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PubMedDate not supplied

Malignant mesothelioma in 2004: How advanced technology and new drugs are changing the perspectives of mesothelioma patients. Highlights from the VIIth Meeting of the International Mesothelioma Interest Group.

Malignant mesothelioma (MMe) is a seemingly uncommon tumour whose incidence has in fact increased steadily and progressively over the last 30 years. Indeed, an actual "epidemic" is expected in the next 20 years, with over 1300 new cases a year till 2020 at least. Despite unquestionable improvement in the diagnostic methods at our disposal and the availability of new treatment strategies, the prognosis of MMe patients remains dramatically poor. For all the above reasons, translational research is the key to success; indeed, ever increasing knowledge of the molecular mechanisms underlying MMe pathogenesis could lead (and is actually leading) to new, hopefully more active, treatment options. To foster discussion among investigators working in this field, and to exchange different viewpoints concerning the newest advances in MMe pathogenesis and treatment, the VII International Mesothelioma Interest Group (IMIG) meeting was held in Brescia (Italy) between 24 and 26 June 2004 in cooperation with the Italian Group for the Study and Therapy of MMe (GIMe). The aim of this report is to summarize the most significant advances in the different disciplines applied to MMe presented and discussed during the IMIG meeting and how these advances will be changing the perspective of patients with MMe.

Angiogenesis Inhibitors↗
PubMed1999

The use of histological and immunohistochemical markers to distinguish pleural malignant mesothelioma and in situ mesothelioma from reactive mesothelial hyperplasia and reactive pleural fibrosis.

Distinguishing malignant mesothelioma from reactive mesothelial hyperplasia and reactive fibrosis can be a diagnostic problem in small pleural biopsies, made more difficult by the recent recognition of mesothelioma-in-situ. Antibodies to epithelial membrane antigen (EMA), p53, and bcl-2 have all been advocated for differentiating reactive from neoplastic conditions, but reports are inconsistent. These antibodies have therefore been applied to 31 cases of malignant mesothelioma, 34 cases of reactive pleural disease (20 reactive mesothelial hyperplasia and 14 reactive pleural fibrosis) and four small biopsies that were initially coded as suspicious, from patients who later developed frank mesothelioma. Thirty out of 31 (97 per cent) cases of mesothelioma showed positive nuclear staining for p53, with a higher incidence of positivity in epithelioid than in sarcomatoid elements and 30/31 (97 per cent) showed diffuse linear membrane staining for EMA, again more intense in the epithelioid elements. No mesothelioma was positive for bcl-2. In seven cases that contained both in situ and invasive mesothelioma, the in situ elements showed similar staining patterns to the invasive epithelioid elements. Thirteen out of 20 (65 per cent) cases of reactive mesothelial hyperplasia showed occasional nuclear positivity for p53 and 5/20 (25 per cent) cases showed focal weak membrane staining for EMA. Three out of 14 (21 per cent) cases of reactive pleural fibrosis showed positive nuclear staining for p53 and 6/14 (43 per cent) cases showed focal membrane staining with EMA. No reactive cases stained for bcl-2. All four suspicious cases showed diffuse linear staining with EMA and three showed focal staining for p53. It is concluded that strong diffuse linear staining for EMA is a good marker of malignancy when differentiating epithelioid malignant mesothelioma and mesothelioma-in-situ from reactive mesothelial hyperplasia, although weak focal staining may occur in reactive conditions. Nuclear staining for p53 is also suggestive of epithelioid mesothelioma, but should be regarded as no more than suspicious. The antibodies used in this investigation are less helpful in differentiating sarcomatoid mesothelioma from reactive pleural fibrosis.

Biomarkers, Tumor↗
PubMed1996

Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma.

