Cutaneous Rosai-Dorfman disease with MAP2K1 mutation, initially mimicking an infection with parasitized histiocytes.

Rarely, Rosai-Dorfman disease (RDD) manifests exclusively in the skin, typically as nodules on the trunk and extremities. Recognition of characteristic histopathologic features enables diagnosis of RDD. A 55-year-old female presented with a 7-year history of cutaneous nodules involving the trunk and extremities. A prior skin biopsy specimen at a different institution had demonstrated a dense dermal lymphohistiocytic infiltrate with histiocytes containing GMS+ forms, favored to represent cryptococcal organisms, with a differential diagnosis including other infections with parasitized histiocytes. Despite antibiotic therapy, lesions persisted. After a presentation to our institution, a biopsy specimen showed a diffuse infiltrate, including histiocytes with voluminous pale cytoplasm with focal emperipolesis of inflammatory cells and S100 immunohistochemical positivity. Clinical and radiologic examinations did not identify significant extracutaneous involvement. A genetic study performed on the biopsy specimen identified a K57Q mutation of MAP2K1. The presence of this mutation correlated with prior reports of MAP2K1 mutation in classic RDD, thereby supporting our histopathologic diagnosis of RDD over an infectious process and further illuminating options for targeted therapies. At 3-year follow-up, the patient has been managed with a course of systemic corticosteroids and excision of bothersome lesions. Consideration of systemic therapy is ongoing.

Synchronous occurrence of primary cutaneous B-cell lymphoma and cutaneous Rosai-Dorfman disease in distinct lesions: A unique association.

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare subtype of reactive histiocytosis which is seldom associated with Hodgkin's and non-Hodgkin's lymphomas. To date, the coexistence in the same patient of extra nodal SHML and primary cutaneous B-cell lymphoma (PCBCL) has been reported in the literature, as metachronous diagnosis in the anatomical area of the original PCBCL or synchronous occurrence in the same lesions. However, no data have been published as for synchronous occurrence of the two pathological entities in distinct anatomical sites. Herein, we report the first ever described synchronous occurrence of PCBCL and SHML, detected in distinct lesions, affecting the same patient. The complete resolution of the patient's PCBCL after rituximab treatment and the concomitant regression of SHML suggest that this clinically benign reactive histiocytic proliferation, potentially triggered by the lymphoma microenvironment itself, may take place not only in the site of the PCBCL lesion, but also in other distant areas not directly affected by the primary cutaneous lymphoma.

Primary Rosai-Dorfman disease of the central nervous system: A clinical, histological, and molecular appraisal.

Rosai-Dorfman disease (RDD) is characterized by clonal proliferation of S-100 positive histiocytes and variable emperipolesis. It commonly affects cervical lymph nodes. Central nervous system (CNS) involvement is extremely rare. We attempted to evaluate the Cyclin D1 expression and frequency of KRAS and BRAF mutations in the RDD involving the CNS. All patients with histopathologically diagnosed RDD involving CNS were recruited from 2011 to 2022. All cases were subjected to immunohistochemistry for CD68, CD163, S100, CD1a, GFAP, CD207, EMA, ALK, BRAFV600E, IgG4, IgG, and CyclinD1. The real-time polymerase chain reaction (RT-PCR) for hotspot mutation analysis of KRAS (exons 2, 3, and 4) and BRAF (V600E) was conducted on formalin-fixed paraffin-embedded tissue using a commercial kit (EntroGen). A total of seven cases were included. The median age was 31 years, with six men and one woman. It showed spinal cord (n = 4) and intracranial (n = 3) involvement. Histologically, all cases showed histiocyte-rich inflammation with evidence of emperipolesis. These histiocytes were positive for S100, CD68, CD163, and Cyclin D1, whereas negative for CD1a, CD207, and EMA. BRAF V600E was expressed in a single case. None of the control cases (demyelination and infarction) with histiocytic infiltrate showed Cyclin D1 expression. Four RDD cases showed increased IgG4-positive plasma cells (>10/HPF) and IgG4/IgG ratio (>40%). BRAF V600E mutation was detected in one case (14.28%), while none showed KRAS mutation. RDD involving CNS is extremely rare and diagnostically challenging. Nuclear Cyclin D1 expression along with S-100 positivity in the tumor cells is a strong diagnostic clue. BRAF and KRAS mutations are rare in CNS RDD.

Surgical resection of pediatric craniocervical junction Rosai-Dorfman histiocytosis-a case report and literature review.

