Lower transfer factor of the lung for carbon monoxide in women with a patent foramen ovale.

NEW FINDINGS: What is the central question of this study? Do individuals with a patent foramen ovale (PFO+ ) have a lower lung transfer factor for carbon monoxide than those without (PFO- )? What is the main finding and its importance? We found a lower rate constant for carbon monoxide uptake in PFO+ compared with PFO- women, which was physiologically relevant (≥0.5 z-score difference), but not for PFO+ versus PFO- men. This suggests that factors independent of the PFO are responsible for our findings, possibly inherent structural differences in the lung. ABSTRACT: The transfer factor of the lung for carbon monoxide (TLCO ) measure assumes that all cardiac output flows through the pulmonary circuit. However, right-to-left blood flow through a shunt can result in a lower transfer factor than predicted. A patent foramen ovale (PFO) is a potential source of right-to-left shunt that is present in ∼35% of the population, but the effect of PFO on TLCO is unknown. We sought to determine the effect of PFO on the TLCO . We conducted a retrospective analysis of TLCO data from 239 (101 women) participants. Anthropometrics and lung function, including spirometry, plethysmography and TLCO , were compiled from our previously published work. Women, but not men, with a PFO had a significantly lower TLCO and rate constant for carbon monoxide uptake (KCO ) (percentage of predicted and z-score) than women without a PFO. Women and men with a PFO had normal alveolar volumes that did not differ from those without a PFO. Correcting the data for haemoglobin in a subset of subjects did not change the results (n = 58; 25 women). The lower KCO in women with versus without a PFO was physiologically relevant (≥0.5 z-score difference). There was no effect of PFO in men. This suggests that factors independent of the PFO are responsible for our findings, possibly inherent structural differences in the lung.

Intrapulmonary arteriovenous anastomoses in humans with chronic obstructive pulmonary disease: implications for cryptogenic stroke?

What is the central question of this study? Do individuals with chronic obstructive pulmonary disease have blood flow through intrapulmonary arteriovenous anastomoses at rest or during exercise? What is the main finding and its importance? Individuals with chronic obstructive pulmonary disease have a greater prevalence of blood flow through intrapulmonary arteriovenous anastomoses at rest than age-matched control subjects. Given that the intrapulmonary arteriovenous anastomoses are large enough to permit venous emboli to pass into the arterial circulation, patients with chronic obstructive pulmonary disease and an elevated risk of thrombus formation may be at risk of intrapulmonary arteriovenous anastomosis-facilitated embolic injury (e.g. stroke or transient ischaemic attack). The pulmonary capillaries prevent stroke by filtering venous emboli from the circulation. Intrapulmonary arteriovenous anastomoses are large-diameter (≥50 µm) vascular connections in the lung that may compromise the integrity of the pulmonary capillary filter and have recently been linked to cryptogenic stroke and transient ischaemic attack. Prothrombotic populations, such as individuals with chronic obstructive pulmonary disease (COPD), may be at increased risk of stroke and transient ischaemic attack facilitated by intrapulmonary arteriovenous anastomoses, but the prevalence and degree of blood flow through intrapulmonary arteriovenous anastomoses in this population has not been fully examined and compared with age-matched healthy control subjects. We used saline contrast echocardiography to assess blood flow through intrapulmonary arteriovenous anastomoses at rest (n = 29 COPD and 19 control subjects) and during exercise (n = 10 COPD and 10 control subjects) in subjects with COPD and age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses was detected in 23% of subjects with COPD at rest and was significantly higher compared with age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses at rest was reduced or eliminated in subjects with COPD after breathing hyperoxic gas. Sixty per cent of subjects with COPD who did not have blood flow through the intrapulmonary arteriovenous anastomoses at rest had blood flow through them during exercise. The combination of blood flow through intrapulmonary arteriovenous anastomoses and potential for thrombus formation in individuals with COPD may permit venous emboli to pass into the arterial circulation and cause stroke and transient ischaemic attack. Breathing supplemental oxygen may reduce this risk in COPD. The link between blood flow through intrapulmonary arteriovenous anastomoses, stroke and transient ischaemic attack is worthy of future investigation in COPD and other populations.

Orchid phylogenomics and multiple drivers of their extraordinary diversification.

