Anatomic Pathology / PERITONEAL MESOTHELIOMA AND SEROUS CARCINOMA
|
|
- Marjorie Flynn
- 8 years ago
- Views:
Transcription
1 Anatomic Pathology / PERITONEAL MESOTHELIOMA AND SEROUS CARCINOMA Immunohistochemical Analysis of Peritoneal Mesothelioma and Primary and Secondary Serous Carcinoma of the Peritoneum Antibodies to Estrogen and Progesterone Receptors Are Useful Robert J. Barnetson, MBChB, 1 Rodney A. Burnett, FRCPath, 1 Ian Downie, MSc, 2 Christina M. Harper, MRCPath, 3 and Fiona Roberts, MRCPath 1 Key Words: Peritoneal mesothelioma; Primary peritoneal carcinoma; Metastatic ovarian carcinoma; Estrogen receptor; Progesterone receptor DOI: /8FCHQ3VPBWM7B5X9 Abstract The role of immunohistochemical markers in distinguishing peritoneal mesothelioma from primary or metastatic serous papillary carcinoma of the peritoneum was evaluated. We immunostained 20 peritoneal mesotheliomas (from 14 men and 6 women), 14 primary peritoneal carcinomas, and 14 metastatic serous ovarian carcinomas with a panel of 16 antibodies. Positive staining for calretinin was identified in 17 (85%) of 20 mesotheliomas, but all carcinomas were negative. Positive staining for Ber- EP4 was identified in 27 (96%) of 28 carcinomas and in 2 (10%) of 20 mesotheliomas. Estrogen receptors were positive in 26 (93%) of 28 carcinomas, and progesterone receptors were positive in 8 (29%) of 28 carcinomas. All mesotheliomas were negative for estrogen and progesterone receptors. The other antibodies evaluated were insufficiently sensitive and/or specific to be diagnostically useful. In conjunction with calretinin and Ber-EP4, estrogen and progesterone receptors are useful discriminatory markers for distinguishing peritoneal mesothelioma from primary or metastatic serous carcinoma. Malignant mesothelioma of the peritoneum (PMM) is less common than its counterpart in the pleural cavity, accounting for only around 10% of all mesotheliomas. 1 However, like pleural mesothelioma, the diagnosis of PMM can be challenging, particularly in the female peritoneum, where it may mimic serous carcinoma of the ovary or peritoneum. Nevertheless, accurate distinction of these tumors is important for clinical and medicolegal reasons. Malignant mesothelioma is a chemotherapy- and radiotherapy-resistant tumor with a dismal prognosis, whereas these treatment modalities can significantly improve patient survival in primary and metastatic peritoneal serous carcinoma (PSC). 2-5 No etiologic relationship has been established between asbestos exposure and PSC. PMM, however, is recognized to occur after asbestos exposure, and this diagnosis, therefore, might lead to medicolegal compensation. 1,6 It should be noted, however, that in women, the proportion of cases with asbestos exposure is lower than in men and it usually is of the paraoccupational (domestic) type. 7 Histologically, epithelioid malignant mesothelioma might have an appearance identical to that of primary or metastatic serous carcinoma. 8,9 Furthermore, mucin stains are considerably less helpful for differentiating between these tumors than for distinguishing epithelioid malignant mesothelioma from metastatic adenocarcinoma in the pleura. 10 Immunohistochemical analysis generally is regarded as the most important ancillary technique to distinguish between these tumors However, these tumors are uncommon compared with pleural mesothelioma and adenocarcinoma, and there are few studies that have addressed this specific problem. The aim of the present study was to identify the most accurate and clinically useful immunohistochemical panel Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9 67
2 Barnetson et al / PERITONEAL MESOTHELIOMA AND SEROUS CARCINOMA that can reliably distinguish epithelioid malignant mesothelioma from primary or metastatic ovarian serous carcinoma of the peritoneum. Our antibody panel included well-recognized markers of mesothelioma and adenocarcinoma. Antibodies to estrogen receptor (ER) and progesterone receptor (PR) also were included. Materials and Methods Tumor Samples Retrospective paraffin-embedded tissue samples were retrieved from the pathology records of the Western Infirmary, Royal Infirmary, and Southern General Hospital, Glasgow, Scotland; the Victoria Infirmary, Kirkaldy, Fife, Scotland; and the Western General, Edinburgh, Scotland. The specimens included 14 samples from men and 8 samples from women initially diagnosed with PMM, 14 samples from women with metastatic ovarian carcinoma (MOC), and 14 samples from women with primary peritoneal carcinoma (PPC). For PMM, the specimens consisted of needle or open biopsy specimens, and the microscopic features were considered consistent with those reported in standard texts. These histologic findings were supported by appropriate immunohistochemical, ultrastructural, or postmortem findings. In each case, the clinical findings were of a diffuse peritoneal tumor with no evidence of a primary tumor elsewhere in the body, and, in most cases, there was a well-documented history of asbestos exposure. By using these criteria, 2 cases initially diagnosed as PMM occurring in women were excluded. In one case, electron microscopy had been undertaken on the tumor showing the presence of short microvilli more in keeping with adenocarcinoma. In the other case, a postmortem examination subsequently showed the presence of a primary ovarian adenocarcinoma. For PPC, the specimens consisted of open biopsy specimens or specimens from debulking surgery. The diagnosis of PPC was based on appropriate microscopic features and confirmation of lack of ovarian involvement at laparoscopy or by surgical pathology. Similar to PMM, the diagnoses were supported by appropriate immunohistochemical, ultrastructural, or postmortem findings. MOCs consisted of open biopsy specimens or peritoneal metastases removed at the time of oophorectomy. All MOCs included in this study were classified as papillary serous adenocarcinomas based on appropriate histopathologic features. Immunohistochemical Analysis Information about the antibodies selected is given in Table 1. For immunohistochemical analysis, 3-µm sections were immunostained by using a DAKO Autostainer using EnVision Peroxidase (DAKO, Ely, England). Briefly, sections were washed with tris(hydroxymethyl)aminomethanebuffered saline containing polysorbate (Tween) buffer (TBS/TB) and then blocked with normal goat serum (dilution 1:20) for 20 minutes. Sections then were incubated with primary antibody for 30 minutes followed by another wash in TBS/TB. Following this step, the sections were incubated with DAKO EnVision for 30 minutes. After a final wash in TBS/TB, color was developed with diaminobenzidine for 10 minutes and sections counterstained with hematoxylin. For antigen retrieval, slides were microwaved under pressure in 1 mmol/l of EDTA, ph 8.0, for 5 minutes or incubated with 0.1% trypsin, ph 7.8, for 25 minutes at 37 C. Appropriate control material (according to the manufacturer s instructions) was used for each run. For negative control samples, the primary antibody was omitted. Table 1 Antibodies Used for Immunohistochemical Analysis Antibody Clone Source Dilution Pretreatment Carcinoembryonic antigen II-7 DAKO, Ely, Cambridge, England 1:400 Trypsin Human epithelial antigen Ber-EP4 DAKO 1:200 Trypsin LeuM1 LeuM1 Becton Dickinson, Oxford, England 1:200 MWPC Mesothelin 5B2 Becton Dickinson 1:20 MWPC CA 125 OV185:1 Vector, Peterborough, England 1:400 MWPC Epithelial-related antigen MOC31 DAKO 1:20 Trypsin Thyroid transcription factor-1 SPT 24 Vector 1:50 MWPC Estrogen receptor 6F11 Vector 1:50 MWPC Progesterone receptor PGR636 DAKO 1:400 MWPC Cytokeratin 5 XM26 Vector 1:200 MWPC Cytokeratin 7 OV-TLR12/30 DAKO 1:500 MWPC Cytokeratin 20 Ks20.8 DAKO 1:500 MWPC Calretinin 5A5 Vector 1:100 MWPC Thrombomodulin 15C8 Vector 1:200 Trypsin WT1 6F-H2 DAKO 1:50 MWPC CD44H F DAKO 1:100 MWPC MWPC, pressure cook, microwave. 68 Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9
