针吸细胞学诊断肝细胞癌的标准探讨

目的 探讨肝细胞癌（ＨＣＣ）的针吸细胞学诊断标准。方法 分析６１例ＨＣＣ针吸细胞学涂片，并与１９例肝转移瘤和１６例肝非肿瘤病变对照，找出与ＨＣＣ有关的形态改变，用逐步Ｌｏｇｉｓｔｉ回归方法选择区别ＨＣＣ与肝转移瘤、ＨＣＣ与肝非肿瘤病变的最有用的形态特征。     

Neuroectodermal tumor of bone. Evidence for neural differentiation in a cultured cell line

A new cell line was established from a "neuroectodermal tumor of bone" affecting the right scapula of an 18-year-old man. The original neoplasm had dense proliferation of small round cells with abundant glycogen content and numerous Homer-Wright rosettes. The culture showed proliferation of small spindle cells with uniform oval nuclei and slender cytoplasmic processes. When the culture reached maximum density, rosette-like structures similar to those in the original tumor were formed. Under the influence of N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphoric acid (dibutyryl cAMP), the cultured cells expressed these rosette-like structures even in the lower cell concentration. Electron microscopy revealed that the cultured cells treated with dibutyryl cAMP contained high-density granules, well-developed microtubules, and abundant 10-nm filaments. By immunocytochemistry, neuron-specific enolase (NSE), and N-myc oncogene product were detected in the cultured cells as well as the original tumor. These results indicated the neuroectodermal origin of some of the small round cell tumors of bone.     

Enzyme-altered Liver Cell Foci in Woodchucks Infected with Woodchuck Hepatitis Virus

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.     

Enzyme-altered liver cell foci in woodchucks infected with woodchuck hepatitis virus

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.     

Hodgkin's disease and myelomonocytic leukemia: an ultrastructural and immunocytochemical study.

The ultrastructual and immunologic features of the initial Reed-Sternberg and Hodgkin cells are compared with the ultimate leukemic cell type in a child with Hodgkin's disease who subsequently developed acute myelomonocytic leukemia (AMML) following 29 months of chemotherapy. Hodgkin tumor cells contained cytoplasmic IgG and ultrastructurally resembled large immunoblasts, containing one or two round nuclei with large bizarre nucleoli, many polyribosomes, sparase endoplasmic reticulum, underdeveloped Golgi lamellae, and few cytoplasmic granules. The Hodgkin tumor cells displayed no evidence of phagocytosis. The leukemic monocytic cells did not contain cytoplasmic IgG and, ultrastrucally, exhibited and indented and irregular nuclear profile with less prominent nucleoli, numerous pleomorphic granules, a moderate number of free ribosomes, short segments of endoplasmic reticulum, and stacked Golgi lamellae. The cell surface was irregular and occasionally appeared involved in endocytic activity. These results indicate that the Hodgkin tumor cells originated from B lymphocytes rather than tissue macrophages, whereas the leukemic monocytes arose from the bone marrow-derived monocyte-macrophage series. The findings suggest further that AMML developing after Hodgkin's disease consitutes a second neoplasm rather than a leukemic transformation of Hodgkin tumor cells.     

Clear cell carcinoma of the ovary: light and electron microscopic studies

Twelve cases of ovarian clear cell carcinoma were studied histologically. Four cases were examined electron microscopically and compared with other conditions. Five tumors were directly connected with ovarian endometriosis. They were histologically classified into a tubular type with hobnail cells and a solid type without tubular pattern or hobnail cells. Electron microscopic figures of the tumor cells are identical having large nuclei, abundant glycogen, lamellated RER, few lipid droplets, and sparse but well-developed microvilli. The basophilic dark cells frequently encountered in the tubular type are morphologically quite similar to clear cells excepting for sparsity of glycogen and lipid droplets. Alveolar arrangement of 6 to 10 tubular structures (honeycomb structure) resembling alveolate structure seen in late secretory endometrium was found in tumor cells of one case. Ultrastructural feature of clear cell carcinoma closely resemble those of Arias-Stella endometrium and clear cell carcinoma of endocervix suggesting their Muellerian origin.     

