Volume 3, Issue 4 , Pages 165-169, December 2008
Multifocal anaplastic large T cell lymphoma of the ethmoid sinuses, temporalis muscle and frontal lobe in a 17-year-old boy
Article Outline
Summary
Sinonasal lymphomas are uncommon malignancies. We report the case of a 17-year-old boy who was diagnosed with ALK-negative anaplastic large T cell lymphoma (ALCL) of the sinonasal tract. This is a unique case because of the involvement of three separate sites. It highlights several important concepts related to sinonasal lymphomas including the fact that the diagnosis is often difficult to make, delays to diagnosis are common, and several biopsies are often necessary to reach an accurate diagnosis. Furthermore, we believe this to be the first reported case of ALK-negative anaplastic T cell lymphoma of the sinonasal tract.
Keywords: Non-Hodgkin's lymphoma, Anaplastic large cell lymphoma, T cell lymphoma, Paranasal sinus neoplasm, CNS, Temporalis
1. Introduction
Lymphomas encompass a diverse group of malignant neoplasms and represent the second most common malignancies of the head and neck. They account for approximately 5% of all malignant neoplasms in this region. They are commonly divided into Hodgkin and non-Hodgkin lymphomas and can arise in both nodal and extranodal sites. Among the extranodal variety, the site most commonly affected is Waldeyer's ring. These make up 15–20% of all lymphomas and nearly half of all extranodal lymphomas of the head and neck. Although lymphomas of the sinonasal tract are third in frequency, with the ocular region being the second most common site of involvement, sinonasal lymphomas are rare and only occur in 1.5% of all cases of non-Hodgkin's lymphoma (NHL) in the United States [1], [2], [3]. They are generally classified using the World Health Organization classification system developed in 1997 which categorizes lymphomas based on cell lineage and then according to their morphology, immunophenotype, genetic features and clinical syndromes [4].
We report the case of a 17-year-old boy who presented with a left temporal mass in whom a diagnosis of NHL was made. It involved the left ethmoid sinus, frontal lobe and left temporal subcutaneous tissue and muscle. There was significant delay to diagnosis due to his unusual presentation and lack of associated symptoms. This is an unusual case of ALK-negative anaplastic large T cell lymphoma presenting in multiple locations with contiguous spread through pre-formed pathways in the skull.
2. Case
A previously healthy 17-year-old boy presented to his physician with a slowly, progressive left periorbital swelling over a period of 4 months. He had no visual disturbances and all extraocular muscles were functionally intact. He was diagnosed with conjunctivitis and a trial of antibiotic eye drops was initiated. Ophthalmology was consulted after no improvement was observed. Their ocular exam was unremarkable but they did notice a marked swelling over the left temporal and zygomatic regions. The periorbital swelling had decreased considerably by this time. A CT of the head was ordered and showed a mass in the region of the left temporalis muscle. Left-sided pansinusitis was also incidentally found. He was asked to come to our hospital's emergency department for a thorough work-up of these findings.
The otolaryngology service was consulted to biopsy the mass in order to help establish a diagnosis. The patient denied any symptoms of fever, weight loss, decreased appetite or night sweats. There was no history of visual disturbances. A nasal symptom survey was unremarkable. There was no history of motor or sensory changes in the distribution of the facial or trigeminal nerves and he denied any pain or headache. On exam, he was found to have a firm, non-erythematous, ill-circumscribed left temporal mass. Eye examination performed in consultation with ophthalmology was unremarkable. His ear, nose and throat exam as well as flexible nasopharyngoscopy were unremarkable. All cranial nerves were functionally intact. His motor and sensory exams including gait and reflexes were normal. His INR (1.38) and ESR (21) were mildly elevated. All other laboratory investigations were within normal limits.
A CT (see Fig. 1) was repeated and an MRI (see Fig. 2) was performed on the day of presentation. In addition to the findings present on his outpatient CT, he was found to have a new left-sided epidural mass in the frontal region measuring 2
cm×1cm×3cm with an associated frontal subdural collection. After correcting his INR with vitamin K, the patient was taken to the operating room for a tissue diagnosis.
Fig. 1.
