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Hürthle cell follicular carcinoma (HCFC) of the thyroid gland is a malignant tumour composed predominantly or entirely of oncocytes (also called “Hürthle” or “Askenazy” cells),1 arranged in a follicular/trabecular pattern without the cytological changes found in papillary carcinoma.1,2 Although most studies have demonstrated that HCFC and follicular thyroid carcinoma share similar clinical behaviour and prognosis,3 recently the World Health Organization (WHO) has classified HCFC as a separate and distinct entity.4 Anaplastic thyroid carcinoma accounts for 5–10% of all thyroid cancers and represents the most aggressive thyroid tumour almost invariably associated with a fatal outcome.5 Most anaplastic thyroid carcinoma cases show evidence of a pre‐existing differentiated, or poorly differentiated, thyroid carcinoma.2,5 At present, to our knowledge, the secondary leptomeningeal localisation of thyroid HCFC has not yet been reported in the literature.
We describe the case of a 56‐year‐old woman who was admitted to the hospital due to a 3‐day history of partial seizures, unsteady walk with frequent falls and dysarthria. She had no history of either neck irradiation or thyroid diseases in her family. Fifteen years before, laboratory and imaging investigations disclosed a euthyroid goitre with a 15 mm hypoechoic, scintigrafically “cold”, nodule in the left thyroid lobe. She was not submitted to fine‐needle aspiration biopsy, and was given L‐thyroxine thyroid stimulating hormone suppressive treatment for about 1 year. On admission, the neurological examination was normal, although the Mini Mental State Evaluation (MMSE) showed only a mild cognitive impairment with deficiency of working memory. A few days later, generalised seizures and lethargy developed. Laboratory testing and imaging procedures were performed. Blood count, renal liver and thyroid function tests, and acid‐base equilibrium were normal, whereas erythrocyte sedimentation rate was elevated at 35 mm/h. Cerebral MRI documented a cortical hyperintensity on T2‐weighted sequences, enhancing after gadolinium administration. Cytological examination of the liquor obtained by lumbar puncture showed clusters of large polygonal cells exhibiting hyperchromatic, markedly atypical nuclei with prominent “cherry pink” nucleoli and abundant eosinophilic granular cytoplasm resembling oncocytes (fig 1A1A).). Immunocytochemical reaction against thyroglobulin, calcitonin and thyroid transcription factor‐1 (TTF‐1) stains was negative. Treatment with dexamethasone 16 mg/d intravenously and oxcarbazepine was started. Investigations performed to detect the source of oncocytes, including whole body CT, scintigraphy of the skeleton and thyroid ultrasound, revealed several metastatic lesions at the lumbar spine and a 22 mm hypoechoic, hypervascularised nodule with undefined margins in the left thyroid lobe. Thyroid fine needle aspiration biopsy yielded highly cellular material composed of follicular‐patterned Hürthle cells lacking nuclear features of papillary carcinoma and finally interpreted as Hürthle cell follicular neoplasm. A biopsy of a lumbar spine lesion was obtained. The smears from lumbar spine biopsy featured a neoplasm composed of oncocytes arranged in small follicles, showing marked atypias and frequent mitotic figures; tumour cells were positive for thyroglobulin (fig 1B1B)) and TTF‐1, and negative for calcitonin and chromogranin: the histological diagnosis was “bone metastasis from HCFC of the thyroid”. The patient underwent total thyroidectomy without complications. Histological examination of thyroid specimen demonstrated a well‐circumscribed, partly encapsulated, lesion in the left lobe. The neoplasm was mostly composed of Hürthle cells arranged in small follicles with scanty colloid (fig 1C1C),), widely invasive into the tumour capsule and vessels. Oncocytes were polygonal to square in shape, had distinct cell borders and abundant eosinophilic granular cytoplasm; nuclei were large, with frequent multinucleation, marked atypias and mitotic activity, and prominent cherry pink nucleoli, in the absence of grooves, clearing, crowding or pseudoinclusions. The neoplasm stained positively for thyroglobulin, TTF‐1 and cyclin D1, whereas it was negative for cytokeratin, S100 protein, Melan A, HMB‐45, ret/PTC, CT, p21, p27, and p53 stainings. In some discreet areas of the neoplasm, contiguous to oncocytes and intermingled with them, a haphazard proliferation of giant pleomorphic, unusual cells was seen (fig 1D1D).). These elements were polygonal to spindle‐shaped, contained pale eosinophilic cytoplasm and large, irregular, markedly atypical nuclei. At immunohistochemical examination, these cells showed positive reaction to p53 and cyclin D1, but did not stain with thyroglobulin, TTF‐1, cytokeratin, S100 protein, Melan A, HMB‐45, ret/PTC, CT, p21, and p27. The final diagnosis was consistent with HCFC of the thyroid gland, including foci of anaplastic thyroid carcinoma. Soon after thyroidectomy, the patient was given L‐thyroxine 100 mcg/d. A 5‐mCi 131I whole body scan was obtained following administration of recombinant thyroid stimulating hormone (Thyrogen), 0.9 mg intramuscularly in two consecutive days; unfortunately, no radioiodine uptake was detected througout the body. The patient died 4 months after diagnosis.
The present report is of particular interest because, to the best of our knowledge, it represents the first documentation of a HCFC of the thyroid presenting with diffuse meningeal carcinomatosis and evolving to anaplastic thyroid carcinoma. The evidence of foci of anaplastic thyroid carcinoma within a HCFC in our patient strongly supports the hypothesis that most anaplastic thyroid carcinoma cases derive from the loss of differentiation of a pre‐existing differentiated neoplasm;2,5 so far, papillary thyroid carcinoma has been indicated as the main precursor of anaplastic thyroid carcinoma.2,5 In this case, the neoplasm displayed overexpression of cyclin D1 and underexpression of p21 and p27 in both HCFC and anaplastic thyroid carcinoma areas, as well as p53‐positive thyroglobulin‐negative cells within anaplastic thyroid carcinoma: a pattern reflecting the progressive tumour undifferentiation.6 The aggressive behaviour of the neoplasm in our patient, showing bone metastases, meningeal carcinomatosis and no radioiodine uptake, likely represented the clinical aspect of such cellular events.
Competing interests: None.