Serial 18 F-FDG PET/CT Revealing Mixed Histiocytosis in a Pediatric Patient.

ABSTRACT: A 6-month-old boy presented with a left parietal soft tissue swelling and CT findings of multiple calvarial lytic lesions. 18 F-FDG PET/CT demonstrated hypermetabolic lesions in the left parietal, right occipital, and right femoral bones. The left parietal lesion was excised, and pathology was consistent with Langerhans cell histiocytosis. Interim PET assessment following induction chemotherapy demonstrated a "mixed metabolic response" with discordant rise in metabolic activity of the right femoral lesion. Subsequent core biopsy of the femoral lesion revealed a non-Langerhans cell histiocytosis, likely juvenile xanthogranuloma. Here we describe a rare pediatric case of mixed histiocytosis, unveiled by serial 18 F-FDG PET/CT.

18 F-FDG PET/CT in Pediatric ALK-Positive Histiocytosis With Isolated CNS Involvement.

ABSTRACT: An 11-year-old girl presented with focal impaired awareness seizures. MRI brain demonstrated a T2 hyperintense cortical lesion in the left temporal lobe with surrounding vasogenic edema. 18 F-FDG PET/CT was arranged to assess metabolic activity of the cerebral lesion, to screen the whole body for other metabolically active lesions, and to assist biopsy planning. The study demonstrated intensely increased FDG uptake within the left temporal lobe lesion without evidence of hypermetabolic lesions elsewhere on the whole-body acquisition. The brain lesion was excised, and histopathology and molecular testing were consistent with ALK-positive histiocytosis.

Histiocytosis and Neoplasms of Macrophage-Dendritic Cell Lineages: Multimodality Imaging with Emphasis on PET/CT.

Histiocytosis is a rare inflammatory process characterized by pathologic infiltration and accumulation of cells derived from the monocytic lineage in normal tissue. It encompasses more than 100 different subtypes of disorders that were recently classified into five main groups: (a) Langerhans-related histiocytosis, (b) Rosai-Dorfman histiocytosis, (c) cutaneous and mucocutaneous histiocytosis, (d) malignant histiocytosis, and (e) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Langerhans cell histiocytosis is the most common histiocytic disorder. Less common types include Erdheim-Chester disease, Rosai-Dorfman disease, adult and juvenile xanthogranuloma, necrobiotic xanthogranuloma, histiocytic sarcoma, interdigitating dendritic cell sarcoma, Langerhans cell sarcoma, and hemophagocytic lymphohistiocytosis. Although the pathogenesis of these disorders may be attributable to mutations in the oncogenic driver, recent discoveries have shown that inflammation and fibrosis secondary to mutated histiocytes, rather than a proliferative cell mechanism, result in manifestation of the disease. Diagnosis, which relies on a multidisciplinary approach, is challenging and often delayed because clinical findings are nonspecific and may mimic malignant processes at radiologic evaluation. Compared with conventional imaging, PET/CT allows detection of the increased metabolic activity in histiocytes. Diagnostic algorithms for histiocytic disorders should include functional imaging with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT, which provides a comprehensive whole-body evaluation of their potential involvement with multiple organ systems and allows monitoring of therapeutic response. The most recent revised classification, pathophysiologic and clinical manifestations, sites of involvement, and imaging features of histiocytosis are described in this review and a multimodality approach is used, with emphasis on 18F-FDG PET/CT evaluation. ©RSNA, 2021.

MRI features of intra-axial histiocytic brain mass lesions.

