Histologic, Phenotypic, and Molecular Characterization of Feline Hodgkin-Like Lymphoma With Classical Reed-Sternberg Cells.

Hodgkin-like lymphoma (HLL) is a rare neoplasm in cats that shares characteristics with the human disease. The hallmark of HLL is the presence of Reed-Sternberg (RS) cells expressing CD30 and CD20. This study aimed to elucidate the clinicopathologic features, immunophenotype and clonality patterns of feline HLL. A comprehensive retrospective review of clinicopathologic and molecular data of nodal lymphomas over a 6-year period was conducted in MyLav laboratory. Twenty-four cases were identified. All cats presented with submandibular or retropharyngeal lymphadenopathy. Histopathologic examination revealed a multifocal to diffuse proliferation of medium-to-large lymphoid cells with low mitotic activity, interspersed RS cells, and a heterogeneous inflammatory infiltrate comprising T-cells, plasma cells and neutrophils. In addition, extensive necrosis was a consistent finding. Immunohistochemistry showed a variable membranous CD20 and nuclear PAX5 expression in neoplastic cells, while RS cells displayed only mild to moderate CD20 positivity and were negative to PAX5. In 21/24 cases (87.5%), RS cells were diffusely CD30-positive. PARR analysis demonstrated clonal B-cell expansion in 60% of cases, with the remaining 40% exhibiting polyclonality. For the 10 cats with available follow-up, the prognosis was generally favourable, with only two cats succumbing to progressive disease. In conclusion, diagnosing feline HLL is challenging. The expression of CD30 and CD20 by RS cells should be considered a hallmark of the disease, but only after excluding differential diagnoses such as anaplastic B-cell lymphoma and granulomatous lymphadenopathy.

A Persistent Pulmonary Puzzle: Diagnosing Hodgkin Lymphoma in a Young Female With Chronic Respiratory Symptoms.

Hodgkin lymphoma (HL), a lymphoid neoplasm characterized by the presence of Reed-Sternberg cells, often presents with painless lymphadenopathy and systemic symptoms. This case report details the diagnostic journey of a 27-year-old non-smoker female with chronic respiratory symptoms, including persistent cough, hemoptysis, and weight loss over two years. Despite multiple treatments for presumed infections and extensive diagnostic procedures, the correct diagnosis of HL was delayed due to atypical pulmonary manifestations, notably necrotizing pneumonia and multiple cavitary lung lesions. Ultimately, histopathology from a third bronchoscopy confirmed HL, highlighting the complexity of diagnosing HL with unusual presentations. Patients with cavitary lesions have a poor prognosis compared to others with typical pulmonary involvement, as cavitation in HL is likely caused by central ischemia necrosis due to the tumor's rapid growth. This case can be considered a primary pulmonary HL, a rare and hard-to-treat presentation since it does not respond well to radiotherapy. It emphasizes the challenge in diagnosing HL when it presents atypically, making it crucial to consider HL in differential diagnoses to avoid delayed diagnosis and improve patient outcomes.

The biology of classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is distinguished by several important biological characteristics. The presence of Hodgkin Reed Sternberg (HRS) cells is a defining feature of this disease. The tumor microenvironment with relatively few HRS cells in an expansive infiltrate of immune cells is another key feature. Numerous cell-cell mediated interactions and a plethora of cytokines in the tumor microenvironment collectively work to promote HRS cell growth and survival. Aberrancy and constitutive activation of core signal transduction pathways are a hallmark trait of cHL. Genetic lesions contribute to these dysregulated pathways and evasion of the immune system through a variety of mechanisms is another notable feature of cHL. While substantial elucidation of the biology of cHL has enabled advancements in therapy, increased understanding in the future of additional mechanisms driving cHL may lead to new treatment opportunities.

Intrasphenoidal cephalocoeles: Knowing the less known.

