June 2004
IMMUNOHISTOCHEMISTRY
The Diagnostic Utility of Immunohistochemistry
in Distinguishing between Mesothelioma and Renal Cell
Carcinoma: A Comparative Study
Nelson G. Ordez
Both mesotheliomas and renal cell carcinomas can present a wide variety of morphological patterns. Because of this, renal cell carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study was to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and renal cell carcinoma. A total of 48 mesotheliomas (40 epithelioid, 8 sarcomatoid), and 48 renal cell carcinomas (24 conventional, 12 chromophobe, 8 papillary, 4 sarcomatoid) were investigated for the expression of the following markers: calretinin, mesothelin, cytokeratin 5/6, WT1, thrombomodulin (TM), N-cadherin, CD15 (leu-M1), MOC-31, Ber-EP4, BG-8 (Lewisy), CD10, renal cell carcinoma marker (RCC Ma), carcinoembryonic antigen (CEA), and B72.3. All (100%) of the epithelioid mesotheliomas reacted for calretinin, mesothelin, and cytokeratin 5/6; 93% for WT1; 78% for TM; 75% for N-cadherin, 48% for CD10, 15% for Ber-EP4, 8% for MOC-31, 8% for RCC Ma, 5% for BG-8, and none for CEA, B72.3, or CD15. Of the sarcomatoid mesotheliomas, 88% expressed calretinin, 75% N-cadherin, 38% CD10, and 13% each expressed cytokeratin 5/6, WT1, and TM. All of the remaining markers were negative. Among the RCCs, 81% expressed CD10, 75% N-cadherin, 63% CD15, 50% RCC Ma, 50% MOC-31, 42% Ber-EP4, 8% BG-8, and 2% TM. The remaining markers were negative. The results indicate that calretinin, mesothelin, and cytokeratin 5/6 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from renal cell carcinomas. The best discriminators among the antibodies considered negative markers for mesothelioma are CD15, MOC-31, and RCC Ma. An accurate differential diagnosis can be reached with the use of any 2 of the 3 recommended positive markers, which should be selected based on availability and on which ones yield the best staining results in a given laboratory. One of the recommended negative markers may be added to the panel if deemed necessary. If confirmation of renal origin is needed, RCC Ma could be useful. Calretinin is the only marker that appears to have any utility in distinguishing between sarcomatoid mesotheliomas and sarcomatoid renal cell carcinomas.
Human Pathology Volume 35, Issue
6, June 2004, Pages 697-710
Immunohistochemistry in Gynaecological Pathology: A Review
Veli-Matti
Marjoniemi
This
paper reviews some aspects of the application of immunohistochemistry
in gynaecological pathology. The use of cytokeratins 7 and 20 are discussed with reference to
applications in ovarian pathology, including metastatic
disease to the ovaries. Developments in utilising
MIB-1 and p16 in cervical squamous and glandular
lesions are discussed. Recent assertions regarding the differential diagnosis
between endocervical and endometrial carcinomas are
also reviewed. Antibodies that may be
of use in the diagnosis of uterine mesenchymal and
ovarian tumours are highlighted, as are antibodies of
use in trophoblastic lesions including the use of p57
in evaluating hydatidiform moles.
Pathology, Volume
36, Number 2, April 2004, pp. 109 - 119
CYTOPATHOLOGY
Fine Needle Aspiration Biopsy of Soft Tissue Sarcomas:
Utility and
Diagnostic Challenges
Singh, Harsharan K; Kilpatrick, Scott E; Silverman, Jan F
The role of fine needle aspiration
biopsy (FNAB) as the primary modality for the initial diagnosis of previously
undiagnosed soft tissue sarcomas presents several important challenges.
Most practicing pathologists are inexperienced with the wide array of soft
tissue neoplasms and their morphologic heterogeneity,
making them susceptible to misdiagnosis. However, in the hands of experienced cytopathologists, FNAB in conjunction with ancillary
techniques has a diagnostic accuracy approaching 95% for the diagnosis of
malignancy. FNAB has been shown to have a diagnostic yield nearly identical
with core needle biopsy while avoiding significant clinical complications.
Nevertheless, FNAB has certain limitations related to the accurate histologic grading and subtyping
of certain subgroups of sarcomas. It may also be difficult to accurately distinguish
between low-grade sarcomas and benign or borderline cellular lesions,
especially in the spindle cell sarcoma subgroup. The aim of this review is to
highlight the utility and limitations of FNAB in the primary diagnosis of soft
tissue sarcomas, highlight diagnostically challenging lesions, and comment on
the limitations of FNAB in providing a definitive diagnosis.
Advances in
Anatomic Pathology, Volume
A Prospective Study of the Use of Fine-needle Aspiration
Cytology and Core Biopsy in the Diagnosis of Breast Cancer
Dennison
G, Anand R, Makar SH, Pain
JA.
