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Entry

Ears, Nose, and Throat in Leukemias and Lymphomas

by
Pinelopi Samara
1,*,
Michail Athanasopoulos
2 and
Ioannis Athanasopoulos
2
1
Children’s Oncology Unit “Marianna V. Vardinoyannis-ELPIDA”, Aghia Sophia Children’s Hospital, 11527 Athens, Greece
2
Otolaryngology-Head & Neck Surgery, Athens Pediatric Center, 15125 Athens, Greece
*
Author to whom correspondence should be addressed.
Encyclopedia 2024, 4(4), 1891-1903; https://doi.org/10.3390/encyclopedia4040123
Submission received: 5 November 2024 / Revised: 3 December 2024 / Accepted: 17 December 2024 / Published: 18 December 2024
(This article belongs to the Section Medicine & Pharmacology)
Browse Figure
Versions Notes

Definition

:
Leukemias and lymphomas, encompassing a spectrum of hematologic malignancies, often exhibit manifestations in various tissues and organs, including the ears, nose, and throat (ENT) region, extending beyond the typical sites of bone marrow and lymph nodes. This manuscript explores these interactions, considering disease-related symptoms and treatment effects. ENT symptoms, such as otalgia, hearing loss, and nasal obstruction, may arise from direct infiltration or treatment complications, with chemotherapy-induced ototoxicity being particularly characteristic. Furthermore, immunotherapy complications, including cytokine release syndrome and mucosal irritation, can also contribute to ENT symptoms. Additionally, targeted therapy and radiotherapy can lead to mucosal dryness, dysphonia, and radiation-induced otitis media. Patients with hematologic malignancies are especially vulnerable to various ENT infections, including bacterial, viral, and fungal infections, due to compromised immunity resulting from both the disease and its treatments. Conditions such as rhinosinusitis, otitis media, and pharyngitis pose significant management challenges. Moreover, patients undergoing hematopoietic stem cell transplantation (HSCT) face unique ENT considerations, including mucositis, opportunistic infections, and graft-versus-host disease in cases of allogeneic HSCT. These patients require specialized pre-transplant evaluations, meticulous post-transplant surveillance, and tailored assistance to mitigate complications. This manuscript underscores the importance of a multidisciplinary approach that integrates diagnostics, pharmacological interventions, and supportive care to address both disease-related and treatment-induced ENT manifestations. Further research is needed to refine management strategies and improve outcomes in this complex clinical population.

Graphical Abstract

1. Introduction

Leukemias and lymphomas represent a diverse group of hematologic malignancies with highly variable clinical presentations. Symptoms commonly include fatigue, fever, night sweats, unintentional weight loss, petechiae, bone pain, and lymphadenopathy [1,2]. While traditionally associated with bone marrow and lymph node involvement, these malignancies can also present in extramedullary sites, including the ears, nose, and throat (ENT) region [3]. Diagnosis typically involves a combination of blood tests, bone marrow or lymph node biopsies, and imaging studies. The clinical management of leukemias and lymphomas is complex due to their heterogeneous characteristics, clinical variability, and evolving treatment approaches [4,5,6]. Treatment strategies depend on the specific type and stage of the disease, as well as molecular and cytogenetic features, and may include chemotherapy, radiation therapy, targeted therapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT) [7,8,9,10]. The primary goals of treatment are to control disease progression, achieve remission and improve overall survival while minimizing treatment-related toxicity. The ENT region can exhibit a range of symptoms and complications in patients with hematologic malignancies. Direct infiltration by leukemia or lymphoma cells can lead to symptoms such as otalgia, hearing loss, nasal obstruction, and dysphagia [11,12]. Additionally, treatment modalities can introduce challenges, including ototoxicity, mucosal dryness, and radiation-induced otitis media [13,14]. Patients with hematologic malignancies are also more susceptible to ENT infections-including bacterial, viral, and fungal, due to compromised immunity from both the disease and its treatments [15]. These infections, along with common conditions like sinusitis and pharyngitis, pose significant management challenges, necessitating tailored care strategies. Furthermore, patients undergoing HSCT may experience ENT complications such as mucositis and opportunistic infections. Graft-versus-host disease (GvHD) is specific to allogeneic HSCT, where donor immune cells attack the recipient’s tissues, a complication not seen in autologous HSCT [16]. The complexities of pre-transplant evaluation, post-transplant surveillance, and individualized support are crucial for minimizing complications and optimizing outcomes in this patient population. Given these intricacies, a multidisciplinary approach that integrates diagnostics, pharmacological interventions, and supportive care is essential for addressing both disease-related and treatment-induced ENT manifestations.
This manuscript aims to investigate the complex relationship between leukemias, lymphomas, and the ENT system, emphasizing the need for further research into preventive strategies and innovative therapies targeting ENT complications-an area often underrepresented in existing literature. Through comprehensive analysis, we seek to improve understanding and optimize management strategies to enhance care and outcomes for individuals with hematologic malignancies involving the ENT region.

