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PubMed1999

[Primary small cell carcinomas and metastatic disease in the head and neck].

Extrapulmonary small cell carcinomas are recognized as a clinicopathologic entity distinct from small cell lung cancer. Such carcinomas as primary tumors have been described in several locations in the head and neck although most cases of metastatic tumor in the neck originate from a pulmonary primary. In this report we present a small cell carcinoma of the larynx, metastasis in the parotid gland as the first manifestation of a small cell lung cancer and a small cell carcinoma of the Merkel cell type in a parotid lymph node. Our review of the current literature shows that most small cell carcinomas in the head and neck are extrapulmonary primary tumors. Since histological criteria are the same, a pulmonary neoplasm has to be excluded in every case. The differentiation between a primary head and neck tumor and metastatic disease as well as the location and staging are essential criteria for therapy and prognosis.

Carcinoma, Merkel Cell↗
PubMed2006

Lymphoepithelioma-like carcinoma of the skin: a case with lymph node metastases at presentation.

We report a case of a primary lymphoepithelioma-like carcinoma (LELC) of the skin. The patient was a 73-year-old man with a lump on his back for 18 months. A biopsy and subsequent excision was performed. He also had axillary node clearance for metastatic disease. The tumor was composed of islands of pleomorphic cells with a lymphocytic infiltrate. Differential diagnoses included squamous cell carcinoma, adnexal carcinoma, Merkel cell tumors, lymphoepithelial lesions, lymphomas, and skin metastases. The histopathologic and immunohistochemical features were those of a LELC of the skin. It was negative for Epstein-Barr virus. Just over 30 cases of primary LELCs arising in the skin have been reported with only 1 documented fatality. We report a case with extensive vascular involvement and bilateral lymph node metastases.

Aged↗
PubMed2004

Sentinel node biopsy for high-risk nonmelanoma cutaneous malignancy.

OBJECTIVE: To evaluate the feasibility of sentinel node staging for detection of occult regional lymph node metastasis in high-risk cutaneous nonmelanoma malignancies. DESIGN: Consecutive clinical case series. SETTING: Referral university medical center. PATIENTS: A consecutive sample of patients with a variety of high-risk nonmelanoma cutaneous malignancies without evidence of regional lymph node metastases. INTERVENTION: Sentinel node biopsies were performed using preoperative lymphoscintigraphy, blue dye, and intraoperative radiolocalization. MAIN OUTCOME MEASURE: Sensitivity, determined by comparing the results of biopsy specimen evaluation with those of completion lymphadenectomy and/or clinical follow-up. RESULTS: Twenty-four patients underwent sentinel node biopsy for the staging of 29 nodal basins identified by lymphoscintigraphy. Primary diagnoses were squamous cell carcinoma (n = 17), Merkel cell carcinoma (n = 5), and adenocarcinoma (n = 2). Seven patients (29%) had a tumor-positive sentinel node. Sentinel node biopsy followed by complete lymphadenectomy was performed in 12 patients and sentinel node biopsy alone in 12 patients. Tumor-positive lymph nodes were noted in 8 patients, 7 of whom also had positive sentinel nodes. There was 1 false-positive result (1/8 [12%]), in a patient with recurrent squamous cell carcinoma of the scalp. At a median follow-up of 10 months, no recurrences in a sentinel node-negative basin have been noted. Compared with all information, the sensitivity of sentinel node staging was 88% and the negative predictive value was 0.94. CONCLUSIONS: Sentinel node biopsy is a minimally invasive staging procedure useful in identifying occult regional lymph node disease in selected patients with nonmelanoma cutaneous malignancies. Further studies to verify these findings and develop formal guidelines are indicated.

Adenocarcinoma↗
PubMed2003

Sentinel lymphonodectomy in nonmelanoma skin malignancies.

BACKGROUND: Whereas the value of sentinel lymphonodectomy (SLNE) in malignant melanoma is established, experience with SLNE in nonmelanoma skin cancers is limited. OBJECTIVES: The feasibility of SLNE in nonmelanoma skin tumours is evaluated. METHODS: Thirty-seven patients with high-risk nonmelanoma skin tumours underwent SLNE: 11 squamous cell carcinomas (SCCs), seven Merkel cell carcinomas (MCCs), five cutaneous lymphomas, eight adnexal carcinomas and six other skin cancers, all clinical stage N0. RESULTS: In nine patients (four MCCs, two SCCs, three lymphomas) the sentinel lymph nodes (SLNs) showed histological evidence of microinvolvement. In five of these nine patients, radical lymph node dissection (RLND) was performed, revealing further micrometastases in three patients (two SCCs, one MCC). No patient with negative SLN showed tumour dissemination during the follow-up over a mean of 2.5 years (range 2 months to 4.5 years, median 2.4 years). CONCLUSIONS: Our data provide evidence that SLNE is a minimally invasive and highly sensitive staging tool in selected patients with high-risk nonmelanoma skin cancers.