Rosai-Dorfman disease (RDD) with craniocervical junction involvement is a rare clinical entity. We present herein a case of a pediatric patient with craniocervical junction RDD which was surgically treated. A 10-year-old female with a history of B-cell acute lymphoblastic leukemia (B-ALL) in remission and RDD presented with frontal migraine headaches. She previously had a right posterior chest wall lesion which was biopsy-proven RDD. She was found on imaging to have a dural-based right craniocervical junction lesion. Given her history of B-ALL, after a multidisciplinary discussion, the decision was made to proceed with resection with possible initiation of cobimetinib or clofarabine. The patient underwent a suboccipital craniotomy, C1 laminectomy, and resection of the dural-based lesion. Gross total resection was achieved, and histopathology confirmed the diagnosis of RDD. She was discharged home on postoperative day 4. No recurrence was seen on follow-up imaging at 3 months. We conducted a systematic literature review examining all cases of pediatric intracranial RDD and all cases of craniocervical junction RDD. This represents, to the best of our knowledge, only the second case of pediatric craniocervical junction RDD. Although RDD is often self-limiting, medical treatment is often considered for intracranial disease, but tissue confirmation is necessary. Surgical resection provides histopathologic diagnosis and can sometimes serve as definitive treatment for a particular lesion.

Extranodal Rosai-Dorfman Disease: a rare presentation involving anterior chest wall in a middle-aged female.

Rosai-Dorfman Disease is a rare benign disorder involving overproduction of immune cells, causing swollen lymph nodes and, in rare cases, the sternum. The sternal involvement may cause chest pain and masses. Diagnosis is confirmed through clinical examination, biopsy, and imaging. Treatment options may include surgery, radiation, or steroids. In this case study, we present an unusual example of extranodal Rosai-Dorfman Disease involving the sternum, bilateral clavicles and first three ribs, and pectoral muscle with no associated lymphadenopathy or systemic symptoms in a 57-year-old female. The etiology, pathology, immunohistochemistry, imaging findings, and treatment options of this unique disease are discussed.

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.

Characterizing Rosai-Dorfman disease with [18F]FDG PET/CT: a retrospective analysis of a single-center study.

OBJECTIVES: Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferative disorder. We performed a retrospective study to characterize the clinical and [18F]FDG PET/CT features of RDD. METHODS: We retrospectively recruited 38 RDD patients with [18F]FDG PET/CT scan in our center. [18F]FDG PET/CT features were assessed, and clinical and follow-up data were recorded. RESULTS: In the recruited patients, 20/38 (52.6%) patients had single-system disease, while others (18/38, 47.4%) had disease affecting multiple system. RDD most commonly involved the upper respiratory tract (47.4%), followed by cutaneous/subcutaneous lesion (39.5%), lymph node (36.8%), bone (31.6%), central nervous system (28.9%), and cardiovascular system (13.2%) in the recruited patients. In PET/CT, the RDD lesions were FDG-avid, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels (r = 0.418, p = 0.014), and negatively correlated with hemoglobin levels (r = -0.359, p = 0.036). The overall response rate of the first-line treatment was 80.8% in newly diagnosed RDD patients, and for patients with relapsed/progressive RDD, the overall response rate was 72.7%. CONCLUSION: [18F]FDG PET/CT could be a useful tool for evaluating RDD. KEY POINTS: • About half of the patients with Rosai-Dorfman disease had single-system disease, while others had disease affecting multiple system. Rosai-Dorfman disease most commonly involved the upper respiratory tract, followed by cutaneous/subcutaneous lesion, lymph node, bone, central nervous system, and cardiovascular system. • In [18F]FDG PET/CT, Rosai-Dorfman disease was usually hypermetabolic, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels. • Rosai-Dorfman disease usually has a high overall response rate after treatment.

Comparison of neuroimaging features of histiocytic neoplasms with central nervous system involvement: a retrospective study of 121 adult patients.

