Low-grade intraosseous osteosarcoma with prominent lymphoid infiltrate.

Low-grade intraosseous osteosarcoma is an uncommon and well-differentiated osteosarcoma with a good prognosis. We report a proximal tibial low-grade intraosseous osteosarcoma with a prominent intratumoral lymphoid infiltrate, which led to an initial diagnosis of probable malignant lymphoma. The importance of this infiltrate, which exhibited reactive features on flow cytometric studies, is not known. Our patient is free of tumor 1 year after limb salvage surgery, without hematologic or lymphoid abnormalities.

Malignant chondroblastoma presenting as a recurrent pelvic tumor with DNA aneuploidy and p53 mutation as supportive evidence of malignancy.

We report a rare case of malignant chondroblastoma, which presented in a 47-year-old man as a recurrent tumor, 18 years following wide excision of a typical pelvic chondroblastoma. Radiologic studies of the recurrent tumor showed a large, lytic, destructive lesion of the right pelvic bones and femur, with a pathologic fracture of the latter, a large pelvic soft tissue mass, and multiple pulmonary metastases. Biopsy tissue showed typical features of chondroblastoma, but also increased nuclear atypia, hyperchromasia, and pleomorphism, compared to the original tumor, and, most significantly, abnormal mitotic figures. Immunohistochemical studies of the recurrent tumor revealed p53 mutation and extensive proliferative activity, and flow cytometric studies showed DNA aneuploidy, none of which was present in the original tumor. The patient received chemotherapy and radiation, but died of disease eight months after presentation. We also review chondroblastoma in general, to assign this unusual lesion to a tumor subtype.

Lesions of the bones of the hands and feet.

Neoplasms and their simulators in the bones of the hands and feet include the majority of those found in other skeletal sites, and a disproportionate number of some. We examined the clinical, radiologic, and pathologic features of 240 lesions of the hand and foot bones. Benign tumors and lesions including reactive and reparative conditions comprised 203 cases. The largest single category of neoplasms was that with cartilaginous differentiation, with enchondromas (29 cases) and chondrosarcomas (15 cases) the most common. Noncartilaginous malignant tumors were infrequent and displayed typical radiologic and pathologic features. Florid reactive periostitis, bizarre parosteal osteochondromatous proliferations, and giant cell reparative granulomas made up a larger percentage of lesions in these locations than in other skeletal sites. Lesions of the bones of the hands and feet may frequently be biopsied or treated at hospitals without large orthopedic tumor services. Thus, it is important for the surgical pathologist to be aware of the frequency and characteristics of lesions which may present in these sites.

Effect of erionite on the pleural mesothelium of the Fischer 344 rat.

OBJECTIVE: This study sought to assess the fibrogenic and carcinogenic potential of erionite (a fibrous zeolite) on the pleural mesothelium of the Fischer 344 rat (n = 24). DESIGN: The study was designed to examine rat pleural mesothelial changes by three independent observers at timed intervals, ranging from 1 to 480 days postinoculation using erionite from the Pine Valley, Nevada (USA) area. The mean length and width of the erionite fibers were 2.29 and 0.48 microns, respectively. Only microscopic observations made by majority (2/3) or unanimity (3/3) were accepted for final diagnosis. RESULTS: Pleural and lung tissue were available for examination in 21 of the 24 rats. Fibrosis, chronic inflammation, and foreign body reaction occurred in 6 of 21 rats. Mesothelial hyperplasia and dysplasia occurred in 9 and 3 of the 21 rats, respectively. A single mesothelioma was identified at 434 days in a rat that had gross nodular pleural lesions. CONCLUSIONS: The findings reported herein confirm the strong fibrogenic potential of erionite but are at variance with previous studies reporting much higher yields of mesothelioma. The reasons for the low yield of mesothelioma in this study are not known, but may be related to the study design, the strict criteria used for histopathologic diagnosis, and/or possible differences in erionite physicochemical properties, associated with its geographic distribution, most previous animal studies having used erionite from the Rome, Oregon (USA) area.

Effect of fibrous glass on rat pleural mesothelium. Histopathologic observations.