A step-wise logistic regression analysis of hepatocellular carcinoma. An aspiration biopsy study

Fine needle aspiration biopsy (FNAB) has become a popular method to diagnose mass lesions of the liver. Although several reports have listed FNAB criteria to be used to diagnose both primary and metastatic tumors of the liver, none have separated key cytologic criteria from secondary criteria. We reviewed the FNAB smears from 35 patients with proven hepatocellular carcinoma and 74 patients with proven metastatic tumors in the liver. All specimens were coded as to the presence or absence of the following variables: polygonal cells with centrally placed nuclei; well-defined, granular cytoplasm; large nucleoli; small cytoplasmic vacuoles; large cytoplasmic vacuoles; bile; polymorphonuclear leukocytes; malignant cells separated by sinusoidal vessels; endothelial cells surrounding tumor cell clusters; multinucleated tumor giant cells; basophilic intracytoplasmic inclusions; eosinophilic intracytoplasmic inclusions; and intranuclear cytoplasmic inclusions. A step-wise logistic regression analysis was performed on the data to determine the variables predictive of hepatocellular carcinoma. The statistical analysis selected polygonal cells with centrally placed nuclei, malignant cells separated by sinusoidal capillaries, and bile as the key cytologic criteria for hepatocellular carcinoma. Endothelial cells surrounding tumor cell clusters and intranuclear cytoplasmic inclusions were selected as secondary criteria by this analysis.     

中枢性原始神经外胚层肿瘤16例临床病理分析

[目的]探讨中枢性原始神经外胚层肿瘤(PNETs)的病理诊断、鉴别诊断及意义。[方法]采用光镜、免疫组织化学、特染及电镜对16例PNETs病例进行观察。[结果]肿瘤细胞排列成巢状、团块状或散在分布,细胞呈小圆形,大小一致,有菊形团形成;免疫组化显示有两项以上神经源性抗体呈阳性表达,以CD99最为显著;特殊染色显示瘤组织间网状纤维明显减少,部分瘤细胞胞浆内有糖原颗粒;电镜下部分瘤细胞胞浆内有神经内分泌颗粒。[结论]中枢性原始神经外胚层肿瘤归于神经上皮组织的胚胎性肿瘤,属高度恶性,诊断时须与髓母细胞瘤等相鉴别。     

Benign clear cell (sugar) tumor of the lung. A light microscopic, histochemical, and ultrastructural study with a review of the literature

A case of a benign clear cell "sugar" tumor of the lung is reported. Light microscopy showed a uniform proliferation of clear cells filled with abundant glycogen. At the ultrastructural level, tumor cells were rich in free monogranular and rosette-forming glycogen, but no membrane-bound glycogen was demonstrated. Some cells showed plasma membrane interdigitations, microvilli, and macula occludens-type junctions. Many polymorphic secretory and sporadic haloed neurosecretory-like granules were observed, but argyrophil stains as well as a large set of immunohistochemical reactions specific for APUD derivation had negative results. A literature review of this puzzling entity with particular emphasis on the histogenetic hypotheses is presented, and a derivation from epithelial nonciliated bronchiolar (Clara) cells or epithelial serous cells is suggested.     

Type 1a glycogen storage disease with hepatoblastoma in siblings

Clinical and histologic details of the two siblings with type 1a glycogen storage disease (GSD-1a) who developed hepatoblastoma are presented. The light microscopic studies on hepatic tumor in both siblings revealed fetal type of hepatoblastoma. Ultrastructural findings in Patient 2 showed markedly altered mitochondria, which were frequently surrounded by the rough endoplasmic reticulum. This is the first known occurrence with this association, and the third report on the familial occurrence of this neoplasm. Glycogen storage disease may increase the risk of hepatocellular carcinoma and hepatoblastoma.     

