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PubMed1987

Trabecular (Merkel cell) carcinoma arising in the wall of an epidermal cyst.

A trabecular (Merkel cell) carcinoma arising in the wall of an epidermal cyst in a 58-year-old white male metastasized, 17 months after local excision, to an inguinal lymph node. Ultrastructural studies showed polygonal tumor cells with typical dense-core granules. Although squamous-cell carcinoma and other malignant neoplasms have been reported rarely to have arisen in epidermal cysts, a literature search failed to find a precedent for the present case.

Adenocarcinoma↗
PubMed2006

Tenascin-C expression in Merkel cell carcinoma lymph node metastasis.

Expression of tenascin-C (Tn-C) has been shown to correlate with invasion and metastasis in Merkel cell carcinoma (MCC). Cytokeratin-20 (CK-20) is used in differential diagnostics of the primary tumour. The aim of this study was to demonstrate the expression of Tn-C in MCC lymph node metastases. Immunohistochemical staining was performed for five metastatic lymph nodes using a monoclonal antibody against Tn-C and CK-20. All five metastatic lymph nodes expressed Tn-C. The expression concentrated around the vascular structures, invasion borders and fibrotic septae. One of the metastatic lymph nodes was strongly positive for CK-20 while the others showed a focal or negative pattern. The normal lymphoid tissue was negative for Tn-C. Tn-C detected metastatic MCC tissue within the lymph nodes undisputedly. There was a clear distinction between the metastatic and normal lymphatic tissue. Furthermore, invasion to the surrounding tissue was easily demonstrated. Contrary to previous studies, CK-20 expression seemed to fluctuate.

Biomarkers, Tumor↗
PubMed1982

Evidence against transmitter function of met-enkephalin and chemosynaptic impulse generation in "Merkel cell" mechanoreceptors.

Using the mechanoreceptors in the cat's sinus hair follicles as a model system the recent hypothesis (Hartschuh and Weihe 1980) was tested that Merkel cells are mechanoreceptive sensory cells releasing met-enkephalin as a neurotransmitter to initiate action potentials in the terminals of type I afferent fibres. Since the met-enkephalin antagonist naloxone, even in high doses, did not affect responses in any type I mechanosensitive afferent it is unlikely that a synaptic mechanism with the release of met-enkephalin underlies impulse generation in Merkel cell-axon complexes, nor did naloxone influence the responses from other types of mechanoreceptors.

Afferent Pathways↗
PubMed1997

Merkel cells are absent in basal cell carcinomas but frequently found in trichoblastomas. An immunohistochemical study.

The possibility of a neuroendocrine differentiation in basal cell carcinomas (BCCs) has been a matter of debate for many years. In the present immunohistochemical study, applying the cytokeratins 8, 18 and 20 as the most established markers for Merkel cells (MCs), we did not find elevated numbers of MCs in any of 205 BCCs. This speaks against a neuroendocrine line of differentiation in BCCs. In contrast, we found various amounts of MCs in 15 of 36 trichoblastomas, which are the main benign differential diagnosis of BCC. In 4 trichoblastomas abundant MCs were spread over the whole epithelial tumor area. Additionally, the trichoblastomas' overlying epidermis exhibited significantly much higher numbers of MCs than the uninvolved adjacent skin or the epidermis overlying the BCCs. These findings might be an additional aid in the distinction between trichoblastomas and BCCs. Furthermore, concerning the recent discussion about the role of MC in growth and development of follicular germ, our observations are another sign of regulative influences of the MC, also in follicular germ under pathological conditions. Trichoblastomas with high numbers of MCs could be characterized as showing advanced differentiation toward the neuroendocrine component of the hair follicle, i.e., the MCs.

Basal Cell Carcinoma↗
PubMed1988

Clinicopathologic correlations of cutaneous neuroendocrine Merkel cell carcinoma.

