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Localization of met-enkephalin like immunoreactivity in the glabrous skin of the cat rhinarium.

The presence of met-enkephalin like immunoreactivity (MEL IR) was investigated immunohisto-chemically in the glabrous skin of the cat rhinarium using the peroxidase-antiperoxidase Sternberger's method. Neither sensory corpuscles nor nerve bundles show MEL IR. MEL IR was found in the epidermal Merkel cells, as well as in Langerhans cells and/or melanocytes. In dermal papillae the reaction results positive in a number of cells which could be identified as Schwann or pigmentary cells.

Animals↗

Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases.

A group of human breast carcinomas shows morphologic and histochemical evidence of neuroendocrine (NE) differentiation. This study presents a structural, immunologic, and electron microscopic analysis of 51 cases in order to establish positive criteria for identification of these tumors, their incidence, variants, and biological behavior. Argyrophilia (by the Grimelius procedure), presence of chromogranin A and/or B, and of synaptophysin are the most reliable histochemical features, correlating with the ultrastructural demonstration of dense-core secretory granules and of clear vesicles of the synaptic type. Structural features alone may be suggestive, but do not prove NE differentiation, which has to be established by additional techniques. Seven histologic types were identified, but those herein described as types A, B, and C, which show cohesive, mucoid, and mixed patterns, respectively, comprise the vast majority of the tumors. Rare NE carcinomas of the breast show structural similarities to Merkel cell and oat cell carcinomas, and behave as highly aggressive tumors. Type B (mucinous) tumors proved to be relatively indolent, while the most frequent types of endocrine tumors (types A and C) have an intermediate grade of malignancy. The analysis of a consecutive series of 100 cases of breast cancer indicates that about 8% of breast carcinomas display some degree of NE differentiation.

Adult↗

[Disseminated neuroendocrine cancers of the skin--a cutaneous merkeliomatosis. Report of 2 cases].

Two nearly identical cases with about 100 multicentric disseminated neuroendocrine carcinomas of the skin are presented. In the Merkel cell tumors a for epithelial cells specific antigen (MAM-6) was found by immunohistochemical methods. Only in one patient generalized metastases arose after a four year course of the disease. The other patient committed suicide after a three year course of the disease. At autopsy no metastases were seen. We assume these diseases to be a systemic proliferation of malignant neuroendocrine differentiated epithelial cells, for which the term "cutaneous Merkeliomatosis" is proposed.

Aged↗

[Epidermotropic reticulosis of the Woringer-Kolopp type (author's transl)].

A 46-year-old female, otherwise healthy, developed erythematous, pseudotumoral nodules, mainly on the hands; biopsies led to the diagnosis of Woringer-Kolopp disease. Anti-anergic chemotherapy with levamisole proved hazardous but, possibly, beneficial. Classification into benign localized, fatal generalized and intermediate disease is briefly commented upon. Differential diagnosis and tumor origin are discussed; while the Merkel cell hypothesis has been recently advanced strong analogies and slight discrepancies with mycosis fungoides advocate the T cell lymphoma theory.

Diagnosis, Differential↗

[Woringer and Kolopp's disease (author's transl)].

Woringer and Kolopp's disease is a rare skin disease. Erythemato-squamous, slightly infiltrated lesions with round-shaped islets of normal skin are the clinical hall-marks of the disease. The histological picture is highly specific: a dense epidermal infiltrate disrupts the stratum spinosum, contrasting with a spared dermis. Three different aspects of the disease have been reported: a localized benign type as in Woringer and Kolopp's patient; a disseminated lethal type without visceral involvement and without preexisting lesions, and a disseminated lethal type in which lesions appear on erythematous patches clinically and histologically similar to "parapsoriasis en plaques". It is the opinion of the authors that the third type is not Woringer and Kolopp's disease but an extremely epidermotropic variant of mycosis fungoides. The two other types seem to be variants of the same disease. Several hypotheses about the nature of that disorder are discussed. Most authors think that Woringer and Kolopp's disease is a cutaneous lymphoma because of clinical, histological and ultrastructural similarities with mycosis fungoides. We are presenting evidence favoring the hypothesis of a Merkel cell proliferative disease.

