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PubMed1993

Peripherin, a neuronal intermediate protein, is stably expressed by neuroendocrine carcinomas of the skin, their xenograft on nude mice, and the corresponding primary cultures.

The histogenesis of neuroendocrine carcinomas of the skin is still controversial. To determine the degree of neural differentiation of these neoplasias, we studied the expression of intermediate filament proteins in tumoral tissues. Expressions of peripherin, the neurofilament protein NF-L, vimentin, and cytokeratin 8 were analyzed by immunohistochemical methods on 12 human primary tumors and 3 tumor xenografts on nude mice. Peripherin was detected in 10 primary tumors by immunofluorescence. The protein and the corresponding messenger RNA were identified by two-dimensional gel electrophoresis and Northern analysis in extracts of an immunofluorescence-negative tumor. Peripherin, NF-L, and cytokeratin 8 were detected in tumoral cells, whereas vimentin was found exclusively in the stroma. The histological and ultrastructural properties of the original cells of neuroendocrine carcinomas of the skin, as well as coexpression of peripherin, cytokeratin 8, and neurofilament polypeptides, were preserved in tumor xenografts and their primary cultures in vitro. These results bring new elements to the knowledge of the biology of neuroendocrine carcinomas of the skin and indicate that peripherin constitutes a marker for tumor identification.

Animals↗
PubMed1990

[Intracranial invasion of neuroendocrine carcinoma: a case report].

A rare case of neuroendocrine carcinoma arising from the nasal cavity is reported. A 57-year-old female, who had been complaining of anosmia for 8 years, was admitted to the otolaryngological department because an intranasal tumor was found. Then, removal of the tumor and radiotherapy was carried out. After these procedures, the patient suffered from a high fever and CSF rhinorrhea. At this stage, our neurosurgical department was consulted. CT scan revealed a partially calcified low density mass with a slight enhancement effect at the left frontal base. Under the diagnosis of intracranial invasion by intranasal neuroendocrine carcinoma, the patient was operated on. Through bifrontal craniotomy and a combination of extra- and intradural approach, the tumor was excised. After that, the dura and the skull base were reconstructed. On histological examination, the tumor was found to consist of NSE positive cells forming some glandular structures. Electron microscopic study disclosed neurosecretory granules in the cytoplasmic process. These findings are typical of neuroendocrine carcinoma and compatible to those of the intranasal tumor previously removed. Neuroendocrine carcinoma is rare in itself and there have been reported only two cases of its invasion of the skull base. The clinical features, diagnostic procedures, pathological findings, and treatment of this tumor are discussed in this report.

Brain Neoplasms↗
PubMedDate not supplied

The unusual spectrum of neuroendocrine lung neoplasms.

Neoplasms of the lungs showing neuroendocrine differentiation are classified histologically into the following groups: (1) carcinoid, (2) atypical carcinoid (well-differentiated neuroendocrine carcinoma and malignant carcinoid, (3) small cell neuroendocrine carcinoma (small cell undifferentiated carcinoma and oat cell carcinoma), and (4) large cell neuroendocrine carcinoma (atypical endocrine tumor of the lung and intermediate neuroendocrine carcinoma). Nine examples of neuroendocrine lung carcinomas are discussed that have unusual histologic features that make it difficult to assign them to one of the above groups, have unusual immunohistochemical features, have unusual ultrastructural features, or exhibit a biologic behavior different from what one would have predicted from their morphologic appearance. The findings in these nine cases suggest that the present classification of neuroendocrine lung neoplasms may be too precise and that these neoplasms, like other nonneuroendocrine pulmonary tumors, exhibit a wider morphologic and biologic spectrum than previously appreciated.

Adenocarcinoma↗
PubMed2003

Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study.

