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Malignant mesothelioma (MM) is a rare primary malignant tumor of the surface serosal cells. The diagnosis of MM is challenging with a broad differential diagnosis. For many decades, studies have focused on distinguishing MM from other types of cancer; however, benign mesothelial cell hyperplasia, especially in small biopsies, has emerged as a major...
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Context 1
... and are inconspicuous microscopically (Fig. 2). Irritation of the pleural surface, however, leads to simple hyperplasia of the mesothelial cell layer. The mesothelial cells in simple hyperplasia form a regular layer of relatively bland cuboidal cells along the surface without any evidence of invasion. Distinct nucleoli may sometimes be present (Fig. 3). Resting mesothelial cells with cuboidal morphology have been identified in the spleen, liver, and diaphragm. 12 Fig. 2. Normal mesothelial cells with flat and inconspicious morphology (HE Â200). In atypical mesothelial hyperplasia (AMH), which is a more florid mesothelial proliferation along the pleural surface than simple ...
Context 2
... and are inconspicuous microscopically (Fig. 2). Irritation of the pleural surface, however, leads to simple hyperplasia of the mesothelial cell layer. The mesothelial cells in simple hyperplasia form a regular layer of relatively bland cuboidal cells along the surface without any evidence of invasion. Distinct nucleoli may sometimes be present (Fig. 3). Resting mesothelial cells with cuboidal morphology have been identified in the spleen, liver, and diaphragm. 12 Fig. 2. Normal mesothelial cells with flat and inconspicious morphology (HE Â200). In atypical mesothelial hyperplasia (AMH), which is a more florid mesothelial proliferation along the pleural surface than simple ...
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Citations
... Similar to their appearance at other body sites such as the liver and spleen, these mesothelial cells can also take on a more cuboidal shape. 12 In these more cuboidal mesothelial cells, the cell's eosinophilic and granular cytoplasmic quality is more evident. The nucleus is round to ovoid and typically displays an even, granular chromatin distribution with a variably distinct nucleolus. ...
... 13 Concurrent reactive changes induced by various etiologies can yield nuclear enlargement (with subsequently increased nuclear to cytoplasmic [N:C] ratio), nuclear contour irregularity, coarse chromatin distribution, prominent nucleoli, and multinucleation. 12,14 Additionally, other cytologic features raising the concern for malignancy may be displayed in reactive mesothelial cells, such as mitotic figures, nuclear atypia, and background necrosis (such as that seen in rheumatoid effusions). 14 While some reactive changes in mesothelial cells may result in the formation of papillary arrangements entrapped in fibrotic stroma, hyperplastic mesothelial cells show no evidence of invasion into underlying supporting tissues and are typically monotonous in appearance. ...
... As mentioned previously, pleomorphism can be identified in malignant processes and reactive mesothelial cells. Conversely, some subtypes of adenocarcinoma may not display overt pleomorphism and instead feature more monotonous malignant cell populations 12,18 (ie, subsets of breast and endometrioid adenocarcinomas). Although frequently associated with cell clusters of adenocarcinoma, the aforementioned "community" borders of cell groups can occasionally be seen in mesothelial proliferations ( Figure 3). ...
Context.—:
Pleural effusions are common cytologic specimens that can be leveraged to make diagnoses of malignancy that drive appropriate patient management. However, the overlap in morphologic features of reactive mesothelial proliferations, mesotheliomas, and adenocarcinomas can create diagnostic pitfalls in the cytologic evaluation of pleural fluids.
Objective.—:
To review the morphologic spectrum of benign and malignant mesothelial proliferations in pleural effusions as well as relevant clinicoradiologic contexts and ancillary tests.
Data sources.—:
Existing scientific and clinical literature as of January 2023.
Conclusions.—:
We can leverage the knowledge of several overlapping morphologic features, clinicoradiologic scenarios, and immunohistochemical studies to enhance the diagnostic accuracy of pleural effusion cytology to appropriately delineate cases of adenocarcinoma, reactive mesothelial proliferation, and mesothelioma. Earlier diagnosis through cytology, particularly in cases of mesothelioma, may positively impact patient treatment options and prognosis.
