The influence of late prematurity on the encephalopathy exam of infants with neonatal encephalopathy.

BACKGROUND: Late preterm (LPT) infants are increasingly treated for hypoxic-ischemic encephalopathy (HIE). However, neurodevelopmental differences of LPT infants may independently influence the neurologic exam and confound care. METHODS: Perinatal and outcome characteristics were extracted along with the worst autonomic and state/neuromuscular/reflex Sarnat components in a cross-section of infants with moderate/severe HIE. Infants were classified as late preterm (LPT, 34-36 weeks) or term (>36 weeks). RESULTS: 250 infants were identified, 55 were late preterm. LPT infants had lower mean gestational age and birthweight and greater length of stay (LOS). LPT infants had higher median scores for the Moro and respiratory autonomic components, but no difference in total score. CONCLUSIONS: LPT infants had increased LOS, worse Moro reflex, and respiratory status, but no clinically or statistically significant differences in total Sarnat scores. Although it is important to note the impact of immaturity on the exam, it is unlikely to independently alter management.

Active normothermia treatment for perioperative temperature management during bedside surgery in the NICU, a case report.

Infants in the NICU setting often require emergent bedside surgical procedures, during which, they are at high risk for developing hypothermia. Reasons for hypothermia in infants include poor temperature regulation, decreased fat stores to maintain temperature, increased insensible losses. Neonatal hypothermia is associated with an increased risk of sepsis, cardiorespiratory failure (pulmonary hypertension), hypoglycemia and death. In this case series, we describe the novel use of servo-controlled water blanket system as a method to actively maintain normothermia during three surgical cases. Although water blanket systems are frequently used in the neonatal ICU to provide active hypothermia treatment, to our knowledge there have been no prior reports of this system being deployed in normal and low-birthweight infants in the perioperative period.

Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs.

BACKGROUND: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO). METHODS: At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO. RESULTS: We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821. CONCLUSION: In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.

Impact of brain injury on functional measures of amplitude-integrated EEG at term equivalent age in premature infants.

OBJECTIVE: To evaluate the association between qualitative and quantitative amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain injury on magnetic resonance imaging (MRI) in preterm infants. STUDY DESIGN: A cohort of premature infants born at <30 weeks of gestation and with moderate-to-severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of gestational age-matched control infants also born at <30 weeks of gestation with none/mild injury on MRI was also recruited. Quantitative aEEG measures, including maximum and minimum amplitudes, bandwidth span and spectral edge frequency (SEF90), were calculated using an offline software package. The aEEG recordings were qualitatively scored using the Burdjalov system. MRI scans, performed on the same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42) weeks and were scored for abnormality in a blinded manner using an established MRI scoring system. RESULTS: Twenty-eight (46.7%) infants had a normal MRI or mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain abnormality. Univariate regression analysis demonstrated an association between severity of brain abnormality and quantitative measures of left and right SEF90 and bandwidth span (ß=-0.38, -0.40 and 0.30, respectively) and qualitative measures of cyclicity, continuity and total Burdjalov score (ß=-0.10, -0.14 and -0.12, respectively). After correcting for confounding variables, the relationship between MRI abnormality score and aEEG measures of SEF90, bandwidth span and Burdjalov score remained significant. CONCLUSION: Brain abnormalities on MRI at TEA in premature infants are associated with abnormalities on term aEEG measures, suggesting that anatomical brain injury may contribute to delay in functional brain maturation as assessed using aEEG.

The effect of therapeutic hypothermia on heart rate variability.

