Primary lymphomas of the liver. Report of six cases and review of the literature

Six cases of diffuse large cell lymphoma (DLCL) of the liver were studied with immunohistochemistry for common leukocyte antigen (CLA), lysozyme, alpha-1-antitrypsin (AAT), and kappa and lambda light chains on paraffin-embedded tissues. All six cases were positive for CLA. Four of the six cases showed staining for lysozyme and AAT (three focal and one diffuse staining). In three cases, frozen tissue for monoclonal antibodies and glutaraldehyde-fixed tissue for electron microscopic examination were available. Two of these showed B-cell phenotypes with monoclonal antibody studies. Electron microscopic examination on these two B-cell lymphomas showed scant cytoplasm and a paucity of cytoplasmic organelles. The third case did not show definite B- or T-cell surface markers but did show strong Leu-M1 and OKM1 staining. Electron microscopic examination of the tumor cells showed a prominent Golgi apparatus, abundant cytoplasm with numerous cytoplasmic organelles and phagolysosomes. However, DNA hybridization studies on this tumor showed immunoglobulin heavy and kappa light chain gene rearrangements typical of a B-cell lymphoma. All six lymphomas were solitary liver masses without evidence of disease elsewhere. The mean age for the six patients was 56.2 years (four males, two females).     

Neuroendocrine carcinoma of the skin. Morphology and differential diagnosis based on 2 clinical cases

Two cases of neuroendocrine carcinomas of the skin were examined by light microscopic and electron microscopic methods. In both patients the disease showed an unusual course characterized by the occurrence of numerous and wide-spread skin nodules. Light microscopically, we found a uniform tumor tissue with trabecular, nest- or cord-like arrangement of cancer cells. At electron microscopic investigation, neurosecretory granules (dense-cored vesicles) were detected. These organelles had a diameter between 90 and 220 nm. Furthermore, small bundles of intermediate filaments and a well-developed Golgi system as well as numerous vesicular structures were recognized. Specialized cell junctions were lacking, tumor cell complexes were often enveloped by a basal lamina-like structure. The light microscopic and electron microscopic observations are in accordance with other reports. The relationship of neuroendocrine skin carcinomas to Merkel cells is discussed. However, we suggest an origin of these carcinomas from multipotent epithelial stem cells. The multicentric development in our cases, the tumor localization, and recent electron microscopic findings in basal cell carcinomas lend the basis for speculations on relations between neuroendocrine carcinomas and basal cell carcinomas of the skin. Lastly, the morphologic differential diagnosis of neuroendocrine carcinomas is presented. Special attention is called to the distinction from melanomas, lymphomas and other neuroendocrine tumors. In spite of the fact that neuroendocrine carcinomas of the skin are well defined and considered to be a clinico-pathologic entity there are some open questions concerning the tumor biology and histogenesis.     

The formaldehyde-fixed and paraffin-embedded tissues for diagnostic transmission electron microscopy: a retrospective and prospective study

The fine structures of tissues processed routinely for light microscopy were studied retrospectively in 44 tissues and tumors and prospectively in 13 tissues and tumors. In the prospective study, we fixed tissues in an ample amount of fixatives, carefully avoiding crushed and air-dried portions, and processed them by five methods. The fine structures of the retrospective cases were mostly poor or passable, whereas those of the prospective cases were generally good. All formaldehyde-fixed tissues showed varied degrees of tissue extraction, notably of lipids, membranous structures, ribosomes, glycogen, and other loose cellular and intercellular matrix materials, that was related to the status and type of tissue as well as the kind and duration of fixation, dehydration, and tissue clearance. Paraffin embedding per se appeared to cause little alteration of the fine structure. Transmission electron microscopy of the paraffin-embedded tissue appeared most useful to identify infective agents, foreign particles, and densely packed organelles or structures, usually in the differential diagnosis of neoplasms. Although many factors are difficult to control, initial careful thin slicing, judicious selection, and fixation of the tissue (even by regular phosphate-buffered formaldehyde solution) can improve the fine structure of paraffin-embedded tissues and be useful in the direct correlation of light and electron microscopic findings.     

