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Ludwig Institute for Cancer Research and PowderMed Initiate A Phase I Clinical Trial for a Novel Therapeutic Cancer Vaccine

Phase I Clinical Trial of Therapeutic Cancer Vaccine Commences in New York, in Patients With Non-small Cell Lung Cancer (NSCLC), Using PowderMed's Novel DNA-on-Gold Technology

OXFORD, England, September 17, 2004 /PRNewswire/ -- PowderMed Ltd (PowderMed), a company focusing on the development of therapeutic DNA vaccines, in collaboration with its partner, the Ludwig Institute for Cancer Research (LICR), have announced that they have initiated a Phase I trial of a novel therapeutic DNA cancer vaccine that uses DNA encoding for the NY-ESO-1 tumour specific antigen and the Particle Mediated Epidermal Delivery (PMED(TM)) technology owned by PowderMed. The trial, being carried out at the Weill Medical College of Cornell University in New York, will be conducted in patients with non-small cell lung cancer (NSCLC) and will recruit up to 18 patients with NSCLC stages IIIA, IIIB or IV.

This clinical trial forms part of the Cancer Vaccine Collaboration (CVC), which is an innovative clinical research program designed and directed by LICR and the Cancer Research Institute in New York. DNA vaccines offer a promising new therapeutic intervention for a wide range of cancers. By stimulating the immune system to produce cytotoxic T-cells and antibodies specifically directed against cancer cells, these vaccines direct the immune system to attack and control or even remove the cancerous tissue. The therapeutic DNA vaccine being developed by PowderMed and LICR elicits an immune response that targets cells expressing the NY-ESO-1 cancer antigen on their surface. NY-ESO-1, discovered and patented by LICR, is expressed by many different types of human tumours and it is one of the most highly immunogenic tumour antigens discovered to date, eliciting both cellular and humoral immune responses, a combination that is best suited to attack tumours.

Such characteristics make vaccines based upon NY-ESO-1 potentially useful for treating a sizeable percentage of cancer sufferers. Dr Clive Dix, CEO of PowderMed, said: "When we launched PowderMed in May of this year we indicated that five of our programmes would enter clinical development before the end of 2005. This trial is our first step towards that commitment, but is also our first step in demonstrating why the PowderMed technology is ideal for cancer therapy." PowderMed's therapeutic vaccines use the company's proprietary PowderJect® DNA particle mediated epidermal delivery (PMED) technology, which uses DNA bound to microscopic gold particles that are propelled at high speed into the skin. PMED is particularly well suited for therapeutic vaccines, which require the induction of both humoral and cellular immunity. Commenting on the clinical trial, Dr. Eric Hoffman, the Director of LICR's Office of Clinical Trials Management, said: "The goal of this CVC trial is to evaluate the ability of NY-ESO-1 DNA formulated on gold particles to induce an antigen-specific immune response. We consider the PMED technology to have great potential as a means of safely and effectively delivering cancer antigens". Notes for Editors 1.

About PowderMed Ltd - www.powdermed.com PowderMed Ltd, a leader in the development of therapeutic DNA vaccines, based in Oxford, UK, was launched in May 2004 as a management spin out of the PowderJect therapeutic DNA vaccine programmes, previously owned by Chiron Vaccines. The Company has the rights to the PowderJect® DNA particle mediated epidermal delivery (PMED) technology which it plans to use, in the first instance, in the development of therapeutic vaccines in the areas of chronic viral diseases and cancer. PowderMed has five preclinical lead programmes targeting genital herpes, hepatitis B, genital warts, HIV/AIDS (partnered with GSK) and lung cancer (partnered with Ludwig Institute for Cancer Research). 2.