Short-term induction of neoplastic nodules in the rat liver. II. Study of their development and the effects of withdrawal of 2-acetylaminofluorene

Neoplastic liver nodules were induced by a single administrationof N-nitrosodiethylamine (NDEA) and selectively stimulated togrowth by 2-acetylamino-fluorene (2-AAF) and partial hepatectomyto provide morphological data on very early and late stagesof pre-neoplastic development. Presumptive preneoplastic livercells were recognizable by light and electron microscopy by2 days after partial hepatectomy, and they developed within2 weeks into large, solid nodules consisting of plates of 2or 3 cell layers thick, that compressed the surrounding non-nodulartissue. The cells showed nuclei with an enlarged nucleolus,tortuously dispersed rough endoplasmic reticulum (RER) and anelectron lucent cytoplasm. These features remained present throughoutthe first 2 weeks of growth. During this period the initiallysmall, distinct smooth endoplasmic reticulum areas proliferatedgradually. They were associated with an increasing incidenceof cytoplasmic membranes whorl formation and incidently withannulate lamellae. After withdrawal of 2-AAF the majority ofthe nodules regressed resulting in slowly disappearing fociof glycogen rich cells. A relatively small number of solid nodulespersisted. They were characterized by large cells with a homogeneouseosinophilic cytoplasm, enlarged nucleoli and dispersed RER.Because these characteristics were absent in nodular cells thathad reverted to normal liver cells, it is not appropriate toconsider these characteristics to represent neoplastic transformationper se.     

Primary cancer of the liver in Kenyan children.

In 9 years in Kenya, 34 examples of primary liver cancer wer diagnosed in patients in the first two decades of life. This represents 4.7% of all liver cancers during this period. The larger proportion (29) were hepatocellular carcinoma. In the second decade, there was a notable association with macronodular cirrhosis. Analogy with experimental work suggests that cells in mitotic cycle may be more vulnerable to the effect of environmental carcinogens. Five examples of hepatoblastoma were identified at ages from 2 months to 14 years; none showed the features of "mixed" tumours. The ratio of hepatoblastoma to hepatocellular carcinoma was the reverse of that found in other large series of juvenile hepatic tumours. The histopathological features of these tumours are described and problems of their classification are discussed.     

Fine-needle aspiration biopsy of chromophobe renal cell carcinoma and oncocytoma: comparison of cytomorphologic features.

BACKGROUND: Chromophobe renal cell carcinoma (ChRCC) is a distinct tumor with a prognosis intermediate between renal oncocytoma (RO) and clear cell renal cell carcinoma. To our knowledge the cytologic features of only a limited number of ChRCC have been described to date. A retrospective review of the cytomorphologic features of ChRCC and a comparison with RO was performed. METHODS: Fine-needle aspiration biopsies (FNABs) of six cases of histopathologically proven ChRCC were reviewed. The material examined was comprised of smears, cytospins, Thin Prep Pap Test preparations, and cell block sections stained with Diff-Quik, Papanicolaou, and hematoxylin and eosin. Six FNABs of ROs were examined similarly. The cytomorphology of each tumor was studied and particular attention was paid to features differentiating the two entities. RESULTS: The characteristic cytomorphologic features of ChRCC (present in all cases) included round/oval, occasionally polygonal, moderately pleomorphic large cells present singly and in small clusters. The abundant cytoplasm was variegated, ranging from dense to flocculent to vacuolated, with prominent cytoplasmic membranes. The nuclei were large and hyperchromatic, with nuclear membrane irregularities and grooves present at least focally. Frequent binucleation was observed. Small nucleoli were present in many cells, but rarely prominent. In contrast, RO showed large cells with homogenous granular cytoplasm. The nuclei showed minimal to no nuclear membrane irregularities, tiny nucleoli, mild pleomorphism, and only an occasional large, more hyperchromatic nucleus was observed. CONCLUSIONS: ChRCC has a distinct combination of cytomorphologic features. Careful attention to cytoplasmic and nuclear features allows for the distinction between ChRCC and RO in cytologic preparations.     