OBJECTIVES: To compare neuroimaging characteristics of three types of histiocytoses, namely Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD), with central nervous system (CNS) involvement. METHODS: A total of 121 adult patients with histiocytoses (77 LCH, 37 ECD, and 7 RDD) and CNS involvement were retrospectively included. Histiocytoses were diagnosed based on histopathological findings combined with suggestive clinical and imaging features. Brain and dedicated pituitary MRIs were systematically analyzed for tumorous, vascular, degenerative lesions, sinus, and orbital involvement and for hypothalamic pituitary axis involvement. RESULTS: Endocrine disorders, including diabetes insipidus and central hypogonadism, were more common in LCH patients than in ECD and RDD patients (p < 0.001). In LCH, tumorous lesions were mostly solitary (85.7%), located in the hypothalamic pituitary region (92.9%), and without peritumoral edema (92.9%), while in ECD and RDD, tumorous lesions were often multiple (ECD: 81.3%, RDD: 85.7%), their distribution was more widespread with meninges mostly involved (ECD: 75%, RDD: 71.4%), and they most likely presented with peritumoral edema (ECD: 50%, RDD: 57.1%; all p ≤ 0.020). Vascular involvement was an exclusive imaging characteristic of ECD (17.2%), which was not observed in LCH or RDD; this was also associated with a higher risk of death (p = 0.013, hazard ratio = 11.09). CONCLUSION: The typical characteristic of adult CNS-LCH was endocrine disorders with radiological findings limited to the hypothalamic pituitary axis. The pattern of multiple tumorous lesions with predominant involvement of meninges was the main manifestation of CNS-ECD and CNS-RDD, while vascular involvement was pathognomonic for ECD and associated with poor prognosis. CLINICAL RELEVANCE STATEMENT: Involvement of the hypothalamic-pituitary axis is the typical imaging characteristic of Langerhans cell histiocytosis. Multiple tumorous lesions, predominantly involving but not limited to meninges, occur in most Erdheim-Chester disease and Rosai-Dorfman disease patients. Vascular involvement occurs only in Erdheim-Chester disease patients. KEY POINTS: • The different distribution patterns of brain tumorous lesions can help differentiate among LCH, ECD, and RDD. • Vascular involvement was an exclusive imaging finding of ECD and was associated with high mortality. • Some cases with atypical imaging manifestations were reported to further expand the knowledge on these diseases.

Neurological Manifestations of Histiocytic Disorders.

PURPOSE OF REVIEW: Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. RECENT FINDINGS: Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.

Intracranial Rosai-Dorfman disease: a case report and review of the literature.

RDD involving the central nervous system is rarely reported. To better understand the disease and explore the treatments, we reported this case and review the literature.

A unique case of isolated thoracic spinal Rosai-Dorfman disease related to IgG4.

Rosai-Dorfman disease (RDD) is a rare benign histiocytosis usually characterized by massive cervical lymphadenopathy and systemic manifestations. Extranodal, especially spinal involvement, is extremely rare. Our case was deemed worthy of presentation because it was the first reported isolated case of spinal RDD related to IgG4 and mimicked meningioma clinically and radiologically. A case with an intradural extramedullary mass causing neurological compression findings in the thoracic spinal region and radiologically mimicking meningioma is presented. In the histomorphological examination of the resection material, polymorphonuclear leukocytes in the dura, histiocytes showing emperipolesis, an increase in collagenized fibrous connective tissue, and intense lymphoplasmacytic cell infiltration accompanied by obliterative phlebitis were observed. Immunohistochemically, the histiocytic cells were found to be S-100 protein, CD68, and CD163 positive and CD1a and langerin negative, and more than half of the plasma cells were immunoglobulin-G4 (IgG4) positive. Although rare, RDD or IgG4-related meningeal disease should be considered in the differential diagnosis of dural-based spinal masses that radiologically suggest meningioma. The pathologist should be aware that these two histopathological entities may coexist. To our knowledge, this is the first case of "isolated spinal RDD related to IgG4" reported in the literature.

The changing landscape of pediatric histiocytoses: Birth, life, and transdifferentiation of pediatric histiocytes.

Histiocytic neoplasms in the children are very rare, and histiocytoses can occur in the perinatal period. The presumed origins and presentation of specific histiocytoses in the pediatric age group are described. Common and newly described histiocytoses are presented including Langerhans cell histiocytosis, Rosai-Dorfman disease, histiocytic sarcoma, ALK positive histiocytosis, and hemophagocytic lymphohistiocytosis. Molecular findings common to pediatric histiocytoses are also discussed.

Primary diffuse Rosai-Dorfman disease in central airway: a case report and literature review.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare benign non-langerhans cell histiocytosis, mainly involving lymph nodes and skin. It is even rarer occurring only in central airway of lung and in diffuse form. Central airway RDD is similar to malignant tumor in imaging by radiological method and in bronchoscopy features. It is difficult to differentiate it from primary airway malignant tumor and to diagnose correctively in time. CASE PRESENTATION: Here we present a rare case of 18-year-old male diagnosed with primary diffuse RDD in central airway. Although the features examined by enhanced chest computed tomography, positron emission tomography/computed tomography, diffusion-weighted imaging of enhanced chest MRI and bronchoscopy indicate to be malignant tumor, the patient was definitely confirmed by multiple transbronchial biopsies and immunohistochemistry. After two transbronchial resections, the patient's symptoms of paroxysmal cough, whistle sound and shortness of breath were significantly reduced, as well as the airway stenosis was significantly improved. After 5 months of follow-up, the patient had no symptoms and the central airway were unobstructed. CONCLUSIONS: Primary diffuse RDD in central airway is characterized by intratracheal neoplasm, which is usually suspected as malignant tumor according to radiological image and bronchoscopy. Pathology and immunohistochemistry are necessary for definite diagnosis. Transbronchial resection is effective and safe for patients with primary diffuse RDD in central airway.

