Single Nucleolus Research Articles

Chromosomal Variation in the Tropical Armored CatfishCallichthys Callichthys(Siluriformes, Callichthyidae): Implications for Conservation and Taxonomy in a Species Complex from a Brazilian Hotspot

The Neotropical catfish family Callichthyidae is characterized by wide karyotype variation, although reports are restricted to a few species/populations. This work provides new chromosomal information in two populations of armoured catfish (Callichthys callichthys) within the Atlantic forest boundaries in northeastern Brazil. Both populations of C. callichthys presented 2n=54 (16 metacentric, 24 submetacentric, 6 subtelocentric, and 8 acrocentric chromosomes) with occurrence of a metacentric B macrochromosome, reported for the first time in "2n=54" karyomorph. The lack of heterochromatin in the supernumerary chromosome suggests a recent origin of Bs with a significant difference in their frequency (p<0.05) between localities. Contrasting to the predominance of single nucleolus organizer regions (NORs) in other populations from South America, a remarkable polymorphism of 18S rDNA and GC-rich sites was detected, inasmuch as NOR phenotypes were unique for each individual, comprising up to 13 NOR-bearing chromosomes. The 5S rDNA was also mapped onto multiple chromosomes nonsyntenic to NORs. Such divergence in a number of NORs and occurrence of an euchromatic B chromosome in relation to other karyomorphs reinforces the divergent evolution of C. callichthys populations. Furthermore, these results also support central and drier Atlantic forest areas in northeastern Brazil as a biodiversity hotspot.

Use of Vaginal Lubrication Containing Carbomer Affects Adequacy of ThinPrep Pap Test

Introduction: High grade tubo-ovarian serous adenocarcinoma is a significant cause of mortality. In recent years attention has turned to the fallopian tube as a primary source of precursor neoplastic lesions. The cytologic features of fallopian tube brushings from low risk patients have not been well described in modern cytology literature. Material and Methods: We describe the cytomorphologic features of tubal epithelium from prospectively collected experimental in vivo brushings of normal fallopian tubes from low risk patients. Both ThinPrep slides and cell blocks were prepared and reviewed in all specimens. P53 and Ki-67 immunostains were also performed when epithelial cells were detected in cell block specimens. Available follow-up histopathologic salpingectomy material was also reviewed. Results: A total of 15 specimens were obtained from 7 patients, ten collected by laparoscopy, 4 by hysteroscopy, and one after hysterectomy and bilateral salpingo-oophorectomy on an ex-vivo specimen. Cytologic findings were as followscellularity: moderate to high (nZ13), low (nZ2); background: granular debris (nZ10), clean (nZ4), blood (nZ1); architecture: mixture of clusters and single cells (nZ11), clusters (nZ3); nuclear overlap: moderate/marked (nZ14), mild/none (nZ1); nuclear pleomorphism moderate/marked (nZ13), mild/none (nZ2); nuclear membrane irregularities moderate/marked (nZ6), mild/none (nZ9); nucleoli: mixture of single and multiple (nZ15); diffusely present (nZ15); mitoses absent (nZ15). Cell blocks of epithelial cells detected in 4 samples found P53 and Ki-67 stains to be negative. Salpingectomy specimens available in 3 patients documented benign histopathologic findings. Conclusions: Nuclear overlap, nuclear pleomorphism, prominent single nucleoli, multiple nucleoli, and background granular debris are all common findings encountered when reviewing direct experimental in vivo fallopian tube brushings from benign specimens. With experience, these cytologic findings should not be misinterpreted as suspicious or malignant.

