Cribriform-morular variant of thyroid carcinoma: a neoplasm with distinctive phenotype associated with the activation of the WNT/ß-catenin pathway.

Cribriform-morular variant of thyroid carcinoma is classically associated with familial adenomatous polyposis but, it can also occur as a sporadic neoplasm. This neoplasm is much more frequently observed in women than in men (ratio of 61:1). In familial adenomatous polyposis patients, tumors are generally multifocal and/or bilateral (multinodular appearance), whereas in the sporadic cases tumors tend to occur as single nodules. The tumors are well delimited, and characteristically show a blending of follicular, cribriform, papillary, trabecular, solid, and morular patterns. Neoplastic cells are tall or cuboidal with the occasional nuclear features of classic papillary thyroid carcinoma. The morules include cells with peculiar nuclear clearing and show positivity for CDX2 and CD10. Angioinvasion and capsular invasion have been described in about 30 and 40% of cases, respectively, with lymph node metastases in less than 10% of patients and distant metastases in 6%. Although this tumor has good prognosis, neuroendocrine and/or poor differentiation have been associated with aggressive behavior. Tumor cells can be focally positive or negative for thyroglobulin, but are always positive for TTF-1, estrogen and progesterone receptors, and negative for calcitonin and cytokeratin 20. Nuclear and cytoplasmic staining for ß-catenin is the hallmark of this tumor type; this feature plays a role in fine needle aspiration biopsy. Cribriform-morular variant of thyroid carcinoma has a peculiar endodermal (intestinal-like) type phenotype, activation of the WNT/ß-catenin signaling pathway, and belongs to the non-BRAF-non-RAS subtype of the molecular classification of thyroid tumors. Elevated expression of estrogen and progesterone receptors and activation of the WNT/ß-catenin pathway may prove useful as putative therapeutic targets in cases that do not respond to conventional therapy. Clinicians should be alerted to the possibility of familial adenomatous polyposis when a diagnosis of cribriform-morular variant of thyroid carcinoma is made. Instead of being considered as a variant of papillary thyroid carcinoma its designation as cribriform-morular thyroid carcinoma seems more appropriate.

Aggressiveness of the tall cell variant of papillary thyroid carcinoma is independent of the tumor size and patient age.

The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is characterized by tall columnar cells with a height of at least three times their width. TCV usually presents at an older age, has a larger size and exhibits more extrathyroidal extension and metastases than classical PTC. The current study compared TCV with the classical and follicular variants (CaFVs) of PTC to determine if, irrespective of the age at diagnosis and tumor size, TCV is more aggressive than its classical and follicular counterparts. A total of 16 (3.66%) patients with TCV were identified in a series of 437 patients with PTC from the Clinical University Hospital (Santiago de Compostela, Spain) between 1990 and 2010. The patient clinicopathological features and B-Raf proto-oncogene (BRAF)V600E mutational status were compared with 34 cases of CaFVs of PTC matched for tumor size and patient age. The TCV series included 11 females and 5 males aged 15-74 years (median, 57 years). In total, 15 (93.8%) patients underwent total or near-total thyroidectomy, 1 underwent lobectomy and 5 (31.3%) underwent lymph node dissection. In the TCV series, the tumor size ranged from 5-45 mm (median, 19 mm). Compared with the CaFVs, the TCV of PTC exhibited a significantly higher prevalence of extrathyroidal extension [9/16 (56.3%) vs. 5/34 (14.7%) cases; P=0.007], lymph node metastases [9/16 (56.3%) vs. 9/34 (26.4%) cases; P=0.04], stage III/IV at presentation [10/16 (62.5%) vs. 7/34 (20.5%) cases; P=0.009] and BRAFV600E mutation [12/16 (80.0%) vs. 7/25 (28.0%) cases; P=0.004]. The TCV series also harbored more multifocal papillary carcinomas (50.0% vs. 26.4%), lymphovascular invasion (37.5% vs. 29.4%) and distant metastases (6.2% vs. 0.0%), as compared with the matched patient cohort. In conclusion, the TCV of PTC is frequently associated with BRAFV600E mutation and is more aggressive than the CaFVs of PTC, regardless of tumor size and patient age at diagnosis.

Comentarios sobre 'Carcinoma de tiroides incidental versus no incidental: presentación clínica, tratamiento quirúrgico y pronóstico' / Comments on 'Incidental versus non-incidental thyroid carcinoma: Clinical presentation, surgical management and prognosis'

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Severe localized lipoatrophy related to therapy with insulin analogs in type 1a diabetes mellitus.

Insulin analog-related lipoatrophy is a rare complication of this type of treatment. We report a case of severe localized lipoatrophy in different locations in a patient with type 1a diabetes mellitus associated with other autoimmune disease.