Sarcomatous tumor of the chest wall with osteochondroid differentiation. Evidence of mesothelial origin.

We describe a case of sarcomatous tumor of the chest wall with differentiation toward bone and cartilage that was observed in an asbestos-exposed worker. Although the mesothelial nature of the tumor was at first considered, it was not proven. Later, the tumor was shown to be a mesothelioma using a panel of pertinent antibodies that included a recently described anti-mesothelial cell marker. In addition, asbestos bodies were found in association with the sarcoma cells. Our findings indicate that whenever physicians encounter any type of primary sarcomatoid tumor involving serous membranes, the possibility of malignant mesothelioma should be regarded a priori.

Minimal pathologic changes of the lung and asbestos exposure.

A group of 199 autopsy subjects was investigated for minimal pathologic pulmonary changes possibly resulting from asbestos exposure. According to the standards proposed by the Pneumoconiosis Committee of the College of American Pathologists, features consistent with asbestosis grade 1 (AG1) include findings of bilateral pleural plaques, high concentrations of asbestos bodies (ABs) in digested lung tissue, and a history of occupational risk. Similar changes without evidence of ABs on histologic section and referred to as small airway lesions (SALs) present a less well-correlated association. In this study, SALs showed significant differences when compared with the features observed in subjects without possible asbestos-related pulmonary fibrotic changes. Minimal bronchioloalveolar fibrotic changes with concomitant presence of ABs can be considered a mild pneumoconiotic lesion (AG1), and SALs may be regarded as an additional indicator of asbestos exposure.

Malignant peritoneal mesothelioma in a 17-year-old boy with evidence of previous exposure to chrysotile and tremolite asbestos.

We describe a case of malignant peritoneal mesothelioma arising in a 17-year-old boy. The diagnosis was based on a comprehensive study including light microscopy, histochemistry, immunohistochemistry, evaluation of the clinical course, and autopsy examination. Analytical transmission electron microscopy showed a concentration of 510,000 asbestos fibers/g dry lung tissue. The fibers were represented by chrysotile (62%) and tremolite (38%) asbestos. About 40% of the total fibers were longer than 5 microns. The presence of tremolite fibers was probably due to environmental exposure to contaminated cosmetic talc. This is the first reported case of pathologically proven exposure to asbestos dust in malignant mesothelioma of childhood and adolescence.

The differential diagnosis of primary lung cancer: inter-observer agreement and contribution of specific diagnostic procedures.

In order to investigate inter-observer variability in the differential diagnosis of primary lung cancer among women and the contribution of specific diagnostic procedures to this diagnosis, a group of 449 suspect cases of this disease was studied. Based on a standard dossier (including clinical data and the reports, if present, of radiology, bronchoscopy and histology) six different physicians independently judged, for each woman, at each diagnostic step, the presence of a primary lung cancer. A final consensus was organized in order to define the true cases. Radiology and especially histology seem to give the most important contribution to the diagnosis. On the other hand bronchoscopy seems to be useful mainly as a guide for biopsy. A predictive value of 90% was found when both radiology and bronchoscopy were positive; in the other cases histology seems to be needed to reach an adequate discrimination. Inter-rater agreement increases with an increasing amount of information but is not very high even when histology is available.

Liposarcoma of the thyroid gland. Fine-needle aspiration cytology, immunohistology, and ultrastructure.

A 56-year-old woman presented with a rapidly growing tumoral mass of the thyroid. In fine-needle aspirates, neoplastic cells were interpreted as undifferentiated (anaplastic) carcinoma. In contrast, histologic examination of tissue samples revealed a tumor with features suggestive of myxoid liposarcoma. The non-epithelial nature was confirmed by immunohistochemical and electron microscopic evaluation. Immunostains for vimentin and S-100 protein were positive, whereas no reactivity was obtained for epithelial markers. Ultrastructurally, the tumor consisted of poorly differentiated mesenchymal cells and lipoblastic elements in various stages of differentiation. Review of the literature reveals only one previous report of thyroid liposarcoma, the diagnosis of which was based on conventional light microscopic studies.

