September 2005
ANATOMIC PATHOLOGY
Importance of Specimen Size in Accurate
Needle Liver Biopsy Evaluation of Patients With
Chronic Hepatitis C
, ,
Background & Aims: In patients with chronic hepatitis C (CHC), percutaneous needle liver biopsy examination establishes the severity of necroinflammatory activity and fibrosis, thus guiding treatment decisions. Optimal biopsy specimen size remains controversial. We sought to determine how varying lengths of biopsy specimens influence the grading and staging of CHC.
Methods: We used 100 liver biopsy specimens from patients with CHC. The slides were evaluated blindly using the METAVIR scoring system, after being covered with paper, so that only specific specimen lengths (5 mm, 10 mm, 15 mm, and ≥20 mm) were visible. In each case, the scores obtained with biopsies 5 mm, 10 mm, or 15 mm long were compared with the scores at 20 mm or greater by weighted κ statistics (κ of >.75 signified excellent agreement). A subset of specimens 20 mm or greater was selected for a blinded repeat scoring to assess intraobserver agreement. The κ statistics for the designated features and lengths were compared using analysis of variance.
Results: In assessing the stage of fibrosis, the weighted κ statistics for agreement with the 20-mm or greater score at 5 mm, 10 mm, and 15 mm were .75, .85, and .92, respectively. In assessing the histologic activity score, the corresponding figures were .73, .81, and .77, respectively. Average κ statistic comparisons showed that intraobserver agreement was significantly better than agreement between the 20-mm or greater scores and those at shorter lengths; the 5-mm κ scores were significantly lower than the others; and there was no significant difference between the 10-mm and 15-mm κ scores.
Conclusions: Liver biopsy specimens measuring at least 10 mm usually reflect the grade and stage of CHC reliably. Relatively little improvement in diagnostic accuracy is obtained with longer specimens.
Clinical Gastroenterology and Hepatology, Volume 3, Issue 9, Pages 930-935, September 2005
Sentinel Lymph Node Status Predicts Melanoma Recurrence
Senior investigator Dr. Susan M. Swetter of
She added: "46% of SLN positive patients developed melanoma recurrence with a median time to recurrence of 8 months, highlighting the effect of SLN status on overall prognosis." In total, 14% of the 221 SLN-negative patients had recurrences at a median of 17 months.
Dr. Swetter and colleagues reached these conclusions following a study of 274 patients with primary melanoma seen between 1997 and 2004. Melanomas were located on the trunk (38%) and the extremities (40%) but were less common on the head and neck (22%). All patients underwent standard wide local excision of their primary tumors and SLE biopsy.
SLN-positivity was associated with American Joint Committee on Cancer tumor classification, location on the trunk and the presence of ulceration.
The researchers conclude that their findings are comparable to those of similar series in the literature and "confirm the accuracy and prognosis value of SLN biopsy in cutaneous melanoma and the low rate of regional nodal recurrence for SLN-negative patients."
Arch Dermatol 2005;141:1016-1022.
Melanocytic nevi are
associated with neurofibromas in neurofibromatosis,
type I, but not sporadic neurofibromas. A study of 226 cases.
Background: Neurofibromatosis, type 1, is associated with cutaneous melanin pigmentation, but an association with ordinary melanocytic nevi has not been described.
Methods: This retrospective case-control study was designed to see if neurofibromas in patients with neurofibromatosis, type 1 (NF-1) differ from sporadic neurofibromas (SN) in their incidence of associated melanocytic nevi and other histologic features. Slides from 114 NF-1 were compared with 112 SN and 300 intradermal melanocytic nevi (IDN).
Results: Small lentiginous melanocytic nevi were identified over 13 NF-1 (11%) but no SN (P = 0.0002). Compared with other NF-1, NF-1 with nevi were more frequently associated with melanocytic hyperplasia, giant melanosomes and diffuse neurofibroma (P < 0.03). Compared with SN, NF-1 were also more frequently associated with melanocytic hyperplasia, lentigo simplex-like changes, diffuse neurofibroma and plexiform neurofibroma (P < 0.001). Sebaceous hyperplasia (14%), dermal elastosis (9%), lipomatous change (8%), epithelial cysts (4%) and keratin granulomas or folliculitis (3%) were not significantly different in prevalence between NF-1, SN and the control group of IDN.
