Ebook Atlas of pulmonary cytopathology: Part 1

Atlas of Pulmonary
­Cytopathology


Christopher J. VandenBussche,
MD, PhD

Assistant Professor of Pathology and Cytopathology
Fellowship Director
The Johns Hopkins University School of Medicine
Baltimore, Maryland

Syed Z. Ali, MD, FRCPath, FIAC

Professor of Pathology and Radiology and Director
of Cytopathology
The Johns Hopkins University School of Medicine
Baltimore, Maryland

Morgan L. Cowan, MD

Assistant of Pathology
The Johns Hopkins University School of Medicine
Baltimore, Maryland

Paul E. Wakely, Jr., MD

Professor of Pathology
Ohio State University Medical Center
Columbus, Ohio

Joyce E. Johnson, MD

Professor of Pathology, Microbiology, and
­Immunology
Director, Anatomic Pathology,
VA Medical Center
Vanderbilt University School of Medicine
Nashville, Tennessee


Atlas of Pulmonary
Cytopathology
With Histopathologic Correlations

An Imprint of Springer Publishing


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Library of Congress Cataloging-in-Publication Data
Names: VandenBussche, Christopher J., author. | Ali, Syed Z., author. |
  Cowan, Morgan L., author. | Wakely, Paul E., Jr., 1949- author. | Johnson,
  Joyce E., 1958- author.
Title: Atlas of pulmonary cytopathology with histopathologic correlations /
  Christopher J. VandenBussche, Syed Z. Ali, Morgan L. Cowan, Paul E.
  Wakely, Jr., Joyce E. Johnson.
Description: New York: Demos Medical Publishing, [2017] | Includes
  bibliographical references and index.
Identifiers: LCCN 2017016470| ISBN 9781936287161 | ISBN 9781617050459 (e-ISBN)
Subjects: | MESH: Lung Diseases—pathology | Lung Diseases—diagnosis |
  Cytodiagnosis | Atlases
Classification: LCC RC756 | NLM WF 17 | DDC 616.2/4—dc23
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To my mother, Carol, and her parents, William and Katharine (“Vicki”). –CJV
To my parents, Bano and Mazhar. –SZA
To my first microscope, monocular and mirror-illuminated, passed on to my childhood self by my mother (and from
Dr. E. L. Caudil of Elizabethton, Tennessee, before her), by which the animated cellular mysteries of the otherwise
still and muddy pond behind my childhood home were first illuminated. And always, for Travis. –MLC
To my former cytopathology fellows in appreciation of the knowledge and stimulation I have received from them. –PEW

To residents and fellows, who are the future; and to patients with lung diseases, who are the reason. –JEJ



Contents
Foreword Fernando Schmitt, MD, PhD, FIAC   ix
Share Atlas of Pulmonary Cytopathology: With Histopathologic Correlations

1. Lung Radiology 
2. Normal Lung 

 

 

1

31

3. Reactive Changes and Benign Lung Lesions 
4. Infectious Lung Lesions 
5. Benign Lung Neoplasms 

 

41

65

 

 

81

6. Malignant Lung Neoplasms 

 

93

7. Unusual and Metastatic Lesions 

 

153

Index  205

vii



Foreword

The practice of cytopathology has undergone significant
­evolution in the last 50 years. Cytopathology is a ­diagnostic
method, not simply a screening method, in most of the areas
in which it is applied and has become an integral part of
­pathology. The importance of cytological techniques for the
­investigation of respiratory conditions has been recognized

since the earliest days of clinical cytology. The study of cellular specimens from the respiratory tract is established as a
vital diagnostic procedure in the evaluation of patients with
suspected lung ­inflammatory/infectious or neoplastic diseases.
The study of sputum, bronchial washings, bronchial aspirates,
bronchial brushings, bronchoalveolar lavage specimens, and
fine needle aspirates (FNAs) provides the morphologic basis for
these diagnoses. With the advent of targeted therapy for lung
cancer, ancillary testing of specimens derived from the lower
respiratory tract has obtained greater importance. Traditionally,
ancillary testing was confined to culture techniques for microbiologic organisms, flow cytometry for lymphoid p
­ roliferations,
and immunohistochemical stains for the classification of pulmonary neoplasms. Targeted therapy has expanded the need
for ancillary and, in particular, molecular testing to document
the presence or absence of certain mutations, amplifications,
inversions, and translocations that indicate a carcinoma susceptibility to specific targeted therapies. In fact, in lung cancer,
small biopsies and cytologic specimens are the primary materials for establishing the diagnosis in most cases, as well as for
studying markers driving tumor classification and providing
prognostic and predictive information. Despite all of these new
advances, the foundation of cytopathology is based in a correct
and ­precise morphologic interpretation.
This Atlas of Pulmonary Cytopathology is an outstanding
work with more than 500 high-quality images documenting

