This disease is characterized by multiple, sharply demarcated nodules and plaques which have a violaceous to red to orange-yellow appearance. There may be central atrophy, ulceration, and telangiectasia. The lesions tend to occur around the eyes and face but may occur on the trunk and limbs. These lesions are chronic and may be progressive.
The importance in correctly identifying this disease lies in its association with a paraproteinemia. Other laboratory abnormalities include bone marrow plasmacytosis, hypocomplementemia, and hyperlipidemia.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/
Other Diagnostic Testing
Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Necrobiotic xanthogranuloma with paraproteinemia INCIDENCE Rare AGE RANGE-MEDIAN Mean 53 years SEX (M:F) 40:60
DISEASE ASSOCIATIONS CHARACTERIZATION Paraprotein Up to 80% of cases Malignant lymphoma
The evolution of Hodgkin's disease and necrobiotic xanthogranuloma syndrome.
Reeder CB, Connolly SM, Winkelmann RK.
Division of Hematology/Oncology, Mayo Clinic Scottsdale, AZ 85259.
Mayo Clin Proc 1991 Dec;66(12):1222-4 Abstract quote
We describe a woman in whom hypogammaglobulinemia and severe granulomatous cutaneous lesions had developed during childhood; subsequently, Hodgkin's disease and necrobiotic xanthogranuloma were diagnosed.
This case illustrates an apparent association with disease activity and raises the question of a direct relationship of necrobiotic xanthogranuloma with lymphoproliferative disease.
Necrobiotic xanthogranuloma with myeloma. A case report.
Venencie PY, Puissant A, Verola O, Kerneis Y, Marchat C, Le Bras P, D'Agay MF, Danon F, Valensi F, Turpin G.
Cancer 1987 Feb 1;59(3):588-92 Abstract quote
Necrobiotic xanthogranuloma is a newly recognized cutaneous manifestation associated with paraproteinemia. Necrobiotic xanthogranuloma is distinctive clinically by yellowish-red nodular lesions, often ulcerated, with predilection for the periorbital area and ocular involvement. Histologically, it is characterized by the combination of inflammatory xanthogranulomas together with areas of necrobiosis. These skin lesions are associated with a dysglobulinemia and preceded the development of an IgG lambda myeloma in a previous patient. Hyperlipidemia may be found in some patients.
A case of necrobiotic xanthogranuloma is reported, occurring in a 46-year-old man and associated with an IgG kappa myeloma.
Necrobiotic xanthogranuloma with IgA multiple myeloma: a case report and literature review.
Valentine EA, Friedman HD, Zamkoff KW, Streeten BW.
Department of Medicine, Veterans Administration Hospital, Syracuse, New York.
Am J Hematol 1990 Dec;35(4):283-5 Abstract quote
The association between necrobiotic xanthogranuloma of the dermis and paraproteinemia and/or B-cell malignancy is best described in the ophthalmologic literature.
We report a case which occurred in the eyelid and orbit of a 64 year old man that led to the diagnosis of an IgA multiple myeloma.
To our knowledge, this is the first report of an IgA type paraproteinemia and IgA type multiple myeloma associated with necrobiotic xanthogranuloma.
Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging.
Plotnick H, Taniguchi Y, Hashimoto K, Negendank W, Tranchida L.
Department of Dermatology, Wayne State University School of Medicine, Detroit, MI 48201.
J Am Acad Dermatol 1991 Aug;25(2 Pt 2):373-7 Abstract quote
We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy.
Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma.
Necrobiotic xanthogranuloma in a human T-lymphotropic virus type 1 carrier.
Nishimura M, Takano-Nishimura Y, Yano I, Hayashi N, Toshitani S.
Department of Clinical Genetics, Kyushu University, Beppu, Japan.
J Am Acad Dermatol 1992 Nov;27(5 Pt 2):886-9 Abstract quote
A 67-year-old man who had necrobiotic xanthogranuloma associated with paraproteinemia is described. He was a human T-lymphotropic virus type 1 (HTLV-1) carrier who had a high titer of circulating anti-HTLV-1 antibodies and neurologic abnormalities that suggested HTLV-1-associated myelopathy.