About the Ludwig Institute for Cancer Research - www.licr.org The Ludwig Institute for Cancer Research (LICR) is the largest international academic institute dedicated to understanding and controlling cancer. With ten Branches in seven countries, and numerous Affiliates and Clinical Trial Centers in many others, the scientific network that is LICR quite literally covers the globe. The uniqueness of LICR lies not only in its size and scale, but also in its philosophy and ability to drive its results from the laboratory into the clinic. LICR has developed an impressive portfolio of reagents, knowledge, expertise and intellectual property, and has also assembled the personnel, facilities, and practices necessary to patent, clinically evaluate, license, and thus translate, the most promising aspects of its own laboratory research into cancer therapies. 3. PowderJect® DNA particle mediated epidermal delivery (PMEDTM) technology Using the PowderJect device, DNA precipitated onto microscopic gold particles, is propelled by pressurised helium gas at near supersonic speeds into the epidermis. The microscopic gold particles (mean particle diameter 1 - 3 microns) are used as the carrier because they have the appropriate size and density needed to deliver the DNA directly into the immunologically active antigen presenting cells (APCs) of the epidermis. These cells have a mean diameter 20 microns and thus the microscopic gold can easily enter the cell.

Studies have shown that once inside the nuclei of APCs, the DNA elutes off the gold and becomes transcriptionally active, producing the encoded protein that when presented by the APCs to lymphocytes, triggers strong T-cell mediated immune responses. It is this ability of PMED to produce a robust and reproducible T-cell mediated immune response to a broad range of viral and cancer antigens, that provides PowderMed with its unique competitive advantage in the field of therapeutic vaccines. 4. Therapeutic vaccines Therapeutic vaccines are a new class of product, which harness the immune system in order to produce a therapeutic effect. The PowderJect technology has previously been tested in the clinic as a vaccine for prophylaxis against Hepatitis B but will be used by PowderMed in the development of therapeutic vaccines for chronic viral diseases and, in the present instance, cancer. 5. Non-Small Cell Lung Cancer Lung cancer is the leading cause of cancer-related deaths. There are 177,000 new cases of lung cancer per year in the United States. Despite continuous development of chemotherapeutic agents, the five-year survival of patients with lung cancer remains at only 13%. Over 80% of lung tumors are non-small cell lung cancer (NSCLC) and only 30% of patients with the diagnosis of NSCLC are surgical candidates.

The remaining 70% are considered unresectable due either to locally advanced (stages IIIA or IIIB) or metastatic (stage IV) disease. Thus, while surgery currently offers the only hope for cure, few patients are amenable to such treatment. While complete resection for early stage NSCLC is possible, patients nonetheless face a high rate of recurrence. The recurrence rate for stage I disease is as high as 40%. 6. A therapeutic vaccine targeting NY-ESO-1 PowderMed has produced a DNA Plasmid (pPJV7611), which encodes the NY-ESO-1 protein. PPJV7611 is precipitated onto the surface of gold particles 1 to 3 microM in diameter and will be administered to patients by particle mediated epidermal delivery (PMED). NY-ESO-1 antigen, which was discovered by LICR, is expressed in a range of human cancers, including melanoma, breast cancer, prostate cancer, lung cancer, ovarian cancer and bladder cancer. NY-ESO-1 shows restricted expression in normal tissues, with high-levels found only in the germ line cells in testis. Since germ line cells do not carry HLA molecules on their surface they cannot present antigens to T cells. To date, over 100 patients with NY-ESO-1 expressing tumors have received NY-ESO-1 vaccination using various formulations. This clinical data has established an extensive safety profile for NY-ESO-1, with toxicities limited to Grade 1 or 2 injection site reactions or flu-like symptoms, e.g., fever, malaise, etc. Vaccination with these agents has generated or enhanced NY-ESO-1 specific antibodies and CD8+ T-cells in the majority of patients whose serum and/or TT blood has been subjected to standardised immune monitoring. 7.

