SPLENOMEGALY

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HUGE SPLENOMEGALYLYMPHOMA

• By Dina Ismail
• Assistant lecturer

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Causes

• Myeloproliferative disorders
• CML
• Myelofibrosis
• Polycythemia
• Essential thombocytopenia

Severe portal hypertension e.g. schistosomiasis

• Inflammation
• Feltys syndrome
• Sarcoidosis

• Heamatologic
• Thalathemia major

• Neoplastic
• Hairy cell leukemia
• Waldenstrom macroglobinaemia
• Lymphomas

• Infiltration
• Amyloidosis
• Gauchers disease

• Infections
• Malaria
• Leishmania

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The causes of splenomegaly are diverse, but they
may be conveniently grouped into the following
categories
INFLAMMATORY
HYPERPLASTIC
HUGE SPLENOMEGALY
INFILTRATIVE
CONGESTIVE
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HYPERPLASTIC SPLENOMEGALY

• Splenomegaly reflects work hypertrophy
• Resulting from the removal of abnormal blood
  cells from the circulation.
• Either cells with intrinsic defects or cells
  coated with antibody
• In some cases, as the result of extramedullary
  hematopoiesis (ie, myeloproliferative disease).

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INFLAMMATORY SPLENOMEGALY

• Acute enlargement of the spleen.
• Develops in association with various infections
  or inflammatory processes.
• Results from an increase in the defense
  activities of the organ.
• The demand for increased antigen clearance from
  the blood may lead to increased numbers of
  reticuloendothelial cells in the spleen and
  stimulate accelerated antibody production with
  resultant lymphoid hyperplasia.

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Continue

• CONGESTIVE SPLENOMEGALY
• Severe portal hypertension e.g.schistosomiasis
• Splenic vein occlusion (thrombosis)
• INFILTRATIVE SPLENOMEGALY
• The result of engorgement of macrophages
  with indigestible materials
• (eg, Gaucher disease, amyloidosis, metastatic
  malignancy).

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Methods for evaluation of splenomegaly

• Physical examination
• Imaging
• Ultrasongraphy
• Computed tomography
• Galluim scanning
• Position emission tomography
• Biopsy
• Needle aspiration (rarely performed)
• Splenectomy
• Laparotomy
• laparoscopy

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An approach to the patient with splenomegaly

• Does the patient have a known illness that
  causes splenomegaly (e.g. infectious
  mononucleosis). Treat and monitor for resolution.
• Search for an occult infection (infective
  endocarditis), heamatologic disorders (hereditary
  spherocytosis), occult liver disease (creptogenic
  cirrhosis), autoimmune disease (SLE), or storage
  disease (Gauchers disease), if found manage
  appropriately.

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ContinueAn approach to the patient with
splenomegaly

• If systemic symptoms are present and suggest
  malignancy and/or focal replacement of the spleen
  is seen on imaging studies and no other site is
  available for biopsy, splenectomy is indicated.
• If none of the above are true, monitor closely
  and repeat studies until the splenomegaly
  resolves or a diagnosis becomes apparent.

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EVALUATION OF A NEW PATIENT WITH SUSPECTED
LYMPHOMA ?

• Biopsy to establish diagnosis.
• lymphadenopathy or focal lesion
• Careful history and physical examination
• Laboratory evaluation
• CBC
• LDH level
• ß2 microglobulin.
• Imaging studies
• Chest radiograph
• CT scan of the chest, abdomen and pelvis
• Position emission tomography scan or galluim
  scan( consider with patient with diffuse large
  B-cell lymphoma and other aggressive histologic
  subtypes.
• Further biopsies
• Bone marrow
• Any other suspicious site if the result of the
  biopsy would change therapy.

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B2
microglobulin

• B2M is a protein associated with the outer
  membrane of many cells including lymphocytes.
• The high level is because it is subsequently
  released into the serum.
• The upper normal ranges from 2.0-2.5 m g/ml.
• B2M is present in small amounts in serum, CSF,
  and urine of normal people.
• B2M is used an adjunct test for active disease,
  cell turnover, and tumor presence.

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Continue B2M

• B2M is seen in inflammatory diseases e.g. R.A.
• Impaired renal function inhibits its clearance
  and results elevation of its level in serum.
• In HIV infections, B2M is frequently elevated.
• B2M is present to a much greater degree in the
  urine and serum of patients
• Acute lymphblastic leukemia.
• Chronic myelogenous leukemia.
• Acute myeloid leukemia.
• Multiple other leukemias.
• Some other malignancies with elevated B2M levels
  are lymphoma (Penz, et al 2001).
• Mulitple myeloma (MM), prostate cancer, ovarian
  cancer and renal cell carcinoma.
• Non-malignant condition associated with high B2M
  levels is pancreatitis.

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Continue B2M

• Although B2M is elevated in tumors
• It is clinically used for lymphoproliferative
  diseases e.g
• leukemia, lymphoma, and multiple myeloma,
• Its serum level is related to tumor cell load,
  prognosis, and disease activity.

