Dermatologic Therapy, Vol. 28, 2015, 282–286 Printed in the United States All rights reserved
C 2015 Wiley Periodicals, Inc. V
DERMATOLOGIC THERAPY ISSN 1396-0296
THERAPEUTIC HOTLINE An unusual case of diffuse Merkel cell carcinoma successfully treated with low dose radiotherapy Foteini Chatzinasiou*, Euaggelia Papadavid*, Penelope Korkolopoulou†, Georgia Levidou†, Ioannis Panayiotides‡, Konstadinos Theodoropoulos*, Vasiliki Pogka§, Charalampos Asimakopoulos¶ & Dimitrios Rigopoulos* *2nd Department of Dermatology, Attikon General University Hospital, Athens, Greece, †Department of Pathology, Laikon General Hospital, National and Kapodistrian University, Athens, Greece, ‡Department of Pathology, Attikon General University Hospital, Athens, Greece, §Hellenic Pasteur Institute, Athens, Greece and ¶Department of Radiotherapy, Attikon General University Hospital, Athens, Greece
ABSTRACT: Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin. MCC should be included in the diagnosis of a rapidly growing infiltrating mass and histology as well as laboratory investigations such as Merkel cell polyoma virus (MCPyV) detection are valuable in its diagnosis. We present an unusual case of giant MCC-positive MCPyV in a Greek woman located on the lower leg. Our patient is very unusual in terms of her extensive MCC and her rapid and complete response to radiotherapy. KEYWORDS: giant Merkel cell carcinoma, immunohistochemistry, Merkel cell polyoma virus, radiotherapy
Introduction Merkel cell carcinoma (MCC) is a rare (ageadjusted incidence rates 0.18–0.41 per 100,000 persons) and highly aggressive neuroendocrine carcinoma that is known for its ability to metastasize, its high recurrence rate and a mortality rate greater than that of malignant melanoma (1,2). In 2008, there were approximately 1500 Address correspondence and reprint requests to: Foteini Chatzinasiou, MD, PhD, 2nd Department of Dermatology, Attikon General University Hospital, Rimini 1, 12462 Athens, Greece, or email: [email protected].
282
MCC cases per year in the United States. More importantly, however, the age-adapted incidence appears to have tripled from 1986 to 2001 with a statistically significant annual increase of 8% (3). MCC develops most often in sun-exposed areas as a solitary dermal nodule red to livid with a smooth, shiny surface. Tumor size is frequently 50 Gy was associated with a better survival. In the literature, also recent, there are several studies reporting on the efficacy of radiotherapy for MCC and the cases described are more than 40 (29,30). Radical radiotherapy is effective in the curative treatment of MCC, especially in patients who would tolerate wide surgical excision poorly, or where it would cause significant cosmetic or functional deficits (29). Patients with MCC treated with radiotherapy alone experience a high likelihood of obtaining in field disease control. Doses of 50–55 Gy in 20–25 fractions are recommended but lower doses (25 Gy in five fractions) are still effective (30). These retrospective studies reported successful results also in some so called “gross tumor.”
Conflict of interest The authors declare that they do not have conflict of interest.
References 1. Schrama D, Ugurel S, Becker JC. Merkel cell carcinoma: recent insights and new treatment options. Curr Opin Oncol 2012: 24 (2): 141–149. 2. Becker JC. Merkel cell carcinoma. Ann Oncol 2010: 21 (Suppl 7): vii81–vii85. 3. Schrama D, Becker JC. Merkel cell carcinomapathogenesis, clinical aspects and treatment. J Eur Acad Dermatol Venereol 2011: 25 (10): 1121–1129. 4. Bichakjian CK, Lowe L, Lao CD, et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer 2007: 110 (1): 1–12. € hler C, 5. Becker JC, Houben R, Ugurel S, Trefzer U, Pfo Schrama D. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol 2009; 129 (1): 248–250. A. 6. Coursaget P, Samimi M, Nicol JT, Gardair C, Touze Human Merkel cell polyomavirus: virological background and clinical implications. APMIS 2013: 121 (8): 755–769. 7. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008: 319 (5866): 1096–1100. 8. Houben R, Dreher C, Angermeyer S, et al. Mechanisms of p53 restriction in Merkel cell carcinoma cells are
285
Chatzinasiou et al.