Phase I Clinical trial in Non-Small Cell Lung Cancer (NSCLC) patients Phase I clinical trials are the first trials of a drug in humans. They are usually short term trials in a small number of individuals designed to evaluate preliminary safety of a compound in the human. In the present trial, up to 18 patients with NSCLC stages IIIA, IIIB or IV expressing either NY-ESO-1 or LAGE-1 (an antigen closely related to NY-ESO-1) will have the vaccine administered via PMED on three occasions over a twelve-week period. Over that time the vaccine's safety will be assessed in the patients through blood tests and an assessment of likely adverse drug reactions. 8. The Cancer Vaccine Collaborative The Cancer Vaccine Collaborative (CVC) is a partnership between two not-for-profit academic institutions, the Cancer Research Institute and the Ludwig Institute for Cancer Research, which has developed an unparalleled programme that conducts a systematic analysis in humans comparing immunological approaches to the creation of therapeutic cancer vaccines through a coordinated global effort. This clinical trial forms part of the CVC. Unlike conventional, stand-alone trials-where data from one trial are often incomparable to data from another because of the number of uncontrolled variables between the two-investigators for the CVC will use standardised tests to evaluate different ways to deliver the same vaccine agent, the antigen NY-ESO-1.

This standardised methodology and data collection will allow for direct comparison with other trials in the CVC and help the researchers understand why certain vaccine strategies might result in a more robust immune response while others might not. 9. The Cancer Research Institute Since its inception in 1953, the Cancer Research Institute (CRI) has had a singular mission-to foster research that will yield an understanding of the immune system and its response to cancer, with the ultimate goal of developing immunological methods for the control and prevention of the disease. To accomplish these goals, CRI supports scientists at all stages of their careers and funds every step of the research process, from basic laboratory studies to clinical trials testing novel immunotherapies. Guided by a Scientific Advisory Council, which includes 4 Nobel Prize winners and 24 members of the National Academy of Sciences, CRI awards fellowships and grants to scientists around the world. Additionally, the Institute has more recently taken on a new leadership role in the areas of preclinical and clinical research by serving as the integrating force and facilitator of collaborations among leading experts. CRI has thus become a catalyst for accelerating the development of cancer vaccines and antibody therapies.

Promising result for mesothelioma drug

Sep 11 2004
The first people to test a new mesothelioma treatment drug were so impressed with the results they asked to keep taking the medication after the trial had ended.

Thirteen people with advanced solid tumours were given the drug, derived from a noxious weed known as Devil's Apple, for just one week during the trial in Perth.

Tumours started to shrink in a number of trial participants, all of whom had been told their cancer was terminal.

"The trial didn't actually set out to find out how well the product worked, it was just trying to find the right dose to use," said Greg Barrington, a spokesman for Solbec, the Perth-based company that makes the drug.

"Right near the beginning of the trial, where the doses were low, we got some positive results.

"It was the last thing we expected but the first thing we wanted, obviously."

Many of the patients elected to continue taking the drug, known as SBP002, beyond the end of the trial, Mr Barrington said.

"To get involved in a trial like that you have cancer that's not responded to anything else, and the doctors have said `perhaps you should enjoy your last few months'," he said.

"So if they get a response as these people have, then clearly they say `can we have more of that', so they've carried on."

A phase two trial of SBP002, in which the drug will be tested on about 40 people, is expected to begin next year in either Australia or the United States.

"Obviously it's early days to know what's going to happen to people taking it longer-term," Mr Barrington said.

"But we've had very encouraging results so the scientists are pretty excited."

US scientists affiliated with Solbec were also testing SBP002 on a variety of human cancer cells in the laboratory, to determine which cancers responded best to the drug.

The asbestos disease mesothelioma and skin cancer melanoma were thought to be the main targets, but the drug may also have an effect on colon, renal and lung cancers.