2. Disease-Related ENT Manifestations: Key Symptoms and Clinical Implications

Both leukemias and lymphomas can present in the ENT regions, highlighting the need for otolaryngologists to consider these hematologic malignancies in their differential diagnoses. These conditions may initially mimic benign ENT disorders, leading patients to seek evaluation from ENT specialists and potentially causing diagnostic delays if a malignant cause is overlooked, especially in atypical cases. While primary ENT involvement is more frequent in lymphomas, advanced leukemias can also result in ENT-related symptoms due to direct infiltration or systemic complications (Table 1). Early recognition and timely referral to hematology are essential, underscoring the vital role of ENT specialists in facilitating prompt diagnosis and improving patient outcomes.

2.1. Extranodal Lymphoma in Waldeyer’s Ring

Extranodal lymphomas, particularly in Waldeyer’s ring, may present with chronic, unresolved sore throat that does not respond to standard treatments such as antibiotics or anti-inflammatories. Main symptoms include asymmetric tonsillar enlargement, localized oropharyngeal pain, dysphagia, and odynophagia [17]. Although rare, primary tonsillar lymphomas are mostly non-Hodgkin types, with diffuse large B-cell lymphoma (DLBCL) being the most common oropharyngeal subtype [18,19,20]. ENT specialists should maintain a high index of suspicion for lymphoma in cases of unilateral tonsillar hypertrophy, especially when systemic symptoms like night sweats or weight loss are present. Vigilance is particularly important when evaluating persistent pharyngeal symptoms in patients with immunosuppression or a prior lymphoma history.

2.2. Leukemia Manifestations in the Oropharynx

In acute leukemias, infiltration of oropharyngeal tissues may lead to persistent throat pain and gingival hyperplasia, with gingival swelling -especially in certain subtypes of acute myeloid leukemia (AML) -manifesting as swollen, bleeding gums that can be mistaken for periodontal disease [21]. Persistent gingival issues should prompt further investigation in these cases.

2.3. Sinonasal Lymphomas

Sinonasal lymphomas, particularly aggressive types like extranodal NK/T-cell lymphoma, can cause chronic unilateral nasal obstruction and epistaxis due to invasion of vascular structures. These tumors may rapidly infiltrate surrounding tissues, leading to facial pain, pressure, and obstruction [22]. Persistent or unilateral nasal symptoms that do not resolve with standard treatments should prompt endoscopic and imaging investigations to rule out malignancy.

2.4. Hemorrhagic Symptoms in Leukemia

Leukemias can also present with bleeding symptoms due to thrombocytopenia, resulting in spontaneous epistaxis and petechiae on mucosal surfaces. Acute leukemias may exhibit frequent nosebleeds that seem disproportionate to minor trauma or irritation [23]. Recurrent, unexplained epistaxis, especially accompanied by other signs of hematologic dysfunction, should prompt further investigation for potential underlying malignancies.

2.5. Lymphoma and Nasopharyngeal Involvement

Lymphoma involvement in the nasopharyngeal or parapharyngeal regions can lead to Eustachian tube dysfunction, causing conductive hearing loss and a sensation of fullness in the ear. Persistent otalgia without signs of infection may occur if adjacent nerves are compressed or infiltrated by tumor mass. Otitis media with effusion in adults, in the absence of an active infection, may indicate a nasopharyngeal mass [24]. While leukemic infiltration in the head and neck is less frequently associated with primary ENT symptoms, similar presentations can occasionally arise [25].

