Classical Hodgkin’s Lymphoma

Presentation

  • Non tender lymphadenopathy most commonly in the upper body
  • Subdiaphragmatic lymphadenopathy is uncommon
  • 1/3 have B symptoms
  • Pel-Ebstein fever describes days to weeks of persistent fevers seperated by an afebrile period
  • Cutaneous manifestations include
    • Erythema nodosum
    • Ichthyosiform atrophy
  • Other presentations
    • Cerebellar degeneration
    • Nephrotic syndrome
    • Immune haemolytic anaemia
    • Thrombocytopaenia
    • Hypercalcemia
    • Lymph node pain on alcohol ingestion

Pathology

  • Reed-Sternbeg cell is the hallmark
  • Rare neoplastic B cells in a polyclonal inflammatory mass

Workup

  • CT chest/abdo/pelvis
  • PET or gallium scan
  • LDH
  • The usual baseline bloods

Treatment

  • Cure rate >90% for localised disease
  • Localised disase – neoadjuvant chemo + radiotherapy
  • Extensive disease – chemotherapy
  • Late side effects important due to very high cure rate
    • Carcinomas
    • Acute leukaemias
    •  Coronary artery disease
    • Hypothyroidism
    • Lhermitte’s sundrome
    • Infertility
Advertisements

Nodular Lymphocyte-Predominant Hodgkin’s Disease

  • Distinct from classical Hodgkin’s disease
  • Pathology shows plentiful small lymphocytes and rare Reed-Sternberg cells
  • Uncommon – <5% of Hodgkin’s disease
  • Clonal proliferation of B cells
  • Immunotype
    • JExpression of J chain
    • CD 45+
    • Epithelial membrane antigen (EMA) +
    • CD 30 –
    • CD 15 –
  • Chronic relapsing course
  • May transform into diffuse large B cell lymphoma
  • Controversial treatment
    • Watchful waiting
    • Radiotherapy for localised disease
    • Classic Hodgkin’s regimens for disseminated disease
  • Long term survival >80%

Aplastic Anaemia

Definition and causes

  • Pancytopaenia with bone marrow hypocellularity
  • Acquired
    • Cytotoxic chemotherapy
    • Radiation
    • Seronegative hepatitis (most common) / HIV / EBV / PB19
    • Graft v. host
    • Paroxysmal nocturnal haemoglobinuria
    • Immune disease
    • Hyperimmunoglobulinaemia
    • Benzene and other chemicals
    • Drugs
  • Genetic
    • Fanconi’s anaemia
    • Dyskeratosis congenita

Presentation

  • Pancytopaenia
  • Striking limitation of disease to haemtological system
    • BLeeding
    • Anaema
    • Infection is uncommon as first presentation
  • Weight loss / systemic symptoms implies another idsease process

Labs

  • Bloods
    • Large RBCs, lack of platelets and neutrophils
    • MCV increased
    • Few retics
    • Lymphocytes may be normal or low
    • Immature myeloid forms implies MDS or AML
  • Marrow
    •  Readily aspirable
    • Haemtopoietic cells <25% space
    • Lots of fat
  • Others
    • In kids, diepoxybutane or mitomycin C to exclude Fanconi’s anaemia
    • Telomere length > telomerase or sheltrin mutatin
    • Chromosome studies should be negative (e.g. Downs etc. implies MDS)
    • Flow cytometry (CD59-, CD55- > PNH)
    • Viral screens
    • Imaging

Treatment

  • HSC transplant
  • ATG + cyclosporin
  • Supportive transfusion

Burkitt’s Lymphoma / Leukemia

Classification

  • Endemic
    • African
  • Sporadic
    • Africa and the West
  • Immunodeficiency associated
    • HIV infection

Diagnosis

  • Histopathological diagnosis
    • Medium cells with round nuclei, basophilic cytoplasm and cytoplasmic vacuoles
  • 3 cytogenetic changes are confirmatory
    • t(8;14)
    • t(2;8) / c-myc and the λ light chain gene
    • t(8;22) / c-myc and the κ light chain gene

Presentation

  • In the West
    • Lymphadenopathy
    • Intraabdominal mass
    • Rapidly progressive
    • Predilection for CNS

Treatment

  • Rapid treatment within 2 days of diagnosis – Burkitt’s is the most aggressive of all human cancers
  • High dose cyclophosphamide
  • CNS prophylaxis essential
  • 70-80% cure rate

 