Adult↗
PubMed1986

Neuroendocrine carcinoma of the skin: an immunohistochemical study of tumor markers and neuroendocrine products.

Fifteen neuroendocrine carcinomas of the skin (Merkel cell tumors) were stained within the constraints of tissue availability by the Grimelius method and immunohistochemically for keratin, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), S-100, common leukocyte antigen (CLA), met-enkephalin, bombesin, calcitonin, ACTH, gastrin, and somatostatin. Focal argyrophilia was present in 5 of 12 tumors. All tumors tested demonstrated immunoreactivity for NSE and 5 tumors were positive for keratin. One tumors appeared to demonstrate focal ACTH-like immunoreactivity, but otherwise no immunoreactivity for the above mentioned polypeptide hormones was noted in 11 completely studied tumors. One tumor contained histologically obvious areas of squamous differentiation in addition to areas of Merkel cell tumor. In various tumors, keratin immunoreactivity was present either in areas of histologically obvious squamous differentiation, in randomly scattered single cells not histologically identifiable as squamous, or in a paranuclear dot-like distribution. Immunoreactivity for CEA, S-100 and CLA was not present in any tumors. The lack of met-enkephalin and the presence of squamous differentiation in these tumors indicates multidirectional differentiation in a fashion not phenotypically typical of Merkel cells.

Adenocarcinoma↗
PubMed1993

Spinal and facial innervation of the skin in the gadid fish Ciliata mustela (Teleostei).

The pattern of innervation of the skin of the rockling Ciliata mustela was investigated to sort out spinal from facial nerve innervation of cutaneous chemosensory and mechanosensory systems. This fish has a variety of appendages with different functional sensory specializations, i.e., the chin barbel, pelvic fin, anterior dorsal fin, and dorsal trunk skin. The carbocyanine dye, diI, was applied to nerve stumps in dissected aldehyde-fixed tissue. In the case of the chin barbel, the dye was applied to both the trigeminal and facial nerve components. In the other cases, the dye was applied either selectively to the spinal nerves, to the facial nerves, or to both components. In the chin barbel, diI labeled nerve fibers associated with taste buds (TBs) and solitary chemosensory cells (SCCs) as well as relatively blunt free nerve endings, which closely approach the epidermal surface. In the pelvic fin, anterior dorsal fin, and dorsal trunk skin, taste buds, solitary chemosensory cells, and their innervation were labeled only after diI was applied to the facial nerve stumps. Application of diI to spinal nerves labeled delicate, free nerve endings and nerve fibers associated with small cells deep in the epidermis with features characteristic of Merkel cells. Transmission electron microscopy supports these results; after denervation of the facial component of the anterior dorsal fin, synaptic contacts with Merkel cells remained intact, whereas the synapses with the SCCs vanished.

Animals↗
PubMed1981

Competitive reinnervation of salamander skin by regenerating and intact mechanosensory nerves.

We have investigated in the salamander the possibility that regenerating mechanosensory nerves might prefer the epidermal Merkel cells (their specific targets) that are located within their segmental domain to those within a "foreign" domain. Since regerating nerves cross domain boundaries with no evidence of the marked delay exhibited by intact sprouting nerves, we examined situations in which the regenerating axons of one segmental nerve were effectively in equal competition for denervated skin with those of another segmental nerve. Additionally, we investigated whether there were differences between regenerating axons and intact sprouting axons of the same segmental nerve, in their ability to innervate available skin both inside and outside the parent domain. No preference was detected of any type of nerve, regenerating or intact, for particular skin regions, or for Merkel cells as indicated by the numbers of mechanosensory thresholds of the touch spots that developed in reinnervated skin. Neither was there any indicating of displacement of "foreign" nerves from a particular region by appropriate axons. When regenerating and intact (sprouting) axons invaded denervated skin more or less simultaneously, the former appeared to have a slight advantage since a significantly greater proportion of skin was innervated by regenerated fibres. With this one exception, all the results were explained most simply by assuming that the axon that first arrives at a denervated Merkel cell establishes a permanent association with that cell and at the same time causes it to lose its "target character" for other axons.