2.6. Cervical Lymphadenopathy

Cervical lymphadenopathy is a characteristic feature of lymphoproliferative disorders, typically presenting as painless, non-tender, and progressive enlargement of lymph nodes. In Hodgkin lymphoma (HL), the cervical region is often the first site affected, whereas non-Hodgkin lymphoma (NHL) can involve both nodal and extranodal areas [26]. Low-grade lymphomas generally exhibit slow, steady growth, while aggressive subtypes, such as DLBCL, may present with rapid enlargement accompanied by systemic B symptoms, including fever, night sweats, and weight loss. Chronic lymphocytic leukemia (CLL) and certain acute leukemias may also manifest with lymphadenopathy, often within a broader systemic picture that includes splenomegaly, hepatomegaly, and cytopenias. Persistent or unexplained lymphadenopathy warrants further evaluation through imaging and, if necessary, histopathologic assessment to determine whether the underlying cause is reactive or malignant.

2.7. Superior Vena Cava Syndrome in Aggressive Lymphomas

In aggressive lymphomas, such as mediastinal large B-cell lymphoma, more commonly seen in adults, and T-cell lymphoblastic lymphoma, more prevalent in children and adolescents, compression of the superior vena cava (SVC) can lead to SVC syndrome, marked by facial edema, distended neck veins, and respiratory distress [27,28]. Although SVC syndrome is not exclusively an ENT presentation, it can cause significant cervical and facial swelling, often leading to initial evaluation by otolaryngologists. This condition is an oncologic emergency requiring urgent imaging and multidisciplinary intervention. While more commonly associated with lymphoma, extensive mediastinal involvement in leukemias, particularly during blast crisis, can also result in SVC syndrome [29,30]. Timely identification and referral are crucial to prevent complications from compromised blood flows.

2.8. Role of ENT Specialists in Early Detection and Referral

Otolaryngologists should maintain a high index of suspicion for malignancy when encountering atypical, unilateral, or refractory ENT symptoms. Since some leukemias and lymphomas may initially present with minimal systemic signs, comprehensive head and neck examinations, endoscopic assessments, and appropriate imaging are crucial for early detection. Leukemias and lymphomas can also present with systemic symptoms which often accompany localized ENT findings. Therefore, unexplained or persistent ENT symptoms alongside systemic signs should prompt further laboratory and imaging evaluations. The overlap of ENT manifestations with benign conditions-such as tonsillitis, sinusitis, or otitis media-presents a diagnostic challenge [31]. Key diagnostic tools include fiberoptic laryngoscopy, high-resolution imaging, and histopathologic assessment via biopsy when clinically indicated. However, biopsy may not be necessary for all cases of lymphadenopathy; decisions should be guided by the clinical context and imaging findings. Recognizing disease-related ENT manifestations and facilitating early hematologic referrals can optimize treatment and improve patient outcomes in cases of head and neck involvement in leukemia and lymphoma.

3. Effects of Leukemia and Lymphoma Treatments on Ear, Nose, and Throat Health

The management of hematologic malignancies frequently involves a combination of antineoplastic therapy or radiotherapy, each of which can lead to specific complications in the ENT regions. Recognizing and addressing these treatment-related effects is essential for optimizing patient care and enhancing quality of life.

3.1. Ototoxicity Induced by Chemotherapy

Although platinum-based chemotherapeutic agents, such as cisplatin and carboplatin, are not typically used as first-line treatments for leukemia and lymphoma, they are occasionally utilized in cases of refractory or relapsed disease, where their potent antitumor effects may offer therapeutic benefits [32]. However, their use carries a considerable risk of ototoxicity, which commonly manifests as sensorineural hearing loss and tinnitus. This side effect is typically dose-dependent, with greater cumulative doses correlating with an increased likelihood and severity of auditory damage. The cochlea is primarily affected, leading to progressive hearing impairment that may develop gradually, often going unnoticed until it becomes more pronounced [33]. Early symptoms can include difficulty understanding speech in noisy environments and the perception of persistent ringing in the ears, which can interfere with daily activities.
In addition to platinum-based drugs, other chemotherapeutic agents used in leukemia and lymphoma-such as vincristine, methotrexate, cytarabine, ifosfamide, and asparaginase-may also carry a risk of ototoxicity, although generally to a lesser extent [34]. Vincristine and methotrexate, frequently used in standard protocols, can lead to hearing loss or tinnitus, particularly at high doses or with intrathecal administration. Similarly, high-dose cytarabine, often employed in leukemia treatment, and ifosfamide, commonly part of salvage regimens for lymphoma, carry ototoxic risks, especially when combined with other ototoxic agents [35]. Although asparaginase is not directly associated with ototoxicity, its use in combination therapies may result in auditory disorders in some patients, potentially due to its neurotoxic effects [36].
To mitigate these effects, it is recommended that patients receiving potentially ototoxic chemotherapy undergo regular audiometric testing to monitor hearing function. This proactive approach allows for timely detection of auditory changes and enables protective interventions, such as auditory rehabilitation programs or the use of hearing aids, aimed at preserving auditory function and enhancing patient well-being throughout treatment.