Histopathology of the human liver in yellow fever with special emphasis on the diagnostic role of the Councilman body

Liver specimens from 10 cases of yellow fever (YF) were studied by light and four by electron microscopy to review morphological aspects of the disease relevant to its diagnosis, with special emphasis on acidophilic bodies (AB) and on the possible presence of the virus within infected cells. The AB were compared with those found in 22 out of 69 liver specimens with other pathological processes. In YF the typical alteration was an acidophilic hepatocellular necrosis with a preferential midzonal distribution. Ceroid pigment was abundant, its amount was proportional to the degree of liver cell damage and it was found in altered hepatocytes and Kupffer cells in the most damaged areas. The inflammatory infiltrate was scanty, not only in portal tracts but also within the lobules. Electron microscopically, no viral particles were found in liver cells or AB. The latter appeared as round or elliptical cytoplasmic masses, surrounded by a conspicuous cellular membrane and densely packed with organelles, fat vacuoles and residual bodies. They differed from AB in other liver diseases by the presence of fat vacuoles and ceroid pigment. Some peculiarities of AB in other liver diseases such as presence of bile pigment and iron, would depend upon the presence of these pigments in the hepatocytes which originated them.     

Early morphologic diagnosis of herpes simplex virus encephalitis: advantages of electron microscopy and immunoperoxidase staining

The authors compared three morphologic techniques that can be used in the diagnosis of herpes simplex virus encephalitis. The pathologic material was derived from brain biopsy, autopsy, or both in ten culture-proven cases. On conventional light microscopic examination, typical intranuclear Cowdry type A inclusions were recorded as absent (one case), rare (six cases), or numerous (three cases). Electron microscopic evaluation, performed in nine cases, revealed intranuclear viral particles in five biopsy and two autopsy cases, including four cases in which inclusions were rare or absent on light microscopy. In one biopsy specimen, unequivocal virus particles could not be identified ultrastructurally, although they were present in subsequent autopsy material. Immunoperoxidase staining using the peroxidase-antiperoxidase (PAP) method and type-specific anti-herpes simplex type 1 antiserum, performed on paraffin-embedded tissue, demonstrated strongly positive specific immunoreactivity in all ten cases. The potential for rapid specimen preparation, the relative sensitivity of electron microscopy, and the extreme sensitivity and specificity of the PAP-immunoperoxidase method offer obvious advantages in the early morphologic diagnosis of herpes simplex virus encephalitis.     

Paracrystalline needle-shaped cytoplasmic liver cell inclusions in chronic hepatic porphyria--light and electron microscopic examination of liver biopsy specimens

Paracrystalline needle-shaped cytoplasmic liver cell inclusions could be identified by light and electron microscopic examinations of 19 liver biopsy specimens in chronic hepatic porphyria. Light microscopically, they occurred in 6 cases, electron microscopically they were found in 13 ones. In the electron microscope these inclusions displayed tubular substructures with enhanced contrast of the membranes. They are specific for chronic hepatic porphyria; their light microscopic identification is of diagnostic value. Membranous material occurring in cisternae of the endoplasmic reticulum and adjacent to pigments and inclusions has not been described so far and is discussed with regard to its origin. Alterations of mitochondria and endoplasmic reticulum, observed in all cases, point to a general liver cell damage in chronic hepatic porphyria. Up to the present, the chemical structure and pathogenesis of the inclusions are still unknown.     

Origin of the desmoplasia in desmoplastic malignant melanoma

Four cases of desmoplastic malignant melanoma were examined light microscopically and immunohistochemically. Electron microscopy was performed in three cases. Light microscopy showed that all tumors were composed of neoplastic spindle cells that infiltrated between mature collagen bundles in the reticular dermis. Some of the spindle cells had bizarre nuclei, whereas other spindle cells resembled normal fibroblasts. Melanin could not be demonstrated in any of the tumors by histochemical techniques. Electron microscopic examination of the spindle cells showed prominence of rough endoplasmic reticulum, which was dilated and filled with flocculent material and occasional collagen fibrils. The same cells contained aggregates of non-membrane-bound melanin granules and pre-melanosomes. Some cells also showed features of myofibroblasts. Immunoperoxidase staining with anti-S100 protein antibody demonstrated positivity of the spindle cells as well as of melanocytes in the basal layer of the epidermis. Scar tissue and fibroblasts did not stain. These findings show that the desmoplastic component of these malignant melanomas derives from melanocytes that have undergone adaptive fibroplasia. Therefore, in assessing depth of invasion in a malignant melanoma, measurements should include the desmoplastic areas.     

