Leukemia 3

Question 0

3 Myeloid Neoplasms

Answer 0

Acute Myelogenous Leukemia
Myelodysplastic Syndromes
Chronic Myeloproliferative Disorders

Question 1

List of Lymphoid Neoplasms

Answer 1

Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia
Follicular Lymphoma
Mantle Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Burkitt Lymphoma
Multiple Myeloma and Related Plasma Cell Disorders
Hodgkin Lymphoma
Miscellaneous Lymphoid Neoplasms

Question 2

Histiocytic Neoplasms

Answer 2

Langerhans Cell Histiocytoses

Question 3

2 Acute leukemias

Answer 3

Acute lymphoblastic leukemia (ALL)

Acute myeloid (myeloblastic) leukemia (AML)

Question 4

3 Chronic leukemias

Answer 4

Chronic lymphocytic leukemia (CLL)
Hairy cell leukemia
Chronic myelogenous leukemia (CML)

Question 5

3 MYELOPROLIFERATIVE DISEASES

Answer 5

Polycythemia vera
Chronic idiopathic myelofibrosis (agnogenic myeloid metaplasia, myelofibrosis with myeloid metaplasia)
Essential thrombocythemia

Question 6

3 Plasma cell disorder

Answer 6

Multiple myeloma (plasma cell myeloma/plasmacytoma)
Waldenström macroglobulinemia
Benign monoclonal gammopathy (monoclonal gammopathy of undetermined significance, or MGUS)

Question 7

2 lymphoid neoplasia

Answer 7

Hodgkin lymphoma (Hodgkin disease)

Non-Hodgkin lymphomas

Question 8

Characteristics of Plasma Cell Disorders

Answer 8

Plasma cell disorders are a diverse group of disorders of unknown etiology characterized by
the disproportionate proliferation of one clone of B cells and
the presence of a structurally and electrophoretically homogeneous (monoclonal) immunoglobulin or polypeptide subunit in serum, urine, or both.
Plasma cell disorders are neoplastic proliferations of well-differentiated immunoglobulin-producing cells.
These disorders include
multiple myeloma
Waldenström macroglobulinemia
benign monoclonal gammopathy
Primary amyloidosis
heavy-chain (Franklin) disease.
Occurrence is most frequent in persons older than 40–50 years of age.

Question 9

Pathophysiology of Plasma Cell

Answer 9

1.After developing in the bone marrow, undifferentiated B cells enter peripheral lymphoid tissues, such as lymph nodes, spleen, gut, and Peyer’s patches.
2.Here, they begin to differentiate into cells, each of which can respond to a limited number of antigens.
3.After encountering the appropriate antigen, some B cells undergo clonal proliferation into plasma cells.
4.Each clonal plasma cell line is committed to synthesizing one specific immunoglobulin antibody that consists of 2 identical heavy chains (gamma [γ], mu [μ], alpha [α], delta [δ], or epsilon [ε]) and 2 identical light chains (kappa [κ] or lambda [λ]).
5. A slight excess of light chains is normally produced, and urinary excretion of small amounts of free polyclonal light chains (≤ 40 mg/24 h) is normal.
Plasma cell disorders are of unknown etiology and are characterized by the disproportionate proliferation of one clone. The result is a corresponding increase in the serum level of its product, the monoclonal immunoglobulin protein (M-protein).
 M-proteins may consist of both heavy and light chains or of only one type of chain.
Some show antibody activity, which may cause autoimmune damage of organs, particularly the kidneys.

Question 10

Multiple myeloma (plasma cell myeloma/plasmacytoma)

Answer 10

is a malignant plasma cell tumor usually affecting older persons that typically involves bone and is associated with prominent serum and urinary protein abnormalities.

Bone lesions and protein abnormalities
The neoplastic cell is an end-stage derivative of B lymphocytes that is clearly identifiable as a plasma cell. The neoplastic cells can easily be identified by bone marrow biopsy or aspiration smears.

$ The tumor cells produce lytic lesions in bone, especially in the skull and axial skeleton.

