2022 Surgpath s2t2 Cardiovascular System

CARDIOVASCULAR SYSTEM SURGICAL PATHOLOGY (PRELIMS)| 2nd SEM
Dr. Michelle Cauan

Atrioventricular (Mitral and Tricuspid) Valves
OUTLINE ● Composed of the annulus (a ring of circumferentially oriented
I. HEART I. Cystic adventitial disease collagen and elastic fibers), leaflets, chordae tendineae, and
A. Normal anatomy J. Fibromuscular dysplasia papillary muscles.
B. Myocardial biopsy K. Mesenteric vascular occlusion ● The leaflets, like those of the semilunar valves, are composed of
C. Cardiac valves L. Acquired arteriovenous fistula three layers:
D. Left atrial appendage M. Arteriovenous malformation
○ Spongiosa – on the atrial side, rich in proteoglycans
E. Coronary artery bypass (congenital)
F. Coronary artery stents N. Thromboangiitis obliterans o Central fibrosa
G. Cardiac tumors O. Arteritis o Ventricularis – on the ventricular side, rich in elastic fibers
H. Pericardium P. Tumors
II. ARTERIES III. VEINS B. MYOCARDIAL BIOPSY
A. Normal anatomy A. Normal anatomy
B. Arteriosclerosis and B. Thrombophlebitis &
● Obtained endovascularly through a catheter inserted in a
atherosclerosis thromboembolism systemic vein directed to the RV or through a transthoracic route
C. Stents and bypass grafts C. Stasis ulcers at the time of surgery for congenital or acquired heart disease
D. Aneurysms D. Varicose veins ● Ultrastructural examination - evaluation of drug toxicity
E. Arterial dissection E. Tumors (Adriamycin toxicity)
F. Coarctation of aorta IV. LYMPH VESSELS ● Inflammatory processes and other diseases with with “patchy
G. Synthetic arterial substitution A. Normal anatomy involvement” of the myocardium - possibility of false-negative
H. Arterial occlusive disease B. Lymphedema
result should be kept in mind
● Most common complication: Hemopericardium and Myocarditis
I. HEART
A. NORMAL ANATOMY
● Surgical Pathology:
○ Methods have been devised to relieve aortic, mitral, and
pulmonary valvular stenosis (often by replacement with
prosthesis) and restore competency to regurgitant mitral,
aortic, and tricuspid valves.
○ Coronary artery bypass graft surgery – less invasive
endovascular coronary artery interventions for the
symptomatic treatment of ischemic heart disease.
○ Cardiac transplantation remains a mainstay of treating
end-stage heart failure
○ Pathologist – rejection monitoring
○ When cardiac transplantation is not possible
▪ Mechanical circulatory support (implanted
ventricular assist device pumps)
● Most operations for congenital cardiovascular malformations are
directed toward increasing or redirecting the flow of blood
○ Ligating a patent ductus Figure 1: Adriamycin cardiotoxicity, manifesting as vacuolar areas of
○ Closing atrial, ventricular (and atrioventricular) septal defects sarcoplasmic myofiber loss (arrows). This change is apparent in both plastic
○ Creating new pulmonary flow conduits embedded thick sections stained with toluidine blue O (left) and by transmission
electron microscopy (right).
○ Reconstructing stenotic arteries and valves orifices.
C. CARDIOMYOPATHIES AND MYOCARDITIS
Major Histologic Components
● Pericardium Hypertrophic Cardiomyopathy
○ Fibrous (parietal) ● Inherited disease of the myocardium
○ Serous (visceral, also known as epicardium) portions ○ Left ventricular hypertrophy - usually in an asymmetric
○ Single layer of mesothelial cells resting on a basement fashion, in the absence of a systemic or secondary cardiac
cause for hypertrophy (such as hypertension or aortic
membrane
stenosis) and with normal or reduced chamber size but
○ Cavity filled with a small amount (~60 cc) of fluid
● Myocardium preserved or hyperdynamic ejection fraction.
● Genetically heterogeneous
○ Consists of bundles of cardiac muscle fibers (myocytes)
○ Most cases are caused by germline mutation in a sarcomeric
separated by fibrous bands.
○ Intercalated discs protein gene - MYH7 and MYBPC3
● Main microscopic features:
○ Nuclei of myocytes are centrally located.
● Endocardium ○ Hypertrophy and interstitial fibrosis with myofiber “disarray.”
○ Single layer of endothelial cells that are continuous with ● Idiopathic hypertrophic myocardiopathy
○ Basophilic degeneration of myocardium – nonspecific
those of the major blood vessels
change
○ Basement membrane
○ Delicate supporting connective tissue ▪ Pale blue (on h&e),
▪ Finely granular material in the cytoplasm of
Semilunar (Pulmonary and Aortic) Valves isolated myocardial fibers
● Composed of three layers: ▪ Consists of polyglucosan deposits
○ Fibrosa – made of dense collagen
○ Spongiosa – containing large amounts of proteoglycans, Idiopathic Dilated Cardiomyopathy
loosely arranged collagen fibers, and scattered fibroblasts ● Common
○ Ventricularis – identified by its profusion of elastic fibers ● Has both genetic and acquired components
○ 30% of cases have inherited basis
○ Autosomal dominant
○ Due to germline mutations in genes encoding sarcomeric
and other cardiomyocyte proteins
● Left ventricular chamber dilation with reduced ejection fraction
● Hypertrophy, fibrosis and degenerative changes
● Leukocytic infiltrates
ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 1 of 22

Prelims (2nd Sem) Cardiovascular System
Dr. Michelle Cauan
PATHOLOGY· February 22, 2021
Restrictive (Obliterative) Cardiomyopathy Left Ventricular Noncompaction (Hypertrabeculation)
● Eosinophilic form (Active Stage) Cadiomyopathy
○ Myocarditis with a heavy component of eosinophils ● Unusual form
○ Eosinophil-rich mural thrombus atleast in the active stage ● Heritable disorder
● Results from embryonic failure of ventricular muscle bands to
condense and coalesce during development, resulting in
abnormal trabeculations in the left ventricle (comprising more than
half of the ventricular wall thickness) and functionally impaired
ejection fraction
● Has been associated with sarcomere and other sarcoplasmic
proteins.
Figure 2: Restrictive eosinophilic endomyocardial disease, with organizing

mural thrombus in the right ventricle apex (left). The thrombus is eosinophil-rich
and there is an associated eosinophilic myocardial infiltrate (right).
● Non-eosinophilic Form (Idiopathic Restrictive

Cardiomyopathy)
○ Left ventricle – normal size
○ Left atrium – markedly enlarged
○ The biopsy findings in this form are nonspecific Figure 4: Left ventricular noncompaction cardiomyopathy with left
ventricular hypertrabeculation comprising more than half of the ventricular
Infiltrative Cardiomyopathies thickness (highlighted by trichrome staining).
● Endomycocardial biopsy can be rewarding
● Diagnosis – obtained more readily in by biopsy of another, more Myocarditis
easily accessible organ ● Diagnosis requires the presence of an inflammatory infiltrate and
○ Amyloidosis myocyte necrosis or degeneration (Dallas criteria)
○ Hemochromatosis ● Infiltrate - lymphocytic in nature, easily identifiable, and often
○ Storage Diseases admixed with histiocytes and occasional granulocytes (neutrophils
● Insidious deposition of exogenous injurious material(s) in the and eosinophils) in routine sections.
interstitium, cardiomyocytes, or resident histiocytes in the heart. ● H&E sections may be supplemented with CD3, CD4, CD20,
○ Interferes with cardiac contractility and function, leading to a CD45, and/or CD68 immunostains to increase sensitivity or clarify
cardiomyopathy phenotype. the nature of any ambiguous mononuclear cell, but this is not
necessary.
D. OTHER CARDIOMYOPATHIES ● Hypersensitivity myocarditis
Ischemic Cardiomyopathy ○ Infiltrate is rich in eosinophils, is predominantly perivascular,
● Not a primary myocardial disease but a result of coronary artery and is accompanied by a lesser degree of myocyte injury
occlusion with myocardial infarction and associated ventricular ● Myocyte alterations in myocarditis of any etiology:
“remodeling” changes. ○ Frank necrosis
● Characteristics: ○ Vacuolization
○ Congestive heart failure ○ Disruption
○ Ventricular arrhythmias ○ Better appreciated in longitudinally oriented cells.
o Left ventricular ● Presence of edema alone should not be used as a criterion for
o Dilation myocarditis.
o Can be distinguished from idiopathic dilated cardiomyopathy ● Fibrosis
by the presence of significant coronary artery disease and ○ Should be quantified (mild, moderate, or severe) and
infarcts in the accompanying myocardial territories. qualified (interstitial, endocardial, or replacement type)
○ Represents a more chronic change not likely to respond to
Arrhythmogenic Cardiomyopathy acute immunosuppressive therapy.
● Formerly “right ventricular dysplasia”
● Inherited cardiomyopathy Diagnostic Terms to be used subsequent biopsies (if obtained),
● Mutations in desmoglein, desmoplakin, plakoglobin, plakophilin- Using the 1st specimen as a Reference point
2, and related cell junction proteins. ● Ongoing or persistent myocarditis
● Its manifestations mainly affect the right ventricle. ○ When both myocyte damage and the inflammation persist
● The anatomic substrate is variable infiltration/replacement of the ● Resolving or healing myocarditis
right ventricular myocardium by adipose and fibrous tissue ○ When these changes are substantially reduced
● Resolved or healed myocarditis
○ When these changes are no longer present (bearing in mind
the high likelihood of sampling error and possible false-
Figure 3: Arrhythmogenic negative results).
cardiomyopathy, with primarily
right ventricular involvement (by
fibrofatty replacement of ventricular
myocardium).

