Touton Giant Cells Research Articles

Multisystem ALK-Positive Histiocytosis With DCTN1::ALKFusion in an Adult, Responsive to Alectinib: Case Report and Literature Review.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.

Recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissue

AbstractJuvenile xanthogranuloma (JXG) is a histiocytic neoplasm that usually presents in the skin. Rarely, extracutaneous localizations occur; the genetic drivers of this clinical variant of JXG remain incompletely characterized. We present detailed clinicopathologic and molecular data of 16 children with extracutaneous JXG and 5 adults with xanthogranulomas confined to the central nervous system (CNS) or soft tissue. Tissue samples were obtained through the Dutch Nationwide Pathology Databank and analyzed with an innovative sequencing technique capable of detecting both small genomic variants and gene rearrangements. Targetable kinase alterations were detected in 16 of 16 children and 1 of 5 adults. Alterations included CLTC::SYK fusions in 6 children and CSF1R mutations in 7 others; all aged <2 years with soft tissue tumors. One child had a CSF1R mutation and MRC1::PDGFRB fusion. Most were treated surgically, although spontaneous regression occurred in 1 of 6 with CLTC::SYK and 2 of 7 with CSF1R mutations, underscoring that treatment is not always necessary. Tumors with CLTC::SYK fusions generally lacked Touton giant cells but exhibited many other histologic features of JXG and concordant methylation profiles. Using multispectral immunofluorescence, phosphorylated–spleen tyrosine kinase expression was localized to CD163+ histiocytes; tumors with CLTC::SYK fusions also demonstrated mTOR activation, cyclin D1 expression, and variable phosphorylated–extracellular signal-regulated kinase expression. BRAFV600E was detected in 1 child and 1 adult with CNS xanthogranulomas; both responded to BRAF inhibition. Finally, a TPM3::NTRK1 fusion or MAP2K1 deletion was detected in 2 children with systemic JXG who experienced spontaneous disease regression. This study advances the molecular understanding of histiocytic neoplasms and may guide diagnostics and clinical management.

Unmasking the Face of a Rare Disease – Progressive Nodular Histiocytosis

Abstract Non-Langerhans cell histiocytoses (NLCHs) are a complex group of disorders which can be difficult to diagnose due to their confounding clinical and microscopic features. Progressive nodular histiocytosis (PNH) is a rare subtype of NLCH characterized by benign, xanthogranulomatous lesions on the skin and mucous membranes. Clinical features of PNH involve the gradual emergence of multiple yellow-brown papules and nodules, with histological examination demonstrating the presence of foamy tissue macrophages, spindle-shaped cells within a fibrocollagenous matrix, and Touton cells. We present a rare case of a 55-year-old female patient with progressively increasing facial nodules, where clinical, histopathological, and immunohistochemical findings clinched the diagnosis of PNH.

Challenges in diagnosis of Erdheim-chester disease: a case report

Background: Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis characterized by the infiltration of lipid-laden macrophages into various tissues, leading to diverse clinical manifestations. Case Presentation: A 53-year-old male presented with a history of recurrent flank pain and obstructive uropathy over seven years, which led to multiple imaging studies and treatments for bilateral renal stones. Recent imaging, including a CT scan of the abdomen and pelvis, revealed bilateral perirenal soft tissue thickening extending into the renal sinus and pelvicalyceal systems, moderate hydronephrosis, and bilateral renal stones, suggestive of ECD. A CT-guided biopsy of the perinephric soft tissue confirmed the diagnosis. Histopathological analysis showed fibrofatty tissue with histiocytes exhibiting foamy cytoplasm, lymphocytes, plasma cells, and Touton cells. Immunohistochemistry stains were positive for Factor 13A and CD68 in histiocytes, confirming ECD. Conclusion: This case underscores the importance of considering ECD in patients with unexplained recurrent flank pain and renal abnormalities. Early recognition and biopsy are crucial for accurate diagnosis and management of this rare disease. The successful identification of ECD in this patient illustrates the critical role of advanced imaging and histopathological evaluation in diagnosing rare conditions.

