Skin Lesions in Melanoma and Kaposi's Sarcoma

DIAGNOSIS IN ONCOLOGY Arthur Skarin, MD, Consultant Editor

Skin Lesions in Melanoma and Kaposi’s Sarcoma

CASE 1. DETECTION OF CIRCULATING MALIGNANT CELLS BY RT-PCR IN A CASE OF CUTANEOUS MELANOMA IN COMPLETE REGRESSION A healthy 37-year-old woman with a familial history of cutaneous melanoma and a recent history (6 months) of atypical nevus was seen in consultation by a dermatologist. Complete skin mapping revealed only an oval, 6 ϫ 4-mm pigmented lesion on her upper left arm that had a history of rapid growth and a variegated chromatic pattern (Fig 1A). In vivo digital epiluminescence microscopy showed digitated radial streaming, grayish-blue reticular patterns, opaque gypseous alabaster lacunas, brown-black dots on a blue-gray background, pseudopodia at the periphery, blue-in-pink areas, and a blue-gray velum (Fig 1B). Surprisingly, histologic examination of the excised lesion (Fig 1C and 1D) displayed all the typical pathologic features of completely regressed melanocytic lesion and led to a diagnosis of atypical pigmented lesion in

Fig 1.

Journal of Clinical Oncology, Vol 20, No 5 (March 1), 2002: pp 1411-1418 1411

Downloaded from ascopubs.org by University of Queensland on February 1, 2017 from 130.102.082.083 Copyright © 2017 American Society of Clinical Oncology. All rights reserved. 1412 PIZZICHETTA ET AL regression and a suspicion of melanoma (uninvolved flattened epidermis, fibrosis parallel to the epidermis together with many melanophages, and chronic inflammatory cell infiltration consisting mainly of lymphocytes). Although partial regression in malignant cutaneous melanoma occurred in 10% to 58% in several large series, spontaneous complete regression of primary melanomas are rarely described in the literature.1,2 The present case did not meet all the stringent criteria for the diagnosis of spontaneous complete regression of primary melanoma because of the absence of clinically tumor-involved lymph nodes draining the area where the regressed pigmented lesion was localized. Because of the diagnostic dilemma, 3 months after surgical excision we performed a reverse transcriptaseÐpolymerase chain reaction (RT-PCR)Ðbased assessment of malignant melanoma cells in three sequential peripheral-blood samplings.3-5 Tyrosinase-positive circulating cells (Fig 1E) were detected in all the samples (lanes 1, 2, and 3: peripheral blood from the patient obtained in three sequential samplings at different time points; lane 4: peripheral blood from a healthy donor; lane 5: A375M melanoma cell line). A skin and systemic search for an occult primary melanoma and systemic staging with axillary ultrasonography, total-body computed tomography, and total-bone scintigraphy were negative. On the basis of these data, a diagnosis of complete spontaneous regression of cutaneous malignant melanoma was suggested and a local surgical resection was performed. Results of an RT-PCR assay for tyrosinase from peripheral blood continued to be positive 10 months after the diagnosis in the absence of any other sign of systemic disease or atypical skin lesions. To the best of our knowledge, this is the first report of a diagnosis of a completely regressed primary cutaneous melanoma formulated with the help of RT-PCR tyrosinase detection. Daniele Santini, Giuseppe Tonini, Bruno Vincenzi, Raffaele Murace, Giulio Ferranti, and Alfonso Baldi Universita` Campus Bio-Medico, Centro Diagnostico, and Istituto Dermopatico dell’Immacolata, Rome, and Seconda Universita` di Napoli, Naples, Italy Copyright © 2002 American Society of Clinical Oncology

REFERENCES 1. Bottger D, Dowden RV, Kay PP: Complete spontaneous regres- 4. Brossart P, Schmier JW, Kruger S, et al: A polymerase chain sion of cutaneous primary malignant melanoma. Plast Reconstr Surg reaction-based semiquantitative assessment of malignant melanoma 89:548-553, 1992 cells in peripheral blood. Cancer Res 55:4065-4068, 1995 2. Menzies SW, McCarthy WH: Complete regression of primary 5. Reinhold U, Berkin C, Bosserhoff A-K, et al: Interlaboratory cutaneous malignant melanoma. Arch Surg 132:553-556, 1997 evaluation of a new reverse transcriptase polymerase chain reactionÐ 3. Smith B, Selby P, Southgate J, et al: Detection of melanoma cells based enzyme-linked immunosorbent assay for the detection of circu- in peripheral blood by means of reverse transcriptase and polymerase lating melanoma cells: A multicenter study of the Dermatologic chain reaction. Lancet 338:1227-1229, 1991 Cooperative Oncology Group. J Clin Oncol 19:1723-1727, 2001

