ANATOMIC PATHOLOGY

 

The value of postmortem examination in cases of metastasis of unknown origin-20-year retrospective data from a tertiary care center

Al-Brahim N, Ross C, Carter B, Chorneyko K.

Metastasis of unknown origin (MUO) is a diagnostic challenge in clinical practice even with the state of current advanced diagnostic technology. To evaluate the value of autopsy in determining the primary site of MUO, this study reviewed the Hamilton experience-over the last 20 years-with patients autopsied with clinical diagnosis of MUO. Methods: All autopsy diagnoses from cases performed at the Hamilton Health Sciences Center and St Joseph's Healthcare from 1980 to 2000 were reviewed. Fifty-three cases of MUO were identified (MUO was defined as a patient with pathological and/or radiological diagnosis of a metastatic tumor for which the primary site of malignancy was unknown). The clinical history and gross and microscopic diagnoses for these cases were reviewed. Results: There were 31 men (58.5%) and 22 women (41.5%) in the study. Their mean age was 66 years. Pathological diagnoses at autopsy were adenocarcinoma (n = 37), small cell carcinoma (n = 6), anaplastic carcinoma (n = 3), and undifferentiated carcinoma (n = 3). Primary tumors were identified in 27 patients (51%), most commonly in the lung (n = 8), large bowel (n = 6), and pancreas (n = 4). Histochemical and immunohistochemical stains were helpful in reaching the diagnosis of a primary tumor in 4 of 27 cases. Conclusions: The following were observed: (1) in this series, autopsy was helpful in establishing the diagnosis of a primary tumor in 51% of the cases, reaffirming the value of postmortem examination in these instances; (2) adenocarcinoma was the most frequent tumor presenting as MUO; (3) the lung and the large bowel were the most frequent sites for primary tumors; and (4) careful gross and histological examinations remain the most important tools in identifying the primary site.

 Ann Diagn Pathol. 9(2): 77-80, 2005

 

 

Immunohistochemical Analysis of c-Myc, c-Jun and Estrogen Receptor in Normal, Hyperplastic and Neoplastic Endometrium

Bircan S, Ensari A, Ozturk S et al

Aim: To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ERalpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.

Pathol Oncol Res. 11(1): 32-9, 2005

 

 

Histologic Dating of the Endometrium: Accuracy, Reproducibility, and Practical Value

Fadare, Oluwole , Zheng, Wenxin

The continued use of the endometrial biopsy for the diagnosis of luteal phase defects (LPDs) and in the general evaluation of the infertile couple is based largely on tradition, the absence of a clearly superior diagnostic modality, the absence of studies that have either validated or repudiated its efficacy with certainty, its ability to assess the endometrial response irrespective of endogenous progesterone levels, its ability to monitor the endometrial response to hormonal therapy in fertility treatments, and, finally, its ability to exclude other intrinsic endometrial anomalies that may be detrimental to the implantation of the conceptus, such as chronic endometritis or neoplasia. However, the intra- and interobserver variability inherent in dating the product of the endometrial biopsy-the endometrium-has led to the current situation, in which, in approximately 20% of cases, variability attributed to the pathologist alone is determinant of whether a given biopsy in "in phase" or out of phase (ie, an assigned postovulatory date that is at least 2 days behind the chronologic date). Thus, studies that clearly delineate which histologic parameters serve as the greatest source of disagreement for pathologists provide a valuable framework for further refinement of the criteria for endometrial dating. Meanwhile, continued use of the criteria of Noyes et al for endometrial dating is recommended until more precise modalities for assessing the adequacy of endometrial maturation are available.

Advances in Anatomic Pathology. 12(2):39-46, 2005.

 

Indications for pancreatic biopsy
[Article in German]

Lohr JM, Kloppel G.
II. Medizinische Universitatsklinik Mannheim

Pancreatic biopsy is an invasive diagnostic method that is only performed when all other diagnostic measures for establishing the diagnosis of a tumorous lesion of the pancreas have failed. Because of the advances in modern imaging techniques, fine needle biopsy of the pancreas guided by ultrasonography, computer tomography or endosonography has become a reliable method that allows the diagnosis of ductal adenocarcinoma or any of the other, rarer pancreatic tumors with high sensitivity and specificity. Complications are rare, particularly with the endosonographically-guided biopsy. A new biopsy indication is the demonstration of certain markers or gene mutations that are needed for the initiation of special treatments, e.g. EGFR-Cetuximab.

