BACKGROUND

Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome caused by PRKAR1A gene mutation and  characterized by lentigines, myxomatous tumors and various endocrine neoplasms.

CASE PRESENTATION

This is a case of a 52-year-old male patient who underwent echocardiogram for intermittent palpitations and near-syncopal attack, which revealed a left atrial myxoma. The patient also exhibited multiple lentigines and had a history of histologicallyconfirmed papillary thyroid carcinoma. Surgical excision and subsequent histopathologic examination confirmed cardiac myxoma, fulfilling three major Stratakis criteria for CNC.

DISCUSSION

This case highlights the importance of a thorough history and physical examination with a strong understanding of the syndrome’s features being key to recognizing the disease. Increasing awareness and reinforcing knowledge of CNC are crucial for preventing misdiagnosis and ensuring effective management of this rare condition. To our knowledge, this is the first published case report of CNC in the Philippines, emphasizing the need for heightened regional awareness.

CONCLUSION

CNC may present with subtle or nonspecific symptoms and atypical tumor locations. Early recognition through a high index of suspicion, targeted imaging and a multidisciplinary approach is critical to optimize outcomes and guide family screening in this rare syndrome.

Human ; Male ; Middle Aged: 45-64 Yrs Old ; Multiple Endocrine Neoplasia ; Carney Complex ; Myxoma ; Syndrome ; Neoplasms ; Mutation ; Lentigo ; Genes

OBJECTIVE: To explore the clinical features and genetic etiology of two Chinese patients with Cowden syndrome (CS). METHODS: Two patients diagnosed with multiple gastrointestinal polyps by gastroenteroscopy at Henan Provincial People's Hospital in September and November 2023 were selected as the study subjects. Clinical data of the patients were collected. Whole exome sequence (WES) was carried out. Candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2018-03-01). RESULTS: The patients were diagnosed with multiple gastrointestinal polyps in addition with polypoid changes of the gallbladder. Genetic testing revealed that patient 1 has harbored a heterozygous c.738dupG (p.Leu247Valfs*6) variant of the PTEN gene, which was unreported previously. Patient 2 has harbored a heterozygous c.469G>T (p.Glu157Ter) variant of the PTEN gene, which was known to be pathogenic. None of their family members was found to harbor the above variants. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were rated as pathogenic (PVS1+PM2_Supporting+PP3+PP4). Bioinformatic analysis suggested that both variants can significantly affect the tertiary structure of the PTEN protein. CONCLUSION The heterozygous variants of the PTEN gene probably underlay the CS in both patients. Discovery of the novel variant has enriched the mutational spectrum of the PTEN gene.
Adult ; Female ; Humans ; Male ; China ; Hamartoma Syndrome, Multiple/genetics* ; Mutation ; Pedigree ; PTEN Phosphohydrolase/chemistry* ; East Asian People/genetics*

Wunderlich Syndrome is a rare potentially life-threatening phenomenon that involves spontaneous non-traumatic retroperitoneal hemorrhage. At present, identifying the course of conservative management in these patients, especially in pregnancy, has not been clinically established. Presented here is a known case of Tuberous Sclerosis Complex with a Bilateral, 10cm Angiomyolipoma in a 31-year-old female, initially managed with active surveillance. At 27 weeks of pregnancy, she presented with a sudden onset of left flank pain with a hematocrit of 22%. Anemia was corrected with blood transfusions. A contrast-enhanced MRI of the abdomen showed a large subcapsular perirenal hematoma of the left kidney. Renal angioembolization of the bleeding segmental renal artery was done. The patient was conservatized until 37 weeks of pregnancy and underwent cesarean section delivery.

Four months after angioembolization, she had a recurrence of the left flank pain associated with gross hematuria and hypovolemic shock. The patient underwent emergency renal exploration of the left kidney via a transabdominal approach. Three liters of hemoperitoneum and a large expanding left retroperitoneal hematoma were noted intraoperatively. Early vascular control before nephrectomy of the left kidney was done. The postoperative course was unremarkable and the patient was discharged with improved condition.

This case displays a unique course in the management of a bleeding angiomyolipoma especially during pregnancy. Renal angioembolization can aid in achieving the age of viability in pregnancy. However, close monitoring for rebleeding should be kept in mind. A lower threshold for conservative management should be utilized when patients have a previous history of bleeding.

Human ; Female ; Adult: 25-44 Yrs Old ; Abdomen ; Anemia ; Angiomyolipoma ; Arteries ; Blood ; Blood Transfusion ; Cesarean Section ; Conservative Treatment ; Emergencies ; Female ; Flank Pain ; Hematocrit ; Hematoma ; Hematuria ; Hemoperitoneum ; Hemorrhage ; History ; Hypovolemia ; Insemination, Artificial, Heterologous ; Kidney ; Life ; Nephrectomy ; Pain ; Patients ; Pregnancy ; Recurrence ; Renal Artery ; Research Report ; Sclerosis ; Shock ; Syndrome ; Tuberous Sclerosis ; Watchful Waiting

Proteus syndrome (PS) is a mosaic disorder characterized by asymmetric overgrowth of a variety of tissues. Diagnostic criteria established in 1999 emphasized the mosaic distribution of lesions, progressive course, and disproportionate overgrowth. We present a case of proteus syndrome in a 12-year-old Filipino male with 9 year-history of enlargement of the left foot with soft, non-tender mass on the sole with a brain-like surface. Skin punch biopsy of the mass showed cerebriform connective tissue nevi which is pathognomonic of PS.