OBJECTIVE: To evaluate the demographic characteristics, clinical course, and outcome in organ transplant recipients with metastatic skin cancer. DESIGN AND SETTING: An international, multicenter, Internet-coordinated collaborative group retrospectively analyzed data from 68 organ transplant recipients with 73 distinct metastatic skin cancers. MAIN OUTCOME MEASUREMENTS: The Kaplan-Meier method was used to estimate the cumulative incidence of relapse, overall survival, and disease-specific survival after metastatic skin cancer. Univariate Cox proportional hazards models were fit to evaluate factors for an association with survival. RESULTS: Metastasis from skin cancer in organ transplant recipients most commonly consisted of squamous cell carcinoma in regional nodal basins. It was predominantly treated with a combination of surgery and irradiation. By 1 year after metastasis, the cumulative incidence of relapse was 29%, and the 3-year disease-specific survival was 56%. Patients whose initial metastases were distant or systemic had a significantly poorer disease-specific survival than those whose initial metastases were in-transit or regional (risk ratio, 6.5; P<.001). CONCLUSIONS: Metastatic skin cancer in organ transplant recipients has a poor prognosis. Preventive, early, and aggressive therapeutic interventions are required to minimize this serious complication of transplant-associated immunosuppression.

Adult↗
PubMed2002

A 10-year prospective study of patients with skin cancer.

BACKGROUND AND OBJECTIVE: To determine the incidence of new skin cancer formation in people who have had a nonmelanoma skin cancer (NMSC) removed. METHODS: A prospective study of Australian outpatients with histologically confirmed nonmelanoma skin cancer (NMSC). RESULTS: Four hundred eighty-one patients were entered in the study and 300 were followed for at least 10 years. Another skin cancer developed in 67.8% and multiple skin cancers (three or more) in 51.8%. A logistical regression analysis found that the main risk factors for new skin cancer formation were male sex and if the patient had multiple skin cancers. A squamous cell carcinoma (SCC) developed in 36% during the study and a melanoma in 4.7% of men and 2.1% of women. Men who had a NMSC were 8 times more likely than the general population to develop a melanoma while women with NMSC were 4 times more likely. Three patients died of metastatic SCC and one of metastatic melanoma during the followup period. A multivariate analysis showed that multiple skin cancer formation was the main risk factor for SCC or melanoma formation. CONCLUSION: Patients with NMSC require careful followup as they have an increased risk of new cancer formation. Those with multiple skin cancer merit particularly careful followup as all develop another NMSC within 10 years and have a significantly increased risk of developing SCC or melanoma.

Australia↗
PubMed1988

Sensory innervation of the hairs of the rat hindlimb: a light microscopic analysis.

The sensory innervation of the hair follicles of the furry skin of the rat hindlimb has been investigated by using the Winkelmann silver technique to stain peripheral axons and their terminals. This technique was found to stain only large- and medium-sized dorsal root ganglion cells and all laminae of the dorsal horn except lamina II, and therefore it is likely that, while A beta and A delta afferent fibres in the skin are stained, C fibres are not. Small vellus hairs were the commonest type of hair on the hindlimb particularly above the ankle. Many were not innervated. Those that were had lanceolate terminals arranged as palisades parallel to the hair shaft with circumferential presumptive Ruffini piloneural complexes and free nerve endings external to this. Circumferential innervation patterns without palisades were not uncommon but palisades without circumferential fibres were rare. Guard hairs which varied considerably in size were the next commonest hair type. Considerably more of these were innervated, by three-to-15 afferents forming both palisades of ten-to-30 lanceolate terminals and circumferential terminals. Both the innervated vellus and guard hairs had an associated vertical fibre projecting toward the epidermis. Tylotrichs, the largest hairs on the hindlimb, were rare (1-2%) and were only found above the ankle, but all were densely innervated by many axons. A prominent single nerve contributed to an annular complex by forming a bilaminar arrangement of lanceolate and circumferential terminals within the outer connective tissue sheath. Each tylotrich had an associated Merkel cell-neurite complex (haarscheiben). Differences in the distribution, innervation density, and phase in the growth cycle of the different hair types were found for skin from different regions of the hindlimb, which, together with the extent of the polyneuronal innervation of most follicles, has important implications for the processing by the somatosensory system of the afferent input generated by brushing hairs.