Pathologe. 26(1):67-72,2005

 

Fine-needle aspiration cytology in parotid masses: our experience in Canterbury, New Zealand

Riley N, Allison R, Stevenson S.

The purpose of the present study was to assess the value of fine-needle aspiration cytology (FNAC) in parotid masses. Methods: A retrospective review was carried out of FNAC results in parotid masses and the findings compared to histology on subsequent parotidectomy. Results: One hundred parotid masses were investigated. Eighty-six had the cytological diagnosis confirmed by histology, 14 had a different diagnosis at histology. In two of these 14, a malignancy was found where a non-neoplastic condition had been detected. In the other 12, various non-malignant lesions were wrongly identified by FNAC. Squamous cell carcinoma was the commonest parotid malignancy in the present study. Conclusion: Fine-needle aspiration cytology was found to be an effective diagnostic tool in the hands of experienced pathologists at Christchurch Hospital, NZ. 

ANZ J Surg. 75(3):144-6,2005

 

CLINICAL PATHOLOGY

 

Troponin I Elevations May Help Predict All-Cause Mortality, Cardiovascular Complications 

Laurie Barclay

Mild transient elevation of troponin I with a cut-off value of 0.1 ng/mL is associated with an increase in all-cause mortality and cardiovascular complications, according to the results of a case-control study published in the April issue of the Archives of Pathology and Laboratory Medicine.

The prognostic value of mild elevation of cardiac-specific troponin I (cTnI) levels is poorly defined, which can make interpretation of such an elevation difficult. There are limited data on the prognostic value of transient mild elevation of cTnI levels (<1.5 ng/mL) in the general patient population.

Of the total 118 patients enrolled, 10 patients were subsequently excluded due to recent surgery, cardiopulmonary resuscitation, or chronically elevated cTnI levels. Of the remaining patients, 71 hospitalized for any cause and who had at least two subsequent transient cTnI measurements between 0.1 ng/mL and less than 1.5 ng/mL were compared with 37 matched control subjects with cTnI levels less than 0.1 ng/mL. In the overall cohort, mean age was 67.4 14.0 years; 35.6% were men; and average follow-up was 11.9 7.9 months. Control subjects were matched to cases for demographics, coronary artery disease risk factors, and reason for admission. Outcome measures were all-cause mortality and major cardiovascular end points, including cardiovascular mortality, myocardial infarction, and revascularization.

Compared with the control group, the case group had a significantly increased total event rate at 12, six, and three months (62.0% vs 24.3%, 59.2% vs 16.2%, and 47.9% vs 5.4%, respectively; P < .001). All-cause mortality at 12, six, and three months was higher in the cases than in the controls (43.7% vs 16.2%, 40.8% vs 8.1%, and 33.8% vs 0.0%, respectively; P = .005), as was the incidence of major cardiovascular end points (26.8% vs 8.1%, 26.8% vs 8.1%, and 21.1% vs 5.4%, respectively; P = .02).

Transient mild elevation of cTnI levels in hospitalized patients is associated with an increase in all-cause mortality and major cardiovascular complications. Such elevations of cTnI levels can be considered a marker for both all-cause and cardiovascular morbidity and mortality.

Possible study limitations include relatively small sample, lack of death certificates of patients who died outside the study institution, most follow-up based on hospital records from a single center, possible bias in selection of case and control subjects, and slightly worse renal function in the cases than in the controls.

Opposed to cases with mild elevation of cTnI level and abnormal cardiac imaging study results who had an increased risk of major cardiovascular end points and death, patients with normal cardiac imaging study results had the same risk as matched controls, suggesting that cardiac imaging can aid in further risk stratification of those cases.

