Renal tissues of 208 autopsied cases were examined. Malignant neoplasm with hematological malignancies often accompanied DIC. Tissue sections were stained with hematoxylin and eosin and Mallory's phosphotungstic acid hematoxylin (PTAH), and were applied for immunoperoxidase method (IP), using antisera against human fibrinogen, FDP-D and FDP-E. Histologically in 80 cases (38%) fibrin or fibrinogen related materials (FRMs) were observed in the glomerular capillary or the intratubular area or in both. FRMs were PTAH or IP positive or both in 23 of the 26 cases (88%) clinically diagnosed as DIC. In the remaining three cases anticoagulants probably interfered with FRMs observation. This study showed the PTAH stain was nonspecific and insensitive to FRMs, and that IP was necessary for a pathological diagnosis of DIC. The presence of FRMs in the renal tubuli is an important finding in confirming DIC. DIC may be present histologically in the absence of clinical DIC symptoms.
A cell line derived from medial smooth muscle cells (SMC) was established from the porcine coronary artery by transfection with ori‐defective simian virus 40 plasmid DNA (SV40 DNA). The characteristics of transfected cells (SV40‐SMC) such as cell growth, collagen and non‐collagen syntheses were investigated. SV40‐SMC expressed SV40 large T antigen, c‐myc and c‐myb encoded proteins in the nuclei. SV40‐SMC demonstrated a ‘hills and valleys’ ‐like arrangement in overconfluence and actin filaments upon immunofluorescent staining. Under electron microscopic observation, SV4O‐SMC had larger amounts of synthetic organelles and smaller amounts of filament bundles than those of SMC. SV40‐SMC demonstrated three times higher growth activity and 4.4 times greater cellular density than SMC. Smooth muscle cells did not grow in media containing 5% plasma derived serum (PDS) instead of normal serum, whereas SV40‐SMC proliferated in this medium. SV40‐SMC did not grow in soft agar gel, while HeLa S3 cells, a cell line of human cervical carcinoma, formed colonies in this gel. By immunofluorescent (IF) staining, collagen phenotypes I, Ill, IV and V were detected in both SV4O‐SMC and SMC. However protein synthesis including collagen and non‐collagen was higher in SV40‐SMC than in the control sample. It was concluded that SV40‐SMC were a continuous cell line for vascular SMC regarding morphological characteristics, and demonstrated a higher growth activity, with increased collagen and noncollagen syntheses. This cell line is useful for the investigation of atherogenesis in relation to a proliferation of SMC and an accumulation of extracellular matrices in vascular Intima.
A case of a malignant nerve sheath tumor with rhabdomyoblastic differentiation arising from the acoustic nerve in a 38 year old man is reported. At autopsy, the tumor was found to be extensively involved in the right cerebellopontine angle of the brain stem. Histologically, the tumor was composed mainly of spindle-shaped tumor cells proliferating in hypercellular fascicles scattered with pleomorphic cells. The tumor cells were characterized by high mitotic activity and invasive growth. Occasional tumor cells had eosinophilic cytoplasm, which in a few cases was cross-striated. Cytoplasmic interdigitations and a thick basal lamina were confirmed ultrastructurally. Immunohistochemical analysis revealed that some tumor cells were positive for myoglobin and desmin, but weakly positive or negative for S-100 protein. The patient did not have von Recklinghausen's disease.
In 1979, a new mechanism of gastric defense named cytoprotection was followed by numerous reports elucidating this interesting and important phenomenon. During this decade, however, the concept and definition of gastric cytoprotection have been modified from the morphological and ultrastructural viewpoints. This review attempts to describe the concept and mechanisms of cytoprotection as well as its pathophysiological features. Specifically, in vitro studies using isolated cells or monolayer cultured cells as well as molecular investigations of signal transduction system have been documented.
Basic fibroblast growth factor (bFGF) was identified in the papillary carcinoma of the human thyroid. Immunohistochemically, it was found that the reactivity for bFGF was localized in the cytoplasm of the neoplastic cells of the five papillary carcinomas. However the extract of the papillary carcinomas contained the mitogenic activity for endothelial cells. This bioactive molecule was determined as bFGF by using the heparin‐Sepharose affinity chromatography and western blot analysis. The bFGF derived from human thyroid papillary carcinoma and the recombinant human bFGF stimulated the bromodeoxyuridine incorporation by the cultured human thyroid papillary carcinoma cells. These cells also showed positive staining for thyroglobulin and cytokeratin. These results indicate that bFGF, probably produced by the neoplastic cells, plays an important role in the development of papillary carcinoma of the thyroid with stimulation of angiogenesis as well as proliferation of the parenchymal cells.