Alimta® and Gemzar®: A Promising Non-Platinum Regimen for NSCLC

An international multi-center phase II trial of pemetrexed (Alimta®) and gemcitabine (Gemzar®) has shown good tolerance and promising overall survival with extended 1- and 2-year survival rates in the treatment of patients with advanced non-small cell lung cancer (NSCLC). [1]

The Food and Drug Administration (FDA) recently approved Alimta® for second-line therapy of NSCLC. Alimta® is the only approved agent for the treatment of malignant mesothelioma and is being evaluated in clinical trials for various types of cancers. The clinical trial that prompted the approval of Alimta® for second-line therapy of NSCLC was a randomized phase III clinical trial that directly compared Taxotere® to Alimta® in 571 patients. [2]

Overall survival and response rates were statistically non-significant between the two groups of patients, while those treated with Alimta® suffered from fewer grade III/IV side effects. Overall survival was 8.3 months for those treated with Alimta®, compared to 7.9 months for those treated with Taxotere®. Patients treated with Alimta® suffered from less severe neutropenia, infection, diarrhea, alopecia and hospitalization from side effects of treatment compared to those treated with Taxotere® and these findings suggested that Alimta® would be the preferred standard second-line therapy for NSCLC.

In the recent international study, 57 patients with advanced NSCLC were treated initially with Alimta® and Gemzar®. The following table summarizes the results of this trial:

Major toxicities were neutropenia, fever and liver-function abnormalities.

Comments: This combination appears to be reasonably active and should be compared to other non-platinum combinations in advanced NSCLC.

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[1] Monnerat C, Le Chevalier T, Kelly K, et al. Phase II study of pemetrexed-gemcitabine combination in patients with advanced-non-small cell lung cancer. Clinical Cancer Research 2004;10:5439-5446.

[2] Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. Journal of Clinical Oncology 2004;22:1589-1597.

RFA effective for easing lung cancer symptoms; CT findings identified that verify successful RFA

1-Oct-2004 - CT-guided radiofrequency ablation (RFA) is effective in easing the symptoms of lung tumors that cannot be removed by surgery, and enhancement pattern and changes in the size of the tumor as shown on CT are the most important factors for determining whether that ablation has been successful, according to a pair of independent studies in the October 2004 issue of the American Journal of Roentgenology.
For the first study, researchers from Caserta's S. Sebastiano Hospital in Italy analyzed 33 patients with malignant lung cancer who could not undergo surgery and opted for CT-guided RFA instead. No major complications occurred for any patient during RFA, and all RFA sessions were deemed successful at follow-up CT.

According to Giuseppe Belfiore, MD, lead author of the article, the study was prompted by the feeling that an alternative to the usual therapies for lung cancer was strongly needed. "We see too many lung cancer patients who, inoperable for a number of different reasons, are left with few chances to obtain an effective palliation," said Dr. Belfiore. "We believe that a powerful alternative/complementary option is now available, although we believe that the full potential of RFA is still to be assessed. For sure, RFA allows a better quality of life for many inoperable patients," Dr. Belfiore added.

In a separate but related study, researchers from Chonbuk National University Hospital in South Korea determined that pattern enhancement--a difference in contrast between a tumor and the surrounding tissue--and changes in tumor size were the most important factors in judging the success of RFA for lung tumors on CT.

The researchers analyzed 21 patients who had undergone CT-guided RFA for lung tumors, nine of whom had complete ablations and 12 of whom had partial ablations performed. For the former group, the researchers found that the tumors were without any enhancement on short-term follow-up CT and that the size of the lesions had decreased by 40% after 12 months. For the partially ablated group, the tumors were enhanced to various degrees at short-term and the tumor size had increased after six months.

"During the past two years there have been increasing reports of RFA being performed for lung tumors, but, to our knowledge, no study has focused on the changes of ablated lung tumors on follow-up CT. Based on our results, we conclude that an enhancement pattern is a reliable finding for assessing the precise therapeutic efficacy of RFA on immediate follow-up CT. In addition, the knowledge of the size changes of the ablated tumors on long-term follow-up CT is helpful in assessing a tumor's response to RFA in lung cancer," said Jeong Min Lee, MD, one of the authors of the study.

