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PubMedDate not supplied

Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine) carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with a propensity for local recurrence, regional and distant metastases. There are no well-defined prognostic factors that predict behavior of this tumor, nor are treatment guidelines well established. METHODS: Staging of patients with a new diagnosis of MCC was attempted using selective lymphadenectomy concurrent with primary excision. Preoperative and intraoperative mapping, excision, and thorough histologic evaluation of the first lymph node draining the tumor primary site [sentinel node] was performed. Patients with tumor metastasis in the sentinel node underwent complete resection of the remainder of the lymph node basin. RESULTS: Twelve patients underwent removal of 22 sentinel nodes. Two patients demonstrated metastatic disease in their sentinel lymph nodes, and complete dissection of the involved nodal basin revealed additional positive nodes. The node-negative patients received no further surgical therapy, with no evidence of recurrent local or regional disease at a maximum of 26 months follow-up (median 10.5 months). CONCLUSIONS: While the data are preliminary and initial follow-up is limited, early results suggest that sentinel lymph node mapping and excision may be a useful adjunct in the treatment of MCC. This technique may identify a population of patients who would benefit from further surgical lymph node excision.

Biopsy↗
PubMed2004

Successful targeted radiotherapy with 90Y-DOTATOC in a patient with Merkel cell carcinoma. A Case Report.

Merkel cell carcinomas (MCC) belong to the family of neuroendocrine tumors. In addition to other markers, they express somatostatin receptors. They are uncommon, highly malignant skin tumors with an aggressive clinical course. They develop in sun-exposed areas of the skin, mostly in elderly patients. In addition to frequent locoregional recurrences, there is a high incidence of distant metastases. Treatment is stage dependent and consists of operation and chemo- and/or radiotherapy, respectively. The advanced age of patients often impedes adequate therapy. (90)Y-DOTATOC is a novel radiolabeled somatostatin analogue containing the active octapeptide of somatostatin. It is very well tolerated and offers the option of treating somatostatin receptor-positive tumors by targeted radiotherapy. We report the case of an 83-year-old woman with recurrent MCC of the left cheek. The primary tumor and several relapses were treated with surgery and locoregional radiotherapy. After the 3rd relapse, she was treated 4 times with (90)Y-DOTATOC and two complete remissions were achieved. The fourth administration after the 2nd relapse was ineffective and conventional chemotherapy was started. There were no side effects of the (90)Y-DOTATOC. We conclude that due to its good tolerability, (90)Y-DOTATOC therapy should be evaluated further as a new therapy for somatostatin receptor-positive MCC.

Aged↗
PubMed1999

Merkel cell carcinoma: spontaneous resolution and management of metastatic disease.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neoplasm. The primary form of initial treatment is wide surgical excision. The use of Mohs micrographic surgery as the primary form of treatment in MCC has been controversial. The course of MCC is often aggressive, with early metastasis, widespread disease, and death. Despite the poor prognosis, spontaneous regression has occasionally been reported. OBJECTIVE: We describe the clinical course of two patients with Merkel cell carcinoma who underwent treatment with Mohs micrographic surgery for the primary MCC. Metastases were excised in the first case and spontaneously regressed in the second. Both patients are without clinical disease at the time of this report. METHODS: Histopathology, clinical records, and the current literature are reviewed. RESULTS: One patients was without recurrence of MCC for 13 years of follow-up. The other patient experienced clinical spontaneous remission after nodal spread of the disease, with no recurrence for 18 months after clinical remission and 24 months after surgery. CONCLUSION: The treatment of Merkel cell carcinoma with Mohs micrographic surgery (MMS) has been successful for the control of primary skin disease, and is at least comparable to wide excision. Spontaneous regression may occur in the course of this usually relentless and aggressive disease. The explanation for spontaneous regression of MCC is unknown.

Aged↗
PubMed2001

[Merkel cell carcinoma].

The authors present 2 cases of Merkel cell carcinoma in the head and neck district, evaluating the characteristics and evolution. Merkel cell carcinoma is a rare, highly aggressive neuroendocrine cutaneous neoplasm which is often located in the head and neck district. This carcinoma has the same characteristics as small cell tumors and tends to significant metastatization both through the lymph nodes and through the blood. It is also prone to frequent recurrence. Today diagnosis is facilitated by electron microscopy and immunohistochemistry to search for neurofilaments and cytocheratin 20. The treatment of choice is radical surgery ensuring a tumor-free edge of at least 3 cm, associated with supplementary local radiotherapy. Recurrence is quite frequent despite the treatment strategies applied.

Aged↗
PubMed1994

Merkel cells of the terminal hair follicle of the adult human scalp.