Female Fisher 344 rats (n = 25) were inoculated intrapleurally with a single 20-mg dose of (JM-100) fibrous glass. The mean length (2.2 microns) and width (0.15 microns) of the fibrous glass particles was within respirable range. Following inoculation, the rats were killed at timed intervals ranging from 2 to 430 d from inoculation. The pleural histopathologic changes were independently observed by a panel of three pathologists blinded to the time elapsed from inoculation. Fibrous adhesions, nodular lesions, and grossly evident tumor were noted in 15, 2, and 1 rat, respectively. In 1 rat there were combined adhesive and nodular changes, and in 6 there were no grossly detectable abnormalities. Chronic inflammation, fibrosis, and foreign body reaction were found in 9, 18, and 10 rats, respectively. Mesothelial hyperplasia and dysplasia were observed in 16 and 9 rats, respectively. Of 16 rats with the severest degree of hyperplasia and dysplasia, 3 developed malignant mesothelioma. This study suggests that a spectrum of rat pleural mesothelial histopathologic changes occurs before development of mesothelioma. The association of severe dysplasia in 3 rats with fully developed mesothelioma suggests that there may be a gradual progression from mesothelial hyperplasia or dysplasia to mesothelioma. Multivariate analysis further suggests that gross pleural nodular lesions and dysplasia may be significantly associated with the development of mesothelioma in this experimental model.

Primitive neuroectodermal tumors of bone and soft tissue. With reference to histologic differentiation in primary or metastatic foci.

Primitive neuroectodermal tumors (PNET) of the bone and soft tissue were reviewed by immunohistochemistry and partly by morphometry, focusing particularly on histologic changes in recurrent or metastatic foci, in order to elucidate their probable histogenetic relationship with Ewing's sarcoma (ES) and its extraskeletal counterpart (EES). Eleven cases of bone tumor (average patient age; 15.1 yr) and 12 cases of soft tissue tumor (average patient age; 22.1 yr) which disclosed unequivocal Homer-Wright rosettes and/or at least foci of ganglion cell differentiation either in a given primary tumor or metastatic (or recurrent) foci were selected from small round cell tumors primarily categorized as ES or EES. Most of the cases for which follow-up biopsy samples were available disclosed prominent Homer-Wright rosettes in the metastases, whereas the primary tumors showed features of ES and lacked rosettes. In only one case, Homer-Wright rosettes were absent in the metastatic tumor. Most cases had been treated by combined intensive chemotherapy and radiotherapy, which might have influenced cell differentiation. Neural markers (neuron-specific enolase, neurofilament protein and others) were positive in most cases. Three cases with otherwise typical histologic features of ES or EES showed minute foci of ganglion cell differentiation, as confirmed by morphometry and neural markers. These results suggest that ES (or EES) and PNET are histogenetically related, but represent different stages of cell differentiation.

Prognostic significance of histopathologic subtype and stage in small cell lung cancer.

A study of 149 light microscopic tissue slides from 147 patients with recorded initial diagnoses of small cell lung cancer (SCLC) (114 cases) and undifferentiated carcinoma (35 cases) was undertaken to test the reproducibility and prognostic impact of a new histopathologic subclassification of SCLC proposed by the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). This study was further designed to test the impact of clinical stage, age, sex, and race on survival. The tissue slides were blindly reclassified as SCLC or non-SCLC by a panel of five pathologists with no knowledge of the initial diagnosis. The SCLCs were divided into the three subtypes outlined by the IASLC pathology panel: small (classic or pure), mixed (small cell/large cell), and combined (small cell/squamous carcinoma or small cell/adenocarcinoma). Small cell lung cancer was clinically staged as local, regional, or distant. Consensus diagnosis (defined as agreement by at least three of the five pathologists) was achieved in 144 (96.6%) of the 149 cases. Of these 144 cases, 124 were reclassified as SCLC (115 [92.8%] small, five [4.0%] mixed, and four [3.2%] combined) and 20 were classified as non-SCLC. The median lengths of survival for the small, mixed, and combined subtypes were 225, 1,110, and 203 days, respectively (P = .025). Adequate staging data were available in 123 of the 124 SCLC cases. Of the 123 SCLC cases, 27 (21.9%) were local, 22 (17.9%) were regional, and 74 (60.2%) were distant stage. The median lengths of survival for the local, regional, and distant stages were 428, 251, and 111 days, respectively. This association was highly significant (P = .0001). We conclude that stage is the major determinant of survival in SCLC. Mixed subtypes had significantly longer survival times than the small or combined subtypes (P = .025). Survival times were longer for women than for men, and the survival time difference between men and women was significant (P = .0028). We found no significant differences in survival according to age or race.