Ambystoma↗
PubMedDate not supplied

[A rare case of Merkel's tumor with intestinal metastases].

A rare case of intestinal metastasis of a neuroendocrine carcinoma of the skin (Merkel Cell Tumor) is reported. The primary tumor was excised from the left arm two years earlier and followed an aggressive course with lymph-nodes, tonsillar and intestinal spread. Histologically, the intestinal lesion was similar to the primary tumor with small, undifferentiated cells. Undifferentiated small cell carcinoma and lymphomas of the gastrointestinal tract are to be considered in the differential diagnosis. Merkel Cells Tumor usually affects head and neck (44%) and extremities (48%), and is a highly malignant neoplasia, with early recurrence and distant metastases. Wide surgical excision of the primary lesion is the treatment of choice, while controversial is the role of prophylactic regional lymphadenectomy. Adjuvant radio- and chemo-therapy is frequently associated.

Carcinoma, Merkel Cell↗
PubMed2004

Small cell carcinoma of the major salivary glands: clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome.

Small cell carcinomas arising in salivary glands, extremely rare high-grade malignant tumors, are subclassified into neuroendocrine and ductal types. The neuroendocrine type may be segregated further into Merkel cell and pulmonary varieties according to cytokeratin 20 immunoreactivity. Whether subclassification of this tumor group has any biologic or clinical significance is not known. We examined 15 cases (11 men, 4 women; mean age, 66.5 years) of small cell carcinoma of major salivary glands from a single institution and analyzed their clinicopathologic profiles, including immunohistochemical features and prognostic factors. Three fourths of small cell carcinomas showed cytokeratin 20-positive immunostaining, often with a paranuclear dotlike pattern of reactivity. All tumors were immunoreactive for at least 2 of 6 neuroendocrine markers examined, and 6 tumors were also positive for neurofilament, with a paranuclear dotlike pattern. Postoperatively, 9 patients developed metastatic disease, and 10 patients died of disease 2 to 45 months (mean, 15.9 months) after diagnosis. By log-rank analysis, overall survival was reduced significantly for patients with a primary tumor larger than 3 cm in diameter (P = 0.032), negative immunostain reaction for cytokeratin 20 (P = 0.012), and decreased immunoreactivity for neuroendocrine markers (P = 0.034). These results indicate that small cell carcinoma of major salivary glands is a highly aggressive tumor, although the prognosis may be better than for extrasalivary neoplasms. Our data also suggest that most salivary gland small cell carcinomas exhibit neuroendocrine differentiation. Immunohistochemical expression of cytokeratin 20 can be used to classify salivary small cell carcinomas into Merkel cell and pulmonary types and may have prognostic significance.

Aged↗
PubMed2002

Distribution and terminal arborizations of cutaneous mechanoreceptors in the glabrous finger pads of the monkey.

Recent electrophysiological studies demonstrated that neurons in the somatosensory cortex of monkeys respond to tangential forces applied to glabrous skin. To unravel the peripheral basis for this cortical response, we determined the distribution of presumptive low-threshold mechanoreceptors innervating the distal finger pads of monkeys. Endings were reconstructed in immunolabeled serial sections imaged by epifluorescence and confocal microscopy. Although classically implicated as cutaneous stretch receptors, no Ruffini corpuscles were found in the glabrous skin. Ruffini-like endings were only detected at the base of the finger nails. Pacinian corpuscles were sparsely distributed in the deep dermis. Meissner corpuscles (MCs) in dermal papillary ridges had a comparably high density in the thumb, index, and fifth fingers. Each MC was innervated by several large-caliber axons. Within the limits of our reconstructions, some of these axons terminated in only one MC, whereas others innervated several MCs. Merkel endings covered about 80% of the base of the intermediate epidermal ridges that form the pattern of fingerprints. In some cases, the distal tip of a Merkel-related axon gave rise to a several terminal branches that supplied endings to tightly circumscribed (30-70 microm) clusters of Merkel cells. In other cases, the nodes of axons gave rise to en passant branches that formed extended chains of endings among Merkel cells spread over territories up to 300 microm long. Based on their relatively diffuse distributions, the axons that innervate multiple MCs or the axons with en passant Merkel terminations seem most suited to transduce tangential forces.

