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PubMed1976

[Hyde's nodular prurigo: an electronmicroscopic study].

Electron microscopic studies were carried out on cutaneous lesions in one case of prurigo nodularis Hyde. The cells of the basal layer partly showed large paranuclear vacuoles, which were sometimes divided by thin membrane structures. The intercellular space of the stratum basale and stratum spinosum was usually dilated, exhibiting acantholytic phenomen. Furthermore, numerous cells of these layers contain vacuolic-like mitochondria and polymorphous granular structures. Melanocytes and Langerhans-cells have not been observed, however, Merkel-cells were found in the basal layer, containing characteristic electrondense granules measuring 80 to 100 nm in diameter. The stratum granulosum frequently showed large intercellular complexes of numerous desmosomes, which sometimes were forming desmosomal bridges crossing the intercellular space. The capillaries in the dermis were usually widened and frequently surrounded by edematous alterations. The cytoplasm of the endothelial cells appeared very electrondens. Numerous unmyelinated axons were observed within the subepidermal zone containing mitochondria and single granules, measuring 80 to 100 nm in diameter.

Adult↗
PubMedDate not supplied

Association of cutaneous side-effects of hydroxyurea and neuroendocrine carcinoma.

Many cutaneous side-effects of long term use of hydroxyurea (HU) therapy are well known. We report the first case, to our knowledge, of a neuroendocrine carcinoma located on the finger associated with other cutaneous changes due to this drug. Our patient received HU for two years for an thrombocytemia. This treatment was stopped because of a dermatomyositis-like eruption. Two years later, she developed multiple keratotic lesions, and eight years later, an Merkel cell carcinoma on the third left finger with metastasic evolution. This case suggests HU could be a cofactor of this neuroendocrine carcinoma but a simple coincidence could not be excluded.

Aged↗
PubMed1998

Possible role of serotonin in Merkel-like basal cells of the taste buds of the frog, Rana nigromaculata.

Merkel-like basal cells in the taste buds of the frog were examined by fluorescence histochemistry, immunohistochemistry and electron microscopy. There were about 16-20 basal cells arranged in a radial fashion at the base of each taste bud. These cells were strongly immunopositive for serotonin antiserum. They were characterised by the presence of numerous dense-cored granules in the cytoplasm ranging from 80 to 120 nm in diameter, and of microvilli protruding from the cell surface. For 4 mo after sensory denervation by cutting the gustatory nerves, all cell types of the taste bud were well preserved and maintained their fine structure. Even at 4 mo after denervation, the basal cells exhibited a strong immunoreaction with serotonin antiserum. To investigate the function of serotonin in the basal cells in taste bud function, serotonin deficiency was induced by administration of p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, and of p-chloroamphetamine (PCA), a depletor of serotonin. After administration of these agents to normal and denervated frogs for 2 wk, a marked decrease, or complete absence, of immunoreactivity for serotonin was observed in the basal cells. Ultrastructurally, degenerative changes were observed in both types of frog; numerous lysosome-like myelin bodies were found in all cell types of the taste buds. The number of dense-cored granules in the basal cells also was greatly decreased by treatment with these drugs. Serotonin in Merkel-like basal cells appears to have a trophic role in maintenance of the morphological integrity of frog taste bud cells.

Animals↗
PubMed1994

[Cutaneous neuroendocrine carcinoma of the external ear canal].

Authors report a case of a neuroendocrine carcinoma (Merkel cell tumor) located in the external meatus. These tumors have a fearsome prognostic. Immunohistochemical study has become indispensable to make the diagnosis. A literature review is presented, and therapeutic choices discussed. Wide and precocious surgical resection is advised.

Aged↗
PubMed1998

Localized limb cutaneous metastases.

Cutaneous metastatic disease may be evident in a variety of forms and locations. Anatomically, it may on occasion be confined as localized limb metastases. We report on two patients with localized limb metastases, one from melanoma and the other from Merkel cell carcinoma. Patients with localized limb metastasis have a poor prognosis; however, treatment options not available for generalized cutaneous metastatic disease, such as amputation or isolated limb perfusion with chemotherapeutic agents, can be at times be beneficially employed.

Aged↗
PubMed2003

Distribution of GAP-43 nerve fibers in the skin of the adult human hand.

Skin is an important region of somatic sensory input, and is one of the most innervated areas of the human body. In this study, we investigated in human hand skin the distribution of nervous structures immunoreactive for the growth-associated protein 43 (GAP-43) and the protein gene product 9.5 (PGP 9.5). GAP-43 is a neuronal presynaptic membrane protein that is generally considered to be a marker of neuronal plasticity. PGP 9.5 is a neuron-specific soluble protein that is widely used as general marker for the peripheral nervous system. The entire neural network of the dermis and epidermis was stained with antibody to PGP 9.5. In the dermis, there were fewer GAP-43-immunostained nerve fibers than PGP 9.5-immunostained nerve fibers, whereas in the epidermis the numbers were equal. Only some Merkel cells and Meissner corpuscles were GAP-43-immunoreactive. In conclusion, our results show that GAP-43 protein is expressed in a subset of PGP 9.5-immunoreactive nerve structures.