3.2. Nasal and Sinus Complications Resulting from Immunotherapy

Immunotherapies for leukemia and lymphoma enhance the body’s immune response against hematologic malignancies [37], which can inadvertently affect various tissues, including those in the ENT region. A notable adverse effect of CAR T-cell therapy is cytokine release syndrome (CRS), characterized by a surge of pro-inflammatory cytokines that can cause sinonasal mucosal swelling and sinusitis, as well as potentially impact ENT health through inflammation or vascular leakage. CRS may also present neurological symptoms, such as headaches, which can heighten ENT pain sensitivity. Additionally, immune effector cell-associated neurotoxicity syndrome (ICANS) can lead to facial swelling and drooping eyelids, further affecting ENT structures [38]. Monoclonal antibodies like rituximab may increase susceptibility to infections and hypersensitivity reactions [39], contributing to sinusitis or pharyngitis. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, nivolumab, and ipilimumab, initially used for treating metastatic melanoma, can induce rhinosinusitis [40,41] or nasal polyps [42] due to localized inflammation. While this immune activation is critical for effective cancer treatment, it may compromise ENT structures, leading to both local and systemic symptoms that require careful management. Continued research is essential to elucidate the underlying mechanisms and develop effective management strategies for these complex adverse effects.

3.3. Effects of Targeted Therapy and Radiotherapy

Targeted therapies, such as tyrosine kinase inhibitors (TKIs), including the well-known imatinib, can also affect the ENT region. Some TKIs are linked to oral mucositis, causing painful inflammation and ulceration in the oral cavity, complicating eating and swallowing [43]. Good oral hygiene and supportive care measures are crucial for managing these effects. Radiotherapy, commonly used for localized lymphomas or as part of leukemia treatment, can cause several acute and long-term effects on the ENT region. Acute side effects may include mucositis, xerostomia, and dysphagia due to damage to the salivary glands and mucosal surfaces, leading to significant discomfort and increased infection risk [44]. Long-term effects of radiotherapy can manifest as fibrosis, scarring, and structural changes in the treated areas, potentially resulting in chronic complications such as swallowing difficulties and altered taste sensation [45]. Clinicians should carefully assess these late sequelae, as they can profoundly impact a patient’s quality of life and long-term health. Addressing treatment-related complications (Table 1) in the ENT region is essential for managing hematologic malignancies and improving overall patient well-being.

4. ENT Infections in Patients with Hematologic Malignancies: Management Challenges

Patients with hematologic malignancies frequently exhibit profound immunosuppression as a consequence of both the malignancy itself and the therapeutic interventions employed, rendering them particularly vulnerable to a spectrum of infections-bacterial, viral, and fungal-that can significantly impact their general health status and therapeutic outcomes [46]. Patients with both leukemia and lymphoma are at an elevated risk of infections primarily due to neutropenia, especially during and after chemotherapy. Bacterial infections are frequently encountered early in a neutropenic episode, while the risk of fungal infections significantly increases if neutropenia persists. Viral infections typically emerge later in the course of neutropenia, particularly when the immune system is severely compromised, such as after prolonged neutropenia or during recovery phases [47].

4.1. Bacterial Infections

Bacterial infections are among the most common complications for immunocompromised patients, arising from disrupted mucosal barriers and weakened host defenses, particularly in the ENT region. Conditions such as sinusitis, otitis media, and pharyngitis occur with increased frequency and severity, often caused by pathogens like Streptococcus pneumoniae, and Hemophilus influenza. Sinusitis typically presents with nasal congestion, facial pain, and purulent nasal discharge [48]. Effective management requires the rapid initiation of broad-spectrum antibiotics, which may need adjustment based on culture results and clinical response. Otitis media is another bacterial complication. Patients often present with ear pain, hearing loss, and fever. The risk of acute otitis media is particularly elevated in children receiving treatment for hematologic malignancies [49]. Management may necessitate a more aggressive approach, including the use of tympanostomy tubes for recurrent infections.

