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PubMed2000

Transient expression of a functional serotonin transporter in Merkel cells during late gestation and early postnatal rat development.

We and others have previously identified serotonin transporter mRNA throughout the trigeminal system in the whisker region, trigeminal ganglion, trigeminal nucleus and thalamic relay stations. In order to further implicate a role for the serotonin transporter in this sensory system, we have now characterized serotonin transporter gene expression and function in primary cultures from the rat snout, at several stages of gestation. In this study, we have demonstrated a transient expression of serotonin transporter mRNA in quinacrine-positive Merkel cells between embryonic day 16 and postnatal day 5. Peak levels of mRNA occurred at embryonic day 20 and postnatal day 1. Merkel cells in culture exhibited a transient, antidepressant-sensitive [3H]-serotonin uptake, which was maximal at a time in culture corresponding to embryonic day 22 (day of birth). This transient uptake of serotonin suggests a role for this monoamine during a critical time period of the developing trigeminal sensory system. Regulation of extracellular serotonin levels by transporter activity may reflect the specific formation of the merkel cell-sensory neuron complex in an analogous mechanism by which serotonin modulates synaptogenesis in the central nervous system.

Aging↗
PubMed1991

Cytogenetic study in a bone marrow metastatic Merkel cell carcinoma.

We report an additional cytogenetic study of a metastatic Merkel cell carcinoma. Even though the cells analyzed were from a metastatic lesion, chromosomal abnormalities were not complex. Similarities between cytogenetic findings described in small-cell lung carcinoma and the present case are observed. However, further studies are needed to define the relationship between these two neuroendocrine small-cell malignancies.

Adult↗
PubMedDate not supplied

Merkel cell carcinoma: the use of surgery and radiotherapy for locoregional control.

Merkel cell tumours are rare skin cancers with an unpredictable clinical course. Correct diagnosis requiring immunohistochemical staining is essential since the treatment differs entirely from that of basalioma. Locally limited disease as well as rapidly fatal course have been observed. In a small series of 5 patients and from literature data, surgery continued with radiotherapy for locoregional control is advocated as optimal approach since this type of tumour can behave differently compared to basal cell carcinomas.

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PubMed2006

Merkel cell carcinoma: does tumor size or depth of invasion correlate with recurrence, metastasis, or patient survival?

OBJECTIVE: The objective of this retrospective study and literature review was to compare the clinical and histologic criteria including tumor size and depth of invasion with outcomes in patients with Merkel cell carcinoma. METHODS: The state cancer registry provided patients (n = 46) diagnosed with Merkel cell carcinoma from 1992 through 2002. Pathology slides were reviewed by the author for tumor size, depth of invasion, Clark level, and margin status. Further clinical information and survival data were gathered from patient records. Statistical analysis was performed using t tests and Kaplan-Meier survival curves. Patients were excluded from specific analysis based on misdiagnosis, unavailability of pathology slides, absent medical records, or those lost to follow up. RESULTS: Disease-free survival rates were 52%, 39%, and 9% at 1, 2, and 5 years, respectively. The average disease-free interval was 18.4 months (range, 1-80 months). No correlation was found between tumor size (P = .49), depth (P = .41), or Clark level (P = .82) to overall survival. A trend was found comparing tumor size or depth of invasion with local recurrence (P = .07) but with no correlation to regional recurrence (P = .93 and P = .60) or distant metastasis (P = .16 and P = .24). Overall recurrence was found in 60.7% of patients with local recurrence occurring in 18.1%, regional recurrence 40.9%, and distant recurrence 47.8%. Comparing patients with positive versus negative margins at initial excision, local recurrence was found in 33.3% versus 9.09% (P = .19), regional recurrence 66.6% versus 27.2% (P = .08), and distant metastasis 66.6% versus 45.4% (P = .36), respectively. CONCLUSIONS: No correlation was found between tumor size or depth of invasion to patient survival or metastasis. However, there was a trend toward increased local and regional recurrence rates when comparing size and depth and in specimens with positive tumor margins. These outcomes are consistent with those reported in recent literature and further characterize the unpredictable nature of this disease. An aggressive approach should be taken, including wide local excision with negative tumor margins and lymph node dissection; however, larger multistate reviews are needed for additional support.

