|Year : 2021 | Volume
| Issue : 1 | Page : 40-44
Cytodiagnosis of anaplastic thyroid carcinoma with osteoclast-like giant cells − A case report with a review of the literature
Padmanaban Krishnan Govindaraman1, Selvaraj Balakumar2, Anthuvan Jeyarani Lawrence3
1 Department of Pathology, Thanjavur Medical College and Hospital; KGP Diagnostic Centre, Government General Hospital, Thanjavur, Tamil Nadu, India
2 Department of Otorhinolaryngology, Government General Hospital, Thanjavur, Tamil Nadu, India
3 Department of Radiodiagnosis, Bharath Scans, Thanjavur, Tamil Nadu, India
|Date of Submission||08-Aug-2021|
|Date of Acceptance||19-Oct-2021|
|Date of Web Publication||29-Oct-2021|
Dr. Padmanaban Krishnan Govindaraman
Department of Pathology, Thanjavur Medical College and Hospital, Thanjavur - 613 005, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Anaplastic thyroid carcinoma (ATC) accounts for 5%–10% of primary thyroid malignancies. Cytodiagnosis of osteoclast-like giant cells (OLGCs) variant of ATC is very rare with only few cases reported in literature. We report a case of ATC with OLGC variant in an 85-year-old female who presented with swelling in the right lobe of thyroid and scalp nodule, which on radiological evaluation and subsequent fine-needle aspiration biopsy (FNAB) was diagnosed as ATC having numerous OLGC with metastases in skull bones. Cytologically, thyroid aspirate revealed sheets of epithelioid neoplastic cells admixed with many OLGC. Aspirate from the scalp nodule showed neoplastic cells with follicular differentiation. She also had radiological evidence of lung metastasis. Such a presentation of this rare variant being diagnosed by FNAB is rarely reported in literature and highlights the importance of this simple procedure in diagnosing and planning management of this rare condition.
Keywords: Anaplastic thyroid carcinoma, osteoclast like giant cells, cytodiagnosis
|How to cite this article:|
Govindaraman PK, Balakumar S, Lawrence AJ. Cytodiagnosis of anaplastic thyroid carcinoma with osteoclast-like giant cells − A case report with a review of the literature. Thyroid Res Pract 2021;18:40-4
|How to cite this URL:|
Govindaraman PK, Balakumar S, Lawrence AJ. Cytodiagnosis of anaplastic thyroid carcinoma with osteoclast-like giant cells − A case report with a review of the literature. Thyroid Res Pract [serial online] 2021 [cited 2022 May 22];18:40-4. Available from: https://www.thetrp.net/text.asp?2021/18/1/40/329689
| Introduction|| |
Anaplastic thyroid carcinoma (ATC) represents the most aggressive of thyroid epithelial neoplasms, with a mortality rate that is over 90% and a mean survival of 6 months after the diagnosis. ATC accounts for 5%–10% of primary thyroid malignancies, usually seen in elderly. Their rapid growth and local invasion tends to clinically overshadow early metastasis to lungs, bone.
ATC reveals three main histological patterns: Spindle cell, giant cell, and squamoid. These patterns often coexist and are not predictive of patients' outcome,,, but used to define their main differential diagnoses. The presence of osteoclast-like giant cells (OLGC) is very rare in ATC with only odd number of cases reported in the literature.,,
We report a case of ATC with OLGC in a female aged 85 years who had multiple metastases in skull bones and lungs.
| Case Report|| |
A female aged 85 years presented with nodular swelling on the right lobe of thyroid for the past 10 years. Swelling was firm to hard in consistency with restricted mobility [Figure 1]. She had developed pain and dysphagia with sudden increase in size for the past 1 month. Her thyroid function test was normal. She also had a scalp nodule in the frontal region [Figure 1].
|Figure 1: Photograph showing swelling in the right lobe of thyroid and scalp nodule|
Click here to view
Her computed tomography (CT) of the neck revealed a large nodule (m) 35 × 34 mm with internal cystic degeneration having rim calcification in right lobe of thyroid with infiltrative margins extending in to adjacent soft tissue [Figure 2]. Multiple well-defined nodules were seen in both upper lobes of lungs suggestive of metastases [Figure 3].
