Cutis

Cutaneous sarcoidosis often masquerades as many other disease entities. We describe the case of a 56-year-old African American man with a 1-year history of progressively enlarging nodules and plaques of the face resulting in a leonine appearance and madarosis. The diagnosis of cutaneous sarcoidosis was made after skin biopsy results revealed noncaseating granulomas without evidence of foreign body, mycobacteria, or deep fungal infection. A thorough systemic workup was void of other comorbidities. The reports of tumoral sarcoidosis or sarcoidosis presenting with leonine facies are rare, and those cases that have been reported have been linked to other systemic findings.

CASE REPORT

A 56-year-old African American man presented with lesions on his face that had been progressively increasing in size over the previous year. Physical examination revealed numerous nontender subcutaneous nodules and plaques on his face, particularly in the forehead region. The nodules ranged in size from 1 to 3.5 cm (Figure 1). Generalized thickening of the facial skin along with marked thinning of the eyebrows resulted in a leonine appearance. In addition to the dramatic facial findings, 1- to 4-mm brown papules were noted on the posterior neck and dorsal right hand. There was no lymphadenopathy or hepatomegaly. Physical examination of the lungs and heart also revealed no abnormalities.

The patient's medical history was significant for hepatitis C and asthma. He had a remote history of seizures from previous alcohol abuse. Results of a complete blood count and serum chemistries, including a liver function test, were normal. Results of serologic tests for syphilis using rapid plasma reagin also were negative.

Skin biopsies from the face and dorsal hand were obtained for histopathologic evaluation (Figure 2). Routine staining of both biopsy specimens with hematoxylin and eosin (H&E) revealed a granulomatous dermatitis with numerous noncaseating epithelioid granulomas (Figure 3). Special stains for acid-fast bacilli using both the Ziehl-Nielsen and Fite-Faraco methods were negative on 6 separate sections. No fungal elements were visualized using Gomori methenamine silver staining technique. Results of fungal, bacterial, and acid-fast bacilli tissue cultures were negative. These changes were compatible with sarcoidosis.

The patient was examined by an ophthalmologist and was noted to have no ocular abnormalities. A chest radiograph showed no hilar adenopathy or pulmonary infiltrates. Pulmonary function test results were normal. Radiographic images of the hands were performed, and no bone changes were seen. A liver biopsy revealed no granulomas to indicate hepatic sarcoidosis. The only pathologic findings present were of mildly active chronic hepatitis C.

An otorhinolaryngologist examined the patient with regard to the swelling around the patient's nose and "sinus problems," possibly from local extension of the tumoral lesions. A computed tomography scan of the sinuses revealed anatomic swelling of the osteomeatal complexes bilaterally, mucosal membrane thickening of the uncinate processes, and nasal septal deviation. The decision was then made to treat the lesions medically and defer any surgery until after a trial of medical management.

Because of the patient's history of hepatitis C, he was not considered to be a candidate for methotrexate therapy. It was decided to give the patient oral prednisone 40 mg per day (approximately 0.5 mg/kg per day) and hydroxychloroquine sulfate 200 mg twice daily. At the patient's 3-week follow-up visit, all lesions had decreased in size with the exception of one of the nodules at his nasal root. His treatment gradually was tapered to prednisone 5 mg per day, and the larger lesions were treated with intralesional triamcinolone acetonide until clearing was obtained. His condition has been maintained successfully for one year on prednisone 5 to 7 mg per day and hydroxychloroquine sulfate 200 mg twice daily. Discontinuation of the prednisone results in flaring of the patient's skin lesions. 

Comment

Approximately 20% to 35% of patients with sarcoidosis have cutaneous disease. Although cutaneous lesions may present at any time during the course of the disease, they often present early after disease onset. The primary lesions most typically found are papules, plaques, nodules, infiltrations of scars, and lupus pernio—a severe, chronic form of cutaneous sarcoidosis with violaceous plaques on the central face.1-4 Given the multitude of manifestations of sarcoidosis, the disease has become known as one of the "great imitators," masquerading as a wide array of disorders from benign appendageal growths to Kaposi sarcoma.5

Of the many descriptions of sarcoidosis, reports of tumoral sarcoidosis are rare. Nodular and other atypical lesions of sarcoidosis most commonly are described in African Americans.6,7 To our knowledge, the largest sarcoidal tumor that has been reported was a 10x20-cm lumbosacral lesion.8 A 3-cm tumor on the chin also has been described, but centrally appearing nodules are the exception. Nodules of sarcoidosis generally are (1) located on the extremities, (2) smaller than 2 cm, and (3) late in the course of disease.8-10

With regard to facial manifestations of sarcoidosis, the most mutilating varieties have been described in the lupus pernio type. In contrast to other forms of sarcoidosis, this type is more closely associated with pulmonary fibrosis, upper respiratory tract involvement, bone lesions, and chronic, persistent disease.1,11,12 One report of an unusual presentation of lupus pernio describes a mutilation of the face with massive plaques and 2- to 3-cm nodules of the infraorbital region of the cheeks. These findings were in conjunction with significant systemic involvement of the upper respiratory tract, lungs, and phalanges.13

The concept of leonine facies traditionally has been described with regard to lymphomas and pseudolymphomas.14,15 We could only find 2 previous reports of sarcoidosis with leonine facies in the literature.16,17 Each of these cases was marked by a significant comorbidity presenting in conjunction with either severe, complete heart block or laryngeal and bone involvement, respectively.

Our patient's presentation was highly unusual in the large tumoral nature and the site of his skin lesions (nodules >2 cm on the face rather than on the extremities), and the disfiguring leonine appearance with madarosis. These significant skin findings, combined with the absence of a severe comorbidity, have not been reported to our knowledge.

The dramatic tumoral nature of the patient's skin lesions warranted consideration of several other disease entities in the clinical differential diagnosis: leprosy, granulomatous rosacea, lymphoma, various histiocytoses, lupus vulgaris, lupoid leishmaniasis, and other infectious granulomas. The diagnosis in this case was supported by the histologic finding of noncaseating granulomas along with a lack of demonstrable foreign bodies, acid-fast organisms, or fungal organisms; however, similar histologic changes can be seen in other diseases, making the diagnosis of sarcoidosis one of exclusion.

