Cytodiagnosis of Metastatic Thyroid Follicular Carcinoma in Left Iliac Bone with Occult Primary: A Case Report

Bone metastasis of Follicular Thyroid Carcinoma (FTC) is an aggressive complication. Typically, follicular carcinoma remains confined to the thyroid gland, with distant metastasis occurring in 4-15% of cases. The lungs are the most frequent site of metastasis, followed by bone (2-13%). A peculiar clinical manifestation of FTC observed is the metastasis with the primary still remaining clinically occult. Solitary bone metastases are exceedingly rare and can easily be misdiagnosed as primary bone tumours on clinicoradiological assessment. This causes delays in the diagnosis and management. In these cases, the cytomorphology of cells on diagnostic Fine Needle Aspiration (FNA) was found to be useful in suggesting the primary origin of FTC. Distant bone metastases from follicular carcinoma on histopathological examination from biopsy specimens have been reported in the literature. The cytodiagnosis and cytomorphology of metastatic FTC by Fine Needle Aspiration Cytology (FNAC) are seldomly described in the literature. Involvement of the iliac bone in the metastasis of FTC is uncommon. The FNAC of such a bony lesion helps immensely not only in the diagnosis of the metastasis but also in suggesting the primary malignancy. Authors, hereby report a clinicopathological profile of one such rare case of a 74-year-old female with cytodiagnosis of FTC with no clinical thyroid swelling. The cytodiagnosis made from the primary lytic lesion involving the left iliac bone led to the retrospective radiological and histopathological work-up of the thyroid gland, confirming the occult primary carcinoma of the thyroid gland. The present case highlights the rare presentation and cytomorphological details of metastatic thyroid follicular carcinoma.

Bony metastasis, Fine needle aspiration cytology, Follicular thyroid, Osteolytic lesion

A 74-year-old female presented at the Orthopaedics Outpatient Department (OPD) of a tertiary care hospital with primary complaints of swelling and pain in the left iliac region for the past two months. The pain was gradually progressive, dull aching in nature, aggravated by walking and hip flexion, and relieved by immobilisation. The patient denied any history of local or regional trauma or falls. She had previously received medical treatment from a private practitioner who prescribed Non steroidal Anti-inflammatory Drugs (NSAIDs) for pain relief. Upon local examination, a diffuse swelling was observed in the left iliac region with the overlying skin appearing normal [Table/Fig-1]. The clinical examination revealed painful and restricted movement of the hip joint. The patient’s general and physical examinations were otherwise normal. Complete blood counts and coagulation profiles were conducted, showing no abnormalities and indicating normal values. She was then referred for radiology investigations. The X-ray of the pelvis revealed a lytic lesion in the left iliac bone [Table/Fig-2]. A Computed Tomography (CT) scan of the pelvis was performed, showing a well-defined hyperdense lesion in the left iliac bone [Table/Fig-3]. The radiodiagnosis suggested a giant cell tumour of the left iliac bone as a possible differential diagnosis, and FNA was advised.

[Table/Fig-1]:

Clinical photograph of globular swelling at the left pelvic region.

[Table/Fig-2]:

X-ray pelvis shows lytic lesion involving the left iliac bone.

[Table/Fig-3]:

CT pelvis shows hyperdense lesion with destruction of the left iliac bone.

The patient underwent FNA of a swelling over the left iliac bone under Ultrasonographic (USG) guidance. The material from the FNA was smeared and fixed to be stained with Papanicolaou and Giemsa stains. The FNA smears revealed follicles and monolayered cell sheets of low cuboidal cells with nuclei showing mild hyperchromasia and pleomorphism. A few cell sheets showed nuclear molding. The cytoplasm of these cells was small and with discernible granularity [Table/Fig-4]. The diagnosis of a metastatic lesion of thyroid follicular carcinoma was suggested based on the findings in the smear. USG of the neck was recommended for the assessment of the thyroid.

[Table/Fig-4]:

Photomicrograph of FNA smears from lytic lesion of left iliac bone: Shows small sheets and follicles of malignant thyroid follicular cells (Papanicolaou stain, 40x).

The patient underwent a neck ultrasound to assess the thyroid status, which revealed multiple centimetre-sized nodules in both lobes of the thyroid. These nodules underwent FNAC, and the cytodiagnosis of Follicular neoplasm (Bethesda category IV) was made [1]. Based on these findings, a total thyroidectomy was performed. The histomorphology of the resected specimen showed an invasive lesion of thyroid follicular carcinoma [Table/Fig-5].