|Figure 2: Computed tomography image showing mass involving the right lobe of thyroid|
Click here to view
|Figure 3: Computed tomography image showing nodular mass in the upper lobe of the lung|
Click here to view
CT of the brain revealed multiple lytic lesions with associated soft-tissue component in right frontal, right parietooccipital, and left high parietal bones, largest (m) 48 mm × 20 mm-suggestive of metastases [Figure 4].
|Figure 4: Computed tomography image showing multiple skull bone secondaries with soft-tissue component|
Click here to view
Fine-needle aspiration cytology/biopsy (FNAB) of thyroid revealed cellular smear composed of pleomorphic squamoid-epithelioid cells, spindle cells, admixed with many OLGC composed of 20–40 nuclei with dense eosinophilic cytoplasm distributed throughout the smear resembling osteoclastoma of the bone, many mitotic figures in a hemorrhagic background [Figure 5] and [Figure 6].
|Figure 5: Photomicrograph of smear showing neoplastic epithelioid cells and osteoclast-like giant cells H and E ×40|
Click here to view
|Figure 6: Photomicrograph of cytology smear showing osteoclast type of giant cells H and E ×40|
Click here to view
As scalp nodule was suspected to be metastasis, FNAB of the swelling was done. Surprisingly, smear showed follicular epithelial cells in monolayered sheets, clusters, repetitive microacini in a hemorrhagic background [Figure 7] and [Figure 8]. As ATC is known to arise from preexisting well-differentiated carcinomas, it is very likely that this patient had preexisting follicular carcinoma that has transformed in to ATC as skull lesion is suggestive of follicular carcinoma metastases. Hence, a final diagnosis of ATC with OLGC variant with skull bone metastases was given. As she had advanced stage of disease, surgical management was deferred and palliative care was given.
|Figure 7: Smear from the scalp nodule showing follicular cells in sheets H and E ×40|
Click here to view
|Figure 8: Smear from the scalp nodule showing follicular cells in repetitive microacini H and E ×40|
Click here to view
| Discussion|| |
ATC is defined by the WHO as a highly malignant tumor wholly or partially composed of undifferentiated cells that retain features indicative of an epithelial origin, on immunohistochemical or ultrastructural ground. It usually affects elderly people, with a mean age in the mid-60s, and shows a female predominance.,,
Grossly, ATC is well recognized as a large, necrotic, and hemorrhagic mass, replacing most of the thyroid parenchyma with infiltration of the surrounding soft tissue in the neck.,, This case had radiological evidence of adjacent soft-tissue infiltration.
ATC with OLGC is an extremely rare morphological type of undifferentiated carcinoma thyroid and was first described by Nadal in 1910. ATC occurs in iodine-deficient regions and individuals with previous coexisting goiter and papillary or follicular carcinoma thyroid.,,,
Three main histological patterns of ATC were described: Spindle cell, giant cell, and squamoid,,, which often coexist and are not predictive of patients' outcome. The small cell category is no longer considered, as it comprised cases of bona fide lymphomas, medullary carcinomas, and insular carcinomas.
FNAB is an important diagnostic tool that can provide a correct diagnosis of ATC in up to 84% of cases. FNAB smears are usually cellular pleomorphic in a necrotic background. The tumor cells are bizarre, oval to spindle-shaped, dyscohesive, and irregular sometimes multiple nuclei, perfectly reflecting the sarcomatoid or epithelioid histological morphology. Although the presence of giant cells in anaplastic carcinoma is common, the occurrence of OLGC is a rare event,,, and the diagnosis of this variant with FNAB is even rarer. The other variants such as squamoid and spindle cell types lack giant cells.
The FNAB of the osteoclastic variant of ATC is characteristic and it shows a cellular smear with two cell populations: Undifferentiated mononuclear cells and multinucleated osteoclast like giant cells. The mononuclear cells are the main neoplastic element. The multinucleated giant cells resemble osteoclasts and they are abundantly admixed with the mononuclear malignant cells., These cells have numerous (up to 100) uniform sized, round to oval, benign nuclei which are often centrally placed. The cytoplasm is abundant and dense eosinophilic. Highly pleomorphic cells were not seen by Han et al. as observed in our case. These osteoclast-like cells are believed to be reactive, nonneoplastic and are positive for CD 68 by immunohistochemical studies and apparently derived from histiocytoid mononuclear cells through cellular fusion.,,,,, They give the tumors an appearance reminiscent of giant cell tumor of bone and soft tissue as seen in this case., Similar OLGC giant cell lesions were reported in breast, pancreas, gall bladder, lung, kidney, and ovary. Our case had epithelioid morphology admixed with few pleomorphic spindle cells, tumor giant cells and many OLGC. Many mitotic figures were noted in a necrotic background.