Erdheim-chester disease with bilateral proptosis, coated aorta and hairy kidney

Erdheim-Chester disease (ECD) is a rare histiocytic disorder with a spectrum of clinical manifestations, ranging from asymptomatic single-organ involvement to multisystem disease. We present a classic case of ECD with detailed radiographic and histopathologic findings. A 63-year-old Thai female with a history of triple vessel disease post-PCI presented with bilateral proptosis and blurred vision for one year. On admission, she exhibited marked proptosis epiblepharon, lagophthalmos, conjunctival injection, chemosis, limited extraocular movement and cranial nerve II palsy. Imaging showed increased bilateral retro-orbital infiltrative lesions, osteosclerotic changes, and soft tissue thickening along the great vessels and retroperitoneum. A retro-orbital soft tissue biopsy showed foamy histiocytic proliferation with Touton giant cells. EDC was confirmed by next-generation sequencing revealing a BRAF V600E mutation. This patient received pegylated interferon-alpha. At 1-year follow-up visit, the disease remained stable. In this report, we present a classic case of EDC. The rarity of this disease makes it challenging to diagnose. The typical presentation characteristics raise awareness for the diagnosis of EDC, which is based on features such as osteosclerotic lesions in the long bones, soft tissue infiltration in medium to large vessels (coated aorta) and the bilateral pelvicalyceal systems (hairy kidney). These findings were confirmed through tissue pathology and molecular diagnostics.

Pediatric Orbital Juvenile Xanthogranuloma: A Case Series and Review of the Literature.

Juvenile xanthogranuloma (JXG) is a subtype of histiocytosis characterised histologically by foamy non-Langerhan cells with Touton giant cells. It typically manifests as a single self-limiting cutaneous nodule in the pediatric population. Orbital JXG is extremely rare, and its clinical course and management are not well understood or defined. Herein we present 3 cases of orbital JXG and provide a detailed literature review. Review of 3 cases with orbital JXG and literature review of all published cases. Three presented cases demonstrate the heterogeneous clinical course of orbital JXG. Although centred around the use of steroids, there is neither robust evidence nor consensus on its management. The wider JXG literature is currently concentrated around the classification of JXG with respect to histiocytosis, especially the exclusion of extracutaneous JXG as separate diseases. This separation is based on clinical, histopathological, and molecular findings. It is unclear where orbital JXG best fits in this emerging classification of JXG. Our review of the cases and literature on orbital JXG show that it may manifest with variable clinical course and its molecular pathogenic mechanism may be different to that of the cutaneous JXG.

Clinical observation of Erdheim–Chester disease: diagnostic difficulties, treatment options

As is known, orphan diseases, which include histiocytosis, including Erdheim-Chester disease (ECD), occur under the guise of other diseases, which complicates timely diagnosis and treatment. The presence of various symptoms in patients with an unspecified diagnosis (weight loss, fever, chills, night sweats, malaise, shortness of breath, thirst, polyuria; pain in the muscles and joints, in the long tubular bones of the upper and lower extremities, in the lower back or abdomen due to kidney damage and/or retroperitoneal fibrosis; exophthalmos; rash, xanthomas; frequent infectious diseases; nystagmus, ataxia, dysarthria) requires doctors to be wary of BEC.The variety of symptoms is due to the involvement of many organs and systems (orbits, kidneys, skin, brain, including the pituitary gland; lungs; heart; blood vessels; tubular bones), which requires a thorough examination, including morphological verification of the pathological process. Histological examination of biopsy specimens for BEC is characterized by histiocytic infiltrates (so-called “foamy histiocytosis”) with signs of inflammation and the presence of Touton giant cells; Immunohistochemistry reveals positive staining of these giant cells for CD68 antigen and factor XIIIa. Bone scintigraphy reveals a pronounced symmetrical accumulation of radiopharmaceuticals in the affected bones; with radiography in places of ossalgia — significant symmetrical bilateral osteosclerosis of the periosteum; according to CT data - “hairy” kidneys, “lined” aorta as a result of infiltration with histiocytes. The BRAF V-600E gene mutation, detected in half of the cases, in combination with one or more clinical and morphological signs allows a correct diagnosis to be made. The treatment of this disease is quite complex due to the lack of multicenter international clinical studies due to the rare occurrence of this pathology. However, clinical studies are currently being conducted on the use of drugs of various groups in the treatment of BEC. There is no doubt that due to the rarity of the disease and the low awareness of doctors, our own clinical experience in managing such patients is of great interest.