A study of 50 consecutive cases (22 men, 28 women; age range, 39 to 84 years; mean age, 65 years) of cutaneous neuroendocrine Merkel cell carcinoma (CNC), 39 of whom had a mean follow-up of 34 months, revealed that the prognostic significance of the histopathologic subtyping in trabecular, solid, and diffuse variants of CNC was not as important as the pathologic postsurgical staging in localized, regional, and extraregional disease. The overall mortality was 23.5%. None of the 19 patients with localized disease died of CNC, while 11% of the 24 patients with regional disease and all seven patients with extraregional disease at presentation died of CNC. A second primary malignancy was found to be associated with the CNC in 15% of the cases. The clinical course in patients with localized disease was favorable in spite of the high number of local recurrences. Also, the presence of regional metastases was not related to an unfavorable prognosis. In 68% of the cases the disease involved the lower limbs or girdle. In ten cases the overt exophytic presentation of primary CNC was replaced by the presence of tumor masses infiltrating the inguinal soft tissues with or without nodal involvement.

Adult↗
PubMed2001

CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin.

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus.

Blotting, Western↗
PubMed2005

Infrahyoid myocutaneous flap reconstruction after wide local excision of a Merkel cell carcinoma.

The case is presented of an 8 1-year-old female coming to our observation after two non radical local excisions of a Merkel cell carcinoma of the sub-mental skin region. After a wide local excision, with en bloc elective bilateral neck dissection, simultaneous reconstruction with an infra-hyoid myocutaneous flap was performed. A brief overview concerning this rare tumour is presented and the surgical technique of the reconstructive procedure is described in detail. The infra-hyoid myocutaneous flap represents a reliable flap, easy and quick to prepare, limiting the time of surgery. The donor site can be primary closed avoiding skin grafting or scars beyond the head and neck area with no significant cosmetic or functional sequelae in the donor area. In this elderly patient, reconstruction with an infra-hyoid myocutaneous flap appears to have been the best option for closing the surgical defect.

Aged↗
PubMed2006

Merkel cells in the oral mucosa.

Ninety-eight consecutive surgical biopsies of oral mucosa from 96 patients were evaluated immunohistochemically with an anti-cytokeratin 20 (CK 20) anti-body to evidence Merkel cells (MC). Fifteen cases, showing the highest number of MC, were additionally studied with chromogranin A, S-100 protein, neuro filaments, epithelial membrane antigen, and double immunostaining for CK 20 and Ki67 antibodies to evaluate MC proliferation. Electron microscopy was performed in 2 cases. MC were observed in 58 cases. The highest number of MC was found in the gingival, buccal, and palate mucosa, especially in chronically damaged oral mucosa (lichen and chronic aspecific inflammation) as well as in the mucosa overlying tumors rather than in normal or acute inflammation. MC were not observed in dysplastic or neoplastic epithelium. MC showed evidence of proliferation, as demonstrated by Ki67 positivity, in 3 cases. In conclusion, MC appear to play a role in the reparative processes of oral mucosa.

Adolescent↗
PubMedDate not supplied

6-[F-18]fluoro-L-DOPA positron emission tomography in the imaging of Merkel cell carcinoma: preliminary report of three cases with 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography or pentetreotide-(111In) SPECT data.

PURPOSE: Merkel cell carcinoma (MCC) is an uncommon and aggressive cutaneous neoplasm of neuroendocrine origin. Somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) have been proposed to stage MCC and to detect early recurrences. As 6-[F-18]fluoro-L-DOPA (FDOPA) is taken up by other neuroendocrine tumors, we speculated that FDOPA-PET could image MCC. PROCEDURE: FDOPA-PET was performed together with FDG-PET (three patients) and SRS (two patients) in different clinical settings: localization of the primary tumor, staging, and suspicion of recurrence. RESULTS: Uptake of FDOPA-(18F) by MCC was observed in the two true-positive cases, with an agreement between the results of FDOPA-PET, FDG-PET, and SRS; however, the contrast was lower on FDOPA-PET than on FDG-PET images. In the last patient suspected of recurrence repeatedly on SRS and with inconclusive FDG-PET, FDOPA-PET was negative, and a 12-month follow-up demonstrated a true-negative result. CONCLUSION: MCC takes up FDOPA-(18F). The potential role of FDOPA-PET in its management warrants clarification.

