CASE OF THE MONTH
DR. SHAILESH MANANDHAR
PAEDIATRIC RESIDENT 1ST YEAR
IOM
Patient’s Profile
Name : Kapindra Regmi
Age / Sex – 12yrs / M
Add : Dolkha
I.P No : 12153
DOA : 2062/7/12 at 9:30 pm
DOD : 2062/8/8 at 11:00 am
Admitting Diagnosis: Lt. Pyopneumothorax with
neck mass ? Lymphoma
Final Diagnosis
: Malignant thymoma Stage 3 with
Lt. chylopneumothorax
Chief complains
1.
2.
3.
Progressive difficulty in breathing for 10 days
Difficulty in swallowing for 10 days
Upper abdominal swelling for 5 days
History of Present Illness
Patient was apparently well 20 days back. Then , he
developed mild to moderate grade fever intermittent
not a/w chills & rigor but with profuse night sweats
lasting for 10 days.
Cough with mucoid expectoration, no hemoptysis, no
vomiting, no dysuria, no pain abdomen
Chest pain more on left side and on coughing.
Complained throat pain during swallowing
Taken treatment for local medical shop tab. Ofloxacin
200mg BD for 7 days – fever subsided but cough not
improved
HOPI
Contd…………..
Subsequently mother noticed swelling in neck ;
followed by swelling of upper abdomen couple of
days later.
Gradual difficulty in breathing and swallowing
Bowel and bladder habit were normal
No noisy breathing
No H/O joint pain or swelling, rashes, swelling of
legs, no hoarseness of voice, no jaundice.
No h/o bony tenderness.
No H/O loss of consciousness or seizure
HISTORY OF PAST ILLNESS
Never needed medical care and
medication.
FAMILY HISTORY
Only child in family
Mother: 35years/ House-wife
Father : expired 4 years back in RTA
Low socio economic class family
Mother earn living by working in own small field and
other people’s houses in village
No H/ O similar illness/ TB in the family or in close
contacts.
No H/O consanguinity of marriage.
No H/O pet in the family.
BIRTH HISTORY FT/S/F/NVD at Home . Ante-natal/intra-partum or
postpartum period: Uneventful
IMMUNIZATION HISTORY –
not immunized
DEVELOPMEENTAL HISTORY Normal for his age
NUTRITIONAL HISTORY Taking less than required calorie.(80
Kcal/kg/day)
TREATMENT HISTORY
Admitted In Kathmandu Model hospital, Dolkha one
week back.
Inj. Ceftriazone 50mg/kg/d q 12hr for 5 days
History of aspiration of thick white fluid from left chest
twice.
Referred from there with discharging diagnosis of left
pyopneumothorax with neck mass ? Lymphoma to cardio
thoracic surgery department for evaluation and
management of neck mass and chest tube insertion.
ON EXAMINATION
Child was conscious oriented to time, place and person
but looked dyspneic and tachypnic.
Vitals: Pulse: 116b/min normo volumic
R/R : 48/min regular
B.P : 90/40 mm Hg
Temp: 1000C
Anthropometry: wt. 25 kg
Ht. 136 cm
wt. for age : 62.5 % of expected
ht. for age : 90 % of expected
wt. for ht. : 83.3 % of expected
Puffy face with mild submandibular region swelling.
Distended neck veins.
Visible swelling on anterior lower part of neck. On
palpation hard fixed mass approx. 3 cm by breadth ill
defined borders arising from retrosternal region.
Can’t get lower border of mass.
Neck mass –doesn’t move on deglutition/ protrusion
of tongue.
Lymphnodes- Single Rt. Axillary 1*1 cm, multiple cervical
and submandibular 0.5 to 1cm
Pallor / jaundice / cyanosis – absent
Clubbing- absent
Pedal edema – absent.
Ear/nose and throat examination- normal
Joints : Normal
Bony tenderness: Absent
Non pitting edematous swelling of anterior chest and
upper abdomen.
