Lian-He Yang

Myeloid Neoplasms Following Solid Organ TransplantationClinicopathologic Studies of 23 Cases

ObjectivesnMyeloid neoplasms (MNs) after solid organ transplant are rare, and their clinicopathologic features have not been well characterized.nnnMethodsnWe retrospectively analyzed 23 such cases.nnnResultsnThe ages ranged from 2 to 76 years, with a median of 59 years at the diagnosis. The median interval between the transplant and diagnosis was 56 months (range, 8-384 months). The transplanted organs included liver in five, kidney in six, lung in five, heart in six, and heart/lung in one case(s). The types of MN included acute myeloid leukemia (AML) in 12, myelodysplastic syndrome (MDS) in five, chronic myelogenous leukemia (CML) in four, and myeloproliferative neoplasms (MPNs) in two cases. Cytogenetics demonstrated clonal abnormalities in 18 (78.3%) cases, including unbalanced changes in 10 (55.6%), Philadelphia chromosome in four (22.2%), and other balanced aberrations in four (22.2%) cases. Thirteen (56.5%) patients died, with an estimated median survival of 9 months. With disease stratification, AML and MDS have short median survivals (3.5 and 7 months, respectively), with an initial precipitous decline of the survival curve.nnnConclusionsnPosttransplant MNs have a latency period between that seen in AML/MDS related to alkylators and that associated with topoisomerase II inhibitors. The cytogenetic profile suggests a mutagenic effect on leukemogenesis. The clinical outcome for AML/MDS is dismal, with death occurring at an early phase of treatment.

Radiological presentation of chondromyxoid fibroma in the sellar region: A CARE-compliant article and literature review

Rationale: Chondromyxoid fibroma (CMF) is a rare benign bone neoplasm which often occurs in the lower extremities. Little is known about the radiological and histological presentation of CMF in the sellar region. Patient concerns: A 16-year-old Asian male presented to the hospital 12 months ago with bilateral diplopia involving right visual fields, intermittent headaches, and dizziness. Interventions: After the patient underwent enough examinations, the lesion was surgically removed by curettage. Diagnosis: Postoperatively, the lesion was pathologically confirmed to be CMF. Outcomes: There was no recurrence at the 12-month follow-up. Lessons: To the best of our knowledge, this is the second reported case of CMF in the sellar region which was clinically suspected to be a pituitary macroadenoma, craniopharyngioma, or schwannoma due to its location and radiographic features. We reviewed the morbidity, symptoms, radiographic features, pathological findings, and differential diagnosis of CMF. Because of its rarity, attention should be paid to avoid misdiagnosis of this lesion.

CD3-positive diffuse large B-cell lymphoma relapses as CD3-negative large B-cell lymphoma: Loss of aberrant antigen expression in B-cell lymphoma after chemotherapy

Aberrant expression of CD3 on diffuse large B-cell lymphoma (DLBCL) is rare, and its mechanism and biological significance are currently unclear. Herein we report a case of Epstein-Barr virus-negative, CD3-positive DLBCL in a 53u202fyear-old male, who had a remote history of renal transplantation. After standard chemotherapy, the patient was in clinical remission. He relapsed three years later, but at this time with apparent loss of CD3 expression. PCR-based IGK gene rearrangement studies demonstrated clonal amplicons with an identical nucleotide size between the primary and secondary DLBCL, confirming the clonal relationship despite their phenotypic differences. To our knowledge, this is the first case of CD3-positive DLBCL that demonstrated a loss of aberrant CD3 on relapse. The chronologic change in phenotype seen in this case suggests that the source of the patients lymphoma relapse may arise from either a quiescent subclone without CD3 expression, or from an upstream neoplastic precursor cell.

Marginal zone lymphoma of palatine tonsil with prominent plasmacytic differentiation: A Care-compliant article and review of literature

Rationale: The palatine tonsil is an important component of Waldeyers ring and a site commonly involved by lymphoma. Interestingly, although it is a site of mucosa-associated lymphoid tissue (MALT), primary MALT lymphoma of the palatine tonsil is rare, especially with prominent plasmacytic differentiation. Patient concerns: A 59-year-old woman presented to the hospital with a 1-month history of odynophagia. The patient had no fever or pruritus during this period and she declared no family history of hematolymphoid malignancy. Diagnosis: Histopathological examination demonstrated effacement of tonsil architecture; normal follicles were replaced by plasmacytoid tumor cells and small lymphocytes. The tumor cells expanded the marginal zone and infiltrated interfollicular regions, as well as scattered residual follicles. Immunostaining showed tumor cells positive for cluster of differentiation (CD)20, CD79a, paired box-5, Mum 1, and B cell lymphoma (Bcl)-2, and negative for CD5, CD 23, cyclin D1, Bcl-6, and CD10. Staining for &kgr; and &lgr; showed prominent light chain restriction. The tumor was classified as tonsil MALT lymphoma with prominent plasmacytic differentiation. Interventions: After the patient was diagnosed with MALT lymphoma with prominent plasmacytic differentiation, she underwent complete surgical resection and radiotherapy. Outcomes: There was no recurrence evident at 6-months follow-up. Lessons: Primary tonsil MALT lymphoma with prominent plasmacytic differentiation is very rare and difficult to distinguish from other B-cell lymphomas with plasmacytoid morphology, such as follicular lymphoma, lymphoplasmacytic lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Accurate diagnosis of this entity is important in guiding therapy so as to avoid overtreatment.