Tumor cell kinetics and DNA contents were investigated by in vitro labeling with bromodeoxyuridine (BrdU) and flow cytometry using paraffin-embedded specimens in both superficially (Sup) and deeply (Deep) infiltrating sites of 28 colorectal adenocarcinomas. Eleven were well differentiated and 17 were moderately differentiated adenocarcinomas. In moderately differentiated adenocarcinoma, histologic low grade types of Deep were frequently associated with lymph node metastasis, but the BrdU labeling indices (LI) or tumor DNA ploidy pattern did not correlate with nodal status. Among the seven aneuploid tumors of moderately differentiated adenocarcinoma, the BrdU LI and histology of Deep tended to correlate with nodal status. These findings suggest that the histology of Deep should have a greater significance than tumor cell kinetics or DNA contents. They also suggest that the tumor DNA ploidy pattern may be heterogeneous and divided into subgroups according to its cell kinetics or histology of Deep in relation to lymph node metastasis.
Two cases of mixed medullary and follicular carcinoma of the thyroid (MFC) and two cases of thyroid carcinoma resembling MFC are reported with a description of their histological and immunohistochemical features. Two cases of MFC with lymph node metastasis were histologically distinguishable from each other because one had a follicular structure filled with a thyroglobulin (TG)‐positive colloid‐like substance and the other did not have it. Although one of the thyroid carcinomas resembling MFC was similar to the case of MFC with a follicular structure in its primary lesion, it showed no lymph node metastasis. The metastatic lesion of the thyroid carcinoma resembling MFC consisted of TG‐ positive cells and neighboring calcitonin (CT)‐positive cells. However the primary lesion exhibited the typical features of papillary carcinoma except for the presence of a small lesion which stained negatively for both TG and CT. The two types of tumor were not intermingled in a single tumor. These cases of thyroid carcinoma resembling MFC have a possibility of being MFC. However they should not be classified as MFC because lymph node metastasis or the coexistence of medullary carcinoma and follicular carcinoma in their primary lesion was not proved.
The effects of platelet‐derived growth factor (PDGF), transforming growth factor‐β1 (TGF‐β1) and interleukin‐1 (IL‐1) on collagen synthesis of cultured human arterial smooth muscle cells in a confluent state were investigated. Synthetic activity of collagenous protein was determined with [3H]‐proline uptake, and subsequent analysis of collagen types by sodium dodecylsulfte‐polyacrylmide gel electrophoresis (SDS‐PAGE) followed by fluorography. Although PDGF (0.5 U/mL and 5.0 U/mL) enhanced total collagen synthesis per dish, it suppressed total collagen synthesis per DNA (DNA content in a dish). TGF‐β1 (10 pmol/L and 100 pmol/L) enhanced total collagen synthesis both per dish and per DNA. IL‐1 (0.1 U/mL and 1.0 U/mL) suppressed total collagen synthesis both per dish and per DNA. A fluorogram revealed that human arterial smooth muscle cells synthesize types I, III, IV and V collagen. Densitometric analysis showed PDGF suppressed the proportion of type V collagen. TGF‐β1 increased the proportions of types IV and V collagen. IL‐1 elicited un‐remarkable change in the proportion of collagen types. These results suggest that, in the event of human atherosclerosis, TGS‐β1 is most effective in enhancing collagen synthesis, and PDGF modulates collagen metabolism by stimulating a cell division of smooth muscle cells with a resultant increase of collagenous protein, especially of type V collagen.
Three hundred and twenty autopsy cases of sarcoidosis during a 32 year period were collected from the Annuals of the Pathological Autopsy Cases in Japan, published yearly since 1958, and from a literature survey. A statistical analysis of these reviewed autopsy cases was carried out on the epidemiological features of the disease and on the causes of death.The proportion of sarcoidosis autopsy cases relative to the total autopsy cases had increased during this 32 year period. The increase of sarcoidosis autopsies during this period was chiefly due to the increase in aged females; the total number of female cases was approximately two times more than that of males. As over half of the total cases had only a pathological diagnosis and not a clinical diagnosis for sarcoidosis, the actual morbidity from sarcoidosis that was estimated from the autopsy data and corrected by autopsy rate was over five times higher than that of the clinically recognized cases.Age and sex distribution of these cases peaked in the thirties for both sexes, while another very high peak was noted in females over 50 years of age. In approximately 60% of the sarcoidosis autopsies, the cause of death related to sarcoid lesions in the heart, lung or nervous system, the majority of which involved cardiac sarcoidosis. In the remaining 40% of the cases, the cause of death was from non‐sarcoidosis diseases.
A patient is described with severe IgA nephropathy associated with psoriatic arthritis, idiopathic interstitial pneumonia and brain hemorrhage that developed serially over one and a half years. The histological findings of the renal biopsy showed severe endo- and extracapillary proliferative glomerulonephritis. Massive IgA deposits were observed by immunofluorescence not only in the mesangium but also along the capillary walls. Electron microscopy revealed abundant electron-dense deposits in the mesangial and subendothelial areas. The overlapping or coexistence of these conditions has rarely been reported.
