CASE OF THE MONTHCASE OF THE MONTH

DR. SHAILESH MANANDHARDR. SHAILESH MANANDHARPAEDIATRIC RESIDENT 1PAEDIATRIC RESIDENT 1STST YEAR YEAR

IOMIOM

Patient’s ProfilePatient’s ProfileName : Kapindra Regmi Name : Kapindra Regmi Age / Sex – 12yrs / MAge / Sex – 12yrs / MAdd : DolkhaAdd : DolkhaI.P No : 12153I.P No : 12153DOA : 2062/7/12 at 9:30 pmDOA : 2062/7/12 at 9:30 pmDOD : 2062/8/8 at 11:00 amDOD : 2062/8/8 at 11:00 amAdmitting Diagnosis: Lt. Pyopneumothorax with Admitting Diagnosis: Lt. Pyopneumothorax with

neck mass ? Lymphoma neck mass ? LymphomaFinal Diagnosis : Malignant thymoma Stage 3 with Final Diagnosis : Malignant thymoma Stage 3 with

Lt. chylopneumothorax Lt. chylopneumothorax

Chief complainsChief complains

1.1. Progressive difficulty in breathing for 10 daysProgressive difficulty in breathing for 10 days2.2. Difficulty in swallowing for 10 daysDifficulty in swallowing for 10 days3.3. Upper abdominal swelling for 5 daysUpper abdominal swelling for 5 days

History of Present IllnessHistory of Present Illness

Patient was apparently well 20 days back. Then , he Patient was apparently well 20 days back. Then , he developed mild to moderate grade fever intermittent developed mild to moderate grade fever intermittent not a/w chills & rigor but with profuse night sweats not a/w chills & rigor but with profuse night sweats lasting for 10 days.lasting for 10 days.Cough with mucoid expectoration, no hemoptysis, no Cough with mucoid expectoration, no hemoptysis, no vomiting, no dysuria, no pain abdomenvomiting, no dysuria, no pain abdomenChest pain more on left side and on coughing.Chest pain more on left side and on coughing.Complained throat pain during swallowingComplained throat pain during swallowingTaken treatment for local medical shop tab. Ofloxacin Taken treatment for local medical shop tab. Ofloxacin 200mg BD for 7 days – fever subsided but cough not 200mg BD for 7 days – fever subsided but cough not improvedimproved

HOPI Contd…………..HOPI Contd…………..

Subsequently mother noticed swelling in neck ; Subsequently mother noticed swelling in neck ; followed by swelling of upper abdomen couple of days followed by swelling of upper abdomen couple of days later. later. Gradual difficulty in breathing and swallowing Gradual difficulty in breathing and swallowing Bowel and bladder habit were normalBowel and bladder habit were normalNo noisy breathingNo noisy breathingNo H/O joint pain or swelling, rashes, swelling of legs, No H/O joint pain or swelling, rashes, swelling of legs, no hoarseness of voice, no jaundice.no hoarseness of voice, no jaundice.No h/o bony tenderness.No h/o bony tenderness.No H/O loss of consciousness or seizureNo H/O loss of consciousness or seizure

HISTORY OF PAST ILLNESSHISTORY OF PAST ILLNESS

Never needed medical care and Never needed medical care and medication.medication.

FAMILY HISTORYFAMILY HISTORYOnly child in familyOnly child in familyMother: 35years/ House-wifeMother: 35years/ House-wifeFather : expired 4 years back in RTAFather : expired 4 years back in RTALow socio economic class familyLow socio economic class familyMother earn living by working in own small field and Mother earn living by working in own small field and other people’s houses in villageother people’s houses in villageNo H/ O similar illness/ TB in the family or in close No H/ O similar illness/ TB in the family or in close contacts.contacts.No H/O consanguinity of marriage.No H/O consanguinity of marriage.No H/O pet in the family.No H/O pet in the family.

