1. Usual interstitial pneumonia (UIP),
Honeycombing, and Traction bronchiectasis:
Rad-Path exercises
Thomas Colby MD
Sara Piciucchi MD

2. Reticular abnormalities
Accordingly to the 2011 ATS/ERS guidelines, UIP pattern is defined by four criteria:
Reticular abnormalities
2. Subpleural and basal predominance
Definite UIP pattern
Lelli cosimo TC del 2014
3. Honeycombing with traction bronchiectasis
4. Absence of features listed as «inconsistent with UIP»

3. Pathologic criteria

4. Usual interstitial pneumonia (UIP/IPF) with Honeycombing

5. Usual interstitial pneumonia (UIP) Histopathology:
Patchy scarring/honeycombing with active fibroblast foci
Subpleural/paraseptal distribution

6. Honeycombing in UIP Honeycombing apparent only histologically
Definition: Architecturally destroyed lung tissue with abnormal airspaces lined by bronchiolar metaplasia and with thick fibrous walls
5 mm
5 mm
Honeycombing apparent only histologically
Honeycombing that could be apparent radiologically

7. Coming back to pathology...
Fleischner Society defines Honeycombing on CT:
Clustered cystic airspaces typically of comparable diameters of
3-10 mm, but occasionally as large as 2.5 cm.
Honeycombing is usually subpleural and characterized by well-defined walls.
Watadani et al (Radiology 2013) reported that agreement among radiologists has a k value from 0.4 to 0.7
Mimickers: traction bronchiectasis and paraseptal emphysema
Recent literature on HC?
Stabile giuliano
Coming back to pathology...

8. Radiologic honeycombing Pathologic honeycombing
What does this mean ??
Radiologic honeycombing ≠
Pathologic honeycombing
When the pathologist says “honeycombing” is present it may or may not be present radiologically.
Some pathologic honeycombing manifests radiologically as ground glass change

9. Problem Areas in Suspected IPF: presence/absence of honeycombing
Radiologic evidence of UIP pattern ---no bx
Possible UIP--- bx
Inconsistent with UIP---bx (may show UIP or something else)
Can radiologic criteria for UIP be loosened?
Gruden et Al. identified the group without honeycombing and assessed the clinical and radiologic course over the time.
Stable or progresive follow-up: increase of degreee of bronchiectasis and progression to HC

10. From clinical practice……

11. 43 years old, male non smoker
Co-morbidities: psoriasis, gastritis with Helicobacter
History of two years of dyspnea on exertion
Lab tests: no autoimmunity

21. Bronchovascular ground glass attenuation + subpleural sparing
D.D. fNSIP vs inconsistent UIP (GG and bronchovascular distribution)

22. Patients underwent transbronchial lung biopsy with cryoprobe

23. Abbondanza crio

24. Mildly fibrotic IP with possible fibroblast foci

25. More extensive fibrosis, relatively diffuse in distribution

26. Organizing pneumonia or Fibroblast foci ??
FAVORED DIAGNOSIS:
Fibrotic NSIP

27. ADDITIONAL HISTORY
Patient underwent five cycles of cyclophosphamide (750 mg/mq).
EKG and LAB tests: Normal/negative
Dyspnea persisted
CT scan was repeated seven months later followed by a VATS Biopsy.....

28. Increase of coarseness

29. Increase of cysts in the contest of reticulation and
ground glass attenuation

30. Progressive decrease of subpleural sparing

33. VATS Bx: Fibrosis with honeycombing, in some areas patchy

34. Microscopic honeycombing, subpleural scarring

35. Fibroblast foci

36. …and still areas resembling NSIP and OP

37. Why is the case important ??
Final diagnosis: interstitial lung disease UIP pattern
Why is the case important ??
Our radiologic and histologic diagnoses are not always right and need to be correlated with patient course as it unfolds over time

38. Interesting cues from recent literature supporting this case

39. 22 patients (20 men, 2 women) transplanted for pulmonary fibrosis were retrospectively evaluated
CT available in 19 patients
14 (64%) were smokers
Mean age at the time of trasplantation was 55 years
41% of UIP/IPF showed an extension of fibrosis around bronchovsacular bundles
NSIP areas were found in 45% of OLB and 59% of esplants

