OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

Non-invasive prenatal testing (NIPT) based on fetal free DNA is a non-invasive technique to screen for common fetal aneuploidies by analyzing cell-free fetal DNA (cffDNA) in the peripheral blood of pregnant women. This technique has opened a new era of prenatal screening for its high safety and reliability. In recent years, it has been shown that NIPT can not only screen for fetal aneuploidies, but may also reveal maternal genomic abnormalities. The incidental detection of maternal tumors has aroused widespread concern in the clinical settings. The aim of this review is to systematically summarize the research progress of NIPT technique in incidental detection of maternal tumors, and to discuss its clinical significance, technical challenges, and future development direction. It has been found that multiple chromosome aneuploidies (MCAs) in NIPT detection is one of the important biomarkers suggesting occult maternal malignant tumors. In this paper, the relevant progress of NIPT technique in the incidental discovery of maternal tumors were reviewed in order to provide a reference for individualized and standardized application of NIPT technique in maternal health monitoring.
Humans ; Female ; Pregnancy ; Cell-Free Nucleic Acids/blood* ; Prenatal Diagnosis/methods* ; Incidental Findings ; Neoplasms/genetics* ; Noninvasive Prenatal Testing/methods* ; Aneuploidy ; Fetus/metabolism*

Bullous hemorrhagic dermatosis (BHD) is a rare cutaneous manifestation characterized by tense hemorrhagic bullae that appear at sites distant from low molecular weight heparin (LMWH) injections, typically within seven days of exposure. As of March 2022, only 94 cases have been reported. It most commonly affects elderly males with predisposing factors for thromboembolism, such as carcinoma, and usually involves the extremities.

This case highlights the importance of maintaining a high index of suspicion for bullous hemorrhagic dermatosis (BHD) in patients receiving low molecular weight heparin, even beyond the typical 7-day window and in demographics not commonly affected. Early recognition and prompt discontinuation of the offending agent, as demonstrated in this atypical presentation involving a Filipino elderly woman with multiple comorbidities and no malignancy, can lead to favorable outcomes. Clinicians should be aware of this rare but reversible complication to avoid misdiagnosis and ensure appropriate management.

Human ; Female ; Aged: 65-79 Yrs Old ; Affect ; Aged ; Blister ; Carcinoma ; Causality ; Demography ; Diagnostic Errors ; Enoxaparin ; Extremities ; Heparin ; Heparin, Low-molecular-weight ; Index ; Injections ; Lead ; Male ; Molecular Weight ; Neoplasms ; Patients ; Research Report ; Skin Diseases ; Thromboembolism ; Women

Introduction: Discordant thyroid function tests (TFTs), characterized by elevated free thyroxine 4 (FT4) with non-suppressed thyroid-stimulating hormone (TSH), pose a significant diagnostic challenge. Differentiating between Resistance to Thyroid Hormone (RTH) and TSH-secreting pituitary adenoma (TSH-oma) is essential, as management strategies differ substantially. Case: A female with a history of hyperthyroidism diagnosed in 2011 was treated with antithyroid drugs for 1 year before defaulting on follow-up. She was later found to have discordant TFTs at a private centre, where a brain computed tomography scan was reportedly normal. She was referred to our centre for optimization of thyroid function prior to planned thyroidectomy for a solitary large right thyroid nodule measuring 4.2 × 2.8 × 4.7 cm. Fine-needle aspiration cytology demonstrated a benign follicular lesion (Bethesda II). Despite restarting antithyroid medication, she remained clinically euthyroid with no overt thyrotoxic symptoms apart from intermittent palpitations without documented tachycardia. Antithyroid therapy was discontinued. Serial TFTs across multiple assay platforms consistently demonstrated elevated FT4 with inappropriately normal TSH levels. Thyroid autoantibodies, including TSH receptor and anti-thyroid peroxidase antibodies, were negative. Pituitary magnetic resonance imaging showed no evidence of adenoma, and serum α-subunit level was normal (0.3 ng/ mL), making TSH-oma unlikely. Dynamic testing was not performed as thyrotropin-releasing hormone stimulation was unavailable at our centre, while T3 suppression testing was deemed inappropriate due to symptomatic palpitations. Family screening was not possible as the patient was not in contact with her relatives. In the absence of pituitary pathology and given her largely euthyroid clinical status, RTH was considered the most likely diagnosis. Conclusion This case highlights the importance of considering RTH in patients with persistent discordant TFTs, particularly when clinical findings do not correlate with biochemical abnormalities. Early recognition and appropriate pituitary evaluation are essential to prevent misdiagnosis and avoid unnecessary antithyroid therapy or thyroidectomy.
Pituitary Neoplasms ; Thyroid Hormones ; Thyrotropin