A prospective study was carried out on 143
consecutive patients with palpable lumps larger than 2 cm in size, which were
clinically suspicious of carcinoma. One hundred and five lumps proved to be
malignant and 38 were benign. Of the 105 patients with malignancy, confirmation
was made in 95 by fine-needle aspiration cytology (FNAC) with a sensitivity of
90.4% and 100 by core biopsy with a sensitivity of 95.2%. The sensitivity of
core biopsies increased with the number of cores taken (one core, 76.2%; two
cores, 80.9%, three cores, 89.2%; four cores, 95.2%). The combined sensitivity
of FNAC and core biopsies was 100%, and so are
complementary in the accurate diagnosis of breast cancer. Patients presenting
to the breast clinic with a solid suspicious breast lump larger than 2 cm can
benefit from FNAC and a minimum of four core biopsies to improve diagnosis.
Breast J. 2003 Nov-Dec; 9(6):
491-3.
MOLECULAR
PATHOLOGY
DNA Fingerprints Provide a Patient-Specific Breast Cancer
Marker
SuEllen Toth-Fejel, Patrick Muller, et. al.
Background: Detection of systemic breast cancer
recurrence is limited by lack of universally expressed tumor cell markers.
Authors hypothesized that a test that detects genetic alterations specific to
breast cancer cells of an individual patient would provide a superior cancer
marker.
Methods: DNA was extracted from blood, primary tumor,
and axillary lymph nodes of 33 breast cancer patients
and normal breast tissue of 12 control patients. A patients genome was scanned
by PCR amplification between Alu sequences. A DNA
fingerprint of approximately 1740 bands was produced for comparison between
normal blood and sampled tissues.
Results: There were 7 stage I, 18 stage II, 7 stage
III, and 1 stage IV breast cancer cases; 33 of 33 cancer cases showed DNA
fingerprint differences between blood and primary tumor (P < .0001).
This test predicted 100% of positive nodes. No false-negatives occurred, and in
two cases malignancy was detected in histologically
negative nodes. Three of the 12 controls showed a single similar band change.
Conclusions: DNA fingerprinting is a method for detecting
and characterizing genetic alterations specific to an individual patients
primary tumor in 100% of cases tested. These specific changes were also
identified in 100% of positive nodes, proving the capacity of the test to
detect metastases.
Annals of Surgical Oncology 11:560-567 (2004)
C Reactive Protein and Microvascular
Function
F Tomai
Emerging data suggest that C reactive protein may be a mediator as well as a marker of atherosclerosis
A large body of evidence has shown that atherosclerosis is an inflammatory disease. Vascular inflammation contributes to the pathogenesis of atherosclerosis and, later in the disease process, is a major contributor to acute coronary syndromes. Recently, it has been suggested that inflammation might play a key role also in microvascular dysfunction of patients with syndrome X (typical exertional chest pain, a positive exercise stress test response, and normal coronary angiogram). Triggers and pathways of inflammation are probably multiple and different in these different settingsthat is, atherogenesis, acute coronary syndromes, and syndrome X. The identification of specific triggers and mechanisms of inflammation in each specific clinical setting might lead to new ways in its management.
Besides their role in atherogenesis and in acute
coronary syndromes, inflammatory mechanisms are likely to also play
a role in coronary microvascular
dysfunction. However, triggers and mechanisms of inflammation in
this setting are largely unknown and probably different to those
involved in the two other pathophysiological conditions.
Therefore, specific mechanisms of microvascular dysfunction
caused by inflammation should be further investigated in order to
establish tailored therapeutic strategies. Of note, emerging data
suggest that CRP may be a mediator as well as a marker of
atherosclerosis. In fact, CRP induces expression of cellular
adhesion molecules, inteleukin-6, and endothelin-1 by endothelial
cells. CRP also mediates monocyte chemoattractant
protein-1 induction, and it has been shown to mediate uptake of
low density lipoprotein by macrophages. Furthermore, CRP attenuates
nitric oxide production and inhibits angiogenesis and, very
recently, has been shown to upregulate angiotensin type 1 receptors in vascular smooth
muscle and to decrease prostacyclin
release from endothelial cells. Thus, lowering CRP concentrations
by, for example, use of statins and/or aspirin, might
improve coronary microvascular dysfunction. Whether
this is a valid approach, however, is still unknown and deserves
further investigation. Indeed, as mediators of inflammation are
multiple, the strategy of indentifying triggers and
mechanisms of inflammation in each specific clinical setting and
directing treatment at the specific triggers or to rate limiting
steps in effector pathways appears more
reasonable.
Heart 2004; 90:727-728
MICROBIOLOGY
Cerebrospinal Fluid Abnormalities in Patients with
Syphilis: Association with Clinical and Laboratory Features
Christina M. Marra,
Clare L. Maxwell, et. al.
