Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Merkel Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,333 records · Page 74Linked to original sources
PubMed2007

Infrahyoid fascio-myocutaneous flap as an alternative to free radial forearm flap in head and neck reconstruction.

BACKGROUND: The use of microvascular free flaps is currently the favored method for the reconstruction of defects after resection of head and neck cancer. The flap most commonly used for head and neck reconstruction is the free radial forearm flap, but the less popular infrahyoid flap represents a good alternative in selected cases. This flap has proven to be helpful in the reconstruction of a wide range of moderate-sized head and neck defects. METHODS: We reviewed a series of 13 patients with defects resulting from cancer of the head and neck, who underwent infrahyoid flap reconstruction as an alternative to free radial forearm flap. The series includes 12 squamous cell carcinomas arising from the oral cavity and oropharynx, and 1 Merkel cell carcinoma of the submental skin. In the harvesting of the flap, the technical modifications recently suggested by Dolivet et al were used in all cases. Furthermore, another technical change has been introduced so creating a new infrahyoid facio-myocutaneous flap (IHFMCF). The surgical technique is described in detail. RESULTS: No total or partial flap necrosis was experienced. All reconstructions healed quickly without wound complications and with good functional results. The healing process in the donor site was excellent in every case with good aesthetic results. CONCLUSIONS: The IHFMCF is a versatile, reliable, and convenient flap suitable for repairing small and medium-sized defects of the oral cavity and oropharynx and obviates the need for a microvascular reconstruction.

Adult↗
PubMed2005

The chemoresistance gene ABCG2 (MXR/BCRP1/ABCP1) is not expressed in melanomas but in single neuroendocrine carcinomas of the skin.

BACKGROUND: As the molecular mechanisms in melanoma chemoresistance remain unknown to date, we hypothesized these tumors to express the ATP-binding cassette (ABC) transporter G2 (ABCG2/MXR/BCRP1/ABCP1), a recently detected membrane transporter and putative stem-cell marker. Besides melanoma, we addressed the neuroendocrine carcinoma of the skin (Merkel cell carcinoma), another cutaneous cancer supposed to originate from neuroectoderm and usually chemoresistant. METHODS AND RESULTS: Upon semiquantitative reverse transcription polymerase chain reaction, ABCG2 mRNA expression was not upregulated in 18 melanoma resection specimens when compared with 19 acquired melanocytic nevi from which melanomas are known to often arise (Mantel-Haenszel test, p=0.3). At protein level, immunohistochemistry was negative in all 66 investigated melanoma resection specimens (50 primary melanomas and 16 cutaneous/subcutaneous metastases) and in 19 acquired melanocytic nevi. Among 29 neuroendocrine carcinomas of the skin, ABCG2 protein was detected in single clusters of cells in three tumors. As a positive control, three dermatofibrosarcomas were also stained and showed ABCG2 protein expression of the endothelial cells of the blood vessels. CONCLUSION: Altogether, chemoresistance of melanomas and neuroendocrine carcinomas of the skin cannot be explained by expression of the ABCG2-chemoresistance gene. Most of these tumors do not exhibit this potential stem-cell feature.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1990

Incidence of cutaneous T cell lymphoma and other rare skin cancers in a defined population.

Between 1970 and 1984 in Rochester, Minnesota, rare skin cancers developed in 15 local residents: cutaneous T cell lymphoma (six subjects), dermatofibrosarcoma protuberans (four), adenocarcinoma of sweat glands (two), Merkel cell carcinoma (one), liposarcoma (one), and extramammary Paget's disease (one). These cases were identified through a unique computerized retrieval system that is maintained at the Mayo Clinic for the population of Rochester, Minnesota. The annual incidences of these cancers in the Rochester population were 0.9, 0.5, 0.3, 0.2, 0.2, and 0.2 per 100,000 residents, respectively (standardized to 1980 U.S. population). To our knowledge, this is the first report of the incidences of these rare skin cancers in a well-defined population.

Adenocarcinoma↗
PubMed1999

Overexpression of brain-derived neurotrophic factor enhances sensory innervation and selectively increases neuron number.

