Abstract

BACKGROUND: Necrobiotic Xanthogranuloma (NXG) is a rare chronic granulomatous disorder of the skin associated with monoclonal gammopathies (MG). Due to its rarity, data on response to various therapies are largely limited to single case reports or small case series. Hence, we described the clinical features in patients with NXG and MG as well as their subsequent disease course and response to treatment.

METHODS: This was a retrospective study evaluating 35 patients with NXG and coexisting MG from 1994-2015 who were evaluated in the Hematology Outpatient Clinic at the Mayo Clinic, Rochester. All patients had a biopsy proven diagnosis of NXG with the concurrent presence of a serum monoclonal gammopathy.

RESULTS: The median age at diagnosis was 56 years (range: 26-88). Most patients had a plasma cell dyscrasia (28 MGUS; 5 Smoldering myeloma) while 2 had chronic lymphocytic leukemia. Themost common monoclonal (M) protein was IgG kappa (60%). The median M-spike was 1.1 g/dL (range: 0-3). The most common site of NXG was periocular (66%). All patients received treatment, with over half requiring >3 different lines of treatment. The treatments were heterogeneous and included excision, intra-lesional injection, radiotherapy as well as systemic treatment. The types of systemic treatment used and clinical response are reported in Table 1. The median follow up was 46 months (range: 4-234) and the median survival was not reached but at the time of analysis 80% were still alive. At last follow-up, 80% of patients had signs of either clinical improvement or stable skin disease. Eight patients (23%) had disease progression to multiple myeloma at a median of 67 months (Range: 21 - 107).

CONCLUSIONS: We report the clinical findings and treatment outcomes of one of the largest series of patients with NXG associated with MG. The clinical course is generally indolent but malignant transformation is not uncommon. Cutaneous objective responses can be achieved with various systemic agents used in the treatment of lymphoproliferative malignancies.

Table 1.

Treatment Types and Clinical Response Rates

Treatment No of patientsA Clinical Benefit Rate B Response rateC 
Chemotherapy
- Chlorambucil +/- Steroids
- Melphalan/Steroids
- Cytoxan/Steroids
- Cladribine
- Vincristine/doxorubicin/dexamethasone
- High dose therapy with stem cell rescue
- Fludarabine/cyclophosphamide/rituximab 
5
3
4
3
2
3
2/5 (40%)
0/3 (0%)
1/4 (25%)
1/3 (33%)
1/2 (50%)
2/3 (67%)
1/1 (100%) 
1/5 (20%)
0/3 (0%)
0/4 (0%)
1/3 (33%)
0/2 (0%)
2/3 (67%)
1/1 (100%) 
Novel agents
- Thalidomide +/- Steroids
- Lenalidomide +/- Steroids
- Bortezomib +/- Steroids
- Bortezomib/Lenalidomide/Dexamethasone 
11
14
4
5/11 (45%)
10/14 (71%)
2/4 (50%)
1/1 (100%) 
4/11 (36%)
7/14 (50%)
1/4 (25%)
1/1 (100%) 
Intravenous immunoglobulin 3/4 (75%) 2/4 (50%) 
Systemic steroids alone 11 4/11 (36%) 4/11 (36%) 
Rituximab 2/6 (33%) 1/6 (17%) 
AntibioticsD 0/3 (0%) 0/3 (0%) 
ImmunosuppressantsE 1/6 (17%) 0/6 (0%) 
Treatment No of patientsA Clinical Benefit Rate B Response rateC 
Chemotherapy
- Chlorambucil +/- Steroids
- Melphalan/Steroids
- Cytoxan/Steroids
- Cladribine
- Vincristine/doxorubicin/dexamethasone
- High dose therapy with stem cell rescue
- Fludarabine/cyclophosphamide/rituximab 
5
3
4
3
2
3
2/5 (40%)
0/3 (0%)
1/4 (25%)
1/3 (33%)
1/2 (50%)
2/3 (67%)
1/1 (100%) 
1/5 (20%)
0/3 (0%)
0/4 (0%)
1/3 (33%)
0/2 (0%)
2/3 (67%)
1/1 (100%) 
Novel agents
- Thalidomide +/- Steroids
- Lenalidomide +/- Steroids
- Bortezomib +/- Steroids
- Bortezomib/Lenalidomide/Dexamethasone 
11
14
4
5/11 (45%)
10/14 (71%)
2/4 (50%)
1/1 (100%) 
4/11 (36%)
7/14 (50%)
1/4 (25%)
1/1 (100%) 
Intravenous immunoglobulin 3/4 (75%) 2/4 (50%) 
Systemic steroids alone 11 4/11 (36%) 4/11 (36%) 
Rituximab 2/6 (33%) 1/6 (17%) 
AntibioticsD 0/3 (0%) 0/3 (0%) 
ImmunosuppressantsE 1/6 (17%) 0/6 (0%) 

ANo of patients who underwent a particular therapy amongst the 35 patients in the study cohort.

BClinical Benefit: Improvement or stable skin disease

CResponse: Improvement in skin disease

DAntibiotics: Fluoroquinolones, Tetracycline

EImmunosuppressants: Cyclosporine, Methotrexate, Plaquenil

Disclosures

Kumar:Celgene, Millennium, Onyx, Novartis, Janssen, Sanofi: Research Funding; Celgene, Millennium, Onyx, Janssen, Noxxon, Sanofi, BMS, Skyline: Consultancy; Skyline, Noxxon: Honoraria.

Author notes

*

Asterisk with author names denotes non-ASH members.