Afferent Pathways↗
PubMed1989

[Diagnosis and therapy of neuroectodermal tumors].

Computed tomography (CT) and 123I- or 131I-meta-iodo-benzyl-guanidine (MIBG) scintigraphy were compared for accuracy in tumor detection in 47 patients with neuroectodermal neoplasms. MIBG concentration was found in 12 of 13 pheochromocytomas, 12 of 12 neuroblastomas, 5 of 9 carcinoids, and 1 of 4 glomus tumors. MIBG uptake was not observed in medullary thyroid carcinomas, oat-cell carcinomas, Merkel tumors, 1 gastrinoma, and 2 unclassified neuroectodermal neoplasms. With regard to the different tumor manifestations, the sensitivity in detecting pheochromocytomas, neuroblastomas, and carcinoids was 87%, 77%, and 100% for CT, and 83%, 100% and 71% for MIBG scintigraphy, MIBG scintiscan was superior in the detection of small adrenal pheochromocytomas (less than 1 cm diameter) and in the depiction of small bone metastases and bone marrow infiltration from neuroblastoma. In all, 25 cycles of high-dose MIBG therapy were performed in eight patients with surgically incurable tumors (4 malignant pheochromocytomas, 1 neuroblastoma, 3 carcinoids). The total therapeutic activity applied was 3.55-43.29 GBq 131I-MIBG. Tumor kinetics of MIBG were investigated before and during treatment. One patient with metastatic pheochromocytoma has been in complete remission for a follow-up period of 36 months since completion of treatment, and another patient is in partial remission. Tumor reduction or no change was observed in four patients. Two patients died of non-concentrating recurrence and metastases.

3-Iodobenzylguanidine↗
PubMed1997

Adaptive differentiations of the skin of the head in a subterranean rodent, Spalax ehrenbergi.

The skin of macroscopically distinct regions (hairy skin, vibrissal fields, buccal ridge, and rhinarium) of the head of the blind mole-rat, Spalax ehrenbergi, was studied by routine histological methods. Few guard and several soft vellus hairs are organized into tufts that grow from a group of hair follicles localized in an invaginated compound cavity. We suggest that this hair arrangement may be a burrowing adaptation to match frictional resistance. The follicles and the compound cavity possess either well developed complex striated musculature or errector pili muscles. There are no structural specializations (sweat glands, glomus bodies) to enhance thermoregulatory (heat dissipative) capacities in the hairy skin of the head. Vibrissae penetrate the epidermal surface as single hairs. They are microscopically normally developed and arranged in vibrissal fields according to a basal mammalian pattern. Most of them are, however, relatively short and inconspicuous. The mystacial vibrissal field is horizontally divided by a prominent buccal ridge which is probably involved in bulldozing. The hairs in the ridge leave the compound cavity singularly. The follicles of guard hairs and bristles are equipped with well developed pilo-Ruffini complexes indicating that the buccal ridge may serve also as a tactile organ. The glabrous skin of the rhinarium has a highly interdigitated dermal-epidermal interface. The dermal papillae possess simple lamellated and/or simple Meissner's corpuscles and few Merkel cell-axon-complexes indicating that the skin of the rhinarium may be particularly sensitive to perception of vibrations.

Adaptation, Biological↗
PubMed2006

Mice lacking the p75 receptor fail to acquire a normal complement of taste buds and geniculate ganglion neurons by adulthood.

