Pediatr Blood Cancer 2014;61:564–566
LETTER TO THE EDITOR CNS Lymphoma in a Patient With Shwachman Diamond Syndrome
To the Editor: Shwachman Diamond syndrome (SDS) is a rare autosomal disorder characterized by pancreatic insufficiency and neutropenia. Patients commonly present in infancy and are at risk for hematological malignancy in life [2,3]. The association of SDS and myelodysplasia, ALL and AML are well described [1]. We present the case of an 18-year-old patient with SDS who is diagnosed with CNS B-cell lymphoma. To our knowledge, CNS lymphoma in a patient with SDS has not been described [4]. Our 18-year-old patient with SDS presented with new onset seizures. He was initially diagnosed with the syndrome at age 8 when he was admitted for a respiratory infection and was noted to be neutropenic during the admission. A bone marrow biopsy was performed which confirmed hypoplasia of myeloid tissue and maturation arrest of myeloid cells. An outside institution confirmed presence of the SDS gene. However, this test was not duplicated at our institution. From age 8 to 18 years, he was maintained on pancreatic enzymes and had no hospitalizations for infections. At 18, he had a
generalized tonic-clonic seizure, which lasted about 10 minutes. A CT of the head was performed which revealed a right frontal hemorrhage or hemorrhagic mass with surrounding edema. An MRI was performed which confirmed a 3 cm right frontal and 1 cm left occipital enhancing lesions (see Fig. 1). These lesions were biopsied and confirmed to be diffuse large B-cell lymphoma. The brain biopsy obtained from the patient shows neoplastic infiltrate of atypical cells in large clusters and in perivascular pattern that are positive for CD45, CD20, PAX5, CD30 and negative for CD2, CD3, CD5, CD10. There are areas of tumor necrosis as well as individual cell necrosis. The morphology and the immunohistochemical staining pattern are consistent with large B-cell lymphoma (see Fig. 2). The patient was treated with rituximab, vincristine, prednisone, and intrathecal methotrexate/hydrocortisone/cytarabine. A followup MRI performed 6 months after initial diagnosis showed minimal improvement in size of the lesions. Time in treatment was complicated by seizures and hospitalizations for neutropenic fever.
Fig. 1. Right parietal mass with surrounding edema and central hemorrhage.
Correspondence to: Archana Sharma, DO, Dept of Pediatics, Rutgers Cancer Institute of NJ, 195 Little Albany St., Room 3507, New Brunswick, NJ 08903. E-mail: [email protected]
Received 13 March 2013; Accepted 26 July 2013
C 2013 Wiley Periodicals, Inc. DOI 10.1002/pbc.24743 Published online 8 November 2013 in Wiley Online Library (wileyonlinelibrary.com).
Letter to the Editor
565
Fig. 2. Brain biopsy shows clusters of large neoplastic cells infiltrating normal brain tissue, surrounded by small lymphocytes (A, H&E, 10 original magnification). Under higher magnification, the neoplastic cells have irregular appearance with vesicular nuclei, prominent nucleoli, and variable eosinophilic cytoplasm; there are occasional mitoses (B, H&E, 40 original magnification). Many of the clusters have perivascular arrangement, surrounded by inflammatory cells, including small lymphocytes (C, H&E, 20 original magnification). Necrotic areas are present (D, H&E, 20 original magnification). The neoplastic cells are strongly positive for B-cell marker (E, PAX-5, 10 original magnification). T-cell marker is positive in the scattered normal lymphocytes but negative in the neoplastic cells (F, CD3, 10 original magnification).
Treatment dosing was decreased to 50% due to prolonged neutropenia. Seizures were difficult to control and the patient opted to discontinue treatment. He expired 3 months later. There are few case reports linking SDS to solid tumors, such as breast cancer [11]. CNS lymphoma is associated with patients with acquired immunodeficiencies, primarily patients infected with HIV. Cerebral lymphomas have also been reported in patients infected with EBV [5]. CNS lymphoma is also a wellknown potential long-term complication of congenital immunodeficiencies [6,7,8,9]. CNS Lymphoma in a patient with SDS is a difficult clinical situation as neutropenia is an underlying characteristic of the disease [10]. This highlights our need for Pediatr Blood Cancer DOI 10.1002/pbc
more effective treatment plan for patients with underlying immunodeficiencies that may be unable to tolerate standard dosing of chemotherapy.
