Am I Missing Something? Dan Simons and Chris Chabris: Video studies - - PowerPoint PPT Presentation

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Kirk D. Jones, MD UCSF Dept of Pathology kirk.jones@ucsf.edu

Is This Normal Lung? Looking Beyond the Interstitium

Am I Missing Something?

Inattentional Blindness

• Ulric Neisser: Selective looking
• Arien Mack and Irvin Rock: Inattentional

blindness

• Dan Simons and Chris Chabris: Video studies

created during Experimental Psychology course

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Inattentional Blindness

• “when our attention is focused on one thing,

we fail to notice other, unexpected things around us—including those we might want to see.”

• In pathology of the lung, there are often two

things that focus our attention:

– The tumor in neoplastic disease – The alveoli in non-neoplastic disease

ALVEOLI

bronchioles vessels pleura

The Neglected Compartments

• Bronchioles

– Inflammatory bronchiolitis – Fibrotic bronchiolitis

• Vessels

– Pulmonary arteriopathy – Pulmonary venopathy

• Pleura

– Pleural inflammation or neoplasm

• Absence of alveoli

– Cystic disease

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Overview of Talk

• Bronchioles

– Bronchiolitis – Diffuse panbronchiolitis – Constrictive bronchiolitis

• Vessels

– Pulmonary arteriopathy – Pulmonary veno-occlusive disease

• Lack of alveoli – cystic disease

– Lymphangioleiomyomatosis

Classification of Bronchiolitis

• Cellular infiltrates (inflammatory)

– Intraluminal

• Neutrophils: Acute bronchiolitis, bronchopneumonia
• Macrophages: Respiratory bronchiolitis

– Mural

• Lymphocytes: Chronic/cellular bronchiolitis
• Lymphoid follicles: Follicular bronchiolitis

– Peribronchiolar/Interstitial

• Macrophages: Diffuse panbronchiolitis

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Adenovirus CC77-111 Respiratory bronchiolitis Respiratory bronchiolitis Follicular bronchiolitis

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Follicular bronchiolitis

Illustrative Case

• 46-year-old woman with

hypogammaglobulinemia treated with IVIG

• Profound progressive dyspnea and sinusitis
• Lung transplant performed

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Diffuse Panbronchiolitis

Diffuse Panbronchiolitis

• First described in the 1960’s in Japan
• Named diffuse panbronchiolitis in 1969 due

to involvement of terminal bronchiole (sinusitis is often also present)

• Progressive inflammatory bronchiolitis with

subsequent bronchiectasis

Diffuse Panbronchiolitis

• Accumulation of foamy macrophages in the

peribronchiolar interstitium

• The bronchioles usually show mixed acute

and chronic mural inflammation

• Similar lesions observed in

hypogammaglobulinemia, inflammatory bowel disease, autoimmune disease

• Often lethal without treatment, but

controllable with low-dose macrolide therapy

Classification of Bronchiolitis

• Fibrotic/Fibroplastic

– Intraluminal polyps: Proliferative bronchiolitis

• This is the old BOOP

– Intramural scarring: Constrictive bronchiolitis

• aka BO, OB, cicatricial bronchiolitis

– Peribronchiolar/Interstitial

• Peribronchiolar metaplasia

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Organizing pneumonia – “Proliferative bronchiolitis”

BOOP

Granulation tissue polyp

Bronchiolitis Obliterans?

• r Organizing Pneumonia

Organizing pneumonia – “Proliferative bronchiolitis”

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Organizing Pneumonia

Organizing pneumonia Organizing pneumonia

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Constrictive Bronchiolitis

Transplant rejection with CB

Illustrative Case

• Legal case with limited history
• Transplanted, worked with artificial flavoring

agents at some point

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Diacetyl-related CB

Popcorn-worker lung

• May 2000: a physician in Jasper, MO identified a

group of 8 former workers from a microwave popcorn plant.

• 4 of the 8 worked in the “mixing room” (of the 425

total workers at the plant, only 13 worked in the mixing room).

• Soybean oil, salt, and flavorings were mixed into a

large heated tank in a process that produces visible dust, aerosols, and vapors with a strong buttery odor

• Analysis of the vapors identified diacetyl as the likely

culprit

• Although originally referred to as “Popcorn-worker

lung” this is occasionally called “flavorings-related lung disease”

CB - Associated Histologic Findings

• Foamy macrophage accumulation

– Often in the region immediately proximal to

• bstruction
• Cholesterol “stasis” granuloma formation

– Often in the alveolar ducts distal to obstruction

• Proximal bronchiectasis and bronchiolectasis

Transplant rejection with CB

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Diacetyl-related CB Transplant rejection with bronchiolectasis Transplant rejection with bronchiolectasis

CB - Increasing Diagnostic Yield

• Clinical context helpful

– PFTs, CT with expiratory views

• Obtain additional sections

– step or level sections (usually 30 micron gap)

• Obtain elastic stains

– Verhoeff-van Gieson Stain (VVG) – Movat Pentachrome

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EVG stain reveals CB

Histologic Mimic/Tissue Artifact

• Ex vivo contraction of smooth muscle can result in narrowing
• f bronchioles
• This effect is less likely to occur when fixation is performed

through bronchi (as in lobectomy or pneumonectomy samples).

