Histiocytosis and adult-onset orbital xanthogranuloma in 2023: a review of the literature and mini case series.

PURPOSE: Within the large umbrella of histiocytosis are a few similar yet heterogenous entities involving the orbit and periocular tissues with or without systemic infiltration, termed adult onset xanthogranuloma or orbital xanthogranuloma. Due to rarity of these conditions, different classifications in use, diverse clinical presentations and still unknown etiology, the aim of this paper was to provide an up-to-date literature review of the actual understanding of histiocytosis and its subgroups involving the orbit and periocular area, diagnostic strategies and therapeutic modalities. METHODS: We present a review of literature and small case series comprising four patients diagnosed and treated in the period from 2001 until 2023 in our hospital. Clinical files of 4 patients with adult-onset xanthogranulomatous disease of the orbit and ocular adnexa (AOXGD) were reviewed retrospectively. Clinical, laboratory, radiological, histopathological, and immunohistochemical findings were reexamined. RESULTS: Reviewing medical records of our patients with AOXGD, we found significant overlap between histiocytosis and different immune disorders. A broad workup should be considered in these patients as they can harbour severe immune disfunctions and hematologic disorders. Preferred treatment modality depends on a histopathologic type of AOXGD, clinical presentation and systemic involvement and should be conducted multidisciplinary. CONCLUSION: The diagnosis is often delayed because of its rarity and diverse clinical findings. Development of molecular genetic tests, detection of BRAF V600E mutation and different types of kinase mutations, mutations in transcriptional regulatory genes as well as tyrosine kinase receptors have shed a new light on the etiopathogenesis and potential targeted treatment of histiocytosis.

Overview of histiocytic and dendritic disorders by the 5th version of WHO Classifi cation of Hematolymphoid Tumours from 2022.

BACKGROUND: Histiocytoses are rare disorders characterized by the accumulation of macrophages, dendritic cells, or monocyte-derived cells in various tissues and organs of children and adults, with a wide range of clinical manifestations, presentations, and histology. The histiocytoses are classified according to the WHO Classification, the last version of which was published in 2022, or according to the Histiocyte Society Classification, with the last version published in 2016. PURPOSE: This text provides an overview of histiocytoses as described in the WHO Classification 2022.

Orbital histiocytosis; From A to Z.

PURPOSE: Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. METHOD: This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. RESULTS: 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. CONCLUSION: Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.

Anaplastic lymphoma kinase-positive histiocytosis with multisystem involvement: A case report.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare disease that usually occurs in infants and young children and is characterized by ALK-positive histiocytes infiltrating organs. We present a case of multisystem involvement of ALK-positive histiocytosis in a female infant with skin nodules as the initial presentation. Despite multiorgan involvement, most tumors had spontaneously regressed, and all bones were partially healed after 40 months of regular follow-up without treatment. However, gait abnormalities persisted, indicating that early treatment may have greater impact in maintaining a child's quality of life when the disease involves the brain or the critical period of bone development.

Intralymphatic histiocytosis of the upper eyelid in a patient of Korean descent: A case report.

RATIONALE: Diagnosing intralymphatic histiocytosis can be challenging due to its rarity. We present a case of intralymphatic histiocytosis in the upper eyelid of a Korean patient. We treated the condition by surgical debulking and intralesional triamcinolone injection. PATIENT CONCERNS: A 59-year-old man was referred to our clinic with a 7-year history of unilateral swelling in the right upper eyelid. He had previously been treated with long-term oral steroids and immunosuppressants, but his eyelid swelling persisted. Unilaterally non-pitting erythematous edema was localized on the right upper eyelid without any itching or pain. His best corrected visual acuity at presentation was 20/20 for both eyes. Enhanced orbital computerized tomography revealed edematous soft tissue thickening in the right upper eyelid. In the laboratory testing, the erythrocyte sedimentation rate showed an increase of 19, and the antinuclear antibody titer was positive with a homogeneous pattern. DIAGNOSES: We diagnosed the patient with intralymphatic histiocytosis based on the histopathological findings. INTERVENTION: We attempted surgical debulking and biopsy on the right upper eyelid due to the persistent symptoms and the absence of a definitive diagnosis. OUTCOMES: The patient has demonstrated significant improvement after receiving an intralesional triamcinolone injection in the right upper eyelid following the surgery and is currently under follow-up with no signs of recurrence. LESSON: Ophthalmologists should consider intralymphatic histiocytosis in cases of persistent eyelid swelling that do not respond to treatment, even in Asian patients. Surgical debulking and intralesional triamcinolone injections may be beneficial for improvement.