OBJECTIVE: Heart rate variability (HRV) reflects integrity of the autonomic nervous system. However, no study has investigated the impact of therapeutic hypothermia (TH) on HRV measures in infants with hypoxic-ischemic encephalopathy (HIE). In this study, we evaluate the influence of temperature on measures of HRV for a group of infants with favorable outcomes, as compared with a control group of infants with unfavorable outcomes. STUDY DESIGN: Term-born infants with moderate-severe HIE underwent standard TH treatment and prospective electroencephalography (EEG) and electrocardiogram (ECG) recording. Infants with favorable outcome (no seizures, normal/mild EEG scores at 96 h, no magnetic resonance imaging brain injury and normal neurodevelopmental scores at 18 to 24 months) were matched on gestational age, sex and worst encephalopathy score to a group of infants with unfavorable outcomes. Time- and frequency-domain HRV measures were calculated from 60 min of ECG data obtained at three time points: 24 h (hypothermia), 48 h (hypothermia) and 96 h (normothermia). The effect of time and temperature were evaluated using repeated-measures analysis of variance. RESULTS: Sixteen infants were included (8 favorable, 8 unfavorable). For both groups of infants, an increase in the HR, RR and HF power was associated with an increase in temperature, but was not associated with any other HRV measure. In contrast, measures of HRV increased over time, as encephalopathy decreased, for infants with favorable outcomes (reflecting increased cortical-autonomic integration), but not for those with unfavorable outcomes. CONCLUSIONS: In general, the effect of hypothermia on measures of HRV is limited to changes in heart rate (bradycardia) and respiratory rate, as opposed to changes in true variability. This supports the hypothesis that persistent changes in HRV are driven by the underlying brain injury and not by the process of TH.

The role of post-mortem MRI in the neonatal intensive care unit.

OBJECTIVE: Post-mortem examination can provide important information about the cause of death and play a significant role in the bereavement process. Autopsies reveal previous unknown medical problems approximately 20 to 30% of the time. A non-invasive magnetic resonance imaging-based post-mortem examination (PM-MRI) may provide an alternative for families who do not consent to an autopsy. STUDY DESIGN: This study was a prospective observational study of recently expired neonates and infants. Subjects underwent a full body MRI scan (brain, chest, abdomen and pelvis) followed by conventional autopsy if the family desired to have one. MRI results were compared with autopsy findings and the ante-mortem clinical diagnosis. A follow-up survey was conducted to investigate family perceptions of the PM-MRI process. RESULTS: Thirty-one infants underwent full PM-MRI. Of 31 infants, 19 (61%) had complete agreement between the clinician's impression and PM-MRI. Twenty-four infants also had conventional autopsy, with 14/24 (58%) infants having PM-MRI results consistent with autopsy findings. PM-MRI was superior at detection of free intraperitoneal/intrathoracic air and hepatic iron overload. Whole-body PM-MRI did not have the resolution to detect focal/microscopic injury, vascular remodeling and some forms of brain injury. Of those families who remembered the PM-MRI findings, the majority felt that the information was useful. CONCLUSIONS: PM-MRI studies may provide an important adjunct to conventional autopsy and a substitute when the latter is not possible for personal or religious reasons. Clinicians should be aware of, and communicate with the family, the resolution limits of the whole-body PM-MRI to detect certain types of injury.

Early hyperoxia burden detected by cerebral near-infrared spectroscopy is superior to pulse oximetry for prediction of severe retinopathy of prematurity.

OBJECTIVE: Fractional tissue oxygen extraction (FTOE) is a measure derived from cerebral near-infrared spectroscopy (NIRS) and simultaneous pulse oximetry (SpO2), capturing the proportion of oxygen delivered in arterial blood that is used by the target tissue. FTOE may provide a better proxy measurement of retinal hyperoxia than pulse oximetry alone and could provide insight into the risk for retinopathy of prematurity (ROP). In this study, we directly compared hyperoxia burden calculated from FTOE with hyperoxia burden calculated from SpO2 alone in order to assess the strength of association between hyperoxia and severe ROP. STUDY DESIGN: Infants born before <30 weeks and weighing <1500 g underwent synchronized SpO2 and FTOE recording over the first 4 days following birth. After error correction of the raw recording, hyperoxia burden was calculated as the percentage of the total SpO2 or FTOE recording with measurements exceeding defined thresholds (90/93/95% and 20/15/10%, respectively) and was compared with the outcome of severe ROP, defined as ROP requiring laser therapy, after controlling for important covariates. RESULT: A total of 63 infants were included with a mean±s.d. gestational age of 25.8±1.5 weeks and birth weight of 898.5±206.9 g; 13/63 (20%) had severe ROP. SpO2 hyperoxia burden was not associated with severe ROP at any threshold. FTOE hyperoxia burden was associated with severe ROP at the 15% (P=0.04) and 10% (P=0.03) thresholds. Infants with severe ROP spent 20% and 50% more time exceeding the 15% and 10% thresholds, respectively, as compared with those without severe ROP. CONCLUSION: In the first 96 h of life, FTOE but not SpO2 hyperoxia burden is associated with severe ROP. These preliminary results suggest that NIRS may be a viable alternative technology for targeted oxygen saturation guidelines.