Aged↗
PubMedDate not supplied

Merkel cell tumor-like neuroendocrine carcinoma associated with the submandibular gland. Report of a case with cytologic, immunohistochemical, electron microscopic and flow cytometric studies.

We report a rare case of primary Merkel cell tumor (MCT)-like neuroendocrine carcinoma (i.e., small cell carcinoma) associated with the submandibular gland in a 73-year-old man. Despite the lack of a known skin primary, the tumor exhibited cytomorphologic (predominant single cells with "intermediate filament buttons" in the background), ultrastructural (dense core granules and a globular aggregate of intermediate filaments) and immunohistochemical (paranuclear globular coexpression of cytokeratin and neurofilaments) features identical to that of MCT. The tumor contained an aneuploid peak with DNA index of 1.1 and an S phase of 20.5%. The tumor measured 5.8 cm and was situated between the skin and submandibular gland, with which it was closely associated but separated by connective tissue. The literature on MCT without a known skin primary is reviewed, and the cytomorphologic features that allow the distinction between MCT, lymphoma and oat cell carcinoma are discussed.

Aged↗
PubMed1990

Relationship between Merkel cells and nerve endings during embryogenesis in the mouse epidermis.

Close relationships between Merkel cells (MC) and nerve endings (NE) exist in the adult mouse. Because MC may serve as targets for the ingrowth of NE during embryogenesis, the purpose of the present study was to analyze the relationship between MC and NE during embryogenesis. Frozen tissue from whisker pads and backs of NMRI mouse embryos (12-17 d gestational age) were studied by double-labeling indirect immunofluorescence (IIF) with a cytokeratin monoclonal antibody that recognizes MC and with a neurofilament anti-serum. Such an approach allowed the analysis of a large number of MC (up to 5000), thus yielding quantitative data. At day 12 of gestational age, no MC were observed by IIF. From day 13 to 17, the number of MC, as well as their association with NE, progressively increased. On day 13, only 57% of whisker pad MC were NE associated, whereas by day 17, 95% were NE associated. These results were confirmed by electron microscopic (EM) observations. On the back, the same chronologic relationship between MC and NE was observed, but was later in the course of embryogenesis. There was also a time- and zone-dependent increase in MC association with NE in the epidermal zones studied (isthmic, parafollicular, interfollicular). These observations 1) establish the time course of MC and NE contacts during embryogenesis in the mouse epidermis, 2) show that MC are present in the epidermis and appendages before NE reach the epithelium, and 3) support the hypothesis that MC could act as targets for the growing NE.

Animals↗
PubMed1987

Merkel cell carcinoma: a review of behaviour patterns and management strategies.

Eleven patients with Merkel cell carcinoma of the skin were reviewed retrospectively. The aggressive nature of this tumour is reflected by the incidence of local recurrence, regional nodal metastases and systemic dissemination, which is 36%, 55%, and 18% respectively. This high frequency of local recurrence and metastases is confirmed in the literature. Management strategies should be planned accordingly, following accurate assessment of the extent of disease. Wide excision, with or without nodal dissection, together with adjuvant wide field irradiation is necessary for loco-regional control of this radiosensitive tumour. Radiotherapy alone may be appropriate treatment for extensive loco-regional tumours or in those that have already metastasized. Although the role of chemotherapy is unclear, there are an increasing number of reports of chemosensitivity and further investigation in this area is required.

Aged↗
PubMed1988

Merkel cell tumour of the face successfully treated with radical radiotherapy.

A case of Merkel cell tumour of the face and its dramatic response to a course of radical radiotherapy is presented below. The patient has been free of recurrence for 18 months and has suffered minimal side-effects from the treatment. This suggests that radical radiotherapy, as opposed to the standard wide excision, may be the preferred first-line treatment for at least some of these rare, but highly malignant tumours.

Aged↗
PubMed2000

Merkel cell carcinoma: clinicopathologic correlation, management, and follow-up in five patients.