Brain-derived neurotrophic factor and neurotrophin-4 are required for normal taste bud development. Although these neurotrophins normally function via the tyrosine kinase receptor, trkB, they also bind to the pan-neurotrophin receptor, p75. The goal of the present study was to determine whether the p75 receptor is required for the development or maintenance of a full complement of adult taste buds. Mice with p75 null mutations lose 34% of their circumvallate taste buds, 36% of their fungiform papillae, and 26% of their fungiform taste buds by adulthood. The reduction of taste buds in the adult circumvallate papilla was similar to that observed previously at postnatal day 7 (Fan et al. Brain Res Dev Brain Res 2004;150:23-39). Taken together, these findings indicate that the p75 receptor is critical for the development of a full complement of taste buds, but is not required for maintenance of circumvallate taste buds in adulthood. Immunolabeling for p75 was not observed in taste buds, indicating that p75 signaling influences taste bud number indirectly. Geniculate ganglion neurons, which provides innervation to fungiform taste buds, express the p75 receptor. Mice with p75 null mutations also have fewer neurons in the geniculate ganglion. Together, these results suggest that the p75 receptor is important for the survival of geniculate neurons and geniculate neuron survival is required for the development of a full complement of taste buds by adulthood.

Aging↗
PubMed1993

Posterolateral neck dissection: technique and results.

Posterolateral neck dissection, alone or combined with a modified radical neck dissection, may be an appropriate method of treating occult and clinically manifest nodal metastases of malignant epithelial tumours of the skin of the posterior scalp. The technique and results are described in 21 patients treated between February 1981 and November 1989. Transformation of nodal status from cN0 to pN+ was seen in five of 13 patients treated electively, who may benefit from such a procedure. During a mean follow-up of 47 months the disease was controlled locally in all patients. Three patients suffered regional recurrence of whom only one had a nodal recurrence within the region previously operated on. The results of this limited retrospective study confirm the value of posterolateral neck dissection in posterior scalp lesions.

Adult↗
PubMed2003

Somatosensory organization and behavior in naked mole-rats: II. Peripheral structures, innervation, and selective lack of neuropeptides associated with thermoregulation and pain.

African naked mole-rats are subterranean rodents that have a robust orienting response to stimulation of unique vibrissa-like body hairs that are widely spaced over an otherwise hairless skin. To determine whether these large body hairs have a specialized organization similar to facial vibrissae, the structure and innervation of facial vibrissa follicles, body hair follicles, and intervening skin in naked mole-rats was compared with that in rats and a furred African mole-rat species (the common mole-rat). Immunofluorescence and lectin-binding analyses revealed that the body hair follicles in naked mole-rats were exceptionally large and well innervated, similar to guard hairs of furred species. However, these body vibrissae lacked the anatomic specializations and unique types of innervation affiliated with follicle sinus complexes of facial vibrissae. In contrast to the furred species, naked mole-rats had a paucity of Abeta-fiber Merkel endings at all peripheral locations. Naked mole-rats also were completely lacking in cutaneous C-fibers immunoreactive for substance P and calcitonin gene-related peptide. In contrast, the hairless skin of the naked mole-rats had an exceptional abundance of presumptive Adelta-fibers. The unusual features of the cutaneous innervation in naked mole-rats are presumably adaptations to their subterranean environment and that they are the only known poikilothermic mammal. The features of this mammalian model system provide unique opportunities to discriminate mechanisms related to tactile spatial orientation, vascular regulation, and nociception.

Afferent Pathways↗
PubMed1986

Degeneration and regeneration of peripheral nerve in the rat trigeminal system. I. Identification and characterization of the multiple afferent innervation of the mystacial vibrissae.