Dr. Michelle Cauan
Etiology of Myocarditis Heart Transplant
● Viral ● Myocardial biopsy
● Bacterial (including Whipple disease, Coxiella, and Bartonella) ○ most sensitive and specific indicator of rejection
● Mycobacterial ○ the main microscopic sign of cellular rejection is a
● Fungal, or perivascular and interstitial inflammatory infiltrate,
● Parasitic predominantly lymphocytic, accompanied by focal
○ Chagas disease necrosis of myocytes (similar to myocarditis) and edema.
○ Toxoplasmosis – often seen in AIDS patients ● Antibody-mediated rejection is assessed by evaluating the
● Autoimmune disease – rheumatic fever “pancarditis”, drug- myocardial interstitial capillaries for “swollen”- appearing
induced reaction, radiation, transplant rejection endothelial cells and accumulation of intravascular macrophages
(collectively referred to as “intravascular activated
Giant Cell Myocarditis mononuclear cells” in the working formulation)
● Particularly aggressive form ● Immunopathology methods are needed (frozen section
○ More widespread multicentric destruction of the cardiac immunofluorescence or paraffin immunohistochemistry) to
myocytes. test for deposition of complement split products and other
○ Inflammatory infiltrate includes cytotoxic T cells, potential indicators of antibody mediated immune mechanisms
eosinophils, and the multinucleated cells that define the ● ISHLT working formulation for cardiac transplant rejection:
entity
○ Well-formed granulomas are not seen in giant cell
myocarditis
Myocardial Biopsy
● Care should be taken to not misinterpret a previous biopsy site as
indicative of rejection:
Figure 5: Giant Cell Myocarditis. Scattered multinucleated giant cells ○ Recent biopsy sites appear as a sharply outlined area of
accompanied by lymphocytes are seen in association with loss of myocardial necrotic myocytes sometimes associated with a thrombus
fibers. There are no granulomas and myocyte damage is widespread, and and granulation tissue.
eosinophils are present in the background. ○ Older biopsy sites show replacement fibrosis-type scarring,
often with associated mononuclear inflammation.
Cardiac Sarcoidosis ○ Quilty or nodular endocardial inflammatory lesion
● Clinical signs: ▪ Another potential mimic of rejection
○ Conduction block ▪ Can be distinguished from cellular rejection on the
○ cardiac arrhythmia basis of their rounded (rather than infiltrative)
● Sarcoid – well-circumscribed, scar-like lesions distributed in contours and subendocardial location
patches throughout the full thickness of the myocardium. ● Cardiac allograft vasculopathy
● Well demarcated histologically without significant associated ○ A form of accelerated “arteriosclerosis”
myocyte necrosis in the surrounding myocardium ○ Major long-term complication of heart transplantation,
occurring in the majority of grafts 10 years
after transplant
● Factors recognized to contribute to this disease:
○ Previous rejection episodes (especially antibody mediated
rejection)
○ Circulating anti-donor antibodies detected by flow
cytometry methods
○ Infections (especially with cytomegalovirus)
● Other clinically impactful findings may be seen on transplant
biopsies:
○ EBV-associated post-transplant lymphoproliferative disorder
○ Opportunistic infections such as Toxoplasma and
Cytomegalovirus
● Immunohistochemical or in situ hybridization techniques may
be helpful in confirming the presence of these.
C. CARDIAC VALVES
1. Mitral Valve
Figure 6: Cardiac sarcoidosis with multinucleated giant cells within well-formed 2. Aortic Valve
granulomas. The surrounding myocytes are relatively intact. 3. Pulmonary valve
4. Tricuspid valve
● Surgeries to correct major valve defects (congenital and acquired)
by resection and prosthetic replacement
● The most frequently performed cardiac surgical procedures
● Gross appearance of the valve often provides the most precise
diagnosis
● Photographic and radiographic examination of the specimen
could also be useful

Dr. Michelle Cauan
Mitral Valve Aortic Valve
● Nearly all cases of mitral valve stenosis (with or without mitral ● Aortic valve specimens that are removed because of
insufficiency) are acquired and postinflammatory (rheumatic) in stenosis:
nature. ○ Degenerative calcification of congenitally bicuspid valves
● Common causes of Mitral insufficiency ○ Calcification of a normally three-leaflet valve without
● myxomatous (floppy) mitral valve disease (mitral valve prolapse), commissural fusion (so-called senile type degeneration)
● postinflammatory, and ischemic complication. ○ Rheumatic changes similar to those described for mitral
leaflets calcification of congenitally unicommissural valves
Rheumatic Valve
● Gross appearance: “repeated dipping in candle wax”
● Commissures are partially fused (from the annulus inward and Figure 8: Gross features of aortic
“fish mouth.” stenosis (note the number and
● Cords are thickened and fused, appearing similar to the proportionality of cusps and presence of
commissural fusion help distinguish
“whiskers/tendrils of a catfish” various disease processes).
● Presence of vessels with the valve layers is a finding specific to
rheumatic valve disease
Congenital Bicuspid Aortic Valve

● It can be difficult to differentiate congenital bicuspid aortic from a
three-leaflet valve that has calcified in a manner such that two of
the leaflets fuse together.
● Clues:
○ Leaflet sizes – nonconjoined cusp in bicuspid valves is often
disproportionately large
○ Midline raphe on the conjoined cusp
● Pure aortic insufficiency
○ Not related to calcification but to causes such:
Figure 7: Gross and microscopic features of common mitral valve diseases
(note the myxoid expansion of myxomatous disease and well-formed vessels in
▪ Aortic root dilation
the valve layers in rheumatic disease). ▪ Bicuspid valve
Features of Aortic Valve Disease:
Myxomatous Valves
● Leaflet thickening and redundancy, leading to the formation of
dome-like deformities reaching above the level of the annulus.
● The annulus itself is also dilated. The chordae are often thin and
attenuated, though with fibrosis
● Chordal rupture is seen in over one-half of the cases, though the
clinical intraoperative impression is often the only way of knowing
this
● Stromal accumulation of glycosaminoglycans is the distinguishing
feature of myxomatous disease
● “myxoid or myxomatous degeneration”
● Not associated with cardiac myxoma
● Whether this alteration is the result of a genetically determined
disease or a degenerative process of nonspecific nature remains
controversial
Ischemic Mitral Insufficiency

● A papillary muscle abnormality, with the leaflets generally
preserved.
● Scarring of the infarcted papillary muscle(s) leads to retraction Pulmonary Valve
and foreshortening of the tendinous cords, impairing coaptation ● Congenital Pulmonary stenosis (Tetralogy of Fallot)
during systole. ● Bicuspid pulmonary valve is the most common structural
● Features of Mitral Valve Disease: anomaly.
● Pulmonary valve endocarditis - another uncommon cause of
surgery at this location.
Tricuspid Valve
● Specimens of tricuspid valve can be:
○ Result of operations for pure insufficiency (by far the most
common)
○ Combined stenosis and insufficiency
○ Pure stenosis (very rare)
● Most common causes of insufficiency:
○ Postinflammatory diseases
o Congenital disorders (such as ebstein anomaly)
o Pulmonary venous hypertension
o Infective endocarditis

Dr. Michelle Cauan
Endocarditis D. LEFT ATRIAL APPENDAGE
● Complications: ● At the time of the correction of a mitral stenosis or other cardiac
○ Stenosis due to obstruction by bulky vegetations (often with disease, the surgeon may “amputate” the left (and right) atrial
associated embolic phenomena), appendage to either remove or prevent later mural thrombus
○ Regurgitation due to leaflet destruction in the form of tears, formation and embolization.
perforations, ● Frequently accompanied by atrial
○ Aneurysms ablation to disrupt atrial fibrillation
● Preexisting valve abnormalities seem to predispose to pathways (the “maze” procedure)
endocarditis, such as bicuspid aortic valve and rheumatic ● Usually abnormal, showing
disease. hypertrophy of the muscle and
● Vegetations are the hallmark of active and subacute endocarditis various other alterations
and grossly appear as fleshy, friable growths arising from the o Aschoff nodules and amyloid
leaflet surfaces. deposits: Incidental findings
● Histologically: which may be seen and often do
○ Fibrin clot that is rich in neutrophils not correlate with rheumatic
○ Bacterial colonies or other microbes may be seen, especially disease or cardiac amyloid in the
with the help of special stains. ventricles or systemically.
● Healed endocarditis Figure 10: Left Atrial Appendage
○ No longer show vegetations grossly or histologically
○ Perforations and/or leaflet aneurysms E. CORONARY ARTERY BYPASS
○ Microscopically, resembles rheumatic valve disease and  A common treatment of coronary artery atherosclerosis
may show disruption of the valve layer architecture and  Bypass grafting is still the preferred procedure for some
replacement fibrosis. coronary lesions and often accompanies open heart surgery
when done for other reasons (e.g. Aortic stenosis and coronary
atherosclerosis)
 Conduits used to construct bypass grafts:
o Veins (usually saphenous)
o Internal mammary arteries (given their proximity to the
heart)
 50%–60%: 10-year patency rate of vein grafts
 80%–90%: 10-year patency rate of internal mammary grafts
 Coronary bypass grafts on cardiac explant specimens
should be evaluated by sampling:
o The graft body at the point of greatest narrowing,
o The anastomotic site, and
o The native artery proximal and distal to the anastomotic
site.
Figure 9: Gross features of aortic valve endocarditis (active and healed)

involving three-leaflet and bicuspid valves.
Prosthetic Valves
● Examination of mechanical and bioprosthetic valve prostheses
○ Fairly straightforward
○ Presence of thrombus, vegetation, calcification, and
○ Degenerative changes (such as leaflet tears for bioprosthetic
valves)
● Neo-endocardium develops at the junction with the heart wall, and
from there it grows centripetally over the sewing cloth toward the Figure 11: Coronary Artery Bypass
valve lumen
● Fibrous ingrowth – Pannus F. CORONARY ARTERY STENTS
○ Cause flow obstruction ● Percutaneous endovascular approaches to treating coronary
atherosclerosis have become the mainstay for this common
Bioprosthetic Valves disease in developed countries.
● May be constructed from porcine valve tissue, bovine ● After performing coronary angiography, it is possible to insert and
pericardium, or preserved cadaveric homograft tissue. expand a balloon in narrowed areas and leave a metallic stent in
● Pathologic changes: place to maintain an adequate luminal diameter
○ Thrombosis, infection, cusp tears and perforations, fibrous ● May be “bare” metal alloy or may be coated with anti-
sheathing, calcification, and several others. inflammatory drug-eluting polymers to calm the foreign body
reaction and prevent early stent thrombosis
Mechanical Valves ○ Endovascular extraction techniques: used to remove
● Thrombosis thrombus, and other obstructive material
● Infection ○ Intravascular ultrasound and optical coherence
● Various alterations associated with the valve design and the tomography: used to characterize plaque morphology and
composition of the various elements composition
● Regurgitation
○ Leaflet abnormalities or partial dehiscence of the sewing ring
with a paravalvular leak

Dr. Michelle Cauan
G. CARDIAC TUMORS ● Hallmark finding is the presence of myxoma cells in a ring that
Myxomas encircles small- and medium-size tumor vessels
● Together with papillary fibroelastomas, are the most common ● Other microscopic variations: surface thrombosis, Gamna–
primary tumors of the heart Gandy bodies, ossification (“petrified” myxoma), chondroid tissue,
● Grossly: soft, polypoid, pale, lobulated masses, often attached by extramedullary hematopoiesis, and presence of thymic and
a stalk to the septum near the foramen ovale foregut remnants
● Areas of hemorrhage may be present ● The most peculiar change that cardiac myxoma can exhibit is the
● Calcification may occur, more common in those located in presence of well-developed mucin-producing glands
the right atrium ● Glandular myxoma, can be confused with metastatic
● Extremely calcified myxomas have been referred to “petrified” adenocarcinoma, particularly when showing atypical
myxoma cytoarchitectural features
● Occur in two settings: sporadic and familial ● Myxoma cells express endothelial markers (CD31, CD34, factor
VIII), as well as calretinin, vimentin, actin, desmin, and smooth
Table 1. 2 SETTINGS OF MYXOMA muscle myosin.
● The mucinous extracellular material stains for membrane-
SPORADIC MYXOMAS FAMILIAL associated MUC1 and less so for secreted mucins MUC2 and
MYXOMAS MUC5AC.
Occur more often in women Slightly more common in men
Most often in middle adulthood Manifest at a younger age
Arise most often in the left Sites outside the left atrium,
atrium and attach to the atrial Multicentric tumors
septum
Figure 12: Gross appearance of Cardiac

Myxoma. The lesion has a polypoid shape and a
hemorrhagic appearance. A portion of atrial
septal wall is attached at the “stalk” base.
Figure 14: “Glandular Myxoma.” The glandular epithelium is tall columnar and
contains intracytoplasmic mucin. This rare type of myxoma should not be
Carney Complex confused with metastatic adenocarcinoma.
● Patients manifest with cardiac myxomas, cutaneous and labial
lentiginosis, eyelid and cutaneous myxomas, myxoid mammary Papillary Fibroelastoma
fibroadenomas (often multiple and bilateral), adrenocortical ● A.k.a fibroelastic hamartoma, fibroma, papilloma, papillary
nodular dysplasia associated with Cushing syndrome, and large fibroblastoma
cell calcifying Sertoli cell tumor of the testis ● It is nearly as common as myxoma, and they appear as small
● Patients harbor inactivating mutation of the protein kinase A papillary (“sea anemone–like”) growths that usually occur on the
regulatory subunit gene PRKAR1A, which encodes a protein surface of the valves but may also be seen in other endocardial
that plays an important role in cardiac development and locations.
myxomagenesis ● It is often an incidental finding at surgery or autopsy.
● Microscopically, the papillary architecture is obvious, with
Left-sided cardiac myxoma individual fronds consisting of a core of hyalinized hypocellular
● Presents with signs of mitral stenosis or insufficiency, and right- stroma that is rich in elastic fibers and a lining of hyperplastic
sided tumors with dyspnea, syncope, distension of neck veins, endocardial cells.
and other symptoms
● May also lead to multiple emboli in the systemic or pulmonary
circulation, depending on their location
● Two-dimensional echocardiography, ct, mri, gated
radionuclide blood-pool scan, or cardiac catheterization
○ Used to visualize myxomas, but cannot differentiate
between other pedunculated tumors or thrombi
● Microscopically: round, polygonal, or stellate cells are seen
surrounded by abundant loose stroma rich in acid
mucopolysaccharides
Figure 15: Gross features of papillary fibroelastoma (note how delicate fronds
become apparent when floating in clear liquid).
Figure 13: Cardiac myxoma showing a concentric arrangement of tumor cells

around vascular spaces; highly characteristic of myxoma.

