Trabecular carcinoma of the skin. An ultrastructural study

Tang, Cheng Yong; Toker, Cyril

doi:10.1002/1097-0142(197811)42:5<2311::aid-cncr2820420531>3.0.co;2-l

Cited by 486 publications

(223 citation statements)

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“…Originally thought to be of eccrine origin, 1 PNC was subsequently believed to originate from Merkel cells, the normal neuroendocrine cell population of the skin, on the basis of the ultrastructural recognition of neuroendocrine granules within the cytoplasm of tumor cells. 2 A more recent hypothesis is that pure PNCs and mixed neuroendocrine-epithelial cutaneous carcinomas are of epithelial (epidermal or adnexal) origin, having undergone complete or partial neuroendocrine differentiation. 43 In …”

Section: Table 4 Mmps and Timps Expression By Neoplastic Cells In 23mentioning

confidence: 99%

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Expression and prognostic significance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin

et al. 2003

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Primary neuroendocrine carcinoma (PNC) of the skin is the currently favored designation for the tumor originally described by Toker in 1972 as trabecular carcinoma, 1 and subsequently termed Merkel cell carcinoma on the basis of the electron microscopic findings of neurosecretory granules. 2 PNC is a rare, highly malignant neuroendocrine tumor that occurs most commonly in elderly Caucasian patients. Clinically, it usually appears as a rapidly growing nodule on sundamaged skin of the head and neck region and on the extremities, often being indistinguishable from other cutaneous neoplasms on clinical grounds alone. Affected patients have a high risk of disease progression: early local recurrences occur in about 33% of cases, and approximately 50% of patients will develop regional lymph node metastases with eventual death due to systemic dissemination in more than 33% of cases. [3][4] Because of its rarity, prognostic factors have not been fully established. However, cumulative data from small series have suggested that stage, size of the primary tumor, and gender may have an influence on survival, whereas the prognostic impact of anatomic location and age are more controversial. [5][6][7][8] Although various factors can determine the aggressiveness of PNCs, the capacity for invasion and metastasis of tumor cells, involving the degradation of components of basement membranes and the extracellular matrix, is certainly important. The matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes 9,10 involved in the degradation of different components of the extracellular matrix. At present, there is considerable evidence indicating that MMPs play important roles in local invasion and tumor spread. [10][11][12] The family of human MMPs comprises several members classified into 4 main classes according to their structure and in vitro substrate specificity: collagenases, gelatinases, stromelysins, and membrane-type MMPs [11][12] (Table 1).Tissue inhibitors of matrix metalloproteinases (TIMPs) are the major natural inhibitors of MMPs. To date, 4 types of TIMPs (TIMP-1, TIMP-2, TIMP-3, and TIMP-4) have been recognized. The TIMPs are secreted proteins that complex MMPs and are involved in the inhibition of individual MMPs and regulation of their activity. 13 Indeed, it is thought that the balance between activated MMPs and TIMPs determines the

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Section: Table 4 Mmps and Timps Expression By Neoplastic Cells In 23mentioning

confidence: 99%

“…2 PNC is a rare, highly malignant neuroendocrine tumor that occurs most commonly in elderly Caucasian patients. Clinically, it usually appears as a rapidly growing nodule on sundamaged skin of the head and neck region and on the extremities, often being indistinguishable from other cutaneous neoplasms on clinical grounds alone.…”

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confidence: 99%

Expression and prognostic significance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin

et al. 2003

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“…5 In 1972, Merkel cell carcinoma was first described by Cyril Toker 6 as 'trabecular carcinoma', based on the growth pattern of the tumor cells. In 1978, Tang and Toker 7 proposed that the normal neuroendocrine Merkel cell in skin is the probable cell of origin for these lesions, given the numerous membranebound dense core neurosecretory granules within the cells of trabecular carcinoma. In 1875, Merkel cells were first described by Friedrich Sigmund Merkel and are thought to be slow-acting mechanoreceptors found in the basal layers of the epidermis.…”

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confidence: 99%

Silent mutations in KIT and PDGFRA and coexpression of receptors with SCF and PDGFA in Merkel cell carcinoma: implications for tyrosine kinase-based tumorigenesis

Kartha

Sundram

2008

Modern Pathology

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Merkel cell carcinoma is a rare and aggressive form of skin cancer of neuroendocrine origin. Its treatment involves wide excision and radiotherapy but no effective therapy exists for advanced disease. Upregulation of the platelet-derived growth factor receptor family of tyrosine kinases, PDGFRA and KIT, has a crucial role in cancer development. Several studies have shown expression of the tyrosine kinase receptor KIT (CD117) in Merkel cell carcinoma. In this study, we examined the expression and mutational status of KIT and PDGFRA in 14 primary and 18 metastatic Merkel cell carcinoma. The expression of KIT and PDGFRA and their respective ligands, stem cell factor (SCF) and PDGFA, was assessed by immunohistochemistry. In addition, we analyzed KIT exons 9, 11, 13 and 17, and PDGFRA exons 10, 12 and 18 for the presence of activating mutations. We found that only 53% of cases of Merkel cell carcinoma expressed KIT, which was mostly seen as diffuse weak staining, and SCF expression was observed only in 31% of cases. In contrast, 87 and 81% of cases expressed PDGFRA and PDGFA, respectively. We observed coexpression of SCF and KIT in only 5 of 32 cases (16%) whereas 25 of 31 cases (81%) showed coexpression of PDGFRA and its ligand PDGFA. While we documented silent mutations in exon 17 of KIT and exons 10, 12 and 18 of PDGFRA, we were not able to identify any known activating mutations. Our results indicate that there is no correlation between positive immunostaining and occurrence of activating mutations in KIT and PDGFRA. Moreover, the presence of KIT/SCF and PDGFRA/PDGFA coexpression in a proportion of cases may indicate an autocrine/paracrine stimulation loop. We think therefore that imatinib mesylate is less likely to be an effective therapy for Merkel cell carcinoma, unless activating mutations exist in other exons of these receptor kinases.

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“…Durch den einige Jahre später erfolgten elektronenmikroskopischen Nachweis neuroendokriner Granula in diesen trabekulären Karzinomen [2][3][4] gingen die Autoren dieser Studien davon aus, dass diese Karzinome ihren zellulären Ursprung von den Merkelzellen der Haut nehmen könnten. Mit dem daraufhin erfolgten immunhistochemischen Nachweis der Expression neuroendokriner und epithelialer Differenzierungsmarker glaubte man, diesen Eindruck bestätigt zu sehen [5,6], und dementsprechend wurde der Begriff des Merkelzellkarzinoms (MZK) verwendet.…”

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Merkelzellkarzinom: kutane Manifestation einer hochmalignen Prä-/pro-B-Zell-Neoplasie?

et al. 2017

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Trabecular carcinoma of the skin. An ultrastructural study

Cited by 486 publications

References 2 publications

Expression and prognostic significance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin

Expression and prognostic significance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin

Silent mutations in KIT and PDGFRA and coexpression of receptors with SCF and PDGFA in Merkel cell carcinoma: implications for tyrosine kinase-based tumorigenesis

Merkelzellkarzinom: kutane Manifestation einer hochmalignen Prä-/pro-B-Zell-Neoplasie?

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