Al-Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2-Related Disorders.

Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Magnetic resonance elastography in evaluation of liver fibrosis in children with chronic liver disease.

BACKGROUND: Magnetic resonance elastography (MRE) has been used to stage liver fibrosis in adults. We aimed to assess the agreement between the Ishak scoring system and magnetic resonance elastography-measured liver stiffness (MRE-LS) in children. This study included all the children who underwent abdominal MRE and liver biopsies between February 2018 and January 2021. The correlation between MRE-LS and Ishak fibrosis stage, MRE parameters, and clinical and biochemical markers affecting this relationship was investigated. RESULTS: A total of 52 patients (31 male; a median age of 11.8 years) were included in the study. The MRE-LS values were significantly different between Ishak fibrosis stages (p = 0.036). With a cut-off value of 2.97 kilopascals, MRE-LS had sensitivity, specificity, PPV, NPV and accuracy values of 90.9%, 82.9%, 58.8%, 97.1%, and 84.6%, respectively, for differentiating mild/moderate fibrosis (F0, 1, 2, 3) from severe fibrosis (F ≥ 4). Although MRE-LS was moderately correlated with Ishak fibrosis score and histological activity index and weakly correlated with aspartate aminotransferase, hepatic steatosis, and R2*, only Ishak fibrosis score was a significant predictor of MRE-LS. MRE-measured spleen stiffness was weakly correlated with the Ishak fibrosis score. CONCLUSIONS: MRE has high sensitivity and specificity for evaluating liver fibrosis in children. MRE may be used to evaluate liver fibrosis in pediatric patients.

Glomerulonephritis with crescents in childhood; etiologies and significance of M2 macrophages.

BACKGROUND: Crescentic glomerulonephritis (CGN) is a rapidly progressive and rare cause of glomerulonephritis in childhood. The aim of this study is to evaluate demographic data of children with crescentic glomerulonephritis, to classify the etiologies and to investigate the correlation between the severity of kidney disease and the expression of CD163+ macrophages. METHODS: Between the years 2000 and 2016 in a single center, patients under 18 years of age with kidney biopsies containing crescents were included in the study. A total of 88 children were enrolled. The expression of CD163 in kidney tissues was detected by immunohistochemistry in 61 patients. Clinical features and outcome were collected from their medical records. RESULTS: The most common etiology was Henoch-Schönlein purpura (HSP) nephritis/Immunglobulin A vasculitis (26.1%), followed by lupus nephritis (22.7%) and idiopathic crescentic glomerulonephritis (18.2%). CD163 positive cell counts in patients with GFR levels less and more than 60 ml/min/1.73 m2 at their last visit were 7.6±6.6 cells vs. 2.0±3.0 cells (p=0.057) per one glomerulus and 52.2±18.2 cells/hpf vs. 33.3±10.0 cells/hpf (p < 0.05) in tubulointerstitium, respectively. Tubulointerstitital CD163+ cells were also found to be higher in patients with end stage kidney disease than complete and partial responders (68 cells/hpf vs 39 cells/hpf, p < 0.05). CONCLUSIONS: CD163 positive cell counts, particularly in tubulointerstitial areas, have been associated with poor prognosis of CGN.

Fetal Mediastinal Fibrosarcoma. Report of Two Cases.

Introduction: One-third of fetal soft tissue tumors are malignant and include congenital fibrosarcoma (CF). We report two fetal CFs arising in the posterior mediastinum. Case Presentation: In case 1, the CF resulted in a mediastinal shift, extensive infiltration of the tumor around adjacent structures, pulmonary hypoplasia, pleural effusion, and rapid growth. The pregnancy was terminated. Case 2 had multiple intrathoracic masses, thoracic hypoplasia, pleural effusion, and fetal death. Both were diagnosed as fibrosarcoma at fetopsy. Discussion: Although congenital CF tends to be locally aggressive with a low metastatic rate, it tends to grow rapidly and the tumor location can affect fetal survival. In Case 1, the tumor demonstrated locally aggressive behavior whereas multiple distant metastases such as lung, liver, adrenals, and left eye were detected in Case 2. The tumor was directly responsible for intrauterine fetal demise in the second case.

