Hamartomas In Patients Research Articles

S1571 Device-Assisted Enteroscopy (DAE) in the Surveillance of Intestinal Polyposis in Peutz-Jeghers Syndrome

Introduction: Peutz-Jeghers Syndrome (PJS) is an autosomal dominant, genetic disorder characterized by the formation of hamartomatous polyps in the gastrointestinal tract. These polyps are a source of significant morbidity and mortality in this population due to associated complications of intestinal obstruction, bleeding, and malignant transformation. Surveillance of intestinal polyposis in patients with PJS has not been extensively studied, although centers which perform a significant volume of device-assisted enteroscopies (DAEs) encounter multiple cases each year. With the progressive adoption of DAE, examination of the deep small bowel for monitoring and prophylactic polypectomy has the potential to prevent complications of PJS and minimize the need for repeated laparotomy. Methods: After obtaining IRB approval, electronic health records were used to identify all DAEs performed on patients with PJS at 3 US referral centers (LSU, Duke, and UMass) between January 1, 2007 and January 1, 2020. Electronic medical records were reviewed to collect and analyze multiple data points. Primary endpoints included the complications associated with DAE performed for removal of intestinal hamartomas and the rate of laparotomy in PJS patients prior to and after index DAE. Secondary data points included patient characteristics, procedural details, and size/location/distribution of small bowel hamartomas. Results: Twenty-four patients met our inclusion criteria. Of these, 18 (75%) had previously undergone small bowel surgery for complications related to small bowel hamartomas. Between 2007 - 2020, a total of 46 DAEs were performed in these patients with an average of one surveillance exam every 2.5 years. A total of 131 polypectomies were performed during our study period with an observed complication rate of 1.5%, including one bowel perforation requiring surgery. Only one patient underwent surgery related to small bowel hamartomas following initial DAE surveillance exam over a total of 366 years of aggregated follow-up (Figure). Conclusion: Endoscopic management of small bowel polyps in patients with PJS using DAE is an effective strategy for prophylactic removal of hamartomas. DAE surveillance and endoscopic polypectomy is safe and may decrease the need for repeated laparotomy due to complications from intestinal hamartomas in patients with PJS.Figure 1.: Hamartomatous polyp in the ileum removed with saline injection-lift technique and hot snare polypectomy

1492 Sporadic Colonic Hamartoma in an Adult Patient: A Rare Finding

INTRODUCTION: Colonic hamartomas are non-neoplastic polypoid lesions that are rare in adults and most commonly encountered in children between the age of 1 and 7 years. They are histologically characterized by cystic dilation of mucus-filled glands, prominent bands of fibrous stroma, and a rich vascular network. Hamartomatous polyps are often diagnosed during endoscopy and require histological identification. CASE DESCRIPTION/METHODS: A 43-year-old male was referred due to intermittent rectal bleeding and positive fecal occult blood test (FOBT). He did endorse a positive family history of colon cancer in his mother. Colonoscopy was performed, revealing: 3 small sessile polyps <3 mm in size and a single 2 cm pedunculated polyp in the sigmoid colon (Figure 1). Polypectomy was performed for each noted polyp. Histopathological examination of the sigmoid polyp revealed a benign hamartomatous polyp with cystic dilation and focal crypt abscess (Figure 2). Pathology of rest of polyps revealed benign colonic mucosa with mild non-specific inflammation. The patient did well and remained symptom-free on follow up visit. DISCUSSION: Hamartomatous polyps are characterized by disorganized growth of tissue native to the organ in which it occurs. The reported prevalence of hamartomatous polyps in the adult population is around 0.15%. The prevalence of hamartomas in patients with colon polyps at index colonoscopy is 0.073%. Colonic hamartomas can occur sporadically or may present with distinct syndromic and hereditary features. The syndromes commonly associated with hamartomatous polyps are Peutz–Jeghers syndrome (PJS), juvenile polyposis, and phosphatase and tensin homolog (PTEN) hamartoma syndrome (PTHS). Endoscopically, these polyps can appear as pedunculated or sessile lesions making them indistinguishable from adenomatous polyps, which makes it prudent for the endoscopist to remove these lesions for histologic examination. In pediatric patients, hamartomas usually are localized to the rectum, the left colon, and may cause rectal bleeding, abdominal pain, and transanal prolapse. In adults, colonic hamartomas are most frequently found in the left colon and the rectosigmoid region. Patients are most commonly referred for colonoscopy due to positive FOBT or rectal bleeding. It is important to distinguish sporadic polyps from syndromic polyps as the sporadic polyps generally have a relatively benign course, while those associated with a syndrome have a higher lifetime malignancy risk.