BIRTH HISTORY -BIRTH HISTORY -FT/S/F/NVD at Home . Ante-natal/intra-partum or FT/S/F/NVD at Home . Ante-natal/intra-partum or postpartum period: Uneventfulpostpartum period: Uneventful

IMMUNIZATION HISTORY –IMMUNIZATION HISTORY – not immunizednot immunized

DEVELOPMEENTAL HISTORY -DEVELOPMEENTAL HISTORY - Normal for his ageNormal for his age

NUTRITIONAL HISTORYNUTRITIONAL HISTORY - -Taking less than required calorie.(80 Kcal/kg/dayTaking less than required calorie.(80 Kcal/kg/day))

TREATMENT HISTORYTREATMENT HISTORYAdmitted In Kathmandu Model hospital, Dolkha one Admitted In Kathmandu Model hospital, Dolkha one week back. week back. Inj. Ceftriazone 50mg/kg/d q 12hr for 5 daysInj. Ceftriazone 50mg/kg/d q 12hr for 5 daysHistory of aspiration of thick white fluid from left chest History of aspiration of thick white fluid from left chest twice.twice.Referred from there with discharging diagnosis of left Referred from there with discharging diagnosis of left pyopneumothorax with neck mass ? Lymphoma to pyopneumothorax with neck mass ? Lymphoma to cardio thoracic surgery department for evaluation and cardio thoracic surgery department for evaluation and management of neck mass and chest tube insertion.management of neck mass and chest tube insertion.

ON EXAMINATIONON EXAMINATIONChild was conscious oriented to time, place and person Child was conscious oriented to time, place and person but looked dyspneic and tachypnic.but looked dyspneic and tachypnic.Vitals: Pulse: 116b/min normo volumic Vitals: Pulse: 116b/min normo volumic

R/R : 48/min regularR/R : 48/min regular B.P : 90/40 mm HgB.P : 90/40 mm Hg Temp: 100Temp: 10000CC

Anthropometry: wt. 25 kg Ht. 136 cmAnthropometry: wt. 25 kg Ht. 136 cm wt. for age : 62.5 % of expectedwt. for age : 62.5 % of expected ht. for age : 90 % of expectedht. for age : 90 % of expected wt. for ht. : 83.3 % of expectedwt. for ht. : 83.3 % of expected

Puffy face with mild submandibular region swelling.Puffy face with mild submandibular region swelling.

Distended neck veins.Distended neck veins.

Visible swelling on anterior lower part of neck. On Visible swelling on anterior lower part of neck. On palpation hard fixed mass approx. 3 cm by breadth ill palpation hard fixed mass approx. 3 cm by breadth ill defined borders arising from retrosternal region. defined borders arising from retrosternal region. Can’t get lower border of mass.Can’t get lower border of mass.Neck mass –doesn’t move on deglutition/ protrusion Neck mass –doesn’t move on deglutition/ protrusion of tongue. of tongue.

Lymphnodes- Single Rt. Axillary 1*1 cm, multiple cervical Lymphnodes- Single Rt. Axillary 1*1 cm, multiple cervical and submandibular 0.5 to 1cm and submandibular 0.5 to 1cm Pallor / jaundice / cyanosis – absentPallor / jaundice / cyanosis – absentClubbing- absentClubbing- absentPedal edema – absent.Pedal edema – absent.Ear/nose and throat examination- normalEar/nose and throat examination- normalJoints : NormalJoints : NormalBony tenderness: AbsentBony tenderness: AbsentNon pitting edematous swelling of anterior chest and Non pitting edematous swelling of anterior chest and upper abdomen.upper abdomen.

RESPIRATORY EXAMINATIONRESPIRATORY EXAMINATIONINSPECTION- Fullness in Lt. anterior chest wall. Reduced INSPECTION- Fullness in Lt. anterior chest wall. Reduced movement on same side. movement on same side.

PALPATION- trachea- deviated to left side. Reduced tactile and PALPATION- trachea- deviated to left side. Reduced tactile and vocal fremitus in Lt. side on lower half.vocal fremitus in Lt. side on lower half.

PERCUSSION- stony dullness on Lt. lower part of chest.PERCUSSION- stony dullness on Lt. lower part of chest. Hyperresonant note on Lt. upper part of chest.Hyperresonant note on Lt. upper part of chest.

AUSCULTATION- absent BS on Lt. side of chest. Normal vesicular AUSCULTATION- absent BS on Lt. side of chest. Normal vesicular breath sound with no added sound on right side of chest.breath sound with no added sound on right side of chest.

PER ABDOMEN :-PER ABDOMEN :-

InspectionInspection: mild distension of upper part of abdomen; visible : mild distension of upper part of abdomen; visible veins with flow up to downward at supraumbilical region, central veins with flow up to downward at supraumbilical region, central umbilicus. No scar marks, No visible peristalsisumbilicus. No scar marks, No visible peristalsis

PalpationPalpation: No tenderness on superficial or deep palpation. : No tenderness on superficial or deep palpation. Liver/Spleen non palpable. No abdominal LN palpable.Liver/Spleen non palpable. No abdominal LN palpable.