Adolescent↗

[Postnatal development of sensory nerve endings in the hairless nose skin of the cat].

The postnatal development of sensory nerve endings has been studied in the skin of the planum nasale of the cat. The Merkel nerve endings develop in the prenatal period; after birth some redundant axons perish. Up to the third postnatal day, sporadic Merkel cells and nerve terminals still can be observed in the stratum papillare of the dermis. The free nerve endings in the dermis appear before birth. In the postnatal period the nerve fibres as well as the nerve endings ramify. A few of them come into contact with the stratum basale of the epidermis, others may perish. Most of these nerve endings are located in the stratum papillare of the dermis. The simple encapsulated corpuscles with an inner core develop after birth. In the depth of the dermis, the corpuscles are arranged mainly in groups, in the stratum papillare, however, they are more isolated. The development of those corpuscles, located in the depth of the dermis, already begins before birth and finishes mostly about the 39th postnatal day. The development of the corpuscles in the stratum papillare starts later and ends between the 3rd and 4th month. The nerve terminal of the corpuscle changes only slightly during development. It elongates, becomes thicker, and the number of mitochondria increases. During all stages it sends cytoplasmic spines in between the lamellar system of the inner core. The inner core is formed by cytoplasmic lamellae of the peripheric glial cells. In the course of development the number of cytoplasmic lamellae increases, they become thinner and gradually each one will be covered by a basal lamina. A mature corpuscle possesses an inner core with one or two longitudinal clefts. These clefts occur more frequently in corpuscles with complete capsules. The connective tissue cells primarily form a primitive capsule around the inner core. During development the layers of the capsule increase in number. Mature corpuscles have a one- to four-layered capsule. The capsular cells are then ensheathed by a basal lamina.

Aging↗

Innervation of the tylotrich-touch dome complexes in rat skin: changing patterns during postnatal development.

The tylotrich-touch dome complexes of the rat were studied in detail at thoracic level, with two objectives: to follow the pattern of innervation of the individual complexes from birth to maturity and to determine the extent of overlap of the segmental nerves supplying them. Techniques included light and electron microscopy and histological observations following section of intercostal nerves. The touch domes were nearly always supplied from a single stem axon; as expected, their terminals increased in number in association with the differentiation of target Merkel cells from the epidermis. In general, they were supplied from the nearest segmental nerves. The tylotrich follicles were each supplied by several stem fibres. The number of palisade terminals applied to the epithelial root sheaths reached a maximum during the 2nd and 3rd postnatal weeks and declined during the following 2 wk. This overshoot can be regarded as another example of hyperinnervation found in the juvenile peripheral nervous system. During the period of decline, the stem fibres extended their territory, resulting in considerable overlap of the territories of the segmental nerves. By the beginning of the 8th week, overlap was relatively scanty, with an irregular distribution.

Animals↗

[Radiotherapy of cutaneous cervical-facial carcinomas].

The main goal of therapy for epithelial skin cancer is cure with the best functional and cosmetic outcome. Both surgery and radiotherapy give similar results for early stage lesions with 5-year local control rates ranging from 85% to 95%. Remarkable technological progress has been made yielding well defined indications to radiotherapy as a single treatment or in the context of a multidisciplinary approach. Selection of treatment should be tailored considering anatomic site, surface conformation, size, histology, grading and characteristics of tumours (new occurrence, relapse), number of localizations, age and medical conditions of the single patient. Surgery, guided by intraoperative control of resection margins, is undoubtedly the therapy of choice for most of early stage lesions. Radiation therapy plays an important role in specific anatomic situations in which the functional or cosmetic result is better than for a surgical modality, electively for the treatment of multiple lesions and for large deep- infiltrating carcinomas that generally are not suitable to excision. Exclusive radiotherapy is also indicated as rescue treatment of surgical relapses no more amenable to reexcision as well as for palliation of advanced cases, mainly for elderly or medically compromised patients. Postoperative irradiation should be considered for macro or microscopic residual disease. Merkel cell or adnexal carcinomas and for highly recurrent lesions after repeated surgery. Treatment results and complications of radiotherapy are discussed, emphasizing high local control rates and good functional and cosmetic outcomes. The main irradiation techniques referred to specific anatomic sites are also presented.

