Patient Presentation
An 80-year-old Caucasian female presented with a history of “cysts,” lateral to and under the right eye. The first “cyst” began as a skin-colored papule and acquired a yellowish hue while increasing in size over a period of 2 years. She also developed yellow papules and nodules in the infero-lateral aspects of both periorbital regions. Complete blood count (CBC) and urinalysis were normal. Serum protein electrophoresis showed an IgG lambda monoclonal gammopathy. An excisional biopsy was performed on one of the nodules, and demonstrated extensive granulomatous dermal inflammation with histiocytes palisading around the areas of necrobiosis. Several atypical multinucleated giant cells were also present.
What is Your Diagnosis?
Diagnosis: Necrobiotic xanthogranuloma
Definition, History and Epidemiology
Necrobiotic xanthogranuloma (NXG) is a rare disorder characterized by cutaneous and subcutaneous xanthomatous lesions with distinctive histopathology, and usually an associated paraproteinemia. The syndrome of xanthomatous granulomas, necrobiosis and associated paraproteinemia has been reported since 1966 under various names, such as atypical necrobiosis lipoidica, atypical multicentric reticulohistiocytosis and atypical xanthoma disseminatum.1 In 1980, Kossard and Winkelmann labeled and characterized this distinct clinicopathologic entity.1 They reported eight patients who presented with cutaneous and subcutaneous xanthomatous plaques that tended to ulcerate and atrophy; paraproteinemia and lymphoproliferative disease were commonly found as well. This non-Langerhans cell histiocytosis resembles necrobiosis lipoidica clinically and histologically, but its distinct pathologic features — an association with paraproteinemia, and the potential evolution of hematologic malignancy — distinguishes NXG as a separate entity.2 Approximately 70 cases of NXG have been reported. Mehregan and Winkelmann have reported the largest review to date of 48 patients.3 The disease seems to affect men and women equally and the average age of onset is 55 years.
Cutaneous and Ophthalmic Findings
Lesions typically consist of indurated papules, nodules and plaques of a violaceous to red-orange color, often with a yellowish (xanthomatous) hue. They tend to enlarge slowly and then show central clearing, atrophy and ulceration. Telangiectasias may appear in areas of atrophy or xanthomatous coloration.1 The lesions most commonly appear in the periorbital location (80% of cases),3,4 but may occur on other parts of the face, the trunk, and also the extremities. There is a predilection for lesions to develop in scars.3,5,6 Most patients have several lesions,3 but cases of solitary lesions have been reported,7 as has a case with approximately 100 lesions.3 Lesions are chronic and often progressive. They are usually painless and non-pruritic, but some patients have reported a burning sensation or pain,3,8 particularly with ulcerated lesions.9 Periorbital lesions are characteristic and have been associated with a number of ophthalmic findings ranging from symptoms of pain and blurred vision to complications of keratitis, iritis, conjunctivitis, scleritis, uveitis, proptosis and cellulitis.2,3,10,11 Periorbital lesions are often bilateral.12,13 In our patient, the lesions were periorbital and bilateral but there was no ophthalmic involvement.
Laboratory Workup and Associations
Paraproteinemia may be the sole laboratory abnormality in patients with NXG.2 This may be seen in up to 80% of cases.2,3,6 Typically, the paraproteinemia is an IgG-k monoclonal gammopathy (occurring in 60% of patients).13 IgG-k is found in about 25% of patients, and cases of IgA have also been described.2,13 NXG is recognized for its association with lymphoproliferative malignancies. Bone marrow examination often illustrates plasma cell proliferation, though progression to true myeloma is less common.3 Other disorders that have developed in NXG patients include macroglobulinemia, amyloidosis,3,12 lymphoma, chronic lymphocytic leukemia,6 and carcinoma.3,11,13 Additional associated laboratory abnormalities include leukopenia, hypocomplementemia (reduced CH50, C3, C4, and C1 inhibitor), and anemia. Cryoglobulinemia, elevated erythrocyte sedimentation rate, and abnormal glucose tolerance test have been reported.2,3,7,10,12 An association with HTLV-1 has also been reported.2 Lipids may be elevated, normal, or reduced.10 Finally, there may be no significant laboratory abnormalities at all.7
Other Systemic Findings
