Extended clinical meeting on T Lymphoblastic Lymphoma

1. WELCOME TO EXTENDED CLINICAL MEETING
Presenter:
Dr. RENESHA ISLAM
Resident, Phase-B (year 4)
Pediatric Hematology & Oncology
BSMMU.

2. “
2
Name : Saif
Age : 2 years 4 months
Sex : Male
Address : Malibag
Date of admission : 05/08/2021
Date of examination : 05/08/2021
Informant : Mother
PARTICULARS OF THE Patient

3. PRESENTING COMPLAINTS
• Fever for 2 ½ months.
• Chest pain for 2 months.
• Breathing difficulty for 12 days.

4. 4
According to statement of the informant mother, Saif was
reasonably well 2½ months back. Then he developed fever which
was initially low grade, then became high grade, intermittent in
nature, highest recorded temperature was 103F, not associated
with chills, rigor, evening rise of temperature or night sweat,
subsided temporarily after taking antipyretics.
Mother also complaints of left sided chest pain for 2 months,
which was increasing day by day, diffuse, dull aching in nature &
aggravated in lying position, associated with non productive
cough but no diurnal variation.
History of present illness

5. 5
On query, Mother also gave history of anorexia, weight loss
but not documented.
He has no H/O contact with TB patient, progressive pallor,
blood transfusion, hemoptysis, headache, convulsion,
unconsciousness or any bleeding manifestation.
With these complaints, at first they visited a registered
physician who prescribed antipyretics, oral antibiotics
(Cefuroxime) with some investigations. As his condition did not
improve, he was admitted in Pediatric Pulmonology department
of BSMMU and treated with injectable antibiotics (Ceftriaxone)
for 14 days. Then, Saif got discharged with the advice of oral
antibiotics (Clarithromycin, Voriconazole) intake.

6. 6
But following 7th day of discharge, Saif developed
breathing difficulty & got admitted in a private hospital
where he received conservative management along with
some investigations. After improvement he was discharged.
But again he developed respiratory distress after 16th days of
discharge & was referred to our department for further
evaluation and better management.

7. ⊹ Birth History :
Delivered by NVD at home at term without any
complication. His antenatal, natal and post-natal period was
uneventful.
⊹ Developmental History :
Developmentally age-appropriate.
⊹ History of past illness :
Nothing significant.

8. Feeding History :
He is on family diet.
Immunization History :
Fully immunized as per EPI schedule.
Family History :
He is the 2nd issue of his non-consanguineous parents.
Other family members and elder sib are in good health.
No family history of cancer or tuberculosis.

9. Socio-economic history:
Father is a small scale businessman and
his monthly income is 15,000 taka. Mother
is a home maker. They live in pacca house
(4 members live in 2 rooms with good
aeration facility), use sanitary latrine and
drink boiled water.
travelling history:
Nothing significant.

10. Treatment history
Syp. Cefuroxime for 5 days.
BSMMU (P. Pulmonology)
⊹ Nebulization with salbutamol.
⊹ Inj. Ceftriaxone for 14 days.
⊹ Syp. Clarithromycin for 15 days.
⊹ Syp. Voriconazole for 21 days.
Private hospital
⊹ Nebulization with salbutamol & steroid.
⊹ Inj. Meropenem for 14 days.
⊹ Inj. Hydrocortisone for 3 days.
⊹ Syp. Prednisolone for 10 days (1mg/kg/day).

11. General
physical
examination

12. General physical examination
⊹ Appearance : Well Alert, Co-operative.
⊹ Decubitus : Preferred to sitting than lying position.
⊹ Mildly pale
⊹ Edema
⊹ Jaundice
⊹ Cyanosis
⊹ Dehydration
⊹ Clubbing
⊹ Leukonychia
⊹ Koilonychia
Absent.

13. General examination (cont…)
⊹ Lymph node examination:
Left anterior cervical and anterior axillary lymph
nodes were enlarged. Largest one measuring about
2×2 cm, non tender, firm in consistency, discrete,
not fixed with underlying structure, overlying skin
was free, there was no discharging sinus.

14. ⊹ JVP : Normal
⊹ Neck veins : Not engorged
⊹ Bony tenderness : Absent
⊹ Skin survey : Normal
⊹ BCG mark : Present
⊹ Signs of meningeal irritation: Absent
⊹ Examination of Eye : Normal
⊹ Examination of Ear, Nose and Throat: Normal.
General physical examination

15. Vital sign
⊹ Pulse : 93 beats/min.
⊹ BP : 90/55 mm Hg.
(Both SBP & DBP lies between 50th-90th centile)
⊹ Respiratory Rate : 38 breaths/min.
⊹ Temperature : 980F.
⊹ SPO2 : 97% in room air.