Response to dopamine in prematurity: a biomarker for brain injury?

OBJECTIVE: To identify factors associated with responsiveness to dopamine therapy for hypotension and the relationship to brain injury in a cohort of preterm infants. STUDY DESIGN: The pharmacy database at St Louis Children's Hospital was retrospectively queried to identify infants who (a) were born <28 weeks gestation between 2012 and 2014, (b) received dopamine and (c) had blood pressure measurements from an umbilical arterial catheter. A control group was constructed from contemporaneous infants who did not receive dopamine. Mean arterial blood pressure (MABP) at baseline, 1 h and 3 h after initiating dopamine were obtained for each dopamine-exposed infant. MABP measurements at matched time points were obtained in the control group. RESULT: Sixty-nine dopamine-treated and 45 control infants were included. Mean ΔMABP at 3 h was 4.5±6.3 mm of Hg for treated infants vs 1±2.9 for the control. Median dopamine starting dose was 2.5 µg kg(-1) min(-1). Dopamine-treated infants were less mature and of lower birth weight while also more likely to be intubated at 72 h, diagnosed with intraventricular hemorrhage (IVH) and to die. Failure to respond to dopamine was associated with greater likelihood of developing IVH (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.1-42.3), while a strong response (ΔMABP>10 mm Hg) was associated with a reduction in risk of IVH (OR 0.1, 95% CI 0.01-0.8). CONCLUSION: Low-moderate dose dopamine administration results in modest blood pressure improvements. A lack of response to dopamine is associated with a greater risk of IVH, whereas a strong response is associated with a decreased risk. Further research into underlying mechanisms and management strategies is needed.

Empirical estimation of the normative blood pressure in infants <28 weeks gestation using a massive data approach.

OBJECTIVE: To determine the expected systolic, mean and diastolic blood pressures at birth and respective rates of change during the first 72 h of life in infants born at <28 weeks estimated gestational age (EGA) with a favorable short-term outcome, defined as survival to 14 days with grade II or less intraventricular hemorrhage (IVH). STUDY DESIGN: Systolic, mean and diastolic blood pressures were continuously sampled at 0.5 Hz via umbilical artery catheter from birth through 72 h. The raw data were aligned by postnatal hour and underwent error correction. For each infant, the mean values of systolic, mean and diastolic blood pressure were calculated for each postnatal hour. The slope and intercept of best-fit line for each of the three blood pressure parameters was then calculated. Infants that received inotropic medications, died in the first 14 days of life, or had IVH grade III or IV were excluded. RESULT: Using 11.9 million valid data points from 35 infants (mean EGA=25.7 ± 1.5 weeks, mean birth weight=865 ± 201 g), we found independent associations of African-American race (P<0.01) and a complete course of antenatal steroids (P<0.01) with higher blood pressures at birth and a slower rate of increase. Acute chorioamnionitis was independently associated (P=0.02) with lower blood pressures at birth and a faster rate of increase. EGA and birth weight were not independently predictive of blood pressure parameters. CONCLUSION: We found that (i) the estimated mean blood pressure at birth is ~33 mmHg in a cohort of very preterm infants, (ii) blood pressure gradually increases with postnatal age, (iii) systolic blood pressure increases at a faster rate than diastolic blood pressure, (iv) race, antenatal steroid exposure and chorioamnionitis are independent modulators of blood pressure whereas EGA and birth weight are not.

