pulmonary maifestaion of hodgkin and non hodgkin lymphoma

1. PULMONARY MANIFESTAION OF
HODGKIN AND NON HODGKIN
LYMPHOMA & MANAGEMENT
PRESENTED BY
DR NASIR ALI ZAKI
PGR PULMONOLGY

2. OBJECTIVES
• INTRODUCTION OF HL & NHL
• CLINICAL FEATUERS
• CHEST LYMPHOMA
• INVESTIGATION
• MANAGEMENT
• PROGNOSIS

3. Hodgkin diseaseHodgkin disease
• A neoplastic transformation of lymphocyte
particular in the lymph nodes.
• The histological hallmark of Hodgkin
lymphoma (HL) is the presence of Reed–
Sternberg cells, large malignant
lymphoid cells of B cell origin

4. Fig. 24.28 Hodgkin lymphoma. In the centre of this lymph node biopsy
is a large typical Reed–Sternberg cell with two nuclei containing a
prominent eosinophilic nucleolus.

5. Epidemiology and aetiology of
Hodgkin lymphoma
• Incidence
• ~4 new cases/100 000 population/yr
• Sex ratio
• Slight male excess (1.5 : 1)
• Age
• Median age 31 yrs; first peak at 20–35 yrs and
second at 50–70 yrs

6. Aetiology
• Unknown
• More common in patients from well-educated
backgrounds and small families

7. Hodgkin disease : ClassificationHodgkin disease : Classification
• Types of Hodgkin lymphoma
– Lymphocyte predominant
• <5% , young patients
– Nodular sclerosing
• 70%
– Mixed cellularity
• 25%
– Lymphocyte depleted
• <5%

8. • Nontender lymph nodes enlargement (localized)
– neck and supraclavicular area
– mediastinal adenopathy
– other (abdominal, extranodal disease)
• systemic symptoms (B symptoms)
– fever
– night sweats
– unexplained weight loss (10% per 6 months)
• other symptoms
– fatigue, weakness, pruritus
– cough , chest pain, shortness of breath, vena cava
syndrome
– abdominal pain, bowel disturbances, ascites
– bone pain
Hodgkin’s Disease/Lymphoma
Clinical Presentation

9. SIGNS & SYMPTOMS % OF PATIENTS
Lymphadenopathy 90
Mediastinal mass 60
“B” symptoms 30
Fever, weight loss, night sweats
Hepatosplenomegaly 25
• Most commonly involved lymph nodes are the
cervical and supraclavicular in 75%
• Bone marrow is involved in 5% of patients
Hodgkin’s Disease/Lymphoma
Clinical Presentation

10. Lymphnodes group

11. Clinical stages of Hodgkin lymphoma
(Ann Arbor classification)
• Stage Definition
• I Involvement of a single lymph node
or SINGLE extralymphatic* site
• II Involvement of two or more lymph node
regions (II)or an extralymphatic site and
lymph node regions on the same side of
(above or below) the diaphragm

12. III Involvement of lymph node regions on both sides
of the diaphragm with or without localised
extralymphatic involvement or involvement of the
spleen .both
IV Diffuse involvement of one or more
extralymphatic, e.g. liver or bone marrow
• Each stage is subclassified:
• A No systemic symptoms
• B Weight loss > 10%, drenching sweats, fever
• *The lymphatic structures are defined as the lymph
nodes, spleen, thymus,
• Waldeyer’s ring, appendix and Peyer’s patches.

13. Non-Hodgkin lymphoma
• Non-Hodgkin lymphoma (NHL) represents a
monoclonal proliferation of lymphoid cells of
B cell (70%) or T cell (30%) origin.
• Heterogenous group of lymphoproliferative
malignancies

14. • Non-Hodgkin lymphomas are classified
as low- or high-grade tumours on the basis of
their proliferation.
• High-grade tumours divide rapidly, are typically
present for a matter of weeks before diagnosis,
and may be life-threatening.
• Low-grade tumours divide slowly, may be present
for many months before diagnosis, and typically
behave in an indolent fashion.

