Epithelial metaplastic changes in ovarian endometriosis

Little is known concerning epithelial metaplastic changes (metaplasia) in ovarian endometriosis. Three hundred fifteen consecutive cases of ovarian endometriosis between 1987 and 1995 were retrieved from hospital files and clinicopathologically analyzed. Two hundred fifty-seven cases were not associated with malignant ovarian epithelial tumor or atypia Four cases were atypical endometriosis. The remaining 54 cases were associated with malignant ovarian epithelial tumor, including borderline tumor. Metaplasias in ovarian endometriosis were observed in 162 (63%) cases not associated with malignant epithelial tumor or atypia. Ciliated cell and eosinophilic metaplasias were the most common (44%, respectively), followed by hobnail (13%) and mucinous (4%) types. Metaplasias in endometriosis were observed in all of the four atypical endometriosis cases and all of the 54 cases with malignant ovarian epithelial tumor. Among these cases, ciliated cell and eosinophilic metaplasia were also the most common. There was no correlation between types of carcinoma and types of metaplasia in endometriosis, but in all of the four Müllerian mucinous borderline tumors, ovarian endometriosis with mucinous metaplasia and hyperplasia was contiguous or intimately associated with the tumor. Metaplasia was often observed in ovarian endometriosis and most frequently was associated with malignant ovarian epithelial tumor or atypia. Metaplastic changes in ovarian endometriosis should not be interpreted as neoplastic features. Mucinous metaplasia and hyperplasia in ovarian endometriosis might be closely associated with the development of Müllerian mucinous borderline tumors.     

Lateral neck cysts--the branchial theory revisited. A critical review and clinicopathological study of 97 cases with special emphasis on cytokeratin expression

Theories regarding the origin of lateral neck cysts (LNC) range from congenital branchial pouch abnormalities to acquired salivary gland inclusions within lymph nodes. We analyzed 97 LNC histologically and evaluated their cytokeratin (CK) profile in a search for their derivation. 77/97 LNC were located in soft tissues, 20/97 within lymph nodes. LNC of young patients and of recent symptomatic presentation in older patients were lined by respiratory epithelium with scant lymphoid tissue, with expression of "simple epithelial" CK in ciliated cells and bimodal expression of "simple" and "stratified-epithelial-type" CK in basal cells. In longer standing symptomatic LNC, respiratory epithelium alternated with transitional-type pseudostratified epithelium with intraepithelial Langerhans cells and lymphoid hyperplasia, or consisted exclusively of squamous epithelium. We propose that respiratory epithelium is the "native" epithelium of LNC and squamous metaplasia results from inflammation induced stem cell hyperplasia in respiratory epithelium, evidenced by co-expression of "simple" and "stratified-epithelial-type" CK in all cells of transitional-type pseudostratified epithelium, the early stage in metaplastic transformation. Respiratory epithelium predominates in early LNC, lines pharyngeal tonsils and the recessus tonsillo-tubalis, and is a minor constituent of palatine tonsil but is not present in salivary glands. None of the LNC contained dysplasia, atypia, or carcinoma, or were associated with a primary carcinoma of tonsils or head and neck. We demonstrate that LNC arise from developmental remnants (congenital) of the 2nd branchial pouch, which may lie dormant for many years. Symptomatic enlargement, squamous metaplasia and lymphoid hyperplasia ensue as a consequence of immunologic stimulation a development reflected in hyperplastic palatine tonsils.     

Reproducibility of the diagnosis of endometrial hyperplasia, atypical hyperplasia, and well-differentiated carcinoma

