June 2007
ANATOMIC PATHOLOGY
Primary Ovarian Leiomyosarcoma: A Review of the Clinical and Immunohistochemical Features of the Rare Tumor
Taşkin S, Taşkin
EA, Uzüm N et al
Primary pure ovarian leiomyosarcomas
constitute a malignant subgroup of ovarian smooth muscle tumors which comprise
only 1% of ovarian tumors. Their origin, etiology, histologic
features, clinical behavior, and optimal treatment are still obscure. Malignant
behavior is almost always associated with any 2 of coagulative
necrosis, cellular atypia, and mitotic index greater
than 10. Immunohistochemical and electron microscopic
evaluations may improve diagnostic accuracy. Traditionally, International
Federation of Gynecology and Obstetrics (FIGO) staging and treatment of ovarian
sarcomas have been the same as for epithelial ovarian carcinomas. Although
surgery was performed for all cases, the extent of surgery is debatable.
Benefit and modality of adjuvant therapy is controversial.
The prognosis of primary pure ovarian leiomyosarcomas
is extremely poor depending on tumor stage, tumor size, grade, and mitotic
index and mostly recurs in abdomen and pelvis. Target Audience: Obstetricians
& Gynecologists, Family Physicians Learning Objectives: After completion of
this article, the reader should be able to state how rare primary ovarian leiomyosarcoma (POLMS) is, explain that because of its
rarity the best diagnostic and treatment modalities are not conclusive, and
recall that the authors reviewed the literature to bring the readership current
on POLMS.
Obstet
Gynecol Surv., 2007 Jul;62(7):480-486.
Advances in Salivary Gland Pathology
This review summarizes the new findings on salivary gland pathology under the following categories: immunohistochemistry; molecular genetics; newly recognized tumour types; known tumour entities with new findings; and progression of salivary gland tumours. In the application of immunohistochemistry, CD117 can aid in highlighting the luminal cell component of various salivary gland tumours, whereas p63 or maspin can aid in highlighting the abluminal cell component. A high Ki67 index remains the most useful marker to predict adverse outcome in salivary gland carcinoma. Specific chromosomal translocations are recognized in pleomorphic adenoma (with translocation involving PLGA1 or HMGA2 gene) and mucoepidermoid carcinoma (with MECT1–MAML2 gene fusion). Newly recognized entities include: sclerosing polycystic adenosis (with recent molecular evidence supporting its neoplastic nature), sclerosing mucoepidermoid carcinoma with eosinophilia, keratocystoma, adenoma with additional stromal component (lymphadenoma, lipoadenoma and adenofibroma), cribriform adenocarcinoma of the tongue and signet ring adenocarcinoma of minor salivary gland. Known tumour entities with new findings include: salivary duct carcinoma (with newly recognized mucinous, micropapillary and sarcomatoid variants), intraductal carcinoma (with controversies in terminology), mucoepidermoid carcinoma (with newly proposed grading parameters and oncocytic variant), epithelial–myoepithelial carcinoma (with newly recognized morphological variants), small cell carcinoma (with most cases being related to Merkel cell carcinoma), extranodal marginal zone B-cell lymphoma (with specific chromosomal translocation) and chronic sclerosing sialadenitis (being a component of IgG4-related sclerosing disease). Progression of salivary gland tumours can take the form of malignant transformation of a benign tumour, progression from low-grade to high-grade carcinoma, dedifferentiation, or stromal invasion of an in situ carcinoma.
