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[Changes in the ultrastructure of Merkel's nerve endings of the sinus hair of rats after denervation].

Merkel nerve endings of sinus hairs in the upper lip of the rat were observed after having cut the nervus infraorbitalis. The nerve terminal of the Merkel nerve ending has already been degenerated 24 hours after denervation and was phagocytised by neighbouring keratinocytes. The Merkel cells did not change in structure after having lost their nerve terminal even within 169 days after nerve crush. Their position in the stratum basale of the sinus hairs remained constant; the number, size and position of the osmiophilic granules in the cytoplasm of the Merkel cells did not change. These results may show, that Merkel cells are not modified keratinocytes. The possibilities of their origin are discussed.

Animals↗

Atypical carcinoid (neuroendocrine carcinoma) of the gingiva: counterpart of a laryngeal tumor.

Intraoral localization of neuroendocrine carcinoma, usually called Merkel cell carcinoma, is extremely rare. A case of neuroendocrine carcinoma that was a counterpart of laryngeal neuroendocrine carcinoma but was not a Merkel cell carcinoma, occurring at the mandibular gingiva in a 69-year-old Japanese man, is described. The tumor formed a cauliflower-like mass, measuring 20 x 20 mm, with a small area of necrosis. A computed tomography image showed metastasis in the right submandibular lymph node. Histopathologically, the tumor was composed of immature, small round cells that formed anastomosing trabecular nests. Few mitotic and no necrotic features were observed in the nests. Immunohistochemical studies showed positive staining for chromogranin, synaptophysin and neuron-specific enolase in the tumor nests. We diagnosed it as an atypical carcinoid (neuroendocrine carcinoma), a counterpart to the same type of tumor occurring in the larynx. The present case is an extremely rare case of neuroendocrine carcinoma without the feature of Merkel cell carcinoma arising from the gingiva.

Aged↗

Neuroendocrine tumours metastatic to the uvea: diagnosis by fine needle aspiration biopsy.

BACKGROUND: Uveal metastasis from a neuroendocrine tumour is rare and can simulate other primary or metastatic uveal tumours, both clinically and cytomorphologically. We describe four cases of uveal metastasis from a neuroendocrine tumour diagnosed by fine needle aspiration biopsy (FNAB). METHODS: Four patients were referred for evaluation of a recently detected fundus mass. Two patients had a history of malignant, non-ocular, neuroendocrine neoplasms (Merkel cell carcinoma and lung carcinoid in one patient each). The third patient had a mediastinal mass that had been biopsied inconclusively, while the last patient reported a persistent cough. RESULTS: Ophthalmic examination revealed an amelanotic ciliochoroidal mass in 2 cases and a lightly melanotic and a pale orange choroidal mass in 1 case each. Partial, non-rhegmatogenous, retinal detachment was present in 3 patients. Ocular ultrasonography revealed moderate to high internal reflectivity of the mass in 3 cases and low internal reflectivity in the 4th. Our differential diagnosis in all cases was metastatic carcinoma versus primary uveal melanoma. FNAB of the intraocular mass was performed in all patients to establish a pathologic diagnosis and guide subsequent management. Cytomorphology and immunohistochemical profiles of the aspirates were consistent with metastatic neuroendocrine neoplasms in all patients. Our final diagnosis was metastatic lung carcinoid in 2 patients and metastatic Merkel cell carcinoma and small cell lung carcinoma in 1 patient each. Immediately after FNAB, the intraocular tumour was treated by plaque radiotherapy (3 patients) or fractionated external beam radiotherapy (1 patient). All tumours treated regressed satisfactorily. Two patients expired due to widespread lung carcinoid 11 and 12 months after our initial evaluation respectively. The other two patients are still alive after 38 and 64 months respectively. CONCLUSIONS: Neuroendocrine tumours are a heterogeneous group of neoplasms whose diagnosis ultimately depends on the identification of specific cell markers (e.g., neuron-specific enolase, chromogranin, synaptophysin), hormones and neurotransmitters (e.g., gastrin, serotonin, adrenocorticotrophic hormone [ACTH]). FNAB with immunohistochemical stains for neuroendocrine markers can establish a pathologic diagnosis in cases of uveal metastasis from a neuroendocrine tumour. To our knowledge, our patient with Merkel cell carcinoma is the first pathologically proven case of uveal metastasis from this primary malignancy.

Adult↗

Monoclonal islet antibody HISL-19 as a tool in the diagnosis of neuroendocrine carcinomas of the skin.