Orchids are the most diverse family of angiosperms, with over 25 000 species,more than mammals, birds and reptiles combined. Tests of hypotheses to account for such diversity have been stymied by the lack of a fully resolved broad-scale phylogeny. Here,we provide such a phylogeny, based on 75 chloroplast genes for 39 species representing all orchid subfamilies and 16 of 17 tribes, time-calibrated against 17 angiosperm fossils. Asupermatrix analysis places an additional 144 species based on three plastid genes. Orchids appear to have arisen roughly 112 million years ago (Mya); the subfamilies Orchidoideae and Epidendroideae diverged from each other at the end of the Cretaceous; and the eight tribes and three previously unplaced subtribes of the upper epidendroids diverged rapidly from each other between 37.9 and 30.8 Mya. Orchids appear to have undergone one significant acceleration of net species diversification in the orchidoids, and two accelerations and one deceleration in the upper epidendroids. Consistent with theory, such accelerations were correlated with the evolution of pollinia, the epiphytic habit, CAM photosynthesis, tropical distribution (especially in extensive cordilleras),and pollination via Lepidoptera or euglossine bees. Deceit pollination appears to have elevated the number of orchid species by one-half but not via acceleration of the rate of net diversification. The highest rate of net species diversification within the orchids (0.382 sp sp(-1) My(-1)) is 6.8 times that at the Asparagales crown.

Convergent evolution of floral signals underlies the success of Neotropical orchids.

The great majority of plant species in the tropics require animals to achieve pollination, but the exact role of floral signals in attraction of animal pollinators is often debated. Many plants provide a floral reward to attract a guild of pollinators, and it has been proposed that floral signals of non-rewarding species may converge on those of rewarding species to exploit the relationship of the latter with their pollinators. In the orchid family (Orchidaceae), pollination is almost universally animal-mediated, but a third of species provide no floral reward, which suggests that deceptive pollination mechanisms are prevalent. Here, we examine floral colour and shape convergence in Neotropical plant communities, focusing on certain food-deceptive Oncidiinae orchids (e.g. Trichocentrum ascendens and Oncidium nebulosum) and rewarding species of Malpighiaceae. We show that the species from these two distantly related families are often more similar in floral colour and shape than expected by chance and propose that a system of multifarious floral mimicry--a form of Batesian mimicry that involves multiple models and is more complex than a simple one model-one mimic system--operates in these orchids. The same mimetic pollination system has evolved at least 14 times within the species-rich Oncidiinae throughout the Neotropics. These results help explain the extraordinary diversification of Neotropical orchids and highlight the complexity of plant-animal interactions.

Evaluation of a clinically intuitive quality assurance method.

There is a pressing need for clinically intuitive quality assurance methods that report metrics of relevance to the likely impact on tumor control of normal tissue injury. This paper presents a preliminary investigation into the accuracy of a novel "transform method" which enables a clinically relevant analysis through dose-volume-histograms (DVHs) and dose overlays on the patient's CT data. The transform method was tested by inducing a series of known mechanical and delivery errors onto simulated 3D dosimetry measurements of six different head-and-neck IMRT treatment plans. Accuracy was then examined through the comparison of the transformed patient dose distributions and the known actual patient dose distributions through dose-volume histograms and normalized dose difference analysis. Through these metrics, the transform method was found to be highly accurate in predicting measured patient dose distributions for these types of errors.

Description of a rule-based system for the i2b2 challenge in natural language processing for clinical data.

The Obesity Challenge, sponsored by Informatics for Integrating Biology and the Bedside (i2b2), a National Center for Biomedical Computing, asked participants to build software systems that could "read" a patient's clinical discharge summary and replicate the judgments of physicians in evaluating presence or absence of obesity and 15 comorbidities. The authors describe their methodology and discuss the results of applying Lockheed Martin's rule-based natural language processing (NLP) capability, ClinREAD. We tailored ClinREAD with medical domain expertise to create assigned default judgments based on the most probable results as defined in the ground truth. It then used rules to collect evidence similar to the evidence that the human judges likely relied upon, and applied a logic module to weigh the strength of all evidence collected to arrive at final judgments. The Challenge results suggest that rule-based systems guided by human medical expertise are capable of solving complex problems in machine processing of medical text.

Molecular phylogenetics and the evolution of fruit and leaf morphology of Dichaea (Orchidaceae: Zygopetalinae).