Histopathology,
Volume 51 Issue 1 Page 1-20, July 2007
Immunohistochemical and Immunochemical Study of Amyloid in Liver affected by Systemic Al Amyloidosis with Antibodies against Three Different Regions
of Immunoglobulin l Light Chain
Makiko Kiyama, Yoshinobu Hoshii, Dan Cui et al
The purpose of the present paper was to investigate the heterogeneous
nature of amyloid deposits in the liver, by immunohistochemical and immunochemical examination of liver
samples from cases of immunoglobulin l light
chain amyloidosis (Al amyloidosis) with
antibodies generated against the peptides corresponding to the three different
regions of the l light chain. Amyloid
deposits in the hepatic artery tended to react better with anti-l(118–134) than with anti-l(159–175). Amyloid deposits in
the space of Disse tended to react weakly or
partially with anti-l(118–134) but well with anti-l(159–175). Amyloid
deposits in the portal vein reacted relatively well with both antibodies. By
western blot- ting of water-extracted amyloid in
which amyloid deposits were not stained with anti-l(118–134) immunohistochemically,
the three antibodies detected 27 kDa bands consistent
with the full-length Ig l chain and some smaller bands. These findings
indicate that amyloid deposits may not be homogeneous
in the liver of
Histological and immunohistochemical findings
In the Al cases of vascular type anti-l(118–134) reacted with amyloid deposits in all
13 cases. With this antibody, immunoreactivity of amyloid deposits in portal
veins and hepatic arteries was relatively good, although that in hepatic arteries was uneven in some cases. In three cases, immunoreactivity was weak but could be determined to be
positive. In 11 of 13 cases, amyloid deposits were
positive with anti-l(159–175), but the immunoreactivity
was variable. In at least five cases there were some areas in which immunoreactivity was stronger in amyloid deposits in the
portal vein and weaker in the hepatic artery. Anti-VlVIFR3 reacted with amyloid
deposits in 12 of 13 cases. However, immunoreactivity
was variable in each case and within each specimen. In the Al cases of diffuse type, anti-l(118–134) reacted with amyloid deposits in six
of seven cases. In four of these cases, this antibody reacted weakly or partially
with amyloid deposits in the space of Disse.
However, even in these cases, relatively good staining of amyloid deposits with anti-l(118–134) was observed in the vessel walls of portal tracts. In two
cases, amyloid deposits in the space of Disse and in the vessel walls of portal tracts were stained
well. Anti-l(159–175)
reacted well with amyloid
deposits in the space of Disse
in all seven cases of diffuse type. However, with anti-l(159–175), the immunoreactivity was
somewhat variable in vessel walls of portal tracts, similar to the
vascular type. In at least five cases,
immunoreactivity of amyloid deposits in
the hepatic artery was weaker than that of the portal vein and the space of
Disse, although in one case, immunoreactivity in the hepatic artery was
improved by formic acid pretreatment. Anti-VlVIFR3
reacted with amyloid deposits in only one Al case of diffuse type, which was negative with
anti-l(118–134). The immunoreactivity
was weak in amyloid deposits in the space of Disse and hepatic artery compared
to that in the portal vein.
The unclassified case
was classified as Al amyloidosis on immunohistochemistry
with newly generated anti- l(159–175) and anti-VlVIFR3. Amyloid deposits reacted with
anti-l(159–175), staining
deposits in the
space of Disse partially and
in the vessel walls. Anti-VlVIFR3 also reacted relatively well with amyloid
deposits in vessel walls, but not clearly with those in the space of Disse.
In Ak and AA amyloidosis
cases, amyloid deposits were negative with anti-l(118–134), anti-l(159–175) and anti- VlVIFR3.
Pathology
International 2007; 57: 343–350
CYTOPATHOLOGY
Role Of Direct Immunofluorescence On Tzanck Smears In Pemphigus Vulgaris
Vijay Aithal, Usha Kini, Elizabeth Jayaseelan
The Tzanck smear is a simple, sensitive, and rapid test to diagnose pemphigus vulgaris (PV), a life threatening autoimmune blistering disorder. The presence of acantholytic cells in cytology is indicative of but not specific for PV. Hence, a direct Immunofluorescence (DIF) test to demonstrate immunoglobulin deposits on the acantholytic cells would make the Tzanck test more specific, in addition to being a rapid test. Twenty untreated patients with PV confirmed histopathologically were enrolled to evaluate the efficacy of using DIF technique using IgG on Tzanck smear samples. The DIF smears were compared with DIF on skin biopsies in the same patient. This prospective pilot study approved by the institutional ethics committee was carried out in a tertiary health care hospital in a developing country. Of the 15 patients presenting within 3 mo of onset of the illness, 40% (n = 6) showed DIF positivity on Tzanck smear, when compared with 46.67% (n = 7) on skin biopsy. On the other hand, of the five patients presenting beyond 3 mo of their illness, only 20% (n = 2) showed positivity on Tzanck, when compared with all 100% (n = 5) on skin biopsy. The study, thus, suggests that DIF on skin biopsy is comparable to biopsy in diagnosing early PV. This preliminary study proposes that the use of DIF on Tzanck smear is a simple, rapid, painless, and user-friendly out-patient procedure for the diagnosis of early PV, even for relatively inaccessible lesions in the oral cavity and flexural regions. This methodology would be of great help in outlying and rural facilities lacking proper histological equipment, thus avoiding the need for a surgical or punch biopsy or heavy investment in laboratory equipment and expertise. Probable reasons for DIF negativity on Tzanck smears are also discussed.