Treatment of Renal Angiomyolipoma and Other Hamartomas in Patients with Tuberous Sclerosis Complex.

Tuberous sclerosis complex is an autosomal dominant genetic disease characterized by growth of benign tumors (hamartomas) in multiple organs, especially the kidneys, brain, heart, lungs, and skin. Tuberous sclerosis complex is usually caused by a mutation in either the tuberous sclerosis complex 1 or tuberous sclerosis complex 2 gene, resulting in constitutive activation of mammalian target of rapamycin signaling. Currently, mammalian target of rapamycin inhibitors are recommended in adult patients with tuberous sclerosis complex for the treatment of asymptomatic, growing renal angiomyolipoma that are >3 cm in diameter and pediatric or adult patients with brain lesions (subependymal giant cell astrocytoma) that either are growing or are not amenable to surgical resection. Clinical evidence suggests that systemic administration of a mammalian target of rapamycin inhibitor may provide concurrent improvements in multiple lesions and symptoms of tuberous sclerosis complex. With the major paradigm shift in consensus guidelines toward screening at diagnosis and ongoing monitoring and with the recent availability of an effective oral treatment, it is important that nephrologists have a thorough understanding of our role in the management of patients with tuberous sclerosis complex. Because the various manifestations of tuberous sclerosis complex typically emerge at different periods during patients' lifetimes, patients will need to be followed throughout their lives. Unlike brain and cardiac lesions, renal lesions are more likely to emerge as patients age and can grow at any time. Considerations regarding long-term medication administration for the potential control of multiple tuberous sclerosis complex manifestations will need to be addressed; these include the most appropriate starting dose, appropriate doses for tumor shrinkage versus prevention of regrowth, and management of adverse events. Best practices and potential obstacles for nephrologists treating patients with tuberous sclerosis complex who have multiple manifestations are considered.

Comparison of Color Fundus Photography, Infrared Fundus Photography, and Optical Coherence Tomography in Detecting Retinal Hamartoma in Patients with Tuberous Sclerosis Complex.

Background:A sensitive method is required to detect retinal hamartomas in patients with tuberous sclerosis complex (TSC). The aim of the present study was to compare the color fundus photography, infrared imaging (IFG), and optical coherence tomography (OCT) in the detection rate of retinal hamartoma in patients with TSC.Methods:This study included 11 patients (22 eyes) with TSC, who underwent color fundus photography, IFG, and spectral-domain OCT to detect retinal hamartomas. TSC1 and TSC2 mutations were tested in eight patients.Results:The mean age of the 11 patients was 8.0 ± 2.1 years. The mean spherical equivalent was −0.55 ± 1.42 D by autorefraction with cycloplegia. In 11 patients (22 eyes), OCT, infrared fundus photography, and color fundus photography revealed 26, 18, and 9 hamartomas, respectively. The predominant hamartoma was type I (55.6%). All the hamartomas that detected by color fundus photography or IFG can be detected by OCT.Conclusion:Among the methods of color fundus photography, IFG, and OCT, the OCT has higher detection rate for retinal hamartoma in TSC patients; therefore, OCT might be promising for the clinical diagnosis of TSC.

Multifocal retinal astrocytic hamartomas: a case series and review of the literature.

