Anaplastic lymphoma kinase-positive large cell lymphoma of the anterior skull base: Report of an unusual case and review of the literature
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.\nMR imaging of the orbital and nasal region demonstrated a homogenous and well-circumscribed mass, with mild homogenous enhancement [] and mild restricted diffusion []. The lesion expands both nasal cavities and extends intracranially through the cribriform plates and through the clivus into the prepontine cistern. The mass encased the right cavernous carotid artery and exert mass effect on the optic nerve and chiasm. Enlarged retropharyngeal lymph nodes [] and upper level IB/II lymph nodes were observed. Maxillofacial CT scan confirmed the MR imaging findings and bony erosion of the anterior clivus, bilateral medial sphenoid bones, and left clinoid process. A staging positron emission tomography (PET)-CT showed hypermetabolism in the tumor tissue. Endonasal biopsy of the mass yielded specimens that showed histologic and immunohistochemical findings diagnostic of an ALK(+) ALCL [ and ].\nThe 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 []. PET-CT revealed markedly reduced hypermetabolism in the skull base mass and complete resolution hypermetabolism of the retropharyngeal lymph nodes. At the 1-year follow-up, the patient's neurologic and general condition remained stable, with unchanged visual acuity/field, stable MR imaging, and normal endocrinology labs.\nHematoxylin and eosin (H&E) sections of the nasal cavity mass biopsy show a diffuse lymphoid infiltrate [] underneath the nonkeratinizing stratified squamous epithelium consistent with the nasopharyngeal location. The lymphoid infiltrate is composed of sheets of large-sized markedly pleomorphic cells with abundant amphophilic cytoplasm, eccentrically located nuclei with vesicular chromatin, and prominent nucleoli. Occasional nuclei demonstrate horseshoe-like shape, consistent with the so-called “hallmark cells” [].\nTo further delineate the nature of this lymphoma, a panel of immunohistochemistry was performed [Figure –]. Immunohistochemistry demonstrates that the neoplastic cells are strongly and diffusely positive for CD30 [], epithelial membrane antigen (EMA) [], and T-cell intracellular antigen-1 (TIA-1) []. The majority of the neoplastic cells are also positive for CD4 [] and CD5, partially positive for CD45, and rarely positive for CD2 []. The neoplastic cells show diffuse nuclear and cytoplasmic staining of ALK-1 []. Epstein–Barr virus (EBV) by in-situ hybridization is negative. These findings were consistent with the diagnosis of ALK(+) ALCL.\nAdditionally, 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 .\nT-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 [].