Clin Med II Exam 2 - HEME (LYMPHOMAS & MYELOMA)

gbalsam

lymphoma

cancer that starts in the lymph nodes or the lymphatic system that invades other organs by unnecessary and uncontrollable growth of lymphoid tissue

myeloma

a type of cancer that occurs in blood-making cells found in the red bone marrow; abnormally dividing plasma cells

Hodgkin's lymphoma

distinguished from other lymphomas by the presence of large, cancerous lymphocytes known as Reed-Sternberg cells

patho of Hodgkin's lymphoma

mature B cells transformed into malignant cells

classic feature of Hodgkin's lymphoma

tendency to arise within single lymph node areas and spread in an orderly fashion to contiguous lymph nodes

most common Hodgkin's lymphoma subtype

nodular sclerosis

etiology of Hodgkin's lymphoma

- unknown

- possible virus (risk linked to EBV as cells are unable to manufacture intact antibodies)

- some evidence for tumor associated antigens

classic Hodgkin's lymphoma

- nodular sclerosis

- lymphocyte rich

- mixed cellularity

- lymphocyte depleted

non-classic Hodgkin's lymphoma

nodular lymphocyte predominant

symptoms of Hodgkin's lymphoma

- often asymptomatic

- painless lymphadenopathy most commonly in the neck

- constitutional "B" symptoms (may be sign of advanced disease)

- generalized and severe pruritis

- pain associated with alcohol ingestion in specific sites or regions (often lymph nodes or bones)

- anemia symptoms

- persistent non-productive cough

- headache and facial fullness

- weakness and numbness

constitutional "B" symptoms

fever, weight loss, or drenching night sweats

pel-ebstein fever

relapsing, high-grade fever that can reach 105-106ºF with a periodicity of 7-10 days

signs of Hodgkin's lymphoma

- non-tender lymphadenopathy in the neck, supraclavicular area, and axilla

- mediastinal mass (may cause dysphagia, dyspnea, cough, stridor, or the superior vena cava syndrome)

- T-cell mediated immune deficiency leading to propensity to infections (i.e., herpes zoster, fungal or mycobacterial infections, etc.)

less common signs of Hodgkin's lymphoma

- splenomegaly and hepatomegaly

- peripheral weakness and numbness with attenuated reflexes

- plethora and distended neck and facial veins

- variety of skin lesions (i.e., ichthyosis, Bazex syndrome, urticaria, etc.)

nodular sclerosis Hodgkin's lymphoma

disease above the diaphragm and mediastinal node involvement

lymphocyte depletion Hodgkin's lymphoma

presents with abdominal nodal involvement and often has extra-nodal disease (advanced with systemic "B" symptoms)

which subtypes of Hodgkin's lymphoma often present with disease of the liver?

mixed cellularity or lymphocyte depletion

nodular lymphocyte-predominant Hodgkin's lymphoma

localized peripheral disease in the upper neck

Waldeyer's ring

the ring of lymphatic tissue formed by the two palatine tonsils, the pharyngeal tonsil, the lingual tonsil, and intervening lymphoid tissue

superior vena cava syndrome

progressive occlusion of the superior vena cava that leads to venous distention of upper extremities and head

immunophenotyping of Hodgkin's lymphoma

CD30 and CD15 markers

diagnosis of Hodgkin's lymphoma

excisional nodal biopsy required; presence of Reed-Sternberg cells in an inflammatory background containing a variable number of small lymphocytes, eosinophils, neutrophils, histiocytes, plasma cells, fibroblasts, and collagen fibers

Hodgkin's lymphoma stage I

single lymph node region involved

Hodgkin's lymphoma stage II

involvement of two lymph node areas on one side of the diaphragm

Hodgkin's lymphoma stage III

lymph node regions involved on both sides of the diaphragm

Hodgkin's lymphoma stage IV

disseminated disease with bone marrow or liver involvement

Hodgkin's lymphoma stage A

lack of constitutional symptoms

Hodgkin's lymphoma stage B

there is a 10% weight loss over 6 months, fever, or night sweats ("B" symptoms)

Hodgkin's lymphoma stage X

bulky disease; mediastinal mass with a maximum width that is ≥1/3 of the internal transverse diameter of the thorax

Hodgkin's lymphoma stage E

(local) extra-nodal disease

standard treatment of Hodgkin's lymphoma

"ABVD"

- adriamycin

- bleomycin

- vinblastine

- dacarbazine

other treatments of Hodgkin's lymphoma

- BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, prednisone)

- standford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone)

- add radiation in stages I-II

treatment of Hodgkin's lymphoma in patients with primary refractory disease

may attain double responses and remissions with second line chemotherapy that incorporates drugs not used in the initial treatment (i.e., ABVD) followed by high dose chemotherapy and autologous hematopoietic cell rescue

treatment of Hodgkin's lymphoma in patients with secondary refractory disease

these patients are high candidates for high dose chemotherapy and autologous hematopoietic cell transplantation as well

complications of Hodgkin's lymphoma

- high incidence of second malignancies (leukemia first 10 years, followed by solid tumors over time)