Introduction: Paediatric glucocorticoid-induced hyperglycemia (GIH) and diabetes are frequently under-recognized complications of cancer therapy. Early identification is essential, as delayed diagnosis may lead to severe metabolic consequences, including diabetic ketoacidosis (DKA). This study aims to characterize the clinical features, risk factors, and outcomes of GIH in a tertiary centre. Methodology: A descriptive cross-sectional study was conducted at the Paediatric Endocrinology Unit, University Malaya Medical Centre, reviewing cases from January 2023 to December 2025. Data were extracted from electronic records, including demographic, clinical, and treatment-related variables. Results: Twelve cases of GIH or diabetes were identified, including two presenting with DKA. Most patients had leukemia (92%), with a male predominance (75%). The median age was 13.6 years, and the median body mass index was 22.1 kg/m². Over half (54%) were overweight or obese, and 45% exhibited acanthosis nigricans. A family history of diabetes was present in 75% of cases. Hyperglycemia developed early in 66% of cases, typically within 2–5 days of initiating high-dose glucocorticoids. Median random blood glucose was 21.9 mmol/L, while median HbA1c was 6.4%. Half were symptomatic, most commonly with polyuria. Insulin therapy was required in 75% of cases, with a median duration of 26 days. Metformin was used in 50% of cases, often in combination with insulin. Most cases resolved following cessation of glucocorticoid therapy, except one who continues to receive metformin for a pre-diabetes state. Conclusion Adolescents, those with obesity, insulin resistance, and a positive family history of diabetes, represent highrisk groups for GIH. Importantly, GIH may present with life-threatening DKA. Routine glucose monitoring and risk stratification during glucocorticoid therapy are recommended. The development of local screening and management guidelines is crucial for improving early detection and optimizing patient outcomes.
Child ; Diabetic Ketoacidosis ; Glucocorticoids ; Neoplasms ; Hyperglycemia

Introduction: Growth hormone deficiency (GHD) is a recognized endocrine complication among childhood cancer survivors resulting from disruption of hypothalamic–pituitary axis due to tumors, neurosurgery, or cranial irradiation. While recombinant human growth hormone (rhGH) therapy improves growth and metabolic outcome, concerns remain regarding its long-term safety with risk of tumor recurrence and secondary neoplasm. We present a case series of five paediatric oncology survivors with confirmed GHD receiving rhGH in Hospital Tunku Azizah, highlighting our clinical experience in comparison with international practice. Case: Five paediatric oncology survivors (acute lymphoblastic leukemia, craniopharyngioma, medulloblastoma, and supratentorial PNET) with GHD were commenced on rhGH therapy 2.5–5.5 years after completion of cancer treatment. All patients had significant short stature with a mean height SDS of −3.22 prior to the initiation of therapy. GHD was confirmed biochemically with low IGF-1 level and dynamic testing (peak GH 0.35–4.61 ng/mL). Among the four patients with brain tumors, two had stable residual disease while the remaining were tumor-free. rhGH therapy was temporarily ceased in two patients due to minor increment in tumor size but was successfully resumed following stabilization without further complications to date. Two patients are concurrently on pubertal induction. Most patients demonstrated catch-up growth with increased height velocity, supporting the efficacy of rhGH in this population. No secondary malignancies or significant adverse events were observed during follow-up. Conclusion Paediatric oncology survivors with GHD in this series demonstrated a favorable response to rhGH therapy, evidenced by improvements in height SDS and growth velocity, while maintaining oncological stability in the majority of cases. Our findings are consistent with international data, supporting cautious but appropriate use of rhGH in this population. Careful patient selection and close multidisciplinary monitoring remain essential.
Child ; Neoplasms ; Growth Hormone ; Survivors