Hernial orifices: IntactHernial orifices: Intact Both testes were palpable at lower end of inguinal canalBoth testes were palpable at lower end of inguinal canal normal size with intact sensation.normal size with intact sensation.

PercussionPercussion: Tympanic. No fluid thrill or shifting dullness: Tympanic. No fluid thrill or shifting dullness

AuscultationAuscultation: normal: normal bowel soundbowel sound

CVS : CVS : apex beat localized at 4apex beat localized at 4thth ICS 3cm medial to left ICS 3cm medial to left nipple. S1,S2 – N , No murmurnipple. S1,S2 – N , No murmur

CNS : CNS :

- conscious, cooperative and oriented to time, place - conscious, cooperative and oriented to time, place

and person. and person. - cranial nerves grossly intact- cranial nerves grossly intact- muscle tone/power/bulk were normal in all limbs- muscle tone/power/bulk were normal in all limbs- no involuntary movements- no involuntary movements- superficial and deep tendon reflexes N- superficial and deep tendon reflexes N- Sensory examination with in normal limit- Sensory examination with in normal limit- Normal Gait.- Normal Gait.

PROVISION DXPROVISION DX:: Lt. Pyopneumothorax with neck Lt. Pyopneumothorax with neck

mass ? Lymphoma ? Tuberculosis mass ? Lymphoma ? Tuberculosis

INVESTIGATIONSINVESTIGATIONS CBC:CBC: Hb: 13.4 gm% TC: 12,100 (N-75, L- 15, E-8, M- 2)Hb: 13.4 gm% TC: 12,100 (N-75, L- 15, E-8, M- 2) Platelet:160,000/mmPlatelet:160,000/mm

ESR : 12ESR : 12 Na: 139 K: 4.5m mol/LNa: 139 K: 4.5m mol/L Urine R/E: normalUrine R/E: normal

Chest tube was inserted on left side - whitish Chest tube was inserted on left side - whitish turbid fluid ~ 2.5 litre drained and admitted in turbid fluid ~ 2.5 litre drained and admitted in Medical Ward.Medical Ward.Inj. Cloxacillin 100mg/kg/dInj. Cloxacillin 100mg/kg/dInj. Amikacin 15mg/kg/dInj. Amikacin 15mg/kg/dTab. Paracetamol 6hrlyTab. Paracetamol 6hrly

D3 of admissionD3 of admission

Reduced dyspnea, puffiness of face and look Reduced dyspnea, puffiness of face and look comfortable.comfortable.Tem. 100Tem. 10000F PR 102/m B.P: 96/60 mm Hg F PR 102/m B.P: 96/60 mm Hg Chest tube drain ~ 1.5 lit of milky white fluid with little Chest tube drain ~ 1.5 lit of milky white fluid with little dirty white fibrinous sediments .dirty white fibrinous sediments .Eating well .urine - NEating well .urine - N

INV: INV: Pleural Fluid Analysis-Pleural Fluid Analysis- TC: 21,900/cumm (L- 91%, N- 9%)TC: 21,900/cumm (L- 91%, N- 9%) protein – 61 micromol / Lprotein – 61 micromol / L

A> Lt. chylopneumothorax ? Lymphoma ? A> Lt. chylopneumothorax ? Lymphoma ? TuberculosisTuberculosis

Plan- pleural fluid triglyceride levelPlan- pleural fluid triglyceride level sr.creatinin, urea, sr.creatinin, urea,

LFTLFT Sputum for AFBSputum for AFB Mantoux test Mantoux test

D4,D5 of admissionD4,D5 of admissionComplains cough and chest pain otherwise comfortable.Complains cough and chest pain otherwise comfortable.Vital stable still have low grade fever.Vital stable still have low grade fever.Non pitting edema of left upper limb noted.Non pitting edema of left upper limb noted.Chest tube draining more milky fluid upto 2.5litres.Chest tube draining more milky fluid upto 2.5litres.No dehydration, passing urine.No dehydration, passing urine.Air entry on left side present.Air entry on left side present.