Dr. Michelle Cauan
5. MESOTHELIAL/MONOCYTIC INCIDENTAL CARDIAC
EXCRESCENCES (CARDIAC MICE)
- Incidental microscopic findings at the time of cardiac
surgery (usually for valvular disease) or in an
endomyocardial biopsy
- May be found attached to the endocardium, free-floating in
the pericardial cavity, or even inside an aortic dissecting
aneurysm
- Lesion is composed of an admixture of keratin-positive
mesothelial cells and cd68-positive histiocytes
- Mice are thought to be an artifact produced by traumatic or
iatrogenic violation of the pericardial cavity with
resultant agglutination of mesothelial cells and the other
constituents in a fashion similar to the “cell block” techniques
Figure 16: Microscopic features of papillary fibroelastoma with highly branched used in cytopathology.
papillary architecture and dense elastin-rich cores lined by flattened - Their main practical importance resides in the fact that a
endothelium.
pathologist unaware of their existence may mistake them for
a metastatic carcinoma or some other neoplasm
OTHER BENIGN TUMORS AND
TUMOR-LIKE CONDITIONS
1. RHABDOMYOMA AND RHABDOMYOMATOSIS
- Mostly seen during the first decade of life, and clinically
documented examples of tumor regression by adolescence
have been reported
- They can also present in adult patients
- Most of the patients have tuberous sclerosis
- Grossly: rhabdomyomas present as one or more firm, white-
yellow, well-circumscribed nodules
- Microscopically: the most distinctive feature is the presence
of “spider cells,” so named because of their radial
sarcoplasmic extensions. Immunohistochemically, they show
reactivity for myoglobin, actin, desmin, vimentin, and
sometimes HMB-45
Figure 18: So-called Cardiac MICE. A. The process is composed of an

admixture of plump histiocytes and ribbons of small cuboidal mesothelial cells.
B. The immunostain for keratin highlights the mesothelial cell component, which
is surrounded by the negative histiocytes and other mononuclear cells.
Figure 17: Spider cells are large, rounded polygonal cells with strands of
cytoplasm interspersed among glycogen-rich vacuoles.
2. FIBROMA
- Seen mostly in the pediatric population; although some are
not detected until adulthood, it is believed fibromas are
present from birth
- Rarely multiple and rarely associated with a syndrome
(namely basal cell nevus [or gorlin], beckwith–wiedemann, or
sotos syndromes)
- Most common in the left ventricle and ventricular septum
and are usually large and intramural Figure 19: Microscopically, mesothelial cells form strips, tubules, and
- Tumor borders are microscopically infiltrative, similar to what micropapillary formations surrounded by the smaller histiocytes. Huge round
is seen in fibromatosis lesions vacuoles are often present and appearance is very similar to that of nodular
mesothelial hyperplasia seen in some hernia sacs.
3. HAMARTOMA OF MATURE CARDIAC MYOCYTES
6. CYSTIC TUMOR OF THE ATRIOVENTRICULAR NODAL REGION
- Resembles hypertrophic cardiomyopathy microscopically but
- Was regarded as a mesothelioma for many years, but there
is confined as a localized process affecting only a discrete
is now conclusive evidence that it represents a
area of myocardium (often in a mass-like fashion)
developmental abnormality of epithelial nature and
- Characterized by myofiber disarray, focal scarring, and
endodermal origin
arterial thickening but no inflammation or calcification
- Been postulated that this condition represents a heterotopia
- Left ventricle is the usual but not exclusive location of this
of the ultimobranchial body analogous to solid cell rests of
lesion
the thyroid gland
- May result in complete heart block or be found at autopsy
4. CALCIFIED AMORPHOUS TUMOR OF THE HEART (CARDIAC
in cases of sudden death.
CAT)
- Microscopically: lesion consists of ductular structures,
- An endocardially based intracavitary cardiac mass
cysts, and solid nests of epithelial-like cells
characterized microscopically by nodular deposition of
- Immunohistochemically: cells are reactive for keratin, cea,
calciumin a background of degenerating blood cell elements
and b72.3 but not for factor viii, calretinin, wt1, or
and chronic inflammation.
thrombomodulin.
- Benign clinical course

Dr. Michelle Cauan
a. “Intimal sarcoma”
 Malignant tumors expressing an endothelial phenotype
that arise in great vessels (particularly the pulmonary
artery but also the aorta and its branches)
 The malignant cells in these tumors often grow along the
surface of mural fibrin thrombus rather than invading
through the vessel wall (hence the designation as
“intimal”)
b. Kaposi sarcoma in its systemic form is another vascular
malignancy that can involve the heart in immunocompromised
(especially AIDS) patients
c. Myosarcoma
 Second most common category of sarcoma, either
leiomyosarcoma or rhabdomyosarcoma
d. Leiomyosarcomas
 Spindle cell, epithelioid, or myxoid features
 Scattered osteoclast-like multinucleated giant cells
e. Other types:
 Myxofibrosarcoma, pleomorphic undifferentiated
Figure 20: So-called cystic tumor of the atrioventricular nodal region. In this
sarcomas, osteosarcoma, fibrosarcoma, liposarcoma,
case, the lining of the cysts had a definite squamoid quality.
synovial sarcoma, Ewing sarcoma/primitive
neuroectodermal tumor (PNET), and malignant
7. ADENOMATOID TUMOR OF THE HEART
peripheral nerve sheath tumor
- Analogous to its more common counterpart in the male and
- Most patients with primary heart sarcomas present with:
female genital system
 Intractable congestive heart failure
- Lesion is of mesothelial nature
 Arrhythmias, or
8. INFLAMMATORY MYOFIBROBLASTIC TUMOR  Signs of superior vena cava obstruction
- Metastatic lesions, especially in the lungs may be the first
- Endocardial-based process
- Positive staining for alk and alk gene rearrangements are a manifestation of cardiac sarcomas
- Right side of the heart – where malignant tumors
fairly constant finding
- No metastases have been reported, but the lesion can (especially angiosarcoma) are more frequently found
- Left side of the heart - where benign neoplasms are more
result in myocardial infarct, syncope, and sudden death
commonly found
9. PARAGANGLIOMA
- Can present as a primary intracardiac neoplasm
- Composed of fibrous tissue, which are separated by
numerous slit-like and pseudotubular spaces.
- Left atrium is the most common location
- Hypertension and elevated urine catecholamine levels
are often present, in which case the term extra-adrenal
pheochromocytoma has been used
- The microscopic, ultrastructural, and immunohistochemical
features are similar to those of paraganglioma elsewhere
OTHER PRIMARY TUMORS OF THE HEART

● Granular cell tumor (not to be mistaken for rhabdomyoma or
histiocytoid cardiomyopathy)
● Hemangioma (including the epithelioid and histiocytoid varieties)
● Lymphangioma
● lipoma (to be distinguished from lipomatous hypertrophy of the
atrial septum)
● Angiolipoma
● Schwannoma
● Ganglioneuroma
● Benign teratoma Figure 22: Primary synovial sarcoma of heart showing typical biphasic
appearance.
OTHER NON-NEOPLASTIC CONDITIONS REPORTED IN THE
HEART 2. LYMPHOMA
● Ectopic thyroid - Presenting as a primary heart tumor is very rare
● extramedullary hematopoiesis - Most of the reported cases have been of diffuse large b-cell
● Rosai–Dorfman disease type, some of which are ebv positive
- In association with cardiac prostheses and mural fibrin
PRIMARY MALIGNANT TUMORS thrombus
1. SARCOMAS OF THE HEART
- Are exceptionally rare but are the most frequent type of 3. METASTATIC TUMORS
primary cardiac malignancy. - Any portion of the heart can be involved by metastatic
- Of those that can be placed into a lineage specific category, disease, including the conducting system, the latter resulting
angiosarcoma is the most common. in heart block
They are typically located in the right - Primary tumor is in the thoracic cavity or contiguous
atrium, where they present as a large areas, and the tumor reaches the heart by metastasizing to
mass. the mediastinal lymph nodes and from there extending in a
retrograde fashion to the cardiac lymph vessels
Figure 21: Gross appearance of a large angiosarcoma - Malignant tumors with a propensity for hematogenous
of the heart (right atrium). spread to the heart are malignant melanoma, renal cell
carcinoma, choriocarcinomas, and rhabdomyosarcoma.