... Reactive mesothelial proliferation is a common mimic of MPM (and metastatic carcinoma) and has numerous causes, including infection, pulmonary infarction, trauma, autoimmune disease and drug reactions [27]. Cytomorphological features overlap with MPM and include high cellularity, numerous mitotic figures and cytologic atypia. ...
For a number of patients presenting with an undiagnosed pleural effusion, frailty, medical co-morbidity or personal choice may preclude the use of pleural biopsy, the gold standard investigation for diagnosis of malignant pleural mesothelioma (MPM). In this review article, we outline the most recent evidence on ancillary diagnostic tests which may be used to support a diagnosis of MPM where histological samples cannot be obtained or where results are non-diagnostic. Immunocytochemical markers, molecular techniques, diagnostic biomarkers and imaging techniques are discussed. No adjunctive test has a sensitivity and specificity profile to support use in isolation; however, correlation of pleural fluid cytology with relevant radiology and supplementary biomarkers can enable an MDT-consensus clinico-radiological-cytological diagnosis to be made where further invasive tests are not possible or not appropriate. Diagnostic challenges surrounding non-epithelioid MPM are recognised, and there is a critical need for reliable and non-invasive investigative tools in this population.
... Pathological observation is the primary reliable determinant used in clinics to evaluate the impact of chemotherapy on tumor growth. Histological analysis of peritoneal tissue and diaphragm of control mice on day 35 revealed proliferated mesothelium with numerous invasive peritoneal implants and highly pleomorphic tumor cells, which is typical of ovarian adenocarcinoma [56,57]. Its invasive nature is pathologically manifested by diverse architectural patterns (micropapillae, irregular glands with round solid nests of cells and stromal invasion) [58][59][60], all of which were noticeable in tumor-bearing control mice. ...
The objective of this study was to evaluate intraperitoneal (IP) metronomic chemotherapy using sustained release paclitaxel (PTX) delivery from electrospun biodegradable polymeric yarns woven into suturable nanotextiles. Following confirmation of in vitro PTX efficacy in ID8-VEGF epithelial ovarian cancer cells, in vivo studies were performed upon surgical peritoneal implantation of nanotextile implants in orthotopic, syngeneic ID8-VEGF tumor-bearing C57BL/6 mice. In comparison to the clinical PTX-solution, there was a significant enhancement of anti-tumor efficacy and safety with PTX-nanotextiles. After 35-days, the peritoneum of tumor-bearing mice with PTX-nanotextiles was completely devoid of tumor nodules and ascitic fluid. Additionally, VEGF levels measured in peritoneal lavage fluid were 300-fold lower compared to PTX-solution and 600-fold lower as compared to untreated tumor-bearing animals. PTX-solution treated group also developed severe metastatic lesions and progressive ascitic fluid buildup. More importantly, no signs of systemic/ organ toxicity were observed in PTX-nanotextile implanted mice, unlike the systemic toxic effects induced by PTX-solution. Collectively, our results show the therapeutic and safety advantages offered by combining clinically translatable metronomic low-dose chemotherapy and IP pharmacokinetics using biodegradable nanotextile implants in addressing the challenges of late-stage ovarian cancer.
... Mesothelial lesions can be categorized into reactive mesothelial proliferation, malignant mesothelioma, and other forms of less aggressive mesothelial tumors (1)(2)(3). Welldifferentiated mesothelial papilloma (WDPM) is a rare tumor that usually occurs in the peritoneum (4)(5)(6). Less frequently, it also arises from the pleura, pericardium, and tunica vaginalis/testis (7)(8)(9). ...
... Thorough sampling is necessary to ensure that there is no evidence of stromal invasion. Additionally, bulky tumor masses with the presence of stromal invasion, severe nuclear pleomorphism, and frequent mitotic figures should warrant the diagnosis of malignant mesothelioma (1)(2)(3). In fact, Churg et al. reported 13 cases of peritoneal WDPM with invasive foci (13). ...