BACKGROUND

The survival advantage of HER2-positive breast cancer from targeted treatment is commonly undermined by catastrophic health expenditure (CHE), particularly in resource-limited areas. Recognizing that financial catastrophe leads to non-adherence to treatment and dissaving practices, we examined the out-of-pocket (OOP) expenses of patients with HER2-positive breast cancer.

OBJECTIVE

The study aimed to estimate the median total per-cycle out-of-pocket expenditure of HER2-positive breast cancer treatment from the patient perspective, in public and private clinics, evaluate the association of catastrophic health expenditure with non-adherence to treatment, and describe dissaving practices.

METHODS

This was a cross-sectional micro-costing analysis of the treatment of HER2-positive breast cancer from the patient perspective from a tertiary cancer center and select private clinics in the Philippines. Random sampling of patients with HER2-positive breast cancer was done. Using a validated questionnaire, a guided interview was administered. Catastrophic health expenditure was estimated as having OOP of >20% of the household income. OOP costs were assessed retrospectively from the time of confirmed HER2 diagnosis up to the date of survey, while household income referred to the corresponding period. The proportion of patients experiencing catastrophic health expenditure was computed. Fisher's exact was used to assess for any association between CHE and non-adherence to treatment. Descriptive statistics were used to report dissaving practices. All statistical analyses were performed using Stata analytical software version 12.

RESULTS

A total of 101 patients participated in the study. The mean age of participants from the tertiary cancer center and private clinics were 52 and 58 years old respectively. Patients from the private clinics had a median total OOP expenditure of PhP 54,737.06 (IQR = PhP 102,670.00), compared with patients from tertiary cancer center who had a median total OOP expenditure of PhP 13,920.66 (IQR = PhP 20,830.00). The overall prevalence of CHE (90.9%, 95% CI 0.81, 0.95) and nonadherence to treatment with trastuzumab (79%, 95% CI 0.70, 0.87) were high, and similar in both groups. A number of dissaving practices such as resignation from work, borrowing money from friends, selling assets were observed.

CONCLUSION

The high rate of CHE and treatment delay among patients with HER2-positive breast cancer were not addressed by the existing cancer programs. Most OOP expenditure was for trastuzumab. Current cancer support programs have potential to address the financial impact of their treatment.

Human ; Therapeutics ; Survival ; Patients ; Neoplasms ; Philippines ; Health Expenditures ; Breast Neoplasms

The spleen is a very hostile environment for tumor cells due to its anatomic location, blood supply, and rich immunological property – which makes it one of the most unique organ to be involved in metastatic diseases.15 Splenic metastases from non-hematologic malignancies are rare ranging from 0.6 to 7.1% base on autopsy reports of cancer patients, and 1.1 to 3.4% base on review of splenectomy cases.14 Moreover, isolated splenic metastases are more infrequent with only 31 cases reported from 1969 to October 2015.16 A splenic abscess is an unusual formation and is usually caused by hematogenous spread from an infection. Such expected frequency varies in different autopsy studies between 0.14% and 0.7%.1 Albeit rare, abscess can also result from migration of gut flora brought about by direct invasion of tumor cells from a neighboring neoplasm.17 This is a case of a 36-year-old female who came in with a history of abdominal pain, chills and fever for seven months. CT scan of the whole abdomen revealed splenic abscess with suspicion of a splenic rupture. The patient underwent exploratory laparotomy with abscess evacuation, splenectomy and double barrel colostomy and given with intravenous antibiotics. Histopathology results showed metastatic adenocarcinoma in the spleen. Thorough deliberation of her case was done and she was eventually managed as a case of Colon Cancer Stage IV and underwent chemotherapy. Splenic abscess developing from splenic metastasis from a colonic adenocarcinoma is rare and with concomitant high mortality rate. More often than not, splenic metastasis is discovered in advanced stage together with metastatic tumor in other organs while isolated splenic metastasis is even more uncommon. A splenic abscess as an initial demonstration of a colon cancer is not a common daily encounter of physicians hence a high index of suspicion coupled with sensitive and specific imaging is necessary in order to provide prompt medical and surgical intervention.