BACKGROUND AND AIMS: The orchid genus Dichaea, with over 100 species found throughout the neotropics, is easily recognized by distichous leaves on long stems without pseudobulbs and flowers with infrastigmatic ligules. The genus has previously been divided into four sections based primarily on presence of ovary bristles and a foliar abscission layer. The aim of this work is to use DNA sequence data to estimate phylogenetic relationships within Dichaea and map the distribution of major morphological characters that have been used to delimit subgenera/sections. METHODS: Sequence data for the nuclear ribosomal internal transcribed spacers and plastid matK, trnL intron, trnL-F spacer and ycf1 for 67 ingroup and seven outgroup operational taxonomic units were used to estimate phylogenetic relationships within Dichaea. Taxa from each of the four sections were sampled, with the greatest representation from section Dichaea, the most diverse and taxonomically puzzling group. KEY RESULTS: Molecular data and morphology support monophyly of Dichaea. Results indicate that section Dichaeopsis is polyphyletic and based on symplesiomorphies, including deciduous leaves and smooth ovaries that are widespread in Zygopetalinae. There are at least three well-supported clades within section Dichaeopsis. Section Pseudodichaea is monophyletic and defined by setose ovaries and leaves with an abscission layer. Sections Dichaea and Dichaeastrum are monophyletic and defined by pendent habit and persistent leaves. Section Dichaeastrum, distinguished from section Dichaea primarily by a glabrous ovary, is potentially polyphyletic. CONCLUSIONS: The leaf abscission layer was lost once, occurring only in the derived sections Dichaea and Dichaeastrum. The setose fruit is a more homoplasious character with several losses and gains within the genus. We propose an informal division of the genus based upon five well-supported clades.

Floral convergence in Oncidiinae (Cymbidieae; Orchidaceae): an expanded concept of Gomesa and a new genus Nohawilliamsia.

BACKGROUND: Floral morphology, particularly the angle of lip attachment to the column, has historically been the fundamental character used in establishing generic limits in subtribe Oncidiinae (Orchidaceae), but it has also been long recognized that reliance on this character alone has produced a highly artificial set of genera. In essence, lip/column relationships reflect syndromes associated with pollinator preferences; most genera of Oncidiinae as previously defined have consisted of a single floral type. Here, the degree to which this has influenced generic delimitation in Brazilian members of the largest genus of Oncidiinae, Oncidium, which previous molecular (DNA) studies have demonstrated to be polyphyletic, is evaluated. METHODS: Phylogenetic analyses of the following multiple DNA regions were used: the plastid psbA-trnH intergenic spacer, matK exon and two regions of ycf1 exon and nuclear ribosomal DNA, comprised of the two internal transcribed spacers, ITS1 and ITS2, and the 5.8S gene. Results from all regions analysed separately indicated highly similar relationships, so a combined matrix was analysed. KEY RESULTS: Nearly all species groups of Brazilian Oncidium are only distantly related to the type species of the genus, O. altissimum, from the Caribbean. There are two exceptions to this geographical rule: O. baueri is related to the type group and O. orthostates, an isolated species that lacks the defining tabula infrastigmata of Oncidium, is not exclusively related to any previously described genus in the subtribe. Several well-supported subclades can be observed in these results, but they do not correspond well to sections of Oncidium as previously circumscribed or to segregate genera as defined by several recent authors. In spite of their floral differences, these groups of Oncidium, formerly treated as O. sections Barbata, Concoloria pro parte, Crispa, Ranifera, Rhinocerotes, Rostrata (only O. venustum), Synsepala, Verrucituberculata pro parte and Waluewa, form a well-supported clade with Gomesa (including Rodrigueziella and Rodrigueziopsis) embedded in it. Two often recognized segregate genera, Baptistonia and Ornithophora, and the recently described Carriella are also embedded within the Brazilian clade. The level of variation within major subclades of the Gomesa clade is low and similar to that observed within other genera of Oncidiinae. CONCLUSIONS: Convergence on a stereotypical syndrome of floral traits associated with pollination by oil-collecting bees has resulted in these characters not being reliable for producing monophyletic taxa, and the genus Oncidium, defined by these characters, is grossly polyphyletic. Vegetative and a few floral/inflorescence characters link these taxa with a mainly Brazilian distribution, and they were all transferred to Gomesa on this basis rather than separated from Gomesa based on their floral differences, which we hypothesize to be simple shifts in pollination strategies. Other authors have described a large number of new genera for these former members of Oncidium, but most of these are not supported by the results presented here (i.e. they are not monophyletic). A new genus, Nohawilliamsia, is described for O. orthostates because it does not fit in any currently recognized genus and is only distantly related to any other member of Oncidiinae.

Molecular phylogeny of the neotropical genus Christensonella (Orchidaceae, Maxillariinae): species delimitation and insights into chromosome evolution.

