- Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, La Jolla, CA, 92093-0815, USA
- Department of Radiology, Veterans Affairs Medical Center, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA
- Department of Radiology, Division of Neuroradiology, University of California San Diego Health System, 3855 Health Science Drive, La Jolla, CA, 92093-0987, USA
- Department of Pathology, Division of Neurosurgery, University of California San Diego Health System, 3855 Health Science Drive, La Jolla, CA, 92093-0987, USA
- Division of Neurosurgery, University of California San Diego Health System, 3855 Health Science Drive, La Jolla, CA, 92093-0987, USA
Clark C. Chen
Division of Neurosurgery, University of California San Diego Health System, 3855 Health Science Drive, La Jolla, CA, 92093-0987, USA
DOI:10.4103/2152-7806.110656Copyright: © 2013 Jamshidi P. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Jamshidi P, Chen JY, Wang H, Chen CC. Anaplastic lymphoma kinase-positive large cell lymphoma of the anterior skull base: Report of an unusual case and review of the literature. Surg Neurol Int 18-Apr-2013;4:57
How to cite this URL: Jamshidi P, Chen JY, Wang H, Chen CC. Anaplastic lymphoma kinase-positive large cell lymphoma of the anterior skull base: Report of an unusual case and review of the literature. Surg Neurol Int 18-Apr-2013;4:57. Available from: http://sni.wpengine.com/surgicalint_articles/anaplastic-lymphoma-kinase-positive-large-cell-lymphoma-of-the-anterior-skull-base-report-of-an-unusual-case-and-review-of-the-literature/
Background:Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare peripheral T-cell lymphoma, accounting for approximately 3% of adult non-Hodgkin lymphomas (NHL). In this report we describe an unusual case of an ALK(+) ALCL, which presented as an aggressive mass involving upper nasal cavity and anterior skull base. The pathogenesis, histopathology with radiologic correlations, and management of this case are reviewed.
Case Description:A 28-year-old Asian female presented with a 3-month history of nasal congestion culminating in epistaxis. Physical examination was notable for a tissue mass obstructing nasal cavity and the sphenoid sinus. Computed tomography (CT) and magnetic resonance (MR) imaging revealed a lesion primarily involving the upper nasal cavity extending intracranially through the cribriform plates into the anterior cranial fossa. Histologic and immunohistochemical analysis of the specimen obtained through a transnasal biopsy revealed an ALK(+) ALCL. The patient underwent two cycles of chemotherapy and focal radiation therapy, achieving minimal residual disease. The patient remained neurologically unchanged with stable minimal residual disease at the 1-year follow-up.
Conclusions:To the best of our knowledge, this is the first case of an ALK(+) ALCL that presented as an aggressive upper nasal cavity and anterior skull base lesion. This case report highlights the importance of multi-modality approaches including preoperative imaging and tissue biopsy for definitive diagnosis.
Keywords: Anaplastic large cell lymphoma, anaplastic lymphoma kinase, anterior skull base, lymphoma, upper nasal cavity
Lymphoma exclusively involving the nasal sinus or the anterior cranial fossa is rare in Western populations. It is, however, more common among Asian populations, constituting 3-8% of non-Hodgkin lymphoma (NHL).[
Peripheral T-cell lymphoma including anaplastic lymphoma kinase (ALK)(+) anaplastic large cell lymphoma (ALCL) is primarily nodal disease, although extranodal sites such as skin, gastrointestinal tract, bone marrow, liver, peripheral blood, head and neck region, and central nervous system can be involved.[
In this report the pathogenesis, correlations of histopathology with radiologic imaging, and management of ALK(+) ALCL are reviewed and discussed.
A 28-year-old Asian female presented with a 3-month history of nasal congestion culminating in epistaxis. Her medical history was otherwise unremarkable. Physical examination was notable for a tissue mass obstructing nasal cavity and compromised visual acuity (OS: No light perception, OD: 20/20). The patient gave a poor history regarding her visual loss but denied acute changes in vision over the weeks preceding admissions. No cutaneous lesions were identified. The absolute lymphocyte count (ALC) was 900/μL. Other laboratory values, including a detailed endocrinology panel, were within normal limits. Computed tomography (CT) and magnetic resonance (MR) imaging were obtained.