Many studies have attempted to identify histologic features that aid in the distinction of atypical hyperplasia (AH) from hyperplasia without atypia and well-differentiated endometrioid carcinoma, but few have evaluated the reproducibility of these diagnoses. Five pathologists independently reviewed 100 endometrial biopsy and curettage specimens chosen to represent the entire spectrum of proliferative lesions of the endometrium, including proliferative endometrium (PEM), hyperplasia without atypia, AH, and well-differentiated endometrioid carcinoma. Slides were reviewed twice for diagnosis, with an intervening evaluation of a checklist of histologic features. Intraobserver and interobserver agreement were assessed using the kappa statistic. Intraobserver kappa values ranged from 0.67 to 0.89 (76% to 89% agreement). Interobserver kappa values by diagnostic category were: proliferative endometrium: 0.86; hyperplasia without atypia: 0.60; AH: 0.47; well-differentiated endometrioid carcinoma: 0.83; with a kappa value of 0.69 for all cases combined. Associations between the selected histologic features and the given diagnoses for each pathologist were analyzed using multiple logistic regressions to identify features that were useful for distinguishing among diagnostic categories. Histologic features determined by univariable and multivariable analyses that were found to be most associated with distinguishing diagnostic categories were: proliferative endometrium versus hyperplasia without atypia: gland crowding (univariable, multivariable), and gland branching (univariable); hyperplasia without atypia versus AH: presence of nucleoli (univariable, multivariable), nuclear enlargement (univariable), vesicular chromatin change (univariable), nuclear pleomorphism (univariable), chromatin irregularities (univariable), and loss of polarity (univariable); hyperplasia without atypia versus carcinoma: glandular confluence/complex cribriform pattern (univariable, multivariable), stromal alteration (univariable, multivariable), and necrosis (univariable). In summary, interobserver agreement was good but was lowest for AH. Only the presence of nucleoli was strongly associated with distinction of AH from hyperplasia without atypia. Individual pathologists use additional features to diagnose atypia, but these features are not consistently associated with that diagnosis. Cribriform architectural pattern and stromal alteration were associated with the distinction of well-differentiated endometrioid carcinoma from AH.     

Carcinoid tumour complicating inflammatory bowel disease. A study of two cases with review of the literature

Two cases of carcinoid tumour complicating inflammatory bowel disease (IBD) are presented. Both tumours were located in the appendiceal tip. The first case occurred in a man with Crohn's disease (CD), and the second one in a woman suffering from ulcerative colitis (UC). Histochemical and immunohistochemical studies were not allowed on case 1 because the tumour was not still present on serial sections of the appendix. On case 2, tumour cells were not reactive with Grimelius and Masson-Fontana stainings, but were strongly stained with anti-keratin and anti-chromogranin monoclonal antibodies (MAb), and faintly expressed neuron specific enolase (NSE), and Leu-7. Both cases occurred in inflammatory or damaged mucosa which exhibited Paneth cell metaplasia and hyperplasia and areas indefinite for dysplasia. Along with these lesions, hyperplasia of enteroendocrine cells was pointed out in the neighbouring appendiceal and colonic mucosa by means of anti-chromogranin MAb. These data suggest that the association of carcinoid tumour with IBD, albeit rare, is not coincidental and is the result of hyperplastic and dysplastic troubles that may involve enteroendocrine cells as well as such other derivatives of digestive stem cells as columnar cells, goblet cells and Paneth cells.     

The influence of time on human breast capsule histology: smooth and textured silicone-surfaced implants