Cytologic Findings on Experimental In Vivo Fallopian Tube Brush Specimens

Introduction: High grade tubo-ovarian serous adenocarcinoma is a significant cause of mortality. In recent years attention has turned to the fallopian tube as a primary source of precursor neoplastic lesions. The cytologic features of fallopian tube brushings from low risk patients have not been well described in modern cytology literature. Material and Methods: We describe the cytomorphologic features of tubal epithelium from prospectively collected experimental in vivo brushings of normal fallopian tubes from low risk patients. Both ThinPrep slides and cell blocks were prepared and reviewed in all specimens. P53 and Ki-67 immunostains were also performed when epithelial cells were detected in cell block specimens. Available follow-up histopathologic salpingectomy material was also reviewed. Results: A total of 15 specimens were obtained from 7 patients, ten collected by laparoscopy, 4 by hysteroscopy, and one after hysterectomy and bilateral salpingo-oophorectomy on an ex-vivo specimen. Cytologic findings were as followscellularity: moderate to high (nZ13), low (nZ2); background: granular debris (nZ10), clean (nZ4), blood (nZ1); architecture: mixture of clusters and single cells (nZ11), clusters (nZ3); nuclear overlap: moderate/marked (nZ14), mild/none (nZ1); nuclear pleomorphism moderate/marked (nZ13), mild/none (nZ2); nuclear membrane irregularities moderate/marked (nZ6), mild/none (nZ9); nucleoli: mixture of single and multiple (nZ15); diffusely present (nZ15); mitoses absent (nZ15). Cell blocks of epithelial cells detected in 4 samples found P53 and Ki-67 stains to be negative. Salpingectomy specimens available in 3 patients documented benign histopathologic findings. Conclusions: Nuclear overlap, nuclear pleomorphism, prominent single nucleoli, multiple nucleoli, and background granular debris are all common findings encountered when reviewing direct experimental in vivo fallopian tube brushings from benign specimens. With experience, these cytologic findings should not be misinterpreted as suspicious or malignant.

Endometrioid adenocarcinoma concurrent with a blue nevus of the endometrium and uterine cervix: A case report

A blue nevus is a benign melanocytic lesion that is composed of spindle-shaped pigmented melanocytes. Although the uterine cervix is believed to be the most common extracutaneous location of blue nevi, the occurrence of these lesions in the endometrial stroma has been reported, albeit rarely. The present study describes a case of endometrioid adenocarcinoma concurrent with a blue nevus of the endometrium and uterine cervix. A 58-year-old female presented with abnormal vaginal bleeding. A biopsy from the endometrium revealed an endometrioid adenocarcinoma and subsequently, a total hysterectomy was performed. Histopathological study revealed the proliferation of columnar cells that formed irregularly-shaped tubular and cribriform glands. The neoplastic columnar cells had large, round to oval nuclei containing a single small nucleolus. Focal squamous differentiation was noted. In the stroma of the non-neoplastic endometrium, single or small aggregates of short spindle-shaped cells containing melanin without atypia were observed. These melanocytes were also present in the endocervix. Therefore, the final diagnosis was of endometrioid adenocarcinoma concurrent with a blue nevus of the endometrium and cervix. This is the first documented case of a blue nevus of the endometrium and endocervix. The pathogenesis of blue nevi of the genital tract is not yet completely understood. Possible origins of these cells include Schwann cells or perineural cells of the peripheral nerve fiber or the abnormal migration of neural crest-derived cells.

Exposure to female pheromones stimulates a specific type of neuronal population in the male but not female magnocellular division of the medial preoptic nucleus (MPN mag) of the Syrian hamster

The magnocellular division of the medial preoptic area (MPN mag) integrates pheromonal and hormonal signals to play a critical role in the expression of male typical sex behavior. The MPN mag contains two morphologically distinct neuronal populations; the percentage of each type within the nucleus is sex specific. Males have more neurons with a single nucleolus whereas females have more with multiple nucleoli. To determine which neuronal subtype mediates pheromonal induction of copulation, tissue from male and female hamsters exposed to female pheromones was immunolabeled for the immediate early protein (EGR-1). Subsequently the tissue was counterstained and the number of ERG-1 neurons with one or two nuclei was determined. The results indicate that pheromones stimulate neurons with single nucleoli in males but fail to stimulate either neuronal subtype in females suggesting that synaptic input to the MPN mag is sexually differentiated.

Pancreatic Endocrine Tumour with Disseminated Pulmonary Thromboembolism in an Owl Monkey (Aotus nancymae)

Pulmonary thromboembolism associated with pancreatic endocrine neoplasia is extremely uncommon in man and animals. Post-mortem examination of an adult owl monkey (Aotus nancymae) revealed extensive pulmonary arterial thromboembolism and a well-demarcated mass attached to the pancreas. Microscopically, the mass consisted of areas of interstitial fibrosis with loss of acini and islets and replacement by nests and sheets of polygonal cells with amphophilic cytoplasm, an eccentric round nucleus with stippled chromatin and, in some cells, with a single prominent eccentric nucleolus. Clusters of these cells were noted within vessels and adjacent lymph nodes. The cells did not express S100 or insulin, but were labelled strongly with SP-1/chromogranin. Rare individual cells expressed glucagon and somatostatin. A few cells in pulmonary thrombi/emboli and the adjacent lymph node also expressed SP-1/chromogranin. Based on cell morphology, location and immunohistochemistry the tumour was classified as pancreatic endocrine (islet cell) carcinoma with metastasis to regional lymph nodes and lung.

