CASE OF THE MONTH

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CASE OF THE MONTH

• DR. SHAILESH MANANDHAR
• PAEDIATRIC RESIDENT 1ST YEAR
• IOM

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Patients Profile

• Name Kapindra Regmi
• Age / Sex 12yrs / M
• Add Dolkha
• I.P No 12153
• DOA 2062/7/12 at 930 pm
• DOD 2062/8/8 at 1100 am
• Admitting Diagnosis Lt. Pyopneumothorax with
  neck mass ? Lymphoma
• Final Diagnosis Malignant thymoma Stage
  3 with Lt. chylopneumothorax

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Chief complains

1. Progressive difficulty in breathing for 10 days
2. Difficulty in swallowing for 10 days
3. Upper abdominal swelling for 5 days

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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

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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

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HISTORY OF PAST ILLNESS

• Never needed medical care and medication.

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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 peoples 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.

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• 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)

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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.

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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

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• 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. Cant get lower border of
  mass.
• Neck mass doesnt move on deglutition/
  protrusion of tongue.

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• Lymphnodes- Single Rt. Axillary 11 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.

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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.

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• 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

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• 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.

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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)
• Platelet160,000/mm
• ESR 12
• Na 139 K 4.5m mol/L
• Urine R/E normal

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• 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

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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 Analysis-
• TC 21,900/cumm (L- 91, N- 9)
• protein 61 micromol / L

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• Agt Lt. chylopneumothorax ? Lymphoma ?
  Tuberculosis
• Plan- pleural fluid triglyceride level
• sr.creatinin, urea,
• LFT
• Sputum for AFB
• Mantoux test

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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

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• 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.

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D6

• Patients condition static
• Mx no induration
• Sputum for AFB- Negative.
• Advice to take high protein diet.

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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

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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.

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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.

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• Plan for CT scan thorax
• Patient party counseled about the disease and
  possible therapy and poor prognosis.

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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.

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D21

• CT scan thorax-
• Large 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

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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.

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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.

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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.

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D26

• On oncology department patient party again
  counseled about the poor prognosis of disease and
  possible expenses.
• Then, they refused treatment.

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• 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.

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THYMOMA
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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

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Differential diagnosis of mediastinal mass by
anatomic location

• ANTERIOR MIDDLE POSTERIOR
• Thymoma Lymphoma Neurogenic tumor
• Teratoma/seminoma Pericardial cyst Bronchogenic
  cyst
• Lymphoma Broncogenic cyst Enteric cyst
• Parathyroid adenoma Metastatic cyst Xanthogranulo
  ma
• Intrathoracic goiter Systemic granuloma Diaphragma
  tic hernia
• Lipoma Meningocele
• Lymphagioma Paravertebral abscess
• Aortic aneurysm

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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 its
  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 bodys own components.
• Embryologically, thymic epithelium is derived
  from both the ectoderm and the endoderm of the
  3rd 4th branchial cleft and pharyngeal pouches.

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Histology of Thymus
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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

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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

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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 -
• 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.

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Masaoka Staging of Thymoma (1981)

• Stage Degree of invasion 5yrs
  survival rate
• 1 Macroscopically completely encapsulated 96
  100
• with no microscopic extracapsular invasion
• 2a Microscopic invasion through the capsule 86
  95
• 2b Macroscopic invasion into mediastenal fat
• or pleura.
• 3 Invasion into adjacent structures 56 -69
• (pericardium, great vessel or lung)
• 4a Pleural or pericardial metastasis 11
  50
• 4b Lymphatic or hematogenous metastasis

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WHO Classification of Thymoma
(1999)

• CLASS CYTOLOGIC FEATURES
• Type A Spindle shaped, Medullary
• Type B Mixed
• Type B1 Lymphocyte rich, lymphocytic,
• predominantly cortical, organoid.
• Type B2 Cortical
• Type B3 Epithelial, atypical, squamous,
• well differentiated thymic carcinoma
• Type C Thymic carcinoma
• ( Referance - cancer
  treatment Review 2000 26 127- 131)

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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

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Common symptoms at presentations are-

• 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
• lt 1 of thymic tumor Stage 4b
• ( Reference -Thymic tumors review article Ann
  Thorac Surg 2004 77 1860 9 )

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Localizing symptoms secondary to tumor invasion
of surrounding structures

• Involved Anatomic structures localizing
  symptoms
• Bronchi / Trachea Dyspnea, post
  obstructive pneumona, atelactasis,
  hemoptysis
• Esophagus Dysphagia
• Spinal cord/vertebral column Paralysis
• Recurrent laryngeal nerve Hoarsness, vocal
  cord paralysis
• Phrenic nerves Diaphragmatic Paralysis
• Stellate ganglion Horners syndrome
• Superior vana cava Superior Vana Cava
  Syndrome

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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

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Contd

• Panhypopituitarism
• Hyperthyroidism
• Addisons disease
• Rheumatoid arthritis
• SLE
• Systemic sclerosis
• Sarcoidosis
• Dermatomyositis
• Inflammatory bowel disease Whipples disease
• Hypertrophic osteoarthropathy

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DIAGNOSIS

• FNAC of tumor USG/ CT guided.
• Excisional Biopsy

• CxR
• CT scan
• MRI

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TREATMENT

• 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 200026127 -131)

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• 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

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• 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.

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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

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Survival rate

• Stage 5yr 10yr 15yr
• 71- 100 87- 100 78
• 60 98 42 98 73
• 46 89 26 78 30
• 40 71 0 - 47 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)

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References

1. Tumor of mediastinum, by American college of
   physicians December 15 2005128
   www.chestjournal.org.
2. Malignant thymoma current status and future
   directions P.N. Lara Cancer treatment Review
   2000 26 127 -131
3. Thymoma state of Art ( review article ) by
   Charles R. Thomas, Jr. , Cameron D. , Patrick J.
   Lochrer, Sr.
4. Thymic tumors ( review article ) by Franck C.
   Detterback, MD Ann Thorac Surg
   2004 77 1860 9
5. Classification of Thymic neoplasm ( original
   article ) Desai Saral et al
   Indian Journal of surgery 2004 vol. 66,
   issue 2 93 96.
6. Thymoma pathological study of 50 cases (
   original article ) Journal of
   postgraduate medicine, 2004 vol. 50, issue 2, 94
   -97.

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