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PubMed2000

Selective deficits of vibrotactile sensitivity in dyslexic readers.

Developmental dyslexia is a disability of literacy skill that has also been associated with sensory processing deficits, primarily for the detection of dynamic auditory and visual stimuli. Here we examined whether analogous deficits extend into the domain of somatosensory perception. Detection thresholds for each of three frequencies of vibration were obtained for 11 readers with a prior history of dyslexia and 14 similarly aged adult controls. The poor readers were significantly less sensitive to vibration at 3 Hz (P<0. 01) but not at either 30 or 100 Hz. Detection of each of these three vibration rates is mediated primarily by a separate somatosensory fiber tract; deficits selective to 3 Hz therefore suggest an impairment within the slow-adapting I (SAI) fiber system beginning with Merkel-cell mechanoreceptors in the glabrous skin. Such evidence is compatible with the hypothesis of a generalized, multisensory deficit of temporal processing functions in dyslexia.

Adolescent↗
PubMed1991

Paragangliomas of the head and neck. Immunohistochemical analysis of 16 cases in comparison with neuro-endocrine carcinomas.

Sixteen cases of paragangliomas of the head and neck including 8 of the vagal body, 3 of the carotid body, 2 jugulotympanic, 2 vagal or jugulotympanic and 1 of the larynx were analysed. Clinically, 13 tumors were benign, 2 showed local aggressivity and 1 showed metastases. All tumors were tested with antisera directed against neuron-specific enolase (NSE), chromogranin A (CGA), S-100 protein, neurofilaments (NF), glial fibrillary acid protein (GFAP) and cytokeratin (CK). Immunohistochemical results were compared with those of 5 cases of neuroendocrine carcinoma (NC) (1 of the oral vestibule, 1 of the larynx, 1 Merkel-cell tumor of the skin and 2 medullary thyroid carcinomas). Immunoreactivity for NSE and/or CGA was always positive in all paragangliomas and NC. S-100 protein was positive in sustenticular cells in all cases of paragangliomas and focally in two cases of NC. NF and GFAP were focally positive in 3 and 2 paragangliomas respectively; and in 1 NC. CK was constantly negative in all cases of paraganglioma and constantly positive in all cases of NC. Antibody anti-CK is the single most useful immunomarker for differential diagnosis between paraganglioma, frequently benign neoplasms and NC commonly aggressive in the head and neck. These findings are consistent with the current concepts of the neuroendocrine system.

Adolescent↗
PubMed2002

Nasopharyngeal rhabdomyosarcoma in a patient with hypohidrotic ectodermal dysplasia syndrome.

Hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) is characterized by partial or complete absence of sweat glands, hypotrichosis, hypodontia, prominent frontal ridges and chin, saddle nose, sunken cheeks, thick, everted lips, large ears and sparse hair. While association of other ectodermal dysplasia syndromes with tumors such a non-Hodgkin's lymphoma, hamartoma, keratoakanthoma, Merkel-cell cancer, squamous-cell carcinoma, syringofibroadenomatosis has been reported, association of hypohidrotic ectodermal dysplasia and a tumor has not been reported. In a five-year-old male patient admitted with nasal obstruction and nasal mass complaints, we have reported firstly an association of hypohidrotic ectodermal dysplasia and nasopharyngeal rhabdomyosarcoma.

Biopsy↗
PubMed1998

Radiotherapy in the treatment of dermatologic malignancies.

Although advances in surgical techniques, particularly micrographic surgery, have considerably expanded its role in the management of dermatologic malignancies, radiotherapy remains of considerable value. Its use should be considered in particular for the appropriate solid tumors in older patients, for metastatic disease, and for the more radioresponsive tumors including Merkel cell carcinoma, Kaposi's sarcoma, and the cutaneous lymphomas.

Clinical Trials as Topic↗
PubMed1999

Primary orbital rhabdomyosarcoma in an adult.

PURPOSE. Rhabdomyosarcoma is the most common primary orbital malignant tumor in children. Though rare above the age of twenty, the authors present a case of primary orbital rhabdomyosarcoma in an adult and review the literature. DESIGN. Clinico-pathologic case report. METHODS. A 34-year-old man presented with a recurrent orbital tumor four years after initial excision. This tumor was initially misdiagnosed elsewhere as Merkel cell tumor on the basis of spurious immunohistochemical studies. Excision biopsy of the recurrent orbital mass was performed. MAIN OUTCOME MEASURES. MRI of the orbit and brain was done as well as histopathologic examination and immunohistochemistry of the excised mass. RESULTS. Histopathologic study of the excised orbital tumor revealed rhabdomyosarcoma. CONCLUSION. Careful microscopic evaluation and immunohistochemical stains are important in confirming the diagnosis of atypical cases of orbital tumors.