The aim of this study was to examine the expression of three putative mesothelioma-binding antibodies, thrombomodulin, OV 632 and HBME-1 in 42 malignant mesotheliomas (27 pleural and 15 peritoneal) and 32 pulmonary adenocarcinomas. Evaluation of their use in differentiating between the mesotheliomas and pulmonary adenocarcinomas was assessed. Thrombomodulin was expressed by 22 of 42 (52%) mesotheliomas but was seen in eight of 12 pure epithelial-type mesotheliomas of the pleura and in all four papillary epithelial peritoneal mesotheliomas. For pure epithelial mesotheliomas thrombomodulin was 75% sensitive. Only two of 32 pulmonary adenocarcinomas were immunoreactive yielding a 94% specificity for thrombomodulin. In comparison, OV 632 and HBME-1 showed 67% and 62% antibody sensitivity, respectively, for malignant mesothelioma but this was accompanied by low specificity (OV 632, 37%; HBME-1, 28%). Both OV 632 and HBME-1 are considered unsuitable for use in differentiating between mesotheliomas and pulmonary adenocarcinomas. We advocate the use of thrombomodulin as a mesothelioma-binding antibody in the standard panel of antibodies used in the evaluation of malignant mesothelioma.

Adenocarcinoma↗
PubMed1994

Immunocytochemical characterization of cell lines from human malignant mesothelioma: characterization of human mesothelioma cell lines by immunocytochemistry with a panel of monoclonal antibodies.

A panel of nine monoclonal antibodies was used to characterize human mesothelioma cell lines that we established from human malignant mesothelioma. The antigens detected were cytokeratin, vimentin, epithelial membrane antigen, carcinoembryonic antigen, Leu-M1 (CD15), desmin, factor VIII-related antigen (von Willebrand factor antigen), OV632, and ME1, a specific monoclonal antibody directed against human malignant mesothelioma. The technique used was the alkaline phosphatase anti-alkaline phosphatase method. All 30 cell lines, either epithelial, sarcomatous, or mixed, showed strong reactivity with cytokeratin and vimentin antibodies. None of the cell lines demonstrated any reactivity with carcinoembryonic antigen, Leu-M1, or factor VIII antibodies; moreover, all of 22 cell lines studied were positive for ME1 antibody and 10 of 12 cell lines studied were positive for OV632. Some interesting features were noted: only two of the 30 cell lines presented a weak positive staining with epithelial membrane antigen, and nine of 19 cell lines tested demonstrated a cytoplasmic staining pattern with desmin antibody. These results show that established human mesothelioma cell lines still possess the immunocytochemical characteristics that are basically consistent with the immunohistochemical features described in tumor tissues of malignant mesothelioma. These characteristics can be used to identify the mesothelioma cells grown from human malignant mesothelioma. Hence, the mesothelioma cell lines will provide a useful tool for the investigation of the cell biology of the tumor and the mechanisms of mesothelial cell transformation, as well as the in vitro evaluation of the effects of some drugs in order to develop new therapies for malignant mesothelioma.

Actins↗
PubMed2001

Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma.

Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial differentiation. SS commonly metastasizes to lung and pleura, and has also been reported as the primary in these locations. The histologic distinction of SS from mesothelioma may be difficult because of the combination of epithelioid and spindle cells, potentially shared locations, and antigenic expression. In this study the authors examined 103 well-documented SSs including 41 biphasic, 44 monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields or foci of calretinin-positive tumor cells. The spindle cell components were more often positive (55%), whereas 14% of tumors had positive epithelial cells. The monophasic and poorly differentiated SSs commonly had foci of calretinin-positive cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly detected in biphasic SS and EM (100% and 87% respectively). Among the other sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12 of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs typically showed prominent membrane staining in epithelial cells. Simple epithelial keratins were present in all epithelial cells of biphasic SS and mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases), whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered positive cells. The potentially shared calretinin patterns in SS and mesothelioma require the use of other markers. The discriminating features include extensive BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns of K14 expression may also be helpful.

Adolescent↗
PubMed1989

The immunohistochemical diagnosis of mesothelioma. Differentiation of mesothelioma and lung adenocarcinoma.

