Fine-needle aspiration cytology of metastatic squamous cell carcinoma thyroid: A rare entity.

Metastasis to the thyroid gland is rare with majority of cases discovered during an autopsy. Clinical presentation with a palpable thyroid or functional disturbances in thyroid is uncommon. We report isolated metastasis of laryngeal squamous cell carcinoma (SCC) to the thyroid gland diagnosed on fine-needle aspiration cytology which is minimally invasive and a preferred preliminary diagnostic modality in palpable thyroid swellings. A diagnosis of extra thyroidal SCC is a diagnosis of exclusion when there is no evidence of a coexistent recognizable primary thyroid cancer and/or molecular signatures suggestive of thyroidal origin.

Introduction

Tumoral metastasis to the thyroid is a rare event. Most of these cases are discovered during an autopsy especially in individuals with widespread tumor dissemination. The incidence ranges from 0.5% to 24% in autopsy series for all histotypes.[1] Clinical presentation with a palpable thyroid or disturbances in thyroid function is uncommon and seen in less than a quarter of cases.[2] The tumors which metastasize to the thyroid include carcinomas of kidney, breast, pancreas, colon, ovary, lung and bladder; and malignant melanoma.[3]

Primary squamous cell carcinoma (SCC) of the thyroid is an extremely rare malignancy with a reported incidence of 0.2-1.1% of all thyroid carcinomas.[4] Therefore, the possibility of metastasis from an occult primary must always be considered and ruled out whenever malignant squamous cells are seen in the thyroid. SCCs metastasizing to the thyroid largely have their origin in the lung, esophagus, and head and neck region.

We report isolated metastasis of laryngeal SCC to the thyroid gland which was picked up on fine-needle aspiration cytology (FNAC) which is minimally invasive and a preferred preliminary diagnostic modality in palpable thyroid swellings.

Case Report

A 45-year-old male presented to the outpatient clinic with a complaint of swelling in front of the neck for 10 years which increased recently over 2 months. He also complained of the recent change in voice. The patient was a chronic smoker for the past 15 years. There was no history of weight loss. On examination, the neck swelling was firm, moved on deglutition and measured 7 cm × 3 cm. The thyroid hormone profile was within normal range. Ultrasonography was not done.

Fine-needle aspiration (FNA) of the thyroid swelling was done using the palpation method by the cytopathologist with a 22-gauge, 4.5-cm long needle without using the handle. Two passes from different sites were taken. Direct smears were air-dried for May-Grόnwald Giemsa staining. Hematoxylin and eosin and Papanicolaou (Pap) staining was done on the smears wet fixed in 95% alcohol. Cell block was also made.

The smears showed sheets, clusters, and scattered malignant squamous cells with moderate anaplasia, hyperchromatic nuclei, and scanty dense cytoplasm [Figure 1a and b]. Benign follicular epithelial cells, macrophages, and bare nuclei were also seen. The tumor cells showed orangeophilia on Pap stain [Figure 1c]. Cell block preparation showed SCC [Figure 1d]. Cytologic diagnosis of SCC likely metastatic was rendered.

Figure 1

(a) The aspirate smear from thyroid showing cluster of malignant squamous cells (block arrow), benign follicular epithelial cells (arrow), macrophages, and bare nuclei (MGG, ×200). (b) Tumor cells with moderate anaplasia, hyperchromatic nuclei, and scanty dense cytoplasm (MGG, ×400). (c) Orangeophilic malignant squamous cells (Pap, 400). (d) Cell block preparation showing keratinizing squamous cell carcinoma (H and E, ×100)

Subsequent to this, the patient underwent computed tomography scan neck which showed a growth in the larynx. The thyroid gland except the right lobe had an altered echo texture. An impression of carcinoma larynx with likelihood of tumor deposits in the thyroid gland was made. A laryngeal biopsy was then taken, and histopathologic examination confirmed the diagnosis of laryngeal SCC.

Discussion

Malignancies metastasizing to the thyroid are uncommon and portend a dismal prognosis. These account for 0.1% of all thyroid nodular lesions investigated by FNA.[5] The plausible reasons for rare metastatic deposits to the thyroid are abundant blood flow through the gland which hinders the seeding of tumor cells, high iodine content, and hyperoxic environment which inhibit the development of metastatic tumor cells.[6] The common primary tumor sites include kidney (33%), lung (16%), breast (16%), esophagus (9%), and uterus (7%).[7] Isolated case reports depicting a large variety of primary sites including pancreas, liver, bile duct, prostate, ovary, placenta, adrenal, and parotid have been reported in the literature.[8]

Metastasis to the thyroid is more commonly an autopsy diagnosis which in some cases can be detected clinically. The patient may present with diffuse thyroid swelling or a nodule, dysphagia, dyspnea, dysphonia, and cough.[39] The indexed case presented with swelling thyroid and dysphonia. Metastatic tumors to the thyroid can easily mimic as primary thyroid cancers. To draw an accurate distinction between them on clinical and radiological assessment alone is not always possible. The thyroid function tests are nonspecific and noncontributory.[8] The diagnosis provided by FNAC in majority of cases is straightforward as the cytomorphology of tumor cells is similar to that of the primary tumor and alien to the more common primary tumors of the thyroid. Some cytologic pointers immediately indicating towards secondary malignancy are the presence of keratin, mucin, melanin, and bile. Information about the history of prior tumor elsewhere, an admixture of normal thyroid follicular cells with tumor cells and absence of papillary or follicular pattern in aspirates also point towards metastasis.

The cytologic differentials of SCC are exuberant squamous metaplasia, papillary and anaplastic carcinomas of thyroid with areas of squamous differentiation and rarely a mucoepidermoid carcinoma.[4] Reactive squamous metaplasia of thyroid follicular epithelial cells has cohesive cell clusters with benign features. There is no mitosis or necrosis. Ancillary markers such as p53, p21, and MIB-I can be used to distinguish between a well-differentiated SCC and squamous metaplasia.[10] A mucoepidermoid carcinoma has an admixture of squamous and mucinous cells.

Cytomorphology can give a correct diagnosis of SCC but not whether primary or secondary. This suffices to carry out a thorough radiological work-up and search for the primary tumor site in metastatic cancers to the thyroid. In the current case, the primary tumor in the larynx was established after the FNA diagnosis which prompted the clinician to search for the primary site. Immunostaining for thyroglobulin or thyroid transcription factor and clinical correlation are mandatory for establishing an unequivocal diagnosis of primary SCC thyroid.[10] A diagnosis of extra thyroidal SCC is a diagnosis of exclusion when there is no evidence of a coexistent recognizable primary thyroid cancer and/or an immunoprofile suggestive of tumor origin in the thyroid.

To conclude, SCC metastasizing to the thyroid gland is uncommon. The differentiation between primary and secondary nature of the neoplasm has both therapeutic and prognostic bearing. The presence of obviously malignant squamous cells in thyroid mandates an extensive search for the primary tumor elsewhere.