A silver colloid technique for nucleolar organizer regions (AgNOR) was applied to paraffin sections of maxillary sinus squamous cell carcinomas (MSSCC) of 25 patients. The patients were divided into two groups, one with MSSCC recurring in the primary lesion after treatment with radiotherapy, chemotherapy and/or surgery and one without recurrence. Notable differences between the numbers of NOR in neoplastic epithelia and the normal mucosa were observed (P = 0.0001), but there were no differences between the numbers of NOR in the recurrent and non-recurrent carcinomas. This investigation found no prognostic importance in the number of AgNOR in MSSCC.
A new human cell line, LC-2/ad was established from pleural effusion of pulmonary adenocarcinoma of a 51 year old Japanese female. The LC-2/ad cells exhibit an epithelial appearance and a tendency to form small domes as observed with phase-contrast microscopy. The modal chromosome number was 53-56. Plating efficiency and doubling time were 6.8% and 58 h, respectively (32th passage). Immunocytochemically, the cells were strongly positive for CEA and cytokeratins including cytokeratin no. 18 which is present in simple epithelia. Ultrastructurally, the cultured cells were characterized by well-formed junctional complexes and microvilli. Subcutaneous injection of 5 x 10(6) cells into a nude mouse resulted in tumor formation classified histologically as a moderately differentiated adenocarcinoma. This cell line produced at least two functionally active trypsin inhibitors together with several proteinases in vitro. The main inhibitor was purified partially from the serum-free conditioned medium and confirmed immunologically as human alpha 1-antitrypsin (AAT). Immunohistochemically, the xenografted tumor was also positive for AAT. The cell line LC-2/ad is useful for the study of tumor-derived serine proteinase inhibitors, in particular AAT.
Twenty‐one renal biopsy specimens obtained from 10 patients with dense deposit disease (DDD) were investigated using light microscopy, electron microscopy and immunohistochemistry. The patients included four females and six males aged 6 to 35 years (mean 16.1 years). A morphological diagnosis of DDD was made following the ultrastructural detection of continuous intramembranous dense deposits (CIMDD) in some capillary loops of at least one of the series of the repeated biopsies from each patient. With light microscopy, six patients showed membranoproliferative glomerulonephritis (MPGN). The other four patients showed diffuse proliferative glomerulonephritis (DPGN) with acute lesions showing intraglomerular neutrophilic infiltration, hump formation and endothelial swelling in three and minor glomerular abnormalities in one. Follow‐up biopsies were obtained in six patients. Two patients progressed from DPGN to MPGN within 7 months, whereas three patients with MPGN showed morphologic improvement that featured increased capillary patency and regional disappearance of dense deposits along with the reduction of proteinuria. Dense deposit disease did not always feature typical amorphous and osmiophilic CIMDD spreading across the whole width of the lamina densa. This classical ultrastructural manifestation was mainly found in the patients with histologic non‐MPGN and a linear peripheral pattern of complement component (C3) deposition. The MPGN patients with a granular peripheral pattern of C3 deposition also had CIMDD, but also additionally featured less dense subepithelial deposits superimposed on the CIMDD to produce an appearance simulating membranous transformation. Humplike epimembranous massive dense deposits were also identified in connection with the deposition of immunoglobulin G (IgG), suggesting that immune complex deposition at the glomerular basement membrane occurs in some cases of DDD. Immunoglobulin M (IgM) or complement component 1q (C1q) deposition was often associated with intraglomerular neutrophilic infiltration and endothelial swelling as well as with ultrastructural subendothelial edema. Continuous dense deposits were found not only in the lamina densa but also just beneath the subendothelium in four patients. Thus, the present investigation demonstrated the morphologic variety of DDD in a correlative study of light microscopy, electron microscopy and immunohlstochemistry.
Epstein-Barr virus (EBV) involvement in gastric carcinoma has been demonstrated by the presence of EBV genomes and EBV-encoded small RNA (EBER) in the carcinoma cells, monoclonal proliferation of EBV-infected carcinoma cells and elevated antibody titers. The present study was conducted to investigate the prevalence of EBV involvement among gastric carcinomas observed in nine Japanese cities with varying gastric cancer rates. In situ hybridization of EBER-1 was applied to paraffin sections from 1848 carcinomas observed in 1795 cases and EBV involvement was detected based on uniform hybridization in carcinoma cells. Epstein-Barr virus was detected in 6.6% of lesions and 6.7% of cases. The rate of EBV involvement did not vary significantly for each city and there was no correlation with underlying gastric cancer mortality rates. Thus, geographic variation of gastric cancer rates within Japan cannot be explained in terms of EBV involvement. Epstein-Barr virus-related gastric carcinoma is one of the most common EBV-related tumors in Japan. The involvement of EBV was significantly more frequent among males than among females, mainly for cancers occurring in the upper and middle part of the stomach, and exhibited more variation by cell type among males. These observations suggest that other factors yet to be discovered may modulate the causal role of EBV in gastric carcinogenesis.
