Heme Flashcards
(377 cards)
Castleman Disease AKA angiofollicular hyperplasia.
Can be unicentric or multicentric. The unicentric type includes the hyaline vascular and plasma cell variants, while the multicentric type is mostly of the plasma cell type. 80% of cases are the hyaline vascular type, are M=F, any age. The multicentric type typically affects older patients, M slightly more than F, and is often seen in HIV patients and is associated with HHV-8.
Examples of pseudoneoplastic lesions in the lymphoreticular system and their related neoplastic mimes.
Selected lymphoid hyperplasias (lymphomas). Florid unilinear hyperplasia in bone marrow recovery (myelodysplasia; leukemia). Infection-related hemophagocytic syndrome (T-cell lymphoma). Epstein-Barr virus-related atypical lymphoid hyperplasias (large-cell lymphoma). Mycobacterial pseudotumors (dendritic-cell tumors).
Intravascular large B-cell lymphoma.
IVLBCL is a rare type DLBCL. Two forms have been described: classical, also known as Western form, with a cutaneous variant; and an Asian form occurring more frequently in the Far East. Intravascular lymphoma is most frequently a disease of B lymphocytes; although rare cases of T-cell and NK–cell disease have been reported, the WHO considers these cases to be a separate entity. M:F = 1.1:1, median age 67 years, range 41–85 years. By the time of presentation, most patients have advanced, disseminated disease. Patients may present with any of a myriad of symptoms, with any tissue potentially being infiltrated. CNS and cutaneous involvement is common, as is the presence of B symptoms. The WHO reports neoplastic cells will be found within the lumina of small and intermediate sized vessels, with prominent nucleoli, scant cytoplasm, and frequent mitotic figures. The cells inconsistently express several of the typical B-cell antigens, with CD19, CD20, CD79a, MUM1/IRF4, and Bcl-2 being the most commonly expressed. IVLBCL has no specific chromosomal alterations, but many abnormalities reported in other B-cell lymphomas may be seen in IVLBCL. The DDx includes lymphomatoid granulomatosis, primary CNS lymphoma, CD5+ diffuse large B-cell lymphoma, reactive lymphoid hyperplasia, CNS vasculitis, HPC-associated disorders other than IVLBCL, the acute leukemias, and lymphomas with an intravascular component.
How are clot sections prepared from bone marrow aspirates?
Clotted bone marrow left over from aspirate smears can be fixed in formalin with or without mercury chloride (B5) and then embedded in paraffin and stained with H&E.
Kikuchi-Fujimoto disease.
KFD, or histiocytic necrotizing lymphadenitis, is a self-limited condition, characterized by acute or subacute onset of benign painful lymphadenopathy with associated fevers and systemic symptoms. It MC affects females <40 yo and of Asian descent. Involved lymph nodes demonstrate circumscribed paracortical areas of apoptotic necrosis with abundant karyorrhectic debris and a proliferation of histiocytes, plasmacytoid dendritic cells, and CD8+ T cells in the absence of neutrophils. The etiology is unknown, although viruses and autoimmune mechanisms have been proposed. No specific laboratory tests contribute to the Dx. Dx requires histopathologic examination and exclusion of other factors by ancillary studies. Lymphoid malignancies, especially non-Hodgkin lymphoma; lymphadenopathy due to autoimmune disorders, primarily SLE; and infectious etiologies, such as EBV, HSV, Bartonella henslae, and toxoplasmosis should be r/o before the Dx of KFD, given the overlapping clinical and histologic features as well as the different therapeutic approaches. Tx involves supportive measures, and the symptoms usually resolve spontaneously within 4 months.
PIOLs?
Primary Intraocular Lymphomas. Is a subset of PCNSL. Is usually a DLBCL. They arise from the retina (a suggested renaming for PIOL is primary retinal lymphoma) and rarely from the uvea. Usually presents as a chronic intermediate uveitis unresponsive to corticosteroids in a median age in the 60s. The Dx is based on ID of atypical lymphoid cells in the eye, but b/c PIOL is a subset of PCNSL, the Dx can be made if the lymphoma cells are found in CSF, and an LP is less invasive than a diagnostic vitrectomy or a vitreous or aqueous aspiration anyway. The atypical lymphoid cells are usually large and pleomorphic, with scant basophilic cytoplasm and large nuclei. Other findings include hypersegmented, round, or clover-shaped nuclei with prominent nucleoli and rare mitoses.