The patient's necrobiotic xanthogranuloma and neurologic symptoms improved after he received four 5-day courses of melphalan, 2 mg/day, and prednisolone, 20 mg/day, at 4-week intervals.
Necrobiotic xanthogranuloma with paraproteinemia. Case report and a pathogenetic theory.
Bullock JD, Bartley GB, Campbell RJ, Yanes B, Connelly PJ, Funkhouser JW.
Ophthalmology 1986 Sep;93(9):1233-6 Abstract quote
Necrobiotic xanthogranuloma with paraproteinemia is a clinical and histopathological entity characterized by xanthelasma-like lesions in the periorbital region and elsewhere, paraproteinemia, leukopenia, and an elevated erythrocyte sedimentation rate. Multiple myeloma has been reported as an accompanying feature in several cases.
We examined a patient with necrobiotic xanthogranuloma and multiple myeloma in whom an IgG kappa monoclonal protein was identified in serum, urine, bone marrow, and bilateral periorbital lesions.
We speculate that increased serum immunoglobulins complexed with lipid may be deposited in the skin, leading to a foreign body giant cell reaction and the subsequent characteristic histopathologic features of necrobiotic xanthogranuloma.
Activation of monocytes in vivo causes intracellular accumulation of lipoprotein-derived lipids and marked hypocholesterolemia--a possible pathogenesis of necrobiotic xanthogranuloma.
Matsura F, Yamashita S, Hirano K, Ishigami M, Hiraoka H, Tamura R, Nakagawa T, Nishida M, Sakai N, Nakamura T, Nozaki S, Funahashi T, Matsumoto C, Higashiyama M, Yoshikawa K, Matsuzawa Y.
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.
Atherosclerosis 1999 Feb;142(2):355-65 Abstract quote
Necrobiotic xanthogranuloma (NXG) is a rare histiocytic disease with generalized xanthomatosis. However, most cases with NXG are normolipidemic or hypolipidemic. The mechanism for the formation of xanthoma in NXG has not yet been clarified.
We observed a case of NXG with severe hypocholesterolemia (total cholesterol: 1.69 mmol/l) and analyzed the function of monocytes in this case. Histological examinations by light microscopy revealed a large amount of lipid deposition in the patient's freshly isolated monocytes. The patient's monocytes showed a 3-fold increase in cholesteryl ester content and a 3-fold enhancement of acetyl low density lipoprotein (LDL) uptake compared with the control monocytes. However, no significant difference was noted in the expression of CD36 protein and the mRNA levels of scavenger receptor-class A (SR-A) between the monocytes of the patient and the control. The phagocytotic ability of the patient's monocytes was enhanced 1.5-fold compared with that of the control monocytes.
These findings suggest that the activated monocytes may have degraded the modified LDL via a pathway other than CD36 or SR-A, and accumulated a great amount of lipids in vivo. In conclusion, the present study has demonstrated a possible pathogenesis of NXG that the activation of monocytes in vivo may contribute to the intracellular accumulation of lipoprotein-derived lipids leading to non-inherited xanthomatosis and the marked hypocholesterolemia.
CHARACTERIZATION Laboratory Markers Paraprotein Present in up to 80% of cases
16/20 with IgG monoclonal gammopathy
Complement consumption in a patient with necrobiotic xanthogranuloma and paraproteinemia.
Hauser C, Schifferli J, Saurat JH.
Department of Dermatology, Hopital Cantonal Universitaire, Geneva, Switzerland.
J Am Acad Dermatol 1991 May;24(5 Pt 2):908-11 Abstract quote
Necrobiotic xanthogranuloma and paraproteinemia have been reported to be associated with acquired deficiency of the early components of the classic pathway of complement.
We describe a patient in whom activation of complement was suggested by a high level of C3d, an accelerated catabolism of C1q, and a rapid consumption of C4 after an intravenous infusion of fresh-frozen plasma. This infusion was followed by an episode of pulmonary edema. Patients with complement deficiency or depletion should be monitored closely while receiving plasma, to avoid this potential complication.
Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases.
Finan MC, Winkelmann RK.
Medicine (Baltimore) 1986 Nov;65(6):376-88 Abstract quote
Cutaneous biopsy specimens from 22 patients showed the distinctive histopathologic pattern of necrobiotic xanthogranuloma within the dermis or subcutaneous tissue (or both).
Twenty of the 22 patients had 1 or more serum protein abnormalities, consisting of an IgG monoclonal protein in 16, multiple myeloma in 3, cryoglobulinemia in 3, and an abnormal serum protein electrophoresis in 1. Cutaneous lesions were seen as discrete, slowly developing red nodules and plaques with a xanthomatized hue and a predilection for the face (periorbital region in particular), trunk, and extremities. Ulceration was a notable finding in 10 patients.
Histologically, the dermis and lobules of subcutaneous tissue were involved with a granulomatous infiltrate containing bands of hyaline necrobiosis and bizarre foreign body, as well as Touton giant cells. Cholesterol clefts, lymphoid nodules with or without germinal centers, and foci of plasma cells were variable but significant features. Leukocyte monoclonal antibody studies in 6 patients demonstrated helper T cells within the granulomas.
Electron microscopy in 3 cases showed lipid vacuoles in macrophages in the dermis and dendritic cells in the epidermis, and study confirmed this entity as a non-X histiocytosis. Pertinent laboratory findings, in addition to the serum protein abnormalities, included elevation of the erythrocyte sedimentation rate, leukopenia with absolute neutropenia, and decreased serum complement levels, as well as decreased levels of C1-esterase inhibitor in some patients. Thirteen of the 22 patients have survived, the mean duration being 9.5 years after the onset of cutaneous disease.
While given to only a few patients in the current series, low-dose chemotherapy seems to induce a favorable response in both the cutaneous and the hematologic disease.
Mehregan DA, Winkelmann RK.
Department of Dermatology, Mayo Clinic, Rochester, Minn.
Arch Dermatol 1992 Jan;128(1):94-100 Abstract quote
We reviewed 32 cases of necrobiotic xanthogranuloma and 16 cases from the world literature. Necrobiotic xanthogranuloma is a destructive dermal and subcutaneous xanthogranuloma that most frequently involves the face (periorbital region) and trunk. Monoclonal gammopathy is common (IgG-kappa in 23 cases and IgG-lambda in nine cases), and cryoglobulins have also been found. Low complement levels, anemia, and leukopenia are frequently present. Bone marrow examination shows plasma cell proliferation and, rarely, true myeloma.
We describe mucosal, muscle, and systemic lesions, including xanthogranulomatous myocardial lesions. The clinical course is chronic and often progressive. Low-dose chlorambucil treatment is safe and effective, but individual patients have responded to treatment with corticosteroids, melphalan, local radiation, and plasma exchange.
Systemic involvment Lungs
Ophthalmic features of necrobiotic xanthogranuloma with paraproteinemia.
Robertson DM, Winkelmann RK.
Am J Ophthalmol 1984 Feb;97(2):173-83 Abstract quote
Necrobiotic xanthogranuloma of the skin is associated with paraproteinemia and, often, with plasma proliferative disorders, including multiple myeloma. Other commonly recognized systemic abnormalities include hepatosplenomegaly, a highly increased erythrocyte sedimentation rate, and leukopenia.
Fifteen of 16 patients (seven men and nine women with a mean age of 54 years) with this condition had ophthalmic manifestations. Thirteen patients had lesions affecting the skin of the eyelids and periorbital tissue; on casual examination these lesions resembled plane xanthoma. Unlike plane xanthoma, however, the lesions of necrobiotic xanthogranuloma were almost always indurated. Further, the lesions frequently became inflamed, leading to superficial ulceration. Deeper lesions occasionally involved the orbit. Yellow lesions were sometimes visible in the episcleral tissues where they were associated with recurrent symptoms of scleritis and episcleritis. Biopsy specimens of the skin lesions disclosed a distinctive pattern of subepidermal granulomatous masses with focal aggregates of histiocytes and giant cells surrounded by hyaline necrobiosis.