4.2. Viral Infections

Viral infections present significant challenges for patients with hematologic malignancies, primarily due to their compromised immune systems, especially in those undergoing intensive treatments such as chemotherapy or HSCT. Common viral pathogens include influenza, respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus, herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV), all of which can lead to severe complications [50]. Influenza can result in acute respiratory distress and secondary bacterial pneumonia, often causing atypical and more severe symptoms in immunocompromised individuals. PIV can cause respiratory infections leading to laryngotracheobronchitis or pneumonia, while adenovirus is linked to severe respiratory and gastrointestinal illnesses. Early administration of antiviral medications, such as oseltamivir, is critical, especially in high-risk populations. Reactivation of HSV can lead to painful oropharyngeal lesions, requiring prompt treatment. CMV is particularly concerning in immunocompromised patients, leading to opportunistic infections such as pneumonia, colitis, and retinitis, which can cause significant morbidity. Additionally, EBV reactivation can result in infectious mononucleosis and is linked to lymphoproliferative disorders, including post-transplant lymphoproliferative disorder [51]. Prophylactic antiviral therapy may be necessary for patients undergoing intensive immunosuppressive treatment to mitigate the risks associated with these infections. Monitoring and early intervention are crucial in managing these viral threats to improve patient outcomes and overall health.

4.3. Fungal Infections

Fungal infections represent a serious risk in patients with hematologic malignancies, especially those with prolonged neutropenia. Common fungal pathogens, such as Candida, Mucor and Aspergillus species, can lead to opportunistic infections. Invasive fungal sinusitis is particularly concerning; it can progress rapidly and may require surgical intervention [52]. Patients may present with sinusitis symptoms that do not respond to standard antibiotic treatment, necessitating prompt imaging studies to assess for potential fungal invasion. Aspergillus fumigatus is the most common pathogen associated with this condition [53]. The management of fungal infections typically involves initiating antifungal therapy, with agents like echinocandins or voriconazole commonly used. However, managing these infections can be complicated by the patient’s underlying condition and the need for ongoing immunosuppressive therapy.
The management of infections in patients with hematologic malignancies is particularly challenging, as the symptoms often resemble those of treatment-related complications, complicating both diagnosis and management. The immunocompromised state can obscure typical clinical presentations, potentially resulting in delays in timely interventions. Therefore, a careful and judicious approach to antiviral therapy, coupled with vigilant monitoring for signs of viral reactivation or infection, is essential to ensure optimal patient outcomes.

5. Important Considerations in Hematopoietic Stem Cell Transplantation (HSCT)

Patients undergoing HSCT encounter distinct challenges related to the ENT due to profound immunosuppression and the aggressive conditioning regimens required for the procedure. The ENT manifestations in these individuals are often multifactorial, significantly affecting morbidity and overall quality of life.
Mucositis is a prevalent and debilitating side effect for HSCT recipients, commonly resulting from high-dose chemotherapy and total body irradiation in conditioning regimens. This condition can affect the oral cavity, pharynx, and larynx, leading to severe pain, difficulty swallowing, and an increased risk of infections due to the breakdown of the mucosal barrier. Management strategies for mucositis may include mouth rinses, pain relief measures, and, in some cases, cryotherapy to mitigate its severity [54]. Another significant consideration is GvHD, particularly chronic GvHD, which can impact the mucosal surfaces of the mouth and upper respiratory tract. Symptoms of GvHD include xerostomia, oral ulcers, and even mucosal fibrosis, which can impair speech, swallowing, and overall oral health [55]. Diagnosing and managing GvHD-related symptoms often requires collaboration between ENT specialists and transplant teams. Opportunistic infections also pose a considerable risk for HSCT patients due to prolonged immunosuppression. Fungal infections, such as candidiasis and aspergillosis, can affect the nasal passages and sinuses [56], while viral infections, including CMV and EBV, can lead to significant ENT morbidity, including nasopharyngeal ulcers or lymphoid hyperplasia [57]. Proactive surveillance for these infections, combined with prompt antifungal, antiviral, and antibiotic treatments, is crucial to prevent further complications.
Personalized care is essential for managing ENT manifestations in leukemia and lymphoma patients undergoing HSCT, ensuring optimal outcomes. Given the variability in patient responses to transplantation and differing risk profiles, individualized management strategies are critical. A thorough pre-transplant evaluation should include a detailed ENT examination to identify any pre-existing conditions, such as chronic sinusitis, dental infections, or oral health issues, that may complicate the transplantation process. Addressing these conditions prior to HSCT could reduce the risk of post-transplant complications.
Post-transplant surveillance is vital for monitoring complications such as GvHD, infections, and mucositis [58]. Regular ENT evaluations, along with imaging or endoscopy when necessary, help detect early signs of infection or tissue damage, facilitating timely interventions. Tailored supportive care is also important for managing side effects like mucositis, xerostomia, and chronic sinusitis. This may involve targeted therapies for pain relief, artificial saliva for dry mouth, and regular nasal irrigation for sinus issues [59]. Close collaboration among hematologists, infectious disease specialists, and other healthcare professionals is crucial to promptly and effectively address ENT complications, ultimately improving the patient’s overall quality of life.