Hairy cell leukemia. Light and microscopic and electron microscopic examinations (author's transl)

Two cases of a typical hairy cell leukemia are presented. The light microscopic findings within the bone marrow, lymph nodes and spleen are documented. The hairy configuration of tumor cells can best be seen in semithin sections of white cells of the peripheral blood. Electron microscopically, the organelle composition of hairy cells (including the characteristic ribosome lamellae complex) is demonstrated. The significance of morphological observations for the diagnosis of hairy cell leukemia and the differential diagnosis of this tumor disease are discussed. From the electron microscopic observations of intercellular cross-banded structures it seems possible that the increase of intercellular material demonstrable light microscopically by silver impregnation is the consequence of synthesis of collagen type IV. The conclusion is drawn from findings in our cases and from reports in the literature that hairy cell leukemia is a clinically and structurally defined syndrome rather than a pathological entity.     

Ultrastructural study of intranuclear inclusion bodies of pulmonary adenocarcinoma

Intranuclear inclusion bodies are sometimes observed in pulmonary adenocarcinoma by light microscopy. Electron microscopic characteristics of lung cancer cells with intranuclear inclusion bodies were studied. In addition, polymerase chain reaction (PCR) was performed using primers coding for human papillomavirus (HPV) types 16, 18, and 33. Eosinophilic intranuclear inclusion bodies were observed in 22 out of 285 cases by light microscopy. Immunohistochemically, cancer cell nuclei stained with PE-10. Three types of intranuclear inclusion bodies were classified electron microscopically. Type A showed aggregation of electron dense particles (30-40 nm) with an electron-dense core and was most frequently observed. Type B consisted of a mass of branching and whirling tubular structures. Type B intranuclear inclusions had a relationship with inner nuclear membrane. In type C, several spherical inclusions were observed in one nucleus. HPV DNA was detected using PCR and type-specific probes in a case with type A inclusion bodies. This study suggests that intranuclear inclusion bodies in pulmonary adenocarcinoma are formed by several different mechanisms.     

Renal proliferative arteriopathies and associated glomerular changes: A light and electron microscopic study

This presentation reports the light and electron microscopic findings relating to the vascular and glomerular changes in the kidney in a series of 25 patients having malignant hypertension, the hemolytic-uremic syndrome, scleroderma, or toxemia of pregnancy. The pathologic changes were generally similar in each of the diseases studied, the changes being related more to the severity and duration of injury than to the specific disease. Vascular narrowing was due mainly to intimal thickening, and by light microscopy the lesions were categorized as onionskin, mucinous, or fibrous with or without associated elastosis. Intimal erythrocyte extravasation, fibrinoid necrosis, and luminal thrombosis were also seen. Electron microscopy provided additional morphologic information: Myointimal cells were found to be the cellular component in each type of intimal thickening; it was possible to distinguish collagen from large intimal accumulations of basement membrane material; mucinous intimal material was characterized ultrastructurally; and fibrinoid necrosis was identified as a lesion inconstantly associated with cellular necrosis and consisting mainly of fibrinoid material and small deposits of fibrin. It seems likely that there is a common pathogenesis for intimal thickening in a variety of diseases and that this involves endothelial cell damage and increased permeability, leakage of serum and crythrocytes into the intima, and a healing reaction of the vessel wall developing from migration of smooth muscle cells into the intima with subsequent myointimal cell proliferation and fibrogenesis.A common glomerular change in all diseases studied was a striking accumulation of electron lucent material between the endothelium and the lamina densa of the basement membrane. This lesion was interpreted as a manifestation of acute ischemia.     

Leigh's disease involving multiple organs.

