Transcript Leukocyte Disorders Part 2 Lymphomas and Other Disorders

Leukocyte Disorders
Part 2
Lymphomas and Other Disorders
Walter C. Bell, MD
Normal Lymph Node
Acute Nonspecific
Lymphadenitis
• Lymph node enlargement due to infection
• Most often involves cervical nodes (teeth,
tonsils) or axillary nodes (skin infections
involving arms)
• Nodes are enlarged due to edema and
tender due to capsular distension
• Nodes may develop abscesses with
redness of overlying skin, drainage
through fistula tract
Chronic Lymphadenitis
• Follicular Hyperplasia:
– Rheumatoid arthritis, toxoplasmosis, early
HIV
• Paracortical Hyperplasia:
– Viral infections (mono), vaccinations
• Sinus histiocytosis:
– Filling of sinuses with histiocytes
– Non-specific
Reactive Follicular Hyperplasia
Lymphoma
• Lymphoid neoplasm producing a mass
either through enlargement of lymph
nodes or involvement of another organ
• Lymphocytic leukemia vs lymphoma
– Leukemia circulating, lymphoma mass effect
– In reality, much overlap
• Non-Hodgkin or Hodgkin: broad grouping
Lymphoma
• Classified by cell type (B or T), growth
pattern, immunophenotype, and genetic
aberrations
• 5 broad categories
–
–
–
–
–
Precursor B-cell neoplasms (immature B cells)
Peripheral B-cell neoplasms (mature B cells)
Precursor T-cell neoplasms
Peripheral T-cell and NK cell neoplasms
Hodgkin lymphoma
• Histologic examination of tissue required for
diagnosis
Lymphoma
• Vast majority of lymphoid neoplasms are
of B-cell origin (80-85%)
Follicular Lymphoma
• 45% of adult lymphoma; most common form of
lymphoma in the US
• Older patients
• Generalized lymphadenopathy, spleen frequently
involved
• Indolent, but difficult to cure
• Bone marrow almost always involved at diagnosis
• Characteristic translocation t(14;18)
• Transformation into more aggressive diffuse large
B-cell lymphoma with survival of less than 1 yr.
Follicular Lymphoma
Diffuse Large B-cell Lymphoma
•
•
•
•
•
20% of adult lymphomas
Older pts as well as children
Diffuse growth pattern
Extranodal disease seen
Marrow involvement uncommon at
diagnosis
• Aggressive, but up to 50% are curable
• May be associated with immunodeficiency
Diffuse Large B-cell Lymphoma
Burkitt Lymphoma
• Three types
– Endemic African Burkitt lymphoma
– Sporadic Burkitt lymphoma
– HIV associated
• Histologically identical
• All forms associated with c-MYC
translocations on chromosome 8 (t(8;14)
most common)
• EBV infection seen in all endemic cases and
20-25% of other types
Burkitt Lymphoma
• Children and young adults
• 30% of childhood NHL in US
• Endemic
– Mass involving mandible; also frequently involves
abdominal organs – kidneys, ovaries, adrenals
• Sporadic
– Abdominal mass involving ileocecum and peritoneum
• Bone marrow involvement uncommon
• In general, children and young adults can be cured
with chemotherapy, older patients have a poorer
prognosis
Burkitt Lymphoma
“Starry Sky” Appearance
Mantle Cell Lymphoma
• 3% of all NHL in US
• Older males
• Painless lymphadenopathy; GI tract
frequently involved
• Most have t(11;14)
• Aggressive
Mantle Zone Lymphoma
Hodgkin Lymphoma
• Arises in a single node and spreads to
contiguous nodes
• In advanced stages may spread to
extranodal sites
• Reed-Sternberg cells (1-5% of tumor
mass)
– B-cell origin
– Induce accumulation of reactive lymphocytes,
histiocytes and granulocytes
Hodgkin Lymphoma
• Four subtypes:
– Nodular sclerosing: most common
– Mixed cellularity: most common over age 50
– Lymphocyte predominance
– Lymphocyte depletion: rare
Hodgkin Lymphoma
• Tumor stage at diagnosis predicts outcome
• Low stage – 90% cure
• Advanced stage – 60 – 70% 5 year disease
free survival
• Long term survivors have increased risk of
developing second cancers secondary to
radiation and chemotherapy (breast cancer
particularly high in females treated with chest
radiation as adolescents)
Reed-Sternberg Cells
Clinical Differences Between Hodgkin’s
and Non-Hodgkin’s Lymphomas
Hodgkin’s Disease
Non-Hodgkin’s Lymphoma
• More often localized
to a single axial group
of nodes
(cervical, mediastinal,
para-aortic)
• Spreads by contiguity
• Mesenteric nodes and
Waldeyer’s ring rarely
involved
• Extranodal
involvement
uncommon
• More frequent
