RHABDOMYOSARCOMA IN A CONGENITAL PIGMENTED NEVUS
Fernando C. Schmitt, MD, PhD
0
Departamento de Patologia, Fac. Med. de
Botucatu, UNESP-SP, Brazil
Achileia Bittencourt, MD, PhD
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
0 LaboratArio de Anatomia Patolbgica do Hospital Martaggo Gesteira, Salvador, Bahia, Brazil
Nubia Mendonca, MD, and Maria Dorea, MD 0 Servico de Oncologia Pediatrica do Hospital Martaggo Gesteira (Liga Baiana contra mortalidade infantil), Salvador, Bahia, Brazil
0 A 7-month-old boy had a giant pigmnted lesion involving the trunk and thighs that exhibited many hyperpigmented hairy and uerrucous nevi. One of the nevi ulcerated and on histological examination consisted of pleomorphic rhabdomyosarcoma cells that stained for muscle-specijic actin (HHF-35), desmin, and myoglobin. Around the tumor, in the dermis, benign pigmented neuus cells were observed. The occurrence of malignant tumors, other than malignant melanoma, in pigmented nevi is rare4 described.
KEY WORDS: rhabdomyosarcoma, melanocytic nevq immunohistochemislry
INTRODUCTION Congenital melanocytic nevi are hairy cutaneous maldevelopmental lesions of the ectoderm found in about 1 % of newborns (1). Those measuring more than 20 cm in greatest diameter are referred to as giant congenital melanocytic nevi (GCMN). The nevi often have the distribution of a garment-a bathing trunk, a cap, a shoulder stole, a coat sleeve, or a stocking. They are usually deeply pigmented and covered with a moderate growth of hair. Malignant transformation in GCMN in variably reported and the lifetime risk of malignancy is estimated at 4.6-6.3% (2, 3). Although malignant melanoma is the most frequent neoplasm occurring in GCMN (2-5), undifferentiated small round cells, spindle cells, heterologous mesenchymal cells, and neuroid cells have all been recognized in neoplasms that arise in congenital melanocytic nevi (6-9). Hendrickson and Ross (8) described a malignant Address reprint requests to Fernando C. Schmitt, MD, PhD, Departamento de Patologia da Fac. de Med. de Botucatu, 18610 Botucatu SP, Brazil. Pediatric Pathology, 12:93-98, I992 Copyright @ 1992 by Hemisphere Publishing Corporation
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mixed neoplasm that had myxoid areas with scattered lipoblasts and rhabdomyoblasts. We report rhabdomyosarcoma that developed within a giant congenital melanocytic nevus.
REPORT OF A CASE
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
Clinical Findings A 7-month-old mulatto boy had a giant pigmented lesion involving the trunk and thighs that exhibited many hyperpigmented hairy and verrucous nevi (Fig. 1). One of the nevi had recently become infiltrated and ulcerated. This lesion and another pigmented lesion were excised. The diagnosis was rhabdomyosarcoma arising in a congenital melanocytic nevus. After resection of the tumor of the child was treated with vincristine, Actinomycin D, Adriamycin, and cyclophosphamide for 1 year. At one-half year of follow-up the patient has no evidence of recurrence or metastasis.
Pathologic Findings The main lesion was ulcerated, measured 3.0 X 2.5 cm, and consisted of an extensive intradermal pigmented nevus with a malignant intradermal neoplasm. The epidermis showed irregular papillomatosis and no junctional activity was observed. The dermis contained broad, bandlike sheets of benign melanocytes. Tumor merged with adjacent congenital nevus and was composed of sheets of small round cells admixed with mitotically active spindle cells (Fig. 2). The cytoplasm of these cells was acidophilic, and they had hyperchromatic and pleomorphic nuclei. The tumor cells contained no melanin granules using the Masson-Fontana stain. The diagnosis was that of an embryonal rhabdomyosarcoma arising in GCMN. The other lesion was a typical intradermal nevus.
lmmunohistochemistry Findings Formalin-fixed, paraffin-embedded tissue sections were studied by the avidin-biotin complex immunoperoxidase method (10) using the following antibodies: monoclonal antibody to melanoma (HMB-45) and anti-musclespecific actin (HHF-35) (kindly provided by Dr. Allen Gown, Washington University, Seattle); monoclonal antibody to cytokeratins (AE 1/ AE3, Hybritech, San Diego); monoclonal antibody to vimentin (DAKO); and polyclonal
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FIGURE 1 . Multiple giant congenital nevi are seen. T h e arrow indicates a large surgical scar where the rhabdornyosarcoma was excised.
