Detection of small abnormal B-Lymphoblast populations at diagnosis of chronic myelogenous leukemia, BCR-ABL1+: Incidence, phenotypic features, and clinical implications.

BACKGROUND: According to the 2008 World Health Organization (WHO) Classification of Tumors of the Haematopoietic and Lymphoid Tissues, the finding of B lymphoblasts in the blood or bone marrow of a patient with chronic myelogenous leukemia, BCR-ABL1+ (CML) should raise a concern for progression of the disease to B-lymphoblastic blast phase. Data addressing the incidence and phenotypic features of abnormal B lymphoblasts in CML, and whether the detection of B lymphoblasts inexorably heralds blast phase in CML, though, are limited. METHODS: We reviewed a consecutive series of patients with newly diagnosed CML who had undergone bone marrow examination with flow cytometric immunophenotyping. Polychromatic immunophenotyping data were reviewed, and clinical follow-up data were obtained. RESULTS: A precursor B-cell population with an abnormal composite immunophenotype was detected in 4 of 36 (11.1%) diagnostic bone marrow samples, at levels ranging from 0.01% to 0.30% of viable single cells acquired. The most common phenotypic aberrations were abnormally bright expression of CD10 and CD19 (seen in four and three cases, respectively), and abnormally dim expression of CD38 (seen in four cases). All three patients with adequate clinical follow-up have achieved and maintained a deep or major molecular response with a tyrosine kinase inhibitor, and none has progressed to B-lymphoblastic blast phase (follow-up duration: 17-46 months). CONCLUSIONS: In chronic-phase CML, a small (<0.5%) abnormal B-lymphoblast population is present in a significant minority of diagnostic bone marrow samples, but does not inevitably herald progression to B-lymphoblastic blast phase. © 2015 International Clinical Cytometry Society.

Can SOX-10 or KBA.62 Replace S100 Protein in Immunohistochemical Evaluation of Sentinel Lymph Nodes for Metastatic Melanoma?

BACKGROUND: Microscopic evaluation of sentinel lymph nodes for metastatic melanoma relies, in part, on the use of immunohistochemical analysis to identify minute metastatic deposits that may be overlooked on routine microscopy. At present S100 protein is widely used in this role, in large part for its superior sensitivity; however, interpretation is hampered by the presence of benign S100 protein-positive cellular elements present in every lymph node, leading to reduced specificity and consequent difficulties in interpretation. In recent years, multiple melanocytic markers have emerged that promise superior sensitivity and specificity, including KBA.62 and SOX-10. SOX-10 shows a nuclear pattern of staining. In normal tissue it is expressed in Schwann cells, melanocytes, and myoepithelial cells of salivary, bronchial, and mammary glands. KBA.62 is also specific except for staining of endothelial cells and shows a membranous staining pattern. This study was undertaken to determine whether KBA.62 or SOX-10 could equal (or surpass) the sensitivity of S100 protein while offering superior specificity in the immunohistochemical evaluation of sentinel lymph nodes for metastatic melanoma. DESIGN: In this study we performed immunohistochemical stains for S100 protein, Sox-10, and KBA.62 on 50 lymph nodes with proven metastatic melanoma. RESULTS: SOX-10 detected all cases of metastatic melanoma (50 of 50 cases; 100%) compared with S100 protein (48 of 50 cases; 96%) and KBA.62 (37 of 50 cases; 74%). There was no "background" staining of normal cellular elements with SOX-10 or KBA.62. In contrast, S100 protein was expressed in scattered dendritic interdigitating reticulum cells in the paracortex of lymph nodes, showing cytoplasmic and nuclear positivity, sometimes posing significant difficulty in differentiating benign reticulum cells from single cell metastatic melanoma. CONCLUSIONS: Our findings suggest that SOX-10 may be superior to S100 protein for identifying metastatic melanoma in a lymph node. KBA.62 was less sensitive than either marker, although more specific than S100 protein.

Pityriasis rosea-like cutaneous eruption as the presenting symptom of Hodgkin lymphoma. Case report and review of the literature.

BACKGROUND: Cutaneous involvement by Hodgkin lymphoma is extremely rare and usually follows extensive involvement of the lymph nodes. Cutaneous manifestations of Hodgkin lymphoma may be divided into specific and non-specific. Generalized pruritus is one of the most common non-specific presentations of Hodgkin lymphoma as is cutaneous granulomas. Such signs and symptoms should prompt thorough physical exam, including evaluation of lymph nodes, especially in a young patient. MAIN OBSERVATION: We report a case of a 22-year-old man who presented with night sweats, weight loss, dry cough, and generalized maculopapular eruption that started with a large patch in the center of the chest and spread to the extremities. Biopsy of the rash revealed pityriasis rosea-like findings. A computerized tomography scan of the chest revealed a mediastinal mass. Biopsy of the mediastinal mass revealed Reed-Sternberg cells in a fibrotic background, diagnostic of Hodgkin lymphoma, nodular sclerosis type. CONCLUSION: In conclusion, the presentation of Hodgkin lymphoma as a pityriasis rosea-like cutaneous eruption is rare and clinicians should be aware of this presentation. In this paper we review the non-specific cutaneous manifestations of Hodgkin lymphoma in an effort to raise awareness of the diversity of early cutaneous signs of Hodgkin lymphoma.

Chronic lymphocytic leukemia/small lymphocytic lymphoma involving the aortic valve.

Chronic lymphocytic leukemia/small lymphocytic lymphoma is a neoplasm composed of monomorphic small B lymphocytes in the peripheral blood, bone marrow, spleen, and lymph nodes, forming proliferation centers in tissue infiltrates (Muller-Hermelink HK, Montserrat E, Catovsky D, et al. Chronic lymphocytic leukaemia/small lymphocytic lymphoma, in Swerdlow SH (ed). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France, International Agency for Research on Cancer, 2008, pp. 180-182). We report a case of a 77-year-old man with a medical history of chronic lymphocytic leukemia who presented with worsening chest pain over 8 weeks. Imaging studies revealed severe aortic stenosis and moderate mitral regurgitation. He subsequently underwent minimally invasive aortic valve replacement and mitral repair at our institution. Grossly, the specimen consisted of a trileaflet valve with multiple yellow-white focally hemorrhagic and calcified nodules over its surface. Histologically, a lymphocytic infiltrate composed of monotonous small cells with scant cytoplasm was seen as well as calcification and fibrosis. Immunohistochemical stains were positive for CD20, PAX5, CD5, and CD23. To our knowledge, this is the first reported case of an immunohistochemically documented chronic lymphocytic leukemia/small lymphocytic lymphoma to involve a cardiac valve.