Acanthosis Nigricans in a Patient Treated With Palifermin

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Systemic Mastocytosis: Classification, Pathogenesis, Diagnosis, and Treatment

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Baer MR


Case Report
A 46-year-old woman presented with a rash that had been present for more than 20 years but had progressed over the past 6 years and was associated with pruritus, burning, and blistering precipitated by temperature changes or anxiety. In addition, she had watery diarrhea for 5 years and also had been found to have osteopenia. She was a healthy-appearing woman with prominent facial erythema. Vital signs were normal. Skin examination revealed facial telangiectases as well as erythema and 2- to 4-mm reddish brown papules and macules on the extensor surfaces of the arms and thighs, chest, abdomen, and back, coalescing into plaques on the thighs (Figure). She had bilateral axillary lymphadenopathy. Liver and spleen were not palpable. Her hemoglobin level was 12.7 g/dL (reference range, 14.0–17.5 g/dL); white blood cell count was 5.2X109/L (reference range, 4.5–11.0X109/L) with 63 neutrophils, 36 lymphocytes, and 1 monocyte; and platelet count was 301X109/L (reference range, 150–350X109/L). Chemistries were within reference range, except for an alkaline phosphatase level of 136 U/L (reference range, 38–126 U/L). Biopsy of a forearm skin lesion showed an unremarkable epidermal layer overlying a dermis without vasculitis but with a mild increase in perivascular and focally interstitial mononuclear cells staining with mast cell tryptase and CD117. Serum tryptase level was greater than 200 ng/mL (reference,

References

 

  1. Mekori YA, Metcalfe DD. Mast cell-T cell interactions. J Allergy Clin Immunol. 1999;104(3, pt 1):517-523.
  2. Weller K, Foitzik K, Paus R, et al. Mast cells are required for normal healing of skin wounds in mice. FASEB J. 2006;20:2366-2368. Epub September 11, 2006.
  3. Nienartowicz A, Sobaniec-Lotowska ME, Jarocka-Cyrta E, et al. Mast cells in neoangiogenesis. Med Sci Monit. 2006;12:RA53-56. Epub February 23, 2006.
  4. Valent P, Akin C, Sperr WR, et al. Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma. 2005;46:35-48.
  5. The World Health Organization. Mastocytosis. In: Jaffe ES, Harris NL, Stein H, et al, eds. WHO Classification of Tumours: Pathology and Genetics of Tumours of Haematopoetic and Lymphoid Tissues. Vol 3. IARC Press: Lyon, France; 2001:293-302.
  6. Wolff K, Komar M, Petzelbauer P. Clinical and histopathological aspects of cutaneous mastocytosis. Leuk Res. 2001;25:519-528.
  7. Valent P, Akin C, Sperr WR, et al. Mast cell proliferative disorders: current view on variants recognized by the World Health Organization. Hematol Oncol Clin North Am. 2003;17:1227-1241.
  8. Stankovic K, Sarrot-Reynauld F, Puget M, et al. Systemic mastocytosis: predictable factors of poor prognosis present at the onset of the disease. Eur J Intern Med. 2005;16:387-390.
  9. Chott A, Guenther P, Huebner A, et al. Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma. Am J Surg Pathol. 2003;27:1013-1019.
  10. Schernthaner GH, Jordan JH, Ghannadan M, et al. Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells. Blood. 2001;98:3784-3792.
  11. Metcalfe DD. Regulation of normal and neoplastic human mast cell development in mastocytosis. Trans Am Clin Climatol Assoc. 2005;116:185-203.
  12. Mickys U, Barakauskiene A, Wolf-Peeters D, et al. Aggressive systemic mastocytosis complicated by protein-losing enteropathy. Dig Liver Dis. 2007;39:693-697. Epub July 14, 2006.
  13. Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14:579-623.
  14. Horny HP, Kaiserling E, Campbell M, et al. Liver findings in generalized mastocytosis. a clinicopathologic study. Cancer. 1989;63:532-538.
  15. Webb TA, Li CY, Yam LT. Systemic mast cell disease: a clinical and hematopathologic study of 26 cases. Cancer. 1982;49:927-938.
  16. Chen CC, Andrich MP, Mican JM, et al. A retrospective analysis of bone scan abnormalities in mastocytosis: correlation with disease category and prognosis. J Nucl Med. 1994;35:1471-1475.
  17. van Toorenenbergen AW, Oranje AP. Comparison of serum tryptase and urine N-methylhistamine in patients with suspected mastocytosis. Clin Chim Acta. 2005;359(1-2):72-77.
  18. Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol. 1990;85: 852-855.
  19. Friedman B, Darling G, Norton J, et al. Splenectomy in the management of systemic mast cell disease. Surgery. 1990;107:94-100.
  20. Quintas-Cardama A, Aribi A, Cortes J, et al. Novel approaches in the treatment of systemic mastocytosis. Cancer. 2006;107:1429-1439.
  21. Casassus P, Caillat-Vigneron N, Martin A, et al. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002;119:1090-1097.
  22. Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, et al. Cladribine therapy for systemic mastocytosis. Blood. 2003;102:4270-4276. Epub August 21, 2003.
  23. Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, et al. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. C
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This article has been peer reviewed and approved by Michael Fisher, MD, Professor of Medicine, Albert Einstein College of Medicine. Review date: December 2008.

