Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Mastocytosis

The most common subtype of cutaneous mastocytosis, termed urticaria pigmentosa, was first described in the 19th century, a decade before mast cells (MCs) were defined by Paul Ehrlich as metachromatic cells of the connective tissue. In 1949, the first histologic proof of involvement of visceral organs by mastocytosis was reported. Since that time, many terms have been introduced to describe mastocytosis. These terms are now obsolete…

Myelodysplastic/Myeloproliferative Neoplasms

The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are clonal myeloid disorders that, at the time of initial diagnosis, have some clinical, laboratory, or morphologic features supporting the diagnosis of a myelodysplastic syndrome (MDS), such as persistent cytopenias and dysplasia involving one or more of the myeloid lineages. Simultaneously, however, they exhibit other features, such as splenomegaly, neutrophilia, monocytosis, or thrombocytosis, that are more in keeping with a myeloproliferative neoplasm…

Myeloproliferative Neoplasms

Definition The myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by proliferation of cells of one or more of the myeloid lineages, erythroid, granulocytic, or megakaryocytic. Initially, the proliferation in the bone marrow is effective and associated with maturation of the neoplastic cells that leads to increased numbers of mature granulocytes, red blood cells (RBCs), and platelets in the peripheral blood. Splenomegaly and hepatomegaly are common…

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous group of diseases representing clonal proliferations of immature, nonlymphoid, bone marrow–derived cells that most often involve the bone marrow and peripheral blood and may present in extramedullary tissues. If untreated, AML follows an aggressive clinical course. AML has traditionally been differentiated from other myeloid neoplasms on the basis of a minimum blast cell count in bone marrow or peripheral…

Myelodysplastic Syndromes

The myelodysplastic syndromes (MDS) are a set of diseases characterized by progressive peripheral cytopenias and dysplastic morphology of hematopoietic cells. MDS affects predominantly the elderly, but it can occur throughout life, including in childhood. MDS is a clonal hematopoietic neoplasm with diverse phenotypes that appear in part to reflect various combinations of acquired genetic mutations. However, its etiology and pathogenesis remain largely unexplained, limiting our ability…

Principles of Classification of Myeloid Neoplasms

The 2016 revision of the fourth edition of the World Health Organization (WHO) classification of myeloid neoplasms, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues , is used in this book. The principles of the WHO classification have been described elsewhere, and the process for developing this consensus classification is summarized in Chapter 13 . Briefly, the classification relies on a combination of clinical, morphologic,…

Acute Leukemias of Ambiguous Lineage

Standard classification criteria for acute leukemia derive from the morphologic, cytochemical, and immunophenotypic characterization of bone marrow specimens and are designed to identify optimal therapy and predict prognosis. On the basis of these criteria, most cases of acute leukemia can be unequivocally assigned to the myeloid, B-lymphoid, or T-lymphoid lineage. However, a small and heterogeneous subset of leukemias cannot be clearly identified with recognized patterns of…

Precursor B- and T-Cell Neoplasms

Classification of Precursor Lymphoid Neoplasms Precursor lymphoid neoplasms encompass acute lymphoblastic leukemias (ALLs) and lymphoblastic lymphomas (LBLs), generally of either B-cell or T-cell origin. The majority of ALLs are derived from precursor B cells, and the majority of LBLs possess a precursor T-cell phenotype. In general, ALLs and LBLs comprising precursor B cells are considered biologically equivalent, as is the case with precursor T-cell ALL and…

Primary Cutaneous T-Cell Lymphomas: Rare Subtypes

Cutaneous T-cell lymphomas (CTCLs) comprise, for the most part, mycosis fungoides (MF) and variants and cutaneous CD30 + lymphoproliferative disorders, but other rare subtypes may be the source of diagnostic and therapeutic challenges. Some of these rare lymphomas show overlapping clinicopathologic features, and distinction from MF may be difficult or even impossible without proper history and complete clinical information. In spite of extensive phenotypic and genotypic…

Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative Disorders

Definition Three types of primary cutaneous CD30 + lymphoproliferative disorders (LPDs) are recognized in the World Health Organization classification: primary cutaneous anaplastic large cell lymphoma (C-ALCL), lymphomatoid papulosis (LyP), and borderline lesions. These entities represent a continuous spectrum of lesions that are not clearly demarcated by clinical appearance or histology in some instances. LyP occurs as multiple recurrent, often centrally necrotic, papulonodular lesions up to 2 cm…