involvement of multiple
peripheral nodes
• Noncontiguous spread
• Waldeyer’s ring and
mesenteric nodes
commonly involved
• Extranodal
involvement common
Multiple Myeloma
• Plasma cell disorder characterized by
multiple masses of neoplastic plasma cells
throughout the skeletal system
(plasmacytoma if solitary)
• Can spread to lymph nodes and skin
• Incidence higher in older men and people
of African descent
Multiple Myeloma
• Infiltration of bone, punched out defects on
radiographs
– Pathologic fractures
– Hypercalcemia
• Production of excess immunoglobulins
– M protein on protein electrophoresis
– Rouleaux formation in peripheral blood
– Renal failure (light chains toxic to renal tubular
epithelial cells)
• Suppression of normal humoral immunity
– Bacterial infections
Multiple Myeloma
Rouleaux Formation
Langerhans Cell Histiocytoses
• Clonal proliferation of Langerhans cells
which are dendritic antigen-presenting
cells in many organs, including skin
• Old name: Histiocytosis X
Langerhans Cell Histiocytoses
• Multifocal multisystem type
– Usually in children before the age of 2 yrs
– Cutaneous lesions on back, trunk, scalp
– Hepatospenomegaly, lymphadenopathy,
pulmonary lesions, destructive bone lesions
– Infiltration of marrow leads to anemia,
thrombocytopenia, infection (otitis media
mastoiditis)
– Rapidly fatal, 50% 5 year survival with therapy
Langerhans Cell Histiocytoses
• Unifocal/Multifocal type
– Eosinophilic granuloma
– Accumulation within medullary cavity of bone with
associated eosinophilic infiltrate
• Pulmonary disease seen in adult smokers
– Can regress spontaneously on cessation of
smoking
– Polyclonal, likely reactive
• Langerhans cells contain the characteristic
Birbeck granule by electron microscopy and
stain for CD1a and S-100
Birbeck Graunules
Pathology of the Spleen
• Acute Splenitis: Associated with
bloodborne infections
– May be painful with necrosis and abcess
formation
• Congestive Splenomegaly:
– Systemic: due to right sided heart failure
– Cirrhosis
– Partal vein thrombosis
Splenic Infarcts
• Due to emboli from
thrombi in the heart
• May be septic if
associated with bacterial
endocarditis
• Wedge shaped infarcts
• May also be associated
with splenomegaly due to
outgrowing blood supply
Splenic Pathology
• Primary neoplasms are rare
– Hemangioma most common primary
neoplasm
• Accessory spleens: common, 20-30%
• Rupture
– Usually associated with crushing injury,
severe blow
– Extensive intraperitoneal hemorrhage;
surgical emergency
Thymic Pathology
Thymic Pathology
• Hyperplasia
– Follicular hyperplasia with prominent lymphoid
follicles
– Associated with myasthenia gravis (present in
70% of cases)
– Occasionally seen in other autoimmune
disorders
Thymoma
•
•
•
•
Neoplasm of thymic epithelial cells
Tumors of adults usually over the age of 40.
Occur in the anterior superior mediastinum
Most are benign, may be malignant (thymic
carcinoma)
• Present due to compression of mediastinal
structures.
• Associated with myasthenia gravis.
Case 1
• A 67- year old male presents with
weakness, fatigue, and weight loss
worsening over several months.
• Headaches
Slide 15.19
Multiple Myeloma
Case 2
• A 12 year old male presents with a
mandibular mass.
X-Ray
• 7 cm expansile mass in mandible
Biopsy
Bx Interpretation
• Lymphoid neoplasm with “starry sky”
appearance, c/w Burkitts lymphoma
• Diagnosis confirmed by flow cytometry
(monoclonal B cell population) and
cytogenetics (t8:14)
Case 3
• A 4 year old child has been increasingly
listless for about a week. He now
complains of pain when picked up and has
bruising on his arms and legs.
CBC
• Anemia
• Thrombocytopenia
• Blasts on smear
Flow Cytometry
• Blasts are CD19 positive (B-cell marker)
Case 3
• Dx: ALL
Case 4
• A 45 year old male experienced gradual
weight loss, weakness, anorexia
increasing over several months. Physical
exam reveals splenomegaly
CBC
• Nl Hct, platelets
• White count 168,000 ( normal 400011000)
Smear
Case 4
• Dx: CML
• Patient treated with chemotherapy with
resolution of symptoms
Case 5
• A 38 year old female presents with
dyspnea.
Chest radiograph
• Mediastinal widening
• CT- 10 cm mediastinal mass impinging on
trachea
Biopsy
Case 5
• Dx: Hodgkin’s Lymphoma
End