Despite numerous histochemical, ultrastructural, and immunohistochemical studies, differentiation between malignant epithelial pleural mesothelioma and adenocarcinoma of the lung remains extremely difficult. Although there is general agreement that immunohistochemical methods can aid in this distinction, some studies have produced conflicting results with some of the proposed markers for mesothelioma. To obtain comparable and reproducible results, 19 unequivocal epithelial mesotheliomas and 23 unequivocal primary lung adenocarcinomas were studied by the avidin-biotin-peroxidase complex method on formalin-fixed, paraffin-embedded tissue specimens. Well-characterized, commercially available antibodies to carcinoembryonic antigen (CEA), a high- and low-molecular-weight keratin, vimentin, epithelial membrane antigen, human milk fat globule, Leu-M1, TAG-72 (identified by monoclonal antibody B72.3), beta 1 pregnancy-specific glycoprotein (SP1), human placental lactogen, secretory component (SC), CA19-9, and S-100 protein were used. Twenty-one adenocarcinomas (91.3%) reacted for CEA, 14 (60.9%) for Leu-M1, 14 (60.9%) for SC, nine (39.1%) for CA19-9, and eight (34.8%) for SP1; no mesotheliomas stained for any of these markers. Nineteen adenocarcinomas (82.6%) and one mesothelioma (5.3%) reacted with B72.3. Adenocarcinomas and mesotheliomas did not significantly vary in reaction to the remaining antibodies. None of the antibodies used was specific for mesothelioma, but CEA was the single most useful marker. One of the two adenocarcinomas negative for CEA was positive for TAG-72, Leu-M1, and SC, and the only B72.3-positive mesothelioma was negative for CEA, Leu-M1, SC, CA19-9, and SP1. These findings indicate that greater sensitivity in differentiating mesothelioma and adenocarcinoma can be achieved by immunostaining for both CEA and one or more of the markers TAG-72 (B72.3), Leu-M1, SC (these three have the highest sensitivity and specificity after CEA), CA19-9, and SP1.

Adenocarcinoma↗
PubMed2001

Malignant mesothelioma--German mesothelioma register 1987-1999.

OBJECTIVES: The study group comprised a collective of 1,605 patients with malignant mesotheliomas and with lung tissue available for lung dust analyses. METHOD: Clinical features, occupational histories, expositions and individual data were evaluated, and the asbestos bodies concentrations (asbestos bodies/cm3 lung tissue or g wet tissue) were determined. RESULTS: Mesotheliomas developed mainly in men (94.5%). Of the cases, 96.4% were of pleural origin and only 3.3% were peritoneal mesotheliomas. The biphasic subtype predominated (61.3%), followed by the epithelioid type (29.3%). The sarcomatoid subtype was rarely developed (9.4%). Mean age at first diagnosis was 60.4 years. The mean survival time from time of symptom onset was 13.5 months. Patients with epithelioid subtypes had a longer survival time (16.9 months) than those with biphasic (13.1 months) and sarcomatoid subtypes (5.5 months). Of the patients, 73% presented pleural effusions as initial symptoms of the disease. An increased asbestos burden was identified by light microscopy in 84.8% of the patients. There was no association between histological subtypes and the asbestos burden of the lungs. Patients with peritoneal mesotheliomas had distinctly higher asbestos burdens in the lungs than patients with pleural mesotheliomas. There exists no association between lung asbestos burdens and survival times. The mean latency period was 37.8 years. A trend: higher asbestos burden of the lung/shorter latency periods was suggested. About 70% of the patients had a history of occupational exposure to asbestos dust. Most patients worked in the building trade, the locksmith and machine building industries and in the steel and blast-furnace industries. Of the patients, 25.6% had asbestos-associated lung fibroses, in 40.7% of the cases pleural plaques were identified. CONCLUSIONS: The most important causal factor for development of mesotheliomas is still asbestos, primarily amphibole asbestos. The recurring occurrence of mesotheliomas in younger people without known asbestos exposure needs the urgent investigation of other inducing factors for mesotheliomas.

Adult↗
PubMed2005

Nonpleural mesotheliomas: mesothelioma of the peritoneum, tunica vaginalis, and pericardium.