The monoclonal islet cell antibody HISL-19 generated after immunization of BALB/c mice with human pancreatic islet cell preparations, demonstrated specific immunoreactivity for neuroendocrine (Merkel) cells of the skin as shown by successive and simultaneous localization of neuron-specific enolase and the antigen detected by mab HISL-19 in the same cells of the bovine epidermis. Following these observations, we tested nine neuroendocrine carcinomas of the skin that were believed to be of Merkel cell origin for their immunoreactivity with mab HISL-19 using an indirect immunoperoxidase technique on formalin-fixed and paraplast-embedded tissues. In contrast to malignant lymphomas, poorly differentiated squamous cell carcinomas, and malignant melanomas, all nine neuroendocrine carcinomas reacted strongly with mab HISL-19, indicating its potential as a useful immunohistochemical probe for the distinction of neuroendocrine carcinomas of the skin from other cutaneous neoplasms with similar histological appearance.

Antibodies, Monoclonal↗

[Merkel's cell cancer].

The authors present histological and immunohistochemical characteristics of a rare skin tumor--merkelioma.

Carcinoma, Merkel Cell↗

Degeneration and regeneration of peripheral nerve in the rat trigeminal system. II. Response to nerve lesions.

The course of vibrissa sensory receptor denervation and subsequent reinnervation was studied following transection or crush of the rat infraorbital nerve. Eighteen hours after nerve lesion, the large-diameter myelinated nerves supplying the lanceolate receptors of the intermediary zone and the Merkel cells of the stratum basale contained areas of focal axoplasmic abnormalities, and some of the nerve terminals exhibited vacuolization, mitochondrial swelling, and disruption of the neurofilament pattern. The Merkel cells and lanceolate receptors of the intermediary zone were completely deafferented by 24 hours after the nerve injuries. The Ruffini complex, free nerve endings and lanceolate receptors of the inner conical body, as well as the free nerve endings and lanceolate receptors of the connective tissue below the Ringwulst, were completely normal 24 hours after crush or transection of the nerve. These receptors underwent progressive degeneration from days 2 through 6 and the vibrissa was totally denervated by day 7. Regenerating axons were first seen entering the vibrissae 2 weeks after the crush lesion and 1 month following nerve transection. Except for a slight decrease in the percentage of Merkel cells innervated, vibrissae from post-crush animals were virtually indistinguishable from normal by 3 months. In contrast, vibrissae from rats subjected to the transection lesion exhibited evidence of misdirected axons and abnormally reinnervated receptors throughout the course of regeneration. Axons entering the hairs with the main vibrissal nerve were observed contributing to the innervation of the inner conical body, an area normally supplied exclusively by the conus nerve. Many of the lanceolate receptors contained multiple unmyelinated axons, and the usually highly ordered circular innervation of the inner conical body was markedly abnormal. It is suggested that these results may help explain the faulty sensory localization and abnormal sensations reported by patients suffering a peripheral nerve injury.

Animals↗

Endogenous neurotrophin-3 supports the survival of a subpopulation of sensory neurons in neonatal rat.

Neurotrophin-3 promotes the differentiation and supports the survival of neuroblasts derived from the neural crest in early development. Neurotrophin-3 also plays an important role in the differentiation and survival of a subpopulation of large sensory neurons after their axons arrive at their targets. Proprioception and mechanoception are lost after gene deletion of neurotrophin-3 or its high-affinity receptor, TrkC. However, the function of neurotrophin-3 during late development and in mature animals is not clear. We have used an antiserum, specific for neurotrophin-3, to neutralize endogenous neurotrophin-3 in postnatal rats to determine its role in late sensory neuron development. Administration of the antiserum for a period of two weeks, but not one week, resulted in a 20% reduction in the number of primary sensory neurons in the dorsal root ganglia and a 19% reduction in the number of myelinated axons in the saphenous nerve. The size distribution histogram also indicated that a subpopulation of large neurons was lost by the neurotrophin-3 antiserum treatment. This neuronal loss was accompanied by reduced cell soma sizes and weights of the ganglia. Immunoreactivities for calbindin and calretinin were reduced in the trigeminal and dorsal root ganglia and nerve fibres surrounding whisker hair follicles. The number of Merkel cells in touch domes labelled with quinacrine and the number of parvalbumin-immunoreactive neurons in the dorsal root ganglia were significantly reduced by the antibody treatment. In contrast, the number of muscle spindles in the gastrocnemius muscle is not reduced by the neurotrophin-3 antiserum. Together, these results indicate that a subpopulation of primary sensory neurons in the neonatal rat requires neurotrophin-3 for their survival and expression of calcium binding proteins. In addition, Merkel cells in touch domes also require neurotrophin-3 for their survival. Thus, endogenous neurotrophin-3 in neonatal rats is critical for the survival and function of a subpopulation of primary sensory neurons and Merkel cells.