Animals↗
PubMed1989

Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies.

Using antibodies to the neuronal cytoplasmic protein, protein gene product 9.5 (PGP 9.5) the cutaneous innervation in man was investigated. The distribution of PGP 9.5 immunoreactive nerve fibers was compared with the distribution of nerve fibers immunoreactive to neuron specific enolase, neurofilament proteins, calcitonin gene related peptide, vasoactive intestinal polypeptide and neuropeptide Y. PGP 9.5 immunoreactive nerve fibers were found in the epidermis, dermis, in Meissner's corpuscles, innervating Merkel cells, around blood vessels, sweat glands and hair follicles. Merkel cells were also PGP 9.5 positive. The labelled nerve fibers included sensory and autonomic fibers, visualizing the whole innervation of the human skin. The number of positive fibers and the intensity of the fluorescence was greater with PGP 9.5 antibodies than with any of the other markers included. Thus, PGP 9.5 antibodies may serve as a tool for investigations of cutaneous innervation, reinnervation and nerve regeneration in different clinical conditions.

Antibodies↗
PubMed1996

Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation.

Neurotrophin-3 (NT-3) is required for the development of most sensory neurons of the dorsal root ganglia. Using electrophysiological techniques in mice with null mutations of the NT-3 gene, we show that two functionally specific subsets of cutaneous afferents differentially require this factor: D-hair receptors and slowly adapting mechanoreceptors; other cutaneous receptors were unaffected. Merkel cells, which are the end organs of slowly adapting mechanoreceptors, are virtually absent in 14-day-old homozygous mutants and are severely reduced in adult NT-3 heterozygous animals. This loss of Merkel cells, together with their innervation, happens in the first postnatal weeks of life, in contrast to muscle spindles and afferents, which are never formed in the absence of NT-3. Thus, NT-3 is essential for the maintenance of specific cutaneous afferents known to subserve fine tactile discrimination in humans.

Afferent Pathways↗
PubMedDate not supplied

[Parotid metastases of a neuroendocrine cutaneous carcinoma].

A case of metastatic Merkel-cell carcinoma to lymph nodes on the left side of the neck nad left parotid is described. Neuroendocrine cutaneous carcinoma, also called Merkel cell carcinoma (MCC), is an uncommon primary skin tumor most often seen in elderly. Literature is reviewed and comment about more important features of these lesions, like differential diagnosis, prognosis and treatment.

Aged↗
PubMed1998

Fine-needle aspiration biopsy of metastatic small cell carcinoma from extrapulmonary sites.

Like a pulmonary counterpart, extrapulmonary small cell carcinoma (SCC) is an aggressive tumor with a high rate of metastasis. Forty-nine fine-needle aspiration biopsies (FNABs) (36 patients) of various primary sites other than the lung diagnosed as metastatic SCC (including Merkel cell carcinoma) were reviewed. FNABs were derived from lymph nodes (20), liver (7), bone (2), breast (1), pancreas (1), and skin/soft tissue (18). Primary tumor sites included the prostate (14), skin (11; Merkel cell carcinoma), cervix (5), urinary bladder (3), urethra (1), ovary (1), and parotid (1). Aspirates revealed predominantly dispersed single tumor cells with occasional clustering. Tumor cells were small with scant cytoplasm, fine powdery chromatin, and inconspicuous nucleoli. Nuclear molding, mitotic figures, and apoptotic bodies were frequently observed. In four cases, findings from the FNABs were used to render the initial diagnosis of SCC. FNAB is useful for determining whether metastases contain a SCC component, a finding that may alter clinical management. Cytologically, SCC from different primary sites cannot be differentiated, and its distinction requires clinical and radiographic correlation.

Adult↗
PubMed1994

Electron microscopic examination of cutaneous lesions by the quick re-embedding method from paraffin-embedded blocks.