CASE 2. DERMOSCOPIC FEATURES OF METASTASES FROM CUTANEOUS MELANOMA MIMICKING BENIGN NEVI AND PRIMARY MELANOMA A 39-year-old woman presented in December 1999 with a 4 ϫ 5-cm brown-black plaque with an irregular margin on the left parietal region of the scalp. The lesion was subsequently excised and histopathologic examination revealed malignant melanoma, Clark level IV, with Breslow thickness of 1.5 mm. At that time, no metastases were detected. Six months later, 11 new pigmented skin lesions, about 4 mm in size, appeared on the right parietal, frontal, and nuchal sites of the scalp and on the upper trunk. Previously, no melanocytic skin lesions were present in these sites. Four of these lesions were examined dermatoscopically, photographed at 10 times magnification, and then excised. The lesions presented clinical and dermatoscopic features simulating either benign melanocytic nevi (Fig 1A and 1B) or primary cutaneous melanoma (Fig 2A and 2B). In three dermatoscopic images, a globular pattern usually ascribed to a benign dermal nevus was recognizable, characterized by grayish-blue globules extending throughout the entire lesion (Fig 1B).1 In contrast, a multicomponent pattern was detectable in one image.2 This was typified by irregular blue-gray pigmentation at the periphery featuring pseudopods and black to grayish dots in the center of the lesion on a reddish background (Fig 2B). Pseudopods have been reported to represent a specific criterion for early invasive melanoma.2 Histopathology of the two lesions revealed metastases from melanoma (Fig 3A and 3B), with dermal involvement only in the former and with dermoepidermal involvement suggestive of a primary cutaneous melanoma in the latter. In January 2001, the patient developed meningeal metastases.

Fig 1.

Fig 2.

The differentiation of cutaneous melanoma metastasis from primary melanoma is often difﬁcult, not only clinically but also dermatoscopically. A series of dermatoscopic variables have been identiﬁed that allow the dermatoscopic diagnosis of cutaneous melanoma metastases.3 However, in our patient, these criteria did not permit differentiation of cutaneous melanoma metastases from benign melanocytic lesions and melanoma in situ. Interestingly enough, other authors described a globular pattern in cutaneous melanoma metastases as well.4

Fig 3.

In conclusion, the evaluation of patients with a history of melanoma and clinically unequivocal pigmented skin lesions cannot rely on dermatoscopic features alone. In cases of recent onset or history of growth, excision is warranted. Maria A. Pizzichetta, Vincenzo Canzonieri, Alessandro Gatti, Clelia de Giacomi, Giusto Trevisan, Andrea Veronesi, and H. Peter Soyer National Cancer Institute, Aviano, and University of Trieste, Trieste, Italy, and University of Graz, Graz, Austria Copyright © 2002 American Society of Clinical Oncology

REFERENCES 1. Kenet RO, Kang S, Kenet BJ, et al: Clinical diagnosis of 3. Schulz H: Epiluminescence microscopy features of cutaneous pigmented lesions using digital epiluminescence microscopy. Arch malignant melanoma metastases. Melanoma Res 10:273-280, 2000 Dermatol 129:157-174, 1993 4. Ferrari A, Peris K, Piccolo D, et al: Dermoscopic features of 2. Menzies SW, Ingvar C, McCarthy WH: A sensitivity and speci- cutaneous local recurrent melanoma. J Am Acad Dermatol 43:722-724, ﬁcity analysis of the surface microscopy features of invasive mela- 2000 noma. Melanoma Res 6:55-62, 1996

CASE 3. FAMILIAL CLASSIC MEDITERRANEAN KAPOSI’S SARCOMA An 82-year-old white man of Syrian descent presented with purplish raised skin lesions involving both feet. The skin lesions on the left foot preceded the occurrence of lesions on the right foot by 4 months and were associated with severe edema of the foot (Fig 1). The lesions progressed gradually and spread to the trunk, involving the right ﬂank and left lateral chest wall.

Fig 1.

Fig 2.