Distinctive Features of Hepatic Steatosis in Children: Is It Primary or Secondary to Inborn Errors of Metabolism?

PURPOSE: The incidence of hepatic steatosis among children has been increasing; however, data distinguishing simple steatosis from a more complex disorder are lacking. METHODS: This study identified the etiologies resulting in hepatic steatosis through a retrospective review of pediatric liver biopsies performed in the last 10 years. A total of 158 patients with hepatic steatosis proven by histopathological evaluation were enrolled in the study, and baseline demographic features, anthropometric measurements, physical examination findings, laboratory data, ultrasonographic findings, and liver histopathologies were noted. RESULTS: The two most common diagnoses were inborn errors of metabolism (IEM) (52.5%) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) (29.7%). The three most common diseases in the IEM group were glycogen storage disorders, Wilson's disease, and mitochondrial disease. The rates of consanguineous marriage (75.6%; odds ratio [OR], 26.040) and positive family history (26.5%; OR, 8.115) were significantly higher (p=0.002, p<0.001, respectively) in the IEM group than those in the NAFLD/NASH group. Younger age (p=0.001), normal anthropometric measurements (p=0.03), increased aspartate aminotransferase levels (p<0.001), triglyceride levels (p=0.001), and cholestatic biochemical parameters with disrupted liver function tests, as well as severe liver destruction of hepatic architecture, cholestasis, fibrosis, and nodule formation, were also common in the IEM group. CONCLUSION: Parents with consanguinity and positive family history, together with clinical and biochemical findings, may provide a high index of suspicion for IEM to distinguish primary steatosis from the consequence of a more complex disorder.

Inflammatory milieu of muscle biopsies in juvenile dermatomyositis.

Juvenile dermatomyositis (JDM) is an inflammatory myopathy which causes severe morbidity and high mortality if untreated. In this study, we aimed to define the T-helper cell profile in the muscle biopsies of JDM patients. Muscle biopsies of twenty-six patients (50% female) were included in the study. Immunohistochemical expression of CD3, CD20, CD138, CD68, IL-17, Foxp3, IFN-É£, IFN-alpha and IL-4 was studied and muscle biopsies were scored using the JDM muscle biopsy scoring tool. Inflammatory cells were in small clusters in perimysium and perivascular area or scattered throughout the endomysium in most biopsies; however in 2 biopsies, lymphoid follicle-like big clusters were observed, and in one, there was a very dense and diffuse inflammatory infiltration nearly destroying all the muscle architecture. Seventy-three per cent of the biopsies had T cells, 88% had B cells, 57% had plasma cells, and all had macrophages. As for T-helper cell subtypes, 80% of the biopsies were Th1 positive, 92% Th17 positive and 30% Treg positive. No IL-4 positive inflammatory cell was detected, and only 2 biopsies showed IFN-alpha positivity. The mean JDM biopsy score was 17.6, meaning moderate to severe muscular involvement. Visual analogue score of the pathologist was strongly correlated with histopathological features. B cells, macrophages, plasma cells and T cells constitute the inflammatory milieu of the JDM muscle biopsies. As for T cells, JDM is a disease mainly related with Th1 and Th17 T-helper cell subtypes and to some extend Treg. Th2 cells are not involved in the pathogenesis.

Primary Paraspinal and Spinal Epidural Non-Hodgkin Lymphoma in Childhood.

Primary paraspinal/spinal epidural lymphoma (PPSEL) is rare in childhood. Here, we retrospectively evaluated patients with PPSEL treated in our department. We also reviewed the cases reported in the literature. Fifteen of 1354 non-Hodgkin lymphoma cases diagnosed over a 38-year period were PPSEPL. There were 11 male individuals and 4 female individuals with a median age of 13 years. Most common symptoms were pain and limb weakness. Physical examination revealed spinal cord compression in 80% of patients. The most common tumor location was the lumbar region. Histopathologic subtypes were lymphoblastic lymphoma in 6 and Burkitt lymphom in 5 patients. Subtotal or near-total excision of the tumor with laminectomy was performed in 6 patients. Thirteen and 9 patients received chemotherapy and radiotherapy, respectively. Neurologic recovery was observed in 70% of patients. Seven patients were alive without disease at a median of 88 months. Overall and event-free survival rates were 61.7% and 50.1%, respectively. We reviewed clinical features, treatment, and outcome of 69 PPSEL cases reported in the literature. Neurologic recovery and long-term survival was achieved in 66.7% of them. Heterogeneity in diagnostic methods and treatment have made it difficult to establish the prognostic indicators for neurologic outcome and survival. Multicenter prospective studies with more cases are necessary to determine the prognostic factors.

Bilateral Wilms tumors: Treatment results from a single center.

Aydin B, Akyüz C, Yalçin B, Ekinci S, Oguz B, Akçören Z, Yildiz F, Varan A, Kurucu N, Büyükpamukçu M, Kutluk T. Bilateral Wilms tumors: Treatment results from a single center. Turk J Pediatr 2019; 61: 44-51. The management of bilateral Wilms tumor (BWT) is challenging, particularly due to its presentation at a younger age, rarity, and difficulty for treatment decisions and surgical evaluation comparing to unilateral WT. In this study, the outcome of BWT patients from a single center who were treated by the Turkish Pediatric Oncology Group (TPOG) Wilms Tumor Regimen were retrospectively reviewed. From 1990 to 2016, 30 patients with synchronous BWT were treated with a preoperative chemotherapy of vincristine and actinomycin-D (VA). Chemotherapy was continued until safe nephron sparing surgery (NSS) could be performed for as long as radiological tumor response continued; otherwise, the chemotherapy was intensified by adding doxorubicin (D) alternating with VA every 6 weeks. The median followup of patients was 59 months (4-297 months). The median duration of preoperative chemotherapy was 81 days and ranged between 14 days and 198 days. Preoperative chemotherapy was modified in seven patients (23%) to the VAD regimen. Twenty-two patients (73%) had a radical nephrectomy on the larger tumor and NSS on the contralateral kidney, and 6 patients (20%) had bilateral NSS. Postoperative tumor stages for stage I, II and III were 60%, 22% and 14%, respectively. The 5-year event free survival (EFS) rates were 100%, 90% and 51% for stages I, II and III (p=0.02), respectively. Unfavorable histology and nephrogenic rests were reported in 20% and 20% of patients, respectively. The 5-year overall survival (OS) and EFS rates were 50% and 25%, respectively, in patients with anaplasia, while the same rates were 96% and 96% in patients with favorable histology tumors (p=0.05 and p < 0.001). The 10-year EFS and OS rates for all patients were 82% and 86%, respectively. Our results are comparable with the literature. VA is effective as initial preoperative treatment of BWT and allows for safe resection.

Determinants of Riboflavin Responsiveness in Multiple Acyl-CoA Dehydrogenase Deficiency.

BACKGROUND: Multiple acyl-CoA dehydrogenase (MADD) deficiency, which is a rare metabolic disorder involving electron transport flavoproteins, has a wide array of clinical phenotypes. In this article, we describe 25 patients with MADD deficiency and present the clinical and laboratory characteristics and diagnostic challenges associated with riboflavin-responsive MADD deficiency. METHODS: Hospital records of patients with biallelic mutations in ETFA, ETFB, or ETFDH genes diagnosed in a single center were analyzed retrospectively. Demographic, clinical, and laboratory characteristics of patients with riboflavin-responsive and riboflavin-unresponsive MADD deficiency were compared using Mann-Whitney U and Fisher's exact tests. RESULTS: Respiratory distress and depressed consciousness were significantly more common in patients with riboflavin-unresponsive MADD deficiency (P = 0.015 and P < 0.001), who presented at a younger age (P < 0.001). Patients with riboflavin-responsive MADD deficiency had favorable outcomes but also had life-threatening complications, longer diagnostic delay (median of two years versus 30 days; P < 0.001), and multiple differential diagnoses, resulting in unnecessary investigations and maltreatment. Biopsies showed lipid storage, and complete autopsy was performed in one newborn with riboflavin-unresponsive MADD deficiency, revealing multiple abnormalities. Metabolic profiles were not distinguishable between riboflavin-responsive and riboflavin-unresponsive MADD deficiency (P > 0.05). Four novel variants were detected in ETFDH, one of which (c.1790C>T) may confer riboflavin responsiveness. Siblings with the common myopathic ETFDH c.1130T>C mutation presented with a new phenotype dominated by chronic fatigue without apparent myopathy. CONCLUSIONS: Symptoms and outcomes significantly differed between riboflavin-responsive and unresponsive MADD deficiency, but metabolic profiles did not. Functional studies are needed to better characterize the novel ETFDH variants. As treatment is available for riboflavin-responsive MADD deficiency, physicians should maintain a high index of suspicion for MADD deficiency in all age groups.

Clinical and histopathological features of immunoglobulin G4-associated autoimmune hepatitis in children.

BACKGROUND AND AIM: We aimed to examine the frequency and the characteristics of immunoglobulin G4 (IgG4)-associated autoimmune hepatitis among pediatric patients with autoimmune hepatitis. METHODS: Immunostaining for IgG and IgG4 was performed in liver biopsies of 40 pediatric patients with autoimmune hepatitis. The patients with more than 10 IgG4-positive plasma cells/high-power field were defined as IgG4-associated autoimmune hepatitis. Clinic, laboratory, and histopathological results were compared between groups. RESULTS: Among the 40 pediatric patients, 34 patients were type 1 and 6 patients were type 2 autoimmune hepatitis. Six patients (15%), four of the type 1 and two of the type 2 autoimmune hepatitis patients, were diagnosed with IgG4-associated autoimmune hepatitis. Clinical, laboratory, and histopathological data were initially similar in both forms. There was a positive correlation between IgG4-positive plasma cell count and degree of portal (r: 0.406, P: 0.009) and lobular inflammation (r: 0.37, P: 0.019), grade of interface hepatitis (r: 0.33, P: 0.03), and fibrosis (r: 0.318, P: 0.046). Time required for normalization of liver transaminases and serum IgG level was significantly shorter in IgG4-associated autoimmune hepatitis (3.3 ± 0.5 vs 6.6 ± 3.5 for alanine aminotransferase, 3.7 ± 0.8 vs 6.7 ± 1.2 for aspartate aminotransferase, 4.3 ± 1.2 vs 7.1 ± 2.7 for gamma-glutamyl transpeptidase, and 7.2 ± 3.1 vs 12.8 ± 4.5 for IgG). CONCLUSIONS: Immunoglobulin G4-associated autoimmune hepatitis can be found in pediatric age group and also in type 2 autoimmune hepatitis patients. As steroid response may be better in IgG4-associated autoimmune hepatitis, biopsy specimens should be evaluated for this entity at diagnosis.

Post-mortem detection of FLAD1 mutations in 2 Turkish siblings with hypotonia in early infancy.

Inherited defects of vitamin B2 (riboflavin) metabolism may cause different phenotypes with common biochemical markers of multiple acyl-CoA dehydrogenase deficiency (MADD). Most recently, mutations in FLAD1, which encodes flavin adenine dinucleotide (FAD) synthase, has been implicated in MADD with combined respiratory chain deficiency in nine patients. Here, we describe two siblings with FAD synthase deficiency, who were diagnosed post-mortem upon suspicion of this newly-described disease. Hypotonia was evident at two months of age in both infants, followed by feeding difficulties, respiratory distress and death in six months despite partial response to riboflavin. The older sibling had documented lipid storage myopathy and biochemical markers of MADD. Our observations support the previous reports of unexpected riboflavin-responsiveness in frameshift mutations in the second exon of FLAD1 and suggest dysmorphic auricular helix and hypospadias as possible additional clinical features. More reports and studies are needed to better describe and treat FAD synthase deficiency.

Non-immune hydrops fetalis: A retrospective analysis of 151 autopsies performed at a single center.