Dr. Michelle Cauan
Metastatic Carcinoma to the Pericardium
● Usually originates in the lung in the form of direct extension or
lymphatic permeation
● May result in constrictive “pericarditis” as a result of the
associated intense desmoplastic reaction or be associated with
recurrent pleural effusion
● Other tumors that commonly give rise to pericardial metastases
are breast carcinoma, malignant melanoma, and malignant
lymphoma (including hhv8-positive primary effusion lymphoma)
● Cytology is the most important technique for the evaluation of
malignant pericardial effusions
● Pericardial biopsy may be necessary in some cases to confirm
the diagnosis
II. ARTERIES
● Blood vessels that transport blood away from the heart.
● Transport/Carry - Oxygenated blood except for the pulmonary
artery
● Oxygen level - quite high; The CO2 level - low
● Volume of blood is Low (About 15%).
● Walls – much stronger and rigid than veins;
● To withstand the pulsatile flow and higher blood pressures in
arteries, arterial walls are generally thicker than the walls of veins.
Arterial wall thickness gradually diminishes as the vessels
Figure 23: Large metastatic carcinoma in left atrium that was continuous with become smaller, but the ratio of wall thickness to lumen diameter
tumor in left pulmonary vein. This mass simulated an atrial myxoma by
becomes greater.
echocardiography. The primary tumor was a mucoepidermoid carcinoma ofleft
submaxillary gland.
● Muscularity/ Flexibility – more muscular than veins and highly
flexible
H. PERICARDIUM ● Lumen – Much narrower
Pericarditis ● Blood pressure – higher; The pressure in the arteries is highest
● A diagnosis of tuberculous pericarditis or sarcoidosis can be when the heart contracts and lowest when relaxed.
made from open pericardial biopsy (or “window” procedure) ● Movement of blood is spurty: No valves (except for semi-lunar)
significantly impacting clinical treatment and prognosis. ● Collapsing of vessel – would generally remain open if blood flow
stopped, due to their thick muscular layer.
Acute Nonspecific Fibrinous, Hemorrhagic, or Purulent ● Injury to the blood vessel – Squirting of blood
Pericarditis ● Contraction of muscle is present; At the time of death, arteries
● Rarely biopsied but may be troublesome because of the reactive empty up.
mesothelial hyperplasia and atypia that may mimic mesothelioma
or other malignancy A. NORMAL ANATOMY
● Central part is the lumen where the blood flows through
Chronic Pericarditis ● 3 Layers
● Often accompanied by fibrosis and calcification and may lead ○ Tunica adventitia
to physiologic constriction (so-called constrictive pericarditis) ▪ Consists of connective tissue or collagen fibers
● May result from tuberculosis and other infections, collagen– ▪ Less developed than the vein;
vascular diseases, malignant tumors, trauma, surgery, radiation ○ Tunica media
therapy, or chemotherapy ▪ Thickest layer; composed of concentrically arranged
● Pathologic examination usually shows only dense fibrosis and a smooth muscle fibers with scanty
scanty inflammatory infiltrate, regardless of etiology ▪ It is separated from the media by a dense elastic
● Residual granulomas - tuberculous etiology membrane called the internal elastic lamina.
● Bizarre atypical fibroblasts – post irradiation setting ▪ The smooth muscle cell layers of the media near the
● Calcification (delicate “egg shell”–like fashion or as hard plate- vessel lumen receive oxygen and nutrients by direct
like deposits) diffusion from the vessel lumen, facilitated by holes in
● Some patients with bona fide constrictive pericarditis the internal elastic membrane
(confirmed intraoperatively) may not have pericardial ▪ The outer limit of the media of most arteries is a well-
thickening, and histologically the pericardium may appear defined external elastic lamina
entirely normal. ○ Tunica intima
▪ Consists of a single layer of endothelial cells with
Multilocular Mesothelial Inclusion Cyst of the Pericardium minimal underlying subendothelial connective tissue
● Morphologically and probably pathogenetically equivalent to the ▪ Endothelial cells are flattened and more elongated.
condition that bears the same name in the peritoneal cavity ● Divided into 3 Types:
● Originally designated as benign multi cystic mesothelioma but it (1) Elastic arteries (large)
probably represents a reactive change secondary to chronic  Stacked layers of elastic tissue throughout the media
irritation layer
 Aorta, and its large branches (particularly the
Mesothelioma of the Pericardium innominate, subclavian, common carotid, and iliac) and
● Reported in the setting of tuberous sclerosis and may present the pulmonary artery
as a single well-circumscribed mass, as multiple tumors, or as (2) Muscular arteries (medium)
a diffuse growth encasing the heart  Presence of two distinct elastic layers, an internal layer
● They are essentially identical to mesothelioma of the pleura and separating intima from media, an external layer
are staged accordingly separating media from adventitia
 Other branches of the aorta (e.g. Coronary and renal
Angiosarcoma of the Pericardium arteries)
● May coat the pericardium in a diffuse fashion, thus simulating the (3) Arterioles (20-100um in diameter) and small arteries
pattern of growth of mesothelioma; some of these have been (< approx. 2mm in dm)
radiation induced.  Composed of only smooth muscle; no discernible
elastic layer; within the substance of tissues and
organs

Dr. Michelle Cauan
B. ARTERIOSCLEROSIS AND ATHEROSCLEROSIS Outward Arterial “remodeling”
● Arteriosclerosis ● Important feature in order to maintain lumen diameter in the face
○ Generalized progressive arterial disease associated with wall of encroaching intimal atheromatous plaque. In the extreme, may
stiffening, localized luminal narrowing (of muscular arteries), lead to formation of a true atherosclerotic aneurysm.
and aneurysms. ● Histologic evidence: thinning (atrophy) of the media underlying
○ Chronic; characterized by abn thickening and hardening of the plaque in comparison to the relatively thicker
the arterial walls with resulting loss of elasticity (hypertrophied) spared wall opposite a plaque.
● Atherosclerosis can begin in childhood but is typically
● Atherosclerosis asymptomatic for decades until it finally manifests itself. One of its
○ A form of arteriosclerosis characterized by lipid-rich mechanisms is Plaque rupture or superficial erosion followed by
“atheroma” in the arterial wall superimposed thrombus causing sudden luminal occlusion.
o An intimal inflammatory process mediated by activated
endothelium and smooth muscle cells of the arterial wall Abrupt Thrombosis
o Slowly progressive; large to medium sized muscular and ● In recent years, the cause of lethal and morbid events relating to
large elastic arteries; atherosclerosis are due to this rather than progressive luminal
o Principal sites – aa, coronary arteries, popliteal, occlusion by plaque.
descending thoracic aorta, internal carotid arteries and ● Results from exposing pro-thrombogenic plaque material to
circle of willis (in descending frequency) luminal blood through disruptions in the intima overlying the
o The principal cause of heart attack and stroke and remains plaque.
the leading cause of death in developed countries. ● Ruptured plaques  indicate inability to withstand the
o In the pathogenesis of atherosclerosis, macrophages that mechanical stresses of vascular shear forces
are transformed from the monocytes that migrated into the ● Plaques showing conditions optimal for this type of event, but
intimal layer, macrophages elaborate growth factor and without actual disruption as-of-yet = “unstable” or “vulnerable.
cytokines that affect cell signaling pathways and lipid These contain large areas of foam cells EC fluid, those with thin
processing. fibrous caps, few SMC and have cluster inflammatory cells and
are more likely to rupture.
● Other factors shown to be important in its pathogenesis include: ● Descriptions in surgical pathology reports should include the
○ Changes in lipid metabolism (especially oxidation of following:
lipoproteins), ○ Relative composition of the plaque: lipid rich
○ Increased endothelial permeability to serum lipoprotein (“soft”), fibrotic (“hard”), calcified, hemorrhagic,
complexes, etc.
○ Endothelial activation/injury due to flow turbulence at major ○ Nature of the intima overlying the plaque (the
bifurcations, “fibrous cap”) in terms of its overall thickness
○ Activation of the clotting cascade resulting in thrombosis. ○ Presence of inflammation or erosion/ulceration
● Atherosclerosis: lipid material infiltrates the tunica intima and Plaque Instability
accumulates in macrophages  stimulates the proliferation of ● Abundant lipid-rich atheromatous material, hemorrhage, and a
intimal fibroblasts and myointimal cells, with collagen deposition thin, inflamed overlying fibrous cap. Apparently, the presence of
to produce a plaque which thickens the intima. thrombus, recent or otherwise, also pertains.
● If severe, the intimal thickening can severely reduce the artery
lumen and limit the blood flow. The plaques commonly rupture
further occluding the vessel lumen. The intimal surface is also
roughened predisposing to aggregation of platelets and fibrin to
form a thrombus which may increase the size of the plaque and
further compromise the vessel lumen. A further consequence of
severe atheroma in elastic arteries is that the muscle cells in the
tunica media are replaced by non-contractile and non-elastic
collagen leading to a weakness in the artery wall which may bulge
and rupture (aneurysm).
Figure 25: Ruptured Atherosclerotic Plaque and Luminal Thrombosis

(Atherothrombosis). An arrow points to the site of probably plaque rupture (note
the inflammatory infiltrate in the plaque and adventitia).
● Arteriosclerosis and atherosclerosis are encountered in surgical

pathology as part of the evaluation of specimens obtained from
endarterectomy (carotid or coronary), heart transplantation,
and amputation of ischemic limbs.
○ To note, ascending aortic aneurysms, though common
surgical specimens, rarely show atherosclerosis.
Figure 24: Arterial Wall Remodelling in Atherosclerosis. The wall segment ● During the placement of synthetic tube grafts (whether during an
underlying the atherosclerotic plaque shows marked thinning (bottom arrow) open vascular procedure or endovascular stenting) in the
compared to the normal wall segment opposite the plaque (top arrow). descending thoracic or abdominal aorta, it is common for the
diseased arterial tissue to be left in situ rather than removed for
examination.

Dr. Michelle Cauan
● *With careful handling, it is possible to preserve cross sections o Essentially, the task with this method is to section the stent-
through endarterectomy plaques in a manner that makes plaque tissue interface with the least amount of disruption of tissue
composition and the degree of narrowing evident, even though and cellular morphology.
only the intima is present. o The stent struts remain in the specimen and appear as black
● In some patients, thrombus may be aspirated endovascularly geometric profiles embedded in the tissue.
during percutaneous intervention.
● Histologic characterization of these clots (recent, degenerating,
organized, etc.) is also clinically relevant although precise dating
based on these features is not currently feasible.
Atheroma
● Atheroma  fatty degeneration of the inner coat of the artery;
abnormal fatty deposit in an artery
● Histologically: plaques are composed of superficial fibrous
caps containing SMC, leukocytes and dense connective
tissue ECM overlying necrotic cores, containing dead cells,
lipid, cholesterol clefts, lipid-laden foam cells (macrophages
and SMC) and plasma proteins; small blood vessels
proliferate at the intimal-medial interface.
● 2 variants:
○ FATTY STREAKS – early lesions
○ COMPLICATED PLAQUES – Calcified, hemorrhagic,
fissured or ulcerated atheromas predisposing to local
thrombosis, medial thinning, cholesterol microemboli
and aneurysmal dilation.
C. STENTS AND BYPASS GRAFTS Figure 26: Cross section of stented artery, using plastic resin embedding
Arterial Stents techniques, metallic stent sections appear opaque (black). The native plaque as
● Angioplasty with stenting well as neo-intimal plaque formation are apparent.
○ Mainstay and first line option for treating Coronary Artery
Disease and its complications. ● Strong Acids or Reverse Electroplating
● Various metal alloys (e.g. cobalt chromium, nickel titanium, ○ More recent method dissolve the metallic stent struts
stainless steel) are used in the stents. ● Post Method Application:
● 2 Categories: ○ Metal-free tissue can be sectioned and submitted for
○ Bare-metal stents paraffin embedding like any other specimen.
• Have no special coating ● Histologic sections:
• Act as scaffolding to prop open blood vessels after ○ Outline of tissue-strut interface, but the opaque
widened with angioplasty. metallic strut profiles are absent.
• As the artery heals, tissue grows around the stent, ○ NOT ALL stents are amendable to dissolution and strut
holding it in place. However, sometimes an overgrowth fractures leave portions undissolved.
of scar tissue in the lining of the artery increases the
risk of reblockage.
o Drug-eluting stents
• Coated with medication (anti-proliferative agents –
Everolimus and Paclitaxel) that is slowly released
(eluted) to help prevent the growth of scar tissue in the
artery lining
• Retard in-stent smooth muscle and fibroblast
proliferation.
● Formation of thrombus within and/or adjacent to the stent
○ Major complication following stent placement.
○ For prevention: aggressive anti-platelet and anticoagulation
therapy for months after stent placement (e.g. Aspirin,
unfractionated heparin)
● Stent Thrombosis and Neointimal Narrowing
○ Primary clinical question to be addressed when stented
specimens are removed and submitted for surgical pathology
examination (whether as part of explanted hearts and other
organs during transplant surgery or as arterial specimens)
● Metallic stent struts become embedded and incorporated into
the vessel wall tissue Figure 27: Cross Section of Stented Artery, Using Stent Dissolution
Techniques. Holes can be seen where the stent struts were situated prior to
○ Poses a major challenge for tissue processing and
dissolving (right). Specimen radiography can be helpful in identifying the location
microtomy in the histology laboratory. of stents, prior to dissolving (left).
○ The mechanism involved is the Activation, proliferation
and migration of vascular smooth muscle cells that lead Arterial Bypass Grafts
to neointimal hyperplasia and then restenosis. ● Coronary bypass grafts = most common type to be encountered
○ Identifying the location of the stent, especially months or in surgical pathology
years after placement, may be a challenge and specimen ● Bypass graft conduits from other anatomic sites = may be
radiography is invaluable in this endeavor. received as well
● Methods for obtaining cross sections through the stented portion ● Cross sections from the anastomotic site, graft body, and distal
include: vessel should be reviewed.
○ Resin embedding followed by sectioning using tungsten ● Atherosclerosis may develop in the graft body, even in grafts of
carbide blade microtomy venous origin since the graft conduits experience flow at arterial
o Sanding/grinding to a specified thickness (~40 µm) before pressures.
routine staining. ● Pseudoaneurysm formation at the anastomotic site as frequent
complication.