Surgical excision of the eyelid lesions was often followed by recurrence and increased activity of the lesions. Low-dose chemotherapy is likely to produce a favorable response, with regard to both the skin lesions and the paraprotein abnormalities.
Necrobiotic xanthogranuloma with IgA paraproteinemia and extracutaneous involvement.
Fortson JS, Schroeter AL.
Department of Dermatology, Wright State University, Dayton, Ohio.
Am J Dermatopathol 1990 Dec;12(6):579-84 Abstract quote
Numerous nodular xanthomatous lesions arose, gradually increasing in number on the back, chest, lips, tongue, and exposed "V" area of the chest on a 78-year-old man.
Painful oral nodules and hoarseness developed subsequently. Histologic examination of the skin revealed a suppurative and granulomatous inflammation with an accumulation of acute polymorphonuclear neutrophils, nuclear dust, and xanthomatous histiocytes. Giant cells were rare and cholesterol clefts were absent. Biopsy of the oral mucosa and the larynx showed a similar process. Direct immunofluorescence was positive for vascular immune reactants at the basement membrane and fibrin in between collagen bundles. The patient had a serum IgA level of 432 mg/dl (normal level, up to 380), with normal IgG and IgM serum concentrations. A Raji cell assay was 240 micrograms/AHGEQ/ml (normal less than 5). CH-50 was decreased and C2, C4, and C3 were within normal limits. The dermatopathology was initially thought to be consistent with erythema elevatum diutinum, and the patient was treated with dapsone and prednisone, with a marginal response. There were no dermatopathologic findings of vasculitis. On review, the patient's dermatopathology was more consistent with necrobiotic xanthogranuloma (NXG).
To our knowledge, this is the first report of an association of NXG with an IgA gammopathy and the second reported case of extracutaneous involvement with NXG.
Varied clinical spectrum of necrobiotic xanthogranuloma.
Cornblath WT, Dotan SA, Trobe JD, Headington JT. W. K.
Kellogg Eye Center, Department of Ophthalmology, University of Michigan, Ann Arbor 48105.
Ophthalmology 1992 Jan;99(1):103-7 Abstract quote
Four cases are presented that illustrate a wide spectrum of ophthalmologic and systemic features of necrobiotic xanthogranuloma (NXG).
Case 1 initially had signs of Cogan syndrome, and then developed chronic lymphocytic leukemia. Case 2, the first case of NXG to undergo autopsy, had progressive cicatricial lid retraction and corneal perforation. Case 3 had a more typical presentation of diplopia and blepharoptosis caused by orbital and periorbital infiltrative masses. Case 4 had nondeforming periocular skin lesions over a 6-year period.
In all four cases, the diagnosis was made on the basis of characteristic histopathologic and laboratory findings. Although the cause of NXG is still obscure, in many cases it appears to be a forerunner of lymphoproliferative diseases.
Necrobiotic xanthogranuloma with myocardial lesions and nodular transformation of the liver.
Novak PM, Robbins TO, Winkelmann RK.
Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI 48073-6769.
Hum Pathol 1992 Feb;23(2):195-6 Abstract quote
A 73-year-old woman with a history of necrobiotic xanthogranuloma (NXG) with paraproteinemia died suddenly while hospitalized for bronchitis and congestive heart failure. At postmortem examination, myocardial lesions histologically typical of NXG were found.
This is the fifth reported autopsy of a patient with NXG. In all five autopsied cases, and in two additional surgical cases, necrobiotic granulomas of internal viscera were present, and in three cases the myocardium was involved. In addition, our patient had nodular transformation of the liver, a rare lesion that was also reported in one of the previous autopsy cases with NXG.
Necrobiotic xanthogranuloma without periorbital lesions.
McGregor JM, Miller J, Smith NP, Hay RJ.
Department of Dermatology, Guy's Hospital, London, United Kingdom.