Intrasphenoidal encephalocoeles are acquired or congenital herniations of meninges and brain parenchyma through a structural sphenoid bone defect. Acquired causes are most common, either iatrogenic, post-traumatic, or spontaneous. However, defects in the lateral wall of the sphenoid sinus are uncommon and cephalocoeles through them relatively underexplored in current literature, warranting dedicated attention to unravel their complexities. Congenital causes such as persistence of Sternberg's canal, which can lead to lateral cephalocoeles, is a rare entity, seen in two of the presented cases, based on the location of the defect with respect to the line connecting the foramen rotundum and the vidian canal (VR line). Three cases of intrasphenoidal cephalocoeles are presented; two patients presented with watery nasal discharge without prior trauma or surgery and the third case was incidentally detected in an elderly patient with intraparenchymal haemorrhage. Imaging with CT cisternography and brain MR were performed to ascertain the exact location of the leak and confirm the presence of herniated brain tissue via the defects. Patients were evaluated by otolaryngology for transnasal endoscopic repair, which was deemed unfeasible, and referred to neurosurgery for transcranial duroplasty. Contribution: These cases provide crucial insights into the aetiology of lateral intrasphenoidal cephalocoeles, offering a practical system to classify cerebrospinal fluid (CSF) leaks based on the bony defect location. The three illustrative cases and emphasis on advanced imaging modalities refine the knowledge of their aetiology, clinical presentation and management, which hold direct clinical relevance for accurate diagnosis and tailored management of these rare anomalies.

A Rare Case of Rapid Lymphadenopathy Progression in Hodgkin's Lymphoma: A Case Report.

Hodgkin's lymphoma is a B-cell neoplasm that typically manifests with gradual lymphadenopathy progression over weeks to months. However, we present an exceptional case of Hodgkin's lymphoma marked by an unusually rapid development of lymphadenopathy within an hour. A 30-year-old male presented with a left neck swelling that occurred within an hour and then remained stable in size for three days, prompting an investigation revealing widespread lymphadenopathy consistent with Hodgkin's lymphoma. This case outlines the importance of recognizing and investigating unusual presentations of Hodgkin's lymphoma promptly, emphasizing the necessity for expedited diagnosis and intervention.

The great imitator: Tuberculosis with lymphadenopathy and splenomegaly.

Tuberculosis (TB) is a leading infectious killer worldwide. Over two-thirds of new TB diagnoses in the United States occur among first-generation immigrants, especially within a year of migration. Hodgkin lymphoma (HL) accounts for a minority of lymphoma cases but presents similarly to disseminated or extrapulmonary TB. Clinical overlap between TB and HL increases patient risk of misdiagnosis. Concomitant presentation of both diseases is not uncommon but infrequently reported. We present a case of isoniazid-resistant TB with progressively worsening lymphadenopathy and splenomegaly despite appropriate TB treatment. The patient was diagnosed with HL following PET/CT and axillary lymph node biopsy.

Brain reserve affects the expression of cognitive reserve networks.

Cognitive reserve (CR) explains differential susceptibility of cognitive performance to neuropathology. However, as brain pathologies progress, cognitive decline occurs even in individuals with initially high CR. The interplay between the structural brain health (= level of brain reserve) and CR-related brain networks therefore requires further research. Our sample included 142 individuals aged 60-70 years. National Adult Reading Test intelligence quotient (NART-IQ) was our CR proxy. On an in-scanner Letter Sternberg task, we used ordinal trend (OrT) analysis to extract a task-related brain activation pattern (OrT slope) for each participant that captures increased expression with task load (one, three, and six letters). We assessed whether OrT slope represents a neural mechanism underlying CR by associating it with task performance and NART-IQ. Additionally, we investigated how the following brain reserve measures affect the association between NART-IQ and OrT slope: mean cortical thickness, total gray matter volume, and brain volumes proximal to the areas contained in the OrT patterns. We found that higher OrT slope was associated with better task performance and higher NART-IQ. Further, the brain reserve measures were not directly associated with OrT slope, but they affected the relationship between NART-IQ and OrT slope: NART-IQ was associated with OrT slope only in individuals with high brain reserve. The degree of brain reserve has an impact on how (and perhaps whether) CR can be implemented in brain networks in older individuals.

Classic central nervous system Hodgkin lymphoma masquerading as left sphenoid wing meningioma- A case report.

