Acta Med Scand 205: 243-245, 1979
Development of Biclonal Gammopathy in a Patient with von Recklinghausen’s Neurofibromatosis Leif E. Wille and Jens g s t b o r g From the Department of Chemical Pathology, @stfold County Hospital, Fredrikstad, Norway
ABSTRACT. A well established case of von Recklinghausen’s neurofibromatosis, in which a biclonal gammopathy developed, has been studied. One of the paraproteins was characterized as IgG kappa, the other as IgG lambda. This combination of anomalies has not been described previously in the literature.
Von Recklinghausen’s neurofibromatosis is characterized by increased pigmentation of the skin (“cafe au lait spots”) and skin tumors, partly o f ectodermal and neural origin. Mental deficiency is often present, as are several organ manifestations, including the skeleton, eyes, feet a n d blood vessels. Hemangioma is often detected, as well as hypertrichosis sacralis. Axillary freckling has been emphasized as an important diagnostic aid (3). T h e pattern of inheritance is autosomally dominant (4). An overall increase of secondary tumors has been observed in neurofibromatosis. However, t o our knowledge n o cases have been reported in t h e literature in which neurofibromatosis coexists with
ing excercise. Physical examination demonstrated a rough systolic cardiac murmur with radiation to the carotides, indicating a stenotic aortic valve. A moderate hepatomegaly was disclosed. Extensive Dupuytren’s contractures were observed in both hands. Otherwise the patient felt well. No musculoskeletal tenderness, back pain or other signs suggesting myelomatosis were demonstrated. Skeletal X-rays did not show any abnormalities. Biopsy of excised tumor material verified the presence of neurofibromas. Plasma cells were not dettxted in the biopsy. Less than 2 % plasma cells were demonstrated in his bone marrow. Chromosome analysis demonstrating 46 XY karyotype did not reveal any abnormalities. Three months after the initial studies reported in this communication, the patient suddenly died (mors subita). His sudden death can be related to the stenotic aortic valves. Analytical procedures
Agarose gel electrophoresis of serum proteins was carried out according to Johansson (7). Immunoelectrophoresis for demonstration of gamma, alpha, mu heavy chains and kappa and lambda light chains was performed conventionally on glass plates in 1 % agarose gel. The antisera were obtained from Boehringwerke. Radial immunodiffusion was adopted from Mancini et al. (10).
monoclonal gammopathy who during t w o years’ observation developed biclonal gammopathy with IgG kappa and IgG lambda specificities. Clinical evidence for the presence of myelomatosis has not been obtained. It is suggested that a n increased chance of somatic mutations might b e present in neurofibromatosis.
Light chains in urine were examined after concentration of morning samples 300 times in Amicon ultrafilters, applying Heller’s and Bradshaw’s tests for protein. In addition, electrophoresis and immunoelectrophoresis of concentrated urine were carried out in agarose gel, Films from bone marrow aspirates were fixed in absolute methanol and stained by May-Griinwald-Giemsa at pH 6.8 for light microscopy.
CASE REPORT
RESULTS
A 68-year-old man has noticed skin tumors, melanotic skin macules and axillary freckling since the age of 35. No knowledge of similar defects in parents or siblings. His son, now aged 29, is disabled by a “neurologic disease”, but he has refused any kind of physical examination. For the last 2 years the patient has complained ofdyspneadur-
At the first examination (Oct. 13th, 1975), agarose gel electrophoresis demonstrated a monoclonal I ~ G kappa protein in the gamma region, which made up approximately 2o gll (Table I). Two years later (OCt. 6th, 1977) t w o monoclonal paraproteins were A
Development of Biclonal Gammopathy in a Patient with von Recklinghausen’s Neurofibromatosis Leif E. Wille and Jens g s t b o r g From the Department of Chemical Pathology, @stfold County Hospital, Fredrikstad, Norway
ABSTRACT. A well established case of von Recklinghausen’s neurofibromatosis, in which a biclonal gammopathy developed, has been studied. One of the paraproteins was characterized as IgG kappa, the other as IgG lambda. This combination of anomalies has not been described previously in the literature.
Von Recklinghausen’s neurofibromatosis is characterized by increased pigmentation of the skin (“cafe au lait spots”) and skin tumors, partly o f ectodermal and neural origin. Mental deficiency is often present, as are several organ manifestations, including the skeleton, eyes, feet a n d blood vessels. Hemangioma is often detected, as well as hypertrichosis sacralis. Axillary freckling has been emphasized as an important diagnostic aid (3). T h e pattern of inheritance is autosomally dominant (4). An overall increase of secondary tumors has been observed in neurofibromatosis. However, t o our knowledge n o cases have been reported in t h e literature in which neurofibromatosis coexists with
ing excercise. Physical examination demonstrated a rough systolic cardiac murmur with radiation to the carotides, indicating a stenotic aortic valve. A moderate hepatomegaly was disclosed. Extensive Dupuytren’s contractures were observed in both hands. Otherwise the patient felt well. No musculoskeletal tenderness, back pain or other signs suggesting myelomatosis were demonstrated. Skeletal X-rays did not show any abnormalities. Biopsy of excised tumor material verified the presence of neurofibromas. Plasma cells were not dettxted in the biopsy. Less than 2 % plasma cells were demonstrated in his bone marrow. Chromosome analysis demonstrating 46 XY karyotype did not reveal any abnormalities. Three months after the initial studies reported in this communication, the patient suddenly died (mors subita). His sudden death can be related to the stenotic aortic valves. Analytical procedures
Agarose gel electrophoresis of serum proteins was carried out according to Johansson (7). Immunoelectrophoresis for demonstration of gamma, alpha, mu heavy chains and kappa and lambda light chains was performed conventionally on glass plates in 1 % agarose gel. The antisera were obtained from Boehringwerke. Radial immunodiffusion was adopted from Mancini et al. (10).
monoclonal gammopathy who during t w o years’ observation developed biclonal gammopathy with IgG kappa and IgG lambda specificities. Clinical evidence for the presence of myelomatosis has not been obtained. It is suggested that a n increased chance of somatic mutations might b e present in neurofibromatosis.
Light chains in urine were examined after concentration of morning samples 300 times in Amicon ultrafilters, applying Heller’s and Bradshaw’s tests for protein. In addition, electrophoresis and immunoelectrophoresis of concentrated urine were carried out in agarose gel, Films from bone marrow aspirates were fixed in absolute methanol and stained by May-Griinwald-Giemsa at pH 6.8 for light microscopy.
CASE REPORT
RESULTS
A 68-year-old man has noticed skin tumors, melanotic skin macules and axillary freckling since the age of 35. No knowledge of similar defects in parents or siblings. His son, now aged 29, is disabled by a “neurologic disease”, but he has refused any kind of physical examination. For the last 2 years the patient has complained ofdyspneadur-
At the first examination (Oct. 13th, 1975), agarose gel electrophoresis demonstrated a monoclonal I ~ G kappa protein in the gamma region, which made up approximately 2o gll (Table I). Two years later (OCt. 6th, 1977) t w o monoclonal paraproteins were A