16. • Height: 87 cm
(lies on 25th centile)
• Weight: 10.4 kg
(lies on 5th centile)
• BSA: 0.46
Anthropometry

17. Systemic examination

18. Respiratory system Examination
Inspection:
• Dyspnoic, Preferred to sit or
right lateral decubitus than
lying position.
• Respiratory rate : 38 breaths/min.
• Lt side of chest bulged out with
fullness of inter costal and supra
sternal space.
• Movement of chest : Diminished
on left side.

19. On examination Left Side Right Side
Palpation
Position of trachea
Position of apex beat
Chest wall expansibility
Vocal fremitus
Deviated towards right side
Left 4th ICS medial to MCL
Diminished
Diminished along left MCL from
3rd to 6th ICS
Normal
Normal
Normal
Percussion note Dull (Above mentioned area) Resonant
Auscultation
Breath sound
Diminished (Above mentioned
area)
Vesicular breath sound
with no added sound
Vocal resonance Diminished (Above mentioned
area)
Normal

20. Gastrointestinal system
Mouth & oral cavity: healthy.
Abdomen proper:
⊹ Inspection:
-Umbilicus centrally placed with vertical slit.
-Abdomen was not distended.
-No scar mark, visible pulsation or engorged
veins.
-Flanks were not full.

21. Palpation:
Abdomen was soft, non-tender, not distended.
⊹ Liver:
- 2cm enlarged from right costal margin along MCL,
- Smooth surface
- Sharp border
- Firm in consistency &
- Upper border of liver dullness at right 4th ICS.
⊹ Spleen : Not palpable.
Gastrointestinal system

22. GASTROINTESTINAL SYSTEM
Percussion:
Percussion note tympanic.
No shifting dullness.
Auscultation:
Bowel sound present.

23. • Urinary bladder : Not palpable
• Genitalia : Male type
• Kidneys: Not ballotable
• Testis: Normal
• Hernial orifices: Intact.
Genitourinary system

24. Cardiovascular system
⊹ Inspection:
No visible pulsation.
⊹ Palpation:
• Position of trachea: Deviated towards right side.
• Position of apex beat: left 4th ICS medial to the MCL.
• Thrill : Absent
• P2 : Not palpable
• Left parasternal heave : Absent
⊹ Auscultation:
• 1st & 2nd heart sounds are audible in all 4 areas
• Murmur : Absent

25. Nervous System Examination
⊹ Higher cerebral function: Intact.
⊹ Examination of cranial nerves: Intact.
⊹ Motor function: Bulk of muscle - Normal
Tone- Normal
Power- Normal
Jerks- Normal.
⊹ Sensory: Intact.
⊹ Cerebeller function: intact.
⊹ Gait: normal.

26. “ ⊹ LOOK
No joints are swollen, no peri articular wasting, No scar mark
present.
⊹ FEEL
Temperature : Normal
Tenderness: Absent
Fluctuation test : Not done
Patellar tap : Not done.
⊹ MOVE
No restriction of movement.
Locomotor System Examination

27. Saif, 2 years 4 months old boy 2nd issue of non consanguineous
parents hailing from Malibag, admitted with the complaints of
fever for 2½ months which was initially low grade then became
high grade, intermittent in nature, highest recorded temperature was
103F, not associated with chills, rigor, evening rise of temperature
or night sweat, subsided temporarily after taking antipyretics.
He also had left sided chest pain for 2 months, which was
increasing day by day, diffuse, dull aching in nature, aggravated in
lying position, associated with non productive cough.
Salient feature

28. He had anorexia, non documented weight loss, but no H/O
contact with TB patient, progressive pallor, blood transfusion,
hemoptysis, headache, convulsion, unconsciousness or any
bleeding manifestation.
With these complaints, Saif was at first admitted in Pediatric
Pulmonology department and then again in a private hospital
due to respiratory distress and got conservative management.
As his condition did not improve, he was referred to our
department for further evaluation and better treatment.
Salient feature (contd)
weight loss

29. Salient feature (contd)
On examination, he was mildly pale,
dyspnoic, orthopnic, R/R- 38 breaths/min,
SPO2 97% in room air. Anthropometrically he
was well thriving and developmentally age
appropriate. Respiratory system examination
revealed features of left sided massive pleural
effusion along shifting of mediastinum,
hepatomegaly and lymphadenopathy.
Other systemic examination revealed no
abnormality.