His 35-year-old son had similar purple-blue skin lesions localized to the face that were histologically proven to be Kaposi’s sarcoma. The son’s serum human immunodeficiency virus (HIV) antibodies were negative. The facial skin lesions had a complete response to intralesional interferon therapy, and this patient remains in complete remission after 3 years. Examination of our elderly patient showed that the skin lesions had irregular borders, were slightly raised, and were nontender to palpation. The rest of the physical examination showed left inguinal lymphadenopathy and edema of the left leg. The biopsy of one of the skin lesions revealed irregular vascular spaces lined by endothelial cells with slightly enlarged and hyperchromatic nuclei (Fig 2). Between the vascular spaces, there were aggregates of spindle cells, extravasated erythrocytes, and hemosiderin pigment (Fig 2, arrows; hematoxylin and eosin, ϫ 100). These features are characteristic of Kaposi’s sarcoma. Serum antibodies to HIV-1, HIV-2, and human T-cell leukemia virus-1 were not present. Computed tomography scans of the chest, abdomen, and pelvis did not reveal visceral metastases. The disease was extensive and not amenable to local treatment with surgery or radiation or to topical treatment with cryotherapy, liquid nitrogen, or intralesional vinblastine. This prompted the initiation of paclitaxel as an antiangiogenic agent at 60 mg/m2 administered for 3 consecutive weeks followed by 1 week of rest. After 12 weeks of therapy, the lesions showed significant improvement, with flattening of surface, decrease in size, and fading of color. The edema of the left leg also showed significant improvement (Fig 3). The lesions continue to improve after 5 months of paclitaxel therapy (Fig 4). The classic form of Kaposi’s sarcoma is rare and is seen primarily in older men of Eastern European and Mediterranean origin. The lesions typically appear initially on the hands and feet and gradually progress up the arms and legs. Lymphedema usually follows the development of skin lesions, but it may precede them. If untreated, the disease can spread to involve the viscera or mucosa. Familial classic Kaposi’s sarcoma is exceedingly rare. Our case adds to the few documented cases reported in the English literature (Table 1).1-6

Fig 4.

Table 1. Reported Cases of Familial Kaposi’s Sarcoma in Two or More Members of the Same Family

First Author (ref) Year of Publication Cases of Familial Non-HIV–associated KS McGinn1 1955 An uncle and a niece of Italian descent Zeligman2 1960 A Jewish father and his son Epstein3 1972 Two Latvian brothers Fig 3. Browstein4 1973 One patient and brother in a series of 100 patients with KS Digiovanna5 1981 A Jewish patient and his brother Perniciaro6 1996 A German/English patient and his sister Abbreviation: KS, Kaposi’s sarcoma.

Single lesions can be treated with excisional biopsy, and patients with a few lesions in a limited area can be treated with radiation therapy. Patients with extensive disease can be treated with chemotherapy including vinblastine, doxorubicin, and dacarbazine alone or in combination, but it has limited efﬁcacy.7 Paclitaxel has antiangiogenic and apoptotic effects.8 Its antitumor activity has been reported in AIDS-associated Kaposi’s sarcoma,9,10 but there are limited data describing efﬁcacy in classic Kaposi’s sarcoma, an unusual form of hemangiosarcoma. We have previously reported paclitaxel to be an active agent in the treatment of angiosarcoma of the scalp and face, a hemangiosarcoma similar to Kaposi’s sarcoma.11 This case reveals that paclitaxel should be considered an appropriate therapy with good palliative effects in the treatment of classic Kaposi’s sarcoma. Farid Fata, Ayoub Mirza, and Albert Bernath Geisinger Medical Center, Danville, PA Copyright © 2002 American Society of Clinical Oncology

REFERENCES 1. McGinn JT, Ricca JJ, Currin JF: Kaposi’s sarcoma following 2. Zeligman I: Kaposi’s sarcoma in a father and son. Bull Johns allergic angiitis. Ann Intern Med 42:921-927, 1955 Hopkins Hosp 107:208-212, 1960

3. Epstein E: Kaposi’s sarcoma and parapsoriasis en plaque in 8. Belotti N, Vergani V, Drudis T: The microtubule-affecting drug brothers. JAMA 219:1477-1478, 1972 (letter) paclitaxel has anti-angiogenic activity. Clin Cancer Res 2:1843-1849, 4. Brownstein MH, Shapiro L, Skolnik P: Kaposi’s sarcoma in 1996 community practice. Arch Dermatol 107:137-138, 1973 (letter) 9. Welles L, Saville W, Lietzau J, et al: Phase II trial with dose 5. Digiovanna J, Safai B: Kaposi’s sarcoma: Retrospective study of titration of paclitaxel for the therapy of human immunodeﬁciency 90 cases with particular emphasis on the familial occurrence, ethnic virus-associated Kaposi’s sarcoma. J Clin Oncol 16:1112-1121, 1998 background and prevalence of other diseases. Am J Med 71:779-783, 10. Gill P, Tulpule A, Byron E, et al: Paclitaxel is safe and effective 1981 in the treatment of advanced AIDS-related Kaposi’s sarcoma. J Clin 6. Perniciaro C, Gross DJ, White JW, et al: Familial Kaposi’s Oncol 17:1876-1883, 1999 sarcoma. Cutis 57:220-2222, 1996 11. Fata F, O’Reilly E, Ilson D, et al: Paclitaxel in the treatment of 7. Antman K, Yuan C: Medical progress: Kaposi’s sarcoma. N Engl patients with angiosarcoma of the scalp or face. Cancer 86:2034-2037, J Med 342:1027-1038, 2000 1999