丙型肝炎病毒核心抗原及HBxAg在肝硬化、肝细胞肝癌中分布的免疫组化研究

研究丙型肝炎病毒核心抗原在肝硬变、肝细胞肝癌中的分布规律及意义。方法以免疫组织化学方法检测丙型肝炎病毒（ｈｅｐａｔｉｔｉｓＣｖｉｒｕｓ，ＨＣＶ）核心抗原及ＨＢｘＡｇ在肝硬化、肝细胞癌及其癌旁肝组织中的定位及分布。结果ＨＣＶ核心抗原既定位于肝细胞或癌细胞胞核中，又可定位于这些细胞的胞浆中。在不同的病例，有时以胞浆阳性为主，有时以胞核阳性为主，或二者同时存在。肝硬化组织中，ＨＣＶ核心抗原胞浆阳性细胞多呈灶性分布，而核阳性病例阳性细胞则为弥漫分布；肝细胞肝癌中ＨＣＶ核心抗原以弥漫胞核阳性多见，癌旁肝组织多为ＨＣＶ核心抗原胞浆阳性。ＨＣＶ核心抗原在肝硬化、肝细胞肝癌及癌旁肝中的阳性率分别为６７．３％（６６／９８），７５．０％（７８／１０４）及４８．１％（２５／５２），χ２检验，肝细胞癌中核心抗原的胞核阳性率明显高于其在肝硬化及癌旁肝中的胞核阳性率（Ｐ＜０．０１）。核心抗原在肝细胞肝癌中，其细胞核阳性率，明显高于细胞浆阳性率（Ｐ＜０．０１）。结论ＨＣＶ感染在我国肝硬化、肝细胞肝癌中比较普遍，除ＨＢＶ以外，ＨＣＶ可能在我国肝硬化、肝细胞癌的发生中起着重要作用     

丙型肝肝炎病毒核心抗原及HBxAg在肝硬化,肝细胞肝癌中分布的免…

目的研究丙型肝炎病毒核心抗原在肝硬变、肝细胞肝癌中的分布规律及意义。方法以免疫组织化学方法检测丙型为病毒核心抗原及ＨＢｘＡｇ在肝硬化,肝细胞癌及其癌旁肝中的定位有分布。结果ＨＣＶ核心抗的既定位于肝细胞或癌细胞胞核中,又可一于这些细胞的胞浆中。在不同的病例,有时以胞浆阳性为主,有时以胞核了性为主,或二者同时直化组织中,ＨＣＶ核心原胞浆阳性细胞多呈生分布,而核阳性病例性细胞则为弥漫分布;肝细胞肝癌中Ｈ     

Pulmonary clear cell carcinoma

A case of pulmonary clear cell carcinoma is demonstrated. A large left lower lobe mass, without lymphadenopathy was detected on a screening chest X-ray, and a left lower lobectomy was performed. The tumor was composed predominantly of clear cells with some areas showing cells typical for small cell carcinoma. Ultrastructurally, the larger clear cell had cytoplasm containing many rough endoplasmic reticuli and free ribosomes, while the smaller dark cell showed a serrated nucleus and scanty cytoplasm having many free ribosomes without neurosecretory granules. This is the first report on pulmonary clear cell carcinoma with small cell carcinoma patterns, and this case will throw doubt on the conclusion of previous studies that clear cell carcinoma is not a separate entity.     

CCAAT/enhancer binding protein alpha knock-in mice exhibit early liver glycogen storage and reduced susceptibility to hepatocellular carcinoma

The CCAAT/enhancer binding protein alpha (C/EBPalpha) is vital for establishing normal hepatic energy homeostasis and moderating hepatocellular growth. CEBPA loss-of-function mutations identified in acute myeloid leukemia patients support a tumor suppressor role for C/EBPalpha. Recent work showed reductions of C/EBPalpha levels in human hepatocellular carcinoma with the reductions correlating to tumor size and progression. We investigated the potential of reactivating c/ebpalpha expression during hepatic carcinogenesis to prevent tumor cell growth. We have developed a c/ebpalpha knock-in mouse in which a single-copy c/ebpalpha is regulated by one allele of the alpha-fetoprotein (AFP) gene promoter. The knock-in mice are physically indistinguishable from wild-type (WT) controls. However, knock-in animals were found to deposit fetal hepatic glycogen earlier than WT animals. Quantitative real-time PCR confirmed early c/ebpalpha expression and early glycogen synthase gene activation in knock-in fetuses. We then used diethylnitrosamine to induce hepatocellular carcinoma in our animals. Diethylnitrosamine produced half the number of hepatocellular nodules in knock-in mice as in WT mice. Immunohistochemistry showed reduced C/EBPalpha content in WT nodules whereas knock-in nodules stained strongly for C/EBPalpha. The p21 protein was examined because it mediates a C/EBPalpha growth arrest pathway. Nuclear p21 was absent in WT nodules whereas cytoplasmic p21 was abundant; knock-in nodules were positive for nuclear p21. Interestingly, only C/EBPalpha-positive nodules were positive for nuclear p21, suggesting that C/EBPalpha may be required to direct p21 to the cell nucleus to inhibit growth. Our data establish that controlled C/EBPalpha production can inhibit liver tumor growth in vivo.     

