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Fibrosing Mediastinitis

• Morning Report
• Liz Thomas
• July 25, 2008

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Overview

• Fibrosing mediastinitis is characterized by an
  excessive fibrotic reaction in the mediastinum
  which can compromise the great vessels, airways,
  or other structures in the mediastinum
• Results from excessive host response to prior
  infectious process which has involved the
  mediastinal lymph nodes, usually thought to be
  due to Histoplasma capsulatum, although has also
  been suggested to result from TB, syphilis,
  blastomycosis, autoimmune process, drugs or trauma

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H. Capsulatum

• Histoplasmosis was first described in 1906 by a
  US Army physician in Panama
• Infection is common and usually subclinical
• H. capsulatum is found worldwide, but in the US,
  infection is most common in the midwestern states
  located in the Ohio and Mississippi River valleys
• The fungus proliferates in soil contaminated with
  bird or bat droppings, commonly chicken coops or
  farms buildings, bird roost sites, caves, and
  wood lots

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Distribution of Pulmonary Histoplasmosis
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Chicken coop
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Pathophysiology

• H. capsulatum conidia or mycelial fragments are
  inhaled and, if they evade nonspecific lung
  defenses, cause a localized or patchy
  bronchopneumonia
• With low-inoculum exposure, most healthy
  individuals remain asymptomatic (fewer than 5
  develop symptomatic disease)
• Patients who inhale a large inoculum often
  develop severe and potentially fatal diffuse
  pulmonary infection

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Histoplasma capsulatam
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Pathophysiology

• Macrophages ingest the fungi and disseminate the
  infection hematogenously during the first 2 weeks
  of infection
• May result in development of H. capsulatum
  containing granulomata in the liver and spleen,
  usually discovered incidentally or at autopsy
• Clinically evident dissemination usually occurs
  only in patients with underlying
  immunosuppressive disorders, those at extremes of
  age, and patients with a heavy exposure

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Pathophysiology

• Cellular immunity develops after 10-14 days,
  first in the lungs and mediastinal lymph nodes
  and then throughout the reticuloendothelial
  system
• Sensitized T lymphocytes activate macrophages and
  the infection is brought under control in
  immunocompetent hosts
• Reinfection with H. capsulatum may bring about a
  heightened immune response, resulting in intense
  inflammation of the pulmonary parenchyma
• This response may play a role in the caseating
  tissue necrosis seen in some patients, including
  those with chronic pulmonary manifestations such
  as fibrosing mediastinitis and a sarcoidosis-like
  syndrome

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Mediastinal granuloma

• Mediastinal lymph nodes invaded by H. capsulatum
  may enlarge and coalesce into an inflamed caseous
  mass referred to as mediastinal granuloma
• Usually presents as a mediastinal mass discovered
  incidentally or because it compresses compliant
  mediastinal structures such as the SVC or
  esophagus.
• The lymph nodes are generally easily removed
  surgically, and the process is more common and
  more benign than fibrosing mediastinitis

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Fibrosing Mediastinitis

• Believed to result from leakage of fungal
  antigens from lymph nodes into the mediastinal
  space, leading to a hypersensitivity reaction and
  fibrotic response
• Fibroblasts adjacent to granulomata are
  stimulated and proliferate, leading to fibrosis,
  entrapment, and invasion of adjacent normal
  structures
• Unclear whether mediastinal granuloma can
  progress to mediastinal fibrosis or if the two
  entities are distinct

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Epidemiology

• Although it is estimated that over 500,000 people
  per year in the US are infected with Histoplasma
  and over 80 of inhabitants of endemic regions
  have a positive Histoplasma skin test, less than
  1 of patients with histoplasmosis develop
  fibrosing mediastinitis
• The largest case series (which describes only 94
  patients) showed that the average age of
  diagnosis was 33, 81 were white, and there was a
  slight male preponderance

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Clinical presentation

• Depends upon the structures involved (airways,
  heart and great vessels, or the esophagus)
• Compression of the tracheobronchial tree can lead
  to dyspnea, postobstructive pneumonia,
  atelectasis or broncholithiasis due to bronchial
  erosion by calcified lymph nodes
• Involvement of heart and great vessels can lead
  to pulmonary artery or vein obstruction, SVC
  syndrome, and constrictive pericarditis
• Esophageal compression can lead to dysphagia or
  odynophagia