Malignant mesothelioma of the pleura: interobserver variability.

AIMS: To assess the consistency of histopathological diagnosis of pleural malignant mesothelioma by estimating interobserver agreement between five pathologists. METHODS: Eighty eight histological sets pertaining to original diagnoses of pleural malignant mesothelioma were reviewed separately by each pathologist. Diagnostic likelihood was graded as definite (A), probable (B), possible (C), improbable (D), and definitely not (E) malignant mesothelioma. The following indexes were estimated: observed proportion of agreement (Po), kappa statistics and proportion of agreement for "positive" (Ppos) and "negative" (Pneg) diagnoses. RESULTS: Sixty cases (68.2%) were rated by at least three reviewers as A or B and by none of the others as D or E. Five (5.7%) were rated by at least two reviewers as D or E and by none of the others as A or B. Nine (10.2%) showed a serious disagreement, rated A or B and D or E. Agreement for sets obtained at necropsy/surgery (median kappa w = 0.57) was similar to that for endoscopic material (median kappa w = 0.54). Agreement was poor on material obtained by needle biopsy (median kappa w = 0.21). The median value of Ppos varied between 0.94 (necropsy/surgery) and 0.67 (needle biopsy) and that of Pneg between 0.78 (necropsy/surgery) and 0.34 (unspecified biopsy). Interobserver agreement on histological typing was good overall (median kappa = 0.59). CONCLUSIONS: Of the original histological diagnoses, 70% were consistently reproduced through panel review. Most indexes of agreement between pathologists ranged from poor (needle biopsy) to moderate (necropsy/surgery). Agreement in confirming malignant mesothelioma was greater than that regarding exclusion of this diagnosis. Of the cases finally considered to have malignant mesothelioma, the reproducibility of histological typing was relatively satisfactory.

Clear cell ("sugar") tumor of the lung is a lesion strictly related to angiomyolipoma--the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC).

We report a comparative study of 3 clear cell tumors of the lung (CCTL) and 3 angiomyolipomas (AML) of the kidney. Morphological analysis shows that the cells of CCTL are identical to the perivascular epithelioid component of AML. Phenotypically they both consistently expressed melanoma-associated antigens recognized by Moabs HMB45 and HMSA-1, while they were negative for HMSA-5. A minority of cells also expressed S-100 protein, vimentin and actin. In addition, one case of CCTL showed mature adipose tissue entrapped in the proliferation, thus suggesting an intermediate form between CCTL and AML. Based on morphological and phenotypical similarities, it is suggested that CCTL and AML belong to the same family of lesions, characterized by the presence of a peculiar muscle cell, expressing different melanoma-associated antigens.

What's new in managing health hazards in pathology departments.

Health hazards related to activities performed in pathology departments have represented, in recent years, an increasing concern among pathologists and pathology technicians. The major occupational health problems encountered in pathology departments are reviewed. They include biological hazards (tuberculosis, hepatitis, HIV, other infectious diseases), chemical hazards (formaldehyde, xylene(s), aromatic amines, methacrylates, glutaraldehyde, latex) and physical hazards (cut injuries, accidental fires, radiation). Current data suggest that infections (particularly, tuberculosis and hepatitis) still represent the more relevant risk. Exposure to HIV and Creutzfeldt-Jakob agent may be highly harmful but containment measures have been proven to be effective. The actual adverse effects due to chemicals seem to be less alarming than was previously believed. Attaining a safe work environment is an inherent element of good quality assurance management. This task is largely a matter of information, education, organization and common sense. Well-designed premises, efficient equipment and well-trained personnel are the keys to preventing and minimizing hazardous exposures. In order to provide current information that may be used by pathology staff to implement the functional quality of the workplace, organizational and preventive measures are described.

Coated and uncoated lung mineral fibres in subjects with and without pleural plaques at autopsy.

