Au Lait Spots Research Articles

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20years. Limited data exist on CMMRD-associated lymphomas and their outcome. We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

Neurofibromatosis type 1: short review and clinical case

Neurofibromatosis type 1 (NF1) is acommon (1/3000) autosomal dominant disorder associated with amutation in the NF1 gene, located on the long arm of chromosome 17 (17q11.2). NF1 is diagnosed using well-known clinical criteria: café au lait spots, axillary and inguinal freckles, cutaneous and subcutaneous neurofibromas, optic pathway gliomas, and specific bone abnormalities. The pathognomonic feature of the disease is plexiform neurofibroma (PN), which is abenign peripheral nerve sheath tumor that occurs in 30-50% of patients with NF1. In addition to awide range of clinical manifestations, such as pain, motor, respiratory disorders, neurological deficits, cosmetic defects, etc., there is about a15% risk for the development of malignant peripheral nerve sheath tumors (MPNST). And it should be noted that the treatment of PN is acomplex task that does not have one standard solution. Thus, surgical treatment, which was the “gold standard” and remains one of the main methods of therapy, carries significant risks, such as postoperative neurological deficit, ahigh risk of intraoperative bleeding and is accompanied by ahigh percentage of relapses. Therefore, the emergence of targeted therapy and its use in the Russian Federation since 2021 has made asignificant contribution to the treatment of symptomatic inoperable plexiform neurofibromas.

The treatment of infantile giant café au lait spot using golden parameter therapy with a high fluence 1064-nm Q-switched Nd: YAG laser

Background Infantile café au lait spot is a brown macule with various sizes (diameter: 0.5 cm–30 cm). Infantile giant café au lait spot (IGCALS) is a huge (diameter >20cm) irregular-shaped benign hyperpigmented skin disorder that arises in infants. There has been no clearly established laser treatment consensus for the treatment of IGCALS because infants are too fragile to receive laser treatment with long hours and broad areas along with the possibility of undesirable cosmetic results. Objectives This study investigated the safety and efficacy of Golden Parameter Therapy (GPT) using a high fluence 1064-nm Q-switched Nd:YAG laser (QSNL) for IGCALS treatment. Methods This study included 24 Korean patients with IGCALS. Twenty-one patients who were treated with a 1064-nm QSNL weekly for 30–50 treatment sessions with GPT. The parameters included a spot size of 7 mm, a fluence of 2.2 J/cm2 and a pulse rate of 10 Hz with one pass using a sliding-stacking technique over the IGCALS. In control group, three patients were treated with a 532-nm picosecond laser monthly for three treatment sessions with a spot size of 3 mm, a fluence of 1 J/cm2 and a pulse rate of 2 Hz. Results After the last treatment, 21 patients with IGCALS reached the complete removal of pigmented lesions, which can be considered optimal cosmetic results without any side effects such as purpura, crust, post-inflammatory hyperpigmentation, iatrogenic punctate leukoderma, and scarring. There are no recurrences in any patients after 6–21 months’ follow-up, but treatment failure occurred in three patients who were treated with 532 nm picosecond laser. Conclusions Convincingly, we argue that early intervention before 12 months of age with GPT using a high fluence 1064 nm QSNL is a safe, applicable and effective treatment for IGCALS, minimizing side effects without any recurrences.

Neurofibroma: Case Series with Clinical Features and Recommendations

Abstract Neurofibroma is an autosomal benign disorder. It can be localized, diffuse or invasive like plexiform neurofibroma that involves the nerves, muscle, tissues, skeleton. It represents itself as a destructive variant of neurofibroma, mostly present as orbital or periorbital neurofibroma or may be associated with autosomal dominant disease. Clinical diagnosis of neurofibromatosis (NF) according to National Institutes of Health (NIH) criteria should have more than two of the seven features including lisch nodules, cafe’- au-lait spots, plexiform neurofibroma, optic glioma, freckling, first degree relative with NF or dysplasia of cortical bones. However, proper early diagnosis is still crucial due to its various presentation such as cheek mass, painless swelling on skin, chalazion, intratracheal tumor, genital swelling or ptosis. It is reported that neurofibroma often represents as ocular or facial swelling. Here we are presenting features of neurofibroma of eight cases of patients from Civil Hospital, Karachi. These cases had main complain of overhanging skin mass mainly on orbital or periorbital region that damage the area and with poor daily activities. Multiple nodules on face and body along with them Cafe’-au-lait spots and lisch nodules were main signs. While, other signs i.e. ptosis, pterygium, telecanthus and muddy discoloration of conjunctiva need further evaluation for correlation with neurofibromatosis. Debulking surgery was planned for most of the cases but the huge disfigurement caused by overhanging skin mass and nodules made it a challenge for plastic surgeons to provide good outcomes with minimum damage.

