Nanobacteria and Psammoma Bodies: Ultrastructural Observations in a Case of Pathological Placental Calcification

Nanobacteria are controversial infectious agents with nanometric size, the capacity to nucleate hydroxyapatite and grow in culture, and present in human diseases associated with calcification and psammoma bodies. The authors report a case of pathological placental calcifications associated with nanobacteria. Electron microscopy and electron energy loss spectroscopy imaging were used to recognize 160-nm-sized calcium-free bodies mainly presenting as extracellular fibrillary tangles and 500-nm-sized calcified bodies; they encrusted the syncito-trophoblast basal membrane and aggregated into miniaturized psammoma bodies. Nanobacteria may be composed of a prionoid protein with self-assembling and self-propagating abilities whose growth is associated with the formation of psammoma bodies.     

Psammoma bodies in endometriosis: Clinical,cytological, and physiopathological implications

This, to the best of our knowledge, is the first report of the cytological observation of psammoma bodies in an endometrioma. Psammoma bodies are laminated, calcified spherites, commonly associated with meningiomas, ovarian serous cystadenocarcinomas, and papillary carcinoma of the thyroid. Many other pathologic processes can produce dystrophic calcification in the form of psammoma bodies. The physiopathological theories of the origin of dystrophic calcification and psammoma bodies will be discussed. The most promising theory implicates matrix vesicles as the nidus for calcification. Diagn Cytopathol 1996;14:331–333. © 1996 Wiley-Liss, Inc.     

Psammoma bodies in cervicovaginal smears: incidence and significance

Psammoma bodies (PB) are seen in a wide variety of gynecologic conditions. However, only a few reports address the incidence or significance of PB in cervicovaginal smears (CVS). Twenty patients with PBs in CVS were identified over a 5-yr period during which time 82,840 CVS were screened. Nine cases were associated with malignancy: six uterine serous/clear cell carcinoma, two serous ovarian carcinoma, and one fallopian tube carcinoma. The remaining 11 were benign: one had an ovarian cystadenofibroma and one had PB associated with benign endometrium and endosalpingiosis. In the remaining nine cases, PB were not found on additional studies, although four gave a history of oral contraception and one each had chronic endometritis and IUD in place. The presence of atypical glandular cells diagnostic of carcinoma was the only single feature that predicted carcinoma (7/7). A combination of clinicopathologic features were helpful predictors of malignancy: postmenopausal bleeding (8/9 cases), age over 45 (9/9 cases), and abnormal clinical examination (5/9 cases). Conversely, benignancy was associated with postmenopausal bleeding in 1/11 cases, age over 45 in 3/11 cases and abnormal clinical examination in 2/11 cases. The incidence of PB in our series consecutively screened smears is 8 per 82,840 smears (0.009%). Unlike prior reports, we found that the presence of PB on CVS is not as ominous a finding as previously indicated, as only 12.5% (1/8) of patients with PB on their CVS harbor carcinoma. PB in a CVS in a young patient merits a thorough examination, but not surgical exploration in the absence of additional clinical findings or atypical cells on the CVS. Older patients (>45 yr) have a higher incidence of malignancy, even in the absence of clinical findings or atypical cells on CVS, and may warrant a surgical exploration.     

Psammoma bodies in fine needle aspiration cytology of the breast: A clinicopathological study of 30 cases