The lung concentration of coated and uncoated mineral fibres of more than 10 micron in length was determined by light microscopy in 57 autopsied subjects (23 out of which professionally exposed to asbestos) with pleural plaques but no other asbestos-related diseases. Comparisons were made with 57 controls matched for sex, age and smoking habits, who did not show any asbestos-associated diseases or history of previous occupational exposure. Subjects with pleural plaques had a median concentration of coated fibres consistently greater than that observed in those without. However, no substantial differences were found between the two studied groups when uncoated and total fibres were considered. The present study suggests that the factors related to the fibre coating and to the pleural plaque formation may be indirectly connected, but not necessarily restricted to the number and nature of the fibres, or to the professional or environmental conditions of exposure.

Malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease.

A case of malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease (MID) is presented. The patient had mesenteric and omental lesions characterized at biopsy by extensive fibrosis of fat tissue with mild to moderate inflammation. One year later, post-mortem examination revealed a well-differentiated epithelial mesothelioma. Immunohistochemical stains for keratin and vimentin were diffusely positive, whereas EMA showed a membranous staining of scattered cells. CEA, Ber-EP4, B72.3 and Leu-M1 were negative. In addition, actin monoclonals decorated groups of cells pertaining to the tumoural component. Immunostains of sections from retrieved paraffin blocks of the previous biopsy showed that the bulk of the spindle-shaped and histiocytic-like cells present in the fibrous streams was strongly labeled by low-molecular-weight keratin, and coexpressed vimentin and actin. EMA showed a membranous staining of sporadic spindle and round cells. The other immunostains were invariably negative. This immunohistochemical pattern closely corresponded to the immunophenotype of the mesothelial tumour detected at autopsy and was very suggestive of myofibroblastic/submesothelial cell origin. The quantitative evaluation of silver nucleolar organizer regions (Ag-NORs) demonstrated high levels of cell proliferation in both surgical and autopsy tissue samples.

Malignant mesothelioma of the pleura. The reproducibility of the immunohistological diagnosis.

The reproducibility of the histopathological diagnosis of pleural malignant mesothelioma (MM), after supplementing routine H&E stain by immunohistochemistry (IH) in 77 cases of original diagnoses of MM, was assessed by examining interobserver variation between five pathologists. A battery of commercial antibodies (cytokeratins, vimentin, HMFG-2, anti Leu-M1 [CD15], BerEP4, B72.3 [TAG-72], carcinoembyonic antigen), considered to be useful in enhancing diagnostic accuracy, was used. The number of definitively classified tumors (accepted MM plus rejected MM) increased from 57 on H&E stain to 60 after IH, with 59 (76.6%) cases being accepted as true MM. Based on IH, the chance-adjusted interobserver agreement was poor (kappa w = 0.29) and lower than that observed on previous H&E alone. The intraobserver agreement for four of the five pathologists was rather good (kappa w = 0.54-0.56). The inter- and intraobserver concordance was higher in accepting than excluding the cases as MM. A larger number of cases were classified by all reviewers as mixed or sarcomatous variants after IH. In the interpretation of each immunostain, kappa values ranged from 0.19 for B72.3 to 0.62 for HMFG-2, which were respectively the least and the most consistently interpreted immunostains. The information additionally contributed by IH did not seem to change the pathologists' diagnoses very much in comparison with those made by routine H&E stain. Until highly specific and sensitive probes for the positive identification of MM become available, a careful scrutiny of routinely stained preparations still remains the most rewarding component of the diagnostic pathway.

Hyaline splenic and hepatic plaques. Correlation with cirrhosis, pulmonary tuberculosis, and asbestos exposure.

Nine hundred twenty-five unselected autopsies were investigated for the presence or absence of hyaline peritoneal (splenic or hepatic) plaques, hyaline pleural plaques, asbestos, liver cirrhosis, heart failure, previous peritoneal dialysis or abdominal surgery, chronic peritonitis, splenomegaly, splenic infarcts, and pulmonary or abdominal tuberculosis. Lung asbestos body concentrations were calculated in 570 subjects. Peritoneal plaques were recorded in 163 cases. In both univariate and multivariate analyses, they were associated with cirrhosis, pulmonary nonactive tuberculosis, pleural plaques, and asbestosis. Association with asbestos body counts was also found, with a significant trend. Peritoneal plaques were described long ago in different pathologic conditions, for some of which (cirrhosis and nonactive pulmonary tuberculosis) the association is confirmed by the present analysis. It is suggested that they are significantly associated, moreover, with indicators of asbestos exposure.