Objective. To define clinical and laboratory features that
identify patients with neurosyphilis.
Methods. Subjects (n = 326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and
Prevention criteria for lumbar puncture underwent standardized history,
neurological examination, venipuncture, and lumbar
puncture. Neurosyphilis was defined as a
cerebrospinal fluid (CSF) white blood cell count >20 cells/ L or reactive
CSF Venereal Disease Research Laboratory (VDRL) test result.
Results. Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but
not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer
Conclusion. Serum RPR titer helps predict the likelihood
of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.
The Journal of
Infectious Diseases 2004; 189:369-376
Genus and Species-specific IgG
and IgM Antibodies for Pulmonary Tuberculosis
Tariq
Butt, Hamid Saeed Malik, Shahid Ahmad Abbassi, Rifat Nadeem Ahmad, Abid Mahmood, Karamat A. Karamat and Masood Anwar
Objective: To evaluate three different enzyme
immunoassays for serological diagnosis of pulmonary tuberculosis and to compare
their diagnostic accuracy in different combinations.
Design: A non-interventional comparative study.
Place and
Duration of Study: The study
was carried out at the Department of Microbiology, Armed Forces Institute of
Pathology,
Subjects and
Methods: Sera from patients
suffering from pulmonary tuberculosis (n=94) with sputum positive for acid fast
bacilli (AFB) and sera from control group of healthy individuals (n=90) with
sputum negative for AFB were tested by Pathozyme-Myco
G EIA, Pathozyme-TB Complex Plus EIA and Pathozyme Myco M EIA kits for the
genus-specific IgG and IgM,
and the species-specific IgG antibodies against
antigens of Mycobacterium tuberculosis.
Results: The detection of IgG
against genus-specific antigens by Pathozyme-Myco G
had a sensitivity of 46% and a specificity of 93%, of IgG
against species-specific antigens by Pathozyme-TB
Complex Plus had a sensitivity of 64% and specificity of 97% and of IgM against genus-specific antigens by Pathozyme
Myco M had a sensitivity of 67% and specificity of
98%. When the results of these immunoassays were evaluated in combination,
their sensitivity improved. Combination of genus specific IgM
and species-specific IgG yielded best results with a
sensitivity of 87% and specificity of 93%.
Conclusion: The sensitivity of serological diagnosis of
tuberculosis is low, but it can be increased by utilizing a combination of
several antigens.
J Coll Physisians Surg Pak February 2004
Volume 14 Number 2
Human Papillomavirus Vaccine as
a New Way of Preventing Cervical
Cancer: A Dream of the Future?
Mandic A, Vujkov
T.
According to many researchers, human papillomavirus (HPV) infection has an important role in the development of cervical neoplasm. The effects of HPV infection on the oncogenesis of cervical carcinoma can be explained to a large degree by the regulation and function of the two viral oncogenes, E6 and E7. About 25 of >80 types infect the genital tract. HPV types are stratified into low, intermediate- and high-risk categories. Today, vaccines are available against many serious human pathogens. It is accepted worldwide that cervical carcinoma is a consequence of infection with HPV viruses. Therefore it is reasonable to assume that vaccine that prevents infection will reduce the incidence of cervical cancer. Virus-like particles are empty viral capsids, and are the leading candidate vaccines for the treatment or prevention of cervical cancer in humans. The HPV type 16 (HPV16) L1 virus-like particle vaccines have been shown to be generally well tolerated and they generate high levels of antibodies against HPV16. Since approximately 50% of cervical cancers are associated with HPV16 infection, the administration of this type of vaccine to young women could reduce the incidence of HPV16 infection, which is related to cervical dysplasia and cervical neoplasm. Vaccination against HPV infection could reduce the risk of infection and, most importantly, decrease the incidence of cervical cancer. A vaccine for cervical cancer is not a dream in the far future, it is happening today.
Ann Oncol.
2004 Feb; 15(2): 197-200.
BOTTOM
LINE
Winds of Change
T Rajalakshmi
There once lived a pathologist by name Joe Pearson,
Like the back of his hand, he knew every
lesion.
He knew them all; hed seen them all,
A great teacher, his students hed enthrall.
"REAL" lymphomas to "pseudo" tumours
he was the master,
There was no man who could be faster.
Our good old man had but one vice,
That hed firmly shut his minds eyes.
Never a new thought could he entertain,
The winds of changehe treated with
disdain.
Stagnant and resistant, the frog-in-a-well,
Till one day, the curtain of wax fell.
Hed made a mistake, which was certainly fatal
putting a newborn through the gates of hell;
He was left a loner in his ivory tower,
Deprived of his glory, shorn of his power.
His work of a lifetime stood by him no more,
cos hed refused to learn and hed chosen
to ignore.
A heavy price he paid, to fathom the secret of living
That if you want to go places, you must keep moving!
Journal
of Clinical Pathology 2003; 56:568