[Table/Fig-5]:

Photomicrograph of follicular carcinoma thyroid, section shows multiple follicles of malignant thyroid follicular cells (H&E, 40x).

After the diagnosis, a Positron Emission Tomography (PET) scan was performed. No evidence of metastasis elsewhere in the abdominal cavity was observed. The tumour board of the institute advised the patient to undergo radiotherapy and chemotherapy. The patient was followed-up by the tumour board of the Institute.

The FTC is the second most common type of thyroid cancer, accounting for about 10-20% of all differentiated thyroid malignancies [2,3]. FTC, in comparison with papillary thyroid carcinoma, is less common, has a more aggressive course, and a higher propensity for distant metastases. FTC spreads through a haematogenous route rather than lymphatic, as seen in Papillary thyroid carcinoma [2,4]. The lungs are the most frequent site of metastasis, followed by bone (3-12%) in FTC. Common locations for osseous metastases include the vertebrae, sternum, pelvis, mandible, ribs, and skull bones [2-9]. Metastatic FTC leads to a poor prognosis, with a 10-year survival rate declining to 25-27% as compared to pulmonary metastasis [10-12]. By the time distant metastasis is detected, the primary lesion has usually already been diagnosed. On occasions, the metastatic lesion of FTC is a presenting lesion even in the absence of an obvious thyroid nodule [5,8]. It is rare for patients to present with solitary bone metastasis as the initial presentation of occult FTC. The presence of large solitary bony masses without an accompanying thyroid nodule can result in a differential diagnosis of primary malignant bone tumours, such as angiosarcoma or malignant fibrous histiocytoma [3,5]. In such cases, the cytomorphology of cells on diagnostic FNA was found to be useful in suggesting the primary of FTC. The most frequent sites of bony metastasis in FTC are vertebrae, sternum, ribs, scalp, and skull, which are reported in the literature [2,4,6,9,10,13,14].

However, a large study conducted by Pal P et al., in 173 patients with FTC observed bony metastases in 34% of patients. Matta-Coelho C et al., in 86 patients with bony metastasis of thyroid follicular neoplasm, concluded that the spine was the commonest site of metastatic involvement in 33.9% and 61.6% of patients, respectively [10,15]. Other rare sites of bony involvement in FTC include the iliac bone, sacrum, mandible, and calcaneum as reported by Chandanwale S et al., Saha K et al., and Rahal MJH et al., respectively [3,8,11]. Metastasis to the appendicular skeleton is rarest; however, one such case has been reported by Varshney S and Pant H [5]. FTC affects women more commonly than men, with peak incidence seen at 40-50 years of age [4,8]. The presented case of bony metastases to the iliac bone in FTC was of a 74-year-old female, which was not the common age of presentation, similar to a few other studies in the literature [2,5,7-9,11,13].

The initial radiological assessment did not offer the diagnosis of metastatic FTC to the iliac bone. Instead, the provisional diagnosis of a primary malignant bone tumour, most likely a giant cell tumour of the iliac bone was provided, similar to the studies reported by Chandanwale S et al., and Varshney S and Pant H [3,5]. These were described as ill-defined, expansile, and osteolytic lesions on X-ray [2,8], Detailed histological features of bony metastasis from FTC on biopsy specimens have been reported in the literature [6,11,14,16]. The literature on cytological interpretation is however scarce. Gupta P et al., conducted a retrospective study in 10 patients diagnosed with metastatic FTC on FNAC [4]. The cytomorphological features in this study were elaborated as follows: i) Predominantly microfollicular arrangement of cells; ii) The follicular cells are small to low cuboidal; iii) Mildly pleomorphic nuclei with low Nuclear-to-cytoplasmic (N:C) ratio containing fine chromatin and inconspicuous nucleoli; iv) These cells have moderate amount of cytoplasm having fire-flare appearance; v) Scanty eosinophilic colloid material may be seen in the background. The above-presented case details an uncommon occurrence of an unusual case of metastatic follicular carcinoma in the iliac bone with occult primary. Cases presenting with bone metastases of the unknown primary have rarely been encountered in cytology except for the study by Kalra R et al., Chandanwale S et al., and Varshney S and Pant H [2,3,5].

The cytodiagnosis performed on the lytic lesion of the left iliac bone, suggesting a malignant thyroid follicular neoplasm, led to a retrospective evaluation of the thyroid. Although the thyroid was not obviously enlarged upon clinical evaluation, it was found to harbour a malignant neoplasm known as follicular carcinoma. The present case provided a unique learning experience.

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