Reports of associated internal organ disease further point to the systemic nature of NXG. Lesions have been documented in the heart, lungs and liver, as well as upper respiratory tract, skeletal muscle, intestine, kidney, spleen, ovaries and lymph nodes.3,6,11,14 Mehregan urged physicians to carefully evaluate NXG patients for mucous membrane, lung and myocardial lesions, in addition to associated malignancies.3 Myocardial evaluation, including echocardiography and dynamic cardiac imaging, is particularly recommended.12-14
Histology
The histopathologic features of NXG are distinctive and may be diagnostic. A granulomatous inflammatory process invades the full thickness of the dermis and extends into the subcutaneous fat. Non-Langerhans cell histiocytes, prominent giant cells, and foam cells form bands of palisading granulomas, which are separated by zones of necrobiosis (hyaline degeneration).15 Atypical, “bizarre” multinucleated giant cells of both the Touton and foreign body type1 are found within the granulomas and necrobiotic zones. Other less consistent changes include cholesterol clefts in the necrobiotic areas, lymphoid nodules (sometimes with germinal center formation) and aggregations of plasma cells.16,17
Etiology and Pathogenesis and Disease Spectrum
Despite the known association of NXG with paraproteinemia, the underlying pathogenesis remains unclear. One theory proposes that complexes of serum immunoglobulins and lipids deposit in the skin inducing a giant-cell foreign body granulomatous reaction.7,12,18 Another theory suggests that paraproteins, having features of lipoproteins, bind to lipoprotein receptors of histiocytes, eliciting granuloma formation.6,12 These hypotheses do not, however, explain the occurrence of NXG lesions in the absence of paraproteinemia. Matsuura et al.19 studied a patient with NXG and hypocholesterolemia, and found that activated monocytes were accumulating lipoprotein-derived lipids. The authors postulated that lipid accumulation within monocytes led to xanthoma formation and serum hypocholesterolemia. This theory, however, does not account for NXG patients who have increased serum lipids.12,19 Other factors speculated to play a role in pathogenesis of NXG include ischemia,12 chronic antigen stimulation,2 and hypocomplementemia contributing to immune-complex formation.10 Several authors have proposed that NXG is part of a granulomatous disease spectrum that culminates in a xanthogranuloma with accompanying paraproteinemia.4,11 Both normolipemic plane xanthoma and necrobiosis lipoidica could be part of this spectrum. There have been two case reports of necrobiosis lipoidica evolving to NXG with development of paraproteinemia.11
Differential Diagnosis
In considering a case of NXG, the first entities to exclude are necrobiosis lipoidica and normolipemic plane xanthoma.1,16 Other diseases in the differential diagnosis include juvenile xanthogranuloma, granuloma annulare, foreign body granuloma, subcutaneous rheumatoid nodules, xanthoma disseminatum, and primary and secondary amyloidosis.6
Clinical Course and Treatment
NXG is a chronic, progressive process, and prognosis depends on the extent of extracutaneous involvement.8 Skin lesions do not necessarily correlate with severity of hematologic disease.10 The risk for development of a lymphoproliferative disorder or carcinoma was cited by Mehregan in 1992 as 13%.3 Ugurlu’s review of 26 patients found that hematologic malignancy appeared anywhere from 8 years prior to 11 years after the appearance of skin lesions.6 Survival rates were 100% at 10 years and 90% at 15 years, corresponding to Mehregan’s observation that the multiple myeloma in NXG patients is not aggressive.3 Treatment has been directed at presumed or known underlying hematological dyscrasias,20 other systemic involvement, widespread skin involvement with ulcerations,5 or singular lesions that cause local irritation or damage (usually ophthalmic). Various treatment modalities have been used with varying degrees of success. These include excision, local corticosteroid injection, radiation therapy, plasmapheresis and systemic chemo-therapy. A common therapy is oral corticosteroids combined with alkylating agents, chlorambucil (Leukeran) or melphalan (Alkeran). Other chemotherapeutic agents include recombinant interferon alpha-2b (Intron A, Rebetron Combination Therapy), methotrexate, cyclophosphamide, azathioprine (Imuran, Azathioprine), and nitrogen mustard.5,6,10-12 Combined chemotherapy and radiation therapy has been effective.6 Management of NXG patients additionally includes lifelong monitoring for the development of internal involvement as well as associated malignancy.4,6,7,11 Our patient, since her initial visit, has continued to developed more nodules, which occasionally ulcerate. Ophthalmic complications or systemic disease have not arisen. Given our patient’s age and negative systemic work-up, we opted for the conservative treatment of nodule excision when requested or when necessary. We continue to follow her regularly.