Mesotheliomas are tumors that arise from the mesothelial cells of the pleura, peritoneum, pericardium, or tunica vaginalis. Although the number of new mesothelioma cases diagnosed each year in the United States seems to be leveling off or decreasing, several other countries are projected to have continued increased incidence of mesothelioma over the next several years. Of the approximately 2500 new cases of mesothelioma in the United States each year, most are pleural mesotheliomas. The peritoneum is the second most common site of mesothelioma development and accounts for approximately 10% to 20% of all mesotheliomas. Mesotheliomas that involve the pericardium or originate from the tunica vaginalis are rare tumors. Given the rarity of these tumors, it is difficult to obtain precise information regarding their incidence, natural history, and optimal management.

Female↗
PubMed1990

Malignant pleural mesothelioma: some aspects of epidemiology, differential diagnosis and prognosis. Histological and immunohistochemical evaluation and follow-up of mesotheliomas diagnosed from 1964 to January 1985.

64 diffuse pleural mesotheliomas diagnosed between 1964 and January 1985 at the Institute of Pathology of the University of Freiburg were analyzed. Since 1980 an increase from one case to 10 cases per year has been observed. The tumor was 3 to 4 times more frequent in men than in women. The age distribution showed a peak between the age of 50 and 60. In 26 cases evidence of exposure to asbestos was detected. In one patient radiotherapy of Hodgkin's disease may have been of etiological significance. The median survival time was 13 months. The five-year survival rate was only 4%. Histologic reevaluation was only possible in cases diagnosed after 1975. Of 43 cases thus evaluated 26 were pure mesothelial, 15 biphasic and 2 of the spindle-cell subtype. A median survival time of 23 months for pure mesothelial mesothelioma in comparison to 13 months for the biphasic mesothelioma indicated a better prognosis for pure mesothelial mesothelioma. Although no other primary tumors were detected, in 10 cases the differential diagnosis of adenocarcinoma had to be considered, and in 3 cases tumors of non-epithelial origin had to be excluded. 35 of 43 mesothelioma were CEA-negative, 38 out of 43 cytokeratin-positive, and 33 out of 43 were EMA-positive. Factor-VIII-related antigen was not demonstrated. 12 of 43 mesotheliomas showed PAS-positive staining, 29 of 43 were stained with Alcian blue. 7 of these 29 showed a positive digestion with hyaluronidase. Although CEA may not be negative in every mesothelioma, this marker seems to be a valid tool for the differential diagnosis of adenocarcinoma. In order to safeguard against a mistaken diagnosis of pleural mesothelioma, the exclusion of other tumors is always indispensable.

Adult↗
PubMed1998

Reactive mesothelial hyperplasia vs mesothelioma, including mesothelioma in situ: a brief review.

In biopsy tissue, discrimination between reactive mesothelial hyperplasia and epithelial mesothelioma can pose a major problem for the surgical pathologist. Confidence in the diagnosis is often proportional to the amount of tissue available for study and depends largely on findings of invasion and the extent and cytologic atypia of the lesion, because there is no marker specific for the mesothelium and that discriminates consistently among normal, hyperplastic, and neoplastic mesothelial tissue. Therefore, mesothelioma in situ is diagnosable only when invasive epithelial mesothelioma is demonstrable in the same specimen, in a follow-up biopsy specimen, or at autopsy. Comparison of 22 cases of mesothelioma in situ that fulfill these requirements for diagnosis with 141 invasive mesotheliomas and 78 reactive mesothelioses indicates that strong linear membrane-related labeling for epithelial membrane antigen and silver-labeled nucleolar organizer region-positive material that occupies 0.6677 microm2 or more of the nucleus in an atypical in situ mesothelial lesion of the pleura are found consistently in neoplastic mesothelial cells. Although these findings may engender suspicion of mesothelioma in situ in high-risk persons, the criteria for diagnosis of pure mesothelial lesions of this type are still under study. Mesothelioma in situ should be considered proved only when unequivocal invasion is identified in a different area of the pleura or at a different time; a diagnosis of pure mesothelioma in situ should not be made in patients not exposed to asbestos.