INV - pleural fluid triglyceride level – 9.3 m mol/LINV - pleural fluid triglyceride level – 9.3 m mol/L( 0.5 – 1.8 m mol/L)( 0.5 – 1.8 m mol/L)

Sr.creatinin – 0.4mg/dl Urea – 20 mg/dl.Sr.creatinin – 0.4mg/dl Urea – 20 mg/dl. Sr. albumin 2g% Total protein – 3g%Sr. albumin 2g% Total protein – 3g% SGPT 15IU SGOT 16 IU SGPT 15IU SGOT 16 IU

Blood C/S – sterile after 96 hrs.Blood C/S – sterile after 96 hrs.Pleural fluid C/S- E.coli isolated Pleural fluid C/S- E.coli isolated sensitive to Imipenamsensitive to ImipenamIntermediate sensitive to AmikacinIntermediate sensitive to Amikacinresistant to Ampi, cipro, genta, ceftazedime,resistant to Ampi, cipro, genta, ceftazedime,tobramycin, cephalexin, cotrim.tobramycin, cephalexin, cotrim.USG - Multiple enlarged LNs in neck, mediastenum and USG - Multiple enlarged LNs in neck, mediastenum and clavicular region with left pleural effusion.clavicular region with left pleural effusion.Liver- enlarged in size, no SOLLiver- enlarged in size, no SOLother viscera WNL.other viscera WNL.X- ray chest Lateral viewX- ray chest Lateral viewPlan for neck mass / lymph node biopsy.Plan for neck mass / lymph node biopsy.

D6D6

Patient’s condition staticPatient’s condition staticMx – no indurationMx – no indurationSputum for AFB- Negative.Sputum for AFB- Negative.Advice to take high protein diet.Advice to take high protein diet.

D8 – D10 D8 – D10 Looked betterLooked betterFever subsided, still complains cough.Fever subsided, still complains cough.Neck swelling and venous prominence reduced than Neck swelling and venous prominence reduced than admission day.admission day.Neck mass felt softening than before.Neck mass felt softening than before.Chest tube functioning; draining still 1 -2 lit/dayChest tube functioning; draining still 1 -2 lit/day

D12D12

Case referred to CTVS department, TUTH for expert Case referred to CTVS department, TUTH for expert opinion and further management. opinion and further management.

Case seen by Dr. P. Sayami, with impression of Case seen by Dr. P. Sayami, with impression of mediastinal lymphoma with left chylothorax, USG guided mediastinal lymphoma with left chylothorax, USG guided FNAC of mediastinal mass and follow up with report was FNAC of mediastinal mass and follow up with report was adviced.adviced.

D15 D15

USG guided FNAC of neck mass done –USG guided FNAC of neck mass done –Mixed population of mature and immature lymphoid Mixed population of mature and immature lymphoid

cells; with few clusters of atypical epithelial cells – moderately cells; with few clusters of atypical epithelial cells – moderately Pleomorphic, oval to spindle nuclei and scanty cytoplasm and few Pleomorphic, oval to spindle nuclei and scanty cytoplasm and few squamous cells in background. squamous cells in background.

Impression: Malignant Thymoma.Impression: Malignant Thymoma.

Plan for CT scan thoraxPlan for CT scan thorax

Patient party counseled about the disease and possible Patient party counseled about the disease and possible therapy and poor prognosis.therapy and poor prognosis.

D17 – D20D17 – D20Patient look dysneic with puffy face.Patient look dysneic with puffy face.Complaining of dysphagia more for solid foodComplaining of dysphagia more for solid foodTemp. 101Temp. 10100F PR 120/m BP- 90/50 mmHgF PR 120/m BP- 90/50 mmHgNo Ptosis, no diplopia, no muscle weaknessNo Ptosis, no diplopia, no muscle weaknessNo rashes, joint pain.No rashes, joint pain.Chest - absent BS on left lower 2/3Chest - absent BS on left lower 2/3rdrd..Chest tube not draining since yesterday.Chest tube not draining since yesterday.Chest tube irrigation done and Chyle started draining.Chest tube irrigation done and Chyle started draining.

D21D21

CT scan thorax-CT scan thorax-Large lobulated soft tissue density well defined mass in Large lobulated soft tissue density well defined mass in

anterior superior mediastenum that shows heterogenous anterior superior mediastenum that shows heterogenous enhancement with contrast; encasing all the major vessels of the enhancement with contrast; encasing all the major vessels of the

mediastenum including aortic arch and pulmonary arteriesmediastenum including aortic arch and pulmonary arteries. . Thick Thick irregular enhancement of pleura with nodular thickening at places.irregular enhancement of pleura with nodular thickening at places.

Impression- Malignant thymic massImpression- Malignant thymic mass

D22D22

Consultation with CTVS team was done for further Consultation with CTVS team was done for further management of case with CT report.management of case with CT report.With impression of advanced thymic carcinoma – With impression of advanced thymic carcinoma – inoperable, case was referred for Radiotherapy from inoperable, case was referred for Radiotherapy from their side.their side.

