Unusual intraparenchymal growth patterns of malignant pleural mesothelioma

AIMS: Malignant pleural mesothelioma is known to mimic morphologically a number of diverse reactive and neoplastic conditions. We describe three unusual intraparenchymal growth patterns of malignant mesothelioma seen in a series of 200 malignant pleural mesotheliomas. The diagnostic pitfalls associated with these findings are described and their potential medico-legal implications are highlighted. METHODS AND RESULTS: The study group comprised 200 malignant pleural mesotheliomas. In each case diagnosis was morphologically confirmed with ancillary immunohistochemistry using a broad panel of both mesothelial and epithelial markers. The patterns of intraparenchymal growth were documented and grouped as: direct subpleural; lymphangitic; and other. The 200 malignant pleural mesotheliomas comprised 118 epithelioid, 57 biphasic and 25 sarcomatoid, subtyped according to the WHO classification. Direct subpleural invasion was seen in 42 cases, lymphangitic spread in 27 cases. Other less well-defined intraparenchymal patterns included three sarcomatoid subtype malignant mesotheliomas exhibiting an intra-alveolar growth pattern mimicking epithelioid haemangioendothelioma. One epithelioid subtype malignant mesothelioma contained an intraparenchymal tumour nodule microscopically comprising lepidic spread of neoplastic cells over maintained alveolar structures mimicking bronchioloalveolar carcinoma. One epithelioid subtype malignant mesothelioma morphologically had areas in which alveoli were distended by discohesive epithelioid neoplastic cells with no interstitial invasion. The appearances mimicked desquamative interstitial pneumonia. Immunohistochemistry played an important role in the definitive diagnosis of each unusual parenchymal tumour deposit. In 126 malignant mesotheliomas no invasion of the subjacent lung parenchyma was identified. CONCLUSIONS: An awareness of the unusual parenchymal growth pattern in malignant mesothelioma is important to prevent misdiagnosis of other entities. In the medico-legal setting, the presence of epithelioid haemangioendothelioma or bronchioloalveolar carcinoma (in the absence of asbestosis) may be deemed to impact upon the patient's anticipated life expectancy and thereby would decrease the compensation settlement.     

The clinical impact of expert pathological review on lymphoma management: a regional experience

The All Wales Lymphoma Panel (AWLP) was established in January 1998 to provide a central expert pathological review service for district general hospital pathologists. A discordance rate of 20% between the submitted and reviewed diagnosis has previously been identified. It has not been known whether this change in diagnosis affects clinical management. Ninety-nine patients whose diagnosis was changed as a result of central pathological review are presented. Between January 1998 and August 2000, 125 of 745 (17%) specimens submitted for AWLP review had a consequent change in pathological diagnosis. Of these 125 specimens, 99 (79%) complete case notes were recovered. In all 99 cases, a hypothetical management plan was generated using collected data, clinical protocols and the submitted pathological diagnosis. These plans were compared with the actual management patients received based on the reviewed diagnosis proffered by the AWLP. Forty-six of 99 (46%) cases had a change in management as a result of central pathological review. Overall, management was changed in 8% of cases referred for central pathological review. In conclusion, expert central pathological review has a direct effect on patient management.     

An approach to industrial post mortems

Industrial-related deaths represent a specialized aspect of autopsy practice. The purpose of this review is to assist the pathologist in the handling of such deaths. The diseases associated with the three most significant mineral dusts (asbestos, coal and silica) are described, together with a selection of less well-known mineral dust diseases. This review addresses the complex issues of ascribing disease to industrial exposures and the role of mineral analysis. The authors discuss the common medical legal issues that are encountered at post mortem and at inquest deposition.     

Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas

Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.     

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center

Introduction

The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a “transitional” (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components.

Molecular pathology of gastric carcinoma: progress and prospects.

Gastric carcinoma is the fourth most common malignancy in Western Europe and a major cause of cancer morbidity and mortality worldwide, particularly in the Far East and in areas of South America. The natural history of the disease is not fully established, and there is a need to elucidate the molecular mechanisms of gastric carcinogenesis in order to understand its pathogenesis and to develop molecular markers for clinical diagnostic use. Molecular analysis of colonic carcinogenesis has increased our understanding of its pathogenesis and has demonstrated multistage carcinogenesis in a human cancer. Research in gastric carcinoma has not achieved such significant progress, although a start has been made. We analyze some of the interpretation problems in molecular pathology affecting progress that are of interest to the histopathologist and review recent studies on the molecular biology of gastric carcinoma involving flow cytometry, cytogenetics, allele loss analysis, and transfection. We also summarize current knowledge about each of the major oncogenes and suppressor genes, attempting, in particular, to correlate gene abnormalities with morphologic appearances. The expanding field of cell proliferation and growth factors is outlined, gastric and colon carcinomas are compared, and gastric carcinoma is considered as a model system for the study of differentiation. This report concludes by suggesting directions for future research.     

Opsonic dysfunction secondary to plasma fibronectin depletion after aortic surgery

Fibronectin is a plasma opsonin which is depleted after major injury or surgery. The effect of major aortic surgery on plasma fibronectin has been studied in patients and in an equivalent experimental model in pigs. On the day after aortic surgery in eleven patients mean fibronectin (+/- s.e.m.) had fallen from 363 +/- 11 mg/l pre-operatively to 179 +/- 19 mg/l (P less than 0.01). No such fall was observed in patients undergoing herniorrhaphy. In fourteen pigs aortic surgery produced reproducible surgical shock and a fall in plasma fibronectin from 331 +/- 10 mg/l to 43 +/- 13 mg/l after resuscitation (P less than 0.01). Whenever plasma fibronectin fell below 190 mg/l the circulating free fibronectin was consumed in complexes of 1000 kDa containing collagenous debris. More severe depletion of plasma fibronectin was related to higher concentrations of circulating nonopsonized collagenous debris and to subsequent mortality in pigs. The depletion of free fibronectin that occurs following major surgery may produce clinically important opsonic dysfunction. The clinical relevance of this fibronectin consumption may be missed if measurement is limited to circulating fibronectin levels without determining that proportion bound in complexes and no longer available as an opsonin.