Conclusions: This study suggests that
there is a difference in the potential for melanocytic
proliferation in NF-1 compared with SN. NF-1, SN and IDN are associated with a
similar range of incidental histologic changes.
J Cutan Pathol. 2005 Sep;32(8):523-32.
CYTOLOGY
Evaluating Metastatic
Carcinoma to the Adrenal: Utility of Fine Needle Aspiration Cytology
Kindelberger, David W. , Cibas, Edmund S.
Fine needle aspiration (FNA) cytology is a powerful tool for the evaluation of adrenal masses. The method is safe and offers high sensitivity, specificity, and diagnostic accuracy, particularly in cases of metastatic disease to the adrenals. Once it has been determined that the mass lesion is metastatic, the clinical history, lesion cytomorphology, and-if needed-immunocytochemistry and other ancillary techniques can be used to identify the primary sites, even when clinically and radiographically occult. Continued improvements in image-guided FNA methods will enhance this useful technique for the initial evaluation of suspected metastatic disease involving the adrenals.
Pathology Case Reviews. 10(5):257-262,
September/October 2005.
Cervical cytology testing in teens
Moscicki A. B.
Although cervical cytology screening programs
have dramatically decreased rates of invasive cancer in developed countries,
most guidelines in the
Curr Opin Obstet Gynecol. 2005 Oct;
17(5):471-5.
MICROBIOLOGY
Diagnosis of extrapulmonary tuberculosis by smear, culture, and PCR
using universal sample processing technology
Chakravorty S, Sen
MK, Tyagi JS.
Definitive and rapid diagnosis of extrapulmonary
tuberculosis is challenging since conventional techniques have limitations.
Authors have developed a universal sample processing (USP) technology for
detecting mycobacteria in clinical specimens. In this
study, this technology was evaluated blindly on 99 extrapulmonary
specimens collected from 87 patients. USP-processed specimens were submitted to
smear microscopy for detection of acid-fast bacilli (AFB), culture, and two PCR
tests targeting devR (Rv3133c) and IS6110 gene
sequences. On the basis of clinical characteristics, histology and cytology,
conventional microbiology results, and response to antitubercular
therapy, 68 patients were diagnosed with tuberculosis. Although USP smear and
culture were significantly superior to conventional microbiology, which was not
optimized (P < 0.0001), these approaches fell short
of PCR tests (P < 0.0001). The low yields by smear and culture are
attributed to the paucibacillary load in the
specimens. The highest sensitivity in PCR was achieved when devR
and IS6110 test results were combined; the sensitivity and specificity values
were 83 and 93.8%, 87.5 and 100%, and 66.7 and 75%, respectively, in pleural
fluid, needle-biopsied pleural tissue, and lymph node
specimens. In conclusion, the application of USP technology, together with clinicopathological characteristics, promises to improve
the accuracy and confidence of extrapulmonary
tuberculosis diagnosis.
J Clin Microbiol. 2005 Sep;43(9):4357-62.
Tuberculous Skin Ulcer
Following Needle-Prick Injury in a Health Care Professional
A Chandramukhi, MV Manjunath, HB Veenakumari, Anita Mahadevan, G Shivaraja,
Cutaneous inoculation tuberculosis (TB), a rare disease, usually occurs in
individuals whose occupation or environment place them at a risk of exposure to
tubercle bacilli. The prosector's wart, acquired by
pathologists from tuberculous cadavers is the most
notable for of primary inoculation tuberculosis. Here
authors report an unusual case of cutaneous
inoculation tuberculosis acquired by a physician working in a TB sanatorium.