Articles / Case Studies on Pericardial Mesothelioma

Primary pericardial mesothelioma:

Yuko Kobayashi1, , Ryusuke Murakami1, Junko Ogura1, Kanae Yamamoto1, Taro Ichikawa1, Kouichi Nagasawa2, Masaru Hosone3 and Tatsuo Kumazaki4
(1) Department of Radiology, Tama-Nagayama Hospital, Nippon Medical School, 1-7-1 Nagayama, Tama-shi, Tokyo 206-8512, Japan
(2) Department of Internal Medicine, Tama-Nagayama Hospital, Nippon Medical School, 1-7-1 Nagayama, Tama-shi, Tokyo 206-8512, Japan
(3) Department of Pathology, Tama-Nagayama Hospital, Nippon Medical School, 1-7-1 Nagayama, Tama-shi, Tokyo 206-8512, Japan
(4) Department of Radiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan

Abstract. The imaging features of primary pericardial mesothelioma have rarely been described. Herein we present a case report of its diagnostic-pathologic features. Chest computed tomography (CT) revealed an irregularly enhanced mass occupying the entire pericardial space and surrounding the superior vena cava. At autopsy, the tumor was found to fill the pericardial space completely, and to extend to the superior vena cava through the superior pericardial sinus. The CT features of the tumor were correlated well with those revealed at autopsy, and provided satisfactory information regarding the presence and the extension of the tumor.

Article/Cases Studies on Desmoplastic Malignant Mesothelioma or Malignant Mesothelioma

Desmoplastic malignant mesothelioma is the growth of fibrous or connective tissues around the tumor of the lining of the lung or chest cavity. The term "desmoplastic" refers to the growth of fibrous or connective tissue. "Desmo-" comes from the Greek "desmos" meaning "a fetter or band" and "-plastic" is also borrowed from the Greek, from "plassein" meaning "to form" = to form a band or fetter

Kannerstein M, Churg J: Desmoplastic diffuse mesothelioma. In: Progress in Surgical Pathology, Vol. II (Fenoglio CM, Wolff M, eds.), New York: Masson Pub., 1980, pp. 19-29.

Machin T, Mashiyama ET, Henderson JAM, McCaughey WTE: Bony metastases in desmoplastic pleural mesothelioma. Thorax 43:155-156, 1988.

Hillerdal G: Malignant mesothelioma 1982: Review of 4710 published cases. Br J Dis Chest 77:321-343, 1983.

McCaughey Wte: Criteria for diagnosis of diffuse mesothelial tumors. Ann NY Acad Sci 132:603-613, 1965.

Adams VI, Unni KK, Muhm JR, Jett JR, Ilstrup DM, Bernatz PE: Diffuse malignant mesothelioma of pleura: Diagnosis and survival in 92 cases. Cancer 58:1540-1551, 1986.

Obers VJ, Leiman G, Girdwood RW, Spiro FI: Primary malignant pleural tumors (mesothelioma) presenting as localized masses: Fine needle aspiration cytologic findings, clinical and radiologic features and review of the literature. Acta Cytolog 32:567-575, 1988.

Solomons K, Polakow R, Marchand P: Diffuse malignant mesothelioma presenting as bilateral malignant lymphangitis. Thorax 40:682-683, 1985.

Alexander E, Clark RA, Colley DP, Mitchell SE: CT of malignant pleural mesothlioma. AJR 137:287-291, 1981.

Mirvis S, Dutcher JP, Haney PJ, Whitley NO, Aisner J: CT of malignant pleural mesothelioma. AJR 140:665-670, 1983.

Lorigan JG, Libshitz HI: MR imaging of malignant pleural mesothelioma. J Comput Asst Tomogr 13:617-620, 1989.

Harwood TR, Gravey DR, Yokoo H: Pseudomesotheliomatous carcinoma of the lung: A variant of peripheral lung cancer. Am J Clin Pathol 65:159-167, 1976.