Virus particles in the basal plate of rhesus monkey and baboon placenta.

C-type virus particles and particles, approximately 35 nm in diameter, were present in the region of the basal plate from the placenta of a rhesus monkey and two baboons. Both particles appeared to bud from the plasma membrane of the cytotrophoblast: large, pleomorphic cells with cytoplasmic extensions, indented nuclei, well-developed endoplasmic reticulum, and glycogen deposits. Extracellular particles were enmeshed within a fibrous matrix. Particles were also observed in the junctional zone, but not in the decidua. C-type virus particles from the rhesus monkey and baboons differed in ultrastructure from each other and from C-type mouse leukemia virus particles. The 35-nm-type particle was spherical with a dense central core.     

Histochemical profile of mouse hepatocellular adenomas and carcinomas induced by a single dose of diethylnitrosamine.

In continuation of earlier studies on murine neoplastic liver lesions, we characterized by histochemical methods the phenotype of hepatocellular adenomas and carcinomas induced by single injections of diethylnitrosamine (1.25, 2.5, or 5.0 micrograms/g of body weight) in 15-day-old C57BL/6 x male C3H F1 mice. The hepatocellular adenomas were composed predominantly of basophilic cells but stored excessive amounts of fat and glycogen in large portions of the tumors. Irrespective of the carcinogenic dose, the adenomas showed a consistent histochemical pattern. Glycogen synthase and phosphorylase were highly active in the hepatocytes that stored glycogen. In cells poor in, or free of, this polysaccharide, these enzymes were only moderately active or even inactive. In glycogen-storing parts of the adenomas, the activity of adenylate cyclase was reduced compared with normal liver parenchyma, but in fat-storing portions it was elevated. In a few adenomas, uniform increase in adenylate cyclase activity could be encountered. The levels of ATPase, acid phosphatase, and glucose-6-phosphatase were either increased or decreased. Glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase showed an increased activity in all adenomas compared with preneoplastic foci, which in turn exhibited a higher glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activity than the surrounding parenchyma or the liver of untreated controls. The hepatocellular carcinomas showed remarkable histochemical changes compared with adenomas. The levels of fat and glycogen and the activities of glycogen synthase, phosphorylase, and in most cases also that of glucose-6-phosphate dehydrogenase, were reduced significantly. In contrast, adenylate cyclase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase, and also alkaline phosphatase showed a striking elevation in developing carcinomas. Similar, although more pronounced, histochemical changes were seen in the advanced hepatocellular carcinomas. These observations indicated that progression from adenomas to hepatocellular carcinomas was associated with a change in the activity of several enzymes involved in cell membrane function, glycogen metabolism, the oxidative pentose phosphate pathway, and glycolysis.     

Hyperplastic foci in precancerous rat liver: light microscopic and electron microscopic study.

4-Dimethylaminoazobenzene was fed to Wistar-derived, male, albino rats after hepatic siderosis had been induced by including ferric citrate in the diet. Iron-free foci of hepatocytes developed and this characteristic enabled them to be recognized macroscopically in the brown parenchyma. Five such lesions, each 1 mm or less in diameter, were studied by light and electron microscopy. The cells in the foci were larger than those surrounding the foci and had a granular and moderately basophilic cytoplasm. Ultrastructurally, the cells closely resembled normal hepatocytes. They possessed well-developed rough endoplasmic reticulum, numerous free ribosomes, peroxisomes, bile canaliculi, and cytoplasmic junctional complexes, but only small stores of glycogen were observed. Occasional ferritin-laden lysosomes persisted in some cells. These foci were regarded as hyperplastic. Possibly, they evolved into hyperplastic nodules either of the basophilic or vacuolated type. These foci should be clearly distinguished from hyperbasophilic foci that consisted of very poorly differentiated cells.