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• W2017709178 abstract "We present the first case of inguinal Merkel cell carcinoma of unknown primary origin in a patient with vulvar Paget's disease. Correlation with immune suppression of both entities warrants further investigation. Additionally, this case highlights the value of ultrasound scanning in the detection of inguinal metastasis. We present the first case of inguinal Merkel cell carcinoma of unknown primary origin in a patient with vulvar Paget's disease. Correlation with immune suppression of both entities warrants further investigation. Additionally, this case highlights the value of ultrasound scanning in the detection of inguinal metastasis. Merkel cell carcinoma (MCC) is a rare form of neuroendocrine cutaneous cancer with high rates of recurrence, metastasis, and poor long-term survival.1Guler-Nizam E. Leiter U. Metzler G. et al.Clinical course and prognostic factors of Merkel cell carcinoma of the skin.Br J Dermatol. 2009; 161: 90-94Crossref PubMed Scopus (34) Google Scholar, 2Eng T.Y. Boersma M.G. Fuller C.D. et al.A comprehensive review of the treatment of Merkel cell carcinoma.Am J Clin Oncol. 2007; 30: 624-636Crossref PubMed Scopus (101) Google Scholar Cases of metastatic MCC with an unidentified primary origin (MCCUP) have been described.3Deneve J.L. Messina J.L. Marzban S.S. et al.Merkel cell carcinoma of unknown primary origin.Ann Surg Oncol. 2012; (Epub ahead of print)Google Scholar, 4Kim E.J. Kim H.S. Kim H.O. et al.Merkel cell carcinoma of the inguinal lymph node with an unknown primary site.J Dermatol. 2009; 36: 170-173Crossref PubMed Scopus (16) Google Scholar, 5Noto R. Giaquinta A. Alessandria I. et al.Right leg swelling as primary presentation of metastatic Merkel cell carcinoma.Minerva Medica. 2008; 99: 341-345PubMed Google Scholar, 6De Cicco L. Vavassori A. Jereczek-Fossa B.A. et al.Lymph node metastases of Merkel cell carcinoma from unknown primary site: report of three cases.Tumori. 2008; 94: 758-761PubMed Google Scholar, 7Nazarian Y. Shalmon B. Horowitz Z. et al.Merkel cell carcinoma of unknown primary site.J Laryngol Otol. 2007; 121: e1Crossref PubMed Scopus (12) Google Scholar, 8Silberstein E. Koretz M. Cagnano E. et al.Neuroendocrine (Merkel cell) carcinoma in regional lymph nodes without primary site.Isr Med Assoc J. 2003; 5: 450-451PubMed Google Scholar, 9Kuwabara H. Mori H. Uda H. et al.Nodal neuroendocrine (Merkel cell) carcinoma without an identifiable primary tumor.Acta Cytol. 2003; 47: 515-517PubMed Google Scholar, 10Fotia G. Barni R. Bellan C. et al.Lymph nodal Merkel cell carcinoma: primary or metastatic disease? A clinical case.Tumori. 2002; 88: 424-426PubMed Google Scholar, 11Heath M. Jaimes N. Lemos B. et al.Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features.J Am Acad Dermatol. 2008; 58: 375-381Abstract Full Text Full Text PDF PubMed Scopus (605) Google Scholar We present the first case of inguinal MCCUP in a patient with noninvasive vulvar Paget's disease. A 69-year-old woman was seen postoperatively following vulvar laser ablation for a history of noninvasive Paget's disease. She has a medical history of invasive right breast cancer status postmastectomy and adjuvant therapy. Postoperatively, she noted a new inguinal lesion. The mass was firm, 3-4 cm in size, painless, and mobile. Ultrasound scans demonstrated a well circumscribed, heterogeneous, cystic 3.7 × 3.7 × 2.1–cm mass in the right inguinal region. Color and power-Doppler scans demonstrated irregular hypervascularity. The mass localized anterior and medial to the proximal femoral vessels (Figure 1) . The differential diagnosis included metastasis from an undiagnosed vulvar carcinoma, new invasive Paget's disease, metastatic breast cancer, or benign mass. Given the additional data that were obtained from ultrasound scanning, core and needle biopsies were deemed inappropriate, and she was taken to the operating room for excision. Intraoperatively, examination redemonstrated no suspicious vulvar or skin findings. The 4-cm mass abutted the femoral vasculature on its inferolateral aspect and the saphenous vein medially. There was no gross invasion, and the mass was excised with clear margins. Pathologic review demonstrated small tumor cells with high nuclear/cytoplasmic ratio and finely staining, dispersed chromatin (Figure 2) . By immunohistochemistry, tumor cells displayed punctate keratin staining (CAM 5.2; AE1/AE3, CK20), positive neuroendocrine markers (synaptophysin, chromogranin, CD56), and negative S-100, CD45, and TTF-1 staining. The final diagnosis was MCC. A work-up for a primary lesion was completed by positron emission tomography–computed tomography with no abnormal findings. An additional, meticulous examination of all skin surfaces was performed with no findings. The patient will undergo adjuvant chemoradiation. The incidence of MCC in the United States is approximately 1500 cases/year.12Lemos B. Nghiem P. Merkel cell carcinoma: more deaths but still no pathway to blame.J Invest Dermatol. 2007; 127: 2100-2103Crossref PubMed Scopus (159) Google Scholar Two retrospective series that have examined MCCUP have placed the incidence at approximately 12-14% of all MCC, although the authors conclude that this is likely an overestimate.3Deneve J.L. Messina J.L. Marzban S.S. et al.Merkel cell carcinoma of unknown primary origin.Ann Surg Oncol. 