BACKGROUND AND AIMS: Species' boundaries applied within Christensonella have varied due to the continuous pattern of variation and mosaic distribution of diagnostic characters. The main goals of this study were to revise the species' delimitation and propose a more stable classification for this genus. In order to achieve these aims phylogenetic relationships were inferred using DNA sequence data and cytological diversity within Christensonella was examined based on chromosome counts and heterochromatin patterns. The results presented describe sets of diagnostic morphological characters that can be used for species' identification. METHODS: Phylogenetic studies were based on sequence data of nuclear and plastid regions, analysed using maximum parsimony and maximum likelihood criteria. Cytogenetic observations of mitotic cells were conducted using CMA and DAPI fluorochromes. KEY RESULTS: Six of 21 currently accepted species were recovered. The results also support recognition of the 'C. pumila' clade as a single species. Molecular phylogenetic relationships within the 'C. acicularis-C. madida' and 'C. ferdinandiana-C. neowiedii' species' complexes were not resolved and require further study. Deeper relationships were incongruent between plastid and nuclear trees, but with no strong bootstrap support for either, except for the position of C. vernicosa. Cytogenetic data indicated chromosome numbers of 2n = 36, 38 and 76, and with substantial variation in the presence and location of CMA/DAPI heterochromatin bands. CONCLUSIONS: The recognition of ten species of Christensonella is proposed according to the molecular and cytogenetic patterns observed. In addition, diagnostic morphological characters are presented for each recognized species. Banding patterns and chromosome counts suggest the occurrence of centric fusion/fission events, especially for C. ferdinandiana. The results suggest that 2n = 36 karyotypes evolved from 2n = 38 through descendent dysploidy. Patterns of heterochromatin distribution and other karyotypic data proved to be a valuable source of information to understand evolutionary patterns within Maxillariinae orchids.

Survival and clinical outcome of SB Charite III disc replacement for back pain.

Between January 1990 and December 2000 we carried out 226 SB Charité III disc replacements for lumbar disc degeneration in 160 patients. They were reviewed at a mean follow-up of 79 months (31 to 161) to determine the clinical and radiological outcome. The clinical results were collected by an independent observer, who was not involved in patient selection, treatment or follow-up, using a combination of outcome measures, including the Oswestry Disability Index. Pain was recorded using a visual analogue score, and the most recent radiographs were reviewed. Survival of the device was analysed by the Kaplan-Meier method and showed a cumulative survival of 35% at 156 months when radiological failure was taken as the endpoint. The mean improvement in the Oswestry disability index scores after disc replacement was 14% (6% to 21%) and the mean improvement in the pain score was 1.6 (0.46 to 2.73), both falling below the clinically significant threshold. Removal of the implant was required in 12 patients, four because of implant failure. These poor results indicate that further use of this implant is not justified.

Treatment Planning and Delivery of Whole Brain Irradiation with Hippocampal Avoidance in Rats.

BACKGROUND: Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. METHODS: The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5 cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13 mA filtered through 0.3 mm of copper using a 40x40 mm square collimator and the lead blocks. A single fraction of 4 Gy was delivered (2 Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4 Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). RESULTS: The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52 Gy compared to 3.93 Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). CONCLUSION: Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique.

Seven New Complete Plastome Sequences Reveal Rampant Independent Loss of the ndh Gene Family across Orchids and Associated Instability of the Inverted Repeat/Small Single-Copy Region Boundaries.

Earlier research has revealed that the ndh loci have been pseudogenized, truncated, or deleted from most orchid plastomes sequenced to date, including in all available plastomes of the two most species-rich subfamilies, Orchidoideae and Epidendroideae. This study sought to resolve deeper-level phylogenetic relationships among major orchid groups and to refine the history of gene loss in the ndh loci across orchids. The complete plastomes of seven orchids, Oncidium sphacelatum (Epidendroideae), Masdevallia coccinea (Epidendroideae), Sobralia callosa (Epidendroideae), Sobralia aff. bouchei (Epidendroideae), Elleanthus sodiroi (Epidendroideae), Paphiopedilum armeniacum (Cypripedioideae), and Phragmipedium longifolium (Cypripedioideae) were sequenced and analyzed in conjunction with all other available orchid and monocot plastomes. Most ndh loci were found to be pseudogenized or lost in Oncidium, Paphiopedilum and Phragmipedium, but surprisingly, all ndh loci were found to retain full, intact reading frames in Sobralia, Elleanthus and Masdevallia. Character mapping suggests that the ndh genes were present in the common ancestor of orchids but have experienced independent, significant losses at least eight times across four subfamilies. In addition, ndhF gene loss was correlated with shifts in the position of the junction of the inverted repeat (IR) and small single-copy (SSC) regions. The Orchidaceae have unprecedented levels of homoplasy in ndh gene presence/absence, which may be correlated in part with the unusual life history of orchids. These results also suggest that ndhF plays a role in IR/SSC junction stability.