Thunnissen E, et al. Arch Pathol Lab Med. 2016 Mar; 140(3): 212-20. PMID: 26927715. Pneumonectomy perfused through mainstem bronchus

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Surgical biopsy in patient with emphysema

Causes and Associations of CB

• Chronic lung transplant rejection
• Graft versus host disease
• Post-infectious
• Connective tissue disease
• Fume or toxin exposure

– SO2 gas – Diacetyl (popcorn worker lung) – Sauropus androgynus tea

• Drug reaction (penicillamine, gold)
• Miscellaneous

– Inflammatory bowel disease – DIPNECH

• Idiopathic

Chronic Rejection, Lung Transplant- CB Chronic Rejection, Lung Transplant- CB

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Chronic Rejection, Lung Transplant- CB Chronic Rejection, Lung Transplant- CB Penicillamine toxicity - CB Penicillamine toxicity - CB

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Constrictive Bronchiolitis

• Subepithelial (often concentric) fibrosis
• Patchy nature can make diagnosis difficult

– Knowledge of clinical and radiologic features – Use of level sections and elastic stains – Recognize “next-to” lesions

• Ex vivo smooth muscle contraction can mimic
• Various causes, but overall low incidence

Pulmonary Vascular Disease

• Pulmonary arteries run alongside bronchioles

and are approximately the same caliber

• Pulmonary veins lie in the interlobular septa,

but small venules are arranged within the lobules

• Vascular disease can manifest as changes in

the vessel wall or changes within the vessel lumen

Normal Pulmonary Vessels

• Pulmonary arteries have two distinct

elastic tissue layers while pulmonary veins have only one.

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Pulmonary arteriopathy

• Plexogenic arteriopathy

– Tufts of capillary-like vessels bulging from artery with damaged elastica – More common in primary pulmonary hypertension

• Thrombotic arteriopathy

– Re-canalized thrombi (Masson lesion) with intact vascular elastica

• Isolated medial and intimal thickening

– Beware of age-related changes

Illustrative Case

• 18-year-old woman with history of systemic

lupus erythematosus, treated with plaquenil and steroid pulses, presenting with persistent progressive dyspnea

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Pulmonary veno-occlusive disease (Occlusive Venopathy)

• My least favorite diagnosis
• Characterized by intimal obliteration of post-

capillary venules in many cases

• Can see associated pathologic findings:

– Pulmonary capillary hemangiomatosis – Alveolar siderosis – Encrustation of vascular elastica

Diseases with Alveolar Loss

• Cystic lung disease

– Pulmonary Langerhans cell histiocytosis

• Upper zone dominant, often with nodules or irregular

shapes, observed in smokers

– Lymphangioleiomyomatosis

• Diffuse involvement, observed in women, can see

angiomyolipoma in kidneys

– Lymphoid interstitial pneumonia (LIP)

• Fewer cysts usually, associated with dense intersitial

infiltrates

– Birt-Hogg-Dube

• More often in lower lung zones, punched-out look

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Illustrative Case

• 65-year-old woman with diffuse bilateral

pulmonary cystic disease

• Transbronchial biopsy with “increased muscle”
• Sent for consultation

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Smooth-muscle actin Estrogen receptor HMB-45

Diagnosis of LAM

• Patients with LAM show increases in

VEGF-D (but not VEGF-A or -C)

Seyama K, et al. Lymphat Res Biol. 2006;4(3):143-52. PMID: 17034294. Young LR, et al. N Engl J Med. 2008 Jan 10;358(2):199-200. PMID: 18184970.

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Diagnosis of LAM

• Cysts on CT? TSC? If both yes – LAM
• Cysts on CT? Send serum VEGF-D. If (+) – LAM
• TBBx
• VATS

Inattentional Blindness

• A key to inattentional blindness is that the event

is unexpected

• Knowledge of possibilities and attention to

normal structures decreases the likelihood of an unexpected event

Drew T, et al. Psychol Sci. 2013 Sep;24(9):1848-53. PMID: 23863753.