1. The bone lesions appear lucent on radiographic examination, with characteristic sharp borders, and are referred to as punched-out lesions. They may be manifest radiographically as diffuse demineralization of bone (osteopenia).
2. The cause is an osteoclast-activating factor secreted by the neoplastic plasma cells.
3. The lesions are often associated with severe bone pain and spontaneous fractures

$$ Multiple myeloma arises from proliferation of a single clone of malignant antibody-producing cells.

Question 11

Other characteristics of Multiple myeloma (plasma cell myeloma/plasmacytoma)

Answer 11

Multiple myeloma arises from proliferation of a single clone of malignant antibody-producing cells.
The tumor cells produce massive quantities of identical immunoglobulin molecules demonstrable electrophoretically as a narrow serum band or, after densitometric scanning, as a sharp spike referred to as an M protein.
The M protein in multiple myeloma is most often an IgG or IgA immunoglobulin of either kappa or lambda light-chain specificity.
Synthesis of normal immunoglobulins is often impaired.
The marked serum immunoglobulin increase is often initially detected by laboratory screening as increased total protein with an increase in serum globulin (hyperglobulinemia).
The urine often contains significant quantities of free immunoglobulin light chains, either kappa or lambda, which are referred to as Bence Jones protein.
As a consequence of hyperglobulinemia, the red cells tend to congregate together in a manner reminiscent of a stack of poker chips (rouleaux formation). There is also a marked increase in the erythrocyte sedimentation rate.

Question 12

Clinical characteristics of Multiple myeloma (plasma cell myeloma/plasmacytoma)

Answer 12

Anemia due to neoplastic encroachment on myeloid precursor cells; possible leukopenia and thrombocytopenia

Increased susceptibility to infection because of impaired production of normal immunoglobulins

Hypercalcemia secondary to bone destruction; in contrast to the increased serum alkaline phosphatase that accompanies most other instances of hypercalcemia, the serum alkaline phosphatase in multiple myeloma is not increased.

Renal insufficiency with azotemia due to myeloma kidney (myeloma nephrosis). The renal lesion is characterized by prominent tubular casts of Bence Jones protein, numerous multinucleated macrophage-derived giant cells, and metastatic calcification, and sometimes by interstitial infiltration of malignant plasma cells.

Amyloidosis of the primary amyloidosis type

Question 13

Signs and symptoms of Multiple myeloma (plasma cell myeloma/plasmacytoma)

Answer 13

Persistent bone pain (especially in the back or thorax)
renal failure
recurring bacterial infections
Pathologic fractures are common, and vertebral collapse may lead to spinal cord compression and paraplegia.
Symptoms of anemia predominate
Peripheral neuropathy
carpal tunnel syndrome
abnormal bleeding
symptoms of hypercalcemia (eg, polydipsia) are common.

Question 14

Diagnosis of multiple myeloma (plasma cell myeloma/plasmacytoma)

Answer 14

CBC with platelets, peripheral blood smear, ESR, and chemistry panel (BUN, creatinine, Ca, uric acid, LDH)
Serum and urine protein electrophoresis followed by immunofixation
X-rays (skeletal survey)
Bone marrow examination

Question 15

Waldenström macroglobulinemia

Answer 15

is a manifestation of lymphoplasmacytic lymphoma, a B-cell neoplasm of lymphoid cells of an intermediate stage between B lymphocytes and plasma cells referred to as plasmacytoid lymphocytes.

In the case of Waldenström macroglobulinemia, the neoplastic cells produce a monoclonal IgM protein (lymphoplasmacytic lymphomas can also occur without protein production).

Defining characteristics
Serum IgM immunoglobulin of either kappa or lambda specificity occurring as an M protein
Plasmacytoid lymphocytes infiltrating the blood, bone marrow, lymph nodes, and spleen
Bence Jones proteinuria in about 10% of cases
Absence of bone lesions

Question 16

Clinical features of Waldenström macroglobulinemia

Answer 16

Most frequently seen in men older than 50 years of age

Slowly progressive course, often marked by generalized lymphadenopathy and mild anemia

Question 17

Complications of Waldenström macroglobulinemia

Answer 17

Hyperviscosity syndrome, which results from marked increase in serum IgM. Features include retinal vascular dilation, sometimes with hemorrhage, confusion, and other central nervous system changes. Sometimes, emergency plasmapheresis is required to prevent blindness.