Archana Sharma, DO Department of Pediatrics Rutgers Cancer Institute of NJ Evita Sadimin, MD Department of Pathology and Laboratory Medicine Robert Wood Johnson Medical School
566
Sharma et al. Richard Drachtman, MD John Glod, MD, PHD Department of Pediatrics Rutgers Cancer Institute of NJ
REFERENCES 1. Shimamura A. Shwachman-Diamond syndrome. Semin Hematol 2006;43:178–188. Review. 2. Dokal I, Vulliamy T. Inherited aplastic anaemias/bone marrow failure syndromes. Blood Rev 2008;22:141–153. 3. Leseve JF, Dugue F, Gregorie MJ, et al. Shwachman Diamond syndrome with late onset neutropenia and fatal acute myeloid leukemia without maturation: A case report. Eur J Haematol 2003;71:393–395.
Pediatr Blood Cancer DOI 10.1002/pbc
4. Baehring J, Hochberg F. Primary lymphoma of the nervous system. Cancer J 2006;12:1–10. 5. Hochberg FH, Miller G, Schooley RT, et al. Central nervous system lymphoma related to Epstein Barr virus. N Engl J Med 1983;309:745–748. 6. Kim SH, Cheong JW, Park KH, et al. Comparison of ataxia-telangiectasia mutated protein expression in diffuse large B cell lymphoma of primary central nervous system and non central nervous system origin. Arch Pathol Lan Med 2007;131:457–467. 7. Mairui F. Central nervous system lymphomas and immunodeficiency. Neurol Res 1989;11:2–5. 8. Nukina S, Fusaoka T, Fukumochi Y, et al. Malignant lymphoma of the central nervous system in a boy with immotile cilia syndrome. Rinsho Ketsueki 1989;30:568–572. 9. Shcherbina A. High incidence of lymphomas in a subgroup of Wiskott Aldrich syndrome patients. Br J Hematol 2003;121:527–532. 10. DeAngelis L. Update on the management of primary CNS lymphoma. Oncology 2000;14:228– 234. 11. Singh SA, Vlachos A, Morgenstern NJ, et al. Breast cancer in a case of Shwachman Diamond syndrome. Pediatric Blood Cancer 2012;59:945–946.
LETTER TO THE EDITOR CNS Lymphoma in a Patient With Shwachman Diamond Syndrome
To the Editor: Shwachman Diamond syndrome (SDS) is a rare autosomal disorder characterized by pancreatic insufficiency and neutropenia. Patients commonly present in infancy and are at risk for hematological malignancy in life [2,3]. The association of SDS and myelodysplasia, ALL and AML are well described [1]. We present the case of an 18-year-old patient with SDS who is diagnosed with CNS B-cell lymphoma. To our knowledge, CNS lymphoma in a patient with SDS has not been described [4]. Our 18-year-old patient with SDS presented with new onset seizures. He was initially diagnosed with the syndrome at age 8 when he was admitted for a respiratory infection and was noted to be neutropenic during the admission. A bone marrow biopsy was performed which confirmed hypoplasia of myeloid tissue and maturation arrest of myeloid cells. An outside institution confirmed presence of the SDS gene. However, this test was not duplicated at our institution. From age 8 to 18 years, he was maintained on pancreatic enzymes and had no hospitalizations for infections. At 18, he had a
generalized tonic-clonic seizure, which lasted about 10 minutes. A CT of the head was performed which revealed a right frontal hemorrhage or hemorrhagic mass with surrounding edema. An MRI was performed which confirmed a 3 cm right frontal and 1 cm left occipital enhancing lesions (see Fig. 1). These lesions were biopsied and confirmed to be diffuse large B-cell lymphoma. The brain biopsy obtained from the patient shows neoplastic infiltrate of atypical cells in large clusters and in perivascular pattern that are positive for CD45, CD20, PAX5, CD30 and negative for CD2, CD3, CD5, CD10. There are areas of tumor necrosis as well as individual cell necrosis. The morphology and the immunohistochemical staining pattern are consistent with large B-cell lymphoma (see Fig. 2). The patient was treated with rituximab, vincristine, prednisone, and intrathecal methotrexate/hydrocortisone/cytarabine. A followup MRI performed 6 months after initial diagnosis showed minimal improvement in size of the lesions. Time in treatment was complicated by seizures and hospitalizations for neutropenic fever.