Psammoma bodies (PBs) in breast lesions are rare and little is known about the role of these structures in breast pathology. This study has looked in to the diagnostic significance of PBs in fine needle aspiration (FNAC) of breast lesions. Over a 5‐year period, FNACs of the breast were done in 4,563 subjects, of which 1,678 were diagnosed to be malignant. On review of all breast aspirates including non‐neoplastic lesions, 30 cases showed PBs to be associated with breast carcinoma (BC). Cytological features were correlated with clinical, radiological, histological, and immunohistochemical findings. All 30 aspirates and their corresponding histological sections showed varying number of PBs and nonpsammomatous bodies (NPBs). For comparison, 31 cases of age‐matched BC without PBs and NPBs in both aspirates and sections were studied. Statistical analysis using Chi‐square test was done to compare BC with and without PBs. BC with PBs was characterized by papillary pattern of malignant cells, mucin in the background, infiltration by macrophages, cellular degeneration, overexpression of estrogen receptor (ER), and progesterone receptor (PR) and moderate positivity (2+) for Her2/neu. Calcium deposition has long been implicated in the pathogenesis of many degenerative diseases; hence the formation of PBs may be relevant in breast oncology. The presence of PBs in FNAC of clinically suspected breast lesions which are cytologically negative for malignancy warrants further histological confirmation. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Observation of Psammoma Bodies in Cultured Meningiomas: Analysis of Three-Dimensional Structure Using Scanning and Transmission Electron Microscopy

In contrast to the inner structure, three-dimensional structure of psammona bodies in meningiomas is not well defined. This study examined three cultured meningiomas, in which surface observation of psammoma bodies might be easier than in the tumor tissues since influence of interposing connective tissue is minimized in tissue culture. Early culture revealed that psammoma bodies with frank calcification were suspended in the tissue culture medium, and so were they collected, centri-fuged, and then processed for electron microscopy. Ultrastructurally, psammoma bodies were mostly spherical in shape and composed of a core of dense calcification and surrounding collagen fiber bundles. Apart from psammoma bodies, round bodies with concentric lamination like a transversely cut onion were frequently noted by light microscopy. These bodies were composed mainly of tangles of collagen fibers emerged from surrounding tumor cell processes. The results suggest that psammoma bodies in meningiomas arise in part from meningothelial whorls due to collagen production by tumor cells followed by obliteration and disappearance of tumor cell processes, although some of the alternative pathways for psammoma body formation proposed by other investigators cannot be ruled out by this study.     

Pituitary Adenoma in Carney Complex: An Immunohistochemical,Ultrastructural, and Immunoelectron Microscopic Study

First described in 1985, Carney complex is a rare, heritable disorder featuring abnormal skin pigmentation, cardiac and cutaneous myxoma, melanotic schwannoma of psammomatous type, and endocrine abnormalities, including pituitary adenomas. Patients with the latter present with elevated growth hormone (GH) levels and acromegaly or gigantism. Prolactin (PRL) elevation may also be seen. The authors have investigated 2 resected pituitary adenomas from patients with Carney complex. One, a 19-year-old female acromegalic with elevated GH, IgF-1, and PRL levels, had a mammosomatotroph adenoma immunoreactive for GH and PRL. Ultrastructurally, GH and PRL were present in the same secretory granules. The second patient, a 27-year-old acromegalic, had a sparsely granulated GH cell adenoma that by immuno-electron microscopy revealed GH immunoreactivity only. The lack of morphologic similarity between the 2 adenomas indicates that pituitary tumors in patients with Carney complex may not exhibit the same phenotype.     

Psammoma bodies in cervical smear in association with keratinizing squamous cell carcinoma of cervix: A case report

The presence of psammoma bodies (PBs) in cervical smears is a rare finding. These structures have been identified in association with a wide range of benign and malignant conditions within the female genital tract. PBs in cervical smears have usually been associated with malignant serous epithelial ovarian tumors. However, many PBs associated with atypical squamous cells were detected in cervical smears of an 83‐year‐old woman with complaint of postmenopausal bleeding. Colposcopic examination revealed an ulceroinfiltrative growth in the cervix. Histological examination of the biopsy specimen from the growth revealed keratinizing squamous cell carcinoma with multiple and singly arranged PBs. This report suggests that cytologists should aware of the possibilities, on finding PBs associated with atypical cells in cervical specimens and report the cases accordingly. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Psammoma body and its precursors in papillary thyroid carcinoma: a study by fine-needle aspiration cytology