- hypothyroidism

- constrictive pericarditis

- infertility (after the use of alkylating agents)

- heart failure after adriamycin treatment

non-Hodgkin's lymphoma

a large group of more than 60 different malignant subtypes that arise from the lymphoid system

subtypes of non-Hodgkin's lymphoma

- B-cell origin (most common)

- T-cell origin

- natural killer cell-origin

essentials of diagnosing non-Hodgkin's lymphoma

- patient presenting with painless lymphadenopathy

- no Reed-Sternberg cells or eosinophilia

- diagnosis is confirmed by excisional tissue biopsy

- nearly all respond to chemotherapy and/or radiation therapy

etiology of non-Hodgkin's lymphoma

- unknown

- higher risk for individuals who have been exposed to chemicals, EBV history, family history, HIV

patho of non-Hodgkin's lymphoma

each type can be viewed as a lymphocyte arrested at a certain stage of development and transformed into a malignant cell

patho of Burkitt lymphoma

proto-oncogene c-myc is translocated from chromosome 8 to heavy chain locus on chromosome 14

patho of follicular lymphomas

t(14,18) translocation is characteristic resulting in an overexpression of bcl-2

prognosis of low grade non-Hodgkin's lymphoma

incurable

prognosis of aggressive non-Hodgkin's lymphoma

potentially curable

symptoms of non-Hodgkin's lymphoma

- isolated or diffuse lymphadenopathy

- constitutional symptoms (fever, night sweats, weight loss)

signs of non-Hodgkin's lymphoma

- lymphadenopathy that may fluctuate or spontaneously remit

- hematogenous spread of disease with no predictable pattern

- extra-nodal primary more common in high grade lymphomas

- Waldeyer's ring involvement frequent in GI lymphomas

- cytopenias

- hepatosplenomegaly

- abdominal pain or abdominal fullness (Burkitt lymphoma)

diagnosis of non-Hodgkin's lymphoma

lymph node and tissue biopsy with paratrabecular lymphoid aggregates

patho of mantle cell lymphoma

t(11,14) translocation resulting in cyclin D1 gene

when would you get a lumbar puncture in working up non-Hodgkin's lymphoma?

if you suspect

- AIDS lymphoma

- T-cell lymphoblastic lymphoma

- high grade lymphoma with positive marrow

T-cell lymphomas

- anaplastic large cell lymphoma

- peripheral T-cell lymphoma

- mycosis fungoides

B-cell lymphomas

- MALT

- hairy cell leukemia

- follicular lymphoma

- mantle cell lymphoma

- diffuse large B-cell lymphoma

- Burkitt lymphoma

most common indolent B-cell lymphoma

follicular lymphoma (grade I and II)

one of the most indolent T-cell lymphomas

mycosis fungoides

most common aggressive B-cell lymphoma

diffuse large B-cell lymphoma

highly aggressive B-cell lymphomas

- Burkitt lymphoma

- precursor B lymphoblastic leukemia/lymphoma

highly aggressive T-cell lymphomas

- adult T-cell lymphoma/leukemia

- precursor T lymphoblastic leukemia/lymphoma

acute treatment of non-Hodgkin's lymphoma

- chemotherapy with alkylating agents (i.e., chlroambucil)

- combo chemotherapy with cyclophosphamide, vincristine, and prednisone

- rituximab as salvage therapy for relapsed low-grade B-cell lymphomas

CHOP therapy in non-Hodgkin's lymphoma

cyclophosphamide, doxorubicin, vincristine, and prednisone plus localized radiation for localized intermediate-grade lymphomas

worse prognosis of non-Hodgkin's lymphoma

- age over 60

- elevated serum LD

- stage III or IV

- poor performance status

Burkitt lymphoma

most rapidly growing human tumor that arises from B-cells

endemic (African) Burkitt lymphoma

jaw tumor that is strongly linked to the Epstein-Barr virus

non-endemic (sporadic) Burkitt lymphoma

usually has an abdominal presentation, most often with massive disease and ascites

treatment of Burkitt lymphoma

multi-drug regimen (urgent and intensive chemotherapy) similar to pediatric leukemia/lymphoma regimens

mycosis fungoides

cutaneous T-cell lymphoma (malignancy of helper T-cells)

presentation of mycosis fungoides

skin lesions include patches or plaques that may be localized or widespread, tumors, and erythroderma

erythroderma

abnormal redness of the entire skin surface

treatment of mycosis fungoides

can be treated with electron beam radiation, UV light therapy, or topical alkylating agents

adult T-cell leukemia/lymphoma

associated with HTLV-1 infection and characterized by hepatosplenomegaly, leukocytosis, lymphadenopathy, skin involvement, lytic lesions of the bone, and hypercalcemia

treatment of adult T-cell leukemia/lymphoma

may respond to AZT and interferon

AIDS lymphoma

aggressive lymphomas of b cell origin (Burkitt, Burkitt-like, and large cell immunoblastic)

