ANATOMIC PATHOLOGY

 

Immunophenotypic analysis of inflammatory breast cancers: identification of an inflammatory signature

Charafe-Jauffret E, Tarpin C, Bardou VJ, Bertucci F, Ginestier C, Braud AC, Puig B, Geneix J, Hassoun J, Birnbaum D, Jacquemier J, Viens P.

Inflammatory breast cancer (IBC) is a rare but very aggressive form of breast cancer. Its definition is based on clinical criteria, but a molecular definition could be useful when data are incomplete or features are missing. Recently, the identification of overexpression of E-cadherin in IBC has improved understanding of the molecular basis of this disease. Consequently, the aim of this study was to try to determine an immunophenotypic 'signature' of IBC. A series of 80 cases of IBC were compared with 552 non-IBC control cases and a model was elaborated to evaluate the probability of an inflammatory carcinoma being present in any clinical situation. Tissue microarrays (TMAs) were used to determine the immunohistochemical profile of eight proteins including E-cadherin, EGFR, oestrogen and progesterone receptor (ER and PR), MIB1, ERBB2, MUC1, and P53. All the parameters tested were differentially expressed between IBC and control cases in univariate analysis (p < 0.001). The five variables that were significantly associated with IBC in multivariate analysis were E - cadherin >/= 300 [HR = 5.64 (2.92-10.87)], ER negative [HR = 3.00 (1.67-5.51)], MIB1 > 20 [HR = 3.54 (1.87-6.71)], MUC1 cytoplasmic staining [HR = 2.72 (1.49-4.96)], and ERBB2 positive 2+ or 3+ [HR = 2.46 (1.26-4.78)]. The probability that a breast cancer with this full phenotype at diagnosis was an IBC was 90.5%. If any one of the five parameters was missing, this probability dropped to 75% and was less than 50% when one, two, or three parameters were present. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) of patients with IBC were not significantly different from those of the non-IBC control group that expressed four or five parameters (nIBC-1), but this nIBC-1 control group had a significantly worse outcome than the non-IBC control group (nIBC-2) with only 0-3 parameters (p=0.0049 for OS and p < 0.0001 for DFS). In conclusion, an immunophenotypic signature was suggested for IBC. This could help to determine the worst cases, independent of clinical criteria.

J Pathol. 202(3): 265-73 2004

Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy

Epstein JI.

The diagnosis of limited adenocarcinoma of the prostate is one of the more difficult challenges in surgical pathology. This paper highlights the methodological approach to diagnosing limited cancer, based on a constellation of features more commonly present in adenocarcinoma than benign glands. In assessing small foci of atypical glands on needle biopsy, one looks for differences between the benign glands and the atypical glands in terms of nuclear features, cytoplasmic features, and intraluminal contents. Only a few features, such as glomerulations, mucinous fibroplasia (collagenous micronodules), and perineural invasion are diagnostic in and of themselves for prostate cancer. Immunohistochemistry may be a useful adjunct in the diagnosis of limited adenocarcinoma of the prostate, although as with any immunohistochemical studies, there are problems with both sensitivity and specificity. Basal cell markers, such as high molecular weight cytokeratin and more recently, p63, highlight basal cells found in benign glands, yet are absent in adenocarcinoma of the prostate. However, not all benign glands label uniformly with basal cell markers. Certain mimickers of adenocarcinoma of the prostate are even less frequently labeled uniformly with these stains. Consequently, negative staining in a small focus of atypical glands for basal cell markers is not diagnostic of adenocarcinoma of the prostate. More recently, a marker has been identified that relatively selectively labels adenocarcinoma of the prostate. AMACR will label the cytoplasm of approximately 80% of limited adenocarcinoma of the prostate cases on needle biopsy. In positive cases, not all of the glands will be positive and those that are positive are often not intensely positive. Certain variants of adenocarcinoma of the prostate that are a little more difficult to recognize, such as foamy glands adenocarcinoma, pseudohyperplastic adenocarcinoma, and atrophic adenocarcinoma, are labeled with AMACR in only approximately 60-70% of cases. In addition to problems with sensitivity, AMACR is not entirely specific for adenocarcinoma, and will label almost all cases of high-grade prostatic intraepithelial neoplasia, some foci of adenosis, and even some entirely benign glands. Finally, this paper describes the significance of atypical or suspicious prostate needle biopsies, and how to report the key diagnostic and prognostic information on needle biopsy.

Modern Pathology 17, 307-315, 2004

 

Proximal small-bowel mucosal villous intraepithelial lymphocytes

                                                                N S Goldstein

Small-bowel biopsies are routinely obtained from adult patients as a screening tool to evaluate the possibility of gluten sensitivity (GS). Previous morphological criteria of GS including completely flattened villi are usually absent. In the context of screening for GS, an altered distribution density pattern of villous intraepithelial lymphocytes (IELs) is probably the most sensitive morphological feature to suggest the possibility of GS and prompt the initiation of further medical evaluation. Altered villous IEL density distribution is a more sensitive screening feature than villous IEL counts. With increased small-bowel GS screening biopsies, occasional adults without GS with complete villous flattening and numerous villous IELs are encountered. These patients are usually incorrectly diagnosed with GS. However, they do not respond to a gluten-free diet and slowly improve over months.