Patient Presentation
An 80-year-old Caucasian female presented with a history of “cysts,” lateral to and under the right eye. The first “cyst” began as a skin-colored papule and acquired a yellowish hue while increasing in size over a period of 2 years. She also developed yellow papules and nodules in the infero-lateral aspects of both periorbital regions. Complete blood count (CBC) and urinalysis were normal. Serum protein electrophoresis showed an IgG lambda monoclonal gammopathy. An excisional biopsy was performed on one of the nodules, and demonstrated extensive granulomatous dermal inflammation with histiocytes palisading around the areas of necrobiosis. Several atypical multinucleated giant cells were also present.
What is Your Diagnosis?
Diagnosis: Necrobiotic xanthogranuloma
Definition, History and Epidemiology
Necrobiotic xanthogranuloma (NXG) is a rare disorder characterized by cutaneous and subcutaneous xanthomatous lesions with distinctive histopathology, and usually an associated paraproteinemia. The syndrome of xanthomatous granulomas, necrobiosis and associated paraproteinemia has been reported since 1966 under various names, such as atypical necrobiosis lipoidica, atypical multicentric reticulohistiocytosis and atypical xanthoma disseminatum.1 In 1980, Kossard and Winkelmann labeled and characterized this distinct clinicopathologic entity.1 They reported eight patients who presented with cutaneous and subcutaneous xanthomatous plaques that tended to ulcerate and atrophy; paraproteinemia and lymphoproliferative disease were commonly found as well. This non-Langerhans cell histiocytosis resembles necrobiosis lipoidica clinically and histologically, but its distinct pathologic features — an association with paraproteinemia, and the potential evolution of hematologic malignancy — distinguishes NXG as a separate entity.2 Approximately 70 cases of NXG have been reported. Mehregan and Winkelmann have reported the largest review to date of 48 patients.3 The disease seems to affect men and women equally and the average age of onset is 55 years.
Cutaneous and Ophthalmic Findings
Lesions typically consist of indurated papules, nodules and plaques of a violaceous to red-orange color, often with a yellowish (xanthomatous) hue. They tend to enlarge slowly and then show central clearing, atrophy and ulceration. Telangiectasias may appear in areas of atrophy or xanthomatous coloration.1 The lesions most commonly appear in the periorbital location (80% of cases),3,4 but may occur on other parts of the face, the trunk, and also the extremities. There is a predilection for lesions to develop in scars.3,5,6 Most patients have several lesions,3 but cases of solitary lesions have been reported,7 as has a case with approximately 100 lesions.3 Lesions are chronic and often progressive. They are usually painless and non-pruritic, but some patients have reported a burning sensation or pain,3,8 particularly with ulcerated lesions.9 Periorbital lesions are characteristic and have been associated with a number of ophthalmic findings ranging from symptoms of pain and blurred vision to complications of keratitis, iritis, conjunctivitis, scleritis, uveitis, proptosis and cellulitis.2,3,10,11 Periorbital lesions are often bilateral.12,13 In our patient, the lesions were periorbital and bilateral but there was no ophthalmic involvement.
Laboratory Workup and Associations
Paraproteinemia may be the sole laboratory abnormality in patients with NXG.2 This may be seen in up to 80% of cases.2,3,6 Typically, the paraproteinemia is an IgG-k monoclonal gammopathy (occurring in 60% of patients).13 IgG-k is found in about 25% of patients, and cases of IgA have also been described.2,13 NXG is recognized for its association with lymphoproliferative malignancies. Bone marrow examination often illustrates plasma cell proliferation, though progression to true myeloma is less common.3 Other disorders that have developed in NXG patients include macroglobulinemia, amyloidosis,3,12 lymphoma, chronic lymphocytic leukemia,6 and carcinoma.3,11,13 Additional associated laboratory abnormalities include leukopenia, hypocomplementemia (reduced CH50, C3, C4, and C1 inhibitor), and anemia. Cryoglobulinemia, elevated erythrocyte sedimentation rate, and abnormal glucose tolerance test have been reported.2,3,7,10,12 An association with HTLV-1 has also been reported.2 Lipids may be elevated, normal, or reduced.10 Finally, there may be no significant laboratory abnormalities at all.7
Other Systemic Findings