Animals↗

The sensory innervation of the nasal glabrous skin in the short-nosed bandicoot (Isoodon macrourus) and the opossum (Didelphis virginiana).

The glabrous skin at the anterior end of the snout of the short-nosed bandicoot and the American opossum was investigated by electron microscopy. In both species of animals, this region was lined by skin with broad epidermal pegs, innervated by three types of intraepidermal nerves. These were intraepidermal nerves which penetrated the epidermis up to the level of the stratum spinosum or the stratum granulosum, intraepidermal nerves in the basal layer of the epidermis partially surrounded by Schwann cell lamellae and intraepidermal nerves associated with Merkel cells. There were two types of free nerve endings in the dermis. The first type was derived from the deep dermal nerve plexus and had the typical characteristics of nerve terminals such as mitochondria, vesicles, irregularly arranged neurotubules and neurofilaments, and glycogen granules. There was a one-to-one relationship between Schwann cell lamellae and these nerve terminals. The second type of nerve ending was brush-like and the ends of the 'brushes' were enclosed in groups by a single Schwann cell lamella. Encapsulated nerve endings in the two types of animals differed in their structure. In the bandicoot, they consisted of a nerve terminal which had one to three branches. These terminals were rounded in profile and were surrounded by Schwann cell lamellae in a stack-like arrangement. An unusual finding was that the terminal sometimes left the corpuscle and made contact with the basal lamina of the epidermis before passing into its basal layer. These corpuscles did not have a perineural capsule. In the opossum, however, simple corpuscles with inner cores completely surrounded by a perineural capsule were seen. The glabrous skin of both types of animals was innervated with Eimer's organs consisting of intraepidermal nerves, Merkel cell nerve endings and encapsulated end-organs, as well as two types of dermal nerve endings.

Animals↗

A comparative electron microscopic analysis of mechanoreceptors in the hard palate of the mouse (Mus musculus; Rodentia) and the musk shrew (Suncus murinus; Insectivora).

These mechanoreceptors were studied with particular regard to their type and the distribution. In both species they were concentrated in the crests of transverse palatine rugae. In the mouse, Meissner corpuscles, glomerular corpuscles, and Merkel cell nerve endings were seen in every palatine ruga, though the first antemolar ruga also contained simple and atypical lamellated corpuscles. In contrast, the palatine rugae of the musk shrew contained only simple corpuscles and Merkel cell nerve endings. Meissner corpuscles in the mouse palate were frequently aggregated to form a palisade-like, huge corpuscle. Anterior intermolar rugae especially contained a larger number of such huge corpuscles. Simple corpuscles in the palate of the musk shrew were more densely distributed in the anterior than in the posterior rugae. In both species Merkel cell nerve endings were localized within epithelial downgrowths of the rugal crest. These downgrowths tended to increase in number anteroposteriorly.

Animals↗

Immunoexpression of villin in neuroendocrine tumors and its diagnostic implications.

BACKGROUND: Villin, a 95-kd cytoskeletal protein associated with axial microfilament bundles of brush border microvilli, is mostly restricted to intestinal glandular tumors. Villin immunoexpression was recently observed in a small number of carcinoids of the intestinal tract and lung, but its significance in a broad category of neuroendocrine tumors has not been evaluated. DESIGN: A total of 114 neuroendocrine tumors of different origins were tested for villin expression. They included gastrointestinal carcinoids (n = 30), lung carcinoids (n = 15), small cell carcinomas of the lung (n = 24), small cell carcinomas of other sites (n = 15), islet cell tumors (n = 8), Merkel cell carcinomas (n = 6), paragangliomas (n = 6), and others (n = 10). Nine round cell sarcomas were tested as well. RESULTS: Villin immunoreactivity was present in 85% of gastrointestinal carcinoids and small cell carcinomas, but was found in only 40% of lung carcinoids. Other tumors tested were virtually negative for villin. In general, while cytoplasmic reactivity was most common, a characteristic apical membranous pattern simulating brush border was seen in 76% of the gastrointestinal carcinoids and in 50% of the lung carcinoids. CONCLUSIONS: We found that villin was predominantly restricted to gastrointestinal neuroendocrine tumors (excluding islet cell tumors), although a small number of bronchial carcinoids may be positive as well. These results suggest a role for villin in the differential diagnosis of neuroendocrine tumors.

Adenoma, Islet Cell↗

Trabecular or Merkel's cell carcinoma.

Two cases of trabecular cell carcinoma of the skin are presented. The clinical presentation and behavior, and the histologic findings, of the tumor are described. Surgical excision of the primary lesion with regional lymph node dissection, if indicated, is the treatment of choice. Distant metastasis is treated by local irradiation.