Diagn. Cytopathol, July. 2007;35: 403-407.
Immunocytochemical Diagnosis of Hepatocellular Carcinoma and Identification of Carcinomas
of Unknown Primary Metastatic to the Liver on
Fine-Needle Aspiration Cytologies
BACKGROUND: Difficulties with cytologic diagnoses on fine-needle aspiration cytology (FNAC) of the liver can be overcome by the application of immunocytochemical panels applied on smears. The aim of the current study was to analyze the performance of a panel of monoclonal antibodies to differentiate hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) or regenerative nodules, and to identify the to date unknown primary sites of carcinomas that had metastasized to the liver.
METHODS: In a validating cohort study, 108 FNACs coin lesions in the liver were routinely evaluated applying immunocytochemistry as an ancillary method. All patients had confirmatory histologic and/or clinical follow-up. A total of 23 HCCs were analyzed for the distinction from MC or regenerative nodules applying a panel of HepPar1, alpha-fetoprotein, BerEP4, CD31, CD68, and Ki-67. A total of 85 cases of unknown primary tumor metastatic to the liver were used to identify the tumor sites applying a panel of CK5/6, CK7, CK20, CA 125, thyroid transcription factor-1 (TTF-1), and Cdx2.
RESULTS: Typing accuracy to differentiate HCC from MC or regenerative nodules was 100% and 90.3%, respectively, to identify the primary tumor site of MC. In 23 cases, the site of the primary tumor remained clinically unknown.
CONCLUSIONS: The application of immunocytochemical panels on the same slide used for microscopic diagnosis is a useful tool in the routine assessment of FNACs of the liver to discriminate HCCs from MC or regenerative nodules and for the identification of primary sites of MC. Their performance should be confirmed in a larger series of cases.
Cancer. 2007 Jun 13; [Epub ahead of
print]
CLINICAL
PATHOLOGY
Three Sputum Samples Help Diagnose
Tuberculosis When Expectorate Inadequate
In patients who cannot produce adequate expectorate, use of 3 sputum samples is more sensitive for diagnosis of tuberculosis (TB) compared with gastric washing, according to the results of a study published in the June 1 issue of Clinical Infectious Diseases.
"Many adults with pulmonary tuberculosis are
unable to expectorate," write Michael Brown from the London School of
Hygiene and Tropical Medicine in
The investigators recruited 140 consecutive adult inpatients who were unable to expectorate and who had chest radiography findings suggestive of TB. Participants provided 3 induced sputum samples for culture on day 1 and additional samples on days 2 and 3, as well as gastric washing specimens on days 1, 2, and 3. A proportion of subjects with negative smear results underwent bronchoalveolar lavage.
In 107 participants who provided 3 gastric washing specimens and at least 3 induced sputum specimens, cultures were positive for Mycobacterium tuberculosis in 43%. Use of 3 induced sputum samples helped with TB diagnosis more frequently than did use of 3 gastric wash samples (39% vs 30%; P = .03).
In 79 participants with culture results for all 5 induced sputum specimens, yield was similar for samples obtained by induced sputum induction performed in a single day and for those performed on 3 days (34% vs 37%; P = .63). Sputum volume was not associated with positive culture results, and no additional cases were diagnosed in the 21 patients who underwent bronchoscopy.
"Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously," the authors write. "Use of bronchoscopy with bronchoalveolar lavage did not increase diagnostic sensitivity. Samples could be collected in 1 day, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay."
Clin Infect Dis. 2007; 44:1415-1420.
Accuracy of Filter Paper Method for Measuring Glycated Hemoglobin
Anjali, FS Geethanjali, R Selva Kumar, MS Seshadri
Background and Objectives: Glycated hemoglobin (HbA1c) provides an accurate and reliable method to assess the glycemic control in patients with Diabetes. Its measurement is limited by the inconvenience of sample collection that requires venipuncture, sample handling and storage factors. The aim of this study was to assess the feasibility of using a dried capillary blood spot on a filter paper to estimate HbA1c, to check its stability at room temperature and to compare these values with the venous sample HbA1c by Turbidimetric Inhibition Immunoassay (TINA, Tina-quant HbA1c II).
Methods: Venous blood samples of seventy-eight patients with Type 1 or type 2 diabetes, were collected in EDTA containing vacutainers. Stability of HbA1c was studied in capillary blood samples blotted on to Whatman number1 filter paper and stored at room temperature, for the first 20 patients enrolled in the study. After establishing the stability over a ten-day period, HbA1c values obtained on the capillary blood spots were compared with those obtained from the venous blood samples of the remaining 58 patients.
Results:
Glycated hemoglobin is found to be stable in dried
capillary blood spots on filter paper till the 10th day, stored at room temperature. It however, shows an inherent
variability of μ15%, which falls with in the permissible variability (18%)
of the quality control material. Seventy nine percent of the capillary HbA1c
values were found to fall within this range. With linear regression, we derived
the relationship between filter paper and venous HbA1c values. The regression
equation was as follows: Cap.HbA1c = 0.95 (Ven.HbA1c) + 1.4. The filter paper
results were highly correlated with the venous sample values (r = 0.889, p <
0.01).
Conclusion:
Measurement of glycated hemoglobin in dried blood
spots on filter paper gives reliable and reproducible results. In our study,
the mean capillary sample HbA1c value was 12% higher compared to the venous
sample HbA1c values. Therefore a higher normal range may have to be used for
interpreting the dried blood spot capillary blood HbA1c values.
JAPI,
Vol. 55, February 2007
Best Practice In Primary Care Pathology: Review 8
Smellie, W S A, Hampton, K K, Bowlees et al
This eighth best practice review examines four series of common primary care questions in laboratory medicine: (i) sodium abnormalities (ii) faecal occult blood testing. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents.
HYPERNATRAEMIA AND HYPONATRAEMIA (CVH AND WSAS)
Disorders of sodium and water balance are very common findings in primary care. The causes in most situations are readily identifiable from the clinical context, such as heart failure and/or diuretic use or dehydration. Frequently the patient’s clinical state and the rate of change of the serum sodium are more important than absolute serum sodium values and the questions practitioners face often relate more to action levels rather than diagnosis. This review offers a guide to action limits when hyponatraemia has been identified and also outlines less common causes of abnormal serum sodium concentration which are important to identify.
How should I investigate a patient with raised serum sodium concentration?
Hypernatraemia can be defined as a serum sodium >145 mmol/l.
Authors recommend:
· Repeat to confirm and establish whether acute and changing or chronic and stable. Changes of up to 5 mmol/l can reflect non-significant variation.
· Establish history of thirst, fluid intake and losses, and current treatments.
· Check for clinical features of dehydration and/or hypovolaemia.
Depending on result:
Persistent serum Na 146-148 mmol/l without clinical features of hypovolaemia may reflect a statistical population outlier.