Normative amplitude-integrated EEG measures in preterm infants.

OBJECTIVE: Assessing qualitative patterns of amplitude-integrated electroencephalography (aEEG) maturation of preterm infants requires personnel with training in interpretation and an investment of time. Quantitative algorithms provide a method for rapidly and reproducibly assessing an aEEG recording independent of provider skill level. Although there are several qualitative and quantitative normative data sets in the literature, this study provides the broadest array of quantitative aEEG measures in a carefully selected and followed cohort of preterm infants with mild or no visible injury on term-equivalent magnetic resonance imaging (MRI) and subsequently normal neurodevelopment at 2 and 7 years of age. STUDY DESIGN: A two-channel aEEG recording was obtained on days 4, 7, 14 and 28 of life for infants born ⩽30 weeks estimated gestational age. Measures of amplitude and continuity, spectral edge frequency, percentage of trace in interburst interval (IBI), IBI length and frequency counts of smooth delta waves, delta brushes and theta bursts were obtained. MRI was obtained at term-equivalent age and neurodevelopmental testing was conducted at 2 and 7 years of corrected age. RESULT: Correlations were found between increasing postmenstrual age (PMA) and decreasing maximum amplitude (R= -0.23, P=0.05), increasing minimum amplitude (R=0.46, P=0.002) and increasing spectral edge frequency (R=0.78, P=4.17 × 10(-14)). Negative correlations were noted between increasing PMA and counts of smooth delta waves (R= -0.39, P=0.001), delta brushes (R= -0.37, P=0.003) and theta bursts (R= -0.61, P=5.66 × 10(-8)). Increasing PMA was also associated with a decreased amount of time spent in the IBI (R= -0.38, P=0.001) and a shorter length of the maximum IBI (R= -0.27, P=0.03). CONCLUSION: This analysis supports a strong correlation between quantitatively determined aEEG measures and PMA, in a cohort of preterm infants with normal term-equivalent age neuroimaging and neurodevelopmental outcomes at 7 years of age, which is both predictable and reproducible. These 'normative' quantitative values support the pattern of maturation previously identified by qualitative analysis.

Elastofibromatous polyp of the sigmoid colon--a case report and review of gastrointestinal elastofibromas.

Elastofibromatous change in the gastrointestinal tract is a rarely reported, usually polypoid lesion of unknown etiology with submucosal stromal change that may mimic amyloid deposition. The constituent amorphous material of the polyp stroma has distinctive features that permit an accurate assessment and diagnosis including: distribution of the material predominantly in the submucosa; distinctive fibrillar and granular appearance of the deposits; thick, irregular, haphazardly arranged bundles of elastic fibres positive for Verhoeff's elastic stain; ultrastructural fibres with an electron dense curvilinear or beaded appearance; lack of amyloid type vascular wall deposits; and lack of amyloid congophilia or crystal violet metachromasia. The clinical, light microscopic, histochemical and ultrastructural characteristics of this deposited material are reviewed in detail in the present report of a patient who presented with an asymptomatic polypoid lesion of the sigmoid colon. Other reported cases are summarized, and their clinical and pathological features are compared with the current case.

Angiogenic polypoid proliferation adjacent to ileal carcinoid tumors: a nonspecific finding related to mucosal prolapse.