Human scalp skins were treated with 20 mM ethylenediaminetetraacetic acid and terminal hair follicles were extracted with the epidermis. Some terminal hair follicles were morphologically preserved well and provided opportunity to examine three-dimensional distribution of CAM5.2 (K8, 52.5 kD) reactive Merkel cells. In anagen terminal hair of the scalp numerous immunoreactive Merkel cells were distributed in the presumptive bulge area. Distinct swelling as in the bulge of human vellus hair was usually absent; however, in rare instances anagen terminal hair demonstrated unilateral prominent swelling with dense aggregation of Merkel cells. In telogen hair the bulge becomes indistinguishable from the regressed end of the club hair follicle but Merkel cells continued to be abundant. We found morphologic variation of the bulge such as formation of knoblike swellings and villous projections. Interestingly, Merkel cells were also located in these structures. Palisading stockade-like nerve endings were observed surrounding the follicular epithelium at the sebaceous gland level. Merkel cells were sparse in this follicular segment. Variable number of Merkel cells were also scattered in the infundibulum of terminal hair in no association with peripheral nerves.

Adult↗
PubMed1988

Development of Merkel cell populations with contrasting sensitivities to neonatal deafferentation in the rat whisker pad.

In this study, we used the quinacrine fluorescence technique to investigate the embryonic and early postnatal development of two distinct populations of Merkel cells in the rat whisker pad and the consequences of neonatal deafferentation on their subsequent development. Annular clusters of Merkel cells first appear in the epidermis near the caudal margin of the mystacial region between embryonic days E14 and E15 at dome sites located on horizontal ridges where the primordial vibrissal follicles develop. The development of these cells progresses in a caudorostral sequence across the whisker pad as does the development of the vibrissal follicles. Each cluster eventually forms a conical ridge or collar of about 130 Merkel cells that surrounds the vibrissal hair shaft as it penetrates the overlying pad epidermis. In the vibrissae, which develop as downgrowths from the horizontal ridges at the dome sites, Merkel cells first appear (caudally) between E16 and E17 and form a cylindrical cuff within the outer root sheath; cells are added progressively until about the end of the first postnatal week when a plateau level of about 750-800 cells is reached. Following unilateral transection of the infraorbital nerve at 24-36 hr after birth, these vibrissal Merkel cells continued to develop along a time course that was indistinguishable from normal, at least over the first 2 weeks of postnatal life. In contrast, all or most of the Merkel cells that normally develop within collars or annular clusters in the pad epidermis (around both the vibrissal and intervibrissal or pelage hairs) either disappeared within a few days or failed to develop. Other light and electron microscopic procedures supported the main findings and confirmed that the denervation was successful. Thus, the vibrissal Merkel cells, like those in the glabrous hindpaw, behaved as a distinct class which develops postnatally and is maintained (at least over a 2-week period) without the presence of sensory nerves. Since both the mystacial vibrissae and glabrous hindpaw have specialized cortical representations, a possible relationship between these findings and the organization of the somatosensory cortex during development is discussed.

Afferent Pathways↗
PubMed2004

Eyelid merkel cell carcinoma: report of three cases.

PURPOSE: To present three cases of Merkel cell carcinoma, a primary cutaneous neuroendocrine tumor that arises from Merkel cells, and to describe their clinical features, diagnosis, and management. METHODS: Case series. RESULTS: In only one case, the disease was clinically recognized. In the others, the diagnosis was confirmed by histology, and chalazion was initially suspected in one of them. Surgery was performed in all patients, and there was no evidence of metastatic disease. CONCLUSIONS: The rarity of eyelid Merkel cell carcinoma and the fact that it can simulate benign entities frequently lead to difficulties in diagnosis and a delay in the establishment of suitable therapy.

Aged↗
PubMed1999

[Merkel-cell carcinoma. A report of 3 clinical cases].

The finding of Merkel cell carcinoma is a rare but important event owing to the highly aggressive nature of this neoplasm. The authors report three cases of Merkel cell carcinoma with different onsets which were representative of the possible range of clinical symptoms and the prognosis of this pathology. In two cases diagnosis was made by chance, but in the third case a preoperative biopsy was initially performed with subsequent radicalization. The authors examine the diagnostic and therapeutic protocols proposed by other authors and compare them to their personal experience to ensure early diagnosis and radical therapy. Surgery is the obligatory initial choice, followed by radiotherapy and an accurate follow-up. The authors evaluate the use of Octeotride therapy for tumours of neuroendocrine origin and hence its application to Merkel cell carcinoma.

Aged↗
PubMed1995

The Merkel cell: recent findings and unresolved problems.