a full range of non­neoplastic and neoplastic lung diseases.
In addition, there is excellent ­documentation of the histopathology and gross examination in some cases, providing
morphologic correlations useful for cytopathologists and
surgical pathologists. The inclusion of a chapter dedicated
to radiology is of paramount importance. In the era where
clinical-pathologic correlation is becoming more and more
important in the management of patients, the knowledge

of how an expert radiologist deals with these correlations
brings an additional value to the Atlas that will be very well
recognized and accepted for the ­readers. From the cytopathology perspective, knowing the imaging characteristics of
lung lesions is extremely valuable in the interpretation of
specimens.
The richness of the Atlas content will be very helpful for
general pathologists, lung pathologists, cytopathologists, and
trainees in their daily practice. Moreover, the work reflects the
extensive practice of cytopathology at Johns Hopkins, especially by Drs. VandenBussche and Ali, internationally recognized experts and respected cytopathologists. I am confident
that this book will aid pathologists in their routine by providing essential information for better diagnosis and management
of patients. Now it is time to enjoy the text and the illustrations
of this Atlas that presents, in a didactic way, ­up-to-date knowledge in lung cytopathology.
Fernando Schmitt, MD, PhD, FIAC
Professor of Pathology at Medical Faculty of Porto University
Head of the Molecular Laboratory and Senior Researcher
Instituto de Patologia e Imunologia Molecular da
Universidade do Porto, Porto, Portugal
General Secretary of the International Academy of Cytology

ix



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Atlas of Pulmonary Cytopathology:
With Histopathologic Correlations


Lung Radiology

1

1


2

INTRODUCTION
Radiologic evaluation of lung lesions can serve many roles
including primary detection, narrowing of the differential diagnosis, treatment or surgical planning, and posttreatment surveillance. Plain radiographs are often the first-line modality for
evaluation of symptomatic individuals and may be the source
of detection of a lung lesion incidentally discovered during the
course of other medical work-up. Nevertheless, CT remains as
the mainstay of imaging characterization of lung disease due to
its widespread access and excellent spatial resolution. CT is also
often used as a rapid method of assessing the entire body for
metastatic disease in the setting of lung malignancy. CT has a
significant advantage over MRI in avoiding motion-related artifacts from breathing, due to the short image acquisition times
possible with CT. MRI, on the other hand, is very useful in certain specific situations where its superior contrast resolution can
better delineate soft tissue anatomy, such as in the evaluation of
mediastinal or superior sulcus invasion by tumor. More recently,
F-18 fluorodeoxyglucose-PET has become another widely used
tool in diagnostic imaging of lung disease. FluorodeoxyglucosePET imaging utilizes the hypermetabolism of most tumors as a
method of tumor localization and can be a very powerful tool in
detection and assessment of tumor location and activity, sometimes revealing malignancy in places that would otherwise be
overlooked by anatomic imaging alone.

Atlas of Pulmonary Cytopathology

In spite of all the technical advances in imaging, clinical

and pathologic correlation are often necessary for accurate
diagnosis. Image guidance with fluoroscopy, CT, ultrasound,
and MRI is commonly used for minimally invasive tissue sampling in the hopes of avoiding or better preparing for a more
extensive surgical approach.
This chapter presents the radiologic imaging of a sample
of lung pathologies presented in the following order: malignant primary lung carcinoma, benign primary lung neoplasms,
metastatic disease, infections, and other miscellaneous lung
lesions, some of which can mimic neoplasm on imaging. The
goal of this chapter is to provide some insight into the strengths
of imaging in diagnosis of lung pathology and to highlight the
crucial role that patient history and pathologic correlation
often play in overcoming the limitations of imaging alone in
order to arrive at a final diagnosis.

Figure 1.1a — Squamous Cell Carcinoma. Chest radiograph shows a
cavitary lesion in the right upper lobe (between arrows). Right minor
fissure thickening is also noted (arrowhead).
Chapter 1 was prepared by Rohan Piyasena, MD: Northside Radiology Associates, Atlanta, Georgia.


Chapter 1: Lung Radiology3

Figure 1.1b — Squamous Cell Carcinoma. Axial CT with contrast
in soft tissue windows shows an irregular, enhancing nodular
component within the cavitary mass. Mediastinal lymphadenopathy
is also noted (arrows).