D23D23

Patient general condition- samePatient general condition- samePatient party were given option for treatment Patient party were given option for treatment after explaining prognosis of disease.after explaining prognosis of disease.Referred to Bhaktapur Cancer Hospital for Referred to Bhaktapur Cancer Hospital for further treatment.further treatment.

D25D25Patient came back from Bhaktapur Cancer Hospital with Patient came back from Bhaktapur Cancer Hospital with a referral letter to oncology department. Patient was a referral letter to oncology department. Patient was advised palliative chemotherapy of Ipbosphamide and advised palliative chemotherapy of Ipbosphamide and adriamycin and asked to come on follow up for adriamycin and asked to come on follow up for radiotherapy.radiotherapy.

D26D26

On oncology department patient party again On oncology department patient party again counseled about the poor prognosis of disease counseled about the poor prognosis of disease and possible expenses.and possible expenses.

Then, they refused treatment.Then, they refused treatment.

Discharged on request on 2062-08-07Discharged on request on 2062-08-07WITHWITH

FINAL DIAGNOIS – Thymic carcinoma ( stage 3)FINAL DIAGNOIS – Thymic carcinoma ( stage 3)with Lt. chylopneumothoraxwith Lt. chylopneumothorax& superior vena cava syndrome& superior vena cava syndromewithout obvious paraneoplastic without obvious paraneoplastic syndromes.syndromes.

THYMOMATHYMOMA

ANATOMYANATOMY : :

Mediastinum –Mediastinum –pleural cavity laterallypleural cavity laterallyThoracic inlet superiorlyThoracic inlet superiorly

Diaphragm inferiorlyDiaphragm inferiorly..

AnteriorAnterior – – Thymus, Fat and LNThymus, Fat and LN

MiddleMiddle – – Heart, pericardium, ascending and transverse aorta, Heart, pericardium, ascending and transverse aorta, branchiocephalic veins, trachea, bronchi, LNbranchiocephalic veins, trachea, bronchi, LN

PosteriorPosterior – – descending thoracic aorta, esophagus, azygos descending thoracic aorta, esophagus, azygos vein, autonomic ganglia and nerves, thoracic LNvein, autonomic ganglia and nerves, thoracic LN

Differential diagnosis of mediastinal mass by Differential diagnosis of mediastinal mass by anatomic locationanatomic location

ANTERIORANTERIOR MIDDLEMIDDLE POSTERIORPOSTERIORThymomaThymoma LymphomaLymphoma Neurogenic tumorNeurogenic tumorTeratoma/seminomaTeratoma/seminoma Pericardial cystPericardial cyst Bronchogenic cystBronchogenic cystLymphomaLymphoma Broncogenic cystBroncogenic cyst Enteric cystEnteric cystParathyroid adenomaParathyroid adenoma Metastatic cystMetastatic cyst XanthogranulomaXanthogranulomaIntrathoracic goiterIntrathoracic goiter Systemic granulomaSystemic granuloma Diaphragmatic herniaDiaphragmatic herniaLipomaLipoma MeningoceleMeningoceleLymphagiomaLymphagioma Paravertebral abscessParavertebral abscessAortic aneurysm Aortic aneurysm

THYMUSTHYMUS : :

Soft, bilobed, pyramidal organ in anterior superior mediastenumSoft, bilobed, pyramidal organ in anterior superior mediastenumAt birth wt. 10 -15 gmAt birth wt. 10 -15 gmAnteriorly – sternum, sternohyoid, sternothyroid musclesAnteriorly – sternum, sternohyoid, sternothyroid musclesPosteriorly – pericardium, arch of aorta & it’s branches, left Posteriorly – pericardium, arch of aorta & it’s branches, left branchiocephalic vein, trachea.branchiocephalic vein, trachea.One of two primary lymphoid organ of body.One of two primary lymphoid organ of body.Provides unique microenvironment in which T cell precursors Provides unique microenvironment in which T cell precursors undergoes development, differentiation & clonal expansionundergoes development, differentiation & clonal expansionDuring this process, exquisite specificity of T cell responses is During this process, exquisite specificity of T cell responses is acquired; also their immune tolerance to body’s own components.acquired; also their immune tolerance to body’s own components.Embryologically, thymic epithelium is derived from both the Embryologically, thymic epithelium is derived from both the ectoderm and the endoderm of the 3ectoderm and the endoderm of the 3rdrd & 4 & 4thth branchial cleft and branchial cleft and pharyngeal pouches.pharyngeal pouches.