Diagnostic cellular abnormalities in neoplastic and non‐neoplastic lesions of the epidermis: a morphological and statistical study

Distinguishing cellular abnormalities in reactive and malignant lesions is challenging. We compared the incidence and severity of cytological abnormalities in malignant/premalignant and benign epidermal lesions. One hundred fifty-two biopsies representing 69 malignant/premalignant squamous lesions and 83 benign conditions were studied. Cytological features, including nuclear hyperchromasia, nuclear overlap (crowding), irregular nuclei, high nuclear/cytoplasmic (N/C) ratio, conspicuous nucleoli, delicate inconspicuous nucleoli, clumped chromatin, pleomorphic parakeratosis, normal and abnormal mitotic figures and necrotic keratinocytes, were evaluated and graded. Statistical analysis was performed. Irregular nuclei, increased N/C ratio, conspicuous single prominent nucleoli, nuclear overlap (crowding), pleomorphic parakeratosis, nuclear hyperchromasia, necrotic keratinocytes, normal and abnormal mitotic figures and coarse chromatin were seen more frequently in malignant neoplasms (p < 0.05). Abnormal mitotic figures, although uncommon (20.3%), were only noted in the malignant/premalignant group. Certain cytological features were common among both malignant and benign lesions, suggesting that they are of little value. In the setting of an atypical cutaneous squamous proliferation, nuclear irregularity, increased N/C ratio, conspicuous nucleoli, crowding and hyperchromasia are the most useful indicators of malignancy. In contrast, mitotic figures, necrotic cells and coarse chromatin are less useful. The presence of abnormal mitotic figures is very helpful when present; however, their overall rarity limits their utility.

関節液の吸引細胞診にて診断しえた膝関節色素性絨毛結節性滑膜炎の 1 例

We report a case of pigmented villonodular synovitis (PVNS) of the knee diagnosed in a 69-year-old woman. The fine-needle aspiration smear of the joint fluid showed loose aggregates of mononuclear cells relatively rich in cytoplasm with bland nuclei containing a single nucleolus. Hemosiderin-containing cells and multinucleated cells were also observed. Histopathological study of the resected synovial tumor confirmed the diagnosis of PVNS.The characteristic cytological features of PVNS are as follows : i) aggregates of bland mononuclear cells, and ii) presence of hemosiderin-containing mononuclear cells and multinucleated cells. Recognition of these features can facilitate the cytodiagnosis of PVNS.

Acinar Cell Carcinoma of the Pancreas: Clinical and Cytomorphologic Characteristics

Acinar cell carcinoma is a rare malignant epithelial neoplasm with predominantly exocrine acinar differentiation and is seen primarily in older men (mean age, 62 years). The presenting symptoms are usually non-specific, and jaundice is often not present. Symptoms relating to the overproduction and release of lipase into the circulation are present in 10-15% of patients. Characteristic cytomorphologic features include a population of cells with minimal pleomorphism, eccentrically placed nuclei with a single prominent nucleoli and moderate hyperchromasia. The cytoplasm is finely granular, and the background may contain granular debris secondary to cytolysis. A significant proportion of the cases also have a minor neuroendocrine component or scattered neuroendocrine cells. Approximately 50% of patients have metastatic disease at presentation, often restricted to the regional lymph nodes and liver. The prognosis is poor, only slightly better than that of pancreatic ductal adenocarcinoma.

Fine Needle Aspiration Cytologic Diagnosis of Lactating Adenoma: Report of two Cases

