclear borders, salt-and-pepper chromatin, and prominent nucleoli [Figure 1]a and [Figure 1]b. Few interspersed multinucleated giant (MNG) cells and few large cells with coarse chromatin were present [Figure 1]c. Cytological differential diagnosis of ATC with osteoclastic-like giant cells versus giant cell variant of medullary carcinoma was considered. Clinical workup revealed normal levels of calcitonin, and contrast-enhanced computed tomography (CT) of the chest showed a space-occupying lesion in the right lung suspicious of metastasis. The patient was then re-aspirated, and the cell block was prepared. Cell block showed round to polygonal to spindle-shaped tumor cells with MNG cells [Figure 1]d, [Figure 1]e, [Figure 1]f. The epithelial cells were immunopositive for pan-cytokeratin, whereas immunonegative for synaptophysin, chromogranin, and calcitonin, whereas MNG cells were immunopositive for CD68, thus confirming the diagnosis of anaplastic carcinoma with osteoclastic-like giant cells [Figure 1]g, [Figure 1]h and [Figure 1]j. CT-guided aspirate from lung lesion also revealed metastasis of high-grade poorly differentiated carcinoma [Figure 2]a, [Figure 2]b, [Figure 2]c. In view of metastatic disease, the patient was managed with cisplatin-based chemotherapy rather than surgical intervention.
Figure 1: Fine-needle aspiration cytology of thyroid nodule shows atypical cells having pale blue cytoplasm, eccentric nuclei, and prominent nucleoli. (a; ×40, b; ×100) Multinucleate giant cells present (c; ×200). Cell block shows osteoclastic giant cells with interspersed pleomorphic cells. (d; ×40, e; ×100, f; ×200) Immunopositivity for PANCK (g; ×200) by tumor cells and CD68 by multinucleate cells (h; ×200) immunonegative for calcitonin (j; ×200)

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Figure 2: Fine-needle aspiration cytology of right lung lesion shows tumor cells with moderate-to-marked nuclear pleomorphism and conspicuous nucleoli (a; ×40, b; ×100, c; ×200)

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  Discussion Top


Anaplastic carcinoma with osteoclastic-like giant cells is an extremely rare morphological type of undifferentiated carcinoma thyroid and was first described by Nadal in 1910. ATC affects predominantly women (F:M = 2:1) with a peak incidence in the sixth to seventh decades. It occurs in iodine-deficient regions and individuals with previous coexisting goiter and papillary or follicular carcinoma thyroid.[2],[3],[4],[5],[6] The patient presented with a rapidly growing, firm, fixed, locally infiltrative neck mass with common symptoms comprising of pain, hoarseness, stridor, dyspnea, and dysphasia. ATC arises from the follicular cells of the thyroid, however does not possess any biological features of the follicular cells.[3],[4],[5],[6],[7] ATC exhibits three histomorphological patterns depending upon the variable proportion of spindle cells, giant cells, and epithelial-squamoid cells, however these patterns do not predict any outcome.[8] Pure giant cell variant comprises of sheets of many giant cells having round-to-oval hyperchromatic nuclei with abundant amphophilic cytoplasm.[5],[9] Similar osteoclast-like giant cell tumors have been described in the breast, gall bladder, colon, lung, kidney, and ovary. MNG cells are present in thyroid aspirates of subacute thyroiditis, Hashimoto's thyroiditis, benign nodular hyperplasia, papillary carcinoma, ATC, MTC, and Langerhans cell histiocytosis. The multinucleated osteoclast-like giant cell has numerous non-neoplastic, bland, uniform, round-to-ovoid, benign, centrally placed nuclei with fuzzy cytoplasmic membrane and abundant dense eosinophilic cytoplasm. These cells represent reactive monocytes/histiocytes and are derived from mononuclear cell fusion. The immunohistochemical profile of ATC shows positivity for PANCK and PAX8 by epithelial cells, vimentin by spindle cells, and CD68 by osteoclast-like MNG cells, whereas negative for thyroid transcription factor-1, thyroglobulin, and calcitonin. ATC arises de novo or by the transformation of more differentiated tumors into poorly differentiated forms through chromosomal instability and sequential molecular alteration. Bonhomme et al. observed a total of 210 intronic and exonic mutations by next-generation sequencing in 144 ATC cases.[10] Among these, TP53 mutations were the most common (54.4%), followed by H/K/N RAS (Harvey/ Kirsten/ Neuroblastoma Rat Sarcoma) gene (43%), P13K AKT (serine/threonine-specific protein kinase) pathway (17%), BRAF (B- Rapidly Accelerated Fibrosarcoma,) mutation (13.8%), both RAS and P13K (6.4%), and both TP53 and PTEN (Phosphatase and tensin homolog ) (4.3%). TERT (Telomerase reverse transcriptase) alteration was observed in 54% of cases. BRAF and β-catenin mutations are generally noted in undifferentiated thyroid carcinoma and represent a more aggressive phenotype. Definitive diagnosis is important as treatment modality for ATC is combined external beam radiation with chemotherapy, followed by surgery, whereas MTC is primarily managed by total thyroidectomy with lymph node dissection of ipsilateral and central compartments. Targeted therapy against tyrosine kinase inhibitor for advanced ATC is under trial.