Target-derived neurotrophin growth factors have significant effects on the development and maintenance of the mammalian somatosensory system. Studies of transgenic mice that overexpress neurotrophins NGF and neurotrophin 3 (NT-3) at high levels in skin have shown increased sensory neuron number and enhanced innervation of specific sensory ending types. The effects of two other members of this family, BDNF and NT-4, on sensory neuron development are less clear. This study examined the role of brain-derived neurotrophic factor (BDNF) using transgenic mice that overexpress BDNF in epithelial target tissues of sensory neurons. BDNF transgenic mice had an increase in peripheral innervation density and showed selective effects on neuron survival. Neuron number in trigeminal ganglia, DRG, and SCG were unchanged, although a 38% increase in neurons comprising the placode-derived nodose-petrosal complex occurred. BDNF transgenic skin showed notable enhancement of innervation to hair follicles as detected by PGP9.5 immunolabeling. In nonhairy plantar skin, Meissner corpuscle sensory endings were larger, and the number of Merkel cells with associated innervation was increased. In trigeminal ganglia, neurons expressing trkB receptor were increased threefold, whereas trkA-positive neurons doubled. Analysis of trkB by Northern, reverse transcription-PCR, and Western assays indicated a modest increase in the expression of the T1 truncated receptor and preferential distribution to the periphery. These data indicate that skin-derived BDNF does not enhance survival of cutaneous sensory neurons, although it does promote neurite innervation of specific sites and sensory end organs of the skin.

Animals↗
PubMed1993

Treatment of metastatic carcinoids and other neuroendocrine tumors with recombinant interferon-alpha-2a. A study by the Italian Trials in Medical Oncology Group.

BACKGROUND: Using a wide range of interferon (IFN) doses and schedules, a number of authors have found them to be active against neuroendocrine tumors. METHODS: To verify the clinical activity of IFN, 49 evaluable patients with advanced stage low- and intermediate-grade neuroendocrine tumors were treated with recombinant IFN-alpha-2a at a daily dose of 6 x 10(6) IU intramuscularly for 8 weeks, and 3 times weekly thereafter. The predominant histotype was carcinoid, although a few cases had malignant islet cell tumors, medullary thyroid carcinoma, Merkel cell carcinoma, or other neuroendocrine tumors. All of the patients had measurable lesions and most had multiple sites. Carcinoid syndrome was present in 14 cases. RESULTS: After a median treatment duration of 6 months, complete regression was achieved in 1 of the 7 cases of medullary thyroid carcinoma, and partial response was observed in 4 of 34 carcinoids. Response duration ranged from 1-11 months. Control of the syndrome was obtained in nine patients and a greater than or equal to 50% reduction of 5-hydroxyindoleacetic acid in eight patients. The treatment was well-tolerated. The most frequently observed side effects were fever, flu-like syndrome, and leukopenia. After 12 months of recombinant IFN-alpha-2a, 15 cases in progression and 4 with stable disease or partial response received another treatment (either radiometabolic therapy with I131 metaiodobenzylguanidine or polychemotherapy with streptozotocin plus epirubicin). CONCLUSIONS: The use of recombinant IFN-alpha-2a at these doses is well-tolerated and effective in controlling carcinoid syndrome (complete remission plus partial remission, 64%), although it has limited activity on tumor growth inhibition. No definitive data can be given for the other protocol treatments.

Adult↗
PubMed2006

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli.

The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca2+. In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steadystate length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells.

Actin Cytoskeleton↗
PubMed2004

Skin cancers in renal-transplant recipients occur more frequently than previously recognized in a temperate climate.

