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Previous Volume 358:649-650 February 7, 2008 Number 6 Next

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To the Editor: We report on the case of a 41-year-old man with a 2.1-cm primary malignant melanoma of the skin, located on the crown of the head. The tumor was stage pT4 (with invasion of contiguous structures), Clark level V, and 6 mm in thickness, with classic morphologic and immunohistochemical features, including strong positivity for the malignant melanoma–specific immunomarkers S100 and MART1 (Figure 1A).

View larger version (107K): [in this window] [in a new window]   Figure 1. Morphologic and Immunohistochemical Features of Primary Malignant Melanoma in a Patient with Metastatic Rhabdomyosarcoma. In primary malignant melanoma, atypical melanocytes show strong immunoreactivity to the melanoma markers S100 and MART1 (Panel A), whereas rhabdomyoblasts in lymph-node metastasis reveal strong positivity for desmin and myogenin, as well as strong overexpression of the subunit of the fetal acetylcholine receptor (AChR) (Panel B, black arrowheads), as compared with the subunit of the primary tumor (Panel A, black arrowheads). The genetic relationship of primary malignant melanoma and rhabdomyosarcoma in lymph-node metastasis was proved by the presence of identical genetic alterations (green and red bands) as seen on comparative genomic hybridization (CGH) (Panels A and B, white arrowheads). Small areas with rhabdoid-like features show overlapping immunoreactivity to markers of melanoma (S100 and MART1) and rhabdomyosarcoma (desmin and myogenin) (Panel C).

 
Three months after complete resection of the tumor, multiple enlarged cervical lymph nodes developed, with the complete morphologic and immunohistochemical phenotype of a rhabdomyosarcoma, including characteristic rhabdomyoblasts that were strongly positive for desmin and myogenin and up-regulation of fetal acetylcholine receptor; the latter was shown to be specific for rhabdomyosarcoma¹ (Figure 1B). In serial sections of the primary tumor, we found small nests of rhabdomyoblasts with overlapping immunoreactivity for both melanoma and rhabdomyosarcoma markers (Figure 1C), in addition to shared genetic alterations (loss of chromosome 1q31, amplification of 1q32, and gain of 12q23-qter), which were detected with the use of comparative genomic hybridization (Figure 1A and 1B).

In spite of intensive radiochemotherapy (56 Gy of cobalt-60 gamma rays and one cycle of dacarbazine [DITC]), the patient died from generalized spread of rhabdomyosarcoma 6 months after primary diagnosis. The metastases involved the lung, mediastinum, and abdominal organs with malignant ascites.

In previous studies of primary and metastatic melanoma with rhabdoidlike features,² neither the morphologic nor the genetic relationship of a primary melanoma with a rhabdoid transdifferentiation in metastasis could be demonstrated. In our patient, the primary lesion had intratumorous rhabdoidlike features and subsequent complete metastatic rhabdomyosarcomatoid transdifferentiation, as shown by morphologic and immunohistochemical analysis and comparative genomic hybridization.

Although the genetic pathways involved in such transdifferentiation still remain unknown, the expression of the mesenchymal and neuroectodermal stem-cell markers CD166, CD133, and nestin³ and of melanoma inhibitory activity (MIA) protein⁴ on differentiating human mesenchymal stem cells highlights the mesenchymal and myogenic potential of melanoma stem cells. These interactions may be a part of the genetic program that is responsible for rhabdoid transdifferentiation in malignant melanoma.

Moreover, since the rhabdoid phenotype is highly associated with a poor prognosis, and since neoplasms with complete rhabdomyosarcomatoid transdifferentiation are not responsive to conventional chemotherapy,⁵ alternative treatments for these advanced-stage diseases must be considered. Such therapies could include immunotherapeutic regimens with the use of chimeric T cells or immunotoxins that target the fetal acetylcholine receptor.¹

Stefan Gattenlöhner, M.D.
Eva-Bettina Brocker, M.D.
Hans-Konrad Muller-Hermelink, M.D.
University of Würzburg
97080 Würzburg, Germany
stefan.gattenloehner{at}mail.uni-wuerzburg.de

Supported by the Wilhelm Sander Foundation and the Help in the Fight against Cancer Foundation.

References

1. Gattenlöhner S, Marx A, Markfort B, et al. Rhabdomyosarcoma lysis by T cells expressing a human autoantibody-based chimeric receptor targeting the fetal acetylcholine receptor. Cancer Res 2006;66:24-28. [Free Full Text]
2. Chang ES, Wick MR, Swanson PE, Dehner LP. Metastatic malignant melanoma with "rhabdoid" features. Am J Clin Pathol 1994;102:426-431. [Web of Science][Medline]
3. Klein WM, Wu BP, Zhao S, Wu H, Klein-Szanto AJ, Tahan SR. Increased expression of stem cell markers in malignant melanoma. Mod Pathol 2007;20:102-107. [CrossRef][Web of Science][Medline]
4. Weber C, Gokorsch S, Czermak P. Expansion and chondrogenic differentiation of human mesenchymal stem cells. Int J Artif Organs 2007;30:611-618. [Web of Science][Medline]
5. Peng HQ, Stanek AE, Teichberg S, Shepard B, Kahn E. Malignant rhabdoid tumor of the kidney in an adult: a case report and review of the literature. Arch Pathol Lab Med 2003;127:e371-e373. [Medline]

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