Aged↗

Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.

The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the central nervous system, the channel is expressed in neurons of the circumventricular organs, neurosensory cells responsive to systemic osmotic pressure. The channel also occurs in other neurosensory cells, including inner-ear hair cells, sensory neurons, and Merkel cells.

Amino Acid Sequence↗

New details of the ultrastructure (TEM, SEM) of taste buds in fishes.

Quantitative distribution of the taste buds (TB) in different parts of the body and the fine structure of the TB components are described in Cobitis taenia L. No evidence of synaptic contacts between any cellular components in the TB has been found. The afferent synapses have been recognized only at the gustatory cells and at the basal cell. The microvillar processes on the upper side of the basal cell are demonstrated for the first time in fishes. These processes resemble those at the basal cells in the TB of tetrapods and at the Merkel cells, scattered in the epidermis of all vertebrates. Since the basal cells of fish TB correspond also to other criteria of the Merkel cells, its mechanoreceptive function in the TB is discussed. A relatively large number of atypical gustatory cells has been found in the studied material. As the examined specimens of C. taenia lived for a long time in aquarium conditions, it may be supposed that these gustatory cells are damaged by pollutants introduced mainly with food such as Tubifex. For purposes of comparison, a related species, Misgurnus fossilis L., was used in the study.

Animals↗

The ultrastructure of taste and touch receptors of the frog's taste organ.

The taste buds from fungiform papillae and the hard palate of frogs were investigated with the scanning and transmission electron microscopes. An immature pre-taste cell and a mature taste cell can be differentiated. Only the mature taste cell exhibits synaptic contact with the afferent taste fibre. Glandular and satellite supporting cells envelop the thin apical processes of the sensory cells. At the base of the taste disc up to 10 Merkel cells form a complex with nerve endings. There are two types of myelinated fibres, large and small. The small fibre innervates the taste cells, the thicker nerve fibre the Merkel cells. The occurrence of two types of receptors explains physiological results.

Animals↗

A clinicopathologic review of lethal nonmelanoma skin cancers in Western Australia.

BACKGROUND: Nonmelanoma skin cancer (NMSC) comprises a heterogeneous group of cancers. A comprehensive review of NMSC mortality has not been performed previously in this region. OBJECTIVE: We sought to document the population affected by lethal NMSC, the types of tumors involved, and their histopathologic features. METHODS: Death certificates of all patients who died from NMSC were examined. Histology of the primary lesion was reviewed in cases when the primary lesion was identified and sections were available. RESULTS: A total of 120 NMSC deaths occurred, including 89 caused by squamous cell carcinoma, 22 by Merkel cell carcinoma, and 9 others. The median age at death was 79 years, unless the patients were immune deficient (68 years). When the primary lesion was identified (n = 45), the median survival after diagnosis was 17 months; 75% of patients died within 3 years. Lethal neoplasms were deeply invasive and infiltrated into the reticular dermis and beyond. Three squamous cell carcinomas were reclassified as adenosquamous carcinoma. CONCLUSION: Lethal NMSC occurs in the elderly and consists mainly of 3 types of deeply invasive cancers.

Adult↗

[Mohs' micrographic surgery: history, principles, critical analysis of its efficacy and indications].

OBJECTIVES: To systematically review the literature for studies reporting on the role of Mohs' micrographic (MMS) surgery in the treatment of skin tumors. To show how it is performed in France. DESIGN: We reviewed with a quality grid all studies indexed in MEDLINE before 2003/01/01 and published in English or French. Data were extracted by two independent reviewers. MAIN OUTCOME MEASURES: Quality of clinical studies, recurrence rates, number of patients lost to follow-up. RESULTS: No randomized study was found among the 493 references found. Studies of lower quality, on procedures similar to MMS, or previous systematic reviews were therefore selected. In tumors such as basal (BCC) or spinous (SCC) cell carcinoma, microcystic adnexal carcinoma, dermatofibrosarcoma protuberans, and Merkel cell carcinoma, MMS commonly induced lower recurrence rates than figures reported for conventional treatments and/or reduced surgical margins. Studies on melanoma were of low quality. CONCLUSIONS: Although no evidence-based guidelines could be developed, MMS should be used mainly for larger, morphea, micronodular or infiltrative-type, or recurrent BCCs located in danger zones, but also (sometimes with a slightly modified procedure) in microcystic adnexal carcinomas, dermatofibrosarcoma protuberans, Merkel cell carcinoma, and in aggressive forms of SCC. Randomized, controlled studies should be performed.

Humans↗