Mycosis Fungoides and Sézary Syndrome

Mycosis fungoides and Sézary syndrome are two closely related conditions in which neoplastic T cells infiltrate the skin and circulate in the peripheral blood. Both conditions are neoplasms that typically have a mature helper T-cell phenotype and a propensity to colonize the epidermis. Because individual patients can have discrete cutaneous lesions at one point in time and erythroderma with circulating neoplastic cells at another time, some…

Enteropathy-Associated T-Cell Lymphoma and Other Primary Intestinal T-Cell Lymphomas

Enteropathy-Associated T-Cell Lymphoma (Type I, Classical) An association between malabsorption and intestinal lymphoma was first reported in 1937, at which time lymphoma was considered responsible for the malabsorption. However, in 1962, Gough and coworkers demonstrated that intestinal lymphoma was a complication of celiac disease or gluten-sensitive enteropathy. In 1978, Isaacson and Wright characterized celiac disease–associated lymphoma as a single entity, originally considered a form of malignant…

Anaplastic Large Cell Lymphoma, ALK Positive and ALK Negative

Definition and Background Among the heterogeneous group of hematopoietic neoplasms with a predominant population of large cells, Stein and colleagues recognized a subgroup of tumors with large cells exhibiting bizarre morphologic features and prominent sinusoidal invasion and expressing the Ki-1 antigen (now referred to as CD30). Based on the strong expression of this molecule, these tumors were designated Ki-1 lymphoma . Because of the lack of…

Angioimmunoblastic T-Cell Lymphoma

Definition Angioimmunoblastic T-cell lymphoma (AITL) is a systemic lymphoproliferative disorder characterized by generalized lymphadenopathy, hepatosplenomegaly, constitutional symptoms, rash, anemia, and polyclonal hypergammaglobulinemia. Histologically, the normal architecture of the lymph node is effaced by a polymorphic cellular infiltrate composed of lymphocytes, plasma cells, eosinophils, histiocytes, and immunoblasts. A hallmark of the disease is a prominent proliferation of high endothelial venules with arborization and a diffuse proliferation of…

Peripheral T-Cell Lymphoma, Not Otherwise Specified

Definition The category of the peripheral T-cell lymphoma, unspecified, introduced in the Revised European-American Lymphoma classification in 1994, was renamed peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) in the 2008 edition of the World Health Organization (WHO) classification, an appellation reflecting the expectations for better specification or subdivisions in the future. It encompasses per definition all mature T-cell neoplasms lacking specific features that would allow…

Hepatosplenic T-Cell Lymphoma

Definition Hepatosplenic T-cell lymphoma (HSTL) is an aggressive subtype of extranodal lymphoma characterized by a hepatosplenic presentation without lymphadenopathy and a poor outcome. The neoplasm results from a proliferation of non-activated cytotoxic T cells, usually monomorphic and medium-sized, that exhibit a unique sinusoidal pattern of infiltration in the spleen, liver, and bone marrow. It is associated with a recurrent cytogenetic abnormality, the isochromosome 7q; has a…

Adult T-Cell Leukemia/Lymphoma

Definition Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm pathogenetically linked to human T-lymphotropic virus 1 (HTLV-1; also called human T-cell leukemia virus ). This is the first retrovirus proved to cause a human neoplasm. The disease is derived from mature CD4-positive T cells, and most patients have widely disseminated disease that can be leukemic or lymphomatous in distribution. A characteristic feature is the marked…

T-Cell Prolymphocytic Leukemia

Definition T-cell prolymphocytic leukemia (T-PLL) is an aggressive disease characterized by a proliferation of small to medium-sized lymphocytes with a postthymic phenotype usually involving blood, bone marrow, lymph nodes, spleen, and skin. This leukemia was first described by Catovsky and colleagues in reference to a patient who presented with cytologic features similar to B-cell prolymphocytic leukemia (B-PLL), but the cells were shown to bind sheep erythrocytes…

T-Cell and NK-Cell Large Granular Lymphocyte Proliferations

History and Classification The first detailed studies of what is now recognized as T-cell large granular lymphocytic leukemia (T-LGL) were published in the 1970s and early 1980s. These manuscripts described a disorder associated with neutropenia or anemia that was associated with a proportionate and absolute increase in circulating granular lymphocytes that were reactive with antisera to T-cells, cell that normally constituted only 10% to 20% of…

Virally Associated T-Cell and NK-Cell Neoplasms

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus with tropism for B cells. More than 90% of humans are infected with EBV, and the infection persists for life. Usually primary infection is asymptomatic and occurs early in life, and when symptomatic is usually a self-limited disease occurring in adolescents or young adults manifested as acute infectious mononucleosis (IM). IM is characterized by a polyclonal expansion of infected…