Biopsy↗
PubMed2001

Pathology of human malignant mesothelioma--preliminary analysis of 1,517 mesothelioma cases.

The author reviewed 1,517 human malignant mesothelioma cases from 1975 through August 2000. These mesothelioma cases were definite or probable in diagnostic certainty. Sources of these cases varied including asbestos insulation workers, UNARCO workers, Cancer and Leukemia B mesothelioma panel cases and random cases. Pathology materials consisted of autopsy, biopsy and rare cytology specimens. 92.3% of these patients were male, and 85.8% were between 50 and 79 years in age. The major primary site of the tumor was the pleura (73.1%). However, in a group of the asbestos insulation workers, the peritoneum was the more common primary site of malignant mesothelioma, compared to the pleura. Histologically, epithelial cell type was the majority (61.1%), followed by biphasic (22.1%) and fibrosarcomatous (16.4%). A double primary tumor (malignant mesothelioma associated with other cancer) was present in 32 of the 1,517 cases. These 32 cancers included lung cancers, renal cell carcinomas, colorectal cancers, pancreatic cancers and a cancer of the larynx, which are known to be at higher risk among asbestos insulation workers. The latency period of the vast majority (98.1%) of these mesothelioma cases were longer than 20 years. It is well accepted that cigarette smoking does not contribute to the induction of malignant mesothelioma. Indeed, the present study confirmed that 19.9% of these mesothelioma patients had never smoked cigarettes.

Adult↗
PubMed1997

Trends in mesothelioma incidence and occupational mesotheliomas in Finland in 1960-1995.

OBJECTIVES: The study analyzed the recent trend in the incidence of mesothelioma in Finland and evaluated the coverage of reporting work-related mesothelioma. METHODS: The incidence of mesothelioma in 1960-1995 was retrieved from the Finnish Cancer Registry, and the number of asbestos-associated work-related mesotheliomas were taken from the Finnish Register of Occupational Diseases. RESULTS: The annual number of mesotheliomas increased rapidly in 1975-1990. In the 1990s, the age-adjusted incidence remained relatively stable for Finnish men. The annual number of cases still increased among men over 65 years of age, but decreased slightly among men under 55 years of age and among women. About 35 annual cases were diagnosed among men and 10-15 among women in the mid-1990s. The reporting of work-related mesotheliomas improved during the Finnish asbestos program in 1987-1992. In 1993-1995 about 30 annual cases (ie, about 90% of all pleural and 50% of the peritoneal mesotheliomas in men) were reported to be work-related. CONCLUSIONS: The increasing trend in the incidence of mesothelioma in Finland has slowed down in the 1990s, and the maximum of asbestos-related cases in the early 2000s will probably be clearly less than the 100 annual cases estimated in the early 1990s. If the observed trend continues up to 2010, about 40-50 cases among men and 10-20 among women will then be diagnosed annually. Altogether 40-50 of these cases would be related to occupational asbestos exposure.

Aged↗
PubMed1987

Comparative studies of human malignant mesothelioma in vivo, in xenografts in nude mice, and in vitro. Cell origin of malignant mesothelioma.

Several decades ago, it was reported that normal and malignant mesothelial cells were transformed into distinct cell types (epithelial to fibrous and fibrous to epithelial) when transferred to in vitro conditions. Those tissue culture data are still cited as evidence supporting that the mesothelial cell has multipotentiality of differentiation and the mesothelial cell is a sole precursor of malignant mesothelioma cells. Six cell lines of heterotransplanted human malignant mesothelioma in nude mice and one cell line of subcultured human malignant mesothelioma in vitro have been established. To establish the validity of the classic concept of multipotentiality of malignant mesothelioma, we studied malignant mesothelioma cells of the seven cases using in vivo cultures, xenografts in nude mice and an in vitro tissue culture, utilizing histology, histochemistry, immunocytochemistry and electron microscopy. The nature of the original malignant mesothelioma cells was clearly shown to be well preserved in both the heterotransplanted and subcultured cells. Data did not support earlier hypotheses that mesothelial cells are capable of differentiating into distinct cell lines. The mesothelial cell and the submesothelial connective tissue cells are the precursors of the neoplastic cells in malignant mesothelioma.

