Pediatric mast cell sarcoma of temporal bone with novel L799F (2395 C>T) KIT mutation, mimicking histiocytic neoplasm.

Mast cell sarcoma (MCS) is an extremely rare neoplasm with a clinically aggressive course. Because of its rarity, its morphologic and molecular characteristics are still not well defined. We report a case of a 15-year-old girl with MCS of the temporal bone extending into the posterior fossa creating a mass effect. The lesion mimicked a histiocytic neoplasm morphologically, but showed a novel KIT missense mutation, L799F (2395 C>T). The KIT D816V mutation is frequently found in systemic mastocytosis, but it has not been documented in the few reported human MCS cases. However, 1 reported case of MCS has shown a different alteration in the KIT gene. Our case is the first MCS case with L799F mutation, located between the catalytic loop (790 to 797) and the activation loop (810 to 837) of the KIT gene, and only the second case of MCS with KIT mutation documented in the literature. Proximity of the L799F mutation to the enzymatic region of the KIT tyrosine kinase domain may induce resistance to tyrosine kinase inhibitors.

Mast cell sarcoma in an infant: a case report and review of the literature.

Mast cell diseases comprise a spectrum of disorders including cutaneous mastocytosis, indolent or aggressive systemic variants including leukemia, and unifocal tumor formations such as benign extracutaneous mastocytoma or aggressive mast cell sarcoma (MCS). Many mast cell diseases are associated with aberrancy of c-KIT proto-oncogene resulting in tyrosine kinase activity, typically exhibiting point mutation in codon 816. MCS is an exceedingly rare clinicopathologic entity characterized by a unifocal accumulation of neoplastic mast cells that grow in a locally destructive manner. We report a case in a 2-year-old boy who was initially diagnosed at 8 months of age with atypical cutaneous mastocytoma of the right ear with subsequent aggressive, destructive growth pattern; features that were most consistent with MCS. So far, MCS has been documented in the literature in at least 6 human cases. To the best of our knowledge, our case represents the first MCS in an infant. Thorough multimodal approach with strict follow-up is relevant in appropriately diagnosing this rare entity, particularly in differentiating this lesion from other neoplasms that are more likely to occur in infancy.

Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features.

Primary gastrointestinal lymphoma comprises 10-15% of all non-Hodgkin lymphomas and encompasses 30-40% of the total extranodal lymphomas. Approximately 60-75% of cases occur in the stomach, and then the small bowel, ileum, cecum, colon and rectum. Lymphoid neoplasms may consist of mature B, T and less commonly extranodal NK/T cells. Of these, the two most frequently encountered histologic subtypes are extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), where Helicobacter pylori infection is implicated in a number of cases, and diffuse large B cell lymphoma. Several B cell lymphomas are associated with chromosomal aberrations. Enteropathy-associated T cell lymphoma, type I in particular, usually arises in a background of celiac disease. T cell gene rearrangement confirms clonality. NK/T cell neoplasms are invariably associated with Epstein-Barr virus infection and are often aggressive; thus, differentiation from a benign NK-cell enteropathy is paramount. Although incidence of other hematopoietic malignancies in the gastrointestinal tract such as plasma cell myeloma associated with amyloidosis, plasmablastic lymphoma, Hodgkin disease, histiocytic sarcoma and mast cell sarcoma is extremely rare, these entities have been documented, with the latter two demonstrating aggressive clinical behavior. Endoscopic ultrasonography is an important adjunct in disease staging and follow-up. Conservative antibiotic treatment of stage I MALT lymphomas with associated Helicobacter pylori infection achieves good clinical outcome with high remission rate. Chemotherapy, radiation and rarely surgery are reserved for advanced diseases or cases resistant to conservative therapy and those not associated with Helicobacter pylori infection.

Subsequent development of diffuse large B-cell lymphomas and Hodgkin lymphoma associated with primary immune disorder in a 6-year-old female: a case report and review of the literature.

Neoplastic lymphoid proliferation may arise from immune deficiency or disordered regulation of the immune system. Often the neoplasms are associated with viral agents, such as Epstein-Barr virus, human immunodeficiency virus, or human herpes virus 8. Lymphoproliferative diseases have been documented in a variety of primary immune disorders. The most commonly encountered neoplastic lesion is diffuse large B-cell lymphoma (DLBCL), although Hodgkin lymphoma (HL), Burkitt lymphoma, and peripheral T-cell lymphomas and/or leukemias have also been documented in rare instances. We report a case of a 6-year-old girl with unclassifiable primary immunodeficiency diagnosed with 2 different clones of DLBCLs and subsequently developed lymphocyte-depleted, classical HL. Both neoplasms were associated with Epstein-Barr virus. To the best of our knowledge, this is the first reported occurrence of primary immune disorder-associated lymphoproliferative disease with sequential development of DLBCLs and HL in a pediatric patient. Thorough surveillance is paramount for accurate assessment of the associated lymphoproliferative disease and in ascertaining likely transformation to, or de novo evolution of a different lymphoid neoplasm. This is also important in evaluating treatment response with appropriate therapeutic adjustments if clinically indicated.

Pancytopenia associated with clonazepam.

We report a case of a 48-year-old Chinese female with end-stage renal disease and chronic anemia on hemodialysis. Clonazepam was prescribed for myoclonus disorder two weeks prior to her hospitalization. Subsequently, she was hospitalized for neutropenic fever with thrombocytopenia and worsening anemia. Bone marrow examination demonstrated a markedly hypocellular marrow (10-20% total cellularity). Clonazepam was discontinued, with gradual improvement of thrombocytopenia, and neutropenia in 1-2 weeks. To our knowledge, this is the first reported case of pancytopenia associated with clonazepam. We recommend patients taking clonazepam to be monitored with regular complete blood count to check for clinically significant pancytopenia or thrombocytopenia.