Langerhans cell histiocytosis (LCH) is caused by a clonal proliferation of Langerhans cells. The condition can present as solitary bone lesions or as a systemic disorder with a wide clinical spectrum. The gastrointestinal tract is usually involved as part of a generalized disease, and only occasional cases with isolated gastrointestinal involvement are reported. Bleeding may be the presenting gastrointestinal complaint in LCH, but the gastrointestinal signs and symptoms often are entirely nonspecific. An increased awareness of the various presentations and symptomatology of LCH may help with the earlier detection of this lesion in the absence of typical bone and cutaneous findings. We report a child with LCH that mainly involved the oral cavity and gastrointestinal tract, including the perianal skin. CASE REPORT A 3-year-old boy with a history of mouth ulcers, frequent oral blisters, and gingival hyperplasia for several weeks was referred for dental evaluation. He did not have any other symptoms, including fever, cough, dysuria, abdominal pain, joint pain, or blurring of vision. He had seborrheic dermatitis of the scalp, but no other rashes were present. He had experienced frequent ear infections and had undergone tympanostomy tube placement at the age of 14 months. He was not receiving medications and had no drug allergies. His weight and height were normal for age and his pulse, temperature, blood pressure, and respiratory rate were normal. Results of his physical examination were normal except for mouth ulcers and gingival hyperplasia. Laboratory evaluation revealed mild anemia with hemoglobin of 9.9 g/dL (normal, 11.5-13.5 g/dL), hematocrit of 32% (normal, 34-40%), a mean corpuscular volume (MCV) of 67.4 fL (normal, 75-87 fL), a white blood cell count of 3.7 × 103/mL (normal, 5-17 103/mL) with normal differential, a platelet count of 304 × 103/mL (normal, 156 × 103/mL-369 × 103/mL), an erythrocytic sedimentation rate of 20 mm/hour (normal, 0-13 mm/hour), a lactate dehydrogenase of 219 IU/L (normal, <170 IU/L), total serum protein concentration of 6.4 g/dL (normal, 6.0-8.0 g/dL), serum albumin concentration of 3.7 g/dL (normal, 3.8-5.4 g/dL), normal serum transaminase concentrations, and normal total and direct bilirubin concentration. He underwent a full mouth dental extraction for caries. Biopsy specimens were taken from the oral cavity, maxillary, mandibular, gingival, and palatal mucosae. The histopathology of the biopsy specimens showed large mucosal lesions with clusters of large cells with convoluted nuclei, which were strongly positive for CD1a in a membrane fashion. The abnormal cells and surrounding inflammatory response were seen extending into the underlying submucosal layer. A diagnosis of LCH was made. To rule out LCH involvement in other systems, a full skeletal survey was performed, and no bony lesions were found. He was registered as a low-risk patient on the LCH-II and was treated with prednisone and vinblastine. One month later, 6-mercaptopurine was added to the regimen. Three months after chemotherapy was started, he reported intermittent headaches, abdominal pain, and vomiting, all of which resolved without specific therapy. During the next 3 months, he continued to receive chemotherapy without complication. However, he continued to have erythema of the gums. Gingival biopsy specimen showed only granulation tissue, with no findings compatible with LCH. A computed tomography scan of the mandible was normal. Eight months later, chemotherapy was discontinued. He continued to be stable with no complaints and normal physical examination during his regular office visits with both the dentist and the hematologist. Four months later, he became constipated and because of increasing reports of pain upon defecation, he was referred for evaluation to the gastroenterology service. At the time of his evaluation in the gastroenterology clinic, he had a 4-month history of straining upon defecation and passing hard stools surrounded by bright red blood streaks without mucous. Review of systems revealed unremarkable results. Results of his physical examination also were unremarkable, except for cerumen in both ears, aphthous ulcers covering the dorsum of the tongue, and gingival erythema surrounding the right upper first premolar tooth. The liver and spleen were normal on palpation. There were three small perianal skin tags at the 2, 5, and 9 o' clock positions (patient supine) with a fissure at the 9 o' clock tag. The stool in the rectal vault was positive on guaiac testing. Laboratory investigations showed hemoglobin 10.4 g/dL, hematocrit 31.4%, MCV 72.4 fL, white blood cell count of 3.7 × 