Kayki G, Güçer S, Akçören Z, Orhan D, Talim B, Yurdakök M, Yigit S, Boduroglu OK, Utine GE, Örgül G, Beksac MS. Non-immune hydrops fetalis: A retrospective analysis of 151 autopsies performed at a single center. Turk J Pediatr 2018; 60: 471-477. We retrospectively evaluated autopsies performed on 151 non-immune hydrops fetalis (NIHF) cases to determine the etiology and pathological findings. Further, cases identified between 1980 and 2004 were compared with those identified between 2005 and 2015 to investigate the improvement of diagnostic performance of our institution. The mean gestational age during the fetal autopsy was 25 weeks. There were 30 live-born infants in the study group. The etiology of NIHF could be determined in 91 cases (60.3%), while it remained undefined in remaining 60 cases. The most commonly associated pathological conditions were cardiovascular malformations (11.3%), followed by chromosomal abnormalities (9.3%). Prior to 20th gestation week, genetic anomalies and cystic hygromas were the most common etiological factors, and after 30 weeks of gestation, cardiac abnormalities were found to be the most common causes. With time, the rate of undefined cases decreased from 48.4% to 33.75%. NIHF is a complex medical condition necessitating a multidisciplinary management approach. Progress in molecular genetics and imaging techniques is expected to improve diagnostic performance for rapid and better identification.

Primary Osteosarcoma of the Rib: A Case Report and Review of the Literature.

Osteosarcoma is the most common primary malignant tumor of the bone. The most common sites of osteosarcoma in children are the metaphysis of long bones, especially the distal femur, proximal tibia, and proximal humerus. It occurs very rarely in flat bones. Here we report a 14-year-old adolescent boy with primary osteosarcoma of the fifth rib and a review of literature.

Flow-volume curve in the diagnosis and follow-up of intrathoracic airway obstruction.

Spirometry is an easy method to measure lung function and to show pathophysiology. It assists not only to determine the severity of bronchial obstruction in asthma but also to differentiate the characteristics of the intrathoracic diseases narrowing the central airways. Different types of benign and malignant tumors of the trachea may cause emergence of symptoms of airway obstruction. Herein a patient who had been initially diagnosed with asthma but later on shown to have intratracheal myofibroblastic tumor is presented. The importance of flow-volume curve in both initial diagnosis of the mass and in the detection of recurrence is discussed.

Fibrous hamartoma of infancy: A case report with typical ultrasonographic findings.

Fibrous hamartoma of infancy (FHI) is a rare, benign lesion which is commonly seen under two years of age. Clinical and radiological features of FHI can mimic malignant soft tissue sarcomas, it is important to make differential diagnosis. Ultrasound (US) examination reveals heterogeneous echogenicity that can be also suggestive for other soft tissue tumors but newly defined "serpentine pattern" of intervening hypoechoic portions in the hyperechoic mass with poorly defined margins and with poor vascularity is special for FHI. Here we report a 15-month-old-boy with FHI with serpentine pattern on US. He initially presented with a painless mass in his left axilla existing for approximately seven months. The mass was successfully excised and he has been followed for three years without any evidence of recurrence. Fibrous hamartoma of infancy should always be considered in differential diagnosis in children under two years of age with a firm and solitary mass in the axilla especially when US reveals serpentine pattern with poorly defined margins and with poor vascularity. If these clinical and ultrasonographic findings are seen in a child under two years old, surgery can be performed without any additional imaging modalities. Awareness and careful assessment are important in order not to misdiagnose this benign mass for which surgical excision is curative.

An Important Finding of Systemic Aspergillosis: Skin Involvement and Amphotericin B Resistance in an Adolescent.

Invasive aspergillosis is a life-threatening infectious complication in immunocompromised patients, especially with malignancy, and in some cases, it causes extensive tissue destruction and subsequent systemic illness, leading to multiorgan failure and death. Skin involvement and amphotericin B resistance are very rare findings of aspergillosis. Herein, we report the case of a primary hemophagocytic syndrome patient who developed subcutaneous nodules in the 3(rd) month of bone marrow transplantation from which Aspergillus fumigatus was cultivated despite the fact that she was under antifungal therapy. In immunocompromised patients with prolonged fever, atypical presentations of invasive mycosis should be kept in mind, and early appropriate therapy should be initiated promptly to decrease morbidity and mortality.

