mocetinostat and Leukemic-Infiltration

Topics: Antineoplastic Combined Chemotherapy Protocols; Diagnosis, Differential; Humans; Leukemia, Myeloid, Acute; Leukemic Infiltration; Maxilla; Maxillary Neoplasms; Peroxidase; Remission Induction; Sarcoma, Myeloid

Leukemia cutis (LC) is a nonspecific term used for cutaneous manifestations of any type of leukemia. LC has a wide range of cutaneous manifestations, which can make it difficult to clinically distinguish LC from other skin lesions. Patients with LC usually have concomitant systemic leukemia, but occasionally skin involvement precedes the involvement of the bone marrow or peripheral blood. Thus, a skin biopsy can be the first indication of the presence of leukemia in a subset of patients. The immunophenotyping of routinely processed skin biopsy specimens is very useful in establishing the diagnosis of LC. Although the molecular mechanisms explaining the pathogenesis of LC are not well defined, chemokine receptors and adhesion molecules may have an important role in skin tropism. We review the literature and recent advances pertaining to LC, with special emphasis on the immunohistochemical assessment and possible mechanisms involved in skin tropism by leukemic cells.

Topics: Biomarkers, Tumor; Biopsy; Humans; Immunohistochemistry; Immunophenotyping; Leukemia; Leukemic Infiltration; Peroxidase; Skin

We describe a new unique case of acute myeloid leukemia (AML) in a 21-yr-old male presenting with abdominal pain, bilateral testicular masses and gynecomastia. Further work-up with computed tomography of the chest, abdomen and pelvis revealed massive retroperitoneal, peripancreatic and mediastinal lymphadenopathy, suggesting primary testicular neoplasm. The patient was subjected to right orchiectomy that showed infiltration of testicular tissue with malignant cells, originally misinterpreted as undifferentiated carcinoma. Immunohistochemistry studies, however, showed these cells to be strongly positive for myeloperoxidase and CD45, indicating a myeloid cell origin. Bone marrow (BM) aspirate and biopsy demonstrated replacement of marrow with immature myeloid cells. Both the morphology and immunophenotype of the blast cells were consistent with AML type M4 (acute myelo-monocytic leukemia), using French-American-British (FAB) classification. The patient received standard induction chemotherapy with cytosine arabinoside (ARA-C) and daunorubicin followed with two cycles of consolidation therapy with high dose ARA-C, which resulted in remission of BM disease and resolution of lymphadenopathy and left testicular masses. After the second cycle of consolidation therapy, the patient developed sepsis that was complicated by refractory disseminated intravascular coagulopathy. He expired with a clinical picture of multiple organ failure. The unique features of this case are presented and the related literature is reviewed.

Topics: Abdominal Pain; Adult; Antigens, CD; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cytarabine; Daunorubicin; Diagnosis, Differential; Diagnostic Errors; Disseminated Intravascular Coagulation; Estradiol; Fatal Outcome; Gynecomastia; Humans; Immunophenotyping; Karyotyping; Leukemia, Myelomonocytic, Acute; Leukemic Infiltration; Male; Multiple Organ Failure; Neoplasm Proteins; Neoplastic Stem Cells; Peroxidase; Testicular Neoplasms; Testis

With present knowledge, the optimal management of individual patients with acute leukemia requires that every case be studied by morphology, cytochemistry, cytogenetic, immunologic and molecular techniques. An algorithm for diagnostic evaluation and classification of ALL is provided in Fig. 11. Other techniques, such as DNA or cDNA [figure: see text] microarray, are at present important research tools but have not yet had a major effect on patient care. More detailed studies of individual patients need to be conducted at specialized cancer centers, where preservation of cells, DNA, RNA, or protein is possible. Such investigations will yield important information on the clinical importance of the expression of various markers, the prevalence and relevance of bilineage and biphenotypic leukemias, and above all will reveal the mechanisms of leukemogenesis and of disease evolution. Such insights will further aid clinicians in treating ALL and in preventing refractory disease.