Surgical management and outcome of primary intracranial Rosai-Dorfman disease: a single-institute experience and pooled analysis of individual patient data.

Primary intracranial Rosai-Dorfman disease (PIRDD) is considered a nonmalignant nonneoplastic entity, and the outcome is unclear due to its rarity. The study aimed to elaborate the clinic-radiological features, treatment strategies, and progression-free survival (PFS) in patients with PIRDD. Patients with pathologically confirmed PIRDD in our institute were reviewed. Literature of PIRDD, updated until December 2019, was systematically searched in 7 databases (Embase, PubMed, Cochrane database, Web of Science, Wanfang Data Knowledge Service Platform, the VIP Chinese Science and Technology Periodical Database (VIP), and the China National Knowledge Infrastructure (CNKI)). These prior publication data were processed and used according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical-radiological characteristics and adverse factors for PFS were evaluated in the pooled cohort. The pooled cohort of 124 cases (81 male and 43 female), with a mean age of 39.7 years, included 11 cases from our cohort and 113 cases from 80 prior studies. Twenty-nine patients (23.4%) had multiple lesions. Seventy-four patients (59.7%) experienced gross total resection (GTR), 50 patients (40.3%) had non-GTR, 15 patients (12.1%) received postoperative adjuvant radiation, and 23 patients (18.5%) received postoperative steroids. A multivariate Cox regression revealed that GTR (HR = 4.52; 95% CI 1.21-16.86; p = 0.025) significantly improved PFS, and multiple lesions (p = 0.060) tended to increase the hazard of recurrence. Neither radiation (p = 0.258) nor steroids (p = 0.386) were associated with PFS. The overall PFS at 3, 5, and 10 years in the pooled cohort was 88.4%, 79.4%, and 70.6%, respectively. The PFS at 5 and 10 years in patients with GTR was 85.4% and 85.4%, respectively, which was 71.5% and 35.8%, respectively, in patients without GTR. Gross total resection significantly improved PFS and was recommended for PIRDD. Radiation and steroids were sometimes empirically administered for residual, multiple, or recurrent PIRDD, but the effectiveness remained arguable and required further investigation.Systematic review registration number: CRD42020151294.

Clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease, RDD).

PURPOSE: To investigate the clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal RDD. METHODS: A retrospective analysis was performed on 16 patients who were initially diagnosed and treated with otolaryngological extranodal RDD in our hospital from January 2013 to January 2019. RESULTS: There were 9 females and 7 males. The mean diagnostic age was 45.35. Nasal, laryngeal and otic RDD were, respectively, accounting for 56.25%, 31.25% and 12.5%. The median interval diagnostic time was individually 1, 0.5 and 0.2 year for nasal, laryngeal and otic RDD. The most common symptoms were separately progressive nasal congestion, dyspnea, otorrhea in nasal, laryngeal and otic RDD. 13 had cervical lymph node swelling on MRI. Surgery or postoperative radiotherapy were conformed. In the end, 14 patients with RDD survived. The survival rate is as high as 87.5%. One of them died of RDD in the fifth year. One case was lost to follow-up 2 years after treatment. Patients survive for at least 2 years and up to 9 years. There was no significant difference in life expectancy of extranodal RDD among different parts of ENT (P = 0.508 > 0.05). The average ages of laryngeal and nasal RDD were similar (P = 0.898 > 0.05). However, the age of both was significantly higher than ear RDD (P = 0.023 and 0.019 < 0.05). CONCLUSIONS: The average diagnostic age was more than 20 years. Nasal RDD was the most common in this area. All laryngeal RDD had infiltrated subglottis. Functional surgery and postoperative radiotherapy can be used to achieve long-term remission and survival.

A Rare Case of Rosai-Dorfman Disease Affecting the Brachial Plexus: A Case Report.

Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease is a rare but well-established entity, commonly affecting the lymph nodes of the head and neck. Extranodal presentation, affecting the central nervous system, eye orbit, kidneys, testis, bones, upper respiratory tract, lungs, thyroid, small intestine, and peritoneum, has been reported. We present a case of a rare presentation of Rosai-Dorfman disease affecting the brachial plexus.