Drs. Bunimovich, Grassi, and Baer report no conflict of interest. The authors discuss off-label use of dasatinib for systemic mastocytosis. Dr. Fisher reports no conflict of interest. The staff of CCME of Albert Einstein College of Medicine and Cutis® have no conflicts of interest with commercial interest related directly or indirectly to this educational activity. Dr. Bunimovich is a resident, Department of Dermatology, State University of New York, Buffalo School of Medicine. Dr. Grassi is Assistant Clinical Professor, Department of Dermatology, and Dr. Baer was Professor, Department of Medicine, both from Roswell Park Cancer Institute, Buffalo. Dr. Baer currently is Professor of Medicine, Greenbaum Cancer Center, University of Maryland, Baltimore.

Olga Bunimovich, MD; Marcelle Grassi, MD; Maria R. Baer, MD

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Baer MR
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This article has been peer reviewed and approved by Michael Fisher, MD, Professor of Medicine, Albert Einstein College of Medicine. Review date: December 2008.

Drs. Bunimovich, Grassi, and Baer report no conflict of interest. The authors discuss off-label use of dasatinib for systemic mastocytosis. Dr. Fisher reports no conflict of interest. The staff of CCME of Albert Einstein College of Medicine and Cutis® have no conflicts of interest with commercial interest related directly or indirectly to this educational activity. Dr. Bunimovich is a resident, Department of Dermatology, State University of New York, Buffalo School of Medicine. Dr. Grassi is Assistant Clinical Professor, Department of Dermatology, and Dr. Baer was Professor, Department of Medicine, both from Roswell Park Cancer Institute, Buffalo. Dr. Baer currently is Professor of Medicine, Greenbaum Cancer Center, University of Maryland, Baltimore.

Olga Bunimovich, MD; Marcelle Grassi, MD; Maria R. Baer, MD

Author and Disclosure Information

 

This article has been peer reviewed and approved by Michael Fisher, MD, Professor of Medicine, Albert Einstein College of Medicine. Review date: December 2008.

Drs. Bunimovich, Grassi, and Baer report no conflict of interest. The authors discuss off-label use of dasatinib for systemic mastocytosis. Dr. Fisher reports no conflict of interest. The staff of CCME of Albert Einstein College of Medicine and Cutis® have no conflicts of interest with commercial interest related directly or indirectly to this educational activity. Dr. Bunimovich is a resident, Department of Dermatology, State University of New York, Buffalo School of Medicine. Dr. Grassi is Assistant Clinical Professor, Department of Dermatology, and Dr. Baer was Professor, Department of Medicine, both from Roswell Park Cancer Institute, Buffalo. Dr. Baer currently is Professor of Medicine, Greenbaum Cancer Center, University of Maryland, Baltimore.

Olga Bunimovich, MD; Marcelle Grassi, MD; Maria R. Baer, MD

Article PDF
083010029.pdf
Article PDF
083010029.pdf


Case Report
A 46-year-old woman presented with a rash that had been present for more than 20 years but had progressed over the past 6 years and was associated with pruritus, burning, and blistering precipitated by temperature changes or anxiety. In addition, she had watery diarrhea for 5 years and also had been found to have osteopenia. She was a healthy-appearing woman with prominent facial erythema. Vital signs were normal. Skin examination revealed facial telangiectases as well as erythema and 2- to 4-mm reddish brown papules and macules on the extensor surfaces of the arms and thighs, chest, abdomen, and back, coalescing into plaques on the thighs (Figure). She had bilateral axillary lymphadenopathy. Liver and spleen were not palpable. Her hemoglobin level was 12.7 g/dL (reference range, 14.0–17.5 g/dL); white blood cell count was 5.2X109/L (reference range, 4.5–11.0X109/L) with 63 neutrophils, 36 lymphocytes, and 1 monocyte; and platelet count was 301X109/L (reference range, 150–350X109/L). Chemistries were within reference range, except for an alkaline phosphatase level of 136 U/L (reference range, 38–126 U/L). Biopsy of a forearm skin lesion showed an unremarkable epidermal layer overlying a dermis without vasculitis but with a mild increase in perivascular and focally interstitial mononuclear cells staining with mast cell tryptase and CD117. Serum tryptase level was greater than 200 ng/mL (reference,