3 Anatomic Pathology / ORIGINAL ARTICLE Interpretation of Results The slides were evaluated semiquantitatively, and the percentage of positive tumor cells was described as follows: 1+, staining 1% to 49% of tumor cells, or 2+, staining 50% to 100% of tumor cells. All cases showing staining of less than 1% of tumor cells were regarded as negative. Weak staining or staining that was difficult to interpret was regarded as equivocal. The pattern of staining was recorded as membranous, cytoplasmic, or nuclear for each antibody. The sections were assessed independently by 2 observers (R.J.B. and F.R.). For cases in which there was substantial disagreement, the slides were assessed by a third observer (R.A.B.), and consensus was reached. Results The results are summarized in Table 2, Table 3, Table 4, Table 5, and Table 6 and shown in Image 1 and Image 2. Ber-EP4, Carcinoembryonic Antigen, LeuM1, and MOC31 Strong, membranous staining for Ber-EP4 was seen in 27 (96%) of 28 carcinomas. Of the PMMs, 2 (10%) of 20 showed 1+ staining for Ber-EP4. All PMMs occurring in both men and women were negative for carcinoembryonic antigen (CEA) and LeuM1. Positive staining for CEA was observed in only 1 (4%) of 28 PSCs (a PPC). Of 28 carcinomas, 14 (50%) were positive for LeuM1, although staining was focal in the majority of cases. Strong membranous staining for MOC31 was seen in all 28 PSCs. Of 20 PMMs, 5 (25%) showed 1+ staining for MOC31. CK5, CK7, and CK20 Of 20 PMMs, 18 (90%) stained strongly with CK5. CK5 staining was seen in 14 (50%) of 28 PSCs. Strong CK7 staining was observed in 17 (85%) of 20 PMMs and in all 28 PSCs (100%). CK20 was negative in all PMMs and PSCs. Table 2 Immunohistochemical Staining of Peritoneal Mesotheliomas and Carcinomas * Tumor Type CEA Ber-EP4 LeuM1 MOC31 CA 125 ER PR CK5 CK7 CK20 Mesothelin Calretinin TM WT1 CD44H TTF-1 Mesothelioma Male (n = 14) Female (n = 6) Total (n = 20) Carcinoma MOC (n = 14) PPC (n = 14) Total (n = 28) CEA, carcinoembryonic antigen; CK, cytokeratin; ER, estrogen receptor; MOC, metastatic ovarian carcinoma; PPC, primary peritoneal carcinoma; PR, progesterone receptor; TM, thrombomodulin; TTF-1, thyroid transcription factor-1; WT1, Wilms tumor 1. * For proprietary information, see Table 1. Table 3 Immunohistochemical Staining of Peritoneal Mesothelioma in 14 Men * Antibody Equivocal Negative CEA Ber -EP LeuM MOC CA ER PR CK CK CK Mesothelin Calretinin Thrombomodulin WT CD44H TTF CEA, carcinoembryonic antigen; CK, cytokeratin; ER, estrogen receptor; PR, progesterone receptor; TTF-1, thyroid transcription factor-1; WT1, Wilms tumor 1. * 1+, staining 1% to 49% of tumor cells; 2+, staining 50% to 100% of tumor cells. For proprietary information, see Table 1. Table 4 Immunohistochemical Staining of Peritoneal Mesothelioma in 6 Women * Antibody Equivocal Negative CEA Ber -EP LeuM MOC CA ER PR CK CK CK Mesothelin Calretinin Thrombomodulin WT CD44H TTF CEA, carcinoembryonic antigen; CK, cytokeratin; ER, estrogen receptor; PR, progesterone receptor; TTF-1, thyroid transcription factor-1; WT1, Wilms tumor 1. * 1+, staining 1% to 49% of tumor cells; 2+, staining 50% to 100% of tumor cells. For proprietary information, see Table 1. Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9 69
4 Barnetson et al / PERITONEAL MESOTHELIOMA AND SEROUS CARCINOMA Table 5 Immunohistochemical Staining of 14 Metastatic Serous Ovarian Carcinomas * Antibody Equivocal Negative CEA Ber -EP LeuM MOC CA ER PR CK CK CK Mesothelin Calretinin Thrombomodulin WT CD44H TTF CEA, carcinoembryonic antigen; CK, cytokeratin; ER, estrogen receptor; PR, progesterone receptor; TTF-1, thyroid transcription factor-1; WT1, Wilms tumor 1. * 1+, staining 1% to 49% of tumor cells; 2+, staining 50% to 100% of tumor cells. For proprietary information, see Table 1. Table 6 Immunohistochemical Staining of 14 Primary Peritoneal Carcinomas * Antibody Equivocal Negative CEA Ber -EP LeuM MOC CA ER PR CK CK CK Mesothelin Calretinin Thrombomodulin WT CD44H TTF CEA, carcinoembryonic antigen; CK, cytokeratin; ER, estrogen receptor; PR, progesterone receptor; TTF-1, thyroid transcription factor-1; WT1, Wilms tumor 1. * 1+, staining 1% to 49% of tumor cells; 2+, staining 50% to 100% of tumor cells. For proprietary information, see Table 1. Thyroid Transcription Factor-1 All PMMs were negative for thyroid transcription factor- 1 (TTF-1). Of 28 PSCs, 1 showed strong nuclear staining for TTF-1. This case had been designated as a PPC. CA 125, ER, and PR Strong staining for CA 125 was seen in 9 (45%) of 20 PMMs. Of 28 PSCs, 26 (93%) showed strong positive staining for CA 125. In the remaining 2 cases, staining was considered equivocal. ER and PR were negative in all 20 PMMs. Of 28 PSCs, 26 (93%) were strongly positive for ER. In 1 of the remaining 2 cases (an MOC), staining was considered equivocal. PR was positive in 8 (29%) of 28 PSCs. In 1 of the remaining 20 cases (a PPC), staining was considered equivocal. Calretinin, Mesothelin, Thrombomodulin, CD44H, and WT1 Calretinin was positive in 17 (85%) of 20 PMMs, with nuclear staining in addition to cytoplasmic staining. None of the PSCs was positive for this antibody. Mesothelin was positive in 13 (65%) of 20 PMMs and in 25 (89%) of 28 PSCs. Thrombomodulin was positive in 9 (45%) of 20 PMMs. One of the PSCs was positive for this antibody. CD44H was positive in 15 (75%) of 20 PMMs. One of the remaining 5 cases showed equivocal staining. Of 28 PSCs, 4 (14%) showed positive staining for this antibody. WT1 positivity was seen in 11 (55%) of 20 PMMs. Of 28 PSCs, 21 (75%) showed strong positive staining for this antibody. Another 3 cases showed equivocal staining. Discussion Immunohistochemical analysis has been used extensively to assist in the distinction between malignant mesothelioma of the pleura and metastatic adenocarcinoma, usually of lung origin In contrast, the immunohistochemical analysis of PMM has received little attention. The peritoneal serosal lining is subject to a different environment from the pleura, and this may be expressed as a different antigen profile. Furthermore, the majority of biopsy specimens obtained from the peritoneum are larger compared with needle biopsy specimens of the pleura such that differences in tissue fixation might alter antigen expression. 19 This is compounded by the apparently decreasing incidence of PMM relative to the dramatic increase in pleural mesotheliomas. 1 In women, however, it is likely that the decrease in incidence is due in part to increased recognition of PSC, which previously might have been misdiagnosed as PMM. 3,20,21 In the present study we had planned to have equal numbers of cases of PMM from men and women but were able to find only 8 cases in women designated as PMM in our archives. There was, however, no difference in the immunostaining pattern between samples from men and women. Indeed, 2 of the 8 cases originally reported as PMM in women were excluded from the study because review of the cases revealed that postmortem and electron microscopic findings were those of adenocarcinoma. Both of these cases yielded an immunophenotype in keeping with that of a peritoneal serous carcinoma. This highlights the diagnostic difficulties associated with distinguishing between these 2 tumors and supports the case for the use of immunohistochemical analysis. 70 Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9
5 Anatomic Pathology / ORIGINAL ARTICLE A B C D E F Image 1 A, Malignant mesothelioma from a man showing diffuse infiltration of peritoneal fat by an epithelioid tumor (H&E, 100). B, Immunohistochemical staining of this mesothelioma for calretinin shows cytoplasmic and nuclear staining of the tumor cells ( 100). C, Negative staining for Ber-EP4 in the same mesothelioma as in A ( 100). D, Primary peritoneal carcinoma showing papillary areas and occasional psammoma bodies (arrows) (H&E, 100). E, Negative staining for calretinin in this primary peritoneal carcinoma. Note the positive staining of the mesothelium lining the peritoneum (arrows) ( 100). F, Immunohistochemical staining of this primary peritoneal carcinoma for Ber-EP4 shows membranous staining of the tumor cells ( 100). Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9 71
6 Barnetson et al / PERITONEAL MESOTHELIOMA AND SEROUS CARCINOMA A B C D E F Image 2 A, Malignant mesothelioma from a woman showing diffuse infiltration of peritoneal tissues by an epithelioid tumor with pseudoglandular spaces (H&E, 100). B, Immunohistochemical staining for estrogen receptor (ER) is negative. The brown pigment is hemosiderin from previous hemorrhage ( 100). C, Immunohistochemical staining for progesterone receptor (PR) is negative. The brown pigment is hemosiderin from previous hemorrhage ( 100). D, Metastatic ovarian serous adenocarcinoma showing papillary and pseudoglandular areas (H&E, 100). E, There is strong nuclear staining for ER in this metastatic ovarian carcinoma ( 100). F, There is focal nuclear positivity for PR in this metastatic ovarian carcinoma ( 100). 72 Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9