15. Non-Hodgkin LymphomaNon-Hodgkin Lymphoma
• 4 x more common than Hodgkin disease
• Intrathoracic involvement in 50% of newly diagnosed
cases ( vs 80% in HD )
• 60% originate in lymph nodes & 40% in extranodal
sites
– 70-85% arise from B-cells and 15% from T-cells
• Increased incidence in patients with altered immune
status
– Transplant patients, AIDS, Collagen vascular
diseases

16. Epidemiology and aetiology of
non-Hodgkin lymphoma
• 12 new cases/100 000 people/year
• Sex ratio
• Slight male excess
• Age
• Median age 65–70 yrs
• Aetiology
• No single causative abnormality described
• Lymphoma is a late manifestation of HIV infection

17. • Specific lymphoma types are associated
with viruses: e.g. Epstein–Barr virus
(EBV) with post-transplant NHL
• human T-cell lymphotropic virus (HTLV)
with adult T-cell leukaemia lymphoma
• Gastric lymphoma can be associated
with Helicobacter pylor iinfection

18. • Some lymphomas are associated with specific
chromosomal translocations; the t(14;18) in
follicular lymphoma results inthe dysregulated
expression of the BCL-2 gene product,which inhibits
apoptotic cell death.
The t(8;14) found in Burkitt lymphoma and the
t(11;14) in mantle cell lymphoma alter function of
c-myc and cyclin D1, respectively, resulting in
malignant proliferation

19. Indolent (35%)
Diffuse large
B-cell (31%)Armitage et al. J Clin Oncol. 1998;16:2780–
2795
Mantle cell (6%)
Peripheral T-cell (6%)
Other subtypes with a
frequency ≤2% (9%)
Frequency of NHL Subtypes in Adults
Composite
lymphomas (13%)

20. • Clinical featuers
Unlike Hodgkin lymphoma, NHL is often widely
disseminated at presentation, including in extranodal
sites.
• systemic upset: weight loss, sweats, fever and
itching.
• extranodal involvement include the bone marrow,
gut, thyroid, lung, skin, testis, brain and, more rarely,
bone
• Compression syndromes may occur, including
gut obstruction, ascites, superior vena cava
obstruction and spinal cord compression.

21. • Hepatosplenomegaly
• . Bone marrow involvement is more common in low-
grade (50–60%) than high- grade (10%)disease.
• The same staging system is used for both HL and
NHL, but NHL is more likely to be stage III or IV at
presentation.

22. Lymphoma : Chest involvementLymphoma : Chest involvement
A. Nodal disease
B. Pulmonary parenchymal involvement
C. Pleura
D. Heart & pericardium
E. Chest wall

23. A) Nodal chest involvementA) Nodal chest involvement
• Hodgkin disease
– Thoracic involvement in 85% of newly diagnosed
cases
– Best diagnostic clue for intrathoracic disease is
mediastinal lymphadenopathy
• Predilection for the anterior mediastinum, especially
thymus
• 65-75% abnormal CXR at presentation
– Prevascular and paratracheal lymph nodes most commonly
involved
– Contiguous progression from one lymph node group to the
next
– Nodes rarely calcify before treated

25. A) Nodal chest involvementA) Nodal chest involvement
• Non-Hodgkin Lymphoma
–Best diagnostic clue :
• bulky mediastinal, bilateral, asymmetrical
hilar lymphadenopathy
• Lobulated lymph node masses
–Superior mediastinal + paratracheal nodes
–Lymph node masses will encase and
displace structures rather than infiltrate
and obstruct

28. B) Pulmonary parenchymalB) Pulmonary parenchymal
involvementinvolvement
• Associated with
– existing or previously treated intrathoracic nodal
disease
– widespread extrathoracic disease
• Primary pulmonary NHL
• Primary pulmonary HD

29. B) Pulmonary parenchymalB) Pulmonary parenchymal
involvementinvolvement
• 3x more frequent in HD than in NHL
• Relatively rare – 10% of cases at initial presentation
• Becomes more common as the disease progresses
• Particularly frequent in pt who relapse after treatment
• In Hodgkin disease
– Lung disease almost invariably accompanied by visible
intrathoracic adenopathy
– If mediastinal nodes have been previously irradiated,
recurrence may be confined to the lungs
• NHL
– Lung disease can be seen in absence of mediastinal
lymphadenopathy

31. B) Pulmonary parenchymalB) Pulmonary parenchymal
involvementinvolvement
• Various radiographic appearances
• Most common patterns are
– One or more areas of pulmonary consolidation
• May contain air bronchograms
• May be segmental or lobar in shape
• Often radiate from hila or mediastinum
– Without conforming to segmental anatomy
– In keeping with concept that extension into lungs is by direct
invasion from involved mediastinal nodes
– Peripheral subpleural masses or areas of
consolidation
• With no connection to mediastinal nodes

32. Secondary pulmonary lymphoma in a 40-year-old male. A chest radiograph demonstrates
bilateral parenchymal consolidation with air bronchograms. Note the presence of abnormal
paratracheal soft tissue opacity, in keeping with lymphadenopathy. This combination of findings
should raise suspicion of lymphoma.