RESPIRATORY EXAMINATION
INSPECTION- Fullness in Lt. anterior chest wall. Reduced
movement on same side.
PALPATION- trachea- deviated to left side. Reduced tactile and
vocal fremitus in Lt. side on lower half.
PERCUSSION- stony dullness on Lt. lower part of chest.
Hyperresonant note on Lt. upper part of chest.
AUSCULTATION- absent BS on Lt. side of chest. Normal vesicular
breath sound with no added sound on right side of chest.
PER ABDOMEN :Inspection: mild distension of upper part of abdomen; visible
veins with flow up to downward at supraumbilical region, central
umbilicus. No scar marks, No visible peristalsis
Palpation: No tenderness on superficial or deep palpation.
Liver/Spleen non palpable. No abdominal LN palpable.
Hernial orifices: Intact
Both testes were palpable at lower end of inguinal canal
normal size with intact sensation.
Percussion: Tympanic. No fluid thrill or shifting dullness
Auscultation: normal bowel sound
CVS : apex beat localized at 4th ICS 3cm medial to left
nipple. S1,S2 – N , No murmur
CNS :
- conscious, cooperative and oriented to time, place
and person.
- cranial nerves grossly intact
- muscle tone/power/bulk were normal in all limbs
- no involuntary movements
- superficial and deep tendon reflexes N
- Sensory examination with in normal limit
- Normal Gait.
PROVISION DX:
Lt. Pyopneumothorax with neck
mass ? Lymphoma ? Tuberculosis
INVESTIGATIONS
CBC:
Hb: 13.4 gm% TC: 12,100 (N-75, L- 15, E-8, M- 2)
Platelet:160,000/mm
ESR : 12
Na: 139 K: 4.5m mol/L
Urine R/E: normal
Chest tube was inserted on left side - whitish
turbid fluid ~ 2.5 litre drained and admitted in
Medical Ward.
Inj. Cloxacillin 100mg/kg/d
Inj. Amikacin 15mg/kg/d
Tab. Paracetamol 6hrly
D3 of admission
Reduced dyspnea, puffiness of face and look
comfortable.
Tem. 1000F PR 102/m B.P: 96/60 mm Hg
Chest tube drain ~ 1.5 lit of milky white fluid with little
dirty white fibrinous sediments .
Eating well .urine - N
INV: Pleural Fluid AnalysisTC: 21,900/cumm (L- 91%, N- 9%)
protein – 61 micromol / L
A> Lt. chylopneumothorax ? Lymphoma ?
Tuberculosis
Plan- pleural fluid triglyceride level
sr.creatinin, urea,
LFT
Sputum for AFB
Mantoux test
D4,D5 of admission
Complains cough and chest pain otherwise comfortable.
Vital stable still have low grade fever.
Non pitting edema of left upper limb noted.
Chest tube draining more milky fluid upto 2.5litres.
No dehydration, passing urine.
Air entry on left side present.
INV - pleural fluid triglyceride level – 9.3 m mol/L
( 0.5 – 1.8 m mol/L)
Sr.creatinin – 0.4mg/dl Urea – 20 mg/dl.
Sr. albumin 2g% Total protein – 3g%
SGPT 15IU SGOT 16 IU
Blood C/S – sterile after 96 hrs.
Pleural fluid C/S- E.coli isolated
sensitive to Imipenam
Intermediate sensitive to Amikacin
resistant to Ampi, cipro, genta, ceftazedime,
tobramycin, cephalexin, cotrim.
USG - Multiple enlarged LNs in neck, mediastenum and
clavicular region with left pleural effusion.
Liver- enlarged in size, no SOL
other viscera WNL.
X- ray chest Lateral view
Plan for neck mass / lymph node biopsy.
D6
Patient’s condition static
Mx – no induration
Sputum for AFB- Negative.
Advice to take high protein diet.