Morphology of bronchial epithelium adjacent to adenocarcinoma of the lung.

Gross unremarkable bronchi and bronchioles from 22 lobectomy specimens containing primary adenocarcinoma were examined microscopically. Sections were taken from the segment containing the carcinoma and compared with sections taken from uninvolved segments in the same specimen to examine for premalignant lesions. The average tumor size was 3.75 cm (1.5 to 11 cm). The average age of patients was 60.4 yr (29 to 79 yr); 13 were men and nine were women; all were smokers, and the average was 44.1 pack-years (20 to 100 pack-years). Six of the specimens (27%) showed no histologic changes. Focal squamous metaplasia was identified in nine specimens (41%), but in four of the nine (44%), it was not seen in the carcinogenic segment. Focal goblet cell metaplasia was seen in six specimens (27%), but in two of the six (33%), it was not in the carcinogenic segment. Focal basal cell hyperplasia was seen in two specimens (9%) within both the carcinogenic segment and elsewhere. A single focus of mild epithelial dysplasia was found in each of two specimens (9%), but these foci were not in the carcinogenic segment. Focal epithelial regeneration was noted in three specimens (14%), but two of these (66) were not in the carcinogenic segment. Such microscopic abnormalities of respiratory epithelium are associated with cigarette smoking, and each is a potentially premalignant change; however, our study demonstrated no histologically identifiable changes in the respiratory epithelium that consistently mark for premalignant atypia in the lung adenocarcinoma.

Immunocytochemical and ultrastructural studies of the histogenesis of Ewing's sarcoma and putatively related tumors.

The histogenesis of Ewing's sarcoma (EW) and extraskeletal Ewing's sarcoma (EEW) is still disputable. Their relationship to the so-called Askin's tumor, neuroectodermal tumor of bone, and peripheral neuroblastoma remains to be established. In an attempt to clarify these points, immunocytochemical and ultrastructural studies were done on tissues from 14 cases of EW, 4 cases of EEW, and 9 cases of primitive neuroectodermal tumor (PNET) and compared with neuroblastoma and olfactory neuroblastoma. Six tumors categorized initially as EW and EEW on biopsy, turned out to be PNET by extensive histologic and/or ultrastructural observations. Abundant glycogen was recognized not only in 16 of 18 cases of EW and EEW, but also in seven of nine cases of PNET. Fine fibrillar cell processes were seen between tumor cells, at least in limited areas even in cases of EW and EEW. Immunocytochemically, neuron-specific enolase (NSE), neuroblastoma cell surface antigen (NBCA), neuron cell surface antigen (NCSA), and neurofilament (NF) were demonstrated not only in neuroblastoma, but also frequently in cases of EW, EEW, and PNET. The results seem to suggest that EW and EEW represent the most immature forms of neuroectodermal tumor. Electron microscopic study showed predominantly primitive cells with occasional areas of cell processes, neurosecretory granules, and microtubules, suggesting a neuroectodermal origin.

Identification of features of metaplastic cells in sputum for the detection of squamous-cell carcinoma of the lung.

Digitized images of 1,556 squamous metaplastic cells from the sputum of 15 patients with confirmed squamous-cell carcinoma of the lung and 13 subjects without apparent neoplasia were analyzed to determine if features existed within these relatively normal cells that could be used to differentiate between the two populations. Results indicate that such marker features do exist. A cross-validation study using an additional 465 cells confirmed the conclusion that squamous metaplastic cells from patients with squamous-cell carcinoma of the lung do differ from those of subjects without cancer. While such marker features alone are not reliable enough to assist pathologists in the diagnosis of squamous-cell carcinoma of the lung, they might, in sufficient numbers, be used to identify patients for whom follow-up testing would be advised.

Gastric adaptation. Studies in humans during continuous aspirin administration.

To study the process of gastric mucosal adaptation to aspirin administration, 14 normal men underwent a study with continued administration of aspirin. Endoscopic assessment, biopsies, and gastric wash collections for acid, mucus, and deoxyribonucleic acid recovery were performed weekly; aspirin was continued until the endoscopy showed minimal damage. Six subjects took 650 mg of aspirin b.i.d., and 8 took 650 mg q.i.d.; adaptation and resolution took longer with the higher dose (median 4.5 wk vs. 1 wk, p less than 0.01). Despite improvement in mucosal appearance, gastric microbleeding remained elevated throughout aspirin administration. In contrast, deoxyribonucleic acid recovery (a marker for cellular exfoliation and regeneration) increased significantly just before the time of resolution, when, on average, it more than doubled. As no other biochemical or histologic changes could be associated with the resolution of damages, we conclude that gastric adaptation to chronic injury may involve increased cellular regeneration.