Histopathology 44: 199-205, 2004

 

Experience With an Automated Microwave-Assisted Rapid Tissue Processing Method Validation of Histologic Quality and Impact on the Timeliness of Diagnostic Surgical Pathology

Azorides R. Morales, MD, Mehdi Nassiri, MD, Rima Kanhoush, MD, Vladimir Vincek, MD, PhD, and Mehrdad Nadji, MD

Authors studied the effect of a fully automated microwave-assisted rapid tissue processor (RTP) on histologic examination and on the turnaround time for surgical pathology reports. A quality assurance program reviewed the histologic sections obtained by the rapid processing method for the last 3 calendar years. In addition, the histologic results from this method were compared blindly with those obtained from the conventional overnight tissue processing (CTP) method by 9 pathologists with different levels of experience. The surgical pathology turnaround times for 1 year of use of the RTP were compared with the last year for CTP. We found that the RTP reproducibly yielded histologic material comparable in quality to CTP. The turnaround time for surgical pathology reports was improved substantially, and, in particular, same-day reporting was achieved in approximately 55% of cases compared with less than 1% before use of the RTP. Moreover, use of the RTP enhanced safety by eliminating formalin and xylene from the procedure.

Am J Clin Pathol121: 528-536, 2004

A review of the emergence of Plasmodium falciparum-dominated malaria in irrigated areas of the Thar Desert, India.

Tyagi BK.

Recently, there has been a resurgence of malaria in several parts of India, and the Thar Desert in north-western India, is currently suffering from the impact of repeated annual epidemics. Nearly all malaria epidemics in the Thar Desert have come about with the progression of canal-irrigation work, particularly the massive Indira Gandhi Nahar Pariyojana (IGNP). Therefore, the Thar Desert provides an excellent model for understanding the underlying factors responsible for the exacerbation of malaria, pathways of evolution of the epidemics, succession in anopheline fauna, changes in the vector breeding and feeding preferences and, most importantly, the possible repercussions of mismanagement of irrigation systems. Before the initiation of canalized irrigation only Anopheles stephensi, breeding exclusively in household and community-based underground water reservoirs, and transmitting malaria at a low level, was prevalent in the interior of the Thar Desert. Since the 1980s, extensive irrigation with water from three different canal systems has altered the desert physiography, vector preponderance, distribution and vectorial capacity, whilst triggering the emergence of Plasmodium falciparum-dominated malaria in the virgin levees of the Thar Desert. The major objective of bringing the Himalayan waters to the xeric environment of the Thar was to transform it into verdure through growing irrigation intensive crops like paddy, groundnut, cotton, mustard, wheat and sugarcane, besides providing drinking water to the desert dwellers. The change in crop pattern, retention of high surface moisture, and excessive canalisation rife with mismanagement of irrigation water have attracted several anophelines, including Anopheles culicifacies, which were earlier unknown in the desert. Thus, A. culicifacies has penetrated into the interior of the Thar Desert, along with irrigation and is now established in vast areas covered by the IGNP project. The distribution of P. falciparum dominated malaria in the Thar Desert is more or less synchronous with the spread of IGNP related irrigated agriculture and of A. culicifacies.

Acta Trop 89(2): 227-39,2004

MICROBIOLOGY

 

Comparison of six biological markers for the diagnosis of tuberculous pleuritis

Hiraki A, Aoe K, Eda R, Maeda T, Murakami T, Sugi K, Takeyama H.

Authors sought a marker to differentiate tuberculous pleural effusions from nontuberculous pleural effusions, which otherwise can be difficult. PATIENTS: Authors studied 55 patients with pleural effusions, 20 (36%) with tuberculous pleuritis and 35 (64%) with a nontuberculous etiology. Measurement and results: Pleural fluid levels of adenosine deaminase, interferon (INF)-gamma, interleukin (IL)-12p40, IL-18, immunosuppressive acidic protein, and soluble IL-2 receptors were measured and were subjected to receiver operating characteristic analysis. INF-gamma had the greatest sensitivity and specificity for tuberculous pleuritis among the six biological markers studied.

CONCLUSION: The determination of INF-gamma levels in pleural fluid is the most informative in the diagnosis of tuberculous effusion.

Chest 125(3): 987-9, 2004

Clinical and laboratory observations of tuberculosis at a Mumbai (India) clinic

D Gothi, J M Joshi

Objectives: To study the positivity of sputum acid fast bacilli (AFB) smears in patients with pulmonary tuberculosis using 24 hour sputum collection. To detect HIV seropositivity in patients suffering from tuberculosis, and to analyse the pattern of tuberculosis disease in this subgroup. To determine the outcome of patients treated with directly observed therapy.

