Download Long-Term

Mediastinal Tumors
Abraham, Alcasabas, Alpuerto,
Asto, Asuncion, Balderia
General Data
• Delos Reyes, Kristina
• 28/F
Chief Complaint
• Chest discomfort
Patient Profile
• (-) diabetes, hypertension, allergies, asthma, goiter,
PTB
History of Present Illness
• 2 mos PTA, sudden onset of (+) bilateral ptosis during the afternoon
followed by difficulty in swallowing and slurred speech.
– Pt consulted at a local hospital and was admitted for 1 week.
– During the hospital stay, pt experienced DOB, Bilateral upper and lower
extremity weakness, and chest discomfort.
– Assessed to have Myasthenia gravis w/ Thymoma; pt was given
Pyridostigmine 60mg 5x a day and Prednisone 20mg OD
• 1 mo PTA, after discharge from the hospital, pt no longer had ptosis and
generalized weakness.
– Pt referred to a private neurologist and CT scan showed a right anterior
mediastinal mass.
– Pt advised to continue current medications and excision of the
thymoma.
– Pt was referred to PGH due to financial constraints.
– Pt currently on Pyridostigmine 60mg 5x a day and Prednisone 10mg
OD.
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Review of Systems
(-) fever
(-) generalized weakness
(-) cough/colds
(-) anorexia
(-) BOV
(-) dysphagia
(-) tremors
(-) palpitations
(-) dyspnea
(-) chest pain
(-) abdominal pain
(-) bowel and urinary complaints
(-) bleeding diathesis
(-) menstrual irregularities
• PMHx: as above
• FMHx:
– No similar illness
– (+) HPN- grandmother
– (+) CA – uncle
– (+) leukemia – cousin
– (-) DM, goiter, allergies, PTB, heart and renal diseases
• PSHx:
– (-) occasional alcoholic drinker, no known exposure to excessive
amounts of radiation
– Worked in a clothing manufacturing company for 7 years
OB-Gyne Hx
• Menarche: 11 y/o
• Regular monthly menses lasting for 3-5 days
consuming 3 ppds
• (+) dysmenorrhea
• (-) intermenstrual bleeding
• G2P2 (2002)
• (-) fetomaternal complications
Physical Examination
• Awake, coherent, NICRD, ambulatory
• Vital signs: BP=120/80; HR=78; RR=12;
afebrile
• HEENT: PC, AS, (-) ANM/TPC/CLAD/NVE
• Chest: ECE, resonant, (-) retractions, (-)
rales/wheezes
• CVS: AP, DHS, NRRR, (-) murmurs
• Abdomen: flabby, soft, NABS, (-)
masses/tenderness
Neurological Examination
• Pupils 3mm EBRTL
• (+) slight lateral rectus paresis, Right
• MMTs:
– Able to sustain arm raising for only 1 min and 5 secs
– Able to sustain upward gaze for 2 mins
– (+) minimal bilateral drooping of eyelids
– Neck flexion: 5/5
– Upper extremities: 4/5
– Lower extremities: 5/5
• Sensory: (-) deficits
• Cerebellar: (-) nystagmus/ataxia/dysdiadochokinesia
Course in the Wards
• 11/24: Pt admitted at W4 B3
• 11/25: Pt cleared by SAPOD for
Thymectomy/GA. Pt seen by Neuro: A>
Myasthenia gravis St. IIA; continue pyridostigmine
and prednisone
• 11/26: Seen by Anesthesiology for Pre-op
• 11/27: Pt requested to be OOP
• 11/30: Pt deferred surgery, no consent
Laboratories
• O+
• CBC:
– 10/29: WBC 7.7 Hgb 138 Hct 0.43 Neut 0.83 Lymp 0.14
Mono 0.02 Eo 0.01 Plt 284
• Blood Chem:
– 11/11: FBS 5.69
• Immunology:
– 10/29: TSH 0.785 FT4 1.63
• U/A:
– 10/29: dark/yellow/hazy/1.015/6.5/CHON neg/CHO neg/WBC 24/RBC 0-1/EC few/Bac Moderate
• PT/PTT:
– 11/09: PT 12.9/9.4/>1.0/1.0
aPTT: 35.4/27.8
The Mediastinum
1) between the sternum
and the anterior
surface of the heart
and great vessels
2) between the great
vessels and the
trachea
3) paravertebral sulci
and periesophageal
area
Usual Location of Mediastinal
Tumors and Cysts
Anterior
compartment
Visceral
Compartment
Paravertebral Sulci
Thymoma
Enterogenous cyst
Neurilemomaschwannoma
Germ cell tumor
Lymphoma
Neurofibroma
Lymphoma
Pleuropericardial cyst
