DIAGNOSIS
MASS, LEFT ORBITAL, EXCISION:
Diagnostic comment
Morphologic examination demonstrates extensive deposition of amorphous congophilic material consistent with amyloid. There are also scattered foci of lymphocytes with occasional follicles with germinal centers. Associated with these follicles are a moderate number of kappa restricted, CD19+, cyclin D1- and CD56- plasma cells. The possibility of a B-cell lymphoma with plasmacytic differentiation is favored over a plasma cell neoplasm. Correlation with the other clinical, laboratory, and radiology findings, as well as the consideration for a bone marrow biopsy would be of great interest in further characterization of this neoplasm. If additional material is collected, fresh tissue for flow cytometric immunophenotypic studies will be helpful. If clinically indicated, material could be sent out for further characterization of amyloid.
Patient Follow-up
The patient had an additional biopsy sent out for further characterization of amyloid, which showed AL kappa type amyloidosis. Serum immunological studies were performed, with the results shown in Table 2. The patient also had serum and urine immunoelectrophoresis performed, which detected no serum or urine monoclonal proteins, and a lumbar puncture performed, with negative cytology.
Table 2. Immunologic Lab Values
As treatment, the patient received radiation, with a total dose of 24 Gy in 12 fractions using a 3D conformal treatment to cover the entire orbital region. At her follow up after radiotherapy, she noted improved visual acuity, particularly in the left lateral visual field. Repeat CT sinus/orbit showed stable to minimal decrease in size of soft tissue mass, see Figure 7.
The patient also agreed to start 4 courses of systemic chemotherapy with Rituxan.
Due to the amyloidosis being of the AL kappa type, an echocardiogram was performed, which showed no evidence of involvement by amyloidosis.
DISCUSSION
Amyloidosis is the disease caused by accumulation of abnormal extracellular aggregates of low-molecular weight proteins, or amyloid fibrils, in tissues which causes damage of affected organs [1-3]. Light chain amyloidosis (AL) is the most common type of amyloidosis affecting approximately 10 patients per million per year, and is often the most lethal, as it can affect the heart, causing a restrictive cardiomyopathy [1-6]. It is caused by deposition of the immunoglobulin light chain in the setting of plasma cell neoplasms [1-6]. Serum amyloid A, an acute phase reactant, is implicated in Amyloid A amyloidosis (AA), which is associated with chronic inflammatory diseases [1-3, 7-8]. Other types of amyloidosis include hereditary, dialysis-related, systemic old-age, and organ-specific amyloidosis [1-3, 9-12].
The patient's amyloid protein was classified as amyloid light chain, kappa type. The periocular soft tissue mass may represent localized AL amyloidosis, or it is possible that it is the first manifestation of systemic AL amyloidosis, which can be primary, or secondary to plasma cell myeloma, or rarely Waldenstrom macroglobulinemia or non-Hodgkin lymphoma [1-6, 20]. The patient's serum and urine protein electrophoreses were unremarkable, along with the patient's serum immunoglobulin and light chains; absence of serum or urine monoclonal proteins occurs in less than 5% of patients with AL amyloidosis [1]. The clinical manifestations of AL amyloid are varied and depend on which organ is affected. There is commonly renal, cardiac, gastrointestinal, and neurological involvement [1-6].
Diagnosis of amyloidosis usually occurs at biopsy, but imaging can sometimes be suspicious of amyloid deposition [1]. For patients with systemic involvement, fat pad biopsy is the recommended site with sensitivity of 57-85% and a specificity of 92-100% for AL [1, 13, 17-18]. Amyloid deposits that are stained with Congo Red show characteristic apple-green birefringence under polarized light [1-6]. Immunohistochemistry can be useful in characterizing amyloid type, particularly for amyloid A and transthyretin amyloid, but has less utility with AL amyloid, as the antigenic epitopes may be lost due to proteolysis during deposition and fibril formation [1, 19]. Additional methods for characterizing amyloid type include mass spectroscopy and amino acid sequencing, which can be performed on formalin-fixed paraffin-embedded tissue via laser capture microdissection [1, 15].
Treatment of AL amyloidosis usually involves treating the underlying plasma cell neoplasm [1-6]. Options for treatment include chemotherapeutics, autologous stem cell transplantation, and radiotherapy for local involvement, among others [1-6, 20]. Our patient received local radiotherapy combined with Rituxin. Treatment with Rituxin, particularly in combination with other agents such as idelalisib has shown efficacy in systemic AL [21].
REFERENCES
Contributed by Terri Jones, MD and Nidhi Aggarwal, MD