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PubMed2005

Merkel cell carcinoma: prognosis and treatment of patients from a single institution.

PURPOSE: Merkel cell carcinoma (MCC) is an uncommon cutaneous malignancy. Most reports consist of single-institution experiences of fewer than 30 patients. The natural history of MCC is poorly defined. PATIENTS AND METHODS: A review was performed of Memorial Sloan-Kettering Cancer Center's MCC database, identifying 251 patients who had been treated between 1970 and 2002. Patient, tumor, and treatment-related factors were analyzed for their association with recurrence and survival. RESULTS: The average follow-up for all patients was 40 months and 46 months for patients alive at last follow-up. The 5-year disease-specific survival rate was 64%. Disease stage was the only independent predictor of survival (stage I, 81%; stage II, 67%; stage III, 52%; stage IV, 11%; P = .001). Pathologic staging of the draining nodal basin was performed in 71 (40%) of 177 patients who presented with clinically negative nodes, and 16 of these patients (23%) were found to have node-positive disease. Pathologic nodal staging was associated with improved stage-specific survival probabilities (clinical node-negative, 75% v pathologic node-negative disease, 97%; P = .009) and decreased nodal recurrence (44% v 11%, P < .001). The median time to recurrence was 9 months, and 102 patients (43%) recurred. Local recurrence developed in 8% of patients after margin-negative excision. CONCLUSION: These data demonstrate that the natural history of MCC is variable and dependent on the stage of disease at presentation. Pathologic nodal staging identifies a group of patients with excellent long-term survival. After margin-negative excision and pathologic nodal staging, local and nodal recurrence rates are low.

Adult↗
PubMed1990

The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma.

Between 1966 and 1987, 54 patients with non-disseminated Merkel cell carcinoma (MCC) were treated with curative intent at the University of Texas M. D. Anderson Cancer Center. The primary tumor site was in the head and neck in 38 patients. The majority of the patients (57%) were referred with locoregionally recurrent disease. For the whole group, survival was 30% after 5 years. Patients who presented with nodal involvement had a median survival of 13 months compared with 40 months for node-negative patients (p less than .04). Only 4/37 patients treated initially by surgery alone were locoregionally controlled, with a median time to recurrence of 4.9 months. Salvage with radiation therapy was attempted in 18 patients (after additional surgery in 14), but was successful in only four. The predominant failure pattern in this subgroup was distant metastases, occurring as a component of initial recurrence in 12/18 patients. Prior to 1982, the philosophy of initial therapy was to give postoperative irradiation only to patients with large primaries or nodal involvement. Subsequently, postoperative radiotherapy has been recommended routinely, and all five patients treated with this approach remain disease-free. In total, 31 patients (including 10 patients with gross disease) were irradiated at M. D. Anderson; only one developed an in-field locoregional recurrence as an initial site of failure. However, three marginal recurrences occurred. The median dose to the primary tumor, first echelon nodes, and supraclavicular nodes was 60, 51, and 50 Gy, respectively. Our current recommendation for initial treatment is excision of the primary tumor followed by irradiation with generous fields to include the primary tumor site and draining regional lymphatics to doses of 46-50 Gy in 2 Gy fractions. For gross unresected disease, 56-60 Gy is recommended. The role of adjuvant systemic therapy remains to be defined.

Adult↗
PubMed2000

Merkel cell carcinoma: report of 10 cases and review of the literature.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary neuroendocrine skin tumor that usually arises in the head and neck or the extremities of elderly patients. Because of the limitation of retrospective data, optimal treatment is not well defined. OBJECTIVE: Our purpose was to present the clinical course and treatment of 10 patients with MCC and review the published literature on MCC. METHOD: We conducted a retrospective analysis and obtained detailed clinical information for all 10 patients treated for MCC at our institution from 1986 through 1998. The medical literature was also reviewed for natural history and treatment recommendations using MEDLINE search. RESULTS: Five men and 5 women received their treatment between 1986 and 1998 for MCC (5 had stage IA disease, 4 stage IB, 1 stage II). The mean age was 70.3 years (range, 47-86 years). Seven tumors were located on the head and neck and 3 on extremities. Five of 10 patients had a relapse (mean time before recurrence, 5.7 months) (range, 2 weeks-20 months); one patient had local recurrence, one had regional lymph node recurrence, and 3 had both local and regional lymph node recurrence. In 4 patients systemic metastases developed. Long survival is also noted (6 to > 164 months); 4 patients died of MCC. After initial surgery, 9 patients received radiotherapy at some point and 3 patients also received chemotherapy. Five of 10 patients had 13 previously treated or coexisting malignant neoplasms. In one patient MCC developed in a previously irradiated field. Review of 875 cases showed a male/female ratio of 1.5:1; location of tumors was as follows: head and neck, 47%; extremities, 40%; trunk, 8%; unknown primary site, 5%. Local recurrence was observed in 25%, regional lymph node involvement in 52%, distant metastasis in 34%, and MCC was a cause of death in 34%. CONCLUSION: MCC has a high incidence of locoregional recurrence with distant metastases that is more common with higher stage lesions. Early local management of smaller lesions results in good long-term survival. It is not known whether prophylactic lymph node dissection and/or radiation and adjuvant radiation increases survival. Long survival can be achieved after treating locoregional recurrence. The role of chemotherapy is still controversial and should be considered in patients with advanced disease and those not thought to be candidates for surgery.