30. Provisional diagnosis

31. 31
👍PROVISIONAL DIAGNOSIS
Non- Hodgkin Lymphoma
with
Superior Mediastinal
Syndrome

32. 32
👉differential diagnosis
Disseminated Tuberculosis
ALL (T Cell)

33. NON HODGKIN LYMPHOMA
Points against :
POINTS
AGAINST:
POINTS IN FAVOUR:
• Fever
• Chest pain
• Breathing difficulty
• Response to steroid
O/E
• Hepatomegaly
• Lymphadenopathy
• F/O pleural effusion

34. POINTS IN FAVOUR:
• Cough
• Prefer to sit than lying
position
• Respiratory distress
• Chest pain
SUPERIOR MEDIASTINAL SYNDROME

35. :
POINTS AGAINST:
- No H/O contact
with TB patient.
- BCG mark present.
POINTS IN FAVOUR:
• Cough not responding to
conventional bronchodilators.
• Fever not responding to
conventional antibiotics.
• Respiratory distress.
• Anorexia, Weight loss.
O/E
• F/O pleural effusion
• Hepatomegaly, Lymphadenopathy
DISSEMINATED TUBERCULOSIS

36. ALL (T CELL)
Points against :
POINTS
AGAINST:
No pallor
POINTS IN FAVOUR:
• Fever not responding to
conventional antibiotics.
O/E
• Hepatomegaly
• Lymphadenopathy

38. Investigations ( before admission-30/07/21)
CBC
⊹ Hb: 13.3 gm/dl.
⊹ Total count of WBC: 14,000/cumm.
⊹ Differential count:
Neutrophils - 38% Monocytes - 6%
Lymphocytes - 51% Eosinophil - 5%
⊹ Platelet Count: 3,35,000/cumm.
⊹ ESR: 15 mm in 1st hour.
PBF: Microcytic hypochromic anemia.

39. ⊹ MT: Negative (02 mm)
⊹ Sputum for AFB: Negative
⊹ Gene Xpert: Negative
⊹ S. LDH: 1123 U/L
⊹ SGPT: 32 U/L
⊹ S. Cr : 0.42 mg/dl
⊹ CRP: 21.79 mg/dl.
Investigations ( before admission)

40. X-ray chest
03/06/2021 25/07/2021

41. ⊹ USG of Chest:
Findings- Evidence of clear fluid collection (about 80 ml in
amount) in left supra diaphragmatic space.
Comment: Left sided pleural effusion.

42. ct chest:06/06/2021

43. ct chest:06/07/2021

44. ct chest:06/07/2021

45. Investigations ( after admission-05/08/21)
CBC
⊹ Hb: 13.2 gm/dl.
⊹ Total count of WBC: 15,000/cumm.
⊹ Differential count:
Neutrophils - 71% Monocytes - 6%
Lymphocytes - 22% Eosinophil - 1%
⊹ Platelet Count: 3,53,0000/cumm.
⊹ ESR: 18 mm in 1st hour.
⊹ PBF: Microcytic hypochromic anemia.

46. ⊹ S. Inorganic phosphate: 5.8 mg/L
⊹ Serum Electrolyte: Na - 138 mmol/l
K - 4.4 mmol/l
Cl - 97 mmol/l
⊹ SGPT: 21 U/L
⊹ S. Creatinine: 0.49 mg /dl.
⊹ S. Calcium: 9.8 mg/dl.
⊹ S. uric acid: 7.9 mg/dl

47. • PT : APTT:
C- 12 sec C- 26 sec
P- 13 sec P- 30 sec
• INR - 1.09
• RBS: 5.8 mmol/l.

48. “
X-ray chest:05/08/2021

49. ⊹CT guided core biopsy with immunohistochemistry:
TdT - Positive
CD99 - Positive
CD3 - Positive
cMYC - Positive
CD20 - Negative
PAX5 - Negative
Impression: T cell Lymphoblastic Lymphoma.

50. ⊹Bone marrow study: Normal uninvolved marrow.
⊹CSF for malignant cell: Negative for malignant cell, CNS-1.
⊹Echocardiography: Normal cardiac anatomy.

51. Final Diagnosis:
NHL
( T Lymphoblastic Lymphoma)
Stage III with Superior Mediastinal
Syndrome

52. Treatment on admission:
⊹ Counseling.
⊹ Supportive :
× Diet – Neutropenic
× Adequate hydration
× Oral Allopurinol
× Oral Prednisolone
× Oral Aluminium hydroxide + Magnesium hydroxide
× Nystatin oral drop
× Chlorohexidine mouth wash
× Acriflavin hip bath.

