Correspondence

Malignant Melanoma with Metastatic Rhabdomyosarcomatoid Transdifferentiation

N Engl J Med 2008; 358:649-650February 7, 2008

Article

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 1AFigure 1Morphologic and Immunohistochemical Features of Primary Malignant Melanoma in a Patient with Metastatic Rhabdomyosarcoma.).

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@mail.uni-wuerzburg.de

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

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Citing Articles (6)

Citing Articles

1. 1

   Bo Young Chung, In Su Ahn, Soo Ick Cho, Hye One Kim, Kwang Ho Kim, Chun Wook Park, Cheol Heon Lee. (2011) Primary Malignant Rhabdoid Melanoma. Annals of Dermatology 23:Suppl 2, S155
   CrossRef

2. 2

   S. Gattenlöhner, H. Jörißen, M. Huhn, A. Vincent, D. Beeson, S. Tzartos, A. Mamalaki, B. Etschmann, H. K. Muller-Hermelink, E. Koscielniak, S. Barth, A. Marx. (2010) A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model. Journal of Biomedicine and Biotechnology 2010, 1-12
   CrossRef

3. 3

   Denisa Kacerovska, Michal Michal, Heinz Kutzner, Jiri Rychnovsky, Dmitry V Kazakov. (2009) Metastatic Desmoplastic Malignant Melanoma Associated With Low-Grade Myofibroblastic Sarcoma. The American Journal of Dermatopathology 31:5, 490-494
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4. 4

   J M. Comstock, C Bruggers, K Moser, G Hedlund, S Chin, J Riva-Cambrin, H Zhou. (2009) Leptomeningeal Melanoma With Foci of Rhabdomyosarcoma in an Infant With Giant Congenital Nevi. Pathology Case Reviews 14:3, 100-103
   CrossRef

5. 5

   Ben Tallon, Jag Bhawan. (2009) Primary Rhabdoid Melanoma With Clonal Recurrence. The American Journal of Dermatopathology 31:2, 200-204
   CrossRef

6. 6

   Hans-Ullrich Völker, Andreas Zettl, Eugenia Haralambieva, Bernd Blume, Rudolf Hagen, Hans-Konrad Müller-Hermelink, Matthias Scheich, Russell B. Smith. (2009) Leiomyosarcoma of the larynx as a local relapse of squamous cell carcinoma-Report of an unusual case. Head & NeckNA-NA
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