Sarcoidosis del adulto de inicio en la infancia: a proposito de un caso / Pediatric-onset adult type sarcoidosis: A case report

La sarcoidosis, un trastorno multiorgánico de etiología desconocida que afecta varios órganos, es poco frecuente en los niños. Se desconocen la incidencia y la prevalencia reales de la sarcoidosis infantil. Al igual que en los adultos, muchos niños con sarcoidosis tal vez no presentan síntomas y la enfermedad cursa sin diagnosticarse. Es fundamental realizar una evaluación completa y sistemática del paciente para establecer el diagnóstico de sarcoidosis en los niños. Se describe el caso de una nina de 12 años con uveítis y hepatoesplenomegalia de dos años de evolución. Mediante una tomografía computarizada del tórax, se hallaron nódulos pulmonares periféricos dispersos y linfadenopatía hiliar bilateral. La aspiración de médula ósea y la biopsia de hígado no fueron diagnósticas. La biopsia de pulmón mostró granulomas de células epitelioides no necrosantes. A la paciente se le diagnosticó sarcoidosis en virtud del hallazgo de inflamación granulomatosa y de la exclusión de entidades confusoras.

Sarcoidosis, a multisystem disorder of unknown etiology that involves multiple organs, is rare in children. The true incidence and prevalence of childhood sarcoidosis is unknown. As in adults, many children with sarcoidosis may be asymptomatic; the disease may remain undiagnosed. A complete and systematic evaluation of the patient is essential for the sarcoidosis diagnosis in children. Here, we describe a case of 12-year-old female who presented with 2 years history of uveitis and hepatosplenomegaly. A chest computerized tomography revealed scattered peripheral pulmonary nodules and bilateral hiliar lymphadenopathy. Bone marrow aspiration and liver biopsy were not diagnostic. A lung biopsy showed non-necrotizing epithelioid cell granulomas. She was diagnosed with sarcoidosis according to demonstration of granulomatous inflammation and the exclusion of confusable entities

[Pediatric-onset adult type sarcoidosis: A case report]. / Sarcoidosis del adulto de inicio en la infancia: a proposito de un caso.

Sarcoidosis, a multisystem disorder of unknown etiology that involves multiple organs, is rare in children. The true incidence and prevalence of childhood sarcoidosis is unknown. As in adults, many children with sarcoidosis may be asymptomatic; the disease may remain undiagnosed. A complete and systematic evaluation of the patient is essential for the sarcoidosis diagnosis in children. Here, we describe a case of 12-year-old female who presented with 2 years history of uveitis and hepatosplenomegaly. A chest computerized tomography revealed scattered peripheral pulmonary nodules and bilateral hiliar lymphadenopathy. Bone marrow aspiration and liver biopsy were not diagnostic. A lung biopsy showed non-necrotizing epithelioid cell granulomas. She was diagnosed with sarcoidosis according to demonstration of granulomatous inflammation and the exclusion of confusable entities

La sarcoidosis, un trastorno multiorgánico de etiología desconocida que afecta varios órganos, es poco frecuente en los niños. Se desconocen la incidencia y la prevalencia reales de la sarcoidosis infantil. Al igual que en los adultos, muchos niños con sarcoidosis tal vez no presentan síntomas y la enfermedad cursa sin diagnosticarse. Es fundamental realizar una evaluación completa y sistemática del paciente para establecer el diagnóstico de sarcoidosis en los niños. Se describe el caso de una niña de 12 años con uveítis y hepatoesplenomegalia de dos años de evolución. Mediante una tomografía computarizada del tórax, se hallaron nódulos pulmonares periféricos dispersos y linfadenopatía hiliar bilateral. La aspiración de médula ósea y la biopsia de hígado no fueron diagnósticas. La biopsia de pulmón mostró granulomas de células epitelioides no necrosantes. A la paciente se le diagnosticó sarcoidosis en virtud del hallazgo de inflamación granulomatosa y de la exclusión de entidades confusoras.