Journal Article↗
PubMed2000

A case of keratin-positive acute myeloid leukemia: a possible role for cytokeratin 19 as a specific epithelial marker.

A patient with relapsed acute myelomonocytic leukemia (AML, FAB M4) developed skin infiltration by leukemic blasts. On immunochemistry, the blasts showed "bot" positive cytoplasmic staining for cytokeratins AE1/AE3 and CAM 5.2, resembling the pattern seen in Merkel cell carcinoma of skin. However, the blasts were positive for myeloid markers and negative for cytokeratin 19 and chromogranin. Aberrant immunochemical staining can lead to misdiagnosis unless a panel of antibodies of known specificity is used in tumor diagnosis, and the clinical context is taken into account. The possible role of cytokeratin 19 as a more specific marker for epithelia than keratin cocktails is discussed.

Acute Disease↗
PubMed2006

Skin diseases in consequence of endocrine alterations.

The skin is a target organ of several hormones. Specific diseases appear in consequence of hypo- or hypersecretion of endocrine organs, particularly in the elderly patient. There, knowledge of skin alterations is important not only for dermatologists, but also for endocrinologists and other physicians, because a clinical diagnosis of the underlying disease is often possible. In this review, a number of representative skin diseases having an endocrinological basis are described. These include acanthosis nigricans, diseases due to alterations of androgen metabolism, carcinoid syndrome, diseases due to alterations of corticosteroid metabolism, diseases in association with diabetes mellitus, diseases due to alterations of estrogen metabolism, genetic syndromes including dermatological and endocrine symptoms, the glucagonoma syndrome, diseases due to dysfunctions of growth hormone secretion, diseases in association with Merkel cells of the skin, diseases due to dysfunctions of the thyroid gland, diseases to alteration of vitamin D metabolism, and vitiligo and disorders of pigmentation.

Androgens↗
PubMed1982

Neuroendocrine carcinoma of the skin in a young adult.

Neuroendocrine (Merkel cell) carcinoma of the skin is usually a tumor found in elderly individuals. Microscopically, the tumor is a small cell carcinoma that involves primarily the dermis. The dominant ultrastructural features are the presence of short cell processes containing small, dense-core, membrane-bound granules. The tumor is often locally aggressive, has the potential to metastasize to lymph nodes, and eventually causes death. The authors report a case of such a neoplasm that affected a 24-year-old man with congenital ectodermal dysplasia. It was associated with a concurrent basal cell carcinoma.

Adenocarcinoma↗
PubMed1987

The expression of subunits of human chorionic gonadotropin (hCG) by nontrophoblastic, nonendocrine, and endocrine tumors.

The value of the subunits of human chorionic gonadotropin (hCG) as tumor markers is controversial. The production of hCG-alpha and hCG-beta by 214 nontrophoblastic exocrine and by 416 endocrine tumors was analyzed by using immunocytochemical technics. hCG-alpha immunoreactivity was found in 131 of 416 endocrine and in 8 of 214 nonendocrine tumors. hCG-beta could not be visualized specifically with the use of two polyclonal antisera and one monoclonal antibody. The authors conclude that (1) hCG-alpha is neither a tissue nor a tumor-specific marker; (2) hCG-alpha is produced by a variable proportion (21-55%) of endocrine tumors arising in various organs but not by ileal carcinoids, paragangliomas, pheochromocytomas, nor Merkel cell tumors; (3) hCG-alpha is a marker of malignancy only in pancreatic endocrine tumors; and (4) hCG-beta is rarely, if ever, produced by tumors.

Carcinoid Tumor↗
PubMed1995

A phase II trial of dacarbazine, fluorouracil and epirubicin in patients with neuroendocrine tumours. A study by the Italian Trials in Medical Oncology (I.T.M.O.) Group.