Figure 1.1c — Squamous Cell Carcinoma. Coronal CT in
lung windows demonstrates the thick wall of the cavitary lesion
(arrows). Differential considerations include Aspergillus colonization

of a preexisting cavity (mycetoma), tuberculosis, or Wegener’s
granulomatosis, although the irregular enhancing nodular
component highly suggests lung carcinoma. Cavitation is more
common with squamous cell lung cancer than other types.

Figure 1.1d — Squamous Cell Carcinoma. Axial postcontrast image
through the upper abdomen shows an enhancing right adrenal nodule
(arrow) compatible with metastatic disease.


4

Figure 1.2a — Squamous Cell Carcinoma. Axial CT image
showing a large, enhancing mass in the left upper lobe invading the
chest wall with associated rib destruction (arrow).

Atlas of Pulmonary Cytopathology

Figure 1.2b — Squamous Cell Carcinoma. PET-CT fusion image
shows marked hypermetabolism in the mass consistent with the
history of carcinoma. Chest wall invasion would make this lesion at
least T3 using the tumor node metastasis staging system.

Figure 1.3a — Squamous Cell Carcinoma With Postobstructive
Pneumonia. Frontal chest radiograph with asymmetric increased
opacification of the left lung and nonvisualization of the left heart
border, suggesting a left upper lobe process.


Chapter 1: Lung Radiology5

Figure 1.3b — Squamous Cell Carcinoma With Postobstructive
Pneumonia. Axial CT with contrast confirms complete loss of aeration
of the left upper lobe secondary to an obstructing mass (between
arrows). The mass invades the visceral pleura and pericardium. There is
a small, malignant pericardial effusion present (arrowhead).

Figure 1.3c — Squamous Cell Carcinoma With Postobstructive
Pneumonia. CT image obtained more superior shows obstructive
atelectasis of the left upper lobe and dilated bronchi filled with low
density mucus and inflammatory cells (arrowheads). Mediastinal
adenopathy is also noted (arrows).

Figure 1.4a — Adenocarcinoma. Chest radiograph showing a right
lung pulmonary nodule with ill-defined margins (arrow).


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Atlas of Pulmonary Cytopathology

Figure 1.4b — Adenocarcinoma. Coronal CT in lung windows
shows the nodule in the right upper lobe with spiculated margins
(arrowheads), often seen with adenocarcinoma. Adenocarcinoma is the
most common primary lung cancer to present as a solitary pulmonary
nodule, as in this case.

Figure 1.5a — Adenocarcinoma. Large, heterogeneous right lower
lobe mass seen on contrast enhanced chest CT. The mass shows
enhancement, with central low density (arrow) compatible with

central necrosis.

Figure 1.5b — Adenocarcinoma. Lung window shows thickening
of the adjacent lung interstitium (arrowheads) representing
lymphangitic spread of the tumor. A small satellite tumor nodule is
also noted (arrow).


Chapter 1: Lung Radiology7

Figure 1.6b — Adenocarcinoma, Pancoast Tumor. Fifty-nineyear-old male smoker presenting with left shoulder pain. CT shows
a medial left apex mass (m) with large amount of pleural contact
suggesting invasion. Note the severe emphysema in the lung apices.

Figure 1.6a — Adenocarcinoma, Pancoast Tumor. Fifty-nineyear-old male smoker presenting with left shoulder pain. Frontal
radiograph shows asymmetric left apical fullness (arrow) and mild
left hemidiaphragm elevation.

Figure 1.6c — Adenocarcinoma, Pancoast Tumor. Fifty-nine-year-old
male smoker presenting with left shoulder pain. Coronal postcontrast
CT image shows the mass (between the arrowheads) encasing the left
subclavian artery (arrow) and left vertebral artery origin (black arrow).


8

Atlas of Pulmonary Cytopathology

Figure 1.6d — Adenocarcinoma, Pancoast Tumor. Fifty-nineyear-old male smoker presenting with left shoulder pain. PET-CT
clearly shows the hypermetabolic tumor at the left apex. In cases

of superior sulcus tumor, MRI is superior to CT for evaluation of
the extent of involvement of adjacent structures including the great
vessels, brachial plexus, ribs, and vertebral column.
Figure 1.6e — Adenocarcinoma, Pancoast Tumor. Fifty-nine-yearold male smoker presenting with left shoulder pain. Sagittal T2
weighted MRI through the left lung apex shows encasement of
the left subclavian artery and left vertebral artery origin (arrow) by
tumor. The tumor (between arrowheads) also extends posteriorly
to involve the brachial plexus, specifically nerve roots C8 and T1
(labelled).