INTRODUCTION AND IMPORTANCE: Classic Hodgkin Lymphoma with an incidence of 2-3 cases per 100,000 population affects the Central Nervous System in 0.02 % of cases (Gerstner et al., 2008; Brice et al., 2021; Morawa et al., 2007). CNS lymphoma, contributing to 0.22 % of Central Nervous System tumors, is the uncommon extra-nodal manifestation of Hodgkin's Disease (Brice et al., 2021; Henkenberens et al., 2014). It affects the nervous system secondary to systemic lymphoma or the relapse of the disease (Gerstner et al., 2008). Only 17 cases of CNS lymphoma are reported which were limited to the CNS at the time of diagnosis (Paul et al., 2017). Only two cases of Dural-Based Hodgkin Lymphoma were reported in the literature (Paul et al., 2017). CASE PRESENTATION: We are reporting the third case of dural-attached extra-axial secondary CNS Hodgkin Lymphoma in a 33 years old female, which appeared and was operated as Left Sphenoid Wing Meningioma. CLINICAL DISCUSSION: Only 17 cases of CNS lymphoma are reported which were limited to the CNS at the time of diagnosis (Paul et al., 2017). Only two cases of Dural-Based Hodgkin Lymphoma were reported in the literature (Paul et al., 2017). Our case consists the third case of dural attached Classic CNS Hodgkin lymphoma and the first case of Classic CNS Hodgkin Lymphoma locating in the Sphenoid Wing. CONCLUSION: It is important to differentiate CNS Hodgkin Lymphoma from other types of brain tumors especially when it resides in an unusual location because the treatment of CNS Hodgkin Lymphoma is mainly combined chemo-radiotherapy than surgical intervention.

Myxoinflammatory Fibroblastic Sarcoma.

MIFS is a low-grade fibroblastic sarcoma that predilects to superficial distal extremity soft tissue. It is composed of plump spindled and epithelioid cells, inflammatory infiltrates, and mucin deposits in a fibrosclerotic stroma. Large epithelioid cells harboring bizarre nuclei and virocyte-like macronucleoli and pleomorphic pseudolipoblasts are characteristic. While conventional MIFS has locally recurrent potential but minimal metastatic risk, tumors with high-grade histologic features have a greater risk for recurrence and metastasis. Wide local excision is the recommended treatment.

Assessing partial errors via analog gaming keyboards in response conflict tasks: A proof-of-concept study with the concealed information test.

The response time-based Concealed Information Test (RT-CIT) is an established memory detection paradigm. Slower RTs to critical information (called 'probes') compared to control items (called 'irrelevants') reveal recognition. Different lines of research indicate that response conflict is a strong contributor to this RT difference. Previous studies used electromyography (EMG) to measure response conflict, but this requires special equipment and trained examiners. The aim of this study was to explore if response conflict can also be measured with an analog gaming keyboard that is sensitive to minimal finger movements. In a preregistered study, participants completed an autobiographical RT-CIT (n = 35) as well as a cued recognition task (modified Sternberg task; n = 33) for validation purposes. Partial errors, partial button presses of the incorrect response key, were more frequent in trials with response conflict than in trials without conflict. Partial errors were rare (CIT: 2.9%; Sternberg: 1.7% of conflict trials), suggesting analogue keyboards have lower sensitivity than EMG. This is the first evidence that analog keyboards can measure partial errors. Although likely less sensitive than EMG measures, potential benefits of analog keyboards include their accessibility, their compatibility with all tasks that use a standard keyboard, that no physical contact with the participant is needed, and ease of data collection (e.g., allowing for group testing).

Endoscopic endonasal repair of encephaloceles of the lateral sphenoid sinus: multiinstitution confirmation of a new classification.