Although the histology of capsular tissue is well described in the literature, most studies in humans do not correlate histologic findings with implant age (number of years an implant was in place before sampling). As such, questions regarding the long-term histology in humans remain. The microanatomy of 93 human periprosthetic capsular tissues surrounding 22 textured and 71 smooth silicone-surfaced prostheses was studied. The implants were divided into two groups according to the time between implantation and capsulectomy: between 0 and 5 years or more than 5 years. Hematoxylin and eosin and Masson trichrome-stained sections were analyzed by light microscopy, with and without polarization. Eighteen of the textured implants contained silicone gel and four contained saline. Sixty of the smooth implants contained silicone gel, eight contained saline, and in three, the filler type was not known. For the majority of patients, surgery was performed for augmentation mammaplasty, and the implants were removed because of capsular contracture. The following histologic features were assessed: synovial-like metaplasia, villous hyperplasia, density of the collagenous capsule, alignment of collagen fibers within the capsule, and the presence of foreign material and of a foreign body reaction. The following trends were observed. In smooth implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia (p = 0.003) and villous hyperplasia; there was no significant difference in the presence of a dense collagenous capsule, the orientation of collagen fibers, or the presence of a foreign body reaction. An increase was observed in the presence of foreign material (p = 0.01). In textured implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia, villous hyperplasia (p = 0.003), dense collagenous architecture, and parallel orientation of collagen fibers (p = 0.017). An increase in the presence of a foreign body type reaction and foreign material (p = 0.024) was observed. In comparing textured and smooth-surfaced implants, synovial-like metaplasia was observed more often in the textured group, both at 0 to 5 years (p = 0.01) and at greater than 5 years (p < 0.01). Textured implants more often had villous hyperplasia at 0 to 5 years (p = 0.03) but not beyond 5 years. Smooth implants more often had a dense collagenous capsule than textured implants after 5 years. No significant difference was seen in the orientation of collagen fibers in capsules around smooth and textured implants at 0 to 5 years. After 5 years, the incidence of capsules with collagen fibers arranged parallel to the implant surface was significantly greater in the smooth group than in the textured group (p = 0.01). The presence of a foreign body type reaction was seen more often in the textured group between 0 and 5 years (p = 0.01) and at greater than 5 years (p < 0.01), and the presence of foreign material was more often seen in the textured group between 0 and 5 years (p = 0.06) and at greater than 5 years (p < 0.01). In summary, the cytologic changes around implants seem to be dynamic in nature, and implantation duration and shell type play a significant role. Synovial-like metaplasia, villous hyperplasia, and foreign material were more often observed in the textured group within the 0 to 5 year interval. Beyond 5 years, synovial-like metaplasia, a foreign body type reaction, and foreign material were more often observed in the textured group. Differences in the density of collagenous capsules were not significant at any time point, and collagen fibers oriented parallel to the implant surface were more often observed in the smooth group after 5 years. The significance of these findings awaits further investigation.     

Senile macular changes in the black African

One thousand black African and 380 white Caucasian patients over the age of 50 were examined for evidence of age-related macular changes, namely, drusen, pigment epithelial atrophy, and disciform macular degeneration. Drusen and pigment epithelial changes were found to occur twice as commonly in Caucasians as in Africans; there was a much greater difference in the prevalence of disciform macular degeneration between the 2 groups. The cause of the differences remains unexplained.     

Ataxia-telangiectasia in the Japanese population: identification of R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being relatively common mutations

Postmenopausal uterine bleeding is an indication to sample the endometrium for diagnostic purposes. The endometrial brush cytologies of 20 advanced postmenopausal women collected at the time of hysterectomy in order to benchmark the expected morphology of postmenopausal endometrial brushings were reviewed. No women had symptoms or gross findings of primary endomyometrial disease. Endometrium was collected at the surgical pathology laboratory using the Tao Brush and CytoRich Fixative System. After formalin fixation of the uterus, the entire endometrium was embedded for routine histology. Sixteen endometrial brushings and matched endometrial sections showed endometrial atrophy, one brushing showed many ciliated epithelial cells, and three brushings showed focal (less than 10%) epithelial-cell atypia. In two atypias, abnormal endometrial epithelial-cell sheets contained enlarged, clear nuclei with nuclear notches and grooves resembling papillary thyroid cancer. One case showed no histological counterpart to this finding. The other case showed thickening of the pericornual fundic endometrium with cystic glands. The third case with epithelial atypia showed abnormal endometrial-cell sheets with nuclei resembling atypical hyperplasia or type I endometrial adenocarcinoma; corresponding endometrial tissue sections showed rare, irregular glands and back-to-back gland clusters with equivalent nuclear features. Atypical epithelium may be found in atrophic uteri in the absence of gross endometrial thickening. This may be a common event related either to de novo intraepithelial dysplasia in a noncycling endometrium or to hyperplasia that has partly regressed with estradiol withdrawal. This study shows that, in addition to endometrial intraepithelial carcinoma (EIC), isolated atypical glands with morphological and immunohistochemical features of atypical hyperplasia or type I endometrial adenocarcinoma may be found in grossly normal advanced postmenopausal endometrium of asymptomatic patients. This atypical epithelium is readily apparent in endometrial brush preparations, but requires serial sectioning of the endometrium to be demonstrated histologically. We have not established the natural history of this lesion, and in the absence of EIC or gross endometrial thickening indicative of atypical hyperplasia, we do not know whether this degree of epithelial atypia should be an indication for hysterectomy.     