Clinicopathologic and genetic spectrum of infantile B-lymphoblastic leukemia: a multi-institutional study

Abstract Acute lymphoblastic leukemia (ALL) in infants <1-year-old is biologically different from ALL in older children. Although KMT2A rearrangement is the predominant genetic signature in infantile B-ALL, disease course is heterogenous, behaving more aggressively in younger infants. We investigated clinicopathological differences throughout the first year to understand the transition to pediatric B-ALL. In a multi-institutional review involving four medical institutions, 54 cases of infantile B-ALL were identified. Patients were divided into congenital and non-congenital groups with multiple age subgroups. Male predominance was seen in congenital cases compared to female in non-congenital cases. There were decreasing trends of hyperleukocytosis, central nervous system involvement, KMT2A rearrangements, lineage switch, and mortality, versus increasing trends of CD10 expression and non-KMT2A abnormalities. Statistically significant differences emerged at 3 and 9 months, the latter was not previously described. Poor-prognostic risk factors decreased with age, the last trimester of infantile B-ALL essentially merging with pediatric B-ALL.

“Faggot” neutrophils in acute promyelocytic leukaemia with ongoing tretinoin therapy

A 25-year-old male presented with epistaxis and was found to have pancytopenia (WBC, 1 9 9 10/l; haemoglobin concentration, 69 g/l; platelet count, 8 9 10/l). A peripheral blood film showed severe neutropenia with 94% lymphocytes. Laboratory evaluation demonstrated evidence of disseminated intravascular coagulopathy with a D-dimer of 11 670 ng/ml fibrinogen-equivalent units (FEU) (reference <500 ng/ml FEU). Bone marrow examination demonstrated markedly increased promyelocytes with an immunophenotypic profile and morphology suggestive of acute promyelocytic leukaemia (APL). The diagnosis was confirmed by fluorescence in situ hybridization (FISH) with PML-RARA fusion seen in 87 5% of the interphase nuclei. Chromosomal analysis detected an abnormal karyotype with evidence of t(15;17)(q24.1;q21.2). All-trans-retinoic acid (tretinoin) therapy was initiated at a dose of 45 mg/m and arsenic trioxide was added 3 days later. Ten days after starting treatment, peripheral leucocytes had increased to 7 2 9 10/l, and a blood film showed 60–70% neutrophils and their precursors. Interestingly, rare neutrophil band forms contained multiple Auer rods (images). These cells with bundles of stick-like Auer rods resembled faggot cells, except that they were apparently mature neutrophils rather than the abnormal promyelocytes typically seen in APL. One month after treatment, bone marrow examination demonstrated trilineage haematopoiesis with maturation with no abnormal promyelocytes being detected. Chromosomal analysis showed a normal male karyotype, and FISH revealed PML-RARA fusion in 0 5% of the interphase nuclei. While mature neutrophils with single or dispersed Auer rods have been described in cases of APL with ongoing tretinoin therapy, “faggot” neutrophils are extremely rare. By recruiting co-repressors, the PML-RARA fusion oncoprotein in APL binds to genes that regulate myeloid differentiation and constitutively blocks their expression, resulting in maturation arrest at the promyelocytic stage. The disease had a dismal prognosis until the discovery of tretinoin. Tretinoin directly targets the molecular foundation of the disease by interacting competitively with the PML-RARA oncoprotein, releasing the genetic repression and allowing cellular differentiation to proceed. Although the drug does not directly induce apoptosis of leukaemic promyelocytes, the differentiated leukaemic cells lose their potential to replicate and are continuously driven to their maturation before eventual apoptosis. The “faggot” neutrophils in this case demonstrate the terminal differentiation of leukaemic promyelocytes, the result of “differentiation” therapy rather than persistent disease.

Chronic Myeloid Leukemia Following Treatment for Primary Neoplasms or Other Medical Conditions

ObjectivesnTherapy-related chronic myeloid leukemia (CML) has been reported, but its clinical presentation and pathologic features have not yet been well characterized.nnnMethodsnTwenty-one cases of CML following treatment for primary diseases were collected and retrospectively analyzed.nnnResultsnThe clinical presentation, pathologic features, and cytogenetic profile were similar to de novo CML. In particular, those with an isolated Philadelphia chromosome constituted 88.9% of our cases, and additional aberrations characteristic of therapy-related acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) were not identified in this study. The patients responded to imatinib/derivatives and survived with limited follow-up.nnnConclusionsnTherapy-related CML has a clinical presentation, pathologic features, and cytogenetic profile akin to de novo CML. Absence of additional significant aberrations seems to suggest a pathogenesis different from therapy-related AML/MDS. Therapy-related CML exhibits a robust therapeutic response to imatinib/derivatives and favorable clinical outcomes similar to de novo CML.

Composite lymphoma of follicular B-cell and peripheral T-cell types with distinct zone distribution in a 75-year-old male patient: a case study

Composite lymphoma of T-/B-cell type is rare, and follicular lymphoma composite with peripheral T-cell lymphoma (PTCL) has not previously been reported. We report such a case with both neoplastic components displaying a unique zone of distribution. A 75-year-old male patient presented with generalized lymphadenopathy. Sections of axillary lymph node demonstrated potentially 2 clonal processes, PTCL with aberrant CD20 expression and follicular lymphoma. Interestingly, the 2 neoplastic components were confined to their respective classic distribution zones, with PTCL occupying the interfollicular areas and follicular lymphoma residing in follicles. Both populations were detected by flow cytometry, but their immunophenotypes were insufficient to define clonality. Nonetheless, biclonality was demonstrated by lymphoid receptor gene rearrangement analyses. Molecular cytogenetics showed IGH/BCL2 fusion in the follicular lymphoma and amplification of IGH gene or trisomy/tetrasomy 14 in the PTCL. The current case underscores the complexity of composite lymphoma and advocates a multimodal approach to establishing the diagnosis.