Spontaneous regression in Merkel cell (neuroendocrine) carcinoma of the skin

Kayashima, K.

doi:10.1001/archderm.127.4.550

Cited by 27 publications

(12 citation statements)

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“…[43][44][45] Much of its natural history, diagnosis, and management are still evolving. Because of the relative rarity of this tumor, it precludes a prospective randomized trial to study the intricate roles of surgery, radiation therapy, and chemotherapy in the treatment of this aggressive tumor.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Merkel Cell Carcinoma

Eng¹,

Boersma²,

Fuller³

et al. 2004

American Journal of Clinical Oncology

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Purpose: The purpose of this study was to evaluate the treatment of Merkel cell carcinoma. Materials and Methods: We reviewed 85 cases of Merkel cell carcinoma. There were 68 males and 17 females. The majority of cases involved head and neck sites (48%), followed by the extremities (38%) and trunk (14%). Sixty-seven percent of the patients had stage I disease that was localized to the skin of origin at presentation. Twenty-five percent and 8% were stage II (nodal metastasis) and stage III (distant metastasis), respectively. Surgical intervention included local or wide local excision Ϯ nodal dissection (68%), radical resection Ϯ nodal dissection (22%), and amputation (4%). Five patients (6%) underwent biopsy only because of metastatic disease or unresectability at presentation. Fifty-one percent received adjuvant therapy consisting of external beam radiation therapy and/or combination chemotherapy. Results: With an average follow-up time of 39.5 months, 12% had persistent disease and 40% had recurrent disease. The median time to recurrence was 8 months with a mean of 10.6 months. Although the addition of adjuvant therapy did not affect survival, the recurrence rate was 32.5% for surgery Ϯ adjuvant radiation therapy Ϯ chemotherapy as compared with 52.7% for surgery-only patients. Although the 40.7% recurrence rate for patients receiving surgery and adjuvant radiation therapy was approximately the same as for patients receiving surgery and adjuvant chemotherapy (40%), the effect of systemic chemotherapy on recurrence is less clear as a result of the small number of patients who received such therapy. Although tumor size and site of presentation were not observed to be statistically significant in overall survival, significant differences were observed based on sex and tumor stage. For females, the median survival time was 96 months (mean, 94.5 months) compared with 63 months (mean, 76.8 months) for males. This difference was significant (P Ͻ 0.01). Patients presenting with low-stage (stage I) disease had a significant (P Ͻ 0.01) survival benefit when compared with high-stage individuals (stages II and III). The 5-year actuarial survival rates were 68% and 42%, respectively. Conclusion:In this retrospective study, surgery remains the primary modality for Merkel cell carcinoma, and adjuvant radiation therapy Ϯ systemic chemotherapy reduces local recurrence. Female patients and those who present with early-stage disease appear to have a better prognosis.

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Section: Discussionmentioning

confidence: 99%

Treatment of Merkel Cell Carcinoma

Eng¹,

Boersma²,

Fuller³

et al. 2004

American Journal of Clinical Oncology

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“…The tumor presents as a firm, dome-shaped, red to deep purple or violaceous nodule, which, in one to several years, metastasizes to regional nodes and, if not resected, to other nodes and distant organs [16,14]. On occasion, Merkel cell carcinomas have been found in a lymph node (most often inguinal) in the absence of a primary skin site, in a manner analogous to the spontaneous regression observed in malignant melanomas [17]. Alternatively, an origin from nodal neuroendocrine cells has been proposed [18].…”