Spinal fluid cells and protein in amyotrophic lateral sclerosis.

The cerebrospinal fluid total protein in 385 cases of sporadic amyotrophic lateral sclerosis showed no relationship to survival, but it was related to survival time in 34 cases of familial amyotrophic lateral sclerosis. Infrequent and mild pleocytosis, and oligoclonal bands seemed to have no clinical significance in well established cases of amyotrophic lateral sclerosis.

Microglandular adenosis of the breast. A clinicopathologic study of 11 cases with ultrastructural observations.

The clinical and pathologic features of 11 examples of microglandular adenosis of the breast are presented. Microglandular adenosis is a rare, benign lesion that is easily confused with carcinoma. It is characterized by a concentrated proliferation of round glands with open lumens in a densely homogeneous stroma that clearly delineates microglandular adenosis from the adjacent uninvolved breast. The glands are lined by a single layer of cells with distinctly vacuolated or granular cytoplasm. Ultrastructurally, the single layer of epithelial cells lacks cytoplasmic protrusions and is surrounded by a thick multilayered basement membrane. Light- and electron-microscopic features that help distinguish microglandular adenosis from well-differentiated (tubular) carcinoma and sclerosing adenosis, entities with which it is easily confused, are discussed.

Cystadenofibromas of the ovary with epithelial atypia.

Epithelial atypia is rarely encountered in ovarian cystadenofibromas. Ten examples are reported with cytological features identical to serous tumors with low malignant potential. In two neoplasms the epithelium resembled an atypical endometrial hyperplasia, and one of these had squamous metaplasia. These two neoplasms probably qualify as endometrioid tumors of low malignant potential. None of the 10 patients had recurrence following excision of their neoplasm, and no similar patients have been encountered with neoplasms in more advanced stages. Even though aggressive behavior has not yet been established, the histologic features suggest a low degree of malignant potential and long-term follow-up of patients is warranted. Cystadenofibromas iwth epithelial atypia probably have less malignant potential than serous tumors of low malignant potential possessing the same epithelial characteristics because cystadenofibromas with atypia have less epithelial surface area and the epithelium is enveloped by connective tissue more than it is in serous tumors of low malignant potential.

Granulosa tumors of the ovary in children: a clinical and pathologic study of 32 cases.

Granulosa tumors in children differ histologically from those occurring in adults. Of 32 neoplasms occurring in girls 16 years of age or younger, 26 were juvenile granulosa tumors and three were cystic granulosa tumors; only three neoplasms resembled typical adult granulosa tumors. The juvenile granulosa tumor differs from the typical adult form in that it is composed of larger cells and has luteinization of its cellular components. Two-thirds of the patients had endocrine abnormalities. Fifteen of 20 premenarcheal patients had isosexual precocious pseudopuberty. Of the 12 postmenarcheal girls, seven had menstrual abnormalities and two of the seven were virilized. All 32 patients had Stage Ia tumors. The clinical outcome was generally favorable since only two of 26 patients with follow-up developed a recurrence. Unilateral salpingo-oophorectomy is appropriate treatment for girls with Stage Ia granulosa tumors; 23 of 25 patients treated by unilateral salpingo-oophorectomy were well without recurrence at last contact.

Sertoli-Leydig tumors of the ovary. A clinicopathologic study of 64 intermediate and poorly differentiated neoplasms.

The clinical and pathologic features of 64 Sertoli-Leydig tumors of the ovary with intermediate and poor differentiation were studied. The neoplasms occurred mainly in young women. Fifty-four percent of the patients presented with clinical evidence of a hormonally active tumor, and 38% were virilized. The remaining 46% had nonspecific symptoms. Sixty-two patients had tumors confined to one ovary at operation (Stage Ia), while only two patients presented with pelvic metastases (Stage III). The prognosis was generally favorable; the 5- and 10-year actuarial survival rates were 92%. Unilateral salpingo-oophorectomy was effective treatment for Stage Ia Sertoli-Leydig tumors in young women. Microscopically, 44 of the neoplasms were of intermediate differentiation and 20 were poorly differentiated. Heterologous elements (mucinous epithelium, striated muscle, cartilage) were present in 16 neoplasms. The pathologic features that correspond with development of metastases were poor differentiation, the presence of heterologous mesenchymal elements, frequent mitotic figures in stromal cells, and rupture of the neoplasm.