Of the disease entities in the clinical differential diagnosis, granulomatous rosacea and infection can be the most difficult to distinguish from sarcoidosis on histology. Granulomatous rosacea often can mimic sarcoidosis clinically because patients present with yellow-brown papules and nodules that are most prominent on the malar cheeks but also can be seen around the mandible and periorally. Granulomatous rosacea was considered less likely in our patient because his skin lesions included the posterior neck and dorsal hand in addition to his facial lesions.18 Also, the histology of granulomatous rosacea shows dermal edema with vascular dilatation and a mixed inflammatory infiltrate with a predilection for the vessels and pilosebaceous units. Granulomas in sarcoidosis generally are without surrounding inflammation (termed naked) and are well-circumscribed. Granulomas in granulomatous rosacea generally are not naked as they are in sarcoidosis, rather they have surrounding inflammation with caseation necrosis sometimes present. They also tend to be less well-circumscribed. These features more commonly are referred to as the tuberculoid type of granuloma.18,19 The results of our patient's biopsy had none of these findings. In addition, although some patients with rosacea initially improve with steroids, continued use invariably results in exacerbation of the disease. Our patient has responded well to steroids.

Infections, particularly tuberculosis, leprosy, and leishmania, are other important considerations in our patient. Clinically, tuberculosis in the skin can manifest in multiple ways depending on both the initial site of infection and the immune status of the patient. The type of tuberculosis that most often would be confused with sarcoidosis clinically is lupus vulgaris. It manifests as red-brown coalescing papules and plaques that are covered by scales. Most of the time, these lesions appear on the head and neck. Regardless of the type of cutaneous tuberculosis, unlike sarcoidosis, there generally is some epidermal change to the lesions, such as scale, verrucous change, or suppuration. In addition, patients often have lymphadenopathy.20,21 Leishmania is another disease that is important to consider. This disease is endemic in Asia Minor, parts of the Middle East, and in countries around the Mediterranean Sea. In the Western Hemisphere, leishmania is found in South America and Central America. Like tuberculosis, these lesions generally exhibit epidermal changes such as ulceration or a verrucous appearance.22-24 With leprosy, most patients present with numbness, with temperature sensation and light touch affected first. Progressive nerve involvement can lead to wasting of the muscles served by the involved nerve. With leprosy, a unique feature that can be associated with skin lesions when they do appear is the loss of hair. On histology, there are distinct subtypes that correlate with the clinical disease spectrum. The histologic type most difficult to distinguish from sarcoidosis is the tuberculoid form in which the numbers of organisms that can be seen on special stains are few or absent. There are numerous granulomas throughout the dermis composed of epithelioid cells, lymphocytes, and Langerhans giant cells. Granulomas can erode into the epidermis or extend into peripheral nerves, both suggestive of leprosy rather than sarcoidosis.25,26

As with granulomatous rosacea, the granulomas seen on histology in all of these infectious disease entities are of the tuberculoid type. If the index of suspicion is high clinically and the diagnosis cannot be made by special stains on histology, polymerase chain reaction techniques can be employed to identify the causative organism. Our patient had no epidermal change to his lesions, no lymphadenopathy, no sensory changes, and no other findings to make us highly suspicious of an infectious cause of his disease. No infectious agent could be found on numerous biopsy sections stained for acid-fast bacilli using both the Ziehl-Nielsen and Fite-Faraco methods; furthermore, tissue cultures were negative. Finally, our patient improved markedly with intralesional and oral steroids, which would not be expected in the case of an infectious etiology.

An important aspect of our patient's history is represented by the presence of chronic hepatitis C. To our knowledge, there are no reports in the literature of granulomatous skin disease such as that in our patient, which was caused by hepatitis C. If our patient's skin disease was related to his underlying hepatitis, we might have expected to see a change in the course of his skin disease as his hepatitis C viral load changed. Although there have been reports implicating the onset of sarcoidosis with the initiation of interferon alfa therapy for treatment of hepatitis C,27,28 our patient had undergone no prior treatment for hepatitis. His underlying hepatitis, however, did limit treatment options for the sarcoidosis by restricting the use of methotrexate.

Treatment of sarcoidosis depends on the extent of the disease. Topical or intralesional glucocorticosteroids often are used for limited cutaneous involvement. Intralesional corticosteroids given at 3-week intervals have proven to be much more effective than the suprapotent topicals because the latter does not provide adequate amounts to the granulomas in the reticular dermis.3,13,29 The most effective systemic agents for the treatment of sarcoidosis are glucocorticoids, reserved for the treatment of widespread lesions, or those that impair function.1 Other agents that have been used with success are methotrexate,30 thalidomide,31 antimalarials,32,33 isotretinoin,34 allopurinol,35 and tranilast.36 In 2 case reports of mutilating lupus pernio of the central face, the only treatment for the cutaneous lesions that resulted in a cosmetically acceptable outcome was surgical excision.13,37 Despite the many agents that have purportedly been used with success, controlled and randomized trials are lacking. 

Cutaneous sarcoidosis often masquerades as many other disease entities. We describe the case of a 56-year-old African American man with a 1-year history of progressively enlarging nodules and plaques of the face resulting in a leonine appearance and madarosis. The diagnosis of cutaneous sarcoidosis was made after skin biopsy results revealed noncaseating granulomas without evidence of foreign body, mycobacteria, or deep fungal infection. A thorough systemic workup was void of other comorbidities. The reports of tumoral sarcoidosis or sarcoidosis presenting with leonine facies are rare, and those cases that have been reported have been linked to other systemic findings.

CASE REPORT

A 56-year-old African American man presented with lesions on his face that had been progressively increasing in size over the previous year. Physical examination revealed numerous nontender subcutaneous nodules and plaques on his face, particularly in the forehead region. The nodules ranged in size from 1 to 3.5 cm (Figure 1). Generalized thickening of the facial skin along with marked thinning of the eyebrows resulted in a leonine appearance. In addition to the dramatic facial findings, 1- to 4-mm brown papules were noted on the posterior neck and dorsal right hand. There was no lymphadenopathy or hepatomegaly. Physical examination of the lungs and heart also revealed no abnormalities.

The patient's medical history was significant for hepatitis C and asthma. He had a remote history of seizures from previous alcohol abuse. Results of a complete blood count and serum chemistries, including a liver function test, were normal. Results of serologic tests for syphilis using rapid plasma reagin also were negative.

Skin biopsies from the face and dorsal hand were obtained for histopathologic evaluation (Figure 2). Routine staining of both biopsy specimens with hematoxylin and eosin (H&E) revealed a granulomatous dermatitis with numerous noncaseating epithelioid granulomas (Figure 3). Special stains for acid-fast bacilli using both the Ziehl-Nielsen and Fite-Faraco methods were negative on 6 separate sections. No fungal elements were visualized using Gomori methenamine silver staining technique. Results of fungal, bacterial, and acid-fast bacilli tissue cultures were negative. These changes were compatible with sarcoidosis.