Aged↗
PubMed1990

[A metastatic Merkel cell carcinoma successfully treated with chemotherapy].

A 68-year-old man referred to the hospital because of a swelling of his bilateral cervical, left supraclavicular, and left axillary lymph nodes, and an ulcerated tumor in the right palatine tonsil. Three years previously, he had undergone a local excision in the left forearm of a skin tumor that had been pathologically diagnosed as a Merkel cell tumor. CT scan demonstrated an abdominal mass and his serum neurospecific-enolase (NSE) was found to be 20.3 ng/ml. Following biopsies of the lymph nodes and the tumor in the right tonsil, a metastatic Merkel cell carcinoma was diagnosed. Systemic chemotherapy thus was begun with doses of cyclophosphamide, doxorubicin and vincristine. After three cycles were completed, tumor were no longer present and his NSE returned to normal. Three months after the discontinuance of chemotherapy, he remains disease-free.

Aged↗
PubMed1988

[Lectin staining of a Merkel cell tumor].

The authors studied a Merkel's cell tumor with lectins. There is pattern of normal epidermis, but we see the N-acetyl-glucosamine an oligosaccharide not present in epidermis.

Acetylglucosamine↗
PubMed1980

Neuroendocrine (Merkel cell) carcinoma of the skin. A histologic and ultrastructural study of two cases.

The clinical, histologic, and ultrastructural features of two cases of a primary cutaneous neuroendocrine neoplasm probably arising from Merkel cells are presented and compared with previously reported examples. This recently described tumor arises in the dermis of elderly individuals, is often locally aggressive, may metastasize to regional lymph nodes, and eventually may cause death. Microscopically, sheets of primitive cells fill and expand the dermis. Ultrastructural study of our cases revealed morphologic similarities to normal cutaneous Merkel cells, including peripherally situated dense-core neurosecretory-like granules, zonula adherens-type intercellular junctions, prominent Golgi apparatus, and varying numbers of mitochondria and rough endoplasmic reticulum. This unusual tumor is readily confused with cutaneous lymphoma and various undifferentiated primary or metastatic neoplasms by conventional light microscopy. The definitive diagnosis can be made only by electron-microscopic examination.

Aged↗
PubMed1990

Immunohistochemical investigations in epidermal Merkel cells--a common phenotype with eccrine sweat gland epithelium.

Mono- and polyclonal antibodies were used for immunofluorescence investigations in cytoskeletal and associated antigens on frozen sections of adult human skin. Epidermal Merkel cells were identified in the stratum basale. Their phenotype was compared with other epithelial cells of human skin. The inner duct epithelium of eccrine sweat glands showed an immunoreactivity similar to that of epidermal Merkel cells. A common origin of both cell types is suggested.

Antibodies↗
PubMed2005

Merkel cell carcinoma: two case reports focusing on the role of fluorodeoxyglucose positron emission tomography imaging in staging and surveillance.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare skin neuroendocrine carcinoma frequently occurring in the head and neck area. It is known for being a locally aggressive disease with a high incidence of regional and distant metastases. Accurate initial staging and close surveillance are critical in the management of the disease. METHODS AND RESULTS: Two cases of MCC are reported in which fluorine-18-fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been beneficial in directing management and predicting clinical course. Pretreatment FDG PET scans detected metastatic disease in subcentimeter lymph nodes that were not appreciated in initial computed tomography images. Posttreatment FDG PET scans predicted response to therapy with the level of FDG uptake correlating in both areas of complete response to treatment and areas of residual diseases. Finally, FDG PET imaging also detected the progression of the disease after initial treatment. CONCLUSION: FDG PET imaging is a very sensitive modality in staging, assessment of treatment response, and surveillance of MCC. Because of the rarity of MCC, multicenter study is warranted to accumulate enough cases to determine the sensitivity and specificity of FDG PET in staging and surveillance of MCC, and the impact on the management and treatment outcome.