7 Anatomic Pathology / ORIGINAL ARTICLE The present study was planned to ascertain the usefulness of commercially available, well-established antibodies in the distinction of PMM from primary or metastatic serous adenocarcinoma. The panel included markers considered relatively specific and sensitive for both mesothelioma and adenocarcinoma. In addition, because serous MOCs and PPCs are tumors of the primary and secondary müllerian systems, respectively, ER and PR also were included. These have been reported to be negative in PMM. 22 Ber-EP4 is a monoclonal antibody produced from the MCF-7 breast carcinoma cell line that recognizes epithelial glycoproteins. 23 It has been used in many studies to discriminate between pleural mesothelioma and adenocarcinoma 11-14,16,24 and to a lesser extent in the peritoneal setting. 8-10,24 Ordóñez 8 found Ber-EP4 positivity in 100% of 45 PSCs, whereas only 11% of PMMs (4/35) showed positivity in a limited number of cells. Similarly Attanoos et al 9 found positivity for Ber-EP4 in 95% of papillary serous ovarian cancers (19/20) and 9% of PMMs (3/32). Our study confirmed the high sensitivity and specificity of Ber-EP4 with strong membranous staining in 96% of PSCs (27/28; 13/14 MOCs and 14/14 PPCs). There was unequivocal positive staining for Ber- EP4 in 10% of PMMs (2/20; in 1 woman and 1 man). Although both of these cases also showed focal positivity for MOC31, there was, in addition, 2+ staining for calretinin and focal staining for thrombomodulin. ER is a ligand-activated transcription factor that mediates the effect of the steroid hormone 17β-estradiol in men and women. 25 PR is an estrogen-inducible protein activated by progesterone and synthetic progestins, provoking its phosphorylation and DNA-binding ability and inducing its regulatory activities. Its expression is indicative of an intact ER pathway and, as such, might identify tumors that are hormonally responsive to estrogen therapy, improving the overall predictive value of steroid receptor assays in selected tumors. 26 Halperin et al 27 found positive staining in PPC for ER and PR in 30.8% and 42%, respectively, whereas MOC showed positive staining for ER and PR in 72.7% and 90.9%, respectively. Henzen-Logmans et al 28 found ER and PR staining in 46% and 34%, respectively, in MOC. There is scant literature describing the use of these markers in PMM, but Trupiano et al 22 found ER and PR staining in 6% and 0%, respectively, in their study of 33 pleural mesotheliomas and PMMs. In our study, none of the 20 cases of PMM stained for either ER or PR. In contrast, 93% of PSCs (13/14 PPCs and 13/14 MOCs) showed strong nuclear staining for ER, yielding a sensitivity of 93% and specificity of 100%. PR was positive in 29% of PSCs (3/14 PPCs and 5/14 MOCs), yielding 29% sensitivity but 100% specificity in our hands. These results suggest that these antibodies, used in an appropriate panel, offer good specificity, and, in the case of ER, good sensitivity in differentiating PSC from PMM. Calretinin is a 29-kd calcium-binding protein, and it is expressed in a range of tissues, including normal and neoplastic mesothelium. 29 It has been studied extensively in malignant mesothelioma of the pleura with some disparate results, although many authors have reported positive staining in 80% to 100% of mesotheliomas with specificities of up to 100% ,16,29 Similar levels of positivity for calretinin have been reported in PMM. 8,9 Ordóñez 13 found that discrepancies with this marker were due mainly to the type of antibody used. Cury et al 17 suggested that only nuclear staining should be regarded as positive in distinguishing mesothelioma from carcinoma. In our study, calretinin was a good positive marker for mesothelioma with strong nuclear and cytoplasmic staining in 85% of PMMs (in 12/14 men and 5/6 women), whereas all PPCs and MOCs were negative (85% sensitivity and 100% specificity). In some cases, the staining was focal, and this, in addition to the slightly lower sensitivity, might reflect the use of a monoclonal rather than a polyclonal antibody. The specificity of this antibody is, however, 100% compared with polyclonal antibodies, which have been shown to stain up to 9% of serous adenocarcinomas. 8,29 CA 125 and CEA have been shown to be of little value in differentiating PMMs from serous adenocarcinomas. 8,10,15 Our results concur with these findings: CA 125 was not specific, staining 42% of PMMs (8/19) and 93% of PSCs (26/28), whereas CEA was not sensitive, staining only 1 case of PPC. Similarly, in our study, LeuM1 showed lower sensitivity than Ber-EP4; although staining was negative in all PMMs, it was positive in 50% of PSCs (14/28). Furthermore, the staining was focal in the majority of cases. Attanoos et al 9 also found LeuM1 to be of low sensitivity with positive staining of 35% of MOCs and 0% of PPCs. Other studies have reported higher sensitivity with positive staining between 57% and 80%. 8,10,30,31 One of these studies, however, showed focal staining in 3 PMMs, and 1 study was of autopsy material, which might show differences in antigen expression. MOC31 is a monoclonal antibody to a cell surface glycoprotein and shows membranous staining in the majority of adenocarcinomas It also has been shown to stain between 2.3% and 20% of mesotheliomas. 33,35,36 In our study, MOC31 was positive in 100% of PSCs with staining of 15% of PMMs (3/20). However, the staining in PMMs tended to be patchy compared with the diffuse membranous staining seen in PSC. In our hands, this antibody does not seem to offer advantages over Ber-EP4. Differential cytokeratins (CK7 and CK20) frequently are used when the pathologist is faced with metastatic carcinoma from an unknown primary site, eg, in the differentiation of ovarian serous metastases (CK7+; CK20 ) from colorectal adenocarcinoma (CK7 ; CK20+). 37,38 In tumors involving the pleura, CK7 and CK20 may be useful additions to an antibody panel because expression of CK20 with or without CK7 Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9 73
8 Barnetson et al / PERITONEAL MESOTHELIOMA AND SEROUS CARCINOMA positivity is more in keeping with metastases from the gastrointestinal tract. 39 However, for distinguishing PMM from PSC, these antibodies have poor sensitivity and specificity. We found CK20 to be negative in all PMMs and PSCs, whereas CK7 was positive in 85% of PMMs (17/20) and 100% of 28 PSCs. TTF-1 is a 38-kd homeodomain containing DNA-binding protein originally identified in follicular cells of the thyroid and subsequently in pneumocytes. Many studies have shown it to be a sensitive and specific marker of lung adenocarcinoma, and, therefore, it is considered an important part of the antibody panel for differentiating pleural mesothelioma from metastatic adenocarcinoma of lung (or thyroid). 13,18 There is scant evidence in the literature on positive staining for TTF-1 in serous carcinomas. A study by Hecht et al 43 on paraffinembedded sections of cell block preparations derived from effusion and fine-needle aspiration specimens showed focal weak reactivity in 1 MOC. In our study, all PMMs were negative for TTF-1, but 1 PSC (a PPC) unexpectedly showed strong nuclear staining for this antibody. This tumor was positive for CK7, Ber-EP4, LeuM1, CA 125, ER, PR, TTF-1, and CD44 and negative for calretinin, CK5, CK20, mesothelin, thrombomodulin, CEA, and WT1. Subsequent staining for thyroglobulin was negative. This diffuse peritoneal-based tumor developed 14 years after hysterectomy and bilateral salpingo-oophorectomy for benign disease in the patient, a nonsmoker. She was treated with systemic chemotherapy (carboplatin) and initially had a response. However, her condition slowly deteriorated, and there was a rising serum CA 125 level. Despite further chemotherapy and hormonal therapy, she died 32 months after diagnosis. The chest radiographic findings were normal until 7 months before death, when multiple pulmonary metastases developed. The behavior of this tumor was entirely in keeping with PPC, and, therefore, we conclude that this represents true TTF-1 staining in a PPC. Studies have shown that strong expression of CK5/6 is a sensitive and specific marker for distinguishing mesothelioma from metastatic adenocarcinoma in the pleura. 44 Ordóñez 13 found that 100% of 60 epithelioid pleural mesotheliomas stained positively for CK5/6, whereas only 1 (2%) of 50 metastatic adenocarcinomas was positive. In addition, Ordóñez, 8 in a study of PMMs and peritoneal and ovarian serous carcinomas, found positive staining for CK5/6 in 100% of 35 PMMs and 11 (24%) of 45 serous carcinomas. In our study, by using CK5, we found positive staining in 90% of PMMs (18/20) and in 50% of PSCs (14/28). The lack of specificity casts doubt on the usefulness of this antibody in the context of differentiating these peritoneal tumors. This is in agreement with the findings of Attanoos et al, 9 who similarly found this antibody to be of limited use in differentiating PMM and PSC. Initial reports suggested that antibodies to CD44H, a receptor for hyaluronic acid, were useful positive markers for mesothelioma. 15 Later reports concluded that this antibody was of limited specificity. 