Histology Histology of of

Thymus:Thymus:

INTRODUCTIONINTRODUCTION

Thymoma is a tumor arising from epithelium of thymus Thymoma is a tumor arising from epithelium of thymus gland.gland.Majority of thymoma looks histological benign.Majority of thymoma looks histological benign.Usually follows indolent course patient surviving for Usually follows indolent course patient surviving for years.years.34% of thymomas invades their own capsules, extending 34% of thymomas invades their own capsules, extending to surrounding structures.to surrounding structures.Less than 10% behave like invasive epithelial Less than 10% behave like invasive epithelial malignancies malignancies

Epidemiology Epidemiology

Incidence 0.15 cases per 100,000Incidence 0.15 cases per 100,000 accounting 0.2 to 1.5% of all malignanciesaccounting 0.2 to 1.5% of all malignancies

( reference - Tumor of mesiastinum by ACP. Dec 15 05’)( reference - Tumor of mesiastinum by ACP. Dec 15 05’)

Thymoma constitute about 50% of anterior Thymoma constitute about 50% of anterior mediastenal neoplasm in adult, Lymphoma -25%mediastenal neoplasm in adult, Lymphoma -25%Peak age of incidence – 4Peak age of incidence – 4thth to 6 to 6thth decades of life decades of lifeSex – no predilection of genderSex – no predilection of genderChildren very rarely affected.Children very rarely affected.Usually associated with the host of unusual Usually associated with the host of unusual paraneoplastic syndromesparaneoplastic syndromes

PATHOLOGY:PATHOLOGY:

Tumor arises from epithelial component of thymus.Tumor arises from epithelial component of thymus.

Most of them are solid tumor; but up to one third may have components Most of them are solid tumor; but up to one third may have components that are necrotic, hemorrhagic or cystic.that are necrotic, hemorrhagic or cystic.

Histologically, 3 groups of thymic tumors can be distinguished :-Histologically, 3 groups of thymic tumors can be distinguished :-

1.1. Typical thymoma - with no cytological features of malignancyTypical thymoma - with no cytological features of malignancy2.2. Atypical thymoma - with organotypic features of thymoma but Atypical thymoma - with organotypic features of thymoma but

with areas of atypia and occasional mitosis (WDTC).with areas of atypia and occasional mitosis (WDTC).3.3. Thymic carcinoma- with abundant mitotic figures and other Thymic carcinoma- with abundant mitotic figures and other

cytological features of malignancy.cytological features of malignancy.

Masaoka Masaoka Staging of ThymomaStaging of Thymoma(1981)(1981)

StageStage Degree of invasionDegree of invasion 5yrs survival rate 5yrs survival rate %%

11 Macroscopically completely encapsulated Macroscopically completely encapsulated 96 – 100 %96 – 100 % with no microscopic extracapsular invasionwith no microscopic extracapsular invasion

2a2a Microscopic invasion through the capsule Microscopic invasion through the capsule 86 – 95 %86 – 95 %2b2b Macroscopic invasion into mediastenal fat Macroscopic invasion into mediastenal fat

or pleura.or pleura.33 Invasion into adjacent structures Invasion into adjacent structures 56 -69 %56 -69 %

(pericardium, great vessel or lung)(pericardium, great vessel or lung)

4a4a Pleural or pericardial metastasis Pleural or pericardial metastasis 11 – 50 %11 – 50 %4b4b Lymphatic or hematogenous metastasis Lymphatic or hematogenous metastasis

WHO Classification of Thymoma WHO Classification of Thymoma

(1999)(1999)CLASS CLASS CYTOLOGIC FEATURESCYTOLOGIC FEATURES

Type AType A Spindle shaped, MedullarySpindle shaped, MedullaryType BType B MixedMixedType B1Type B1 Lymphocyte rich, lymphocytic, Lymphocyte rich, lymphocytic,

predominantly cortical, organoid.predominantly cortical, organoid.Type B2Type B2 CorticalCorticalType B3Type B3 Epithelial, atypical, squamous, Epithelial, atypical, squamous,

well differentiated thymic carcinomawell differentiated thymic carcinomaType CType C Thymic carcinomaThymic carcinoma

( Referance - cancer treatment Review 2000 ; 26: 127- 131)( Referance - cancer treatment Review 2000 ; 26: 127- 131)

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS::

One third to one half of patient present with asymptomatic One third to one half of patient present with asymptomatic mediastinal mass on chest radiography.mediastinal mass on chest radiography.

one third present with local symptoms related to intrathoracic one third present with local symptoms related to intrathoracic mass.mass.