Aged↗
PubMed1993

Merkel cell tumor of the head and neck. Five new cases with literature review.

Merkel cell carcinoma (MCC) of the skin is an uncommon, but highly aggressive neoplasm with a marked propensity for local and distant metastasis. Despite the fact that more than half of the 600 cases of MCC reported in the literature involved primary sites in the head and neck, MCC has rarely been discussed in otolaryngology publications. We present five new cases of MCC of the head and neck and summarize 89 additional cases from the literature in which detailed treatment and survival data were given. Our findings again emphasize the difficulty in making the initial histopathologic diagnosis of MCC and demonstrate the necessity of early diagnosis and multimodality treatment.

Adult↗
PubMed2006

Impact of sentinel lymph node biopsy in patients with Merkel cell carcinoma: results of a prospective study and review of the literature.

PURPOSE: Merkel cell carcinoma (MCC) is the most aggressive of the cutaneous malignancies, showing a propensity to spread to regional lymph nodes (LNs). The aim of this prospective study was to examine the feasibility and clinical impact of sentinel lymph node biopsy (SLNB) in this cutaneous malignancy. METHODS: The study population comprised 23 patients with stage I MCC (median age 70 years, range 50-85 years). Lymphoscintigraphic mapping with( 99 m)Tc-nanocolloid was performed in all patients. Sentinel lymph nodes (SLNs) were identified, excised and analysed in serial sections by conventional histopathology and cytokeratin-20 immunohistochemistry. RESULTS: Metastatic disease was determined in the SLNs of 11 patients (47.8%). Elective lymph node dissection (ELND) was performed in eight of these 11 patients, four of whom had additional positive LNs. During follow-up (median 36.1 months, range 3-79 months), seven of the 23 patients (30%) relapsed: four had a local recurrence and three, in-transit metastases. Recurrence developed in two SLN-negative patients with local LN metastases and in one SLN-positive patient with distant metastases. This patient died, representing the only tumour-related death in our sample. Median survival was 49.1 and 35.5 months for SLN-negative and SLN-positive patients, respectively. This difference was not statistically significant (p=0.3452). CONCLUSION: SLNB allows for exact nodal staging in patients with MCC. Whether additional ELND is of further benefit remains unclear.

Aged↗
PubMed1992

[Primary neuroendocrine cutaneous carcinoma or Merkel cell carcinoma. Review of the literature].

The neuroendocrine carcinomas of the skin, also called Merkel cell carcinomas, are unusual malignancies mostly observed in the elderly. They are diagnosed by a pathologist: ultrastructural studies and immunohistochemistry support the diagnosis. The prognosis is poor. Lymph nodes and metastases quickly arise although sometimes, they are discovered immediately. A combination of surgery and radiotherapy is recommended. Metastases and unresectable tumors should be treated by chemotherapy.

Carcinoma, Merkel Cell↗
PubMed2004

Merkel cell carcinoma.

PURPOSE: To determine the natural history and treatment outcomes for patients with Merkel cell carcinoma. METHODS: Review of the literature. RESULTS: The probability of regional node involvement at presentation exceeds 50%; few patients present with distant metastases. Comprehensive treatment of the primary site and regional lymphatics with surgery or radiotherapy results in the highest likelihood of cure. The role of adjuvant chemotherapy remains investigational. CONCLUSION: The probability of regional dissemination at diagnosis is high. The optimal treatment is resection of the primary tumor and treatment of the regional lymphatics. Resection of all gross tumor should be accomplished followed by local-regional radiotherapy in most patients.

Adolescent↗
PubMed2002

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

In the general population, Merkel cell carcinoma (MCC) is a very rare neuroendocrine primary skin cancer, known for its high propensity for local recurrence and distant metastases. Treatment for this neoplasm is individualized on the grounds of clinical staging at presentation, and may include surgical excision, radiotherapy and chemotherapy. Several studies suggest that MCC occurs more frequently and with a more aggressive course in immunocompromised patients such as organ transplant recipients and those infected with human immunodeficiency virus (HIV). A case of this cutaneous malignancy, characterized by a short-term local recurrence and systemic fatal spread in spite of surgical treatment, radiotherapy and chemotherapy, is described in a patient with advanced HIV infection.

