ABSTRACT
Juvenile xanthogranuloma is the most frequent form of non-Langerhans cell histiocytosis in children. Clinically, it presents as well defined, yellowish papules that are typically located on the head, neck, upper trunk, and proximal region of the extremities. Although solitary lesions are the most common presentation, few cases of multiple juvenile xanthogranuloma have been described, more frequently associated with extracutaneous involvement. We report a 2-month-old girl with 22 cutaneous papules, clinically and histologically compatible with juvenile xanthogranulomas. Screening of visceral involvement was performed with no evidence of systemic disease. Identifying high-risk factors of systemic disease in patients with multiple juvenile xanthogranuloma is essential to perform an appropriate management of this entity.
Subject(s)
Xanthogranuloma, Juvenile , Humans , Xanthogranuloma, Juvenile/pathology , Xanthogranuloma, Juvenile/diagnosis , Female , InfantABSTRACT
BACKGROUND: The "C group" of the histiocytic disorders is characterized by non-Langerhans-cell histiocytic lesions in the skin, mucosal surfaces, or both, out of which Juvenile xanthogranuloma (JXG) is the most common typically affecting the skin. The eye is the most common extra-cutaneous site of JXG., we aim at providing our clinical and histopathological experience with this group of diseases including the adult-onset xanthogranuloma (AXG). METHODS: This is a retrospective cohort study of all patients with the tissue diagnosis of ocular and periocular cutaneous and mucocutaneous non-LCH disorders who presented to us over a period of 25 years (January 1993 to December 2018). RESULTS: Twenty patients were diagnosed as "Group C" disease with an age range of 2 months-60.9 years. Eleven patients were females (55%) and nine were males (45%). The involvement was mostly unilateral in 80.9%. All cases fell into the xanthogranuloma family with 11 JXG patients, 8 AXG patients of skin and ocular surface, and one patient with solitary reticulohistiocytoma (SRH). The clinical site of involvement in JXG was primarily in the eyelid in 5 patients (45%), ocular surface lesions in 2 (18%), iris in 2 (18%), choroidal and bilateral orbital lesions in 1 patient each (9%). The group of AXG, presented equally with eyelid lesions in 4/8 and ocular surface lesions in 4/8. The non-Langerhans' histiocytic infiltrate showed supportive immunohistochemical staining properties (reactive to CD68 marker and negative to S-100 and langerin markers). CONCLUSION: Among the rare histiocytic disorders, xanthogranulomatosis is the commonest and has wide clinical manifestations. Accurate diagnosis needs to be supported by typical histopathological findings. JXG was the commonest in our study with relatively older mean age at presentation and frequent eyelid rather than iris involvement. AXG is often confused with xanthelasma when involving the eyelids with corneal limbal involvement is relatively frequent.
Subject(s)
Skin Neoplasms , Xanthogranuloma, Juvenile , Male , Adult , Female , Humans , Infant , Retrospective Studies , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/metabolism , Xanthogranuloma, Juvenile/pathology , Face , IrisABSTRACT
Juvenile xanthogranuloma is a benign self-limiting lesion commonly described in infants and young children. It most commonly involves the skin presenting as single or multiple yellowish-brown papules. Clinical scenario with the classic histomorphology showing histiocytic aggregates in the dermis with xanthomatous cytoplasm, toutan type giant cells, immunohistochemistry with positive CD68, CD163, factor XIIIa and negative CD1a and S-100 help in diagnosis. However, diagnosis becomes challenging with predominant systemic bone marrow involvement in post-B-lymphoblastic leukemia settings.
Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Xanthogranuloma, Juvenile , Xanthomatosis , Infant , Child , Humans , Child, Preschool , Bone Marrow/pathology , Skin/pathology , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/pathology , Histiocytes/pathology , Xanthomatosis/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathologyABSTRACT
Juvenile xanthogranuloma (JXG) is usually identified by Touton giant cells, so their absence can complicate diagnosis. We encountered a case of non-typical neonatal JXG lacking Touton giant cells, which was difficult to differentiate from aleukemic leukemia cutis because of overlapping histopathological characteristics. A 1 month-old girl presented with a blueberry muffin rash and multiple 1-2 cm nodules within the subcutaneous and deeper soft tissues. Blood tests revealed pancytopenia. The initial nodule biopsy showed mononuclear cell infiltration, suggestive of mature monocytes or histiocytes, but no Touton giant cells. Bone marrow examination showed no evidence of leukemia. Despite worsening of the rash, pancytopenia, and weight gain over the following month, the results of the second biopsy remained consistent with the initial findings. Consequently, we provisionally diagnosed aleukemic leukemia cutis and initiated chemotherapy. After two courses of chemotherapy, the pancytopenia improved, but the nodules only partially regressed. A third biopsy of the nodule was performed to evaluate the histological response, and revealed Touton giant cells, confirming the diagnosis of JXG. In conclusion, distinguishing non-typical JXG from aleukemic leukemia cutis is challenging. This case highlights the importance of multiple biopsies and the potential for histopathological maturation.
Subject(s)
Exanthema , Leukemia , Pancytopenia , Skin Neoplasms , Xanthogranuloma, Juvenile , Female , Humans , Infant , Exanthema/pathology , Histiocytes/pathology , Leukemia/pathology , Pancytopenia/pathology , Skin Neoplasms/pathology , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/complications , Xanthogranuloma, Juvenile/pathologySubject(s)
Humans , Infant , Child, Preschool , Child , Polyneuropathies/diagnosis , Vision Disorders/diagnosis , Epilepsies, Partial/diagnosis , Xanthogranuloma, Juvenile/diagnosis , Neurofibromatoses/complications , Neurofibromatoses/diagnosis , Neurofibromatoses/diagnostic imaging , Meningioma/diagnosis , Intellectual Disability/diagnosis , Neurilemmoma/diagnosis , Diagnosis, DifferentialABSTRACT
Giant Juvenile Xanthogranuloma (GJXG) corresponds to an infrequent variant of Juvenile Xantho- granuloma (JXG) and is characterized by a lesion larger than 2 cm in diameter. It usually presents as a plaque but infrequently, presents as an ulcerated nodule. OBJECTIVE: To report two cases of atypical presentation of GJXG, highlighting the importance of considering them in the differential diagnosis of large, ulcerated tumors in infants. CLINICAL CASES: Case 1: A 4-month-old healthy male infant presented with a rapid and progressive growing left inguinal nodule, present since 2 months of age. At physical examination he presented with a 2.6 cm indurated erythematous nodule with central ulceration. Histological study of an incisional biopsy was compatible with JXG. Ophthalmologic involvement was ruled out. Because of functional impairment and parents worry complete surgical removal was performed. The patient had favorable evolution without local recurrence at 4 years of follow-up. Case 2: A 6-month-old healthy male infant presented with a 2.4 cm scapular crusted nodule of rapid and progressive growth, present since birth. Histological study of an incisional biopsy confirmed JXG. Ophthalmologic involvement was ruled out. After 18 months of periodic clinical follow-up, there was a progressive reduction in size of the lesion. CONCLUSIONS: The cases presented highlight the importance of considering JXG in the differential diagnosis of large, ulcerated tumors in infants. When encountered to atypical JXG presentations, histologic studies help to confirm the diagnosis. Given the favorable prognosis of this diagnosis, periodic clinical follow-up is advised; in exceptional cases, surgical or ablative treatments may be considered.
Subject(s)
Neoplasms , Xanthogranuloma, Juvenile , Humans , Infant , Male , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/surgery , Xanthogranuloma, Juvenile/pathology , Biopsy , Diagnosis, Differential , Neoplasms/diagnosisABSTRACT
This observational case series examines the diagnosis and treatment of 2 patients with systemic juvenile xanthogranuloma treated with alectinib.
Subject(s)
Lung Neoplasms , Xanthogranuloma, Juvenile , Humans , Piperidines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Receptor Protein-Tyrosine Kinases , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/drug therapyABSTRACT
Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. Its systemic form affects 4% of patients. Lesions in the Central Nervous System (CNS) occur in 2% of systemic cases. Sellar JXG should be one of the differential diagnoses for sellar lesions in young. This is a 15-year-old patient with non-specific headache, progressive visual loss and magnetic resonance imaging showing sellar lesion with suprasellar extension. The patient underwent microsurgery by pterional craniotomy with partial resection of the tumor. Pathology evidenced JXG. It progressively evolved with impairment of neuroendocrine functions, new lesions in different CNS locations and death two years after diagnosis. Sellar JXG without cutaneous manifestations is rare. There are no specific findings of the disease. Diagnosis requires additional tests, being defined by pathological analysis. Total resection presents a greater potential control comparing to partial resection. Even so, some patients may have progressive disease with poor clinical outcome.
Subject(s)
Xanthogranuloma, Juvenile , Adolescent , Humans , Diagnosis, Differential , Headache , Magnetic Resonance Imaging , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/surgery , Xanthogranuloma, Juvenile/pathologySubject(s)
Xanthogranuloma, Juvenile , Xanthomatosis , Humans , Infant , Xanthogranuloma, Juvenile/diagnosis , Skin , Xanthomatosis/diagnosisABSTRACT
BACKGROUND: Juvenile Xanthogranuloma (JXG) is a non-hereditary, self-limiting disease which is usually presented in infancy or early childhood and in males over females. CASE PRESENTATION: We report a rare case of oral Juvenile Xanthogranuloma with recurrent progressive gingival hyperplasia and concomitant presentation of osteolysis in a 21-year-old adult male with no significant medical history. Patient presented with generalized gingival hyperplasia, osteolysis of the maxilla and mandible, and a round, firm, nodular mass with clear circumference on the left shoulder. Results of gingival tissue biopsy, karyotype, bone marrow biopsy and immunohistochemistry were suggestive of a diagnosis of Juvenile Xanthogranuloma with no association to hematologic malignancy. Unfortunately, patient declined treatment and elected to be transferred back to local hospital for future evaluation. CONCLUSIONS: Juvenile Xanthogranuloma in adults can have atypical manifestations including generalized gingival hyperplasia and osteolysis of the maxilla and mandible. It should be differentiated between Langerhans cell histiocytosis, Papillon-Lefevre Syndrome, and Pyogenic Granulomas. Despite uncommon incidence, it should be included in differential diagnoses in cases of similar clinical presentations.
Subject(s)
Gingival Hyperplasia , Histiocytosis, Langerhans-Cell , Osteolysis , Xanthogranuloma, Juvenile , Female , Humans , Adult , Male , Child, Preschool , Young Adult , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/pathology , Osteolysis/etiology , Gingival Hyperplasia/diagnosis , Gingival Hyperplasia/etiology , Histiocytosis, Langerhans-Cell/diagnosis , ImmunohistochemistryABSTRACT
Background The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. Patients and methods Casecontrol study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. Results The prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.499.96%] and a positive predictive value (PPV) of 98.80% [92.5499.94%] were estimated for NA and a specificity of 99.27% [95.499.96%] and a PPV of 92.86% [64.1799.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). Conclusions NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated (AU)
Antecedentes El diagnóstico de la neurofibromatosis tipo 1 (NF1) se demora normalmente en niños sin antecedentes familiares. Nuestro objetivo fue definir la prevalencia y características de las manifestaciones cutáneas prevalentes en NF1, en comparación con la población general, que siguen siendo excluidas de los criterios diagnósticos para NF1. Pacientes y métodos Estudio de casos y controles, pareado por grupos de edad, en el que se incluyeron 108 pacientes diagnosticados de NF1 y 137 controles sanos. Resultados La prevalencia de nevus anemicus (NA) (p < 0,001) y xantogranuloma juvenil (XJ) (p < 0,001) fue significativamente superior en la población afectada de NF1, en comparación con el grupo control. Se estimaron una especificidad del 99,27% [Intervalo de confianza (IC): 95,4-99,96%] y un valor predictivo positivo (VPP) del 98,80% [92,54-99,94%] para NA, y una especificidad del 99,27% [95,4-99,96%] y VPP del 92,86% [64,17-99,63%] para XJ en el diagnóstico de NF1 en niños que presentan 6 o más manchas café con leche. También se evidenciaron diferencias estadísticamente significativas en la distribución por fototipos (p 0,025), y con relación al prurito generalizado sin ninguna otra causa (p <,001). Conclusiones Los NA y los XJ son hallazgos clínicos relevantes para el diagnóstico de NF1, especialmente durante los primeros años de vida. Consideramos que debería evaluarse su inclusión en los criterios diagnósticos de la enfermedad (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Cafe-au-Lait Spots/diagnosis , Neurofibromatosis 1/diagnosis , Pigmentation Disorders/diagnosis , Xanthogranuloma, Juvenile/diagnosis , Case-Control Studies , Cross-Sectional StudiesABSTRACT
Antecedentes El diagnóstico de la neurofibromatosis tipo 1 (NF1) se demora normalmente en niños sin antecedentes familiares. Nuestro objetivo fue definir la prevalencia y características de las manifestaciones cutáneas prevalentes en NF1, en comparación con la población general, que siguen siendo excluidas de los criterios diagnósticos para NF1. Pacientes y métodos Estudio de casos y controles, pareado por grupos de edad, en el que se incluyeron 108 pacientes diagnosticados de NF1 y 137 controles sanos. Resultados La prevalencia de nevus anemicus (NA) (p < 0,001) y xantogranuloma juvenil (XJ) (p < 0,001) fue significativamente superior en la población afectada de NF1, en comparación con el grupo control. Se estimaron una especificidad del 99,27% [Intervalo de confianza (IC): 95,4-99,96%] y un valor predictivo positivo (VPP) del 98,80% [92,54-99,94%] para NA, y una especificidad del 99,27% [95,4-99,96%] y VPP del 92,86% [64,17-99,63%] para XJ en el diagnóstico de NF1 en niños que presentan 6 o más manchas café con leche. También se evidenciaron diferencias estadísticamente significativas en la distribución por fototipos (p 0,025), y con relación al prurito generalizado sin ninguna otra causa (p <,001). Conclusiones Los NA y los XJ son hallazgos clínicos relevantes para el diagnóstico de NF1, especialmente durante los primeros años de vida. Consideramos que debería evaluarse su inclusión en los criterios diagnósticos de la enfermedad (AU)
Background The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. Patients and methods Casecontrol study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. Results The prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.499.96%] and a positive predictive value (PPV) of 98.80% [92.5499.94%] were estimated for NA and a specificity of 99.27% [95.499.96%] and a PPV of 92.86% [64.1799.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). Conclusions NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Cafe-au-Lait Spots/diagnosis , Neurofibromatosis 1/diagnosis , Pigmentation Disorders/diagnosis , Xanthogranuloma, Juvenile/diagnosis , Case-Control Studies , Cross-Sectional StudiesABSTRACT
OBJECTIVE: To explore the genetic basis for a child with café-au-lait macules and juvenile xanthogranuloma. METHODS: Clinical data and peripheral blood samples of the patient and her family members were collected and subjected to targeted capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: A deletional variant in exon 23 of the NF1 gene was detected in the proband. Sanger sequencing has verified it as a de novo variant, which was highly correlated with the clinical manifestations of the patient and her mother. The diagnosis of neurofibromatosis 1 (NF1) was established. The variant was unreported previously. CONCLUSION: Targeted capture and next-generation sequencing combined with Sanger sequencing can facilitate early diagnosis of NF1 and provide a basis for the clinical treatment, genetic counseling and prenatal diagnosis.
Subject(s)
Neurofibromatosis 1 , Xanthogranuloma, Juvenile , Child , Female , Humans , Cafe-au-Lait Spots/diagnosis , Cafe-au-Lait Spots/genetics , Genes, Neurofibromatosis 1 , Neurofibromatosis 1/diagnosis , Neurofibromatosis 1/genetics , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/geneticsABSTRACT
A 4-month-old boy was admitted to the hospital after his parents noticed fog in his right eye for 27 days. Physical examination revealed multiple light brown macules on the skin. The intraocular pressure (IOP) of the right eye was 34.4 mmHg (1 mmHg=0.133kPa) and the corneal was enlarged and edema while the aqueous humor was cloudy with blood in the right eye. Yellow peripheral anterior synechia was seen on the temporal and inferior iris. Ultrasound biomicroscopy (UBM) showed extensive adhesion closure of the anterior chamber angle and the local thicken iris with the nodule. No obvious abnormality was observed in the left eye. It was confirmed as juvenile xanthogranuloma by skin lesion biopsy. IOP was normal after systemic and local therapy with corticosteroids and local IOP lowering medication. Follow up 35 months, IOP is normal without medication.
Subject(s)
Glaucoma, Angle-Closure , Glaucoma , Xanthogranuloma, Juvenile , Child , Glaucoma/complications , Glaucoma, Angle-Closure/diagnosis , Humans , Infant , Intraocular Pressure , Iris , Male , Tonometry, Ocular , Xanthogranuloma, Juvenile/complications , Xanthogranuloma, Juvenile/diagnosisABSTRACT
Abstract: Neurofibromatosis type 1 (NF1), is a rare genetic disorder that may involve almost every organ system in the body such as cutaneous, ophthalmologic and central and peripheral nervous system. Cutaneous findings are usually the first sign of the disease. In this study, we investigate the real prevalence of xanthogranulomas juvenile (JXG) and possible correlation with lymphoproliferative diseases. This is a retrospective study conducted on a population with NF1 followed by February 1983 to February 2022 at the "Sapienza" University of Rome, Italy. We investigate the real prevalence of juvenile xanthogranuloma in NF1 and possible correlation with lymphoproliferative diseases. JXG was present in 39 cases (3.1%). JXG is more frequent in NF1 than in the general population while the possible association with lymphoproliferative diseases in NF1 remains controversial.
Subject(s)
Neurofibromatosis 1 , Xanthogranuloma, Juvenile , Humans , Neurofibromatosis 1/complications , Neurofibromatosis 1/diagnosis , Neurofibromatosis 1/epidemiology , Prevalence , Retrospective Studies , Skin , Xanthogranuloma, Juvenile/complications , Xanthogranuloma, Juvenile/diagnosis , Xanthogranuloma, Juvenile/epidemiologyABSTRACT
Juvenile xanthogranuloma, a form of non-Langerhans cell histiocytosis can be defined as the proliferation of cells with macrophage like characteristics. It has been described as a benign, asymptomatic and common self-healing disorder of non-Langerhans cell histiocytosis (LCH), affecting mostly infants, children and rarely adults. We have documented a case of a 40 year old male who presented to us with extensive insidious papulonodulous growth over the face. The facial disfigurement caused was catastrophic. An extensive surgical excision and reconstruction was performed followed by histopathological evaluation. Microscopic study and immune histochemistry revaled Juvenile Xanthogranuloma of adult. The article highlights the presentation, diagnosis and management of this mammoth, rare disease.