Prognostic factors in idiopathic (primary) osteomyelofibrosis

BACKGROUND: Prognostic variables for idiopathic (primary) osteomyelofibrosis (IMF) are ill-defined because of the lack of large control studies based on uniform diagnostic criteria. METHODS: A retrospective clinicopathologic study was performed on 250 consecutively recruited patients (115 males and 135 females) with an established diagnosis of IMF. In contrast to previous studies, the current study cohort encompassed the full spectrum of initial to advanced stages of the disease process according to laboratory data and particularly histology. Because of the relatively high patient age on admission (median, 66.5 years), relative survival rates with corresponding life expectancies and disease specific life loss were calculated. Moreover, a classification and regression tree (CART) analysis was performed to segregate the study patients into subgroups with significantly different prognosis. RESULTS: Analysis of the life expectancy and the proportion of deaths attributable to IMF showed a global reduction in life expectancy of 31%. Further calculation disclosed a consistently greater impact of disease in older patients. Age, hemoglobin level on admission, and leukocyte and thrombocyte counts remained as the most relevant parameters for prognosis in multivariate consideration (CART analysis) and facilitated a clear-cut separation into three risk groups. The life expectancy of low risk patients was approximately 10 times higher than that of high risk patients (22.07 years vs. 2.25 years). CONCLUSIONS: These results are in keeping with the assumption that features signaling bone marrow insufficiency are associated with a worsening of survival. Generalization, indicated by myeloid metaplasia, can occur at every stage, even in so-called hypercellular phases of IMF. Conversely, myelofibrosis alone is not necessarily predictive of poor survival.     

Serum leptin concentration and insulin sensitivity in men with abdominal obesity

Papillary immature metaplasia (PIM) of the cervix (immature condyloma) is a variant of low-grade squamous intraepithelial lesions (LSIL). It is frequently associated with human papillomavirus (HPV) types 6 and 11. The purpose of this study was to characterize the cytologic changes associated with this lesion. We analyzed 10 cases of PIM from our files and reviewed the Papanicolaou smears taken proximate to the time of the biopsy. Four cases had either reactive epithelial changes (2 cases) or cytologic findings typical of low-grade SIL, with koilocytosis (2 cases). Six cases displayed a spectrum of metaplastic cells with varying maturation that ranged from atypical reactive cells to atypical immature metaplastic cells. Binucleation was common. Some cells exhibited features characteristic of SIL, although the degree of nuclear atypia generally was less than that associated with high-grade SIL. Papanicolaou smears from all cases were interpreted as atypical (ASCUS) metaplasia or low-grade SIL. Follow-up biopsy in one case revealed a PIM in association with a high-grade SIL, the latter undiagnosed by smear alone. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings. Its recognition histologically can resolve some cytologic/histologic discrepancies. Confusion with an immature HSIL or atypical immature metaplasia can occur in some instances and the diagnosis of PIM by cytology alone is not recommended, unless the diagnosis is qualified.     

A community based stroke register in a high risk area for stroke in north west England