Whitaker D, Shilkin KB: Diagnosis of pleural malignant mesothelioma in life: A practical approach. J Pathol 143:147-175, 1984.

Roberts GH, Campbel GM: Exfoliative cytology of diffuse mesothelioma. J Clin Pathol 25:577-582, 1972.

Sterrett GF, Whitaker D, Shilkin KB, Walters MNI: Fine needle aspiration cytology of malignant mesothelioma. Acta Cytologica 31:185-193, 1987. Churg J, Rosen SH, Moolten S: Histological characteristics of mesothelioma associated with asbestos. Ann NY Acad Sci132:614-622, 1965.

Adams VI, Unni KK: Diffuse malignant mesothelioma of pleura: Diagnostic criteria based on an autopsy study. AM J Clin Pathol 82:15-23, 1984.

Yousem SA, Hochholzer L: Malignant mesotheliomas with osseous and cartilaginous differentiation. Arch Pathol Lab Med 111:62-66, 1987.

The onset of pleural diffuse malignant mesothelioma is usually insidious. Chest pain and dyspnea are the most frequent initial complaints; cough, weight loss, and asthenia tend to develop somewhat later. Infrequently, diffuse malignant mesothelioma may present as recurrent pneumothorax. (Situnayake RD, Middleton WG.

Recurrent pneumothorax and malignant pleural mesothelioma. RespirMed 1991;85:255-6.) , miliary dissemination in the absence of clinically identifiable pleural- based tumor. (Musk AW, Dewar J, Shilkin KB, Whitaker D. Miliary spread of malignant pleural mesothelioma without a clinically identifiable pleural tumor. Aust NZ J Med 1991;21:460-2.) , or enlargement of ipsilateral supraclavicular lymph nodes (Sussman J, Rosai J. Lymph node metastasis as the initial manifestation of malignant mesothelioma: report of six cases. Am J Surg Pathol 1990;14:819-28.)

The most distressing symptom as the disease progresses is pain due to infiltration of the chest wall. The pain is often of an aching, nonpleuritic type and may be referred to the abdomen or shoulder. Evidence of pleural effusion is the most frequent finding on initial physical and radiographic examination.
(Legha SS, Muggia FM.

Pleural mesotheliomas. Clinical features and therapeutic implications. Ann Intern Med 1977;87:613-21.) , and a small proportion of diffuse malignant mesotheliomas are preceded for periods ranging from 1 to 7 years by recurrent pleural effusions. Close to 10 percent of patients have radiologic evidence of tumor without effusion.

Asbestos workers may have recurrent pleural effusions with associated fibrous pleurisy (asbestos pleurisy) in the absence of any tumor. (Gaensler EA, Kaplan AI. Asbestos pleural effusion. Ann Int Med 1971;74:178-91.) Chest roentgenogram and computerized tomographic (CT) scan may show a diffusely nodular or irregularly thickened pleura , hilar or mediastinal masses, or masses of apparent pulmonary origin. (Heller RM, Janower ML, Weber AL. The radiological manifestations of malignant pleural mesothelioma. Am J Roentgenol 1970;108:53-9.) .

The radiologic appearance may change markedly within a short time . Radiologic evidence of asbestosis is uncommon, whereas pleural plaques are seen quite frequently. Effusions are often blood stained, and may be massive and require frequent tapping.

They tend to disappear in the later stages of the disease with advancing neoplastic thickening of the pleura and obliteration of the pleural cavity. Contraction of the affected hemithorax often occurs in the late stages, with pulling of the mediastinal structures to the affected side.

Subcutaneous tumor nodules may appear in the chest wall, especially in relation to aspiration needle or thoracoscopy tracts and thoracotomy scars The tumor may occasionally present as a mass in the chest wall or mimic Pancoast's tumor.