Fig. 1. Right parietal mass with surrounding edema and central hemorrhage.
Correspondence to: Archana Sharma, DO, Dept of Pediatics, Rutgers Cancer Institute of NJ, 195 Little Albany St., Room 3507, New Brunswick, NJ 08903. E-mail: [email protected]
Received 13 March 2013; Accepted 26 July 2013
C 2013 Wiley Periodicals, Inc. DOI 10.1002/pbc.24743 Published online 8 November 2013 in Wiley Online Library (wileyonlinelibrary.com).
Letter to the Editor
565
Fig. 2. Brain biopsy shows clusters of large neoplastic cells infiltrating normal brain tissue, surrounded by small lymphocytes (A, H&E, 10 original magnification). Under higher magnification, the neoplastic cells have irregular appearance with vesicular nuclei, prominent nucleoli, and variable eosinophilic cytoplasm; there are occasional mitoses (B, H&E, 40 original magnification). Many of the clusters have perivascular arrangement, surrounded by inflammatory cells, including small lymphocytes (C, H&E, 20 original magnification). Necrotic areas are present (D, H&E, 20 original magnification). The neoplastic cells are strongly positive for B-cell marker (E, PAX-5, 10 original magnification). T-cell marker is positive in the scattered normal lymphocytes but negative in the neoplastic cells (F, CD3, 10 original magnification).
Treatment dosing was decreased to 50% due to prolonged neutropenia. Seizures were difficult to control and the patient opted to discontinue treatment. He expired 3 months later. There are few case reports linking SDS to solid tumors, such as breast cancer [11]. CNS lymphoma is associated with patients with acquired immunodeficiencies, primarily patients infected with HIV. Cerebral lymphomas have also been reported in patients infected with EBV [5]. CNS lymphoma is also a wellknown potential long-term complication of congenital immunodeficiencies [6,7,8,9]. CNS Lymphoma in a patient with SDS is a difficult clinical situation as neutropenia is an underlying characteristic of the disease [10]. This highlights our need for Pediatr Blood Cancer DOI 10.1002/pbc
more effective treatment plan for patients with underlying immunodeficiencies that may be unable to tolerate standard dosing of chemotherapy.
Archana Sharma, DO Department of Pediatrics Rutgers Cancer Institute of NJ Evita Sadimin, MD Department of Pathology and Laboratory Medicine Robert Wood Johnson Medical School
566
Sharma et al. Richard Drachtman, MD John Glod, MD, PHD Department of Pediatrics Rutgers Cancer Institute of NJ
REFERENCES 1. Shimamura A. Shwachman-Diamond syndrome. Semin Hematol 2006;43:178–188. Review. 2. Dokal I, Vulliamy T. Inherited aplastic anaemias/bone marrow failure syndromes. Blood Rev 2008;22:141–153. 3. Leseve JF, Dugue F, Gregorie MJ, et al. Shwachman Diamond syndrome with late onset neutropenia and fatal acute myeloid leukemia without maturation: A case report. Eur J Haematol 2003;71:393–395.
Pediatr Blood Cancer DOI 10.1002/pbc
4. Baehring J, Hochberg F. Primary lymphoma of the nervous system. Cancer J 2006;12:1–10. 5. Hochberg FH, Miller G, Schooley RT, et al. Central nervous system lymphoma related to Epstein Barr virus. N Engl J Med 1983;309:745–748. 6. Kim SH, Cheong JW, Park KH, et al. Comparison of ataxia-telangiectasia mutated protein expression in diffuse large B cell lymphoma of primary central nervous system and non central nervous system origin. Arch Pathol Lan Med 2007;131:457–467. 7. Mairui F. Central nervous system lymphomas and immunodeficiency. Neurol Res 1989;11:2–5. 8. Nukina S, Fusaoka T, Fukumochi Y, et al. Malignant lymphoma of the central nervous system in a boy with immotile cilia syndrome. Rinsho Ketsueki 1989;30:568–572. 9. Shcherbina A. High incidence of lymphomas in a subgroup of Wiskott Aldrich syndrome patients. Br J Hematol 2003;121:527–532. 10. DeAngelis L. Update on the management of primary CNS lymphoma. Oncology 2000;14:228– 234. 11. Singh SA, Vlachos A, Morgenstern NJ, et al. Breast cancer in a case of Shwachman Diamond syndrome. Pediatric Blood Cancer 2012;59:945–946.