Recently acquired knowledge about the Merkel cell is reviewed, and unresolved problems on the development and function of the cell are discussed. Concerning its developmental origin, the epidermal origin hypothesis has become prevalent since the discovery of cytokeratin polypeptides in it. While the significance of this cell is still unclear, the following functions are presumed: 1) the release of neurotransmitters or neuromodulators to the SAI mechanosensory nerve terminals; 2) the attraction and trophic action on peripheral nerve fibers; 3) the stimulation of the proliferation of keratinocytes leading to the three-dimensional development of the epidermal anlagen; 4) the maintenance of the normal differentiation of keratinocytes; and 5) the release of bioactive substances to subepidermal structures. These multiple functions imply a possibility that one Merkel cell sequentially performs all these different roles during its life span. However, it is also possible that Merkel cells consist of several functionally different subpopulations.

Animals↗
PubMed2003

Friedrich Sigmund Merkel and his "Merkel cell", morphology, development, and physiology: review and new results.

Merkel nerve endings are mechanoreceptors in the mammalian skin. They consist of large, pale cells with lobulated nuclei forming synapse-like contacts with enlarged terminal endings of myelinated nerve fibers. They were first described by F.S. Merkel in 1875. They are found in the skin and in those parts of the mucosa derived from the ectoderm. In mammals (apart from man), the largest accumulation of Merkel nerve endings is found in whiskers. In all vertebrates, Merkel nerve endings are located in the basal layer of the epidermis, apart from birds, where they are located in the dermis. Cytoskeletal filaments consisting of cytokeratins and osmiophilic granules containing a variety of neuropeptides are found in Merkel cells. In anseriform birds, groups of cells resembling Merkel cells, with discoid nerve terminals between cells, form Grandry corpuscles. There has been controversy over the origin of Merkel cells. Results from chick/quail chimeras show that, in birds, Merkel cells are a subpopulation of cells derived from the neural crest, which thus excludes their development from the epidermis. Most recently, also in mammals, conclusive evidence for a neural crest origin of Merkel cells has been obtained. Merkel cells and nerve terminals form mechanoreceptors. Calcium ions enter Merkel cells in response to mechanical stimuli, a process which triggers the release of calcium from intracellular stores resulting in exocytosis of neurotransmitter or neuromodulator. Recent results suggest that there may be glutamatergic transmission between Merkel cell and nerve terminal, which appears to be essential for the characteristic slowly adapting response of these receptors during maintained mechanical stimuli. Thus, we are convinced that Merkel cells with associated nerve terminals function as mechanoreceptor cells. Cells in the skin with a similar appearance as Merkel cells, but without contact to nerve terminals, are probably part of a diffuse neuroendocrine system and do not function as mechanoreceptors. Probably these cells, rather than those acting as mechanoreceptors, are the origin of a highly malignant skin cancer called Merkel cell carcinoma.

Animals↗
PubMed2003

Merkel cell (neuroendocrine) carcinoma of the anal canal: report of a case.

Merkel cell tumors are rare neuroendocrine tumors typically found on sun-exposed areas such as extremities. We describe the case of a 42-year-old female with a Merkel cell tumor arising in the anal canal. The tumor was initially thought to represent a hemorrhoid arising during pregnancy and was excised locally after confirmation of extensive metastatic disease. The patient died 13 months after diagnosis with extensive metastatic disease involving the liver. In our search of the world literature there are several reports of neuroendocrine tumors in the rectum; however, no cases of documented Merkel cell tumors arising in the anal canal have been reported. These tumors seem to behave in a very aggressive manner when found in other atypical areas. The presentation symptoms were perianal discomfort and bleeding. Local excision may be the only surgical treatment necessary to control symptoms, given the propensity to early metastases and short life expectancy.

Adult↗
PubMedDate not supplied

[Palpebral Merkel cell tumors apropos of 3 cases].

The Merkel-cell tumor is a recently individualized (1972) malignant skin tumor. The diagnosis is made on the pathology. It consists of an intra-dermal proliferation of small regular cells with large nucleus and reduced cytoplasm. The evidence of neurosecretory granules and paranuclear intermediate filaments by electron microscopy is suggestive of a Merkel-cell tumor. Following a review of the literature and 3 personal observations the authors have detailed the clinical, anatomopathologic and evolutional characteristics of palpebral localizations.

Aged↗
PubMed1998

Neuroendocrine carcinoma of the breast with Merkel cell carcinoma-like features.