Case Report: A 25 year old junior medical doctor presented with a
history of chronic, slightly painful non-healing ulcer of 1 centimetre
diameter, with irregular indurated margins on the
left middle finger (lateral aspect) over proximal interphalangeal
joint, of three months duration with no other contributory symptoms or past
history of tuberculosis or Hansen's disease in him or other family members. He
had suffered a needle-stick injury at the site of the lesion while performing a
pleural tap in a known TB patient, 2 weeks before the ulcer developed. He was
vaccinated with BCG during childhood. The patient had received antibiotic for
two months with no response. On examination the ulcer was confined to the skin
and subcutaneous tissue with no bone or lymphnode
involvement. Chest X-ray was normal and blood profiles including ESR were
within normal limits. Mantoux test performed with 5
tuberculin units of PPDS, through
intradermal route, was negative. He was nonreactive for HIV-1 and 2 antibodies by indirect ELISA.
Surgical debridement of the wound was attempted to
promote healing. Swabs from the ulcer showed no acidfast
bacilli by Ziehl-Neelsen's staining and routine
aerobic bacterial culture yielded normal skin flora. Fungal culture did not
yield any growth. The histopathological examination
of a biopsy taken from the ulcer edge showed a thickened, hyperkeratotic
epidermis bordering the ulcer edge. The underlying reticular dermis had a
multiple epithelioid granulomas
with Langerhans giant cells along the dermal
papillae, some with central zone of caseous necrosis
(Figs. 1 and 2). The epithelioid cell clusters were
rimmed by a thin cuff of lymphoplasmacytic cells.
Many thick-walled vessels were seen expanding the papillary dermis reflecting
the chronicity ulcer. Neither acid-fast bacilli by Ziehl-Neelsen stain nor fungal elements by periodic acid
Schiff and Gomori's methenamine
silver stains could be demonstrated in the tissue sections. Subsequent to biopsy,
a repeat swab specimen from the lesion was taken after three days for mycobacterial culture. Two weeks later, BACTEC 460TB radiometirc method yielded growth of mycobacteria
belonging to the Mycobacterium tuberculosis complex, which was
demonstrated by the inhibition of growth in BACTEC 460 TB NAP (para-nitro alpha-acetyl amino beta-hydroxy
propiophenone) test.3 Lowenstein Jensen (LJ)
medium did not yield any growth after 8 weeks. The isolate was found to be
sensitive to streptomycin (2mg/l), isoniazid (0.1 g/ml), rifampicin
(2.0 g/ml) and ethambutol (2.5 g/ml). Serum of the
subject was negative for anti-lipoarabinomannan (LAM)
antibodies and mycobacterial immune-complexes by
indirect ELISA. The patient was administered shortcourse
anti-tubercular therapy with isoniazid, rifampicin, ethambutol and pyrazinamide for two months followed by isoniazid
and rifampicin for four months. There was a dramatic
response in two weeks with complete healing of the ulcer. Thus, the combined
surgical-medical therapy resulted in more rapid healing of the skin lesion.
Positive BACTEC radiometric culture and dramatic response to anti-tuberculous therapy established that the pathogenic
organism belonged to Mycobacterium tuberculosis complex.
JAPI, Vol. 53,
September 2005
CLINICAL PATHOLOGY
Bombay
James S. O'Donnell,
Thomas A. J. McKinnon et al
ABO blood group is an important determinant of
plasma von Willebrand factor antigen (VWF:Ag) levels, with lower levels
in group O. Previous reports have suggested that ABO(H)
sugars affect the susceptibility of VWF to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 repeats-13) cleavage. To further
test this hypothesis, we collected plasma from individuals with the
rare
Blood,
Implications of the new definition of
myocardial infarction
C-K Wong and H D White
The new definition of acute myocardial infarction is based primarily on raised troponin levels because of the sensitivity and specificity of these markers and their correlation with the pathophysiology of acute coronary syndromes with plaque fissuring or rupture and embolisation of platelets causing myocyte necrosis. Raised troponin levels are associated with increased risks of death and recurrent myocardial infarction. Greater treatment benefit with low molecular weight heparin, IIb/IIIa antagonists and revascularisation is seen when troponin levels are raised. There are many implications for patients and society of the new definition including changes in insurability and ability to continue certain occupations. Many more patients, who would previously been diagnosed as having unstable angina, will now be diagnosed as having had an acute myocardial infarction. In addition case fatality rates will fall and comparison with previous epidemiological studies using the old definition will be problematic. However, the new definition may result in greater use of evidence based therapies with improved patient outcomes and decreased community death rates.