The patient was examined by an ophthalmologist and was noted to have no ocular abnormalities. A chest radiograph showed no hilar adenopathy or pulmonary infiltrates. Pulmonary function test results were normal. Radiographic images of the hands were performed, and no bone changes were seen. A liver biopsy revealed no granulomas to indicate hepatic sarcoidosis. The only pathologic findings present were of mildly active chronic hepatitis C.

An otorhinolaryngologist examined the patient with regard to the swelling around the patient's nose and "sinus problems," possibly from local extension of the tumoral lesions. A computed tomography scan of the sinuses revealed anatomic swelling of the osteomeatal complexes bilaterally, mucosal membrane thickening of the uncinate processes, and nasal septal deviation. The decision was then made to treat the lesions medically and defer any surgery until after a trial of medical management.

Because of the patient's history of hepatitis C, he was not considered to be a candidate for methotrexate therapy. It was decided to give the patient oral prednisone 40 mg per day (approximately 0.5 mg/kg per day) and hydroxychloroquine sulfate 200 mg twice daily. At the patient's 3-week follow-up visit, all lesions had decreased in size with the exception of one of the nodules at his nasal root. His treatment gradually was tapered to prednisone 5 mg per day, and the larger lesions were treated with intralesional triamcinolone acetonide until clearing was obtained. His condition has been maintained successfully for one year on prednisone 5 to 7 mg per day and hydroxychloroquine sulfate 200 mg twice daily. Discontinuation of the prednisone results in flaring of the patient's skin lesions. 

Comment

Approximately 20% to 35% of patients with sarcoidosis have cutaneous disease. Although cutaneous lesions may present at any time during the course of the disease, they often present early after disease onset. The primary lesions most typically found are papules, plaques, nodules, infiltrations of scars, and lupus pernio—a severe, chronic form of cutaneous sarcoidosis with violaceous plaques on the central face.1-4 Given the multitude of manifestations of sarcoidosis, the disease has become known as one of the "great imitators," masquerading as a wide array of disorders from benign appendageal growths to Kaposi sarcoma.5

Of the many descriptions of sarcoidosis, reports of tumoral sarcoidosis are rare. Nodular and other atypical lesions of sarcoidosis most commonly are described in African Americans.6,7 To our knowledge, the largest sarcoidal tumor that has been reported was a 10x20-cm lumbosacral lesion.8 A 3-cm tumor on the chin also has been described, but centrally appearing nodules are the exception. Nodules of sarcoidosis generally are (1) located on the extremities, (2) smaller than 2 cm, and (3) late in the course of disease.8-10

With regard to facial manifestations of sarcoidosis, the most mutilating varieties have been described in the lupus pernio type. In contrast to other forms of sarcoidosis, this type is more closely associated with pulmonary fibrosis, upper respiratory tract involvement, bone lesions, and chronic, persistent disease.1,11,12 One report of an unusual presentation of lupus pernio describes a mutilation of the face with massive plaques and 2- to 3-cm nodules of the infraorbital region of the cheeks. These findings were in conjunction with significant systemic involvement of the upper respiratory tract, lungs, and phalanges.13

The concept of leonine facies traditionally has been described with regard to lymphomas and pseudolymphomas.14,15 We could only find 2 previous reports of sarcoidosis with leonine facies in the literature.16,17 Each of these cases was marked by a significant comorbidity presenting in conjunction with either severe, complete heart block or laryngeal and bone involvement, respectively.

Our patient's presentation was highly unusual in the large tumoral nature and the site of his skin lesions (nodules >2 cm on the face rather than on the extremities), and the disfiguring leonine appearance with madarosis. These significant skin findings, combined with the absence of a severe comorbidity, have not been reported to our knowledge.

The dramatic tumoral nature of the patient's skin lesions warranted consideration of several other disease entities in the clinical differential diagnosis: leprosy, granulomatous rosacea, lymphoma, various histiocytoses, lupus vulgaris, lupoid leishmaniasis, and other infectious granulomas. The diagnosis in this case was supported by the histologic finding of noncaseating granulomas along with a lack of demonstrable foreign bodies, acid-fast organisms, or fungal organisms; however, similar histologic changes can be seen in other diseases, making the diagnosis of sarcoidosis one of exclusion.

Of the disease entities in the clinical differential diagnosis, granulomatous rosacea and infection can be the most difficult to distinguish from sarcoidosis on histology. Granulomatous rosacea often can mimic sarcoidosis clinically because patients present with yellow-brown papules and nodules that are most prominent on the malar cheeks but also can be seen around the mandible and periorally. Granulomatous rosacea was considered less likely in our patient because his skin lesions included the posterior neck and dorsal hand in addition to his facial lesions.18 Also, the histology of granulomatous rosacea shows dermal edema with vascular dilatation and a mixed inflammatory infiltrate with a predilection for the vessels and pilosebaceous units. Granulomas in sarcoidosis generally are without surrounding inflammation (termed naked) and are well-circumscribed. Granulomas in granulomatous rosacea generally are not naked as they are in sarcoidosis, rather they have surrounding inflammation with caseation necrosis sometimes present. They also tend to be less well-circumscribed. These features more commonly are referred to as the tuberculoid type of granuloma.18,19 The results of our patient's biopsy had none of these findings. In addition, although some patients with rosacea initially improve with steroids, continued use invariably results in exacerbation of the disease. Our patient has responded well to steroids.

Infections, particularly tuberculosis, leprosy, and leishmania, are other important considerations in our patient. Clinically, tuberculosis in the skin can manifest in multiple ways depending on both the initial site of infection and the immune status of the patient. The type of tuberculosis that most often would be confused with sarcoidosis clinically is lupus vulgaris. It manifests as red-brown coalescing papules and plaques that are covered by scales. Most of the time, these lesions appear on the head and neck. Regardless of the type of cutaneous tuberculosis, unlike sarcoidosis, there generally is some epidermal change to the lesions, such as scale, verrucous change, or suppuration. In addition, patients often have lymphadenopathy.20,21 Leishmania is another disease that is important to consider. This disease is endemic in Asia Minor, parts of the Middle East, and in countries around the Mediterranean Sea. In the Western Hemisphere, leishmania is found in South America and Central America. Like tuberculosis, these lesions generally exhibit epidermal changes such as ulceration or a verrucous appearance.22-24 With leprosy, most patients present with numbness, with temperature sensation and light touch affected first. Progressive nerve involvement can lead to wasting of the muscles served by the involved nerve. With leprosy, a unique feature that can be associated with skin lesions when they do appear is the loss of hair. On histology, there are distinct subtypes that correlate with the clinical disease spectrum. The histologic type most difficult to distinguish from sarcoidosis is the tuberculoid form in which the numbers of organisms that can be seen on special stains are few or absent. There are numerous granulomas throughout the dermis composed of epithelioid cells, lymphocytes, and Langerhans giant cells. Granulomas can erode into the epidermis or extend into peripheral nerves, both suggestive of leprosy rather than sarcoidosis.25,26

As with granulomatous rosacea, the granulomas seen on histology in all of these infectious disease entities are of the tuberculoid type. If the index of suspicion is high clinically and the diagnosis cannot be made by special stains on histology, polymerase chain reaction techniques can be employed to identify the causative organism. Our patient had no epidermal change to his lesions, no lymphadenopathy, no sensory changes, and no other findings to make us highly suspicious of an infectious cause of his disease. No infectious agent could be found on numerous biopsy sections stained for acid-fast bacilli using both the Ziehl-Nielsen and Fite-Faraco methods; furthermore, tissue cultures were negative. Finally, our patient improved markedly with intralesional and oral steroids, which would not be expected in the case of an infectious etiology.

