Keratotic Nodule on The Heel: A Quiz.

A 51-year-old man, with a medical history of medullary thyroid carcinoma excised under thyroxine treatment presented with a painful enlarging lesion on his right heel since one year. A 3-cm diameter, greyish, infiltrated nodule with spicules was seen on physical examination (Fig. 1a). A 5-mm surgical excision was made and a total skin graft was used for reconstruction. Histopathology of the total resected tumour revealed pseudoepitheliomatous hyperplasic epidermis and a proliferation located between rete ridges, dermis and superficial hypodermis (Fig. 1b). The proliferation was composed of nets and cordons of cells with granular and abundant PAS-positive cytoplasm. Immunostains showed cytoplasmic positivity for s100 and inhibin (Fig. 1c). Three years later the patient is asymptomatic.

Thyroid metastasis as initial presentation of clear cell renal carcinoma.

INTRODUCTION Metastatic tumors account for 1.4-2.5% of thyroid malignancies. About 25-30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. PRESENTATION OF THE CASE A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles "suggestive" of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. DISCUSSION Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. CONCLUSION The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of "de novo" thyroid nodules in oncologic patients must be always considered and studied.

Luteinizing hormone (LH) and prolactin-releasing pituitary tumor: possible malignant transformation of the LH cell line.

A pituitary tumor was diagnosed in a prepubertal 13-yr-old girl, who had elevated plasma LH (58 mIU/ml) and PRL (93 ng/ml) levels; decreased GH, ACTH, and FSH secretion; and diabetes insipidus. After surgery, plasma LH and PRL declined, but not to normal levels. Conventional external radiotherapy to the pituitary was immediately followed by a decrease in LH to prepubertal values (0.7 mIU/ml), while PRL levels became normal only after a long course of bromocriptine therapy. The pituitary tumor was composed of two distinct cell types: small polygonal cells, which were PRL positive by immunohistochemistry, and clusters of pleomorphic large frequently mitotic polynucleated cells, which were LH positive, some of them also being positive for the alpha-subunit or beta LH but not for beta FSH. Four years after surgery and radiotherapy, the patient deteriorated neurologically. Computed tomographic scan showed widespread frontal and periventricular tumor, which had the histological features of a poorly differentiated carcinoma. No PRL, LH, or alpha- or beta-subunits were detectable on immunocytochemistry. While the PRL-positive cells of the pituitary tumor displayed the histological and clinical features of PRL adenomas, the morphological characteristics of LH cells and the sharp decline of plasma LH levels after radiotherapy were suggestive of malignant transformation. In this context, the later brain tumor could have been the result of subependymal spread of the pituitary tumor after it lost its hormone-secreting capacity.

Thyrotropin-releasing hormone-stimulated thyrotropin expression involves islet-brain-1/c-Jun N-terminal kinase interacting protein-1.

Islet-brain-1 (IB1)/c-Jun N-terminal kinase interacting protein 1 (JIP-1) is a scaffold protein that is expressed at high levels in neurons and the endocrine pancreas. IB1/JIP-1 interacts with the c-Jun N-terminal kinase and mediates the specific physiological stimuli (such as cytokines). However, the potential role of the protein in the pituitary has not been evaluated. Herein, we examined expression of the gene encoding IB1/JIP-1 and its translated product in the anterior pituitary gland and a pituitary cell line, GH3. We then examined the potential role of IB1/JIP-1 in controlling TSH-beta gene expression. Exposure of GH3 cells to TRH stimulated the expression of IB1/JIP-1 protein levels, mRNA, and transcription of the promoter. The increase of IB1/JIP-1 content by transient transfection study of a vector encoding IB1/JIP-1 or by the stimulation of TRH stimulates TSH-beta promoter activity. This effect is not found in the presence of a mutated nonfunctional (IB1S59N) IB1/JIP-1 protein. Together, these facts point to a central role of the IB1/JIP-1 protein in the control of TRH-mediated TSH-beta stimulation.

Biochemical markers of fatal hypothermia.

The aim of this study was to investigate the usefulness of postmortem biochemical investigations in the diagnosis of fatal hypothermia. 10 cases of fatal hypothermia and 30 control cases were selected. A series of biochemical parameters, such as glucose, acetone, 3-beta-hydroxybutyrate, isopropyl alcohol, free fatty acids, adrenaline, growth hormone, adrenocorticotropic hormone, thyroid-stimulating hormone, cortisol, calcium, magnesium, C-reactive protein, procalcitonin as well as markers of renal and cardiac functions were measured in blood, postmortem serum from femoral blood, urine, vitreous and pericardial fluid. The results suggested that deaths due to hypothermia, especially in free-ethanol cases, are characterized by increased ketone levels in blood and other biological fluids, increased adrenaline concentrations in urine, increased cortisol levels in postmortem serum from femoral blood and increased free cortisol values in urine. Increased or decreased levels of other biological parameters are either the result of terminal metabolic changes or the expression of preexisting diseases and may provide information to elucidate the death process on a case-by-case basis.