The occurrences of histologic changes in the central nervous system of very low birth weight infants (500 to 1500 grams) according to gestational age and postnatal age are incompletely reported. In order to better understand the abnormalities present in this patient population, the brains of 67 very low birth weight infants who died after having had at least one cranial ultrasound scan were studied. More than half the infants were born at gestational ages of 24 to 26 weeks, and only 28% died within 24 hours (h) of birth. The slides of the brains of all 67 infants were reviewed simultaneously by 3 neuropathologists who had to agree on the presence and/or absence of each histologic characteristic. Among infants who died within 24 h of birth, fully one quarter had parenchymal hemorrhage, 42% had petechial hemorrhages in the white matter, and more than 20% had hypertrophic astrocytes. These data indicate that in utero, prepartum, injury to the nervous system was common. Compared with infants who died before the sixth day, those who survived at least 6 days were twice as likely to have moderate/severe ventriculomegaly, rarefaction, amphophilic globules, hypertrophic astrocytes, macrophage foci, coagulative necrosis, and hemorrhagic necrosis than those who died before the 7th postnatal day. Parenchymal hemorrhage and moderate/severe ventriculomegaly decreased in frequency with increasing gestational age. On the other hand, the older the gestational age, the higher the likelihood of finding amphophilic globules, hypertrophic astrocytes, macrophage foci, and zones of coagulative necrosis upon neuropathologic examination. Our data indicate that several central nervous system abnormalities appear to increase with both older gestational age and older postnatal age for infants born weighing less than 1500 grams. We were unable, however, to determine the relative contribution of gestational age and postnatal age to the specific neuropathologic findings in this study.     

Gastric gland metaplasia in the small and large intestine

Fifty-six surgical specimens with various ulcerative intestinal disorders were microscopically investigated for evidence of gastric gland metaplasia. Thiry-one specimens (55-4%) showed pyloric gland metaplasia. Among the 31 patients with pyloric gland metaplasia, five showed true gastric metaplasia, consisting of parietal cells, chief cells, and mucous neck cells. The percentage of true gastric metaplasia among pyloric gland metaplasia was as high as 16%, an overall frequency of 9% among various ulcerative intestinal disorders. The mechanism of pyloric gland metaplasia and true gastric metaplasia is not understood, but may occur secondary to submucosal response to ulcer healing and subsequent alteration of the intraluminal condition in the intestine.     

Nodular regenerative hyperplasia of the liver in hematologic disorders: a possible response to obliterative portal venopathy. A morphometric study of nine cases with an hypothesis on the pathogenesis

Nodular regenerative hyperplasia was found in nine patients who had hematological disease including polycythemia vera, agnogenic myeloid metaplasia, primary thrombocythemia, rheumatoid arthritis with thrombocytosis, multiple myeloma, and erythrocytosis associated with polycystic renal disease. Portal hypertension was suspected in three and features of hypersplenism were present in four. 2. Nodular regenerative hyperplasia occurred in livers which had widespread obliteration of portal vein radicals (obliterative portal venopathy). Morphometric analysis indicated that the portal vein lesions were predominately located in veins up to 0.2 mm in diameter and were significantly more frequent than similar lesions occurring in elderly persons. 3. The following pathogenesis of nodular regenerative hyperplasia is proposed: Thrombi, perhaps largely composed of platelet aggregates formed in the portal venous circulation or spleen, embolize to the liver and results in obliterative vascular lesions. Atrophy and regenerative nodule formation occur in response to the interruption of the portal blood supply.     

Epididymal tumors (author's transl)

Six cases of benign primary epididymal tumor have been investigated in our patients. The tumor size fluctuated between 3 and 35 mm in diameter. Frequency, histology and medical development are described. The majority of epididymal tumors (53%) is comprised of so-called adenomatoid tumors of benign nature and their histogenesis is being discussed. The difficulties of differential diagnosis are pointed out. Since malignity exists in 26% of the cases, the surgical exposure and diagnosis by frozen section is being postulated, when suspicion of epididymal tumor becomes evident.     

Apocrine adenosis: a precursor of aggressive breast cancer?

AIM: To investigate overexpression of c-erbB2, expression of the p53 protein product and proliferation rates in benign breast lesions with specific reference to apocrine adenosis. METHODS: Twenty one cases of apocrine adenosis were stained with monoclonal antibodies to p185, the protein product of the c-erbB2 oncogene, the protein product of the p53 tumour suppressor gene and to the cell cycle related protein Ki67. Three cases were associated with concomitant ductal carcinoma in situ of large cell type and two were associated with invasive tubular or cribriform carcinoma. RESULTS: Twelve (57.1%) cases showed membrane staining for c-erbB2 oncoprotein of apocrine cells within sclerosing adenosis and six (28.6%) had occasional p53 protein positive cells. One case not associated with carcinoma showed extensive staining of apocrine metaplasia outside the area of apocrine adenosis. The proliferation rate, as measured by Ki67 staining, was increased in some of the lesions and all lesions showed at least some of the cells to be in the cell cycle. CONCLUSIONS: The expression of abnormal oncogene products and increased proliferation in some of these apocrine lesions questions the supposed degenerative nature of the atypia seen in such cases and suggests that there may be an association between these lesions and large cell ductal carcinoma in situ and hence invasive carcinoma.     