Surgical treatment of a massive soft tissue neurofibroma in neurofibromatosis type 1

Introduction. Neurofibromas developing in neurofibromatosis type 1 rarely grow to a large size. However, in cases of massive lesions, selection of optimal treatment tactics can be complicated. Clinicians usually resort to surgical treatment which currently serves as an effective instrument for improving patients’ quality of life and for achieving good cosmetic results.Aim. To describe a successful experience of surgical treatment in a patient with giant neurofibroma type 1 affecting a massive pool of soft tissues.Clinical case. Patient, 22 years, sought medical help at the N.N. Blokhin National Medical Research Center of Oncology with diagnosis of neurofibromatosis type 1 with massive lesions in the tissues of the lower third of the back, gluteal region, thighs. The disease has existed since birth, family medical history is fraught: father died of malignant manifestation of a neurogenic tumor. The younger sister is also diagnosed with neurofibromatosis affecting the brain and manifesting through cafe au lait spots on the body. Due to massive tumors significantly decreasing the patient’s quality of life, cytoreductive surgical treatment was prescribed aimed at maximally radical resection of all available tumors to alleviate the patient’s condition.Conclusion. The presented clinical case demonstrates successful experience of surgical treatment of a patient with giant neurofibroma affecting a massive pool of soft tissues.

Unusual Presentations of Plexiform Neurofibroma: A Series of Three Cases

Neurofibroma is a benign peripheral nerve sheath tumour, and Plexiform Neurofibroma (PN) is pathognomonic of Neurofibromatosis Type 1 (NF1). It occurs equally in males and females and presents at birth or a very early age. The incidence is 1 in 2500 births per year, with an estimated genital association of 1.8%, where clitoral involvement is very rare in the Indian population. In the present case series, three patients were diagnosed with PN through surgical histopathology and Immunohistochemical (IHC) stains like S-100 and Cluster Differentiation 34 (CD34) at a tertiary care hospital. All three patients were children who had painless, gradually increasing swellings that underwent surgical treatment. Among them, a five-year-old girl presented with painless clitoromegaly, multiple café- au-lait spots, and underwent plastic surgery. She was later clinically diagnosed with NF1 after histopathological and IHC correlation. A two-year-old boy with a firm swelling over his left leg showed hyperintensity and multilobulation on magnetic resonance imaging. A 10-year-old boy with a similar swelling in his right upper arm showed multiple hypoechoic masses on ultrasonography. Both of them were later diagnosed with PN using the same methodology. Although it is benign, there is a risk of malignant transformation in diffuse PNs, and they should be managed by wide excision with a safety margin to prevent recurrence.

Plexiform Neurofibroma: Case Report

Plexiform neurofibroma (PNF) is a benign nerve tumor, most often developing in the cephalic region. It is usually considered pathognomonic for neurofibromatosis type 1 (NF1) or Von Recklinghausen disease. We report the case of a patient treated in our training for plexiform neurofibroma on NF1. This is a 28-year-old patient, without any particular ATCD, who consulted for a left scalpo-fronto-palpebral subcutaneous swelling that had been present for 12 years, causing major aesthetic discomfort. Furthermore, it presented numerous (> 6) café au lait spots greater than 15mm in diameter. The patient underwent excision of the left scalpo-fronto-palpebral tumor under general anesthesia with direct closure. The pathological examination confirmed the diagnosis of plexiform neurofibroma. The postoperative course was simple and the result satisfactory. Surgical excision remains the only treatment for plexiform neurofibomas in Von Recklinghausen disease.