Section: Merkel Cell Carcinomamentioning

confidence: 99%

Merkel Cells, Normal and Neoplastic: An Update

Sidhu

Chandra

Cassai

2005

Ultrastructural Pathology

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Merkel cells (MC) occur in the basal epidermal layer, hair follicles, and oral mucosa, as complexes with sensory axons. The axons transduce slowly adapting type I mechanoreception, and MC modulate their sensitivity. MC also determine and maintain the 3-dimensional epidermal structure. They have neuroendocrine granules, rigid spinous processes, and desmosomal junctions with each other and with keratinocytes. Rare MC are dermaWl. Current evidence supports a basal cell origin. Merkel cell carcinomas (MCC) occur mostly in sun-exposed skin in old age. Trabecular, intermediate, or small cell in pattern, MCC have neuroendocrine granules, intercellular junctions, rigid spinous processes, and a paranuclear collection of intermediate filaments staining for cytokeratin 20. Most MCC behave indolently, but those with the small cell pattern, and some with the intermediate pattern, are aggressive and rapidly fatal.

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“…It remains to be determined whether apoptosis is important in spontaneous regression of NB. Initially, we predicted that a regression-prone tumour in stage IV-S or detected by mass screening would undergo extensive apoptosis, as implied by several studies [12,19,36]. In fact, two of the four tumours that displayed electrophoretic DNA ladders were found during mass screening (Fig.…”

Section: Discussionmentioning

confidence: 85%

“…In a tumour, a balance between cell proliferation and apoptotic cell death is a crucial determinant of its net growth rate [3,38]. Accordingly, apoptosis may lead to tumour regression when its extent exceeds that of cell proliferation [12,19,36]. The immunological and maturation hypotheses that have been advanced to explain disappearance of stage IV-S tumour [28] are not well supported, and the idea that apoptosis produces spontaneous NB regression seems plausible.…”

Section: Discussionmentioning

confidence: 99%

“…Ultimately the apoptotic signal activates endonuclease(s) causing DNA self-cleavage [39], resulting, morphologically, in cell shrinkage and hyperchromatic nuclear fragments [20,33] and, biochemically, in chromatin cleavage into nucleosomal oligomers (DNA ladder) [2,9,39]. Among the various roles for apoptosis in tumour biology [21], our particular interest is in the fact that apoptosis seems to be capable of leading to tumour regression, which has been suggested to occur with rhabdomyoma of the heart [36], Merkel cell tumour of the skin [19], and infantile myofibromatosis [12]. This raises the strong possibility that spontaneous regression of NB may also be mediated by apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Demonstration of apoptosis in neuroblastoma and its relationship to tumour regression

Koizumi

Wakisaka

Nakada

et al. 1995

Vichows Archiv A Pathol Anat

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The in vivo occurrence of apoptosis in neuroblastomas was investigated. Histologically, a number of tumour cells showed typical apoptotic changes, including cell shrinkage, condensed and fragmented nuclei, eosinophilic cytoplasm, and absence of the inflammatory response. These cells coincided closely with the so-called karyorrhectic cells. An electrophoretic DNA ladder, a functional hallmark of apoptosis, was demonstrated in four of six tumours, and DNA fragmentation was detected in situ by terminal deoxytransferase-mediated nick end-labelling in 26 of 35 tumour specimens (74%). The labelled cell counts ranged from 5 to 62 per 5000 tumour cells (mean +/- SD: 15.0 +/- 14.5). Immunoperoxidase staining revealed that an apoptosis-suppressing protein, bcl-2, was expressed abundantly in advanced-stage tumours, whereas it was absent from karyorrhectic-apoptotic cells. Several tumours with the potential for spontaneous regression were bcl-2-deficient. Immunostaining of the Fas receptor for apoptosis demonstrated that the tumour cells expressed this molecule on their cell surfaces. Our results provide evidence of apoptosis in neuroblastomas and suggest that bcl-2 and the Fas receptor may play a role in its regulatory mechanisms.

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Spontaneous regression in Merkel cell (neuroendocrine) carcinoma of the skin

Cited by 27 publications

References 0 publications

Treatment of Merkel Cell Carcinoma

Treatment of Merkel Cell Carcinoma

Merkel Cells, Normal and Neoplastic: An Update

Demonstration of apoptosis in neuroblastoma and its relationship to tumour regression

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