12 We found that 75% of PMMs (15/20) were positive for CD44H, whereas 14% of PSCs were positive (4/28), suggesting a limited role for this antibody in an appropriate panel. We found thrombomodulin to be positive in only 45% of PMMs (9/20). One of the PSCs was immunoreactive for this antibody, but this case also showed staining for MOC31, Ber- EP4, and LeuM1. Studies have shown positivity for thrombomodulin in 80% to 100% of pleural mesotheliomas and 10% to 15% of adenocarcinomas. 45,46 In PMMs, Ordóñez 8 and Attanoos et al 9 reported 74% and 56% positivity, respectively. In the majority of our cases, staining for thrombomodulin was focal. This patchy reactivity is well recognized 47 and suggests that staining for thrombomodulin might be affected by tissue fixation in larger specimens. This may be one reason for its limited usefulness in PMM. Similarly, mesothelin that is known to be positive in nonmucinous ovarian carcinomas 48 was positive in 65% of PMMs (13/20) and 89% of PSCs (25/28) and was not considered helpful for distinguishing these tumors. The level of positivity for mesothelin in PMM is somewhat lower than that reported in studies by Ordóñez 48,49 of 100%; however, this antibody has not been studied extensively in PMM. WT1 has been studied in the context of pleural mesothelioma in which positive nuclear staining has been reported in 70% to 93% of pleural mesotheliomas. 13,33,50,51 WT1 also has been shown to be positive in most ovarian serous carcinomas, and staining with this marker is useful for excluding metastases from other sites to the peritoneum. 52,53 Studies have reported positivity for WT1 in 93% to 100% of ovarian serous carcinomas We found positive staining for WT1 in 55% of PMMs (11/20) and in 75% of PSCs (21/28). The explanation for this lower level of positivity is unclear but might reflect the archival nature of the tissue samples used in this study with resultant degradation of nuclear antigens. Regardless of the low rate of expression in both PMM and PSC, in the present study, WT1 was not helpful for distinguishing PMM from PSC. As highlighted by previous studies, we have shown that there is no single marker that is diagnostic for PMM or PSC Similarly, immunohistochemical analysis cannot distinguish MOC of the serous type from PPC. When faced with the dilemma of diagnosing a mesothelioma in which the differential diagnosis includes metastatic adenocarcinoma, a panel of antibodies comprising a series of positive and negative markers for mesothelioma and adenocarcinoma should be used. This also applies to the peritoneum in which mesothelioma has to be separated from histologically similar tumors such as primary and secondary serous carcinoma. A diagnostic error in this situation might have therapeutic implications and/or 74 Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9
9 Anatomic Pathology / ORIGINAL ARTICLE medicolegal consequences. This study showed that ER and PR are useful additions to a diffuse peritoneal malignancy workup and, in combination with Ber-EP4 and calretinin, form a sensitive and specific diagnostic panel. From the Departments of Pathology, 1 University of Glasgow Western Infirmary, 2 Glasgow Royal Infirmary, and 3 Southern General Hospital, Glasgow, Scotland. Supported by the June Hancock Mesothelioma Research Fund, Sheffield, England. Address reprint requests to Dr Roberts: Dept of Pathology, Western Infirmary, Dumbarton Rd, Glasgow, G11 6NT, Scotland. Acknowledgments: We are grateful to A. Lessels, FRCPath, Edinburgh, Scotland, and I. Nawroz, FRCPath, Kirkaldy, Scotland, for supplying additional material. References 1. Britton M. The epidemiology of mesothelioma. Semin Oncol. 2002;29: Cormio G, Di Vagno G, Di Gesu G, et al. Primary peritoneal carcinoma: a report of twelve cases and a review of the literature. Gynecol Obstet Invest. 2000;50: Fowler JM, Nieberg RK, Schooler TA, et al. Peritoneal adenocarcinoma (serous) of müllerian type: a subgroup of women presenting with peritoneal carcinomatosis. Int J Gynecol Cancer. 1994;4: Zhou J, Iwasa Y, Konishi I, et al. Papillary serous carcinoma of the peritoneum in women: a clinicopathologic and immunohistochemical study. Cancer. 1995;76: Loggie BW. Malignant peritoneal mesothelioma. Curr Treat Options Oncol. 2001;2: Ehrenreich T, Selikoff IJ. Diseases associated with asbestos exposure: diagnostic perspectives in forensic pathology. Am J Forensic Med Pathol. 1983;4: Attanoos RL, Gibbs AR. Pathology of malignant mesothelioma. Histopathology. 1997;30: Ordóñez NG. Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas. Am J Surg Pathol. 1998;22: Attanoos RL, Webb R, Dojcinov SD, et al. Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum. Histopathology. 2002;40: Bollinger DJ, Wick MR, Dehner LP, et al. Peritoneal malignant mesothelioma versus serous papillary carcinoma of the ovary and peritoneum. Histopathology. 1989;40: Abutaily AS, Addis BJ, Roche WR. Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol. 2002;55: Attanoos RL, Webb R, Dojcinov SD, et al. Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern. Histopathology. 2001;39: Ordóñez NG. The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg Pathol. 2003;27: Roberts F, Harper CM, Downie I, et al. Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma: a study of thirteen antibodies. Am J Clin Pathol. 2001;116: Attanoos RL, Webb R, Gibbs AR. CD44H expression in reactive mesothelium, pleural mesothelioma and pulmonary adenocarcinoma. Histopathology. 1997;30: Carella R, Deleonardi G, D Errico A, et al. Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis. Am J Surg Pathol. 2001;25: Cury PM, Butcher DN, Fisher C, et al. Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol. 2000;13: Ordóñez NG. Value of thyroid transcription factor-1, E- cadherin, BG8, WT1, and CD44S immunostaining in distinguishing epithelial pleural mesothelioma from pulmonary and nonpulmonary adenocarcinoma. Am J Surg Pathol. 2000;24: Roberts F, McCall AE, Burnett RA. Malignant mesothelioma: a comparison of biopsy and postmortem material by light microscopy and immunohistochemistry. J Clin Pathol. 2001;54: Chu CS, Menzin AW, Leonard DG, et al. Primary peritoneal carcinoma: a review of the literature. Obstet Gynecol Surv. 1999;54: Nielsen AM, Olsen JH, Madsen PM, et al. Peritoneal mesotheliomas in Danish women: review of histopathological slides and history of abdominal surgery. Acta Obstet Gynecol Scand. 1994;73: Trupiano JK, Geisinger KR, Willingham MC, et al. Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers. Mod Pathol. 2004;17: Latza U, Niedobitek G, Schwarting R, et al. Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. J Clin Pathol. 1990;43: Friedman MT, Gentile P, Tarectecan A, et al. Malignant mesothelioma: immunohistochemistry and DNA ploidy analysis as methods to differentiate mesothelioma from benign reactive mesothelial cell proliferation and adenocarcinoma in pleural and peritoneal effusions. Arch Pathol Lab Med. 1996;120: Enmark E, Gustafsson JA. Oestrogen receptors: an overview. J Intern Med. 1999;246: Osborne CK. Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat. 1998;51: Halperin R, Zehavi S, Hadas E, et al. Immunohistochemical comparison of primary peritoneal and primary ovarian serous papillary carcinoma. Int J Gynecol Pathol. 2001;20: Henzen-Logmans SC, Fieret EJ, Berns EM, et al. Ki-67 staining in benign, borderline, malignant primary and metastatic ovarian tumors: correlation with steroid receptors, epidermal-growth-factor receptor and cathepsin D. Int J Cancer. 1994;57: Doglioni C, Tos AP, Laurino L, et al. Calretinin: a novel immunocytochemical marker for mesothelioma. Am J Surg Pathol. 1996;20: Rothacker D, Mobius G. Varieties of serous papillary carcinoma of the peritoneum in northern Germany: a thirtyyear autopsy study. Int J Gynecol Pathol. 1995;14: Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9 75
