An Unusual Self-limited Clonal Mott Cell Proliferation With Lymphoplasmacytic Lymphoma-like Features In A Child With The Wiskott-aldrich Syndrome And Von Recklinghausen's Neurofibromatosis
Rampisela, D., & Donner, L. R. (2010). An unusual self-limited clonal Mott cell proliferation with lymphoplasmacytic lymphoma-like features in a child with the Wiskott-Aldrich syndrome and Von Recklinghausen's neurofibromatosis. Pathology, research and practice, 206(7), 467–471. https://doi.org/10.1016/j.prp.2009.07.003
View Original Source →Abstract
Patients with the Wiskott-Aldrich syndrome are at high risk for development of lymphomas, which are predominantly extranodal and of the immunoblastic type. We present a case of a self-limited lymphoproliferation with features of lymphoplasmacytic lymphoma arising in a patient with the Wiskott-Aldrich syndrome. The patient also had stigmata of von Recklinghausen's neurofibromatosis. The tumor was composed of CD138+, IgGkappa+, CD20-, PAX-5- Mott cells and CD5-, CD10-, CD19+, CD20+, CD43- small lymphoid B-cells that partially expressed CD23. The lymphadenopathy spontaneously resolved after a period of less than a year, and the patient had remained free of detectable lymphoproliferation for almost 4 years. He then developed Burkitt's lymphoma of the left parapharyngeal space. It is remarkable that both known lymphoproliferations with features of lymphoplasmatic lymphoma arising in patients with the Wiskott-Aldrich syndrome, this one and the previously described one, have spontaneously resolved. This observation is truly intriguing and requires further clinico-pathologic studies.
Case Details
Disease Location
Lymph nodes neck and spine
Personal Characteristics
14 -year-old male, black wiskott-aldrich syndrome and stigmata of von recklinghausen's neurofibromatosis treated for congenital thrombocytopenia, skin rash and recurrent infections since 6 months old he was hospitalized multiple times for recurrent pneumonias, recurrent otitis media, paraspinal abscess, osteomyelitis of the l5-s1 vertebrae, and several episodes of epistaxis that caused severe anemia family history was significant for von recklinghausen's neurofibromatosis in his mother, aunt, grandmother, and great grandmother
Clinical Characteristics
Prior ultrastructural exams of the bone marrow and peripheral blood revealed degranulated thrombocytes containing few cytoplasmic organelles and decreased amounts of glycogen on admission, he had numerous café-au-lait spots over the trunk and extremities as well as lisch nodules in both irides in nov 2004, at 13 years old he presented with a 2.5cm left inguinal ln CT of the chest and abdomen revealed the presence of axillary, mesenteric, retroperitoneal, periaortic and inguinal lymphadenopathy, there was no evidence of hepatosplenomegaly bone marrow want examined and the left inguinal and retroperitoneal lymph nodes were biopsied in nov 2004 and feb 2005, respectively he was lymphopenic (8-14% lymphocytes), severely thrombocytopenic and anemic. Serum IGG was determined only after the regression and was normal (839mg/dl) no chemo or radiotherapy was administered. In april 2005, there was no evidence of lymphadenopathy except for a 2.1cm left inguinal ln during CT scans and examination in march 2009, the patient developed decreasing hearing in the left ear, left facial pain, and palsy of the left 7th cranial nerve. His neurologic deficit progressed to involvement of the 3rd, 4th, and 6th cranial nerves. MRI of the head revealed a 4.3cm mass in the left parapharyngeal space that bulged into the nasopharynx, penetrated the left middle meatus and almost filled the left external auditory canal. Scans of the spine found the presence of multiple cervical and lumbar nerve root masses consistent with neurofibromas biopsy of the left parapharyngeal mass and bone marrow biopsy occured in march 2009, the bone marrow exam was negative. He is currently receiving intrathecal chemo for burkitt's lymphoma the left inguinal ln was 3.8cm and the retroperitoneal lymph nodes 3.5-5cm in greatest dimension. They were histologically similar. Their parenchyma contained many follicles with reactive germinal centers and the paracortex was suffused by numerous mott cells admixed with scanty CD20+, pax-5+, CD43-, small b-cells, and mature polyclonal plasma cells. The CD3+ t-cells formed a minor component of the lymphoid population and were present mostly in the perifollicular areas with sprinkling in the follicles and the paracortex. Staining of both specimens failed to reveal a presence of any dutcher bodies. The mott cells were CD20-, pax-5-, CD138+, kappa+, lambda-, IGA-, IGA-, igd-, igg+, and IGM-. They had a greatly distended cisterna of rough endoplasmic reticulum filled with a fine granular material proliferation rate was low, 5% of the lymphoid cells expressed proliferation marker ki-67. The lymph nodes contained scattered epithelioid granulomata, the epithelioid granulomata in the left inguinal ln underwent suppurative necrosis. No microorganisms were identified by various stains flow cytometric studies of both specimens found small lymphoid b-cells were negative for CD5, 10, and fmc7, and positive for CD19, 20, and partially for CD23. No immunoglobulin light chain restirction was detected. T-cells were immunophenotypically normal. Immunostaining for ebv-lmp1 and in situp hybridization for eber1 , 2 were negative. Igh gene was not translocated the left parapharyngeal mass was very necrotic and displayed a starry sky pattern and was composed of sheets of medium-sized lymphoid cells with round nuclei, dispersed chromatin, several small nucleoli and basophil cytoplasm. This mass was diagnosed as burkitt's lymphoma the lymphoid cells were positive for CD10, 20, 79a, pax-5, bcl-6, and negative for mum-1, bcl-2, tdt, and CD34. Nearly 100% of them expressed ki-67 in situ hybridization for immunoglobulin light chains was negative, translocation of the c-myc was detected in 80% of interphase nuclei using fish but not with vysis no ebv was detected and the retroperitoneal ln was negative for for c-myc gene rearrangement
Remission Characteristics
Between 2004 and april 2005, regression occurred remains free of lymphadenopathy during the last exam in june 2009
Treatment & Mechanisms
Proposed Remission Mechanisms
Immune response, apoptosis, and oncogene induced senescence possible role of co-existing suppurative granulomatous lymphadenitis possibility of defective immorightalization leading to expanded, but limited lifespan of the lymphoma cells. Immorightalization requires overcoming of the arf/p53/p21 tumor suppression pathway
Clinical Treatment
Amoxicillin prophylaxis and months IV immunoglobulin intrathecal chemotherapy for burkitt's lymphoma
Non-Clinical Treatment
None reported