Sir/Madam, Benign breast lesions are known to occur in pregnancy and in the post partum period, which are related to hormonal changes. Both de novo breast lesions and changes in the pre-existing benign conditions are well known. Lactating adenomas are one such group of tumours that can be diagnosed on cytology. We are reporting cases of two lactating female patients aged 20 and 23 years, who presented with gradually growing lumps in their left breasts, which had one and two years of growth respectively. Examination of the breasts of these patients revealed that the lumps were well defined, firm and mobile. The breast lumps were subjected to fine needle aspiration (FNA), yielded scanty thin milky-white fluidy material. The cytologic findings of both the patients showed cellular smears with cohesive monolayers of monomorphic cells, exhibiting round nuclei with prominent single nucleoli and abundant foamy vacuolated cytoplasm. Only a minimal number of bipolar naked nuclei were appreciable in a granular proteinaceous background, that showed numerous tiny lipoid vacuoles. Both the cases showed no nuclear/cellular atypia. On correlating the cytologic and clinical findings, a diagnosis of lactating adenoma was offered in these patients. The interesting fact that was found in these two cases was the presence of monomorphic population of cells and the absence of bipolar cells, which are the characteristic features of all benign breast lesions. Another factor to be considered was the cellularity of the smears, which usually favours diagnosis of a malignant lesion of the breast in cytologic aspirates. The clue to the diagnosis in these cases lay in the observation of the background foaminess of the cells and the scattered and few dispersed bipolar cells [Table/Fig-1,​,22,​,33 and ​and44]. [Table/Fig-1]: High Power View Showing Cohesive Monolayered Clusters of Benign Epithelial Cells Pap 400x [Table/Fig-2]: Low Power View of the 2 Dimensional Clusters of Benign Epithelail Cells Mgg 100x [Table/Fig-3]: Low Power View Showing the Magenta Matrix with Cells Having Vacuolated Cytoplasm Mgg 200x [Table/Fig-4]: High Power View Showing the Lipoid Background (Block Arrow) Mgg 400x Hence, I would like to conclude that an accurate diagnosis of lactating adenoma is possible on cytology, with a clinical correlation. FNA plays an important role in the appropriate management of patients with lactating adenoma; it thus helps in avoiding invasive procedures[1–4].

Morphologic and Gene Expression Criteria for Identifying Human Induced Pluripotent Stem Cells

Induced pluripotent stem (iPS) cells can be generated from somatic cells by the forced expression of four factors, Oct3/4, Sox2, Klf4, and c-Myc. While a great variety of colonies grow during induction, only a few of them develop into iPS cells. Researchers currently use visual observation to identify iPS cells and select colonies resembling embryonic stem (ES) cells, and there are no established objective criteria. Therefore, we exhaustively analyzed the morphology and gene expression of all the colonies generated from human fibroblasts after transfection with four retroviral vectors encoding individual factors (192 and 203 colonies in two experiments) and with a single polycistronic retroviral vector encoding all four factors (199 and 192 colonies in two experiments). Here we demonstrate that the morphologic features of emerged colonies can be categorized based on six parameters, and all generated colonies that could be passaged were classified into seven subtypes in colonies transfected with four retroviral vectors and six subtypes with a single polycistronic retroviral vector, both including iPS cell colonies. The essential qualifications for iPS cells were: cells with a single nucleolus; nucleus to nucleolus (N/Nls) ratio ∼2.19: cell size ∼43.5 µm2: a nucleus to cytoplasm (N/C) ratio ∼0.87: cell density in a colony ∼5900 cells/mm2: and number of cell layer single. Most importantly, gene expression analysis revealed for the first time that endogenous Sox2 and Cdx2 were expressed specifically in iPS cells, whereas Oct3/4 and Nanog, popularly used markers for identifying iPS cells, are expressed in colonies other than iPS cells, suggesting that Sox2 and Cdx2 are reliable markers for identifying iPS cells. Our findings indicate that morphologic parameters and the expression of endogenous Sox2 and Cdx2 can be used to accurately identify iPS cells.

Nucleoli from Two-Cell Embryos Support the Development of Enucleolated Germinal Vesicle Oocytes in the Pig1

Recent research has shown that nucleoli of oocytes at the germinal vesicle (GV) stage (GV nucleoli) are not necessary for oocyte maturation but are essential for early embryonic development. Nucleoli of 2-cell embryos (2-cell nucleoli) have morphology similar to that of nucleoli in oocytes at the GV stage. In this study, we examined the ability of 2-cell nucleoli to substitute for GV nucleoli in terms of supporting early embryonic development by nucleolus aspiration (enucleolation) and transfer into metaphase II (MII) oocytes or 2-cell embryos that were derived from enucleolated oocytes at the GV stage in the pig. When 2-cell embryos were centrifuged to move the lipid droplets to one side of the blastomere, multiple nucleoli in the nucleus fused into a single nucleolus. The nucleoli were then aspirated from the 2-cell embryos by micromanipulation. The injection of 2-cell nucleoli to GV enucleolated oocytes at the MII stage rescued the embryos from the early embryonic arrest, and the resulting oocytes developed to blastocysts. However, the injection of 2-cell and GV nucleoli to 2-cell embryos derived from GV enucleolated oocytes rarely restored the development to blastocysts. These results indicate that 2-cell nucleoli support early embryonic development as GV nucleoli and that the presence of nucleoli is essential for pig embryos before the 2-cell stage.