Severe atypical endometrial changes and sequential contraceptive use

Of eight young women, seven had a diagnosis of well-differentiated endometrial adenocarcinoma and one had atypical endometrial hyperplasia. The average age was 40.1 years, with 6.04 years of dimethisterone-ethinyl estradiol (Oracon) sequential contraceptive use. The patients were not typical of those in whom endometrial carcinoma develops. Although these cases do not prove that long-term administration of dimethisterone-ethinyl estradiol causes endometrial adenocarcinoma or atypia, they indicate that it may do so.     

Correlation between serious ovarian tumors and extra-ovarian peritoneal tumors of the same histology

The occurrence of serous peritoneal tumors (SPT) with the same histology as serous neoplasms arising within the ovary is explained by the common origin of the peritoneum and the ovaries from the coelomic epithelium. They occur alone or in combination with analogous tumors of the ovary and are often misinterpreted as metastatic ovarian carcinomas. Their histology shows considerable variations. As lesions with and without invasive properties may coexist, visible lesions should be resected and examined as completely as possible. The prognostic significance of some histological findings is still under study. It appears that besides invasion the grade of nuclear atypia is of importance. It is therefore possible that the use of cytometry provides new prognostic criteria, allowing the identification of high risk groups. This holds also for the malignant forms of SPT, which seem to have a similar prognosis to analogous tumors of the ovary. For this purpose, peritoneal cytology is of special value and constitutes an integral part of the investigations.     

Segment-specific morphological changes in aging Brown Norway rat epididymis

In aging Brown Norway rats, both spermatogenesis and steroidogenesis decrease. Little is known about changes in the epididymis during aging. However, since the two major components entering the epididymis from the testis change, we hypothesized that epididymal histology would be affected by advancing age. The epididymides of Brown Norway rats ranging in age from 3 to 24 mo were prepared for light and electron microscopy. Striking quantitative and qualitative changes were noted. There was an age-dependent increase in the thickness of the basal membrane and in the number of halo cells. There were also major segment-specific changes in the appearance of cells along the epididymis with age. At 12 mo, basal cells in the initial segment emitted pseudopods into the basement membrane. By 18 mo, in the caput epididymidis, clear cells were filled with lysosomes; these cells frequently showed bulging protrusions into the lumen. In the corpus epididymidis, the cytoplasm of principal cells had numerous large lysosomes both below and above the nucleus; apical cells were usually occupied by one giant membranous lysosome. In the proximal cauda, clear cells became filled with dense lysosomes, and principal cells presented large clear vacuoles; debris from spermatozoa was found in the larger vacuoles. In summary, aging of the epididymis was accompanied by the emergence of characteristic features of aging and activation of the immune system. Furthermore, there were many cell- and segment-specific changes. Finally, these changes were not related to the presence of spermatozoa, often preceding their disappearance, thus indicating that there may be an intrinsic mechanism of aging in epididymal epithelial cells.     

Pediatric malignant glioma with tubuloreticular inclusions and MYCN amplification. Report of a case with immunohistochemical, ultrastructural, flow cytometric, karyotypic, and Southern blot analysis