Prognostic indicators for survival in stage I carcinoma of the lung: a histologic study of 47 surgically resected cases.

In a previous study of 91 consecutive lung cancer cases, we reported that tumor stage was the only significant predictor of survival, with all 5-yr survivors having Stage I disease. Approximately half of the 47 Stage I cases survived 5 yr, so the present study was initiated to determine which histologic features were predictive of survival for Stage I cases. An average of 10 slides per case was evaluated independently by three pathologists, and each slide was subjectively scored using previously agreed criteria for the following parameters: vascular or lymphatic invasion; anaplasia; mitotic rate; inflammatory host response; and the presence or absence of necrosis, tumor giant cells, a central scar, mucin production, benign giant cell reaction, or desmoplasia. Survival was also correlated with patient's age, sex, tumor (T) and nodal (N) status, tumor cell type, and histologic heterogeneity. All three observers found the extent of tumor necrosis to be a significant negative predictor of survival (P less than 0.05). One observer found tumor giant cells to be an adverse factor, another observer found scar carcinomas to have worse survival, and a third observer found lymphocytic inflammatory host response to be a positive predictor and venous invasion to be a negative predictor of survival (P less than 0.05). All other parameters showed no significant correlation with survival. The finding of some parameters which correlated with survival according to one but not the other two observers indicates that the results of studies of histologic prognostic indicators by a single observer may not be valid for other pathologists attempting to use the same subjective criteria.

Microcystic adenoma (serous cystadenoma) of the pancreas. A study of 14 cases with immunohistochemical and electron-microscopic correlation.

Microcystic adenoma (serous cystadenoma) of the pancreas (MA) is an unusual benign tumor of uncertain histogenesis. We have studied 14 cases of MA from 11 women and three men. The average age at diagnosis was 64 years. Six tumors were discovered incidentally. Tumors varied from 2.5 to 12 cm in greatest dimension and all were multicystic; eight tumors were located in the pancreatic head, two in the body, and three in the tail. Each tumor was composed of variably sized cysts lined by simple cuboidal or flattened, focally glycogen-rich epithelium. The stroma was variably collagenized and showed highly vascularized, delicate to broad fibrous septae, which focally contained dystrophic calcification, cholesterol clefts, and hemosiderin. Immunohistochemical studies were performed on eight cases to determine the cell of origin. Epithelial membrane antigen and a low-molecular-weight keratin, detected by monoclonal antibodies PKK1 or AE1/AE3, were diffusely seen in tumor cells of all cases. Tumor cells were uniformly negative for carcinoembryonic antigen, chromogranin, insulin, glucagon, somatostatin, vasoactive intestinal peptide, pancreatic polypeptide, and a low-molecular-weight keratin detected by monoclonal antibody PKK2. Tumor cell antigen reactivity most resembled that seen in normal centroacinar and ductal cells. Electron microscopy of seven cases showed primitive tumor cells with irregularly spaced, short, blunt microvilli, luminal occluding junctions and belt desmosomes, bundles of filaments including dense bodies in both apical and basal cell cytoplasm, sparse organelles, and variable but often pronounced amounts of glycogen. These ultrastructural features most closely resembled the normal pancreatic centroacinar cell. Based on both immunohistochemical and ultrastructural features described above, we conclude that the centroacinar cell is the cell of origin of MA.

Use of fresh placental membranes for bladder reconstruction.

Several biodegradable and artificial materials have been used in the urinary tract for partial or total replacement of the bladder. Most of the graft materials have resulted in stone formation, collapse, rejection, or extrusion of the graft without adequate reconstruction of a functional bladder. In this paper, we present our assessment of the use of placental membranes as a feasible, economic, and acceptable organic agent for bladder reconstruction. Eight mongrel dogs were subjected to supratrigonal cystectomy, and then a 10 X 10 centimeter patch of human placental membrane was sutured to the remaining trigone in a watertight fashion. The dogs were sacrificed twelve weeks after surgery. Histologic examinations revealed evidence of regeneration of normal-appearing smooth muscle along the path of a retracting placental patch, and thus of reconstitution of a normal-appearing and functioning bladder. On the basis of this study, we believe that placental membranes, because of their low antigenic properties and easy availability, provide an excellent graft material for the urinary tract. Further studies concerning the application of this graft material in various pathological conditions are now in progress.