Retinal astrocytic hamartoma is a benign glial tumor found in the nerve fiber layer, and it is most commonly reported as a solitary lesion. Multiple or bilateral lesions may be indicative of systemic disease, such as tuberous sclerosis complex or neurofibromatosis 1. We present three unique cases of multifocal and bilateral retinal astrocytic hamartomas in patients with suspected tuberous sclerosis complex. The typical features, diagnosis, management, and systemic implications of these retinal lesions are discussed. Consecutive case series at a university-based ophthalmology clinic. The age of the patients ranged from 9 years to 27 years. The patients came from different ethnic backgrounds and had no known family history of tuberous sclerosis complex or neurofibromatosis. Two of the three patients had asthma, along with brain and kidney tumors. Two of the three patients had a seizure disorder, and one of the three patients had mental retardation. Only one patient presented with an ocular complaint of decreased vision, as a result of a presumed unrelated process. All patients had bilateral and multifocal astrocytic hamartomas. Multifocal retinal astrocytic hamartomas are unique and can be the first manifestation of a systemic disease such as tuberous sclerosis complex or neurofibromatosis 1. Prompt referral for imaging and workup with the appropriate medical subspecialty can help prevent or delay the morbidity related to these systemic conditions.

Folliculocystic and collagen hamartoma of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by tumors and hamartomas in several organs including the skin. We sought to describe a new type of complex hamartoma in patients with TSC. This was a retrospective clinical and histopathologic evaluation of 6 cases. The skin lesions consisted of large, painless, infiltrated plaques that were first noticed at birth or during early infancy on the abdomen, thigh, back, or scalp. In time, the plaques became studded with numerous follicular comedo-like openings and cysts containing and draining a keratinous or purulent material. The main histopathologic features were: abundant collagen deposition in the dermis and extending into the underlying fat; concentric, perifollicular fibrosis surrounding hair follicles; and comedones and keratin-containing cysts lined by infundibular epithelium, some of which were ruptured with secondary granulomatous reaction. Five of the 6 patients had a clinical diagnosis of TSC. Genetic testing was performed in only one patient. This distinctive folliculocystic and collagen hamartoma has not been recognized previously in association with TSC.

Surgical management of hypothalamic hamartomas in patients with gelastic epilepsy

Gelastic epilepsy (GE) associated with hypothalamic hamartomas (HHs) is now a well-characterized clinical syndrome consisting of gelastic seizures starting in infancy, medically refractory seizures with or without the development of multiple seizure types, and behavioral and cognitive decline. It has been postulated that the development of the HH-GE syndrome is a result of a progressive epileptic encephalopathy or secondary epileptogenesis, which is potentially reversible with treatment of the HH. A variety of surgical options for the treatment of HHs exist, including open and endoscopic procedures, radiosurgery, interstitial radiotherapy, and stereotactic radiofrequency thermocoagulation. Surgical treatment can result in seizure freedom in up to 50% of patients and can be accompanied by significant improvements in behavior, cognition, and quality of life. Partial treatment of HHs may be sufficient to reduce seizure frequency and improve behavior and quality of life with less risk. A component of reversible cognitive dysfunction may be present in some patients with an HH-GE syndrome.

Possible mechanisms of disease development in tuberous sclerosis

The two-hit hypothesis presented by Knudson in 1971 explains the development of tumours deficient in anti-oncogenes. Hamartomas in patients with tuberous sclerosis usually fit into this model, the first hit is a congenital lesion of either of the tuberous sclerosis genes (TSC1 or TSC2), and the second hit is loss of heterozygosity of this gene. Although this mechanism is true for most tumours associated with tuberous sclerosis, only 30-60% of brain and cardiac tumours show loss of heterozygosity--the remaining tumours develop despite the presence of an intact allele. Tumours in which loss of heterozygosity is rare, such as subependymal giant-cell astrocytoma, might all share a common feature that mimics loss of heterozygosity either by inactivation of the TSC complex or by direct activation of mammalian target of rapamycin (mTOR) or its downstream targets. Because phosphorylation of the TSC complex can inactivate it, expression and activation patterns of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), two potent protein kinases that are activators of the mTOR pathway, have been implicated. AKT activation is detected only in few samples, whereas ERK is hyperactive in all subependymal giant-cell astrocytomas. We postulate that ERK activation consistently detected in different tuberous-sclerosis-associated tumours is a molecular trigger for the development of these neoplasms.