10 Barnetson et al / PERITONEAL MESOTHELIOMA AND SEROUS CARCINOMA 31. Wick MR, Mills SE, Swanson PE. Expression of myelomonocytic antigens in mesotheliomas and adenocarcinomas involving the serosal surfaces. Am J Clin Pathol. 1990;94: Delahaye M, van der Ham F, van der Kwast TH. Complementary value of five carcinoma markers for the diagnosis of malignant mesothelioma, adenocarcinoma metastasis, and reactive mesothelium in serous effusions. Diagn Cytopathol. 1997;17: Oates J, Edwards C. HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma. Histopathology. 2000;36: Gonzalez-Lois C, Ballestin C, Sotelo MT, et al. Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura. Histopathology. 2001;38: Ordóñez NG. Value of the MOC-31 monoclonal antibody in differentiating epithelial pleural mesothelioma from lung adenocarcinoma. Hum Pathol. 1998;29: Leers MP, Aarts MM, Theunissen PH. E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma. Histopathology. 1998;32: Park SY, Kim HS, Hong EK, et al. Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary. Hum Pathol. 2002;33: Cathro HP, Stoler MH. Expression of cytokeratins 7 and 20 in ovarian neoplasia. Am J Clin Pathol. 2002;117: Tot T. The value of cytokeratins 20 and 7 in discriminating metastatic adenocarcinomas from pleural mesotheliomas. Cancer. 2001;92: Ordóñez NG. Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. Adv Anat Pathol. 2000;7: Lau SK, Luthringer DJ, Eisen RN. Thyroid transcription factor-1: a review. Appl Immunohistochem Mol Morphol. 2002;10: Tan D, Li Q, Deeb G, et al. Thyroid transcription factor-1 expression prevalence and its clinical implications in non small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study. Hum Pathol. 2003;34: Hecht JL, Pinkus JL, Weinstein LJ, et al. The value of thyroid transcription factor-1 in cytologic preparations as a marker for metastatic adenocarcinoma of lung origin. Am J Clin Pathol. 2001;116: Chu PG, Weiss LM. Expression of cytokeratin 5/6 in epithelial neoplasms: an immunohistochemical study of 509 cases. Mod Pathol. 2002;15: Kennedy AD, King G, Kerr KM. HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of pleura. J Clin Pathol. 1997;50: Ordóñez NG. Value of thrombomodulin immunostaining in the diagnosis of mesothelioma. Histopathology. 1997;31: Ordóñez NG. The immunohistochemical diagnosis of epithelial mesothelioma. Hum Pathol. 1999;30: Ordóñez NG. Application of mesothelin immunostaining in tumor diagnosis. Am J Surg Pathol. 2003;27: Ordóñez NG. Value of mesothelin immunostaining in the diagnosis of mesothelioma. Mod Pathol. 2003;16: Foster MR, Johnson JE, Olson SJ, et al. Immunohistochemical analysis of nuclear versus cytoplasmic staining of WT1 in malignant mesotheliomas and primary pulmonary adenocarcinomas. Arch Pathol Lab Med. 2001;125: Miettinen M, Limon J, Niezabitowski A, et al. Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma. Am J Surg Pathol. 2001;25: Hwang H, Quenneville L, Yaziji H, et al. Wilms tumor gene product: sensitive and contextually specific marker of serous carcinomas of ovarian surface epithelial origin. Appl Immunohistochem Mol Morphol. 2004;12: Shimizu M, Toki T, Tagaki Y, et al. Immunohistochemical detection of the Wilms tumor gene (WT1) in epithelial ovarian tumors. Int J Gynecol Pathol. 2000;19: Goldstein NS, Bassi D, Uzieblo A. WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms. Am J Clin Pathol. 2001;116: Hashi A, Yuminamochi T, Murata S, et al. Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum. Int J Gynecol Pathol. 2003;22: Al-Hussaini M, Stockman A, Foster H, et al. WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma. Histopathology. 2004;44: Goldstein NS, Uzieblo A. WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas. Am J Clin Pathol. 2002;117: Am J Clin Pathol 2006;125: DOI: /8FCHQ3VPBWM7B5X9
20 Diagnostic Cytopathology, Vol 36, No 1 ' 2007 WILEY-LISS, INC.
Utility of WT-1, p63, MOC31, Mesothelin, and Cytokeratin (K903 and CK5/6) Immunostains in Differentiating Adenocarcinoma, Squamous Cell Carcinoma, and Malignant Mesothelioma in Effusions Robert T. Pu,
More informationThe Value of Thyroid Transcription Factor-1 in Cytologic Preparations as a Marker for Metastatic Adenocarcinoma of Lung Origin
Anatomic Pathology / TTF-1 IN CYTOLOGY OF BODY FLUIDS The Value of Thyroid Transcription Factor-1 in Cytologic Preparations as a Marker for Metastatic Adenocarcinoma of Lung Origin Jonathan L. Hecht, MD,
More informationPractical Effusion Cytology
Practical Effusion Cytology A Community Pathologist s Approach to Immunocytochemistry in Body Fluid Cytology Emily E. Volk, MD William Beaumont Hospital Troy, MI College of American Pathologists 2004.
More informationOutline. Workup for metastatic breast cancer. Metastatic breast cancer
Metastatic breast cancer Immunostain Update: Diagnosis of metastatic breast carcinoma, emphasizing distinction from GYN primary 1/3 of breast cancer patients will show metastasis 1 st presentation or 20-30
More informationUpdate on Mesothelioma
November 8, 2012 Update on Mesothelioma Intro incidence and nomenclature Update on Classification Diagnostic specimens Morphologic features Epithelioid Histology Biphasic Histology Immunohistochemical
More informationAcadémie internationale de Pathologie - Division arabe XX ème congrès 24-26 novembre 2008 Alger. Immunohistochemistry in malignant mesotheliomas
Académie internationale de Pathologie - Division arabe XX ème congrès 24-26 novembre 2008 Alger Immunohistochemistry in malignant mesotheliomas Françoise Thivolet-Béjui Groupement Hospitalier Est Lyon-Bron
More informationMALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY
MALIGNANT MESOTHELIOMA CLASSIFICATION MALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY Sisko Anttila, MD, PhD Jorvi Hospital Laboratory of Pathology Helsinki University Hospital Espoo,
More informationMALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY
MALIGNANT MESOTHELIOMA UPDATE ON PATHOLOGY AND IMMUNOHISTOCHEMISTRY Sisko Anttila, MD, PhD Jorvi Hospital Laboratory of Pathology Helsinki University Hospital Espoo, Finland 2nd Nordic Conference on Applied
More informationDiagnosis of Mesothelioma Pitfalls and Practical Information
Diagnosis of Mesothelioma Pitfalls and Practical Information Mary Beth Beasley, M.D. Mt Sinai Medical Ctr Dept of Pathology One Gustave L Levy Place New York, NY 10029 (212) 241-5307 mbbeasleymd@yahoo.com
More informationDisclosures. Learning Objectives. Effusion = Confusion. Diagnosis Of Serous Cavity Effusions - Beware The Mesothelial Cell!
Disclosures Diagnosis Of Serous Cavity Effusions - Beware The Mesothelial Cell! No Relevant Financial Relationships with Commercial Interests Syed Z. Ali, M.D. Syed Z. Ali, M.D. Associate Professor of
More informationHow To Test For Cancer
Diagnosis Of Serous Cavity Effusions - Beware The Mesothelial Cell! Effusion = Confusion Syed Z. Ali, M.D. Professor of Pathology and Radiology The Johns Hopkins Hospital Baltimore, Maryland Diagnostic
More informationThe develpemental origin of mesothelium
Mesothelioma Tallinn 14.12.06 Henrik Wolff Finnish Institute of Occupational Health The develpemental origin of mesothelium Mesodermal cavities (pleura, peritoneum and pericardium ) are lined with mesenchymal
More informationCase of the. Month October, 2012
Case of the Month October, 2012 Case The patient is a 47-year-old male with a 3-week history of abdominal pain. A CT scan of the abdomen revealed a suggestion of wall thickening at the tip of the appendix
More informationPATHOLOGY OF THE PLEURA: Mesothelioma and mimickers Necessity of Immunohistochemistry. M. Praet
PATHOLOGY OF THE PLEURA: Mesothelioma and mimickers Necessity of Immunohistochemistry M. Praet Pathology of the Pleura Normal serosa: visceral and parietal layers Inflammation Neoplasia: Primary: mesothelioma
More informationA 70-year old Man with Pleural Effusion
Mesothelioma Diagnosis: Pitfalls and Latest Updates S Klebe and DW Henderson Recommendations Indisputable malignant cells on cytomorphological criteria which demonstrate a mesothelial phenotype, which
More informationBRIEF REPORTS. Introduction
BRIEF REPORTS WT1, Monoclonal CEA, TTF1, and CA125 Antibodies in the Differential Diagnosis of Lung, Breast, and Ovarian Adenocarcinomas in Serous Effusions Weijian Zhu, M.D., Ph.D. and Claire W. Michael,
More informationToday s Topics. Tumors of the Peritoneum in Women
Today s Topics Tumors of the Peritoneum in Women Charles Zaloudek, M.D. Department of Pathology 505 Parnassus Ave., M563 University of California, San Francisco San Francisco, CA USA charles.zaloudek@ucsf.edu
More informationDiagnostic Challenge. Department of Pathology,
Cytology of Pleural Fluid as a Diagnostic Challenge Paavo Pääkkö,, MD, PhD Chief Physician and Head of the Department Department of Pathology, Oulu University Hospital,, Finland Oulu University Hospital
More informationPRIMARY SEROUS CARCINOMA OF PERITONEUM: A CASE REPORT
PRIMARY SEROUS CARCINOMA OF PERITONEUM: A CASE REPORT Dott. Francesco Pontieri (*) U.O. di Anatomia Patologica P.O. di Rossano (CS) Dott. Gian Franco Zannoni Anatomia Patologica Facoltà di Medicina e Chirurgia
More informationHKCPath Anatomical Pathology Peer Review and Scores : PDF version for download
AP2003R1 http://hkcpath.org. Correspondence: pkhui@ha.org.hk 1of 10 07/08/2003 HKCPath Anatomical Pathology Peer Review and Scores : PDF version for download AP141 Bone Marrow: Metastatic Carcinoma from
More informationEffusions: Mesothelioma and Metastatic Cancers
Effusions: Mesothelioma and Metastatic Cancers Malignant Mesothelioma Incidence: 2,500 cases/year ~60-80% pts with pleural MM relationship with asbestos exposure Other risk factors: radiation, other carcinogens,
More informationSeattle. Case Presentations. Case 1. 76 year old female with a history of breast cancer 12 years ago. Now presents with a pleural effusion.
Seattle Montreal IAP September 2006 Case Presentations Allen M. Gown, M.D. Medical Director and Chief Pathologist PhenoPath Laboratories Clinical Professor of Pathology University of British Columbia Case
More informationNotice of Faculty Disclosure
The Diagnosis of Malignant Mesothelioma Andrew Churg, MD Department of Pathology University of British Columbia Vancouver, BC, Canada achurg@mail.ubc.ca Notice of Faculty Disclosure In accordance with
More informationNo Difference Between Mesothelioma and Pulmonary and Nonpulmonary Adenocarcinoma DO NOT DUPLICATE. Malignancy is a common cause of effusions of the
NONGYNECOLOGIC CYTOPTHOLOGY CK5/6 in Effusions No Difference etween Mesothelioma and Pulmonary and Nonpulmonary denocarcinoma nnika Dejmek, M.D., Ph.D. Objective To test the performance of CK5/6 for the
More informationAbstract. Introduction. Material and Methods
Original Article Expression of Mesothelial Markers in Malignant Mesotheliomas: an Immunohistochemical Evaluation of 173 Cases I.N. Soomro, R. Oliveira*, J. Ronan, Z. R. Chaudry, J. Johnson Department of
More information264 Diagnostic Cytopathology, Vol 38, No 4 ' 2010 WILEY-LISS, INC.
Podoplanin Is a Useful Marker for Identifying Mesothelioma in Malignant Effusions Atef Hanna, M.D., Ph.D., 1 Yijun Pang, M.D., Ph.D., 1 Carlos W. M. Bedrossian, M.D., 2 Annika Dejmek, M.D., Ph.D., 3 and
More informationBer-EP4 and Anti-Calretinin Antibodies: A Useful Combination for
Tohoku J. Exp. Med., Differential 2005, 206, Diagnosis 31-40 of Ovarian Cancer Cells and Mesothelial Cells 31 Ber-EP4 and Anti-Calretinin Antibodies: A Useful Combination for Differential Diagnosis of
More informationImmunohistochemical differentiation of metastatic tumours
Immunohistochemical differentiation of metastatic tumours Dr Abi Wheal ST1. TERA 3/2/14 Key points from a review article written by Daisuke Nonaka Intro Metastatic disease is the initial presentation in
More informationMOC-31 Exhibits Superior Reactivity Compared With Ber-EP4 in Invasive Lobular and Ductal Carcinoma of the Breast. A Tissue Microarray Study
RESEARCH ARTICLE MOC-31 Exhibits Superior Reactivity Compared With Ber-EP4 in Invasive Lobular and Ductal Carcinoma of the Breast A Tissue Microarray Study Reetesh K. Pai, MD and Robert B. West, MD Abstract:
More informationA Cytokeratin- and Calretinin-negative Staining Sarcomatoid Malignant Mesothelioma
A Cytokeratin- and Calretinin-negative Staining Sarcomatoid Malignant Mesothelioma MICHAEL G. HURTUK and MICHELE CARBONE Cardinal Bernadin Cancer Center, Cancer Immunology Program, Department of Pathology,
More informationProtocol applies to all primary borderline and malignant epithelial tumors, and malignant mesothelial neoplasms of the peritoneum.
Peritoneum Protocol applies to all primary borderline and malignant epithelial tumors, and malignant mesothelial neoplasms of the peritoneum. Protocol revision date: January 2004 No AJCC/UICC staging system
More informationProtocol for the Examination of Specimens From Patients With Tumors of the Peritoneum
Protocol for the Examination of Specimens From Patients With Tumors of the Peritoneum Protocol applies to all primary borderline and malignant epithelial tumors and malignant mesothelial neoplasms of the
More informationHow To Use Calretinin
Product Code: MP-092-CR01 (0.1ml concentrate) MP-092-CR05 (0.5ml concentrate) MP-092-CR1 (1ml concentrate) MP-092-PR6 (6ml RTU) Product Description: Calretinin Concentrated and Prediluted Polyclonal Antibody
More informationOvarian tumors Ancillary methods
Ovarian tumors Ancillary methods Ovarian tumor course Oslo, 24-25/11/14 Prof. Ben Davidson, MD PhD Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway Division of
More informationHow To Diagnose And Treat A Tumour In An Effusion
Effusions of the Serous Cavities Annika Dejmek Professor/Consultant in Cytopathology Clinical Pathology; Department of Laboratory Medicine, Malmö, Lund University 5th EFCS Tutorial Trondheim 2012 Pleura
More informationCytopathology Case Presentation #8
Cytopathology Case Presentation #8 Emily E. Volk, MD William Beaumont Hospital, Troy, MI Jonathan H. Hughes, MD Laboratory Medicine Consultants, Las Vegas, Nevada Clinical History 44 year old woman presents
More informationOriginal Article Differential diagnosis of sarcomatoid mesothelioma from true sarcoma and sarcomatoid carcinoma using immunohistochemistry
Pathology International 2008; 58: 75 83 doi:10.1111/j.1440-1827.2007.02193.x Original Article Differential diagnosis of sarcomatoid mesothelioma from true sarcoma and sarcomatoid carcinoma using immunohistochemistry
More informationImmunostain Update: Diagnosis of Metastatic Breast Carcinoma, Emphasizing the Distinction from Gynecologic Cancers
Immunostain Update: Diagnosis of Metastatic Breast Carcinoma, Emphasizing the Distinction from Gynecologic Cancers Yunn-Yi Chen, M.D., Ph.D. UCSF Pathology Department yunn-yi.chen@ucsf.edu June 3, 2010
More informationThe diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion
Malaysian J Path01 2002; 24(1) : 53-58 The diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion Pavai STHANESHWAR MD, Sook-Fan YAP FRCPath, FRCPA and Gita JAYARAM MDPath, MRCPath
More informationRecommendations for the Reporting of Pleural Mesothelioma
Recommendations for the Reporting of Pleural Mesothelioma Association of Directors of Anatomic and Surgical Pathology * DOI: 10.1309/6A30YQHBMTHEJTEM It has been evident for decades that pathology reports
More informationThe Use of Immunohistochemistry to Distinguish Reactive Mesothelial Cells From Malignant Mesothelioma in Cytologic Effusions
The Use of Immunohistochemistry to Distinguish Reactive Mesothelial Cells From Malignant Mesothelioma in Cytologic Effusions Farnaz Hasteh, MD 1 ; Grace Y. Lin, MD, PhD 1 ; Noel Weidner, MD 1 ; and Claire
More informationPleural Mesothelioma: An Institutional Experience of 66 Cases
The Korean Journal of Pathology 2014; 48: 91-99 ORIGINAL ARTICLE Pleural Mesothelioma: An Institutional Experience of 66 Cases Soomin Ahn In Ho Choi Joungho Han Jhingook Kim 1 Myung-Ju Ahn 2 Departments
More informationImmunohistochemistry on cytology specimens from pleural and peritoneal fluid
Immunohistochemistry on cytology specimens from pleural and peritoneal fluid Dr Naveena Singh Consultant Pathologist Bart health NHS Trust London United Kingdom Disclosures and Acknowledgements I have
More informationDistinguishing benign from malignant mesothelial
ORIGINAL ARTICLE IMP3 and GLUT-1 Immunohistochemistry for Distinguishing Benign From Malignant Mesothelial Proliferations Anna F. Lee, MDCM, PhD,*w Allen M. Gown, MD,wz and Andrew Churg, MD*w Abstract:
More informationMALIGNANT MESOTHELIOMA: A TYPICAL PRESENTATION IN AN ATYPICAL PATIENT
MALIGNANT MESOTHELIOMA: A TYPICAL PRESENTATION IN AN ATYPICAL PATIENT Written by: Karyn Varley MS, SCT(ASCP) The donating laboratory would like to remain anonymous. PATIENT HISTORY 28 year old female Lived
More informationEffects of Herceptin on circulating tumor cells in HER2 positive early breast cancer
Effects of Herceptin on circulating tumor cells in HER2 positive early breast cancer J.-L. Zhang, Q. Yao, J.-H. Chen,Y. Wang, H. Wang, Q. Fan, R. Ling, J. Yi and L. Wang Xijing Hospital Vascular Endocrine
More informationMATERIALS AND METHODS
Short title running head: Immunohistochemistry of mesothelioma Authors running head: K. Kushitani et al. Correspondence: Kouki Inai, MD, PhD, Department of Pathology, Postgraduate School of Biomedical
More informationISOLATED PANCREATIC METASTASIS OF A MALIGNANT PLEURAL MESOTHELIOMA
ISOLATED PANCREATIC METASTASIS OF A MALIGNANT PLEURAL MESOTHELIOMA Yi-Ting Lin, 1 Bing-Shiun Wu, 2 Sheau-Fang Yang, 3 and Huang-Chi Chen 4 Departments of 1 Family Medicine, 2 Internal Medicine, and 3 Pathology,
More informationHow To Distinguish Between A Metastatic Renal Cell Carcinoma And A Diffuse Malignant Mesothelioma
Expression of Renal Cell Carcinoma Associated Markers Erythropoietin, CD10, and Renal Cell Carcinoma Marker in Diffuse Malignant Mesothelioma and Metastatic Renal Cell Carcinoma Kelly J. Butnor, MD; Andrew
More information3-F. Pathology of Mesothelioma
3-F. Pathology of Mesothelioma Kouki Inai Professor of Department of Pathology, Graduate School of Biomedical Science, Hiroshima University Introduction Mesothelioma is a peculiar type of malignancy, which
More informationCytology : first alert of mesothelioma? Professor B. Weynand, UCL Yvoir, Belgium
Cytology : first alert of mesothelioma? Professor B. Weynand, UCL Yvoir, Belgium Introduction 3 cavities with the same embryologic origin the mesoderme Pleura Exudates Pleura Peritoneum Pericardium 22%
More informationCase presentation. Awatif Al-Nafussi
Case presentation Awatif Al-Nafussi Case History 49 year old DVT & small PE June 08, Pelvic mass Ca125 33 Laparotomy-TAHBSO, drainage of ascites Ovarian carcinoma Clinical diagnosis Multiple specimens
More informationUse of a Panel of Markers in the Differential Diagnosis of Adenocarcinoma and Reactive Mesothelial Cells in Fluid Cytology
Anatomic Pathology / IMMUNOCYTOCHEMICAL PANEL FOR FLUID SPECIMENS Use of a Panel of Markers in the Differential Diagnosis of Adenocarcinoma and Reactive Mesothelial Cells in Fluid Cytology Ellen C. Ko,
More informationCase based applications part III
Case based applications part III Los Angeles Society Of Pathologists January 25, 2014 Sanja Dacic, MD, PhD University of Pittsburgh Medical Center 1 CASE 1 A 44-year-old woman with multiple lung nodules.