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Imaging studies

• CXR May see hilar or mediastinal adenopathy,
  lobar or segmental consolidation, unilateral
  small pulmonary artery, septal lines, pleural
  effusion, or cardiomegaly
• CT Can show infiltrative mediastinal process
  with or without discrete mass, often shows
  calcifications within the mediastinal process
• MRI Typically reveals a heterogeneous mass
  decreased signal intensity on T2 weighted images
  suggests fibrosis

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CT of a 30 year old man with SVC syndrome
secondary to fibrosing mediastinitis

• Contrast-enhanced CT scan (mediastinal window)
  shows an infiltrating soft-tissue attenuation
  mass in the middle mediastinum. Note encasement
  and narrowing of the distal superior vena cava
  (white arrowhead) and right pulmonary artery
  (black arrowheads) and distention of the azygous
  vein (arrow).

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Biopsy

• The differential diagnosis for noncalcified
  mediastinal mass includes lymphoma and carcinoma,
  so patients with fibrosing mediastinitis usually
  undergo biopsy to confirm the diagnosis
• Biopsy is done first and foremost to exclude
  malignancy
• Histology generally shows abundant collagen
  containing cellular fascicles of fibroblasts
  associated with a chronic inflammatory
  infiltrate. Aggregates of lymphocytes and plasma
  cells are found within a hyalinised fibrous
  connective tissue

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Histology

• Fibrous tissue infiltrating mediastinal adipose
  tissue

• Paucicellular, eosinophilic mature collagen

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Treatment

• There are no known effective medical therapies
  for fibrosing mediastinitis
• Some case reports have found symptomatic
  improvement with steroids and it has been
  suggested that autoimmune processes respond more
  favorably
• Case reports have also shown improvement of
  symptoms with Tamoxifen
• Antifungal agents are generally ineffective
• Surgery is sometimes performed to relieve
  vascular and airway obstruction, with variable
  success

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Surgical treatment

• SVC obstruction SVC bypass has been performed
  successfully in some patients, both with spiral
  vein grafts and with endovascular stents
• Airway compression Relief of airway obstruction
  generally requires resection of the airway and/or
  lung parenchyma, as dilation of the airways is
  usually not feasible. This type of surgery is
  associated with significant mortality
• Esophageal involvement Esophageal compression
  and tracheoesophageal fistula may be managed with
  stents and/or surgical correction

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SVC stent
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Prognosis

• Fibrosing mediastinits is a progressive disease
  with no definitive treatment and with a variable
  natural history
• One series of 23 patients found that 10 had
  improvement in symptoms, 11 had no significant
  change, and two had progressive disease
• Another series of 71 patients noted a worse
  prognosis, with 21 patients dying during
  follow-up. The mean interval between development
  of symptoms and death was less than 6 years in
  these patients.

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References

• Manali ED, Saad CP, Krizmanich G, Mehta AC.
  Endobronchial findings of fibrosing
  mediastinitis. Respir Care. 2003
  Nov48(11)1038-42.
• Flieder DB, Suster S, Moran CA. Idiopathic
  fibroinflammatory (fibrosing/sclerosing) lesions
  of the mediastinum a study of 30 cases with
  emphasis on morphologic heterogeneity. Mod
  Pathol. 1999 Mar12(3)257-64.
• Bays S, Rajakaruna C, Sheffield E, Morgan A.
  Fibrosing mediastinitis as a cause of superior
  vena cava syndrome. Eur J Cardiothorac Surg.
  2004 Aug26(2)453-5.
• Pompeo E, Stella F, Ippoliti A, Mineo TC.
  Extra-anatomic bypass of the superior vena cava
  after successful stenting for fibrosing
  mediastinitis. J Thorac Cardiovasc Surg. 2008
  Jan135(1)220-1, 221.e1
• Ikeda K, Nomori H, Mori T, Kobayashi H, Iwatani
  K, Yoshimoto K, Yoshioka M. Successful steroid
  treatment for fibrosing mediastinitis and
  sclerosing cervicitis. Ann Thorac Surg. 2007
  Mar83(3)1199-201.
• UpToDate 2008