Leigh''s disease is a rare progressive neurological disorder that is characterized light microscopically by focal spongy necrosis in the brain and electron microscopically by mitochondriopathy. We report an autopsy case of Leigh''s disease that showed abnormalities in the liver, kidney and skeletal muscle as well as the central nervous system. The patient was an 18-month-old girl who has carried a diagnosis of cerebral palsy ever since her birth to a 20-year-old mother. The baby was generally hypertonic and mentally retarded. She died of severe metabolic acidosis. Postmortem examination showed growth retardation, fatty liver, fatty kidney and soft brain. Brain section showed multifocal softenings in the brainstem, basal ganglia and periventricular areas. Microscopically increased capillaries with endothelial proliferation, vacuolar degeneration and mild gliosis were seen in the brain. The axons were relatively preserved. Liver and kidneys showed microvesicular fatty change. Myofiber degeneration of the skeletal muscle was also noted. Electron microscopic examination showed markedly increased mitochondria in the parenchymal cells of the brain, liver and kidney. The mitochondria showed round to ovoid ballooned appearance including electron-dense core-like structures and pseudoinclusions of glycogen granules.     

Gamma heavy chain disease. Ultrastructural and immunohistochemical study

Electron microscopic and immunohistochemical studies were carried out on materials obtained from three patients of gamma heavy chain disease (gamma-HCD). Electron microscopically, proliferating cells showed various stages of maturation from immunoblast to plasma cell, and the majority of proliferating cells were proplasmacytes and plasma cells. From the intracytoplasmic immunoglobulin studies by immunoperoxidase method (PAP method) and electron microscopical enzyme-labeled antibody technique, proliferating cells, such as the immunoblast, plasmablast, proplasmacyte, and plasma cell, showed positive reaction to anti-gamma-heavy chain serum and anti-Fc fragment (IgG) serum, and also in a third case with Bence Jones protein, proliferating cells showed positive reaction to anti-kappa light chain serum. We would conclude that proliferating cells in gamma-HCD might be a single clone proliferation of B-cell synthesizing gamma-HCD protein, and the predominant proliferation cells are proplasmacytes and plasma cells situated near mature plasma cells in the B-cell line.     

Two distinctive types of lipid histiocytes appearing in the spleen of idiopathic thrombocytopenic purpura. Sea-blue histiocyte and foam cell

In 11 of 18 spleens surgically removed from patients with idiopathic thrombocytopenic purpura (ITP), the occurrence of sea-blue histiocytes or foam cells were observed. In a few cases, sea-blue histiocytes were found in the lymph nodes or bone marrow. Histochemically the sea-blue histiocytes were proved to contain ceroid or ceroid-like pigments in their cytoplasm. Ultrastructurally numerous intracytoplasmic membrane-bound inclusions, mostly containing tightly laminated materials and intermingling electron-dense amorphous materials or osmiophilic lipid droplets, were present in these cells. In the foam cells, accumulation of excess amounts of phospholipids was histochemically demonstrated in frozen sections, often accompanied by deposition of cholesterol, particularly in advanced cases. Electron microscopically, vacuolar membrane-bound inclusions were found to predominate in their cytoplasm, most of which contained irregularly or loosely laminated materials. Transitional cells between both types of cells were also found light or electron microscopically and ultrastructural transition of sea-blue histiocytes to foam cells was traced. Enhanced phagocytosis of blood cells, including platelets, by sea-blue histiocytes, and gradual transition of the ingested blood cells to the inclusions were confirmed.     

A light and electron microscopic study of perineuronal glial cells and processes in the rabbit neocortex

The morphology of satellite cells was determined by examining brom formalin fixed tissue stained by the silver carbonate technique, and tissue fixed in gluteraldehyde, post-fixed in osmium and prepared for electron microscopy. Light microscopy indicated that oligodendrocytes and astrocytes were the predominant perineuronal cell types. Cells with intermediate morphological characteristics were also observed. The light microscopic criteria for cellular indentification were the comparative size and shape of the cell bodies, and the number and nature of glial processes. Electron microscopy revealed perineuronal cells with round to oval shaped cell bodies, dense nuclear and cytoplasmic matrices, and a rich compliment of organelles. A second, less numerous, type of satellite cell had a larger, oval, elongate, or somewhat angular cell body, light nuclear and cytoplasmic matrices, and gliofibrils and glycogen. The former correlated well with the light microscopic oligodendrocyte and the latter with the astrocyte. “Dark cells” were not observed in a satellite position with the electron microscope nor were cells observed that conform to Hortega's “spiny microglia” in our silver preparations. Specializations of the plasma membranes of satellite glial cells and neurons were observed, and were interpreted as possible morphological evidence for “transport” between neurons and neuroglia.     

Acute radiation nephritis. Light and electron microscopic observations.