Abnormal bleeding, which may be due to vascular and platelet dysfunction secondary to the serum protein abnormality

Question 18

Diagnosis of Waldenström macroglobulinemia

Answer 18

CBC with platelets, RBC indices, and peripheral blood smear
Serum protein electrophoresis followed by serum and urine immunofixation
Serum viscosity assay
Bone marrow examination
Sometimes lymph node biopsy

Question 19

Benign monoclonal gammopathy (monoclonal gammopathy of undetermined significance, or MGUS)

Answer 19

Monoclonal gammopathy of undetermined significance (MGUS) is the production of M-protein by noncancerous plasma cells in the absence of other manifestations typical of multiple myeloma.

The incidence of MGUS increases with age, from 1% of people aged 25 yr to > 5% of people > 70 yr.

MGUS usually is asymptomatic, but peripheral neuropathy can occur.

 Although most cases are initially benign, up to 25% (1%/yr) progress to myeloma or a related B-cell disorder, such as macroglobulinemia, amyloidosis, or lymphoma.

Diagnosis is usually suspected when M-protein is incidentally detected in blood or urine during a routine examination.

 MGUS is differentiated from other plasma cell disorders because M-protein levels remain relatively stable over time and lytic bone lesions, anemia, and renal dysfunction are absent.

However, patients show enhanced bone loss and a higher rate of fractures. Thus, baseline evaluation with a skeletal survey and bone densitometry should be done.

Question 20

LYMPHOID NEOPLASMS are…

Answer 20

Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems.
The major types are Hodgkin lymphoma and non-Hodgkin lymphoma

Question 21

Features of Hodgkins Lymphoma

Answer 21

Nodal involvement: Localized to a specific group of nodes

Spread: Tends to spread in an orderly, contiguous fashion

Effect on Waldeyer’s ring and mesenteric lymph nodes:
Usually does not affect

Extranodal involvement: Infrequent

Stage at diagnosis: Usually early

Histologic classification in children: Usually one with a favorable prognosis

Question 22

Features of non-hodgkins lymphomas

Answer 22

Nodal involvement: Usually disseminated among > 1 nodal group

Spread: Spreads noncontiguously

Effect on Waldeyer’s ring and mesenteric lymph nodes: Commonly affects mesenteric nodes; May affect Waldeyer’s ring

Extranodal involvement: Frequent

Stage at diagnosis: Usually advanced

Histologic classification in children: Usually high grade

Question 23

Characteristics, symptoms, diagnosis, and treatment of Hodgkin’s lymphoma

Answer 23

Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow.

Symptoms include painless lymphadenopathy, sometimes with fever, night sweats, unintentional weight loss, pruritus, splenomegaly, and hepatomegaly.

Diagnosis is based on lymph node biopsy.

Treatment is curative in about 75% of cases and consists of chemotherapy with or without radiation therapy.

Question 24

General characteristics of Hodgkin's lymphoma

Answer 24

Hodgkin lymphoma characteristically affects young adults (predominantly young men); an exception is nodular sclerosis, which frequently affects young women. Associated manifestations often include pruritus, fever, diaphoresis, and leukocytosis reminiscent of an acute infection. This neoplasm is characterized in all forms by the presence of Reed-Sternberg cells. The diagnosis of Hodgkin lymphoma depends on this histologic finding Reed-Sternberg cells are binucleated, or multinucleated, giant cells with eosinophilic inclusion-like nucleoli that may be the actual malignant cells of Hodgkin lymphoma. Differing numbers are found in varying forms of Hodgkin lymphoma, and the severity of the disease variants is directly proportional to the number of Reed-Sternberg cells found in the lesions. Conversely, the greater the number of reactive lymphocytes in the Hodgkin lymphoma variant, the better the prognosis