Psammoma bodies (PBs) form an important diagnostic criterion of papillary thyroid carcinoma (PTC), but their mechanism of formation is not clear. Following our observation in a case of PTC that laminated hyaline globules may be the precursor form of PBs, the present study was undertaken to find out their relation to PBs in PTC cases. Fifty-four cases of PTC and 14 follicular neoplasms, diagnosed by fine-needle aspiration (FNA) cytology, were studied by one of the investigators (DKD) to find out the PBs, irregular calcifications, hyaline globules, and other forms made of similar material. PBs along with irregular calcification were present in five PTC cases, PB alone was present in 1 case, and irregular calcification alone was present in 4 cases. Large hyaline globules (LHGs), small hyaline globules (SHGs), branching hyaline cylinders (BHCs), and irregular hyaline deposits (IHDs) were identified in 10, 14, 6, and 9 cases, respectively. One or more of these four forms were present altogether in 18 (33.3%) of PTC cases and none of the follicular neoplasms (P=0.0142). These forms were present in 80.0% of cases with PB/irregular calcifications as opposed to 22.7% in cases without them (P=0.0012). Our observations suggest that LHGs, SHGs, and BHCs are precursors of PBs and IHDs serve as a nidus for irregular calcification.     

Papillary thyroid carcinoma: evidence for intracytoplasmic formation of precursor substance for calcification and its release from well-preserved neoplastic cells

Psammoma bodies (PBs) are believed to represent a process of dystrophic calcification over nonviable and dying tissues. Light microscopic and ultrastructural observations suggest that PB formation follows the intracellular assembly of precursor substances and their calcification leading to death of tumor cells and their release. It may also be the result of local secretion of precursor substances like collagen by tumor cells into extracellular space and their calcification. In an earlier reported study, we demonstrated the extracellular localization of various precursor forms of PBs and of irregular calcification in fine-needle aspiration (FNA) smears of papillary thyroid carcinoma (PTC). In this report, we describe a PTC case with intracellular formation precursor substances for calcification and their release from the well-preserved neoplastic cells before undergoing calcification. Ultrasound-guided FNA smears from a small nodule in the left lobe of thyroid in a 40-year-old woman revealed a PTC with numerous intracytoplasmic targetoid bodies, which were magenta colored in MGG stain. On their release from the neoplastic cells, these targetoid precursor bodies were found to be forming pools of matrix material, some of which showed evidence of calcification. The cytologic findings were confirmed by histopathology of the tumor in the thyroidectomy specimen. For the first time, we demonstrate through cytomorpholgy the intracytoplasmic formation of targetoid bodies as precursor substances for calcification and their release from well-preserved cells in PTC. We suggest that the calcification in PTC may not necessarily be taking place over nonviable and dying cells.     

Pituitary Corticotroph Adenoma Containing Many Apoptotic Cells: A Histologic,Immunohistochemical, Ultrastructural and Molecular Study

Apoptosis regulates cell turnover in normal tissues and occurs during the neoplastic process. Owing to difficulties in recognizing apoptotic cells by histology alone, several complementary approaches have been introduced, which disclosed the presence of cells with typical nuclear and cytoplasmic changes characteristic of apoptosis. Electron microscopy remains the most conclusive method to reveal the structural changes. Identification of caspase cleaved keratin 18 intermediate filament rearrangements can contribute to the identification of early apoptotic changes. The authors present here an unusual case of a pituitary corticotroph adenoma removed surgically from a young woman with Cushing disease. The tumor contained many apoptotic cells identified by histology. In addition, the apoptotic events were investigated using various morphologic techniques, including electron microscopy, the in situ end-labeling technique, and immunohistochemistry to confirm the caspase-cleaved keratin 18 rearrangements.     

