Journal of Cancer Research and Therapeutics

CORRESPONDENCE
Year
: 2019  |  Volume : 15  |  Issue : 3  |  Page : 704--707

Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity


Divya Shelly, Divya Gupta, Shashank Mishra, Reena Bharadwaj 
 Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India

Correspondence Address:
Dr. Divya Shelly
Department of Pathology, Armed Forces Medical College, Sholapur Road, Pune - 411 040, Maharashtra
India

Abstract

Anaplastic thyroid carcinoma (ATC) is a rare, highly malignant thyroid tumor with dismal prognosis. Osteoclastic giant cell variant of ATC is extremely rare and is characterized by the presence of a large number of multinucleated giant cells resembling osteoclasts. We report here this unusual variant in a 67-year-old female with a history of long-standing goiter of 13 years duration. Histologically, many multinucleated osteoclast-like giant cells were seen accompanying the malignant spindle cell component. Despite extensive sampling, no evidence of differentiated thyroid malignancy could be elucidated.



How to cite this article:
Shelly D, Gupta D, Mishra S, Bharadwaj R. Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity.J Can Res Ther 2019;15:704-707


How to cite this URL:
Shelly D, Gupta D, Mishra S, Bharadwaj R. Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity. J Can Res Ther [serial online] 2019 [cited 2020 Oct 29 ];15:704-707
Available from: https://www.cancerjournal.net/text.asp?2019/15/3/704/244211


Full Text



 Introduction



Anaplastic thyroid carcinoma (ATC) represents the most aggressive extreme of the clinical spectrum of thyroid epithelial neoplasms. Although it constitutes <5% of recognized thyroid malignancies, it accounts for more than half of the deaths for thyroid cancer, with a mortality rate that is over 90%.[1]

The World Health Organization defines it as a highly malignant tumor wholly or partially composed of undifferentiated cells that retain features indicative of an epithelial origin, on immunohistochemical or ultrastructural grounds.[2] Microscopically, three patterns have been described: spindle cell, epithelioid-squamoid, and giant cell.[3] Tumor histomorphology depends on the predominant pattern or mixture of the components present. Very rarely, osteoclast-like multinucleated giant cells may be seen in spindle cell tumors, giving rise to resemblance to giant cell tumor of bone. Here, we present a case of osteoclastic variant of ATC, in a 67-year-old female, with a history of long-standing goiter.

 Case Report



A 67-year-old hypertensive and diabetic female was referred to our hospital for the management of a large swelling over anterior aspect of neck associated with dyspnea and dysphagia. The swelling started as a small globular mass and had been there for the last 13 years. For the past 1 month, there was sudden increase in size and it was associated with difficulty in breathing and dysphagia. Local examination revealed a diffuse, firm to hard, nontender lump over the anterior aspect of the neck, measuring 20 cm × 12 cm in size. Retrosternal extension was noted; however, overlying skin was free. Thyroid function tests were within normal limits. Ultrasonography-guided fine-needle aspiration cytology was attempted; however, it revealed only necrotic material.

Contrast-enhanced computerized tomography neck done at the referring hospital revealed an 8 cm × 11 cm × 13 cm right thyroid mass displacing trachea and great vessels; however, no invasion was seen. The possibility of likely benign etiology was suggested. With high degree of suspicion of carcinoma and to alleviate symptoms of dyspnea and dysphagia, the patient underwent total thyroidectomy.

Gross examination of total thyroidectomy specimen revealed right lobe of thyroid measuring 10 cm × 12 cm × 7 cm with overlying skin flap measuring 9.5 cm × 6.5 cm. Cut surface revealed replacement of the entire right lobe by a tumor having a variegated appearance. Grayish white solid areas were interspersed with large areas of necrosis [Figure 1]. Areas of hemorrhage were also noted. The tumor was grossly infiltrating outside the thyroid capsule. Left lobe of thyroid was grossly unremarkable.{Figure 1}

The routine hematoxylin and eosin-stained sections examined from the tumor showed spindle cell tumor arranged in predominantly storiform pattern [Figure 2]a. The spindle cell component exhibited marked nuclear pleomorphism and brisk mitotic activity (7–9/10HPF). Areas of extensive palisading necrosis were noted [Figure 2]b. Numerous osteoclasts-like giant cells with 10–30 bland looking vesicular nuclei were seen scattered within the entire tumor [Figure 2]c. These two tumor components showed area of intermingling and occasional area showed transition. Heavy lymphocytic infiltration was noted throughout the tumor. Despite extensive sampling, no evidence of differentiated thyroid malignancy could be elucidated. Extra-thyroidal extension of the tumor was seen. Of nine lymph nodes dissected, five showed metastatic deposits of the tumor with perinodal extension.{Figure 2}

On immunohistochemistry, spindle tumor cells were diffusely positive for vimentin [Figure 2]d and were focally positive for epithelial membrane antigen (EMA). CD68 highlighted the osteoclastic giant cells [Figure 2]e, whereas spindle tumor cells were negative for CD68. The tumor cells and giant cells were negative for cytokeratin [Figure 2]f, smooth muscle actin, thyroid transcription factor 1 (TTF-1), p63, carcinoembryonic antigen (CEA), and thyroglobulin.

