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Five weeks later&#44; when the patient was seen in the operating room&#44; the lesions had regressed &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; Biopsy of the residual lesion where the primary tumor had been showed only fibrosis and an inflammatory infiltrate &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C &#38; D&#41;&#46; No adjuvant treatment was administered&#46; After 4 years of follow-up&#44; there have been no recurrences or metastasis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second patient was a 72-year-old woman with a history of type 2 diabetes mellitus and a cerebrovascular accident with serious sequelae&#46; She was referred to our unit with 2 polylobulated nodular lesions of 3 to 4 months&#8217; duration located in the left pretibial region&#46; The lesions were ulcerated and measured 2&#46;5<span class="elsevierStyleHsp" style=""></span>cm &#40;proximal&#41; and 5<span class="elsevierStyleHsp" style=""></span>cm &#40;distal&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; Biopsy showed a proliferation of basophilic cells that were positive for both synaptophysin and cytokeratin in the immunohistochemical study and exhibited a dot-like paranuclear pattern &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; Merkel cell polyomavirus was detected by immunohistochemistry&#46; The patient was referred to the Plastic Surgery Department for wide excision and sentinel lymph node biopsy&#46; At the time of the operation 4 weeks after the biopsy&#44; the lesions were no longer elevated and had the appearance of 2 nonspecific ulcers&#46; They were excised using the same elliptical incision&#46; The histologic study showed intense residual fibrosis and an accompanying infiltrate in the 2 ulcers&#46; At the base of the proximal ulcer&#44; there was a 2&#46;5-mm tumor nest formed by basophilic that stained positive for synaptophysin and cytokeratin 20 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#46; The sentinel lymph node biopsy was negative&#46; Adjuvant therapy was not administered because of the patient&#39;s underlying disease&#46; The patient died of urosepsis 2 years after diagnosis of the MCC&#46; There were no signs of tumor recurrence in this period&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Complete regression is defined as the spontaneous disappearance of an entire tumor without treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> The estimated incidence of regression in MCC is 1&#46;7&#37; to 3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> Most cases have been reported in women aged around 80 years old with head and neck lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">5&#44;6</span></a> In most cases&#44; regression was observed after a biopsy or incomplete resection and often within 3 months of the initial clinical presentation&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> Some authors have suggested that biopsy might trigger the spread of viral components capable of stimulating an immune response to tumor cells infected by Merkel cell polyomavirus&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> The mechanism responsible for this regression&#44; however&#44; has not been established&#46; Some authors have suggested cell immunity as a possible cause&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> while others have proposed apoptosis of neoplastic cells&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Complete regression seems to have a better prognosis in MCC than in other tumors such as melanoma&#46; None of the patients who have experienced complete regression of MCC in the reports in the literature died because of recurrence during follow-up&#44; but there have been many reports of metastasis in patients with melanoma following complete regression&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although it has not been possible to detect polyomavirus in some cases of MCC that have undergone complete regression&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> it has been suggested that the infectious etiology of this tumor might make the neoplastic cells more susceptible to the host&#39;s immune response&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> Merkel cell polyomavirus cells were detected in both our patients&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Fifty-one patients have been diagnosed with MCC at our hospital since 1988 and 2 of them have experienced complete spontaneous regression of a primary MCC&#46; This corresponds to an incidence rate of 3&#46;92&#37;&#46; Coinciding with reports in the literature&#44; neither of the patients showed signs of recurrence&#46; In our experience&#44; complete regression of MCC is not uncommon and appears to be associated with a good prognosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Case and Research Letters
Complete Spontaneous Regression of the Primary Tumor in Merkel Cell Carcinoma
Regresión completa espontánea del tumor primario en el carcinoma de células de Merkel
J. Marcovala,
Autor para correspondencia
jmarcoval@bellvitgehospital.cat

Corresponding author.