Aged↗
PubMed1991

Immunocytochemistry of malignant mesothelioma: OV632 as a marker of malignant mesothelioma.

In pleural or ascitic effusions the cytomorphological distinction of adenocarcinoma cells, reactive mesothelial cells, and malignant mesothelioma cells often causes a diagnostic dilemma. The value of immunocytochemistry was investigated on cytological smears of 24 well-established cases of malignant mesothelioma, a selected series of 31 metastatic adenocarcinomas, and 20 smears of patients without known malignancy. In these smears we scored the immunoreactivity with a panel of four monoclonal antibodies. In addition to antibodies for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), the monoclonal antibody MOC31 and the ovarian carcinoma specific antibody OV632 were incorporated in the panel. With none of these four antibodies was immunostaining of reactive mesothelial cells found. CEA- and MOC31-positive tumour cells were frequent in metastatic adenocarcinomas, but occurred rarely in malignant mesotheliomas. EMA-positive tumour cells were found in all metastatic adenocarcinomas (100 per cent) and in most malignant mesotheliomas (83 per cent). In addition to the expected reactivity of OV632 with ovarian carcinomas, 22 of 24 malignant mesotheliomas contained immunopositive tumour cells, while only a small proportion of non-ovarian adenocarcinomas reacted with this antibody. This selective staining of malignant mesothelioma cells, but not reactive mesothelial cells, with OV632 now permits the positive identification of malignant mesothelioma cells in male patients.

Adenocarcinoma↗
PubMed1993

The frequency of p53 immunostaining in asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas.

It has been suggested that asbestos might have an important role in the development of p53 mutations in mesotheliomas. The objective of this study was to examine asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas to establish whether the frequency of p53 immunostaining and, by implication, p53 gene mutation is related to asbestos exposure. Immunopositivity for p53 was found in seven (44%) of the 16 mesotheliomas examined. The frequency was approximately the same in both the asbestos-associated mesotheliomas and the non-asbestos-associated mesotheliomas. It is concluded that the frequency of p53 immunostaining in mesotheliomas and, by implication, the frequency of p53 gene mutation is probably not related to asbestos exposure.

Asbestos↗
PubMed2000

Image analysis of mesothelioma. I. differentiation of mesothelioma from adenocarcinoma of the lung.

OBJECTIVE: To explore the usefulness of nuclear micromorphometric analysis for the differentiation between epithelial mesothelioma and metastatic adenocarcinoma in the chest wall. STUDY DESIGN: High-resolution images of 2,100 nuclei from 27 cases of epithelial mesothelioma and 15 cases of adenocarcinoma of the lung were recorded. Stepwise discriminant analysis and a nonparametric classifier were applied to derive estimates for a case diagnosis correct classification rate. RESULTS: Nuclei from epithelial mesothelioma and adenocarcinoma of the lung showed statistically significantly different properties, but there was a region of overlap in feature space such that approximately 15-20% of cases could not be correctly classified. The lesion signatures derived from the mesothelioma cases with discriminant function scores that might result in case misclassification and the cases of adenocarcinoma of the lung spanned a similar range of degree of nuclear abnormality. However, the distribution of nuclear abnormality values for the mesothelioma cases has a mode at 0.87 SD from normal, whereas the distribution seen in lung adenocarcinoma cases had a mode at about 3.7 SD. CONCLUSION: Cases of epithelial mesothelioma and adenocarcinoma of the lung have nuclei with a wide range of deviation from normal in the spatial and statistical distribution of their nuclear chromatin. For approximately 80% of cases, correct case classification can be provided by nuclear micromorphometric analysis. Cases of epithelial mesothelioma with highly abnormal nuclei overlap in feature space with nuclei from adenocarcinoma of the lung. However, it is possible that characterization by a lesion signature may allow correct assignment for those cases.

Adenocarcinoma↗