Case 4 -
Necrotizing Granulomatous Inflammation with Rare AFB Consistent with MAC
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A 32-year-old woman presented with a 4-month history of progressively worsening
nonproductive cough. Her history was notable for frequent use of her neighbors' outdoor hot tub. A
chest radiograph (CXR) was suspicious for a cavitary lesion in the left base. Due to worsening cough and
dyspnea, she was hospitalized for further evaluation. A CT scan of the chest confirmed a cavitary lesion
in the left lower lobe (LLL). Sputum cultures and bronchial washings revealed Mycobacterium avium
intracellulare complex (MAC). She was initially treated with ethambutol and azithromycin. Over the
course of a week, fevers with temperatures up to 102.4°F, night sweats, progressive dyspnea, and a
worsening, now productive cough developed. A repeat chest CT scan revealed the development of bilateral
lower lobe infiltrates and a persistent LLL cavity. Therapy with ciprofloxacin was added without
noticeable benefit. After 23 days of hospitalization, she was transferred to our facility for further
evaluation. On presentation, she was febrile. The physical examination revealed a very toxic-appearing,
tachypneic, thin white female. She became dyspneic after walking < 20 feet. Her CXR revealed
ill-defined, multifocal airspace consolidation in both the mid and lower lung zones. On admission to our
institution, therapy with ethambutol, azithromycin, and ciprofloxacin was discontinued. Further
evaluation included a chest CT scan, which revealed dense areas of consolidation in the lingula and
bilateral lower lobes. A 2.8 X 2.9 cm cavitary lesion was present in the LLL. There were scattered
small centrilobular nodular opacities in the upper lobes that were consistent with bronchiolitis. A new
sputum smear revealed 4+ acid-fast bacilli (AFB), and the culture grew 4+ MAC identified by DNA probe. A
BAL from the LLL produced seven colonies of MAC; no other organisms were identified. Transbronchial
biopsy specimens revealed a single vaguely formed granuloma. An open lung biopsy specimen was obtained
to exclude other etiologies and to confirm the diagnosis of MAC infection.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
obtained from the right middle and lower lobes revealed granulomatous inflammation with well-formed,
necrotizing granulomas. Ziehl-Neelsen stain revealed rare AFB. GMS stain was negative for fungal
organisms. MAC was isolated from cultures of the lung tissue. Fungal culture and bacterial cultures for
both aerobic and anaerobic bacteria from the lung tissue were negative. Cultures of the hot tub water
failed to grow MAC.
Case 4 - Slide 1
Case 4 - Figure 4
Same area as Fig 3 at medium power showing granulomatous inflammation with necrosis (x3.9).
Case 4 - Figure 5
Granulomatous inflammation with necrosis and giant cells (x8.4)
Case 4 - Figure 6
High power view showing granulomatous inflammation with necrosis, epithelioid histiocytes and multinucleated giant cell (x20).
Differential diagnoses for necrotizing granulomas
Differential diagnoses for MAC lung disease
- Non-tuberculous mycobacteria
- Granulomatous bacterial infections
- Wegener's granulomatosis
- Churg-Strauss syndrome
- Necrotizing sarcoid granulomatosis
- Bronchocentric granulomatosis
- Rheumatoid nodules
- Fibrocavitary MAC
- MAC in association with immunodeficiency
- Reticulonodular MAC with cylindrical bronchiectasis (Lady Windermere syndrome)
- Hot tub lung
Necrotizing granulomatous inflammation with rare AFB consistent with MAC. Comment:
The clinical and pathologic features do not conveniently fit into any of the known categories of MAC lung
The biopsy showed granulomatous inflammation with well formed necrotizing
granulomas. Differential diagnoses for necrotizing granulomas are included in the "Differential
Diagnoses" section. Most necrotizing granulomas are caused by infection, usually mycobacterial or
fungal. In our case, Ziehl-Neelsen stain revealed rare AFB, and MAC was isolated from cultures of the
lung tissue. Therefore, we had convincing evidence that the patient's granulomatous lung disease was
caused by MAC. The real question was: What kind of MAC associated lung disease does this patient have?
Four distinct clinicopathologic forms of MAC lung disease have been reported in
1) Fibrocavitary MAC: Fibrocavitary MAC has been described in older patients with a history
of smoking and underlying structural lung disease, most commonly COPD. Other associated conditions
include pulmonary fibrosis, rheumatoid lung, healed tuberculosis, silicosis and other pneumoconioses,
previous chest surgery, and lung cancer. Children and young adults with cystic fibrosis represent a
special subgroup of this presentation. Symptoms of fibrocavitary MAC are usually insidious.