MR imaging of the orbital and nasal region demonstrated a homogenous and well-circumscribed mass, with mild homogenous enhancement [
MR images important for the correct differential diagnosis: ADC map (a) demonstrating mild restricted-diffusion, suggesting hypercellularity. Axial T2 (b) at the level of the nasopharynx demonstrates enlarged retropharyngeal lymph nodes, suggesting either primary lymphoid-disease or typical nodal spread of esthesioneuroblastoma
The patient underwent Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxyldaunorubicin (EPOCH) chemotherapy regimen for one cycle. Because of iatrogenic anemia, the patient was switched to the Ifosfamide, Mesna, Esoposide, Cytarabine (IVAC) chemotherapy regimen for another cycle. The patient additionally underwent conformal radiation therapy to the residual lesion was added (40 Gy in 20 fractions). Repeated MR imaging 6 months after completion of the treatment regimen showed a dramatic decrease in tumor size, such that the optic nerve no longer showed signs of compression [
Hematoxylin and eosin (H&E) sections of the nasal cavity mass biopsy show a diffuse lymphoid infiltrate [
To further delineate the nature of this lymphoma, a panel of immunohistochemistry was performed [Figure
Additionally, the negative CD3, CD7, and CD56 rule out NK-cell lymphoma; the negative CD138 rules out plasma cell neoplasia; the negative pan-keratin rules out a metastatic carcinoma; furthermore, the negative GFAP, chromogranin, synaptophysin, neuron-specific enolase, and S100 rule out tumors from the central nervous system and melanoma. The detailed immunohistochemistry of all the markers used and their results are listed in
T-cell receptor (TCR) gene rearrangement studies performed by ARUP Laboratory (Salt Lake City, Utah) showed monoclonal TCR gamma gene rearrangement. Chromosomal analysis of the rearrangements suggest that the positive ALK expression was most likely due to the translocation of ALK located on chromosome 2p23 and nucleophosmin located on 5q35 namely t(2;5)(p23;q35), based on the both nuclear and cytoplasmic granular staining pattern [
Lesions in the upper nasal cavity and skull base constitute a diverse group of pathologic conditions that present unique management challenges. Therapeutic strategies are largely dictated by the radiation sensitivity of the lesion and local anatomy. Cyto-reduction through surgery or neo-adjuvent chemotherapy is warranted for radiation resistant tumors in close proximity to the optic apparatus. In the case presented here, the decision to proceed with chemotherapy and radiation is grounded on the well-known sensitivity of ALK(+) ALCL to these agents.[
While there are lymphomas of NK/T- and B-cell origin that present in the nasal cavity or anterior skull base, ALK(+) ALCL of T-cell origin has not been reported in this anatomical location. In the current World Health Organization (WHO) classification, ALCL is divided into cutaneous and systemic types, with the latter further delineated by the presence or absence of ALK protein expression. ALK gene encodes a tyrosine kinase receptor belonging to the insulin receptor superfamily, which is expressed within the central nervous system in the early stage of embryogenesis.[
The presence of ALK protein defines a group of T-cell ALK(+) ALCL with favorable prognosis when treated with standard chemotherapy.[
At molecular genetic level, all ALK(+) ALCL harbor ALK translocation at chromosome 2p23 locus but with different partner genes, the most frequent of which is nucleoplasmin (NPM) gene on chromosome 5q35 locus.[
In sum, we report an unusual case of ALK(+) ALCL that presented as an aggressive neoplasm involving upper nasal cavity and anterior skull base. To the best of our knowledge, this is the first report of an ALK(+) ALCL in this anatomical location. This case illustrates the importance of multi-modality approaches in the diagnosis and management of neurologic malignancies.
The authors would like to thank Dr. Bob S. Carter for his constructive comments on the manuscript, UCSD healthcare providers involved in the care of this patient, including Drs. Erik Curtis, Jacob Husseman, and Dr. Ke Li for his contribution in preparing the Immunohistochemistry Table.
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