Case reports have highlighted angiogenic polypoid proliferation in the mucosa adjacent to ileal carcinoid tumors, describing them as granulation tissue polyposis and florid angiogenesis. Some authors have proposed that the ileal carcinoid tumors themselves produce growth factors that cause the change. The purpose of this study was to determine the frequency of angiogenic polypoid proliferation in a large cohort of resected ileal carcinoid tumors compared with control groups. Search of the Cleveland Clinic and Summa Health System pathology files (1985 to 1999) yielded 65 resected ileal carcinoid tumors. Mucosal abnormalities adjacent to the ileal carcinoid tumors were graded 0 to 4+. Twenty ileal resection margins from colonic carcinoma cases served as normal controls. Ileal mucosa adjacent to 22 noncarcinoid neoplasms were also examined. The mucosa adjacent to 54/65 ileal carcinoid tumors (83%) showed mucosal abnormalities (vs. 3/20 normal controls), including mucosal edema, capillary ectasia, muscularis mucosae hypertrophy, fibrosis/smooth muscle proliferation within the lamina propria, club-shaped villi, and intramucosal capillary proliferation. Forty ileal carcinoid tumor cases (61%) showed some degree of angiogenic polypoid proliferation characterized by club-shaped villi and prominent intramucosal capillaries, with 17 (26%) graded as 3+ or 4+. Angiogenic polypoid proliferation was associated with hypertrophy of the muscularis mucosae, lamina proprial fibrosis/smooth muscle proliferation, and capillary ectasia similar to that described with gastrointestinal mucosal trauma/prolapse. This trauma/prolapse change was identified in 45 cases (69%) and was graded 3+ or 4+ in 23 (35%). Seventeen (77%) of the noncarcinoid neoplasms showed trauma/prolapse changes, with 7 (32%) graded as 3+ or 4+. Angiogenic polypoid proliferation also correlated with trauma/prolapse change in the noncarcinoid neoplasm controls. Neither APP (P =.24) nor the prolapse changes (P =.33) were found to be statistically different between the two tumor groups. Angiogenic polypoid proliferation of the adjacent ileal mucosa is common in patients with ileal carcinoid tumors and with noncarcinoid neoplasms. Angiogenic polypoid proliferation almost invariably coexists with fibromuscular change and capillary ectasia within the lamina propria, suggesting that mucosal trauma/prolapse plays a role in the histogenesis. The association of angiogenic polypoid proliferation with a variety of different neoplasms makes it unlikely that the tumors themselves secrete growth factors.

Cytologic diagnosis of vaginal papillary squamotransitional cell carcinoma. A case report.

BACKGROUND: Papillary squamous and squamotransitional cell carcinomas of the cervix and vagina are infrequent morphologic variants of squamous cell carcinoma that may be underdiagnosed due to a bland histologic appearance. To our knowledge, this entity has not been previously detected by Pap smear evaluation. CASE: Vaginal wall pap smears were collected from a patient with a previous hysterectomy for microinvasive cervicovaginal squamous cell carcinoma and extensive carcinoma in situ. The smears were characterized by: (1) large, darkly staining, three-dimensional, branching, papillary epithelial fragments with prominent fibrovascular cores and lined with loosely cohesive epithelial cells; (2) a highly cellular background population of dissociated single epithelial cells with features of severe dysplasia, including hyperchromatic, coarse chromatin; scant, delicate, frayed cytoplasm and karyorrhectic debris; (3) syncytial aggregates of severely dysplastic epithelial cells morphologically similar to the single cells; and (4) lack of a recognizable, morphologically distinct "transitional cell" population. CONCLUSION: Papillary squamotransitional cell carcinoma of the vagina is a rare morphologic variant of squamous cell carcinoma that should be distinguished from benign vaginal squamous papillomas, condylomatous lesions and verrucous carcinoma. However, this lesion is also related to human papillomavirus infection, particularly the high-risk types. Papillary squamotransitional cell carcinoma can be suspected on Pap smear when high grade squamous intraepithelial lesion features are found in combination with three-dimensional papillary tissue fragments with prominent fibrovascular cores.

Fine needle aspiration cytology of cellular hemangioma of infancy. A case report.