OBJECTIVE: Encephaloceles of the lateral sphenoid sinus are rare. Originally believed to be due to defects in a patent lateral craniopharyngeal canal (Sternberg canal), they are now thought to originate more commonly from idiopathic intracranial hypertension, not unlike encephaloceles elsewhere in the skull base. A new classification of these encephaloceles was recently introduced, which divided them in relation to the foramen rotundum. Whether this classification can be applied to a larger cohort from multiple institutions and whether it might be useful in predicting outcome is unknown. Thus, the authors' goal was to divide a multiinstitutional cohort of patients with lateral sphenoid encephaloceles into four subtypes to determine their incidence and any correlation with surgical outcome. METHODS: A multicenter retrospective review of prospectively acquired databases was carried out across three institutions. Cases were categorized into one of four subtypes (type I, Sternberg canal; type II, medial to rotundum; type III, lateral to rotundum; and type IV, both medial and lateral with rotundum enlargement). Demographic and outcome metrics were collected. Kaplan-Meyer curves were used to determine the rate of recurrence after surgical repair. RESULTS: A total of 49 patients (71% female) were included. The average BMI was 32.8. All encephaloceles fell within the classification scheme. Type III was the most common (71.4%), followed by type IV (16.3%), type II (10.2%), and type I (2%). Cases were repaired endonasally, via a transpterygoidal approach. Lumbar drains were placed in 78% of cases. A variety of materials was used for closure, with a nasoseptal flap used in 65%. After a mean follow-up of 47 months, there were 4 (8%) CSF leak recurrences, all in patients with type III or type IV leaks and all within 1 year of the first repair. Two leaks were fixed with ventriculoperitoneal shunt and reoperation, 1 with ventriculoperitoneal shunt only, and 1 with a lumbar drain only. Of 45 patients in whom detailed information was available, there were 12 (26.7%) with postoperative dry eye or facial numbness, with facial numbness occurring in type III or type IV defects only. CONCLUSIONS: Endoscopic endonasal repair of lateral sphenoid wing encephaloceles is highly successful, but repair may lead to dry eye or facial numbness. True Sternberg (type I) leaks were uncommon. Failures and facial numbness occurred only in patients with type III and type IV leaks.

Endoscopic endonasal repair of temporal lobe meningoencephalocele in the lateral recess of the sphenoid sinus, complicated by intracerebral hematoma: illustrative case.

BACKGROUND: Anomalies in the anatomical structure of the nasal cavity and paranasal sinuses often serve as a potential cause of spontaneous cerebrospinal fluid (CSF) leakage and may result in the development of a meningoencephalocele. In this report, the authors present a case of surgically treated intrasphenoidal meningoencephalocele attributed to the persistence of the lateral craniopharyngeal canal, which was further complicated by the occurrence of an intracerebral hematoma. OBSERVATIONS: A temporal lobe meningoencephalocele located in the lateral recess of the sphenoid sinus was successfully managed using endoscopic endonasal transpterygoid repair (EETR). However, an intracerebral hematoma developed after resection of the meningoencephalocele, necessitating additional surgical interventions. Despite this complication, the patient exhibited a favorable clinical outcome after the surgical interventions. LESSONS: This case highlights the potential risk of intracerebral hematoma associated with EETR of a lateral sphenoid sinus meningoencephalocele. A thorough examination of magnetic resonance imaging scans, especially identifying vascular structures, is crucial during surgical planning. This knowledge can help to prevent the occurrence of complications, including intracerebral hematoma.

Prospective effects of food safety trust on brand evangelism: a moderated-mediation role of consumer perceived ethicality and brand passion.

BACKGROUND: The current study integrates brand management literature with food consumption research and develops an integrative framework by combining food safety trust, consumer perceived ethicality, brand evangelism, and brand passion into a single conceptual model. METHOD: This quantitative study included 228 ready-to-eat consumers in China using purposive sampling. Data were collected at two periods in time, resulting in a time-lag study in which respondents provided data on independent and moderating variables at time 1 and mediating and dependent variables at time 2 with the same respondents from time 1. The hypothesized correlations were tested using SEM and PROCESS Macro techniques. RESULTS: According to the findings, trust in food safety has a significant impact on brand evangelism and passion. Furthermore, consumer perceived ethicality (CPE) found to have a substantial moderating role between food safety-FS and brand passion. Moreover, we validated the brand passion role as a mediator between brand evangelism and food safety trust, and investigated whether consumer perceived ethicality conditionally affects the strength of the indirect relationship among food safety trust and brand evangelism through brand passion, indicating a moderated-mediation mechanism. ORIGINALITY: Drawing on Sternberg theory of love, current study is the first of its kind to evaluate the boundary role as well as the conditional indirect influence of customer perceived ethicality among the study's variables and provides useful information for ready-to-eat food brand managers on how to keep them interested in their risk-free food products.

Composite Classical Hodgkin Lymphoma and Mantle Cell Lymphoma: A Case Report.

Composite lymphoma implies the presence of two or more morphological and immunophenotypical subtypes of lymphoma in a single tissue or organ. Composite lymphoma with concurrent mantle cell lymphoma (MCL) and classical Hodgkin lymphoma is extremely rare. In this case report, we present the case of a 70-year-old male who was diagnosed with a composite of MCL and classical Hodgkin lymphoma (cHL) and achieved near-complete resolution with chemoimmunotherapy. To the best of our knowledge, this is the first case of this kind demonstrating the effectiveness of a combination chemoimmunotherapy regimen leading to complete remission in composite lymphoma involving MCL and cHL. We report the history, imaging findings, and pathology and illustrate the challenges in therapeutic decision-making in managing composite lymphoma patients involving MCL and cHL. We also review the literature on this rare entity and discuss its clinical implications.

How I do it? Endoscopic endonasal transpterygoid repair of sphenoid lateral recess cerebrospinal fluid leak after previous unsuccessful transcranial surgery.

BACKGROUND: Direct access to the sphenoid lateral recess offers the best chance of sealing spontaneous cerebrospinal fluid (CSF) rhinorrhea caused by lateral sphenoid encephaloceles of the Sternberg canal defect. METHOD: We present a case of spontaneous left-sided sphenoid lateral recess CSF leak after previous unsuccessful transcranial surgery managed with an endoscopic endonasal transpterygoid approach (EETA). An anatomical-based step-by-step illustration of the EETA was presented in the surgical video. CONCLUSION: This case demonstrates the value of endoscopic endonasal transpterygoid corridor in the exposure and manipulation of the sphenoid lateral recess.

Exoftalmos y dolor ocular como presentación clínica de linfoma de Hodgkin con afectación intracraneal al diagnóstico / Exophthalmos and ocular pain as clinical debut of intracranial Hodgkin's lymphoma at diagnosis

La afectación intracraneal del linfoma de Hodgkin (LH) es extremadamente rara, especialmente como forma de presentación de la enfermedad. Muestra un patrón radiológico inespecífico, pudiendo ser confundido con otras entidades de mayor frecuencia y pronóstico radicalmente distinto. Anatomopatológicamente se caracteriza por la presencia de células grandes binucleadas (células de Reed-Sternberg) eIntracranial involvement in Hodgkin's lymphoma (HL) is extremely unusual, especially at the time of diagnosis. Because of its non-specific radiological behaviour, it can be confused with more common entities with a radically different prognosis. Pathologically, large and bi-nucleated cells, called Reed-Sternberg cells, embedded in an inflammatory network.

In this report we describe the clinical case of a patient, with no medical history, with left ocular pain and exophthalmos as presentation of intracranial HL at diagnosis and review the most current literature. Intracranial involvement is often associated with extracranial disease. Therefore, a systemic study including body computed tomography, bone marrow biopsy and ophthalmological evaluation is necessary. Intracranial lesions respond favourably to treatment and the prognosis depends on the extracranial involvement. To date, there is no standardised management scheme for these patients. For us, the primary role of surgery in this context is to perform a biopsy to confirm the histological diagnosis (AU)mbebidas en un entramado inflamatorio. Presentamos el caso de una paciente con dolor ocular y exoftalmos izquierdo como presentación clínica de afectación intracraneal por LH al diagnóstico de su enfermedad y revisamos la literatura más reciente al respecto. En pacientes con LH intracraneal es necesario realizar un estudio de extensión con tomografía computarizada corporal, biopsia de médula ósea y examen oftalmológico. Se asocia con gran frecuencia a enfermedad extracraneal, que marca el pronóstico. La lesión intracraneal presenta buena respuesta al tratamiento, que no sigue un esquema estandarizado. El papel de la cirugía es la realización de una biopsia para confirmar el diagnóstico (AU)

Triple Lymphoma and Transformation to Diffuse Large B-Cell Lymphoma Finding at the Time of Diagnosis.

In this report, we present the case of a patient with an uncommon triple diagnosis of (1) follicular (nodular) lymphoma, (2) nodular lymphocyte predominant Hodgkin lymphoma, and (3) diffuse large B-cell lymphoma non-germinal center B-cell (non-GCB) subtype. Although transformation of follicular lymphoma and nodular lymphocyte predominant lymphoma to more aggressive forms such as diffuse large B-cell lymphoma is possible; it generally happens many years after diagnosis. Moreover, there have been reported cases of follicular lymphoma with transformation and nodular lymphocyte predominant Hodgkin lymphoma with transformation at the time of diagnosis, but it is very uncommon to see all three present on initial diagnosis. Our patient presented with a large right axillary mass, which, upon excisional biopsy and subsequent histology, showed the aforementioned lymphomas. The patient did not present with a prodrome of any symptoms except intermittent night sweats. The unique aspect of our case is that transformation and all three lymphomas were seen at the time of diagnosis. The R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy regimen is still the standard method of treatment as it has been shown to be effective in treating follicular lymphoma and nodular lymphocyte predominant Hodgkin lymphoma with and without transformation. However, there is insufficient literature on its efficacy when all three are present concurrently.

Exophthalmos and ocular pain as clinical debut of intracranial Hodgkin's lymphoma at diagnosis.

Intracranial involvement in Hodgkin's Lymphoma (HL) is extremely unusual, especially at the time of diagnosis. Because of its non-specific radiological behaviour, it can be confused with more common entities with a radically different prognosis. Pathologically, large and bi-nucleated cells, called Reed-Sternberg cells, embedded in an inflammatory network. In this report we describe the clinical case of a patient, with no medical history, with left ocular pain and exophthalmos as presetation of intracranial HL at diagnosis and review the most current literature. Intracranial involvement is often associated with extracranial disease. Therefore, a systemic study including body computed tomography, bone marrow biopsy and ophthalmological evaluation is necessary. Intracranial lesions respond favourably to treatment and the prognosis depends on the extracranial involvement. To date, there is no standardised management scheme for these patients. For us, the primary role of surgery in this context is to perform a biopsy to confirm the histological diagnosis.

BET inhibitors induce NF-κB and E2F downregulation in Hodgkin and Reed-Sternberg cells.

The prognosis of patients with relapsed and/or refractory classic Hodgkin lymphoma (cHL) continues to be poor. Therefore, there is a continuing need to develop novel therapies and to rationalize the use of target combinations. In recent years there has been growing interest in epigenetic targets for hematological malignancies under the rationale of the presence of common alterations in epigenetic transcriptional regulation. Since Hodgkin and Reed-Sternberg (HRS) cells have frequent inactivating mutations of the CREBBP and EP300 acetyltransferases, bromodomain and extra-terminal (BET) inhibitors can be a rational therapy for cHL. Here we aimed to confirm the efficacy of BET inhibitors (iBETs) using representative cell models and functional experiments, and to further explore biological mechanisms under iBET treatment using whole-transcriptome analyses. Our results reveal cytostatic rather than cytotoxic activity through the induction of G1/S and G2/M cell-cycle arrest, in addition to variable MYC downregulation. Additionally, massive changes in the transcriptome induced by the treatment include downregulation of relevant pathways in cHL disease: NF-kB and E2F, among others. Our findings support the therapeutic use of iBETs in selected cHL patients and reveal previously unknown biological mechanisms and consequences of pan-BET inhibition.

Assessment of tumor microenvironment expression and clinical significance of immune inhibitory molecule CTLA-4, ligand B7-1, and tumor-infiltrating regulatory cells in Hodgkin lymphoma.

Classical Hodgkin lymphoma represents a paradigm of tumor cell-microenvironment interactions as the neoplastic Hodgkin Reed-Sternberg (HRS) cells typically constitute less than 1% of the total tumor volume. CTLA-4, a member of the CD28/B7 immunoglobulin superfamily, and CD28 and their ligands B7-1 and B7-2 are critically important for the initial activation of naive T cells. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of the HL microenvironment. The study included 50 histopathological confirmed cases of Hodgkin lymphoma. IHC staining for CTLA-4 and B7-1 was performed on archival paraffin-embedded biopsy. SPSS version 17 was used for statistical analysis. CTLA-4 IHC expression in HRS cells was negative in all cases, while in immune cells, CTLA-4 expression was observed in 45 (90%) cases. CD80 expression was present in all cases, both in HRS and immune cells. There was a significant association between HRS cell percentage and IPS score (p-value=0.001). Mean survival duration was longer in <50% immune cells compared to >50% groups, with an overall mean survival of 67.633 months. Considering the CTLA4 expression in immune cells within the microenvironment and the availability of targeted drugs like Iplimumab, which act through CTLA4 blockade, it may be appropriate to use this as targeted therapy in HL cases, particularly in those with refractory disease who are unable to achieve cure prior to ASCT.