More informationChanges in Breast Cancer Reports After Second Opinion. Dr. Vicente Marco Department of Pathology Hospital Quiron Barcelona. Spain
Changes in Breast Cancer Reports After Second Opinion Dr. Vicente Marco Department of Pathology Hospital Quiron Barcelona. Spain Second Opinion in Breast Pathology Usually requested when a patient is referred
More informationFrequently Asked Questions About Ovarian Cancer
Media Contact: Gerri Gomez Howard Cell: 303-748-3933 gerri@gomezhowardgroup.com Frequently Asked Questions About Ovarian Cancer What is ovarian cancer? Ovarian cancer is a cancer that forms in tissues
More informationREVIEW. Introduction. King J E, Thatcher N, Pickering C A C & Hasleton P S (2006) Histopathology 48, 223 232
Histopathology 2006, 48, 223 232. DOI: 10.1111/j.1365-2559.2005.02331.x REVIEW Sensitivity and specificity of immunohistochemical markers used in the diagnosis of epithelioid mesothelioma: a detailed systematic
More informationDiagnosis of epithelial mesothelioma using tree-based regression analysis and a
Diagnosis of epithelial mesothelioma using tree-based regression analysis and a minimal panel of antibodies, Running title: Tree regression analysis for mesothelioma SONJA KLEBE*^, MARKKU NURMINEN, JAMES
More informationMalignant Mesothelioma Diagnosed by Bronchoscopic Biopsy
CASE REPORT http://dx.doi.org/10.4046/trd.2015.78.3.297 ISSN: 1738-3536(Print)/2005-6184(Online) Tuberc Respir Dis 2015;78:297-301 Malignant Mesothelioma Diagnosed by Bronchoscopic Biopsy Yeon-Hee Park,
More informationCarcinosarcoma of the Ovary
Carcinosarcoma of the Ovary A Rare Finding Presented By: Kathryn Kiely Anisa I. Kanbour School of Cytotechnology of the University of Pittsburgh Medical Center Pittsburgh, PA Patient History 55 year old
More informationASBESTOS EXPOSURE AND SARCOMATOID MALIGNANT PLEURAL MESOTHELIOMA Gorantla Sambasivarao 1, Namballa Usharani 2, Tupakula Suresh Babu 3
ASBESTOS EXPOSURE AND SARCOMATOID MALIGNANT PLEURAL MESOTHELIOMA Gorantla Sambasivarao 1, Namballa Usharani 2, Tupakula Suresh Babu 3 HOW TO CITE THIS ARTICLE: Gorantla Sambasivarao, Namballa Usharani,
More informationVideo Microscopy Tutorial 5
Video Microscopy Tutorial 5 Lool Alikes in Effusion Cytology:Review of Diagnostic Challenges Claire Michael, MD There are no disclosures necessary. Look-Alikes in Effusion Cytology: Review of Diagnostic
More informationTumour Markers. What are Tumour Markers? How Are Tumour Markers Used?
Dr. Anthony C.H. YING What are? Tumour markers are substances that can be found in the body when cancer is present. They are usually found in the blood or urine. They can be products of cancer cells or
More informationLymphohistiocytoid Mesothelioma An Often Misdiagnosed Variant of Sarcomatoid Malignant Mesothelioma
Anatomic Pathology / LYMPHOHISTIOCYTOID MESOTHELIOMA Lymphohistiocytoid Mesothelioma An Often Misdiagnosed Variant of Sarcomatoid Malignant Mesothelioma Hasan S. Khalidi, MD, 1 L. Jeffrey Medeiros, MD,
More informationMale. Female. Death rates from lung cancer in USA
Male Female Death rates from lung cancer in USA Smoking represents an interesting combination of an entrenched industry and a clearly drug-induced cancer Tobacco Use in the US, 1900-2000 5000 100 Per Capita
More informationMesothelioma. 1. Introduction. 1.1 General Information and Aetiology
Mesothelioma 1. Introduction 1.1 General Information and Aetiology Mesotheliomas are tumours that arise from the mesothelial cells of the pleura, peritoneum, pericardium or tunica vaginalis [1]. Most are
More informationCase Report Epithelioid angiosarcoma at chest wall which needs to be carefully distinguished from malignant mesothelioma: report of a rare case
Int J Clin Exp Pathol 2014;7(12):9056-9060 www.ijcep.com /ISSN:1936-2625/IJCEP0002446 Case Report Epithelioid angiosarcoma at chest wall which needs to be carefully distinguished from malignant mesothelioma:
More informationNational Coverage Determination (NCD) for Tumor Antigen by Immunoassay - CA 125 (190.28)
National Coverage Determination (NCD) for Tumor Antigen by Immunoassay - CA 125 (190.28) Tracking Information Publication Number Manual Section Number 100-3 190.28 Manual Section Title Tumor Antigen by
More informationTUMORS OF THE TESTICULAR ADNEXA and SPERMATIC CORD
TUMORS OF THE TESTICULAR ADNEXA and SPERMATIC CORD Victor E. Reuter, MD Memorial Sloan-Kettering Cancer Center reuterv@mskcc.org 66 th Annual Pathology Seminar California Society of Pathologists Short
More informationSelection of Calretinin and D2-40 Expression For Malignant Mesothelioma
& 2007 USCAP, Inc All rights reserved 0893-3952/07 $30.00 www.modernpathology.org D2-40 and calretinin a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation
More informationPrimary malignant gonadal mesotheliomas and asbestos
Histopathology 2000, 37, 150±159 Primary malignant gonadal mesotheliomas and asbestos R L Attanoos & A R Gibbs Department of Histopathology, University Hospital of Wales and Llandough Hospital, Cardiff,
More informationNovocastra Liquid Mouse Monoclonal Antibody CD141 (Thrombomodulin)
Novocastra Liquid Mouse Monoclonal Antibody CD141 (Thrombomodulin) Product Code: NCL-L-CD141 Leica Biosystems Newcastle Ltd Balliol Business Park West Benton Lane Newcastle Upon Tyne NE12 8EW United Kingdom
More informationClinicopathological Study on Malignant Pleural Mesotheliomas
Table of Contents Clinicopathological Study on Malignant Pleural Mesotheliomas PL-4-03 Kenzo Hiroshima Kenzo Hiroshima 1, Akira Iyota 1, Kiyoshi Sibuya 1, Toshikazu Yusa 2, Takehiko Fujisawa 1 and Yukio
More informationMalignant Mesothelioma in Body Fluids - with Special Reference to Differential Diagnosis from Metastatic Adenocarcinoma -
The Korean Journal of Pathology 2009; 43: 458-66 DOI: 10.4132/KoreanJPathol.2009.43.5.458 Malignant Mesothelioma in Body Fluids - with Special Reference to Differential Diagnosis from Metastatic Adenocarcinoma
More informationRole of immunohistochemistry
Tumors of serous membranes of difficult diagnosis: Dr. Hector Battifora Role of immunohistochemistry Abstract: The most common differential diagnosis of tumors involving serosal surfaces is adenocarcinoma
More informationCase Report Epithelioid malignant mesothelioma presenting with features of gastric tumor in a child
Int J Clin Exp Pathol 2014;7(5):2636-2640 www.ijcep.com /ISSN:1936-2625/IJCEP0000187 Case Report Epithelioid malignant mesothelioma presenting with features of gastric tumor in a child Qihan You 1, Jing
More informationCombined CA125 and Mesothelin Levels for the Diagnosis of Malignant Mesothelioma*
CHEST Combined CA125 and Mesothelin Levels for the Diagnosis of Malignant Mesothelioma* Jenette Creaney, PhD; Ivonne van Bruggen, BSc; Michelle Hof, BSc; Amanda Segal, MBBS; Arthur W. Musk, MBBS, MD, FCCP;
More informationPNL2 MELANOCYTIC MARKER IN IMMUNOHISTOCHEMICAL EVALUATION OF PRIMARY MUCOSAL MELANOMA OF THE HEAD AND NECK
ORIGINAL ARTICLE PNL2 MELANOCYTIC MARKER IN IMMUNOHISTOCHEMICAL EVALUATION OF PRIMARY MUCOSAL MELANOMA OF THE HEAD AND NECK Luc G. Morris, MD, 1 Yong Hannah Wen, MD, PhD, 2 Daisuke Nonaka, MD, 2 Mark D.