BACKGROUND: Cellular hemangioma is a common benign vascular neoplasm of infants and children. The lesion typically occurs within the superficial dermis, where it is recognized as a strawberry nevus. Occasionally, this neoplasm is situated within deep soft tissues of the head or neck, with a particular predilection for the parotid gland region. Fine needle aspiration cytology (FNAC) of cellular hemangioma involving the parotid gland has been reported previously, but never confirmed by cytologic findings alone. We report the first case of infantile cellular hemangioma with sufficient characteristic cytologic features to be diagnosed by FNAC. CASE: A 3-month-old male presented with a rapidly enlarging, sensitive, solid, supraparotid mass. Ultrasound and computed tomography were performed but were nondiagnostic. Subsequent FNAC of the mass demonstrated a highly cellular specimen composed predominantly of elongated spindled cells arranged in three-dimensional coils and arcades. Immunohistochemistry demonstrated the endothelial origin of the spindled cells and confirmed the diagnosis of cellular hemangioma. CONCLUSION: Deeply situated cellular hemangiomas may pose a difficult diagnostic challenge to the clinician as well as to the radiologist. The infantile variant of this tumor enlarges rapidly, simulating an aggressive malignant tumor, and is occasionally accompanied by substantial compressive symptoms. Radiographic presentation of the lesion may be that of a solid tumor mass, unlike most other hemangiomas. Precise cytologic diagnosis of infantile cellular hemangioma can be rendered on aspirated material and is crucial in planning conservative medical treatment.

Pseudomembranous enteritis after proctocolectomy: report of a case.

Intestinal pseudomembrane formation, sometimes a manifestation of antibiotic-associated diarrheal illnesses, is typically limited to the colon but rarely may affect the small bowel. A 56-year-old female taking antibiotics, who had undergone proctocolectomy for idiopathic inflammatory bowel disease, presented with septic shock and hypotension. A partial small-bowel resection revealed extensive mucosal pseudomembranes, which were cultured positive for Clostridium difficile. Intestinal drainage contents from an ileostomy were enzyme immunoassay positive for C. difficile toxin A. Gross and histopathologic features of the small-bowel resection specimen were similar to those characteristic of pseudomembranous colitis. The patient was treated successfully with metronidazole. These findings suggest a reservoir for C. difficile also exists in the small intestine and that conditions for enhanced mucosal susceptibility to C. difficile overgrowth may occur in the small-bowel environment of antibiotic-treated patients after colectomy. Pseudomembranous enteritis should be a consideration in those patients who present with purulent ostomy drainage, abdominal pain, fever, leukocytosis, or symptoms of septic shock.

Collagenous gastritis: a case report, morphologic evaluation, and review.

Collagenous gastritis is rare; there are only four previous case reports. Histologic features seem to overlap with the other "collagenous enterocolitides"; however, pathologic criteria are not yet established for the diagnosis of collagenous gastritis. We describe an additional case of ostensible collagenous gastritis in a patient who initially presented with celiac sprue and subsequently developed colonic manifestations of mucosal ulcerative colitis. Endoscopic biopsies of the stomach revealed deposition of patchy, very thick bandlike subepithelial collagen in gastric antral mucosa, focal superficial epithelial degeneration, numerous intraepithelial lymphocytes, and a dense lamina propria lymphoplasmacytic infiltrate. Image analysis evaluation of gastric antral biopsies demonstrated a mean thickness of subepithelial collagen of 27.07 micron. Morphologic comparison was made with age-matched control groups of 10 patients who had normal gastric mucosal biopsies and 10 patients who had "chronic" gastritis, which revealed mean subepithelial collagen measures of 1.37 micron and 1.19 micron, respectively. We compared these morphologic findings with those of all previous case reports of collagenous gastritis and propose a pathologic definition based on the limited combined data. It seems that subepithelial collagen is dramatically thickened in reported cases of collagenous gastritis, with a cumulative mean measure of 36.9 micron. It is also apparent from this and previous reports that the thickened subepithelial collagen is accompanied by a chronic or chronic active gastritis and sometimes intraepithelial lymphocytes and surface epithelial damage. Recently described associations of lymphocytic gastritis, sprue, and lymphocytic colitis as well as collagenous and lymphocytic colitis suggest a common pathogenesis that empirically may include collagenous gastritis in the same disease spectrum. We propose that collagenous gastritis can be confidently identified by using analogous defined features of collagenous colitis: subepithelial collagen more than 10 micron in a patchy distribution, lamina propria lymphoplasmacytic infiltrates, intraepithelial lymphocytes, and surface epithelial damage. Collagenous gastritis also seems to have the same spectrum of associated clinical findings as collagenous colitis, including frequent coexistence of celiac sprue, watery diarrhea syndrome, and female predominance.