, F. Valentí-Medinaa, R.M. Penínb, J. Bermejoc
a Servicio de Dermatología, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
b Servicio de Anatomía Patológica, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
c Servicio de Cirugía Plástica, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
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Four months before being seen at our unit&#44; he developed a fast-growing polylobulated nodular lesion with a diameter of 3<span class="elsevierStyleHsp" style=""></span>cm in the parietal region&#46; He also had 2 papules indicative of satellite metastases that measured 4 to 5<span class="elsevierStyleHsp" style=""></span>mm and were located in the right parietal region&#44; about 3 to 4<span class="elsevierStyleHsp" style=""></span>cm from the primary tumor &#40;Fig&#46;&#160;1A&#41;&#46; Biopsy showed a proliferation of basophilic cells that stained positive for synaptophysin and negative for cytokeratin 20&#46; Merkel cell polyomavirus was detected by polymerase chain reaction&#46; A primary neuroendocrine tumor involving the internal organs was ruled out and despite the negative staining for cytokeratin 20&#44; a diagnosis of primary cutaneous MCC was made&#46; The patient was referred to the Plastic Surgery Department and scheduled for wide excision of the lesions and sentinel lymph node biopsy&#46; Five weeks later&#44; when the patient was seen in the operating room&#44; the lesions had regressed &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; Biopsy of the residual lesion where the primary tumor had been showed only fibrosis and an inflammatory infiltrate &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C &#38; D&#41;&#46; No adjuvant treatment was administered&#46; After 4 years of follow-up&#44; there have been no recurrences or metastasis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second patient was a 72-year-old woman with a history of type 2 diabetes mellitus and a cerebrovascular accident with serious sequelae&#46; She was referred to our unit with 2 polylobulated nodular lesions of 3 to 4 months&#8217; duration located in the left pretibial region&#46; The lesions were ulcerated and measured 2&#46;5<span class="elsevierStyleHsp" style=""></span>cm &#40;proximal&#41; and 5<span class="elsevierStyleHsp" style=""></span>cm &#40;distal&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; Biopsy showed a proliferation of basophilic cells that were positive for both synaptophysin and cytokeratin in the immunohistochemical study and exhibited a dot-like paranuclear pattern &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; Merkel cell polyomavirus was detected by immunohistochemistry&#46; The patient was referred to the Plastic Surgery Department for wide excision and sentinel lymph node biopsy&#46; At the time of the operation 4 weeks after the biopsy&#44; the lesions were no longer elevated and had the appearance of 2 nonspecific ulcers&#46; They were excised using the same elliptical incision&#46; The histologic study showed intense residual fibrosis and an accompanying infiltrate in the 2 ulcers&#46; At the base of the proximal ulcer&#44; there was a 2&#46;5-mm tumor nest formed by basophilic that stained positive for synaptophysin and cytokeratin 20 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#46; The sentinel lymph node biopsy was negative&#46; Adjuvant therapy was not administered because of the patient&#39;s underlying disease&#46; The patient died of urosepsis 2 years after diagnosis of the MCC&#46; There were no signs of tumor recurrence in this period&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Complete regression is defined as the spontaneous disappearance of an entire tumor without treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> The estimated incidence of regression in MCC is 1&#46;7&#37; to 3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> Most cases have been reported in women aged around 80 years old with head and neck lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">5&#44;6</span></a> In most cases&#44; regression was observed after a biopsy or incomplete resection and often within 3 months of the initial clinical presentation&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> Some authors have suggested that biopsy might trigger the spread of viral components capable of stimulating an immune response to tumor cells infected by Merkel cell polyomavirus&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> The mechanism responsible for this regression&#44; however&#44; has not been established&#46; Some authors have suggested cell immunity as a possible cause&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> while others have proposed apoptosis of neoplastic cells&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Complete regression seems to have a better prognosis in MCC than in other tumors such as melanoma&#46; None of the patients who have experienced complete regression of MCC in the reports in the literature died because of recurrence during follow-up&#44; but there have been many reports of metastasis in patients with melanoma following complete regression&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although it has not been possible to detect polyomavirus in some cases of MCC that have undergone complete regression&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> it has been suggested that the infectious etiology of this tumor might make the neoplastic cells more susceptible to the host&#39;s immune response&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> Merkel cell polyomavirus cells were detected in both our patients&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Fifty-one patients have been diagnosed with MCC at our hospital since 1988 and 2 of them have experienced complete spontaneous regression of a primary MCC&#46; This corresponds to an incidence rate of 3&#46;92&#37;&#46; Coinciding with reports in the literature&#44; neither of the patients showed signs of recurrence&#46; In our experience&#44; complete regression of MCC is not uncommon and appears to be associated with a good prognosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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