Rosai-Dorfman disease with spinal and multiple intracranial involvement: a case report and literature review.

Rosai-Dorfman disease (RDD) is a condition of unknown etiology, and characterized by the proliferation of histiocytes. RDD most commonly affects lymph nodes, and central nervous system (CNS) involvement is rare. Here, we describe the case of a 43-year-old man who presented with an intradural tumour of the thoracic spine. The patient underwent a laminectomy for tumour resection and pathology results diagnosed the tumour as a RDD. Two years later, brain magnetic resonance imaging (MRI) revealed multiple intracranial dural-based lesions. Prednisolone treatment was initiated and led to resolution of the disease. We reviewed the literature to the investigate clinical characteristics, imaging features, diagnosis and treatment protocols pertaining to such cases.

Rosai-Dorfman disease mimicking cavernous hemangioma: a case report.

A 31-year-old female presented to the clinic with a 2 year history of proptosis of the right eye. She was diagnosed with cavernous hemangioma during her initial ophthalmologic consult and was advised monitoring. However, after a considerable increase in proptosis, she underwent an excision biopsy of the right orbital mass. A diagnosis of Rosai Dorfman disease was made after the histopathology report revealed a fibrosclerotic tissue with histiocytic proliferation showing emperipolesis that is mixed with numerous small lymphocytes and plasma cells. Rosai Dorfman disease is a rare disease presenting with lymphadenopathy and sinus histiocytosis. Orbital involvement can be the principal manifestation with proptosis as the most common presentation. Resection of the orbital lesion helped in the resolution of the mild ophthalmic symptoms but since the disease has other systemic associations, a complete systemic workup should be done to monitor recurrence.

Limited sinonasal Rosai-Dorfman disease presenting as chronic sinusitis.

AIMS: The sinonasal tract is a common extranodal site for Rosai-Dorfman disease (RDD). Recently, histiocytes with features of RDD were identified in the clinical setting of chronic sinusitis. This study evaluates whether this phenomenon should be considered part of the RDD spectrum or classified separately as RDD-like histiocytes. METHODS AND RESULTS: We prospectively collected 13 cases showing histological features of RDD in chronic sinusitis patients and identified 14 with similar findings (3.5%) via retrospective review of 403 sinus contents over 2 years. All 27 cases displayed nodular aggregates of eosinophilic histiocytes with intermixed lymphoplasmacytic inflammation, prominent eosinophils and emperipolesis. The histiocytes were positive for S100 protein and cyclin D1 and negative for CD1a and CD207. All patients presented with severe chronic sinusitis without tumour formation or systemic symptoms. Twelve patients with follow-up (55%) required repeat sinus surgery compared with just 43 other sinusitis patients evaluated (11%); features of RDD were present in their additional specimens. Two cases that underwent targeted next-generation sequencing (20%) had oncogenic mutations in NF1 and KEAP1. CONCLUSIONS: Overall, these findings confirm diagnostic histological and immunohistochemical features of RDD in a subset of chronic sinusitis specimens. While patients uniformly lack systemic involvement or tumefactive growth, they have a high risk of recurrent sinus disease. Although the relatively subtle nature of the findings raises consideration of separate classification, the presence of occasional oncogenic mutations and evidence of consistent MAPK/ERK pathway activation via cyclin D1 positivity suggests that this phenomenon represents a unique limited manifestation of RDD.

Hodgkinoid histiocytosis: an atypical nodal CD30 and S100-positive histiocytosis with eosinophilia.

Histiocytes and dendritic cells may display cytological atypia and an aberrant immunophenotype even in reactive processes. Herein, we describe two cases of "Hodgkinoid histiocytosis" that show distinctive clinicopathological features, mimicking morphologically classic Hodgkin lymphoma (CHL), but suggesting reactive histiocytic/dendritic cell proliferation in lymph nodes. Both the patients presented with peripheral lymphadenopathy and blood eosinophilia with skin manifestations. Lymph node biopsy revealed scattered large histiocytes resembling Hodgkin cells with a round or stellate shape, abundant cytoplasm, and distinct nucleoli admixed in a predominant inflammatory background. The Hodgkinoid histiocytes occasionally showed emperipolesis. They expressed CD30, S100, and PD-L1 proteins but lacked PAX5 and CD1a expressions, Epstein-Barr association, BRAF V600E mutation, and PD-L1 gene amplification. Neither of the patients showed overt progression to malignant haematopoietic neoplasms during the disease course. An identical case series of four patients has been reported to date. Both these series highlight the potential of being interpreted as CHL due to the presence of Hodgkinoid histiocytes with CD30 positivity.