More informationEp-CAM/Epithelial Specific Antigen (MOC-31)
Ep-CAM/Epithelial Specific Antigen (MOC- Product Identification Cat. No. Description 44588 EP-CAM 0,1 M (MOC- 44589 EP-CAM 1 M (MOC- 44283 EP-CAM RTU M (MOC- Symbol Definitions P C A E S DIL DOC# DIS ready-to-use
More informationJ of Evidence Based Med & Hlthcare, pissn- 2349-2562, eissn- 2349-2570/ Vol. 2/Issue 33/Aug. 17, 2015 Page 5063
PERITONEAL MALIGNANT MESOTHELIOMA: A RARE S. R. Dhamotharan 1, S. Shanthi Nirmala 2, F. Celine Foustina Mary 3, M. Arul Raj Kumar 4, R. Vinothprabhu 5 HOW TO CITE THIS ARTICLE: S. R. Dhamotharan, S. Shanthi
More informationReport series: General cancer information
Fighting cancer with information Report series: General cancer information Eastern Cancer Registration and Information Centre ECRIC report series: General cancer information Cancer is a general term for
More informationDESMOPLASTIC SMALL ROUND CELL TUMOR: A RARE PATHOLOGY PUZZLE
DESMOPLASTIC SMALL ROUND CELL TUMOR: A RARE PATHOLOGY PUZZLE Ryan Granger University of Rhode Island Cytotechnology program May 2, 2015 ASCT Annual Meeting Nashville, Tennessee DESMOPLASTIC SMALL ROUND
More informationRenal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD
Renal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD Department of Pathology University of Szeged, Hungary ISUP Vancouver Classification of Renal Neoplasia Am J Surg Pathol 37:14691489, 2013 13 histologic
More informationThe Diagnosis of Cancer in the Pathology Laboratory
The Diagnosis of Cancer in the Pathology Laboratory Dr Edward Sheffield Christmas Select 74 Meeting, Queen s Hotel Cheltenham, 3 rd December 2014 Agenda Overview of the pathology of cancer How specimens
More informationبسم هللا الرحمن الرحيم
بسم هللا الرحمن الرحيم Updates in Mesothelioma By Samieh Amer, MD Professor of Cardiothoracic Surgery Faculty of Medicine, Cairo University History Wagner and his colleagues (1960) 33 cases of mesothelioma
More informationJOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH How to cite this article: DEBNATH S, MISRA V, SINGH PA, SINGH M. LOW GRADE CYSTIC MESOTHELIOMA OF RECTUS SHEATH.Journal of Clinical and Diagnostic Research [serial
More informationTargeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma
The Use of Kinase Inhibitors: Translational Lab Results Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma Sheelu Varghese, Ph.D. H. Richard Alexander, M.D.
More informationOvarian Cancer: A Case Report
Ovarian Cancer: A Case Report Abstract Ovarian cancer is a very common cancer among women. It is an extremely diverse disease requiring several treatment options. Occasionally ovarian cancer is diagnosed
More informationOvarian mucinous lesions. Ovarian mucinous lesions: Common diagnostic dilemmas. Ovarian mucinous lesions: problematic issues
Ovarian mucinous lesions Ovarian mucinous lesions: Common diagnostic dilemmas Karuna Garg, MD University of California San Francisco Intestinal or usual type Seromucinous (Endocervical mucinous or Mullerian
More informationImmunohistochemical Expression of Osteopontin in Epithelioid Mesotheliomas and Reactive Mesothelial Proliferations
natomic Pathology / OSTEOPONTIN IN MESOTHELIL PROLIFERTIONS Immunohistochemical Expression of Osteopontin in Epithelioid Mesotheliomas and Reactive Mesothelial Proliferations Dean-Yar Tigrani, MD, and
More informationBreast cancer or metastasis? An unusual case of metastatic malignant pleural mesothelioma to the breast
Framarino-dei-Malatesta et al. World Journal of Surgical Oncology (2015) 13:79 DOI 10.1186/s12957-015-0491-z WORLD JOURNAL OF SURGICAL ONCOLOGY CASE REPORT Open Access Breast cancer or metastasis? An unusual
More informationFine Needle Aspiration Cytologic Features of Well-Differentiated Papillary Mesothelioma in the Pleura
The Korean Journal of Pathology 2009; 43: 583-8 DOI: 10.4132/KoreanJPathol.2009.43.6.583 Fine Needle Aspiration Cytologic Features of Well-Differentiated Papillary Mesothelioma in the Pleura - A Case Report
More informationNeoplasms of the LUNG and PLEURA
Neoplasms of the LUNG and PLEURA 2015-2016 FCDS Educational Webcast Series Steven Peace, BS, CTR September 19, 2015 2015 Focus o Anatomy o SSS 2000 o MPH Rules o AJCC TNM 1 Case 1 Case Vignette HISTORY:
More informationThe evolving pathology of solitary fibrous tumours. Luciane Dreher Irion MREH / CMFT / NSOPS
The evolving pathology of solitary fibrous tumours Luciane Dreher Irion MREH / CMFT / NSOPS Historical review Haemangiopericytoma (HPC) first described primarily as a soft tissue vascular tumour of pericytic
More informationYOUR LUNG CANCER PATHOLOGY REPORT
UNDERSTANDING YOUR LUNG CANCER PATHOLOGY REPORT 1-800-298-2436 LungCancerAlliance.org A GUIDE FOR THE PATIENT 1 CONTENTS What is a Pathology Report?...3 The Basics...4 Sections of a Pathology Report...7
More informationCase Report Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast
Case Reports in Oncological Medicine Volume 2015, Article ID 298523, 4 pages http://dx.doi.org/10.1155/2015/298523 Case Report Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast
More informationDiagnostic Utility of MOC-31, HBME-1 and MOC-31mRNA in Distinguishing Between Carcinoma Cells and Reactive Mesothelial Cells in Pleural Effusions
Diagnostic Utility of MOC-31, HBME-1 and MOC-31mRNA in Distinguishing Between Carcinoma Cells and Reactive Mesothelial Cells in Pleural Effusions Ying Sun, M.D., Guang-Ping Wu, Ph.D., Chang-Qing Fang,
More informationPathology of the Female Peritoneum, Common and Uncommon Problems
Pathology of the Female Peritoneum, Common and Uncommon Problems An Update on Gynecologic Pathology Florence, Italy Anaís Malpica, M.D. Professor of Pathology Pathology of the Female Peritoneum Keratin
More informationPRODYNOV. Targeted Photodynamic Therapy of Ovarian Peritoneal Carcinomatosis ONCO-THAI. Image Assisted Laser Therapy for Oncology
PRODYNOV Targeted Photodynamic Therapy of Ovarian Peritoneal Carcinomatosis ONCO-THAI Image Assisted Laser Therapy for Oncology Inserm ONCO-THAI «Image Assisted Laser Therapy for Oncology» Inserm ONCO-THAI
More informationINTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER Prospective Mesothelioma Staging Project
INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER Prospective Mesothelioma Staging Project Data Forms and Fields in CRAB Electronic Data Capture System - Reduced Set - Pivotal data elements for developing
More information