Cytogenetic analysis of fanconi anemia patients: An hospital based study

: Fanconi anemia is a rare genetic disorder caused by mutations in genes whose protein products are involved in replication, cell cycle control and DNA repair and is associated with a very high frequency of bone marrow failure and many other manifestations including, but not restricted to, severe birth defects.The diagnosis of FA is confirmed by a specific test known as chromosomal breakage study, a differential technique in which clastogenic substances, such as DEB (diepoxy butane) or MMC (mitomycin C), lead to sections of the chromosome being deleted, added, or rearranged.In this retrospective study, peripheral blood smears of patients with Aplastic Anemia were analyzed to diagnose Fanconi Anemia.: A total of 135 cases of Aplastic anemia were analyzed and screened by chromosomal breakage analysis for ruling in/out Fanconi anemia.: A total of 9 (6.66%) out of 135 patients showed a significant increase in the number of chromosomal breaks in comparison to their control. An analysis of the variable clinical manifestations was also done and correlated to the diagnosis of Fanconi Anemia. : This study throws light on the importance of cytogenetic analysis as being the most classical test for FA which involves detection of chromosomal breakage or aberrations in metaphase spreads. This relatively inexpensive assay may be useful for screening patients for whom FA is in the differential diagnosis, such as those with radial ray anomalies, short stature, hypogonadism, or café au lait spots, or for population-based FA incidence studies.

Spontaneous Primary Pneumothorax as A Complication of Neurofibromatosis Type 1.

NF1 is a genetic disease that results in cutaneous conditions, including neurofibroma, axillary, inguinal lentigines and café au lait spots. In some cases (5-20%) it can also affect the lungs, causing neurofibroma, infiltrative and cystic lesions, emphysema or bullae, leading to chronic respiratory failure.SSP is a clinical presentation of NF1 caused by the rupture of lung cysts or bullae, with an unclear relationship to smoking.Early diagnosis of pulmonary manifestations in patients with NF1 is crucial as surgical removal of lung cysts and bullae seems to prevent recurrence of SSP.

THU614 Neurofibromatosis Type 1 Presenting With Pheochromocytoma And Severe Vascular And Hematological Manifestations Due To A Novel NF1 Mutation

Abstract Disclosure: L.A. Alobaid: None. O. Alsagheir: None. M. Alswailem: None. B. Alghamdi: None. A.S. Alzahrani: None. Neurofibromatosis (NF) type 1 is an autosomal dominant condition caused by germline mutations in NF1, a tumor suppressor gene encoding neurofibromin. Pheochromocytomas (PCC) and paragangliomas can develop in up to 8% of patients with NF type 1. Vasculopathy leading to vascular narrowing and malformations are also well described manifestations of NF. Finally, a number of hematological manifestations have been described including thrombocytosis, leukocytosis, myelodysplastic syndrome, acute myeloid leukemia, and lymphoma. We present a young woman who has NF type 1 and presented with all of these unusual manifestations including PCC, leukemoid reaction, severe thrombocytosis, vascular malformations and narrowing, extensive skin freckling and café au lait spots. She was found to have a novel truncating NF1 mutation, which explains the severity of her disease. Case description: A 21-year-old lady referred to our hospital with a 4-year history of episodic headaches, blurred vision, on/off palpitations, sweating, and facial redness. She was found to be severely hypertensive at 200-230/95-140 mm Hg. Family history was positive for skin freckling, nodules and café au let spots in her father, two aunts and four siblings. On examination, BP 195/100 mmHg, Pulse 120 bpm. She has widespread skin freckling, and cafe au lait spots of different sizes and shapes. Systemic examination was otherwise normal. Urine metanaphrine was 9.34 umol/day (0-1.49) and normetanephrine 42.16 umol/day (0-3.43). A CT scan of the abdomen showed an 8-cm left adrenal heterogeneously enhancing hypervascular mass and narrowing of the infrarenal abdominal aorta with sever stenosis of celiac artery origin and severe diffuse narrowing of the left external iliac artery. Gallium 68 PET CT scan revealed an uptake at the same mass without other foci of uptake. Laboratory investigations: HbA1c 11.9%, WBC 18-24x109/L, Platelets 850-1,350x109/L. Bone marrow examination was refused by the patient so the exact underlying hematological disorder could not be accurately diagnosed. She was prepared with phenoxybenzamine and labetalol and underwent an open left adrenalectomy. Post operatively, she developed a large right anterior cerebral artery ischemic stroke as a complication of narrow cerebral vessels and the severe thrombocytosis. Histopathological examination confirmed the diagnosis of PCC with Ki67∼20%. Molecular testing revealed a novel truncating NF1 mutation (c.7606C>T, p.Gln2536X). Conclusion: We describe unusually severe haematological and vascular manifestations of NF type 1 in a young girl who presented with a large PCC. These severe manifestations reflect the broad manifestations of NF type 1 due to the important role of neurofibromin in different organs and the significant effects of the underlying NF1 truncating mutation in this patient. Presentation: Thursday, June 15, 2023