XANTHOGRANULOME JUVENILE SIMULANT UN HYGROMA DU COUDE : A PROPOS DUN CAS ET REVUE DE LA LITTERATURE

Juvenile xanthogranuloma is a non-Langerhansian histiocytosis that is clinically manifested by a yellowish nodule. The objective of this work is to discuss the anatomo-clinical aspects of this condition and its differential diagnoses. We report the case of a 38-year-old patient with juxta-articular swelling of the elbow clinically simulating hygroma. Xanthogranuloma is a benign, self-involutive form of non-Langerhansian histiocytosis that appears early in life. Diagnosis is usually clinical in the most typical forms. In other cases, histological analysis is necessary to support the diagnosis by the demonstration of a dense dermal infiltrate delimiting foamy histiocytes mixed with very characteristic Touton giant cells. The differential diagnosis is made with the other etiologies of histiocytic proliferations namely langerhansian histiocytosis, papularxanthoma and dermato fibroid hence the interest of carrying out an immunohistochemical supplement before retaining the histological diagnosis of xanthogranuloma. To conclude, the diagnosis of juvenile xanthogranuloma is often clinical in the most typical forms. In other cases, histological study is essential to support the diagnosis. The immunohistochemical study, as well as the comparison with clinical and paraclinical data are of great help in eliminating differential diagnoses.

Recurrent petit mal seizures in Erdheim-Chester disease mimicking an intra-axial brain tumor: illustrative case.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized histologically by foamy histiocytes and Touton giant cells in a background of fibrosis. Bone pain with long bone osteosclerosis is highly specific for ECD. Central nervous system involvement is rare, although dural, hypothalamic, cerebellar, brainstem, and sellar region involvement has been described. A 59-year-old man with a history of ureteral obstruction, medically managed petit mal seizures, and a left temporal lesion followed with serial magnetic resonance imaging (MRI) presented with worsening seizure control. Repeat MRI identified bilateral amygdala region lesions. Gradual growth of the left temporal lesion over 1 year with increasing seizure frequency prompted resection. A non-Langerhans cell histiocytosis with a BRAF V600E mutation was identified on pathology. Imaging findings demonstrated retroperitoneal fibrosis and long bone osteosclerosis with increased fluorodeoxyglucose uptake that, together with the neuropathologic findings, were diagnostic of ECD. This case of biopsy-proven ECD is unique in that the singular symptom was seizures well controlled with medical management in the presence of similarly located bilateral anterior mesial temporal lobe lesions. Although ECD is rare intracranially, its variable imaging presentation, including the potential to mimic seizure-associated medial temporal lobe tumors, emphasizes the need for a wide differential diagnosis.

Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.

The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC :: SYK fusion in 3 cases of a histopathologically distinct histiocytic neoplasm arising as solitary soft tissue lesions in children identified by next-generation sequencing and fluorescence in situ hybridization is described. Morphologically, all 3 neoplasms were composed of sheets of cells with round-oval nuclei and vacuolated eosinophilic cytoplasm but, in contrast to classic juvenile xanthogranuloma (JXG), Touton giant cells were absent. A separate cohort of classic JXG cases subsequently profiled by fluorescence in situ hybridization were negative for the presence of a CLTC::SYK fusion suggesting that CLTC::SYK fusion-positive histiocytoma is genetically and histologically distinct from JXG. We postulate that the CLTC::SYK fusion leads to aberrant activation of the SYK kinase, which is involved in variable pathways, including mitogen-activated protein kinase. The identification of a novel CLTC::SYK fusion may pave the way for the development of targeted therapeutic options for aggressive disease.