The differential diagnoses of multinucleated giant cells seen in FNAB of thyroid include ATC, papillary carcinoma, subacute thyroiditis, Hashimoto's thyroiditis, nodular hyperplasia. In the conventional ATCs, the giant cells are mostly the pleomorphic type and there are not so many OLGC as in the osteoclastic variant of ATC.,, However, the mononuclear cells could be differentiated from the papillary carcinoma cells, as the latter usually reveal the characteristic nuclear features. Subacute thyroiditis and Hashimoto's thyroiditis can be excluded by the lack of an inflammatory background. Nodular hyperplasia reveals abundant colloid material and some multinucleated giant cells that show foamy cytoplasm rather than dense cytoplasm as seen in this case.,
The association between well-differentiated thyroid carcinoma (WDTC) and anaplastic carcinoma ranges from 7% to 89% of cases. The better differentiated tumor is usually a papillary carcinoma or its variants, follicular carcinoma, or an insular carcinoma. It has been suggested that if an extensive sampling is performed, foci of WDTC are eventually found in every specimen of ATC.
In this case, patient had bone metastasis which revealed follicular pattern [Figure 7] and [Figure 8] in FNAB suggestive of follicular carcinoma metastasis. Hence, it is very likely that this is a case of follicular carcinoma of thyroid with anaplastic transformation and bone secondaries. As this case is inoperable due to advanced disease, histopathological examination was not possible, highlighting the importance of role of FNAB in diagnosing advanced disease. Anaplastic transformation may also take place in a metastatic focus, supporting the idea that these lesions originate through the dedifferentiation of pre-existing well-differentiated cancer. However, in our case, contrarily, we were able to pick up differentiated component in metastatic focus which is again an unusual presentation.
ATC cells are not immunoreactive for thyroglobulin, calcitonin, and Thyroid transcription factor (TTF).,,,,, PAX 8 (also known as paired box gene 8) is sensitive marker seen in 79%–92% of ATCs, whereas it is negative in head and neck squamous carcinoma and lung carcinoma.,, Spindle cells are consistently positive for vimentin.,, Cytokeratin is variably positive ranges from 40% to 100% of cases.,
Somatic mutations in the promoter of the Telomerase Reverse Transcriptase (TERT) gene have been detected in up to 50% of ATCs.,, Intriguingly, TERT mutations seem to occur prevalently in those tumors harbouring mutated BRAF or RAS, suggesting that TERT alteration is acquired later during tumor development enabling acquisition of additional genetic defects leading to disease progression.
| Conclusion|| |
ATC is a very aggressive malignancy with poor prognosis. OLGC variant of ATC is a very rare and its presentation with multiple bone and lung metastases is very rarely reported in literature. This case highlights the role of FNAB in diagnosing such rare entity presenting in advanced stage and planning further management. This patient was put on palliative chemotherapy as surgery was avoided in this old moribund patient with advanced disease.
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
Conflicts of interest
There are no conflicts of interest.
| References|| |
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;2014:1-13.
Squamoid, spindle and giant cell lesions. In: Boerner SL, Asa SL, editors. Biopsy Interpretation of the Thyroid. 2nd
ed., Ch. 12. Lippincott williams & wilkins, philadelphia: Wolters Kluwer; 2017. p. 254-80.
Joseph L, Ravi A, Rekha A, Rao S, Aarthi R, Panicker V. Osteoclastoma-like anaplastic carcinoma of the thyroid. J Cytol 2008;25:65. [Full text]
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.
de Lellis RA, Lloyd RV, Heitz PU, Eng C. Pathology and Genetics of Endocrine Organs. Lyon, France: IARC; 2004.
Gahlot GP, Chatterjee T, Tewari R, Singh V, Ahuja A, Singh K, et al
. 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 2020;22:255-7. [Full text]
Venkatesh YS, Ordonez NG, Schultz PN, Hickey RC, Goepfert H, Samaan NA. Anaplastic carcinoma of the thyroid. A clinicopathologic study of 121 cases. Cancer 1990;66:321-30.
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.
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.
Mehta N, Patel J, Shah N, Hiryu P. A rare case of osteoclastic variant of anaplastic thyroid carcinoma diagnosed by fine needle aspiration cytology. IAIM 2019;6:132-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]