53. F/U on 07.08.21 (HS- D2)
Subjective Objective Assessment Plan
No new
complaints
Well alert, Ill looking
Temp: 98◦ F
Mildly pale
Oral cavity: Healthy
H/R: 96 b/min
R/R: 34 b/min
BP: 90/60 mmHg
Heart: S1+S2+0
Lungs: Breath sound diminished along left
MCL (3rd to 6th ICS)
P/A- Soft, Not distended, Non tender
Liver: 2 cm enlarged
B/S: Present
SPO2: 97% in room air
Bowel & bladder habit: Normal
Improving Start
chemotherapy

54. “ Specific treatment:
Protocol based
chemotherapy started from
07/08/2021 according to
BFM-95 protocol

55. F/U on 14.08.21 (HS- D10)
Subjective Objective Assessment Plan
No new
complaints
Well alert
Afebrile, Temp: 98◦ F
Mildly pale
Oral cavity: Healthy
H/R: 89 b/min
R/R: 20 b/min
BP: 100/65 mmHg
Heart: S1+S2+0
Lungs: Vesicular breath sound,
no added sound
P/A: soft, Non tender
Bowel sound: Present
Bowel & Bladder habit : Normal
SPO2: 98% in room air.
Improving Continue
Chemotherapy
Repeat chest
x-ray

56. Comparison of X-ray chest
14/08/21
Previous 05/08/21

57. “
57
P. Gastroenterology consultation
Investigation 22/08/21
SGPT 555 U/L
PT
APTT
INR
12 sec
26 sec
0.99
HBsAg Negative
Anti HAV IgM Negative
Anti HEV IgM Negative
Anti HBs Positive
- Hold
chemotherapy
- Continue
Ursodeoxycholic
acid
Rising trend of SGPT (From 12/08/21)
Vitally stable
Add Ursodeoxycholic acid
Start
Chemotherapy
From 29/08/21

58. F/U on 31.08.21 (HS- D26)
Subjective Objective Assessment Plan
No new
complaints
Well alert
Moon face, Hypertrichosis
Afebrile, Temp: 98◦ F
Mildly pale
Oral cavity: Healthy
H/R: 89 b/min
R/R: 20 b/min
BP- 110/75 mmHg
Heart: S1+S2+0
Lungs: V/B/S, no added sound
P/A: soft, Not distended, non tender
Bowel sound: Present
Bowel & Bladder habit : Normal
SPO2: 99% in room air.
Steroid toxicity Add oral anti
Hypertensive
Continue
Chemotherapy

60. 60
EXTENDED PART

61. “
61
C/C:
⊹ Fever for 2½ months.
⊹ Chest pain for 2 months.
⊹ Breathing difficulty for
12 days.
Patient overview
INV:
CXR: Pleural effusion on left side
Immunophenotyping:
T lymphoblastic lymphoma
O/E:
- Mildly pale, Dyspnoic
- F/O pleural effusion present (left)
- Lymphadenopathy
(Left cervical & axillary)
- Hepatomegaly
Diagnosis:
⊹ T Lymphoblastic Lymphoma
(Stage 111)

62. LYMPHOMA
62
T
Cell
Non
Hodgkin
Lymphoma
LYMPHOMA
Hodgkin
Lymphoma
B
Cell
ALCL
Lymphoblastic
Lymphoma
BL
DLBCL
Lymphoma is the third most common cancer
among children (age 14 years or younger)

63. 63
LYMPHOBLASTIC LYPHOMA
 Accounts for 15-20% of childhood NHL and share many clinical
and biologic features with ALL.
 More than 90% of LL has precursor T immunophenotype.
Cytologically the neoplastic cells of LL is indistinguishable from
the blasts seen in ALL.
 Bone marrow involvement occurs at diagnosis in 15-20% of
patient.

64. T LYMPHOBLASTIC LYMPHOMA
64
⊹ Incidence rate of 0.4/100,000 in children
<15 years of age and 0.1/100,000 in adolescents
and young adults.
(Burkhardt et al, 2013; Geyer & Jacobson, 2012).
⊹ Majority of children with T-LL present with
rapidly enlarging neck and mediastinal
lymphadenopathy.
⊹ Occurs more commonly in males.
(Altekruse et al, 2010).

