Hematology 2 - Lecture - 12 - Malignant Lymphoproliferative Disorders - Complete

Lymphoproliferative disorders

Represent a group of clonal disorders that originate from cells of the lymphoreticular system.

Leukemia

When the neoplastic cells involve mainly the bone marrow and the blood, the disorder is known as:

Lymphoma

When the disease is limited mainly to lymph nodes or organs, the disease is known as:

Leukemia

Occasionally, a lymphoma can develop into a ___ when the cells of the diseased organ spreads to the bone marrow and then to the blood.

Peripheral smear findings, Bone marrow aspirate studies, CBC findings

Lymphoproliferative disorders can be detected through:

Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, Hairy Cell Leukemia

Lymphoproliferative disorders MTs should know about

Acute leukemia

Refers to the rapid, clonal proliferation in the bone marrow of lymphoid or myeloid progenitor cells known as lymphoblasts and myeloblasts.

When these blastic proliferations overwhelm the bone marrow, the blasts spill over into the blood and are seen in peripheral smears

Anemia, Thrombocytopenia

The signs and symptoms of leukemia reflect the suppression of normal hematopoiesis by these abnormally proliferating blasts, thus causing ___ and ___ commonly.

Acute lymphoblastic leukemia

ALL meaning

Acute lymphoblastic leukemia

Systemic, neoplastic proliferation of lymphoblasts originating in lymphocyte progenitor cells of the bone marrow or thymus

Acute lymphoblastic leukemia

Most common type of leukemia in pediatric patients

70%

About what % of cases of ALL occurs in patients under 17 years of age?

2-10

What age is ALL most common in?

Rare

ALL frequency in adults

25-41%

ALL cure rate in adults; has poorer outlook

60%

ALL cure rate if response to treatment is good

Unknown

ALL etiology

Radiation

Children exposed to ___ in utero or at a young age appear to have an increased incidence of ALL

Genetic factors

These presumably play a role in some cases of ALL

Acute myeloid leukemia

The presenting signs and symptoms of ALL are similar to those of ___ and are usually related to blood cytopenias

Immunophenotyping techniques

T-cell ALL and B-cell ALL are primarily differentiated by:

Flow cytometry, Immunohistochemistry

Methods to what cell surface markers are present on the proliferating neoplastic lymphoblasts.

B-cell ALL

Type of ALL

Lymph node enlargement is often found.

T-cell ALL

Type of ALL

There may be a large mass in the mediastinum leading to compression of regional anatomic structures.

B-cell ALL

Type of ALL

Splenomegaly & hepatomegaly less so but may also be present.

Anemia, Thrombocytopenia, Organomegaly, Bone pain

Symptoms present in both B-cell and T-cell ALL

T-cell ALL

Type of ALL that present Anemia, Thrombocytopenia, Organomegaly, and Bone pain to a lesser degree

World Health Organization classification

ALL classification that emphasizes the immunophenotype and cytogenetic findings, which have more clinical and prognostic relevance than morphology

20%

World Health Organization classification for ALL

A finding of at least (how much %) blasts in the bone marrow is required for diagnosis of majority of acute leukemias and testing must be done to detect the presence or absence of genetic abnormalities.

World Health Organization classification

ALL classification that is not a very popular classification because only very specialized laboratories are able to perform cytogenetic testing.

7

B-cell ALL amount of subtypes associated with recurrent cytogenetic abnormalities which are linked with unique clinical or prognostic features.

French-American-British classification

ALL classification that more popular

L1, L2, L3

French-American-British ALL classification

Subtypes

French-American-British classification

ALL classification that more popular based on morphologic examination to distinguish lymphoblasts from myeloblasts.

ALL-3

French-American-British ALL classification

Subtype with: Large, homogenous cell population. Nuclei regular with fine chromatin and 1- 2 nucleoli. Moderate to abundant vacuolated cytoplasm

ALL-1

French-American-British ALL classification

Subtype with: Small uniform cell. Nuclei regular with condensed chromatin, inconspicuous nucleoli. Scant cytoplasm.

ALL-2

French-American-British ALL classification

Subtype with: Large, heterogenous cell population. Nuclei irregular / clefting with occasional nucleoli. Mild to moderate cytoplasm.

80-88%

French-American-British ALL classification

What % of pediatric ALL cases are L1?

8-18%

French-American-British ALL classification

What % of pediatric ALL cases are L2?

1-5%

French-American-British ALL classification

What % of pediatric ALL cases are L3?

35-40%

French-American-British ALL classification

What % of adult ALL cases are L1?

60%

French-American-British ALL classification

What % of adult ALL cases are L2?

1-5%

French-American-British ALL classification

What % of adult ALL cases are L3?