Carcinoma↗

Intercellular adhesion molecule-1 (ICAM-1) immunoreactivity in well-differentiated thyroid papillary carcinomas.

Fifty-nine cases of tumors, 51 taken from the thyroid gland including 17 well-differentiated papillary, 1 medullary and 3 follicular carcinomas, 14 follicular adenomas, 16 nodular goiters and 8 cases selected from other sites; 5 breast carcinomas; 1 melanoma; 1 Merkel cell tumor; and 1 squamous cell carcinoma of the uterine cervix, were investigated for intercellular adhesion molecule-1 (ICAM-1) expression. All cases of well-differentiated papillary thyroid carcinoma showed positivity for ICAM-1, whereas the follicular carcinomas, follicular adenomas, and all but one nodular goiters were negative. It is suggested that the occurrence of ICAM-1 on the thyroid cell surfaces in well-differentiated papillary thyroid carcinomas may contribute to the understanding of their biology and could be of potential significance for diagnostic purposes.

Carcinoma, Papillary↗

Metastatic carcinoid tumor imaged with CT and a radiolabeled somatostatin analog: a case report.

Radiolabeled somatostatin analogs have shown uptake in a variety of tumors. These include carcinoid, Merkel cell carcinoma, pheochromocytoma, islet cell tumor, and other tumors with somatostatin receptors. Radiolabeled somatostatin analog imaging with Indium-111-DTPA-pentetreotide permits whole body imaging, providing a new safe and effective means for detection of primary tumors and metastatic foci in neoplasms with somatostatin receptors. This imaging modality is helpful in screening the entire body as well as evaluating questionable foci of disease identified by conventional imaging modalities. This case report demonstrates the utility of computed tomography (CT) and radiolabeled somatostatin imaging as complementary modalities in the workup of a patient with metastatic carcinoid tumor.

Aged↗

Non-pigmented nodular plantar melanoma in 12 Japanese patients.

In the Japanese, melanoma most commonly involves the plantar surface. Among 61 patients with plantar melanoma, we diagnosed 50 patients as acral lentiginous melanoma (ALM), nine as nodular melanoma, and two as superficial spreading melanoma. Partial or complete loss of pigment was observed in four of the nine nodular melanoma cases and in the nodular portions of eight ALM cases. All 12 such nodular lesions were ulcerated. The clinical diagnosis of malignant melanoma was easily made in the eight patients with ALM by the characteristic pigmentary changes around the nodule. The presence of some remaining pigment was found to be helpful in making the diagnosis in two lesions of nodular melanoma which, at first, had been clinically diagnosed as eccrine poromas. One of two completely amelanotic nodular melanomas was strongly suspected to be a melanoma because there was a history of a pre-existing pigmented macule before the development of the nodule. The other one required histopathological differentiation from Merkel cell carcinoma. Based on these findings and compared with melanoma on other parts of the body, pigmentation noted in the ulcerative nodule of plantar melanoma seems to disappear easily. This causes difficulty in distinguishing it from other skin tumours.

Aged↗

[Neuro-immuno-cutaneous system (NICS)].

The concept of neuro-immuno-cutaneous system (NICS) means narrow interrelations between nervous system, immunity and skin. Indeed, there are numerous cellular contacts between nerve fibers, cutaneous cells and immune cells; cutaneous cells can synthesize neuromediators and they express receptors to these molecules; neuromediators are able to modulate functions of cutaneous and/or immune cells. Using confocal or electron microscopy, connexions between nerve fibers and cutaneous cells have been observed. In the skin, nerve fibers may secrete neuromediators: substance P, vaso-active intestinal peptide (VIP), somatostatin, calcitonin-gene related peptide (CGRP), gastrin-releasing peptide (GRP), neuropeptide Y, peptide histidine-isoleucine (PHI), neurotensin, neurokinins A et B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melano-stimulating hormone (MSH) or adreno-corticotrophic hormone (ACTH) are also expressed in the skin. Neuromediators and neurohormones are also secreted by cutaneous cells and these cells express receptors. Functions of epidermal or dermal cells are modulated by these substances. Immune cells transiently present in the skin (macrophages, lymphocytes...) are modulated by neuromediators through receptors. In the course of skin diseases, especially inflammatory diseases, the NICS is destabilized. Psoriasis and atopic dermatitis are good examples. This phenomenon might be due to inflammation but is also responsible for induction and maintenance of the inflammation.

