Mucosal Schwann Cell Hamartoma on Screening Colonoscopy: An Unusual Finding.

Schwann cells are found in the peripheral nervous system and can sometimes appear as benign hamartoma lesions in various parts of the body. Although rare in the gastrointestinal (GI) tract, they have been observed in the colon. Recently, mucosal Schwann cell hamartomas of the GI tract have been studied, and it was discovered that they had yet to be investigated up to 2009. In this context, we present the case of a 60-year-old man who was found to have lesions in the transverse colon during a routine colonoscopy. No further investigations were conducted since these lesions have not been associated with any risk of malignancy transformation and have not been linked to any inherited syndromes. LEARNING POINTS: Mucosal Schwann cell hamartomas are rare types of polyps that can be found anywhere in the gastrointestinal tract.They are benign lesions not usually associated with any inherited syndrome and they are usually found incidentally by endoscopy.These polyps are benign and might not require further follow-up once diagnosed.

Arterial embolization in the treatment of multiple renal and hepatic hamartomas with spontaneous hemorrhage and 2-year follow-up: a case report.

BACKGROUND: Hamartoma is a common benign tumor that usually occurs in the kidney, liver, lung, and pancreas. Large renal hamartomas may spontaneously rupture and hemorrhage, which is potentially life-threatening. CASE PRESENTATION: This report describes a 46-year-old Han Chinese female patient with multiple renal and hepatic hamartomas with rupture and hemorrhage of giant hamartoma in the left kidney. She underwent arterial embolization three times successively, and her condition was stable during the 2-year follow-up. This report includes a review of the relevant literature CONCLUSIONS: the findings in this report and previous literature suggest that arterial embolization can not only rapidly treat hamartoma hemorrhage in the acute phase but can also effectively control multiple lesions in the long term after repeated multisite arterial embolization.

Histologic correlates of "Choroidal abnormalities" in Neurofibromatosis type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder characterized by proliferation of cells from neural crest origin. The most common manifestations are cutaneous, neurologic, skeletal and ocular. The distinction of NF1 from other syndromes with multiple café-au-lait macules may be difficult in the pediatric age group, and ocular findings, especially Lisch nodules (i.e., melanocytic hamartomas on the irides), are a useful, early diagnostic tool. In recent years, novel ocular manifestations descriptively referred to as "choroidal abnormalities", choroidal "hyperpigmented spots" and "retinal vascular abnormalities" have been recognized in NF1. Choroidal abnormalities (CA) appear as bright patchy nodules that can be best detected with near-infrared ocular coherence tomography imaging (NIR-OCT). Because of their high specificity and sensitivity for NF1, CA have been added as an ocular diagnostic criterion of NF1 as an alternative to Lisch nodules. Although CA are important ocular diagnostic criteria for NF1, the histologic correlates are controversial. We present the postmortem ocular pathology findings of an NF1 patient for whom clinical notes and ocular imaging were available. Findings in this patient included choroidal hyperpigmented spots on funduscopy and retinal vascular abnormalities, both of which have been reported to be closely associated with CA. Histologic examination of the eyes showed multiple clusters of melanocytes of varying sizes in the choroid. Pathologic review of 12 additional postmortem eyes from 6 NF1 patients showed multiple, bilateral choroidal melanocytic aggregates in all eyes. These findings suggest that the CA seen on NIR-OCT and the hyperpigmented spots seen clinically in NF1 patients are manifestations of multifocal choroidal melanocytic clusters, consistent with choroidal melanocytic hamartomas. Lisch nodules, often multiple, were present in all eyes with morphology that differed from the choroidal hamartomas. As such, although CA and Lisch nodules are melanocytic hamartomas, there are clear phenotypical differences in their morphologies.

Advances in epileptic network findings of hypothalamic hamartomas.

Hypothalamic hamartomas (HHs) are congenital developmental malformations located in the hypothalamus. They are associated with a characteristic clinical manifestation known as gelastic seizures (GS). However, the traditional understanding of HHs has been limited, resulting in insufficient treatment options and high recurrence rates of seizures after surgery. This is consistent with the network hypothesis of focal epilepsy that the epileptogenic zone is not only limited to HH but may also involve the distant cerebral cortex external to the HH mass. The epilepsy network theory, on the other hand, provides a new perspective. In this study, we aim to explore HH-related epilepsy as a network disease, challenging the conventional notion of being a focal lesional disease. We analyze various aspects of HHs, including genes and signaling pathways, local circuits, the whole-brain level, phenotypical expression in terms of seizure semiology, and comorbidities. By examining HHs through the lens of network theory, we can enhance our understanding of the condition and potentially identify novel approaches for more effective management and treatment of epilepsy associated with HHs.