Adult↗
PubMed1992

[Merkel's tumor. Some comments and the authors' personal cases].

The clinical features of 7 cases of primary neuroendocrine carcinoma of the skin (Merkel cell tumor) are reported. This cancer arises in the dermis and subcutaneous tissues of elderly individuals. Natural history is characterized by local recurrences (30%), regional lymph node metastases (65%) and distant metastases (40%). Surgery is the elective treatment, chemotherapy and radiotherapy resulted in only short-term palliative response.

Aged↗
PubMed2006

Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat.

Hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic spontaneous neuronal activity has been implicated in the development and maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain. Previously, we documented that systemic administration of ZD7288, a specific blocker of pacemaker current (I(h)), decreased ectopic activity in dorsal root ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief clinical manifestation of peripheral nerve injury; however, a role for I(h) in spontaneous pain has not been described. Here, in further rat studies, we report that systemic administration of ZD7288 reversed spontaneous pain induced by mild thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast, ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears to be in the skin since intraplantar (local) administration of ZD7288 completely suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous pain due to MTI. Immunohistochemical staining of plantar skin sections detected HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles and Merkel cells). Collectively, these data suggest that expression and modulation of I(h) in the peripheral nervous system, including specialized sensory structures, may play a significant role in sensory processing and contribute to spontaneous pain and tactile allodynia.

Acute Disease↗
PubMedDate not supplied

Antibodies to cerebellar nerve fibres in two patients with paraneoplastic cerebellar ataxia.

The aim of this study was to characterize two new atypical anti-neuronal antibodies using an immunohistochemical method on rat cerebellum and Western blot techniques with primate cerebellar tissue and with recombinant neuronal proteins. Atypical sera from two patients with paraneoplastic neurological syndromes associated with different tumours were detected. Case number 1 presented cerebellar degeneration and Merkel cell carcinoma and case number 2 paraneoplastic brainstem encephalitis and malignant fibrous histiocytoma. By immunohistochemistry, the two new atypical antibodies showed a similar fibrillar positivity in the molecular and granular layers and around the Purkinje cells. The dot blot with recombinant neuronal proteins (HuD, NOVA-1, CDR62/Yo, Amphiphysin) was negative, whereas the Western blot with neuronal antigens of primate cerebellum identified two different proteins with molecular weights (64 kD in case number 1, and 70 kD in case number 2). In conclusion, the two new antibody reactivities against nerve fibres should be integrated into the diagnostic paraneoplastic neurological syndromes guidelines.

Animals↗
PubMed1998

[Primary neuroendocrine carcinoma of the skin: clinical case].

A case of Merkel cell carcinoma of the skin is described. It is a rare primary skin tumor originating within the dermis with an aggressive biologic behavior. Clinical presentation of these tumors are not sufficiently distinctive to allow the preoperative diagnosis. Wide surgical excision with postoperative irradiation to the local site and regional lymphatics is recommended as the therapy of choice. Indications for chemotherapy are discussed and the guidelines for an appropriated follow-up are reported.

Aged↗
PubMed1999

Sentinel node biopsy as a surgical staging method for solid cancers.

The sentinel node is the first lymph node that drains a primary tumour. If this lymphatic drainage occurs in a step-wise fashion, this lymph node reflects the pathological status of the remaining lymph node basin. The day before the operation, a total dose of 60 MBq 99mTc nanocolloid is injected around the primary tumour for lymphoscintigraphy. On the day of surgery, 1 ml of blue dye is injected around the primary tumour to facilitate sentinel lymph node detection. After making a small incision over the regional lymph node region, the sentinel node can be detected using a hand-held gamma ray detection probe; the sentinel lymph node and the afferent lymphatic vessels will be stained blue. Sentinel node biopsy has proved useful for malignant melanoma, breast cancer, penile cancer, vulvar cancer, Merkel cell carcinoma and thyroid cancer. New studies are described on breast cancer and malignant melanoma. Gamma-probe-guided localization of radiolabelled lymph nodes can direct the surgeon non-invasively to the exact location of the sentinel node. Once localized with a gamma probe, it is quick and easy to remove the sentinel node through a small incision. Discriminating the node from other tissue can be aided by blue dye which stains the lymph node. It appears that both radioactivity and blue dye are complementary for locating the sentinel node.

Biopsy↗
PubMed1992

An analysis of prognostic factors in cutaneous neuroendocrine carcinoma.

Since the first report of cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) in 1972, knowledge of the biological behavior of this tumor has continued to increase. This study reviews three previously unreported cases in addition to reports on 429 patients collected from the literature. The presenting features of these 306 patients were analyzed for frequency and then were analyzed by the Cox proportional hazard model for the relationship of each to recurrence and outcome. This study confirms that cutaneous neuroendocrine carcinoma is an aggressive disease; that the most common cause of death in these patients is by distant metastasis; and that men have succumbed more frequently than women. As a result of this study, aggressive treatment of cutaneous neuroendocrine carcinoma is recommended, especially in the male patient.