Endoscopic Resection of Nonadenomatous Ampullary Neoplasms

The safety and effectiveness of endoscopic management of ampullary adenomas is well known. However, data on the endoscopic treatment and long-term outcome of nonadenomatous ampullary neoplasms are lacking. We describe our experience with the endoscopic management and the follow-up of 4 patients with nonadenomatous ampullary neoplasms viz, ampullary carcinoid, gangliocytic paraganglioma, ampullary hamartoma in patients with Peutz-Jegher syndrome and Cowdens syndrome.

Assessment of cognitive functions before and after stereotactic interstitial radiosurgery of hypothalamic hamartomas in patients with gelastic seizures

We assessed cognitive functions before and 3 months after interstitial radiotherapy in 14 patients with gelastic seizures caused by hypothalamic hamartoma. Cognitive functioning was assessed before temporary implantation of 125I-seed and 3 months after seed explantation. Performance was compared with that of a selected control group of conservatively treated patients with symptomatic focal epilepsy tested before add-on treatment with a new antiepileptic drug and after reaching steady state. No short-term negative side effects of the interstitial radiosurgery could be observed for the domains of attention and executive functions and verbal and figural memory performance. Cognitive development of the patients treated with seeds was comparable to that of the control group at both assessments. Thus, the stereotactic implantation of 125I-seeds in this patient group with gelastic seizures caused by hypothalamic hamartoma provides a well-tolerated minimally invasive method in the treatment of this severe epileptic syndrome without negative cognitive side effects.

Sporadic colonic hamartomas in adults: a retrospective study

Colonic hamartomas are uncommon in adults. The aims of this study were to determine (1) the prevalence of colonic hamartomas in an adult population undergoing colonoscopy and (2) the clinical, endoscopic, and histologic features of colonic hamartomas in adult patients. A pathology database identified 19 adult patients of 12,707 patients with colonic hamartomas in the 11-year study period from January 1992 to October 2002. An endoscopic computer database provided information about the number of colonoscopies performed and the presence or the absence of colonic polyp(s) in study patients. Charts of patients with colonic hamartomas were reviewed, and clinical and demographic data were collated. Nineteen patients were found to have colonic hamartomas. The mean age of these patients was 55 years, with an age distribution ranging from 25 to 81 years. The prevalence of colonic hamartomas in this study population was 0.15%. The prevalence of hamartomas in patients with colon polyps at index colonoscopy was 0.073%. Colonic hamartomas were more common in men than in women. The indication for colonoscopy for the majority (68%) of patients was hematochezia or the presence of occult blood in the stool. Three fourths of the polyps were greater than 1 cm in diameter, and 89% were pedunculated. Two thirds of the hamartomatous polyps were localized to the rectosigmoid region. Endoscopic characteristics of hamartomas were indistinguishable from adenomas. Colonic hamartomas in adults are rare. They tend to be single, pedunculated, and localized predominantly in the rectosigmoid region. Endoscopic resection of colonic hamartomas was successful in all patients.

Nasal Chondromesenchymal Hamartoma in Older Children and Adults: Series and Immunohistochemical Analysis