DP20 Necrobiotic santhogranuloma of the scalp with nonprogressive thrombocytopenia: a case report

Abstract We present the case of an 84-year-old woman referred with a 6-month history of a lesion on her occipital scalp. Examination revealed a creamy-white, nonscaly nodule measuring 15 × 15 mm with surface telangiectasia. Her past medical history included basal cell carcinoma, stage 3 kidney disease, cardiovascular disease and osteoporosis. A diagnosis of necrobiotic xanthogranuloma (NXG) was confirmed on incisional biopsy, and the patient went on to have full excision. Given the association with haematological malignancies, and following discussion with our local haematologist, investigations included full blood count, bone profile, immunoglobulins, serum and urinary protein electrophoresis and serum free light chains. This revealed a low platelet count of 108 × 109 cells L–1 (reference interval 150–450) but no other significant abnormalities. Our local haematologist considered a bone marrow biopsy, but after discussion with the patient, this was declined. Necrobiotic xanthogranuloma is a rare non-Langerhans histiocytosis. It classically presents as a yellow, red or purplish papule or nodule in the periorbital region, so this case had an unusual site. The mean age of onset is in the sixth decade of life, with an equal sex distribution. Pathogenesis is unknown. Necrobiotic xanthogranuloma is associated with haematological malignancies, particularly paraproteinaemia and lymphoproliferative disease. Differential diagnoses include xanthelasma, chronic lupus erythematosus, sarcoidosis and necrobiosis lipoidica. Where lesions become infiltrative and plaque-like, mycosis fungoides and psoriasis can also be considered. Given the relatively rare nature of NXG, there is no consensus for optimal treatment. In localized skin lesions such as in our patient, surgical excision is often undertaken. Other reported treatments are directed at the associated paraproteinaemia and include chlorambucil and small-dose corticosteroids, cyclophosphamide, melphalan, azathioprine, thalidomide, interferon-α and intravenous immunoglobulin. Classical features on histology include palisading xanthogranulomas with foci of necrobiosis in the mid-dermis and diffuse granulomatous panniculitis with foreign body-type reaction and Touton giant cells. Our histology slides showed a relatively atrophic epidermis with a dense dermal and subcutaneous infiltrate consisting of lymphocytes, foamy macrophages, plasma cells and Touton-type multinucleate giant cells with areas of necrobiosis. There were also reactive lymphoid follicles with germinal centres. Given the association with internal malignancy, it is important to diagnose these lesions correctly. To date, our patient has not developed any haematological malignancy, although is at increased risk in the future and has been counselled and monitored accordingly. It remains unclear whether the presence of thrombocytopenia alongside NXG is a coincidental finding or marker for future lymphoproliferative disease, as there are no other published case reports of such an association.

Myalgia in a Patient with Adult-Onset Asthma with Periocular Xanthogranuloma (AAPOX) due to Myotonic Dystrophy type 2 (P6-8.013)

<h3>Objective:</h3> To report a patient with myotonic dystrophy type 2 (DM2) and an adult-onset asthma with periocular xanthogranuloma (AAPOX). <h3>Background:</h3> AAPOX is a rare systemic non-Langerhans histiocytosis, clinically characterized by periocular yellowish plaques, adult-onset asthma, and lymphadenopathy, and pathologically characterized by non-caseating granulomas consisting of foamy histiocytes and Touton giant cells. The etiology of AAPOX is unknown, but recent studies suggested a possible link to IgG4-related disease. Autoimmune diseases occur in up to 30% of myotonic dystrophy type 2 (DM2) patients but concomitant AAPOX and DM2 have never been reported. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 38-year-old man with hyperlipidemia presented with 1.5-year history of progressive bilateral periorbital swelling and periocular yellowish plaques, 1-year history of asthma and exercise intolerance, and 4-month history of rosuvastatin-associated myalgias and difficulty climbing stairs. Periorbital soft tissue biopsy revealed characteristic pathological features of AAPOX. Neurologic examination revealed neither weakness nor clinical myotonia. Family history was significant for bradyarrhythmia requiring pacemaker in his mother and maternal grandfather. The patient’s creatine kinase was elevated at 606 U/L (normal &lt; 308 U/L). HMGCR-IgG was negative. IgG4 level was normal. Electromyography revealed diffuse myotonic discharges and a mild proximal myopathy without fibrillation potentials. A triceps brachii biopsy showed a marked increase of fibers harboring internal nuclei, scattered pyknotic nuclear clumps, and type 1 fiber smallness without granulomas. Genetic testing revealed a heterozygous CCTG repeat expansion &gt; 15,600 base pairs in intron 1 of <i>CNBP</i>, consistent with a diagnosis of DM2. His cardiac evaluation was unrevealing. The patient was treated with prednisone and methotrexate with improvement of his periocular disease. Myalgias persisted despite discontinuation of rosuvastati <h3>Conclusions:</h3> We first report the cooccurrence of AAPOX and DM2. Our finding supports the increased risk of autoimmune diseases in DM2 patients. <b>Disclosure:</b> Dr. Skolka has nothing to disclose. The institution of Shreyasee Amin has received research support from NIH. Dr. Liewluck has nothing to disclose.