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PubMed1996

Merkel cells participate in the induction and alignment of epidermal ends of arrector pili muscles of human fetal skin.

The follicular proximal ends of arrector pili muscles anchor the bulge areas of human hair follicles. However, the location of the ends of these muscles towards the epidermis, especially the fine points of attachment, is not fully understood. Conventional serial sections of the scalp skin of a 12-month-old infant were examined. Most of the distal ends were situated in the upper dermis, while some seemed to be in close contact with the epidermal basal layers. In vertical sections of the scalp skin of 36-week-old fetus, double immunoenzyme staining showed a close topographic correlation between the epidermal ends of the arrector pili muscles and the epidermal and dermal Merkel cells. These findings allow speculation that fetal Merkel cells participate in the induction and alignment of arrector pili muscles.

Fetus↗
PubMed1997

Merkel cell carcinoma arising after therapeutic immunosuppression.

Azathioprine and cyclosporin have been used as immunosuppressants for many years, but long-term use has also been associated with neoplasia. We report three cases of rapidly fatal Merkel cell carcinoma in patients who had been treated with azathioprine for many years either for rheumatoid arthritis or following organ transplantation. Two of these patients had also received cyclosporin. We suggest that Merkel cell carcinoma may be seen more commonly in immunosuppressed patients than in the normal population and that the oncogenic potential of azathioprine and cyclosporin should be borne in mind when prescribing these drugs.

Aged↗
PubMedDate not supplied

VIP-immunoreactivity in the skin of various mammals: immunohistochemical, radioimmunological and experimental evidence for a dual localization in cutaneous nerves and merkel cells.

In the present study VIP-immunoreactive (IR) nerve fibers were found in the skin of several mammalian species (cat, dog, pig and man). They supplied predominantly the arteries and arterial portions of arteriovenous anastomoses. Far fewer VIP-IR nerve fibers innervated veins and arterioles. Capillaries were supplied by VIP-IR fibers only in sweat and Meibomian glands. Some non-vascular VIP-IR nerve fibers were seen in contact with dermal smooth muscle strands. In eccrine sweat glands and in Meibomian glands VIP-IR fibers were targeting glandular cells. In addition, VIP-IR nerve fibers innervated the upper parts of facial hair follicles. In non-neuronal localization VIP-IR occurred in Merkel cells in all species and sites, while the intraepidermal axons consistently were not VIP-IR. Radioimmunoassay of different skin regions of cats also suggested both a neuronal and a Merkel cell origin of VIP-IR. Under physiological conditions VIP which is released from its neuronal and non-neuronal cutaneous pools may have an impact on thermoregulation by influencing blood flow and sweat production. It may also modulate axon-endings in Merkel cell-axon complexes and hair follicle receptors. Under pathological conditions an enhanced release of cutaneous VIP may lead to local inflammatory processes partly mediated via release of histamine from cutaneous mast cells.

Animals↗
PubMed1992

Pagetoid intraepidermal spread in Merkel cell (primary neuroendocrine) carcinoma of the skin.

Pagetoid intraepidermal spread of neoplastic cells was noted in six cases of Merkel (primary neuroendocrine) cell carcinoma of the skin. In two cases, the volume of the intraepidermal portion of the neoplasm was either equal to or more extensive than the dermal component. The intraepidermal component in all six cases was remarkable because of the following findings: the presence of cells with scant cytoplasm arranged both individually and as nests, sometimes along the dermoepidermal junction; splaying of the apical portions of basal keratinocytes by solitary neoplastic cells; incomplete rims of compressed basal keratinocytes at the peripheries of some junctional nests; and occasional contiguity of neuroendocrine carcinoma cells with those of Bowen's disease or solar keratosis. These features can be used to distinguish these Merkel cell carcinomas from other lesions that have a pagetoid pattern, even in superficial biopsies, and immunohistochemistry can confirm the diagnosis or resolve problematic cases. The occurrence of cutaneous neuroendocrine carcinoma situated largely in the epidermis raises the possibility that some of these tumors may arise from intraepidermal Merkel cells.

Adult↗
PubMed1992

[Orbital invasiveness of Merkel cell tumor of the eyelid].