Case Report
A 46-year-old woman presented with a rash that had been present for more than 20 years but had progressed over the past 6 years and was associated with pruritus, burning, and blistering precipitated by temperature changes or anxiety. In addition, she had watery diarrhea for 5 years and also had been found to have osteopenia. She was a healthy-appearing woman with prominent facial erythema. Vital signs were normal. Skin examination revealed facial telangiectases as well as erythema and 2- to 4-mm reddish brown papules and macules on the extensor surfaces of the arms and thighs, chest, abdomen, and back, coalescing into plaques on the thighs (Figure). She had bilateral axillary lymphadenopathy. Liver and spleen were not palpable. Her hemoglobin level was 12.7 g/dL (reference range, 14.0–17.5 g/dL); white blood cell count was 5.2X109/L (reference range, 4.5–11.0X109/L) with 63 neutrophils, 36 lymphocytes, and 1 monocyte; and platelet count was 301X109/L (reference range, 150–350X109/L). Chemistries were within reference range, except for an alkaline phosphatase level of 136 U/L (reference range, 38–126 U/L). Biopsy of a forearm skin lesion showed an unremarkable epidermal layer overlying a dermis without vasculitis but with a mild increase in perivascular and focally interstitial mononuclear cells staining with mast cell tryptase and CD117. Serum tryptase level was greater than 200 ng/mL (reference,

References

 

  1. Mekori YA, Metcalfe DD. Mast cell-T cell interactions. J Allergy Clin Immunol. 1999;104(3, pt 1):517-523.
  2. Weller K, Foitzik K, Paus R, et al. Mast cells are required for normal healing of skin wounds in mice. FASEB J. 2006;20:2366-2368. Epub September 11, 2006.
  3. Nienartowicz A, Sobaniec-Lotowska ME, Jarocka-Cyrta E, et al. Mast cells in neoangiogenesis. Med Sci Monit. 2006;12:RA53-56. Epub February 23, 2006.
  4. Valent P, Akin C, Sperr WR, et al. Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma. 2005;46:35-48.
  5. The World Health Organization. Mastocytosis. In: Jaffe ES, Harris NL, Stein H, et al, eds. WHO Classification of Tumours: Pathology and Genetics of Tumours of Haematopoetic and Lymphoid Tissues. Vol 3. IARC Press: Lyon, France; 2001:293-302.
  6. Wolff K, Komar M, Petzelbauer P. Clinical and histopathological aspects of cutaneous mastocytosis. Leuk Res. 2001;25:519-528.
  7. Valent P, Akin C, Sperr WR, et al. Mast cell proliferative disorders: current view on variants recognized by the World Health Organization. Hematol Oncol Clin North Am. 2003;17:1227-1241.
  8. Stankovic K, Sarrot-Reynauld F, Puget M, et al. Systemic mastocytosis: predictable factors of poor prognosis present at the onset of the disease. Eur J Intern Med. 2005;16:387-390.
  9. Chott A, Guenther P, Huebner A, et al. Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma. Am J Surg Pathol. 2003;27:1013-1019.
  10. Schernthaner GH, Jordan JH, Ghannadan M, et al. Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells. Blood. 2001;98:3784-3792.
  11. Metcalfe DD. Regulation of normal and neoplastic human mast cell development in mastocytosis. Trans Am Clin Climatol Assoc. 2005;116:185-203.
  12. Mickys U, Barakauskiene A, Wolf-Peeters D, et al. Aggressive systemic mastocytosis complicated by protein-losing enteropathy. Dig Liver Dis. 2007;39:693-697. Epub July 14, 2006.
  13. Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14:579-623.
  14. Horny HP, Kaiserling E, Campbell M, et al. Liver findings in generalized mastocytosis. a clinicopathologic study. Cancer. 1989;63:532-538.
  15. Webb TA, Li CY, Yam LT. Systemic mast cell disease: a clinical and hematopathologic study of 26 cases. Cancer. 1982;49:927-938.
  16. Chen CC, Andrich MP, Mican JM, et al. A retrospective analysis of bone scan abnormalities in mastocytosis: correlation with disease category and prognosis. J Nucl Med. 1994;35:1471-1475.
  17. van Toorenenbergen AW, Oranje AP. Comparison of serum tryptase and urine N-methylhistamine in patients with suspected mastocytosis. Clin Chim Acta. 2005;359(1-2):72-77.
  18. Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol. 1990;85: 852-855.
  19. Friedman B, Darling G, Norton J, et al. Splenectomy in the management of systemic mast cell disease. Surgery. 1990;107:94-100.
  20. Quintas-Cardama A, Aribi A, Cortes J, et al. Novel approaches in the treatment of systemic mastocytosis. Cancer. 2006;107:1429-1439.
  21. Casassus P, Caillat-Vigneron N, Martin A, et al. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002;119:1090-1097.
  22. Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, et al. Cladribine therapy for systemic mastocytosis. Blood. 2003;102:4270-4276. Epub August 21, 2003.
  23. Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, et al. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. C
References