Figure 1.7 — Adenocarcinoma in Situ, Nonmucinous Subtype. CT
image in lung windows shows the classic appearance of nonmucinous
adenocarcinoma in situ with a left upper lobe ground glass nodule
containing air bronchograms (arrow). PET is often of limited value as
bronchoalveolar carcinomas often show only mild fluorodeoxyglucose
uptake. Other differential considerations for a ground glass nodule
include hypersensitivity pneumonitis, pneumonias (particularly
Pneumocystis, viral), pulmonary edema, pulmonary hemorrhage, and
bronchiolitis obliterans organizing pneumonia.


Chapter 1: Lung Radiology9

Figure 1.8a — Bronchoalveolar Carcinomas, Mucinous Subtype.
Axial CT through the lung bases shows bilateral multifocal
consolidation (arrows).

Figure 1.8b — Bronchoalveolar Carcinomas, Mucinous Subtype.
Postcontrast images show vessels coursing through the area of
consolidation in the right lower lobe (CT angiogram sign, arrow),

confirming that this is an area of alveolar filling, rather than a large
mass. The differential for such consolidation is large and includes
pulmonary edema, pneumonia, and hemorrhage, among several
others. This case proved to be bronchoalveolar carcinomas. The
mucin produced by the tumor can cause consolidation and can
demonstrate endobronchial spread.

Figure 1.9a — Small Cell Carcinoma. Left superior parahilar mass
(between arrowheads) with enhancement and probable areas of necrosis.
Mediastinal adenopathy (arrow) is present.


10

Atlas of Pulmonary Cytopathology

Figure 1.9b — Small Cell Carcinoma. The mass shows marked
fluorodeoxyglucose (FGD) uptake. Some increased uptake is also seen
in the mediastinal lymph node (arrow).

Figure 1.10a — Small Cell Carcinoma. Chest radiograph shows a
right infrahilar mass (arrows) and blunting of the right costophrenic
angle, suggesting a pleural effusion.

Figure 1.10b — Small Cell Carcinoma. Contrast-enhanced CT
shows the right hilar mass narrowing the bronchus intermedius
(arrow). Enhancing pleural metastases (arrowheads) and a malignant
pleural effusion (e) are present. Pleural tumor nodules, as well as
malignant pleural or pericardial effusion, are all considered M1 in
the 2009 tumor node metastasis staging system.

Chapter 1: Lung Radiology11

Figure 1.11a — Carcinoid Tumor. Coronal image from CT with
contrast shows a well-defined, enhancing mass (m) in the central
right lower lobe.

Figure 1.12a — Mucoepidermoid Carcinoma. Contrast CT shows an
enhancing mass in the left hilum (arrow).

Figure 1.11b — Carcinoid Tumor. Axial image in the lung
windows show the well-defined, smooth margins of the tumor (t)
consistent with a low-grade malignancy. Carcinoids often involve
the central bronchi and are often highly vascular.


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Figure 1.12b — Mucoepidermoid Carcinoma. Sagittal image
through the mass shows finger-like endobronchial extension of the
tumor into the superior segment of the left lower lobe (arrows).
There is evidence of decreased lung attenuation in the obstructed
segment of the lung from decreased ventilation, causing decreased
perfusion. Differential considerations include carcinoid, adenoid
cystic carcinoma, lung cancer, or metastatic disease.

Atlas of Pulmonary Cytopathology

Figure 1.13a — Pulmonary Hamartoma. Axial contrast enhanced

CT shows a nodule in the left lower lobe (between arrows)
predominantly of fat density. Also noted on the image is an aortic
dissection (dissection flap indicated by arrowhead).


Chapter 1: Lung Radiology13

Figure 1.14 — Laryngeal Papillomatosis. CT image shows
multiple bilateral cavitary lesions in the lungs (arrows) in this
patient with a history of laryngeal papillomas. Metastatic disease
(particularly squamous cell metastases), bland and septic pulmonary
emboli, Wegener’s granulomatosis, and fungal infections can have a
similar appearance.

Figure 1.13b — Pulmonary Hamartoma. Bone windows nicely
show the course calcification in the mass (arrow). The combination
of fat and calcification make this pathognomonic for a hamartoma.

Figure 1.15a — Ewing’s Family Tumor of the Chest Wall and Pleural
Space. Scout image from a CT shows a large mass occupying the mid
and lower left pleural cavity with mass effect on the heart and a few air
bronchograms (arrow).