J Am Acad Dermatol 1993 Sep;29(3):466-9 Abstract quote
Cutaneous necrobiotic xanthogranuloma is rare and closely resembles widespread necrobiosis lipoidica. It is important to recognize this skin disorder because of its strong association with paraproteinemia and, in some cases, with a hematologic malignancy.
We describe two patients with necrobiotic xanthogranuloma who are unusual in that they had no periorbital involvement, a feature previously believed to be diagnostic of this condition.
Necrobiotic xanthogranuloma with cardiac involvement.
Umbert I, Winkelmann RK.
Mayo Clinic, Scottsdale, AZ 85259, USA.
Br J Dermatol 1995 Sep;133(3):438-43 Abstract quote
A patient with necrobiotic xanthogranuloma (NXG) and paraproteinaemia, who was followed-up for several years, and treated with low-dose chlorambucil, died as a result of a respiratory illness. The significant findings at autopsy were a xanthogranuloma of the spleen and giant cell myocarditis. The myocardial lesions were composed of macrophages, giant cells and lymphocytes.
This finding is important because four of five known autopsied patients with NXG have had giant cell myocardial disease, and an effort at antemortem diagnosis should be made.
Giant cell granulomatous pulmonary and myocardial lesions in necrobiotic xanthogranuloma with paraproteinemia.
Winkelmann RK, Litzow MR, Umbert IJ, Lie JT.
Department of Dermatology, Mayo Clinic Scottsdale, Arizona, USA.
Mayo Clin Proc 1997 Nov;72(11):1028-33 Abstract quote
OBJECTIVE: To report three cases of pulmonary or myocardial disease (or both) and necrobiotic xanthogranuloma.
MATERIAL AND METHODS: Giant cell granulomas of the lung and myocardium were demonstrated in three patients who had pulmonary and myocardial lesions of necrobiotic xanthogranuloma in conjunction with skin lesions, leukopenia, paraproteinemia, and complement deficiencies. The patients were two men who were 47 and 64 years of age and a 39-year-old woman.
RESULTS: Biopsies of skin and visceral lesions showed asteroid and cytoplasmic inclusions. B-cell lymphoid nodules were found. In one of the male patients, a major clonal T-cell receptor gene rearrangement was detected in the peripheral blood. Prednisone was ineffective in two of the patients. The other patient experienced regression of skin lesions and diminishment of a chest nodule after receiving alkylating agent therapy.
CONCLUSION: Establishing the correct diagnosis is important, and apparently it is possible to establish the nature of the myocardial and pulmonary lesions with use of appropriate scans and by biopsy. Successful treatment of necrobiotic xanthogranuloma skin lesions with corticosteroids or alkylating agents (or both) implies that evolution of serious disease that compromises the heart and lungs could be controlled.
Necrobiotic xanthogranuloma presenting as a solitary tumor.
Stork J, Kodetova D, Vosmik F, Krejca M.
Department of Dermatology, General Faculty Hospital, Charles University, Praha, Czech Republic.
Am J Dermatopathol 2000 Oct;22(5):453-6 Abstract quote
We report on a 60-year-old overweight white woman who presented with an asymptomatic flat, hard, yellow-brown subcutaneous plaque on her right hip.
A total excision was performed. Histopathologic examination showed all the major features of a necrobiotic xanthogranuloma (NX) involving the entire dermis and subcutis, including areas of necrobiosis with cholesterol clefts, granulomatous infiltrate with some bizarre giant cells, numerous Touton cells, foamy cells, lymphoid follicles with germinal centers, foci of plasma cells, and "Touton cell panniculitis." A laboratory investigation revealed only slightly increased titers of cholesterol, strong positivity of anti-Borrelia antibodies, and diffuse skeletal osteoporosis with fractures of seven vertebrae. After 4 years of close follow-up, the osteoporosis was improved, and there were no signs of paraproteinemia, malignancy, or new skin lesions.
The authors suggest that this case could represent a solitary clinical variant of NX without paraproteinemia.
Necrobiotic xanthogranuloma with two monoclonal paraproteins and no periorbital involvement at presentation.
Chave TA, Hutchinson PE.