  Conclusion Top


The case highlights the importance of cytological diagnosis of a very rare and aggressive osteoclastic variant of ATC by simple FNAC with accuracy, thereby offering the treatment modality as chemotherapy, especially in old moribund patient with lung metastasis.

Acknowledgment

We acknowledge the support of our patient, as with his support, the study had been feasible.

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ragazzi M, Ciarrocchi A, Sancisi V, Gandolfi G, Bisagni A, Piana S. Update on anaplastic thyroid carcinoma: morphological, molecular, and genetic features of the most aggressive thyroid cancer. Int J Endocrinol. 2014;2014:790834. doi:10.1155/2014/790834.  Back to cited text no. 1
    
2.
Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon: IARC; 2017. p. 104-5.  Back to cited text no. 2
    
3.
Mehdi G, Ansari HA, Siddiqui SA. Cytology of anaplastic giant cell carcinoma of the thyroid with osteoclast-like giant cells – A case report. Diagn Cytopathol 2007;35:111-2.  Back to cited text no. 3
    
4.
Joseph L, Ravi A, Rekha A, Rao S, Aarthi R, Panicker V. Osteoclastoma-like anaplastic carcinoma of the thyroid. J Cytol 2008;25:65.  Back to cited text no. 4
  [Full text]  
5.
Sharma M, Sharma V, Sharma A, Khajuria A. Anaplastic thyroid carcinoma and its osteoclastic variant. Natl J Med Res 2014;4:98-100.  Back to cited text no. 5
    
6.
Mourouguessine V, Tukkaram C. Anaplastic carcinoma of thyroid: With osteoclast like giant cells: An extremely unusual finding in fine needle aspiration cytology. Int J Res Med Sci 2016;4:666-8.  Back to cited text no. 6
    
7.
Shelly D, Gupta D, Mishra S, Bharadwaj R. Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity. J Cancer Res Ther 2019;15:704-7.  Back to cited text no. 7
    
8.
Han KM, Kim DH, Lee W. Aspiration cytology of the osteoclastic variant of anaplastic thyroid carcinoma: With special emphasis on the undifferentiated mononuclear cells. Korean J Pathol 2010;44:682.  Back to cited text no. 8
    
9.
El Naggar, Baloch ZW, Eng C, Evans HL, Fagin JA, Faquin WC, et al. Anaplastic thyroid carcinoma. In: Lloyd RV, Osamura RY, Kloppel G, Juan R, editors. WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon, France: IARC; 2017. p. 104 5.  Back to cited text no. 9
    
10.
Bonhomme B, Godbert Y, Perot G, Al Ghuzlan A, Bardet S, Belleannée G, et al. Molecular pathology of anaplastic thyroid carcinomas: A retrospective study of 144 cases. Thyroid 2017;27:682-92.  Back to cited text no. 10
    


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