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Continue B2M

• CSF levels of B2M are sometimes elevated in CNS
  acute lymphoblastic leukemia (ALL), lymphoma, and
  lymphoproliferative diseases.
• It only correlates with improvement of
  neurological disease in myeloproliferative
  disorders.

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NON-HODGKINS LYMPHOMA

• Malignant monoclonal proliferation of lymphoid
  cells in sites of the immune system, including
  lymph nodes, bone marrow, spleen, liver, and GI
  tract.
• The course varies from indolent and initially
  well tolerated to rapidly fatal.
• A leukemia-like picture may develop in up to 50
  of children and about 20 of adults with some
  types of NHL.

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• In about 30 of cases, the lymphomas are preceded
  by generalized lymphadenopathy.
• Response to chemotherapy is possible.
• Immunophenotyping reveals that 80 to 85 of NHLs
  arise from B cells, 15 from T cells, and lt 5
  from true histiocytes (monocyte-macrophages) or
  undefined null cells.

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Incidence

• Internationally
• NHL is the most prevalent hematopoietic neoplasm.
• Four of all cancer diagnoses
• Seventh in frequency among all cancers.
• NHL is more than 5 times as common as Hodgkin
  disease
• The incidence is increasing with age.

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MORTALITY MORBIDITY

• The potential for cure varies
• The different histologic subtypes.
• Directly relates to the stage at presentation.
• Patient response to initial therapy.
• In general
• low-grade lymphomas are indolent tumors median
  survival time of 5-10 years.
• Intermediate-grade and high-grade lymphomas are
  more aggressive but are more responsive to
  chemotherapy with median survival time of 2-5
  years and less than 2 years, respectively.

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• Race
• White people have a higher risk than black and
  Asian American people.
• Sex
• Male-to-female ratio 1.41, but the ratio may
  vary depending on the subtype of NHL.
• Age
• The median age at presentation for all subtypes
  of NHL is older than 50 years,
• Except for patients with high-grade lymphoblastic
  and small non-cleaved lymphomas, which are the
  most common types of NHL observed in children and
  young adults.

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ETIOLOGY

• Chromosomal translocations and molecular
  rearrangements play an important role in the
  pathogenesis of many lymphomas and correlate with
  histology and immunophenotype.
• t(1114)(q13q32) This translocation has a
  diagnostic non-random association with mantle
  cell lymphoma.

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Continue etiology Some viruses

• Probably because of their ability to induce
  chronic antigenic stimulation and cytokine
  dysregulation,? uncontrolled B- or T-cell
  stimulation, proliferation, and lymphomagenesis.
• Epstein-Barr virus (EBV) ? Burkitt lymphoma.
• Hepatitis C virus (HCV) is associated with the
  development of clonal B-cell expansions and
  certain subtypes of NHL (ie, lymphoplasmacytic
  lymphoma, Waldenström macroglobulinemia),
  especially in the setting of essential (type II)
  mixed cryoglobulinemia.

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Environmental factors

• Chemicals
• (eg, pesticides, herbicides, solvents organic
  chemicals, wood preservatives, dusts, hair dye),
• Chemotherapy.
• radiation exposure.
• Continue
  etiology

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IMMUNE SYSTEM ABNORMALITIES

• Immunodeficiency states are associated with
  increased incidence of NHL
• Characterized by a relatively high incidence of
  extranodal involvement, particularly of the GI
  tract and with aggressive histology.
• Primary CNS lymphomas can be observed in about 6
  of patients with AIDS.
• 
  Continue etiology

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CHRONIC INFLAMMATION

• Sjögren syndrome ? 30-40 fold ? with MALT.
• Hashimoto thyroiditis, which occurs in 16-23 of
  middle-aged and elderly females, is a preexisting
  condition in 23-56 of primary thyroid lymphomas.
• Helicobacter pylori infection is associated with
  the development of primary GI lymphomas,
  particularly gastric MALT lymphomas.
• Continue
  etiology

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PATHOPHYSIOLOGY

• NHL represents a progressive clonal expansion of
  B cells or T cells and/or natural killer (NK)
  cells, arising from the accumulation of genetic
  lesions that affect proto-oncogenes or tumor
  suppressor genes, resulting in cell
  immortalization.
• These oncogenes can be activated by chromosomal
  translocations.
• Tumor suppressor loci can be inactivated by
  chromosomal deletion or mutation.

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Continue PATHOPH

• The genome of certain lymphoma subtypes can be
  altered with the introduction of exogenous genes
  by various oncogenic viruses.
• Several cytogenetic lesions are associated with
  specific NHLs, reflecting the presence of
  specific markers of diagnostic significance in
  subclassifying various NHL subtypes

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The Working Formulation Classification

• Low-grade lymphomas (38)
• Intermediate-grade lymphomas (40)
• High-grade lymphomas (20)
• Miscellaneous lymphomas (2)

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WHO CLASSIFICATION OF NON-HODGKINS LYMPHOMA

• B CELL LYMPHOMA
• Precursor B-cell lymphoma
• Mature B-cell lymphoma
• T/NK-CELL LYMPHOMAS
• Precursor T-cell lymphoma
• Mature T/NK-cell lymphoma

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CLINICAL PRESENTATION

• Various clinical manifestations exist
• The most common presentation is lymphadenopathy.
• Which may be
• Asymptomatic peripheral lymphadenopathy.
• Symptomatic retroperitoneal or mediatinal
  e.g.chest pain, abdominal pain superior vena cava
  syndrome or renal insufficiency with ureteral
  compression.
• Enlarged lymph nodes are rubbery and discrete and
  later become matted.
• B symptoms fever, night sweat, unexplained
  weight loss and asthenia indicate disseminated
  disease.
• Lymphoma may involve any organ of the body.