Lung cancer heterogeneity. Prognostic implications.

Although histologic heterogeneity of lung cancer is well recognized, little information is available related to possible effects of this heterogeneity on prognosis. We collected 100 consecutive lung cancer cases, including 35 autopsies and 65 surgical resections, which were extensively sampled (average, ten blocks per case) and analyzed for histologic heterogeneity. Slides were randomized and classified by five pathologists using the 1981 World Health Organization (WHO) classification scheme. Five-year follow-up data were obtained for the surgical cases, and detailed information on staging and survival from time of diagnosis was available in 91 cases. Survival time was analyzed with respect to the patient's age, sex, stage, predominant histologic pattern, and presence or absence of major heterogeneity. The latter is defined as the presence on at least one slide of a major histologic pattern different from that of the remaining slides for that case. The only statistically significant predictor of survival was tumor stage (P less than 0.0001). Heterogeneous tumors appeared to have a worse survival, but this did not reach statistical significance. There was no relationship between survival and predominant histologic pattern (cell type), sex, or age.

Jejunitis cystica profunda in a hamartomatous polyp. Report of a case.

A patient with a history of abdominal discomfort and rectal bleeding was discovered to have two hamartomatous polyps, one of the jejunum and one of the colon. The former was associated with mucinous cysts at its base. The findings were similar to those described for colitis cystica profunda. This case is a rare example of cystica profunda disease of the small bowel. Uniquely, it was associated with a hamartomatous polyp.

Morphometric markers for the evaluation of preneoplastic lesions in the lung. Diagnostic evaluation by high-resolution image analysis of atypical cells in sputum specimens.

A review is presented of the Baylor College of Medicine/NASA/Lyndon Johnson Space Center high-resolution image analysis system for the detection of preneoplastic lesions of the lung in sputum specimens. For each specimen, 200 cells are graded as to their Atypia Status Index (ASI), a numerical classification based on a weighted composite of morphometric markers identified in the digitized images. The ASI values, which place individual cells within categories ranging from squamous metaplastic to carcinomatous, form the basis of the Cell Atypia Profile (CAP), which reflects the overall status of the patient's bronchial epithelium and can be used to diagnose and monitor epithelial atypias. Initial studies have shown the ASI and CAP to be accurate indices, whose application in the studies of sputum of individuals at high risk for the development of lung cancer (cigarette smokers over 45 years of age and industrially exposed workers) could lead to the early detection of preneoplastic lung lesions and to effective early clinical intervention, including the cessation of smoking or the application of beta-carotone or retinoids, which reportedly arrest the progression of bronchial epithelial atypias. Computer-assisted cell image analysis of morphometric markers in cells in sputum specimens appears to be uniquely applicable for surveillance of individuals at risk for carcinoma of the lung.

Ewing's sarcoma.

This patient had Ewing's sarcoma of the femur, which was originally misinterpreted by radiograph and by biopsy as osteomyelitis. For approximately 1 year the patient was treated for osteomyelitis. The lesion was slowly progressive and near the end of the first year became more active, and pulmonary metastases appeared. The natural behavior of this one case of Ewing's sarcoma demonstrates that it is not necessarily an overwhelmingly aggressive tumor. In addition, the point is made that pathologists should pay careful attention to necrotic material so that the suggestion of necrotic tumor can be made rather than dismissing the biopsy as nondiagnostic.

The reliability of cytopathologists' classifications of bronchial epithelial atypias from Kodachrome slides.

The accuracy of computerized cell image analysis techniques for classification of atypical cells is determined by comparing computer-generated classifications with those made by cytopathologists. This measure of accuracy depends not only on the reliability of the computer classifications but also on the reliability of the cytopathologists' classifications. This study reports on the observed reliability of cytopathologists' classifications of squamous epithelial atypias in sputum across cytopathologists and two different classification times. Results indicated the percentage agreement among cytopathologists and computerized cell image analysis techniques. It is recommended that, in the future, all analyses of computerized classification schemes by interpreted in light of the consistency of the cytopathologists' classifications.