Department of Dermatology, Leicester Royal Infirmary, Leicester, UK.
Clin Exp Dermatol 2001 Sep;26(6):493-6 Abstract quote
A patient with necrobiotic xanthogranuloma is presented to highlight the clinico-pathological features of this rare condition which must be differentiated from atypical necrobiosis lipoidica.
The patient is unusual in that he has two associated monoclonal paraproteins and did not have periorbital involvement at presentation.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Necrobiotic granulomas with histiocytes, foam cells, and giant cells. Occasionally, there are cholesterol clefts with cellular debris
Touton type giant cells may be present and sometimes extensive in the subcutaneous fat (Touton-cell panniculitis)
Histopathology of necrobiotic xanthogranuloma with paraproteinemia.
Finan MC, Winkelmann RK.
J Cutan Pathol 1987 Apr;14(2):92-9 Abstract quote
Fifty-three cutaneous biopsies from 22 patients with necrobiotic xanthogranuloma (NXG) were reviewed.
One or more biopsies from each patient displayed a typical pattern of palisading histiocytic xanthogranuloma with bands of hyaline necrobiosis. Multiple foam cells and Touton giant cells were present, and atypical, bizarre-appearing foreign body giant cells were characteristic. Cholesterol clefts were found in 18 specimens, and lymphoid nodules were found in 24, 8 of which had germinal center formation. Twenty-one specimens contained foci of plasma cells, and these were located perivascularly, at the periphery of lymphoid nodules, and, as infiltrates, between dermal collagen bundles.
Unique features were xanthogranulomatous panniculitis, often appearing as Touton cell panniculitis, and a rare but distinctive palisading cholesterol cleft granuloma. The cytoplasm of giant cells and histiocytes contained PAS-positive, diastase-resistant polysaccharide. Examination of 3 cases by electron microscopy revealed dendritic cells in the epidermis and vacuolated dermal histiocytes.
S-100 antibody was negative in 3 cases. Leukocyte monoclonal antibody studies in 6 patients showed predominantly T-helper lymphocytes within the granuloma. NXG is a T-helper cell, non-X histiocytic granuloma with a distinctive histopathology.
Necrobiotic xanthogranuloma: a case without paraproteinemia but with transepithelial elimination.
Dupre A, Viraben R.
Dermatology Service, Purpan Hopital, Toulouse, France
J Cutan Pathol 1988 Apr;15(2):116-9 Abstract quote
We report a female patient, now aged 60, followed for 20 years for lesions originally diagnosed as necrobiosis lipoidica diabeticorum. In fact, the anatomical and clinical features of her disorder correspond to the new entity described as necrobiotic xanthogranuloma.
Two elements distinguish this from earlier cases: 1) two examinations failed to reveal paraproteinemia; 2) there was transepithelial elimination of cholesterol crystals and degenerated xanthomatous cell debris via hair follicles.
This demonstrates the characteristic histology of the disorder and indicates that the diagnosis of necrobiotic xanthogranuloma should be considered even in the absence of paraproteinemia.
Asteroid bodies and other cytoplasmic inclusions in necrobiotic xanthogranuloma with paraproteinemia.
Winkelmann RK, Dahl PR, Perniciaro C, Dahl PM.
Mayo Clinic Scottsdale, Ariz, USA.
J Am Acad Dermatol 1998 Jun;38(6 Pt 1):967-70 Abstract quote
BACKGROUND: Necrobiotic xanthogranuloma (NXG) with paraproteinemia is a distinctive palisading granuloma of the skin. Extracutaneous lesions are rarely present.
OBJECTIVE: The purpose of this study was to confirm the presence and significance of giant cell asteroid bodies and other cytoplasmic inclusions in NXG with paraproteinemia.
METHODS: Skin biopsy specimens from 24 patients with NXG with paraproteinemia were reviewed; autopsy and lung biopsy specimens from two patients were stained for iron, calcium, and polysaccharide.
RESULTS: Giant cell asteroid bodies were observed in skin biopsy specimens of 8 (33%) of the 24 patients. In addition, large acidophilic polygonal cytoplasmic inclusions were observed in myocardial tissue of one of the autopsy cases. Iron and calcium were not found.