The most common primary lymphoma subtype occuring in the ocular adnexa?
Low-grade, malignant, extranodal, marginal zone B-cell lymphoma of MALT type.
What are clonotypic B lymphocytes?
Clonotypic B lymphocytes (CBLs) are monoclonal B lymphocytes identified in patients with multiple myeloma, that share identical rearranged IGH-CDR3 sequences with the patient’s myeloma cells. CBLs are putative precursors of neoplastic plasma cells, and have been postulated to act as a therapy-resistant tumor reservoir that drives recurrence. CBLs show somatic mutations of IgH gene in a nonrandom fashion, without intraclonal variation, suggesting a postgerminal-center B-cell origin. Evidence, including oncogene expression, DNA aneuploidy, stem cell-like characteristics, and the clonal homogeneity, suggests that most of these B cells are malignant or premalignant and may represent precursors of neoplastic plasma cells. It is proposed that these B cells originate outside the marrow (lymph nodes and other lymphoid organs) and give rise to plasma cells only after migration to the bone marrow, which provides a microenvironment suitable for terminal plasma-cell differentiation. CBLs similar to those in MM are also detected in MGUS, although at a lower frequency.
What fixative and stain is used for bone marrow aspirate smears?
After the spread aspirate smears are allowed to air dry, they are fixed in methanol then stained with May-Grunwald-Giemsa or Wright stains.
What is the LAP score?
Alkaline phosphatase activity is found in the cytoplasm of neutrophils, osteoblasts, vascular endothelial cells, and some lymphocytes. The alk phos level of peripheral blood neutrophils is quantitated by the leukocyte alkaline phosphatase (LAP) score and is a useful screening test to differentiate chronic myelogenous leukemia from leukemoid reactions and other myeloproliferative disorders. The LAP score is usually performed using the Kaplow procedure. The LAP score is determined by evaluation of the staining intensity (ranging from 0 to 4+) of 100 counted neutrophils or bands. Normal LAP scores range from 15 to 130, but there may be variation in these ranges between laboratories. Entities with a low LAP score (130): Infections, growth factor therapy, myeloproliferative disorders other than CML, inflammatory disorders, pregnancy, oral contraceptives, stress, drugs (lithium, corticosteroids, estrogen). There is rapid loss of alk phos activity in samples drawn in EDTA anticoagulant. The test is optimally performed on fresh capillary blood fingerstick smears or on blood anticoagulated with heparin and should be performed within 48 hours after collection of the sample. The blood smears may be held in the freezer for 2-3 weeks with little loss of activity.
What is the MC cytogenetic abnormality in ALK positive ALCL?
t(2;5)(p23;q35). The t(2;5) fuses the ALK gene on 2p23 to the nucleophosmin (NPM) gene on 5q35, resulting in the constitutive activation of ALK kinase.
What stain is used for blood smears?
Romanowsky first used in 1890 a mixture of eosin and methylene blue. Subsequent modifications are May-Grunwald-Giemsa and Wright stains. Both contain eosin and methylene azures, which are derivatives of methylene blue.
ALL may primarily involve tissues, and when this is the primary manifestation, this process is called ___. AML may involve the tissues as well and when present is designated ___.
ALL may primarily involve tissues, and when this is the primary manifestation, this process is called lymphoblastic lymphoma. AML may involve the tissues as well and when present is designated myeloid sarcoma.
What is MPAL?
Mixed phenotype acute leukemia is a rare subset of acute leukemia, accounting for less than 5% of newly diagnosed cases, that includes both biphenotypic acute leukemia, in which markers of more than one lineage are expressed on a single blast population, and bilineal acute leukemia, in which two distinct blast populations of different lineages are present.
What are hematopoietic markers for identification of myeloblasts? Give patterns of CD34, TdT, CD10, c-kit, HLA-DR, sIg, and lineage specific markers.
CD34 +/-, TdT - (rarely + in M0), CD10 - (rarely +), c-kit +/-, HLA-DR +/-, sIg -. Lineage specific markers: CD13, CD33, CD15, CD11b, c-kit. CD34 and/or c-kit are typically present in AML, although some forms of AML may be entirely negative for CD34 and c-kit, notably AML with monocytic differentiation. Most AMLs express HLA-DR, but some myeloid leukemias (i.e. acute promyelocytic (M3) and AML with NPM1 mutations and cup-like nuclear invaginations) are HLA-DR negative. Myeloid sarcoma (chloroma) can be identified by immunostains for blast markers (CD34, c-kit), myeloid/monocytic markers (MPO, lysozyme) and CD43.
