AN APPROACH TO MYOCARDIAL BIOPSY INTERPRETATION DR. SAURAV SINGH
Transcript
DR. SAURAV SINGH
Endomyocardial Biopsy(EMB) The endomyocardial biopsy remains
the gold standarad mode of investigation for diagnosing many
primary and secondary cardiac conditions. EMB a diagnostic
interventional procedure after development and application of
cardiac catheterisation and cardiothoracic surgery. In
sophisticated centers, evaluation of cardiomyopathic patients
includes a detailed history and physical examination, coronary
angiography and EMB.
Importance of EMB to clinicians Differentiating between
established dilated cardiomyopathy with no evidence of myocardial
inflammation and active myocarditis. Cardiac amyloidosis and
myocarditis that can be definitely diagnosed. Used to diagnose
specifically various types of myocarditis.
INSTRUMENTS Newer Flexible Bioptomes used due to less
complication rates Commonly used bioptomes are: Single use 50cm
Novatome Argon endomyocardial biopsy forceps Bipal 7 bioptome
Fluoroscopy is the standard imaging modality used to guide the
biopsy catheter.
The easily assessable anatomy of venous return to the heart
with peripheral access makes the right ventricle an attractive
location for tissue sampling. The interventricular septum is the
preferred biopsy site due to: Its thickness compared with the right
ventrical wall Its continuity with the left ventricle Its location
in the natural path of blood flow facilitating vascular access.
Myocyte disarray is normally encountered in the region of
ventricular apex and its junction with inter-ventricular septum.
Free wall perforation and haemopericardium is a major reason for
avoiding the free ventricular wall for biopsy.
Left ventricular biopsies(LVB) Infrequently done Performed by
needle biopsy at the time of open heart surgery or via a
trans-septal approach Procedure performed percutaneously through
the femoral artery, retrograde through the aortic valve into the
left ventricle. Disease affecting L.V. walls and L.V. masses are
the only indications for LVB.
TISSUE HANDLING Proper tissue procurement and handling are
essential for optimal diagnostic evaluation Biopsy specimens should
be gently extracted from the bioptome with a needle tip. 10%
neutral buffered formalin is needed to diagnose: Transplant
rejection Unexplained cardiomyopathy Myocarditis Infiltrative
cardiomyopathies Cardiac tumors
Zeus fixative or saline (used primarily for immunofluorescence
studies to evaluate antigen-antibody rejection) can be used to
assess allograft rejection. Trumps fixative or 4% glutaraldehyde
used for: Unexplained cardiomyopathy Drug induced cardiotoxicity.
Specimen in trumps fixative or 4% glutaraldehyde can be viewed with
Transmission electron microscopy(TEM) in assessing: Drug toxicity
Metabolic/ storage disorders Light chain deposition disease
Snap freezing tissue is optimal for preserving tissue for
molecular analysis like PCR and real-time PCR in evaluation of
viral pathogens. For routine diagnostic evaluation, overnight
processing and parrafin embedding are sufficient. All of the biopsy
pieces should be embedded in the same block.
A minimum of 3-6 slides prepared at 4-5micronM thickness within
the paraffin block. Multiple paraffin ribbons are placed on each
slide. Routinely stain with hematoxylin and eosin. For emergent
cases, a 90min rapid(ultra) processing cycle is available, and
slides can be prepared within 2-3hrs. Immunohistochemical,
immunofluorescence, and molecular studies are used for specific
studies.
Paraffin section immunohistochemistry is used to evaluate for
infectious endocarditis by CMV, EBV. In situ hybridization is
helpful to demonstrate the presence of EBV or other viral genome.
For diagnostic EMB, a sample should always be set aside for
transmission electron microscopy(TEM) The sensitivity of detecting
transplant rejection can approach 98% with five adequate biopsy
fragments.
The adequacy of tissue fragments is very important for correct
diagnostic accuracy and interpretation. The greatest limitation to
EMB is Sampling error.
Special studies TEM(transmission electron microscopy) are
indicated for conditions like: Cardiomyopathy Infiltrative
disorders(such as amyloidosis or glycogen storage disorders) Viral
myocarditis Drugs cardiotoxicity Universal fixative is recommended,
although any 2% glutaraldehyde based fixative is suffice.
