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Metastasis of a caecal neuroendocrine carcinoma to the thyroid gland
  1. G Papi1,
  2. S Corrado2,
  3. C Carani3,
  4. S L Asa4
  1. 1Department of Internal Medicine, Section of Endocrinology, University of Modena and Reggio Emilia, Modena I-41012, Italy; papigiampaolohotmail.com
  2. 2Department of Forensic and Morphologic Sciences, Section of Pathology, University of Modena and Reggio Emilia
  3. 3Department of Internal Medicine, Section of Endocrinology, University of Modena and Reggio Emilia
  4. 4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

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Metastatic tumours to the thyroid have been reported to arise from several organs.1,2 We describe a unique case of caecal neuroendocrine carcinoma (NEC) metastatic to the thyroid gland, mimicking a primary medullary thyroid carcinoma (MTC).

A 56 year old woman was referred after complaining of dysphagia and hoarseness. Fifteen months before, she underwent surgery because of a well differentiated caecal NEC, low grade malignant, with metastases to the left ovary, the omentum, and the abdominal lymph nodes (World Health Organisation classification).3 The tumour was composed of spindle shaped cells, exhibiting scanty eosinophilic cytoplasm, salt and pepper nuclei, and inconspicuous nucleoli (fig 1). Neoplastic cells showed intense reactivity with antibodies against CAM 5.2, AE1/AE3, cytokeratin 7, cdx-2, chromogranin A, synaptophysin, serotonin, and neurone specific enolase; there was weak reactivity for calcitonin and carcinoembryonic antigen. In contrast, no immunoreactivity was detected for thyroid transcription factor 1 or vimentin.

Figure 1

 Primary neuroendocrine carcinoma of the caecum. Haematoxylin and eosin stain; original magnification, ×10.

On examination, a firm nodule was felt in the left lobe of the patient’s thyroid gland; attempts at fine needle aspiration biopsy did not yield adequate material for a cytological diagnosis. The patient underwent thyroidectomy, and histological examination disclosed a tumour in the left thyroid lobe, with the same pathological and immunohistochemical features as the previously excised caecal lesion (fig 2). Nonetheless, it was negative for Congo red, S-100 protein, and thyroglobulin stain; again, cdx-2 staining was positive, further confirming the caecal origin of this tumour (fig 3). Twenty one months after thyroidectomy, the patient died as a result of multiple organ failure.

Figure 2

 The caecal neuroendocrine tumour (right side of the figure) metastatic to the thyroid gland (on the left side) grew in a predominantly solid and trabecular architectural pattern, surrounded by a fibrovascular stroma. Haematoxylin and eosin stain; original magnification, ×10.

Figure 3

 The thyroid metastasis was composed of spindle shaped cells with poorly defined cell borders, exhibiting scanty eosinophilic cytoplasm, salt and pepper nuclei, and inconspicuous nucleoli. The tumour cells showed intense nuclear staining for cdx-2; in contrast, thyroid epithelium was negative for this marker. Cdx-2 staining; original magnification, ×40.

To the best of our knowledge, this is the first case of a rare caecal NEC with metastasis to the thyroid to be reported. The differential diagnosis included several primary neoplasms. MTC is characterised by positive immunostaining for calcitonin4; nonetheless, calcitonin can also be produced ectopically.5 In our patient, weak positivity for calcitonin was found at immunohistochemical examination; however, staining for thyroid transcription factor 1, a marker of thyroid or lung origin,6 was negative, whereas cdx-2, a transcription factor involved in the proliferation and differentiation of intestinal epithelial cells encoded by a homeobox gene,7 was positive, excluding MTC. Paraganglioma was ruled out by both the intense reactivity of neoplastic cells for cytokeratins, and the absence of sustentacular cells, as shown by negativity for S-100 protein.8 Insular carcinoma could be excluded by the absence of a microfollicular pattern, the negative immunoreaction against thyroglobulin, and the positive immunostaining for neuroendocrine markers. Finally, a few cases of primary small cell carcinoma of the thyroid have been described,9 which share identical pathological and immunohistochemical features with primary lung small cell carcinoma. Some of them are positive for calcitonin, and are therefore regarded as small cell variants of MTC. In our patient, small cell carcinoma was ruled out firstly because of patient history and also by positive immunostaining for cdx-2.

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