Radiographic findings include bilateral thin walled cavities and fibrocavitary disease. Histologic
examination reveals necrotizing granulomas, which can be indistinguishable from tuberculosis. The course
is usually slowly progressive. Antimycobacterial therapy is often beneficial, but recurrence is common
and resection is required in some cases. The treatment of underlying lung disease is critical to the
2) MAC in association with immunodeficiency: The second form of MAC lung disease was first
described in patients with AIDS. It has also been reported in patients with immune deficiency due to
steroids, organ transplants, leukemia, lymphoma, and severe combined immunodeficiency. These patients
often present with severe disseminated MAC and the pulmonary manifestation is frequently destructive and
cavitary. Histologic examination often reveals necrotizing granulomatous inflammation and accumulation
of foamy macrophages filled with AFB. There is considerable mortality even with treatment, but
prophylaxis can be effective.
3) Reticulonodular MAC with cylindrical bronchiectasis (Lady Windermere syndrome): This form
of pulmonary MAC is characterized by slowly progressive nodular opacities and cylindrical bronchiectasis
with a predilection for the right middle lobe, lingula, and dependent areas of the lung. Typical
patients are thin, immunocompetent elderly females with no history of smoking or pre-existing lung
disease. Prince et al have hypothesized that fastidiousness among these women contributes to disease
development and dubbed this form of pulmonary MAC as Lady Windermere syndrome. Histologically,
granulomatous inflammation, with or without necrosis, is present. Antimycobacterial therapy, in
conjunction with bronchial hygiene, often leads to clinical and radiographic improvement, but the disease
is chronic with a course that is characterized by frequent relapses.
4) Hot tub lung: Lung disease secondary to aerosolized MAC from hot tubs has more recently
been described as a new form of MAC lung disease. Patients are typically young and immunocompetent.
Most cases occur with indoor hot tubs since they are believed to allow maximal concentration of the
aerosolized water in a confined space. Typical signs and symptoms at presentation include cough,
dyspnea, chest tightness, fatigue, and hypoxia that progresses over the course of several weeks to months
prior to diagnosis. Diffuse interstitial or nodular infiltrates are noted on the CXRs of virtually all
of the documented cases. A high resolution CT scan of the chest typically demonstrates ground-glass
opacities and scattered nodules with upper lobe predominance. Cavitary disease has not been described in
this population. Sputum cultures from patients with hot tub lung are consistently positive for MAC. It
is also helpful to grow MAC from the implicated hot tub water to confirm the diagnosis. Histologic
examination most commonly reveals discrete nonnecrotizing granulomas. Other reported histopathologic
findings include organizing pneumonia, patchy interstitial pneumonia, and occasional necrotizing
granulomas. The histologic findings of hot tub lung are in distinct contrast to those found in patients
with hypersensitivity pneumonia, which generally demonstrate vaguely formed granulomas with prominent
interstitial infiltrates. Some authorities have postulated that hot tub lung is a hypersensitivity
pneumonia reaction; others have argued that it is an infectious process. Proponents of hypersensitivity
pneumonia cite several salient points including the rapid onset of symptoms, temporal relationship to hot
tub exposure, and rapid clinical improvement after removal of the exposure.
Our patient's clinicopathologic characteristics are not fully consistent with any
of the previously described categories of MAC lung disease:
1) Fibrocavitary MAC: The patient had no preexisting clinical or radiographic evidence of
chronic lung disease.
2) MAC in association with immunodeficiency: She was immunocompetent without a history of
recurrent infections and had negative HIV test findings.
3) Reticulonodular MAC with cylindrical bronchiectasis (Lady Windermere syndrome): Our patient
was female and a life-long nonsmoker, and had evidence of nodular infiltrates that are similar to those
found in patients with Lady Windermere syndrome, but she was much younger than is typical for patients
with this syndrome. More importantly, the severe, rapidly progressive nature of her disease, her toxic
appearance at presentation, as well as the radiographic appearance of early cavitary disease, diffuse
consolidation, and absence of bronchiectasis would be most atypical for patients with this form of MAC
4) Hot tub lung: Our patient's demographics and clinical history would be appropriate for hot
tub lung. The inability to grow MAC from water from her neighbor's hot tub does not exclude this
diagnosis; other water sources could have been origin of the infection. Her radiologic manifestation of
cavitary disease, however, has not been described in patients with hot tub lung. The diffuse necrotizing
granulomatous inflammation found on her lung biopsy specimen is not characteristic of hot tub lung and is
more characteristic of an infectious process rather than a hypersensitivity reaction. The patient's
condition did not improve with simple removal from the source and continued to worsen during her hospital
course prior to effective treatment.
Review of the Literature/Treatment Options :
The initiation of treatment with
appropriate antimycobacterial agents combined with a 1-month course of steroids led to rapid and dramatic
improvement in both symptoms and gas exchange, as well as to improvement in radiographic findings.
Complete radiographic improvement did not occur within the typical period of 2 to 3 months as described
with most cases of hot tub lung.
This case may represent a more severe, fulminant form of hot tub lung or an entirely
new form of MAC associated lung disease. Either way, the possibility of MAC should be considered in
young, otherwise healthy individuals with fulminant cavitary lung disease.
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