Mixed medullary-papillary carcinoma of the thyroid: report of a case and review of the literature.

BACKGROUND: Mixed medullary-follicular thyroid carcinoma denotes a rare and heterogeneous group of tumors displaying morphological and immunophenotypical features of both origins within the same lesion. METHOD: We report a case of a 41-year-old woman with a lump in the right side of the neck, increasing in pain and size over several weeks. Serum levels of calcitonine (1140 ng/L) and carcinoembryonic antigen (288 microg/L) were very high. Fine-needle aspiration cytology suggested a diagnosis of medullary thyroid carcinoma. Total thyroidectomy, along with bilateral functional neck and mediastinal lymph-node dissection, were performed. RESULTS: The histopathological examination yielded a diagnosis of medullary carcinoma in the right thyroid lobe, closely intermingled with a nonencapsulated classical papillary carcinoma. One ipsilateral lymph node showed micrometastasis of the medullary counterpart. CONCLUSION: When compared with other cases reported in literature, this particular presentation should be recognized, if required, morphologic and functional criteria are used. The treatment is mostly surgical, driven by the medullary component. The presence of micrometastasis in 1 ipsilateral cervical lymph-node underlines the importance of cervicomediastinal lymph-node dissection and careful searching for metastatic disease.

Altered growth in male peroxisome proliferator-activated receptor gamma (PPARgamma) heterozygous mice: involvement of PPARgamma in a negative feedback regulation of growth hormone action.

The peroxisome proliferator-activated receptor gamma (PPARgamma) plays a major role in fat tissue development and physiology. Mutations in the gene encoding this receptor have been associated to disorders in lipid metabolism. A thorough investigation of mice in which one PPARgamma allele has been mutated reveals that male PPARgamma heterozygous (PPARgamma +/-) mice exhibit a reduced body size associated with decreased body weight, reflecting lean mass reduction. This phenotype is reproduced when treating the mice with a PPARgamma- specific antagonist. Monosodium glutamate treatment, which induces weight gain and alters body growth in wild-type mice, further aggravates the growth defect of PPARgamma +/- mice. The levels of circulating GH and that of its downstream effector, IGF-I, are not altered in mutant mice. However, the IGF-I mRNA level is decreased in white adipose tissue (WAT) of PPARgamma +/- mice and is not changed by acute administration of recombinant human GH, suggesting an altered GH action in the mutant animals. Importantly, expression of the gene encoding the suppressor of cytokine signaling-2, which is an essential negative regulator of GH signaling, is strongly increased in the WAT of PPARgamma +/- mice. Although the relationship between the altered GH signaling in WAT and reduced body size remains unclear, our results suggest a novel role of PPARgamma in GH signaling, which might contribute to the metabolic disorder affecting insulin signaling in PPARgamma mutant mice.

A high prevalence of dual thyroid ectopy in congenital hypothyroidism: evidence for insufficient signaling gradients during embryonic thyroid migration or for the polyclonal nature of the thyroid gland?

BACKGROUND: Thyroid ectopy results from the failure of the thyroid precursor cells to migrate from the primordial pharynx to the anterior part of the neck. Most ectopic thyroids are revealed by congenital hypothyroidism and present as a single round mass at the base of the tongue, with no other thyroid tissue. However, some cases have dual ectopy, with part of the tissue having partially migrated. We hypothesized that this occurs more frequently than previously reported.¦METHODS: To determine the prevalence of dual ectopy, we reviewed the pertechnetate scintigraphies of 81 patients with congenital hypothyroidism from thyroid ectopy diagnosed between 2002 and 2011 at our institution.¦RESULTS: We report a series of seven cases (9%) of dual ectopy, representing an incidence ranging from 1:50,000 to 1:70,000.¦CONCLUSIONS: Almost one in 10 cases with congenital hypothyroidism due to thyroid ectopy has dual ectopy. This suggests that two populations of cells diverged at an early stage of development, which may arise from insufficient signaling gradients in surrounding tissues during early organogenesis or may indirectly support the polyclonal nature of the thyroid.

Thyroid carcinoma with papillary and squamous features: report of a case with histogenetic considerations.