Topics: Adult; Algorithms; Biomarkers, Tumor; Bone Marrow; Bone Marrow Examination; Child; Chromosome Aberrations; Diagnosis, Differential; DNA Nucleotidylexotransferase; Flow Cytometry; Humans; Immunophenotyping; Leukemia, Myeloid; Leukemic Infiltration; Lymphoma; Neoplasm Proteins; Neoplasms; Neoplastic Stem Cells; Peroxidase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Pseudolymphoma; Specimen Handling; Staining and Labeling; Terminology as Topic; Translocation, Genetic

Topics: Acute Disease; Chromosomes; Humans; Leukemia; Leukemic Infiltration; Loss of Heterozygosity; Lung; Peroxidase; Phenotype

Topics: Antigens, CD34; Female; Humans; Leukemia, Myeloid, Acute; Leukemic Infiltration; Middle Aged; Peroxidase; Skin

Acute myeloid leukemia (AML) is a clonal expansion of myeloid blasts in peripheral blood, bone marrow, or other tissues. Cutaneous manifestations of leukemia are either specific or nonspecific. Specific lesions result from direct infiltration of the skin by leukemic cells. We present a case of myeloid leukemia cutis manifested by erythematous asymptomatic nodules and plaques distributed on the chest, abdomen and back. The clinical and histopathologic features of the cutaneous infiltrate were suggestive of hematolymphoid malignancy, more towards lymphoma. However, the immunohistochemical features were against the diagnosis of lymphoma and were highly suspicious of myeloid leukemia, which were concomitantly confirmed by bone marrow biopsy and blood smear. In any poorly differentiated malignant skin infiltrate of confirmed hematopoietic lineage, myeloid differentiation should be considered and excluded by an appropriate panel. CD56+ AML is a rare type of AML that has special features like the great liability of extramedullary involvement including skin, monocytic characteristic of leukemia cells, and absence of myeloperoxidase expression.

Topics: CD56 Antigen; Humans; Immunohistochemistry; Leukemia, Myeloid, Acute; Leukemic Infiltration; Male; Middle Aged; Peroxidase; Skin

Leukemia cutis is defined as a skin infiltration by leukemic cells. The diagnosis of myeloid leukemia cutis (MLC) can represent a challenge, especially in those cases without symptoms of systemic disease. The clinical appearance, histopathological analysis and immunohistochemical profile can be indistinguishable from those observed in cases of hystiocitoid Sweet syndrome (HSS). We present a case of MLC in which the cutaneous affectation was the first sign of the systemic leukemia. In this setting, the myeloperoxidase stain was the clue to rule out the possibility of HSS. We discuss the role and the utility of the myeloperoxidase stain in the differentiation of these two entities.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cytarabine; Diagnosis, Differential; Humans; Idarubicin; Leukemia, Myeloid, Acute; Leukemic Infiltration; Male; Peroxidase; Skin; Skin Neoplasms; Staining and Labeling; Sweet Syndrome; Treatment Outcome

Leukemias are neoplasms of hematolymphoid cells that predominantly involve the peripheral blood. Cutaneous involvement (leukemia cutis) occurs in chronic myeloid leukemia, chronic lymphocytic leukemia, and in monocytic leukemia. Here, we report a case of a 49-year-old female patient known to have chronic myeloid leukemia presented with multiple cutaneous lesions. The clinicopathologic features were presented and the relevant literature was discussed.

Topics: Antigens, CD; Cell Differentiation; Cell Transformation, Neoplastic; Diagnosis, Differential; Erythema; Female; Granulocyte Precursor Cells; Humans; Immunophenotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemic Infiltration; Middle Aged; Peroxidase; Skin; Solitary Pulmonary Nodule

Therapy-related leukemia cutis has not yet been described. We report a 55-year-old male who developed aleukemic leukemia cutis 15 months after chemotherapy and radiotherapy for non-Hodgkin's lymphoma. Despite intensive therapy including allogeneic hematopoietic stem cell transplantation, the patient died of progressive disease. Sequence analysis of the TP53 gene and screening for defective DNA mismatch repair revealed no abnormalities. This case demonstrates that therapy-related aleukemic leukemia cutis is an aggressive disorder resistant to conventional antineoplastic treatment approaches. As the number of patients developing therapy-related myelodysplasia or leukemia is increasing, clinicians might be confronted more frequently with atypical, extramedullary presentations of these disorders.