新生儿前、后囟穿刺的应用解剖

解剖观测了32具新生儿前囱和后囱。针对前、后囱穿刺术,进针处穿刺厚度、上矢状窦横断面面积和穿刺点的定位等,对有关项目进行了观测。     

Intercellular Communication Within the Rat Anterior Pituitary: XIV Electron Microscopic and Immunohistochemical Study on the Relationship Between the Agranular Cells and GnRH Neurons in the Dorsal Pars Tuberalis of the Pituitary Gland

Although numerous investigators in 1970s to 1980s have reported the distribution of LH‐RH nerve fibers in the median eminence, a few LH‐RH fibers have been shown to be present in the pars tuberalis. The significance of the finding remains to be elucidated, and there are few studies on the distribution of LH‐RH neurons in the pars tuberalis, especially in the dorsal pars tuberalis (DPT). Adult male Wistar‐Imamichi rats were separated into two groups: one for electron microscopy and the other for immunohistochemistry to observe LH‐RH and neurofilaments. Pituitary glands attached to the brain were fixed by perfusion, and the sections were prepared parallel to the sagittal plane. The typical glandular structure of the pars tuberalis was evident beneath the bottom floor of the third ventricle, and the thick glandular structure was present in the foremost region. Closer to the anterior lobe, the glandular structure changed to be a thin layer, and it was again observed at the posterior portion. Then the pituitary stalk was surrounded with the dorsal, lateral, and ventral pars tuberalis. LH‐RH and neurofilaments fibers were noted in the bottom floor, and some of them vertically descended to the gland. Adjacent to the glandular folliculostellate cells in the pars tuberalis, Herring bodies with numerous dense granules invading into the gland were present between the pituitary stalk and DPT. It was postulated that the “message” carried by LH‐RH might have been transmitted to the cells in the DPT to aid in the modulation of LH release. Anat Rec, 290:1388–1398, 2007. © 2007 Wiley‐Liss, Inc.     

Are Bunina Bodies of Endoplasmic Reticulum Origin? An Ultrastructural Study of Subthalamic Eosinophilic Inclusions in a Case of Atypical Motor Neuron Disease

We carried out an electron microscopic study of eosinophilic intracytoplasmic inclusions in the subthalamic neurons in a case of atypical motor neuron disease. These inclusions were identical in light microscopic morphology and staining characteristics to Bunina bodies. Ultra-structurally, most of the intracytoplasmic inclusions observed were divisible into two different types (I and II). Type I inclusions had features essentially identical to those of Bunina bodies demonstrated previously in the anterior horn cells in cases of motor neuron disease; they consisted of electron-dense, granular material without a particular limiting membrane and often contained a number of translucent areas with entrapped cell organelle like structures. Type II inclusions were very similar to structures known as multilaminated bodies; at their margin, they sometimes showed continuity with the cisternae of endoplasmic reticulum. The remainder of the inclusions were considered to be transitional forms between these two types, and some of them showed the respective features of both types I and II. These findings suggest that Bunina bodies are of endoplasmic reticulum origin. Acta Pathol Jpn 41: 889-894, 1991.     

Origin, Possible Function and Fate of “Follicular Cells” in the Anterior Lobe of the Human Pituitary: An Electron Microscopic Study

In human anterior pituitaries, follicular structures were found to develop by transformation of various types of glandular cells around foci of ruptured granulated cells undergoing destruction. In phase I, junctional complexes between granulated cells, as well as microvilli at the luminal surfaces of cell membranes, are formed. In phase II, degranulation and dedifferentiation of cytoplasm dominate the picture. Phase III follicular cells are practically devoid of secretory granules and other ultrastructural features characteristic of granulated cells. The participation of cell types in follicle formation does not appear to be limited. The follicular content in phase I-II is clearly recognizable as cellular debris from adenohypophysiocytes. These findings indicate that neither follicles nor junctional complexes are necessarily permanent structures of the anterior pituitary. It can be assumed that substances escaping from ruptured granulated cells may induce the formation of junctional complexes between adjacent cells.     