Hypothalamic hamartomas (HHs) are unusual brain malformations present from birth in the hypothalamus region. They often lead to a distinctive type of seizures known as GSs. However, our current understanding of HHs is limited, and this has made it challenging to treat them effectively. Many patients continue to experience seizures even after surgery. We've typically considered HH-related epilepsy as a localized problem, but a new theory suggests that it may involve a network of brain areas. In our study, we aim to change the way we view HH-related epilepsy. Instead of thinking of it as a single lesion in the brain, we explore the idea that it's a network disease. To do this, we'll investigate various aspects of HHs, such as the genes and pathways involved, how different parts of the brain interact, the impact on the whole brain, the types of seizures experienced, and any related health issues. By looking at HHs through this network theory, we hope to gain a deeper understanding of the condition and potentially discover new ways to manage and treat epilepsy associated with HHs. This shift in perspective could offer hope to those living with HH-related epilepsy and lead to more effective treatments, ultimately improving their quality of life.

Differentiation of Hamartomas and Malignant Lung Tumors in Single-Phased Dual-Energy Computed Tomography.

This study investigated the efficacy of single-phase dual-energy CT (DECT) in differentiating pulmonary hamartomas from malignant lung lesions using virtual non-contrast (VNC), iodine, and fat quantification. Forty-six patients with 47 pulmonary lesions (mean age: 65.2 ± 12.1 years; hamartomas-to-malignant lesions = 22:25; male: 67%) underwent portal venous DECT using histology, PET-CT and follow-up CTs as a reference. Quantitative parameters such as VNC, fat fraction, iodine density and CT mixed values were statistically analyzed. Significant differences were found in fat fractions (hamartomas: 48.9%; malignancies: 22.9%; p ≤ 0.0001) and VNC HU values (hamartomas: -20.5 HU; malignancies: 17.8 HU; p ≤ 0.0001), with hamartomas having higher fat content and lower VNC HU values than malignancies. CT mixed values also differed significantly (p ≤ 0.0001), but iodine density showed no significant differences. ROC analysis favored the fat fraction (AUC = 96.4%; sensitivity: 100%) over the VNC, CT mixed value and iodine density for differentiation. The study concludes that the DECT-based fat fraction is superior to the single-energy CT in differentiating between incidental pulmonary hamartomas and malignant lesions, while post-contrast iodine density is ineffective for differentiation.

Characteristics and onset of presentation of pediatric stiff skin syndrome: A retrospective cohort study of 11 patients in a tertiary care center.

BACKGROUND/OBJECTIVE: Stiff skin syndrome (SSS) is a rare disorder characterized by "rock hard" indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS. METHODS: This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies. RESULTS: A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI) and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site. CONCLUSION: The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions.

Multiple rhabdomyomatous mesenchymal hamartomas in a patient with mosaic Barber-Say syndrome.

Barber-Say syndrome (BSS) is a rare congenital ectodermal dysplasia with few cases reported in the literature. We describe a 9-year-old boy with congenital generalized hypertrichosis and multiple rhabdomyomatous mesenchymal hamartomas (RMHs) on his nose and periocular region. Next-generation sequencing, performed in DNA from a blood sample, and RMH tissue, revealed a pathogenic variant in the TWIST2 gene, which was not detected in a salivary sample of the patient, nor in his parents. Therefore, we consider this variant as de novo mosaicism. To our knowledge, this is the first case of multiple RMHs associated with BSS.

Biliary microhamartomas (von Meyenburg complexes), liver metastasis simulators: a series of eight cases.

BACKGROUND: Von Meyenburg complexes are benign hamartomatous lesions, they are part of the spectrum of ductal plate malformations. They are rare, reported in 0.35-5.6% of the general population, predominantly in adults, with no clear predilection for sex. OBJECTIVE: To present the clinical characteristics of Von Meyenburg complexes in our region. METHOD: We searched all cases with diagnosis of Von Meyenburg complexes in a period from 2012 to 2022, in our institutions. RESULTS: We identified eight cases, with an average age of 59.25 years, with a predominance of females and with one case associated with gastric carcinoma. CONCLUSIONS: It is important to adequately recognize this entity, since due to its multifocal nature it can easily simulate metastasis, additionally, and its presence does not rule out other synchronous neoplasms.