Dr. Michelle Cauan
D. Aneurysms False aneurysms (“pseudo” aneurysms or pulsating hematoma)
● Focal abnormal vascular dilations being at least 1.5 times larger ● Are merely contained ruptures resulting from some kind of
than its expected normal diameter penetrating wall injury and tend to occur at sites of traumatic
● Develop as a dynamic consequence of arterial wall weakening in injury, vasculitis, or prior surgical vascular anastomoses.
the face of intraluminal arterial pressure. ● An extravascular hematoma that communicates with the
intravascular space; part of the vessel wall is missing.
Morbidity and death due to these are secondary to:
1. Rupture
2. Impingement of adjacent structures
3. Occlusion of proximal vessels by extrinsic pressure or
superimposed thrombosis
4. Embolism from a mural thrombosis
Arterial Dissection
● Splitting apart of medial smooth muscle cause by an infiltration of
luminal blood under arterial pressure.
● Often results in narrowing or occlusion of the true lumen and
blockages in small arterial branches arising from the dissected
artery
Figure 30: Arterial aneurysm types and their

morphologic and clinical associations.
Aortic Aneurysms (AA)

● Aorta
○ Most common site of arterial aneurysm.
Figure 28: Routine Histologic Sampling of Bypass Grafts. The anastomotic ● Size (diameter) and rate of change in size
site should be serially sectioned to locate the joining point of native vessel and ○ Reliable predictors of aortic aneurysm rupture risk.
graft (arrow). Step sections through the block may be helpful in visualizing this ○ Site-specific guidelines exist for different anatomic
histologically. locations.
● The 2 most important disorders that predispose to AA
● The wall changes leading to aneurysms may be: ○ Atherosclerosis is a greater factor in AAA.
○ Atherosclerotic as with abdominal aortic aneurysm (AAA) ○ HPN is the most common condition associated with
o Developmental (cerebral Berry aneurysm) Ascending AA.
o Degenerative (ascending aortic aneurysm)
o Traumatic/vasculitic (pseudoaneurysms), Laminated Mural Thrombus
o Infectious (mycotic aneurysm) in nature ● Endovascular stent placement has largely replaced open surgical
procedures for abdominal aortic aneurysms in most centers, so
Arterial Aneurysms Types and their Morphologic and Clinical surgical specimens from the abdominal aorta have become
Associations scarce.
● True aneurysms contain all three arterial layers (intima, media, ● Frequently present in saccular abdominal aneurysms and
and adventitia), although the usual dual elastic layers may not be presents a potential source of emboli downstream.
distinguishable due to wall remodeling changes. ● Luminal stenosis and occlusive
● Degenerative aneurysms tend to be “fusiform” with gradual, atherothrombosis are rare in the aorta.
symmetric tapering contours, whereas nearly all other ● Histology of the atheromatous plaques is
aneurysm types are asymmetric, abrupt, and “saccular.” similar for atherosclerotic aneurysms in
comparison to those of smaller muscular
arteries (with the addition of ulceration,
inflammation, and laminated thrombus).
Figure 31: Abdominal aortic aneurysm with

mural thrombus(note the presence of
atherosclerotic changes and the asymmetric
(saccular) configuration of the aneurysm.
Degenerative aneurysms in the ascending aorta

● Often show disruptions of the normal elastic laminar architecture.
● Degenerative processes in ascending aorta  cystic medial
degeneration  affect the medial layer by varying degrees of
elastic fibre fragmentation and smooth muscle loss.
● Although fragmentation of elastic fibre is a normal process of
aging, it may occasionally accelerate and cause partial or
Figure 29: Arterial aneurysm types and their morphologic and clinical complete loss of elastic fibres and smooth muscle cells in the
associations. medial layer of the aorta.
● The aortic wall then loses its strength and elasticity, becoming
aneurysmal: it may then dissect or rupture.

Dr. Michelle Cauan
● For the purpose of routine surgical pathology reporting, it is ● Typically, the intimal surface shows severe complicated
probably sufficient to state: atherosclerosis with destruction and thinning of the
○ When degenerative changes are present in the media, underlying aortic media. The aneurysm frequently contains a
○ Realizing that correlation between histology and bland laminated poorly organized mural thrombus that may fill
aneurysm etiology or size is poor (e.g. grossly impressive some or all of the dilated segment.
aneurysms may show normal media histologically). ● In Mycotic, lesions are infected with lodged circulating
● Thorough sampling is encouraged (at least 6 pieces submitted). microorganisms in the wall
Immunostaining for various proteins in the TGF-β signaling ● Inflam AAAs, there is characterization of dense periaortic fibrosis
pathway, implicated in these diseases, may be useful in routine containing abundant lymphoplasmacytic inflamm with many macs
diagnosis but awaits further development. and often giant cells.
Aortitis Inflammatory Aneurysms

● Inflammation of the wall of the aorta with or without disruption of ● Recognized as part of the continuum with IgG4-related disease
elastic fibers, aortic wall necrosis, or fibrosis. and sclerosing mesenteritis
● Its primary manifestation is aortic aneurysm. ● Show mixed inflammatory infiltrate containing eosinophils, lymph
● Identified in approximately 12% of all thoracoabdominal follicles, storiform fibrosis, perineurial inflammation, obliterative
aneurysms. phlebitis, and numerous IgG4-positive plasma cells.
● The most common subtype of inflammatory aortitis: ● Fistulas may develop as a complication of abdominal aortic
○ Giant Cell Aortitis followed by Lymphoplasmacytic aneurysms in particular, usually with catastrophic results
Aortitis ● In contrast to atherosclerotic AA, the inflammatory variant is
● The gross features of noninfectious aortitis are similar across all characterised pathologically by:
of the histologic subtypes. 1) marked thickening of the aneurysm wall
● Aortitis can affect any site in the aorta, but has a predilection for 2) fibrosis of the adjacent retroperitoneum
the ascending aorta, which usually manifests the disease by 3) adherence of the adjacent structures
increased diameter, dissection, and/or rupture.
● Clinically: giant cell and lymphoplasmacytic aortitis may be a E. ARTERIAL DISSECTION
large vessel manifestation of systemic vasculitis (namely Giant ● Refers to a splitting apart of medial smooth muscle caused by an
Cell Or Temporal Arteritis, especially in the elderly) but organ- infiltration of luminal blood under arterial pressure
limited or isolated forms of aortitis are also recognized for which ● Results in narrowing or occlusion of the “true” lumen and
surgical resection may be curative. blockages in small arterial branches arising from the dissected
● Thorough rheumatologic assessment of the patient and possibly artery
wider vascular imaging studies are often needed to guide
management in these cases.
Figure 32: Aortic

Dissection,
Cross Section.
Thrombus fills the
intra-medial
“false” lumen,
compressing the
true lumen
beneath.
Cross Sectional view (H & E with Elastin staining), of a temporal artery in a

patient with Giant Cell Arteritis demonstrating a lymphocytic infiltrate (yellow
arrow), multinucleate gaint cell (red arrow), fragmentation of the internal elastic
● Dissection begin as a transverse intimal tear that may be
lamina(F), intimal hyperplasia(H) & luminal occlusion (blue arrow). associated with intimal plaque located either in the ascending
aorta or in the upper descending thoracic aorta near the origin of
Giant Cell and Lymphoplasmacytic Aortitis the left subclavian artery
● Share overlapping features; presence of giant cells in the former, ○ Regardless of the underlying etiology, the ultimate trigger for
typically arrayed in collars and cuffs surrounding islands of the intimal tear and initial intramural aortic hemorrhage is not
collapsed elastic laminae devoid of smooth muscle nuclei. known in most cases
● The presence of penetrating vasa vasorum in the mid to inner ● After the development of the tear, the intramural layers of the
portion of the elastic media and increased medial collagen are aorta are rapidly separated by the force of the blood entering the
also seen wall
Aortitis of the Abdominal Aorta Clinical factors associated with dissection

● Distinctly different and represents either infection (often by ● Hypertension
Salmonella and other enteric organisms) or so-called o Hypertension is the major risk factor for aortic dissection.
inflammatory Abdominal Aortic Aneurysms. Aortas of hypertensive patients have medial degenerative
● Infections may be primary in nature or secondary to seeding of changes with SMC loss and altered ECM content
thrombus within an existing atherosclerotic aneurysm. ● Connective tissue disorders
● Aneurysms associated with atherosclerosis occur most commonly o Associated with defective TGF-β signaling or defective ECM
in the abdominal aorta. synthesis or degradation (e.g. Marfan syndrome)
● The pathogenesis of the AAA shows several hallmarks of ● Pregnancy
atherosclerotic and atherothrombotic disease, but comprises an o Rarely associated with aortic dissection
additional, predominant feature of proteolysis resulting in the o Roughly 10 to 20 cases per 1 million births
degradation and destabilization of the aortic wall involving o Occurring during or after the third trimester
the accumulation of neutrophils in the intraluminal thrombus o Related to hormonally induced vascular remodeling and the
● Morphology of AAA is usually positioned below the renal hemodynamic stresses of the perinatal period
arteries and above the bifurcation of the aorta. ● Bicuspid aortic valve
● Can be saccular or fusiform up to 15cm in dm and up to 25cm in ● Traumatic (iatrogenic)
length.