Nasal chondromesenchymal hamartoma is a benign mass lesion of the nasal cavity predominantly described in young infants. These unusual lesions are composed of a proliferation of mesenchymal and cartilaginous elements. Their pathogenesis is unknown, but they may be derived from embryologic rests. To our knowledge, only 1 case in an older child has been reported, and no cases have been reported in adults. To report 4 cases of nasal chondromesenchymal hamartoma occurring in older children and adults, including immunohistochemical analysis of these unusual lesions. Cases identified from our archives were examined to confirm the diagnosis of nasal chondromesenchymal hamartoma. Immunohistochemical analysis was performed using a panel of antibodies (epithelial membrane antigen, smooth muscle actin, all muscle actin, cytokeratin, S100, and KP1) to evaluate for epithelial, smooth muscle, neural, chondroid, and histiocytic differentiation. Four cases of nasal chondromesenchymal hamartoma in patients of 11, 69, 17, and 25 years of age demonstrated histologic evidence of mesenchymal and cartilaginous elements underlying a chronically inflamed respiratory mucosa. Bony and adipose elements and rare glandular elements were interspersed. Cartilaginous elements stained strongly with S100, whereas mesenchymal regions showed variable and weaker staining. Smooth muscle differentiation was seen primarily in the mesenchymal areas. Epithelial membrane antigen was focally positive in all cases. Nasal chondromesenchymal hamartomas can rarely occur in the older child and adult. Mesenchymal areas show both myofibroblastic and cartilaginous differentiation. We speculate that inflammation or a recapitulation of developmental signals may be components in the pathogenesis of these lesions.

Transcallosal resection of hypothalamic hamartomas in patients with intractable epilepsy

ABSTRACT A variety of surgical treatments for intractable epilepsy with hypothalamic hamartoma (HH) are described, although most are derived from limited patient experience gathered from several centres. We describe the results of transcallosal resection of HH in 29 consecutive patients undergoing surgery at one centre. Twenty‐nine patients aged 4‐23 years (mean 10 years) underwent HH surgery with a minimum of 12 months follow‐up. A comprehensive, presurgical epilepsy evaluation, supplemented with endocrine and ophthalmological assessments was performed in all cases. HH were resected via a transcallosal, interforniceal approach to the third ventricle, with the assistance of frameless stereotaxy, limiting the resection to the margins of the third ventricular walls and floor and minimising traction and diathermy. Complete or near‐complete (> 95%) resection of the HH was achieved in 18/29 patients, 75‐95% resection was achieved in seven patients (four of whom had complete or near‐complete disconnection of residual HH) and less than 50% resection was achieved in four. Postoperatively (follow‐up 12‐70 months, mean 30 months), 15 became seizure‐free (nine off antiepileptic medication), seven had > 90% reduction in seizure frequency, three had 55‐80% reduction in seizure frequency, and four had less than 40% reduction in seizure frequency. Of 16 patients who had seizures in the early postoperative period, six became seizure. No patient or lesion characteristics were associated with postoperative seizure freedom, including features of symptomatic generalised epilepsy. Neurobehavioural improvement and resolution of EEG abnormalities were seen in the majority. Complications were transient hemiparesis in two, transient hypernatraemia in 17, short‐term memory impairment in 14 (persistent in four), weight gain in ten (persistent in five), need for supplemental thyroxine in five, and lowered growth hormone (uncertain clinical significance) in six. Transcallosal resection of HH is an effective treatment for intractable epilepsy, with 76% patients in our seizures being seizure‐free or having > 90% seizure reduction. The operative risks include stroke, short‐term memory disturbance, weight gain and minor endocrine disturbances. Based on published data, the transcallosal approach appears to be safer and more effective than other operative strategies.

Long-term Observation of Retinal Lesions in Tuberous Sclerosis

To obtain long-term photographic follow-up of retinal astrocytic hamartomas in patients with tuberous sclerosis to learn about their stability or possible growth patterns. Sixteen patients with a confirmed diagnosis of tuberous sclerosis and in whom retinal astrocytic hamartomas were photographed before 1986 at the Mayo Clinic underwent a complete ophthalmic examination, and fundus photographs were taken. The new photographs were compared with previous photographs, and changes in size, character, or number of retinal hamartomas were determined. The minimum follow-up period was five years. A total of 37 astrocytic hamartomas were found. Follow-up ranged from almost six years to more than 34 years, with an average of 16 years. Hamartomas in three patients showed progressive or new calcification. In a fourth patient a retinal hamartoma appeared to originate from a site that had been previously photographically documented to be normal. The remaining hamartomas appeared unchanged over the follow-up period. Although most retinal lesions in tuberous sclerosis remain stable, some become calcified over time. Additionally, new lesions may develop from previously normal-appearing retina.