Sabato 27 ottobre 2012 - Pacini Editore

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Tab. I.
RB-ILD DIP LCH
olitis (RB), consisting in finely pigmented, iron-containing
(“smoker’s”) macrophages within the lumen of bronchioles
and peribronchiolar alveoli. Frequently smoker’s macrophages
are associated with subtle histological features of
chronic bronchiolitis including mild lymphocytic inflammation
and mild fibrosis of the bronchiolar wall and surrounding
alveolar septa, sometimes with rigidity and distortion of the
bronchiolar lumen, bronchioloectasia and mucostasis. The
changes are patchy at low magnification with a striking bronchiolocentric
distribution, however smoker’s macrophages
may variably extend to the peripheral alveoli occasionally
involving the entire lobule.
RB is very frequent in smokers, and probably is the most sensitive
and specific histological marker of tobacco smoke: it is
present in almost 100% of current smokers, in about 50% of
ex-smokers (sometimes many years after smoking cessation),
and only exceptionally in never smokers. RB is generally an
histological incidental finding in smokers (and the biopsy is
obtained for another reason, for example a carcinoma), and
only rarely RB causes an ILD. Although patients with ILD
have in general more severe histological alterations, histology
alone is unable to predict the presence of ILD in the single
case. Once the clinician has established the presence of an
ILD due to RB, the distinction between RB-ILD and DIP is
mostly based on the extension of smoker’s macrophages: in
RB-ILD the latter are restricted to the centrilobule, whereas
in DIP they involve the lobule more diffusely. Moreover
interstitial fibrosis (see below), lymphoid follicles, giant cells
and eosinophils are more frequent in DIP than RB-ILD, and
in some patients with DIP the number of eosinophils (both
in tissue and BAL) is high enough to raise concern about the
possibility of chronic eosinophilic pneumonia. However, the
limits between RB-ILD and DIP are blurred and in practice
the distinction can be difficult and in some cases is probably
quite arbitrary. For these reasons some Authors suggest that
RB-ILD and DIP should be lumped into one category. We
share the majority’s opinion that they should be classified
separately whenever possible, because of the differences in
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
Smoking 100% 80-90% > 90%
age 3-5th decade 3-5th decade 3-4th decade
male/female Slight male predominance Slight male predominance 1-1
Symptoms insidious onset of dyspnea and cough insidious onset of dyspnea
and cough
insidious onset of dyspnea and
cough
function Mixed or normal Restrictive Restrictive and/or obstructive
Prognosis always favourable generally favourable generally favourable
ct scan Upper-lobe predominant centrilobular Mid and lower-lobe
Upper-lobe predominant stellate
ground-glass opacities, centrilobular predominant ground-glass nodules, sometimes cavitated,
emphysema and bronchial wall
opacities, reticular opacities thick-walled and thin-walled cysts
thickening
with bizarre shape
histology Smoker’s macrophages within
Smoker’s macrophages Stellate bronchiolocentric nodules,
bronchiolar lumens and surrounding diffusely involving the lobule, cellular in the active phase and
alveolar spaces, frequently with mild frequently associated with fibrotic/cavitated in the chronic
bronchiolar fibrosis/inflammation and uniform interstitial fibrosis, phase
emphysema (centrilobular and/or lymphoid follicles and
subpleural). Some interstitial fibrosis can
occur, typically jaline in character and
surrounding emphysematous holes
increased eosinophils
clinical-radiological presentation and prognosis, acknowledging
that in rare cases the distinction can be impossible.
Fibrosis and emphysema. Despite emphysema is classically
defined as permanent airspace enlargement without “obvious”
(macroscopic) fibrosis, in reality some microscopic
fibrosis is quite frequent in centrilobular and particularly in
paraseptal emphysema. Sometimes fibrosis is quite prominent,
but generally does not produce clear clinical abnormalities
being an incidental finding in smokers operated
for other reasons. Reported in the literature with different
synonymous (RB-ILD with fibrosis, airspace enlargement
with fibrosis, smoking-related interstitial fibrosis), fibrosis
in this setting has a typical jaline, amyloid-like character and
is more prominent in subppleural and peribronchiolar parenchyma,
where frequently surrounds emphysematous spaces:
sometimes large emphysematous holes are criss-crossed by
bands of fibrosis. Fibrosis can also occur unassociated with
emphysema.
In some smokers with ILD, fibrosis is so prominent to make
the differential diagnosis between DIP and fibrotic NSIP (and
sometimes also with UIP) difficult, both histologically and
radiologically. Moreover, some Authors suggest that DIP can
evolve into NSIP, and that some cases of fibrotic NSIP can be
related to tobacco smoke. Although compelling, these hypotheses
are unproved yet. In our practice we try to separate DIP
and fibrotic NSIP whenever possible, particularly because
prognosis of DIP appears to be better than fibrotic NSIP, again
acknowledging that in occasional cases the distinction is difficult
and probably arbitrary.
Increase in Langerhans cells. Another common effect of
smoking is the increase in the number of Langerhans cells,
detectable both in lung tissue and BAL. Langerhans cells are
characteristic both on morphology (moderate amount of pale
cytoplasm, deeply infolded nuclei) and on immunophenotype
(positivity for S-100 protein, CD1a and Langerin). By definition,
in LCH Langerhans cells form clusters, but the limits
between LCH and a simple increase in Langerhans cells in a
smoker are conventional and sometimes blurred. LCH begins