BACKGROUND: Renal-transplant recipients are at increased risk of developing skin cancers, especially squamous cell carcinoma. We have carried out a comprehensive epidemiologic review of skin cancers occurring in a population receiving transplants in Oxford over a 21-year period, where nearly all patients have remained under the care of the Oxford Transplant Centre. METHODS: Between 1975 and 1996, 1,360 renal transplants were performed in 1,115 patients. Skin cancer data were reviewed in 979 patients from this group who remained under the care of the Oxford Transplant Centre. The lesions included in the analysis were histologically confirmed basal cell carcinoma, Bowen's disease, squamous cell carcinoma, keratoacanthoma, malignant melanoma, Merkel cell tumor, and sebaceous carcinoma. RESULTS: One hundred eighty-seven (19.1%) transplant patients developed at least one skin malignancy. The rate of skin cancer was 141 per 1,000 person years at risk. Sixty-four percent of patients with skin cancer had multiple lesions (maximum 50). Squamous cell carcinoma was the most common skin cancer to develop and the most common first skin cancer to present. The mean time to presentation of the first skin cancer was 8 years. Six patients developed nodal metastases, and two patients died secondary to skin cancer. Risk factors identified were increasing age at transplantation, recipient sex, total time of exposure to immunosuppression, increased creatinine levels at 1 year, and graft relation. The cumulative incidence of skin cancer reached 61% at 20 years after transplantation. CONCLUSION: The data from this study suggest that more patients develop skin malignancies than previously reported from Europe. It is important to advise patients before transplantation in regard to skin complications, provide regular dermatological follow-up, and tailor immunosuppressive regimen to minimum doses to be compatible with good graft function.

Carcinoma, Squamous Cell↗
PubMed1975

The epidermal-dermal junction.

Ultrastructurally, the epidermal-dermal junction is composed of four component areas:(1) the basal cell plasma membrane with its specialized attachment devices or hemidesmosomes, (2) an electron-lucent area, the lamina lucida, (3) the basal lamina, and (4) the sub-basal lamina fibrous components, including anchoring fibrils, dermal microfibril bundles, and collagen fibers. The light microscopic "basement membrane" comprises only the sub-basal lamina fibrous zone. Other cell types, including melanocytes and Merkel cells, are also found at the epidermal-dermal junction. Structures at the junction derive their origin from the epidermis and dermis: the basal lamina is primarily of epidermal origin, the anchoring fibrils of dermal origin. The junction serves the following functions: (1) epidermal-dermal adherence, (2) mechanical support for the epidermis, and (3) a barrier to the exchange of cells and of some large molecules across the junction.

Animals↗
PubMed1981

Ultrastructure of trichoepithelioma papulosum multiplex.

The following features of trichoepithelioma papulosum multiplex (TPM) were revealed by electron microscopy: 1. Proliferation of basaloid cells similar to that in basal cell epithelioma (BCE). 2. Abortive hair shafts and hair papillae. 3. Keratinous cysts surrounded by flat keratinocytes, the cytoplasm of which had small-sized keratohyalin and Odland's bodies. 4. Glycogen deposition near the nuclei, vacuoles filled with amorphous materials and lipid droplets in the cytoplasm of tumor cells. 5. Extracellular compartments, in which fibrous materials, cell fragments, and mucinous substance were found. 6. Melanocytes containing melanosomes in stage II, Langerhans cells involving Birbeck's granules, Merkel cells and other dendritic cells.

Adult↗
PubMed2006

Immunohistochemical staining for adipophilin, perilipin and TIP47.

BACKGROUND: The presence of lipid in the cell cytoplasm is useful for supporting the diagnosis of sebaceous gland carcinoma (SGC). Currently this requires histochemical stains that are carried out on frozen sections of unprocessed tissue. Recently, several anti-adipocytic antibodies that recognise proteins associated with lipid vesicles have been described. These antibodies can be applied to paraffin-wax sections. AIM: To assess the ability of anti-adipocytic antibodies to identify intracytoplasmic lipid in SGC. METHODS: Immunohistochemistry with a monoclonal antibody to adipophilin and polyclonal antibodies to perilipin and TIP47/PP17 was carried out on archival, formalin-fixed, paraffin-wax-embedded sections of 26 samples of SGC. The immunostaining was compared with 22 other eyelid tumours (11 basal cell carcinomas (BCC), 10 squamous cell carcinomas (SCC) and 1 Merkel cell tumour). RESULTS: Immunohistochemical staining was positive in 23, 10 and 2 cases of 26 SGC with adipophilin, perilipin and TIP47, respectively. The positive staining identified cytoplasmic lipid vesicles. Anti-adipophilin was positive in five other eyelid tumours (4 BCC and 1 SCC) staining small cytoplasmic granules that can be easily distinguished from the staining in SGC. CONCLUSIONS: Immunohistochemical staining for adipophilin and perilipin is a useful ancillary technique for the demonstration of lipid in SGC that may be applied to paraffin-wax sections.