Serum Na 149-154 mmol/l
Request serum potassium, urea, creatinine, calcium, and plasma glucose to evaluate further hydration status and renal function and exclude diabetes mellitus and hypercalcaemia as causes of dehydration
Request serum lithium in lithium-treated patients
Request urine and serum osmolality if diabetes insipidus suspected (in DI there is high serum osmolality (>300 mosm/kg) and inappropriately dilute urine (less than serum))
Consider specialist advice if clinical cause not apparent and oral rehydration, if indicated, is not realistically practical
Serum Na >=155 mmol/l
Seek specialist advice or admission in addition to above
Hypernatraemia may be defined as a serum sodium concentration above the top of the population reference range (145 mmol/l). This range, however, reflects the 95% range within healthy populations. In addition to variations caused by imprecision of analysis, values outside the reference range will include 5% of a healthy population. Values of more than 3 standard deviations above the population mean (>=148 mmol/l) will exclude many of the statistical anomalies and are more likely to be of clinical significance.
The clinical context will in most cases indicate the cause (usually net water loss in mild to moderate hypernatraemia).
A repeat specimen to confirm the result is prudent to exclude sampling and laboratory errors. Differences in sequential serum sodium measurements of up to 5 mmol/l may reflect analytical and biological variation, highlighting the need to confirm results, although such factors rarely produce results significantly outside the reference range. Serum sodium can change rapidly, within days or weeks depending on the clinical context, so retesting intervals will depend on the suspected underlying pathology.
While rare, excessive salt ingestion should be considered, particularly in situations of severe hypernatraemia, which would normally warrant urgent referral.
Laboratory investigations
The recommended initial investigations include serum potassium, urea, and creatinine (most of which will usually be reported with the sodium result), serum calcium and lithium (in lithium-treated patients) and plasma glucose. If diabetes insipidus is suspected, random urine osmolality measurement will identify failure to concentrate urine and, if present, should guide rapid referral. Urine osmolality <150 mosmol/kg water in the presence of hypernatraemia and polyuria is cited as diagnostic of diabetes insipidus.
How should I investigate a patient with low serum sodium concentration?
Authors recommend:
Establish history of fluid intake and current treatments.
Assess fluid status, to identify whether hypovolaemia or hypervolaemia is present.
Repeat to confirm and establish whether acute and changing or chronic and stable. Changes of up to 5 mmol/l can reflect non-significant variation.
Depending on result:
Persistent and stable serum Na 132-135 mmol/l in a clinically well patient may reflect a statistical population outlier and may not require investigation unless there has been a large recent fall.
Serum Na 125-131 mmol/l
Check serum potassium, urea, creatinine, triglycerides, protein and plasma glucose
If cause not clinically apparent, check urine Na and osmolality if syndrome of inappropriate antidiuretic hormone secretion (SIADH) suspected. Urine Na >30 mmol/l and urine osmolality significantly higher than serum osmolality suggests SIADH
Consider Addison’s disease and hypothyroidism
Consider reset osmostat syndrome in patients with chronic illness and stable hyponatraemia
Consider artefactual causes: hyperproteinaemia (e.g. myeloma) and severe hyperlipidaemia
Serum Na 115-124 mmol/l
Check as above
Seek specialist advice unless long-term stable and cause established
Consider immediate admission if Na falling rapidly or neurological signs or symptoms present
Serum Na <115 mmol/l
Immediate admission usually indicated
FAECAL OCCULT BLOOD TESTING IN ADULTS WITH BOWEL SYMPTOMS (SMM AND SCM)
Faecal occult bloods have long been contentious because of false positive and, particularly, false negative results and the implications of missing the potential diagnosis of malignancy. Cancer referral guidelines now place the emphasis on rapid secondary care investigation of suspected cancer patients, and the primary care use of investigations such as faecal occult blood testing is increasingly changing to endoscopic techniques. This question and answer set attempts to identify patients in whom this test may be appropriate in primary care and the means of obtaining the best results from the test.
When should I do a faecal occult blood test in an adult with lower gastrointestinal symptoms?
Patients under 60 years of age with change in bowel habit towards looser or more frequent stools >= 6 weeks, without rectal bleeding, palpable abdominal mass, intestinal obstruction or iron deficiency anaemia.