A case of neuroendocrine carcinoma of the breast with Merkel cell carcinoma-like features occurring in a 38-year-old female is described. A 2.5 x 2.5 x 1.3 cm tumor in the upper-outer quadrant of the right breast was ill-defined, yellowish white and rubbery. Microscopically, the tumor was characterized by a diffuse proliferation of non-cohesive round cells. The tumor cells had round nuclei with finely dispersed chromatin and inconspicuous nucleoli. The cytoplasm was generally scant, pale to eosinophilic, and argyrophilic. There were scattered foci of small nests or intraductal proliferations. Immunohistochemically, many tumor cells showed positive reaction for CAM5.2, vimentin, chromogranin A, and synaptophysin. The tumor was also positive for neuron-specific enolase (NSE), Leu-7, calcitonin, S-100 protein, and glial fibrillary acidic protein. Flow cytometric analysis showed that the tumor was DNA diploid. An axillary lymph node was positive for metastasis. The patient was well, without disease, for 6 years after mastectomy. It is suggested that the tumor might originate from ductal cells and show Merkel cell carcinoma-like neuroendocrine differentiation.

Adult↗
PubMed1990

Radiotherapy as an adjunct in the management of Merkel cell carcinoma.

Four patients with a diagnosis of Merkel cell carcinoma initially underwent surgery followed by radiotherapy. Recurrent disease prompted use of radiation in three cases. The three cases of recurrent disease illustrate the aggressiveness of Merkel cell carcinoma and also provide further documentation of the radiosensitivity of this tumor. Additionally, these cases suggest that surgery alone frequently is inadequate to achieve local control of disease.

Aged↗
PubMed1996

Selective phototoxic destruction of quinacrine-loaded Merkel cells is neither selective nor complete.

Experiments were performed on slowly adapting type I mechanoreceptors in an isolated rat skin-nerve preparation (SA I receptors) and in an isolated rat sinus hair preparation (St I receptors). Merkel cells were stained in vitro with the fluorescent dye quinacrine and irradiated with ultraviolet (UV) light (2 mW for up to 1 h) while recording receptor responses to standard mechanical stimuli every 30 s. In addition, thresholds for electrically evoked action potentials were tested by applying electrical stimuli to the skin through the same stylus used for mechanical stimulation. UV irradiation resulted in abrupt failure to respond to mechanical stimuli in 73% of the SA I receptors examined (n = 37) within less than 1 h. This confirms previous reports of phototoxic destruction of Merkel cells. However, several minutes after the receptors failed to respond to mechanical stimulation, thresholds for electrical stimuli applied to the receptive field increased sharply. About 40% of the St I receptors (n = 13) irradiated with UV light following quinacrine staining stopped responding to bending of the hair within 1 h. In contrast, none of the seven St II receptors treated in the same way showed significant changes in the responses. Electron microscopic examination of sinus hairs after quinacrine staining alone showed slight changes in the appearance of Merkel cells, and in particular enlargement of the perinuclear space. These changes did not affect receptor responses. Electron microscopic studies of sinus hairs with receptors that had maintained normal responses to mechanical stimuli after quinacrine staining and 1 h of UV irradiation revealed that a substantial number of Merkel cells still had a normal ultrastructure while adjacent nerve terminals were severely swollen and partially compressing the Merkel cells. No changes were observed in lanceolate nerve terminals forming the morphological substrate of St II receptors. These results demonstrate that sensitivity to phototoxic destruction following quinacrine staining varies greatly among Merkel cells, with some maintaining normal function and ultrastructural appearance even after 1 h of UV irradiation. On the other hand there is clear evidence that the phototoxic damage affects the nerve terminals as well. Such experiments can therefore not provide conclusive proof about the role of Merkel cells in these mechanoreceptors.

Adaptation, Physiological↗
PubMed2001

Merkel cell carcinoma in the setting of HIV infection.

Merkel cell carcinoma has been found to have an increased incidence among immunosuppressed patients, specifically organ transplant recipients receiving immunosuppressive therapy. HIV similarly depresses the immune response of infected persons. We report a case of Merkel cell carcinoma (MCC) in an HIV-infected patient who died from liver metastases 2 years after his tumor was diagnosed. The purpose of this report is to describe the possible relationship between HIV and MCC and to emphasize the importance of early diagnosis and aggressive management of MCC.

Carcinoma, Merkel Cell↗
PubMed1989

Merkel cell carcinoma. Long term survival in a patient with proven brain metastasis and presumed choroid metastasis.

Merkel cell carcinoma (Trabecular carcinoma) is a rare malignant tumor of the skin. Because these tumors tend to spread locally via the lymphatic system, very few papers have dealt with the treatment of distant metastasis. Systemic disease is uncommon and usually fatal. In this paper, we report a case of Merkel cell carcinoma with proven brain metastasis and a solid choroidal tumor. The patient responded well to radiation and chemotherapy and is alive and neurologically intact three years after diagnosis. All previous patients with metastatic Merkel cell carcinoma to the brain died within two months of the diagnosis. We use this case to discuss possible routes of metastatic dissemination and to review the treatment options in patients with distant metastatic disease. To our knowledge, this is the first reported case of presumed choroidal metastasis of Merkel cell carcinoma and the longest documented survival in a patient with brain involvement.

Brain Neoplasms↗