BACKGROUND: Previous experiences in the treatment of neuroendocrine tumours have demonstrated some activity of single agents such as adriamycin, fluorouracil (FU), streptozotocin and dacarbazine (DTIC). Opinions concerning the usefulness of polychemotherapy in carcinoid tumours are discordant, whereas better results have been achieved in other endocrine pancreatic neoplasms. Based on this background, we used multidrug chemotherapy with DTIC, FU and epirubicin in the treatment of different neuroendocrine tumours. METHODS: The study involved 38 pts with progressive and measurable disease. The treatment schedule was FU 250 mg/m2 i.v., epirubicin 25 mg/m2 i.v., and DTIC 200 mg/m2 i.v. on days 1, 2 and 3 every 3 weeks. RESULTS: The responses achieved by histologic types were carcinoids 2/20, medullary thyroid carcinoma 1/7, neuroendocrine tumours 1/6; and Merkel cell carcinoma 3/5. The median duration of response was 5 months (range 2-11). Stable disease was observed in 13 cases (34%). Out of the 18 cases in progression, 17 had not responded to previous medical treatment. No symptom control was observed in 4 pts with carcinoid syndrome. Treatment toxicity was moderate and included nausea and vomiting, alopecia, leukopenia and mucositis. CONCLUSIONS: Our results document the moderate efficacy of the regimen in all of the histologic types. The major difference in comparison with previous studies was the lower response rate observed in patients with neuroendocrine tumours.

Adult↗
PubMed2002

The onychomatricoma: additional histologic criteria and immunohistochemical study.

Onychomatricoma (OM) is a tumor of the nail matrix typified histologically by multiple distal fibroepithelial projections and a thick keratogenous zone forming multiple V-shaped invaginations at the level of epithelial ridges, with the formation of a thick nail plate. In its proximal portion, the thickness of the nail looks like a spur originating from the ventral part of the nail plate. In its distal part, beyond the lunula, the nail plate is globally thickened and filled with cavities containing serous fluid. Often, however, the pathologist is not provided with the nail plate. The diagnosis then rests on the presence of a fibroepithelial tumor. In this article the histologic criteria of OM without nail plate are refined and OM is characterized immunohistochemically using three tumors fixed in liquid nitrogen and examined separately from the nail plate. On longitudinal section OM without nail plate appears as a unique pedunculated fibroepithelial tumor i.e., the multiple distal epithelial digitations arranged along a transversal plane are not seen. The feature is reminiscent of fibrokeratoma. When OM is visualized in longitudinal section, 3 main criteria differentiate OM from fibrokeratoma: the presence of epithelial-lined invaginations around optical cavities, a stroma organized in 2 layers, and the absence of horny corn. Patterns of expression of cytokeratins and integrins in OM are identical to that observed in the normal nail matrix. Involucrin finds expression from the basal layer through to the top of the epithelium, where it is more marked and where transglutaminase 1 is restricted. Merkel cells detected by CK 20 are increased in number and sometimes disposed in clusters. The fibrous component of OM is composed of 2 layers: a superficial stroma made of numerous fines fibrils of collagen IV intermingled with collagen I, and deep stroma made principally of collagen I. Antibody AE13, specific to trichocytic keratins Ha 1-4, represent a good potential marker of OM. Its V-shaped expression in epithelium ridges offers early identification of the keratogenous zone of OM, on tumors separated from their nail plates and limited to their fibroepithelial components.

Biomarkers, Tumor↗
PubMed2004

Value of FDG PET imaging in the management of patients with thyroid, neuroendocrine, and neural crest tumors.