Synchronous occurrence of collagenous colitis and pseudomembranous colitis.

Synchronous collagenous and pseudomembranous colitis has not been previously reported. A 73-year-old woman presented with chronic watery diarrhea and abdominal cramping of six weeks' duration. Biopsies of the colon revealed findings of collagenous colitis involving the endoscopically normal right colon, and superimposed collagenous and pseudomembranous colitis involving the rectosigmoid colon. Endoscopically, the left colon revealed discrete ulcerative plaques, and Clostridium difficile toxin A assay was positive. The patient partially responded to a three-week regimen of metronidazole, and symptoms resolved completely with subsequent steroid therapy. At follow-up endoscopy four months later, colon biopsies demonstrated persistence of subepithelial collagen but no pseudomembranes. The patient remained asymptomatic during this interval. Collagenous colitis has been reported in association with other inflammatory bowel diseases, including lymphocytic colitis, sprue and idiopathic inflammatory bowel disease. This unique association of collagenous colitis with an endotoxigenic inflammatory bowel disease is presented with a review of related disease features.

Carcinoid-related angiomatous polyposis simulating Crohn disease.

Polyposis associated with ileal carcinoid tumors is a rarely described pathologic mucosal transformation that may simulate inflammatory or neoplastic polyps. We describe a case with innumerable sessile polyps and groups of large filiform-like polyps of the terminal ileum associated with submucosal carcinoid tumors and a large mesenteric carcinoid tumor mass. The clinical, radiographic, and endoscopic presentation of the polyposis, together with the presence of multiple small bowel stenotic lesions, simulated Crohn disease. We propose the descriptive terminology angiomatous polyposis to describe the striking microscopic vascular proliferation that characterizes these polyps. The distribution of these lesions, with the most profuse polyposis in the immediate proximity of the carcinoid nests, and the immunohistochemical demonstration of growth factor substances, such as transforming growth factor alpha within neoplastic cells and adjacent polyps, suggest a tumor factor-mediated stromal proliferation.

Fine-needle aspiration biopsy of postradiation epithelioid angiosarcoma of breast.

Angiosarcoma of breast skin and parenchyma is a rarely reported complication of irradiation for breast carcinoma. We report a case of a subareolar epithelioid angiosarcoma arising 8 years subsequent to lumpectomy and irradiation of the ipsilateral breast for infiltrating carcinoma. The epithelioid appearance of the neoplastic cells on fine-needle aspiration biopsy (FNA) biopsy suggested a recurrence of the primary carcinoma. Careful attention to certain cytomorphologic features and cell block immunohistochemistry were useful in the distinction from recurrent carcinoma. Cytologic features that identified this neoplasm as an angiosarcoma included marked cell discohesiveness, elongate cytoplasmic processes or "pseudopodia," heterogeneous cell size, large nucleoli or macronucleoli, and cytoplasmic lumina. Immunohistochemical markers, including Factor VIII antigen, CD31, and CD34, were positive, confirming the vascular nature of the neoplasm. Other markers ruled out morphologically similar neoplasms such as recurrent carcinoma and melanoma. Epithelioid angiosarcoma should be included in the differential diagnosis of a suspected recurrence of breast carcinoma several years postirradiation therapy. Diagn. Cytopathol. 2000;22:172-175.