Limfom difuz cu celulă B mare bulky, cu localizare nazo-oro-hipofaringiană, cu obstrucţie de căi aeriene, la un pacient vârstnic

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and represents a clinically and biologically heterogeneous entity, characterized by an aggressive course^(1,2). At diagnosis, DLBCL may involve nodal and extranodal sites, with extranodal disease reported in up to 40% of cases, most frequently affecting the gastrointestinal tract, bone marrow, central nervous system and Waldeyer’s ring^(2,3). Primary or extensive involvement of the naso-oro-hypopharyngeal region is uncommon, and may lead to severe local complications, including airway obstruction, dysphagia and secondary infections.

Advanced age at presentation is common in DLBCL, with a median age at diagnosis of approximately 65-70 years old⁽¹⁾. Elderly patients often present with multiple comorbidities, reduced functional reserve and increased vulnerability to treatment-related toxicity, which complicates therapeutic decision-making and may limit the use of standard immunochemotherapy regimens⁽⁴⁾. Furthermore, infectious complications, viral reactivations and organ dysfunction are more frequent in this population, necessitating individualized treatment strategies and close multidisciplinary collaboration.

Herein, we present a rare case of bulky naso-oro-hypopharyngeal DLBCL in an elderly patient with life-threatening airway obstruction and multiple comorbidities, highlighting the diagnostic challenges, therapeutic adaptations and the importance of a multidisciplinary approach in achieving long-term disease control.

Case report

We report the case of a 67-year-old woman who presented for initial evaluation in September 2021. At presentation, the patient was conscious but unable to speak, markedly cachectic and in significant distress. The clinical examination revealed fetid halitosis, the presence of both tracheostomy and gastrostomy, and an obvious tumoral mass at the oropharyngeal level. Additionally, bilateral submandibular and laterocervical lymphadenopathy were noted, with lymph nodes measuring approximately 2.5-3 cm and showing a tendency to coalesce. Purulent discharge was observed from the tracheostomy tube. The laboratory tests performed at the moment of diagnosis are presented in Table 1.

The histopathological examination of the biopsy specimen obtained from the right tonsillar mass established the diagnosis of diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), of the non-germinal center B-cell (non-GCB) subtype, with a high proliferative index (Ki-67) of approximately 80%. The tumor was bulky, measuring 97×91×131 mm, with an ulcero-vegetative appearance, areas of necrosis and secondary infection. The lesion extended from the naso-, oro- and hypopharyngeal regions to the level of the vocal cords, resulting in near-complete airway obstruction (Figure 1). Bone marrow biopsy showed no evidence of malignant infiltration.

The initial contrast-enhanced CT scan demonstrated that the tumor encased both the left and right jugular-carotid vascular bundles, with associated thrombosis of the right internal jugular vein. The only associated lymphadenopathy was located in the anterior cervical region. Thoracic imaging findings were suggestive of bronchopneumonia, while abdominal imaging revealed diffuse edematous thickening of the gastric wall. Upper gastrointestinal endoscopy could not be performed to complete the diagnostic staging because of the complete obstruction of the oro- and hypopharynx; however, gastrointestinal involvement was considered possible. We established the diagnosis of DLBCL, NOS, non-CGB stage IV B, bulky, R-IPI of four points.

Given the complete obstruction of the oropharynx, the emergency initiation of systemic chemotherapy was necessary. In the context of a newly diagnosed hepatitis B virus infection and a concomitant Klebsiella pneumoniae infection at the tracheostomy site, the monoclonal antibody was omitted during the first treatment cycle, and dose-adjusted CHOP chemotherapy was initiated. The imaging assessment after two cycles of chemotherapy demonstrated a favorable response, with an approximately 50% reduction in tumor size, to 40×31×72 mm. Hematologic treatment was continued with an additional cycle of R-CHOP; however, in the light of significant and progressive cachexia compared to the initial admission, severe cytopenias despite dose-adjusted chemotherapy, and recurrent infectious episodes, local radiotherapy was considered appropriate. The patient subsequently underwent involved-site radiotherapy with a total dose of 45 Gy delivered in 25 fractions.

Throughout the course of treatment, the patient experienced multiple infectious complications, all of them being resolved under appropriate targeted therapy. Notable infections included Clostridioides difficile-associated colitis, coagulase-negative staphylococcal infection at the gastrostomy insertion site, recurrent urinary tract infections caused by Klebsiella pneumoniae and Escherichia coli, as well as SARS-CoV-2 infection.

After three cycles of immunochemotherapy combined with radiotherapy, a PET-CT scan was performed. The examination revealed bilateral pulmonary consolidations and bilateral hilar lymph node uptake with a maximum SUV of 3.36, in the absence of metabolically active disease at the naso-, oro- or hypopharyngeal levels and without evidence of other metabolically active lymphadenopathy. The tracheostomy was subsequently decannulated, while the gastrostomy was maintained. The patient ultimately completed a total of six cycles of R-CHOP. Following completion of chemotherapy, the gastrostomy tube was also removed.