Adenocarcinoma, Sebaceous↗
PubMed2000

Expression of the chemokine receptor CXCR2 in normal and neoplastic neuroendocrine cells.

BACKGROUND: Chemokines effect their proinflammatory and growth regulatory roles through interaction with serpentine receptors. One such receptor, CXCR2, binds multiple CXC chemokines, including interleukin 8, GRO-alpha, GRO-beta, GRO-gamma, and NAP-2. We have previously identified CXCR2 expression on myeloid cells, notably mature granulocytes, and projection neurons. OBJECTIVE: To determine the expression of CXCR2 by cells of the neuroendocrine system. DESIGN: Archival specimens from normal neuroendocrine tissues and their malignant counterparts were analyzed by immunohistochemistry with monoclonal antibodies specific for CXCR1 and CXCR2. RESULTS: Immunohistochemical analysis revealed high-level expression of CXCR2 by cells in the pituitary, adrenal medulla, pancreatic islets, thyroid C cells, scattered Kulchitsky cells in the bronchi, and counterpart neuroendocrine cells in the stomach, small bowel, colon, and appendix. Neuroendocrine neoplasms that demonstrated high-level CXCR2 expression included (1) primary carcinoids localized to the stomach, small bowel, colon, appendix, fallopian tube, ovary, and lung; (2) atypical carcinoids of the lung; (3) metastatic carcinoids; (4) pituitary adenomas; (5) pheochromocytomas; and (6) medullary carcinomas of the thyroid. Small cell lung carcinomas, large cell neuroendocrine carcinomas of the lung, small cell carcinoma of the cervix, Merkel cell carcinomas, neuroblastomas, and malignant melanomas lacked evidence of CXCR2 expression. CONCLUSIONS: The expression of CXCR2 by normal neuroendocrine cells and neoplastic counterparts that have retained phenotypic features of this differentiation program suggests that chemokines may play an important role in functions that are characteristic of this cell type. In addition, this raises the possibility that chemokines may modulate secretion of biologically active products of these cells and their neoplastic counterparts.

Antibodies, Monoclonal↗
PubMed2000

Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases.

PURPOSE: To study the use of chemotherapy for Merkel cell carcinoma (MCC) of the skin. PATIENTS AND METHODS: Twenty-five cases of MCC were treated at the London Regional Cancer Center between 1987 and 1997. Thirteen cases treated with chemotherapy were reviewed with 191 cases from the literature. RESULTS: At presentation, 24 patients had localized skin lesions (stage I) and one had locoregional involvement (stage II). Among the nine cases with recurrent nodal disease, six had chemotherapy as a component of salvage treatment. They were all free of disease at a median of 19 months (range, 12 to 37 months). In contrast, two patients who had salvage radiotherapy alone died of disease. Overall survival (OS) and disease-free survival (DFS) were 59% and 43%, respectively, at two years. Median OS and DFS were 29 months (range, 1 to 133 months) and 9 months (range, 1 to 133 months), respectively. Nodal disease developed in 12 (50%) of 24 patients with stage I disease, and distant metastases developed in six (25%) of 24. Including those from the literature, there were 204 cases treated with chemotherapy. Cyclophosphamide/doxorubicin (or epirubicin)/vincristine combination +/- prednisone was the most commonly used chemotherapy regimen (47 cases), with an overall response rate of 75.7% (35.1% complete, 35. 1% partial, and 5.4% minor responses). Etoposide/cisplatin (or carboplatin) was the next most commonly used regimen (27 cases), with an overall response rate of 60% (36% complete and 24% partial responses). The difference in response rate was not statistically significant (P =.19). Among the 204 cases, there were seven (3.4%) toxic deaths. CONCLUSION: Chemoradiation for locally recurrent or advanced disease may be an option for patients with a good performance status.