D8 – D10
Looked better
Fever subsided, still complains cough.
Neck swelling and venous prominence reduced than
admission day.
Neck mass felt softening than before.
Chest tube functioning; draining still 1 -2 lit/day
D12
Case referred to CTVS department, TUTH for expert
opinion and further management.
Case seen by Dr. P. Sayami, with impression of
mediastinal lymphoma with left chylothorax, USG guided
FNAC of mediastinal mass and follow up with report was
adviced.
D15
USG guided FNAC of neck mass done –
Mixed population of mature and immature lymphoid
cells; with few clusters of atypical epithelial cells – moderately
Pleomorphic, oval to spindle nuclei and scanty cytoplasm and few
squamous cells in background.
Impression: Malignant Thymoma.
Plan for CT scan thorax
Patient party counseled about the disease and possible
therapy and poor prognosis.
D17 – D20
Patient look dysneic with puffy face.
Complaining of dysphagia more for solid food
Temp. 1010F PR 120/m BP- 90/50 mmHg
No Ptosis, no diplopia, no muscle weakness
No rashes, joint pain.
Chest - absent BS on left lower 2/3rd.
Chest tube not draining since yesterday.
Chest tube irrigation done and Chyle started draining.
D21
CT scan thoraxLarge lobulated soft tissue density well defined mass in
anterior superior mediastenum that shows heterogenous
enhancement with contrast; encasing all the major vessels of the
mediastenum including aortic arch and pulmonary arteries. Thick
irregular enhancement of pleura with nodular thickening at places.
Impression- Malignant thymic mass
D22
Consultation with CTVS team was done for further
management of case with CT report.
With impression of advanced thymic carcinoma –
inoperable, case was referred for Radiotherapy from
their side.
D23
Patient general condition- same
Patient party were given option for treatment
after explaining prognosis of disease.
Referred to Bhaktapur Cancer Hospital for
further treatment.
D25
Patient came back from Bhaktapur Cancer Hospital with
a referral letter to oncology department. Patient was
advised palliative chemotherapy of Ipbosphamide and
adriamycin and asked to come on follow up for
radiotherapy.
D26
On oncology department patient party again
counseled about the poor prognosis of disease
and possible expenses.
Then, they refused treatment.
Discharged on request on 2062-08-07
WITH
FINAL DIAGNOIS – Thymic carcinoma ( stage 3)
with Lt. chylopneumothorax
& superior vena cava syndrome
without obvious paraneoplastic
syndromes.
THYMOMA
ANATOMY :
Mediastinum –
pleural cavity laterally
Thoracic inlet superiorly
Diaphragm inferiorly.
Anterior
– Thymus, Fat and LN
Middle – Heart, pericardium, ascending and transverse aorta,
branchiocephalic veins, trachea, bronchi, LN
Posterior – descending thoracic aorta, esophagus, azygos
vein, autonomic ganglia and nerves, thoracic LN
Differential diagnosis of mediastinal mass by
anatomic location
ANTERIOR
MIDDLE
POSTERIOR
Thymoma
Teratoma/seminoma
Lymphoma
Parathyroid adenoma
Intrathoracic goiter
Lipoma
Lymphagioma
Aortic aneurysm
Lymphoma
Pericardial cyst
Broncogenic cyst
Metastatic cyst
Systemic granuloma
Neurogenic tumor
Bronchogenic cyst
Enteric cyst
Xanthogranuloma
Diaphragmatic hernia
Meningocele
Paravertebral abscess
THYMUS :
Soft, bilobed, pyramidal organ in anterior superior mediastenum
At birth wt. 10 -15 gm
Anteriorly – sternum, sternohyoid, sternothyroid muscles
Posteriorly – pericardium, arch of aorta & it’s branches, left
branchiocephalic vein, trachea.
One of two primary lymphoid organ of body.