Tumors of the Serosal Membranes.
Battifora H, McCaughey WT. Tumors of the serosal membranes.
Atlas of Tumor Pathology, 3rd Series Fascicle 15.
Washington, D.C., Armed Forces Institute of Pathology, 1995.
key words: AFIP, serosa, peritoneum, peritoneal, pleura, pleural

Packet No.: 2
68658

Nodules of fibrous tumor sometimes infiltrate alveolar spaces in the adjacent lung or the soft tissues of the chest wall. In most instances, cellular areas with sarcomatous characteristics can be found in parts of the tumor, although a careful search is sometimes necessary.

In about one third of cases, epithelial- type tumor elements, usually of tubular or papillary form, are seen at least focally and may be accompanied by obvious sarcomatous areas. Zones of bland infarct-like necrosis are quite common. As such zones are rarely seen in inflammatory fibrosis, they help to distinguish desmoplastic mesothelioma from fibrous pleurisy.

It has been suggested that the most cellular tissue found in desmoplastic mesothelioma is at the mediastinal aspect of the pleura. (Henderson DW, Shilkin KB, Whitaker D, et al. Unusual histological types and anatomic sites of mesothelioma. In: Henderson DW, Shilkin KB, Langlois SL, Whitaker D, eds.

Malignant mesothelioma. New York: Hemisphere Publishing, 1992:140-63.) A feature frequently seen in desmoplastic mesothelioma and rarely, if ever, in fibrosing pleuritis is focal invasion into the underlying pulmonary parenchyma along interlobular septa and fissures and into subserosal adipose tissue in the parietal pleura . Such areas of focal invasion may be made apparent by immunostaining with antibodies to low molecular weight cytokeratins . (Battifora H. The pleura. In: Sternberg SS, ed. Diagnostic surgical pathology. New York: Raven Press, 1989:829-55.)

Nonetheless, even when abundant decortication material is available, and numerous samples are taken, confident differentiation between desmoplastic mesothelioma and fibrous pleurisy may be difficult or impossible.

It should be remembered that there are many causes of benign diffuse pleural fibrosis, one of which is asbestos. (Gaensler EA, Kaplan AI. Asbestos pleural effusion. Ann Int Med 1971;74:178-91.) Asbestos is also the main cause of the discrete fibrous plaques that are frequently seen on the parietal pleura in persons exposed to asbestos.

Tumors of the Serosal Membranes.
Battifora H, McCaughey WT. Tumors of the serosal membranes.
Atlas of Tumor Pathology, 3rd Series Fascicle 15.
Washington, D.C., Armed Forces Institute of Pathology, 1995.
key words: AFIP, serosa, peritoneum, peritoneal, pleura, pleural

Packet No.: 4
68659

In cases in which only small biopsy specimens are available, localized malignant fibrous tumors of the pleura (so-called malignant localized mesothelioma) may enter into the differential diagnosis because of the dense fibrosis that occurs in some of them.

Immunostaining for low molecular weight keratins helps in diagnosis since desmoplastic mesotheliomas nearly always express keratin, whereas benign localized fibrous tumors do not. Ultrastructurally, desmoplastic mesothelioma is similar to conventional sarcomatoid mesothelioma, but with more cells with the appearance of myofibroblasts. (d'Andiran G, Gabbiani GA. Metastasizing sarcoma of the pleura composed of myofibroblasts. In: Fenoglio CM, Woolf M, eds. Progress in surgical pathology. New York: Masson Publishing, 1980:34-40.)

However, the frequent expression of cytokeratins by the cells of desmoplastic mesothelioma sets them apart from myofibroblasts. (Battifora H. The pleura. In: Sternberg SS, ed. Diagnostic surgical pathology. New York: Raven Press, 1989:829-55.) .

Tumors of the Serosal Membranes.
Battifora H, McCaughey WT. Tumors of the serosal membranes.
Atlas of Tumor Pathology, 3rd Series Fascicle 15.
Washington, D.C., Armed Forces Institute of Pathology, 1995.
key words: AFIP, serosa, peritoneum, peritoneal, pleura, pleural.