B Cell Chronic Lymphoid Leukemia / Small Lymphocytic Lymphoma

  • Most common lymphoid leukemia
  • 7% of all NHL when presenting as lymphoma
  • Rare in children

Clinical Presentation

  • B symptoms in 1/3
  • Typically found incidentally
  • Lymphoma presentation
    • Asymptomatic lymphadenopathy
    • +/- splenomegaly
  • Autoimmune complications are not uncommon
    • 50/50 split between normal Ig genes and mutated Ig genes
    • AIHA
    • AI thrombocytopaenia
    • Hypogammaglobulinaemia
    • Red cell aplasia

Diagnosis

  • Increased number of monoclonal CD5+ B cells in peripheral blood of FNA if presenting as lymphoma
    • Even when presenting as lymphoma 75% will have BM involvement
  • Bone marrow infiltration clinches the diagnosis
  • Peripheral smear shows
    • Smudge / basket cells (nuclear remnants of cells damaged by shear stress of making smear)
  • Cytogenetics
    • Trisomy 12 in 30%
    • Chromosome 13 abnormalities

Treatment

  • Watchful waiting
    • If only BM involvement and lymphocytosis
    • If adequate circulating blood counts, asymptomatic despite lymphadenopathy +/- splenenomegaly
  • Manage AI complicaitons independent of treating CLL
  • FCR (fludarabine/cyclophosphamide/rituximab) for well patients
  • Chlorambucil more gentle but fludarabine has better outcomes – chlorambucil can be given in elderly patients
  • Bendamustine also highly effective
  • RCHOP can be used in lymphoma presentation
  • Allogenic BM transplant can be curative but has major mortality

Prognosis

  • Patients with unmutated Ig genes tend to have worse outcomes
    • ZAP 70 cirrekateds with unmutated Ig genes but not validated yet
    • CD38 anecdotally is low in mutated Ig genes and high in unmutated genes but not validated yet
  • 50% 5-year survival

Diffuse Large B Cell Lymphoma

  • Most common NHL
  • 1/3 of all cases
  • Histopathological diagnosis

Presentation

  • Either primary LN site or extranodally
  • 50% have extranodal involvement at diagnosis
  • 15% have GIT involvement
  • 15% have bone marrow involvement
  • 25% of childhood NHL
  • 1/3 have B symptoms

Workup

  • Labs
    • FBC
    • LFT
      Uric acid
    • Calcium
    • QEPP
    • β2-microglobulin
  • Imaging
    • CXR
    • CT chest/abdo/pelvis
    • SPECT/PET scan
  • Bone marrow biopsy
  • LP if positive marrow

Management

  • RCHOP
  • 90% cure rate in Stage I
  • 70%  cure rate in Stage II
  •  40% will require salvage therapy
    • Long term disease free with alternate chemo <10%
    • Long-term disease free with autologous bone marrow transplant  – 40%

MALT lymphoma

  • 8% of NHL
  • Most MALT lymphomas are gastric of which 95% are associated with H. pylori
  • May occur in
    • Stomach
    • Orbit
    • Gut
    • Lung
    • Thyroid
    • Salivary gland
    • Skin and soft tissues
    • Bladder
    • Kidney
    • CNS
  • Diagnosis is given by infiltration of CD5- monoclonal B cells on histopathology
  • May transform to diffuse large B cell lymphoma

Genetics

  • Two main forms
    • t(11;18)
      • Usually not gastric (H. pylori related MALT lymphomas do not show t(11:18))
      • t(11:18) > of NF-κB activation > cell survival
      • Genetically stable and do not progress to diffuse large B cell lymphoma
    • Multiple sites of instability including trisomies 3, 7, 12, and 18
      • Often acuire BCL6 mutations > aggresive lymphoma

Clinical Picture

  • Rare in children
  • B symptoms in 20%
  • Localised to organ in 40%
  • Organ and LN group in 30%
  • Associations with
    • Sjoegren’s
    • Hashimoto’s
    • H. pylori gastritis
    • C. psittaci conjunctivitis
    • Borrelia skin infections

Workup

  • Labs
    • FBC
    • LFT
    • Uric acid
    • Calcium
    • QEPP
    • Serum β2-microglobulin
  • Imaging
    • CXR
    • CT abdo / pelvis / chest
  • Bone marrow biopsy

Treatment

  • Eradication of H. pylori = 80% of cases will resolve
  • Chlorambucil
  • Combinations with rituximab

Prognosis

  • 75% 5-year survival
  • 90% 5-year survival with low IPI score
  • 40% 5-year survival with high IPI score