Light and electron microscopy were used to observe acute radiation nephritis. By light microscopy the changes were of fibrinoid necrosis of the arteries and atrerioles with segmental necrosis of the glomerular tufts. By electron microscopy the endocapillary cells reacted by hypertrophy and hyperplasia with increase in cytoplasmic organelles. In addition, disruption of endothelial and epithelial cells from the basement membranes were seen. It is concluded that the electron microscopic changes were unique and may be helpful in differentiating the necrotizing glomerulitis seen in other conditions, especially malignant hypertension.     

Giant Cell Pneumonia: Light Microscopy, Immunohistochemical, and Ultrastructural Study of an Autopsy Case

An autopsy case of measles giant cell pneumonia with intranuclear inclusion bodies is reported. This case of giant cell pneumonia was studied by light microscopy and immunohis-tochemistry using monoclonal and polyclonal antibody to measles and by electron microscopy (EM). Light microscopic examination showed multinucleated epithelial giant cells with intranuclear and intracytoplasmic inclusions. The giant cells contained prominent, sharply marginated, eosinophilic intranuclear inclusions typical of classic measles pneumonia. Presence of measles antigen was confirmed using both monoclonal and polyclonal antibodies by peroxidase antiperoxidase method. Monoclonal antibody stained positively for intracytoplasmic and intranuclear inclusions. Electron microscopic examination of lung tissue showed intranuclear inclusions of filamentous or worm like nucleocapsid materials in multinucleated epithelial giant cells. The results suggest that this is a case of measles giant cell pneumonia and the intranuclear inclusion bodies are measles viral particles.     

GAMMA HEAVY CHAIN DISEASE

Electron microscopic and immunohistochemical studies were carried out on materials obtained from three patients of gamma heavy chain disease ( λ -HCD). Electron microscopically, proliferating cells showed various stages of maturation from immunoblast to plasma cell, and the majority of proliferating cells were proplasmacytes and plasma cells. From the intracytoplasmic immunoglobulin studies by immunoperoxidase method (PAP method) and electron microscopical enzyme-labeled antibody technique, proliferating cells, such as the immunoblast, plasmablast, proplasmacyte, and plasma cell, showed positive reaction to anti- λ -heavy chain serum and anti-Fc fragment (IgG) serum, and also in a third case with Bence Jones protein, proliferating cells showed positive reaction to anti_-K light chain serum. We would conclude that proliferating cells in λ -HCD might be a single clone proliferation of B-cell synthesizing λ -HCD protein, and the predominant proliferation cells are proplasmacytes and plasma cells situated near mature plasma cells in the B-cell line.     

子宫平滑肌肉瘤组织发生的电镜观察

选用光镜论断为子宫平滑肌肉瘤的相应电镜用样品三例。电镜样品常规制样。电镜观察到子宫平滑肌肉瘤由明、暗两种细胞群和少量胶原组成。明细胞占极大多数。暗细胞周围均有胶原纤维。依瘤细胞内所含肌丝数量的增加，发现瘤细胞有分化移行过程，肌丝的含量与其他细胞器的数量成反比。     

Herpes simplex viral infection in human neonates: an immunohistochemical and electron microscopic study

Specimens obtained at autopsy from six neonates with herpes simplex virus (HSV) infections were examined microscopically, electron microscopically, and immunohistochemically. Coagulative necrosis with inclusions was found in the livers and adrenal glands in all cases, as well as in various other organs, including the spleen, bone marrow, lungs, esophagus, tongue, and thymus, in some cases. Distinct hemorrhagic diathesis was found in three cases. No characteristic clinical findings, such as skin rashes or elevated titers of the antibody to HSV, were found, and clinical diagnosis was therefore difficult. In three cases isolation and typing of the causative virus were performed virologically, and type 1 HSV (HSV-1) was identified as the causative virus. Immunohistochemically, the type and distribution of the virus were evaluated in all cases with type-specific antisera to types 1 and 2 (HSV-2) antigens by the peroxidase-antiperoxidase method. In five cases the infections were found to be due to HSV-1 and in only one case to HSV-2. In the placenta in one case of HSV-2 infection, HSV antigen was demonstrated in the chorionic villi. Electron microscopic study confirmed the existence of viral particles in the placenta in that case and, thus, the possibility of a transplacental route of infection.