Dr. Michelle Cauan
● Atherosclerosis G. SYNTHETIC ARTERIAL SUBSTITUTION
o Dissection is unusual in the presence of substantial ● GoreTex and Dacron synthetic tube grafts, as well as synthetic
atherosclerosis because the medial fibrosis inhibits fabric lined stents, are often used in vascular surgery
propagation of the dissecting hematoma ● Require revision and replacement
● Inflammatory injuries of the aortic media ● Over time these grafts reendothelialize and develop a neo-
intimal coating
Classification systems ○ There is an excessive accumulation of fibroblast and SMC
● Stanford accumulation in the intima with extracellular matrix (ECM)
o Most widely used deposition.
o Type A: focuses on involvement of the ascending aorta ○ Excessive cellular deposition results in the expansion of the
regardless of what other segments may be involved intimal layer which is associated with loss of luminal area.
o Type B: not involving the ascending portion are often ● Pathologic examination of these specimens should include
managed medically and more expectantly evaluation of calcification, inflammation, thrombus, and the
presence of anastomotic pseudoaneurysms.
● DeBakey systems
o Type I: begins in the ascending aorta and extends beyond H. ARTERIAL OCCLUSIVE DISEASE
o Type II is confined to the ascending aorta; ● A condition in which the arteries throughout the body gradually
o Type IIIA: begins in the descending aorta and stops above become narrowed. It can affect arms and legs. Often, patients
the diaphragm who suffer from lower extremity arterial occlusive disease also
o Type IIIB: also begins in the descending aorta but extends have other conditions, such as carotid artery disease and heart
below the diaphragm. disease. The condition is associated with significant morbidity and
mortality.
● Thrombotic occlusions of the major arteries are often associated
with arteriosclerotic changes (wall stiffening, localized luminal
narrowing, and aneurysms)
● The process of occlusion is clinically insidious, although final
thrombotic obliteration of the lumen is occasionally quite rapid and
may be clinically indistinguishable from embolization.
● In the distal aorta, thrombotic occlusion probably begins in the
iliac arteries near the aortic bifurcation and propagates cephalad,
occasionally to the level of the renal arteries.
● Thrombi and emboli can become secondarilyinfected by fungi
(Aspergillus and Mucor).
Risk factors
● Age
● High levels of cholesterol and triglyceride,
● High blood pressure, diabetes,
Figure 33: Classification systems for dissections. ● Smoking
● History of plaque build-up in the arteries
F. COARCTATION OF AORTA
● Coarctation is from the Latin “coartare” meaning “to press Leriche syndrome
together.” ● Also known as Aortoiliac occlusive disease
● Common congenital structural anomaly ● Manifests with gradual progression of symptoms of pain and easy
● Twice as common in males as in females fatigability in the legs, hips, and back; intermittent claudication;
● Females with Turner syndrome are also frequently affected and sexual impotence.
● In this condition, arterial insufficiency in the lower extremities
Classified according to its relation to the usually is manifested clinically by the absence of pulses below the
ductus arteriosus umbilicus.
● Pre-ductal coarctation:
○ “Infantile form” Treatment
o Narrowed segment proximal to the ductus arteriosus ● Include surgical bypass using synthetic conduit, open
o Usually found early in life thromboembolectomy with or without endarterectomy, and
o Often symptomatic in early childhood endovascular interventional thrombolysis.
o Systemic dependence on pulmonary artery flow (via the ● Microscopically, specimens from thromboendarterectomy may be
ductus—duct dependent) fibrinous, organized, or some combination of the two, depending
● Post-ductal coarctation: on the stage of the process and relative success of intrinsic
○ “Adult form” thrombolytic activity
o Most common
o Narrowed segment distal to theductus. I. CYSTIC ADVENTITIAL DISEASE
o As such, flow is only potentially restricted in the abdomen ● Rare vascular condition which most commonly causes localized
o Classically manifests as upper extremity stenosis or occlusions of the popliteal artery
o Hypertension and lower extremity hypotension ● It is characterized by the presence of unilocular or multilocular
o Intercostal rib notching notable on x-rays mucin-containing cysts localized in the adventitial layer of the
o Collateral blood flow through the intercostal affected vessel.
arteries ● Presence of these cysts commonly results in narrowing of the
arterial lumen, leading to intermittent claudication with relatively
Treatment sudden onset and rapid progression.
● Treatment options: balloon angioplasty, stenting, stent grafting, or
hybrid repair
● Surgery is still the gold standard
● Repair of coarctation is performed to restore flow but also prevent
complications: such as
○ Aortic rupture
o Endocarditis
o Hypertension
o Congestive failure

Dr. Michelle Cauan
● Complications:
○ Arterial stenosis, aneurysm, or dissection.
● Clinical presentation includes secondary hypertension from renal
artery stenosis (RAS), neurologic deficits from cerebrovascular
involvement, claudication due to limb involvement, and intestinal
angina from mesenteric artery disease.
● Diagnosis:
○ CT Scan, MRI and Angiography
● On angiography, the vessels are said to have a “string of beads”
appearance), leading to vascular outpouchings (aneurysms) that
can rupture
Figure 36: The characteristic beaded

appearance of FMD is due to areas of
medial thinning alternating with areas
of stenosis.
● Invasive testing: Digital

subtraction angiography
(DSA)
○ Reference standard
○ Catheter-based
procedure
Figure 33: Cystic Adventitial Disease.Multiple irregular cystic space are seen ○ Dye is injected and
surrounding the adventitia of this popliteal artery. Some may appear to contain imaged with serial
mucoid material
radiographs.
○ Used when there is a
● Etiology is unknown high suspicion of FMD
● Diagnosis: and revascularization is
○ Ankle brachial pressures with exercise planned
○ Duplex Ultrasound ● Negative diagnostic markers include the absence of necrosis,
○ Computed tomographic angiography (CTA) calcification, inflammation, and fibrinoid necrosis
○ Magnetic Resonance Angiography (MRA) ● Treatment:
● Treatment: o Balloon dilation with stenting or resection
○ Ultrasound-guided cyst aspiration o Replacement with conduit such as saphenous vein or
○ Cyst resection with arterial preservation synthetic tube graft
○ Excision of involved arterial segment with interpositional
bypass graft
Multifocal FMD
J. FIBROMUSCULAR DYSPLASIA ● Most common type
● A non-arteriosclerotic, noninflammatory vascular disease of ● “String of beads” appearance on angiography
unknown pathogenesis ● Primarily corresponds to medial fibroplasia
● It involves large- and medium-sized muscular arteries, such as ● Due to alternating collagen-containing fibromuscular webs and
the renal, carotid, axillary, and mesenteric arteries. aneurysmal dilation
● Characterized by a disorderly arrangement and proliferation of the ● Internal elastic lamina may be absent in the dilated areas.
cellular and extracellular elements of the wall, particularly the ● May also be due to perimedial fibroplasia
media, with the resulting distortion of the vessel lumen ● Outer zone of the media is replaced with collagen, resulting in
irregular thickening
Figure 34. Fibromuscular dysplasia

of the renal artery, medial type
(elastic tissue stain). The media shows
marked fibrous thickening, and the
lumen is stenotic.
Figure 35. A carotid fibromuscular

dysplasia with typical characteristics Figure 37: Fibromuscular dysplasia of the right renal artery. The classic
of multiple stenoses with intervening “beads on a string” appearance is typical of multifocal fibromuscular dysplasia,
aneurysmal outpouching dilatations. the most common type of FMD.
The disease involves the media,
with the smooth muscle being Focal FMD
replaced by fibrous connective ● Tubular or circumferential stenosis on angiography
tissue. ● Primarily corresponds to intimal fibroplasia (caused by
circumferential collagen deposition in the intima)
● Rare manifestations:
○ Medial hyperplasia (smooth muscle hyperplasia)
○ Periarterial hyperplasia (fibrous adventitia expansion)

Dr. Michelle Cauan
M. ARTERIOVENOUS MALFORMATION (CONGENITAL)
● Are rare malformations of arteriovenous channels that failed to
regress during development
● Found in soft tissue, lung, gastrointestinal organs, kidney, and the
central nervous system
● Fast flow vascular lesions associated with risk of hemorrhage and
development of neurologic symptoms.
● In the newborn period large avms can lead to congestive heart
failure because of shunt effects
● Treatment for AVM is surgery which includes arterial embolization
before complete excision of the nidus/tangle of vessels and
initiated when signs and symptoms of ischemic pain, ulceration,
bleeding, or hemodynamic instability are evident
● Also stereotactic radiosurgery (srs).
Figure 38: Fibromuscular dysplasia of the right renal artery. The smooth,
concentric narrowing (arrow) has the typical appearance of focal FMD. In this Figure 39: Gross AVM of the
case, there is severe narrowing of the artery, and the patient was treated with Brain. Showing wedge shaped
balloon angioplasty. tangled irregularly dilated vessels
with varying wall thickness and
K. MESENTERIC VASCULAR OCCLUSION/ENTEROCOLIC luminal size
LYMPHOCYTIC PHLEBITIS
● Rare cause of GI tract ischemia, involving only the mural and
mesenteric veins, which are surrounded by a lymphocytic and
sometimes granulomatous infiltrate.
● The mesenteric arterial system and the systemic vasculature are
characteristically spared
● The inflammation can lead to thrombotic obstruction and
fibrointimal proliferation with subsequent venous occlusion, Figure 40:
causing edema and ischemia of the involved intestinal segment. Microscopic: Soft
● Commonly affected sites are in the large bowel, predominantly tissue AVM
showing irregular
right colon
vascular spaces
● Clinically, the presenting feature of ELP is subacute to acute with varying wall
intestinal ischemia manifested as abdominal pain, hematochezia, thickness
and bloody diarrhea.
● Computed tomography scanning often showed thickened and
edematous bowel walls.
● Infarction of the bowel depends on the location, extent of
occlusion, rapidity of its onset, and state of the collateral
circulation, as well as the general physical condition of the patient.
L. ARTERIOVENOUS FISTULA
● An abnormal connection between an artery and a vein.
● This leads to shunting of blood between the two vessels, causing
a pulsatile flow of blood within the vein. N. THROMBOANGIITIS OBLITERANS (BUERGER DISEASE)
● Congenital arteriovenous fistulas are uncommon. It occurs in ● Progressive nonatherosclerotic segmental inflammatory disease
isolation or as a part of a complex arteriovenous (AV) that most often affects medium-sized arteries, and veins
malformation. ● Unknown etiology
● Acquired arteriovenous fistulas can be caused by any injury that ● Common in men, between 20 and 35 years
damages an artery and a vein that lie side by side. ● Initially: foot, leg, arm, or hand claudication, can be mistaken for
○ Typically, the injury is a piercing wound, as from a knife or joint or neuromuscular problems
bullet. ● Angiographic findings:
○ The fistula may appear immediately or may develop after a ○ Disease confinement to the distal circulation
few hours. ○ Segmental occlusions showing “skip” lesions with
○ The area can swell quickly if blood escapes into the extensive collateralization, called “corkscrew
surrounding tissues collaterals.”
Acquired Arteriovenous Fistulas

● Patients present with a continuous pulsating (bruit) mass in the
region of injury.
● The dilation of the major artery entering an arteriovenous fistula
may be marked, and the degenerative arterial wall changes may
be extensive
● Arteriovenous fistulas are associated with increase in cardiac
output, pulse rate, and blood volume, which may lead to
congestive heart failure
● Diagnosis:
○ Doppler ultrasonography is used to confirm the diagnosis
and to determine the extent of the problem.
○ For fistulas between deeper blood vessels (such as the aorta Figure 41: Angiograph of Lower Extremities Affected with Thromboangiitis
and vena cava), magnetic resonance imaging (MRI) is more Obliterans showing “corkscrew collaterals”
useful.
○ When a fistula is serious enough to require treatment,
doctors may do angiography, in which they inject a liquid
contrast agent into a blood vessel

Dr. Michelle Cauan
● Microscopic examination of early arterial lesions shows Takayasu Arteritis (Pulseless Disease)
panarteritis, often associated with thrombosis. ● Rare, systemic, inflammatory large-vessel vasculitis of unknown
● Inflammatory process: involve entire thickness of the vessel wall etiology
and perivascular tissues, internal elastic lamina is preserved
● Treatment is largely symptomatic and includes the control of pain ● Chronic inflammation and fibrosis of the arterial wall, predilection
and the avoidance of tobacco. Late in the course, amputations for the ascending aorta and primary aortic branches (arch vessels
may be necessary. and renal arteries).
● Microscopically :Recanalization of thrombi may be seen but
often incomplete with numerous small vascular channels passing ● Begins with a “prepulseless” phase( fever, anorexia, weight loss,
through the remaining fibrous tissue general malaise, arthralgias, and malnutrition). Progression to
reduced blood pressure and weak pulses in the carotids and
upper extremities; visual defects, retinal hemorrhages, and total
blindness; neurologic deficits.
● Most patients are young, asian, and female.
● Angiography is the gold standard for diagnosis showing
narrowing or occlusion of the entire aorta or its primary
branches, or focal or segmental changes in large arteries in
the upper or lower extremities.
● Treatment
○ Steroid therapy initially, cytotoxic agents for patient who
do not achieve remission.
● Surgical treatment
○ Only in advanced stages, and bypass needs to be
delayed during active phases of inflammation
○ In focal lesions - reports of success with angioplasty
● In the image
○ Transmural fibrous thickening of the aorta—particularly
Figure 42: Thromboangiitis Obliterans (Buerger Disease). Hallmark the aortic arch and great vessels—with severe luminal
features include transmural inflammation (of veins and arteries), narrowing of the major branch vessels
recanalized luminal thrombus, and preservation of the internal elastic
lamina.
Figure 43: Macroscopic: Thromboangiitis Obliterans
O. ARTERITIS
● Inflammatory diseases of the arteries
● Classified based on etiologic agent involved, the caliber and
location of the vessel affected, and the type of microscopic
change
Classification of Vasculitis based on Vessel Involvement