PURPOSE: To review the clinicopathologic features, management and follow-up in five patients with periocular Merkel cell carcinoma (MCC). METHODS: In this case series study we reviewed the clinical records and histopathologic findings of five consecutive patients with MCC, treated and followed between May 1991 and November 1998. RESULTS: Four patients were female and one was male. Their mean age at the time of surgery was 80 years (range: 69-86 years). Patients presented with a painless, nonulcerated, rapidly growing, solitary reddish or violaceous nodule, ranging in size from 11 to 21 mm, located in the upper eyelid in 4 patients and in the left eyebrow in one patient. Management included excision with frozen section control in three patients, and excision with wide surgical margins in two patients. Histopathologically, all tumors exhibited round cells of intermediate size and scanty cytoplasm, and large, round to oval vesicular nuclei with finely dispersed chromatin and one to three inconspicuous nucleoli. Mitotic figures were numerous. No patient had regional or extraregional metastases at diagnosis. Local recurrence or distant metastases were not detectable during a mean follow-up period of 45 months (range: 32-61 months). This outcome contrasts with the high incidence of local recurrence and early nodal metastasis reported in previous publications. CONCLUSIONS: Early diagnosis and aggressive, histologically controlled surgical treatment of this rare, highly malignant tumor may provide a longer disease-free period. Further investigation is necessary to determine the prognostic factors for recurrence and survival.

Aged↗
PubMedDate not supplied

Cytomorphologic features of Merkel cell carcinoma in fine needle aspiration biopsies. A study of two atypical cases.

OBJECTIVE: To report atypical cytomorphologic features in fine needle aspiration biopsies (FNABs) from two cases of Merkel cell carcinoma (MCC), a primary neuroendocrine neoplasm of skin. STUDY DESIGN: Retrospective review of FNABs with histologic correlation from six patients with MCC and a report of findings from two whose smears showed atypical features. RESULTS: Typically the aspirates produce highly cellular smears of loosely clustered and individual, relatively monomorphic, small tumor cells with round to oval, regularly contoured nuclei. In two of our cases, the tumor cell nuclei exhibited a spectrum of pleomorphism ranging from moderately complex nuclear membranes with cleaves, indentations and protrusions in one case to large, markedly bizarre, convoluted nuclei and multinucleate tumor cells in the extreme case. Both cases were primary neoplasms, and the diagnosis was based on clinical, histologic and immunohistochemical data. Additionally, electron microscopy was performed on the tumor with bizarre nuclei and demonstrated rare, dense core neurosecretory granules and paranuclear bundles of intermediate filaments.

Aged↗
PubMed1994

Neuroendocrine carcinoma of the skin (Merkel cell carcinoma). An immunoelectron-microscopic case study.

An unusual tumor with a controversial name as well as histogenesis, the neuroendocrine carcinoma of the skin (also known as "Merkel cell carcinoma," "trabecular carcinoma of the skin") has previously been extensively studied by immunohistochemical methods at the light-microscopic level. Ultrastructural descriptions of this tumor have also been extensive, although immunocytochemical study of this neoplasm at the electron-microscopic level has been limited. In this report, we have used postembedding protein A-gold immunocytochemistry on thin sections from tumor embedded in Lowicryl K4M to investigate the expression and ultrastructural localization of a panel of commercially available, diagnostically useful antibodies. Antibodies associated with epithelial derivation included anti-keratin monoclonal antibody AE1/AE3, polyclonal anti-keratin, and monoclonal anti-cytokeratin cocktail (MAK-6), as well as a monoclonal antibody against epithelial membrane antigen (EMA). Antibodies associated with neuroendocrine derivation included monoclonal anti-chromogranin A and monoclonal anti-synaptophysin. Although staining with a polyclonal antibody directed against neuron-specific enolase (NSE) was equivocal, there was no labeling with a monoclonal anti-neurofilament antibody. The finding of positive keratin labeling of filaments arranged in paranuclear aggregates correlates well with the previously described immunohistochemical staining pattern at the light-microscopic level. Moreover, the presence of cytoplasmic synaptophysin and chromogranin positivity over dense-core granules exemplifies the neuroendocrine differentiation present in this fascinating tumor of the skin.

Aged↗