6. Selected Case Reports of Special Interest: Uncommon ENT Manifestations in Patients with Leukemia and Lymphoma

Certain rare presentations may conceal an underlying diagnosis of lymphoma or leukemia, particularly in cases of disease recurrence, highlighting the critical need for heightened diagnostic awareness among clinicians, especially when conventional treatments fail to alleviate symptoms and the underlying pathology remains obscured. Five such cases are presented below.
Vigier et al. [60] reported an intriguing case involving a 7-month-old girl diagnosed with Burkitt leukemia, who initially presented with acute mastoiditis and elevated white blood cell counts. The clinical presentation was atypical for a straightforward infectious process, prompting further diagnostic evaluation. Imaging and microbiological tests confirmed a Streptococcus pneumoniae infection along with leukemic blast infiltration of the temporal bone, leading to her definitive diagnosis. After initiation of chemotherapy, the patient achieved remission, illustrating that atypical mastoiditis in young patients can sometimes serve as a harbinger of an underlying hematologic malignancy. This case underscores the importance of considering hematologic disorders in differential diagnoses for pediatric mastoiditis.
In a study by Helbig et al. [61], a 44-year-old woman with acute promyelocytic leukemia (APL) exhibited severe and multifaceted symptoms, including significant hearing loss and persistent headaches, which indicated an atypical relapse involving extramedullary disease affecting both the ear and central nervous system. Initially, she achieved remission through standard treatment protocols; however, she later experienced a rare relapse characterized by leukemic infiltration of the external auditory canals and mastoid area. Despite aggressive treatment regimens, the patient’s condition unfortunately deteriorated, underscoring the complex nature of extramedullary APL relapse involving ENT structures. This case suggests that relapses in these regions may necessitate specialized therapeutic strategies tailored to the unique challenges posed by ENT involvement, highlighting the need for further research into the mechanisms underlying this phenomenon.
A notable case reported by Davis et al. [62] from Australia involved a 53-year-old man with CLL who presented with a cutaneous lesion in the external auditory canal, associated with conductive hearing loss. While CLL is known to infiltrate the head and neck regions, isolated involvement of the external ear canal is particularly rare. This case underscores the diverse clinical manifestations of CLL and highlights the necessity for healthcare providers to remain vigilant in considering CLL as a potential cause of unilateral conductive hearing loss, especially in atypical presentations that may initially suggest other diagnoses.
Similar cases have also revealed the presence of lymphomas. Kim et al. [31] reported a case of unilateral tonsillar enlargement initially misdiagnosed as acute tonsillitis. Despite antibiotic treatment, the patient’s symptoms persisted, leading to further investigations that revealed lymphoma. This case highlights the importance of considering hematologic malignancies in persistent tonsillar symptoms and the need for thorough evaluation to distinguish between infectious processes and underlying malignancies. Lymphomas can also affect the nasal cavity and paranasal sinuses, often presenting with non-specific symptoms such as nasal obstruction. These manifestations can mimic chronic sinusitis or other benign conditions, leading to delays in diagnosis. Kennedy et al. [63] reported an unusual case of an 81-year-old woman who experienced acute nasal blockage caused by a large mass, later identified as DLBCL. This case stands out for its favorable prognosis, as the patient responded well to chemotherapy, achieving complete resolution of the mass within a year, contrasting with the generally poor outcomes seen in sinonasal lymphomas [64].
Together, these case reports illuminate the complex interplay between hematologic malignancies and their often-overlooked ENT manifestations, reinforcing the importance of a multidisciplinary approach to diagnosis and management in affected patients.