● Large-Vessel Vasculitis
o Takayasu’s arteritis
o Giant cell arteritis
o Behçet’s disease
● Medium-Vessel Vasculitis
o Polyarteritis nodosa
Figure 44: Takayasu Arteritis. A. Aortic arch angiogram showing narrowing of
o Kawasaki’s disease brachiocephalic, carotid, and subclavian arteries. B. Gross: marked intimal
o Buerger’s disease thickening and adventitial fibrosis with minimal residual lumen C. Microscopic:
● Small-Vessel Vasculitis destruction and fibrosis of the arterial mediaassociated with mononuclear
o Hypersensitivity angiitis infiltrates and inflammatory giant cells (arrows).
Large Vessel Arteritis

● Aorta and its main branches
● Characterized by chronic inflammation and patchy destruction of
the elements of the media.
● May result in aneurysm formation, aortic root dilatation and
valvular insufficiency, aortic arch syndrome, and aortic dissection.

Dr. Michelle Cauan
Giant Cell (Temporal) Arteritis
● Large vessel vasculitis syndrome
○ Most common after age 70, classically characterized by
pain in the distribution of the temporal artery and localized
tenderness.
○ Other extracranial carotid artery branches may be affected
as well, leading to jaw claudication, facial pain, and
blindness (the most feared complication).
○ Begins with a prodromal phase of constitutional symptoms,
(headache, fever, malaise, and myalgias).
○ The pathogenesis is unknown, autoimmune factors may
have a role
Figure 45: Takayasu Aortitis. Marked adventitial fibrosis and patchy Figure 47: Temporal Artery of an Elderly
lymphoplasmacytic inflammation, characteristic (although not entirely Man showing thickened nodular tender
specific for) Takayasu disease. arteries in Giant Cell Arteritis
● Pattern of involvement include granulomas and multinucleated

giant cells, there are also areas of more active inflammation
including basophilic “dirty“ necrosis
● Coronary artery involvement by Takayasu arteritis ● The syndrome of polymyalgia rheumatica, muscle pain and
○ Fibrotic wall thickening with lymphoplasmacytic tenderness involving mainly the muscles of the neck,
inflammation and intimal multinucleated giant cells shoulder, and pelvic girdle, and with elevated erythrocyte
sedimentation rate, in at least half of these patients.
● Responsive to corticosteroid therapy and anti-TNF therapies
● Complications related to ascending aortic aneurysm.
● Microscopically:
● Partial destruction of the wall by a lymphohistiocytic
inflammatory infiltrate, often with multinucleated giant cells.
● Temporal artery biopsy(diagnostic gold standard)
● Transmural Inflammation (Diagnostic hallmark)
● (+)perivascular inflammation in the absence of inflammatory
changes in the vessel wall is not diagnostic
● negative biopsy does not rule out
Figure 48: Microscopic: Giant cell aortitis with ribbon-like areas of elastic
laminar collapse, cuffed by lymphohistiocytic inflammation including
*notes based on Dr. Cauan’s Lecture multinucleated giant cells (inset).
Figure 46: Coronary artery involvement by Takayasu arteritis, manifesting as
fibrotic wall thickening with lymphoplasmacytic inflammation and intimal ● In elastic arteries (especially the ascending aorta), this
multinucleated giant cells (again the clinical context of aortitis with primary branch inflammation is found surrounding “islands” of acellular collapsed
involvement in a young woman is needed to confirm Takayasu disease).
elastic lamellae

Dr. Michelle Cauan
Figure 51: Microscopic: Kawasaki Disease
Figure 49: Microscopic: Giant cell—temporal arteritis showing transmural

lymphohistiocytic inflammation with multinucleated giant cells near the internal
elastic lamina.
Medium-sized Vessel Arteritis

● Primarily affect muscular arteries, and all are characterized by
active necrotizing inflammation leading to (often segmental)
fibrinoid necrosis of the arterial wall.
● As this process resolves and evolves, pseudoaneurysms
develop.
● Necrotizing arteritis and pseudoaneurysm formation are the
hallmarks.
Kawasaki Disease
● Pediatric condition that first presents as a mucocutaneous
syndrome with lymphadenopathy which later manifests as
medium vessel arteritis with a particular predilection for the Figure 52: Coronary (Pseudo)aneurysm in Kawasaki Disease. Coronary
angiogram showing a proximal (pseudo)aneurysm (left). The aneurysm wall
coronary arteries.
shows wisps of internal elastic lamina at one edge (confirming contained rupture
● Fever, lymphadenopathy, skin rash, oral/conjunctival erythema — pseudoaneurysm).
● Etiology:
○ T-cell hypersensitivity to unidentified antigens Polyarteritis Nodosa
● If unrecognized in childhood may only manifest later in adulthood ● Visible nodular lesions at the points of arterial branchings, within
as acute coronary syndrome due to complications of coronary the liver, spleen, and kidneys. (sparing the pulmonary
pseudoaneurysm. circulation)
● Recognition of the acute phase of this illness and treatment with ● Strong association with chronic hepatitis B infection
aspirin and intravenous immunoglobulin are critical in preventing ● Skin and peripheral nerves may also be involved.
and forestalling the coronary artery complications . ● It develops subacutely, constitutional symptoms last for weeks to
● Microscopically : months. Intermittent, low-grade fevers, malaise, weight loss, and
○ Transmural involvement of at least a segment of artery myalgias
viewed in cross section. ● Treatment: Immunosupressants
● Neutrophil-rich inflammation, and abundant fibrin in the active ● Vascular lesions of varying ages or “temporal heterogeneity” with
phase. active and healed lesions seen in the same biopsy or surgical
● Healed lesions show disruption of the internal and/or external specimen.
elastic lamina(e) with replacement-type fibrosis. ● Nodular lesions are confirmed to be pseudoaneurysms or
● Confirmation of Pseudoaneurysm relying on complete disruption contained hemorrhages and the vessel walls involved by
of the elastic media and near-rupture contained only by adventitial vasculitis with an active (fibrinoid) necrotizing arteritis process
connective tissue confirm pseudoaneurysm.
Figure 50: Gross: Kawasaki Disease

A, cord-like thickening of the left anterior descending (arrows) and left diagonal Figure 53: Polyarteritis nodosa. There is segmental fibrinoid necrosis and
coronary artery (arrowheads) thrombotic occlusion of the lumen of this small artery. Note that part of the
B, left anterior descending artery demonstrates marked fibrointimal thickening vessel wall at the upper right (arrow) is uninvolved.
with a near-pinpoint lumen

Dr. Michelle Cauan
Single Organ Vasculitis
● Confined to a particular organ (and apparently cured by removal,
where possible).
● Involve the arterial or venous vessels in the particular organ.
● Testicular vasculitis,uterine vasculitis, cutaneous vasculitis,
gallbladder vasculitis, CNS vasculitis, and isolated aortitis.
● A thorough and systemic rheumatologic evaluation is necessary
to confirm the isolated nature of disease in these patients.
P. TUMORS
Great Vessels
Figure 54: Polyarteritis Nodosa. Vascular lesions in the liver (elastic stains - ● Primary tumors of the “great vessels” (aorta or pulmonary artery)
cause of the dark stain which is the black appearance of the lumen) showing are malignant
features of active/ subacute fibrinoid necrotizing arteritis (left) and segmental wall ● Represent various types of sarcoma (fibrosarcoma,
destruction with contained rupture (pseudoaneurysm) (right). Temporal variability
(active and healed lesions in the same organ) is a hallmark feature of polyarteritis leiomyosarcoma, rhabdomyosarcoma, fibromyxosarcoma, and
nodosa. pleomorphic high-grade sarcoma).
● These intravascular tumors lead to embolic metastases, overall
 Acute phase  lesions are typified by fibrinoid necrosis of the prognosis is dismal
arterial walls, with a marked neutrophilic infiltrate.
● It is important to distinguish “intimal sarcoma” from other vascular
 As the lesions progress, medial and adventitial fibrosis becomes
more prominent, numbers of lymphocytes and plasma cells sarcomas in these vessels.
increase, and intimal proliferation may occur. ● There may not be any involvement of the underlying vessel wall.
 The arterial lumen may narrow due to thrombus formation.
Complete occlusion, aneurysm formation, and recanalization of
thrombi may occur in later stages
Figure 55: Cutaneous Manifestations of PAN
Small Vessel Vasculitis

● Encompass those entities that preferentially affect arterioles, Figure 56: Intimal Sarcoma of the Descending Thoracic Aorta. Pleomorphic
capillaries, and the venous side of circulation and spindled sarcoma cells are seen associated with fibrin thrombus overlying a
● Acute and necrotizing pattern of inflammation similar to medium bed of necrotic organizing fibrin debris.
vessel vasculitis syndromes
 (In the yellow box: Upon increased magnification, epithelioid /
● Show pronounced cellular infiltration in the adventitia, thickened
intimal fibrosis, and organized thrombus. These disease spindled cells are seen as Intensely dark blue color cells, and
processes may clinically mimic atherosclerosis, and most are each of the nucleus is darkly stained and called
treated by corticosteroid therapy or chemotherapeutic agents Pleomorphic/hyperchromatic nuclei and the reason for the
● They may be broadly classified into three groups: hyperchromatic appearance is because of the transformation into
(1) anca-mediated vasculitis, malignant cell.
(2) immune complex–mediated vasculitis, and  The cells are called Sarcoma because they are spindle shaped. -
(3) vasculitis caused by direct antibody-mediated injury.
● ANCA-mediated: *Based on Dr. Cauan’s Lecture)
○ Microscopic polyangiitis, polyangiitis with
granulomatosis, and eosinophilic granulomatosis with Intimal Sarcoma of the Descending Thoracic Aorta
polyangiitis. ● Pleomorphic and spindled sarcoma cells are seen associated with
● Microscopic polyangiitis (hypersensitivity vasculitis or fibrin thrombus overlying a bed of necrotic organizing fibrin debris.
leukocytoclastic vasculitis ● Growth pattern that consists of highly pleomorphic cells with
○ Generally affects capillaries, small arterioles and
either epithelioid or spindled morphology spreading in a
venules.
● Unlike polyarteritis nodosa, all lesions of microscopic polyangiitis plaquelike fashion along the surface of acellular fibrin
tend to be of the same age, and are distributed more widely. necrotic/thrombotic material lining the involved vessel
● Immune complex vasculitide: SLE, HSP and other related ● Lymphomas and high-grade sarcomas have also occurred at the
disorders. site of synthetic vascular prostheses and stents, as well as at the
● Direct antibody-induced injury: Goodpasture syndrome(prototype) site of a surgically constructed arteriovenous fistula.
● Chronic immune stimulation by the foreign material role in
pathogenesis.