OBJECTIVES: The purpose of this study was to evaluate the value and impact on management of FDG PET imaging in patients with biopsy-proved neuroendocrine and neural crest tumors, as well as thyroid carcinoma of various types. MATERIALS AND METHODS: This is a retrospective review of imaging and clinical data of 60 consecutive patients presenting for evaluation of suspected recurrence who underwent FDG PET imaging between August 1993 and February 2002. All patients were referred for PET because of equivocal findings on conventional evaluation (most often increasing tumor markers and negative conventional workup) or for restaging. The final diagnosis was established with pathology (n = 19) or at least 6 months of follow-up (n = 41). The FDG images were acquired 1 hour after the intravenous administration of 10 mCi FDG with 1 of 2 dedicated PET tomographs (Siemens ECAT 933, CTI, Knoxville, TN; and GE Advance, General Electric Medical Systems, Milwaukee, WI). RESULTS: Thirty-four patients had recurrent disease and 26 had no evidence of recurrence. FDG PET imaging revealed at least as many focal abnormalities as concurrent CT, magnetic resonance, or other nuclear imaging modalities in 46 of 60 patients (77%). There were 17 patients (28%) in whom FDG PET found abnormalities not seen with other modalities. In the small group (n = 18) of cases of carcinoid, pheochromocytoma, Merkel cell tumor, and neuroblastoma, all cases were true positive (T+) or true negative (T-). In the group of 42 cases of thyroid carcinoma, the sensitivity was 67%. There were 16 T+, 18 T-, and 8 false-negative (F-) cases. Six F- cases presented with increasing thyroglobulin levels and negative whole-body I-131 scans. Four of these 6 F- cases were proved by surgery, 1 by a positive post I-131 therapy scan, and 1 by normalization of thyroglobulin levels after I-131 therapy. Two of the 8 F- PET cases had a positive I-131 scan. FDG PET imaging had an impact on the management of 13 of 60 of these patients (22%) by demonstrating extensive metastases and cancelling surgery (n = 2), and by detecting recurrence and guiding surgery (n = 5) or radiation therapy (n = 6). CONCLUSIONS: FDG PET is helpful in the evaluation of thyroid, neuroendocrine, and neural crest tumors. Although the sensitivity was only 76%, there were no false-positive findings, and FDG PET findings changed the management of 22% of the patients.

Fluorodeoxyglucose F18↗
PubMed1991

Evidence for gamma-melanocyte stimulating hormone containing nerves and neutrophilic granulocytes in the human skin by indirect immunofluorescence.

gamma-melanocyte stimulating hormone (gamma-MSH)-like immunoreactivity has been found by indirect immunofluorescence in nerve fibers and terminals as well as in neutrophilic granulocytes of normal human skin. A preferential localization to sensory nerves was seen; abundant nerve fibers displaying gamma-MSH immunoreactivity were observed as free nerve endings in the basal layer of the epidermis and in the upper dermis, close to the Merkel cells, in Meissner's corpuscles, around the external root sheath of the lower part of the hair follicles, and in nerve bundles of the deeper parts of the dermis. Very few fibers were seen to be associated with sweat glands and most blood vessels, although arterioles were densely innervated. Thus, gamma-MSH should be considered for possible role as a sensory or axon-reflex chemical messenger. Furthermore, the presence of gamma-MSH in neutrophilic granulocytes raises the possibility that gamma-MSH may play a role in the genesis of post-inflammatory hyperpigmentation, nevi, and melanomas.

Adult↗
PubMed1990

Binocular dissecting microscopic studies on the density of toruli tactile in the La Mancha goat.

The Merkel cells and associated nervous terminal plates have been called toruli tactiles (TT). These structures can be ubiquitously seen on the shaved hairy skin after staining with a methylene blue solution. Four La Mancha goats of both sexes were examined for the density of TT. TT were visually located under a binocular dissecting microscopic (14x) and then the number of TT in the field was directly counted. The density of TT in different corporal areas of the body surface was estimated from the mean of several two-cm square samples of skin. The results obtained are as follows: The mean number per two-cm square on the whole body surface ranged from 10.06-11.36 in the male specimen and from 12.98-14.32 in the female specimen. The density of TT was rather high in the temporal and buccal areas, on the neck, chin and cranial breast, and on the lateral surface of the arm, thigh and leg. Density was moderate in the fronto-parieto-occipital area (female), on the loin and buttocks, in the upper costal, lower caudo-costal, xiphoid-umbilical and umbilical-pubic areas, and on the lateral surface of the forearm. TT were absent or very few in number on the nose and chin, the scrotum, caudal-pubic area of males, the udder, the vulva, and the digitorum manus et pedis.

Animals↗
PubMed1981

Rudimentary polydactyly (cutaneous neuroma) case report with ultrastructural study.

A case of rudimentary polydactyly (cutaneous neuroma) on the ulnar aspect of the left fifth finger of a 38-year-old male was examined and the skin was studied by light and electron microscopy. In addition to a proliferation of nerve fibers and encapsulated corpuscles, normal Merkel cells were often present in the basal portion of the epidermis. It is suggested that proliferation of various neural components is the essential feature of the affected skin.

Adult↗
PubMed1990

Acute effects of neomycin on slowly adapting type I and type II cutaneous mechanoreceptors in the anaesthetized cat and rat.

