On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997-2016).

BACKGROUND: Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices. METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1977-2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping. RESULTS: Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases. CONCLUSIONS: Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.

Iron signature in asbestos-induced malignant pleural mesothelioma: A population-based autopsy study.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The development of MPM is frequently linked to inhalation of asbestos fibers. A genetic component of susceptibility to this disease is suggested by the observation that some individuals develop MPM following lower doses of asbestos exposure, whereas others exposed to higher quantities do not seem to be affected. This hypothesis is supported also by frequent reports of MPM familial clustering. Despite the widely recognized role of iron (Fe) in cellular asbestos-induced pulmonary toxicity, the role of the related gene polymorphisms in the etiology of MPM has apparently not been evaluated. Eighty-six single-nucleotide polymorphisms (SNPs) of 10 Fe-metabolism genes were examined by exploiting formalin-fixed paraffin-embedded postmortem samples from 77 patients who died due to MPM (designated AEM) and compared with 48 who were exposed to asbestos but from died in old age of cause other than asbestos (designated AENM). All subjects showed objective signs of asbestos exposure. Three SNPs, localized in the ferritin heavy polypeptide, transferrin, and hephaestin genes, whose frequencies were distributed differently in AEM and AENM populations, were identified. For ferritin and transferrin the C/C and the G/G genotypes, respectively, representing intronic polymorphisms, were significantly associated with protection against MPM and need to be considered as possible genetic markers of protection. Similarly, the C/C hephaestin SNP, a missense variation of this multicopper ferroxidase encoding gene, may be related, also functionally, with protection against MPM. In conclusion, it is proposed that three Fe metabolism-associated genes, significantly associated with protection against development of MPM, may serve as protective markers for this aggressive tumor.

Primary pericardial mesothelioma in an asbestos-exposed patient with previous heart surgery.

We present a case of primary pericardial mesothelioma occurring in an asbestos-exposed 67-year-old man who underwent four aortocoronary bypass grafting seven years prior to the onset of the mesothelioma. Primary pericardial mesothelioma is a rare tumor whose association with asbestos is more infrequent than that of the much more common pleural form. Factors other than asbestos that may play a role include genetic predisposition, immune impairment, infections, radiation, dietary factors, and recurrent serosal inflammation. We consider that, in the presented case, inflammation and healing resulting from pericardiotomy might have had a synergistic effect with asbestos in the pathogenesis of the tumor. To our knowledge, this is the first reported case of primary pericardial mesothelioma arising in a patient exposed to asbestos who previously underwent cardiac surgery.

Carcinoma of the uterine cervix with squamous and sebaceous differentiation.

Sebaceous neoplasms, including carcinoma, can exceptionally arise in extracutaneous sites. We present the third known case of carcinoma with sebaceous differentiation in the uterine cervix. Histologic and immunohistochemical features suggested a metaplastic process within an otherwise usual squamous cell carcinoma. We speculate that, by analogy with the skin where the epidermis and the 3 types of adnexa have a common embryologic origin from basal cell layer of the superficial ectoderm, it is possible that endocervical reserve cells, in addition to the well-known capacity of squamous differentiation, retain the potential to give rise to appendages including sebaceous glands.

Apoptosis-related factors (TRAIL, DR4, DR5, DcR1, DcR2, apoptotic cells) and proliferative activity in ameloblastomas.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a recently identified death factor that acts as a potent apoptosis inducer in ameloblastomas. MATERIALS AND METHODS: The expression of TRAIL and its receptors (TRAIL-R), and the location of apoptotic cells were evaluated in 15 cases of ameloblastoma using immunohistochemistry and an in situ DNA nick-end labeling method. The proliferative activity of ameloblastomas was analyzed by determining the Ki-67 labeling index. RESULTS: TRAIL and TRAIL-R were diffusely expressed in ameloblastomas, without clear correlation with the location of apoptotic cells. Apoptosis and proliferation were opposite in the peripheral and central components of the ameloblastomas. In some ameloblastoma variants, apoptosis and proliferation seemed to modify in the same direction. CONCLUSION: TRAIL and its receptors might be involved in neoplastic transformation of odontogenic epithelium and might suggest some intrinsic regulation of neoplastic cell proliferation and death in ameloblastomas, thus explaining their slow growth and inability to metastasize.

Intra-abdominal ovarian-type mucinous cystadenoma associated with fallopian tube-like structure and aberrant epididymal tissue in a male patient.

Ovarian-type mucinous tumors may occasionally occur in the retroperitoneum, pancreas, and liver exclusively or almost exclusively in women. In men, only few cases of such neoplasms arising within or around the testis have been reported. We describe a unique case of an ovarian-type mucinous cystadenoma occurring in the peritoneal cavity of a 65-year-old male patient with secondary adrenocortical insufficiency and hypogonadism. There was a typical fallopian tube enclosed in the capsule of the tumor. Contiguous to that, accessory ectopic epididymal tissue was found. We have interpreted this case as the result of a minor disorder of embryonic development involving structures of both müllerian and wolffian origin. The disproportion of sexual hormones might have had a role in inducing intra-abdominal müllerian remnants to give rise to the mucinous cystadenoma.

Familial mesothelioma of the pleura--a report of 40 cases.

A survey of 610 pleural mesotheliomas disclosed 40 familial cases. The diagnosis was histologically based in 39 cases, and confirmed by necropsy in 30. Occupational data were collected from the patients or from their relatives by personal interviews. Routine lung sections were examined for asbestos bodies in 32 cases. In 15 cases asbestos bodies were isolated after chemical digestion of lung tissue. Familial mesotheliomas included 31 men and 9 women (age range 44-93 yr, mean 70.7, median 71.0). In 15 families there were blood relations between (or among) the members involved. All the patients had been exposed to asbestos, mostly in the shipyards. Asbestos bodies were found on routine lung sections in 27 cases. Asbestos bodies after isolation ranged from 70 bodies to about 900,000/g dried lung tissue. Latency periods (time intervals between first exposure to asbestos and diagnosis) ranged between 25 and 70 yr (mean 52.0, median 54.0). The occurrence of mesothelioma among subjects with blood relations suggests that genetic factors might play a role in determining the susceptibility to asbestos-related cancer. Familial cases among persons without blood relations raise the question if environmental factors that members of a family share, may act as co-factors in asbestos-related mesothelioma.

A tumor with composite pilo-folliculosebaceous differentiation harboring a recently described new entity--melanocytic matricoma.

We report on a case of a peculiar tumor of the pilosebaceous unit showing a composite histologic appearance. The case presented as a pigmented crusted lesion on the back of the nose of a 62-year-old woman with markedly sun-damaged skin. Histologically, the superficial portion of the neoplasm was composed of buds and nests of basaloid epithelium with varying degrees of pilar and sebaceous differentiation. Adjacent to this component, lobules of squamous cells with cytoplasmic glycogenation suggesting the mature outer root sheath were seen. In the underlying dermis, there was a well-defined nodular proliferation composed of variably pigmented basaloid matrical cells forming clusters of "shadow" or "ghost cells" admixed with numerous melanized dendritic melanocytes; this last component of the neoplasm was identical to a recently described entity, melanocytic matricoma. The small size, circumscription, and absence of necrosis favored benignity, although the cytologic atypia of matrical cells did not exclude malignancy. The case is interesting not only because it is the third reported case of a peculiar neoplasm imitating the epithelial-melanocytic interaction in the embryonal hair follicle or bulb of the anagen follicle but because the part resembling melanocytic matricoma presented as a component of a complex lesion. We believe that sunlight may have played a role in the development of this peculiar neoplasm.