Langerhans Cell Histiocytosis Evolving into Juvenile Xanthogranuloma: Two Linked Entities.

Langerhans cell histiocytosis (LCH) represents a myeloid clonal proliferation that involves the skin and other organs. Occasionally, cases of LCH evolve into juvenile xanthogranuloma (JXG). A 7-month-old boy presented with an itchy, flaky rash resembling seborrheic dermatitis affecting the scalp and eyebrows. The lesions started at 2 months old. On physical examination, there were reddish/brown lesions on the trunk, denuded areas on the groin and neck, and a large lesion behind his bottom teeth. In addition, there were thick white plaques in his mouth and thick whitish material in both ears. A skin biopsy showed features of LCH. Radiologic examination demonstrated several osteolytic lesions. Chemotherapy produced marked improvement. A few months later, the patient developed lesions with clinical and histologic features of XG. A possible association between LCH and XG is explained by lineage maturation development. Chemotherapy may play a role in modifying the production of cytokines that enhance the transformation or 'maturation' of Langerhans cells into multinucleated macrophages (Touton cells) characteristic of a more favorable proliferative inflammatory condition.

Adult-Onset Asthma With Periocular Xanthogranuloma: Clinical-Histological Correlation.

A 48-year-old male presented with 10 years of gradually enlarging yellow eyelid lesions. Past medical history was notable for adult-onset asthma diagnosed 5 years ago. He denied pain, diplopia, bone/joint pain, or systemic findings such as weight loss or fatigue. His father had similar eyelid lesions. Preoperative photograph demonstrated bilateral upper eyelid yellowish lesions with prominent edema and tissue expansion inducing bilateral ptosis (Fig. 1A). MRI demonstrated eyelid inflammation, enlargement of the extraocular muscles, especially the right lateral rectus (Fig. 1B, white arrow), and enlargement and enhancement of lacrimal gland (Fig. 1C, black arrow). He desired debulking excisional biopsies with bilateral blepharoplasty. Intraoperative photos show significant soft tissue inflammatory infiltration, particularly the lacrimal gland (Fig. 1D, red arrows).FIG. 1.Histopathologically, xanthogranulomatous inflammation is characterized by diffuse inflammatory infiltrate composed of histiocytes and lymphocytes (Fig. 2A, H&E, 100×). Specifically, the presence of foamy macrophages (Fig. 2B, H&E, 400×, red arrows) and Touton Giant cells (Fig. 2C, H&E, 400×, black arrow) are the histological hallmarks of the disease. The differential diagnosis of xanthogranulomatous inflammation includes adult-onset xanthogranuloma, adult-onset asthma with periocular xanthogranuloma (AAPOX), Erdheim-Chester disease (ECD), necrobiotic xanthogranuloma (NBX), and juvenile xanthogranuloma.FIG. 2.The patient was diagnosed with AAPOX given the association with adult-onset asthma. While the vast majority of yellow eyelid lesions are clinically benign, ECD and NBX are must-not-miss diagnoses, given their potential life-threatening systemic manifestations. These include vital organ (heart/kidney/lung) involvement in ECD, and association with serum protein abnormalities and hematological malignancies in NBX.