CBC, PBS, BM aspiration, Trephine biopsy morphologic exam, Appropriate cytochemical studies on blood and bone marrow, Immunophenotyping of leukemic blasts by flow cytometry, Immunohistochemistry, BM cytogenetic studies, Molecular studies as indicated, CSF examination, Radiographic studies for assessment of extramedullary mass disease as indicated, Other biochemical and microbiologic studies as indicated

Tests for diagnosing ALL

90%

% of ALL patients with abnormal blood counts

Bicytopenia, Pancytopenia

Blood cell interpretation in ALL (Either of the 2 answers)

Anemia

Most common blood cell finding in ALL

Normochromic, Normocytic

ALL PBS finding

Decreased

ALL reticulocyte count (Qualitative answer)

25%

% of ALL patients present leukopenia in the low normal range

50%

% of ALL patients that have WBC counts between 5-25x10^9/L

10%

% of ALL patients that have WBC counts >100x10^9/L

Lymphoblasts

ALL WBC present in blood smears for majority of patients, including most who present with leukopenia.

Atypical lymphocytes

Lymphocytes that display paler staining areas in the nucleus that are easily confused as nucleoli (often confused with blasts because of their fairly large cells and rich basophilic cytoplasm).

Reduced

ALL Neutrophil count (Qualitative answer)

Neutropenia

ALL

Rate of infection parallels the severity of the ___

Lymphoblast, myeloblast morphology

First tool to distinguish ALL from AML

Large, often uniform

AML blast size

Usually finely dispersed

AML nuclear chromatin

1-4, often prominent

AML nucleoli

Moderately abundant, granules often present

AML cytoplasm

Present in 60-70% of cases

AML Auer rods

Myeloblasts

AML cells

Variable, small to medium

ALL blast size

Coarse to fine

ALL nuclear chromatin

Absent or 1-2, often indistinct

ALL nucleoli

Usually scant, coarse granules sometimes present 7%

ALL cytoplasm

Not present

ALL Auer rods

Lymphoblasts

ALL cells

Small, Large

Lymphoblast 2 morphological types

Small lymphoblast

Lymphoblast morphologic type

Nucleus & Cytoplasm: Scant blue cytoplasm, indistinct nucleoli

Large lymphoblast

Lymphoblast morphologic type

Size: 2 to 3x the size of a normal lymphocyte

Large lymphoblast

Lymphoblast morphologic type

Nucleus & Cytoplasm: Prominent nucleoli, nuclear membrane irregularities

Small lymphoblast

Lymphoblast morphologic type

Most common

Small lymphoblast

Lymphoblast morphologic type

Size: 1 to 2.5x the size of a normal lymphocyte

Large lymphoblast

Lymphoblast morphologic type

Easy to confuse with myeloblasts in acute myeloid leukemia

Lymphoblasts

ALL BM smears are hypercellular and consist mostly of:

Markedly reduced

ALL

Amount of normal hematopoietic cells

Sparsely scattered, Overrun the bone marrow space

ALL

Lymphoblasts distribution in the bone marrow

Decreased

ALL

Amount of RBC, granulocytic cells, megakaryocytes, PLT ct, Absolute neutrophil ct (Qualitative answer)

Infection, Bleeding, Pale, Fatigue, Tachycardia

Typical presentation of patients with ALL

Infection

Presentation of patients with ALL because:

They have little neutrophils to fight off the infection.

Bleeding

Presentation of patients with ALL because:

Due to thrombocytopenia.

Tachycardia

Presentation of patients with ALL because:

Due to anemia

Immunophenotyping, Genetic analysis

Most reliable indicators of a cell's origin.

CD34, TdT, HLA-DR

Surface markers common to both B and T cells

Terminal deoxynucleotidyl transferase

TdT meaning

CD19, 20, 22, 24, 79a, 10, Cytoplasmic u, PAX-5

B cell cell markers

CD2, 3, 4, 5, 7, 8

T cell cell markers

Cytochemical stains

Primarily to help distinguish ALL from AML.

Cytochemical stains

Procedure that is useful in determining whether a cell in question is a lymphoblast, an atypical lymphocyte, or a large granular lymphocyte,

Negative

Lymphoblast result for myeloperoxidase

Positive

Myeloblast result for myeloperoxidase

Brown

Myeoblast granule color in Cytochemistry stain

Positive

Periodic acid-Schiff stain result in most cases of ALL

Periodic acid-Schiff stain

This cytochemical stain is distributed in coarse granules or clumps in the cytoplasm corresponding to glycogen deposits.

ALL-L3

ALL classification according to FAB classification that stains positively with Oil Red O stain.

Vacuole

What specific component of cells are stained positively with Oil Red O stain in ALL?

Terminal deoxynucleotidyl transferase

Unique DNA polymerase found normally in a small number of bone marrow lymphoid cells

5-10%

% of AML positive for TdT, less than ALL