Jonathan Smith, MD Co- Authors Article in ENT Journal
07/08/2010 in news
Diffuse large B-cell lymphoma of the maxillary sinus
by Ryan M. O'Connor, MD, Matthew Vasey, MD, and Jonathan C. Smith, MD, FACS
Diffuse large B-cell lymphoma (DLBCL) accounts for nearly 40% of all cases of B-cell non-Hodgkin lymphoma in the Western world.1 But because its clinical presentation is so variable, many authors believe that it actually represents more than one disease process-or at least various subtypes of one disease process. We report a case of DLBCL that was initially diagnosed as osteomyelitis. This case highlights the importance of maintaining a high level of clinical suspicion for malignancy when faced with a presumed infectious process in the maxillary sinuses.
A 25-year-old man who had sustained left facial trauma 6 weeks earlier presented with a mildly painful swelling of the left maxilla and nasal obstruction. His history also included chronic nasal congestion, which had progressively worsened over the preceding year. He had already been treated elsewhere with 10 days of cefalexin followed by a course of amoxicillin/clavulanate, but he did not improve. He had no known drug allergies and he did not smoke tobacco, although he did drink alcohol. He denied vision disturbances, sinus drainage, fever, and chills.
On physical examination, the patient's vital signs were normal. In addition to the swelling over the left maxilla, he also had a hard, nontender, nonerythematous mass over the left side of his nose and an obvious deformity of the left nasal bones, his nasal pyramid was deviated to the right. Findings on the remainder of the physical examination were unremarkable.
An otolaryngology consult was requested, and a working diagnosis of left maxillary sinus osteomyelitis secondary to undiagnosed and untreated left maxillary sinus fractures was proposed. Nasal endoscopy revealed that the left nostril was filled with soft tissue, which made identification of landmarks difficult. Needle aspiration through the gingivobuccal sulcus yielded no purulent secretions. Computed tomography (CT) of the sinuses, maxillary bones, and nasal bones demonstrated soft-tissue obstruction of the left maxillary sinus and significant osteogenesis with heavy bone growth and coexisting bony destruction (figure). A radiolucent area over the left upper molars was also evident.
Figure. CTs demonstrate the soft-tissue obstruction of the left maxillary sinus and significant osteogenesis with heavy bone growth and coexisting bony destruction. The radiolucent area over the left upper molars is also seen .
The patient was taken to the operating room, and the soft tissue was removed from the left maxillary sinus for biopsy. In view of the patient's distorted intranasal anatomy, a Caldwell-Luc approach was used. Based on the pathology, the patient was diagnosed with DLBCL.
During 3 years of follow-up, the patient underwent regular nasal endoscopy, CT, and magnetic resonance imaging (MRI), and no evidence of persistent or recurrent disease was found.
Approximately half of all immunocompetent patients diagnosed with DLBCL undergo activation of either the BCL-6 or the BCL-2 proto-oncogene, while the other half display one molecular lesion that corresponds with the activation of the proto-oncogenes REL, MUC-1, BCL-8, and c-MYC.1 In immunodeficient patients, on the other hand, DLBCL is highly associated with Epstein-Barr virus infection.1 Overall, the molecular aspects of DLBCL have proven to be important in both diagnosis and treatment.
Imaging studies can assist in the diagnosis of non-Hodgkin lymphoma, but it is difficult to distinguish it from Hodgkin lymphoma on imaging alone.2 One significant difference between the two is the prevalence of extranodal involvement, in non-Hodgkin lymphoma, the prevalence of extranodal involvement is close to 30%, as opposed to only 6% in Hodgkin lymphoma.2
DLBCL commonly occurs in the paranasal sinuses, mandible, maxilla, and Waldeyer ring.2 Maxymiw et al studied 88 patients with extranodal maxillofacial involvement and found that the most common site was the maxillary sinus.3 Most of the patients in that study had presented with a nonpainful mass, intraoral swelling, dental pain, and loose teeth.