An important aspect of our patient's history is represented by the presence of chronic hepatitis C. To our knowledge, there are no reports in the literature of granulomatous skin disease such as that in our patient, which was caused by hepatitis C. If our patient's skin disease was related to his underlying hepatitis, we might have expected to see a change in the course of his skin disease as his hepatitis C viral load changed. Although there have been reports implicating the onset of sarcoidosis with the initiation of interferon alfa therapy for treatment of hepatitis C,27,28 our patient had undergone no prior treatment for hepatitis. His underlying hepatitis, however, did limit treatment options for the sarcoidosis by restricting the use of methotrexate.

Treatment of sarcoidosis depends on the extent of the disease. Topical or intralesional glucocorticosteroids often are used for limited cutaneous involvement. Intralesional corticosteroids given at 3-week intervals have proven to be much more effective than the suprapotent topicals because the latter does not provide adequate amounts to the granulomas in the reticular dermis.3,13,29 The most effective systemic agents for the treatment of sarcoidosis are glucocorticoids, reserved for the treatment of widespread lesions, or those that impair function.1 Other agents that have been used with success are methotrexate,30 thalidomide,31 antimalarials,32,33 isotretinoin,34 allopurinol,35 and tranilast.36 In 2 case reports of mutilating lupus pernio of the central face, the only treatment for the cutaneous lesions that resulted in a cosmetically acceptable outcome was surgical excision.13,37 Despite the many agents that have purportedly been used with success, controlled and randomized trials are lacking. 

Cutaneous sarcoidosis often masquerades as many other disease entities. We describe the case of a 56-year-old African American man with a 1-year history of progressively enlarging nodules and plaques of the face resulting in a leonine appearance and madarosis. The diagnosis of cutaneous sarcoidosis was made after skin biopsy results revealed noncaseating granulomas without evidence of foreign body, mycobacteria, or deep fungal infection. A thorough systemic workup was void of other comorbidities. The reports of tumoral sarcoidosis or sarcoidosis presenting with leonine facies are rare, and those cases that have been reported have been linked to other systemic findings.

CASE REPORT

A 56-year-old African American man presented with lesions on his face that had been progressively increasing in size over the previous year. Physical examination revealed numerous nontender subcutaneous nodules and plaques on his face, particularly in the forehead region. The nodules ranged in size from 1 to 3.5 cm (Figure 1). Generalized thickening of the facial skin along with marked thinning of the eyebrows resulted in a leonine appearance. In addition to the dramatic facial findings, 1- to 4-mm brown papules were noted on the posterior neck and dorsal right hand. There was no lymphadenopathy or hepatomegaly. Physical examination of the lungs and heart also revealed no abnormalities.

The patient's medical history was significant for hepatitis C and asthma. He had a remote history of seizures from previous alcohol abuse. Results of a complete blood count and serum chemistries, including a liver function test, were normal. Results of serologic tests for syphilis using rapid plasma reagin also were negative.

Skin biopsies from the face and dorsal hand were obtained for histopathologic evaluation (Figure 2). Routine staining of both biopsy specimens with hematoxylin and eosin (H&E) revealed a granulomatous dermatitis with numerous noncaseating epithelioid granulomas (Figure 3). Special stains for acid-fast bacilli using both the Ziehl-Nielsen and Fite-Faraco methods were negative on 6 separate sections. No fungal elements were visualized using Gomori methenamine silver staining technique. Results of fungal, bacterial, and acid-fast bacilli tissue cultures were negative. These changes were compatible with sarcoidosis.

The patient was examined by an ophthalmologist and was noted to have no ocular abnormalities. A chest radiograph showed no hilar adenopathy or pulmonary infiltrates. Pulmonary function test results were normal. Radiographic images of the hands were performed, and no bone changes were seen. A liver biopsy revealed no granulomas to indicate hepatic sarcoidosis. The only pathologic findings present were of mildly active chronic hepatitis C.

An otorhinolaryngologist examined the patient with regard to the swelling around the patient's nose and "sinus problems," possibly from local extension of the tumoral lesions. A computed tomography scan of the sinuses revealed anatomic swelling of the osteomeatal complexes bilaterally, mucosal membrane thickening of the uncinate processes, and nasal septal deviation. The decision was then made to treat the lesions medically and defer any surgery until after a trial of medical management.

Because of the patient's history of hepatitis C, he was not considered to be a candidate for methotrexate therapy. It was decided to give the patient oral prednisone 40 mg per day (approximately 0.5 mg/kg per day) and hydroxychloroquine sulfate 200 mg twice daily. At the patient's 3-week follow-up visit, all lesions had decreased in size with the exception of one of the nodules at his nasal root. His treatment gradually was tapered to prednisone 5 mg per day, and the larger lesions were treated with intralesional triamcinolone acetonide until clearing was obtained. His condition has been maintained successfully for one year on prednisone 5 to 7 mg per day and hydroxychloroquine sulfate 200 mg twice daily. Discontinuation of the prednisone results in flaring of the patient's skin lesions. 