One third are detected during evaluation of Myasthenia One third are detected during evaluation of Myasthenia gravis.gravis.

Distant metastasis are rare at initial presentation.Distant metastasis are rare at initial presentation.When present, most common metastatic site is PleuraWhen present, most common metastatic site is Pleura

Common symptoms at presentations are:-Common symptoms at presentations are:-

1.1. Cough -Cough - 60% 60%2.2. Chest pain - 30%Chest pain - 30%3.3. Fever / Chill - 20%Fever / Chill - 20%4.4. Dyspnea - 16%Dyspnea - 16% ( reference - Tumor of mesiastinum by ACP. Dec 15 05’)( reference - Tumor of mesiastinum by ACP. Dec 15 05’)

At presentationAt presentation~ 40 % of thymic tumor – Stage 1~ 40 % of thymic tumor – Stage 1~ 25 % of thymic tumor – Stage 2 or 3~ 25 % of thymic tumor – Stage 2 or 3~ 10 % of thmic tumor – Stage 4a~ 10 % of thmic tumor – Stage 4a< 1 % of thymic tumor – Stage 4b< 1 % of thymic tumor – Stage 4b( Reference -Thymic tumors – review article Ann Thorac Surg 2004 ; 77 : 1860 – 9 )( Reference -Thymic tumors – review article Ann Thorac Surg 2004 ; 77 : 1860 – 9 )

Localizing symptoms secondary to tumor Localizing symptoms secondary to tumor invasion of surrounding structures invasion of surrounding structures

Involved Anatomic structuresInvolved Anatomic structures localizing symptomslocalizing symptomsBronchi / TracheaBronchi / Trachea Dyspnea, post obstructive Dyspnea, post obstructive

pneumona, atelactasis, pneumona, atelactasis, hemoptysis hemoptysis

EsophagusEsophagus Dysphagia DysphagiaSpinal cord/vertebral columnSpinal cord/vertebral column Paralysis ParalysisRecurrent laryngeal nerveRecurrent laryngeal nerve Hoarsness, vocal cord Hoarsness, vocal cord paralysisparalysisPhrenic nervesPhrenic nerves Diaphragmatic Paralysis Diaphragmatic ParalysisStellate ganglionStellate ganglion Horner’s syndrome Horner’s syndromeSuperior vana cavaSuperior vana cava Superior Vana Cava Syndrome Superior Vana Cava Syndrome

Paraneoplastic syndromes associated Paraneoplastic syndromes associated with Thymomawith Thymoma

(Thymoma- state of art, jour of clin oncol 17 : 2280 – 2289 (Thymoma- state of art, jour of clin oncol 17 : 2280 – 2289 by American society of clinical oncology)by American society of clinical oncology)

Myasthenia gravis – most common (30 – 50%)Myasthenia gravis – most common (30 – 50%)Pure red cell aplasiaPure red cell aplasiaAcquired hypogammaglobulinemia Acquired hypogammaglobulinemia Auto immune hemolytic anemiaAuto immune hemolytic anemiaAgranulocytosisAgranulocytosisPeripheral neuropathyPeripheral neuropathyPernicious anemiaPernicious anemiaLimbic encephalopathyLimbic encephalopathyNephrotic syndromeNephrotic syndromeAlopecia areataAlopecia areata

Contd…Contd…

Panhypopituitarism Panhypopituitarism HyperthyroidismHyperthyroidismAddison’s diseaseAddison’s diseaseRheumatoid arthritisRheumatoid arthritisSLESLESystemic sclerosisSystemic sclerosisSarcoidosis Sarcoidosis DermatomyositisDermatomyositisInflammatory bowel disease & Whipple’s diseaseInflammatory bowel disease & Whipple’s diseaseHypertrophic osteoarthropathyHypertrophic osteoarthropathy

DIAGNOSIS DIAGNOSIS

CxRCxRCT scanCT scanMRIMRI

FNAC of tumor – FNAC of tumor – USG/ CT guided.USG/ CT guided.Excisional BiopsyExcisional Biopsy

TREATMENTTREATMENT1.1. Surgery- mainstay of treatment because majority of Surgery- mainstay of treatment because majority of

these tumors 90 – 95% are localized.these tumors 90 – 95% are localized.Stage 1 – completely resectableStage 1 – completely resectableStage 2 – 42 – 100 % resectableStage 2 – 42 – 100 % resectablestage 3 – 0 to 89 % resectablestage 3 – 0 to 89 % resectableStage 4Stage 4 - 0 to 78% resectable (- 0 to 78% resectable (Jour of onco vol 17,no 7(july)1999Jour of onco vol 17,no 7(july)1999))Extensive resections seem justifiable since complete resection is Extensive resections seem justifiable since complete resection is probably most important prognostic factorsprobably most important prognostic factorsrecurrence rate is less than 2% and 28% resp. for non – invasive and recurrence rate is less than 2% and 28% resp. for non – invasive and invasive tumors (invasive tumors (cancer treatment review 2000;26:127 -131)cancer treatment review 2000;26:127 -131)