AIM: To describe MRI features, including diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and perfusion-weighted imaging (PWI), of intra-axial tumour-like presentations of four different subtypes of histiocytosis. MATERIAL AND METHODS: The brain MRI findings of 23 patients with histologically proven histiocytosis were reviewed retrospectively (11 Langerhans cell histiocytosis [LCH], eight Erdheim-Chester disease [ECD], one overlap form LCH/ECD, two Rosai-Dorfman disease [RDD], and one haemophagocytic lymphohistiocytosis [HLH]) with single or multiple enhancing intraparenchymal brain lesions. RESULTS: Histiocytic brain mass lesions show some similar MRI features including Supra and/or infratentorial and/or paraventricular subcortical well-delineated masses, linear ependymal enhancement along the ventricles and brain stem lesions. Masses always present with mixed hyper- and hypointense signal on T2-weighted imaging (WI). Their enhancement is often homogeneous. Apparent diffusion coefficient (ADC) values are often normal or elevated. CONCLUSION: The presence of multiple periventricular and subcortical enhancing lesions with mixed signal intensity on T2WI and normal or high ADC values should lead radiologists to consider the diagnosis of histiocytic lesions and search for associated systemic lesions.

Imaging features of immune-mediated genitourinary disease.

PURPOSE: Imaging features of immune-mediated genitourinary diseases often overlap, and the same disease may manifest in different ways, so understanding imaging findings in the context of the patient's entire clinical picture is important in providing the correct diagnosis. METHODS: In this article, diseases mediated by the immune system which affect the genitourinary system are reviewed. Examples of immune-mediated genitourinary disease including IgG4-related disease, post-transplant lymphoproliferative disorder, immunodeficiency-associated lymphoproliferative disorder due to immunosuppressive and immunomodulatory medications, lymphoma, leukemia, myeloma, amyloidosis, and histiocytosis. RESULTS: Clinical and imaging features will be presented which may help narrow the differential diagnosis for each disease. CONCLUSION: Recognition of immune-related genitourinary disease is important for appropriate medical management as they may mimic other diseases both by imaging and clinical presentation.

Imaging of Histiocytosis in the Era of Genomic Medicine.

Histiocytosis describes a group of diseases that have long been considered enigmatic in the history of medicine. Recently, novel genomic analyses have identified somatic oncogenic driver mutations responsible for the pathogenesis of these entities. These discoveries have led to the recharacterization of histiocytoses as neoplastic diseases and have opened a new era of precision medicine approaches for treatment. The histiocytic disorders demonstrate a variety of imaging manifestations involving multiple organ systems, and radiologists play a major role in diagnosis and monitoring. An up-to-date knowledge of the novel genomic discoveries and their implications is essential for radiologists to understand the new approaches to treating histiocytic disorders and to contribute as key members of the multidisciplinary treatment team. This article provides a cutting-edge review of the novel concepts in histiocytosis, with a focus on recent genomic discoveries and precision medicine approaches to treating the disease, and describes imaging manifestations with correlative histologic and genomic findings, with an emphasis on adult-onset cases and uncommon subtypes. ©RSNA, 2018.

PET/MR in the Assessment of Pediatric Histiocytoses: A Comparison to PET/CT.

PURPOSE: The aim of this study was to analyze the feasibility and diagnostic performance of F-FDG PET/MR compared with F-FDG PET/CT in a cohort of pediatric histiocytosis patients with regard to image quality, lesion detection, and FDG quantification. METHODS: Children with a diagnosis of Langerhans cell histiocytosis or Rosai-Dorfman disease were prospectively recruited. Seventeen PET/CT and PET/MR examinations were performed on 9 patients (mean age, 6.2 years) following a single-injection dual-imaging protocol. The indication was Langerhans cell histiocytosis in 10 examinations and Rosai-Dorfman disease in 7 examinations. The anonymized data were evaluated for image quality and lesion detection. SUV quantification of each lesion was compared between modalities. RESULTS: All PET/MR examinations had good or excellent image quality and were deemed clinically acceptable. There was substantial agreement of PET image quality among readers of PET/MR images. Per patient, PET/MR and PET/CT had complete concordance in identifying active disease. PET/MRI correctly classified 74 (96%) of 77 foci of disease identified on PET/CT. The per-lesion maximum SUVs were strongly correlated between modalities with a Spearman correlation coefficient of 0.73 (P < 0.001). CONCLUSIONS: The use of PET/MR is clinically feasible in pediatric patients with a histiocytic disease. PET/MR demonstrates comparable image quality and lesion detection to PET/CT while maintaining strongly correlated quantitative performance. Given the significant radiation dose savings, PET/MR represents an appealing alternative to PET/CT in the care of children with histiocytic disorders.

Multicentric Reticulohistiocytosis Mimicking Malignancy on 18F-FDG PET/CT.

We report the case of a 75-year-old woman who underwent F-FDG PET/CT to evaluate the recurrence of urothelial carcinoma. PET/CT showed F-FDG-avid muscles and lymph nodes, mimicking recurrence. However, F-FDG uptake was also seen in multiple joints and subcutaneous tissue, representing an uncommon finding for recurrence. Further history taking revealed she had been pathologically diagnosed with multicentric reticulohistiocytosis (MRH) from skin biopsy, and the F-FDG PET/CT findings were consistent with MRH, a rare systemic inflammatory granulomatous disease of unknown etiology. Knowledge of the characteristic F-FDG PET/CT features of MRH is important to differentiate MRH from malignancy.

A case of gastric crystal-storing histiocytosis.

A 54-year-old male patient underwent upper gastrointestinal endoscopy, which revealed a 25-mm brown region in the angular section of the greater curvature of the stomach. The region was histologically determined to be gastric mucosa with an accumulation of histiocytes containing eosinophilic substances in the cytoplasm and chronic inflammatory cell infiltration. Histiocytes were immunohistologically positive for CD68, IgG, and κ. Based on these findings, the patient was diagnosed with gastric crystal-storing histiocytosis comprised of histiocytes phagocytosing IgG-κ-type immunoglobulin. This is a rare disease of which there have been no previous reports that included long-term follow-up. Here, we report the case with a literature review.

Abdominal manifestations of histiocytic disorders in adults: imaging perspective.

Histiocytic disorders (HDs) are a diverse group of diseases characterized by pathologic infiltration of normal tissues by cells of the mononuclear phagocyte system. The spectrum of these diseases ranges from treatable infectious diseases to rapidly progressive, life-threatening conditions. Although they are rare and difficult diagnoses, HDs can be diagnosed with the help of clinical and laboratory analyses, imaging features and tissue biopsy. The clinicopathology and imaging spectrum of select entities belonging to this disorder are presented in this review.

Crystal-storing histiocytosis associated with marginal-zone lymphoma.

We report a rare case of crystal-storing histiocytosis (CSH) associated with marginal-zone lymphoma. A 91-year-old woman with a history of breast cancer presented with masses of the posterior neck, right breast, and left upper arm. An enlarging mass of the neck was removed and was histologically diagnosed as CSH, associated with marginal-zone lymphoma. Masses in the breast and upper arm were evaluated by needle biopsy and revealed as CSH. CSH is a rare condition characterized by the intrahistiocytic accumulation of crystallized immunoglobulins, and is associated with disorders in which monoclonal immunoglobulins are expressed. To the best of our knowledge, there are few previous descriptions of CSH which include the imaging features of this disease. In the present case, the masses showed hypoechogenicity with internal patchy hyperechoic areas on ultrasonography, and an iso-signal to slight hyperintensity compared with muscle on T2-weighted magnetic resonance imaging. We report the imaging findings in CSH and discuss their diagnostic implications.

Multicentric reticulohistiocytosis with extra-mammillary Paget's disease: a case report.

Multicentric reticulohistiocytosis (MRH) is a very rare systemic disease with variable phenotypic presentation and a high rate of misdiagnosis. Here we describe a patient with MRH and extra-mammillary Paget's disease (EMPD), a diagnosis that has not previously been described in the literature.

Crystal-storing histiocytosis complicating primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue.

Crystal-storing histiocytosis is an uncommon form of nonneoplastic histiocytic proliferation that in most patients complicates an underlying lymphoproliferative or plasma cell disorder. Lung is a common site of involvement in patients with localized disease. We present an illustrative example from a 54-year-old woman with an asymptomatic solitary lung nodule. The tumor was characterized by sheets of histiocytes with abundant cytoplasm expanded by distinctive eosinophilic inclusions. Focal necrosis was present. Aggregates of monocytoid lymphocytes and clusters of peribronchiolar plasma cells were overshadowed by the histiocytic infiltrate. Immunohistochemical stains showed CD68 staining in nonneoplastic histiocytes and CD20 staining in monocytoid lymphocytes. In situ hybridization studies showed κ light-chain restriction in plasma cells. These results, combined with the histologic findings, supported the diagnosis of crystal-storing histiocytosis complicating marginal zone lymphoma of mucosa-associated lymphoid tissue. We review the literature pertaining to pulmonary crystal-storing histiocytosis, highlighting the differential diagnosis for this rare phenomenon.