FIGURE 2. T h e predominant tumor pattern is composed of small round cells admixed with spindle cells that have an acidophilic cytoplasm. X 400.
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
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FIGURE 3. Some tumor cells demonstrate strong HHF-35 staining in the cytoplasm. Unstained cells are nevus cells. X 400.
antibodies to desmin (DAKO), myoglobin (DAKO), SlOO protein (DAKO), and neuron-specific enolase (DAKO). The avidin, biotinylated peroxidase, and biotinylated secondary antibodies were from Vector Laboratories, Burlingame, California. The neoplastic cells showed diffuse cytoplasmic staining for HHF-35 (Fig. 3), desmin, and vimentin. Focal reactivity for myoglobin was observed, while anti-S100 protein stained only the nevus cells. Tumor cells did not react with the HMB-45, SlOO protein, cytokeratins, or neuron-specific enolase antibodies.
DISCUSSION Most of the neoplasms that arise in the setting of GCMN have been termed malignant melanomas, although unusual morphologic features have been commented on (5-8). Mesenchymal elements in GCMN that are neither neural supportive nor melanocytic have been reported only in isolated instances. Reed et al. (6) reported the presence of benign cartilage in three of their “neuroid” congenital nevi. One of the cases of Harkin and Reed (11) and one of Hendrickson and Ross (8) contained rhabdomyoblasts. The problem of explaining the presence of mesenchymal constituents in a lesion derived from neural crest has
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
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97
been solved by the finding that various elements previously thought to be purely mesodermal in origin could originate from the cranial portion of the neural crest. Thus, the cranial skeleton, odontoblasts, dermis of the head and neck regions, and even smooth muscle cells of some cranial blood vessels and cranial skin are derived from neural crest (12, 13). In birds it has been shown that neural crest cells can differentiate into striated muscle and fat cells (14). The demonstrated potential of ectoderm to give rise to mesenchymal tissues has been incorporated into embryologic theory, and the terms ectomesenchyme and ectomesoderm are now used to denote this expanded capacity of the cephalic portion of the neural crest in certain higher vertebrates. This concept rationalizes the seemingly random mixtures of neoplastic tissues found in some cases of GCMN (8). Immunocytochemistry confirmed that the tumor was indeed a rhabdomyosarcoma. Gown et al. (15) have produced a monoclonal antibody that reacts with melanocytic tumors (HMB-45). The neoplastic cells of our case failed to stain for this marker, making malignant melanoma unlikely. SlOO protein, another marker frequently expressed by neural crest-derived neoplasms (16), including malignant melanomas, was also unreactive. The neoplastic cells did express muscle differentiation markers such as muscle-specific actin (HHF-35) (17), desmin, and myoglobin.