THU205 A Case Of Infant With Familial-Male Limited Precocious Puberty (FMPP) Inherited From Father Due To An Activating Mutation Of The Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene

Abstract Disclosure: H. Yoo: None. J. Ha: None. M. Jung: None. Y. Choi: None. E. Yoo: None. We present an extremely rare case of FMPP with an activating mutation of the LHCGR gene in a Korean infant. A 16-month-old-boy was brought to the out-patient clinic with complaints of pubic hair, acne and rapid growth acceleration. His father had become aware of the symptoms 4 month before. His grandfather and father had a family history of precocious puberty and profound short stature (Height of grandfather and father: 148 cm and 158 cm respectively). At physical examination, his height was 83 cm (+1.2 SDS) and his weight was 14.3 kg (+2.8 SDS). The testicular volume was 2 mL and pubic hair was appropriate for Tanner stage 2. Stretched penile length was 7 cm (>2 SDS). He did not have any café au lait spots or hyperpigmentation. His bone age was significantly advanced to that of a 4 year old. Laboratory findings showed abnormally elevated serum testosterone (5.74 ng/mL) and slightly elevated α-fetoprotein (14.1 ng/ml; reference 0-10 ng/mL) with suppressed LH level (<0.07 mIU/mL). Serum levels of β-human chorionic gonadotropin, cortisol, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone sulfate were within normal range. A gonadotropin releasing hormone (GnRH) stimulation test revealed a prepubertal response(peak LH 0.52). Brain magnetic resonance imaging study was reported to be normal. Ultrasound of the scrotum and adrenal gland were both normal. Due to the patient’s classic presentation and his family history of male-limited precocious puberty, a genetic analysis for LHCGR gene was performed. Molecular genetic analysis identified a pathogenic variant of LHCGR (c.1730 C>T, p.Thr577Ileu), which was previously reported in a FMPP patient. His father and paternal grand father also carry the same mutation. Anti-androgen treatment with bicalutamide (25mg/day) and aromatase inhibition with anastrozole (1mg/day) were initiated. After treatment, there was improvement in pubertal progression, accelerated growth velocity and rate of skeletal maturation without any specific side effects. Presentation: Thursday, June 15, 2023

Jejunal gastrointestinal stromal tumor that developed in a patient with neurofibromatosis type 1: a case report

BackgroundNeurofibromatosis type 1 (NF1) is known to be associated with the frequent occurrence of unique gastrointestinal stromal tumors (GISTs), preferably occurring in the small intestine, with no mutations in the c-kit proto-oncogene or platelet-derived growth factor receptor-alpha (PDGFRA), with a high tendency for multifocal development, indolent nature, with low proliferation activity and favorable prognosis.Case presentationA woman in her forties visited her local doctor complaining of menstrual pain; a large mass was detected in her lower abdomen, and she was referred to our hospital. The patient had hundreds of skin warts and café au lait spots. The patient’s mother had been diagnosed with type 1 neurofibromatosis. The patient met the diagnostic criteria for NF1 and was diagnosed with NF1. Ultrasonography showed a large heterogeneous cystic mass with various echo patterns, solid compartments and multiple septations. Magnetic resonance imaging showed a multilocular cystic mass with liquid content exhibiting various intensities, including that of blood. A small round solid mass was also observed close to the cystic tumor. Contrast-enhanced computed tomography showed that the round solid mass showed strong enhancement in the early phase, unlike the cystic tumor component. Open laparotomy revealed a multicystic exophytic tumor measuring 11.5 cm originating from the jejunal wall, 20 cm distal to the duodenojejunal flexure. A solid tumor measuring 2.1 cm was also found on the anal side of the large tumor. We resected the short segment of the jejunum, including the two lesions. Microscopic findings revealed that the cystic and solid tumors consisted of spindle-shaped tumor cells showing little atypia with a fascicular or bundle arrangement. Nuclear mitosis was scarce. Immunostaining of the tumor cells showed positive staining for KIT and DOG1 and negative staining for S100 and desmin. The NF1 patient was diagnosed with multiple GISTs accompanied by intratumoral hemorrhagic denaturation arising from the jejunum. The TNM staging was pT4N0M0, stage IIIA.ConclusionWe report a case of GISTs associated with NF1 that showed a jejunal origin, multifocal development and few mitotic figures. The recurrence risk, survival prognosis and need for adjuvant chemotherapy, particularly in cases where the initial GIST exhibits a very indolent pathology in NF1-related GISTs, remain to be elucidated.