Relative Importance of Fine Needle Aspiration Features for Breast Cancer Diagnosis: A Study Using Information Gain Evaluation and Machine Learning

Introduction: Objectives: Use machine learning methods and information gain evaluation to estimate the relative importance of nine attributes (features) derived from Fine Needle Aspirates (FNA) of breast lesions for the correct classification of breast malignancy. The nine attributes evaluated are: Clump thickness, Cell Size Uniformity, Bare Nuclei, Cell Shape Uniformity, Marginal Adhesion, Single Epithelial (Epi) Cell Size, Bland Chromatin, Normal Nucleoli and Mitoses. Knowledge of the importance of these attributes will be helpful to pathologists even if they never use machine learning methods. Materials and Methods: A Breast Cancer dataset from the University of Wisconsin at Madison was used. It consists of 699 real FNA cases (458 benign,241 malignant,9 attributes each and correct diagnosis). A tissue biopsy was used as the gold standard. The WEKA software package from the University of Waikato for used for all machine learning (ML) experiments. Performance of the ML algorithms was evaluated using stratified tenfold cross validation. Three performance measures were used: correct classification rate, area under ROC curve (AUC) and the Kappa statistic. Sixty four supervised ML algorithms were evaluated. Next the 9 attributes of the data set were ranked based on an information gain evaluation. The five best performing algorithms were evaluated again after successively reducing the number of attributes form 9 to 1. The least relevant attributes were eliminated first. Results: The best performing ML algorithm was BaysNet with a correct classification rate of 97.1388%, AUC of 0.992 and Kappa of 0.9374. The control algorithm, ZeroR, had the worst performance with a classification rate of 66%, AUC of 0.496 and a Kappa of 0. More than half the tested algorithms had correct classification rates in excess of 95%.

Eight cases of malignant mixed müllerian tumor (carcinosarcoma) of the uterus: Findings in surepath™ cervical cytology

Malignant mixed Müllerian tumor (MMMT)/carcinosarcoma is a rare neoplasm of the female genital tract characterized by a mixture of epithelial and mesenchymal components. There are published reports of conventional cervical smear findings in uterine MMMT, but to the best of our knowledge the cytomorphology of MMMT in SurePath™ liquid-based cytology samples has not been described. We present a series of eight cases of uterine MMMT in SurePath™ cervical samples. The mean age of the women was 65.5 years (range, 60-82 years) and the most common presenting symptom was postmenopausal bleeding. Three out of the eight cases had both epithelial and sarcomatous elements in highly cellular cervical samples. In two cases, abnormal glandular cell clusters were closely associated with the mesenchymal component. The glandular component was usually represented by three-dimensional clusters of malignant glandular cells and a dispersed population of large, round to oval malignant epithelial cells with single prominent nucleoli. Necrosis or tumor diathesis was not seen in any cases. Six out of the eight cases were initially reported as adenocarcinoma, endometrial type, and two cases as normal. Five cases had an atrophic background and tiny atypical glandular clusters that could easily be overlooked. Although cervical sample is not the method of choice for primary uterine carcinosarcoma screening, the possibility of the same should be kept in mind, when reporting a cervical sample from a woman with postmenopausal vaginal bleeding.

An unusual case of Primary Effusion Lymphoma with aberrant T-cell phenotype in a HIV-negative, HBV-positive, cirrhotic patient, and review of the literature

Primary effusion lymphoma (PEL) is an unusual, human herpes virus-8 (HHV-8)–associated type of lymphoma, presenting as lymphomatous effusion in body cavities, without a detectable tumor mass. It primarily affects human immunodeficiency virus (HIV)-infected patients, but has also been described in other immunocompromised individuals. Although PEL is a B-cell lymphoma, the neoplastic cells are usually of the ‘null’ phenotype by immunocytochemistry. This report describes a case of PEL with T-cell phenotype in a HIV-negative patient and reviews all the relevant cases published until now. Our patient suffered from cirrhosis associated with Hepatitis B virus (HBV) infection and presented with a large ascitic effusion, in the absence of peripheral lymphadenopathy or solid mass within either the abdomen or the thorax. Paracentesis disclosed large lymphoma cells with anaplastic features consisting of moderate cytoplasm and single or occasionally multiple irregular nuclei with single or multiple prominent nucleoli. Immunocytochemically, these cells were negative for both CD3 and CD20, but showed a positive reaction for T-cell markers CD43 and CD45RO (VCHL-1). Furthermore, the neoplastic cells revealed strong positivity for EMA and CD30, but they lacked expression of ALK-1, TIA-1, and Perforin. The immune status for both HHV-8 and Epstein-Barr virus (EBV) was evaluated and showed positive immunostaining only for the former. The combination of the immunohistochemistry results with the existence of a clonal rearrangement in the immunoglobulin heavy chain gene (identified by PCR), were compatible with the diagnosis of PEL. The presence of T-cell markers was consistent with the diagnosis of PEL with an aberrant T-cell phenotype.