Prodigy guidance, which follows that of NICE, cites the following criteria for urgent referral of suspected colorectal cancer and recommends that apart from a full blood count, abdominal and rectal examination, no other tests be performed, in order not to delay referral.
Patients >=40 years old, with rectal bleeding and change of bowel habit towards looser and/or increased stool frequency lasting >=6 weeks.
Patients >=60 years old, with rectal bleeding persisting for >=6 weeks without a change in bowel habit and without anal symptoms.
Patients >=60 years old, without rectal bleeding with a change in bowel habit to looser and/or more frequent stools >=6 weeks.
All patients presenting with a right lower abdominal mass consistent with involvement of the large bowel.
Patients presenting with palpable rectal mass (intraluminal and not pelvic).
All men with unexplained iron deficiency anaemia and haemoglobin <=11 g/100 ml.
Non-menstruating women with unexplained iron deficiency anaemia and haemoglobin <=10 g/100 ml.
The Scottish SIGN guideline differs slightly, using a threshold of 50 years old and specifically adds intestinal obstruction as an indication for referral.
Rectal bleeding with a change in bowel habit to looseness or increased frequency.
Rectal bleeding without anal symptoms.
Palpable abdominal or rectal mass.
Intestinal obstruction.
All patients with iron-deficiency anaemia (Hb <11 g/100 ml in men or <10 g/100 ml in postmenopausal women) without overt cause should be thoroughly investigated for colorectal cancer.
It follows from this that only lower risk patients who would not require urgent referral should be considered for FOB testing, in order to expedite referral of positive cases, who are more likely to have bowel pathology.
What faecal occult test type should I use and how many samples are required?
Authors recommend:
Guaiac based tests (such as Haemoccult) offer the best balance of specificity and sensitivity.
Three samples should be collected over 3 days.
Faecal occult blood testing (FOB) is a non-invasive, simple and rapid near patient test. Typical tests use a Guaiac impregnated paper, which produces a colour change in the presence of blood when a hydrogen peroxide developing solution is dropped onto the test.
A number of FOB kits are available, which vary in specificity and sensitivity. One study in 1990 compared three tests in symptomatic patients (Haemoccult, Fecatwin and EZ Detect). These were used to test stool specimens from three sequential days. Using double contrast barium enema as a diagnostic test, the authors found Fecatwin to be the most sensitive. This test, however, gave three times as many false positive results as Haemoccult. The authors therefore concluded that a Haemoccult positive symptomatic patient had approximately a 50% probability of mucosal disease, and suggested this was the best of the three tests to use in the community, as long as the tester is aware that a negative result does not exclude serious pathology. EZ detect is a patient interpreted test, where a sheet of benzidine impregnated paper is floated in the toilet in the presence of stool. This was less sensitive for blood than Haemoccult, and was not recommended in this study.
Other tests are available for patients to perform themselves, such as the Coloscreen Self-Test, a floating card the patient places in the toilet pan. However, when compared to the Haemoccult in symptomatic patients, while patient preference was greater for the self-test method, compliance was better with Haemoccult tests distributed for the patients to spot with faeces, again, over three consecutive days, and return to their practitioner. In this study, Coloscreen Self-Test was also less sensitive.
Immunological tests also exist. One, Hemeselect, was compared with Haemoccult, in a population with gastrointestinal symptoms on three consecutive daily bowel motions. The immunological test was more sensitive but produced a higher false positive rate, with poorer specificity. The authors, however, concluded that due to the increased sensitivity for carcinoma, trials in asymptomatic patients may be justified.
Faecal [alpha]1-antitrypsin assay has also been described as a marker of gastrointestinal bleeding. This quantitative test is slightly more specific than Haemoccult, but neither test was considered sensitive enough to justify routine use in high-risk patients. Guaiac based testing appears to offer the best compromise between sensitivity and specificity, is most commonly used in the UK, and will be used in the planned asymptomatic screening programmes.
How do I interpret faecal occult blood test results in adult patients with lower gastrointestinal symptoms?
Authors recommend:
Specific dietary advice should be given prior to obtaining specimens to minimise the false positive rate.