Comment

Approximately 20% to 35% of patients with sarcoidosis have cutaneous disease. Although cutaneous lesions may present at any time during the course of the disease, they often present early after disease onset. The primary lesions most typically found are papules, plaques, nodules, infiltrations of scars, and lupus pernio—a severe, chronic form of cutaneous sarcoidosis with violaceous plaques on the central face.1-4 Given the multitude of manifestations of sarcoidosis, the disease has become known as one of the "great imitators," masquerading as a wide array of disorders from benign appendageal growths to Kaposi sarcoma.5

Of the many descriptions of sarcoidosis, reports of tumoral sarcoidosis are rare. Nodular and other atypical lesions of sarcoidosis most commonly are described in African Americans.6,7 To our knowledge, the largest sarcoidal tumor that has been reported was a 10x20-cm lumbosacral lesion.8 A 3-cm tumor on the chin also has been described, but centrally appearing nodules are the exception. Nodules of sarcoidosis generally are (1) located on the extremities, (2) smaller than 2 cm, and (3) late in the course of disease.8-10

With regard to facial manifestations of sarcoidosis, the most mutilating varieties have been described in the lupus pernio type. In contrast to other forms of sarcoidosis, this type is more closely associated with pulmonary fibrosis, upper respiratory tract involvement, bone lesions, and chronic, persistent disease.1,11,12 One report of an unusual presentation of lupus pernio describes a mutilation of the face with massive plaques and 2- to 3-cm nodules of the infraorbital region of the cheeks. These findings were in conjunction with significant systemic involvement of the upper respiratory tract, lungs, and phalanges.13

The concept of leonine facies traditionally has been described with regard to lymphomas and pseudolymphomas.14,15 We could only find 2 previous reports of sarcoidosis with leonine facies in the literature.16,17 Each of these cases was marked by a significant comorbidity presenting in conjunction with either severe, complete heart block or laryngeal and bone involvement, respectively.

Our patient's presentation was highly unusual in the large tumoral nature and the site of his skin lesions (nodules >2 cm on the face rather than on the extremities), and the disfiguring leonine appearance with madarosis. These significant skin findings, combined with the absence of a severe comorbidity, have not been reported to our knowledge.

The dramatic tumoral nature of the patient's skin lesions warranted consideration of several other disease entities in the clinical differential diagnosis: leprosy, granulomatous rosacea, lymphoma, various histiocytoses, lupus vulgaris, lupoid leishmaniasis, and other infectious granulomas. The diagnosis in this case was supported by the histologic finding of noncaseating granulomas along with a lack of demonstrable foreign bodies, acid-fast organisms, or fungal organisms; however, similar histologic changes can be seen in other diseases, making the diagnosis of sarcoidosis one of exclusion.

Of the disease entities in the clinical differential diagnosis, granulomatous rosacea and infection can be the most difficult to distinguish from sarcoidosis on histology. Granulomatous rosacea often can mimic sarcoidosis clinically because patients present with yellow-brown papules and nodules that are most prominent on the malar cheeks but also can be seen around the mandible and periorally. Granulomatous rosacea was considered less likely in our patient because his skin lesions included the posterior neck and dorsal hand in addition to his facial lesions.18 Also, the histology of granulomatous rosacea shows dermal edema with vascular dilatation and a mixed inflammatory infiltrate with a predilection for the vessels and pilosebaceous units. Granulomas in sarcoidosis generally are without surrounding inflammation (termed naked) and are well-circumscribed. Granulomas in granulomatous rosacea generally are not naked as they are in sarcoidosis, rather they have surrounding inflammation with caseation necrosis sometimes present. They also tend to be less well-circumscribed. These features more commonly are referred to as the tuberculoid type of granuloma.18,19 The results of our patient's biopsy had none of these findings. In addition, although some patients with rosacea initially improve with steroids, continued use invariably results in exacerbation of the disease. Our patient has responded well to steroids.

Infections, particularly tuberculosis, leprosy, and leishmania, are other important considerations in our patient. Clinically, tuberculosis in the skin can manifest in multiple ways depending on both the initial site of infection and the immune status of the patient. The type of tuberculosis that most often would be confused with sarcoidosis clinically is lupus vulgaris. It manifests as red-brown coalescing papules and plaques that are covered by scales. Most of the time, these lesions appear on the head and neck. Regardless of the type of cutaneous tuberculosis, unlike sarcoidosis, there generally is some epidermal change to the lesions, such as scale, verrucous change, or suppuration. In addition, patients often have lymphadenopathy.20,21 Leishmania is another disease that is important to consider. This disease is endemic in Asia Minor, parts of the Middle East, and in countries around the Mediterranean Sea. In the Western Hemisphere, leishmania is found in South America and Central America. Like tuberculosis, these lesions generally exhibit epidermal changes such as ulceration or a verrucous appearance.22-24 With leprosy, most patients present with numbness, with temperature sensation and light touch affected first. Progressive nerve involvement can lead to wasting of the muscles served by the involved nerve. With leprosy, a unique feature that can be associated with skin lesions when they do appear is the loss of hair. On histology, there are distinct subtypes that correlate with the clinical disease spectrum. The histologic type most difficult to distinguish from sarcoidosis is the tuberculoid form in which the numbers of organisms that can be seen on special stains are few or absent. There are numerous granulomas throughout the dermis composed of epithelioid cells, lymphocytes, and Langerhans giant cells. Granulomas can erode into the epidermis or extend into peripheral nerves, both suggestive of leprosy rather than sarcoidosis.25,26

As with granulomatous rosacea, the granulomas seen on histology in all of these infectious disease entities are of the tuberculoid type. If the index of suspicion is high clinically and the diagnosis cannot be made by special stains on histology, polymerase chain reaction techniques can be employed to identify the causative organism. Our patient had no epidermal change to his lesions, no lymphadenopathy, no sensory changes, and no other findings to make us highly suspicious of an infectious cause of his disease. No infectious agent could be found on numerous biopsy sections stained for acid-fast bacilli using both the Ziehl-Nielsen and Fite-Faraco methods; furthermore, tissue cultures were negative. Finally, our patient improved markedly with intralesional and oral steroids, which would not be expected in the case of an infectious etiology.

An important aspect of our patient's history is represented by the presence of chronic hepatitis C. To our knowledge, there are no reports in the literature of granulomatous skin disease such as that in our patient, which was caused by hepatitis C. If our patient's skin disease was related to his underlying hepatitis, we might have expected to see a change in the course of his skin disease as his hepatitis C viral load changed. Although there have been reports implicating the onset of sarcoidosis with the initiation of interferon alfa therapy for treatment of hepatitis C,27,28 our patient had undergone no prior treatment for hepatitis. His underlying hepatitis, however, did limit treatment options for the sarcoidosis by restricting the use of methotrexate.

Treatment of sarcoidosis depends on the extent of the disease. Topical or intralesional glucocorticosteroids often are used for limited cutaneous involvement. Intralesional corticosteroids given at 3-week intervals have proven to be much more effective than the suprapotent topicals because the latter does not provide adequate amounts to the granulomas in the reticular dermis.3,13,29 The most effective systemic agents for the treatment of sarcoidosis are glucocorticoids, reserved for the treatment of widespread lesions, or those that impair function.1 Other agents that have been used with success are methotrexate,30 thalidomide,31 antimalarials,32,33 isotretinoin,34 allopurinol,35 and tranilast.36 In 2 case reports of mutilating lupus pernio of the central face, the only treatment for the cutaneous lesions that resulted in a cosmetically acceptable outcome was surgical excision.13,37 Despite the many agents that have purportedly been used with success, controlled and randomized trials are lacking. 

We report the case of a 6-week-old girl who presented with a pedunculated embryonal rhabdomyosarcoma arising in a giant congenital melanocytic nevus (GCMN) on her lower back. There was no associated leptomeningeal involvement. The patient underwent surgical resection of the rhabdomyosarcoma at age 2 months, with subsequent chemotherapy consisting of actinomycin D and vincristine. No recurrences of metastases of tumor have been noted at 5 months of age.

Giant congenital melanocytic nevus (GCMN), defined as measuring or predicted to measure greater than 20 cm in diameter by adulthood, uncommonly occurs in newborns.1 Concerns arise regarding malignant degeneration, with melanoma developing in 4.5% to 8.5% of cases.2,3 Other malignancies rarely have been reported in a GCMN, including rhabdomyosarcoma, melanosarcoma, undifferentiated spindle cell tumor, neuroblastoma, melanoblastoma, myoblastic sarcoma, liposarcoma, and malignant peripheral nerve sheath tumor.1,4 We report a case of rhabdomyosarcoma arising in a GCMN. 

CASE REPORT

A 6-week-old infant girl presented with an 18x13-cm pigmented hairy nevus extending from the lower back onto the abdomen. A rapidly enlarging, soft pink pedunculated polyp measuring 3 cm in diameter had been present centrally at birth (Figure 1). An ultrasound of the spine revealed no abnormalities.

The polyp was surgically resected, along with a portion of the GCMN. Results of the histologic examination disclosed a rhabdomyosarcoma, embryonal type, located superficially within the dermis (Figure 2). The deep and lateral margins showed no evidence of tumor. Immunohistochemistry results of the neoplastic cells showed marked positivity for desmins, smooth muscle actin, and vimentin; results of tests for S100, neuron-specific enolase, chromogranins, synaptophysin, leukocyte common antigen, and CD57 were negative. Myoglobin stain was noncontributory.

No evidence of metastatic disease was noted on computed tomography of the chest, abdomen, and pelvis; bone scan; and bone marrow examination. The patient was started on a chemotherapy regimen consisting of actinomycin D and vincristine.

Comment

Although controversy exists regarding the precise risk of malignant degeneration in GCMN, it presents a major concern. Often, extensive surgical procedures are undertaken to eliminate or manage the risk of malignancy, primarily to minimize the risk of melanoma, the most commonly associated malignancy.5

Rhabdomyosarcoma is the most common soft tissue sarcoma and the third most common extracranial solid tumor of childhood. It is responsible for up to 25% of malignant cutaneous neoplasms in the pediatric population.6 Most tumors occur in the head and neck region, as well as the genitourinary tract; other areas include the extremities and trunk. Rhabdomyosarcoma occurring in the skin de novo may present as an asymptomatic, firm red nodule or as a lobulated mass with a shiny erythematous surface and telangiectatic vessels.6,7 The differential diagnosis includes hemangioma, lymphangioma, hygroma, lymphoma, leukemia cutis, amelanotic melanoma, and angiofibroma.7

The 4 most common histologic subtypes of rhabdomyosarcoma include the following: embryonal, embryonal-botryoid, alveolar, and pleomorphic. The embryonal and embryonal-butryoid subtypes account for 50% to 60% of childhood rhabdomyosarcomas. The alveolar pattern is seen more commonly in older children, and the pleomorphic pattern is seen more in adults.7

Immunohistochemical stains used to identify rhabdomyosarcoma include the intermediate filaments vimentin and desmins. Vimentin highlights undifferentiated cells of mesenchymal origin, whereas desmins become positive as a cell becomes committed to rhabdomyoblastic differentiation. Because myoglobin is also found in skeletal muscle, myoglobin stains less consistently in rhabdomyosarcomas. This is most likely a result of its expression later in the development of skeletal muscle.7,8 Other muscle-specific proteins used in identification are Myo-D, myogenin, muscle- specific actin, and Z-band protein.9

Staging of rhabdomyosarcoma by the Intergroup Rhabdomyosarcoma Study (IRS) initially was based on a clinical grouping that sorted patients according to the extent of disease after surgical resection: group I, complete resection; group II, microscopic residual disease after gross resection, with or without nodal involvement; group III, gross residual disease after surgery; and group IV, metastatic disease at diagnosis. Now, the IRS is incorporating a more prognostically significant TNM staging. The TNM Staging System, in addition to clinical grouping, includes favorable versus unfavorable sites, along with increasing the stage number for bulky disease measuring greater than 5 cm in diameter or for nodal involvement. Favorable sites include the orbit, eyelid, head and neck, nonparameningeal, and genitourinary areas not including bladder or prostate. Unfavorable areas include extremities, bladder, prostate, parameningeal, retroperitoneum, and, as in our patient, the trunk.8,9 According to the latest IRS staging, our patient falls into the clinical group I, TNM stage II category, which places her in the low-risk rhabdomyosarcoma group.

The treatment of rhabdomyosarcoma in a GCMN consists of surgical resection and combination chemotherapy with or without radiation therapy, depending on the clinical grouping of the patient. According to the IRS definition of low-risk patients, the chemotherapy regimen consists of actinomycin D and vincristine with or without cyclophosphamide, depending on stage and location. Radiation therapy is added for patients with groups II through IV disease and for some unfavorable locations with a high risk of recurrence.9,10

Rhabdomyosarcoma arising in a GCMN has been reported rarely, with only 4 cases to date in the literature (Table).4,5,11,12 Three of the 4 cases occurred in infants, with a fatal outcome reported in one of the infants. In 3 of 4 cases, the trunk was indicated as the site of the rhabdomyosarcoma, with only one case associated with leptomeningeal involvement. In all cases, the rhabdomyosarcoma was excised, with subsequent chemotherapy in 2 of the 4 previously reported cases.

The occurrence of rhabdomyosarcoma arising in a GCMN could be explained by the pluripotential nature of undifferentiated neural crest cells. These cells likely maintain the ability for rhabdomyoblastic differentiation. This mesenchymal derivative originates from the cranial or cephalic portion of the neural crest. The term ectomesenchyme applies to the potential of the ectoderm to give rise to mesenchymal tissue and indeed may be the pathway by which a rhabdomyosarcoma arises.5

Conclusion

We report a fifth case of rhabdomyosarcoma arising in a GCMN. Our patient underwent surgical resection of the rhabdyomyosarcoma at age 2 months, with subsequent chemotherapy consisting of actinomycin D and vincristine. She has tolerated outpatient chemotherapy well, with no gross evidence of local recurrence, and will complete 12 months of therapy for her low-risk rhabdomyosarcoma. 

We report the case of a 6-week-old girl who presented with a pedunculated embryonal rhabdomyosarcoma arising in a giant congenital melanocytic nevus (GCMN) on her lower back. There was no associated leptomeningeal involvement. The patient underwent surgical resection of the rhabdomyosarcoma at age 2 months, with subsequent chemotherapy consisting of actinomycin D and vincristine. No recurrences of metastases of tumor have been noted at 5 months of age.

Giant congenital melanocytic nevus (GCMN), defined as measuring or predicted to measure greater than 20 cm in diameter by adulthood, uncommonly occurs in newborns.1 Concerns arise regarding malignant degeneration, with melanoma developing in 4.5% to 8.5% of cases.2,3 Other malignancies rarely have been reported in a GCMN, including rhabdomyosarcoma, melanosarcoma, undifferentiated spindle cell tumor, neuroblastoma, melanoblastoma, myoblastic sarcoma, liposarcoma, and malignant peripheral nerve sheath tumor.1,4 We report a case of rhabdomyosarcoma arising in a GCMN. 

CASE REPORT

A 6-week-old infant girl presented with an 18x13-cm pigmented hairy nevus extending from the lower back onto the abdomen. A rapidly enlarging, soft pink pedunculated polyp measuring 3 cm in diameter had been present centrally at birth (Figure 1). An ultrasound of the spine revealed no abnormalities.

The polyp was surgically resected, along with a portion of the GCMN. Results of the histologic examination disclosed a rhabdomyosarcoma, embryonal type, located superficially within the dermis (Figure 2). The deep and lateral margins showed no evidence of tumor. Immunohistochemistry results of the neoplastic cells showed marked positivity for desmins, smooth muscle actin, and vimentin; results of tests for S100, neuron-specific enolase, chromogranins, synaptophysin, leukocyte common antigen, and CD57 were negative. Myoglobin stain was noncontributory.

No evidence of metastatic disease was noted on computed tomography of the chest, abdomen, and pelvis; bone scan; and bone marrow examination. The patient was started on a chemotherapy regimen consisting of actinomycin D and vincristine.

Comment

Although controversy exists regarding the precise risk of malignant degeneration in GCMN, it presents a major concern. Often, extensive surgical procedures are undertaken to eliminate or manage the risk of malignancy, primarily to minimize the risk of melanoma, the most commonly associated malignancy.5

Rhabdomyosarcoma is the most common soft tissue sarcoma and the third most common extracranial solid tumor of childhood. It is responsible for up to 25% of malignant cutaneous neoplasms in the pediatric population.6 Most tumors occur in the head and neck region, as well as the genitourinary tract; other areas include the extremities and trunk. Rhabdomyosarcoma occurring in the skin de novo may present as an asymptomatic, firm red nodule or as a lobulated mass with a shiny erythematous surface and telangiectatic vessels.6,7 The differential diagnosis includes hemangioma, lymphangioma, hygroma, lymphoma, leukemia cutis, amelanotic melanoma, and angiofibroma.7

The 4 most common histologic subtypes of rhabdomyosarcoma include the following: embryonal, embryonal-botryoid, alveolar, and pleomorphic. The embryonal and embryonal-butryoid subtypes account for 50% to 60% of childhood rhabdomyosarcomas. The alveolar pattern is seen more commonly in older children, and the pleomorphic pattern is seen more in adults.7

Immunohistochemical stains used to identify rhabdomyosarcoma include the intermediate filaments vimentin and desmins. Vimentin highlights undifferentiated cells of mesenchymal origin, whereas desmins become positive as a cell becomes committed to rhabdomyoblastic differentiation. Because myoglobin is also found in skeletal muscle, myoglobin stains less consistently in rhabdomyosarcomas. This is most likely a result of its expression later in the development of skeletal muscle.7,8 Other muscle-specific proteins used in identification are Myo-D, myogenin, muscle- specific actin, and Z-band protein.9

Staging of rhabdomyosarcoma by the Intergroup Rhabdomyosarcoma Study (IRS) initially was based on a clinical grouping that sorted patients according to the extent of disease after surgical resection: group I, complete resection; group II, microscopic residual disease after gross resection, with or without nodal involvement; group III, gross residual disease after surgery; and group IV, metastatic disease at diagnosis. Now, the IRS is incorporating a more prognostically significant TNM staging. The TNM Staging System, in addition to clinical grouping, includes favorable versus unfavorable sites, along with increasing the stage number for bulky disease measuring greater than 5 cm in diameter or for nodal involvement. Favorable sites include the orbit, eyelid, head and neck, nonparameningeal, and genitourinary areas not including bladder or prostate. Unfavorable areas include extremities, bladder, prostate, parameningeal, retroperitoneum, and, as in our patient, the trunk.8,9 According to the latest IRS staging, our patient falls into the clinical group I, TNM stage II category, which places her in the low-risk rhabdomyosarcoma group.

The treatment of rhabdomyosarcoma in a GCMN consists of surgical resection and combination chemotherapy with or without radiation therapy, depending on the clinical grouping of the patient. According to the IRS definition of low-risk patients, the chemotherapy regimen consists of actinomycin D and vincristine with or without cyclophosphamide, depending on stage and location. Radiation therapy is added for patients with groups II through IV disease and for some unfavorable locations with a high risk of recurrence.9,10

Rhabdomyosarcoma arising in a GCMN has been reported rarely, with only 4 cases to date in the literature (Table).4,5,11,12 Three of the 4 cases occurred in infants, with a fatal outcome reported in one of the infants. In 3 of 4 cases, the trunk was indicated as the site of the rhabdomyosarcoma, with only one case associated with leptomeningeal involvement. In all cases, the rhabdomyosarcoma was excised, with subsequent chemotherapy in 2 of the 4 previously reported cases.

The occurrence of rhabdomyosarcoma arising in a GCMN could be explained by the pluripotential nature of undifferentiated neural crest cells. These cells likely maintain the ability for rhabdomyoblastic differentiation. This mesenchymal derivative originates from the cranial or cephalic portion of the neural crest. The term ectomesenchyme applies to the potential of the ectoderm to give rise to mesenchymal tissue and indeed may be the pathway by which a rhabdomyosarcoma arises.5

Conclusion

We report a fifth case of rhabdomyosarcoma arising in a GCMN. Our patient underwent surgical resection of the rhabdyomyosarcoma at age 2 months, with subsequent chemotherapy consisting of actinomycin D and vincristine. She has tolerated outpatient chemotherapy well, with no gross evidence of local recurrence, and will complete 12 months of therapy for her low-risk rhabdomyosarcoma. 

We report the case of a 6-week-old girl who presented with a pedunculated embryonal rhabdomyosarcoma arising in a giant congenital melanocytic nevus (GCMN) on her lower back. There was no associated leptomeningeal involvement. The patient underwent surgical resection of the rhabdomyosarcoma at age 2 months, with subsequent chemotherapy consisting of actinomycin D and vincristine. No recurrences of metastases of tumor have been noted at 5 months of age.

Giant congenital melanocytic nevus (GCMN), defined as measuring or predicted to measure greater than 20 cm in diameter by adulthood, uncommonly occurs in newborns.1 Concerns arise regarding malignant degeneration, with melanoma developing in 4.5% to 8.5% of cases.2,3 Other malignancies rarely have been reported in a GCMN, including rhabdomyosarcoma, melanosarcoma, undifferentiated spindle cell tumor, neuroblastoma, melanoblastoma, myoblastic sarcoma, liposarcoma, and malignant peripheral nerve sheath tumor.1,4 We report a case of rhabdomyosarcoma arising in a GCMN. 

CASE REPORT

A 6-week-old infant girl presented with an 18x13-cm pigmented hairy nevus extending from the lower back onto the abdomen. A rapidly enlarging, soft pink pedunculated polyp measuring 3 cm in diameter had been present centrally at birth (Figure 1). An ultrasound of the spine revealed no abnormalities.

The polyp was surgically resected, along with a portion of the GCMN. Results of the histologic examination disclosed a rhabdomyosarcoma, embryonal type, located superficially within the dermis (Figure 2). The deep and lateral margins showed no evidence of tumor. Immunohistochemistry results of the neoplastic cells showed marked positivity for desmins, smooth muscle actin, and vimentin; results of tests for S100, neuron-specific enolase, chromogranins, synaptophysin, leukocyte common antigen, and CD57 were negative. Myoglobin stain was noncontributory.

No evidence of metastatic disease was noted on computed tomography of the chest, abdomen, and pelvis; bone scan; and bone marrow examination. The patient was started on a chemotherapy regimen consisting of actinomycin D and vincristine.

Comment

Although controversy exists regarding the precise risk of malignant degeneration in GCMN, it presents a major concern. Often, extensive surgical procedures are undertaken to eliminate or manage the risk of malignancy, primarily to minimize the risk of melanoma, the most commonly associated malignancy.5

Rhabdomyosarcoma is the most common soft tissue sarcoma and the third most common extracranial solid tumor of childhood. It is responsible for up to 25% of malignant cutaneous neoplasms in the pediatric population.6 Most tumors occur in the head and neck region, as well as the genitourinary tract; other areas include the extremities and trunk. Rhabdomyosarcoma occurring in the skin de novo may present as an asymptomatic, firm red nodule or as a lobulated mass with a shiny erythematous surface and telangiectatic vessels.6,7 The differential diagnosis includes hemangioma, lymphangioma, hygroma, lymphoma, leukemia cutis, amelanotic melanoma, and angiofibroma.7

The 4 most common histologic subtypes of rhabdomyosarcoma include the following: embryonal, embryonal-botryoid, alveolar, and pleomorphic. The embryonal and embryonal-butryoid subtypes account for 50% to 60% of childhood rhabdomyosarcomas. The alveolar pattern is seen more commonly in older children, and the pleomorphic pattern is seen more in adults.7

Immunohistochemical stains used to identify rhabdomyosarcoma include the intermediate filaments vimentin and desmins. Vimentin highlights undifferentiated cells of mesenchymal origin, whereas desmins become positive as a cell becomes committed to rhabdomyoblastic differentiation. Because myoglobin is also found in skeletal muscle, myoglobin stains less consistently in rhabdomyosarcomas. This is most likely a result of its expression later in the development of skeletal muscle.7,8 Other muscle-specific proteins used in identification are Myo-D, myogenin, muscle- specific actin, and Z-band protein.9

Staging of rhabdomyosarcoma by the Intergroup Rhabdomyosarcoma Study (IRS) initially was based on a clinical grouping that sorted patients according to the extent of disease after surgical resection: group I, complete resection; group II, microscopic residual disease after gross resection, with or without nodal involvement; group III, gross residual disease after surgery; and group IV, metastatic disease at diagnosis. Now, the IRS is incorporating a more prognostically significant TNM staging. The TNM Staging System, in addition to clinical grouping, includes favorable versus unfavorable sites, along with increasing the stage number for bulky disease measuring greater than 5 cm in diameter or for nodal involvement. Favorable sites include the orbit, eyelid, head and neck, nonparameningeal, and genitourinary areas not including bladder or prostate. Unfavorable areas include extremities, bladder, prostate, parameningeal, retroperitoneum, and, as in our patient, the trunk.8,9 According to the latest IRS staging, our patient falls into the clinical group I, TNM stage II category, which places her in the low-risk rhabdomyosarcoma group.

The treatment of rhabdomyosarcoma in a GCMN consists of surgical resection and combination chemotherapy with or without radiation therapy, depending on the clinical grouping of the patient. According to the IRS definition of low-risk patients, the chemotherapy regimen consists of actinomycin D and vincristine with or without cyclophosphamide, depending on stage and location. Radiation therapy is added for patients with groups II through IV disease and for some unfavorable locations with a high risk of recurrence.9,10

Rhabdomyosarcoma arising in a GCMN has been reported rarely, with only 4 cases to date in the literature (Table).4,5,11,12 Three of the 4 cases occurred in infants, with a fatal outcome reported in one of the infants. In 3 of 4 cases, the trunk was indicated as the site of the rhabdomyosarcoma, with only one case associated with leptomeningeal involvement. In all cases, the rhabdomyosarcoma was excised, with subsequent chemotherapy in 2 of the 4 previously reported cases.

The occurrence of rhabdomyosarcoma arising in a GCMN could be explained by the pluripotential nature of undifferentiated neural crest cells. These cells likely maintain the ability for rhabdomyoblastic differentiation. This mesenchymal derivative originates from the cranial or cephalic portion of the neural crest. The term ectomesenchyme applies to the potential of the ectoderm to give rise to mesenchymal tissue and indeed may be the pathway by which a rhabdomyosarcoma arises.5

Conclusion

We report a fifth case of rhabdomyosarcoma arising in a GCMN. Our patient underwent surgical resection of the rhabdyomyosarcoma at age 2 months, with subsequent chemotherapy consisting of actinomycin D and vincristine. She has tolerated outpatient chemotherapy well, with no gross evidence of local recurrence, and will complete 12 months of therapy for her low-risk rhabdomyosarcoma.