A new case of neuroendocrine carcinoma (Merkel cell tumor) of the eyelid is reported. Local recurrence, spread to the orbit, led to exenteration and death of the patient. This trabecular carcinoma can be identified by histology, immuno-histochemistry and electron structural microscopy.

Aged↗
PubMed1996

Cytogenetic study of neuroendocrine carcinoma of Merkel cells.

We describe the cytogenetic study of a neuroendocrine tumor of Merkel cells which appeared in a patient following a heart transplant. An abnormal karyotype was observed in a metastatic lymph node. The abnormality includes two markers derived from the long arm of chromosome 1, while maintaining two normal chromosomes 1.

Aneuploidy↗
PubMed1992

Merkel cell tumor masquerading as granulation tissue on a teenager's toe.

Merkel cell tumor (MCT) typically occurs on the head or neck of elderly patients. A case is presented of a teenage girl with an MCT on her toe. The diagnosis was made 5 years after an ingrown nail on the toe was avulsed. During the interim 5 years, the periungual skin looked like granulation tissue and thus no biopsy was performed. This case of MCT is unique in three aspects: (a) extraordinarily young age, (b) atypical site, and (c) deceptive clinical appearance. Awareness of the possible occurrence of MCT in younger patients and in unusual locations will facilitate earlier diagnosis.

Adolescent↗
PubMed2002

Merkel cell carcinoma in a black human immunodeficiency virus-infected patient.

Merkel cell carcinoma (MCC) is a rare malignant tumour that develops in sun-exposed areas in immunocompromised patients (chronic lymphocytic leukaemia, transplant recipients) older than 50 years. We report MCC in a young black woman with human immunodeficiency virus (HIV) infection. A 2-cm binodular violaceous lesion developed on her left ear lobe. Extensive work-up, including computed tomographic scans of the neck, chest, abdomen and pelvis, octreotide scan and sentinel node biopsy, did not demonstrate any metastasis. A wide excision was performed and the patient remained free of disease after 9 months. This case is the fourth observation of MCC in an HIV-infected patient.

Adult↗
PubMed1998

[Merkel cell carcinoma. Report of 4 cases].

We report four cases of Merkel cell carcinoma, a rare cutaneous neuroendocrine neoplasm with a high malignant potential. The first patient is a 90 years old male presenting with a tumor in the left superior eyelid. Surgical excision was the only treatment and seven months later, a local and regional tumoral relapse caused the death of this patient. The second patient is a 83 years old female with a tumor in her left ear. She was treated surgically and with radiotherapy, being free of disease after five years of follow up. The third patient is a 45 years old male with a tumor in the left forearm. Treatment was surgical excision of the primary tumor and axillary lymph nodes. He received post operative radiotherapy and is free of disease after three years of follow up. The last case is a 76 years old male, who was subjected only to an excisional biopsy of a lesion located in the left knee. He had a tumor relapse with inguinal and crural lymph node involvement that caused his death 12 months later.

Age Factors↗
PubMed2006

Merkel cell carcinoma in South East Scotland, 1993-2003.

BACKGROUND AND AIMS: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. The aims of this study were to look at the incidence and distribution of MCC in a predominantly skin type I Caucasian population, review overall management of the disease and assess patient outcomes. METHODS: Cases were identified through the regional pathology database. Twenty patients were diagnosed with MCC over a 10-year period (1993-2003) and managed at the Regional Plastic Surgery Unit at St John's Hospital, Livingston. RESULTS: The disease incidence was found to be 0.133 per 100,000 per annum. All patients were Caucasian, seven males and 13 females (1:1.9 ratio). The mean age at presentation was 77 years (range 58-93 years). The majority of lesions were found to be stage IA (80%), located in the head and neck region. There were two cases (10%) with stage II disease and two (10%) with stage III disease (both with liver metastases) at the time of diagnosis. All patients were managed operatively. Seventeen of the 20 had wide local excisions; of the remaining three, two were only suitable for debulking procedures and one patient (stage II) had only a diagnostic biopsy, refusing intervention thereafter. One patient received adjuvant chemoradiotherapy. CONCLUSION: Surgery remains the mainstay of treatment but adjuvant therapy, in particular chemotherapy, is problematic in a frail, elderly population.

