Plasmacytoma with amyloidosis masquerding as tuberculosis on cytology.

Amyloid material on lymph node cytology smears can mimic caseous necrosis. We report one such case where a 50-year-old lady presented with a nasal mass and cervical lymphadenopathy. Fine needle aspiration cytology smears of the cervical lymph node were interpreted as tuberculous lymphadenitis based on the presence of an occasional epithelioid cell and caseous material. The patient did not respond to antituberculous therapy and was revaluated. Repeat aspiration from the lymph node showed numerous plasma cells and myeloma cells in addition to the amorphous material which was confirmed to be amyloid on staining with congo red. A diagnosis of plasmacytoma with amyloidosis was rendered. Imprint smears from nasal mass, detailed hematology workup and subsequent histology confirmed the diagnosis.

Introduction

Plasmacytomas are malignant tumors of monoclonal plasma cells. They originate either in bone (osseous plasmacytoma) or in soft tissues (extramedullary plasmacytoma). Extramedullary plasmacytoma is a rare plasma cell neoplasm. It can occur as the sole manifestation of plasma cell neoplasm, as a metastasis from another extramedullary plasmacytoma or as a consequence of multiple myeloma.[1] It has no characteristics of multiple myeloma, but the development of multiple myeloma has been observed in 8–36% of patients months or years later.[2]

These plasma cell tumors can occur anywhere and have to be differentiated from other neoplasms, infectious processes and chloromas.[1] Approximately 80–90% extramedullary plasmacytoma occur in the head and neck region.[3]

Occasionally, amyloidosis also occurs in association with plasmacytoma. It can be localized or systemic. The head and neck region has been reported as a frequent site for amyloid deposits. One of the most common forms of amyloid proteins are amyloid light chain (AL-type), which is derived from plasma cells, contains immunoglobulin light chains and is associated with plasma cell dyscrasias.[4]

Case Report

Fine needle aspiration smears of a 50-year-old female patient with cervical lymphadenopathy were sent to the Department of Pathology without any clinical details. Cytology smears (Giemsa stain) showed sparse cellular aspirate with amorphous granular basophilic material, predominantly scattered lymphocytes, plasma cells and occasional epithelioid cells [Figure 1]. This amorphous material was interpreted as caseous necrosis and the possibility of tuberculous lymphadenitis was suggested. However, Ziehl Neelson staining for acid fast bacilli was negative. Subsequently, patient's clinical findings were provided with the request for review of slides as the patient had not responded to antituberculous treatment. In the details provided, a nasal growth was also mentioned to be present in the lateral wall of the nasal cavity, which was globular, firm and pink in colour and measured 3 × 2 × 2 cm. The review of the slides did not show any additional findings.

Figure 1

Lymph node aspirate showing amorphous granular basophilic material which mimicked caseous necrosis (Giemsa, × 400)

Repeat aspiration from the cervical lymph node, imprint smears and biopsy from the growth were performed. Repeat aspiration and imprint smears revealed high cellularity with amorphous basophilic material, large number of plasma cells with varying degree of maturity, myeloma cells and occasional scattered epithelioid cells. An occasional foreign body type, multinucleated giant cell with intracytoplasmic amorphous basophilic material was also seen. Plasma cells had prominent eccentric nuclei, coarse chromatin, perinuclear halo and basophilic cytoplasm and myeloma cells had fine chromatin, prominent nucleoli and little or no halo. Binucleate cells were also identified. Presence of numerous plasma cells and myeloma cells raised the possibility of plasmacytoma [Figure 2]. The amorphous extracellular material and similar intracytoplasmic material within giant cells raised the possibility of amyloid within the cells. Subsequent congo red staining of the cytology and histopathology slides, showed the amorphous material to be orange-red in color. It gave an apple-green birefringence when viewed under polarized light, confirming it to be amyloid. Thus, the diagnosis of plasmacytoma with amyloidosis was suggested and confirmed by a histopathology study of the biopsy tissue. There was no clinical, radiological or laboratory evidence of plasma cell dyscrasias or systemic amyloidosis.

Figure 2

Repeat lymph node aspirate showing plasma cells (uninucleate and binucleate), myeloma cells, scattered lymphocytes and amorphous basophilic material (Giemsa, × 400)

Discussion

Extramedullary plasmacytoma is a soft tissue neoplastic lesion that is made up of monoclonal plasma cells (plasma cell dyscrasias). It can be primary, without evidence of disease in other foci, or part of a systemic process during the course of multiple myeloma. Thus, these patients should be carefully evaluated for the presence of disseminated disease/multiple myeloma before arriving at a diagnosis of extramedullary plasmacytoma. Studies should include complete blood cell count, serum calcium levels, radiologic skeletal survey, magnetic resonance imaging (MRI) of the spine, pelvis, humeri and femurs, immunoelectrophoretic examination of serum and urine, β2 microglobulin assay and bone marrow biopsies. Diagnosis should be made only if all studies for disseminated disease are negative,[5] as was seen in our case.