We describe a case of well differentiated adenocarcinoma of the gall-bladder that arose from a localized type of adenomyomatosis. Grossly, the cancer was located in the fundus and exhibited a polypoid and well demarcated nodule with multiple small cysts. Histologically, the nodule consisted of glandular structures and stroma containing bundles of smooth muscle cells. The glandular epithelia were varied in appearance, ranging from malignant to benign glands. The adenocarcinoma was limited to the nodule, with normal surface mucosal epithelia and without obvious stromal invasion.
Three cases of lung carcinomas with unusual histologic appearances that have received little or no comment in the literature are presented. They were initially confused with malignant lymphoma because of a diffuse proliferation of relatively monotonous cells simulating large-cell immunoblastic lymphoma. In each case, the possibility of malignant lymphoma was excluded with confidence after the immunohistochemical study (leucocyte common antigen negative and cytokeratins positive), although with conventional microscopy several foci of cohesive groups of tumor cells were observed. The tumors were ranked at the clinical stage II or III when they were initially discovered, but all patients died of disease within 1 year. The present three tumors show an aggressive behavior and could be classified into a peculiar variant of 'large cell' carcinoma. It is necessary for surgical pathologists to have an idea of these variants of lung carcinoma in order to avoid erroneous diagnosis.
Recent reports of Ewing's sarcoma (EW) and extraskeletal Ewing's sarcoma (EEW) support the hypothesis that these tumors are neuroectodermal in origin. Primitive neuroectodermal tumors (PNET) of bone (32 cases) and soft tissue (25 cases) including those previously categorized as EW in 27 cases and EEW in 15 cases were carefully studied histologically, immunocytochemically and morphometrically, focusing on tumor cell differentiation. This study attempts to subclassify these tumors on the basis of the size of tumor cells and nuclei, their variations (uniformity or diversity), arrangement of tumor cells (rosette or non-rosette), focal differentiation to larger ganglion-like cells, and staining intensity for neural markers. All tumors were histologically subclassified as small, medium or large cell types, three basic subtypes (rosette type, abortive rosette type, non-rosette type) and four complementary subtypes (fibrillary type, non-fibrillary type, angiomatoid type, ganglion cell type). Classic EW or EEW is consistent with small or medium, non-rosette, non-fibrillary type tumors, previously described large cell EW with large, non-rosette, fibrillary or non-fibrillary type tumors, and classic neuroectodermal tumor with small or medium, rosette, fibrillary type tumors, according to the present subclassification. Clinicopathologic correlations with the different subtypes are discussed. Long-term survival, more than 5 years, was seen in patients with small cell type, and those younger than 14 years of age.
Senile Nagoya, Shibata, Yasuda (NSY) mice developed amyloidosis and died from renal failure as a result of amyloidosis. NSY mice were first reported as experimental congenital diabetic mice by Shibata et al. in 1980. This study questioned whether NSY mice died from diabetic nephropathy. The authors of the present study investigated the life span and cause of death in these micde. The life span of NSY mice was found to be 618.7 ± 72.5 days. NSY mice that lived for more than 400 days showed rising blood uread nitrogen and large amounts of amyloid deposits in the glomerulus of the kidneys. NSY mice died of renal amyloidosis. Immunological methods revealed that AApoAll was evident in the amyloid deposits of NSY mice. Apart from the kidneys, amyloid deposition was also found in the tongue, esojphagus, stomach, small intestine, large intestine, rectum, lung, heart and adrenal glands. Amyloid deposits were found to a slight degree In the liver and the spleen. The most dominant amyloid deposition in NSY mice was seen in the glomerulus of the kidneys. From the point of view of amyloid depositional distribution, NSY mice were unique compared with other spontaneous amyloid mice.
We report a rare case of cerebellar degeneration that was diagnosed at autopsy in a patient who developed lithium intoxication accompanied by neuroleptic malignant syndrome. This 63 year old female, who suffered from manic depressive psychosis, had received lithium bicarbonate at a daily dose of about 1000 mg for 4 years. She developed a high fever and extrapyramidal symptoms resembling a neuroleptic type of malignant syndrome and died 1 month later. Autopsy revealed an almost complete loss of Purkinje cells with a mild reduction of granule cells in most areas of the cerebellar hemisphere and vermis, except for the tonsil and flocculus, and mild gliosis in the dentate nucleus. In cases of suspected lithium intoxication, one must be alert to the possibility of neuroleptic malignant syndrome and to prevent cerebellar degeneration.