103/mL, neutrophils 86%, lymphocytes 13%, monocytes 1%, eosinophils 0%, platelets 282 × 103/mL, erythrocytic sedimentation rate of 15 mm/hour, total serum protein concentration 6.8 g/dL, serum albumin of 4.8 g/dL, SGOT 14 IU/L (normal, <40 IU/L), SGPT 5 IU/L (normal, <40 IU/L), total serum bilirubin concentration of 0.5 mg/dL (normal, 0.2-1.3 mg/dL), and direct bilirubin 0.1 mg/dL (normal, 0.0-0.3 mg/dL). Senna fruit extract, lactulose syrup, and enemas were tried, but the patient experienced no improvement. At a subsequent clinic visit, he was given polyethylene glycol 17 g/day. On his next clinic visit, his stools were reported to be softer, and the polyethylene glycol dose was decreased to 8.5 g/day. However, the patient continued to experience pain upon defecation and experienced periumbilical abdominal pain severe enough to awaken him at night. On physical examination, he had mild epigastric abdominal tenderness, and the perianal skin tags had become larger, with a more prominent fissure at the 9 o' clock tag. Esophagogastroduodenoscopy (EGD) and colonoscopy were performed. The EGD showed subepithelial hemorrhages and multiple superficial ulcerations in the gastric body. The mucosa of the esophagus and duodenum appeared normal. Colonoscopy revealed a large perianal skin tag extending into the anal verge (Fig. 1) and nodular hyperplasia or the mucosa of the colon and the terminal ileum. Directly after the endoscopic procedures, a biopsy of an ulcer of the mucosa of the right hard palate was obtained. Gastric biopsy specimens showed a proliferation of large cells with pale amphophilic cytoplasm and convoluted nuclei with some indentations, consistent with Langerhans cells. Scattered eosinophils were present. The infiltrate was located in the lamina propria and extended into the surface epithelium between the glands. A CD1a stain showed strong membrane reaction on these large cells consistent with Langerhans cells. Duodenal, esophageal, and colonic biopsy specimens showed no atypical cells, and CD1a stains of these tissues were negative. The biopsy taken from the perianal skin tag extending into the anal verge showed ulcerated squamous mucosa. The underlying submucosal tissue showed proliferating capillaries with mixed inflammatory infiltrate and a few larger cells with amphophilic cytoplasm, convoluted nucleus, and CD1a membrane staining consistent with Langerhans cells (Fig. 2). The hard palate tissue biopsy showed a similar infiltrate.FIG. 1: Large perianal skin tag.FIG. 2: High magnification showing large cells with convoluted and grooved nuclei (arrows) representing Langerhans cells in the infiltrate (stain, hematoxylin and eosin; original magnification, × 400).A chest x-ray and skeletal survey were normal. Because of disease recurrence, the patient was placed on daily prednisone, weekly vinblastine, and VP-16 for 6 weeks. He then received a maintenance regimen of daily 6-mercaptopurine, with vinblastine and VP-16 given at 3-week intervals. In less than a month, his symptoms of abdominal pain and dyschezia resolved, and there was complete involution of the perianal skin tag. Three months after the diagnosis was established, the patient continues to receive chemotherapy and has been clinically stable and symptom free. DISCUSSION We have presented a case of LCH that was treated, remitted but then recurred exclusively in the gastrointestinal tract with disease involving the gingiva, gastric body, and perianal region. We believe that the gastrointestinal involvement by LCH was the cause of the patient's symptoms. LCH is a systemic disorder that largely affects children, with an incidence of 1:200,000 to 1:350,000 (1). Langerhans cell histiocytosis, previously known as histiocytosis X, is a disease of varied clinical presentation, histologically characterized by accumulation of Langerhans cells along with lymphocytes, eosinophils, and macrophages. The histopathology of LCH has been extensively described (2,3). On light microscopic analysis, LCH is suggested by the presence of large mono-nucleated cells with abundant eosinophilic cytoplasm and "coffee bean" or convoluted nucleus. The gold standard of diagnosis of LCH has been the identification of the ultrastructural Birbeck or Langerhans cell granule. The Langerhans cells express CD1a and S100 protein, so the demonstration of CD1a by immunohistochemistry helps confirms the diagnosis. LCH occurs in a wide variety of clinical forms, affecting different systems and different sites in the same system with widely variable clinical outcomes (4). Gastrointestinal manifestations of LCH are quite unusual and varied. Vomiting (5), abdominal pain, constipation, intractable