ANTECEDENTES: Los complejos de Von Meyenburg son lesiones hamartomatosas benignas que forman parte del espectro de las malformaciones de la placa ductal. Son poco frecuentes, se reportan en un 0.35-5.6% de la población general, predominantemente en adultos, sin clara predilección por un sexo. OBJETIVO: Presentar las características clínicas de los complejos de Von Meyenburg en nuestro medio. MÉTODO: Se buscaron todos los casos con diagnóstico de complejos de Von Meyenburg en nuestras instituciones entre 2012 y 2022. RESULTADOS: Identificamos ocho casos, con un promedio de edad de 59.25 años, con predominio por el sexo femenino y con un caso asociado a carcinoma gástrico. CONCLUSIONES: Es importante reconocer y diagnosticar adecuadamente esta afección, ya que por su naturaleza multifocal fácilmente puede simular metástasis, y además su presencia no descarta otros procesos neoplásicos sincrónicos.

Retinal hamartomas at different stages in a patient with tuberous sclerosis: A OCT-SS description.

Retinal astrocytic hamartoma (RAH) is a benign glial tumor that may be present in patients with tuberous sclerosis (TS), contributing to the diagnosis of this syndrome. While hamartomas identified through indirect ophthalmoscopy are often large enough to affect vessels and optic disc anatomy, RAH not detected in previous fundoscopies may become apparent in optical coherence tomography (OCT). The purpose of this report was to describe and characterize RAH with OCT with swept-source technology (OCT-SS), aiming to establish a more comprehensive classification for these hamartomas due to their diverse presentations. Fundus examination of a 11-year-old girl revealed retinal tumors in both eyes. OCT-SS confirmed the diagnosis of TS, revealing dome-shaped hyperreflective masses at different stages of evolution. Lesion 1: maximum thickness (MT) of 336 µm and ganglion cell layer disorganization. Lesion 2: MT of 438 µm and preserved outer plexiform layer. Lesion 3: posterior shadow, MT of 1478 µm and complete rupture of retinal anatomy. Lesion 4: MT of 342 µm and preserved retinal anatomy. OCT is a noninvasive method which assists the diagnosis of subclinical lesions and clinical characterization of TS patients.

Ophthalmic manifestations in children with tuberous sclerosis complex.

PURPOSE: To report on the ophthalmic findings in children with tuberous sclerosis complex (TSC) in southern Sweden, and to investigate the frequency of refractive errors, strabismus and cerebral visual impairment associated with this condition. METHODS: This was a retrospective cohort study including all paediatric patients with TSC in southern Sweden born between 1983 and 2020. Medical records were reviewed regarding retinal findings, visual acuity, refractive error, strabismus, full-field electroretinography results and cerebral visual impairment. RESULTS: Ophthalmological records were available for 50 of the 52 children in the region diagnosed with TSC. The mean age at the last visit was 12.4 (SD 7.2) years. Monocular visual acuity had been measured in 38 patients, and the median value did not deviate from that expected for their age in the better eye, but by -0.2 Snellen decimal acuity in the worse eye. Refractive errors were found in 62% of the patients, and strabismus in 16%. Retinal astrocytic hamartomas were found in 34% and achromatic patches in 34%. Ten of the patients on medication with vigabatrin were examined with full-field electroretinography and treatment had to be stopped or lowered in three (30%), due to a reduced response. Investigation of cerebral visual impairment had not been conducted in any of the children. CONCLUSION: Refractive errors and strabismus were common among children with TSC. None of the patients in this cohort had undergone investigation for cerebral visual impairment. The general awareness of cerebral visual impairment among ophthalmologists is poor and constitutes an important area for improvement.