Dr. Michelle Cauan
● Exclusive intravascular tumors are: ● Localized (microenvironment) hypoxia develops in the venous
● Epithelioid hemangioendothelioma, pyogenic granuloma, valve pockets, as oxygen is consumed by the endothelium and
intravascular papillary endothelial hyperplasia, intravascular venous wall, exhausting the local pool of static venous blood.
○ This results in local hypoxia with injury to leukocytes and
nodular fasciitis, synovial sarcoma, and intravascular
endothelial cells with possible platelet activation.
leiomyomatosis. ○ When new blood enters this environment (through leg
muscle contraction or postural change), the “fresh” intact
Metastatic Tumors leukocytes and platelets participate in the formation and
● These can lodge in large vessels and produce occlusion. propagation of a thrombus.
● Cases of major arterial occlusion from carcinoma of lung and
other sites have been well documented. Treatment
● Anticoagulant therapy (Heparin, Warfarin, and newer
III. VEINS anticoagulants)
A. NORMAL ANATOMY ● Elevation
● Veins have a three-layer histoarchitecture similar to arteries, but ● Rest with the maintenance of good hydration
they lack an internal elastic layer separating the intima and media. ● Elastic support
● The medial thickness is much thinner compared to arteries as ● Placement of upstream intravenous filters in IVC
well; in fact the adventitial layer is typically the thickest and most
prominent layer in most veins. C. STASIS ULCERS
○ The adventitial smooth muscle is also arranged in bundles ● An important “upstream” consequence occurring long term
oriented in varying directions around the vessel circumfer- ● Chronic venous insufficiency leads to manifestations of
ence. ○ Cutaneous pigmentation,
● The outer elastic layer is also less distinct than in arteries and ○ Brawny edema,
may show fragmentation and splitting. ○ Dermal and subcutaneous fibrosis,
● Another important feature distinguishing veins from arteries is the ○ Extensive secondary varicosities, and
presence of fibrous intimal valves in larger veins. ▪ Recanalization of the major deep veins
○ Ulceration of the skin develops in the lower extremity.
B. THROMBOPHLEBITIS AND THROMBOEMBOLISM ● Histologic features:
● Thrombophlebitis is a thrombotic disease of veins accompanied ○ Diffuse edema,
by varying degrees of inflammation. ○ Granulation tissue,
● Microscopically: ○ Hemosiderophages, and
○ The venous wall is edematous and the intimal endothelium ○ Collagen-bundle degeneration,
focally eroded with resultant thrombus formation. ○ With fibrosis
○ This may be accompanied by transmural infiltration with ● Other rare causes of ulceration such as specific infections and
chronic inflammatory cells. neoplasms can be excluded by biopsy and culture.
▪ During the acute phase, attachment of the ● Management:
thrombus to the intima may be tenuous. ○ The use of elastic supports to help control any dependent
○ As the acute inflammatory phase of the disease subsides, edema in the extremity is generally effective and may be
fibrosis develops, especially in the adventitia and media. required for many months or years.
○ The thrombus in this later phase may show organization or ○ Significant varicosities in the postphlebitic extremity may be
degenerative changes and becomes more fixed to the wall removed surgically.
(or even incorporated into the fibrotic process).
● Thrombophlebitis may involve superficial veins, deep veins, or D. VARICOSE VEINS
both. ● Occur more frequently in women than in men; incidence is much
● Clinical signs of deep vein thrombosis: higher in obese women, particularly those who have had several
○ The vein may be acutely inflamed and tender, and with pregnancies (presumably through prolonged compression of
superficial veins the overlying skin is red. pelvic veins by the gravid uterus)
○ When the thrombosis is limited to the superficial veins, there ● Often develop in the 2nd and 3rd decades of life and may be
is usually little edema. present for many years
○ However, thrombophlebitic edema may develop with marked ● Grossly, superficial veins of the leg become dilated and tortuous
rapidity and may be of great volume if the process extends and lose valvular function.
into the deep venous system. ● Microscopically:
● In the most severe instances, “third spacing” of extracellular fluid ○ Fibrosis beneath the endothelium and in the wall,
in the leg may be sufficiently massive to cause shock and be ○ With secondary elastosis and loss of muscle
accompanied by cutaneous blebs and necrosis (phlegmasia ○ Calcification may occur
cerulea dolens). ○ Abnormalities in matrix metalloproteins that may explain the
● There is a statistically significant association between deep vein extracellular matrix (collagen) changes in varicose veins
thrombosis and the presence of cancer in an internal organ, ▪ Help explain a hereditary or intrinsic susceptibility
known as the Trousseau syndrome. Many of the tumors to varicose vein formation
associated with this paraneoplastic complication are mucin- ● When severely symptomatic, or to prevent propagation to deeper
producing adenocarcinomas, often of the pancreas. veins and possibly increase thrombotic risk, surgical removal of
● Pulmonary embolism may occur in all forms of thrombophlebitis, varicosities may be performed.
but it should be noted that sudden massive pulmonary embolism
frequently occurs in patients without antecedent symptoms or E. TUMORS
signs of peripheral thrombophlebitis. Leiomyosarcoma
● 75% of the venous thrombi arose in the veins of the thigh and ● Extremely rare malignant tumors arising from the smooth muscle
pelvis and 25% in the smaller veins of the calf and feet, with 92% lining the walls of the inferior vena cava and other larger veins
arising in the lower extremities ● “Staghorn” pattern in histopathologic sections
● The development of deep venous thrombus and thrombophlebitis
was attributed to the “Virchow’s triad” hypothesis and the
interaction of (1) hypercoagulability, (2) stasis, and (3) intimal
injury.
● Blood pooling in the venous valve pockets was felt to serve as the
nidus for thrombus formation in this scenario.

Dr. Michelle Cauan
IV. LYMPH VESSELS Milroy Disease
A. NORMAL ANATOMY ● Congenital idiopathic lymphedema
● The smallest lymphatics resemble capillaries but often with a ● Mainly due to faulty FLT4 gene, which encodes for VEGF 3, a
“gaping” lumen and elongated or irregular contours. signaling factor that is essential for the development of lymphatic
● The walls of large caliber lymphatic vessels also resemble vasculature.
capillaries, lacking elastic tissue and with only thin wisps of ● Autosomal dominant inheritance
muscular media.
● Intimal valves may be seen in larger caliber lymphatics (similar to Treatment
veins). ● Elevation of the affected extremity
● Podoplanin (recognized by antibody clone D2-40) and LYVE-1 ● Compression
are antigens expressed specifically in lymphatic endothelium. ● Massage
○ While arterial and venous endothelium lacks expression of ● Antibiotics
podoplanin, it is present in other cell types, such as ● Operative therapy
mesothelium, and may be expressed in several epithelial ● Microsurgical techniques (fluorescence lymphography)
and vascular malignancies as well.
References
B. LYMPHEDEMA
● The only primary lymphatic disease encountered clinically with Goldblum, J., Lamps, L., McKenney, J. and Myers, J., 2018. Rosai and
some frequency Ackerman's surgical pathology. Philadelphia, PA: Elsevier.
● Chylothorax and chylous ascites also occur, but in nearly all
instances these processes are secondary to trauma, neoplastic
disease, or some infectious process.
● Stems from inadequate lymphatic drainage. It may be classified
into postinfectious, post-traumatic, obstructive, and idiopathic
etiologies.
● Most common cause of lymphedema worldwide
is filariasis caused by infection by Wuchereria bancrofti, Brugia
malayi and Brugia timori.
● In developed countries, most secondary lymphedema cases are
due to malignancy or related to the treatment of malignancy.
● Lymphedema can also be seen in patients who give a history of
as little trauma as a severely sprained ankle or following such
infections as a furuncle.
● The swelling is slowly progressive in nature.
○ There is dilation of the dermal lymphatics, as well as the
deeper fascial lymphatics.
○ When the degree of swelling is advanced, there is a
depression of hair follicles and gross dermal edema.
○ In such cases, the cutaneous lymphatics may be sufficiently
dilated to be associated with lymphorrhea following minor
cutaneous abrasions or needle punctures.
○ associated with dermal thickening and collagenous
deposition in the subcutaneous tissues and fascia.
○ Bouts of superficial cellulitis and lymphangitis often become
superimposed on the lymphedema in an extremity.
○ The presence of recurrent infection in such an extremity
appears to hasten the deposition of collagen and may result
in such a large amount of fibrotic replacement of
subcutaneous fat and normal dermal structures as to make
demonstration of dermal lymphatics impossible.
● Signs and symptoms:
○ Swelling of an arm or leg
○ Fibrosis, pitting edema
○ Restricted range of movement
○ Skin changes
○ Pain and altered sensation
○ Limb heaviness
○ Difficulty fitting into clothings

2022 Surgpath s2t2 Cardiovascular System

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

2022 Surgpath s2t2 Cardiovascular System

Uploaded by

Copyright:

Available Formats

CARDIOVASCULAR SYSTEM SURGICAL PATHOLOGY (PRELIMS)| 2nd SEM

Dr. Michelle Cauan

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 1 of 22

Figure 2: Restrictive eosinophilic endomyocardial disease, with organizing

● Non-eosinophilic Form (Idiopathic Restrictive

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 2 of 22

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 3 of 22

Congenital Bicuspid Aortic Valve

Ischemic Mitral Insufficiency

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 4 of 22

Figure 9: Gross features of aortic valve endocarditis (active and healed)

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 5 of 22

Occur more often in women Slightly more common in men

Most often in middle adulthood Manifest at a younger age

Figure 12: Gross appearance of Cardiac

Figure 13: Cardiac myxoma showing a concentric arrangement of tumor cells

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 6 of 22

Figure 18: So-called Cardiac MICE. A. The process is composed of an

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 7 of 22

OTHER PRIMARY TUMORS OF THE HEART

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 8 of 22

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 9 of 22

Figure 25: Ruptured Atherosclerotic Plaque and Luminal Thrombosis

● Arteriosclerosis and atherosclerosis are encountered in surgical

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 10 of 22

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 11 of 22

Figure 30: Arterial aneurysm types and their

Aortic Aneurysms (AA)

Figure 31: Abdominal aortic aneurysm with

Degenerative aneurysms in the ascending aorta

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 12 of 22

Aortitis Inflammatory Aneurysms

Figure 32: Aortic

Cross Sectional view (H & E with Elastin staining), of a temporal artery in a

Aortitis of the Abdominal Aorta Clinical factors associated with dissection

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 13 of 22

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 14 of 22

Figure 36: The characteristic beaded

● Invasive testing: Digital

Figure 34. Fibromuscular dysplasia

Figure 35. A carotid fibromuscular

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 15 of 22

Acquired Arteriovenous Fistulas

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 16 of 22

Figure 43: Macroscopic: Thromboangiitis Obliterans

Classification of Vasculitis based on Vessel Involvement

Large Vessel Arteritis

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 17 of 22

● Pattern of involvement include granulomas and multinucleated

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 18 of 22

Figure 51: Microscopic: Kawasaki Disease

Figure 49: Microscopic: Giant cell—temporal arteritis showing transmural

Medium-sized Vessel Arteritis

Figure 50: Gross: Kawasaki Disease

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 19 of 22

Figure 55: Cutaneous Manifestations of PAN

Small Vessel Vasculitis

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 20 of 22

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 21 of 22

ACEBEDO | DAVIS | ERNI | GUIEB | MANGABAT | PALATAN | ROLLON 22 of 22

You might also like