Provides unique microenvironment in which T cell precursors
undergoes development, differentiation & clonal expansion
During this process, exquisite specificity of T cell responses is
acquired; also their immune tolerance to body’s own components.
Embryologically, thymic epithelium is derived from both the
ectoderm and the endoderm of the 3rd & 4th branchial cleft and
pharyngeal pouches.
Histology
of
Thymus:
INTRODUCTION
Thymoma is a tumor arising from epithelium of thymus
gland.
Majority of thymoma looks histological benign.
Usually follows indolent course patient surviving for
years.
34% of thymomas invades their own capsules, extending
to surrounding structures.
Less than 10% behave like invasive epithelial
malignancies
Epidemiology
Incidence 0.15 cases per 100,000
accounting 0.2 to 1.5% of all malignancies
( reference - Tumor of mesiastinum by ACP. Dec 15 05’)
Thymoma constitute about 50% of anterior
mediastenal neoplasm in adult, Lymphoma -25%
Peak age of incidence – 4th to 6th decades of life
Sex – no predilection of gender
Children very rarely affected.
Usually associated with the host of unusual
paraneoplastic syndromes
PATHOLOGY:
Tumor arises from epithelial component of thymus.
Most of them are solid tumor; but up to one third may have components
that are necrotic, hemorrhagic or cystic.
Histologically, 3 groups of thymic tumors can be distinguished :1.
2.
3.
Typical thymoma - with no cytological features of malignancy
Atypical thymoma - with organotypic features of thymoma but
with areas of atypia and occasional mitosis (WDTC).
Thymic carcinoma- with abundant mitotic figures and other
cytological features of malignancy.
Masaoka Staging of Thymoma
(1981)
Stage
1
2a
2b
3
4a
4b
Degree of invasion
5yrs survival rate %
Macroscopically completely encapsulated
with no microscopic extracapsular invasion
Microscopic invasion through the capsule
Macroscopic invasion into mediastenal fat
or pleura.
Invasion into adjacent structures
(pericardium, great vessel or lung)
96 – 100 %
Pleural or pericardial metastasis
Lymphatic or hematogenous metastasis
11 – 50 %
86 – 95 %
56 -69 %
WHO Classification of Thymoma
(1999)
CLASS
CYTOLOGIC FEATURES
Type A
Type B
Type B1
Spindle shaped, Medullary
Mixed
Lymphocyte rich, lymphocytic,
predominantly cortical, organoid.
Cortical
Epithelial, atypical, squamous,
well differentiated thymic carcinoma
Thymic carcinoma
Type B2
Type B3
Type C
( Referance - cancer treatment Review 2000 ; 26: 127- 131)
CLINICAL MANIFESTATIONS:
One third to one half of patient present with asymptomatic
mediastinal mass on chest radiography.
one third present with local symptoms related to
intrathoracic mass.
One third are detected during evaluation of Myasthenia
gravis.
Distant metastasis are rare at initial presentation.
When present, most common metastatic site is Pleura
Common symptoms at presentations are:1.
2.
3.
4.