MALT lymphoma

aka "mucosa-associated lymphoid tissue;" chronic infection of the stomach by H. pylori

treatment of MALT lymphoma

combination antibiotics with proton pump inhibitor acid blockade

ocular adnexal lymphoma (OAL)

lymphoma affecting the tissues surrounding the eye that may arise after chronic inflammation

treatment of ocular adnexal lymphoma

may response to antibiotic therapy against chlamydia (i.e., doxycycline)

follicular lymphoma

neoplastic proliferation of small B cells (CD20+) that form follicle-like nodules

most common presentation of follicular lymphoma

new, painless lymphadenopathy (with multiple sites common)

diagnosis of follicular lymphoma

small cleaved and large cells in varying proportions organized in a follicular pattern of growth

treatment of follicular lymphoma

highly responsive to radiation/chemo but unlikely to be cured

diffuse large B-cell lymphoma

neo-plastic proliferation of large B cells (CD20+) that grow diffusely in sheets

signs/symptoms of diffuse large B-cell lymphoma

- rapidly enlarging symptomatic mass, most usually nodal enlargement in the neck or abdomen

- systemic "B" symptoms in 30%

- bone marrow involvement in 30%

- extra-nodal extramedullary disease in 40%

diagnosis of diffuse large B-cell lymphoma

- large, transformed B-cells with prominent nucleoli and basophilic cytoplasm

- diffuse growth pattern

- B-cell markers CD20 and CD79a

treatment of diffuse large B-cell lymphoma

chemo (R-CHOP)

international prognostic index

used to categorize patients with intermediate-grade lymphoma into risk groups

international prognostic index (0-1 risk factor)

80% complete response rate to standard chemotherapy

international prognostic index (2 risk factors)

70% complete response rate to standard chemotherapy

international prognostic index (more than 2 risk factors)

lower response rates and poor survival with standard regimens; early treatment with high-dose therapy and autologous stem cell transplantation

complications of non-Hodgkin's lymphoma

- cytopenias secondary to bone marrow infiltration

- bleeding secondary to thrombocytopenia

- infection

- cardiac problems secondary to large pericardial effusion

- respiratory problems secondary to pleural effusion

- SVC syndrome secondary to large mediastinal mass

- spinal cord compression secondary to vertebral metastases

- neurologic problems

- GI obstruction, perforation, and bleeding

- pain secondary to tumor invasion

- leukocytosis

multiple myeloma

a collection of abnormal plasma cells that accumulate in the bone marrow where they interfere with the production of normal blood cells

overview of multiple myeloma

- disease of malignant B-lymphocytes

- plasma cell dyscrasia/cancer characterized by the presence of anemia, hypercalcemia, lytic bone lesions, and renal failure

- associated with increased levels of a monoclonal immunoglobulin detectable on SPEP or UPEP

prognosis of multiple myeloma

treatment with chemotherapy or autologous hematopoietic cell transplantation can improve renal function, decrease fracture risk, and improve cytopenias resulting in prolonged survival, but treatment is rarely curative

etiology of multiple myeloma

- unknown

- possible predisposing factor of viral infection of human herpes virus 8 (HHV 8)

- MGUS (monoclonal gammopathy of undetermined significance)

clinical features of multiple myeloma

- bone marrow failure: anemia, thrombocytopenia, neutropenia

- renal failure

- bone disease with skeletal destruction (lytic lesions, generalized decrease in bone density)

- hypercalcemia

- hyperviscosity syndrome

- recurrent infections

- amyloidosis

- neurological symptoms

hyperviscosity syndrome

clinical sequelae of increased blood viscosity; increased serum viscosity results from increased circulating serum immunoglobulins

amyloidosis

rare disease that occurs when amyloid builds up in your organs

bone "break" in multiple myeloma

- bone pain

- recurrent infection

- elevated calcium

- anemia

- kidney failure

labs found in multiple myeloma

- anemia

- RBC morphology normal but rouleaux formation common

- hypercalcemia

- proteinuria (Bence-Jones proteins)

- ESR elevated

- plasma cells rarely visible on peripheral blood smear

- monoclonal spike in B- or γ-globulin region

- clonal plasma cells on bone marrow biopsy

poor survival associated with multiple myeloma

B-microglobulin level >3 mg/L

dismal outcome associated with multiple myeloma

if bone marrow cytogenetic analysis shows deletions of chromosome 13q

lytic bone lesions

"punched out" lesions found especially in axial skeleton (i.e., skull, spine, proximal long bones, and ribs)

diagnosis of multiple myeloma

≥10% clonal plasma cells in the bone marrow or biposy-proven bony/soft tissue plasmacytoma plus one of the following:

- presence of related organ or tissue impairment (i.e., increased calcium, renal deficiency, anemia, lytic lesions)

- presence of a biomarker associated with near inevitable progression to end-organ damage