Nuclear RNase P of Trypanosoma brucei: A Single Protein in Place of the Multicomponent RNA-Protein Complex

SummaryRNase P is the endonuclease that removes 5′ extensions from tRNA precursors. In its best-known form, the enzyme is composed of a catalytic RNA and a protein moiety variable in number and mass. This ribonucleoprotein enzyme is widely considered ubiquitous and apparently reached its highest complexity in the eukaryal nucleus, where it is typically composed of at least ten subunits. Here, we show that in the protist Trypanosoma brucei, two proteins are the sole forms of RNase P. They localize to the nucleus and the mitochondrion, respectively, and have RNase P activity each on their own. The protein-RNase P is, moreover, capable of replacing nuclear RNase P in yeast cells. This shows that complex ribonucleoprotein structures and RNA catalysis are not necessarily required to support tRNA 5′ end formation in eukaryal cells.

Abstract A44: The Pi3K inhibitor GSK2126458 is highly toxic in ovarian dysgerminoma

Abstract Introduction: Mutations in PI3K/PTEN/Akt/mTOR have been implicated in the pathogenesis of numerous human carcinomas. Moreover, inhibitors of the phosphatidylinositol 3-kinase (PI3K) pathway are shown to be potent in several tumors, including ovarian adenocarcinomas. The effect of this class of agents on ovarian germ cell tumors, however, has not been previously studied. The aim of this work was to investigate cytotoxicity of the PI3K inhibitor GSK2126458 (a highly potent and selective compound) in ovarian dysgerminoma from a patient. Methods: The studied ovarian dysgerminoma was collected immediately following resection. Tumor sections (0.5×0.5×0.1 cm) were immersed in ice-cold RPMI medium gassed with 95% O2:5% CO2. The samples were then incubated at 37°C in RPMI (continuously gassed as above) with and without 50 nM GSK2126458 (Selleck Chemicals, cat. #S2658) for 150 min. At the end of the incubation period, specimens were processed for hematoxylin and eosin histologic stain. Results: Sections from untreated tissue revealed variable-sized tumor nests separated by fibrous stromal bands. Neoplastic cells were characterized by uniformly round central nuclei, clear-to-eosinophilic cytoplasm and prominent single nucleoli. Mitotic figures were abundant. Sections from treated tissue revealed a decrease in cellular density. Neoplastic cells demonstrated cytoplasmic disintegration, vacuolar degeneration and nuclear basophilia. Apoptotic bodies were numerous. Conclusions: GSK2126458 induced remarkable necrosis in the ovarian dysgerminoma. This preliminarily observation suggests sensitivity of this tumor to PI3K inhibition. The described in vitro methodology provides rapid assessment of the cytotoxicity of PI3K/PTEN/Akt/mTOR inhibitors.

Fibrolamellar hepatocellular carcinoma presenting with budd-chiari syndrome, right atrial thrombus, and pulmonary emboli