Cough - 60%
Chest pain - 30%
Fever / Chill - 20%
Dyspnea - 16%
( reference - Tumor of mesiastinum by ACP. Dec 15 05’)
At presentation
~ 40 % of thymic tumor – Stage 1
~ 25 % of thymic tumor – Stage 2 or 3
~ 10 % of thmic tumor – Stage 4a
< 1 % of thymic tumor – Stage 4b
( Reference -Thymic tumors – review article Ann Thorac Surg 2004 ; 77 : 1860 – 9 )
Localizing symptoms secondary to tumor
invasion of surrounding structures
Involved Anatomic structures
Bronchi / Trachea
Esophagus
Spinal cord/vertebral column
Recurrent laryngeal nerve
Phrenic nerves
Stellate ganglion
Superior vana cava
localizing symptoms
Dyspnea, post obstructive
pneumona, atelactasis,
hemoptysis
Dysphagia
Paralysis
Hoarsness, vocal cord paralysis
Diaphragmatic Paralysis
Horner’s syndrome
Superior Vana Cava Syndrome
Paraneoplastic syndromes associated
with Thymoma
(Thymoma- state of art, jour of clin oncol 17 : 2280 – 2289
by American society of clinical oncology)
Myasthenia gravis – most common (30 – 50%)
Pure red cell aplasia
Acquired hypogammaglobulinemia
Auto immune hemolytic anemia
Agranulocytosis
Peripheral neuropathy
Pernicious anemia
Limbic encephalopathy
Nephrotic syndrome
Alopecia areata
Contd…
Panhypopituitarism
Hyperthyroidism
Addison’s disease
Rheumatoid arthritis
SLE
Systemic sclerosis
Sarcoidosis
Dermatomyositis
Inflammatory bowel disease & Whipple’s disease
Hypertrophic osteoarthropathy
DIAGNOSIS
CxR
CT scan
MRI
FNAC of tumor –
USG/ CT guided.
Excisional Biopsy
TREATMENT
1.
Surgery- mainstay of treatment because majority of
these tumors 90 – 95% are localized.
Stage 1 – completely resectable
Stage 2 – 42 – 100 % resectable
stage 3 – 0 to 89 % resectable
Stage 4
- 0 to 78% resectable (Jour of onco vol 17,no 7(july)1999)
Extensive resections seem justifiable since complete resection is
probably most important prognostic factors
recurrence rate is less than 2% and 28% resp. for non – invasive and
invasive tumors (cancer treatment review 2000;26:127 -131)
Adjuvant Radio therapy – moderatively radio sensitive.
a retrospective study has shown that without post – operative
radiation for invasive thymoma, the relapse rate was 26%.
10 years survival rate after non – invasive thymomas range between
67 – 80 % while those for invasive disease range from 35 – 53 %
Chemotherapy- candidates for cytotoxic chemotherapy are
- who presents with metastatic disease not amenable to local
treatment modalities.
- surgery and/ or radiation therapy fails.
Combined modality therapy- advanced invasive thymoma.
Salvage therapy- somatostatine analogues
used in chemotherapy refractory/ recurrence cases.
Indium labelled octreotide and prednisone.
High dose chemotherapy and stem cell support – investigational
approach.
Novel therapies
Recent chemotherapeutic agents –
- taxoids, topoisomerase 1 inhibitors and gemcitabine
- somatostatine analogs
- High dose chemotherapy with stem cell rescue
- Investigational agents – flavonoids, signal transduction
inhibitors, and anti – angiogenic agents
Survival rate %
Stage
1
2
3
4
5yr
71- 100%
60 – 98%
46 – 89%
40 – 71%
10yr
87- 100%
42 – 98%
26 – 78 %
0 - 47%
15yr
78%
73%
30%
8%
( Kunda and MOnden, Regnand et al, Maggi et al, Verley and Hollman, Comen et L, Nikin et all,
Monden et al, Blumber et al, Rruffinin et al, Quintanilla – Martinea et al)
References
1.
2.
3.
4.
5.
6.
Tumor of mediastinum, by American college of physicians; December 15
2005;128 www.chestjournal.org.
Malignant thymoma: current status and future directions – P.N. Lara
Cancer treatment Review 2000; 26; 127 -131
Thymoma; state of Art ( review article ) by Charles R. Thomas, Jr. ,
Cameron D. , Patrick J. Lochrer, Sr.
Thymic tumors ( review article ) by Franck C. Detterback, MD
Ann Thorac Surg 2004; 77 : 1860 – 9
Classification of Thymic neoplasm ( original article ) – Desai Saral et al
Indian Journal of surgery 2004 vol. 66, issue 2; 93 – 96.
Thymoma – pathological study of 50 cases ( original article )
Journal of postgraduate medicine, 2004 vol. 50, issue 2, 94 -97.
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