We attempted to evaluate whether Widéhn's quick re-embedding method from paraffin blocks is useful for dermatopathological diagnosis. Regarding fine preservation of nuclei, tono-fibrils and desmosomes of keratinocytes in normal skin, we could recognize no difference between the quick re-embedding method and traditional re-embedding methods. However, preservation of mitochondria and Birbeck granules in Langerhans cells was poor regardless of the method used. Furthermore, we studied the ultrastructural features of some viral skin diseases including molluscum contagiosum, herpes simplex, varicella-zoster and verruca vulgaris, and some skin tumors, including angioleiomyoma, angiosarcoma, Merkel cell carcinoma and amelanotic melanoma using the quick re-embedding method. We determined that all viral structures were sufficiently preserved by the quick method to observe the virions and development of the virus. Myofilaments and dense bodies of angioleiomyoma, Weibel-Palade bodies of angiosarcoma, neurosecretory granules of Merkel cell carcinoma and melanosomes of amelanotic melanoma were recognized by the quick method. From these results, we concluded that the quick re-embedding method is useful for the diagnosis of skin diseases, especially viral skin diseases and some skin tumors.

Angiomyoma↗
PubMed1996

Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group.

BACKGROUND: The unsatisfactory control of neuroendocrine tumor growth with chemotherapy and/or interferon (IFN-2a) stimulated us to investigate the role of the somatostatin analogue octreotide (SMS 201.995), which is reported to be highly effective in controlling carcinoid syndrome symptoms. Octreotide has been used in a wide range of doses, and it was postulated that higher doses might lead to an objective response. METHODS: The aim of the present multicenter Phase II study was to determine the safety and efficacy of SMS 201.995 in controlling carcinoids and other neuroendocrine tumors. Fifty-eight patients were treated subcutaneously with 2 sequential doses of the drug (Sandostatina, Sandoz, Inc., S.b.A. Pharmaceuticals, Basel, Switzerland). The first 23 patients received 500 micrograms 3 times a day and the remaining 35 patients received 1000 micrograms 3 times a day. The treatment was continued until the tumor progressed. RESULTS: All of the patients were adequately treated and evaluated. The predominant histotype was carcinoid, although there were instances of medullary thyroid carcinoma, pancreatic islet cell tumors, and Merkel cell carcinoma. Carcinoid syndrome was documented in 16 patients and abnormal urinary 5-hydroxyindoloacetic acid excretion in 15. The median treatment duration was 5 months (range, 2-31 months). The responses were evaluated in three categories: tumor regression for tumor growth control, symptom response, and biochemical response. There was an effect on tumor growth in two patients with carcinoids. Symptomatic control was achieved in 73% of patients and a biochemical response in 77% of patients. In twenty-seven patients, the disease stabilized for at least 6 months (range, 6-32+). The median survival time for all patients was 22 months (range, 1-32+). CONCLUSIONS: In terms of tumor regression, octreotide is disappointing (partial response: 3%); symptomatic response and biochemical control are satisfactory. These data confirm that somatostatin analogues are comparable to interferons in the treatment of carcinoid syndrome, although other efforts are necessary to control tumor regression.

Adenoma, Islet Cell↗
PubMed1992

Immunohistological and immunoelectron microscopic identification of TNF alpha in normal human and murine epidermis.

The presence, distribution and cellular localization of tumour necrosis factor-alpha (TNF alpha) were investigated in normal human and murine epidermis using immunohistological and immunoelectron microscopic methods with monoclonal and polyclonal antibodies. The immunostaining revealed an intercellular plasma membrane and cytoplasmic labelling of the epidermal keratinocytes, but no labelling of Langerhans cells, melanocytes and Merkel cells. Large amounts of TNF alpha were regularly found in the sebaceous glands. These findings demonstrate that epidermal keratinocytes and especially sebocytes produce and release TNF alpha and that this keratinocyte-derived cytokine may be important for the structural and functional homeostasis of normal epidermis.

Adult↗
PubMed1991

Development of taste organs in Rana temporaria. Transmission and scanning electron microscopic study.

In tadpoles of Rana temporaria two successive generations of taste organs: taste buds (TBs) and taste disks were studied. The TBs are located in the apices of oral premetamorphic papillae. Each TB consists of vertically elongated receptor cells (probably taste) and supporting cells. No basal (Merkel) cells were observed there. Morphologically, two types of receptor cells have been distinguished in a TB. Complete synaptic structures were observed in the TBs between the 30th and 41st of Gosner's (1960) developmental stages, though synaptic vesicles occur already at stage 26. The taste disks consist of taste cells, supporting cells and basal cells. Dense-core synaptic vesicles occur in the gustatory cells at stage 41, but complete synaptic structures were not observed earlier than at stage 45. Synaptic junctions observed at some of the gustatory cells seem to be reciprocal (bidirectional).

Animals↗