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PS is a very rare disease with prevalence of less than 1 in 1,000,000 live births. Management of PS is extremely challenging, owing to the combination of the individuality of each case, the severity of the disease, and the risks of complications from procedures. A multidisciplinary clinical approach is strongly recommended to obtain the best possible management plans for individual patients.

Human ; Male ; Child: 6-12 Yrs Old ; Proteus Syndrome ; Mosaicism

Tuberous sclerosis complex (TSC) is a rare, autosomal dominant multisystem disorder affecting the brain, heart, kidneys, lungs, and skin leading to significant morbidity and mortality. We report a case of TSC and highlight the need for prompt diagnosis and proper surveillance to minimize life‑threatening complications. A 20‑year‑old female presented with facial and ungual papulonodular lesions 4 years after being diagnosed with epilepsy at the age of eight. No family history of genetic diseases was reported. Eight years later, the patient developed recurrent cough, shortness of breath, and blurring of vision. Biopsy of facial and digital nodule showed angiofibroma and ungual fibroma (Koenen tumor), respectively. Chest computed tomography scan revealed extensive cystic lesions diffusely scattered throughout the entire lung parenchyma suggestive of lymphangioleiomyomatosis. Cranial MRI revealed cortical and subependymal tubers, compatible with TSC. The patient had multidisciplinary management. However, her symptoms progressed, and she eventually succumbed to death. Cutaneous lesions such as facial angiofibromas and ungual fibromas along with multisystemic manifestations should alarm the clinician to TSC. Given its highly variable expressivity, awareness of different TSC‑associated signs and symptoms is essential for prompt diagnosis, proper treatment, disease monitoring, and early recognition of TSC complications.
Angiofibroma ; Lymphangioleiomyomatosis ; Tuberous Sclerosis

OBJECTIVE: To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients. METHODS: The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively. RESULTS: A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival. CONCLUSION In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.
Humans ; East Asian People ; Hematologic Neoplasms/complications* ; Lymphoma/complications* ; Multiple Myeloma/complications* ; Neoplasms, Second Primary ; Retrospective Studies ; Survival Analysis

OBJECTIVE: To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. METHODS: The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. RESULTS: A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). CONCLUSION The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/complications* ; Leukemia, Plasma Cell ; Retrospective Studies ; Esophageal Neoplasms/complications* ; Esophageal Squamous Cell Carcinoma/complications* ; Prognosis ; Neoplasms, Second Primary

Objective: To explore the reasonable time of prophylactic thyroidectomy for RET gene carriers in multiple endocrine neoplasia(MEN) 2A/2B families. Methods: From May 2015 to August 2021, RET gene carriers in MEN2A/MEN2B families were dynamically followed up at the Department of Thyroid Head and Neck Surgery, Beijing Tongren Hospital of Capital Medical University. The high-risk patients were encouraged to undergo prophylacitc total thyroidectomy according to the principle of "graded early warning system", namely the evaluation of gene detection, calcitonin value and ultrasound examination successively. Seven cases underwent the surgery, including 3 males and 4 females, aged from 7 to 29 years. According to the risk stratification listed in the guidelines of the American Thyroid Association in 2015, there were 2 cases of the highest risk, 2 cases of the high risk and 3 cases of the modest risk. Calcitonin index remained within the normal range in 3 cases and elevated in 4 cases before operation. All 7 patients underwent thyroidectomy with lymph node dissection of the level Ⅵ performed in 4 patients. Results: The time from suggestion to operation was 2 to 37 months, with an average of 15.1 months. The 6 patients were medullary thyroid carcinoma and 1 case with C-cell hyperplasia. The follow-up time was 2 to 82 months, with an average of 38.4 months. Postoperative serum calcitonin levels of all cases decreased to normal level, with biochemical cure. There was no sign of recurrence on ultrasound examination. All 7 patients had no serious complications, no obvious thyroid dysfunction. Their height, weight and other indicators of pediatric patients were similar to those of their peers, with normal growth and development. Conclusion: For healthy people with MEN2A/MEN2B family history, prophylactic thyroidectomy can be carried out selectively based on the comprehensive evaluation of "graded early warning system" with strict screening and close monitoring.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Multiple Endocrine Neoplasia Type 2b/surgery* ; Thyroidectomy ; Multiple Endocrine Neoplasia Type 2a/surgery* ; Calcitonin ; Germ-Line Mutation ; Proto-Oncogene Proteins c-ret/genetics*

OBJECTIVE: To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). METHODS: Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. RESULTS: Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.
Humans ; Infant ; Male ; Family ; Genetic Testing ; Genomics ; Mutation ; Tuberous Sclerosis/genetics* ; Child, Preschool ; East Asian People

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.
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Humans ; Lung Neoplasms/therapy* ; Early Detection of Cancer ; Lung/surgery* ; Treatment Outcome ; Radiosurgery/methods* ; Neoplasms, Multiple Primary/pathology*