CONCLUSION: Asteroid bodies and other inclusions can be present in the giant cells of NXG with paraproteinemia. They are as frequent as, or more frequent than, in other granulomatous diseases and should be considered in the diagnosis of NXG with paraproteinemia.
Necrobiosis lipoidica: a case with prominent cholesterol clefting and transepithelial elimination.
De la Torre C, Losada A, Cruces MJ.
Service of Dermatology, Hospital Provincial, Pontevedra, Spain.
Am J Dermatopathol 1999 Dec;21(6):575-7 Abstract quote
Transepithelial elimination of degenerated collagen through the hair follicle in necrobiosis lipoidica is rare, clinically manifesting as comedo-like plugs. Also unusual in necrobiosis lipoidica is the finding of cholesterol cleft formation.
We report a case of necrobiosis lipoidica with transepithelial elimination of cholesterol crystals through hair follicles. This has been described in necrobiotic xanthogranuloma, demonstrating some overlap in the histopathologic findings in both necrobiotic granulomas. Additional criteria should be used to establish the diagnosis.
Lipid and giant cell poor necrobiotic xanthogranuloma.
Kossard S, Chow E, Wilkinson B, Killingsworth M.
Skin and Cancer Foundation Australia, Darlinghurst, New South Wales.
J Cutan Pathol 2000 Aug;27(7):374-8 Abstract quote
An 88-year-old man over a 7-month period developed multiple yellow firm focally ulcerative papules and nodules over his face, neck and forearms.
Seven skin biopsies showed a diffuse infiltrate of epithelioid histiocytes associated with areas of necrosis with neutrophilia. Two biopsies showed xanthogranulomatous foci, but cholesterol clefts, prominent giant cells or lymphoid aggregates were not evident. Necrosis with leukocytoclastic debris overshadowed the presence of hyaline necrobiosis. Ultrastructural examination and oil red-o stains on frozen sections revealed focal lipid vacuoles within histiocytes. A paraprotein was detected in the patient's serum.
This presentation may represent a lipid and giant cell poor variant of necrobiotic xanthogranuloma (NXG) and may potentially lead to a delay in diagnosis.
CHARACTERIZATION Special stains Immunoperoxidase S100 negative Direct immunofluorescence (DIF) Vascular staining for IgM, C3, and fibrinogen Indirect immunofluorescence (IIF) Electron microscopy (EM) Multilaminar bodies but no Langerhans granules
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
Necrobiosis lipoidica diabeticorum with cholesterol clefts in the differential diagnosis of necrobiotic xanthogranuloma.
Gibson LE, Reizner GT, Winkelmann RK.
Department of Dermatology, Mayo Clinic, Rochester, MN 55905.
J Cutan Pathol 1988 Feb;15(1):18-21 Abstract quote
The histopathologic findings in 331 cases of necrobiosis lipoidica diabeticorum seen during a 50-year period were reviewed.
Three cases showing cholesterol cleft formation were found. All 3 cases were associated with severe diabetes mellitus. The differential diagnosis of importance is necrobiotic xanthogranuloma. Common features included extensive hyaline necrobiosis and foreign-body giant cells. Atypical and Touton-type giant cells are more common in necrobiotic xanthogranuloma. Vascular changes in necrobiotic xanthogranuloma may include granulomatous involvement of muscular walls with thrombosis. Explanations for cholesterol cleft formation are offered.
When cholesterol clefts are seen in biopsy specimens of necrobiosis, necrobiotic xanthogranuloma must be ruled out. In addition, when found in necrobiosis lipoidica diabeticorum, these clefts may imply diabetes mellitus with complications.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Necrobiotic xanthogranuloma: long-term outcome of ocular and systemic involvement.
Ugurlu S, Bartley GB, Gibson LE.
Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Am J Ophthalmol 2000 May;129(5):651-7 Abstract quote
PURPOSE: To report long-term outcomes of patients with necrobiotic xanthogranuloma, to investigate the propriety of therapeutic surgical excision or debulking, and to study tissue specimens by immunoperoxidase staining and in situ hybridization.