Dermatitis↗

111In octreotide scintigraphy in the evaluation of head and neck lesions.

PURPOSE: To evaluate indium 111 octreotide scintigraphy for the detection of suspected neuroendocrine lesions of the head and neck. METHODS: After receiving 6 mCi of 111In octreotide, 22 patients with suspected lesions of the head and neck were examined with both planar and single-photon emission CT (SPECT). Static images, obtained at 4 hours, included the head/neck, chest, abdomen, and pelvis. Additional SPECT images were obtained at 4 or 24 hours. Studies were compared with available conventional radiologic examinations (12 CT, 11 MR, and three angiographic studies) as well as with clinical and pathologic findings. RESULTS: Eighteen of the 22 patients had abnormal findings at scintigraphy. Eleven paragangliomas were seen in 10 patients, metastatic medullary thyroid carcinoma in three patients, thyroid adenoma in two patients, and Merkel cell tumor, carcinoid, and plasmacytoma in one patient each. Surgical confirmation was available in 13 patients. The smallest lesion detected was 1.5 cm. There was one false-positive and one false-negative examination. CONCLUSION: 111In octreotide scintigraphy is a useful imaging tool for the detection of primary and metastatic neuroendocrine tumors of the head and neck that are larger than 1.5 cm. This technique enables distinction of glomus tumors from other masses (such as neuromas) and can be used in the postoperative setting to distinguish scar from recurrent paraganglioma. Since it is an examination of the entire body, it has great utility for detecting multicentric paraganglioma and for screening patients with familial paraganglioma.

Adult↗

Radiation therapy for nonmelanoma skin carcinomas.

Radiotherapy plays an important role in the management of appropriately selected skin carcinomas. Tumors of the eyelid, nose, and ear can be treated successfully with preservation of adjacent normal tissues. Tumors located in the embryologic fusion planes of the face can be irradiated with wide margins, either as primary or postoperative therapy. Radiotherapy has a significant role in the postoperative setting for patients with high-risk features in their pathologic specimens. Patients with NECS (Merkel cell carcinoma) have a high recurrence rate after surgical excision; these patients should undergo radiotherapy after resection of the clinically evident disease.

Basal Cell Carcinoma↗

Universal application of intraoperative lymphatic mapping and sentinel lymphadenectomy in solid neoplasms.

PURPOSE: Regional lymph node involvement is the most important prognostic indicator in patients with solid tumors. Conventional lymph node dissection has not been shown to affect survival and is often associated with considerable morbidity. Intraoperative lymphatic mapping and sentinel lymph node dissection were therefore designed as a minimally invasive alternative to routine elective lymph node dissection in patients with primary cutaneous melanoma. This study examined whether introperative lymphatic mapping and sentinel lymph node dissection were accurate in staging patients with other solid malignancies. PATIENTS AND METHODS: Between 1985 and 1998, 107 patients with breast cancer, 17 with thyroid tumors, 14 with gastrointestinal/gynecologic cancers, six with Merkel cell cancers, and five with squamous cell carcinomas of the head and neck have undergone mapping and sentinel lymph node dissection at the John Wayne Cancer Institute. RESULTS: The sentinel node was identified in 96% of patients (98% melanoma). In 36% of patients the sentinel node was the only tumor-positive node (71% melanoma). Eighteen percent of sentinel nodes were negative by hematoxylin and eosin staining but were positive by immunohistochemical staining (15% melanoma). CONCLUSION: These data suggest that many solid neoplasms have a primary lymphatic channel and lymph node to which it drains. Although sentinel lymph node dissection has been popularized in melanoma therapy, we have found it feasible for treatment of other solid malignancies. This technique may ultimately replace conventional dissection with more accurate staging.

Adult↗

Argyrophilic cells and ectocervical epithelium.