Aged↗
PubMed1995

Innervation of the human vaginal mucosa as revealed by PGP 9.5 immunohistochemistry.

In order to obtain a description of the innervation of the vaginal wall we employed an antiserum against the general neuronal marker, protein gene product 9.5, on normal human vaginal mucosa. Specimens were taken from the anterior and posterior fornices, from the anterior vaginal wall at the bladder neck level and from the introitus vaginae region, and then processed for indirect immunohistochemistry. All regions studied revealed a profound innervation, although regional differences were noted. The more distal areas of the vaginal wall had more nerve fibers compared to the more proximal parts. Also, biopsies from the anterior wall generally were more densely innervated than the posterior wall. Some large nerve coils were observed in lamina propria of the anterior wall as well as gatherings of thick-walled medium-sized blood vessels. Free intraepithelial nerve endings were only detected in the introitus vaginae region. These fibers were very thin, always varicose and could be observed just a few cell layers from the surface. In this part of the vagina, protein gene product 9.5 antibodies also stained cells within the basal parts of the epithelium. These cells were also neurone-specific enolase positive and resembled, from a morphological point of view, Merkel cells.

Female↗
PubMed1996

Scanning electron microscopy of the basal surface of the epidermis of human digits.

The epidermal-dermal junction of the volar skin of human digits was examined by scanning electron microscopy (SEM). Fixed specimens obtained from cadavers were treated with 6 N NaOH to exfoliate the epithelium. The three-dimensional features of the basal surfaces were clearly visualized by SEM. Epithelial prolongations (intermediate and limiting ridges) protruded towards the dermis, and transverse ridges were visible between them. Nerve fibers and Schwann cells were aggregated around the sweat ducts on the intermediate ridges. Discoid structures were visible among the nerve fibers and Schwann cells. Examination by transmission electron microscopy of ultrathin sections of re-embedded specimens confirmed that the discoid structures were nerve endings that covered the Merkel cells. Minute projections were studded on the basal surfaces of basal keratinocytes. The projections in the intermediate ridges appeared to be villous, whereas the profiles of those in the limiting ridges resembled cobblestones. This morphological difference might be a reflection of function.

Aged↗
PubMed2004

Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody.

FLI-1 nuclear transcription factor has been proposed as a useful tool in the differential diagnosis of small round cell sarcomas. Recently, FLI-1 has been reported as the first nuclear marker of endothelial differentiation. However, its clinical use has been hampered by major interpretation problems, due to the presence of background staining as well as staining variation between different lots of the same antiserum. In this study, a novel monoclonal antibody raised against the carboxyl terminal of the FLI-1 protein (clone GI146-222, BD Pharmingen) was tested in a series of small round cell and vascular neoplasms. Furthermore, in order to assess FLI-1 specificity, we analyzed its expression in a series of common epithelial and nonepithelial malignancies. In total, 15 Ewing's sarcomas, 10 rhabdomyosarcomas, 5 desmoplastic small round cell tumors, 10 synovial sarcomas, 10 high-grade pleomorphic sarcomas, 10 malignant melanomas, 5 Merkel's carcinomas, 10 colonic adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, 20 angiosarcomas, 5 epithelioid hemangioendotheliomas, 10 Kaposi's sarcomas and 10 benign hemangiomas, were stained. A strong FLI-1 immunoreactivity was detected in all Ewing's sarcomas and vascular neoplasms, highlighting the high sensitivity of FLI-1 monoclonal antibody. However, 2/5 Merkel's carcinomas and 1/10 malignant melanomas showed a strong nuclear immunostaining, suggesting that FLI-1 may not be so helpful in the differential diagnosis of cutaneous Ewing's sarcoma. In addition, a weak immunoreactivity was found in 3/5 Merkel cell carcinomas, 3/10 synovial sarcomas, 5/10 malignant melanomas, 6/10 lung adenocarcinomas and in 1/10 breast carcinomas. In contrast, all the rhabdomyosarcomas, desmoplastic small round cell tumors, high-grade pleomorphic sarcomas and colonic adenocarcinomas tested were negative. Importantly, in contrast with previous studies, no background staining was observed. Our results indicate that FLI-1 monoclonal antibody can be reliably applied to the differential diagnosis of small round cell neoplasms of soft tissue, and confirm its important role as nuclear marker of endothelial differentiation, mainly helpful in those cases in which technical artifacts are seen by using the traditional membranous and cytoplasmic endothelial markers.