Light and electron microscopic techniques were utilized to examine the sensory innervation of the rat mystacial vibrissa. Each vibrissa is innervated by a large nerve bundle that enters the hair below the level of the Ringwulst and a smaller bundle (conus nerve) that pierces the capsule at the top of the hair. The main nerve bundle innervates four types of sensory receptors: (1) free nerve endings (FNEs), (2) lanceolate receptors in the connective tissue below the Ringwulst, (3) Merkel cell-neurite complexes in the outer root sheath, and (4) lanceolate receptors in the intermediary zone. The smaller nerve bundle innervates the area of the sinus hair referred to as the conical body and supplies (1) a Ruffini corpuscle, (2) FNEs, and (3) lanceolate receptors in the inner conical body. The Ruffini complex of the inner conical body and the FNEs of the dense connective tissue below the Ringwulst have not been identified in previous morphological studies of the rat sinus hair. The Ruffini corpuscle, characterized by the compartmentalization of collagen bundles by Schwann cells and fibroblasts (septal cells), encircles the hair shaft in a manner analogous to the Ruffini complexes of nonsinus hairs. Identification of this receptor in the rat vibrissa provides an anatomic explanation for physiological recordings of mystacial primary afferents with slowly adapting type II properties in the rat.

Animals↗
PubMed1997

Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR.

The impact of null mutations of the genes for the NGF family of neurotrophins and their receptors was examined among the wide variety of medium to large caliber myelinated mechanoreceptors which have a highly specific predictable organization in the mystacial pad of mice. Immunofluorescence with anti-protein gene product 9.5, anti-200-kDa neurofilament protein (RT97), and anti-calcitonin gene-related product was used to label innervation in mystacial pads from mice with homozygous null mutations for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), the three tyrosine kinase receptors (trkA, trkB, trkC), and the low-affinity nerve growth factor receptor p75. Specimens were sacrificed at birth and at 1, 2, and 4 weeks for each type of mutation as well as at 11 weeks and 1 year for p75 and trkC mutations, respectively. Our results demonstrate several major concepts about the role of neurotrophins in the development of cutaneous mechanoreceptors that are supplied by medium to large caliber myelinated afferents. First, each of the high-affinity tyrosine kinase receptors, trkA, trkB, and trkC, as well as the low-affinity p75 receptor has an impact on at least one type of mechanoreceptor. Second, consistent with the various affinities for particular trk receptors, the elimination of NGF, BDNF, and NT-3 has an impact comparable to or more complex than the absence of their most specific high-affinity receptors: trkA, trkB, and trkC, respectively. These complexities include potential NT-3 signaling through trkA and trkB to support some neuronal survival. Third, most types of afferents are dependent on a different combination of neurotrophins and receptors for their survival: reticular and transverse lanceolate afferents are dependent upon NT-3, NGF, and trkA; Ruffini afferents upon BDNF and trkB; longitudinal lanceolate afferents upon NGF, trkA, BDNF, and trkB; and Merkel afferents on NGF, trkA, NT-3, trkC, and p75. NT-4 has no obvious detrimental impact on the mechanoreceptor development in the presence of BDNF. Fourth, NT-4 and BDNF signaling through trkB may suppress Merkel innervation and NT-3 signaling through trkC may suppress Ruffini innervation. Finally, regardless of the neurotrophin/receptor dependency for afferent survival and neurite outgrowth, NT-3 has an impact on the formation of all the sensory endings. In the context of these findings, indications of competitive and suppressive interactions that appear to regulate the balance of innervation density among the various sets of innervation were evident.

Animals↗
PubMed1990

Primary neuroendocrine carcinoma of the eyelid, immunohistochemical and ultrastructural study.

Primary neuroendocrine carcinomas of the skin were recognized as distinctive neoplasms and clinicopathologic information on their location on the eyelids have been reported. The authors present one case of primary neuroendocrine carcinoma occurring on the right lower lid in a 73-year-old woman. The clinical history, light and electron microscopic findings as well the results of an immunohistochemical study are described. The ultrastructural study demonstrated the characteristic membrane-bound dense-core neurosecretory granules. Immunoreactivity for neuron-specific enolase, keratin filaments, epithelial membrane antigen and calcitonin were observed and are strongly suggestive of a neuroendocrine differentiation in a neoplasm of epithelial origin. Various hypothesis concerning the origin of this tumor are discussed on the basis of the immunohistochemical findings. The authors also provide a brief review of the literature.

Aged↗