1. Slowly adapting type I (SAI) and type II (SAII) mechanoreceptors in the skin were studied in anaesthetized cats and rats employing mechanical stimuli every 30 s. Individual stimuli rose within 200 ms to a plateau force which was kept constant through a feedback control unit for 2000 ms. 2. In cats, close arterial infusion of neomycin (2.5 mg/min) as sulphate was given through a side branch into the femoral blood stream for 5, 10 or 20 min at a rate of 0.025 ml/min. At other times saline was infused at the same rate. 3. After 20 min of neomycin infusion (total 50 mg) nervous discharge of cat SAI receptors was suppressed to about 30% of the control responses before neomycin infusion. Nervous responses were reduced more profoundly during the plateau phase of stimulation than during the dynamic phase. The interspike interval histogram was severely distorted. 4. In contrast, cat SAII receptors maintained about 70% of their control response after 20 min of neomycin infusion. The interspike interval histogram showed an orderly shift towards longer intervals maintaining its normal shape. 5. In rats, intradermal microinfusion of neomycin (30 micrograms/min) through a glass micropipette into the immediate vicinity of the receptor under investigation resulted in severe transient suppression of SAI receptor responses to about 10% of the control level. Receptor responses recovered almost completely about 1 h after the end of neomycin application. 6. It is concluded that the observed differences between the two types of slowly adapting mechanoreceptors are consistent with the hypothesis that the SAI receptor functions as a secondary sensory receptor, with a synaptic link between the Merkel cell and the primary afferent neurone.

Animals↗
PubMed2006

Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody.

BACKGROUND: Friend leukaemia integration-1 (FLI-1) antibody is a useful marker for Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and vascular tumours. However, it is also expressed in subsets of lymphoblastic lymphoma, Merkel cell carcinoma (MCC) and desmoplastic small round cell tumour (DSRCT). AIM: To determine expression of FLI-1 in various benign and malignant neoplasms, by immunohistochemical analysis on 4323 tumours using multiple tumour microarrays, as well as on whole sections. RESULTS: FLI-1 was expressed in 46/62 EWS/PNETs, 2/3 olfactory neuroblastomas, 7/102 small cell carcinomas of the lung, 10/34 MCCs, 1/14 rhabdomyosarcoma, 19/132 non-Hodgkin's lymphomas, 2/3 DSRCTs, and in 53/74 benign and malignant vascular tumours. In addition, 27/508 squamous cell carcinomas, 19/837 adenocarcinomas, 10/400 urothelial bladder cancers, 1/40 basal cell carcinomas, 3/29 liposarcomas, 1/40 glioblastoma multiforme and 9/29 medullar carcinomas of the breast expressed FLI-1. The sensitivity and specificity of FLI-1 to distinguish EWS/PNET from all types of malignancies were 74.2% and 96.0%, respectively. Finally, the sensitivity and specificity of FLI-1 to distinguish EWS/PNET from other small round cell tumours (SRCTs) were 74.2% and 91.6%, respectively. CONCLUSION: This study was the first to show that FLI-1 can be seen in a variety of solid tumours, some of which had never been explored before. This finding should be kept in mind, especially when using FLI-1 as a marker for finding the primary origin of poorly differentiated metastatic tumour. Finally, despite the expression of FLI-1 in numerous malignancies, it is still considered to be highly sensitive and specific in distinguishing EWS/PNET from other tumour types in general and from other SRCTs in particular.

Biomarkers, Tumor↗
PubMed1998

Neurotrophin-3 is increased in skin in human diabetic neuropathy.

Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been shown to be necessary for the development of muscle spindle and Merkel cell afferent nerve fibres in animal models. The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres terminate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of endogenous NT-3 in skin of 24 patients at different stages of diabetic polyneuropathy have been investigated. NT-3 concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32 (1.18) pg/mg v control skin 1.28 (0.05) (mean (SEM)); p<0.004, Mann-Whitney U test), particularly in the later stages. The optical density of NT-3-immunostaining was also significantly greater in the epidermis in diabetic patients (diabetic epidermis 0.30 (0.06) v controls 0.24 (0.01); p<0.02). No correlation was found between individual quantitative sensory tests and the increase of NT-3 concentration. The increase of NT-3 seems to reflect the degree of skin denervation in diabetic neuropathy, and may represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.

Adult↗