Unilateral gingival enlargement in a patient with neurofibromatosis type 1 - Case report

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal disease caused by mutations in the NF1 tumor suppressor gene. NF1 affects bones, nerves, soft tissues and skin. Oral manifestations of NF1 consist of soft tissue tumors, bone defects, periodontal and dental changes, and altered salivary flow. We report one such case, a 26-year-old man with Gingival enlargement, Café au lait spots, axillary freckling, and multiple nodules on his body.

Neurofibromatosis type 1, from gene mutation to clinical presentation

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with a prevalence of about1/3000. The clinical diagnosis of NF1 is based on the presence of two or more of the followingcriteria: six or more café au lait spots, >2 neurofibromas of any type, freckling in the axillary oringuinal region, optic glioma, a distinctive osseous lesion such as sphenoid dysplasia or thinning oflong bone cortex with or without pseudoarthrosis, and a first degree relative with NF1.We report A 7-year-old male with multiple café au lait spots diagnosed with Neurofibromatosisin Kigali-Rwanda by using next-generation sequencing and copy number variation analysis, thepatient presented with painless nodular skin lesions that first developed 4 years earlier. Skinnodules initially appeared on the anterior chest wall and progressed to the posterior chest wallextending to the axilla region. His medical history and that of his family were unremarkable. To ourknowledge, this is the first case to be diagnosed using this technology; The disease has numerouscomplications. The mutation rate for NF1-gene is high; 50% of all cases of NF1 are from newmutations. The gene protein product - neurofibromin plays an important role in tumor genesis asa tumor-suppressor gene.Combining both clinical findings and molecular genetic evaluation to identify disease-causingmutations is paramount in confirming the diagnosis. Patient care is best done in a multidisciplinarysetting approach for proper patient satisfaction and better prediction of future prognosis.

Neurofibromatosis 2: A Case Report

Neurofibromatosis 2 (NF2) is caused by inactivating alterations in the NF2 gene on chromosome 22q12.2. The 100-kb NF2 gene is encoded by 17 exons. Patients with NF2 may present with distinctive “plaque-like” cutaneous schwannomas, ophthalmologic findings, or neurologic deficits such as hearing loss or peripheral neuropathies which may prompt further radiologic or genetic evaluation. Café au lait spots may be present in up to 50% of patients but they are typically fewer in number and not associated with freckling as in NF1. This is a case report of a 20 year old female who presented to us with left parapharyngeal schwannoma along with bilateral vestibular schwannoma. Keywords: NF 2- Neurofibromatosis 2, VS- Vestibular Schwannoma, CECT-Contrast enhanced computed tomography, MRI-Magnetic resonance imaging

The Role of Magnetic Resonance Imaging in the Diagnosis of Spinal Dumbell Neurofibromatosis: A Case Report from a Specialist Hospital in Port Harcourt