The purpose of this study was to determine the nature of the argyrophilic cells in the ectocervix and to analyze the different morphologic varieties of argyrophil cell-containing ectocervical epithelia, notably to reappraise the degree of analogy with transitional epithelium. A systematic study of 39 ectocervices was carried out using histochemical and immunohistochemical techniques. Immunodetection of cytokeratins was used to specify the differentiation of the ectocervical linings. Argyrophilic cells were detected in 43% of our specimens. They have been found in several varieties of ectocervical lining: normal-appearing or hyperkeratotic squamous epithelium, "transitional-like" epithelium extending onto the portio, and immature squamous metaplasia from the transformation zone. The term "transitional-like" refers to a stratified nonsquamous epithelium that differs from true urothelium by the absence of superficial differentiation leading to the layer of "umbrella" cells. Two main types of argyrophilic cells have been delineated: serotonin cells and Merkel-type cells. The nature of the argyrophilic cells was dependent on the type of epithelium: Serotonin cells were essentially associated with "transitional-like" epithelium and Merkel-type cells with squamous epithelium. The latter cells were particularly frequent in hyperkeratotic squamous epithelium from uterine prolapse, reinforcing the homology with epidermis.

Adult↗

Evolution of taste and solitary chemoreceptor cell systems.

Vertebrates possess four distinct chemosensory systems distinguishable on the basis of structure, innervation and utilization: olfaction, taste, solitary chemoreceptor cells (SCC) and the common chemical sense (free nerve endings). Of these, taste and the SCC sense rely on secondary receptor cells situated in the epidermis and synapsing on sensory nerve fibers innervating them near their base. The SCC sense occurs in anamniote aquatic craniates, including hagfish, and may be used for feeding or predator avoidance. The sense of taste occurs only in vertebrates and is always utilized for feeding. The SCC system achieves a high degree of specialization in two teleosts: sea robins (Prionotus) and rocklings (Ciliata). In sea robins, SCCs are abundant on the three anterior fin rays of the pectoral fin which are free of fin webbing and are used in active exploration of the substrate. Behavioral and physiological studies show that this SCC system responds to feeding cues and drives feeding behavior. It is connected centrally like a somatosensory system. In contrast, the specialized SCC system of rocklings occurs on the anterior dorsal fin which actively samples the surrounding water. This system responds to mucus substances and may serve as a predator detector. The SCC system in rocklings is connected centrally like a gustatory system. Taste buds contain multiple receptor cell types, including a serotonergic Merkel-like cell. Taste receptor cells respond to nutritionally relevant substances. Due to similarities between SCCs and one type of taste receptor cell, the suggestion is made that taste buds may be compound sensory organs that include some cells related to SCCs and others related to cutaneous Merkel cells. The lack of taste buds in hagfish and their presence in all vertebrates may indicate that the phylogenetic development of taste buds coincided with the elaboration of head structures at the craniate-vertebrate transition.

Animals↗

Protein gene product 9.5-immunoreactive nerves and cells in human oral mucosa.

BACKGROUND: Current conflicting information on the innervation of the human oral cavity indicates technical problems such as different detectability of the neural structures according to the various staining methods used and difficulties in reproducibility. The possibility of intraoral regional differences has not been properly considered. METHODS: Human biopsies of mucosa from different intraoral regions were prepared for immunohistochemistry using protein gene product 9.5 (PGP 9.5; a marker for neuronal structures). RESULTS: Nerves were found consistently in all the biopsies. The neural pattern showed clear regional differences. Intraepithelial nerve fibers were found in the gingiva, labia, palate, within certain fungiform papillae, and in some salivary excretory ducts. Organized nerve endings were found in varying frequencies in all but one (sublingual) region, appearing as lamellar (Meissner-like), coiled or glomerular neural structures. Merkel cell-neurite complexes were observed in the buccal, gingival, and palatal epithelia. Immunoreactive cells with many similarities to Merkel cells but without a neural connection were also encountered. CONCLUSIONS: Conflicting results from earlier innervation studies of the oral cavity could be attributed to regional innervation differences. The distribution of the nerves also casts doubt on some of the present theories concerning the function(s) of intraoral nerves, such as the free nerve endings and the Merkel cell-neurite complexes.

Adolescent↗