REFERENCES 1, Walton RG, Jacobs AH, Cox AJ. Pigmented lesions in newborn infants. Br J Dermatol 1976;95:38996. 2. Kaplan EN. The risk of malignancy in large congenital nevi. Plast Reconstr Surg 1974;53:421-8. 3. Lorentzen M , Pers M , Bretteville-Jensen G . The evidence of malignant transformation in giant pigmented nevi. Scand J Plast Reconstr Surg 1977;2:163-7. 4. Kopf AW, Bart RS, Hennessey P. Congenital nevocytic nevi and malignant melanomas. J Am Acad Dermatol 1979;1:123-30. 5. Illig L, Weidner F, Hundeiker M, et al. Congenital nevi less than or equal to 10 cm as precursors to melanoma. 52 cases, a review and a new conception. Arch Dermatol 1985;121:1274-81. 6. Reed WB, Becker SW Sr, Becker SW Jr, Nickel WR. Giant pigment nevi, melanoma and leptomeningeal melanocytosis: A clinical and histopathological study. Arch Dermatol 1965;91:100-19. 7. Slaughter JC, Hardman JM, Kempe LG, Earle KM. Neurocutaneous melanosis in children. Arch Pathol Lab Med 1969;88:298-304. 8. Hendrickson MR, Ross JC. Neoplasms arising in congenital giant nevi: Morphologic study of seven cases and a review of the literature. Am J Surg Pathol 1981;5:109-35. 9. Weidner N, Flanders DJ, Jochimsen PR, Stamler FW. Neurosarcomatous malignant melanoma arising in a neuroid giant congenital melanocytic nevus. Arch Dermatol 1985;121:1302-6. 10. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison of ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 198 1 ;29:5 77-80. 1 1 . Harkin C , Reed RJ. Tumors of the peripheral nervous system. Washington DC: Armed Forces Institute of Pathology, 1969. Atlas of Tumor Pathlogy, 2nd series, fasc. 3. 12. Le Douarain NM. Cell recognition based on natural morphological nuclear markers. Med Biol 1974;52:231-319.
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13. Weston JR. The migration and differentiation of neural crest cells. Adv Morphog 1970;8:41-114. 14. Le Lidvre CS, de Dauarain NM. Mesenchymal derivatives of the normal crest: Analysis of chimaeric quail and chick embryos. J Embryo1 Exp Morphol 1975;34:124-54. 15. Gown AM, Vogel AM, Hoak D, Gough F, McNutt MA. Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol 1986;123:195-203. 16. Schmitt FC, Bacchi CE. S-100 protein: Is it useful as a tumour marker in diagnostic immunocytochemistry? Histopathology 1989;15:281-8. 17. Tsukada T, McNutt MA, Ross R , Gown AM. HHF35, a muscle actin-specific monoclonal antibody. J. Reactivity in normal, reactive and neoplastic human tissues. Am J Pathol 1987;127:389-402.
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
Received December 24, 1990 Revision accepted June 7, 1991
Fernando C. Schmitt, MD, PhD
0
Departamento de Patologia, Fac. Med. de
Botucatu, UNESP-SP, Brazil
Achileia Bittencourt, MD, PhD
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
0 LaboratArio de Anatomia Patolbgica do Hospital Martaggo Gesteira, Salvador, Bahia, Brazil
Nubia Mendonca, MD, and Maria Dorea, MD 0 Servico de Oncologia Pediatrica do Hospital Martaggo Gesteira (Liga Baiana contra mortalidade infantil), Salvador, Bahia, Brazil
0 A 7-month-old boy had a giant pigmnted lesion involving the trunk and thighs that exhibited many hyperpigmented hairy and uerrucous nevi. One of the nevi ulcerated and on histological examination consisted of pleomorphic rhabdomyosarcoma cells that stained for muscle-specijic actin (HHF-35), desmin, and myoglobin. Around the tumor, in the dermis, benign pigmented neuus cells were observed. The occurrence of malignant tumors, other than malignant melanoma, in pigmented nevi is rare4 described.
KEY WORDS: rhabdomyosarcoma, melanocytic nevq immunohistochemislry
INTRODUCTION Congenital melanocytic nevi are hairy cutaneous maldevelopmental lesions of the ectoderm found in about 1 % of newborns (1). Those measuring more than 20 cm in greatest diameter are referred to as giant congenital melanocytic nevi (GCMN). The nevi often have the distribution of a garment-a bathing trunk, a cap, a shoulder stole, a coat sleeve, or a stocking. They are usually deeply pigmented and covered with a moderate growth of hair. Malignant transformation in GCMN in variably reported and the lifetime risk of malignancy is estimated at 4.6-6.3% (2, 3). Although malignant melanoma is the most frequent neoplasm occurring in GCMN (2-5), undifferentiated small round cells, spindle cells, heterologous mesenchymal cells, and neuroid cells have all been recognized in neoplasms that arise in congenital melanocytic nevi (6-9). Hendrickson and Ross (8) described a malignant Address reprint requests to Fernando C. Schmitt, MD, PhD, Departamento de Patologia da Fac. de Med. de Botucatu, 18610 Botucatu SP, Brazil. Pediatric Pathology, 12:93-98, I992 Copyright @ 1992 by Hemisphere Publishing Corporation
93
94
F. C. SCHMITT E l AL.
mixed neoplasm that had myxoid areas with scattered lipoblasts and rhabdomyoblasts. We report rhabdomyosarcoma that developed within a giant congenital melanocytic nevus.