Reports of associated internal organ disease further point to the systemic nature of NXG. Lesions have been documented in the heart, lungs and liver, as well as upper respiratory tract, skeletal muscle, intestine, kidney, spleen, ovaries and lymph nodes.3,6,11,14 Mehregan urged physicians to carefully evaluate NXG patients for mucous membrane, lung and myocardial lesions, in addition to associated malignancies.3 Myocardial evaluation, including echocardiography and dynamic cardiac imaging, is particularly recommended.12-14
Histology
The histopathologic features of NXG are distinctive and may be diagnostic. A granulomatous inflammatory process invades the full thickness of the dermis and extends into the subcutaneous fat. Non-Langerhans cell histiocytes, prominent giant cells, and foam cells form bands of palisading granulomas, which are separated by zones of necrobiosis (hyaline degeneration).15 Atypical, “bizarre” multinucleated giant cells of both the Touton and foreign body type1 are found within the granulomas and necrobiotic zones. Other less consistent changes include cholesterol clefts in the necrobiotic areas, lymphoid nodules (sometimes with germinal center formation) and aggregations of plasma cells.16,17
Etiology and Pathogenesis and Disease Spectrum
Despite the known association of NXG with paraproteinemia, the underlying pathogenesis remains unclear. One theory proposes that complexes of serum immunoglobulins and lipids deposit in the skin inducing a giant-cell foreign body granulomatous reaction.7,12,18 Another theory suggests that paraproteins, having features of lipoproteins, bind to lipoprotein receptors of histiocytes, eliciting granuloma formation.6,12 These hypotheses do not, however, explain the occurrence of NXG lesions in the absence of paraproteinemia. Matsuura et al.19 studied a patient with NXG and hypocholesterolemia, and found that activated monocytes were accumulating lipoprotein-derived lipids. The authors postulated that lipid accumulation within monocytes led to xanthoma formation and serum hypocholesterolemia. This theory, however, does not account for NXG patients who have increased serum lipids.12,19 Other factors speculated to play a role in pathogenesis of NXG include ischemia,12 chronic antigen stimulation,2 and hypocomplementemia contributing to immune-complex formation.10 Several authors have proposed that NXG is part of a granulomatous disease spectrum that culminates in a xanthogranuloma with accompanying paraproteinemia.4,11 Both normolipemic plane xanthoma and necrobiosis lipoidica could be part of this spectrum. There have been two case reports of necrobiosis lipoidica evolving to NXG with development of paraproteinemia.11
Differential Diagnosis
In considering a case of NXG, the first entities to exclude are necrobiosis lipoidica and normolipemic plane xanthoma.1,16 Other diseases in the differential diagnosis include juvenile xanthogranuloma, granuloma annulare, foreign body granuloma, subcutaneous rheumatoid nodules, xanthoma disseminatum, and primary and secondary amyloidosis.6
Clinical Course and Treatment
NXG is a chronic, progressive process, and prognosis depends on the extent of extracutaneous involvement.8 Skin lesions do not necessarily correlate with severity of hematologic disease.10 The risk for development of a lymphoproliferative disorder or carcinoma was cited by Mehregan in 1992 as 13%.3 Ugurlu’s review of 26 patients found that hematologic malignancy appeared anywhere from 8 years prior to 11 years after the appearance of skin lesions.6 Survival rates were 100% at 10 years and 90% at 15 years, corresponding to Mehregan’s observation that the multiple myeloma in NXG patients is not aggressive.3 Treatment has been directed at presumed or known underlying hematological dyscrasias,20 other systemic involvement, widespread skin involvement with ulcerations,5 or singular lesions that cause local irritation or damage (usually ophthalmic). Various treatment modalities have been used with varying degrees of success. These include excision, local corticosteroid injection, radiation therapy, plasmapheresis and systemic chemo-therapy. A common therapy is oral corticosteroids combined with alkylating agents, chlorambucil (Leukeran) or melphalan (Alkeran). Other chemotherapeutic agents include recombinant interferon alpha-2b (Intron A, Rebetron Combination Therapy), methotrexate, cyclophosphamide, azathioprine (Imuran, Azathioprine), and nitrogen mustard.5,6,10-12 Combined chemotherapy and radiation therapy has been effective.6 Management of NXG patients additionally includes lifelong monitoring for the development of internal involvement as well as associated malignancy.4,6,7,11 Our patient, since her initial visit, has continued to developed more nodules, which occasionally ulcerate. Ophthalmic complications or systemic disease have not arisen. Given our patient’s age and negative systemic work-up, we opted for the conservative treatment of nodule excision when requested or when necessary. We continue to follow her regularly.