Carcinoma, Merkel Cell↗
PubMed2002

Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes.

BACKGROUND: Sentinel lymph node biopsy (SLNBx) can identify Merkel cell carcinoma (MCC) micrometastasis. OBJECTIVE: We attempted to examine the effectiveness of immunostaining and identify antibodies most appropriate for evaluation of SLNBxs for MCC. METHODS: Histopathologic material from 10 patients with MCC who had SLNBx was reviewed. RESULTS: Twenty-three SLNBxs from 10 patients appeared tumor-free in routine hematoxylin-eosin (H&E)-stained sections. However, tumor cells were detected in immunostained sections from 5 (22%) of 23 SLNBxs in 4 (40%) of 10 patients. Immunostains with pancytokeratin (panCK), cytokeratin-20 (CK-20), neurofilament protein, and chromogranin A were used for all primary and SLNBx specimens. All 5 (100%) micrometastatic foci stained strongly for CK-20 and panCK. Background normal lymph node tissue also stained for panCK but not for CK-20. CONCLUSION: Examination of H&E sections alone is insufficient for excluding micrometastatic MCC in sentinel lymph nodes. We observed the greatest sensitivity and specificity with anti-CK-20 antibody in identifying micrometastatic MCC in sentinel lymph nodes.

Aged↗
PubMedDate not supplied

Lymph nodal Merkel cell carcinoma: primary or metastatic disease? a clinical case.

We report a case of Merkel cell carcinoma (MCC) presenting in the lymph nodes in the absence of a primary cutaneous site. The MCC was treated by palliative radiotherapy, which controlled the disease locally. Eight months after diagnosis a mass appeared on the ipsilateral knee; histopathological examination of this lesion confirmed the diagnosis of MCC. The patient died two months later due to the development of pulmonary metastases. Interestingly, the neoplastic tissue was confined to the regional lymph nodes for several months before the primary site appeared. Primary lymph nodal MCC is rare and the diagnosis is difficult. In our opinion the only way to make a diagnosis of primary lymph nodal MCC is by appropriate clinical follow-up.

Aged↗
PubMed1995

Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas.

Keratin 20 is a recently identified keratin protein distributed particularly in the epithelial cells of the gastrointestinal tract. In this study, keratin 20 was immunohistochemically evaluated in 788 epithelial tumors of different organs. Keratin 20 was consistently present in colonic adenocarcinomas and their metastases in lymph nodes, liver, lung, and ovaries; most primary and metastatic colon carcinomas showed high numbers of positive cells independent of their level of differentiation. Adenocarcinomas of the upper gastrointestinal tract, pancreas, and cholangiocarcinomas showed variable reactivity. Hepatocellular carcinomas and carcinoid tumors often showed focal reactivity limited to scattered tumor cells. In contrast, keratin 20 was virtually absent in primary adenocarcinomas of lung, ovaries, and endometrium. Notable exceptions among ovarian tumors were the mucinous neoplasms that showed variable, sometimes significant keratin 20 reactivity. Transitional cell carcinomas irrespective of grade were usually positive, whereas most prostatic and renal adenocarcinomas were negative or showed only single positive cells. Typically negative were squamous cell carcinomas of all organs and carcinomas of the breast. Merkel cell carcinomas of the skin showed consistent reactivity, whereas small cell carcinomas of the lung were negative. On the basis of these observations, keratin 20 seems to be a suitable adjunct marker to evaluate the primary origin of carcinomas in specific contexts, especially to separate adenocarcinomas of gastrointestinal versus nongastrointestinal origin.

Adenocarcinoma↗
PubMed1984

Antibodies to Merkel cells in human sera. Incidence and significance.

Antibodies to Merkel cells (MC) are not known to occur in human sera. Using a newly described technic, we looked for the presence of antibodies directed against skin structures in sera from 2,300 patients with various dermatologic and hematologic disorders, as well as graft-versus-host disease (GVHD). Three of these sera (0.1%) were found to react with MC. One monoclonal IgM antibody was present in serum obtained from a patient with chronic cold agglutinin disease, the second from a patient with GVHD, and the third from a patient with pemphigus vulgaris. The present inadequate knowledge about normal MC function and the absence of described symptoms of MC dysfunction preclude analysis of the pathogenic significance of these MC antibodies in human sera.

Aged↗