Malignant schwannoma
Lymphangioma
Mediastinal granuloma
Ganglioneuroma
Hemangioma
Lymphoid hamartoma
Ganglioneuroblastoma
Lipoma
Mesothelial cyst
Neuroblastoma
Fibroma
Neuroenteric cyst
Paraganglioma
Fibrosarcoma
Paraganglioma
Pheochromocytoma
Thymic cyst
Pheochromocytoma
Fibrosarcoma
Parathyroid adenoma
Thoracic duct cyst
Lymphoma
Mediastinal Tumors in Adults
Tumor Type
Incidence (%)
Location
Neurogenic tumors
21
Posterior
Cysts
20
All
Thymomas
19
Anterior
Lymphomas
13
Anterior/middle
Germ cell tumors
11
Anterior
Mesenchymal tumors
7
All
Endocrine tumors
6
Anterior/middle
Approach to Mediastinal
Masses
• History and PE
• Diagnostic Evaluation
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imaging
serum markers
diagnostic nonsurgical biopsies
Surgical biopsies and resection
History and PE
• Symptoms
Chest pain
Cough
Dyspnea
Stridor
Hoarseness
• may suggest a specific diagnosis
Imaging
Serum Markers
• AFP
• hCG
• PTH
Nonsurgical Biopsies
• FNA biopsy
– mediastinal thyroid tissue, cancers, carcinomas,
seminomas, inflammatory processes, cysts
• Core-needle biopsy
– lymphoproliferative disorders, thymomas, other benign
tumors
• Thoracoscopic biopsy
Surgical Biopsies and Resection
• median sternotomy
• lateral thoracotomy
• lateral thoracotomy with sternal extension (hemiclamshell)
• cervical incision with a sternal retractor
• VATS
Thymoma
• Lymphoid organ located in the anterior
mediastinum
• In early life, responsible for development and
maturation of cell-mediated immunological
factors
• Originates from thymic epithelial cells
• Uncommon but usually associated with
myasthenia gravis
• Usually benign and frequently encapsulated
• If malignant, distant metastasis is rare
• Reaches maximum weight at puberty and
involutes afterwards
Signs and symptoms
• 1/3 of patients have symptoms caused by
compression of adjacent structures
– SVC syndrome
– Dysphagia
– Cough
– Chest pain
• 1/3 are associated with autoimmune diseases
– Myasthenia gravis (10-15%); other sources: almost
75%
– Pure red cell aplasia
– Good’s syndrome
• 1/3 are asymptomatic; seen in:
– Chest x-ray
– CT scan
Myasthenia gravis
• Neuromuscular disorder characterized by weakness and fatigability of
skeletal muscles
• Main defect: decrease in the number of available Acetylcholine
receptors (AChRs) at neuromuscular junctions due to antibody
mediated autoimmune attack
– Accelerated turnover of AChRs by rapid endocytosis
– Blockade of the active site of the AChRs
– Damage to the post synaptic muscle membrane
• Antibodies are IgG and are T cell dependent
• 75% of MG pts have abnormal thymus glands; 10% have thymomas
Clinical Features
• Not rare (1-7/10000); more common in women (3:2) in
their 20s and 30s; men in their 50s and 60s
• Cardinal feature: weakness and fatigability of muscles
• Weakness increases during repeated use and may improve
following rest or sleep
• Muscles involved: lid and extraocular muscles, facial
muscles, chewing muscles, palate, tongue, pharynx, proximal
muscles, chest muscles.
• (-) loss of reflexes and sensation
Laboratory testing
• Anti-AChR radioimmunoassay: 85% positive in
generalized MG; 50% in ocular MG; negative
results do not exclude MG
• Repetitive nerve stimulation: > 15% reduction in
the amplitude of the evoked responses at 3Hz
• Edrophonium chloride (Tensilon) 2mg + 8mg IV:
high probable diagnosis is positive
Management
Pharmacologic Management
• Thymectomy leads to improvement or resolution of
symptoms of myasthenia gravis in only about 25% of
patients with thymomas.
• Advanced thymomas have been shown to respond to
platinum-based chemotherapy and to corticosteroids.