Aged↗
PubMed1990

Detection of somatic mutations in tumours of diverse types by DNA fingerprinting with M13 phage DNA.

Hybridization of M13 phage DNA to Southern blots of human DNA produces an individual-specific DNA fingerprint. In this study, tumour and lymphocyte DNA from a series of patients with melanoma, Merkel-cell carcinoma, Burkitt's lymphoma and Wilms' tumour was probed with M13 DNA to detect somatic mutations in the DNA of the tumours. Somatic changes were observed in tumour DNA of 16 out of the 28 cases examined. This frequency compared favourably with the frequency with which tumour-specific changes have been found when using the Jeffreys DNA fingerprinting probe 33.15, and demonstrates that M13 DNA provides a useful additional probe for the study of somatic changes in tumours. The finding that multiple DNA fragments were lost or gained in DNA fingerprints from individual tumours indicates a marked degree of complexity in the genetic changes involved in the evolution of certain human cancers.

Bacteriophages↗
PubMed1985

Expression of neurofilament and neuron-specific enolase in small cell tumors of skin using immunohistochemistry.

Trabecular carcinoma of the skin (Merkel cell tumor), a neoplasm of putative neural origin, must be differentiated from other small cell tumors primary or metastatic to skin. In order to provide more objective diagnostic criteria, four were examined using monoclonal antibodies against neurofilament proteins (NF) and antiserum specific for neuron-specific enolase (NSE). Immunohistochemistry demonstrated immunoreactive NF in three and NSE in four cases. NF immunoreactivity was arranged in paranuclear balls, consistent with ultrastructural observations of aggregated intermediate filaments. A case of pulmonary oat cell carcinoma metastatic to the skin also contained immunoreactive NF and NSE. Although NF and NSE do not discriminate metastatic oat cell carcinoma from trabecular carcinoma of skin, they are useful antigens that provide objective criteria for recognizing tumors of neural histogenesis or neural differentiation. They should make it possible to exclude non-neural lesions from the differential diagnosis of small cell tumors of the skin.

Adolescent↗
PubMedDate not supplied

[Skin neuroendocrine carcinoma metastasis: a case report].

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive skin tumour with a highly malignant nature whose appropriate treatment is still debated. The Authors report a case of cutaneous metastasis from neuroendocrine carcinoma and analyse new diagnostic and therapeutic options of neoplasms that occurs in sun-exposed areas. METHODS: The authors present the clinical, immunocytochemical characteristic of primary and secondary skin localization of a neuroendocrine tumor that affected a woman. RESULTS: Histological and immunocytochemical analysis demonstrated that the secondary cutaneous localization appeared to be compared to the primary tumour. CONCLUSIONS: The case confirm the high incidence of regional metastasis; a wide surgical excision of tumor and regional lymphadenectomy is therefore recommended for primary treatment of MCC; the radiation treatment minimized the local recidives with long time survival.

Aged, 80 and over↗
PubMed2001

Sentinel lymph node mapping in melanoma with technetium-99m dextran.

PURPOSE: The aim of this work is to evaluate the capability of Tc99m B Dextran as a lymphoscintigraphic agent in the detection of the sentinel node in skin lesions. MATERIALS AND METHODS: Forty-one patients with melanomas (39) and Merkel cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours before surgery. Serial gamma camera images and a handheld gamma probe were used to direct sentinel node biopsy. RESULTS: In 39/41 patients, lymph channels and 52 sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one patient, with a dorsal melanoma, no lymph channels or lymph nodes could be demonstrated on the images and only minimal radioactivity was found in the regional nodes with the probe. Another patient with a facial lesion failed to demonstrate lymph channels or nodes. No adverse reactions were observed. CONCLUSION: Tc99m-Dextran provided good definition of lymph channels and sentinel node localization, without the risks related to the use of potentially hazardous labeled materials of biological origin.

Adolescent↗
PubMed2005

[Neuroendocrine tumor of the skin of head and neck].

BACKGROUND: Merkel cell carcinom is a rare neuroendrocine tumor of skin which manifests it self through aggressive growth and early regional metastasis. It develops mainly in older population. Locally, the tumor spreads intracutaneously. CASE REPORT: We showed two cases (females of 89 and 70 years old) hospitalized within the last two years. The first patient was treated surgically three times. After the surgery, the patient was treated with radio therapy, and died 3 years from the begining of the treatment. The second patient with this neuroendocrine tumor with the high malignacy potential and huge regional metastasis, was treated surgiclly, and died a month and a half after the operation. CONCLUSION: These two cases confirmed the aggressive and recidivant growth of this tumor with the difficut pathologic investigetion, and the extremlly bad prognosis inspite of the treatment.

Aged↗