Human ; Female ; Adult: 25-44 Yrs Old ; Abdomen ; Adenocarcinoma ; Autopsy ; Colostomy ; Gastrointestinal Microbiome ; Pain ; Research Report ; Infections ; History ; Splenic Rupture ; World Health Organization ; Neoplasms ; Disease ; Fever ; Hematologic Neoplasms

BACKGROUND

Central diabetes insipidus (CDI) is a common complication following transsphenoidal surgery for pituitary adenomas, but CDI as an initial presentation in pituitary adenomas is extremely rare. We report a case of a 67-year-old Filipino male with pituitary macroadenoma presenting as central diabetes insipidus, manifesting as a two-month history of severe frontotemporal headache, increased thirst, and polyuria, which was managed with desmopressin followed by transsphenoidal surgery. Three months postoperatively, the thyroid and adrenocorticotropic axis remained intact, and pituitary bright spot recovery was observed. He was clinically stable; hence, desmopressin was gradually tapered and discontinued. This case report presents a unique case of a pituitary adenoma that initially presented with central DI but later showed a complete resolution of symptoms along with the normalization of the "bright spot" seen on MRI, a hallmark of the posterior pituitary. Treatment options for preoperative CDI may include surgical or medical management, with some cases reported as self-limiting. However, the rarity of such cases underscores the urgent need for more clinical studies to fully understand the course of this condition. This case highlights a unique presentation of central diabetes insipidus in a pituitary macroadenoma and the possibility of complete resolution of symptoms coinciding with pituitary bright spot recovery post operatively.

Adenoma ; Diabetes Insipidus ; Diabetes Insipidus, Neurogenic ; Neoplasms ; Pituitary Neoplasms ; Research Report

Intraoperative hemorrhage is a life-threatening complication during neurosurgery, especially in posterior fossa surgery, where critical vasculature and brain structures are present. Adenosine has been used in neurovascular surgery, particularly in the management of intraoperative aneurysm rupture and hemorrhage for its ability to produce transient flow arrest. This case report describes a novel application for adenosine, in which adenosine-induced flow arrest was used to facilitate control of a vascular injury sustained during meningioma surgery.

A 46-year-old female diagnosed with a petroclival meningioma after presenting with a several-month history of headache, dizziness, and loss of balance underwent craniotomy and excision of the meningioma. The patient received general endotracheal anesthesia, and was maintained on remifentanil, propofol, and low-dose sevoflurane. During posterior excision of the meningioma, the basilar artery was inadvertently lacerated, resulting in significant blood loss. Adenosine was given through a subclavian catheter, and produced severe bradycardia, hypotension, then asystole for approximately 50 seconds. Adenosine-induced flow arrest allowed for initial control of the vascular injury through coagulation, while further hemostasis was achieved through hemostatic agents and muscle tamponade.

This case report demonstrates the usefulness of adenosine-induced flow arrest in the management of intraoperative hemorrhage from an intracranial vascular injury. Adenosine-induced flow arrest has documented safety and efficacy in other neurosurgical applications. As the management of intraoperative hemorrhage is an essential component of neuroanesthesia, this technique may be considered in similar circumstances of major vascular injury to facilitate hemostasis.

Human ; Female ; Middle Aged: 45-64 Yrs Old ; Adenosine ; Basilar Artery ; Meningioma