33. a) Diffuse large B-cell lymphoma in a 32-year-old male. A chest radiograph
demonstrates a large opacity in the right middle lobe obscuring the right heart border.
(b) A multidetector CT scan in the same patient demonstrates a well-circumscribed
right middle lobe mass with central low attenuation, consistent with necrosis (arrow

34. Secondary pulmonary lymphoma in a 42-year-old male with a
history of non-Hodgkin lymphoma. Multidetector CT scan
demAonstrates two peripheral pulmonary masses (arrows).

35. Lymphangitis carcinomatosis

37. B) Pulmonary parenchymalB) Pulmonary parenchymal
involvementinvolvement

38. B) Pulmonary parenchymalB) Pulmonary parenchymal
involvementinvolvement
• Primary pulmonary Hodgkin Disease is
extremely rare
– Single or multiple pulmonary nodules
• Upper lobe predominance
• High incidence of cavitation

39. C) PleuraC) Pleura
• Pleural effusion
– Usually in presence of mediastinal lymphadenopathy
– At presentation
• In 10% of NHL
• In 7% of HD
Nodular pleural thickening
Most often due to central lymphatic /venous
obstruction rather than direct malignant involvement
• Clear after treatment of mediastinal disease
• Focal pleural masses + effusion is seen in
recurrent disease

40. E) Chest wallE) Chest wall
• Hodgkin disease
– Spread into chest wall from anterior mediastinal
mass
• In Hodgkin and Non-Hodgkin lymphoma
– Chest wall masses can also spread from axillary or
supraclavicular nodes
– Bony destruction is rare
Consider carcinoma

41. D) Heart and pericardiumD) Heart and pericardium
• Rarely involved
• Direct involvement can occur in high grade
peripheral T-cell and large B-cell lymphomas
– More often (but still rare) in
• AIDS related lymphoma
• Post-transplant lymphoproliferative disorders
• Pericardial effusion
• Acute onset heart block, congestive cardiac
failure or cardiac tamponade

42. Investigations
• Treatment of HL depends upon the stage at
presentation;therefore investigations aim not only to
diagnose lymphoma but also to determine the extent
of disease
• FBC . anaemia or lymphopenia eosinophilia or a
neutrophilia
• ESR may be raised.
• •Renal function tests are required to ensure function
is normal prior to treatment.

43. • Liver function may be abnormal in the absence of
disease or may reflect hepatic infiltration. An
obstructive pattern may be caused by nodes at the
porta hepatis.
• LDH measurements showing raised levels are an
adverse prognostic factor.
• Chest X-ray may show a mediastinal mass
• CT scan of chest, abdomen and pelvis permits
staging. Bulky disease (> 10 cm in a single node
mass) is an adverse prognostic feature.

44. Lymph node biopsy
may be undertaken
surgically or
by percutaneous
needle biopsy
under radiological
guidance
CT-guided percutaneous needle biopsy of
retroperitoneal nodes involved by
lymphoma.

45. IN additiont following investigation are performed in
NON HODJKIN LYMPHOMA.
• Bone marrow aspiration and trephine.
.. Immunophenotyping of surface antigens to
distinguish T from B cell tumours. This may be done
on blood,marrow or nodal material.
.. Cytogenetic analysis to detect chromosomal
translocations and molecular testing for T cell
receptor or immunoglobulin gene rearrangements,
If available.

46. • Immunoglobulin determination. Some lymphomas
are associated with IgG or IgM paraproteins, which
Serve as markers for treatment response.
- Measurement of uric acid levels. Some very
aggressive high-grade NHLs are associated with
very high urate levels, which can precipitate renal
failure when treatment is started.
• HIV testing
.