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Continue CL PC

• Anemia is initially present in about 33 of
  patients and eventually develops in most.
• A leukemic phase develops in 20 to 40 of
  lymphocytic lymphomas and rarely in
  intermediate-grade lymphomas. High-grade
  lymphomas may frequently be leukemic.
• Lymphocytosis with circulating malignant cells.
• Thrombocytosis.

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Continue CL PC

• Elevated lactate dehydrogenase (LDH) - Poor
  prognostic factor, correlation with increased
  tumor burden.
• Beta2-microglobulin may be elevated and
  correlates with a poor prognosis.
• Hypogammaglobulinemia occurs in 15 of patients
  and may predispose to serious bacterial
  infection.
• Immunologic abnormalities can be the presenting
  manifestations
• Immune heamolytic anemia with positive Coombs
  test.
• Immune thrombocytopenias.

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Diagnosis

• Diagnosis can be made only by histologic study of
  excised tissue.
• Excisional lymph node biopsy is required for
  careful assessment of altered nodal architecture
  accompanying lymphomatous infiltrates.
• Fine-needle aspiration (FNA) is insufficient for
  establishing a diagnosis
• The usual histologic criteria are
• Destruction of normal lymph node architecture and
  invasion of the capsule and adjacent fat by
  characteristic neoplastic cells
• Immunophenotyping studies determine the cell of
  origin that will identify specific subtypes and
  help define prognosis and may aid in management
  decisions

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STAGING PROGNOSIS

• Localized NHL does occur, but the disease is
  disseminated in about 90 of follicular lymphomas
  and 70 of diffuse lymphomas when first
  recognized.
• The most common staging system is the Ann Arbor
  classification.
• International prognostic index The IPI considers
  five categories
• Agegt60 yrs, performance status, ? LDH level, gt1
  extranodal sites, and Ann Arbor stage III- IV.
• Prognostic groups of low, low intermediate, high
  intermediate, and high risk may be defined.

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Marginal Zone B-Cell Lymphoma

• Marginal zone B-cell lymphoma tends to progress
  slowly
• If this disease directly affects the lymph nodes,
  it is called monocytoid B-cell lymphoma
• If it affects lymphatic tissues at other sites
  (e.g., stomach, thyroid, skin), it is called
  mucosa-associated lymphatic tissue, or "MALT"
  lymphoma.
• Most low-grade gastric (stomach) lymphomas, and
  nearly half of all other gastric lymphomas, are
  MALT" lymphoma.
• MALT" lymphoma may arise in the stomach as well
  as the lungs, eye sockets, intestines, thyroid,
  salivary gland, bladder, kidney, and even the
  central nervous system (CNS).

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Continue.. Marginal Zone B-Cell Lymphoma

• It affects more women than men
• The average age at diagnosis is 65 years
• The majority of patients are diagnosed with
  localized, early-stage (Stage 1 or 2) extranodal
  disease
• Many patients have
• History of autoimmune disease e.g. Sjögrens
  syndrome or Hashimoto's thyroiditis.
• Bacterial infection of the stomach with
  Helicobacter pylori
• Research findings suggest that antibiotic therapy
  for Helicobacter pylori infection may prolong
  remission in early gastric MALT lymphoma.

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SPLENIC MARGINAL ZONE LYMPHOMA

• is a rare, slow-growing cancer.
• It also is known as "splenic lymphoma with
  villous lymphocytes"
• Uncommon form of B-cell chronic lymphocytic
  leukemia (B-CLL).
• Considered the splenic counterpart of MALT
  lymphoma.

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CONTINUESPLENIC MARGINAL ZONE LYMPHOMA

• Typically involves the spleen
• Occurs in adults
• Slightly more frequent in women than in men.
• Patients usually have splenomegaly
• No enlargement of the peripheral lymph nodes.
• Most patients show bone marrow involvement and
  modest increases in blood lymphocyte counts.

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Leukemic phase of non-Hodgkin lymphoma
Blood, Vol. 103, Issue 11,
4002, 2004

• Peripheral blood smear from a patient with a
  transformed low-grade lymphoma. The circulating
  lymphoma cells have a blastic appearance with
  intensely basophilic cytoplasm and prominent
  nucleoli.
• The leukemic phase is an adverse prognostic
  factor, being associated with poor response to
  therapy and aggressive disease.

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• By DINA ISMAIL

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