Endometrioid proliferative and low malignant potential tumors of the ovary. A clinicopathologic study of 46 cases.

We evaluated 41 endometroid neoplasms with features intermediate between a benign endometrioid tumor and endometrioid carcinoma. Although these tumors showed various degrees of epithelial proliferation, they lacked the destructive stromal invasion of carcinoma. Intermediate endometrioid tumors were subdivided into proliferative endometrioid tumors (PET), endometrioid tumors of low malignant potential (ETLMP), and ETLMP with microscopic areas of invasion. PET were adenofibromas with solid aggregates of epithelial proliferation not exceeding 5 mm in any dimension, whereas ETLMP either had noninvasive cytologically malignant epithelium or aggregates of atypical epithelium measuring at least 5 mm in any dimension uninterrupted by fibromatous stroma. Of the seven PET, five were purely adenofibromatous, while two were mixtures of adenofibromatous and papillary components. Of the 31 ETLMP, 12 were adenofibromatous and 19 were either purely papillary or had mixtures of papillary and adenofibromatous components. An additional three ETLMP had one or more areas of microscopic invasion of the stroma in the form of an irregular or cribriform infiltration by atypical glands, often with squamous differentiation. These three neoplasms were designated "ETLMP with microinvasive carcinoma." The only neoplasm with extraovarian implantation at presentation, however, was an ETLMP with mixed adenofibromatous and papillary features, without microinvasion. None of the other patients with ETLMP had a metastasis or developed one within a follow-up period of between 0.8 and 11.2 years. Because they are very low-grade neoplasms, ETLMP should be separated from endometrioid carcinoma and not confused with PET, because PET have no malignant potential.

Intermediate filaments in endometrial and endocervical carcinomas. The diagnostic utility of vimentin patterns.

We examined the distribution of high- and low-molecular-weight cytokeratins, vimentin, and carcinoembryonic antigen (CEA) in normal endometrial glands and endocervical glands (20 cases each) and in endometrial and endocervical adenocarcinomas (29 cases and 15 cases respectively). Low- and high-molecular-weight cytokeratin staining was present in normal endometrial and endocervical epithelium and in carcinomas. Coexpression of vimentin and cytokeratin was universally present in normal proliferative endometrial glands, with marked decrease or absence of vimentin staining in secretory phase patterns. Vimentin staining had a perinuclear distribution within the cells, in contrast to the cytokeratins, which stained diffusely. Vimentin was found in only 65% of endometrial adenocarcinomas. Staining was typically focal as well as regional in portions of the tumors. Vimentin was never observed in normal or neoplastic endocervical epithelium. Ultrastructural studies corroborate the perinuclear vimentin immunostaining pattern we observed in endometrial adenocarcinomas. CEA staining results were similar to those previously reported. These data indicate that the presence of vimentin may readily distinguish endometrial from endocervical carcinoma and is diagnostically useful in the study of metastatic adenocarcinomas.

Myofibroblastoma of the breast. Sixteen cases of a distinctive benign mesenchymal tumor.

The clinical and pathologic findings of 16 examples of a distinctive stromal tumor of the breast designated as "myofibroblastoma" are reported. Eleven of the 16 patients were men, and the average age at presentation was 63 years. Fourteen were treated by local excision and two by simple mastectomy. None of the lesions recurred or metastasized. The tumors were grossly nodular and well-demarcated from the surrounding mammary tissue. Ducts and lobules were not engulfed by the neoplasm. Microscopically, the lesions were formed by uniform, slender, bipolar spindle cells haphazardly arranged in fascicular clusters separated by broad bands of hyalinized collagen. Ultrastructural examination of four lesions identified a predominance of myofibroblasts. Immunoreactivity for S-100 protein and cytokeratin was absent in the 10 tumors examined, but desmin immunoreactivity was focally present in three lesions. The differential diagnosis of myofibroblastoma includes reactive processes and benign neoplasms such as nodular and proliferative fascititis, fibromatosis, spindle-cell lipoma, neurofibroma, neurilemmoma, and leiomyoma. Malignant neoplasms such as stromal sarcoma, malignant fibrous histiocytoma, and spindle-cell or metaplastic carcinoma should not be confused with a myofibroblastoma. The clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm.