MR Spectroscopy for Detecting Fumarate Hydratase Deficiency in Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.

Background Noninvasive in vivo detection of fumarate accumulation may help identify fumarate hydratase deficiency in renal cancer related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Purpose To investigate the feasibility of MR spectroscopy (MRS) in detecting elevated fumarate levels in HLRCC-associated renal cancers. Materials and Methods This study included an experimental xenograft mouse model and prospective clinical cohort. First, MRS was performed on patient-derived tumor xenograft models and control models to detect fumarate. Then, consecutive participants with clinical suspicion of HLRCC-associated renal tumors were enrolled. For the detection of fumarate, MRS results were classified as detected, borderline, undetected, or technical failure. The sensitivity, specificity, and accuracy of MRS for diagnosing HLRCC-associated renal cancer were assessed. The signal-to-noise ratio (SNR) of the fumarate peak was calculated and evaluated with receiver operating characteristic curve analysis. Results Fumarate peaks were detected at 6.54 parts per million in all three patient-derived xenograft models. A total of 38 participants (21 men; mean age, 47 years [range, 18-71 years]) with 46 lesions were analyzed. All primary HLRCC-associated renal cancers showed a fumarate peak; among the seven metastatic HLRCC-associated lesions, a fumarate peak was detected in three lesions and borderline in two. When only detected peaks were regarded as positive findings, the sensitivity, specificity, and accuracy of MRS at the lesion level were 69% (nine of 13 lesions), 100% (33 of 33 lesions), and 91% (42 of 46 lesions), respectively. When borderline peaks were also included as a positive finding, the sensitivity, specificity, and accuracy reached 85% (11 of 13 lesions), 88% (29 of 33 lesions), and 87% (40 of 46 lesions), respectively. The SNR of fumarate showed an area under the receiver operating characteristic curve of 0.87 for classifying HLRCC-associated tumors. Conclusion MR spectroscopy of fumarate was sensitive and specific for hereditary leiomyomatosis and renal cell carcinoma-associated tumors. © RSNA, 2022 Online supplemental material is available for this article.

Pancreas in Hereditary Syndromes: Cross-sectional Imaging Spectrum.

A wide spectrum of hereditary syndromes predispose patients to distinct pancreatic abnormalities, including cystic lesions, recurrent pancreatitis, ductal adenocarcinoma, nonductal neoplasms, and parenchymal iron deposition. While pancreatic exocrine insufficiency and recurrent pancreatitis are common manifestations in cystic fibrosis and hereditary pancreatitis, pancreatic cysts are seen in von Hippel-Lindau disease, cystic fibrosis, autosomal dominant polycystic kidney disease, and McCune-Albright syndrome. Ductal adenocarcinoma can be seen in many syndromes, including Peutz-Jeghers syndrome, familial atypical multiple mole melanoma syndrome, Lynch syndrome, hereditary breast and ovarian cancer syndrome, Li-Fraumeni syndrome, and familial pancreatic cancer syndrome. Neuroendocrine tumors are commonly seen in multiple endocrine neoplasia type 1 syndrome and von Hippel-Lindau disease. Pancreatoblastoma is an essential component of Beckwith-Wiedemann syndrome. Primary hemochromatosis is characterized by pancreatic iron deposition. Pancreatic pathologic conditions associated with genetic syndromes exhibit characteristic imaging findings. Imaging plays a pivotal role in early detection of these conditions and can positively affect the clinical outcomes of those at risk for pancreatic malignancies. Awareness of the characteristic imaging features, imaging-based screening protocols, and surveillance guidelines is crucial for radiologists to guide appropriate patient management. ©RSNA, 2021.

Hereditary ovarian tumour syndromes: current update on genetics and imaging.

Hereditary ovarian tumour syndromes are a diverse group of hereditary syndromes characterised by the development of specific histotypes of ovarian neoplasms. While BRCA syndromes are exclusively associated with high-grade serous carcinomas, patients with Lynch syndrome show a preponderance of endometrioid subtype of ovarian and endometrial carcinomas. Distinct non-epithelial phenotypes, such as sex cord stromal tumours with annular tubules, Sertoli-Leydig cell tumours, and small cell carcinoma of the hypercalcaemic type occur in patients with Peutz-Jeghers, DICER1, and rhabdoid tumour predisposition syndromes, respectively. Gorlin-Goltz syndrome is characterised by the development of bilateral, multiple ovarian fibromas in 14-24% of patients. Ovarian steroid cell tumours and broad ligament papillary cystadenomas are characteristically found in women with von Hippel-Lindau syndrome. Recent studies have allowed the characterisation of tumour genetics and associated oncological pathways that contribute to tumourigenesis. Implications of the diagnosis of these syndromes on screening, management, and prognosis are discussed.

Constitutional mismatch repair deficiency (CMMRD) presenting with high-grade glioma, multiple developmental venous anomalies and malformations of cortical development-a multidisciplinary/multicentre approach and neuroimaging clues to clinching the diagnosis.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare cancer-predisposition syndrome associated with a high risk of developing a spectrum of malignancies in childhood and adolescence, including brain tumours. In this report, we present the case of an 8-year-old boy with acute headache, vomiting and an episode of unconsciousness in whom brain imaging revealed a high-grade glioma (HGG). The possibility of an underlying diagnosis of CMMRD was suspected radiologically on the basis of additional neuroimaging findings, specifically the presence of multiple supratentorial and infratentorial developmental venous anomalies (DVAs) and malformations of cortical development (MCD), namely, heterotopic grey matter. The tumour was debulked and confirmed to be a HGG on histopathology. The suspected diagnosis of CMMRD was confirmed on immunohistochemistry and genetic testing which revealed mutations in PMS2 and MSH6. The combination of a HGG, multiple DVAs and MCD in a paediatric or young adult patient should prompt the neuroradiologist to suggest an underlying diagnosis of CMMRD. A diagnosis of CMMRD has an important treatment and surveillance implications not only for the child but also the family in terms of genetic counselling.

The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex.

Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to "ash-leaf like" hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance.

Hereditary vs Familial Pancreatic Cancer: Associated Genetic Syndromes and Clinical Perspective.

Pancreatic ductal adenocarcinoma (PDAC) is a disease marked by high rates of mortality; it is mostly incurable at the time of diagnosis. Only about 7% of patients survive 5 years after diagnosis. Diagnosis at a late stage and rapid progression with minimal response to available treatments are the main reasons for this poor outcome. It is crucial to identify individuals at high risk of developing PDAC so preventive and early detection measures can be employed. Approximately 10% to 15% of PDAC cases have a hereditary or familial basis. In the majority of PDAC cases, no main causative gene has been identified, but several known germline pathogenic mutations have been shown to be related to an increased risk of this cancer. The presence of 2 or more patients with pancreatic cancer within the circle of first-degree relatives, without the presence of a causative germline mutation, is defined as familial pancreatic cancer; this accounts for 4% to 10% of PDAC. Based on the growing evidence supporting the benefit of germline genetic testing in patients with PDAC, both the American Society of Clinical Oncology and the National Comprehensive Cancer Network recently updated their guidelines to include recommendations around genetic testing for patients with pancreatic cancer. However, there is no general consensus on the group of patients and individuals who should be studied and screened. We present a demonstrative case and review the available data on hereditary and familial PDAC.

BRCA and Beyond: Comprehensive Image-rich Review of Hereditary Breast and Gynecologic Cancer Syndromes.

In addition to the well-characterized BRCA1 and BRCA2 hereditary breast and ovarian cancer syndromes, many other syndromes that are associated with genetic mutations predispose individuals to an increased risk of breast and gynecologic malignancies. Many mutated genes encode for tumor-suppressor products and are inherited in an autosomal dominant manner. Mutations markedly increase an individual's lifetime risk of cancers in different organ systems, depending on the associated syndrome. These syndromes include Lynch syndrome, the most common hereditary cause of endometrial cancer, and Peutz-Jeghers syndrome, which increases the risks of breast cancer, ovarian cancer, and cervical adenoma malignum. Li-Fraumeni syndrome and Cowden syndrome increase the risk of breast cancer, and Gorlin syndrome increases the risk of ovarian fibromas. With advances in genetic testing, clinicians' knowledge and awareness of the numerous additional genes associated with breast and ovarian cancers, such as ATM, CHEK2, and PALB2, are rapidly expanding. Radiologists have essential roles in patient management, which include developing optimal screening protocols for these patients and closely monitoring them for the development or recurrence of disease-specific malignancies. Radiologists' roles continue to increase and evolve as more mutations are identified and high-risk imaging screening recommendations expand to identify these patients. Understanding the epidemiologic, genetic, and pathophysiologic features and the cancers associated with these syndromes enables radiologists to appropriately contribute to patient management, ensure accurate and timely diagnosis, and make syndrome-specific imaging recommendations. ©RSNA, 2020.

Hereditary Gastrointestinal Cancer Syndromes: Role of Imaging in Screening, Diagnosis, and Management.

Hereditary gastrointestinal (GI) cancer syndromes due to specific germline mutations are characterized by an increased risk of GI tract malignancies, extra-GI tract cancers, and benign abnormalities. These syndromes include Lynch syndrome, familial adenomatous polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome, Cowden syndrome, hereditary diffuse gastric cancer, and hereditary pancreatic cancer. Timely identification of the responsible genes will help predict future cancer risks in these patients and their family members. Early detection of cancers is possible with appropriate screening methods; risk-reducing measures will help in cancer prevention. Select malignancies and benign conditions associated with these syndromes have distinctive imaging features that can aid in classifying the syndromes. Imaging also plays a pivotal role in screening and surveillance of patients as well as their at-risk relatives and is invaluable for follow-up of treated malignancies. The American College of Gastroenterology has established specific guidelines for diagnosis and management of hereditary GI cancer syndromes. Knowledge of the imaging features of various pathologic conditions and screening strategies will guide appropriate management of patients and at-risk family members. ©RSNA, 2019.

Current and Emerging Roles of Whole-Body MRI in Evaluation of Pediatric Cancer Patients.

Imaging is fundamental to diagnosis and management of pediatric patients with cancer and cancer predisposition syndromes (CPSs). Whole-body MRI has emerged as a versatile tool for pediatric oncologic imaging, with the potential to spare children from ionizing radiation imparted by conventional modalities such as CT and PET. Whole-body MRI also enables simultaneous high-resolution local-regional staging and wide field-of-view distant staging in the same imaging session, with superior evaluation of the brain, spine, liver, and marrow. Recent technical advances have reduced imaging times and enhanced image quality, with continued advances on the near horizon. Pulse sequences such as whole-body diffusion-weighted imaging have also broadened the range of diagnostic information obtainable. In addition, increasing identification of children with CPSs has compelled efforts to establish surveillance imaging strategies for affected individuals, with whole-body MRI playing a pivotal role in screening algorithms for several CPSs. In light of these emerging trends, a working knowledge of oncologic whole-body MRI applications and evolving CPS surveillance algorithms is vital to providers who participate in the care of pediatric patients affected by or predisposed to cancer. Recognizing both the strengths and limitations of whole-body MRI not only enables more thoughtful implementation but also improves the accuracy of image interpretation. ©RSNA, 2019 See discussion on this article by Khanna .

Radiologist's Primer on Imaging of Common Hereditary Cancer Syndromes.

Recent advances in pathology and genetics have improved our understanding of the pathogenesis of inherited and sporadic malignancies. Detailed studies of hereditary cancer syndromes-which contribute to 5%-10% of the overall cancer burden-have shed new light on the important role of genetic abnormalities in tumor metabolism, oncologic pathways, and clinicobiologic behavior. Many inherited cancer syndromes are characterized by development of pathognomonic histotypes of neoplasms in specific target organs. Cross-sectional imaging plays an integral role in diagnosis, screening, surveillance, and treatment of patients with a wide spectrum of cancer syndromes. This article focuses on the imaging spectrum of select hereditary cancer syndromes, featuring imaging features of associated common and uncommon tumors and conditions in each syndrome, along with screening and surveillance recommendations for each condition. MRI has proved to be a useful screening modality in such patients, as these patients are often young and require prolonged screening; MRI has the added advantage of better soft-tissue contrast without ionizing radiation. The whole-body MRI protocol is also briefly discussed. The radiologist is sometimes the first physician to encounter such patients, and knowledge of these syndromes can help identify these patients earlier and impact their care by timely diagnosis and intervention. This also benefits the family members, as they can also undergo genetic testing and obtain an early diagnosis and screening. ©RSNA, 2019.

Neurocristopathies: Enigmatic Appearances of Neural Crest Cell-derived Abnormalities.

The neural crest is an important transient structure that develops during embryogenesis in vertebrates. Neural crest cells are multipotent progenitor cells that migrate and develop into a diverse range of cells and tissues throughout the body. Although neural crest cells originate from the ectoderm, they can differentiate into mesodermal-type or endodermal-type cells and tissues. Some of these tissues include the peripheral, autonomic, and enteric nervous systems; chromaffin cells of the adrenal medulla; smooth muscles of the intracranial blood vessels; melanocytes of the skin; cartilage and bones of the face; and parafollicular cells of the thyroid gland. Neurocristopathies are a group of diseases caused by the abnormal generation, migration, or differentiation of neural crest cells. They often involve multiple organ systems in a single person, are often familial, and can be associated with the development of neoplasms. As understanding of the neural crest has advanced, many seemingly disparate diseases, such Treacher Collins syndrome, 22q11.2 deletion syndrome, Hirschsprung disease, neuroblastoma, neurocutaneous melanocytosis, and neurofibromatosis, have come to be recognized as neurocristopathies. Neurocristopathies can be divided into three main categories: dysgenetic malformations, neoplasms, and combined dysgenetic and neoplastic syndromes. In this article, neural crest development, as well as several associated dysgenetic, neoplastic, and combined neurocristopathies, are reviewed. Neurocristopathies often have clinical manifestations in multiple organ systems, and radiologists are positioned to have significant roles in the initial diagnosis of these disorders, evaluation of subclinical associated lesions, creation of treatment plans, and patient follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

Imaging of DICER1 syndrome.

DICER1 syndrome is a highly pleiotropic tumor predisposition syndrome that has been increasingly recognized in the last 10 years. Diseases in the syndrome result from mutations in both copies of the gene DICER1, a highly conserved gene that is critically implicated in micro-ribonucleic acid (miRNA) biogenesis and hence modulation of messenger RNAs. In general, susceptible individuals carry an inherited germline mutation that disables one copy of DICER1; within tumors, a very characteristic second mutation alters function of the other gene copy. About 20 hamartomatous, hyperplastic or neoplastic conditions comprise DICER1 syndrome. Most are not life-threatening, but some are aggressive malignancies. There are many unaffected carriers because penetrance is generally low; however, clinically occult thyroid nodules and lung cysts are frequent. Rare diseases of early childhood were the first recognized conditions in DICER1 syndrome, while other conditions affect adolescents and adults. The hallmarks of DICER1 syndrome are certain rare tumors including pleuropulmonary blastoma; cystic nephroma; ovarian Sertoli-Leydig cell tumor; sarcomas of the cervix, kidneys and cerebrum; pituitary blastoma; ciliary body medulloepithelioma; and nasal chondromesenchymal hamartoma. Radiologists are often the first practitioners to observe these diverse manifestations and play a primary role in recognizing DICER1 syndrome.

Whole-body magnetic resonance imaging of pediatric cancer predisposition syndromes: special considerations, challenges and perspective.

Cancer predisposition syndromes increase the incidence of tumors during childhood and are associated with significant morbidity and mortality. Imaging is paramount for ensuring early detection of neoplasms, impacting therapeutic interventions and potentially improving outcome. While conventional imaging techniques involve considerable exposure to ionizing radiation, whole-body MRI is a radiation-free modality that allows continuous imaging of the entire body and has increasingly gained relevance in the surveillance, diagnosis, staging and monitoring of pediatric patients with cancer predisposition syndromes. Nevertheless, widespread implementation of whole-body MRI faces several challenges as a screening tool. Some of these challenges include developing clinical indications, variability in protocol specifications, image interpretation as well as coding and billing practices. These factors impact disease management, patient and family experience and research collaborations. In this discussion we review the aforementioned special considerations and the potential direction that might help overcome these challenges and promote more widespread use of whole-body MRI in children with cancer predisposition syndromes.

Gastric cancer and paraneoplastic dermatomyositis as complications of an unrecognized juvenile polyposis syndrome.

Juvenile polyposis syndrome is a rare autosomal-dominant disorder characterized by multiple hamartomatous polyps in the gastrointestinal tract. It is associated with an increased risk of gastrointestinal cancer. We report the case of a 49-year-old woman presenting with proximal muscle weakness, weight loss, severe anemia, and melena. One year before, the diagnosis of a "fundic gland polyposis" was presumed after endoscopic evaluation for iron deficiency anemia had shown numerous polyps limited to the gastric mucosa. On admission, the diagnosis of dermatomyositis was made based on laboratory results with a marked elevated creatine kinase as well as the presence of characteristic clinical findings and muscle histology. Upper endoscopy revealed multiple pedunculated, edematous polyps in the stomach without apparent cancerous lesions intraluminally. Infiltration of the muscular layer was not detectable on endoscopic ultrasound. Histopathological examination of the polyps showed smooth outer surfaces and multiple dilated cystic glands, consistent with hamartomatous juvenile-type polyps. Magnetic resonance imaging revealed a peritoneal mass close to the greater curvature of the stomach, which was identified as a poorly differentiated adenocarcinoma by laparoscopic sampling. Immunohistochemical analysis of resected polyps was remarkable for a loss of SMAD4 expression, a finding that is very commonly observed in patients with gastric juvenile polyposis syndrome. Despite initial treatment response to glucocorticoids and chemotherapy, the patient died 5 months later due to progressive illness. Patients with gastric juvenile polyposis and SMAD4 mutations are at a high risk of developing gastric cancer; hence, early gastrectomy should be considered.

Effective Immunotherapy of Glioblastoma in an Adolescent with Constitutional Mismatch Repair-Deficiency Syndrome.

BACKGROUND: Individuals with constitutional mismatch repair-deficiency syndrome (CMMR-D) are characterised by early occurrence of colon cancer, haematological malignancies, and brain tumors (malignant gliomas, high-grade gliomas) in childhood, adolescence, and early adulthood. High mutational tumor burden is typical of glioblastoma in CMMR-D patients and could be a reason why this type of glioblastoma responds well to immunotherapies, including those that employ checkpoint inhibitors. OBSERVATION: We describe a case of an adolescent with CMMR-D that had been genetically proven by whole exome sequencing (c.2T>A/p.M1K and c.2521delT/p.W841fs PMS2 gene mutation). The patient presented successively with colon cancer and glioblastoma with a high mutational burden. The individualized glioblastoma therapy was based on the biological tumor profile and included immunotherapy with a combination of vaccination with autologous dendritic cells producing IL-12 and nivolumab, in addition to radiotherapy with metronomic temozolomide. The patient is still alive 21 months after the initial glioblastoma diagnosis and shows a complete therapeutic response documented by repeated magnetic resonance examinations. CONCLUSION: Individuals with CMMR-D should be regularly examined using established algorithms. Whole body magnetic resonance imaging can play a key role, because it enables the early diagnosis of malignancy during the asymptomatic period. Malignancies in CMMR-D patients usually exhibit a hypermutated genotype and respond to immunotherapy. Conventional glioblastoma therapy is only palliative. Patients can benefit from an individualized therapeutic plan based on the tumor biological profile. Extensive molecular analysis of the tumor tissue is necessary. Key words hereditary cancer predisposition syndromes - glioblastoma - whole exome sequencing - immunotherapy - vaccines - checkpoint inhibitors This study was supported by the research project of the Czech Ministry of Health AZV 16-33209A (Next generation sequencing and express profiling as diagnostic tools for personalized therapeutic plans in children with solid tumors). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 26. 9. 2018 Accepted: 18. 11. 2018.

Inherited pulmonary cylindromas: extending the phenotype of CYLD mutation carriers.

BACKGROUND: Germline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas. OBJECTIVES: To search for clinical and radiological features of multiple pulmonary cylindromas in a cohort of 16 patients with CYLD mutations. METHODS: A retrospective case-note review was carried out in a tertiary dermatogenetics clinic where CYLD mutation carriers are reviewed on an annual basis. In-depth investigation was carried out for patients with pulmonary tumours. RESULTS: Four patients had radiological imaging of their lungs, of which two had multiple pulmonary cylindromas that were confirmed histologically. Serial computed tomography monitoring allowed for pre-emptive endobronchial laser ablation, preventing major airway obstruction and pulmonary collapse. CONCLUSIONS: Pulmonary cylindromas are an unrecognized, but infrequently symptomatic, aspect of the phenotype in these patients that can have implications for patient care. They should be considered in patients with a high tumour burden that present with respiratory symptoms, and where appropriate, monitored with serial imaging.

Novel Fumarate Hydratase Mutation in Siblings With Early Onset Uterine Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.

Hereditary leiomyomatosis renal cell cancer syndrome is an autosomal dominant disorder characterized by uterine and cutaneous leiomyomas and increased predisposition to renal cell carcinoma, papillary type II. The syndrome is caused by heterozygous mutations to the fumarate hydratase (FH) gene located on chromosome 1. Affected females generally present with early onset, atypical uterine leiomyomas and cutaneous findings, however, delays in diagnosis are very common in patients with isolated uterine findings. We present a case series of 2 sisters in their 20s who presented with isolated uterine leiomyomas and were found to carry a novel mutation for the fumarate hydratase gene. One patient was referred for treatment of infertility and recurrent miscarriages and the other was referred for acute symptomatic anemia due to myomas. Prompt diagnosis of hereditary leiomyomatosis renal cell cancer was made due to a high index of clinical suspicion based on early onset disease and familial clustering as well as characteristic pathologic findings on uterine leiomyoma surgical specimen. Timely diagnosis not only allowed for genetic counseling and renal cancer surveillance, but also for fertility counseling given the increased morbidity associated with uterine leiomyoma due to hereditary leiomyomatosis and renal cell cancer syndrome.

Imaging for Screening and Surveillance of Patients with Hereditary Forms of Renal Cell Carcinoma.

PURPOSE OF REVIEW: To summarize the literature providing the basic genetic and clinical characteristics of renal cell carcinoma (RCC) familial syndromes, as well as to describe associated unique imaging characteristics and appropriate imaging protocols. RECENT FINDINGS: At least 5-8% of RCC cases are associated with hereditary syndromes. These patients are prone to developing multiple renal tumors or associated malignancies and require more intense diagnostic and follow-up imaging studies. New familial types of RCC are continuously discovered, vis-à-vis recent characterization of BAP1 associated RCC and MITF associated cancer syndrome. With increasing number of recognizable familial syndromes associated with RCC, physicians should be familiar with the different syndromes, the associated risks of malignancy and appropriate imaging protocols.

Intralesional Bleomycin Injection for Propranolol-Resistant Hemangiomas.

Propranolol has been the first-line treatment for alarming hemangiomas. However, some hemangiomas are propranolol-resistant. The authors reported 1 propranolol-resistant hemangioma which was treated with intralesional bleomycin injections. Sixteen months after 3 injections, the lesion still remained stable. Its potential mechanism was clarified by ultrasonic monitoring. Intralesional bleomycin injection can be considered an ideal option in treating propranolol-resistant hemangiomas.