Vascularity in Nontumorous Human Pituitaries and Incidental Microadenomas: A Morphometric Study

The aim of the present study was to determine the microvascular angioarchitecture in the lateral and central portions of the anterior lobe as well as of the posterior lobe. The possible association between vascularity and age, sex, and pregnancy was also examined. In addition the vascular density of incidental microadenomas was investigated and compared to that of nontumorous gland. Blood vessels of 120 nontumorous pituitaries and 11 incidental microadenomas obtained at autopsy were examined by immunohistochemistry using the endothelial marker CD 34. Microvascular density (MVD) and microvessel surface density (MSD) were determined by morphometry using an automatic computer image analysis system. MVD and MSD were higher in the anterior than in the posterior lobe. Age, gender, or pregnancy did not affect the angioarchitecture of these sites. No statistical differences in MVD and MSD were observed between central and lateral areas of the anterior lobe, although MVD appeared to be lower in the lateral zones. A marked difference was noted in the vascularity of microadenomas compared to nontumorus tissue; both MVD and MSD were significantly lower in adenomatous tissue. Our studies suggest that the capillary network of the anterior and posterior lobes differ. They also indicate that the microvascular architecture is not significantly affected by age, gender, or pregnancy. Lack of significant angiogenesis in pituitary microadenomas may underlie the low growth rate and infrequency of metastasis of pituitary adenomas.     

Incidence,Pathology, and Recurrence of Pituitary Adenomas: Study of 647 Unselected Surgical Cases

The incidence of various types of unselected pituitary adenomas based on correlation of pathologic and clinical data was assessed. We investigated 647 cases of unselected pituitary adenomas, which were surgically removed between 1980 and 1993. All cases were examined by immunohistochemistry and electron microscopy. The mean age of patients was 44.0 years with 40.0 years for women (55.2%) and 49.1 years for men (44.8%). Age distribution indicated a remarkable sex difference: 52.4% of women and 26.8% of men were between 21 and 40 years at the time of surgery. Based on immunohistochemistry and electron microscopy, prolactin (PRL) cell adenomas represented 26.3% of tumors, growth hormone (GH) cell adenomas 12.5%, adrenocorticotrophic hormone (ACTH) cell adenomas 12.4%, oncocytomas 12.4%, and gonadotroph cell adenomas 9.4%. Seventy-three percent of the prolactinomas occurred in women and 73.8% of the oncocytomas were found in men. The incidence of pediatrics pituitary adenomas was 4.6%. All 647 cases were followed up; the mean follow-up period was 96.6 months. In 40 patients (6.2%), the adenoma recurred. Recurrence was common in functioning ACTH cell adenomas (8 cases: 9.5%) followed by silent adenomas (7 cases: 25.9%). Recurrence was noted after 2–96 months (average 28.7 months) following surgery. The shortest remission period was found in a patient with oncocytoma followed by a patient with prolactinoma.     

Placental Site Trophoblastic Tumor of the Uterus: An Ultrastructural and Immunohistochemical Study and Immunohistochemical Study

Ultrastructural and immunohistochemical studies in a case of placental site trophoblastic tumor (PSTT) of the uterus were carried out in order to define the nature of the abnormal tissue. By electron microscopy, the large cells, whether mononuclear or syncytial, showed numerous ribosomes, prominent Golgi elements, and abundant rough endoplasmic reticulum (RER) filled with granular material. Pseudopods and microvilli were found on the cell surfaces. By immunofluorescence, the well-developed filamentous cyto-skeleton proved to be actin-rich. (3-HCG (human chorionic gonadotropin) and SP, (0,-specific pregnancy glycoprotein) were detected in only a few tumor cells, whereas most of them stained for HPL (human placental lactogen). The present results show the secretory nature of most of the tumor cells, which resemble the intermediate trophoblast of the placental bed. Together with previous studies, they suggest that a varying spectrum of syncytiotrophoblastic differentiation exists in PSTT. Decidual, myometrial, or histiocytic cells do not seem involved in the histogenesis of the tumor tissue.     