47. Lymphoma : Goals of imagingLymphoma : Goals of imaging
1. Initial staging of lymphoma
2. Monitoring radiological response to therapy
3. Imaging complications of treatment
4. Detecting evidence of relapse

48. •POOR PROGNOSTIC FACTOR:
- large mediastinal lymphadenopathy
- Stage IIIB, IV
- B symptoms
- Bulky disease
- High ESR >50

49. Management

50. HODGKIN LYMPHOMA MANAGEMENT
• Clinical trials have shown that patients with
earlystage disease have better outcomes if
chemotherapy is included in their treatment.
• The majority of HL patients are now treated
with chemotherapy and adjunctive
radiotherapy.
• The ABVD regimen (doxorubicin, vinblastine,
bleomycin and dacarbazine) is widely used

51. Chemotherapy
25mg/m2
10
6
375

52. • Standard therapy of early-stage patients usually
includes additional treatment with radiotherapy to
the involved lymph node after four courses of ABVD
-- Treatment response is assessed clinically and by
repeat CT and newer scanning modalities such as
positron emission tomography (PET).
-- ABVD chemotherapy can cause cardiac and
pulmonary toxicity, due to doxorubicin .bleomycin,
respectively.
• The incidence of infertility and secondary
myelodysplasia/AML is low

53. • Patients with advanced-stage disease are
most commonly managed with chemotherapy
alone.
• Standard treatment in the UK is 6–8 cycles of
ABVD, followed by an assessment of response.
-- Overall, the long-term disease control/
cure rates are lower with advanced disease
--Patients with disease which is resistant to
therapy may be considered for autologous
HSCT

54. PROGNOSIS
• Over 90% of patients with early-stage HL achieve
complete remission when treated with
chemotherapy followed by involved field
radiotherapy(iFR) and the great majority are cured.
• Between 50 and 70% of those with advanced-stage
HL can be cured.
• Patients who fail to respond to initial chemotherapy
or relapse within a year have a poor prognosis but
some may achieve long-term survival after
autologous HSCT.
• Patients relapsing after 1 year may obtain long-term
survival with further chemotherapy alone.

55. NON HODGKIN LYMPHOMA
MANAGEMENT
• Low-grade NHL
• Indications for treatment include marked systemic
symptoms,lymphadenopathy causing discomfort or
disfigurement,bone marrow failure or compression
syndromes.
• In follicularlymphoma, the options are:
• • Radiotherapy. This can be used for localised stage I
• disease, which is rare.
• Chemotherapy. Most patients will respond to oral
therapy with chlorambucil, which is well tolerated
but not curative.

56. • The anti-CD20 antibody rituximab has been
shown to induce durable clinical responses in
up to 60% of patients when given alone, and
acts synergistically when given with
chemotherapy.
• Rituximab (R) in combination with
cyclophosphamide, vincristine and
prednisolone(R-CVP) is commonly used as
first-line therapy.

57. High-grade NHL
• Patients with diffuse large B-cell NHL need treatment
at Initial presentation:
• Chemotherapy. The majority (> 90%) are treated with
intravenous combination chemotherapy, typically
with the CHOP regimen (cyclophosphamide,
doxorubicin, vincristine and prednisolone).
• When combined with CHOP chemotherapy, the
biological therapy rituximab (R) increases the
complete response rates and improves overall
survival.

59. • R-CHOP is currently recommended as first-
linetherapy for those with stage II or greater
diffuse large B-cell lymphoma
• Radiotherapy. A few stage I patients without
bulky disease may be suitable for
radiotherapy.
• Radiotherapy is also indicated for a residual
localised site of bulk disease after
chemotherapy,and for spinal cord and other
compression syndromes
• HSCT. Autologous HSCT benefits patients with
relapsed chemosensitive disease.

60. Prognosis
• Low-grade NHL runs an indolent remitting and
relapsingcourse, with an overall median
survival of 10 years.
• Transformation to a high-grade NHL occurs in
3% per annum and is associated with poor
survival.
• In diffuse large B-cell high-grade NHL treated
with R-CHOP, some 75% of patients overall
respond initially to therapy and 50% will have
disease-free survival at 5 years.

61. • Relapse is associated with a poor response to
further chemotherapy (< 10% 5-year survival),
but in patients under 65 years, HSCT improves
survival.

62. THANKS