diarrhea (6), malabsorption (7), bloody stools (5), protein-losing enteropathy (5), and even intestinal perforation are some of the reported symptoms, all of which are common presentations for other gastrointestinal diseases, including inflammatory bowel disease. Egeler et al. (5) reported patients with LCH with gastrointestinal involvement, all younger than 1 year of age at presentation. Esophagogastroduodenoscopy showed superficial erosions and hemorrhagic ulcerations. There were a large number of histiocytes on biopsy specimens. Geissmann et al. (8) reviewed nine cases of LCH with digestive tract involvement that presented with skin and mucosal lesions, failure to thrive, diarrhea, bloody stools, vomiting, and/or hypoalbuminemia. Sites of gastrointestinal involvement were gingival, stomach, duodenum, jejunum, colon, rectum, or liver. None had stomach ulcerations. Although our patient presented with gastrointestinal symptoms and blood in the stools, the presence of perianal skin tags and fissures has not been described before. Despite the poor prognosis reported in other cases of LCH with gastrointestinal tract involvement, our patient experienced dramatic improvement with chemotherapy and experienced resolution of the gastrointestinal symptoms. It may be that early detection of LCH and the limited involvement in the gastrointestinal tract along with prompt chemotherapy favored a good response in this child. In conclusion, the gastrointestinal system may be the only system involved in LCH, either primary or recurrent. LCH should always be included in the differential diagnosis list for children with nonspecific gastrointestinal symptoms. In patients with documented LCH, a high index of suspicion for gastrointestinal involvement with CH should be maintained in the presence of common gastrointestinal symptoms such as abdominal pain and dyschezia. Gastrointestinal involvement with LCH may have a good response to chemotherapy, but the long-term prognosis is difficult to predict, especially in view of an observed rapid recurrence after cessation of chemotherapy.
In infants, hematochezia must be approached with a broad differential diagnosis, including anal fissure, allergic colitis, Meckel's diverticulum, intestinal malrotation, necrotizing enterocolitis, and less commonly arteriovenous malformations, gastrointestinal duplications, and hemangiomas. Infantile hemangiomas, the most common tumor of infancy, are typically cutaneous lesions. Those arising from viscera are much less common but can cause significant morbidity and mortality if not diagnosed early and managed appropriately. We present a 6-week-old male with recurrent hematochezia who was initially diagnosed with milk protein intolerance but ultimately found to have a diffuse intestinal hemangioma. He was treated with propranolol, methylprednisolone, and exclusively parenteral nutrition. Repeat imaging suggested the lesion responded to pharmacotherapy and the patient is tolerating enteral nutrition.
ABSTRACT Objectives: We sought to determine the reliability of morphometric measurements on infant esophageal biopsies using a light microscope with eyepiece micrometer. Methods: We measured epithelial thickness, basal layer thickness (B), papillary height (P) and epithelial lymphocyte and eosinophil numbers on ≈500 existing esophageal suction biopsies from infants previously evaluated for reflux esophagitis. We tested these measurements for interobserver, test‐retest and internal consistency reliability. Results: Infants ages 0.25 to 23.75 (median, 6.25) months provided 497 biopsies. Both investigators scoring the biopsies independently judged 93% of them scorable. Of the biopsies scored by both, the 2 readings were within 0.15 of each other for P in 97% and for B in 81%. In addition to these correlative measures of consistency, categoric measures demonstrated that 373 (89%) of the 420 scorable biopsies with visible papillae produced agreement as to P being abnormal (317, 85%) or normal (56, 15%). Similarly, 360 (78%) of the 463 scorable biopsies produced agreement as to B being abnormal (339, 94%) or normal (21, 6%). P values were 0.17 to 0.94 (median, 0.67), and B values were 0.13 to 0.91 (median, 0.34). Lymphocytes numbered 0 to 40 (median 5) per high‐power field. Only 12% had any eosinophils; none of those with completely normal morphometrics had any eosinophils; and only 2% had >5 eosinophils per high‐power field. Conclusions: Simple quantitative esophageal histological morphometric parameters are reliably measurable on suction biopsies from infants using a light microscope fitted with an ocular micrometer, even by nonpathologists.
