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带状疱疹引起的黑色素瘤

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带状疱疹引起的黑色素瘤Cutaneous zosteriform melanoma metastases arising after herpes zoster infection: a case report and review of the literature Cutaneous zosteriform melanoma metastases arising after herpes zoster infection: a case report and review of the literature Iris Zalaudek, Ber...
带状疱疹引起的黑色素瘤
Cutaneous zosteriform melanoma metastases arising after herpes zoster infection: a case report and review of the literature Cutaneous zosteriform melanoma metastases arising after herpes zoster infection: a case report and review of the literature Iris Zalaudek, Bernd Leinweber, Erika Richtig, Josef Smolle and Rainer Hofmann-Wellenhof Melanoma Research 2003, 13:635–639 Department of Dermatology, University of Graz, Graz, Austria. Correspondence to Rainer Hofmann-Wellenhof, Department of Dermatology, University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria. Tel: +43 316 385 2423; fax: +43 316 385 2466; e-mail: rainer.hofmann@uni-graz.at Cutaneous metastases are a form of tumour progression to the skin in patients with cutaneous or systemic malignancies. It has been shown that skin metastases may occur on various body sites, but seem to appear preferentially close to the site of the primary tumour [1] or in particular regions such as the acral areas [2]. Occasionally, skin metastases can arise as the first manifestation of an underlying malignancy, such as the so-called ‘Sister Joseph’s nodule’ [3,4], which is highly indicative for the presence of intra-abdominal cancer. The clinical spectrum of cutaneous metastases is variable, including solitary or multiple nodules, indurated plaques, ulcerations, inflammatory and erythematous lesions, or rarely vesicles or bullae [5]. Particular manifestations include carcinoma en cuirasse, lymphangitis erysipeloides and metastatic alopecia. Additionally, cutaneous metastases in a zosteriform distribution have been observed in a few cases. We report a 59 year old woman with zosteriform melanoma metastases arising in a dermatome that was affected by herpes zoster years before the development of the primary melanoma. Case report We report a 59 year old woman presenting with numerous black to blue nodules on her right back, right lateral thorax and right breast. The previous history revealed a nodular melanoma with satellite metastases (Clark level IV, tumour thickness 4.0 mm) on her right lower back in line with the ninth vertebral body (Fig. 1) 2 years ago and a chronic polyarthritis treated by immunosuppressants. The primary melanoma had been treated by wide surgical excision and sentinel node biopsy of the right axilla, and there was no evidence of metastatic spread. Four months ago, the patient noticed a few black nodules in the scar of the primary melanoma on her right back. Clinically, a diagnosis of cutaneous melanoma metastases was made, and the lesions were excised. Histopathology confirmed the clinical diagnosis of cutaneous metastases located in the dermis and subcutaneous fat. In the following weeks, numerous new black to blue to red nodular cutaneous metastases developed with a typical zosteriform distribution along the right thoracic dermatomes D7 to D9 (Fig. 2), corresponding to the seventh, eighth and ninth right thoracic nerves. Remarkably, the patient mentioned a herpes zoster infection in exactly the same dermatomes 10 years previously (Fig. 3), which had been photodocumented by the patient. We performed a polymerase chain reaction (PCR) for herpes simplex virus and for varicella zoster virus from the primary melanoma and from two excised cutaneous metastases, but viral DNA was not detectable in any of the specimens. In further staging examinations, lymph node metastases in the right axilla were found. The patient is currently receiving radiotherapy for the cutaneous metastases in combination with hyperthermia and irradiation of the right axilla. Discussion Cutaneous metastases may derive from various cutaneous or internal malignancies. Their incidence varies from 4.7% [6] to 9.0% [7], but a more recent study reported an incidence of 10.4% in 4020 patients with metastatic carcinoma [8]. Though the clinical spectrum of cutaneous metastases is highly variable, skin metastases in a zosteriform distribution are extremely rare, although some cases have been reported in the literature [6–26]. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Letter to the Editor 635 0960-8931 & 2003 LippincottWilliams &Wilkins DOI: 10.1097/01.cmr.0000056279.15046.c5 Kikuchi et al. [1] reported 18 cases of zosteriform skin metastases and observed that in approximately 50% of these, skin metastases developed on a site near to the primary tumour, which is consistent with our observation of the initial onset of cutaneous metastases in the scar of the primary melanoma. Hence, the occurrence of cutaneous metastases from an unknown primary could give important information about the location of the underlying malignancy. In addition, Kikuchi et al. [1] found that the majority of skin metastases were derived from adenocarcinomas of the breast, lung and ovary, and warned about the misdiagnosis of herpes zoster, since one third of the patients were initially treated as suffering from herpes zoster. However, in contrast to our observation, none of their patients had a history of herpes zoster. In another study of cutaneous metastases in 4020 patients with metastatic carcinoma, it was reported that skin metastases are not uncommon (10.4%), and melanoma was shown to have the highest overall frequency of skin metastases (44.8%), followed by carcinomas of the breast (30.0%) and nasal sinuses (20.0%). Remarkably, in 7.6% of cases skin metastases were the first sign of extranodal metastatic spread; in the majority of patients with melanoma, skin metastases appeared as pigmented nodules and were the first sign of extranodal metastatic spread. However, a zosteriform pattern of cutaneous melanoma metastases was not seen in these patients [8]. To date, only a few reports have been published on zosteriform skin metastases arising from cutaneous malignancies in particular; these are listed in Table 1. Cuq-Viguier and Viraben [30] reported on zosteriform skin metastases from a squamous cell carcinoma in an 83 year old man, in whom an initial clinical diagnosis of herpes zoster led to a delay in appropriate treatment. In another report, Kato et al. [31] described a 72 year old Japanese woman who developed zosteriform and epidermotropic metastases from a squamous cell carcinoma along the right L1 to L3 dermatomes. There have been some further reports on zosteriform skin metastases derived from primary squamous cell carcinomas, but again, with the exception of one report [37], no herpes zoster infection was found in these patients [32]. It is known that immunosuppression enhances the risk for the development of malignancy, and two cases of zosteriform metastases from squamous cell carcinoma in immunosuppressed renal transplant patients [33,34] and one in a patient suffering from infection with immunodeficiency virus [35] have been reported. In our patient there was also a medical history of immunosuppressant therapy for chronic polyarthritis. Although melanoma has been reported to have the highest frequency of cutaneous metastases [8], we found only three cases of cutaneous melanoma metastases with a zosteriform distribution in the literature, which indicates the unusual nature of this particular manifestation of melanoma skin metastases. Itin et al. [27] reported a 29 year old female with a zosteriform pattern of cutaneous melanoma metastases along the right dermatome D5. As in our patient, the first metastases occurred in the scar of the primary tumour and subsequently spread along the dermatome and to the regional lymph node. However, in contrast to our observations, there was no history of herpes zoster infection or immunosuppressant therapy. In another two cases of cutaneous melanoma metastases with a zosteriform pattern [28,29], there was also no history of herpes zoster infection. In addition, Mac Williams et al. [38] reported a patient with cutaneous melanoma metastases with a vesicular zosteriform appearance, but in this case the skin metastases did not arise along a distinct dermatome. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Fig. 1 Nodular primary melanoma (Clark level IV, tumour thickness 4.0 mm) with satellite metastases on the patient’s back parallel to the ninth vertebral body. 636 Melanoma Research 2003, Vol 13 No 6 The mechanism of the zosteriform distribution of metastases is unknown, but proposed theories include (i) perineural lymphatic spread; (ii) surgical implantation of tumour cells; (iii) neural spread via the dorsal root ganglia; and (iv) koebnerization. In the latter case, the zosteriform metastases probably developed as a consequence of a Koebner-like phenomenon in a site of diminished resistance, which is also called a ‘locus minoris resistentiae’ [39] or an ‘isomorphic response’. However, the mechanism of the ‘isomorphic response’ should be clearly distinguished from the ‘isotopic response’ introduced by Wolf et al. [40] In the former case, the same disease is spreading into diminished skin, whereas the latter describes the occurrence of new and unrelated disease at the previously injured site of resolved disease (see Table 2). It should be noted that in most cases the isotopic response is seen in herpes zoster or herpes simplex scars. Recently, Ruocco et al. [48] reported on the pathogenesis of the isotopic response after herpes virus infections, and outlined four possible types of mechanism for this phenomenon: viral, immunological, vascular or neural. They suggested that it is the result of a neural alteration caused by herpes virus, with a subsequent impairment of the immunological function of the overlying skin. Furthermore, they suggested that a viral background may only function as a cofactor in the pathogenesis, since only one group had been able to detect viral DNA in an ‘isotopic’ squamous cell carcinoma at the site of previous herpes simplex manifestations [49]. In contrast, Serfling et al. [50] failed to detect viral DNA in two out of three specimens of granulomatous skin lesions following a herpes zoster infection. The remaining specimen showed evidence of varicella DNA, but the tissue was sampled in the resolving phase of the disease. In addition, Requena et al. [51] could not identify any varicella zoster virus DNA among 16 patients with cutaneous lesions that had developed in the scars of a previous herpes zoster infection. Since we also failed to demonstrate viral DNA by PCR of the primary melanoma and the cutaneous metastases in our patient, we also suggest that a pathogenetic mechanism other than viral is involved in the development of the isotopic response. In summary, clinicians dealing with oncological patients presenting with skin lesions in a zosteriform distribution should consider this rare form of cutaneous metastases in the differential diagnosis of herpes zoster to avoid delayed and inadequate treatment. The case described here is unusual because, to our best knowledge, there have been no other documented cases of zosteriform cutaneous melanoma metastases arising in a dermatome previously infected by herpes zoster. Moreover, this case underlines the probable role of the isotopic response in the pathogenesis of zosteriform metastases. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Fig. 2 Numerous cutaneous melanoma metastases (asterisks) along the seventh thoracic dermatome. Letter to the Editor Zalaudek et al. 637 References 1 Kikuchi Y, Matsuyama A, Nomura K. Zosteriform metastatic skin cancer: report of three cases and review of the literature. Dermatology 2001; 202:336–338. 