7. A Multidisciplinary Strategy for Managing ENT Manifestations

A multidisciplinary approach for handling ENT manifestations in patients with leukemia and lymphoma is vital for delivering comprehensive care and enhancing patient outcomes. These issues can result from the malignancies themselves or as side effects of antineoplastic therapy, immunosuppressive therapies, or radiation treatment. Effective collaboration among various medical specialties is essential to address these complex challenges. Central to this multidisciplinary tactic is accurate diagnostics, which enable the early detection of ENT-related complications. This involves the regular use of imaging techniques to identify sinus infections, soft tissue masses, or lymphadenopathy, as well as endoscopic evaluations for direct visualization of mucosal health in the upper respiratory and digestive tracts. For instance, quick identification of sinusitis or airway obstruction can prevent progression to more severe infections or respiratory distress, while timely biopsies of suspicious lesions can facilitate the diagnosis of lymphoma involvement. Pharmacological intervention is also a fundamental component of symptom management. Patients may require antibiotics, antifungals, or antivirals to prevent or treat infections in the ENT region, particularly those experiencing chemotherapy-induced neutropenia or other forms of immunosuppression. Additionally, steroids and other immunosuppressive agents can be employed to manage complications such as airway inflammation or specific ENT manifestations of the disease, such as laryngeal involvement in lymphoma.
Supportive care is another vital aspect of this approach [65]. Addressing common treatment-related side effects, such as mucositis, xerostomia, and voice changes, requires collaboration among ENT specialists, oncologists, hematologists, and rehabilitation teams. Interventions may include pain management, hydration therapy, and speech or swallowing rehabilitation. Nutritional support is particularly critical for patients with significant oral or pharyngeal involvement, ensuring they maintain adequate intake despite swallowing difficulties. Finally, integrating psychosocial support services is essential for addressing the emotional and mental health needs of patients who may experience distress due to the physical and cosmetic effects of ENT complications. Incorporating psychosocial care into the overall treatment plan enhances the quality of life for patients facing complex ENT issues during their leukemia and lymphoma treatment.

8. Advancing Research Strategies for ENT Health in Leukemia and Lymphoma Patients

There is considerable potential for advancing research aimed at improving the management of ENT manifestations in patients with leukemia and lymphoma. Despite recent progress in treatment and supportive care, several knowledge gaps remain, presenting opportunities for innovative solutions.
One promising avenue is the development of novel therapeutic strategies to prevent or alleviate ENT complications, particularly mucositis and sinusitis. Although existing treatments provide some relief, there is a need for more effective and targeted therapies to reduce the severity of these conditions and enhance patient comfort. Biologics, for example, could pave the way for managing inflammatory disorders of the upper airways resulting from either the malignancy or its treatments. Another critical area of investigation is the creation of predictive models or biomarkers to better identify patients at risk for severe ENT complications. Early detection of patients predisposed to serious infections in the sinuses or oral cavity could facilitate preemptive interventions, minimizing the need for emergency care and prolonged hospital stays. Such predictive tools could leverage genetic, molecular, or microbiome profiling, advancing the principles of precision medicine in ENT care for patients with leukemia and lymphoma.
Infection prevention remains a significant concern for this population, underscoring the need for further research into strategies to combat opportunistic infections affecting the ENT region. Further investigation into the efficacy of antimicrobial prophylaxis tailored to individual risk profiles, along with the exploration of vaccine development for specific pathogens, could help reduce the incidence and severity of infections. Long-term follow-up studies assessing ENT-related sequelae in survivors of leukemia and lymphoma are also crucial. While acute complications during treatment are well documented, the long-term effects of these therapies on ENT health are less understood. Survivors may experience chronic conditions such as sinusitis, hearing loss, or vocal cord dysfunction, necessitating further research to determine the prevalence and impact of these issues over time. This information could guide the creation of survivorship care plans that include routine ENT monitoring and early interventions to prevent late-stage complications.
Additionally, further research into the impact of radiation therapy on ENT structures in patients with head and neck lymphoma is essential. Gaining a deeper understanding of the long-term effects of radiation on salivary glands, sinuses, and the throat could inform the development of radiation-sparing techniques or protective strategies that minimize damage while ensuring effective oncological control. Finally, as immunotherapies and targeted therapies become more prevalent in treating leukemia and lymphoma, future research should focus on how these treatments specifically affect the ENT region. Investigating the unique side effects associated with these newer therapies and their interactions with the upper airway and digestive tract will aid in developing more effective guidelines for managing their complications.