Topics: Base Pair Mismatch; DNA Repair; Fatal Outcome; Genes, p53; Humans; Leukemia; Leukemic Infiltration; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mutation; Peroxidase; Skin

Topics: Antineoplastic Combined Chemotherapy Protocols; Colitis; Colon; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Gastrointestinal Hemorrhage; Humans; Immunohistochemistry; Infant; Leukemia, Myeloid, Acute; Leukemic Infiltration; Leukocyte Common Antigens; Peroxidase; Sigmoidoscopy; Thioguanine

We report on two patients with chronic myeloid leukemia (CML) who presented blastic transformation involving the skin, with leukemic infiltrates showing unusual morphologic and immunohistologic characteristics. Both patients were elderly men with a 36-month and a 40-month history of CML, respectively. They presented with disseminated, reddish to violaceous papules and plaques (case 1), and with localized reddish nodules on the left temporal area (case 2). Concurrent features of blastic transformation in the bone marrow were observed in one patient (case 1). Histopathologic examination of skin lesions revealed similar features in both cases. There was a moderate to dense dermal infiltrate composed mainly of medium-sized atypical mononuclear myeloid precursor cells with only few relatively well-differentiated cells of the granulocytic series. Histochemical staining for naphthol-ASD-chloroacetate esterase revealed strong positivity (>50% of neoplastic cells) in case 2 and only scattered positivity (< 10% of neoplastic cells) in case 1. Immunohistologic analysis performed on paraffin-embedded sections showed in both cases variable reactivity of neoplastic cells for leucocyte common antigen (CD45), lysozyme, myeloperoxidase, CD11c, CD15, CD43, CD66, CD68, HLA-DR, and the neural cell adhesion molecule (NCAM) CD56. A negative reaction was observed for CD3, CD34, and TdT. The immunohistologic findings were remarkably similar to those reported for acute myeloid leukemia (AML) with monocytic differentiation (French-American-British [FAB] classification, subtype M4). Examination of blasts from the bone marrow performed in one patient (case 1) revealed a similar phenotype also with CD56 expression. In conclusion, our observations show that specific cutaneous infiltrates in CML may show morphologic and immunohistochemical characteristics similar to those observed in AML with monocytic differentiation. Moreover, specific cutaneous manifestations of CML may express CD56.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Marrow Cells; CD56 Antigen; HLA-DR Antigens; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemic Infiltration; Lymphocyte Activation; Male; Middle Aged; Muramidase; Naphthol AS D Esterase; Peroxidase; Skin Neoplasms; T-Lymphocytes

Acute promyelocytic leukemia (APL) is a type of acute leukemia showing unique clinical, morphological and cytogenetic features. A skin infiltration by APL cells is an extremely rare occasion, but there have been several case reports of leukemia cutis in APL, in which all-trans retinoic acid (ATRA) may have induced the skin infiltration. However, no immunohistochemical analyses of the APL cells in the skin have been done to date. A 30-year-old woman with APL developed multiple reddish purple nodules on the extremities in her second complete remission. Histological findings revealed a dense infiltration of medium to large atypical cells, which were positive for myeloperoxidase, throughout the dermis. Despite the conventional chemotherapy and ATRA therapy she died from disseminated intravascular coagulation during her third relapse. Leukemic cells in the peripheral blood before the treatment with ATRA revealed CD3-/CD4-/CD5-/CD7-/CD8-/CD10-/CD13++/CD14-/CD19 -/ CD20-/CD33++/CD38++/CD41-/Ia-, but they expressed CD3-/CD4-/CD5-/CD7++/ CD8-/CD10-/CD13++/CD14-/CD19-/CD20-/CD33++ /CD38++/CD41+/Ia+ after the treatment. We suggest that the alternation of the surface molecules on the tumor cells is closely associated with the skin infiltration of APL cells.

Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Adult; Antigens, CD; Antigens, CD19; Antigens, CD20; Antigens, CD7; Antigens, Differentiation; Antigens, Differentiation, Myelomonocytic; Antineoplastic Agents; Cause of Death; CD13 Antigens; CD3 Complex; CD4 Antigens; CD5 Antigens; CD8 Antigens; Cell Adhesion Molecules; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Histocompatibility Antigens Class II; Humans; Keratolytic Agents; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Lipopolysaccharide Receptors; Membrane Glycoproteins; N-Glycosyl Hydrolases; Neprilysin; Peroxidase; Platelet Glycoprotein GPIIb-IIIa Complex; Sialic Acid Binding Ig-like Lectin 3; Skin; Tretinoin