SPECIAL STAINS Congo red or sulfated Alcian blue stain for
amyloid fibrils. Prussian blue stain for Iron deposition. Massons
trichome or Movat pentachrome stains to confirm the presence of
myocyte necrosis or interstitial fibrosis. Gomori methanamine
silver for Fungi Gram stains for Bacteria(endocarditis)
ROLE OF ARTIFACTS IN EMB Commonest artifact is contaraction
bands in myocyte identical to linear bands on acute ischaemic
necrosis and catecholamine (pressor) effect. Intussusception or
telescoping of small arteries confused with transplantation-related
arteriosclerosis and luminal occlusion by thrombus. Accumulation of
fresh platelet/ fibrin rich thrombus may be identified along the
endocardial surface of biopsy fragments.
(A) Section showing the typical pattern of myofibre disarray
that can be seen at previous biopsy sites.(B) Biopsy artifact
showing intussusception of an intramural vessel, not evidence of
occlusion/vasculitis (arrow) .
Ventricular perforation is identified by the prescence of
mesothelial cells. Other commonest is Crush artifact occur while
cutting large specimen. Bioptome-induced tissue distortion or Crush
artifact can occur.
Crush artifact
(A) Biopsy artefact showing pinching of the sample at the time
of procurement (arrows). Also note the region of
fibrosis,represents the site of an earlier biopsy. (B) Tissue
fragment from transplant showing endocardial fibrosis, secondary to
a healed biopsy site (thick arrow). Also note the region of
interstitial fibrosis and mixed inflammatory infiltrate consistent
with a vasopressor effect and probably not the site of a healed
episode of rejection.
Indication s of EMB: Diagnosis and monitoring of acute
transplantatio n rejection Diagnosis of tumors Diagnosis of storage
disorders Evaluation of restrictive heart disease such as
amyloidosis Classification of myocarditis Grading of drugs(anthrac
ycline, adriamycin) cardiotoxicity Evaluation of recent onset heart
failure in the absence of coronary artery disease
CARDIAC ALLOGRAFT REJECTION: TYPIFIED BY LYMPHOCYTIC INFILTRATE
WITH ASSOCIATED DAMAGE TO CARDIAC MYOCYTES
. Graft rejection reaction: (A)Early rejection: Foci of
lymphocytic infiltrates. (B)Severe rejection: Significant lymohoid
infiltration and myocyte necrosis
Allograft vasculopathy: Graft coronary arteriosclerosis,shows
severe diffuse concentric intimal thickening. The internal
lamina(arrow) and media are intact
EMB provides useful information in the following disorders:
Idiopathic hypertrophic cardiomyopathy: Shows changes : Myofibrils
disarray Myocyte Hypertrophy Interstitial fibrosis Endocardial
fibrosis Fibrous changes in intramyocardiac arteries. Commonest
finding is basophilic degenerationof myocardium appears as finely
granular basophilic.
Hypertrophy myocarditis:disarray, extreme hypertrophy,
branching of myocytes as well as characteristic interstitial
fibrosis(collagen is blue in this masson trichome stain).
Contd.. Idiopathic dilated cardiomyopathy: Endocardial
fibrosis, interstitial fibrosis Hypertrophy of myocardial fibers
Degenerative changes of myocardial fibers Leukocytic infiltrates
are commonly present Restrictive myocardiopathy: Variable myocyte
hypertrophy In active stage, heavy component of eosinophils is
present In inactive stage, various nonspecific changes are
seen
DCM demostrates variable myocyte hypertrophy and interstitial
fibrosis(collagen is highlighted as blue in Masson trichome
stain)
Classification of Myocarditis : Diagnosis of myocarditis
requires presence of inflammation infiltrate and myocyte necrosis
or degeneration. Etiology can be viral, bacterial, fungal,
parasitic, collagen vascular disease, drug and radiation induced or
transplant rejection Infiltrate is of lymphocytic in nature admixed
with histiocytes. Fibrosis if present should be quantified(mild,
moderate, severe) and qualified(interstitial, endocardial
replacement)
Contd Hypersensitivity myocarditis: Eosinophilic infiltrate
Predominantly perivascular Lesser degree of necrotizing changes.