 

  1. Mekori YA, Metcalfe DD. Mast cell-T cell interactions. J Allergy Clin Immunol. 1999;104(3, pt 1):517-523.
  2. Weller K, Foitzik K, Paus R, et al. Mast cells are required for normal healing of skin wounds in mice. FASEB J. 2006;20:2366-2368. Epub September 11, 2006.
  3. Nienartowicz A, Sobaniec-Lotowska ME, Jarocka-Cyrta E, et al. Mast cells in neoangiogenesis. Med Sci Monit. 2006;12:RA53-56. Epub February 23, 2006.
  4. Valent P, Akin C, Sperr WR, et al. Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma. 2005;46:35-48.
  5. The World Health Organization. Mastocytosis. In: Jaffe ES, Harris NL, Stein H, et al, eds. WHO Classification of Tumours: Pathology and Genetics of Tumours of Haematopoetic and Lymphoid Tissues. Vol 3. IARC Press: Lyon, France; 2001:293-302.
  6. Wolff K, Komar M, Petzelbauer P. Clinical and histopathological aspects of cutaneous mastocytosis. Leuk Res. 2001;25:519-528.
  7. Valent P, Akin C, Sperr WR, et al. Mast cell proliferative disorders: current view on variants recognized by the World Health Organization. Hematol Oncol Clin North Am. 2003;17:1227-1241.
  8. Stankovic K, Sarrot-Reynauld F, Puget M, et al. Systemic mastocytosis: predictable factors of poor prognosis present at the onset of the disease. Eur J Intern Med. 2005;16:387-390.
  9. Chott A, Guenther P, Huebner A, et al. Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma. Am J Surg Pathol. 2003;27:1013-1019.
  10. Schernthaner GH, Jordan JH, Ghannadan M, et al. Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells. Blood. 2001;98:3784-3792.
  11. Metcalfe DD. Regulation of normal and neoplastic human mast cell development in mastocytosis. Trans Am Clin Climatol Assoc. 2005;116:185-203.
  12. Mickys U, Barakauskiene A, Wolf-Peeters D, et al. Aggressive systemic mastocytosis complicated by protein-losing enteropathy. Dig Liver Dis. 2007;39:693-697. Epub July 14, 2006.
  13. Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14:579-623.
  14. Horny HP, Kaiserling E, Campbell M, et al. Liver findings in generalized mastocytosis. a clinicopathologic study. Cancer. 1989;63:532-538.
  15. Webb TA, Li CY, Yam LT. Systemic mast cell disease: a clinical and hematopathologic study of 26 cases. Cancer. 1982;49:927-938.
  16. Chen CC, Andrich MP, Mican JM, et al. A retrospective analysis of bone scan abnormalities in mastocytosis: correlation with disease category and prognosis. J Nucl Med. 1994;35:1471-1475.
  17. van Toorenenbergen AW, Oranje AP. Comparison of serum tryptase and urine N-methylhistamine in patients with suspected mastocytosis. Clin Chim Acta. 2005;359(1-2):72-77.
  18. Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol. 1990;85: 852-855.
  19. Friedman B, Darling G, Norton J, et al. Splenectomy in the management of systemic mast cell disease. Surgery. 1990;107:94-100.
  20. Quintas-Cardama A, Aribi A, Cortes J, et al. Novel approaches in the treatment of systemic mastocytosis. Cancer. 2006;107:1429-1439.
  21. Casassus P, Caillat-Vigneron N, Martin A, et al. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002;119:1090-1097.
  22. Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, et al. Cladribine therapy for systemic mastocytosis. Blood. 2003;102:4270-4276. Epub August 21, 2003.
  23. Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, et al. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. C
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