2 Soyer HP, Cerroni L, Smolle J, Kerl H. ‘Clown nose’ – skin metastasis of breast cancer. Z Hautkr 1990; 65:929–931. 3 Bailey H. Demonstrations of Physical Signs in Clinical Surgery. Baltimore: Williams and Wilkins; 1949. 4 Holzki G, Kaufmann R, Weber L. ‘Sister Joseph’s nodule’– umbilical metastases of internal tumors. Hautarzt 1989; 40:312–315. 5 Golmann L. Melanoma with vesiculo-bullous metastatic lesions. Arch Dermatol 1966; 93:233–234. 6 Lookingbill DP, Spangler N, Sexton FM. Skin involvement as the presenting sign of internal carcioma. J Am Acad Dermatol 1990; 22:19–26. 7 Spencer PS, Helm TN. Skin metastases in cancer patients. Cutis 1987; 39:119–121. 8 Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. J Am Acad Dermatol 1993; 29:228–236. 9 Brownstein MH, Helwig EB. Spread of tumors to the skin. Arch Dermatol 1973; 107:80–86. 10 Niedt GW, Prioleau PG. Kaposi’s sarcoma occurring in a dermatome previously involved by herpes zoster. J Am Acad Dermatol 1988; 18:448–451. 11 Aberer W, Zonzits E, Soyer HP, Kerl H. Postzosterische spezifische Hautinfiltrate bei chronischer lymphatischer Leuka¨ mie. Hautarzt 1990; 41:455–457. 12 Bluefarb SM, Wallk S, Gecht M. Carcinoma of the prostate with zosteriform cutaneous lesions. Arch Dermatol 1957; 76:402–406. 13 Matarasso SL, Rosen T. Zosteriform metastasis: case presentation and review of the literature. J Dermatol Surg Oncol 1988; 14:774–777. 14 Williams LR, Levine LJ, Kauh YC. Cutaneous malignancies mimicking herpes zoster. Int J Dermatol 1991; 30:432–434. 15 Barney RE. Leukemia cutis resembling herpes zoster. Arch Dermatol Syph 1932; 25:1150–1151. 16 Manteaux A, Cohen PR, Rapini RP. Zosteriform and epidermotropic metastasis. Report of two cases. J Dermatol Surg Oncol 1992; 18: 97–100. 17 Aloi FG, Appino A, Piattini P. Lymphoplasmocytoid lymphoma arising in herpes zoster scars. J Am Acad Dermatol 1990; 22:130–131. 18 Hudson CP, Hanno R, Callen JP. Cutaneous angiosarcoma in a site of healed herpes zoster. Int J Dermatol 1984; 23:404–407. 19 Jaworsky C, Bergfeld WF. Metastatic transitional cell carcinoma mimicking zoster sine herpete. Arch Dermatol 1986; 122:1357–1358. 20 Torne R, Su WPD, Winkelmann RK, Smolle J, Kerl H. Clinicopathologic study of cutaneous plasmacytoma. Int J Dermatol 1990; 29:562–566. 21 Akiyoshi E, Nogita T, Yamaguchi R, Toyoda H, Kawashima M, Hidano A. Eccrine porocarcinoma. Dermatologica 1991; 182:239–242. 22 Roth JS, Grossmann ME. Linear Karposi’s sarcoma in HIV disease. J Am Acad Dermatol 1993; 29:488. 23 Barney RE. Zosteriform leukaemia cutis. Arch Dermatol Syph 1938; 37:238–246. 24 Ruocco V, Astarita C, Guerrera V, Lo Schiavo A, Moscariello CG, Satriano RA, Pisani M. Kaposi’s sarcoma on a lymphedematous immunocompromised limb. Int J Dermatol 1984: 23:56–60. 25 Cecchi R, Brunetti L, Bartoli L, Pavesi M, Giomi A. Zosteriform skin metastases from breast carcinoma in association with herpes zoster. Int J Dermatol 1998; 37:476–477. 26 Caroti A, Torregrossa F, Caroti S. Metastasi cutanee di adenocarcinoma papillifero ovario in sede di Herpes zoster. Chron Dermatol 1987; 18:769–773. 27 Itin HP, Lautenschlager S, Buechner SA. Zosteriform metastases in melanoma. J Am Acad Dermatol 1995; 32:854–857. 28 North S, Mackey JR, Jensen J. Recurrent malignant melanoma presenting with zosteriform metastases. Cutis 1998; 62:143–146. 29 Cuerda Galindo E, Sanchez de Paz F, Mansilla Perez I, Poza Madalena O, Casellas Bravo M. Malignant melanoma with zosteriform metastases. Cutis 2000; 65:312–314. 30 Cuq-Viguier L, Viraben R. Zosteriform cutaneous metastases from squamous cell carcinoma of the stump of an amputated arm. Clin Exp Dermatol 1998; 23:166–168. 31 Kato N, Aoyagi S, Sugarwara H, Mayuzumi M. Zosteriform and epidermotropic metastatic primary cutaneous squamous cell carcinoma. Am J Dermatopathol 2001; 23:216–220. 