Multisystem ALK-positive histiocytosis: a multi-case study and literature review

BackgroundAnaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated.ResultsHere, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between 32 and 51 years. Two patients’, whose main manifestations were intracranial mass and numerous micronodules in the thoracoabdominal cavity organs and skin papules respectively, had a partial response to ALK inhibitors after surgery. One patient presented with mediastinal neoplasm without surgical treatment, and progressive disease occurred after two years of ALK inhibitor therapy. The fourth patient was a 17-month-old male with a large intracranial mass and presented with a poor response to ALK inhibitor and chemoradiotherapy; he died eight months after surgery. Pathologically, the histiocytes were large, with abundant eosinophilic cytoplasm, and mixed with variable numbers of foamy cells and Touton giant cells. Interstitial fibrosis was also observed. Histiocytes were positive for macrophage markers (CD68 and CD163) and ALK. KIF5B-ALK fusions were detected in two cases, EML4-ALK in one, and both DCTN1-ALK and VRK2-ALK fusions were detected in one case.ConclusionsWe observed that ALK inhibitors present robust and durable responses in adult patients but a poor response in young children with central nervous system involvement. There is no consensus on the optimal treatment regimen and long-term prognosis requires further observation. Moreover, every unusual histiocytic proliferative lesion, especially unresectable and multisystem involvement, should be routinely tested for ALK immunohistochemical staining to identify this rare disease.

Eruptive papules on axillary folds of an adolescent.

Eruptive papules on axillary folds of an adolescent.

Xanthogranulomatous osteomyelitis of Tibia in a case of 43 years old male patient: A rare entity diagnosed in a tertiary care hospital

Xanthogranulomatous inflammation is a form of chronic inflammatory process with collection of foamy macrophages in sheets, often with presence of giant cell reaction. Here, we present a case of xanthogranulomatous osteomyelitis of tibia in a 43 years old patient, which is a rare pathological entity and possibly was reported first in 1984. The histopathological sections revealed dense collection of lympho-plasmacytic infiltrate in the marrow spaces with syncytial sheets of foamy macrophages admixed with numerous classical Touton giant cells.

Giant cell tumor of the bone of maxillary sinus: A rare uncommon manifestation implicated in a new mosaic of disorders?

The goal is to show a rare case of Giant Cell Tumor of Bone in the maxillary sinus implicated in a process coincidentally or casually with another type of lesion primarily developed. A 33-year-old male patient attended a surgical service, presenting swelling, obstruction and firm mass externalizing through the right nostril and perceived during 6 months. During the anamnesis, the patient stated to been underwent an incisional biopsy 4 years ago of a tumor with histopathological diagnosis of the Nasal Paraganglioma, however the immunohistochemical study was negative for this tumor. During the Computed Tomography evaluate was observed a hyperdense mass occupying the entire maxillary sinus. In the Nuclear Magnetic Resonance evaluation, it was showed a hypersignal image in the entire maxillary sinus, invading the nasal cavity and portion of skull base. A bone window was performed in the right maxillary sinus and excisional biopsy was made. In the new histopathological examination, the diagnose was consistent with Giant Cell Tumor of Bone, being observed a large number of multinucleated giant cells, some with disorganized nuclei and others similar to Touton giant cells. A large proliferation of xanthomatous-looking cells was also observed without features of malignity. At the 3-year follow-up, the patient reported no complications such as facial paralysis, infection, relapse or spread. The association between lesions occurring in the same location requires further study, possibly implicated in a new model of clinical, microscopic, and genetic disorders. Thus, masses originating from chronic inflammatory tissue may have the potential to transform into GCTB?

The clinicopathological features of adult orbital xanthogranulomatous disease with lacrimal gland reactive lymphoid hyperplasia