Positive results indicate a significantly high likelihood of organic disease (although only about 30% will have malignancy) and may guide urgency of referral.
Negative results do not exclude organic pathology, and in symptomatic patients the test will only detect 2 out of 3 colonic cancers.
Results must be therefore interpreted within the clinical context and risk setting.
The accuracy and value of Guaiac testing for symptomatic patients was investigated in 1983 using Haemoccult tests in a prospective study of 802 symptomatic patients referred from secondary care. The authors found a low false positive rate of 8.6%, although the false negative rate was 45.4% when patients examined two samples from each of three consecutive stools. This could, they claim, be improved when combined with a “proper digital anorectal and proctosigmoidoscopic examination” to identify rectal tumours. There was, however, some debate about the interpretation of the data presented.
A study of symptomatic referrals to secondary care in 1993, where 3 consecutive days’ stools were tested, found 11% to be positive for occult blood using Haemoccult.
Of these, 63% were found to have colonic pathology. In comparison, fewer than 10% of those with a negative FOB test had significant findings when investigated. The authors concluded that although a positive FOB test was highly specific, a negative test did not adequately exclude colonic pathology, and they suggest that the FOB test could be used as a guide to the urgency of investigation.
An older Australian study using Haemoccult tests on symptomatic patients also supported the belief that a positive FOB test can indicate higher likelihood, but not exclude, organic disease.
Journal Of
Clinical Pathology, Volume 60(7), July
2007, pp 740-748
Meta-analysis:
Diagnostic Accuracy of Anti-Cyclic Citrullinated
Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis
Background: Rheumatoid factor (RF) and autoantibodies against cyclic citrullinated peptide (CCP) are markers that might help physicians diagnose rheumatoid arthritis.
Purpose: To determine whether anti-CCP antibody more accurately identifies patients with rheumatoid arthritis and better predicts radiographic progression than does RF.
Data Sources: MEDLINE through September 2006 and reference lists of retrieved studies and review articles.
Study Selection: Studies in any language that enrolled at least 10 participants and that examined the role of anti-CCP antibody and RF in the diagnosis or prognosis of known or suspected rheumatoid arthritis.
Data Extraction: Two authors independently evaluated studies for inclusion, rated methodological quality, and abstracted relevant data.
Data Synthesis: The DerSimonian-Laird random-effects method was used to summarize sensitivities, specificities, and positive and negative likelihood ratios from 37 studies of anti-CCP antibody and 50 studies of RF. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CCP antibody were 67% (95% CI, 62% to 72%), 95% (CI, 94% to 97%), 12.46 (CI, 9.72 to 15.98), and 0.36 (CI, 0.31 to 0.42), respectively. For IgM RF, the values were 69% (CI, 65% to 73%), 85% (CI, 82% to 88%), 4.86 (CI, 3.95 to 5.97), and 0.38 (CI, 0.33 to 0.44). Likelihood ratios among IgM RF, IgG RF, and IgA RF seemed to be similar. Results from studies of patients with early rheumatoid arthritis were similar to those from all studies. Three of 4 studies found that risk for radiographic progression was greater with anti-CCP antibody positivity than with IgM RF positivity.
Limitations: Many studies had methodological limitations. Studies of RF were heterogeneous and had wide ranges of sensitivity and specificity.
Conclusions: Anti-CCP antibodies are more specific than RF for diagnosing rheumatoid arthritis and may better predict erosivedisease.
Annals of Internal Medicine
Volume 146(11),
BOTTOM LINE
Lymphomania
Rajalakshmi, T
The urge to classify
A Pathologist can never defy.
An example of this, in its full splendour
Are the Lymphomas they plunder!
From Rap to
From WHO to REAL,
Sifting through clefts and cleaves,
Is a terrifying ordeal.
Sometimes they FISH, sometimes they
May also end up counting stars in the sky.
In a
Despite this, none can they fathom.
But now, we no longer need fear
For microarrays are here;
To wipe our frowns from across the mile,
And tackle lymphomas with a smile!!
Journal of Clinical Pathology, Volume 60(7), July
2007, p 739