Axial CT scan post intravenous contrast administration displaying a diffusely enlarged left temporalis muscle (large arrowhead). Bilateral ethmoid opacification (thin arrow) was also incidentally noted.
Fig. 2.
Axial T2 (left) and T1 (right) weighted MRI post intravenous gadolinium administration. Note the solid epidural mass which does not enhance on T2 (arrowhead) and enhances on T1 (thick arrow). A hyper intense subdural collection is also noted on T2 (thin arrow). There is also an obvious left temporal swelling as was seen in Fig. 1.
The goal of the surgery was to establish a diagnosis. The easiest access point was felt to be the superficial temporalis muscle. Exposure was created by making a small incision over the muscle. The temporalis muscle was found to be grossly abnormal, appearing pale and edematous. Multiple biopsies of the muscle were taken and sent to pathology for intraoperative and permanent analysis. Reactive tissue was seen showing fibroinflammatory changes, destruction of skeletal muscle fibers, necrosis and chronic inflammation. Atypical cells were present but no definite tumour cells were observed. Thus the incision was closed, and a functional endoscopic sinus surgery was performed to obtain further tissue specimens. The maxillary, ethmoid, sphenoid and frontal sinuses were all explored. The maxillary sinus contained large amounts of mucopurulent secretions that were sent to microbiology for bacterial and fungal cultures. The left ethmoid sinuses contained a small, white, casseous-like tissue. Biopsies were sent for intraoperative analysis by frozen section revealing reactive tissue similar to that found in the temporalis muscle. Immunohistochemical analysis of the permanent sections from the ethmoid and sphenoid sinus was consistent with an ALK-negative anaplastic large T cell lymphoma (ALCL). All fungal and bacterial cultures and special stains were negative.
The patient received CHOP chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) as well as radiotherapy to the brain and cervical region. He showed partial response in the early phases of treatment. During the course of his treatment, he complained of progressively worse frontal headaches and nasal congestion. A repeat CT head was performed and revealed a residual mass within the sinuses. The patient was taken to the operating room once more to rule out persistent disease. Multiple biopsies of the sinuses were taken. These were negative for the presence of malignant cells, but were positive for aspergillus. He was started on Voriconazole. He has tolerated his treatment very well. A follow-up PET scan 1 year after initiation of treatment showed no evidence of disease.
3. Discussion
The differential diagnosis of pediatric sinonasal lymphoma is broad. Lesions are predominantly benign in nature and include allergic polyps and polyps associated with cystic fibrosis. Fibroosseous lesions and tumours of dental origin are the most common true neoplasms of the sinonasal tract. Rhabdomyosarcoma is the most common malignancy in this region. Although epithelial tumours such as squamous cell carcinoma and nasopharyngeal carcinoma are rare in the pediatric population, they should also be considered. Other possibilities include infectious causes such as invasive fungal sinusitis and systemic diseases such as Wegener's granulomatosis [5].
The diagnosis of non-Hodgkins lymphoma of the sinonasal tract is difficult to make. Historically, sinonasal tract lymphomas have often mistakenly been diagnosed as being non-malignant processes. Labels such as “polymorphic reticulosis”, “lethal midline granuloma”, and “malignant midline reticulosis” were given to them. This is largely due to the presence of other cell types including plasma cells, eosinophils, histiocytes, and acute inflammatory cells. They are often so abundant that the atypical lymphoid cells are scant and therefore difficult to identify [6].
Furthermore, given the anatomical location of this disease, access to the location for physical examination is difficult which often delays diagnosis. The tissue available for analysis by pathology is often very limited because of the difficulty of access and the tools used to biopsy the lesion [7], [8]. Moreover, the initial clinical symptoms are often vague and the diagnosis can be mistaken for other benign diseases. Finally, the lack of experience many clinicians have with sinonasal lymphomas makes the diagnosis even more difficult to make [2], [7], [9], [10].