9.
10. 11.
12. 13.
14.
15.
16.
17.
18.
19.
independent of the Merkel cell polyoma virus T antigens. J Invest Dermatol 2013: 133 (10): 2453–2460. Lemos BD, Storer BE, Iyer JG, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol 2010: 63 (5): 751–761. Toker C. Trabecular carcinoma of the skin. Arch Dermatol 1972: 105 (1): 107–110. Rywlin AM. Malignant Merkel-cell tumor is a more accurate description than trabecular carcinoma. Am J Dermatopathol 1982: 4 (6): 513–515. Kanitakis J. Merkel cell carcinoma. Cancer Treat Res 2009: 146: 329–341. Heath 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 (3): 375–381. Dong HY, Liu W, Cohen P, Mahle CE, Zhang W. B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in Merkel cell carcinoma and small cell carcinomas. Am J Surg Pathol 2005: 29 (5): 687–692. Torlakovic E, Slipicevic A, Robinson C, et al. Pax-5 expression in nonhematopoietic tissues. Am J Clin Pathol 2006: 126 (5): 798–804. Sahi H, Koljonen V, Kavola H, et al. Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless of the presence of Merkel cell polyomavirus. Virchows Arch 2012: 461 (5): 553–559. Waltari M, Sihto H, Kukko H, et al. Association of Merkel cell polyomavirus infection with tumor p53, KIT, stem cell factor, PDGFR-alpha and survival in Merkel cell carcinoma. Int J Cancer 2011: 129 (3): 619–628. Almeida MW, Lopes CC, Almeida Junior HL, Costa LE. Merkel cell carcinoma in lower end. Rev Col Bras Cir 2012: 39 (2): 165–167. Bognet R, Thompson C, Campanelli C. Giant metastatic Merkel cell carcinoma. Skinmed 2013: 11 (3): 179–180.
286
lez CI, Jime nez FJ, Rubio T, 20. Cires Bezanilla M, Gonza Amat I. Merkel cell carcinoma. On one case. An Sist Sanit Navar 2008: 31 (2): 193–196. 21. Hapcic K, Panchal J, Stewart J, Levine N. Giant Merkel cell carcinoma involving the upper extremity. Dermatol Surg 2001: 27 (5): 493–494. 22. Lebas D, Carpentier O, Martin De Lassalle E, Vilain MO, Piette F. Giant primitive neuroendocrine cutaneous carcinoma of the leg. Ann Dermatol Venereol 2004: 131 (6–7 Pt 1): 579–582. 23. Marchesi A, Parodi PC, Brioschi M, Sileo G, Marchesi M, Vaienti L. Giant Merkel cell carcinoma of the lower limb: case report and review of the literature. J Cutan Med Surg 2013: 17 (5): 351–355. 24. Pinto-Almeida T, Oliveira A, Sanches M, Alves R, Caetano M, Selores M. Giant Merkel cell carcinoma. Eur J Dermatol 2011: 21 (4): 603–604. 25. Sivelli R, Ghirarduzzi A, Del Rio P, Ricci R, Sianesi M. Giant Merkel cell carcinoma of the left arm. Case report. Ann Ital Chir 2009: 80 (6): 489–492. 26. Stone N, Burge S. Guess What! Cutaneous Merkel cell carcinoma of the left lower leg. Eur J Dermatol 1998: 8 (4): 285–286. €ber M, Schmitt-Gra €ff A, Kohl 27. Strobel ES, Feyer P, Steingra PK. An unusual case of Merkel cell carcinoma. J Cancer Res Clin Oncol 2008: 134 (2): 119–123. 28. Tada J, Toi Y, Yamada T, et al. Giant neuroendocrine (Merkel cell) carcinoma of the skin. J Am Acad Dermatol 1991: 24 (5 Pt 2): 827–831. 29. Harrington C, Kwan W. Outcomes of Merkel cell carcinoma treated with radiotherapy without radical surgical excision. Ann Surg Oncol 2014: 21 (11): 3401– 3405. 30. Veness M, Howle J. Radiotherapy alone in patients with Merkel cell carcinoma: The Westmead Hospital experience of 41 patients. Australas J Dermatol 2015: 56 (1): 19–24.