Based on morphological and immunohistochemical findings, a diagnosis of ATC (osteoclastic variant) was rendered.

 Discussion



ATC is a highly aggressive and rare thyroid tumor with higher incidence in endemic regions for goiter.[3],[4] The patients are usually elderly in their sixth or seventh decade of life, with a female preponderance of around 2.5:1.[4] Personal history of goiter may be seen in approximately 11% of cases.[3] Clinical presentation includes rapidly enlarging neck mass associated with compressing symptoms such as dysphagia, hoarseness, and stridor.[4],[5] Our patient had a long-standing history of goiter for almost 13 years and she presented for the first time due to recent onset of dysphagia and difficulty in breathing.

Grossly, ATC is recognized as a large mass that is typically widely invasive, often replacing most of the thyroid gland parenchyma and shows infiltration of the surrounding soft tissue and adjacent structures of the neck.[1],[4],[6] Cut surface is usually variegated, reflecting the presence of hemorrhagic and necrotic foci.[1],[2],[6] Our patient also presented with a large tumor, variegated in appearance, replacing the right lobe of thyroid and showed infiltration of soft tissue.

Microscopically, the appearance of ATC depends on the admixture of three main histological patterns: spindle cell, giant cell, and squamoid.[2] These patterns often coexist in variable proportions and are historically used to group ATC in major histological categories and to define their main differential diagnoses. However, none of these patterns is predictive of patient outcome.[1],[2],[6] Pure giant cell pattern is characterized by solid pattern of growth with presence of numerous giant cells having round to oval shape, bizzare hyperchromatic nuclei and abundant amphophilic, and somewhat granular cytoplasm.[2],[6] Giant cell pattern needs to be differentiated from unusual variant associated with many bland looking multinucleated giant cells resembling the osteoclasts and called osteoclastic variant. It is extremely uncommon variant with only a few immunohistochemical and cytological well documented cases in the literature.[6],[7] Microscopically, the osteoclastic variant of ATC characteristically reveals many multinucleated osteoclast-like giant cells scattered among neoplastic elements.[1],[2],[6] 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.[1],[2],[6] These nuclei never show mitotic division. These osteoclast-like cells are believed to be nonneoplastic, derived from cellular fusion of blood-borne or indigenous monocytes or histiocytes.[8]

ATCs show a variable immunophenotype depending upon the predominant histological pattern of the growth. Vimentin is consistently present in the spindle cell component, whereas EMA and CEA are particularly expressed in the squamoid cells.[1] Other markers such as TTF-1, calcitonin, and thyroglobulin are usually negative.[1],[9] PAX8 is positive in found in 79% of ATCs and it is negative in head and neck squamous carcinoma and lung carcinoma and thus can be used in differential diagnosis.[10]

Although ATC is a rare neoplasm, ample information regarding genetic alterations associated with these tumors is available in literature. Point mutations (RAS and BRAF gene mutations) are more common in these tumors than thyroid specific genetic rearrangements (RET/PTC and PAX8/PPARγ).[11] While RAS gene point mutations have been described in 6%–50% of cases, BRAF gene mutations have been identified in 10%–44% of ATC. It has been hypothesized that ATC may progress from BRAF-mutated papillary thyroid carcinoma by acquisition of p53 mutations.[12] This mutation is an extremely rare event in differentiated Almost all the mutations reported are located in the known hot-spots (exons 5-9).[11] In a recent study by Bonhomme et al., next-generation sequencing of 144 cases of ATC yielded total of 210 mutations (intronic and exonic). p53 mutations were the most frequent (54.4%) followed by RAS gene mutations (43%). BRAF gene mutation (V600E) was identified in 13.8% of cases.[13] Another set of somatic mutations which have been described in up to 50% of ATC are in the promoter of the TERT (Telomerase Reverse Transcriptase) gene. Expression of TERT measures telomerase activation. Thyroid cancers display less frequent telomerase activation than other human carcinomas, being present in about 66% of all the thyroid carcinomas.[11] Telomerase activation has been rarely reported in differentiated thyroid cancer; it is primarily seen in poorly differentiated and undifferentiated cancer. Bonhomme et al. identified a TERT promoter alteration in 54.0% cases.[13] In addition, there are b-catenin gene (CTNNB1) mutations that are more commonly seen in poorly differentiated and ATC, rarely identified in well differentiated thyroid carcinomas and are associated with more advanced disease.[11]

ATC is a deadly disease with dismal prognosis. Treatment includes surgical resection with negative margins and neo- or adjuvant chemotherapy and radiotherapy. In addition, newer treatment modalities including target therapies against driver mutations such as tyrosine kinase inhibitors for advanced ATC are still under trials.

 Conclusion



ATC with osteoclast-like giant cells is a rare, aggressive thyroid tumor having a very poor prognosis. Tumors with similar histomorphology have been described in neoplasms of parenchymal organs such as breast, colon, lung, ovary, kidney, and bladder.

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.

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