An Adult With Undifferentiated Embryonal Sarcoma of the Liver: A Case Report of a Rare Encounter.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare, aggressive tumor mainly found in children but can also appear in adults. Its diagnosis in adults remains a conundrum; it is often identified late due to its non-specific symptoms and resemblance to benign lesions. A comprehensive treatment regimen involving surgical intervention, chemotherapy, and possibly radiation significantly boosts survival rates. Imaging often yields inconclusive outcomes, further complicating the diagnostic process. Here, we report the case of a 28-year-old female diagnosed with UESL, emphasizing the need for timely intervention. Undifferentiated embryonal sarcoma of the liver requires differentiation from a variety of hepatic tumors in adults. Though there are no distinctive characteristics to differentiate UESL from other hepatic masses, its morphology and immunohistochemical profiles significantly vary. The staging often reveals UESL as a large, well-defined mass with the potential for diverse differentiation. Its prognosis has been considerably improved with the advent of multidisciplinary treatment. Surgical resection remains a cornerstone, often combined with chemotherapy. While pediatric cases exhibit better overall survival rates than adults, outcomes heavily depend on the chosen treatment regimen. A combination of chemotherapy and complete tumor removal has been found to significantly elevate survival chances. Disease recurrence remains a challenge and is influenced by treatment strategy. In conclusion, the diagnosis and treatment of UESL are fraught with challenges, particularly in adults. A multidimensional approach, combining various therapies, is paramount for better outcomes. Continuous research and enhanced awareness are crucial for improving diagnostic precision and treatment outcomes for UESL patients.

A New Frameshift Mutation of PTEN Gene Associated with Cowden Syndrome-Case Report and Brief Review of the Literature.

Cowden syndrome (CS) is a rare disease that was first described in 1963 and later included in the large group of genodermatoses. It is the most common syndrome among the PTEN-associated hamartomatous tumor syndromes (PHTS). CS has an autosomal dominant inheritance pattern, with increased penetrance and variable expressivity, making early diagnosis difficult. Mutations in the PTEN gene (phosphatase and TENsin homolog) are involved in its pathogenesis, involving many organs and systems originating in the three embryonic layers (ectodermum, endodermum, and mesodermum). The consequence is the development of hamartomatous lesions in various organs (brain, intestines, thyroid, oropharyngeal cavity, colon, rectum, etc.). Multiple intestinal polyps are common in patients with CS, being identified in over 95% of patients undergoing colonoscopy. The authors describe the case of a patient who presented the first signs of the disease at 3 ½ years (tonsil polyp) but was diagnosed only at the age of 20 following a colonoscopy that revealed hundreds of intestinal polyps, suggesting further molecular testing. A heterozygous frameshift mutation was identified in the PTEN gene, classified as a potentially pathogenic variant (c.762del.p(Val255*)). The authors present this case to highlight the path taken by the patient from the first symptoms to the diagnosis and to emphasize the clinical aspects of this mutational variant that have still not been identified in other patients with this syndrome.

Best imaging signs identified by radiomics could outperform the model: application to differentiating lung carcinoid tumors from atypical hamartomas.

OBJECTIVES: Lung carcinoids and atypical hamartomas may be difficult to differentiate but require different treatment. The aim was to differentiate these tumors using contrast-enhanced CT semantic and radiomics criteria. METHODS: Between November 2009 and June 2020, consecutives patient operated for hamartomas or carcinoids with contrast-enhanced chest-CT were retrospectively reviewed. Semantic criteria were recorded and radiomics features were extracted from 3D segmentations using Pyradiomics. Reproducible and non-redundant radiomics features were used to training a random forest algorithm with cross-validation. A validation-set from another institution was used to evaluate of the radiomics signature, the 3D 'median' attenuation feature (3D-median) alone and the mean value from 2D-ROIs. RESULTS: Seventy-three patients (median 58 years [43‒70]) were analyzed (16 hamartomas; 57 carcinoids). The radiomics signature predicted hamartomas vs carcinoids on the external dataset (22 hamartomas; 32 carcinoids) with an AUC = 0.76. The 3D-median was the most important in the model. Density thresholds < 10 HU to predict hamartoma and > 60 HU to predict carcinoids were chosen for their high specificity > 0.90. On the external dataset, sensitivity and specificity of the 3D-median and 2D-ROIs were, respectively, 0.23, 1.00 and 0.13, 1.00 < 10 HU; 0.63, 0.95 and 0.69, 0.91 > 60 HU. The 3D-median was more reproducible than 2D-ROIs (ICC = 0.97 95% CI [0.95‒0.99]; bias: 3 ± 7 HU limits of agreement (LoA) [- 10‒16] vs. ICC = 0.90 95% CI [0.85‒0.94]; bias: - 0.7 ± 21 HU LoA [- 4‒40], respectively). CONCLUSIONS: A radiomics signature can distinguish hamartomas from carcinoids with an AUC = 0.76. Median density < 10 HU and > 60 HU on 3D or 2D-ROIs may be useful in clinical practice to diagnose these tumors with confidence, but 3D is more reproducible. CRITICAL RELEVANCE STATEMENT: Radiomic features help to identify the most discriminating imaging signs using random forest. 'Median' attenuation value (Hounsfield units), extracted from 3D-segmentations on contrast-enhanced chest-CTs, could distinguish carcinoids from atypical hamartomas (AUC = 0.85), was reproducible (ICC = 0.97), and generalized to an external dataset. KEY POINTS: • 3D-'Median' was the best feature to differentiate carcinoids from atypical hamartomas (AUC = 0.85). • 3D-'Median' feature is reproducible (ICC = 0.97) and was generalized to an external dataset. • Radiomics signature from 3D-segmentations differentiated carcinoids from atypical hamartomas with an AUC = 0.76. • 2D-ROI value reached similar performance to 3D-'median' but was less reproducible (ICC = 0.90).