• One summary of chemotherapy trials showed an overall
response rate of about 70%.
• Combining radiotherapy and chemotherapy for local
progression also has been successful in some small series the
combination appears to prolong survival, although most
advanced-stage, unresectable thymomas will recur
Anticholinesterase Meds
• Pyridostigmine
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Provides partial improvement
Onset of action: 15-30min
Duration: 3-4hrs.
Dose: 30-60mg 3-4x daily (max: 120mg q3-6h)
side effects: ↑weakness, GI symptoms
For GI sxs: Atropine/diphenoxylate/loperamide
Immunosuppressive Drugs
• Short-Term
IV Immunoglobulin
- usual dose: 2g/kg x 5 days (400mg/kg/day)
- unknown mechanism
- effect not consistent w/ amt. of circulating AChR
antibody
- adverse reactions: headache, fluid overload
*plasmapheresis: 5 exchanges over 10-14day period
Immunosuppresive Drugs
• Intermediate-Term:
A) glucocorticoids
- initial dose: 15-25mg/d OD
- increased stepwise by 5mg/d at 2-3 day intervals
- maintained for 3 mos.
- tapered (alternate day regimen) for 1-3mos.
B) cyclosporine/tacrolimus
- adjunct to glucocorticoids
- side effects: HTN and nephrotoxicity
Immunosuppressive Drugs
• Long-Term:
A) Azathioprine
- initial dose: 50mg/d (test for adverse effect)
- ↑ until WBC dec. to ~3k-4k/µL
- idiosyncratic reactions: bone marrow depression, flulike
sxs, abnormal liver function
- avoid intake w/ allopurinol
- beneficial effect: begin at 3-6 mos. & longer to peak
Immunosuppressive Drugs
• Long-Term:
B) Mycophenolate Mofetil
- Dose: 1-1.5g BID
- inhibits proliferation of lymphocytes but not that
of other cells
- ↓ adverse effect but expensive
• For refractory MG: high-dose cyclophosphamide
Surgical Management
• The prognosis of a person with a thymoma is based
on the tumor's gross characteristics at operation,
not the histological appearance.
– Benign tumors are noninvasive and encapsulated.
– Malignant tumors are defined by local invasion into the
thymic capsule or surrounding tissue.
Surgical Approach
• For resection of thymoma, an open median
sternotomy surgical approach is recommended.
• Minimally invasive approaches (e.g., video-assisted
thoracic surgery [VATS]) are not considered the
standard of care and are not recommended at this
time.
• Cervical approach is adequate.
Benign Thymoma
• Total thymectomy with contiguous removal of
mediastinal fat
Stages I-II
• Complete surgical resection of the entire thymus
gland, including:
– all mediastinal tissues anterior to the pericardium, aorta,
and superior vena cava from phrenic nerve to phrenic
nerve laterally and from the diaphragm inferiorly to the
level of the thyroid gland superiorly
– the upper poles of the thymus
Resectable or Potentially
Resectable Stage III Disease
• For stage IIIA, surgery should be considered either
initially or following neoadjuvant therapy, with the
aim being complete removal of the tumour with
wide surgical margins.
Resectable or Potentially
Resectable Stage III Disease
• In stage IIIB, patients should be assessed for surgery
following neoadjuvant chemoradiotherapy.
Resectable or Potentially
Resectable Stage III Disease
• If at thoracotomy complete resection is not found
to be possible, maximal debulking (with appropriate
vascular reconstruction) should be undertaken.
Clips should be placed to mark residual tumour for
adjuvant radiation.
Resectable or Potentially
Resectable Stage III Disease
• Bilateral phrenic nerve resection is not
recommended because of the severe respiratory
morbidity that results.
Resectable or Potentially
Resectable
Stage IVA Disease
• Surgery should be considered either initially or
following neoadjuvant therapy, with the aim being
complete removal of the tumour with wide surgical
margins.
• Surgery is recommended only if pleural and
pericardial metastases can be resected.
Stage IVB
• Surgery is not applicable
Recurrent Disease
• Surgical resection should be considered in patients
with a localized recurrence after apparently
successful initial therapy.
Recurrent Disease
• For stage IV disease, the resection of isolated
pleural metastases is an appropriate initial approach.
For cases with multiple pleural metastases,
chemotherapy, with or without subsequent surgery,
is often appropriate.
Thank You