Localized pleuropulmonary crystal-storing histiocytosis: 5 cases of a rare histiocytic disorder with variable clinicoradiologic features.

Crystal-storing histiocytosis (CSH) localized to the thoracic region is a rare occurrence, often secondary to lymphoproliferative or plasma cell diseases. About 10 case reports have been previously published, and 3 of these have no relationship with clonal hematologic disorders. We collected here the first series of 5 consecutive cases of CSH involving lungs (4 cases) and pleura (1 case). There were 3 women and 2 men with a mean age at diagnosis of 65 years. All cases had an underlying hematologic disorder (2 B-cell marginal-zone lymphomas, 2 monoclonal gammopathy of undetermined significance and 1 pulmonary plasmacytoma). Despite a common morphology characterized by a dense and irregular growth of large eosinophilic histiocytes with intracytoplasmic refractile crystals, 2 cases presented with cystic changes at gross and imaging examinations, calcified amyloid was found in 2 cases, and 1 case showed an interstitial lung disease with nonspecific interstitial pneumonia pattern. Histiocytes were immunoreactive for CD68 (clones PGM-1 and KP-1) but were not for CD1a and S100; the associated lymphoplasmacellular disorder had a clonal profile on molecular analysis with κ light-chain restriction. Two cases were originally misdiagnosed as cystic fibrohistiocytic tumor and carcinoid tumor, thus confirming that CSH localized to this site may result in a diagnostic challenge with a broad spectrum of differential diagnoses. The presence of intracytoplasmic crystals and a plasma cell infiltrate around a histiocytic proliferation should alert the pathologist to consider CSH and to carefully investigate the presence of clonal hematologic disease.

The diagnostic value of 18F-FDG PET and MRI in paediatric histiocytosis.

PURPOSE: To analyse the diagnostic value of (18)F-FDG PET and MRI for the evaluation of active lesions in paediatric Langerhans cell histiocytosis. METHODS: We compared 21 (18)F-FDG PET scans with 21 MRI scans (mean time interval 17 days) in 15 patients (11 male, 4 female, age range 4 months to 19 years) with biopsy-proven histiocytosis. Primary criteria for the lesion-based analysis were signs of vital histiocyte infiltrates (bone marrow oedema and contrast enhancement for MRI; SUV greater than the mean SUV of the right liver lobe for PET). PET and MR images were analysed separately and side-by-side. The results were validated by biopsy or follow-up scans after more than 6 months. RESULTS: Of 53 lesions evaluated, 13 were confirmed by histology and 40 on follow-up investigations. The sensitivity and specificity of PET were 67 % and 76 % and of MRI were 81 % and 47 %, respectively. MRI showed seven false-positive bone lesions after successful chemotherapy. PET showed five false-negative small bone lesions, one false-negative lesion of the skull and three false-negative findings for intracerebral involvement. PET showed one false-positive lesion in the lymphoid tissue of the head and neck region and two false-positive bone lesions after treatment. Combined PET/MR analysis decreased the number of false-negative findings on primary staging, whereas no advantage over PET alone was seen in terms of false-positive or false-negative results on follow-up. CONCLUSION: Our retrospective analysis suggests a pivotal role of (18)F-FDG PET in lesion follow-up due to a lower number of false-positive findings after chemotherapy. MRI showed a higher sensitivity and is indispensable for primary staging, evaluation of brain involvement and biopsy planning. Combined MRI/PET analysis improved sensitivity by decreasing the false-negative rate during primary staging indicating a future role of simultaneous whole-body PET/MRI for primary investigation of paediatric histiocytosis.