PET-CT evaluation performed after completion of six cycles of chemoimmunotherapy combined with radiotherapy showed no residual metabolic activity at the hypo-, oro- or nasopharyngeal levels; however, vertebral compression fractures at T11 and L1 were identified. Endocrinological assessment established the diagnosis of severe osteoporosis, and specific therapy was initiated. Subsequent periodic imaging evaluations confirmed sustained complete metabolic response.

At present, 4.5 years after the diagnosis, the patient is fully independent, ambulatory, capable of self-care, able to speak and eat normally, and maintains a good quality of life adapted to her associated comorbidities. This case highlights the critical importance of management within a multidisciplinary team, involving hematology, oncology, infectious diseases, radiology, otolaryngology, surgery and endocrinology.

Discussion

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and it is characterized by aggressive clinical behavior but potential curability with appropriate treatment⁽¹⁾. Extranodal involvement is observed in a significant proportion of cases; however, extensive disease affecting the naso-oro-hypopharyngeal region remains rare^(1,2). The reported cases in the literature usually describe limited involvement of a single anatomical subsite, such as the nasopharynx, oropharynx, hypopharynx, larynx or base of tongue, most often with smaller tumor burden and partial airway compromise^(2,6,7). To our knowledge, cases describing a single bulky mass with continuous extension across the naso-, oro- and hypopharynx, resulting in near-complete airway obstruction, are exceedingly rare.

The clinical presentation in our patient was dominated by life-threatening local complications, including complete obstruction of the upper aerodigestive tract, severe cachexia, secondary infections and vascular involvement with internal jugular vein thrombosis. Such a presentation poses significant diagnostic challenges, as tumors of the upper airway are more commonly attributed to squamous cell carcinoma, especially in elderly patients⁽⁸⁾. In this context, timely biopsy and histopathological confirmation were essential to avoid delays in initiating appropriate systemic therapy.

Airway compromise due to lymphoma is an uncommon but well-recognized oncologic emergency. While airway obstruction has been described in mediastinal or central airway lymphomas, reports involving upper airway obstruction caused by extranodal DLBCL are scarce^(1,5). The need for tracheostomy and gastro­stomy prior to diagnosis underscores the severity of local disease in our case, and highlights the importance of close collaboration between hematologists, otolaryngologists, anesthesiologists and surgeons in managing such patients.

Standard first-line therapy for DLBCL consists of rituximab-based immunochemotherapy⁽¹⁾. However, elderly patients frequently present with comorbidities that limit the immediate use of standard regimens⁽¹⁾. In our patient, newly diagnosed hepatitis B virus infection and concomitant bacterial infection at the tracheostomy site necessitated the omission of rituximab during the first treatment cycle and the initiation of dose-adjusted CHOP chemotherapy. Despite these limitations, a rapid and clinically meaningful tumor response was achieved, emphasizing the chemosensitivity of DLBCL even in extensively bulky disease, as previously reported in extranodal head and neck localizations^(7,8).

The subsequent treatment course was complicated by severe cytopenias, progressive cachexia and recurrent infections, reflecting the increased vulnerability of elderly patients to treatment-related toxicity⁽¹⁾. In this context, involved-site radiotherapy was employed as part of a tailored therapeutic strategy, aiming to maximize local disease control while limiting further systemic toxicity. This approach proved effective, resulting in complete metabolic response on PET-CT imaging, consistent with outcomes reported in selected cases of extranodal DLBCL treated with combined-modality therapy^(2,7).

The long-term follow-up demonstrated durable remission, with the patient remaining disease-free 4.5 years after diagnosis and regaining functional independence and satisfactory quality of life. Notably, late treatment-related complications, including vertebral compression fractures secondary to severe osteoporosis, required additional multidisciplinary management, further emphasizing the complexity of care in this population.

This case illustrates several important points: firstly, that DLBCL should be considered in the differential diagnosis of rapidly progressive obstructive tumors of the upper aerodigestive tract, secondly, that even extreme local disease with airway compromise can be successfully managed with prompt, individualized therapy, and thirdly, that optimal outcomes in such complex cases depend on coordinated multidisciplinary care. The rarity of this presentation and the favorable long-term outcome underscore the value of reporting this case to expand the existing knowledge regarding unusual localizations and management strategies for DLBCL^(1,2,5-8).

Conclusions

This case highlights the exceptional rarity of extensively bulky diffuse large B-cell lymphoma involving the naso-oro-hypopharyngeal region with near-complete airway obstruction. Despite the unfavorable biological profile of a non-germinal center B-cell subtype and the presence of significant comorbidities, the patient achieved a durable complete remission, underscoring that individualized, multidisciplinary management can lead to favorable outcomes even in biologically high-risk and clinically complex presentations.   

Corresponding author: Andreea Neculcea E-mail: andreea_neculcea23@yahoo.com

Conflict of interest: none declared.

Financial support: none declared.

This work is permanently accessible online free of charge and published under the CC-BY licence.