Adjuvant Radio therapy – moderatively radio sensitive.Adjuvant Radio therapy – moderatively radio sensitive.a retrospective study has shown that without post – operative a retrospective study has shown that without post – operative radiation for invasive thymoma, the relapse rate was 26%.radiation for invasive thymoma, the relapse rate was 26%.10 years survival rate after non – invasive thymomas range between 10 years survival rate after non – invasive thymomas range between 67 – 80 % while those for invasive disease range from 35 – 53 %67 – 80 % while those for invasive disease range from 35 – 53 %

Chemotherapy- candidates for cytotoxic chemotherapy areChemotherapy- candidates for cytotoxic chemotherapy are- who presents with metastatic disease not amenable to local - who presents with metastatic disease not amenable to local treatment modalities.treatment modalities.- surgery and/ or radiation therapy fails.- surgery and/ or radiation therapy fails.

Combined modality therapy- advanced invasive thymoma.Combined modality therapy- advanced invasive thymoma.Salvage therapy- somatostatine analoguesSalvage therapy- somatostatine analoguesused in chemotherapy refractory/ recurrence cases.used in chemotherapy refractory/ recurrence cases.Indium labelled octreotide and prednisone.Indium labelled octreotide and prednisone.High dose chemotherapy and stem cell support – investigational High dose chemotherapy and stem cell support – investigational approach.approach.

Novel therapiesNovel therapies

Recent chemotherapeutic agents –Recent chemotherapeutic agents –- taxoids, topoisomerase 1 inhibitors and gemcitabine- taxoids, topoisomerase 1 inhibitors and gemcitabine- somatostatine analogs- somatostatine analogs- High dose chemotherapy with stem cell rescue- High dose chemotherapy with stem cell rescue- Investigational agents – flavonoids, signal transduction - Investigational agents – flavonoids, signal transduction inhibitors, and anti – angiogenic agentsinhibitors, and anti – angiogenic agents

Survival rate %Survival rate %

Stage Stage 5yr5yr 10yr10yr 15yr15yr11 71- 100%71- 100% 87- 100%87- 100% 78%78%22 60 – 98%60 – 98% 42 – 98%42 – 98% 73%73%33 46 – 89%46 – 89% 26 – 78 %26 – 78 % 30%30%44 40 – 71%40 – 71% 0 - 47%0 - 47% 8%8% ( Kunda and MOnden, Regnand et al, Maggi et al, Verley and Hollman, Comen et L, Nikin et all, ( 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)Monden et al, Blumber et al, Rruffinin et al, Quintanilla – Martinea et al)

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2005;128 2005;128 www.chestjournal.orgwww.chestjournal.org..2.2. Malignant thymoma: current status and future directions – P.N. Lara Malignant thymoma: current status and future directions – P.N. Lara

Cancer treatment Review 2000; 26; 127 -131Cancer treatment Review 2000; 26; 127 -1313.3. Thymoma; state of Art ( review article ) by Charles R. Thomas, Jr. , Thymoma; state of Art ( review article ) by Charles R. Thomas, Jr. ,

Cameron D. , Patrick J. Lochrer, Sr.Cameron D. , Patrick J. Lochrer, Sr.4.4. Thymic tumors ( review article ) by Franck C. Detterback, MD Thymic tumors ( review article ) by Franck C. Detterback, MD

Ann Thorac Surg 2004; 77 : 1860 – 9Ann Thorac Surg 2004; 77 : 1860 – 95.5. Classification of Thymic neoplasm ( original article ) – Desai Saral et al Classification of Thymic neoplasm ( original article ) – Desai Saral et al

Indian Journal of surgery 2004 vol. 66, issue 2; 93 – 96. Indian Journal of surgery 2004 vol. 66, issue 2; 93 – 96.6.6. Thymoma – pathological study of 50 cases ( original article ) Thymoma – pathological study of 50 cases ( original article )

Journal of postgraduate medicine, 2004 vol. 50, issue 2, 94 -97.Journal of postgraduate medicine, 2004 vol. 50, issue 2, 94 -97.

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