We present a case of an 82-year-old female with a painless left latero-cervical swelling, which increased in size over the course of 6 months, compressing adjacent organs. The histopathological examination, following dissection of the left thyroid lobe and ipsilateral cervical lymph nodes, yielded two intermingled morphologically distinct histotypes that included conventional papillary thyroid carcinoma (PTC) and poorly differentiated squamous cell carcinoma (SCC) with cystic features. The clinical presentation, the immunophenotype, and the genotype, especially of the malignant squamous component with partial expression of TTF1, marked expression of p63 and mutation of BRAF, were consistent with the diagnosis of a papillary thyroid carcinoma with squamous component. The possibility of a squamous cell carcinoma of unknown origin metastasizing to a primary papillary thyroid carcinoma cannot be completely ruled out. This particular presentation of thyroid carcinoma carries a poor prognosis in 20% of cases, with high recurrence rates and distant metastasis.

Variability of radioiodine measurements in the thyroid.

Monte Carlo simulations were carried out to study the response of a thyroid monitor for measuring intake activities of (125)I and (131)I. The aim of the study was 3-fold: to cross-validate the Monte Carlo simulation programs, to study the response of the detector using different phantoms and to study the effects of anatomical variations. Simulations were performed using the Swiss reference phantom and several voxelised phantoms. Determining the position of the thyroid is crucial for an accurate determination of radiological risks. The detector response using the Swiss reference phantom was in fairly good agreement with the response obtained using adult voxelised phantoms for (131)I, but should be revised for a better calibration for (125)I and for any measurements taken on paediatric patients.

Epidermal growth factor and bovine growth hormone stimulate differentiation and myelination of brain cell aggregates in culture.

Bovine growth hormone (bGH) and epidermal growth factor (EGF) increased the activity of ornithine decarboxylase (ODC) in brain cell aggregates cultured in a serum-free chemically defined medium. ODC is considered as a marker of cell growth and differentiation. The effect of bGH and EGF on myelination was investigated by measuring two myelin markers, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and myelin basic protein (MBP). EGF treatment at days 2 and 5 caused a dose-dependent increase of both myelin markers at culture day 12. This increase could still be observed at culture day 19, indicating a prolonged action of EGF. The continual presence of bGH in the culture medium produced a large accumulation of MBP at day 19. This effect was dose-dependent and required the presence of triiodothyronine (T3). In contrast, the effect of bGH on CNP activity did not require the presence of T3. This is the first report showing a direct effect of bGH on CNS myelination in vitro and of EGF on both MBP accumulation and ODC activity.

Cricotracheal resection for laryngeal invasion by thyroid carcinoma: our experience.

Invasion of the laryngeal framework by thyroid carcinoma requires specific surgical techniques and carries a higher rate of complications that deserve to be highlighted. We reviewed our data from 1995 to 2012 and found six patients with laryngotracheal invasion by thyroid carcinoma. All underwent total thyroidectomy and single-stage cricotracheal resection, plus anterolateral neck dissection. Three had airway obstruction that necessitated prior endoscopic debulking. None of the patients needed a tracheotomy. There were four cases of papillary carcinoma, and two cases of undifferentiated carcinoma. One patient died of complications of the procedure (anastomotic dehiscence and tracheo-innominate artery fistula). Another died 2 months after the procedure from local recurrence and aspiration pneumonia. One case presented recurrence at 15 months, which was managed by re-excision and adjuvant radiotherapy; after 26 months of follow-up, he has no evidence of locoregional recurrence. The three other patients are alive without evidence of disease at 6, 18 and 41 months, respectively. Cricotracheal resection for subglottic invasion by thyroid carcinoma is an effective procedure, but carries significant risks of complications. This could be attributed to the devascularisation of the tracheal wall due to the simultaneous neck dissection, sacrifice of the strap muscles or of a patch of oesophageal muscle layer. We advocate a sternocleidomastoid flap to cover the anastomosis. Cricotracheal resection for subglottic invasion can be curative with good functional outcomes, even for the advanced stages of thyroid cancer. Endoscopic debulking of the airway prior to the procedure avoids tracheotomy.

Undetectable serum anti-Müllerian hormone levels and occurrence of ongoing pregnancy.

OBJECTIVE: To discuss, on the basis of the experience of two clinical cases and extensive literature review, the significance of extremely low levels of anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance, in infertile women. DESIGN: Case report. SETTING: University-based infertility clinic at a medical center in Switzerland. PATIENT(S): Two women, 29 and 41 years of age and with a 2- and 4-year history of secondary infertility, respectively. INTERVENTION(S): Clinical, radiological, and biological investigation of infertility, including repeated measurements of the serum AMH with serial ELISA assays. MAIN OUTCOME MEASURE(S): Levels of AMH and development of ongoing pregnancy. RESULT(S): Both women had a spontaneous ongoing pregnancy despite undetectable AMH levels. CONCLUSION(S): Although it is helpful for day-to-day management of infertile patients, the predictive value of AMH for the occurrence of a spontaneous ongoing pregnancy has limits.