BACKGROUND: The authors described unusual pathologic features in a left frontal lobe malignant glioma in a 31/2-year-old boy. The pathology was similar in the initial excision and two subsequent recurrences at 9 and 11 months and at autopsy, when extensive subarachnoid spread was noted. METHODS: The tumor was studied by conventional histology, immunohistochemistry, flow cytometry, transmission electron microscopy (TEM), immune electron microscopy (IEM), and cytogenetic and Southern blot analysis. RESULTS: The tumor revealed two different histologic patterns. One component showed large cells with eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli, eosinophilic perinuclear inclusions, and immunoreactivity for glial fibrillary acidic protein (GFAP) and vimentin. The other component consisted of undifferentiated cells with hyperchromatic nuclei and scanty cytoplasm. By TEM, the perinuclear aggregates were composed of tubuloreticular inclusions, which were also observed in endothelial cells within the tumor vasculature. By IEM, the intermediate filaments in the tumor cell cytoplasm were decorated with GFAP. Flow cytometric results revealed a marked increase in the S-phase (48%), whereas cytogenetic analysis of short-term cultures showed an abnormal karyotype containing marker chromosomes and double minutes. In the second resection, additional karyotypic abnormalities were noted, including 1p- and several additional markers. The first and second resections showed MYCN amplification by Southern Blot analysis in the 60- to 80-fold range. CONCLUSIONS: This tumor presents unique histologic, ultrastructural, and cytogenetic findings as well as MYCN amplification that is notable for a pediatric malignant glioma. Tubuloreticular inclusions were a prominent feature in this tumor, which again is unique for a glioma.     

Amyotrophic lateral sclerosis with numerous axonal spheroids in the corticospinal tract and massive degeneration of the cortex

The use of biomarkers is a promising approach to the study of human cancer risk. Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies. We recently performed a randomized, controlled trial in smokers on the effect of 14 weeks beta-carotene (20mg/day) on markers for DNA damage. We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene. Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum samples (n = 29), or because samples were unsatisfactory (n = 46). The eligible group was older (41 vs 37 years) and had smoked longer (23 vs 19 years), but had similar cigarette consumption (mean 21/day) and plasma cotinine levels. Metaplasia was graded in seven categories. Only 11 subjects (15%) showed minor or mild atypia on study entry. Agreement within and between observers was 95% within the same or an adjacent category. We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene (Spearman R = 0.18, P = 0.3) or placebo group (Spearman R = 0.17, P = 0.3). Initial metaplasia scores were somewhat higher in the beta-carotene group (n = 33) than in the placebo group (n = 42) (P = 0.06). Final metaplasia scores were similar in both groups (P = 0.69), and there was no decrease in metaplasia scores in the beta-carotene group (P = 0.75). This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population, because many smokers do not spontaneously produce sputum, more severe lesions are rare, and variation over time in the minor lesions in large. Therefore, the preliminary evidence that beta-carotene has no influence should be interpreted with care.     

Antidepressant efficacy and cardiovascular safety of venlafaxine in young vs old patients with comorbid medical disorders

OBJECTIVE: To determine whether venlafaxine exerts a differential effect on blood pressure in young versus old depressed patients. METHOD: We compared thirty-four consecutive patients treated with 50-250 mg/day venlafaxine for major depressive disorder or another major mood disorder at our medical college's ambulatory neuropsychiatry program. We obtained baseline and follow-up blood pressure measurements. Each patient also received a baseline and final Clinical Global Impressions (CGI) score; global improvement was determined by consensus of two clinicians. RESULTS: Sixteen nongeriatric patients (age, 13 to 56 years) were compared with eighteen elderly patients (age, 65 to 86 years). Most patients (88%) had serious medical comorbidities or histories. Despite a higher mean daily venlafaxine dosage for patients in the young group, no significant changes in systolic blood pressure were noted in either group. For the older group, we found a non-statistically significant 4.7 mm Hg mean increase in diastolic blood pressure. No patient became hypertensive. We also found a negative correlation between baseline diastolic blood pressure and change in diastolic blood pressure during treatment with venlafaxine. This inverse relationship was statistically significant in the older patients. CONCLUSIONS: Venlafaxine was not associated with significant, sustained changes in blood pressure in any patient receiving dosages of 50-250 mg/day. Minimal changes in diastolic blood pressure were no more likely to occur in older venlafaxine-treated patients than in younger ones. Higher baseline diastolic blood pressure in older patients, but not in younger ones, seemed to protect against diastolic adrenergic blood pressure effects of venlafaxine.