Patient Presentation
An 80-year-old Caucasian female presented with a history of “cysts,” lateral to and under the right eye. The first “cyst” began as a skin-colored papule and acquired a yellowish hue while increasing in size over a period of 2 years. She also developed yellow papules and nodules in the infero-lateral aspects of both periorbital regions. Complete blood count (CBC) and urinalysis were normal. Serum protein electrophoresis showed an IgG lambda monoclonal gammopathy. An excisional biopsy was performed on one of the nodules, and demonstrated extensive granulomatous dermal inflammation with histiocytes palisading around the areas of necrobiosis. Several atypical multinucleated giant cells were also present.
What is Your Diagnosis?
Diagnosis: Necrobiotic xanthogranuloma
Definition, History and Epidemiology
Necrobiotic xanthogranuloma (NXG) is a rare disorder characterized by cutaneous and subcutaneous xanthomatous lesions with distinctive histopathology, and usually an associated paraproteinemia. The syndrome of xanthomatous granulomas, necrobiosis and associated paraproteinemia has been reported since 1966 under various names, such as atypical necrobiosis lipoidica, atypical multicentric reticulohistiocytosis and atypical xanthoma disseminatum.1 In 1980, Kossard and Winkelmann labeled and characterized this distinct clinicopathologic entity.1 They reported eight patients who presented with cutaneous and subcutaneous xanthomatous plaques that tended to ulcerate and atrophy; paraproteinemia and lymphoproliferative disease were commonly found as well. This non-Langerhans cell histiocytosis resembles necrobiosis lipoidica clinically and histologically, but its distinct pathologic features — an association with paraproteinemia, and the potential evolution of hematologic malignancy — distinguishes NXG as a separate entity.2 Approximately 70 cases of NXG have been reported. Mehregan and Winkelmann have reported the largest review to date of 48 patients.3 The disease seems to affect men and women equally and the average age of onset is 55 years.
Cutaneous and Ophthalmic Findings
Lesions typically consist of indurated papules, nodules and plaques of a violaceous to red-orange color, often with a yellowish (xanthomatous) hue. They tend to enlarge slowly and then show central clearing, atrophy and ulceration. Telangiectasias may appear in areas of atrophy or xanthomatous coloration.1 The lesions most commonly appear in the periorbital location (80% of cases),3,4 but may occur on other parts of the face, the trunk, and also the extremities. There is a predilection for lesions to develop in scars.3,5,6 Most patients have several lesions,3 but cases of solitary lesions have been reported,7 as has a case with approximately 100 lesions.3 Lesions are chronic and often progressive. They are usually painless and non-pruritic, but some patients have reported a burning sensation or pain,3,8 particularly with ulcerated lesions.9 Periorbital lesions are characteristic and have been associated with a number of ophthalmic findings ranging from symptoms of pain and blurred vision to complications of keratitis, iritis, conjunctivitis, scleritis, uveitis, proptosis and cellulitis.2,3,10,11 Periorbital lesions are often bilateral.12,13 In our patient, the lesions were periorbital and bilateral but there was no ophthalmic involvement.
Laboratory Workup and Associations
Paraproteinemia may be the sole laboratory abnormality in patients with NXG.2 This may be seen in up to 80% of cases.2,3,6 Typically, the paraproteinemia is an IgG-k monoclonal gammopathy (occurring in 60% of patients).13 IgG-k is found in about 25% of patients, and cases of IgA have also been described.2,13 NXG is recognized for its association with lymphoproliferative malignancies. Bone marrow examination often illustrates plasma cell proliferation, though progression to true myeloma is less common.3 Other disorders that have developed in NXG patients include macroglobulinemia, amyloidosis,3,12 lymphoma, chronic lymphocytic leukemia,6 and carcinoma.3,11,13 Additional associated laboratory abnormalities include leukopenia, hypocomplementemia (reduced CH50, C3, C4, and C1 inhibitor), and anemia. Cryoglobulinemia, elevated erythrocyte sedimentation rate, and abnormal glucose tolerance test have been reported.2,3,7,10,12 An association with HTLV-1 has also been reported.2 Lipids may be elevated, normal, or reduced.10 Finally, there may be no significant laboratory abnormalities at all.7
Other Systemic Findings
Reports of associated internal organ disease further point to the systemic nature of NXG. Lesions have been documented in the heart, lungs and liver, as well as upper respiratory tract, skeletal muscle, intestine, kidney, spleen, ovaries and lymph nodes.3,6,11,14 Mehregan urged physicians to carefully evaluate NXG patients for mucous membrane, lung and myocardial lesions, in addition to associated malignancies.3 Myocardial evaluation, including echocardiography and dynamic cardiac imaging, is particularly recommended.12-14
Histology
The histopathologic features of NXG are distinctive and may be diagnostic. A granulomatous inflammatory process invades the full thickness of the dermis and extends into the subcutaneous fat. Non-Langerhans cell histiocytes, prominent giant cells, and foam cells form bands of palisading granulomas, which are separated by zones of necrobiosis (hyaline degeneration).15 Atypical, “bizarre” multinucleated giant cells of both the Touton and foreign body type1 are found within the granulomas and necrobiotic zones. Other less consistent changes include cholesterol clefts in the necrobiotic areas, lymphoid nodules (sometimes with germinal center formation) and aggregations of plasma cells.16,17
Etiology and Pathogenesis and Disease Spectrum
Despite the known association of NXG with paraproteinemia, the underlying pathogenesis remains unclear. One theory proposes that complexes of serum immunoglobulins and lipids deposit in the skin inducing a giant-cell foreign body granulomatous reaction.7,12,18 Another theory suggests that paraproteins, having features of lipoproteins, bind to lipoprotein receptors of histiocytes, eliciting granuloma formation.6,12 These hypotheses do not, however, explain the occurrence of NXG lesions in the absence of paraproteinemia. Matsuura et al.19 studied a patient with NXG and hypocholesterolemia, and found that activated monocytes were accumulating lipoprotein-derived lipids. The authors postulated that lipid accumulation within monocytes led to xanthoma formation and serum hypocholesterolemia. This theory, however, does not account for NXG patients who have increased serum lipids.12,19 Other factors speculated to play a role in pathogenesis of NXG include ischemia,12 chronic antigen stimulation,2 and hypocomplementemia contributing to immune-complex formation.10 Several authors have proposed that NXG is part of a granulomatous disease spectrum that culminates in a xanthogranuloma with accompanying paraproteinemia.4,11 Both normolipemic plane xanthoma and necrobiosis lipoidica could be part of this spectrum. There have been two case reports of necrobiosis lipoidica evolving to NXG with development of paraproteinemia.11
Differential Diagnosis
In considering a case of NXG, the first entities to exclude are necrobiosis lipoidica and normolipemic plane xanthoma.1,16 Other diseases in the differential diagnosis include juvenile xanthogranuloma, granuloma annulare, foreign body granuloma, subcutaneous rheumatoid nodules, xanthoma disseminatum, and primary and secondary amyloidosis.6
Clinical Course and Treatment
NXG is a chronic, progressive process, and prognosis depends on the extent of extracutaneous involvement.8 Skin lesions do not necessarily correlate with severity of hematologic disease.10 The risk for development of a lymphoproliferative disorder or carcinoma was cited by Mehregan in 1992 as 13%.3 Ugurlu’s review of 26 patients found that hematologic malignancy appeared anywhere from 8 years prior to 11 years after the appearance of skin lesions.6 Survival rates were 100% at 10 years and 90% at 15 years, corresponding to Mehregan’s observation that the multiple myeloma in NXG patients is not aggressive.3 Treatment has been directed at presumed or known underlying hematological dyscrasias,20 other systemic involvement, widespread skin involvement with ulcerations,5 or singular lesions that cause local irritation or damage (usually ophthalmic). Various treatment modalities have been used with varying degrees of success. These include excision, local corticosteroid injection, radiation therapy, plasmapheresis and systemic chemo-therapy. A common therapy is oral corticosteroids combined with alkylating agents, chlorambucil (Leukeran) or melphalan (Alkeran). Other chemotherapeutic agents include recombinant interferon alpha-2b (Intron A, Rebetron Combination Therapy), methotrexate, cyclophosphamide, azathioprine (Imuran, Azathioprine), and nitrogen mustard.5,6,10-12 Combined chemotherapy and radiation therapy has been effective.6 Management of NXG patients additionally includes lifelong monitoring for the development of internal involvement as well as associated malignancy.4,6,7,11 Our patient, since her initial visit, has continued to developed more nodules, which occasionally ulcerate. Ophthalmic complications or systemic disease have not arisen. Given our patient’s age and negative systemic work-up, we opted for the conservative treatment of nodule excision when requested or when necessary. We continue to follow her regularly.