Because of the heterogeneous nature of DLBCL, predicting patient outcomes can be difficult. However, establishing a prognosis can be facilitated by the use of the International Prognostic Index, which predicts survival based on five significant risk factors: age, tumor stage, serum lactate dehydrogenase concentration, performance status, and extranodal involvement.4 Five-year survival for patients with two or more risk factors ranges from 26 to 51%.4 Heterogeneity has also been described in gene-array studies, which have revealed the existence of two distinct variants of DLBCL: germinal center-like DLBCL and activated peripheral B-cell-like DLBCL .
The treatment of DLBCL has evolved over the years, as doses have been increased, intervals between cycles have been shortened, and rituximab has been added to chemotherapeutic regimens.5 The current standard of care for all patients with advanced-stage DLBCL is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab. A short-term study by Knight et al showed that in patients older than 60 years, the addition of rituximab to CHOP increased the likelihood of a complete response by 20% without significantly increasing the risk of serious adverse events, the addition of rituximab also lowered mortality by 47% and relapse by 45%.6 Park et al conducted a retrospective analysis and found that the addition of rituximab improved survival in high-risk patients regardless of age, but they found no evidence of greater survival in low-risk patients.7 Other ideas being studied are (1) dose intensification, (2) initial treatment with chemotherapy plus allogeneic stem cell transplantation, and (3) infusional chemotherapy.8
Aggressive B-cell lymphoma frequently resembles an infection such as osteomyelitis. Plath et al documented a case of B-cell lymphoma that masqueraded as chronic osteomyelitis on both clinical and radiographic examinations.9 That case illustrated the necessity of obtaining an intraoperative biopsy to distinguish between infection and malignancy and to make a definitive diagnosis. Our case represents a classic example of a B-cell lymphoma that had many of the same radiographic features as osteomyelitis. Both of the CT scans presented here (figure) demonstrate evidence of both osteogenesis and bony destruction, a finding that is indicative of a chronic process. The bony thickening and opacification of the left maxillary sinus could have been attributable to either an infection or a malignant process. The radiolucent area over the left upper molars was suggestive of bony resorption and therefore a possible infectious process. Our patient's presentation could also have been confused with a maxillary abscess secondary to poor dental hygiene. Cases of DLBCL that resembled an odontogenic infection have been reported.10,11
Distinguishing between DLBCL and squamous cell carcinoma (SCC) is also imperative. SCC is the most common malignant tumor in the sinonasal cavity, and the maxillary sinus is the most common site of involvement.12 Non-Hodgkin lymphoma is the second most common malignant tumor in the head and neck.13 Sinonasal SCC demonstrates bone destruction on CT in approximately 80% of cases.14 Just like sinonasal SCC, sinonasal DLBCL can present as a mass with obstructive symptoms. High-grade aggressive lymphomas can also present with osseous or soft-tissue destruction and can produce lesions of both remodeling and erosion.15 Because the radiographic appearances of DLBCL and SCC are often similar, a biopsy for histologic analysis and immunochemistry is required to make a definitive diagnosis.
In conclusion, it is imperative that physicians entertain the idea of more devastating diseases in the differential diagnosis of a patient with presumed osteomyelitis secondary to persistent orofacial pain and swelling. Diseases such as DLBCL, SCC, and tumors of the minor salivary glands may present in such a way. Our case highlights the importance of maintaining a high level of clinical suspicion for malignancy when faced with a presumed infectious process in the maxillary sinuses.
From the St. George's University School of Medicine, Grenada, West Indies (Dr. O'Connor and Dr. Vasey), and ENT and Allergy Associates, Bronx, N.Y ., and the Department of Otorhinolaryngology-Head and Neck Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, N.Y. (Dr. Smith).
Jonathan C. Smith, MD, ENT and Allergy Associates, 1200 Waters Place, 2nd Floor, Bronx, NY 10461. E-mail: email@example.com
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