Esclerosis tuberosa / Tuberous sclerosis

La esclerosis tuberosa es un síndrome genético infrecuente caracterizado por la mutación patogénica de los genes TSC1 o TSC2, que condiciona la activación descontrolada de la vía mTOR y la aparición subsecuente de hamartomas. Presenta una expresión clínica muy variable, siendo el diagnóstico genético y clínico. Puede producir afectación neurológica, dermatológica, dental, cardiaca, renal, ocular, pulmonar o a otros niveles. Se trata de una patología probablemente infradiagnosticada, en la que el diagnóstico precoz es fundamental para el tratamiento precoz de las complicaciones, mejorando así el pronóstico de la enfermedad. En este documento se revisan las principales manifestaciones que puede producir esta patología, así como los criterios diagnósticos actualizados y las recomendaciones de estudio al diagnóstico y durante el seguimiento de esta patología. (AU)

Tuberous sclerosis is a rare genetic syndrome characterized by the pathogenic mutation of the TSC1 or TSC genes, thus inducing an uncontrolled overactivation of the mTOR pathway and subsequent hamartoma formation. Clinical manifestations include neurological, dermatological, dental, cardiac, renal, ophthalmologic and pulmonary, although it can affect other systems. A timely diagnosis is essential to promptly institute proper management measures and treat complications, thus improving the patient’s prognosis. In this manuscript, authors review the main clinical manifestations, current diagnostic criteria and present-day recommendations on diagnosis and follow-up in these patients. (AU)

Folliculosebaceous Cystic Hamartoma with Spindle Cell Lipomatous and Neural Components.

Folliculosebaceous cystic hamartoma is a cutaneous malformation composed of a cystic folliculosebaceous structure associated with mesenchymal elements, generally consisting of fibrous stroma, adipocytes and small vascular channels. We report the case of a 55-year-old female patient with a cutaneous nodule of the right nasal wing. Microscopically, the lesion showed a dilated hair follicle with multiple sebaceous glands, surrounded by a mesenchymal component composed of fibromyxoid stroma, spindle cells, mature-appearing adipocytes and collagen bundles, resembling spindle cell lipoma, associated with an additional neural component, consisting of small nerve bundles. In folliculosebaceous cystic hamartoma, the association of spindle cell lipomatous and neural components has not previously reported.

Correlating Thermodynamics with Cognitive Outcomes in Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) of a Pediatric Hypothalamic Hamartoma.

OBJECTIVE: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a commonly used clinical method of destroying intracranial brain foci. Our objective was to correlate the thermal damage estimate transition zone with cognitive outcomes in MRgLITT of a pediatric hypothalamic hamartoma. METHODS: Uncomplicated MRgLITT was used to disconnect an 8-mm left Delalande grade II hypothalamic hamartoma (HH) revealed on neuroimaging of a 17-year-old male patient with drug-resistant epilepsy and a "gelastic +" semiology including both gelastic and tonic-clonic seizures. Despite meticulous planning, submillimetric stereotactic accuracy, and reassuring intraoperative thermography, the patient experienced transient, but profound, global amnesia. Retroactively, we applied a new iteration of thermographic software that overlays a magenta-colored transition zone (TZ) around the necrotic zone defined by the orange-pigmented thermal damage estimate (TDE). RESULTS: Clear involvement of the bilateral mesial circuits was demonstrated by the overlay of the TZ on the TDE. CONCLUSIONS: Involvement of the bilateral mesial circuits visualized with TDE and TZ could account for the neurocognitive outcomes of our patient. We highlight this case as our understanding of thermography analysis evolves, emphasizing principles of technique and trajectory planning, as well as considerations during thermablation to help inform surgical decision-making.