65. 65
IN BSMMU from 2019-2021

66. 66
FAB/LMB 96 trial (Feb.1997- Dec. 2003, total 79 children) founds
that-
 Mediastinal involvement: 71 patients (89%). 5 of
whom also had involvement of the cervical nodes.
 Other primary- site involvements: 8 patients (10%)
 Peripheral lymph nodes: 4 patients (5%)
 Cervical lymph nodes: 2 patients (2.5%)
 Testicles: 1 patient (1.2%)
 Liver/spleen: 1 patient (1.2%)
 Pleural effusion: 39 Patients (47%)
 Pericardial effusion: 25 Patients (31%)
Bergeron et al 2015

67. An approach to t-LL
History taking
Lab investigations
Physical findings
 Duration & onset
 Symptoms of SMS,
SVS
• General physical
examination
• Respiratory system
examination

68. Plan of Investigation
⊹ Preliminary investigation:
- CBC with ESR, PBF
- CXR
⊹ To see extension of disease:
- CSF study
- Bone marrow study
⊹ To exclude differential:
- MT
- Sputum for AFB.

69. • To see complication:
S. Calcium, S. Inorganic phosphate,
S. uric acid, S. Electrolyte, S. Creatinine.
• For management purpose:
Coagulation profile
SGPT
Blood grouping & Rh typing
Echocardiography.

70. Establishment of diagnosis
- By cytological and immunological
examination of malignant cells from
effusions
- By cytology, histopathology and
immunohistochemistry of lymph node or
-Tumor biopsy.

71. HISTOLOGY

72. Immunohistochemistry
72
 TdT
 CD 99
 CD1a
 CD2
 CD3
 CD5
 CD7
 CD4 and CD8 frequently co-expressed
 CD10- 15-40% cases

73. 73
CD3 TdT
Immunohistochemistry

74. 74
STAGE DESCRIPTION
I • A single tumor (extranodal) or single anatomic area (nodal), with the exclusion of
mediastinum or abdomen
II • A single tumor (extranodal) with regional node involvement
• Two or more nodal areas on the same side of the diaphragm
• Two single (extranodal) tumors with or without regional node involvement on the
same side of the diaphragm
• A primary gastrointestinal tract tumor, usually in the ileocecal area, with or
without involvement of associated mesenteric nodes only, which must be grossly
(>90%) resected
III • Two single tumors (extranodal) on opposite sides of the diaphragm
• Two or more nodal areas above and below the diaphragm
• Any primary intrathoracic tumor (mediastinal, pleural, or thymic)
• Any extensive primary intra-abdominal disease
IV • Any of the above, with initial involvement of central nervous system or bone
marrow at time of diagnosis

75. 75
TREATMENT

76. 76
BFM Treatment Strategy for Lymphoblastic Lymphoma

77. BFM95 PROTOCOL FOR T LYMPHOBLASTIC LYMPHOMA
77

78. COMPARISON OF SURVIVAL RATE
78
NHL-BFM 95 NHL-BFM 90
Target group
(no)
156 163
5 yr EFS (%) 82 88
5 yr DFS (%) 88 91
5 yr OS (%) 85 89

79. 79
CRANIAL
radiotherapy

80. Impact of Cranial Radiotherapy on Central Nervous System
Prophylaxis in Children and Adolescents With Central Nervous
System – Negative Stage III or IV Lymphoblastic Lymphoma
80
Conclusion: For CNS-negative patients with stage III or IV
LBL and sufficient response to induction therapy,
treatment without PCRT may be non inferior to treatment
including PCRT.

81. PROGNOSIS
• BFM 90/95 Trial: EFS 80-90%
• 10-20% patient experience-
-Treatment failure/Non response/Refractory
disease
-Progressive disease or
-Relapse
• Survival rates of relapse patients: 10–30% .
Burkhardt et al. 2016

82. 82
Prognosis in PHO, BSMMU
• Excellent with BFM 95 protocol.
• From 2019-till now, All patients (10)
under chemotherapy survived.
• 1 participated in international childhood
cancer day 2021 programme.

83. The Risk of Developing Tuberculosis in Cancer Patients Is Greatest
in Lymphoma: A Large Population-Based Study
Blood & Cancer 130:3583
Conclusion: The rate of TB incidence following cancer
diagnosis was 27.2/100,000 for persons diagnosed with
hematological malignancies and 12.7/100,000 among
those with non-hematological malignancies. The
highest TB incidence was found among patients with
lymphoma (30.1 TB cases per 100,000 person/Yr).

84. “
84
⊹ LL is a common cause of Non-hodgkin lymphoma in
children.
⊹ Majority of the patient presented with mediastinal mass and
pleural effusion.
⊹ Early clinical judgment, prompt investigation including tissue
diagnosis is mandatory.
⊹ Immediate initiation protocol based therapy can cure this
highly malignant disorder.
⊹ Awareness is needed for TB among newly diagnosed
patients with lymphoma.
TAKE HOME MESSAGE

85. THANK YOU
85