Neurofibromatosis occurring in the spine also known as spinal neurofibromatosis (SNF) is a rare disease entity and they occur either unilaterally or bilaterally at the spinal roots. The low prevalence rate of the disease and scarcity of previous literatures is the main aim for this report.
 Our case study is a 29-years-old lady who presented to the Radiology department for a lumbosacral spine MRI, on account of both lower limb weakness, paresthesia, unsteady gait and finally inability to walk. The symptoms have been there since she was 14 years (15 years of progressive symptoms). She also presented with multiple macules on the skin (café au lait spots). Magnetic Resonance Imaging (MRI) of the lumbosacral spine revealed bilateral spinal neurofibromas at the spinal roots of the fourth lumbar vertebra to the sacral/coccygeal vertebrae with destruction of the sacro-coccygeal bones. MRI of the brain revealed no abnormalities in the brain and optic tract. The patient fulfilled the National Institutes of Health (NIH) criteria and that of revised diagnostic criteria for Neurofibromatosis (NF1).
 The patient also presented with lack of pain which could be due to impairment in sensory neurons. We describe a case of spinal neurofibromatosis diagnosed by MRI in a young lady with progressive lower limb weakness, paresthesia, sensory loss, café-au- lait spots and paraplegia.

Strabismus and Exophthalmos in Children: Think of Optic Nerve Glioma

Introduction: Optic nerve gliomas are rare tumors that are mainly observed in children. Exophthalmos and strabismus are the main signs of the disease. Neuroimaging and in particular magnetic resonance imaging is of great help in the diagnosis and follow-up of these tumors. The therapeutic management of these gliomas involves different means: surgical removal, chemotherapy, radiotherapy or abstention under surveillance. The indications must be discussed on a case-by-case basis. We report in this work a case of optic nerve glioma revealed by a strabismus and a unilateral exophthalmos. Case Report: This is a 3-year-old girl from a non-consanguineous marriage, with no specific pathological ATCD, who presented with divergent strabismus with left exophthalmos evolving for 3 months. The ophthalmologic examination noted a constant wide-angle divergent strabismus on the left eye with moderate exophthalmos on the same side. Corrected visual acuity was reduced to near finger count on the left and 5/10 on the right. Somatic examination found café au lait spots on the back and trunk. Cerebral CT showed a bilateral thickening of the optic nerves, fusiform and regular, more marked on the left, isodense to spontaneous contrast, homogeneously enhancing after injection of PDC. On the left, it is responsible for a downward refoulement of the eyeball with grade 1 exophthalmos. An MRI was ordered revealing a regular well-limited fusiform thickening of the optic nerves in T1 isosignal, intermediate in T2 and FLAIR, in diffusion hypersignal without ADC restriction, intensely and finely heterogeneous enhancing after injection of contrast medium. This thickening is responsible for a grade I left exophthalmos, with widening of the optic canals posteriorly and filling of the intraconical fat evoking a glioma appearance. The child was referred to neurosurgery for management. Conclusion: The diagnosis of optic nerve glioma in children is rare, with atypical presentations both in terms .........

A rare case of superficial temporal artery pseudoaneurysm in a patient with neurofibromatosis type 1

Pseudoaneurysm of the superficial temporal artery (STA) is a rare clinical entity that has been linked with traumatic causes. Neurofibromatosis type I (NF-1) is an autosomal dominant disorder with known but uncommon vascular abnormalities that comprise stenoses, occlusions, aneurysms, fistulas and arteriovenous malformations. We presented a 46-year-old man with clinical features of NF-1 (e.g., café au lait spots, skin neurofibromas) coming to hospital because of a progressively enlarging and painful right temporal mass of about ping-pong ball size. He remembered having slapping a mosquito with his hands at the same area four days ago. CT angiography suggested development of a pseudoaneurysm and emergency surgery was performed to dissect the mass. Histopathological examination revealed disruption of arterial wall structures, including interruption of elastic lamina, expansion of smooth muscle layer, focal thrombosis and positive CD31 and smooth muscle actin staining, consistent with diagnosis of pseudoaneurysm. This is the first report of a STA pseudoaneurysm in patient with NF-1. Deficiency of neurofibromin may impact the integrity of vascular wall structures and predispose it to the development of pseudoaneurysm in the event of minor trauma like current case. Reference 1. Saliba E, Goldberg LJ. Superficial temporal artery pseudoaneurysm: report of two cases and review. J Cutan Pathol 2022; 49: 482–486.