Widespread keratinocytic epidermal nevus with an associated chylous pericardial effusion.

A 17-year-old male presented for review of a widespread keratinocytic epidermal nevus (KEN) in the setting of a chronic pericardial effusion. Biopsy of the epidermal nevus revealed a KRAS mutation. Pericardiocentesis revealed a chylous effusion and magnetic resonance lymphangiogram demonstrated an underlying lymphatic malformation. There are rare case reports of KEN with an associated KRAS mutation. This case highlights the importance of being alert to epidermal nevus syndrome, particularly in patients with a widespread nevus and seemingly unrelated pathology.

White epidermal nevus as an early sign of tuberous sclerosis complex-A case series.

Tuberous sclerosis complex (TSC) is a rare genetic disease with neurocutaneous manifestations, often presenting initially to the dermatology clinic. We report a cohort of neonates who presented with a novel finding of white epidermal nevus and were eventually diagnosed with TSC. White epidermal nevus may be yet another dermatological finding that may aid in the early diagnosis of TSC.

Managing Different Spectrums of Tuberous Sclerosis Facial Angiofibroma: A Report of Two Cases.

Tuberous sclerosis is one of the rarest genetically linked disorders that can affect a multitude of body systems in various forms. Patients with facial angiofibroma may face issues arising from the various modalities and approaches that can be applied. Moreover, surgeons also face challenges in preparing patients for specific interventions. Here, we are reporting the two spectrums of this condition that may present, along with how we managed patients in our center. The first case is a severe form of tuberous sclerosis involving the skin as well as neurological manifestation, while the second case is a milder form. Both were treated with serial excision and electrosurgery, respectively. Facial angiofibroma in tuberous sclerosis can present in various spectrums. Serial excision and electrosurgery are deemed acceptable. Few advancements have been made in the management of this condition, and combination therapies have shown favorable outcomes. Optimizing patient comorbidities is imperative before intervention and multidisciplinary team involvement would ensure patient safety.

Tuberous Sclerosis, Type II Diabetes Mellitus and the PI3K/AKT/mTOR Signaling Pathways-Case Report and Literature Review.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous syndrome. It is manifested mainly in cutaneous lesions, epilepsy and the emergence of hamartomas in several tissues and organs. The disease sets in due to mutations in two tumor suppressor genes: TSC1 and TSC2. The authors present the case of a 33-year-old female patient registered with the Bihor County Regional Center of Medical Genetics (RCMG) since 2021 with a TSC diagnosis. She was diagnosed with epilepsy at eight months old. At 18 years old she was diagnosed with tuberous sclerosis and was referred to the neurology department. Since 2013 she has been registered with the department for diabetes and nutritional diseases with a type 2 diabetes mellitus (T2DM) diagnosis. The clinical examination revealed: growth delay, obesity, facial angiofibromas, sebaceous adenomas, depigmented macules, papillomatous tumorlets in the thorax (bilateral) and neck, periungual fibroma in both lower limbs, frequent convulsive seizures; on a biological level, high glycemia and glycated hemoglobin levels. Brain MRI displayed a distinctive TS aspect with five bilateral hamartomatous subependymal nodules associating cortical/subcortical tubers with the frontal, temporal and occipital distribution. Molecular diagnosis showed a pathogenic variant in the TSC1 gene, exon 13, c.1270A>T (p. Arg424*). Current treatment targets diabetes (Metformin, Gliclazide and the GLP-1 analog semaglutide) and epilepsy (Carbamazepine and Clonazepam). This case report presents a rare association between type 2 diabetes mellitus and Tuberous Sclerosis Complex. We suggest that the diabetes medication Metformin may have positive effects on both the progression of the tumor associated with TSC and the seizures specific to TSC and we assume that the association of TSC and T2DM in the presented cases is accidental, as there are no similar cases reported in the literature.