CT, computed tomography; FLHCC, fibrolamellar hepatocellular carcinoma; HCC, hepatocellular carcinoma; IVC, inferior vena cava. A 24-year-old man was evaluated for 3 months of abdominal pain and new onset of shortness of breath, increased abdominal girth, and leg swelling. On physical examination, he was tachypneic, had dullness in flanks, and bilateral lower extremity edema. Liver biochemical tests were notable for marginal derangement and a normal alpha-fetoprotein. An abdominal computed tomography (CT) scan showed an 11.5-cm hepatic mass with satellite lesions, ascites, tumor extension into the inferior vena cava (IVC) causing obstruction, and bland thrombus extending from the lower IVC to the femoral veins bilaterally (Fig. 1A). A chest CT showed bilateral pulmonary emboli and bilateral pleural effusions. A 2D echocardiogram showed a presumed right atrial tumor thrombus (Fig. 1B). A liver biopsy showed large polygonal tumor cells with eosinophilic granular cytoplasm (positive stain for Heppar-1) surrounded by abundant fibrous stroma in parallel lamellae, consistent with a well-differentiated fibrolamellar variant of hepatocellular carcinoma (Fig. 1C,D). Given his advanced disease, he was not a candidate for hepatectomy, systemic chemotherapy, vascular intervention, or liver transplantation and was discharged to hospice care with symptomatic palliation. (A) Abdominal CT shows the presence of a large hepatic mass invading the inferior vena cava with ascites and bland thrombus in the lower inferior vena cava extending to the iliac veins. (B) 2D echocardiogram showing the presence of a right atrial thrombus. (C) Liver biopsy showing large polygonal tumor cells with eosinophilic granular cytoplasm surrounded by abundant fibrous stroma in parallel lamellae. (D) Liver biopsy showing cytologic features that include large nuclei with a single prominent nucleolus and pale pink globules in the cytoplasm. Fibrolamellar hepatocellular carcinoma (FLHCC) differs from traditional hepatocellular carcinoma (HCC) in patient demographics (mean age 25 years, equal sex distribution), and absence of underlying cirrhosis or usual risk factors. 1 Our patient presented with rare manifestations that included secondary Budd-Chiari syndrome and significant clot burden causing lower extremity edema and ascites, bilateral pulmonary emboli causing shortness of breath, and a right atrial thrombus. 2 He had both tumor thrombus and bland thrombus, with the latter likely related to a hypercoagulable state. Alpha-fetoprotein levels are usually normal. On imaging a heterogeneous mass characterized by hypervascularity and a central scar in the background of normal liver parenchyma is appreciated. Metastatic tumor burden, hepatic adenoma, focal nodular hyperplasia, traditional HCC, and hemangioma are in the differential diagnosis. In contrast to the central scar of focal nodular hyperplasia (FNH), the central scar has low attenuation on T2 images. 3 On biopsy, the presence of large polygonal tumor cells with vesicular nuclei and large nucleoli, eosinophilic granular cytoplasm, and abundant fibrous stroma in thin parallel lamellae around tumor cells support the diagnosis. 1, 4 Immunohistochemistry shows staining for both hepatocellular (Heppar-1) and biliary differentiation (cytokeratin-7 and epithelial membrane antigen), with the latter contrasting FLHCC and HCC. 4 There are limited data on survival stratified by treatment modalities or by disease stage for FLHCC as compared to HCC arising in noncirrhosis livers. In a multicenter study of patients without metastatic disease undergoing resection, the 5-year survival of patients with FLHCC was similar to those patients with HCC without underlying cirrhosis but higher than patients with HCC and concomitant cirrhosis (62% versus 58% versus 27%). 5 Chemotherapeutic options are limited. Given its increased expression in FLHCC, selective targeting of epidermal growth factor receptor may play a role. Modest 5-year survival rates (35%-50% survival rates) after transplantation have been reported. 6

The changes in chromosome 6 spatial organization during chromatin polytenization in the Calliphora erythrocephala Mg. (Diptera: Calliphoridae) nurse cells

Localization of Calliphora erythrocephala chromosome 6 in a 3D nuclear space at different stages of nurse cell chromatin polytenization was analyzed by fluorescence in situ hybridization and 3D microscopy. The obtained results suggest a large-scale chromatin relocation in the C. erythrocephala nurse cell nuclei, which is accompanied by a change in the chromosome territory of chromosome 6 associated with the change in expression activity of the nucleus and formation of reticular chromatin structure. It was revealed that the relocation of chromosome 6 (nucleolus organizer chromosome) is accompanied by fragmentation of the single large nucleolus into micronucleoli, which are spread over the entire nuclear space being associated with their nucleolar organizer regions. Presumably, the chromosome 6 material during transition to a highly polytenized structure is redistributed in the nucleus so that the inactive pericentromeric regions are displaced to the nuclear periphery, while the chromosome regions carrying rDNA sequences loop out beyond the chromosome territory. Being dispersed over the entire nuclear space, rDNA sequences are likely to be amplified, thereby providing numerous small signals from the chromosome 6-specific DNA probe. Micronucleoli are formed around the actively transcribed nucleolar organizer regions.