These tumors can occur anywhere in the body, but nearly 80–90% of all extramedullary plasmacytoma occur in the head and neck region. Most of these cases arise in the aerodigestive tract, probably because of the abundance of lymphatic tissue in this area. In one study the frequently affected sites in decreasing order of frequency included nasal cavity or paranasal sinuses, nasopharynx, oropharynx and larynx.[3] Extramedullary plasmacytoma occurs in patients between 50 and 60 years of age, and is more common in men (4:1).

Plasmacytomas arising in the nasal cavity or nasopharynx usually present as a soft bleeding mass or as a polypoid mass, covered mostly by an intact overlying mucosa. Most common symptoms include nasal obstruction, nasal mass and epistaxis. Cervical lymphadenopathy and nasal discharge may be the associated presenting symptoms in an occasional patient. Microscopic examination of cytological smears show numerous plasma cells, including binucleate, multinucleate and pleomorphic forms. On histopathological examination, plasmacytomas are very vascular tumors with minimal stromal component and sheets of plasma cells with varying degrees of differentiation and immature plasma cells.

Differential diagnosis of plasmacytoma includes plasma cell granuloma, plasmacytoid lymphoma and large cell lymphoma of immunoblastic type. Immunocytochemical study with antibody to kappa and lambda light chains is an important approach to differentiate these conditions. Kappa or lambda light chain-restricted population confirms the diagnosis of plasmacytoma[5] and suggests a pathogenetic relationship between plasmacytoma and amyloid deposition.[6] Sakai et al.[7] diagnosed extramedullary plasmacytoma of the tonsil by demonstrating diffuse immunoreactivity for lambda light chains within plasmacytoid cells. Plasma cell granulomas show a balanced proliferation of kappa and lambda-reacting cells. Plasmacytoid lymphoma comprises a mixture of lymphocytes and plasma cells. Immunoblastic lymphomas usually involve lymph nodes and show cytoplasmic IgM heavy chain (IgG and IgA heavy chains in plasmacytomas) and express pan B cell surface antigens.[5]

Rarely, plasmacytomas are also associated with amyloid. Amyloid was present in 25% of the lesions in one series.[8] Eilam et al.[9] reported a case of plasmacytoma of the nasal cavity that involved the palate, ethmoidal and maxillary sinuses and contained deposits of amyloid. Ustun et al.[10] reported a case of extramedullary plasmacytoma of the parotid gland with extensive amyloid deposition masking the cytologic and histopathologic picture.

Amyloid refers to the extracellular fibrillar proteinaceous substance deposited in various tissues and organs of the body in a wide variety of clinical settings. It may be systemic or localised. Primary amyloidosis, a subtype of systemic pattern, is associated with immunocyte dyscrasias. Clinically, the symptoms depend on the magnitude of the deposits and on the particular sites or the organs affected.[11] Regarding its imaging appearance, affected bony conchae and sinus walls show a fluffy appearance adjacent to amyloid deposit on computed tomography scan; calcification has been mentioned as a nonspecific finding.[12] Foreign body giant cell reaction may be evoked about the amyloid deposits, as was also seen in our case. This reaction to amyloid has to be differentiated from plasma cell granulomas.[13] It can be seen on MRI as a peripheral enhancement in the region of amyloid deposits with contrast material administration.[12] Amyloid appeared as amorphous basophilic material on cytology smears in our case. Differential diagnosis of this material on lymph node cytology smears include caseous necrosis, tumor necrosis and colloid. Completely amorphous granular material without identifiable cell remnants suggest caseous necrosis, seen predominantly in tuberculosis caused by mycobacteria and other bacterial diseases and fungal infections. The type of granulomatous reaction, clinical details and bacteriological data are necessary to differentiate these conditions. Neoplastic conditions, specially the lymphomas (non-Hodgkin's and Hodgkin's) and metastatic carcinomas, show tumor necrosis and therefore should be excluded. Tumor necrosis appears as numerous cell shadows with pyknotic nuclei it may be homogenous or granular, resembling caseous necrosis. Colloid appears as a dense, blob-like material with sharp outlines on cytology smears from the thyroid.

Careful examination is necessary to distinguish localized amyloidosis from systemic amyloidosis. Rectal/bone marrow biopsy and fine needle aspiration of abdominal subcutaneous fat is suggested to rule out systemic amyloidosis.[14] The diagnosis of amyloid is based almost entirely on its staining characteristics. With light microscope and standard tissue stains, amyloid appears as an amorphous, eosinophilic, hyaline, extracellular substance.[11] Differentiation between amyloid and other amorphous eosinphilic substances, such as hyaline material, collagen and fibrin, is impossible. Thioflavin T and other fluorescent dyes offer greater sensitivity in detection of amyloid but both hyaline and fibrin give positive results. Thus, the gold standard for diagnosis of amyloid is congo red staining, which stains the tissue pink or red in color by light microscopy and gives green birefringence by polarized microscopy due to a β-pleated sheet conformation of amyloid fibrils.[14]