The difficulty in making the pathological diagnosis was apparent in this case. Our original operative plan was to take biopsies of only the temporalis muscle. However, given that the intraoperative frozen section revealed no definite tumour cells in multiple temporalis muscle biopsy specimens, we opted to perform an ethmoid sinus biopsy in an effort to obtain diagnostic tissue. Frozen section analysis of the ethmoid sinus tissue also revealed reactive inflammatory cells with necrosis, without the presence of tumour cells. Malignant cells were only observed on the fresh tissue pathology sections of the ethmoid sinuses. Had ethmoid sinus biopsies not been taken, the tissue would unlikely have been diagnostic. This outlines the previously reported fact that multiple biopsies must be taken when non-Hodgkin's lymphoma of the sinonasal tract is in the differential diagnosis [11].
The difficulty associated with making the diagnosis of sinonasal lymphoma often leads to a delay in diagnosis. In our case, this delay along with the aggressive nature of this lymphoma allowed for the invasion of adjacent structures. Although it is unclear exactly where this tumour originated given its multiple sites of involvement, we believe it to be a primary ethmoid sinus lymphoma due to the significant presence of tumour cells in the specimens from this region.
The exact method of spread to adjacent structures is unclear. We believe the tumour first extended from the ethmoids into the anterior cranial fossa. It then likely made its way laterally across the calvarium into the temporalis region. Another possible explanation for the temporal swelling is that a periosteal reaction without tumour infiltration occurred in that region. This is a documented feature of lymphoma [12]. The periosteal reaction hypothesis would account for the absence of tumour cells in both the intraoperative and fresh tissue specimens of temporalis muscle.
The presence of disease in the frontal lobe is of particular interest. Although primary cranial vault lymphoma and recurrences of systemic lymphoma in the cranial vault after treatment are not uncommon, the direct spread of lymphoma into the cranial vault is [6], [13], [14]. Other authors have speculated on the exact method of direct spread to the cranial vault. These include hematogenous spread from more distant sites and direct invasion of the cranial vault. Speculations as to the direct method of spread include perineural spread along cranial nerves, spread along the emissary veins, invasion via the choroid plexus, and direct spread following extensive bony destruction by the primary lesion. Lymphatic spread is unlikely given the virtual absence of the lymphatic system in the CNS [14], [15], [16]. We speculate two likely methods of direct spread to the frontal lobe in our case are perineural spread and/or spread via the emissary veins of the skull based on the widespread presence of tumour extending up to the roof of the ethmoids (see Fig. 3).
Fig. 3.
Coronal CT scan post intravenous contrast administration showing widespread disease within the left ethmoid air cells (arrow) and extending up to the level of the fovea ethmoidalis.
In the western world, most of the NHLs found in the sinonasal tract are of the diffuse large B cell type. In contrast, there seems to be a predominance of the NK and T cell phenotypes in both East Asian and South American patients [1]. Furthermore, T and NK cell lymphomas predominate in the nasal cavity whereas B cell lymphomas predominate in the paranasal sinuses [17]. Based on immunohistochemistry, our specimen is consistent with an ALCL. The diagnosis was based on the strong and uniform positivity of CD30 and the presence of a T cell phenotype (CD2, CD3, and CD4). Given the site and presence of extensive vascular invasion, the diagnosis of sinonasal NK/T cell lymphoma was considered but ruled out given the absence of CD56 expression.
ALCL is relatively uncommon in the sinonasal region and a review of 120 cases of sinonasal lymphoma [2] found only one case of anaplastic large cell lymphoma. Furthermore, our specimen showed absence of ALK expression. The absence of this chromosomal aberration confers a poor prognosis and is rare in the pediatric population [18].
4. Conclusion
In conclusion, this case has several important teaching points worth highlighting. It outlines the difficulty associated with making the diagnosis of lymphoma of the sinonasal tract often leading to a delay in diagnosis. The delay to diagnosis and the aggressive nature of this T cell lymphoma led to the involvement of three separate anatomical locations. Many biopsy specimens from several separate sites are often necessary to make a prompt diagnosis and to prevent a delay in treatment. After an extensive review of the literature, we believe this to be the first case of an ALK-negative ALCL of the sinonasal tract in the pediatric population.
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PII: S1871-4048(08)00024-5
doi:10.1016/j.pedex.2008.03.004
© 2008 Elsevier Ireland Ltd. All rights reserved.
Volume 3, Issue 4 , Pages 165-169, December 2008