Question 25

Classification of Hodgkin lymphoma

Answer 25

``` Lymphocyte-predominance Hodgkin lymphoma Lymphocyte-rich Hodgkin lymphoma Mixed cellularity Hodgkin lymphoma Lymphocyte depletion Hodgkin lymphoma Nodular sclerosis Hodgkin lymphoma ```

Question 26

Lymphocyte-predominance Hodgkin lymphoma

Answer 26

 Features include large numbers of lymphocytes and histiocytes, as well as a paucity of Reed-Sternberg cells. There is no association with EBV infection. Peak incidence occurs in young and middle-aged men. The prognosis is relatively good.

Question 27

Lymphocyte-rich Hodgkin lymphomas

Answer 27

There is an association with EBV infection in 40% of cases. This variant is more common in men than in women.  The clinical course is moderately aggressive

Question 28

Mixed cellularity Hodgkin lymphoma

Answer 28

This variant is the one found most often in older persons. It is more common in men than in women. Characteristic features include a polymorphic infiltrate of eosinophils, plasma cells, histiocytes, and Reed-Sternberg cells, as well as areas of necrosis and fibrosis. There is an association with EBV infection in 70% of cases. The clinical course is moderately aggressive.

Question 29

Lymphocyte depletion Hodgkin lymphoma

Answer 29

This variant is the least frequently occurring form of Hodgkin lymphoma. Few lymphocytes, numerous Reed-Sternberg cells, and extensive necrosis and fibrosis are apparent. There is an association with EBV infection in the great majority of cases; this variant is also more common in persons with human immunodeficiency virus infection. This type of Hodgkin lymphoma has the poorest prognosis among all the variants.

Question 30

Nodular sclerosis Hodgkin lymphoma

Answer 30

This variant is the most frequently occurring form of Hodgkin lymphoma. Unlike other forms of Hodgkin lymphoma, this variant occurs more frequently in young women. Nodular division of affected lymph nodes by fibrous bands and the presence of lacunar cells, Reed-Sternberg cell variants, are characteristic. The neoplasm often arises in the upper mediastinum or lower cervical or supraclavicular nodes. There is rarely an association with EBV infection. The prognosis is relatively good.

Question 31

Clinical staging: Ann Arbor classification Hodgkin's lymphoma

Answer 31

This system of classification is based on the degree of dissemination, involvement of extralymphatic sites, and presence or absence of systemic signs such as fever . It is an essential part of the diagnostic evaluation of patients with Hodgkin lymphoma. Although grading of histopathologic variants roughly correlates with clinical behavior, prognosis is better predicted by staging (Ann Arbor classification).

Question 32

Ann Arbor Classification of Hodgkin and | Non-Hodgkin Lymphomas

Answer 32

I. Involvement of a single lymph node region (I) or involvement of a single extralymphatic organ or site (IE) II. Involvement of two or more lymph node regions on the same side of the diaphragm alone (II) or with involvement of limited contiguous extralymphatic organ or tissue (IIE) III. Involvement of lymph node regions on both sides of the diaphragm (III), which may include the spleen (IIIS), limited contiguous extralymphatic organ or site (IIIE), or both (IIIES). IV. Multiple or disseminated foci of involvement of one or more extralymphatic organs with or without lymphatic involvement

Question 33

Non-Hodgkin's lymphoma

Answer 33

Non-Hodgkin lymphomas (NHL) are a heterogeneous group of disorders involving malignant monoclonal proliferation of lymphoid cells in lymphoreticular sites, including lymph nodes, bone marrow, the spleen, the liver, and the GI tract. Presenting symptoms usually include peripheral lymphadenopathy. However, some patients present without lymphadenopathy but with abnormal lymphocytes in circulation. Tumor involvement of the periaortic lymph nodes is frequent. Compared with Hodgkin lymphoma, there is a greater likelihood of disseminated disease at the time of diagnosis. Diagnosis is usually based on lymph node or bone marrow biopsy or both.  Treatment involves radiation therapy, chemotherapy, or both. Stem cell transplantation is usually reserved for salvage therapy after incomplete remission or relapse.

Question 34

•Benign tumor of blood vessels

Answer 34

* Are the most common tumor of infancy * Two types: cavernous and capillary * Locations: usually on skin, especially face and scalp * Irregular red-blue masses (port-wine stains) * Regress spontaneously in many cases before 5 years old * Sometimes are part of Von Hippel-Lindau (VHL) disease ( CNS hemangioblastomas, pheochromocytoma, renal cell carcinoma + pancreatic cysts)