Cytogenetics in the management of acute myeloid leukemia and histiocytic/dendritic cell neoplasms: Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH).

Genetic data are becoming increasingly essential in the management of hematological neoplasms as shown by two classifications published in 2022: the 5th edition of the World Health Organization Classification of Hematolymphoid Tumours and the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias. Genetic data are particularly important for acute myeloid leukemias (AMLs) because their boundaries with myelodysplastic neoplasms seem to be gradually blurring. The first objective of this review is to present the latest updates on the most common cytogenetic abnormalities in AMLs while highlighting the pitfalls and difficulties that can be encountered in the event of cryptic or difficult-to-detect karyotype abnormalities. The second objective is to enhance the role of cytogenetics among all the new technologies available in 2023 for the diagnosis and management of AML.

A Rare Autoimmune Disease Detected in the Differential Diagnosis of Immunodeficiency: Histiocytosis-lymphadenopathy Plus Syndrome.

Mutations in the SLC29A3 gene cause histiocytosis-lymphadenopathy plus (H) syndrome, a rare autosomal recessive genetic condition that affects numerous systems. We present a 7-year-old Syrian patient with pericardial effusion whose acute phase reactants did not decrease despite treatment. In order to emphasize the variety and raise awareness of H syndrome in the hopes of achieving an early diagnosis and appropriate treatment, molecular investigation of SLC29A3-related disorders is crucial. H syndrome is an uncommon genetic condition with a broad spectrum of phenotypes. Therefore, early genetic testing is essential for the accurate diagnosis of patients. Doctors should be aware of this condition and its symptoms and consider autoimmune diseases as a possible alternative diagnosis in patients with suspected immunodeficiency.

H syndrome treated with Tocilizumab: two case reports and literature review.

H syndrome is a rare autosomal recessive genetic disorder characterized by the following clinical features: cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature, hallux valgus, hyperglycemia, fixed flexion contractures of the toe joints, and the proximal interphalangeal joints. In rare cases, autoinflammatory and lymphoproliferative manifestations have also been reported. This disorder is due to loss-of-function mutations in SLC29A3 gene, which encode the equilibrative nucleoside transporter ENT3. This deficiency leads to abnormal function and proliferation of histiocytes. H syndrome is part of the R-group of histiocytosis. We report two different cases, one was diagnosed in adulthood and the other in childhood. The first case reported is a 37-year-old woman suffering from H syndrome with an autoinflammatory systemic disease that begins in adulthood (fever and diffuse organ's infiltration) and with cutaneous, articular, auditory, and endocrinological manifestations since childhood. The second case reported is a 2-year-old girl with autoinflammatory, endocrine, and cutaneous symptoms (fever, lymphadenopathy, organomegaly, growth delay, and cutaneous hyperpigmentation). Homozygous mutations in SLC29A3 confirmed the diagnosis of H syndrome in both cases. Each patient was treated with Tocilizumab with a significant improvement for lymphoproliferative, autoinflammatory, and cutaneous manifestations. Both cases were reported to show the multiple characteristics of this rare syndrome, which can be diagnosed either in childhood or in adulthood. In addition, an overview of the literature suggested Tocilizumab efficiency.

Crystal storing histiocytosis forming a mass lesion in temporal lobe.

Crystal storing histiocytosis is a disorder characterized by local or diffuse infiltration of histiocytes containing crystalline inclusions. This entity has been reported in several organs, however the involvement of the central nervous system (CNS) is extremely rare and to date only 7 cases of crystal storing histiocytosis (CSH) of CNS have been reported in the English literature. More than 90% patients with CSH had an underlying lymphoproliferative or plasma cell disorders, especially multiple myeloma, lymphoplasmacytic lymphoma or monoclonal gammopathy. Radiologically and intraoperatively, CSH may mimic an infectious process or neoplasm, hence its histopathological confirmation is important to facilitate appropriate treatment. In this report, we describe an additional case of crystal storing histiocytosis in a 48 year old female who presented with a mass lesion in the right temporal lobe of the cerebrum.