Unusual Cause of a Massive Abdominal Cystic Tumor

Question: A 74-year-old Chinese woman presented to the gastroenterology unit with a 3-day history of abdominal distention. This was associated with intractable vomiting and an inability to tolerate food. There had been no bowel movement for the last 2 days. She had a history of total hysterectomy and bilateral salpingo-oopherectomy 19 years ago for ovarian granulosa theca cell tumor, but was otherwise healthy. Physical examination revealed a large, firm, immobile abdominal mass, with no hepatosplenomegaly. Computed tomography revealed a massive cystic lobulated and septated lesion measuring 21 cm in maximal diameter in the right peritoneal cavity (Figure A). Superiorly, it extended to the subhepatic space indenting the gallbladder. Laterally and anteriorly, it was inseparable from the anterior abdominal wall (Figure B). Blood investigations revealed anemia, with hemoglobin of 10.9 g/dL (normal, 11.7–14.7). Chest radiography was unremarkable. Tumor markers alpha-fetoprotein, CA19-9, CA12-5, CA15-3, and carcinoembryonic antigen levels were not elevated. The patient underwent resection of the tumor. Operative findings included a large, multiloculated, cystic tumor weighting 2.1 kg arising from the greater omentum, with no gross peritoneal disease. The tumor was removed, together with the greater omentum and the right-sided peritoneum. Figure C demonstrates hematoxylin and eosin-stained histologic section. What does the black arrow indicate? What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The patient had recurrence of adult granulosa cell ovarian tumor (GCT). Figure C demonstrates oval tumor cells with fine chromatin, single small nucleoli and an occasional longitudinal groove (black arrow), which is a characteristic feature of GCT. Figure D demonstrates uniform cytoplasmic staining with S-100. Of GCTs, 50% are positive for S-100 protein. Figure E shows patchy membranous staining for inhibin (white arrows) in tumor cells. The tumor cells were negative for AE 1/3, calretinin, CD117, CD34, and desmin. Our case illustrates the importance of considering late recurrence of GCT as a cause for an abdominal cystic mass. Accounting for 70% of ovarian sex cord-stromal tumors,1Schumer S. Cannistra S. Granulosa cell tumor of the ovary.J Clin Oncol. 2003; 21: 1180-1189Crossref PubMed Scopus (481) Google Scholar GCTs mainly presents in peri- or postmenopausal women with a median age at presentation of 50 years.2Fox H. Agrawal K. Langley F.A. A clinicopathologic study of 92 cases of granulosa cell tumor of the ovary with special reference to the factors influencing prognosis.Cancer. 1975; 35: 231-241Crossref PubMed Scopus (260) Google Scholar Infertility and treatments for infertility have been suggested as risk factors for the disease.3Unkila-Kallio L. Tiitinen A. Wahlstrom T. et al.Reproductive features in women developing ovarian granulosa cell tumour at a fertile age.Hum Reprod. 2000; 15: 589-593Crossref PubMed Scopus (53) Google Scholar GCTs are known to recur many years after the disease, with the greatest reported time from primary presentation to recurrence being 37 years.4East N. Alobaid A. Goffin F. et al.Granulosa cell tumour: a recurrence 40 years after initial diagnosis.J Obstet Gynaecol Can. 2005; 27: 363-364Abstract Full Text PDF PubMed Scopus (39) Google Scholar Prognostic factors predicting early recurrence include fewer Call-Exner bodies and higher mitotic rates on pathologic examination, as well as more advanced stage and larger tumor size. However, none of these is a significant predictor of late recurrence.5Auranen A. Sundström J. Ijäs J. et al.Prognostic factors of ovarian granulosa cell tumor: a study of 35 patients and review of the literature.Int J Gynecol Cancer. 2007; 17: 1011-1018Crossref PubMed Scopus (54) Google Scholar A typical radiologic appearance of GCT recurrence is discrete round or lobulated masses. Because the patient had undergone total hysterectomy and bilateral oophorectomy, nongynecologic differential diagnoses with similar radiologic appearances should also be considered, including cystic mesothelioma and peritoneal carcinoma. However, cystic mesothelioma tends to occur in a younger age group, and peritoneal carcinoma tends to be characterized by omental caking and calcification. Pseudomyxoma peritonei is also a consideration, but it tends to cause multiple complex masses with scalloping of the liver. Operative resection of GCT recurrence remains the treatment of choice, but several other treatment options have been tried, with responses for radiotherapy, chemotherapy, gonadotrophin-releasing hormone agonists, and aromatase inhibitors. Because the patient was well, she declined any adjuvant therapy, and has been recurrence free 1 year after the surgery.