40. Correlation between CT findings and histology on explants
1. Honeycombing:
In 18 cases of 19 CT scan available: honeycomb changes were identified
and confirmed by pathology
2. NSIP and UIP:
Focal ground glass opacities in CT present in 10 cases and correlated with NSIP areas in 8 cases
and in 3 cases with acute exacerbation
NSIP areas in 60% of UIP/IPF co-existing with UIP

41. Retrospective study of comparison of CT scan and histologicl diagnosis in a large IPF population enrolled in three studies
CT scan available for 539 subjects
Patients with definite UIP pattern and rad-path concordant groups were older and had lower DLCO % pred compared to those with possible.
2. No significant difference (concordant vs discordant): duration of illness, DLCO % pred, history of exposure to antigen or GERD, survival.
ERJ 2016 in press

42. Traction bronchiectasis in UIP pattern
________
Increasing relevance
Traction bronchiectasis rarely has good radiology-pathology correlation and thus the importance of its radiologic definition, recognition and diagnostic and prognostic significance

43. Strongest correlation: between FF scores and traction bronchiectasis
Rad:
CT scan of 162 patients with diagnosis of UIP
Or fibrotic NSIP scored
Path: profusion of fibroblastic foci
Low score of Fibrosis and FF in fNSIP
Traction bronchiectasis score 2; FF: 0.5
High score of fibrosis and FF in UIP -RA
Traction bronchiectasis score 3; FF: 3.5
Univariate analysis:
Strongest correlation: between FF scores and traction bronchiectasis
2. Weaker, but significant, between FF scores and reticulation and Honeycomnbing

44. Carloni A, Chilosi M, Colby TV, Poletti V.
From “traction bronchiectasis” to honeycombing in Idiopathic Pulmonary Fibrosis: a spectrum of bronchiolar remodeling also in radiology?
Piciucchi S, Tomassetti S, Ravaglia C, Gurioli Ch, Gurioli C, Dubini A,
Carloni A, Chilosi M, Colby TV, Poletti V.
Pulmonary Medicine, accepted
Our hypothesis

45. Key -Concepts

46. Role of bronchiolar epithelium in the development of UIP pattern - in IPF subjects- has been widely emphasized.
Remodeling mechanism (first described by Chilosi in 2002) includes:
-senescence,
-alveolar stem cell exhaustion
- aberrant activation of the wnt-β-catenin and hedgehog pathways
Loss of cellular
integrity
Epigenetic
reprogramming
Telomere attrition
Epithelial senescence
Aberrant reaction of
epithelial cells
Migration and
Proliferation of fibroblasts

47. If we analyze morphological aspects
in light of the pathogenic events
we identify some interesting key points
in CT findings

48. Carloni A. et Al. Journal of theoretical biology 2013
1. Mechanical stress and remodeling are highest in that areas in which traction bronchiectasis and honeycombing appear.
2007
2014
2010
2. Most of the "scarred" tissue is in the region distal to the traction bronchiectasis, beneath the pleura and does not concentrically surround the dilated bronchi.
Score 1 bronchiectasis
Score 3 bronchiectasis
Honeycombing

49. 3. In Nonspecific Interstitial Pneumonia (NSIP), traction bronchiectasis are completely surrounded by the fibrotic tissue a b
Fibrotic NSIP
2009
2013
NSIP in the course of the years

50. Summary:
Traction bronchiectasis observed in IPF subjects is better interpreted as resulting from bronchiolar proliferation rather than from pure mechanical traction of a single airway by scarring tissue.

51. Lung aging Lung development
UIP: culmination of the «dying back» process of acini within the secondary pulmonary
lobule reversing the lung embryogenesis
Kradin RL Honeycomb Lung- Time for a change Arch Pathol Lab Med 2015
Honeycomb lung in IPF
Chilosi et al. Translational Research 2013
Lung aging
Lung development

52. Thank you