9. Conclusions

ENT manifestations in leukemia and lymphoma patients present unique challenges, complicating diagnosis and treatment. Complications such as mucositis, infections, and chronic issues like sinusitis and voice dysfunction require prompt recognition and targeted management to improve patients’ well-being. Emphasizing a multidisciplinary approach that includes collaboration among ENT specialists, oncologists, hematologists, and other healthcare providers enhances integrated care and informs future research directions. This comprehensive perspective is essential for advancing management and improving health outcomes in patients with leukemia and lymphoma.

Author Contributions

Conceptualization, visualization, P.S. and I.A.; methodology, investigation, M.A. and P.S.; writing—original draft preparation, M.A. and P.S.; supervision, review, and editing, I.A. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this paper.

Conflicts of Interest

The authors declare no conflicts of interest.

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Table 1. Common ear, nose, and throat (ENT) symptoms observed in patients with leukemia and lymphoma, along with complications arising from their treatment.
Table 1. Common ear, nose, and throat (ENT) symptoms observed in patients with leukemia and lymphoma, along with complications arising from their treatment.
ENT AreaSymptom or ComplicationCommon Cause
EarOtalgia, discomfort in the earInfections, leukemic cell infiltration, immunotherapy complications
Hearing LossChemotherapy-induced ototoxicity, leukemic infiltration
Tinnitus Lymphoma, chemotherapy effects
Otitis MediaImmunosuppression-related infections, radiation-induced
NoseNasal Obstruction/RhinorrheaLeukemic or lymphomatous infiltration, mucosal swelling or treatment-related edema
SinusitisImmunosuppression, cytokine release syndrome
Nasal PolypsLymphoma, immunotherapy (immune checkpoint inhibitors) or chronic inflammation
Epistaxis (Nosebleeds) Thrombocytopenia, mucosal fragility or treatment effects
ThroatSore Throat/Pharyngitis Leukemia, infections, mucositis from chemotherapy
Dysphonia, changes in voice quality Lymphoma, chemotherapy effects
Dysphagia/OdynophagiaChemotherapy-induced mucositis, lymphadenopathy, lymphoma, leukemic infiltration
Oral
Cavity		Gingival Enlargement/BleedingLeukemic infiltration, particularly in acute myeloid leukemia
UlcersMucositis from chemotherapy, infections
Oropharyngeal Lesions Reactivation of herpes or fungal infections due to immunosuppression
Salivary Gland Dysfunction/Xerostomia Radiation therapy, certain chemotherapeutic agents
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Samara, P.; Athanasopoulos, M.; Athanasopoulos, I. Ears, Nose, and Throat in Leukemias and Lymphomas. Encyclopedia 2024, 4, 1891-1903. https://doi.org/10.3390/encyclopedia4040123

AMA Style

Samara P, Athanasopoulos M, Athanasopoulos I. Ears, Nose, and Throat in Leukemias and Lymphomas. Encyclopedia. 2024; 4(4):1891-1903. https://doi.org/10.3390/encyclopedia4040123

Chicago/Turabian Style

Samara, Pinelopi, Michail Athanasopoulos, and Ioannis Athanasopoulos. 2024. "Ears, Nose, and Throat in Leukemias and Lymphomas" Encyclopedia 4, no. 4: 1891-1903. https://doi.org/10.3390/encyclopedia4040123

APA Style

Samara, P., Athanasopoulos, M., & Athanasopoulos, I. (2024). Ears, Nose, and Throat in Leukemias and Lymphomas. Encyclopedia, 4(4), 1891-1903. https://doi.org/10.3390/encyclopedia4040123

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