Definition of myocardial
infarction based on the European Society of Cardiology and
Criteria for acute, evolving, or recent myocardial infarction
Either one of the following criteria satisfies the diagnosis for an acute, evolving, or recent myocardial infarction:
- Typical rise and gradual fall (troponin) or more rapid rise and fall (CKMB) of biochemical markers of myocardial necrosis with at least one of the following:
ischaemic symptoms;
development of pathological Q waves on the ECG;
ECG changes indicative of ischaemia (ST segment elevation or depression); or coronary artery intervention (for example, coronary angioplasty).
- Abnormal findings of an acute myocardial infarction
Criteria for established myocardial infarction
Any one of the following criteria satisfies the diagnosis for established myocardial infarction:
- Development of new pathological Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalised, depending on the length of time that has passed since the infarct developed.
- Abnormal findings of a healed or healing myocardial infarction.
Postgraduate Medical
Journal 2005;81:552-555
BOTTOM LINE
Researchers find human fat cells produce
C-reactive protein
HOUSTON, TX -- September 16, 2005 -- Researchers at The University of Texas
M.D. Anderson Cancer Center and The University of Texas Health Science Center
at Houston have found that human fat cells produce a protein that is linked to
both inflammation and an increased risk of heart disease and stroke.
They say the discovery, reported in Journal of the American College of Cardiology, goes a long way to explain why people who are overweight generally have higher levels of the molecule, known as C-reactive protein (CRP), which is now used diagnostically to predict future cardiovascular events.
And they also report some good news: the researchers found that aspirin and statin drugs, now commonly used to treat heart diseases, effectively damp down production of CRP from fat cells.
This study is the first to show how body fat participates in the inflammatory process that leads to cardiovascular disease, but also demonstrates that this process can be blocked by drugs now on the market. Adipose tissue has been lately regarded as a separate body organ that produce a number of different biologically active molecules -- such as cytokine proteins that are associated with inflammation, and the hormone resistin, which is linked to insulin resistance and the development of type two diabetes.
Even if they are healthy, people with more
adipose tissue also tend to have higher levels of CRP. Previous research,
however, had only found CRP to be produced in liver tissue, although Drs. Yeh, Willerson and
"But that didn't explain obesity's
connection to high levels of CRP and it also was not clear why CRP is higher in
patients who have metabolic disorders," Dr. Yeh
said.
So the research team decided to see whether fat cells themselves could be
stimulated by inflammatory cytokines or resistin to
produce CRP. To help find out, plastic surgery patients at M.D. Anderson
donated adipose tissue that would have been discarded, and the research team
then isolated fat cells, cultured them and stimulated them under a number of
different conditions.
They found the cells produced cytokines that resulted in inflammation and that this process triggered production of high levels of C-reactive proteins.
The researchers also discovered that resistin, the hormone associated with diabetes and insulin
resistance, could stimulate production of CRP proteins. "And this is
interesting because it is known that resistin is
itself produced by fat cells," Dr. Yeh said.
"We know that patients with metabolic syndromes have higher levels of CRPs, as well as a higher risk of developing heart disease
and stroke, but no one understands why that is," Yeh
said. "If fat cells by themselves produce inflammatory signals that
trigger cells to produce CRPs, and if CRPs also produce biological effects on vascular walls,
that could explain the higher risk of cardiovascular disease."
The investigators then solved the other part of
the puzzle -- why it is that aspirin, statin drugs
and an agent known as troglitazone, used to treat
diabetes, can reduce CRP levels. They exposed the cultured fat cells that were
producing high levels of CRPs to these drugs, and
found production of the proteins declined. "We knew from studying patients
that these drugs can reduce C-reactive proteins, but now we have direct proof
of their benefit."
Even as the CRP picture becomes clearer, there is still much that is not known,
the researchers say, including the reason why fat tissue produces an
inflammatory response, and just precisely how CRP participates in that process.
"Inflammation is a very complicated
phenomenon, but at least we now have a few more clues as to what it does and
how the damage it produces can be prevented," Dr. Yeh
noted.
SOURCE: The University of