Antibodies, Monoclonal↗
PubMed1996

Degeneration and regeneration of cutaneous sensory nerve formations.

Auxiliary structures of the cutaneous sensory nerve formations (SNF) are dependent on sensory innervation during their critical period of development. Denervation of mature cutaneous corpuscles results in survival of the terminal Schwann cells and the capsular structures which are probably responsible for successful reinnervation of the cutaneous SNF. In addition, the basal lamina tubes of Schwann cells are connected with the terminal Schwann cells and play an important role in the guidance of regrowing axons to their original targets. Long-lasting denervation causes atrophic changes of the terminal Schwann cells and alterations of their molecular equipment. These atrophic changes in the terminal Schwann cells may be responsible for erroneous reinnervation of cutaneous SNF. A population of the cutaneous Merkel cells surviving denervation may also serve as targets for regrowing sensory axons. The basal laminae of terminal Schwann cells are produced under control of the sensory terminals during maturation of cutaneous SNF. In adult animals, the basal laminae are capable of stimulating differentiation of migrated Schwann cells to the terminal Schwann cells without the presence of the sensory terminals. Nonspecific cholinesterase (nChE) is secreted by the terminal Schwann cells and is attached to their extracellular matrix. The synthesis of these molecules in adult animals is not influenced by the sensory terminals. However, the presence of nChE molecules is associated with living terminal Schwann cells. Fetal orthotopically grafted dorsal root ganglion (DRG) neurons have the ability to reinnervate cutaneous SNF of adult hosts. When cutaneous areas are denervated, axons from adjacent sensory nerves may extend collateral branches into this area. The capacity for such extension is dependent on: (1) type of sensory nerve ending, C and A delta fibers having significantly greater capacity than sensory axons of larger caliber; (2) age of the animal, immature animals generally showing a greater capacity for collateral sprouting; (3) the state of the adjacent axons, those already in a growth mode being more capable than "resting" ones; and (4) the regional and mechanical conditions at the site of denervation, hindpaw skin being much less extensively reinnervated by collateral fibers than that of the trunk.

Animals↗
PubMed2005

Mohs micrographic surgery: established uses and emerging trends.

Mohs micrographic surgery is a surgical technique that seeks to ensure the clearance of cutaneous tumors while maximizing normal tissue conservation. This is accomplished through the sequential removal of thin layers of tissue in which the entire peripheral and deep margins are examined for residual tumor. This approach appears to be superior to conventional surgical excision in the treatment of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), the two most common cancers of the skin. Its efficacy in treating BCC and SCC has led clinicians to explore the role of Mohs micrographic surgery in the management of less common cutaneous neoplasms, such as melanoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans, extramammary Paget's disease, and microcystic adnexal carcinoma.

Adenoma↗
PubMed1998

Unusual cutaneous malignancies.

The most commonly occurring cutaneous malignancies are basal cell and squamous cell carcinoma. There are, however, other rare malignancies that are encountered and should be included in the differential, in which both the clinical and the histological diagnosis may be difficult. Here, the clinical and histological features, management, and prognostic factors of merkel cell carcinoma, microcystic adnexal carcinoma, leiomyosarcoma, dermatofibrosarcoma protuberans, and angiosarcoma are reviewed.

Adenocarcinoma↗