C 2015 Wiley Periodicals, Inc. V
DERMATOLOGIC THERAPY ISSN 1396-0296
THERAPEUTIC HOTLINE An unusual case of diffuse Merkel cell carcinoma successfully treated with low dose radiotherapy Foteini Chatzinasiou*, Euaggelia Papadavid*, Penelope Korkolopoulou†, Georgia Levidou†, Ioannis Panayiotides‡, Konstadinos Theodoropoulos*, Vasiliki Pogka§, Charalampos Asimakopoulos¶ & Dimitrios Rigopoulos* *2nd Department of Dermatology, Attikon General University Hospital, Athens, Greece, †Department of Pathology, Laikon General Hospital, National and Kapodistrian University, Athens, Greece, ‡Department of Pathology, Attikon General University Hospital, Athens, Greece, §Hellenic Pasteur Institute, Athens, Greece and ¶Department of Radiotherapy, Attikon General University Hospital, Athens, Greece
ABSTRACT: Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin. MCC should be included in the diagnosis of a rapidly growing infiltrating mass and histology as well as laboratory investigations such as Merkel cell polyoma virus (MCPyV) detection are valuable in its diagnosis. We present an unusual case of giant MCC-positive MCPyV in a Greek woman located on the lower leg. Our patient is very unusual in terms of her extensive MCC and her rapid and complete response to radiotherapy. KEYWORDS: giant Merkel cell carcinoma, immunohistochemistry, Merkel cell polyoma virus, radiotherapy
Introduction Merkel cell carcinoma (MCC) is a rare (ageadjusted incidence rates 0.18–0.41 per 100,000 persons) and highly aggressive neuroendocrine carcinoma that is known for its ability to metastasize, its high recurrence rate and a mortality rate greater than that of malignant melanoma (1,2). In 2008, there were approximately 1500 Address correspondence and reprint requests to: Foteini Chatzinasiou, MD, PhD, 2nd Department of Dermatology, Attikon General University Hospital, Rimini 1, 12462 Athens, Greece, or email: [email protected].
282
MCC cases per year in the United States. More importantly, however, the age-adapted incidence appears to have tripled from 1986 to 2001 with a statistically significant annual increase of 8% (3). MCC develops most often in sun-exposed areas as a solitary dermal nodule red to livid with a smooth, shiny surface. Tumor size is frequently 50 Gy was associated with a better survival. In the literature, also recent, there are several studies reporting on the efficacy of radiotherapy for MCC and the cases described are more than 40 (29,30). Radical radiotherapy is effective in the curative treatment of MCC, especially in patients who would tolerate wide surgical excision poorly, or where it would cause significant cosmetic or functional deficits (29). Patients with MCC treated with radiotherapy alone experience a high likelihood of obtaining in field disease control. Doses of 50–55 Gy in 20–25 fractions are recommended but lower doses (25 Gy in five fractions) are still effective (30). These retrospective studies reported successful results also in some so called “gross tumor.”
Conflict of interest The authors declare that they do not have conflict of interest.
References 1. Schrama D, Ugurel S, Becker JC. Merkel cell carcinoma: recent insights and new treatment options. Curr Opin Oncol 2012: 24 (2): 141–149. 2. Becker JC. Merkel cell carcinoma. Ann Oncol 2010: 21 (Suppl 7): vii81–vii85. 3. Schrama D, Becker JC. Merkel cell carcinomapathogenesis, clinical aspects and treatment. J Eur Acad Dermatol Venereol 2011: 25 (10): 1121–1129. 4. Bichakjian CK, Lowe L, Lao CD, et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer 2007: 110 (1): 1–12. € hler C, 5. Becker JC, Houben R, Ugurel S, Trefzer U, Pfo Schrama D. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol 2009; 129 (1): 248–250. A. 6. Coursaget P, Samimi M, Nicol JT, Gardair C, Touze Human Merkel cell polyomavirus: virological background and clinical implications. APMIS 2013: 121 (8): 755–769. 7. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008: 319 (5866): 1096–1100. 8. Houben R, Dreher C, Angermeyer S, et al. Mechanisms of p53 restriction in Merkel cell carcinoma cells are
285
Chatzinasiou et al.