REPORT OF A CASE
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
Clinical Findings A 7-month-old mulatto boy had a giant pigmented lesion involving the trunk and thighs that exhibited many hyperpigmented hairy and verrucous nevi (Fig. 1). One of the nevi had recently become infiltrated and ulcerated. This lesion and another pigmented lesion were excised. The diagnosis was rhabdomyosarcoma arising in a congenital melanocytic nevus. After resection of the tumor of the child was treated with vincristine, Actinomycin D, Adriamycin, and cyclophosphamide for 1 year. At one-half year of follow-up the patient has no evidence of recurrence or metastasis.
Pathologic Findings The main lesion was ulcerated, measured 3.0 X 2.5 cm, and consisted of an extensive intradermal pigmented nevus with a malignant intradermal neoplasm. The epidermis showed irregular papillomatosis and no junctional activity was observed. The dermis contained broad, bandlike sheets of benign melanocytes. Tumor merged with adjacent congenital nevus and was composed of sheets of small round cells admixed with mitotically active spindle cells (Fig. 2). The cytoplasm of these cells was acidophilic, and they had hyperchromatic and pleomorphic nuclei. The tumor cells contained no melanin granules using the Masson-Fontana stain. The diagnosis was that of an embryonal rhabdomyosarcoma arising in GCMN. The other lesion was a typical intradermal nevus.
lmmunohistochemistry Findings Formalin-fixed, paraffin-embedded tissue sections were studied by the avidin-biotin complex immunoperoxidase method (10) using the following antibodies: monoclonal antibody to melanoma (HMB-45) and anti-musclespecific actin (HHF-35) (kindly provided by Dr. Allen Gown, Washington University, Seattle); monoclonal antibody to cytokeratins (AE 1/ AE3, Hybritech, San Diego); monoclonal antibody to vimentin (DAKO); and polyclonal
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
RHABDOMYOSARCOMA IN A CONGENITAL NEVUS
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FIGURE 1 . Multiple giant congenital nevi are seen. T h e arrow indicates a large surgical scar where the rhabdornyosarcoma was excised.
FIGURE 2. T h e predominant tumor pattern is composed of small round cells admixed with spindle cells that have an acidophilic cytoplasm. X 400.
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
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FIGURE 3. Some tumor cells demonstrate strong HHF-35 staining in the cytoplasm. Unstained cells are nevus cells. X 400.
antibodies to desmin (DAKO), myoglobin (DAKO), SlOO protein (DAKO), and neuron-specific enolase (DAKO). The avidin, biotinylated peroxidase, and biotinylated secondary antibodies were from Vector Laboratories, Burlingame, California. The neoplastic cells showed diffuse cytoplasmic staining for HHF-35 (Fig. 3), desmin, and vimentin. Focal reactivity for myoglobin was observed, while anti-S100 protein stained only the nevus cells. Tumor cells did not react with the HMB-45, SlOO protein, cytokeratins, or neuron-specific enolase antibodies.