Setting: The tuberculosis referral unit of a tertiary care hospital.

Design: A total of 893 consecutive patients with tuberculosis, diagnosed between 1 November 2000 and 30 September 2002, were included in the study. An HIV test was performed in all patients, with adequate counselling and informed consent. Treatment was prescribed as per World Health Organisation treatment categories.

Results: Out of 893 patients with tuberculosis, 695 had pulmonary tuberculosis and 198 had extrapulmonary tuberculosis. Out of the 695 pulmonary tuberculosis patients, 673 (96.8%) were sputum smear AFB positive. Overall, 71 patients (8.0%) were HIV positive. The pattern of tuberculosis was the same in HIV seropositive and seronegative patients. Treatment outcome could be analysed in 112 out of 150 patients: 78 patients (70%) were declared cured or completed treatment.

Conclusions: Sputum smear AFB could be a very sensitive test when a large quantity of sputum is used. The presence of HIV coinfection does not alter the clinical presentation. Only 70% of patients treated were cured/completed treatment, in spite of a strict directly observed therapy.

Postgrad Med J 80:97100, 2004

 

The diagnosis of tuberculosis: what's old, what's new

                                                                  Schluger NW.

The approach to the diagnosis of both active tuberculosis and latent infection has changed very little in the past several decades. For active disease, sputum smears with or without chest radiographs to aid in diagnostic accuracy, form the cornerstone of the diagnostic approach in many high-burden countries. These tests usually are supplemented by cultures when resources permit. The diagnosis of latent infection still relies on the use of the tuberculin skin test using purified protein derivative. The current global tuberculosis epidemic, which features large numbers of patients with human immunodeficiency virus infection and increasing rates of multidrug-resistant tuberculosis, makes accurate and rapid diagnosis of tuberculosis more urgent than ever before. Currently available technologies, most involving techniques of DNA amplification, can substantially improve the accuracy of the diagnosis of tuberculosis, although the use of such assays has been sharply limited because of concerns about cost. However, economic analyses suggest that these assays can be cost effective if they lead to sharp reductions in transmission through earlier treatment of infectious cases.

Semin Respir Infect. 18(4): 241-8, Dec. 2003

Bird flu (avian influenza)

Bird flu is an infection of birds caused by type A strains of the influenza virus. According to the Centers for Disease Control and Prevention (CDC), type A influenza virus can infect several species of animals, including birds, pigs and horses. Influenza viruses that infect birds are called avian influenza viruses.

Health experts once thought that avian flu could only infect birds and animals. But several cases of human infections have been reported since 1997, including in Thailand and Vietnam in 2004.

According to the CDC, avian influenza virus usually doesn't affect wild birds. But it can make domesticated birds, such as chickens and turkeys, very sick and often kills them. Avian flu is transmitted to humans by direct contact with the droppings of an infected bird. In humans, avian flu is typically severe and fatal.

Signs and symptoms may include:

• Influenza-like symptoms, such as fever, cough, sore throat and muscle aches
• Eye infection (conjunctivitis)
• Pneumonia
• Acute respiratory distress syndrome

At this time, there's no evidence that avian flu can spread from one person to another. However, there's concern that if someone acquires avian influenza at the same time as human influenza, the avian virus may mutate and develop the ability to spread from person to person, leading to a human epidemic.

Treatment of bird flu in humans may include antiviral medications. Current influenza vaccines don't protect against avian influenza strains. But such vaccines may be developed.

By Mayo Clinic staff, February 9, 2004

 

BOTTOM LINE

                   Popular Pathology Requisitions: The Hidden Meaning

T Rajalakshmi

Department of Pathology, St. Johns Medical College , Bangalore 560 034

 rajtiru@hotmail.com

1. For urgent processing: pleeeaase, the boss is breathing down my neck, and I havent the faintest clue what this is, save me!
2. Diffuse mildly enlarged thyroid: I didnt feel it, the boss did.
3. Ill defined nodularity in the upper, outer quadrant of the right breast for FNAC: I saw you joblessly loitering in the canteen, so Im sending some business your way; enjoy the hide and seek!
4. 22 year old woman with vaginal bleeding every 28 days, to rule out endometrial pathology: now, I am jobless.
5. FNAC benign, frozen section to rule out malignancy: buddy, I dont trust you.
6. Please issue duplicate slides for further management: I still dont trust you.
7. 2500 ml of urine from a dipsomaniac, to look for malignant cells: I didnt know how to discard it.
8. 5 x 0.5 cm axillary node for FNAC, patient is HIV positive: I dont have the nerve to biopsy it.
9. Please look for Helicobacter pylori: the consumer forum president has become flatulent; scopys normal, tummys no trouble; dig into that haystack, find a needle, and save us all from the ordeal.
10. Request for a complete necropsy on a patient who died 420 days after an aspirate from a lipomatous swelling on his right little toe: we dont know why he died, but were hoping to pin the blame on you.

J Clin Pathol 57:368 April 2004