Objective: To investigate the clinicopathological features of adult orbital xanthogranulomatous disease (AOXGD) with lacrimal gland reactive lymphoid hyperplasia. Methods: Retrospective case series study. The clinical and pathological data of AOXGD cases diagnosed and treated in Tianjin Eye Hospital from January 2002 to December 2021 was reviewed, and the clinical characteristics, radiologic findings and pathological characteristics of periocular and lacrimal gland lesions of 5 cases were retrospectively analyzed. The expression of IgG4 and IgG protein in periocular and lacrimal gland lesions was detected by immunohistochemical staining, and the role of IgG4 in AOXGD was preliminarily studied. Results: There were four females and one male with an average age of 53.8 years (39 to 77 years). Among the five AOXGD cases, there were three cases of adult-onset xanthogranuloma, one case of adult-onset asthma and periocular xanthogranuloma, and one case of necrobiotic xanthogranuloma. All cases involved both eyes. The swelling of eyelids was observed in five cases, and the yellow or pale yellow eyelid skin was found in two cases. Imaging examinations showed the tumor mainly involved the eyelids, subcutaneous tissues, anterior orbit and lacrimal gland. A large number of foam cells and typical Touton giant cells were found in the periorbital lesions, accompanied by different degrees of fibrosis. The fibrinoid necrosis was detected in one case of necrobiotic xanthogranuloma. The lacrimal gland lesions showed different types of reactive lymphoid hyperplasia, including IgG4-related disease in two cases, follicular lymphoid hyperplasia in two cases and focal lymphoid hyperplasia in one case. IgG4 levels of periorbital and lacrimal gland lesions were elevated in four cases. Asthma and elevated serum IgG4 were found in one case of adult-onset periocular xanthogranuloma. Three patients underwent surgical resection and adjuvant hormone or immunosuppressive therapy, and two patients underwent simple surgical resection. The patients were followed up for 1.5 to 10.0 years, one patient was lost, and four patients had no recurrence. Conclusions: AOXGD with lacrimal gland reactive lymphoid hyperplasia is a group of rare diseases. The periorbital lesions of that are characterized by proliferation of foamy histiocytes and Touton giant cells, and the lacrimal gland lesions of that manifest as IgG4-related disease in some cases.

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

There are several activated forms of macrophages: 2 main groups are designated M1 and M2. While M1 macrophages have proinflammatory, bactericidal, and phagocytic functions and are the dominant phenotype observed in the early stages of inflammation, M2 macrophages are involved in constructive processes such as tissue repair; they play a role in wound healing and are required for revascularization and re-epithelialization. Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis. Its pathogenesis is not well understood, but it is not considered a neoplastic entity. JXGs possibly appear as a reaction to a nonspecific injury such as trauma or viral infection, although a genetic predisposition has been suggested in some cases. Tissue damage leads to a histiocytic response. JXGs appear, evolve toward maturation, and then most of them spontaneously regress. Young JXGs are characterized by small macrophages scattered in the dermis, in apposition close to the epidermis. As the lesion matures, the number of foamy macrophages and Touton cells increases and other cell types such as plasma cells, lymphocytes, and polymorphs are observed. Regressing xanthogranulomas will show numerous spindle cells in Significant values are in bold.a storiform distribution, interstitial fibrosis, and few foamy and Touton cells. In this study, we studied the immunophenotypic profile of macrophages found in cutaneous JXGs according to their stage of maturation. We examined the skin biopsies from 25 patients; all were embedded in paraffin and stained with hematoxylin and eosin and for immunohistochemistry. Typically, all JXGs were positive for factor XIIIa and CD4, and were negative for CD1a. The following histiocyte markers were used: CD68, CD204, CD163, MAC387, and HAM56. Images were analyzed by Image J software; data were statistically evaluated by SAS 9.0 software. The cases showed a slight predominance of males and the preference of the JXGs for the axial skin. Lesions occupied the papillary and reticular dermis in 85% of the cases and extended to the subcutaneous fat in the remainder. Compared with mature and regressing JXGs, younger lesions had a higher density of M1 macrophages, stained with MAC387. This antibody labels the histiocytes that have recently arrived in the areas of inflammation. As the lesions matured, there was an overwhelming predominance of M2 macrophages. These cells tended to cluster against the epidermis, except in the 2 cases in phase of regression. This suggests that there is a cross-talk between the epidermis and macrophages and that receptors, cytokines, chemokines, and adhesion molecules may play a role in the development and evolution of JXGs. These results indicate that, for most of their life, JXGs are formed by repairing M2 macrophages and are not just an M1 macrophagic response to a local antigen. The process appears to be influenced by chemical-mediator epidermal-macrophage cross-talking, considering the tendency of these cells to accumulate against the dermoepidermal junction.