32 Bauza A, Redondo P, Idoate MA. Cutaneous zosteriform squamous cell carcinoma arising in an immunocompetent patient. Clin Exp Dermatol 2002; 27:199–201. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Fig. 3 (a) Typical herpes zoster lesions following the seventh to ninth thoracic nerve dermatomes. The arrow indicates the location of the primary melanoma that developed 10 years later. (b) Typical herpes zoster lesions along the right seventh thoracic dermatome. Table 1 Skin neoplasms with zosteriform cutaneous metastases Melanoma [27–29] Squamous cell carcinoma [30–35] Cutaneous adnexal neoplasm [16] Basal cell carcinoma [36] Table 2 Skin neoplasms associated with herpes virus infection Lymphoma [17,41,42] Kaposi’s sarcoma [10] Angiosarcoma [18] Squamous cell carcinoma [37] Leukaemia [11,43–46] Basal cell carcinoma [36] Eccrine porocarcinoma [47] 638 Melanoma Research 2003, Vol 13 No 6 33 Buecker JW, Ratz JL. Cutaneous metastatic squamous-cell carcinoma in zosteriform distribution. J Dermatol Surg Oncol 1984; 10:718–720. 34 Shafqat A, Viehman GE, Myers SA. Cutaneous squamous cell carcinoma with zosteriform metastasis in a transplant recipient. J Am Acad Dermatol 1997; 37:1008–1009. 35 Fearfield LA, Nelson M, Francies N, Bunker CB. Cutaneous squamous cell carcinoma with zosteriform metastases in a human immunodeficiency virus-infected patient. Br J Dermatol 2000; 142:573–574. 36 Scheicher-Gottron E, Matheis H. Development of a basal cell carcinoma into a completely undifferentiated tumor. Metastasis formation in zoster scar? Dermatol Wochenschr 1965; 151:1235–1237. 37 Wyburn-Mason R. Malignant change arising in tissues affected by herpes. BMJ 1955; 2:1106–1109. 38 Mac Williams P, Noojin RO. Vesicular metastatic melanoma. South Med J 1974; 67:1365–1367. 39 Gennaro AR, Nora AJ, Nora JJ, Stander R, Weiss L (editors). Blakiston’s Gould Medical Dictionary, 4th edn. New York: McGraw-Hill; 1979, p.778. 40 Wolf R, Brenner S, Ruocco V, Filioli FG. Isotopic response. Int J Dermatol 1995; 34:341–348. 41 Raab W. Herpes zoster als isomorpher Reizeffekt bei chronischer lymphatischer Leuka¨ mie. Arch Clin Exp Dermatol 1984; 218:215–221. 42 Marzano AV, Berti E, Alessi E. Primary cutaneous B-cell lymphoma with a dermatomal distribution. J Am Acad Dermatol 1999; 41:884–886. 43 Cerroni L, Zenahlik P, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia arising at the sites of herpes zoster and herpes simplex scars. Cancer 1995; 76:26–31. 44 Cerroni L, Kerl H. Cutaneous localization of B-cell chronic lymphatic leukemia at the site of varicella/herpesvirus eruptions. J Am Acad Dermatol 1997; 37:1022. 45 Bahadoran P, Lacour JP, Del Giudice P, Perrin C, Dubois D, Samak R, Ortonne JP. Localisation cutane`e du´ne leuce`mie lymphoide chronique dans le territoire du´n zona. Ann Dermatol Venerol 1996; 123:471–473. 46 Anhalt AW, Forsey RR. Herpes zoster, leukemia cutis and leukemic infiltration of the lesions of herpes zoster. CMAJ 1956; 75:750–751. 47 Landa NG, Winkelmann RK. Epidermotropic eccrine porocarcinoma. J Am Acad Dermatol 1991; 24:27–31. 48 Ruocco V, Ruocco E, Ghersetich I, Bianchi B, Lotti T. Isotopic response after herpesvirus infection: an update. J Am Acad Dermatol 2002; 46:90–94. 49 Claudy AL, Chignol MC, Chardonnet Y. Detection of herpes simplex virus DNA in a cutaneous squamous cell carcinoma by in situ hybridization. Arch Dermatol Res 1989; 281:333–335. 50 Serfling U, Penneys NS, Zhu WY, Sisto M, Leonardi C. Varicella-zoster virus DNA granulomatous skin lesions following herpes zoster. A study by the polymerase chain reaction. J Cutan Pathol 1993; 20:28–33. 51 Requena L, Kutzner H, Escalonilla P, Ortiz S, Schaller J, Rohwedder A. Cutaneous reactions at sites of herpes zoster scars: an expanded spectrum. Br J Dermatol 1998; 138:161–168. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Letter to the Editor Zalaudek et al. 639
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