Aged↗
PubMed2001

Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases.

BACKGROUND: Merkel cell carcinoma (MCC) is an unusual and potentially aggressive cancer of the skin. There is no consensus regarding the optimal therapeutic approach, and the relative roles of surgery, radiotherapy, and chemotherapy still are controversial The aim of this study is to analyze the roles of these therapeutic options. METHODS: The medical records of 16 patients with a diagnosis of localized, primary MCC treated at the University of Alabama at Birmingham were reviewed. An extensive review of the English-language literature also was performed. The Kaplan-Meier method was used to develop the survival curves. Comparisons were made using Fisher's exact test. Significance was defined as P < .05. RESULTS: MCC presented primarily in Caucasians (98.3%) with a median age of 69 years. Immunosuppressive therapy appeared to play a role in the development of this cancer. In the UAB experience, 3-year actuarial survival was 31%. The only factor significantly associated with overall survival was the stage of disease at presentation: median survivals were 97 vs. 15 months for stages I and II, respectively (log-rank, P = .02). From the literature review, adjuvant radiotherapy was associated with a reduced risk of local recurrence (P < .00001). CONCLUSIONS: MCC is an aggressive cancer, with a high tendency for local recurrence and distant spread. Surgery and adjuvant radiotherapy appear to provide optimal local control. The role of chemotherapy remains to be defined.

Adult↗
PubMed1999

Merkel cell carcinoma: the role of radiation therapy in general management.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignant, locally aggressive tumor of the skin. Because few data exist about the clinical course of irradiated patients, we reviewed the 17 patients treated at our institution since 1982. PATIENTS AND METHODS: The median age at diagnosis was 71 years (range 47 to 88 years). Twelve patients presented with lymph node involvement (Stage II), 5 patients with negative lymph nodes (Stage I). Five patients were irradiated immediately after initial surgical excision of the primary tumor. Eleven patients underwent a surgical treatment of recurrence prior to the first irradiation. Only 1 patient received primary radiotherapy. A median dose of 52.8 Gy (range 40 to 60 Gy) in the region of the primary tumor and a median dose of 49.5 Gy (range 30 to 54 Gy) in the regional lymph nodes were delivered. RESULTS: The median overall survival after first diagnosis was 45 months. Three-year overall survival was 57%, 5-year cause-specific survival was 73% (Kaplan Meier). Local control could be achieved in the 5 patients irradiated immediately after surgical treatment of the primary tumor. In contrast, an in-field recurrence occurred in 5 of 12 patients irradiated after surgical excision of relapsed disease. Five patients developed distant metastases. None of these patients was irradiated immediately after surgical excision of the primary tumor. CONCLUSIONS: With respect to our experience, a local control can be achieved with an immediate postoperative radiotherapy of the primary tumor site and the adjacent lymph nodes.

Aged↗
PubMed2005

Merkel cell carcinoma in patients with long-term ingestion of arsenic.

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma of the skin, mostly occurring late in life on sun-exposed body parts. Little is known about the specific etiological factors in the pathogenesis of MCC. A previous report indicated that arsenic exposure might cause MCC, which might be another specific type of skin cancer associated with arsenic exposure. On the southwest coast of Taiwan, high arsenic levels in artesian well water have been documented, and various diseases associated with arsenic exposure have been found to be prevalent in this area. We report two pathologically confirmed cases of MCC in patients who had histories of long-term ingestion of arsenic from drinking water. The tumors were on the anterior chest wall, an area less exposed to the sun, in both cases. The literature on the dose-response relationship between arsenic exposure and MCC is limited. We estimated that the total arsenic ingested by these two cases was around 14.7 and 2.6 gm, respectively. We also tried to assess the cancer risk on the basis of the estimated doses of arsenic exposure and the cancer risk model developed by the U.S. Environmental Protection Agency (EPA). The estimated lifetime target cancer risk was 1.3 x 10(-2) in Case 1 and 2.3 x 10(-3) in Case 2. Both are much higher than the 10(-6) upper limit on lifetime cancer risk put forth by the U.S. EPA health protection standard. We believe that arsenic intoxication played an important role in the carcinogenic process of MCC in our cases.

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