Diffuse Mallory Bodies in the Liver, Diffuse Lewy Bodies in the Brain and Diffuse Fat Replacement (Lipomatous Pseudohypertrophy) of the Pancreas in a Patient with Juvenile Parkinson's Disease

A 38-year-old male patient with the juvenile variant of Parkinson's disease, in whom onset had occurred at the age of 24 yr, was autopsied. There were no clear symptoms of pancreatic or hepatic insufficiency during the entire clinical course. The only notable features were a slightly delayed decrease of the blood glucose level in an oral glucose tolerance test, slightly elevated levels of serum alkaline phosphatase and serum lactate dehydrogenase, and episodic loose stools. Autopsy revealed uniform enlargement of the pancreas due to massive fat replacement (lipomatous pseudohypertrophy): the exocrine glandular elements showed marked atrophy and loss, while the islets of Langerhans were preserved. The liver exhibited a histology closely mimicking alcoholic hepatitis associated with the diffuse presence of Mallory bodies (MBs), possibly indicative of a disturbance of protein metabolism. The nervous system showed the diffuse presence of Lewy bodies (LBs) in the cerebrum in addition to the ordinary lesions of Parkinson's disease. Although the etiopathogenesis of none of these three lesions has been well elucidated, common epitopes of MBs and LBs have recently been demonskated. Therefore, the present case study suggests that a specific underlying toxic agent may cause diffuse LBs in the brain on the one hand, and diffuse MBs in the liver and lipomatous pseudohypertrophy of the pancreas on the other. Acta Pathol Jpn 42: 826–831, 1992.     

Immunohistochemical demonstration of cytokeratins in endocrine cells of the human pituitary gland and in pituitary,adenomas

Summary Ten non-neoplastic pituitary glands and 22 pituitary adenomas producing different hormones were studied by immunofluorescence microscopy as well as peroxidase-antiperoxidase and biotin-avidin techniques on frozen sections and formalin-fixed, paraffin-embedded material using antibodies to cytokeratin, vimentin, GFAP, neurofilament protein and different pituitary hormones. The endocrine cells in non-neoplastic pituitary glands as well as in most pituitary adenomas were cytokeratin-positive. The cytoplasmic cytokeratin distribution patterns of non-neoplastic and tumor cells were similar and typical of the type of hormone produced: GH-producing normal cells showed a paranuclear condensation of cytokeratin-reactive intermediate filaments; this accumulation was even further accentuated in GH-producing adenomas resulting in fibrous bodies (Kovacs and Horvath 1978) decorated by cytokeratin antibodies. Prolactin-producing cells showed a less intense cytoplasmic cytokeratin-specific staining with focal paranuclear accentuation in non-neoplastic as well as in neoplastic glands. ACTH-producing cells in normal pituitary glands as well as in adenomas exhibited a strong and more uniform cytoplasmic cytokeratin staining. The cytokeratin reactivity in glycoprotein hormone-producing cells of non-neoplastic tissue and adenomas was weak. Vimentin and GFAP reactivity was confined to agranular folliculo-stellate cells. The specific and different distribution patterns of cytokeratins in pituitary cells can, therefore, provide an (indirect) indication to the production of a specific hormone if immunocytochemistry fails to demonstrate hormone production.Dedicated to Prof. Dr. J.H. Holzner on the occasion of his birthday     

Anatomy in the Third Reich: An outline,part 2. Bodies for anatomy and related medical disciplines

All anatomical departments of German universities used bodies of the executed and other victims of the National Socialist (NS) regime for their work. Many of these victims had been executed in prisons and were members of the German political opposition; others had perished in camps for prisoners of war or forced laborers and concentration camps, and were of various European and other descent. Anatomists generally welcomed the increased influx of “fresh material” for purposes of research and education of the growing numbers of medical students. No anatomist is known to have refused work with the bodies of NS victims. Other medical disciplines also made use of these bodies, among them were racial hygienists and neuropathologists. In the late 19th and early 20th century, the fields of anatomy, physical anthropology, and racial hygiene (eugenics) were closely related in their subject matter. Anatomists were involved in the biological foundation of racial hygiene, most prominently among them Eugen Fischer. The discipline was established as part of the medical curriculum after 1920. Racial hygiene became the scientific justification for NS policies that led to racial discrimination, involuntary sterilization and ultimately mass murder. Anatomists taught racial hygiene throughout the Third Reich and did research in this area. Some were actively involved in NS policies through propaganda and evaluations for the so‐called Genetic Health Courts, whereas others became victims of their own science in that they were dismissed for racial reasons. 22:894–905, 2009. © 2009 Wiley‐Liss, Inc.