Persistent myocarditis: When both the myocyte damage and the
inflammation persist on subsequent biopsies. Resolving or healing
myocarditis: When both the myocyte damage and the inflammation are
substantialy reduced, and resolved or healed.
Contd Giant cell myocarditis: Characterised by multicentric
destruction of the cardiac myocytes by cytotoxic cells and the
multinucleated cells. Recently described newer form of myocarditis
characterised by T lymphocytes that express the gamma-delta
receptor and runs a fulminant course. Lymphocytic myocarditis:
Active disease: Interstitial inflammatory infiltrate Focal myocyte
necrosis. Diffuse, mononuclear, lymphocytic infiltrate
GIANT CELL MYOCARDITIS: Mononuclear inflammatory infiltrate
containing lymphocytes, macrophages, extensive loss of muscle and
multinucleated giant cells.
LYMPHOCYTIC MYOCARDITIS: Lymphocyte infiltrate with myocyte
injury
Contd. CHAGAS DISEASE: Parasitization of myofibrils by
trypanosomes Inflammatory infiltrate by neutrophils, lymphocytes,
macrophages and occasional eosinophils. Myofibrils distended with
trypanosomes infiltration.
CHAGAS DISEASE: Myofibrils distended with trypanosomes(arrow)
is present along with inflammation and necrosis of individual
myofibrils.
Contd Infiltrative myocardiopathies: It includes various
infiltrating conditions like: Amyloidosis Hemosiderosis
Hemochromatosis Glycogenosis
AMYLOIDOSIS
AMYLOIDOSIS
AMYLOIDOSIS ON EM
Contd Drug induced and radiation induced cardiomyopathies:
Adriamycin shows changes like: Vacuolisation of cardiac myocytes is
the earliest change Appearance of adria cell(characterised by loss
of cross striations and myofilamentous bundles and basophilic
staining) Inflammation is nil or absent, which differentiates it
from other myocardinal lesions. Changes are diffuse, dose dependent
and tend to occur in subendocardial region.
FINDINGS AND IMPORTANCE Surgical pathology report should
provide as much as diagnostic information as possible, it includes:
Number of pieces of myocardium Appearance of myocyte
nuclei(hypertrophied, pkynotic, attenuated, or atrophic) Prescence
of cytoplasmic pigments Pattern of necrosis(focal or diffuse)
FINDINGS AND IMPORTANCE Composition of interstitium(e.g.,
cellularity, fibrosis, edema, amyloid deposits) Prescence of
endocardial inflammation
DIFFERENTIAL DIAGNOSIS ENDOCARDIUM FIBROSIS ULCERATION/
NECROSIS Healed myocarditis Cardiomyopathy Drug toxicity Organised
thrombus Healed biopsy site Healed acute rejection site Endocardial
hyperelastosis Graft procurement injury Healing biopsy site
Hypereosinophilic syndrome
COMPLICATIONS The current complication rate with the
intravascular procedure at specialised centres is less than 1%.
Sampling error( if focal in nature or limited to L.V)
Hemopericardium(most common) Cardiac perforation(most serious)
Nerve injuries Hematomas Cardiac arrhythmias Tricuspid valve
apparatus damage Pericardial fibrosis/ Thickening Air embolism and
pneumopericardium
TAKE HOME MESSAGE The endomyocardial biopsy remains the gold
standard mode of investigation, as there is considerable limitation
to non-invasive imaging techniques. EMB is used to follow allograft
rejection after heart transplantation. EMB is used to diagnose
conditions like Cardiomyopathies Myocarditis Infiltrative lesions
Arrhythmias Drug toxicities
EMB is used as a research tool to investigate the natural
history of disease. EMB is a safe, simple, and effective
interventional procedure with a very low rate of morbidity and
mortality. Interpretation of EMB specimens requires knowledge of
patients clinical history. It also requires appropriate
understanding of cardiovascular pathophysiolgy.
An approach to endomyocardial biopsy interpretation --
Cunningham et al_ 59 (2) 121 -- Journal of Clinical Pathology Rosai
and Ackermanns Sternberg surgical pathology Internet Robbins