Arch Pathol Lab Med 129:474-480, 2005

 

Urine diacetylspermine as a novel tumor marker
[Article in Japanese]

Yamaguchi K, Kaku T, Enjoji M et al

A urine tumor marker, diacetylspermine, was examined in patients with recurrent pancreato-biliary carcinoma, liver tumor, lung carcinoma and gynecologic malignancies. The urine marker increased together with recurrence, suggesting a recurrence monitoring marker at the outpatient ward. Regarding hepatocellular carcinoma, the sensitivity of the urine marker was as high as conventional markers such as AFP and PIVKA II. Synchronous examination of serum and urine markers showed a higher sensitivity than the single serum or urine marker for hepatocellular carcinoma. The sensitivity for non-advanced hepatocellular carcinoma was 50%, while that for advanced hepatocellular carcinoma was 83%. The urine marker may be useful to detect non-advanced hepatocellular carcinoma. The sensitivity for lung cancer was 83% and that for Stage I or II was 82%. Concerning uterine cervical tumor, the value of the urine marker increased with the grade of dysplasia. The sensitivity for ovarian carcinoma was 100%, while that for benign ovarian tumor was 0%. These findings suggest that urine diacetylspermine is a useful tumor marker in hepatocellular carcinoma, lung cancer and gynecologic malignancy as well as pancreatobiliary carcinoma.

 Rinsho Byori. 53(2):130-5,2005

 

Chronic hepatitis C with normal level of alanine-aminotransferase

[Article in Italian]

Rossi G.

Persistently normal levels of alanin-aminotransferase are often found in patients with chronic hepatitis C. The role of liver biopsy and the effectiveness of the antiviral therapy with peg-interferon and ribavirin in these patients are briefly discussed.

 Recenti Prog Med. 95(11):509-11, 2004

 

BOTTOM LINE

 Indian proposals to revalidate doctors get mixed reception

Ganapati Mudur

A proposal by Indias health minister that doctors should take exams every five years to keep themselves updated on medical advances and reregister to retain their licenses has triggered debate in the medical community.

The health minister, Anbumani Ramadoss, is a medical doctor, and his proposals are in line with recommendations first made by the Indian health ministry five years ago but which were never implemented. The United Kingdom has similar plans to revalidate its doctors. Due to take effect next month, these were postponed after the Shipman inquiry recommendations (BMJ 2005;330:271).

The fresh proposals in India prompted swift criticisms from medical associations there last week. But some doctors said a move to reregister doctors in India was "long overdue."

A statement from the Indian Medical Association said that it favoured voluntary programmes of continuing medical education instead and that the idea of a qualifying exam for doctors to reregister has "no logic." The association said that although the process of updating knowledge has no boundaries, an examination would require a syllabus and course material. Without well-defined course material, exams to test doctors would be "impractical," it said.

"We need to improve the quality of continuing medical education rather than force doctors into taking examinations," said Dr Krishan Aggarwal, president of the Delhi Medical Association. Continuing medical education in India is not subject to standards, and it is not known whether doctors attending such programmes benefit from them.

Doctors say it will take time for the medical community to get used to the idea of repeat registrations. "Its human nature. We cant expect doctors who are used to a particular system to embrace something like this in a hurry," said Dr Arun Agarwal, dean at the Maulana Azad Medical College in New Delhi and president of the Delhi Medical Council.

The Delhi Medical Council, which has 28 000 doctors on its registers, was the first medical body in India to make it mandatory for doctors to reapply for registration every five years. By July this year 3800 doctors will have applied for their second registrations. But the process requires no more than a declaration that the doctor has participated in 100 hours of continuing medical education.

Doctors in academic institutions have emphasised the need for structured continuing medical education that leads to credits. They say that India could borrow from Western countries, where each programme ends in tests for doctors to earn credits.

"But the first move should be to make continuing medical education mandatory," said Dr Sanjiv Lewin, associate professor of pediatrics at St Johns Medical College in Bangalore. "Today, a doctor whos got a degree and registration doesnt have to pick up a book or a journal ever again."

BMJ  330:748 (2 April),2005