Lung asbestos bodies and pulmonary cancer in subjects without occupational exposure.

Lung asbestos bodies were searched for in 65 subjects with pulmonary cancer and without occupational exposure and in 65 matched controls. No significant association between the presence of asbestos bodies and occurrence of lung cancer was found. Nevertheless, adenocarcinoma was significantly associated with the presence of lung asbestos bodies in men. The latter result suggest that, even in non-professionally exposed subjects, the possibility of relationships between asbestos exposure and lung cancer cannot be excluded.

Villoglandular papillary adenocarcinoma of the uterine cervix: report of a case.

Villoglandular papillary adenocarcinoma is a recently described form of adenocarcinoma of the uterine cervix, which apparently affects young women and seems to have a favorable course with an excellent prognosis. We report on a case of villoglandular papillary adenocarcinoma in a 26-year-old woman. The patient was treated by conization alone and is disease free after a 40-month follow-up.

[Active tuberculosis unsuspected until autopsy]. / La tubercolosi attiva ignorata fino all'autopsia.

A series of 3195 necropsies performed in cases of natural death at the "S. Giovanni" Hospital in Turin, and covering the years 1969-1978, was studied for the prevalence of active tuberculosis. Active tuberculosis was found in 61 cases (1,9%); in 60 a complete clinical history was available. Forty-two out of these 60 cases (70%) were diagnosed only at autopsy, with higher frequency in the old patients. In the 42 patients with undiagnosed active tuberculosis, the acid fast bacilli resulted to have been searched for only in 3 cases, and a chest-film was recorded in 23 cases; in 27 cases of this group, the period between the admission and the death was longer than 8 days (mean 29 days). The clinical diagnosis of active tuberculosis displays intrinsic difficulties; however it must be stressed that an higher proportion of cases could be recognized if one keeps in mind the possibility of this polymorphic disease, so that adequate clinical, laboratory and x-ray investigations should carried out.

Screening of autopsy populations for previous occupational exposure to asbestos.

A screening procedure to select, in autopsy populations, subjects having a major likelihood of previous occupational exposure to asbestos is described. To test our necropsy population we searched for pleural plaques (PPs); the optical count of both lung asbestos bodies (ABs) and uncoated mineral fibers (UMFs) at least 10 microns in length was recorded. In the adult autopsy population studied in the Turin area, the predictive value given by a positive test for large-size PPs (mostly bilateral) was about 55%. This level of probability did not rise in relation to the AB counts, whereas an increase to over 75% was observed if more than 10,000 UMFs/g dry lung were present. In subjects without PPs or with small-size plaque lesions (mostly unilateral), predictive values of positive tests were 20 to 30% when ABs and UMFs were found to be below 100 and 10,000/g, respectively, and increased to approximately 40% if the AB count exceeded 500/g and to almost 70% for an UMF count above 100,000/g. In subjects without PPs or with small-size plaque lesions, the probability of being nonexposed was greater than 90% if neither ABs nor UMFs were found. This autopsy screening may be a reliable tool in selecting cases most probably related to occupational exposure.

Ki-67 scores and AgNor counts in transitional cell carcinoma of the bladder: apparent lack of prognostic value.

The cellular proliferative state of 18 incident cases of transitional cell carcinomas of the bladder treated with transurethral resection was blindly determined by two independent observers using Ki-67 monoclonal antibody and silver stain for nucleolar organizer regions (AgNORs). Ki-67 scores were significantly related to histological grade (WHO) (rs = 0.65, p < 0.01) and clinical stage (UICC) (rs = 0.46, p < 0.05). However, the follow-up analysis over a six year period did not demonstrate significant relationship between Ki-67 values and survival. AgNOR counting did not show significant association with any of the variables under study. The results of this investigation and the review of the pertinent literature suggest that the assessment of cell proliferation of bladder carcinoma by means of Ki-67 and AgNOR techniques is far from having immediate direct influence on patient management.