What are hematopoietic markers for identification of B-lymphoblasts? Give patterns of CD34, TdT, CD10, c-kit, HLA-DR, sIg, and lineage specific markers.
CD34 + (may be -), TdT +, CD10 + (occasionally -), c-kit -, HLA-DR + (rarely -), sIg - (or dim +). Lineage specific markers: CD19, CD79a, CD20 (+/-). DDx: Burkitt lymphoma has a mature B cell phenotype (sIg+, kappa or lambda +, CD20+, CD10+, Bcl-2 -) and is negative for blast markers (CD34, TdT).
What are hematopoietic markers for identification of T-lymphoblasts? Give patterns of CD34, TdT, CD10, c-kit, HLA-DR, sIg, and lineage specific markers.
CD34 +/-, TdT +, CD10 +/-, c-kit - (very rarely +), HLA-DR - (rarely +), sIg -. Lineage specific markers: CD3 (often cytoplasmic only).
All LGBCLs are positive for what hematopoietic markers?
CD45, pan-B markers CD19/20/22/79a and sIg.
What is typically seen on flow cytometry for CLL/SLL, MCL, FL, MZL, LPL, and HCL?
CLL/SLL: small FMC7- B-cells, light chain dim, CD20 dim. MCL: small FMC7+ B-cells, light chain bright, CD20 bright. FL: small-medium size light chain restricted CD10+ B-cells. MZL: often mixture of neoplastic and non-neoplastic B-cells; may be CD23+. LPL: light chain restricted small B-cells + plasma cells. HCL: CD20 bright, CD22 bright, CD103+, CD11c+, CD25+; very few monocytes in PB or BM.
WHO grading system for follicular lymphoma.
3 grades and 4 patterns. Grades are based on the number of centroblasts per HPF (40x objective; number should be based on the average of 10 fields). Grade 1 has 0-5 centroblasts per HPF. Grade 2 has 6-15 centroblasts per HPF. Grade 3 has >15, subdivided into 3A (residual centrocytes present) and 3B (centroblasts form solid sheets with no residual centrocytes). Patterns are based on the proportion of the follicular pattern. Follicular has >75% follicular pattern. Follicular and diffuse has 25-75% follicular pattern. Focally follicular/predominantly diffuse has <25% follicular pattern. Diffuse has 0% follicular pattern.
What are the diagnostic criteria for MGUS?
All three criteria must be met: 1. Serum monoclonal protein less than 3 g/dL. 2. Bone marrow plasma cells less than 10%. 3. Absence of end-organ damage and bone lytic lesions (end-organ damage=CRAB: hyperCalcemia, Renal insufficiency, normochromic normocytic Anemia, and/or Bone marrow lesions that can be attributed to the plasma cell proliferative disorder).
Diagnostic criteria for smoldering multiple myeloma.
Requires both: 1. Serum monoclonal protein (IgA or IgG) >3g/100mL and/or clonal bone marrow plasmacytosis > or = 10%. 2. Absence of end-organ damage or myeloma-related symptoms. (end-organ damage=CRAB: hyperCalcemia, Renal insufficiency, normochromic normocytic Anemia, and/or Bone marrow lesions that can be attributed to the plasma cell proliferative disorder).
Diagnostic criteria for multiple myeloma.
Requires all 3: 1. Clonal bone marrow plasmacytosis (typically >10%, but a minimal % is not designated in the setting of symptomatic myeloma). 2. Serum and/or urine M protein (except in patients with a non-secretory myeloma). 3. Evidence of end-organ damage, hyperviscosity, amyloidosis, or recurrent infections (end-organ damage=CRAB: hyperCalcemia, Renal insufficiency, normochromic normocytic Anemia, and/or Bone marrow lesions that can be attributed to the plasma cell proliferative disorder).
Diagnostic criteria for Waldenstrom’s macroglobulinemia.
Requires both: 1. IgM monoclonal gammopathy of any concentration. 2. Lymphoplasmacytic lymphoma with bone marrow involvement.