2012; (Epub ahead of print)Google Scholar, 11Heath M. Jaimes N. Lemos B. et al.Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features.J Am Acad Dermatol. 2008; 58: 375-381Abstract Full Text Full Text PDF PubMed Scopus (605) Google Scholar Histologically, the differential diagnosis of MCC includes lymphoma, high-grade neuroendocrine carcinoma, undifferentiated carcinoma, and melanoma. Our case demonstrated the histopathologic features of MCC, which included (1) typical cytologic findings with high nuclear-cytoplasmic ratio and finely dispersed (“dusty”) chromatin and micronucleoli, (2) typical immunohistochemical findings (punctate staining pattern for keratins that included positivity for CK20 [a low molecular weight cytokeratin that rarely is expressed in carcinomas]), and (3) positivity for neuroendocrine markers. Negative stains for thyroid transcription factor 1, melanoma, and lymphoma markers further supported the diagnosis.13McCardle T.W. Sondak V.K. Zager J. et al.Merkel cell carcinoma: pathologic findings and prognostic factors.Curr Probl Cancer. 2010; 34: 47-64Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar The pathogenesis of MCCUP is unknown. Some investigators have documented regression of primary lesions; other investigators suggest the immune status of the host leads to delayed primary recognition. Other investigators hypothesize that MCCUP does not exist and that these are a primary form of MCC.4Kim E.J. Kim H.S. Kim H.O. et al.Merkel cell carcinoma of the inguinal lymph node with an unknown primary site.J Dermatol. 2009; 36: 170-173Crossref PubMed Scopus (16) Google Scholar, 7Nazarian Y. Shalmon B. Horowitz Z. et al.Merkel cell carcinoma of unknown primary site.J Laryngol Otol. 2007; 121: e1Crossref PubMed Scopus (12) Google Scholar Proposed MCC causes include cellular transformation secondary to sun exposure or viral infection; in addition, an association with other carcinomas is described.14Feng H. Shuda M. Chang Y. et al.Clonal integration of a polyomavirus in human Merkel cell carcinoma.Science. 2008; 319: 1096-1100Crossref PubMed Scopus (2292) Google Scholar, 15Kaae J. Hansen A.V. Biggar R.J. et al.Merkel cell carcinoma: incidence, mortality, and risk of other cancers.J Natl Cancer Inst. 2010; 102: 793-801Crossref PubMed Scopus (154) Google Scholar, 16Howard R.A. Dores G.M. Curtis R.E. et al.Merkel cell carcinoma and multiple primary cancers.Cancer Epidemiol Biomarkers Prev. 2006; 15: 1545-1549Crossref PubMed Scopus (136) Google Scholar Our patient had 2 previous primary neoplastic processes. Breast cancer has not been associated with subsequent MCC. Squamous cell carcinoma has been associated with an approximate 13.5-fold increase in regional MCC.15Kaae J. Hansen A.V. Biggar R.J. et al.Merkel cell carcinoma: incidence, mortality, and risk of other cancers.J Natl Cancer Inst. 2010; 102: 793-801Crossref PubMed Scopus (154) Google Scholar Our patient has a history of Paget's disease without associated invasion or adenocarcinoma. Paget's disease has been linked to immunomodulation and suppression.17Press J.Z. Allison K.H. Garcia R. et al.FOXP3+ regulatory T-cells are abundant in vulvar Paget's disease and are associated with recurrence.Gynecol Oncol. 2011; 120: 296-299Crossref PubMed Scopus (16) Google Scholar Given the location of our patient's disease, her MCC is unlikely related to sun-exposure; therefore, one could speculate that immune suppression may have played a role in her MCC development. Treatment for MCC involves radiotherapy for local control and individualized decision regarding adjuvant chemotherapy.13McCardle T.W. Sondak V.K. Zager J. et al.Merkel cell carcinoma: pathologic findings and prognostic factors.Curr Probl Cancer. 2010; 34: 47-64Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Of further interest was the preoperative diagnosis of metastatic carcinoma by ultrasound scanning. Ultrasound scanning has been studied in vulvar cancer for identification of patients who require sentinel node mapping, full lymph-node dissection, or no further surgical intervention.18Land R. Herod J. Moskovic E. et al.Routine computerized tomography scanning, groin ultrasound with or without fine needle aspiration cytology in the surgical management of primary squamous cell carcinoma of the vulva.Int J Gynecol Cancer. 2006; 16: 312-317Crossref PubMed Scopus (55) Google Scholar Although this modality remains controversial, this case further suggests that ultrasound scanning could have a screening role in these patients to detect inguinal metastases preoperatively and to help to dictate the need for biopsy vs full excision and/or dissection. In conclusion, we present the first known case of inguinal MCCUP in a patient with vulvar Paget's disease. The clinicopathologic connection of MCC to Paget's disease has never been elucidated; correlation with immune suppression in both entities warrants future investigation. Additionally, our report suggests that ultrasound scanning may be valuable in the evaluation of inguinal lymph nodes with suspected metastases." @default.
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• W2017709178 title "Merkel cell carcinoma in a patient with noninvasive vulvar Paget's disease" @default.
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