A novel approach to diagnosing crystal-storing histiocytosis: utility of scanning electron microscopy for formalin-fixed paraffin-embedded tissue specimens.

Crystal-storing histiocytosis (CSH) is a rare disorder that shows infiltration of histiocytes with an aberrant cytoplasmic accumulation of crystalline structures and is often accompanied by lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH requires identification of crystalline structures that accumulate in the infiltrating histiocytes, which may be challenging by optical microscopy alone. In this case report, we describe an atypical course of systemic CSH with multifocal fibrosclerosis of an unknown background disease that was diagnosed by ultrastructural observation, including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), in pathological autopsy. In addition, crystalline structures were successfully identified by scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens taken before death. Since CSH was identified by SEM in a tiny biopsy specimen, observation of histiocytic infiltrative lesions by SEM using FFPE tissue may lead to early detection of and initiation of treatment for CSH.

[Pulmonary crystal-storing histiocytosis: a case report].

A 45-year-old female patient was found to have a nodule in the right lower lobe on physical examination. Chest CT showed the nodule was lobulated measuring 24 mm×23 mm, with obvious enhancement and adjacent pleural traction. As the PET-CT showed increased 18F-FDG uptake suggesting malignancy, the wedge resection of the right lower lobe was performed. Grossly, the mass was adjacent to the pleural area with indistinct boundary. On cut sections, the lesion was solid and tough, with a greyish-pink colour. Microscopically, the lesion had an ill-defined margin, and was composed of spindle and polygonoid histiocytes with rich eosinophilic cytoplasm similar to rhabdoid muscle cells. The cytoplasm of histiocytes was filled with diamond-shaped or club-shaped crystals. Immunohistochemistry (IHC) showed the histiocytes were positive for CD68, κ, λ, IgG, IgM and IgA. The patient had been followed up for 41 months and had shown neither recurrences nor new diseases. CSH is a rare non-neoplastic histiocytic proliferative disease. Pulmonary CSH should be differentiated from multiple diseases. Accurate pathological diagnosis depends on its morphology and immunophenotype. This disease is often related to potential lymphoproliferative or plasma cell disorder. After diagnosis, a systemic examination is required and long-term follow-up is recommended.

PU.1 is a useful nuclear marker to distinguish between histiocytosis and histiocyte-rich tumours.

AIMS: The aim was to test the expression of PU.1 on different types of histiocytoses and to test the utility of PU.1 in confirming or excluding a histiocytic origin in tumour samples with suspicion of histiocytosis. METHODS AND RESULTS: We analysed 66 biopsies of nonmalignant histiocytoses represented by Langerhans-cell histiocytosis (n = 13), Erdheim-Chester disease (ECD) (n = 19), Rosai-Dorfman disease (RDD) (n = 14), mixed ECD-RDD (n = 3), ALK-positive histiocytosis (n = 6), and juvenile xanthogranuloma (n = 11). All cases were positive for PU.1 in reactive and neoplastic histiocytes. In addition, 39 cases of tumours with high-grade cytological atypia were referred to our center as suspicion of malignant histiocytosis/histiocytic sarcoma and only 18 were confirmed. Indeed, more than half of these tumours (21/39) were either undifferentiated malignant tumours with a stroma rich in histiocytes, diffuse large B-cell lymphoma, or high-grade dedifferentiated liposarcoma. PU.1 was useful to distinguish between the negativity of large atypical nuclei and the positivity of stromal reactive histiocytes. CONCLUSION: PU.1 is expressed by all types of histiocytosis. It distinguishes histiocytosis from histiocyte-rich tumours with an easy interpretation due to its sharp nuclear staining. Its negativity in lesional/tumour cells in histiocyte-like lesions is useful to eliminate a histiocytosis.