METHODS: Medical records of all patients at the Mayo Clinic, Rochester, Minnesota, with necrobiotic xanthogranuloma between 1980 and 1997 were reviewed. A follow-up letter was sent to each patient inquiring about the current status of the lesions, the treatment regimen, and associated systemic diseases.
RESULTS: The average age (+/- standard deviation) of the 15 men and 11 women was 56.8 +/- 14.8 years. Of the 26 patients, 21 (81%) had lesions of the ocular adnexa. Ulceration of the lesions occurred in 11 patients (42%). The lesions recurred after surgical removal in 11 patients (42%) and on prior incision sites from unrelated operations in three patients (12%). The average duration of follow-up from the appearance of characteristic skin lesions was 10 +/- 6.1 years. Four patients had multiple myeloma, five had a plasma cell dyscrasia, and one had a lymphoproliferative disorder during this period. Time to development of associated malignancy ranged from 8 years before the skin lesions to 11 years after the skin lesions. Overall survival was 100% at 10 years and 90% at 15 years (95% confidence limit, 0.73 to 1.00). Immunoperoxidase stains demonstrated that most histiocytes are not of Langerhans cell lineage. Monoclonal immune globulins were not identified in tissue specimens.
CONCLUSION: Care of patients with necrobiotic xanthogranuloma should include avoidance of surgical removal, if possible, and lifelong follow-up to detect the development of associated malignancy.
Plasmapheresis, a treatment modality for necrobiotic xanthogranuloma.
Finelli LG, Ratz JL.
J Am Acad Dermatol 1987 Aug;17(2 Pt 2):351-4 Abstract quote
A case of necrobiotic xanthogranuloma treated with plasmapheresis is reported.
This entity is characterized by multiple inflammatory, ulcerative nodules and atrophic plaques with a xanthomatous quality that develop in conjunction with a paraproteinemia.
Successful healing of ulcerated lesions and lowering of the paraproteinemia was achieved by plasmapheresis in our patient with necrobiotic xanthogranuloma when cytotoxic therapy failed.
Recombinant interferon alfa-2b treatment of necrobiotic xanthogranuloma with paraproteinemia.
Venencie PY, Le Bras P, Toan ND, Tchernia G, Delfraissy JF.
Department of Dermatology, CHU Bicetre, Le Kremlin Bicetre, France.
J Am Acad Dermatol 1995 Apr;32(4):666-7
Cutaneous necrobiotic xanthogranuloma (NXG)--successfully treated with low dose chlorambucil.
Machado S, Alves R, Lima M, Leal I, Massa A.
Service of Dermatology, Hospital Geral Santo Antonio, Rua D. Manuel II, Edificio ex: Cicap, 4099-001 Porto, Portugal.
Eur J Dermatol 2001 Sep-Oct;11(5):458-62 Abstract quote
We report a case of necrobiotic xanthogranuloma in a 51 year-old white male patient presenting with a 6-year history of multiple indurated violaceous nodules and plaques involving the eyelids, trunk and extremities. He had an associated paraproteinemia (Ig G lambda), elevated sedimentation rate, cryoglobulinemia and hypocomplementemia. No extracutaneous involvement was detected.
He was successfully treated with chlorambucil (2 mg/d for 7 months), leading to disappearance of all skin lesions.
Recalcitrant necrobiotic xanthogranuloma responding to pulsed high-dose oral dexamethasone plus maintenance therapy with oral prednisolone.
Chave TA, Chowdhury MM, Holt PJ.
Department of Dermatology, University Hospital of Wales, Cardiff CF14 4XN, UK.
Br J Dermatol 2001 Jan;144(1):158-61 Abstract quote
A patient with the rare condition necrobiotic xanthogranuloma was treated from 1992 to 1999 with multiple therapies, none of which was effective. Her disease was progressive, causing significant disability.
In September 1999 a trial of high-dose pulsed oral dexamethasone with maintenance corticosteroids led to a substantial improvement in her condition.
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