DISCUSSION Most of the neoplasms that arise in the setting of GCMN have been termed malignant melanomas, although unusual morphologic features have been commented on (5-8). Mesenchymal elements in GCMN that are neither neural supportive nor melanocytic have been reported only in isolated instances. Reed et al. (6) reported the presence of benign cartilage in three of their “neuroid” congenital nevi. One of the cases of Harkin and Reed (11) and one of Hendrickson and Ross (8) contained rhabdomyoblasts. The problem of explaining the presence of mesenchymal constituents in a lesion derived from neural crest has
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
RHABDOMVOSARCOMA IN A CONGENITAL NEVUS
97
been solved by the finding that various elements previously thought to be purely mesodermal in origin could originate from the cranial portion of the neural crest. Thus, the cranial skeleton, odontoblasts, dermis of the head and neck regions, and even smooth muscle cells of some cranial blood vessels and cranial skin are derived from neural crest (12, 13). In birds it has been shown that neural crest cells can differentiate into striated muscle and fat cells (14). The demonstrated potential of ectoderm to give rise to mesenchymal tissues has been incorporated into embryologic theory, and the terms ectomesenchyme and ectomesoderm are now used to denote this expanded capacity of the cephalic portion of the neural crest in certain higher vertebrates. This concept rationalizes the seemingly random mixtures of neoplastic tissues found in some cases of GCMN (8). Immunocytochemistry confirmed that the tumor was indeed a rhabdomyosarcoma. Gown et al. (15) have produced a monoclonal antibody that reacts with melanocytic tumors (HMB-45). The neoplastic cells of our case failed to stain for this marker, making malignant melanoma unlikely. SlOO protein, another marker frequently expressed by neural crest-derived neoplasms (16), including malignant melanomas, was also unreactive. The neoplastic cells did express muscle differentiation markers such as muscle-specific actin (HHF-35) (17), desmin, and myoglobin.
REFERENCES 1, Walton RG, Jacobs AH, Cox AJ. Pigmented lesions in newborn infants. Br J Dermatol 1976;95:38996. 2. Kaplan EN. The risk of malignancy in large congenital nevi. Plast Reconstr Surg 1974;53:421-8. 3. Lorentzen M , Pers M , Bretteville-Jensen G . The evidence of malignant transformation in giant pigmented nevi. Scand J Plast Reconstr Surg 1977;2:163-7. 4. Kopf AW, Bart RS, Hennessey P. Congenital nevocytic nevi and malignant melanomas. J Am Acad Dermatol 1979;1:123-30. 5. Illig L, Weidner F, Hundeiker M, et al. Congenital nevi less than or equal to 10 cm as precursors to melanoma. 52 cases, a review and a new conception. Arch Dermatol 1985;121:1274-81. 6. Reed WB, Becker SW Sr, Becker SW Jr, Nickel WR. Giant pigment nevi, melanoma and leptomeningeal melanocytosis: A clinical and histopathological study. Arch Dermatol 1965;91:100-19. 7. Slaughter JC, Hardman JM, Kempe LG, Earle KM. Neurocutaneous melanosis in children. Arch Pathol Lab Med 1969;88:298-304. 8. Hendrickson MR, Ross JC. Neoplasms arising in congenital giant nevi: Morphologic study of seven cases and a review of the literature. Am J Surg Pathol 1981;5:109-35. 9. Weidner N, Flanders DJ, Jochimsen PR, Stamler FW. Neurosarcomatous malignant melanoma arising in a neuroid giant congenital melanocytic nevus. Arch Dermatol 1985;121:1302-6. 10. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison of ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 198 1 ;29:5 77-80. 1 1 . Harkin C , Reed RJ. Tumors of the peripheral nervous system. Washington DC: Armed Forces Institute of Pathology, 1969. Atlas of Tumor Pathlogy, 2nd series, fasc. 3. 12. Le Douarain NM. Cell recognition based on natural morphological nuclear markers. Med Biol 1974;52:231-319.
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13. Weston JR. The migration and differentiation of neural crest cells. Adv Morphog 1970;8:41-114. 14. Le Lidvre CS, de Dauarain NM. Mesenchymal derivatives of the normal crest: Analysis of chimaeric quail and chick embryos. J Embryo1 Exp Morphol 1975;34:124-54. 15. Gown AM, Vogel AM, Hoak D, Gough F, McNutt MA. Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol 1986;123:195-203. 16. Schmitt FC, Bacchi CE. S-100 protein: Is it useful as a tumour marker in diagnostic immunocytochemistry? Histopathology 1989;15:281-8. 17. Tsukada T, McNutt MA, Ross R , Gown AM. HHF35, a muscle actin-specific monoclonal antibody. J. Reactivity in normal, reactive and neoplastic human tissues. Am J Pathol 1987;127:389-402.
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of Newcastle on 01/07/15 For personal use only.
Received December 24, 1990 Revision accepted June 7, 1991