A rare case of concomitant hypophosphatemic osteomalacia and neurofibromatosis type 1

Abstract Introduction Neurofibromatosis type 1 is a rare genetic disorder with an increased susceptibility to develop skeletal abnormalities. However, the association of hypophosphatemic osteomalacia and neurofibromatosis type 1 is extremely rare. Herein, we report a case of hypophosphatemic osteomalacia in concomitant with neurofibromatosis type 1. Clinical Case A 45-year-old Turkish female patient, who was followed up in another hospital due to osteoporosis and kyphoscoliosis, applied to us with the complaints of persistent bone pain and inability to walk. She had no chronic diseases other than osteoporosis. The physical examination revealed widespread freckling over her trunk and proximal parts of upper and lower extremities and multiple neurofibromas and cafe au lait spots all over her body (figure 1). It was learned that her 2 brothers, mother and daughter also had the widespread freckling. They have no known chronic diseases. She had a severe degree of kyphoscoliosis. She had not have any complaints up to 24 years of age, and low back pain started after delivery. She was diagnosed with osteoporosis at the age of 29. In about 15 years, her height decreased from 167 cm to 135 cm. She had a severe degree of kyphoscoliosis and severe bone pain and was unable to walk on her own because of pain. Bilateral ophthalmic examination revealed no Lisch nodules. Audiometer revealed no abnormalities. Laboratory findings were as follows: Ca: 9.4 (8.4–10.6 mg/dl), phosphorus: 1.8 (2.3–4.7 mg/dl), albumin: 4.2 g/dl, parathormone: 88.3 (11–80 pg/ml), 25 hydroxy vitamin D: 26.1 ug/L, creatinine: 0.4 mg/dl, alkaline phosphatase: 79 (35–105 U/L), the 24-hour urinary excretion of calcium: 187.5 mg/24 h, the 24-hour urinary excretion of phosphorus: 253 mg/24 h, fractional excretion of phosphate: %8.5 and maximum transport of phosphorus in the renal proximal tubules (TmP/GFR): 0.74 (0.88–1.42 mmol/L). According to laboratory data there was a hyperphosphaturia. On the basis of the physical examination, laboratory and radiological findings, she was diagnosed with neurofibromatosis type 1 and hypophosphatemic osteomalacia. Oral phosphate solution (1.5 gram as elemantary phosphorus per day in 3 divided doses) and calcitriol (1 microgram per day in 2 divided doses) were started. After 6 months of therapy, bone pain was significantly decreased and her serum phosphorus level increased. The results of genetic analysis are awaited. Conclusion The coexistence of hypophosphatemic osteomalacia and neurofibromatosis type 1 have been reported in less than 50 cases in the literature. The underlying mechanism is not clarified. The diagnosis of hypophosphatemic osteomalacia should be kept in mind in patients with neurofibromatosis type 1, as they will benefit greatly from oral phosphorus solution and active vitamin D.

Congenital pseudoarthrosis of the tibia and fibula is managed with plate osteosynthesis and the Ilizarov method

Pseudo means false, and arthrosis means joint formation. Congenital pseudoarthrosis (C.P.T.) of the tibia is a rare congenital anomaly. The incidence of it is one in 190,000 live births. Although rare, C.P.T. of the tibia poses one of the most challenging management problems in pediatric orthopaedics. It is characterized by de-ossification, bending, and pathological fracture, followed by the inability to form a normal callus at the fracture site. Fifty-five percent of cases of pseudoarthrosis are associated with neurofibromatosis-1 (NF-1), and 6% of patients with NF-1 develop pseudoarthrosis of the tibia. A 9-year-old male came to the orthopaedic outpatient department with a deformity over his right leg since birth. There were multiple café au lait spots on the front and back of the trunk. The right leg had a bony deformity in the lower third with anterior convexity, with typical features of pseudarthrosis tibia and fibula, along with gross abnormal mobility and 2 cm shortening. The left leg was normal. There is no evidence of any new bone formation at the non-union sites. The patient was managed with refreshing the bone ends to produce bleeding bone ends with good contact and open removal of aberrant fibrous tissue from the region of the tibia´s pseudoarthrosis. Bone fragments were reduced and fixed with a locking plate. Corticotomy was done at the proximal end of the tibia to improve the limb length discrepancy via the distraction osteogenesis method, and an Ilizarov ring fixator was applied. Postoperatively, distraction was done at 1 mm per day.