9.
10. 11.
12. 13.
14.
15.
16.
17.
18.
19.
independent of the Merkel cell polyoma virus T antigens. J Invest Dermatol 2013: 133 (10): 2453–2460. Lemos BD, Storer BE, Iyer JG, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol 2010: 63 (5): 751–761. Toker C. Trabecular carcinoma of the skin. Arch Dermatol 1972: 105 (1): 107–110. Rywlin AM. Malignant Merkel-cell tumor is a more accurate description than trabecular carcinoma. Am J Dermatopathol 1982: 4 (6): 513–515. Kanitakis J. Merkel cell carcinoma. Cancer Treat Res 2009: 146: 329–341. Heath 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 (3): 375–381. Dong HY, Liu W, Cohen P, Mahle CE, Zhang W. B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in Merkel cell carcinoma and small cell carcinomas. Am J Surg Pathol 2005: 29 (5): 687–692. Torlakovic E, Slipicevic A, Robinson C, et al. Pax-5 expression in nonhematopoietic tissues. Am J Clin Pathol 2006: 126 (5): 798–804. Sahi H, Koljonen V, Kavola H, et al. Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless of the presence of Merkel cell polyomavirus. Virchows Arch 2012: 461 (5): 553–559. Waltari M, Sihto H, Kukko H, et al. Association of Merkel cell polyomavirus infection with tumor p53, KIT, stem cell factor, PDGFR-alpha and survival in Merkel cell carcinoma. Int J Cancer 2011: 129 (3): 619–628. Almeida MW, Lopes CC, Almeida Junior HL, Costa LE. Merkel cell carcinoma in lower end. Rev Col Bras Cir 2012: 39 (2): 165–167. Bognet R, Thompson C, Campanelli C. Giant metastatic Merkel cell carcinoma. Skinmed 2013: 11 (3): 179–180.
286
lez CI, Jime nez FJ, Rubio T, 20. Cires Bezanilla M, Gonza Amat I. Merkel cell carcinoma. On one case. An Sist Sanit Navar 2008: 31 (2): 193–196. 21. Hapcic K, Panchal J, Stewart J, Levine N. Giant Merkel cell carcinoma involving the upper extremity. Dermatol Surg 2001: 27 (5): 493–494. 22. Lebas D, Carpentier O, Martin De Lassalle E, Vilain MO, Piette F. Giant primitive neuroendocrine cutaneous carcinoma of the leg. Ann Dermatol Venereol 2004: 131 (6–7 Pt 1): 579–582. 23. Marchesi A, Parodi PC, Brioschi M, Sileo G, Marchesi M, Vaienti L. Giant Merkel cell carcinoma of the lower limb: case report and review of the literature. J Cutan Med Surg 2013: 17 (5): 351–355. 24. Pinto-Almeida T, Oliveira A, Sanches M, Alves R, Caetano M, Selores M. Giant Merkel cell carcinoma. Eur J Dermatol 2011: 21 (4): 603–604. 25. Sivelli R, Ghirarduzzi A, Del Rio P, Ricci R, Sianesi M. Giant Merkel cell carcinoma of the left arm. Case report. Ann Ital Chir 2009: 80 (6): 489–492. 26. Stone N, Burge S. Guess What! Cutaneous Merkel cell carcinoma of the left lower leg. Eur J Dermatol 1998: 8 (4): 285–286. €ber M, Schmitt-Gra €ff A, Kohl 27. Strobel ES, Feyer P, Steingra PK. An unusual case of Merkel cell carcinoma. J Cancer Res Clin Oncol 2008: 134 (2): 119–123. 28. Tada J, Toi Y, Yamada T, et al. Giant neuroendocrine (Merkel cell) carcinoma of the skin. J Am Acad Dermatol 1991: 24 (5 Pt 2): 827–831. 29. Harrington C, Kwan W. Outcomes of Merkel cell carcinoma treated with radiotherapy without radical surgical excision. Ann Surg Oncol 2014: 21 (11): 3401– 3405. 30. Veness M, Howle J. Radiotherapy alone in patients with Merkel cell carcinoma: The Westmead Hospital experience of 41 patients. Australas J Dermatol 2015: 56 (1): 19–24.