Background/aim:
Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases.
Materials and methods:
The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining.
Results:
The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1.
Conclusion:
We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.
Pleural abnormalities are often a manifestation of intrathoracic and systemic diseases caused by an extensive list of neoplastic and nonneoplastic conditions. Both neoplastic and nonneoplastic pleural diseases can present with similar clinical features. Nonneoplastic disorders of the pleura may result from a variety of infectious as well as drug- and trauma-related causes. Primary pleural disease owing to a myriad of inflammatory and neoplastic pleural disorders is less common, but nonetheless relevant due to its potential to cause devastating respiratory compromise. Moreover, many of the benign tumors of the pleura closely mimic malignant disease in their radiographic and histologic appearance. In this chapter, we will discuss the clinical, radiographic, and pathologic correlates of the spectrum of primary and secondary diseases of the pleura. The intent of this multidisciplinary approach is to provide a detailed overview and update of diseases of the pleura that can be directly applied to clinical practice and to stimulate basic research investigations in areas where there are unanswered questions.KeywordsMalignant primary mesotheliomaPleural tumorsPleural metastasisPleural effusionFibrous pleuritisTNM staging 8th edition
Although distinguishing transudates from exudates through the Light criteria is still considered a pragmatic first step in the diagnostic work-up of pleural effusions, the measurement of various pleural fluid biomarkers may aid in the identification of common and specific entities, such as heart failure (natriuretic peptides), tuberculosis (adenosine deaminase), malignancy (mesothelin, fibulin-3, immunocytochemical stains), or bacterial pleural infections (C-reactive protein). The use of these biomarkers is currently encouraged as a routine diagnostic procedure.
The differentiation of benign mesothelial cells from malignant tumor cells, primary, or metastatic, in serous effusions based on cytomorphologic features alone can be problematic.
This study was conducted to evaluate the utility of p53 and ki67 immunocytochemical markers in differentiating benign from malignant tumor cells in serous effusions.
Archival Papanicolaou-stained smears of 91 pleural and peritoneal effusions were retrieved from Cytology Unit, Pathology Department, NCI, Cairo University between 2008 and 2010. Forty-one cases were positive for malignant cells and 50 cases were benign based on cytomorphologic features. Cases having doubt were excluded from the study. The slides were destained and subjected to immunocytochemical staining for p53 and ki67. Histologic sections of colonic carcinoma and tonsillar tissue were used as positive control for p53 and ki67, respectively. Smears having >5% positively stained nuclei for p53 were taken as positive and labeling index ⩾10% of ki67 was considered positive. Frequencies of the individual immunocytochemical stains; p53 and ki67, in benign and malignant effusion as well as the combination of both stains were calculated.
p53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions (75.6%) and in 3 out of 50 benign effusions (6%), p<0.005. p53 had 75.6% sensitivity, 94% specificity, 91.2% PPV, and 82.5% NPV. ki67 immunostaining was positive in 30 out of 41 malignant effusions (73.2%) and in 17 out of 50 benign effusions (34%), p<0.05. ki67 had 73.2% sensitivity, 66% specificity, 63.8% PPV, and 75% NPV. Cases were then analyzed for combined immunoprofile of p53 and ki67. Among the 24 cases that coexpressed both antigens, 22 cases (91.7%) were malignant. Thirty two out of 34 cases (94.1%) that showed negative results for both antigens were benign. For the cases that showed p53 immunostaining only, 9 out of 10 cases (90%) were malignant. Fifteen out of 23 cases (65.2%) that showed ki67 immunostaining were benign.
Benign and malignant effusions showed significantly different staining pattern for p53 and ki67. When used individually, p53 immunostaining can truly diagnose 75.6% and 94% of the malignant and benign cases, respectively. ki67 immunostaining can correctly identify 73.2% and 66% of the malignant and benign cases, respectively. When used in combination, 91.7% of p53 and ki67 positive cases were malignant while 94% of p53 and ki67 negative cases were benign. Hence they could be used when the cytomorphology fails to provide a definitive diagnosis.