Introduction: Successful strategy for bowel preparation (prep) for colonoscopy aims at administering small–volume oral cathartics coupled with restricted solid food intake. An effective, safe, and standardized bowel preparation in children that is easily administered and acceptable has not yet been determined for children undergoing colonoscopy. Methods: This study compared the efficacy and acceptability of oral sodium phosphate (NaP) regimen 1 day prior to the examination at 1 mL/kg/day with a maximum 90 mL (2/3 dose in the morning, a maximum 45 mL, the remainder in the evening) (regimen A) to our standard prep regimen magnesium citrate 4 mL/kg/day in the morning (maximum 240 mL) for 3 days prior to, and a NaP enema the morning of the colonoscopy (regimen B). Both groups were only allowed clear liquids on prep days and nothing by mouth after midnight. After informed consent, 45 children (22 females) were randomized. Weight, vital signs, electrolytes, calcium, phosphorus and magnesium were taken at screening and on the day of the colonoscopy. Questionnaires were given to the subjects to assess acceptability and 10 possible side effects with intensity rating at none, mild, moderate or severe. An endoscopist blinded to the medication rated the bowel prep on a 4-level scale of excellent, good, fair or poor for overall quality of the colon prep and within each of its 5 segments. Results: Median [range] age (yr) and weight (kg) at screening was 13 [9–17], 53 [27–88], and 15 [8–18], 51 [28–109] in A and B, respectively. Mean weight loss of 0.88 and 1.05, SD ± 1.04 kg for A and B, respectively was not significantly different between groups. The mean increase in serum magnesium (mEq/L) was −0.01 vs 0.14 (p=0.001), and the mean increase in serum phosphorus (mg/dL) was 0.40 vs 0.33 (p=NS) in A vs B, respectively. No statistically significant difference was observed in other electrolytes between both groups. There were no serious adverse events reported from both regimens. The side effects were not statistically significant between both regimens, apart from higher nausea intensity in regimen A (p=0.012). Bowel cleansing was similar between the groups; 71% were rated excellent or good. Willingness to repeat the prep was higher in A vs B (77% vs 32%, p<0.006). Ten subjects in regimen A had prior colonoscopies using regimen B; 9 rated A better, 1 rated A the same. Conclusion: Oral NaP is safe and effective for bowel cleansing prior to colonoscopy in children and adolescents. It has a shorter prep time, comparable side effects and is more acceptable than our standard magnesium citrate regimen.
The second oil cisis consttitued a new era in the financial evolution of the arab gulf countries. The large reserves in this region creates a substantial comparative advantage in the hydrocarbon sector. The revenues derived after this crisis enabled these states to industrialize rapidly and develop their economic infrastructure, the massive public spending however did not succeed in generating a healthy private sector. In fact the crash of the souk-al-manakh in kuwait in 1982 severly damaged priavte entrprise in the gulf countries. In the same year, several other important events occured such as the fall of oil prices in the spot market, the first iranian victory in the gulf war, the ressurgence of the islamic world and the deregulation of the international financial markets. The accumulated effect of these events has resulted in a serious challenge to the arab financial institution in the gulf region as well as around the world. The islamic financial institutions are trying to find their place amond the other financial intermediaries in the gulf. The importance of the oil revenues to the gulf states and the dramatic fall of oil prices since 1986 have motiveted me to begin this study of the future prospects of petrolum in the gulf region.
To the Editor: We thank Drs. Kader and Maller for directing us to their paper on a similar perianal presentation of Langerhans cell histiocytosis. It is true that the morphology of the perianal lesion appears similar, and we agree with the authors that such a finding should lead one to think of the possibility of Langerhans cell histiocytosis in children. Although the initial presentation of our patient was with three distinct perianal tags, the appearance of the confluent lesion with fissure formation was much later, after failure of supportive therapy. The aim of our paper was to highlight the fact that even early innocuous appearing skin tags in any location, including the perianal skin, in a patient with evidence of Langerhans cell histiocytosis elsewhere should alert the concerned physician to the possibility of skin involvement and high-risk disease. Gastrointestinal tract may be the sole site of initial involvement by Langerhans cell histiocytosis, but subsequent lesions may manifest in other sites including skin and bones. Mahmoud Sabri S. Ranganathan Department of Pathology Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania
'/%3e%3cpath d='m450 224.315-44.467 136.87 116.401-84.559h-143.87l116.403 84.559z' style='fill:none;stroke:%23006233;stroke-width:14.62993431;stroke-miterlimit:4;stroke-dasharray:none'/%3e%3c/svg%3e)